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Browse Health
Neurologist (brain, nervous system)
5 years of experience
Accepting new patients

Credentials

Education ?

Medical School
Des Moines Univ Col Of Osteo Med (2007)

Awards & Distinctions ?

Associations
American Board of Psychiatry and Neurology

Affiliations ?

Dr. Clark is affiliated with 5 hospitals.

Hospital Affiliations

Score

Rankings

  • Sacred Heart Medical Center
    1255 Hilyard St, Eugene, OR 97401
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    Top 25%
  • Cottage Grove Hospital
    1515 Village Dr, Cottage Grove, OR 97424
    •  
    Top 25%
  • Peace Harbor Hospital
    400 9th St, Florence, OR 97439
    •  
    Top 50%
  • McKenzie - Willamette Medical Center
    1460 G St, Springfield, OR 97477
    •  
  • Sacred Heart Medical Center At Riverbend
    3333 Riverbend Dr, Springfield, OR 97477
  • Publications & Research

    Dr. Clark has contributed to 247 publications.
    Title The Prothrombinase Activity of Fgl2 Contributes to the Pathogenesis of Experimental Arthritis.
    Date October 2011
    Journal Scandinavian Journal of Rheumatology
    Excerpt

    Fibrin deposition is integral to the pathogenesis of collagen-induced arthritis (CIA), an experimental model of rheumatoid arthritis (RA). Membrane-associated fibrinogen-like protein 2 (mFGL2), a novel inducible prothrombinase, generates fibrin by an alternate pathway and has been reported to be involved in the pathogenesis of a number of immune-mediated diseases. We hypothesized that expression of mFGL2 in inflamed synovium contributes to the fibrin deposition and subsequent inflammation in arthritis.

    Title Defining the Computational Structure of the Motion Detector in Drosophila.
    Date August 2011
    Journal Neuron
    Excerpt

    Many animals rely on visual motion detection for survival. Motion information is extracted from spatiotemporal intensity patterns on the retina, a paradigmatic neural computation. A phenomenological model, the Hassenstein-Reichardt correlator (HRC), relates visual inputs to neural activity and behavioral responses to motion, but the circuits that implement this computation remain unknown. By using cell-type specific genetic silencing, minimal motion stimuli, and in vivo calcium imaging, we examine two critical HRC inputs. These two pathways respond preferentially to light and dark moving edges. We demonstrate that these pathways perform overlapping but complementary subsets of the computations underlying the HRC. A numerical model implementing differential weighting of these operations displays the observed edge preferences. Intriguingly, these pathways are distinguished by their sensitivities to a stimulus correlation that corresponds to an illusory percept, "reverse phi," that affects many species. Thus, this computational architecture may be widely used to achieve edge selectivity in motion detection.

    Title Symptom Dimensions in Obsessive-compulsive Disorder: from Normal Cognitive Intrusions to Clinical Obsessions.
    Date August 2011
    Journal Journal of Anxiety Disorders
    Excerpt

    Cognitive behavioral models of obsessive-compulsive disorder (OCD) assume continuity between normal obsessional intrusive thoughts (OITs) and obsessions. However, this assumption has recently been criticized. This article examines this issue using a new instrument (the Obsessional Intrusive Thoughts Inventory, INPIOS) specifically designed to assess the frequency and content of 48 OITs, which was completed by 734 community subjects and 55 OCD patients. Confirmatory factor analysis suggests six first-order factors included in two second-order factors, one containing aggressive, sexual, religious, immoral and repugnant OITs, and the other containing contamination, doubts and checking, symmetry and order, and superstition OITs. This structure integrates the research on OC symptoms and OITs. The INPIOS showed excellent known-groups validity, and it adequately represented obsessions as well as OITs. OCD and community subjects experience OITs representative of all types of obsessional contents. The dimensional structure is discussed in terms of OIT/obsessive-compulsive symptom structures currently proposed.

    Title The Novel Immunoregulatory Molecule Fgl2: a Potential Biomarker for Severity of Chronic Hepatitis C Virus Infection.
    Date March 2011
    Journal Journal of Hepatology
    Excerpt

    This report describes the use of a novel sensitive and specific ELISA for the measurement of human fibrinogen-like protein 2 (FGL2/fibroleukin), a novel effector of natural regulatory T (Treg) cells, to predict the course of chronic hepatitis C viral infection (HCV).

    Title Cognitive Theory and Therapy of Anxiety and Depression: Convergence with Neurobiological Findings.
    Date February 2011
    Journal Trends in Cognitive Sciences
    Excerpt

    In this review paper a modified cognitive neurophysiological model of Aaron T. Beck's cognitive formulation of anxiety and depression is proposed that provides an elaborated account of the cognitive and neural mediational processes of cognitive therapy (CT). Empirical evidence consistent with this model is discussed that indicates the effectiveness of cognitive therapy could be associated with reduced activation of the amygdalohippocampal subcortical regions implicated in the generation of negative emotion and increased activation of higher-order frontal regions involved in cognitive control of negative emotion. Future cognitive neuroscience research is needed on the unique brain substrates affected by CT and their role in facilitating symptom change. This future research would have important implications for improving the efficiency and efficacy of this treatment approach.

    Title Teaching Colorectal Surgery in the Laparoscopic Era; is It Safe?
    Date January 2011
    Journal Journal of Surgical Education
    Excerpt

    With the introduction of laparoscopic colorectal surgery, the question is raised as to whether laparoscopic colectomies can safely be performed by surgical registrars, when supervised by experienced laparoscopic surgeons. In this study we have compared surgical outcomes of surgical registrars, fellows, and staff surgeons in a Dutch teaching hospital.

    Title Salvage of a Failed Sauve-kapandji Procedure Using a Total Distal Radio-ulnar Joint Replacement.
    Date November 2010
    Journal Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-pacific Federation of Societies for Surgery of the Hand
    Excerpt

    This is the first report in the literature of a patient treated with a DRUJ replacement after Sauvé-Kapandji procedure failed due to pain and instability. The DRUJ replacement is an unconstrained, biomechanically more advantageous implant which can confer stability in cases where soft tissues are inadequate. We describe the treatment and outcome of persistent ulnar instability with a distal radio-ulnar joint replacement following failed salvage procedures for a malunion of a distal radius fracture.

    Title A New Use for Fine Needle Aspiration Cytology in the Management of Patients with Breast Cancer.
    Date November 2010
    Journal Acta Cytologica
    Title Upper Limb Deep Vein Thrombosis: a Potentially Fatal Complication of a Clavicle Fracture.
    Date August 2010
    Journal Annals of the Royal College of Surgeons of England
    Excerpt

    We present a case a 48-year-old man who was diagnosed with an upper limb deep vein thrombosis post clavicle fracture. He was successfully investigated with a computed tomography (CT) venogram, thrombophilia was excluded, and he was subsequently treated with a 3-month course of anticoagulation. We illustrate this case with photographs and a three-dimensional colour reconstruction of a CT venogram to raise awareness of the condition. A suitable level of clinical suspicion should be maintained by the orthopaedic surgeon; delayed arm swelling with venous congestion following a clavicle fracture should be investigated with CT venography and thrombophilia should be excluded.

    Title Height is More Important Than Light in Determining Leaf Morphology in a Tropical Forest.
    Date July 2010
    Journal Ecology
    Excerpt

    Both within and between species, leaf physiological parameters are strongly related to leaf dry mass per area (LMA, g/m2), which has been found to increase from forest floor to canopy top in every forest where it has been measured. Although vertical LMA gradients in forests have historically been attributed to a direct phenotypic response to light, an increasing number of recent studies have provided evidence that water limitation in the upper canopy can constrain foliar morphological adaptations to higher light levels. We measured height, light, and LMA of all species encountered along 45 vertical canopy transects across a Costa Rican tropical rain forest. LMA was correlated with light levels in the lower canopy until approximately 18 m sample height and 22% diffuse transmittance. Height showed a remarkably linear relationship with LMA throughout the entire vertical canopy profile for all species pooled and for each functional group individually (except epiphytes), possibly through the influence of gravity on leaf water potential and turgor pressure. Models of forest function may be greatly simplified by estimating LMA-correlated leaf physiological parameters solely from foliage height profiles, which in turn can be assessed with satellite- and aircraft-based remote sensing.

    Title Watching the Fly Brain in Action.
    Date July 2010
    Journal Nature Methods
    Title Effects of Reduced Frequency of Milk Removal on Gene Expression in the Bovine Mammary Gland.
    Date June 2010
    Journal Physiological Genomics
    Excerpt

    Regulation of milk synthesis and secretion is controlled mostly through local (intramammary) mechanisms. To gain insight into the molecular pathways comprising this response, an analysis of mammary gene expression was conducted in 12 lactating cows shifted from twice daily to once daily milking. Tissues were sampled by biopsy from adjacent mammary quarters of these animals during the two milking frequencies, allowing changes in gene expression to be assessed within each animal. Using bovine-specific, oligonucleotide arrays representing 21,495 unique transcripts, a range of differentially expressed genes were found as a result of less frequent milk removal, constituting transcripts and pathways related to apoptotic signaling (NF-kappaB, JUN, ATF3, IGFBP5, TNFSF12A) mechanical stress and epithelial tight junction synthesis (CYR61, CTGF, THBS1, CLDN4, CLDN8), and downregulated milk synthesis (LALBA, B4GALT1, UGP2, CSN2, GPAM, LPL). Quantitative real-time PCR was used to assess the expression of 13 genes in the study, and all 13 of these were correlated (P < 0.05) with values derived from array analysis. It can be concluded that the physiological changes that occur in the bovine mammary gland as a result of reduced milk removal frequency likely comprise the earliest stages of the involution response and that mechano-signal transduction cascades associated with udder distension may play a role in triggering these events.

    Title The Prognosis of Fasciectomy for Abductor Digiti Minimi and Pretendinous Cords in Dupuytren's Disease of the Little Finger.
    Date May 2010
    Journal Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-pacific Federation of Societies for Surgery of the Hand
    Excerpt

    Thirty-nine consecutive patients with little finger Dupuytren's contracture underwent open fasciectomy. Diseased abductor digiti minimi (ADM) pretendinous (PT) cords were identified. The mean pre-operative PIPJ contracture was 77 degrees in the PT group and 66 degrees in the ADM group. Mean residual deformity was 12 degrees in the PT group and 9 degrees in the ADM group. At six months, ten out of 27 patients had developed a recurrent deformity in the PT group (mean 24 degrees ) and seven out of 11 in the ADM group (mean 18 degrees ). There was no statistically significant difference between the two groups at any stage. Dupuytren's contracture of the little finger is as a result of an ADM cord in 29% of cases. In this series it led to an isolated contracture of the PIPJ in the majority of cases and rarely affected the MCPJ. Disease of the ADM cord was not associated with a difference in contracture or prognosis compared to a PT cord.

    Title Tolerance Mechanisms in Pregnancy: a Reappraisal of the Role of Class I Paternal Mhc Antigens.
    Date March 2010
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Allogeneic pregnancies have a survival advantage over syngeneic pregnancies, and paternal Class I MHC antigens have been implicated. In humans, HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described. However, the mechanism of prevention of embryo demise in utero has not been critically assessed, and a number of conflicting ideas have not been addressed. The alphabeta T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC.

    Title Importance of Chromosomally Integrated Hhv-6a and -6b in the Diagnosis of Active Hhv-6 Infection.
    Date December 2009
    Journal Herpes : the Journal of the Ihmf
    Excerpt

    Human herpesvirus-6 (HHV-6) exists as two closely related variants: A and B. Whereas no disease has been firmly associated with HHV-6A, variant B causes febrile illness in young children and is pathogenic in immunosuppressed transplant recipients. Chromosomally integrated HHV-6 (with either variant A or B) occurs in a minority of people. This phenomenon has the potential to confound the diagnosis of active HHV-6 infection, since chromosomally integrated HHV-6 DNA sequences are inherited through the germline. Therefore, viral DNA is in every nucleated cell in the body and can be found in a range of body fluids including whole blood, serum, plasma and cerebrospinal fluid. There are characteristically very high viral loads in whole blood (> 6 log10 HHV-6 genomes/ml) and serum (5 log10 HHV-6 genomes/ml); these can be used to differentiate individuals with viral chromosomal integration from those with active HHV-6 infection, where viral loads are significantly lower. Increasingly, the polymerase chain reaction (to detect viral nucleic acid) is used for diagnosis; therefore, it is important to exclude HHV-6 chromosomal integration before concluding that there is evidence of active HHV-6 infection.

    Title A Time to Grow and a Time to Die: a New Way to Analyze the Dynamics of Size, Light, Age, and Death of Tropical Trees.
    Date November 2009
    Journal Ecology
    Excerpt

    In tropical rain forests, rates of forest turnover and tree species' life-history differences are shaped by the life expectancy of trees and the time taken by seedlings to reach the canopy. These measures are therefore of both theoretical and applied interest. However, the relationship between size, age, and life expectancy is poorly understood. In this paper, we show how to obtain, in a dynamic environment, age-related population parameters from data on size and light transitions and survival of individuals over single time steps. We accomplish this goal by combining two types of analysis (integral projection modeling and age-from-stage analysis for variable environments) in a new way. The method uses an index of crown illumination (CI) to capture the key tree life-history axis of movement through the light environment. We use this method to analyze data on nine tropical tree species, chosen to sample two main gradients, juvenile recruitment niche (gap/nongap) and adult crown position niche (subcanopy, canopy-emergent). We validate the method using independent estimates of age and size from growth rings and 14C from some of the same species at the same site and use our results to examine correlations among age-related population parameters. Finally, we discuss the implications of these new results for life histories of tropical trees.

    Title Ecology of Danger-dependent Cytokine-boosted Spontaneous Abortion in the Cba X Dba/2 Mouse Model: Ii. Fecal Lps Levels in Colonies with Different Basal Abortion Rates.
    Date November 2009
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Previous data have shown that 'danger' signals, such as bacterial lipopolysaccharide (LPS) acting via toll-like receptors (TLR), are conditions antecedent to early pregnancy failure in several murine abortion models. Indeed, the abortion rate increased in the CBA x DBA/2 model after injection of tumor necrosis factor-alpha (TNF-alpha) + interferon (IFN-gamma) on gestation day (GD) 7.5 only if the LPS-TLR signaling pathway was intact. High rates of cytokine-boosted abortion >80% loss can be demonstrable in certain animal colonies that have a high endogenous (spontaneous) rate of resorption (30-50%). A specific role for LPS on GD 0.5 determines the endogenous loss rate and on GD 6.5 the responsiveness to cytokine boosting of losses. Th1 cytokines (or the stress that induces these cytokines) increase intestinal permeability and absorption of luminal contents. It was predicted that intestinal availability of LPS was a major factor in the endogenous and cytokine-boosted resorption rates.

    Title Microarray-based Determination of the Lytic Cascade of Human Herpesvirus 6b.
    Date October 2009
    Journal The Journal of General Virology
    Excerpt

    The lytic gene expression of several members of the human herpesvirus family has been profiled by using gene-expression microarrays; however, the lytic cascade of roseoloviruses has not been studied in similar depth. Based on the complete DNA genome sequences of human herpesvirus 6 variant A (HHV-6A) and variant B (HHV-6B), we constructed a cDNA microarray containing DNA probes to their predicted open reading frames, plus 914 human genes. Gene-expression profiling of HHV-6B strain Z29 in SupT1 cells over a 60 h time-course post-infection, together with kinetic classification of the HHV-6B genes in the presence of either cycloheximide or phosphonoacetic acid, allowed the placement of HHV-6B genes into defined kinetic classes. Eighty-nine HHV-6B genes were divided into four different expression kinetic classes: eight immediate-early, 44 early, 33 late and four biphasic. Clustering of genes with similar expression profiles implied a shared function, thus revealing possible roles of previously uncharacterized HHV-6B genes.

    Title Influence of Towing Force Magnitude on the Kinematics of Supramaximal Sprinting.
    Date October 2009
    Journal Journal of Strength and Conditioning Research / National Strength & Conditioning Association
    Excerpt

    The purpose of this study was to determine the influence of towing force magnitude on the kinematics of supramaximal sprinting. Ten high school and college-age track and field athletes (6 men, 4 women) ran 60-m maximal sprints under 5 different conditions: Nontowed, Tow A (2.0% body weight [BW]), Tow B (2.8% BW), Tow C (3.8% BW), and Tow D (4.7% BW). Three-dimensional kinematics of a 4-segment model of the right side of the body were collected starting at the 35-m point of the trial using high-speed (250 Hz) optical cameras. Significant differences (p < 0.05) were observed in stride length and horizontal velocity of the center of mass during Tow C and Tow D. For Tow D, a significant increase (p = 0.046) in the distance from the center of mass to the foot at touchdown was also observed. Contact time decreased significantly in all towing conditions (p < 0.01), whereas stride rate increased only slightly (<2.0%) under towed conditions. There were no significant changes in joint or segment angles at touchdown, with the exception of a significant decrease (p = 0.044) in the flexion/extension angle at the hip during the Tow D condition. We conclude that towing force magnitude does influence the kinematics of supramaximal running and that potentially negative training effects may arise from towing individuals with a force in excess of 3.8% BW. Therefore, we suggest that coaches and practitioners adjust towing force magnitude for each individual and avoid using towing forces in excess of 3.8% of the athlete's BW.

    Title Temporal Analysis of Stochastic Turning Behavior of Swimming C. Elegans.
    Date September 2009
    Journal Journal of Neurophysiology
    Excerpt

    Caenorhabditis elegans exhibits spontaneous motility in isotropic environments, characterized by periods of forward movements punctuated at random by turning movements. Here, we study the statistics of turning movements-deep Omega-shaped bends-exhibited by swimming worms. We show that the durations of intervals between successive Omega-turns are uncorrelated with one another and are effectively selected from a probability distribution resembling the sum of two exponentials. The worm initially exhibits frequent Omega-turns on being placed in liquid, and the mean rate of Omega-turns lessens over time. The statistics of Omega-turns is consistent with a phenomenological model involving two behavioral states governed by Poisson kinetics: a "slow" state generates Omega-turns with a low probability per unit time; a "fast" state generates Omega-turns with a high probability per unit time; and the worm randomly transitions between these slow and fast states. Our findings suggest that the statistics of spontaneous Omega-turns exhibited by swimming worms may be described using a small number of parameters, consistent with a two-state phenomenological model for the mechanisms that spontaneously generate Omega-turns.

    Title Humoral Immune Response to Ebv in Multiple Sclerosis is Associated with Disease Activity on Mri.
    Date August 2009
    Journal Neurology
    Excerpt

    Evidence suggests that Epstein-Barr virus (EBV) plays a role in triggering or perpetuating disease activity in multiple sclerosis (MS).

    Title Advances in Pasture Management for Animal Productivity and Health.
    Date May 2009
    Journal New Zealand Veterinary Journal
    Excerpt

    A wide range of management techniques is available to enhance quantity and quality of forage supply to grazing animals throughout the annual production cycle. Within broad limits, dry matter (DM) production is relatively insensitive to management of defoliation frequency, severity and duration. However defoliation management has effects on feed quality which can be enhanced, in particular, by control of pasture growth in the spring through maintenance of relatively low average pasture masses. Treading damage can have significant immediate and ongoing effects on pasture production and farmers can use a range of management techniques to minimise these. Fertiliser application practices have a potent influence on pasture production and seasonality of that production. Available soil nitrogen is the primary nutrient deficiency limiting production in New Zealand's characteristically grass-dominant pastures. Nitrogen fertiliser usage has increased markedly in recent years, particularly to grow substantially greater amounts of forage during the cool season, and this trend looks set to continue. However, the use of nitrogen fertiliser has important environmental implications. Pasture renewal and forage crop use has also increased in recent years. Care needs to be taken in conducting cost-benefit analyses, selecting the options that best meet the needs, and in establishment and subsequent management practices. Ryegrass (perennial and hybrids) and white clover remain the primary choice for permanent pasture renewal, the availability of safe endophytes having largely alleviated effects of endophyte toxicosis. Special-purpose mixtures are used, especially in dry environments. Italian ryegrasses, brassicas and chicory are common choices for forage crops. A range of management techniques can be used to alleviate deleterious effects of some forages, including ryegrass endophyte toxicosis, facial eczema, and toxins associated with Fusarium fungi. Generally these techniques are not totally effective. More research is required to increase our understanding of these disorders, and in order to develop more effective and reliable management practices.

    Title Feeding Value of Pastures for Ruminants.
    Date May 2009
    Journal New Zealand Veterinary Journal
    Excerpt

    Perennial ryegrass is the primary forage component of ruminant diets in New Zealand. It is persistent and palatable, and immature ryegrass has a high nutritive value (NV). However, seedhead development substantially lowers its feeding value (FV) as fibre concentration increases, the rate and extent of digestibility decreases, and voluntary intake declines. Ryegrass pastures are susceptible to accumulation of endophytic and saprophytic fungi in dead material at the base of the sward, especially when mature and laxly grazed. Feeding forage legumes to ruminants grazing grass-dominant pastures will improve animal performance and lessen the reliance on a single species to meet all nutritional requirements. The FV of forage is a function of intake and NV, measured by chemical analyses and animal feeding trials. Performance of individual animals grazing forages is usually limited by energy intake because structural fibre can slow digestion and clearance from the rumen and because of competition between individuals for available feed. The use of metabolisable energy (ME) content of forage to signify FV can give a reasonable indication of animal performance, but it should be used in conjunction with chemical analyses to improve the accuracy of predictions. The relationship between FV, pasture production, animal performance and profitability is complex. The importance of skilled management to maintain pasture quality and optimise animal performance under inconsistent climatic conditions should not be underestimated. Acceptable animal performance with minimal veterinary intervention requires good nutrition, but the genetic potential of livestock in New Zealand cannot be met solely by grazing pasture, especially when a high utilisation of pasture is required to maintain quality and profitability. Producers are responding to industry demands to reduce the seasonality in supply of milk and meat by changing lambing and calving dates, and extending lactation length in dairy cows. Social changes include adoption of once-daily milking in the dairy industry. Some changes have necessitated increased use of supplements and others can be met by feeding forages with a higher FV than ryegrass, all of which require an improved knowledge of feed quality. This information is available through rapid and inexpensive near infrared spectroscopy (NIRS) analysis, enabling animal nutritional needs to be balanced by appropriate nutrient supply. It is essential that producers continue to improve animal welfare, limit excessive use of fertilisers and meet the demands of overseas consumers. Good nutrition, with an increased use of legumes and other forages to complement ryegrass pastures, will enable these objectives to be achieved.

    Title The Novel Cd4+cd25+ Regulatory T Cell Effector Molecule Fibrinogen-like Protein 2 Contributes to the Outcome of Murine Fulminant Viral Hepatitis.
    Date March 2009
    Journal Hepatology (baltimore, Md.)
    Excerpt

    Fulminant viral hepatitis (FH) remains an important clinical problem in which the underlying pathogenesis is not well understood. Here, we present insight into the immunological mechanisms involved in FH caused by murine hepatitis virus strain 3 (MHV-3), indicating a critical role for CD4(+)CD25(+) regulatory T cells (Tregs) and production of the novel Treg effector molecule FGL2. Before infection with MHV-3, susceptible BALB/cJ mice had increased numbers of Tregs and expression of fgl2 messenger RNA (mRNA) and FGL2 protein compared with resistant A/J mice. After MHV-3 infection, plasma levels of FGL2 in BALB/cJ mice were significantly increased, correlating with increased percentage of Tregs. Treatment with anti-FGL2 antibody completely inhibited Treg activity and protected susceptible BALB/cJ mice against MHV-3-liver injury and mortality. Adoptive transfer of wild-type Tregs into resistant fgl2(-/-) mice increased their mortality caused by MHV-3 infection, whereas transfer of peritoneal exudate macrophages had no adverse effect. Conclusion: This study demonstrates that FGL2 is an important effector cytokine of Tregs that contributes to susceptibility to MHV-3-induced FH. The results further suggest that targeting FGL2 may lead to the development of novel treatment approaches for acute viral hepatitis infection.

    Title The Fgl2-fcgammariib Pathway: a Novel Mechanism Leading to Immunosuppression.
    Date January 2009
    Journal European Journal of Immunology
    Excerpt

    Fibrinogen-like protein 2 (FGL2) is a multifunctional protein, which has been implicated in the pathogenesis of allograft and xenograft rejection. Previously, FGL2 was shown to inhibit maturation of BM-derived DC and T-cell proliferation. The mechanism of the immunosuppressive activity of FGL2 remains poorly elucidated. Here, we focus on identification of FGL2-specific receptor(s) and their ability to modulate APC activity and allograft survival. Using flow cytometry and surface plasmon resonance analysis, we show that FGL2 binds specifically to Fc gamma receptor (FcgammaR)IIB and FcgammaRIII receptors, which are expressed on the surface of APC, including B lymphocytes, macrophages and DC. Antibody to FcgammaRIIB and FcgammaRIII, or deficiency of these receptors, abrogated FGL2 binding. FGL2 inhibited the maturation of BMDC from FcgammaRIIB+/+ mice but not from FcgammaRIIB(-/-) mice and induced apoptosis in the FcgammaRIIB+ mouse B-cell line (A20) but not the A20IIA1.6 cell line that does not express FcgammaRIIB. Recombinant FGL2 infused into FcgammaRIIB+/+ (C57BL/6J, H-2b) mice but not FcgammaRIIB(-/-) mice inhibited rejection of fully mismatched BALB/cJ (H-2d) skin allografts. The identification of specific receptor binding has important implications for the pathogenesis of immune-mediated disease and suggests a potential for targeted FGL2 therapy.

    Title Enyne Cross-metathesis with Strained, Geminally-substituted Alkenes: Direct Access to Highly Substituted 1,3-dienes.
    Date December 2008
    Journal Organic Letters
    Excerpt

    Angle strain in methylene cyclobutane was used to drive a cross-enyne metathesis with 1-alkynes, giving 1,1,3-trisubstituted 1,3-dienes in good isolated yields. An extensive survey of Grubbs' second-generation catalysts led to an optimized reaction conducted at 0 degrees C.

    Title Milking Cows Once Daily Influences Behavior and Udder Firmness at Peak and Mid Lactation.
    Date September 2008
    Journal Journal of Dairy Science
    Excerpt

    Our aim was to evaluate the effects of once-daily milking on the welfare of dairy cows in a pastoral-based farming system. There are concerns that cows milked only once daily may experience discomfort associated with udder distension. We evaluated the behavior, including lying time and postures, grazing patterns, and kicking behavior in the parlor, and measures of udder firmness in cows milked once daily in 2 experiments: 1) at peak lactation, comparing cows milked once (1x) or twice-daily (2x) from the time of calving (n = 4 groups; 1x and 2x treatments); and 2) during the transition from 2x to 1x milking at mid lactation (n = 12 groups; 1x, 2x, and 2x to 1x treatments or TRANS). At peak lactation, cows milked 1x were more likely to lie with their hind legs touching the body than cows milked 2x. There were no differences in udder firmness (1x: 10.0 vs. 2x: 9.9 +/- 0.13 g of force) or kicking (1x: 25 vs. 2x: 24 +/- 7.8%) behavior in the parlor. In the second experiment, milking frequency was reduced from 2x to 1x and this change resulted in an increase in udder firmness (1 x: 9.1, 2x: 9.3, and TRANS: 9.5 +/- 0.14 g of force). Despite these differences in udder firmness, lying time (1x: 10.1, 2x: 9.5, and TRANS: 9.6 +/- 0.38 h/24 h), postures, and concentrations of fecal glucocorticoid metabolites (1x: 10.0, 2x: 10.5, and TRANS: 10.4 +/- 0.49 ng/g of feces in the 3 d after transition) in cows milked 1x or 2x were similar. Although milking frequency did not influence total time spent grazing, the diurnal grazing pattern of cows milked 2x was disrupted by afternoon milking at both peak and mid lactation. Cows milked 2x were able to compensate for this by grazing more after the return to pasture (DIM 153 to 155, 1x: 52 vs. 2x: 66 +/- 6.2 min/90 min of grazing). Cows milked 1x had slightly longer strides than 2x cows at mid lactation (1x: 0.73, 2x: 0.70, and TRANS: 0.70 +/- 0.014 strides/m). In conclusion, under our experimental conditions, we found no overt changes in behavior or physiology to indicate that the welfare of cows milked 1x is impaired.

    Title Prevention of Spontaneous Abortion in the Cba X Dba/2 Mouse Model by Intravaginal Tgf-beta and Local Recruitment of Cd4+8+ Foxp3+ Cells.
    Date August 2008
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    PROBLEM: Activation of latent transforming growth factor (TGF)-beta in seminal plasma has been suggested by Robertson et al. to promote maternal tolerance to paternal antigens. A possible consequence reported by Tremellen et al. is increased pregnancy rates in women undergoing IVF. A decreased spontaneous abortion rate has also been postulated. Seminal plasma contains many factors besides TGF-beta, and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF-beta. METHOD OF STUDY: Pharmaceutical grade bioactive TGF-beta3 with a bovine serum albumin (BSA) carrier 0.1-1% in phosphate-buffered saline (PBS) was given into the vaginal tract of CBA/J female mice at the time of mating with DBA/2 males. One microgram Salmonella enteritidis lipopolysaccharide was given intraperitoneally to augment occult losses and spontaneous resorptions assessed on day 13.5 of pregnancy. The effect of TGF-beta3 on recruitment of lymphomyeloid cells to the vaginal wall and vaginal lumen of unmated mice in estrus was assessed using immunohistochemistry and flow cytometry. RESULTS: Two nanogram of intravaginal TGF-beta3 in 0.1% BSA-PBS or 20 ng in 1% BSA-PBS reduced abortion rates. Protection was comparable to that achieved by immunization with BALB/c spleen cells. Fraction V BSA, a binder of TGF-betas, had some activity, and could reduce availability of added TGF-beta3. CD11c dendritic cells, CD3+ T cells, and CD25+ cells were recruited to the vaginal wall by 48 hr after TGF-beta3 treatment, and cellularity of vaginal exudates increased. Foxp3+ cells were present in increased numbers, and appeared to be CD8+ and CD4+ 8+. Semen, but not TGF-beta3, stimulated a physiological polymorphonuclear leukocyte exudate. CONCLUSION: Intravaginal bioactive TGF-beta3 can enhance success of pregnancy in vivo in an established model of abortion. The result could be explained by the independent ability of TGF-beta to promote a regulatory T-cell response.

    Title Transfusion-related Immunomodulation Due to Peripheral Blood Dendritic Cells Expressing the Cd200 Tolerance Signaling Molecule and Alloantigen.
    Date July 2008
    Journal Transfusion
    Excerpt

    The transfusion of allogeneic blood products containing white cells (WBCs) has been reported to reduce resistance to infection, stimulate the growth of some types of tumors in animal models, and prevent abortion of allogeneic embryos in the CBAxDBA/2 murine model.

    Title Alkenol-alkyne Cross Metathesis.
    Date July 2008
    Journal Organic Letters
    Excerpt

    Allyl alcohols and their homologues were used in the enyne cross metathesis to prepare hydroxy-functionalized dienes. An isomerization was found to occur under prolonged heating, and a method for conversion to ( E)-diene product is also reported.

    Title Synthesis of Insecticidal Fluorinated Anthranilic Diamides.
    Date June 2008
    Journal Bioorganic & Medicinal Chemistry
    Excerpt

    A series of highly active fluorinated anthranilic diamide insecticides have been prepared and their biological activity assessed on two aphid species in the search for systemically active compounds that control Hemiptera. In addition, we have demonstrated a new synthesis of N-aryl 3-fluoropyrazoles.

    Title Immunological Factors in Pregnancy Wastage: Fact or Fiction.
    Date June 2008
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Whether maternal immune effector mechanisms with the exception of anti-phospholipid antibodies cause pregnancy loss, and whether effective treatment is possible are subjects of controversy. Hence, in this study the current literature was searched and critically reviewed. In both animals and humans, similar immune effector mechanisms are linked to pregnancy failure. Several levels of evidence indicate that treatments such as aspirin + heparin, intravenous immunoglobulins, corticosteroids, and transfer of allogeneic blood cells bearing paternal antigens may improve the live birth rate. Combination therapy appears promising, but better diagnosis of subgroups responsive to specific therapies is critical. There are fallacies and flaws in the logic of previous arguments against immunological mechanisms and therapeutic interventions. In order to select patients most likely to benefit from known treatments, more extensive immunological testing is required. It is also important to determine the karyotype of all failing embryos.

    Title Cd200-dependent and Noncd200-dependent Pathways of Nk Cell Suppression by Human Ivig.
    Date May 2008
    Journal Journal of Assisted Reproduction and Genetics
    Excerpt

    Intravenous immunoglobulin (IVIG) has been used to suppress autoimmune and inflammatory disorders by a variety of mechanisms. Recently, the CD200 tolerance-promoting signal has been found to play a role in IVIG suppression of blood natural killer (NK) cells. Further, different types of IVIG have been reported to differ in this activity, and that has been related to efficacy (and inefficacy) of treatment of women with pregnancy failure. CD200 acts by binding to CD200 receptors (C200R). The objective of this study was to determine if CD200-dependent NK suppression by IVIG involved direct binding of IVIG-associated CD200 molecules to CD200R on NK cells.

    Title Cd56+ Cells Are Recruited to the Uterus in Two Waves: at Ovulation and During the First 2 Weeks After Missed Menses.
    Date April 2008
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Uterine natural killer (uNK) cells are enriched in the post-ovulatory uterus and during pregnancy. Whether these cells arise from blood pre-cursors or from stem cells in the uterus is undefined. To support a hypothesis that precursors of uNK cells are recruited from blood, adhesive function of blood CD56+ subsets were assessed during one cycle and during pregnancy.

    Title Preoperative Ultrasound of Axillary Lymph Nodes in Patients with Breast Cancer.
    Date March 2008
    Journal Anz Journal of Surgery
    Title Temperature and Food Mediate Long-term Thermotactic Behavioral Plasticity by Association-independent Mechanisms in C. Elegans.
    Date March 2008
    Journal The Journal of Experimental Biology
    Excerpt

    Thermotactic behavior in the nematode Caenorhabditis elegans exhibits long-term plasticity. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered set-point (T(S)) corresponding to its previous cultivation temperature. When navigating at temperatures above its set-point (T>T(S)), C. elegans crawls down spatial thermal gradients towards the T(S) in what is called cryophilic movement. The T(S) retains plasticity in the adult stage and is reset by approximately 4 h of sustained exposure to a new temperature. Long-term plasticity in C. elegans thermotactic behavior has been proposed to represent an associative learning of specific temperatures conditioned in the presence or absence of bacterial food. Here, we use quantitative behavioral assays to define the temperature and food-dependent determinants of long-term plasticity in the different modes of thermotactic behavior. Under our experimental conditions, we find that starvation at a specific temperature neither disrupts T(S) resetting toward the starvation temperature nor induces learned avoidance of the starvation temperature. We find that prolonged starvation suppresses the cryophilic mode of thermotactic behavior. The hen-1 and tax-6 genes have been reported to affect associative learning between temperature and food-dependent cues. Under our experimental conditions, mutation in the hen-1 gene, which encodes a secreted protein with an LDL receptor motif, does not significantly affect thermotactic behavior or long-term plasticity. Mutation in the tax-6 calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food.

    Title Targeted Deletion of Fgl2 Leads to Impaired Regulatory T Cell Activity and Development of Autoimmune Glomerulonephritis.
    Date March 2008
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild-type recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, Th 1 polarization, and increased numbers of Ab-producing B cells following immunization with T-independent Ags. Dendritic cells were more abundant in fgl2-/- mice and had increased expression of CD80 and MHCII following LPS stimulation. Treg cells were also more abundant in fgl2-/- mice, but their suppressive activity was significantly impaired. Ab to FGL2 completely inhibited Treg cell activity in vitro. FGL2 inhibited dendritic cell maturation and induced apoptosis of B cells through binding to the low-affinity FcgammaRIIB receptor. Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease.

    Title Lps-induced Occult Loss in Mice Requires Fgl2.
    Date March 2008
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    FGL2 prothrombinase is required for spontaneous abortion (resorptions) in the CBA x DBA/2 model, and for abortions in C57Bl/6 (B6) mice triggered by Salmonella enteritidis lipopolysaccharide (LPS). Unlike abortions, occult losses in B6 mice, which begin before gestation day 9.5 in mice, do not require the tumor necrosis factor-alpha receptor type 1, and may be triggered by either Salmonella enteritidis or Escherichia coli LPS. Heterozygous matings of fgl2+/-xfgl2+/- B6 mice also have a high spontaneous occult loss of fgl2-/- and to a lesser extent, fgl2+/- embryos caused by hemorrhage between trophoblast and Reichert's membrane. However, the frequency of such losses appears to vary among breeding periods and between laboratories.

    Title First Direct Landscape-scale Measurement of Tropical Rain Forest Leaf Area Index, a Key Driver of Global Primary Productivity.
    Date February 2008
    Journal Ecology Letters
    Excerpt

    Leaf Area Index (leaf area per unit ground area, LAI) is a key driver of forest productivity but has never previously been measured directly at the landscape scale in tropical rain forest (TRF). We used a modular tower and stratified random sampling to harvest all foliage from forest floor to canopy top in 55 vertical transects (4.6 m(2)) across 500 ha of old growth in Costa Rica. Landscape LAI was 6.00 +/- 0.32 SEM. Trees, palms and lianas accounted for 89% of the total, and trees and lianas were 95% of the upper canopy. All vertical transects were organized into quantitatively defined strata, partially resolving the long-standing controversy over canopy stratification in TRF. Total LAI was strongly correlated with forest height up to 21 m, while the number of canopy strata increased with forest height across the full height range. These data are a benchmark for understanding the structure and functional composition of TRF canopies at landscape scales, and also provide insights for improving ecosystem models and remote sensing validation.

    Title Letters to the Editor.
    Date January 2008
    Journal American Journal of Public Health and the Nation's Health
    Title Decline in Number of Elevated Blood Cd3(+) Cd56(+) Nkt Cells in Response to Intravenous Immunoglobulin Treatment Correlates with Successful Pregnancy.
    Date December 2007
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Patients with elevated blood natural killer (NK) cells may be offered intravenous immunoglobulin (IVIG) treatment, but there is controversy about the utility of blood NK cell testing. Human CD56(+) NK cells include several subpopulations that include the putatively cytotoxic CD56(+) CD16(+) subset. In mouse models of pregnant failure, NKT cells appear to be important. However, a mouse model may only be pertinent to a subset of patients, as recurrent pregnancy failure is a heterogenous group.

    Title Tolerance Signaling Molecules and Pregnancy: Ido, Galectins, and the Renaissance of Regulatory T Cells.
    Date December 2007
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Is the concept of maternal tolerance preventing rejection of the semi-allogeneic 'fetal allograft' still valid?

    Title Introduction to Special Issue on Implantation.
    Date November 2007
    Journal Journal of Assisted Reproduction and Genetics
    Title Transmission of Integrated Human Herpesvirus-6 in Allogeneic Hematopoietic Stem Cell Transplantation.
    Date November 2007
    Journal Bone Marrow Transplantation
    Excerpt

    Human herpesvirus 6 (HHV-6) viremia, as detected by polymerase chain amplification, occurs in approximately half of allogeneic hematopoietic stem cell transplant recipients. The significance of such viremia is incompletely understood, but HHV-6 encephalitis and bone marrow suppression are increasingly being recognized in patients with high viral DNA. We report two patients in whom donor-to-recipient transmission occurred through hematopoietic transplant by means of chromosomally integrated (CI) HHV-6. Iatrogenic transmission manifested at engraftment as asymptomatic elevation of HHV-6 viral DNA of 3600 and 15 400 DNA copies/ml in plasma and 6.1 x 10(6) and 9.7 x 10(5) DNA copies/ml in the whole blood. Both donors had elevated plasma HHV-6 PCR at 5.6 x 10(4) and 1.3 x 10(5) DNA copies/ml and strikingly elevated whole blood HHV-6 levels at 4.1 x 10(6) and 4.7 x 10(6) DNA copies/ml, respectively. CI of the virus was traced to the mother of one patient and his donor. CI of HHV-6 may confound the interpretation of HHV-6 viremia after stem cell transplantation; consideration of the possibility of CI HHV-6 will avoid unnecessary antiviral therapy.

    Title Fgl2 Deficiency Causes Neonatal Death and Cardiac Dysfunction During Embryonic and Postnatal Development in Mice.
    Date October 2007
    Journal Physiological Genomics
    Excerpt

    We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in fibrinogen-like protein 2 (Fgl2) knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset of heart beating) and postnatal day (P)28 (weaning) were within 3 days after birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested that death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos at E13.5. Indexes of systolic and/or diastolic cardiac function were also abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic chamber dimension, although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.

    Title Mechanosensation and Mechanical Load Modulate the Locomotory Gait of Swimming C. Elegans.
    Date September 2007
    Journal The Journal of Experimental Biology
    Excerpt

    Animals move through their environments by selecting gaits that are adapted to the physical nature of their surroundings. The nematode Caenorhabditis elegans swims through fluids or crawls on surfaces by propagating flexural waves along its slender body and offers a unique opportunity for detailed analysis of locomotory gait at multiple levels including kinematics, biomechanics and the molecular and physiological operation of sensory and motor systems. Here, we study the swimming gait of C. elegans in viscous fluids in the range 0.05-50 Pa s. We find that the spatial form of the swimming gait does not vary across this range of viscosities and that the temporal frequency of the swimming gait only decreases by about 20% with every 10-fold increase in viscosity. Thus, C. elegans swims in low gear, such that its musculature can deliver mechanical force and power nearly 1000-fold higher than it delivers when swimming in water. We find that mutations that disrupt mechanosensation, or the laser killing of specific touch receptor neurons, increase the temporal frequency of the undulating gait, revealing a novel effect of mechanosensory input in regulating the putative central pattern generator that produces locomotion. The adaptability of locomotory gait in C. elegans may be encoded in sensory and motor systems that allow the worm to respond to its own movement in different physical surroundings.

    Title On High Explosive Launching of Projectiles for Shock Physics Experiments.
    Date September 2007
    Journal The Review of Scientific Instruments
    Excerpt

    The hydrodynamic operation of the "Forest Flyer" type of explosive launching system for shock physics projectiles was investigated in detail using one and two dimensional continuum dynamics simulations. The simulations were numerically converged and insensitive to uncertainties in the material properties; they reproduced the speed of the projectile and the shape of its rear surface. The most commonly used variant, with an Al alloy case, was predicted to produce a slightly curved projectile, subjected to some shock heating and likely exhibiting some porosity from tensile damage. The curvature is caused by a shock reflected from the case; tensile damage is caused by the interaction of the Taylor wave pressure profile from the detonation wave with the free surface of the projectile. The simulations gave only an indication of tensile damage in the projectile, as damage is not understood well enough for predictions in this loading regime. The flatness can be improved by using a case of lower shock impedance, such as polymethyl methacrylate. High-impedance cases, including Al alloys but with denser materials improving the launching efficiency, can be used if designed according to the physics of oblique shock reflection, which indicates an appropriate case taper for any combination of explosive and case material. The tensile stress induced in the projectile depends on the relative thickness of the explosive, expansion gap, and projectile. The thinner the projectile with respect to the explosive, the smaller the tensile stress. Thus if the explosive is initiated with a plane wave lens, the tensile stress is lower than that for initiation with multiple detonators over a plane. The previous plane wave lens designs did, however, induce a tensile stress close to the spall strength of the projectile. The tensile stress can be reduced by changes in the component thicknesses. Experiments verifying the operation of explosively launched projectiles should attempt to measure porosity induced in the projectile: arrival time measurements are likely to be insensitive to porous regions caused by damaged or recollected material.

    Title Neural Circuits Mediate Electrosensory Behavior in Caenorhabditis Elegans.
    Date August 2007
    Journal The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    Excerpt

    The nematode Caenorhabditis elegans deliberately crawls toward the negative pole in an electric field. By quantifying the movements of individual worms navigating electric fields, we show that C. elegans prefers to crawl at specific angles to the direction of the electric field in persistent periods of forward movement and that the preferred angle is proportional to field strength. C. elegans reorients itself in response to time-varying electric fields by using sudden turns and reversals, standard reorientation maneuvers that C. elegans uses during other modes of motile behavior. Mutation or laser ablation that disrupts the structure and function of amphid sensory neurons also disrupts electrosensory behavior. By imaging intracellular calcium dynamics among the amphid sensory neurons of immobilized worms, we show that specific amphid sensory neurons are sensitive to the direction and strength of electric fields. We extend our analysis to the motor level by showing that specific interneurons affect the utilization of sudden turns and reversals during electrosensory steering. Thus, electrosensory behavior may be used as a model system for understanding how sensory inputs are transformed into motor outputs by the C. elegans nervous system.

    Title No Association Between Adra2a Polymorphisms and Schizophrenia.
    Date July 2007
    Journal American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
    Excerpt

    There is evidence to suggest that the alpha(2A)-adrenergic receptor may be involved in schizophrenia. With attention directed at the upstream regulatory region of the gene which codes for this receptor (ADRA2A), we proposed that single nucleotide polymorphisms (SNPs) within this region influences susceptibility to schizophrenia by altering the expression of this receptor. We opted to test for an influence on susceptibility by association study using 112 schizophrenic/schizoaffective disorder patients and 159 controls. The region of interest was screened for SNPs using a combination of bioinformatic searches and sequencing. A total of nine SNPs were discovered, of which four (-5972-G/A, -2211-A/T, -1291-C/G and -261-G/A) were genotyped in the entire clinical sample. No associations were evident, suggesting no influence for these SNPs in susceptibility to schizophrenia.

    Title Defining a Strategy for Chemical Imaging of Industrial Pharmaceutical Samples on Raman Line-mapping and Global Illumination Instruments.
    Date July 2007
    Journal Applied Spectroscopy
    Excerpt

    The performance of line-mapping and global illumination Raman systems for two pharmaceutical tablets and a powder blend are assessed in this study. The chemical images were obtained from the placebo, real tablets, and powder blend by using x20, x50, and x100 objectives, as well as via the (pseudo) confocal set-up. The chemical images were produced via univariate wavenumbers and as re-folded principal component (PC) scores (known as score images). In most cases it was easy to image two or three major components of the tablets directly, while the minor components were only imaged via PC scores. The active pharmaceutical ingredients (APIs) were located relatively easily even if present in quite low concentrations (less than 1%) owing to the high Raman scattering coefficients of these materials. The strength of the Raman signal of the API makes it almost ubiquitous in the chemical images of real tablets. Thorough discussion is given on the strategies used to produce chemical images, the prospects of making composite images of all components present in the tablets, and the effects of packing density with relation to the diffusion of the excitation laser light inside the sample. The strengths and weaknesses of the Raman imaging techniques used are emphasized and suggestions are given regarding which instrument is preferable with respect to the goal of the experiment and material under study. For example, mapping technology is preferred for analyzing minor components, while the global illumination approach is recommended for imaging of spatially isolated strong Raman scatterers.

    Title Sensorimotor Control During Isothermal Tracking in Caenorhabditis Elegans.
    Date July 2007
    Journal The Journal of Experimental Biology
    Excerpt

    In order to purposefully navigate their environments, animals rely on precise coordination between their sensory and motor systems. The integrated performance of circuits for sensorimotor control may be analyzed by quantifying an animal's motile behavior in defined sensory environments. Here, we analyze the ability of the nematode C. elegans to crawl isothermally in spatial thermal gradients by quantifying the trajectories of individual worms responding to defined spatiotemporal thermal gradients. We show that sensorimotor control during isothermal tracking may be summarized as a strategy in which the worm changes the curvature of its propulsive undulations in response to temperature changes measured at its head. We show that a concise mathematical model for this strategy for sensorimotor control is consistent with the exquisite stability of the worm's isothermal alignment in spatial thermal gradients as well as its more complex trajectories in spatiotemporal thermal gradients.

    Title Temporal Activity Patterns in Thermosensory Neurons of Freely Moving Caenorhabditis Elegans Encode Spatial Thermal Gradients.
    Date July 2007
    Journal The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    Excerpt

    Our understanding of the operation of neurons and neuronal circuits has come primarily from probing their activity in dissected, anesthetized, or restrained animals. However, the behaviorally relevant operation of neurons and neuronal circuits occurs within intact animals as they freely perform behavioral tasks. The small size and transparency of the nematode Caenorhabditis elegans make it an ideal system for noninvasive, optical measurements of neuronal activity. Here, we use a high signal-to-noise version of cameleon, a fluorescent calcium-binding protein, to quantify the activity of the AFD thermosensory neuron of individual worms freely navigating spatial thermal gradients. We find that AFD activity is directly coupled to the worm's exploratory movements in spatial thermal gradients. We show that the worm is able, in principle, to evaluate and guide its own thermotactic behaviors with respect to ambient spatial thermal gradients by monitoring the activity of this single thermosensory neuron.

    Title Short-term Adaptation and Temporal Processing in the Cryophilic Response of Caenorhabditis Elegans.
    Date May 2007
    Journal Journal of Neurophysiology
    Excerpt

    When navigating spatial thermal gradients, the nematode C. elegans migrates toward colder temperatures until it reaches its previous cultivation temperature, exhibiting cryophilic movement. The strategy for effecting cryophilic movement is the biased random walk: C. elegans extends (shortens) periods of forward movement that are directed down (up) spatial thermal gradients by modulating the probability of reorientation. Here, we analyze the temporal sensory processor that enables cryophilic movement by quantifying the movements of individual worms subjected to defined temperature waveforms. We show that step increases in temperature as small as 0.05 degrees C lead to transient increases in the probability of reorientation followed by gradual adaptation to the baseline level; temperature downsteps leads to similar but inverted responses. Short-term adaptation is a general property of sensory systems, allowing organisms to maintain sensitivity to sensory variations over broad operating ranges. During cryophilic movement C. elegans also uses the temporal dynamics of its adaptive response to compute the time derivative of gradual temperature variations with exquisite sensitivity. On the basis of the time derivative, the worm determines how it is oriented in spatial thermal gradients during each period of forward movement. We show that the operating range of the cryophilic response extends to lower temperatures in ttx-3 mutants, which affects the development of the AIY interneurons. We show that the temporal sensory processor for the cryophilic response is affected by mutation in the EAT-4 glutamate vesicular transporter. Regulating the operating range of the cryophilic response and executing the cryophilic response may have separate neural mechanisms.

    Title Tandem Enyne Metathesis and Claisen Rearrangement: a Versatile Approach to Conjugated Dienes of Variable Substitution Patterns.
    Date February 2007
    Journal Journal of the American Chemical Society
    Excerpt

    To extend the versatility of the ruthenium carbene-promoted enyne metathesis, it was combined with an Ireland ester enolate Claisen rearrangement. This reaction sequence provided conjugated dienes of higher substitution pattern than that obtained through a cross-enyne metathesis alone. The Ireland-Claisen was conducted across both acyclic and cyclic dienes produced from cross-metathesis and methylene-free enyne metathesis, respectively. In the case of cyclodienes, the Ireland-Claisen rearrangement produced s-trans locked dienes which underwent mode-selective ene reaction. The tandem, sequential use of the Ireland-Claisen rearrangement also proved suitable for chirality transfer originating from chiral propargylic alcohols. Last, the tandem metathesis/Ireland-Claisen was utilized to access 4-substituted-3,5-cyclohexadiene diol derivatives, which are valuable chiral intermediates for natural product synthesis. The combination of this pericyclic reaction with a catalytic metathesis reaction extends the versatility of cross-metathesis since additional diene motifs can be accessed.

    Title Nurses' Guide to Early Detection of Umbilical Arterial Catheter Complications in Infants.
    Date February 2007
    Journal Advances in Neonatal Care : Official Journal of the National Association of Neonatal Nurses
    Excerpt

    Umbilical arterial catheters (UAC) are routinely used in the care of critically ill newborns. Complications related to UACs include vascular compromise, hemorrhage, complications related to malposition, severance of the catheter itself, and infection. This article is Part II in a series dedicated to assessing infants with an umbilical catheter. Part I focused on infants with umbilical venous catheters; this article will focus on the physical assessment relevant to infants with an UAC. Complications related to UACs can occur during any phase of treatment: insertion, while indwelling, or after discontinuing the catheter. Review of clinical signs of complications along with clinical photographs, will assist caregivers in promptly recognizing UAC-related complications.

    Title A Diacylglycerol Kinase Modulates Long-term Thermotactic Behavioral Plasticity in C. Elegans.
    Date February 2007
    Journal Nature Neuroscience
    Excerpt

    A memory of prior thermal experience governs Caenorhabditis elegans thermotactic behavior. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered temperature we call the thermotactic set-point (T(S)). The T(S) corresponds to the previous cultivation temperature and can be reset by sustained exposure to a new temperature. The mechanisms underlying this behavioral plasticity are unknown, partly because sensory and experience-dependent components of thermotactic behavior have been difficult to separate. Using newly developed quantitative behavioral analyses, we demonstrate that the T(S) represents a weighted average of a worm's temperature history. We identify the DGK-3 diacylglycerol kinase as a thermal memory molecule that regulates the rate of T(S) resetting by modulating the temperature range of synaptic output, but not temperature sensitivity, of the AFD thermosensory neurons. These results provide the first mechanistic insight into the basis of experience-dependent plasticity in this complex behavior.

    Title Human Herpesvirus 6 Chromosomal Integration in Immunocompetent Patients Results in High Levels of Viral Dna in Blood, Sera, and Hair Follicles.
    Date November 2006
    Journal Journal of Clinical Microbiology
    Excerpt

    Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and beta-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log(10) copies/milliliter) in blood was 7.0 (>/=1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (>/=1 HHV-6 DNA copies/lysed cell). The mean HHV-6 DNA load (log(10) copies)/hair follicle was 4.2 (>/=1 copies/hair follicle cell), demonstrating that viral integration is not confined to blood cells. The characteristically high HHV-6 DNA levels in chromosomal integration may confound laboratory diagnosis of HHV-6 infection and should be given due consideration.

    Title Raman Line Mapping As a Fast Method for Analyzing Pharmaceutical Bead Formulations.
    Date September 2006
    Journal The Analyst
    Excerpt

    This paper describes the use of principal component analysis (PCA) to de-noise Raman spectra and considerably shorten data acquisition time in Raman mapping experiments. A solid dosage pharmaceutical material (bead) is mapped by a Raman line-mapping system. The mapping acquisition time was varied from 30 s (usually employed in practice) to only 3 s. Apparently excessive noise in the maps measured for 3 s is removed by PCA and the maps of all three components of the bead are then binarized and compared. It is found that spatial difference is negligible despite the remarkably different acquisition times employed. The spectra acquired for 3 s and reconstructed via PCA are found to largely overlap with the spectra acquired for 30 s. The signal to noise ratio of the Raman mapping spectra does not obey the expected root t dependence, thereby preventing straightforward estimation of the shortest usable acquisition time (which is to a lesser extent also a function of the binarization threshold). The results reveal that Raman microscopy can be considered a fast method for mapping some materials, in contrast to the established opinion that it is an inherently slow technique.

    Title Expression of the Alpha1a-adrenergic Receptor in Schizophrenia.
    Date September 2006
    Journal Neuroscience Letters
    Excerpt

    The alpha1-adrenergic receptors may contribute to cognitive functions relevant to schizophrenia. Following the discovery of an association between polymorphisms in the regulatory region of the alpha1A-adrenergic receptor and schizophrenia we investigated the expression of mRNA for this receptor between schizophrenics (n=19) and controls (n=19) using a TaqMan approach in post-mortem brains. No differences were found suggesting that mRNA levels are not altered in schizophrenia. Genotypic data for the subjects found that possession of the previously associated genotypes did not convey a difference in mRNA expression suggesting that these polymorphisms do not affect the level of transcription.

    Title Yields and Persistency of Lactation in Friesian and Jersey Cows Milked Once Daily.
    Date August 2006
    Journal Journal of Dairy Science
    Excerpt

    Effects of milking cows once daily throughout lactation at high stocking rates (17% more cows/ha than for those milked twice daily) were studied in 2 Friesian and 2 Jersey herds during 3 lactations. Cows were allocated to 2 herds within breed and were milked either once or twice daily, based on age, genetic merit, and previous performance. Cows remained in their original herd and were milked at the same milking frequency during all lactations. Culled cows (20% per year) were replaced by 2-yr-old heifers. Yields of milk, lactose, protein, and fat were measured every 2 wk by commercial herd test. Cubic splines (5 knots) were used to approximate the lactation curve for each cow-yr to provide estimates of performance for each day of lactation. Yields of milk were greater for Friesian and Jersey cows milked twice daily (4,751 +/- 89 and 3,067 +/- 81 kg/cow) than for cows milked once daily (3,329 +/- 80 and 2,431 +/- 75 kg/cow), respectively. Cows milked once daily had lesser total and peak yields of milk, lactose, protein, and fat than cows milked twice daily. Friesians had greater total and peak yields than Jerseys. Peak production for all milk components occurred earlier in lactation for cows milked once daily than twice daily (d 24 to 39 vs. 32 to 44). Three measures of persistency of lactation were considered for each cow with 2 measures (Pers1 and Pers2) indicating that cows milked twice daily had better persistency than those milked once daily. Ranking of herds in persistency tended to match the ranking based on total yields. Measures of persistency (Pers1 and Pers2) were positively related to total yield in the Jerseys milked once daily and negatively related to peak yield in the Friesians. The third persistency measure (Pers3) ranked once-daily Jerseys first and twice-daily Friesians last, and was negatively correlated with total yield in the Friesian herds and negatively correlated with peak yield in all herds. For most performance measures, cows milked twice daily had better total yields and persistency than cows milked once daily.

    Title The Afd Sensory Neurons Encode Multiple Functions Underlying Thermotactic Behavior in Caenorhabditis Elegans.
    Date July 2006
    Journal The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    Excerpt

    The thermotactic behaviors of Caenorhabditis elegans indicate that its thermosensory system exhibits exquisite temperature sensitivity, long-term plasticity, and the ability to transform thermosensory input into different patterns of motor output. Here, we study the physiological role of the AFD thermosensory neurons by quantifying intracellular calcium dynamics in response to defined temperature stimuli. We demonstrate that short-term adaptation allows AFD to sense temperature changes as small as 0.05 degrees C over temperature ranges as wide as 10 degrees C. We show that a bidirectional thermosensory response (increasing temperature raises and decreasing temperature lowers the level of intracellular calcium in AFD) allows the AFD neurons to phase-lock their calcium dynamics to oscillatory thermosensory inputs. By analyzing the thermosensory response of AFD dendrites severed from their cell bodies by femtosecond laser ablation, we show that long-term plasticity is encoded as shifts in the operating range of a putative thermoreceptor(s) in the AFD sensory endings. Finally, we demonstrate that AFD activity is directly coupled to stimulation of its postsynaptic partner AIY. These observations indicate that many functions underlying thermotactic behavior are properties of one sensory neuronal type. Encoding multiple functions in individual sensory neurons may enable C. elegans to perform complex behaviors with simple neuronal circuits.

    Title Latent Plaque Rupture in a Patient Undergoing Stenting for Acute Coronary Syndrome and Diffuse Coronary Disease: a Case Report and Review of Literature.
    Date July 2006
    Journal Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions
    Excerpt

    Secondary prevention of plaque rupture following percutaneous coronary intervention in patients with acute coronary syndrome is not well studied. This case report describes a 53-year-old man who experienced plaque rupture between two previously successfully implanted stents in the right coronary artery, as documented during the 3rd intervention using intravascular ultrasound.

    Title A Systems Comparison of Once- Versus Twice-daily Milking of Pastured Dairy Cows.
    Date July 2006
    Journal Journal of Dairy Science
    Excerpt

    The objective of this study was to compare the effect of milking frequency (once vs. twice-daily milking) and breed (Holstein-Friesians vs. Jerseys) on milk and milk solids (MS; milk fat + milk protein), yield per cow, milk composition, somatic cell count and lactation length; cow body weight, body condition score, and reproductive performance over a 4-yr period. Total cow numbers in each herd were 30, 35, 36, and 42 for Holstein-Friesians milked once or twice daily, and Jerseys milked once or twice daily, respectively. Forty hectares of pasture were subdivided into 4 smaller pastures of 10 ha each. Stocking rates for the once-daily herds were 16.7% greater than the twice-daily herd in their respective breed. An increased stocking rate was chosen to achieve equal milk and MS per ha from the 2 milking frequencies. Annual milk, fat, protein, and lactose yields per cow were less for once-daily than for twice-daily milking. Interactions were detected between milking frequency and breed for annual milk, fat, protein, and lactose yields per cow, because Jerseys were relatively less affected by once-daily than by twice-daily milking than Holstein-Friesians. Holstein-Friesian cows milked once daily produced 31.2% less milk and 29.4% less MS per cow than their twice-daily counterparts. In contrast, Jersey cows milked once daily produced 22.1% less milk and 19.9% less MS per cow than their twice-daily counterparts. Milk per ha was 17.7 and 9% less for the once-daily Holstein-Friesians and once-daily Jersey herds, respectively, compared with their twice-daily counterparts, because the greater stocking rate for the once-daily herds did not fully compensate for the milk loss per cow. Milking once daily increased somatic cell count throughout the year in both breeds. Cows milked once daily conceived 3 d earlier, took 5 d less from calving to conception, and needed 11% fewer controlled internal drug release devices than those milked twice daily. Milking once daily is a viable milking option for New Zealand farmers who are prepared to trade-off loss of MS income for increased time to accomplish other non-milking activities.

    Title The Role of the Afd Neuron in C. Elegans Thermotaxis Analyzed Using Femtosecond Laser Ablation.
    Date June 2006
    Journal Bmc Neuroscience
    Excerpt

    Caenorhabditis elegans actively crawls down thermal gradients until it reaches the temperature of its prior cultivation, exhibiting what is called cryophilic movement. Implicit in the worm's performance of cryophilic movement is the ability to detect thermal gradients, and implicit in regulating the performance of cryophilic movement is the ability to compare the current temperature of its surroundings with a stored memory of its cultivation temperature. Several lines of evidence link the AFD sensory neuron to thermotactic behavior, but its precise role is unclear. A current model contends that AFD is part of a thermophilic mechanism for biasing the worm's movement up gradients that counterbalances the cryophilic mechanism for biasing its movement down gradients.

    Title Is Intravenous Immunoglobulins (ivig) Efficacious in Early Pregnancy Failure? A Critical Review and Meta-analysis for Patients Who Fail in Vitro Fertilization and Embryo Transfer (ivf).
    Date June 2006
    Journal Journal of Assisted Reproduction and Genetics
    Excerpt

    PROBLEM: Intravenous Immunoglobulins (IVIG) are widely used off label in the treatment of early reproductive failure. As IVIG is expensive, and may have side-effects, evidence of efficacy is needed. Previous results have suggested that the pre-conception treatment of primary recurrent abortion patients might be effective, but the data set has been too small for adequate statistical power. More recently it has been suggested that IVIG may improve the success rate of in vitro fertilization and embryo transfer (IVF) in patients with prior IVF failures, but clinical trials have given conflicting results that need explanation. Systematic reviews generating inconclusive results have focused on methodological rigor to the exclusion of biological plausibility. METHODS: Review of current basic science of design, measurement, and evaluation of clinical trials and basic science mechanisms providing a rationale for treatment. Meta-analysis of published randomized controlled and cohort-controlled trials (updated with two unpublished data sets) evaluating IVIG treatment in IVF failure patients. Live birth rate was used as the most relevant endpoint. The ability of different sources of IVIG to suppress natural killer (NK) cell activity was determined using a standard (51)Cr-release assay in vitro. RESULTS AND CONCLUSIONS: Meta-analysis of three published randomized controlled trials (RCTs) of IVIG in IVF failure patients shows a significant increase in the live birth rate per woman (p = 0.012; Number Needed to Treat for 1 additional live birth, NNT = 6.0 women). Using live birth rate per embryo transferred, and adding data from two cohort-controlled trials to the meta-analysis further supports this conclusion (overall p = 0.000015, NNT = 3.7 women). Relevant variables appear to include properties and scheduling of the IVIG, and selection of patients with abnormal immune test results. Different IVIG preparations vary significantly in their ability to suppress NK activity in vitro. A rationale for use of IVIG is provided by a review of mechanisms of IVIG action and mechanisms underlying failure of chromosomally normal embryos.

    Title Prism: a Data Management System for High-throughput Proteomics.
    Date May 2006
    Journal Proteomics
    Excerpt

    Advanced proteomic research efforts involving areas such as systems biology or biomarker discovery are enabled by the use of high level informatics tools that allow the effective analysis of large quantities of differing types of data originating from various studies. Performing such analyses on a large scale is not feasible without a computational platform that performs data processing and management tasks. Such a platform must be able to provide high-throughput operation while having sufficient flexibility to accommodate evolving data analysis tools and methodologies. The Proteomics Research Information Storage and Management system (PRISM) provides a platform that serves the needs of the accurate mass and time tag approach developed at Pacific Northwest National Laboratory. PRISM incorporates a diverse set of analysis tools and allows a wide range of operations to be incorporated by using a state machine that is accessible to independent, distributed computational nodes. The system has scaled well as data volume has increased over several years, while allowing adaptability for incorporating new and improved data analysis tools for more effective proteomics research.

    Title Focus on "cognition" in Cognitive Behavior Therapy for Ocd: is It Really Necessary?
    Date December 2005
    Journal Cognitive Behaviour Therapy
    Excerpt

    The past decade has witnessed a significant shift toward a more cognitive emphasis in our understanding and treatment of obsessive-compulsive disorders (OCD). This article discusses the shortcomings in more standard behavioral treatment of OCD, which despite its demonstrated efficacy, led to the recent cognitive-behavioral approaches to the disorder. Current cognitive behavior therapy for OCD is described and a short critical review of the comparative treatment outcome literature on cognitive behavior therapy vs exposure and response prevention is provided. The article concludes that although the clinical utility of a more cognitive approach to OCD has not been consistently demonstrated, it would be premature to abandon cognitive formulations until some key research questions have been addressed.

    Title Polymorphisms in the Promoter Region of the Alpha1a-adrenoceptor Gene Are Associated with Schizophrenia/schizoaffective Disorder in a Spanish Isolate Population.
    Date December 2005
    Journal Biological Psychiatry
    Excerpt

    Animal models have implicated the alpha(1)-adrenergic subtypes in cognitive functions relevant to schizophrenia, but no consensus exists with regard to the status of noradrenergic receptor populations in psychiatric patients. We focused on one alpha(1)-adrenergic subtype, the alpha(1A)-adrenergic receptor, and proposed that genetic variants within the regulatory region of this gene (ADRA1A) alter the expression of this receptor, influencing susceptibility toward schizophrenia.

    Title Tolerance Signaling Molecules.
    Date November 2005
    Journal Chemical Immunology and Allergy
    Excerpt

    Mechanisms explaining maternal tolerance of her semiallogeneic histoincompatible fetus have been proposed to include a number of unique signaling molecules including CD200, novel MHC class I-b molecules such as HLA-G and HLA-E, Th2,3 cytokines, apoptosis-inducing molecules such as FASL, and indoleamine 2,3-dioxygenase. Novel CD4+ CD25+ Treg cells and gammadelta T cell receptor-positive regulatory cells appear to play key roles in responding to and in generating signals. This chapter will critically review current data concerning the mechanisms and relevance of the various proposed mechanisms.

    Title Combined Donor Leucocyte Administration and Immunosuppressive Drug Treatment for Survival of Rat Heart Allografts.
    Date September 2005
    Journal Transplant Immunology
    Excerpt

    Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drugs to combine with DL administration was examined in a rat heart transplant model.

    Title Production of Eosinophil Chemoattractant Activity by Ovine Gastrointestinal Nematodes.
    Date September 2005
    Journal Veterinary Immunology and Immunopathology
    Excerpt

    Eosinophilia is a well documented feature of helminth infections but the precise nature of the interaction between parasite and eosinophil remains an enigma. This paper describes experiments demonstrating that ruminant gastrointestinal trichostrongyles produce potent chemoattractant activity for ovine bone marrow-derived eosinophils in vitro. This activity was initially identified as a constituent of whole worm extracts of third and fourth larval (L3, L4), and adult stages of Teladorsagia circumcincta, and adult Haemonchus contortus. Similar activity was detected in excretory/secretory (E/S) material derived from live T. circumcincta L3. Subsequently, by adapting the assay technique to incorporate live worms directly into the system, it was shown that L3 of both T. circumcincta and H. contortus produced eosinophil chemoattractant activity. In contrast, neither whole worm extracts, or E/S preparations from mixed stages of the free-living nematode Caenorhabditis elegans contained eosinophil chemoattractant activity, and there was no evidence of chemoattractant production by live C. elegans. The results described are challenging to the traditional dogma that eosinophils are host-protective effector cells, and raise the intriguing possibility that ovine nematodes actively encourage recruitment of eosinophils. Local eosinophil-mediated mucosal damage, comparable to that seen in the asthmatic lung, may then provide a permissive local microenvironment for the parasite. Moreover, if they prove important for pathogenicity, nematode chemoattractants could offer future potential as novel therapeutic targets.

    Title Screening for Obsessive and Compulsive Symptoms: Validation of the Clark-beck Obsessive-compulsive Inventory.
    Date September 2005
    Journal Psychological Assessment
    Excerpt

    The 25-item Clark-Beck Obsessive-Compulsive Inventory (CBOCI) was developed to assess the frequency and severity of obsessive and compulsive symptoms. The measure uses a graded-response format to assess core symptom features of obsessive-compulsive disorder (OCD) based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria and current cognitive-behavioral formulations. Revisions were made to the CBOCI on the basis of psychometric and item analyses of an initial pilot study of clinical and nonclinical participants. The construct validity of the revised CBOCI was supported in a subsequent validation study involving OCD, nonobsessional clinical, and nonclinical samples. A principal-factor analysis of the 25 items found 2 highly correlated factors of Obsessions and Compulsions. OCD patients scored significantly higher on the measure than nonobsessional anxious, depressed, and nonclinical samples. The questionnaire had strong convergent validity with other OCD symptom measures but more modest discriminant validity.

    Title Analyzing Raman Maps of Pharmaceutical Products by Sample-sample Two-dimensional Correlation.
    Date September 2005
    Journal Applied Spectroscopy
    Excerpt

    Sample-sample (SS) two-dimensional (2D) correlation spectroscopy is applied in this study as a spectral selection tool to produce chemical images of real-world pharmaceutical samples consisting of two, three, and four components. The most unique spectra in a Raman mapping spectral matrix are found after analysis of the covariance matrix. (This is obtained by multiplying the original mapping data matrix by itself.) These spectra are identified by analyzing the slices of the covariance matrix at the positions where covariance values are at maxima. Chemical images are subsequently produced in a univariate fashion by visually selecting the wavenumbers in the extracted spectra that are least overlapped. The performance of SS 2D correlation is compared with principal component analysis in terms of highlighting the most prominent spectral differences across the whole data set (which typically comprises several thousand spectra) and determining the total number of species present. In addition, the selection of the unique spectra by SS 2D correlation is compared with the selection obtained by the orthogonal projection approach (OPA). Both comparisons are found to be satisfactory and demonstrate that a quite simple SS 2D correlation routine can be used for producing reliable images of unknown samples. The main benefit of using SS 2D correlation is that it is based on a few data processing commands that can be executed separately and produce results that are closely related to the chemical features of the system.

    Title The Bacterial Chemotactic Response Reflects a Compromise Between Transient and Steady-state Behavior.
    Date August 2005
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Swimming bacteria detect chemical gradients by performing temporal comparisons of recent measurements of chemical concentration. These comparisons are described quantitatively by the chemotactic response function, which we expect to optimize chemotactic behavioral performance. We identify two independent chemotactic performance criteria: In the short run, a favorable response function should move bacteria up chemoattractant gradients; in the long run, bacteria should aggregate at peaks of chemoattractant concentration. Surprisingly, these two criteria conflict, so that when one performance criterion is most favorable, the other is unfavorable. Because both types of behavior are biologically relevant, we include both behaviors in a composite optimization that yields a response function that closely resembles experimental measurements. Our work suggests that the bacterial chemotactic response function can be derived from simple behavioral considerations and sheds light on how the response function contributes to chemotactic performance.

    Title Breast Intraoperative Ultrasound: Prospective Study in 112 Patients with Impalpable Lesions.
    Date August 2005
    Journal Anz Journal of Surgery
    Excerpt

    Preoperative hookwire localizations have been used for some years to guide excision of subclinical breast lesions. With the availability of ultrasonography in the operating theatre, these localizations can be done intraoperatively.

    Title Recognizing the Clinical Features of Trisomy 13 Syndrome.
    Date May 2005
    Journal Advances in Neonatal Care : Official Journal of the National Association of Neonatal Nurses
    Excerpt

    Recognition of the clinical features of Trisomy 13 syndrome, a common autosomal trisomy, provides the basis for diagnostic testing and counseling of families. This article provides a systematic guide to physical assessment and photographs to enhance recognition of this genetic disorder. The principles of numerical chromosomal abnormalities as related to trisomies are reviewed. An abnormal development of the forebrain, holoprosencephaly, is the most common cranial abnormality in infants with Trisomy 13. The embryology and implications of holoprosencephaly are described. A discussion of antenatal diagnosis of Trisomy 13 and delivery room management is also provided. The diagnosis of Trisomy 13 is confirmed antenatally or after delivery with genetic testing. Prognosis of infants with Trisomy 13 and implications for the infants development are described.

    Title The Chemistry of Exploding Ants, Camponotus Spp. (cylindricus Complex).
    Date February 2005
    Journal Journal of Chemical Ecology
    Excerpt

    A detailed comparative analysis of the exocrine chemistry of nine Bruneian Camponotus species in the cylindricus complex is reported. Workers of these species are known to have hypertrophied mandibular glands and release their glandular contents suicidally from the head by rupturing the intersegmental membrane of the gaster. All of the species produce mixtures of polyacetate-derived aromatics, including hydroxyacetophenones, which display pH-dependent color changes, and aliphatic hydrocarbons and alcohols. In addition, three species contained (6R)-2,6-dimethyl-(2E)-octen-1,8-dioic acid (9) or (3S)-8-hydroxycitro-nellic acid (10a), previously unreported from insects. These compounds were characterized from their spectral data, and confirmed by comparison with synthetic samples. The allomonal role of these compounds is based on numerous field observations, and their chemotaxonomic value is presented.

    Title Anca-positive Vasculitis of the Breast.
    Date February 2005
    Journal Pathology
    Title Structural and Functional Heterogeneity in the Cd200r Family of Immunoregulatory Molecules and Their Expression at the Feto-maternal Interface.
    Date February 2005
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    We have shown that CD200Fc, a chimeric molecule including the extracellular domain of CD200 and a murine immunoglobulin (Ig)G2a Fc region, regulates immune responses and prevents T helper (Th)1 cytokine-triggered spontaneous abortions in mice. CD200 is expressed on a subpopulation of uterine decidua cells and on trophoblast, both in the mouse and human. The receptor(s) for CD200, CD200R(s), was not previously well-characterized.

    Title Fine Needle Aspiration Cytology of Pleomorphic Adenoma of the Breast.
    Date January 2005
    Journal Acta Cytologica
    Title Gordonia Terrae-induced Suppurative Granulomatous Mastitis Following Nipple Piercing.
    Date December 2004
    Journal Pathology
    Title The Ronald Mcdonald House As an Alternative to Antepartum Hospitalization.
    Date December 2004
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    OBJECTIVE: We sought to evaluate the use of the Ronald McDonald House (RMH) for selected high-risk pregnant women. METHODS: Beginning in November of 1999, women on the Maternal Fetal Medicine service at Albany Medical Center Hospital (AMCH) were candidates for antepartum lodging at the Ronald McDonald House (RMH). Women whose only indication for antepartum hospitalization was to maintain proximity to a tertiary care center were offered stays at the RMH. Antenatal and neonatal outcomes were reviewed. RESULTS: A total of 41 antepartum subjects stayed at the RMH during the study period. No adverse perinatal outcomes were identified due to utilization of the RMH. Patients stayed at the RMH instead of staying at AMCH as inpatients for a total of 586 days during the study period. CONCLUSIONS: Outpatient management at the RMH is a cost-effective alternative for selected high-risk pregnancies. No adverse outcomes in the study population were attributable to the utilization of the RMH.

    Title The Fgl2 Prothrombinase/fibroleukin Gene is Required for Lipopolysaccharide-triggered Abortions and for Normal Mouse Reproduction.
    Date September 2004
    Journal Molecular Human Reproduction
    Excerpt

    Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia. Defining the physiological and pathological role of the fgl2/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2 protein was determined by immunostaining with specific antibody. Fgl2 knockout mice were generated and typed by PCR for presence of the altered gene. Immunostaining of timed CBAxDBA/2 mouse matings in a low-abortion-rate colony showed a distinct pattern of development of fgl2 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fgl2 +/-x+/- matings with a similar low abortion rate showed selective occult loss of both +/- and, to a greater extent, -/- embryos prior to gestation day 11.5, in association with haemorrhage at the anti-mesometrial pole of fgl2-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fgl2 +/+x+/+ matings, but not -/-x-/- matings. Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology.

    Title Shall We Properly Re-examine the Status of Allogeneic Lymphocyte Therapy for Recurrent Early Pregnancy Failure?
    Date August 2004
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    How to evaluate immunological therapy advocated for recurrent spontaneous abortion and implantation failure. I was invited to comment on the opinion article of Chaouat (AJRI December 2003).

    Title Sources or Sinks? The Responses of Tropical Forests to Current and Future Climate and Atmospheric Composition.
    Date July 2004
    Journal Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
    Excerpt

    How tropical rainforests are responding to the ongoing global changes in atmospheric composition and climate is little studied and poorly understood. Although rising atmospheric carbon dioxide (CO2) could enhance forest productivity, increased temperatures and drought are likely to diminish it. The limited field data have produced conflicting views of the net impacts of these changes so far. One set of studies has seemed to point to enhanced carbon uptake; however, questions have arisen about these findings, and recent experiments with tropical forest trees indicate carbon saturation of canopy leaves and no biomass increase under enhanced CO2. Other field observations indicate decreased forest productivity and increased tree mortality in recent years of peak temperatures and drought (strong El Niño episodes). To determine current climatic responses of forests around the world tropics will require careful annual monitoring of ecosystem performance in representative forests. To develop the necessary process-level understanding of these responses will require intensified experimentation at the whole-tree and stand levels. Finally, a more complete understanding of tropical rainforest carbon cycling is needed for determining whether these ecosystems are carbon sinks or sources now, and how this status might change during the next century.

    Title Fine Needle Aspiration Cytology of a Primary Amyloid Tumor of the Breast.
    Date May 2004
    Journal Acta Cytologica
    Title Placental Trophoblast from Successful Human Pregnancies Expresses the Tolerance Signaling Molecule, Cd200 (ox-2).
    Date April 2004
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Th1 cytokine-dependent abortions in the CBA x DBA/2 mouse model have been linked to down-regulation of expression of the CD200 (OX-2) 'tolerance' signal on trophoblast and in decidua prior to onset of the abortion process. Abortions could be prevented by administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy?

    Title Md-1 is a Critical Part of the Mechanism Causing Th1-cytokine-triggered Murine Fetal Loss Syndrome.
    Date December 2003
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Fetal loss syndrome (abortion/resorption) occurring on or after gestation day (gd) 9.5 in CBA/JxDBA/2 matings is dependent upon presence of TNF-alpha + IFN-gamma, which act by increasing expression of fg12 prothrombinase at the feto-maternal interface. The magnitude by which the abortion rate can be boosted by an injection of these cytokines on gd 7.5 depends on endogenous rate of loss, and appears to depend on microbial flora. Is cytokine-triggered abortion dependent upon a third signaling pathway that senses 'danger'?

    Title Cytomegalovirus, Human Herpesvirus-6, and Human Herpesvirus-7 in Hematological Patients.
    Date December 2003
    Journal Seminars in Hematology
    Excerpt

    The prototype member of the Betaherpesvirinae subfamily, cytomegalovirus (CMV), is the most important infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts. Overt CMV disease such as pneumonitis is notoriously difficult to treat. Antiviral prophylaxis, rapid diagnostic tests to identify CMV infection, and preemptive antiviral chemotherapy are significant improvements in the management of CMV. As the kinetics of the immune response to CMV become better defined, immunotherapeutic approaches should be introduced to complement current management strategies. Two newly identified betaherpesviruses, human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV. Both are highly prevalent in the general population and infections post-bone marrow transplantation are common. These viruses are not as pathogenic as CMV but HHV-6 at least can cause disease such as encephalitis, hepatitis, and bone marrow suppression. Both of these newer herpesviruses are potentially susceptible to existing and licensed antiherpesvirus drugs.

    Title Th1 Cytokines and the Prothrombinase Fgl2 in Stress-triggered and Inflammatory Abortion.
    Date December 2003
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up-regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up-regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin-12 (IL-12) triggered abortion model.

    Title Nutrition in the Neonatal Intensive Care Unit: How Do We Reduce the Incidence of Extrauterine Growth Restriction?
    Date December 2003
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    Extrauterine growth restriction is a major clinical problem for prematurely born neonates, especially critically ill preterm neonates, and malnutrition in the neonatal intensive-care unit remains common. There are numerous perceived risks to initiation of adequate nutritional support. How many of these factors pose a real risk to health outcomes is less clear. Current nutritional support does not prevent extrauterine growth restriction and the consequences of malnutrition are both acute and delayed. Our clinical approach to providing nutritional support impacts neonatal morbidity and long-term neuro developmental outcomes. While more and better evidence is needed to help guide best practices, this gap should not prevent neonatologists from using the observations in this review to improve their current practice. There is evidence that changes in nutritional support can have a positive influence on growth. These include early administration of intravenous amino acids and lipids, minimal enteral nutrition, and supplemented formula and human milk. Simply recognizing the degree of growth failure by monitoring weight and focusing on the accruing deficit should encourage clinicians to increase nutritional support to enhance recovery growth. Continued research is needed to define the efficiency of early feeding, more rapid advancements in nutritional support, protein needs, the optimal composition of breast-milk supplements, the etiology of necrotizing enterocolitis, and perhaps most importantly, the health consequences of extrauterine growth restriction.

    Title The Meta-cognitive Beliefs Questionnaire: Development of a Measure of Obsessional Beliefs.
    Date September 2003
    Journal Behaviour Research and Therapy
    Excerpt

    A 67 item self-report questionnaire called the Meta-Cognitive Beliefs Questionnaire (MCBQ) was developed to assess endorsement of beliefs about the importance of control and negative consequences associated with unwanted, ego-dystonic intrusive thoughts, images and impulses. The MCBQ and a battery of questionnaires that assessed symptoms and cognitions of worry, obsessive-compulsive disorder, anxiety, and depression were administered to large samples of undergraduate students. Beliefs about control of intrusive thoughts and perceived negative consequences due to uncontrolled mental intrusions had a unique significant relationship with obsessions, and to a lesser extent, worry. These findings are consistent with current cognitive behavioral theories that suggest an important role for meta-cognitive beliefs in the pathogenesis of obsessions.

    Title A Critical Analysis of the Routine Testing of Newborn Stools for Occult Blood and Reducing Substances.
    Date August 2003
    Journal Advances in Neonatal Care : Official Journal of the National Association of Neonatal Nurses
    Excerpt

    Stool tests for occult blood or reducing substances were introduced in the neonatal intensive care unit (NICU) as potential aids in the early recognition of necrotizing enterocolitis (NEC) in high-risk neonates, and have been recommended by some as routine nursing procedures. Neither the performance characteristics of these tests with respect to NEC, nor their indirect impact, were evaluated formally before widespread adoption into clinical care. The published evidence suggests that these tests are not useful as diagnostic or screening tools. There is no evidence that routine stool screening for occult blood or reducing substances predicts NEC or decreases the rate or severity of this disease. The direct costs of the tests are significant. A greater concern is their potential unintended consequences, which include the cost of secondary tests, restricted nutritional intake, and the accumulation of distracting, useless data. The logistics of maintaining quality control, the demands on nursing time, and the cost of testing are increasingly important considerations. This installment of Focus on the Physical diverges from a step-by-step systematic physical assessment by addressing the utility of testing neonatal stools for occult blood and reducing substances as aids in the early diagnosis or prevention of NEC. Using the information from these tests requires a framework for understanding their rationale, the test performance characteristics in the NICU setting, and the potential benefits, costs, and risks of their routine use.

    Title The Fgl2/fibroleukin Prothrombinase Contributes to Immunologically Mediated Thrombosis in Experimental and Human Viral Hepatitis.
    Date July 2003
    Journal The Journal of Clinical Investigation
    Excerpt

    Fibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin-deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin-/- mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.

    Title Tropical Rain Forest Tree Growth and Atmospheric Carbon Dynamics Linked to Interannual Temperature Variation During 1984-2000.
    Date June 2003
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    During 1984-2000, canopy tree growth in old-growth tropical rain forest at La Selva, Costa Rica, varied >2-fold among years. The trees' annual diameter increments in this 16-yr period were negatively correlated with annual means of daily minimum temperatures. The tree growth variations also negatively covaried with the net carbon exchange of the terrestrial tropics as a whole, as inferred from nearly pole-to-pole measurements of atmospheric carbon dioxide (CO(2)) interpreted by an inverse tracer-transport model. Strong reductions in tree growth and large inferred tropical releases of CO(2) to the atmosphere occurred during the record-hot 1997-1998 El Niño. These and other recent findings are consistent with decreased net primary production in tropical forests in the warmer years of the last two decades. As has been projected by recent process model studies, such a sensitivity of tropical forest productivity to on-going climate change would accelerate the rate of atmospheric CO(2) accumulation.

    Title Gene Transcription of Fgl2 in Endothelial Cells is Controlled by Ets-1 and Oct-1 and Requires the Presence of Both Sp1 and Sp3.
    Date June 2003
    Journal European Journal of Biochemistry / Febs
    Excerpt

    The immune coagulant fgl2/fibroleukin has been previously shown to play a pivotal role in the pathogenesis of murine and human fulminant hepatitis and fetal loss syndrome. Constitutive expression of fgl2 transcripts at low levels are seen in cytotoxic T cells, endothelial, intestinal and trophoblast cells, while specific factors (such as virus and cytokines) are required to induce high levels of fgl2 expression in other cell types including monocytes/macrophages. To address the transcriptional mechanisms that regulate constitutive expression of fgl2, murine genomic clones were characterized and the transcription start site was defined by 5'-RACE and primer extension. A comprehensive assessment of basal fgl2 promoter activity in murine vascular endothelial cells defined a minimal 119 bp region responsible for constitutive fgl2 transcription. A complex positive regulatory domain (PRD) spanning a 39-bp sequence from -87 to -49 (relative to the transcription start site) was identified. Electrophoretic mobility shift assay studies in vascular endothelial cells revealed that the nucleoprotein complexes that form on this positive regulatory domain (PRD) contain Sp1/Sp3 family members, Oct-1, and Ets-1. Heterologous expression studies in Drosophila Schneider cells confirmed that the constitutive expression of this gene is controlled by Ets-1 and requires the presence both of the Sp1 and Sp3 transcription factors. The presence of this complex multicomponent PRD in the fgl2 proximal promoter is consistent with the observation that, in vivo, fgl2 expression is tightly regulated. Moreover, viral induced fgl2 expression also requires the presence of this PRD. These results clearly demonstrate that multiple cis DNA elements in a clustered region work cooperatively to regulate constitutive fgl2 expression and interact with inducible elements to regulate viral-induced fgl2 expression in endothelial cells.

    Title Anaplastic Large Cell Lymphoma Arising in a Silicone Breast Implant Capsule: a Case Report and Review of the Literature.
    Date April 2003
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    Anaplastic large cell lymphoma is a rare type of primary breast lymphoma. We report a case of anaplastic large cell lymphoma, T-cell phenotype, occurring in the periprosthetic capsule of a silicone breast prosthesis 9 years after implantation for augmentation mammoplasty. This case is unique for its unusual presentation.

    Title Human Herpesvirus 6: Relevance of Infection in the Immunocompromised Host.
    Date March 2003
    Journal British Journal of Haematology
    Title The Same Immunoregulatory Molecules Contribute to Successful Pregnancy and Transplantation.
    Date January 2003
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    At least two dendritic cell-associated molecules have been shown to contribute to the successful outcome of organ and tissue allografts in mice, namely CD200 and MD-1. CD200 is up-regulated in rodent transplantation models where successful inhibition of rejection is accomplished, and is believed to signal immunosuppression following engagement of a receptor, CD200R, on macrophages and/or gammadelta T-cell receptor (gammadelta TCR+ cells MD-1 is implicated in controlling expression of costimulatory molecules including CD80/CD86 which induce an immunorejection response, and thus inhibition of MD-1 expression also facilitates increased graft survival MD-1 also stabilizes expression of CD14, part of the receptor complex for LPS. As well as the inhibition of rejection which follows blockade of MD-1 expression and/or augmentation of CD200 expression, an altered polarization in cytokine production is seen, with increased expression of interleukin-4 (IL-4), IL-10 and transforming growth factor-beta (TGF-beta), and decreased IL-2, interferon-gamma (IFN-gamma) and tumor nerosis factor-alpha (TNF-alpha). Successful pregnancy in allopregnant mice also depends upon control of graft rejection mechanisms. Proinflammatory T-helper 1 (Th1) cytokines (TNF-alpha + IFN-gamma + IL-1) have been shown to cause spontaneous abortion in mice by activating a novel prothrombinase, fibrinogen-like peptide (fibroleukin) fgl2, which may promote fibrin deposition in the graft rejection process; expression of IL-10, TGF-beta, and progesterone-induced blocking factor (PIBF) in contrast leads to lowering of abortion rates. Interestingly, the spontaneous abortion rates in abortion-prone CBA x DBA/2 matings and in the low abortion rate CBA x BALB/c matings were lower than the frequency of implantation sites showing fibrin(hi) + fgl2 (mRNA)hi, implying regulation of the pro-abortion consequences of fgl2 expression.

    Title Oliguric Acute Renal Failure in Mycosis Fungoides with Lymphomatous Infiltrates in the Kidneys.
    Date January 2003
    Journal International Urology and Nephrology
    Excerpt

    OBJECTIVE: To present the clinical picture of acute renal failure in patients with mycosis fungoides (MF) and renal lymphomatous infiltrates. To analyze the pathogenesis of renal failure. METHODS: Correlation of clinical picture, urinary findings, imaging reports and autopsy findings in two patients with long-standing MF who died with renal failure. CASE SUMMARIES: Both subjects had sustained oliguria in the last 2 weeks. One patient had persistent hypotension, normal urinalysis, normal renal sonogram, and scarce interstitial lymphomatous infiltrates with preservation of renal parenchymal architecture. He was thought to have ischemic acute renal failure not directly linked to the lymphomatous infiltrates. The second patient developed hypertension one month prior to death, and had moderate proteinuria, hematuria, pyuria, grossly enlarged kidneys with hypoechoic masses, and extensive replacement of the renal parenchyma by lymphomatous infiltrates. This picture is typical of renal failure secondary to lymphomatous replacement of the kidneys. CONCLUSIONS: The development of oliguric renal failure in MF with renal lymphomatous infiltrates may have varying clinical and imaging manifestations and pathogeneses. Potentially reversible pathogenic mechanisms should be systematically investigated, particularly if the overall clinical picture is not characteristic of renal failure secondary to lymphomatous replacement of the parenchyma.

    Title Thinking Outside the Box: Mechanisms of Environmental Selective Pressures on the Outcome of the Materno-fetal Relationship.
    Date December 2002
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Study of mechanisms causing spontaneous abortion of the vascularized placenta have focused primarily on the feto-maternal immunological relationship within the pregnant mother. The Th1 cytokines such as tumor necrosis factor (TNF)-alpha + interferon (IFN)-gamma derived in part from natural killer (NK) and NKgammadeltaT cells have been implicated in causing abortion via up-regulation of the novel prothrombinase fgl2 at the feto-maternal interface; Th2/3 cytokines such as interleukin (IL)-10, progesterone-induced blocking factor (PIBF), and TGF-beta2 derived from gammadeltaT cells stimulated by embryo antigens in the context of the OX-2 (CD200) tolerance signal have been viewed as counteracting the Th1 effect. These mechanisms are distinct from those causing and preventing occult pregnancy loss during the periimplantation phase of pregnancy prior to development of a vascularized placenta. Spontaneous abortions in the CBA/J x DBA/2 can be boosted by injecting TNF-alpha + IFN-gamma, but the boosted abortion rates can range from < or = 30 to > 80%, depending on the loss rate in uninjected mice, and this is not explainable by the endogenous level of these cytokines. Furthermore, there is a poor correlation between Th1/Th2.3 cytokine ratios and abortion rates. Could there be a third factor involved, and if so, what might this mean?

    Title Defining the Roles of Perforin, Fas/fasl, and Tumour Necrosis Factor Alpha in T Cell Induced Mucosal Damage in the Mouse Intestine.
    Date September 2002
    Journal Gut
    Excerpt

    Mucosal flattening and epithelial cell apoptosis are typical features of T cell induced inflammatory diseases of the bowel, such as coeliac disease and graft versus host disease. Mice injected with a T cell activating anti-CD3 antibody develop a severe diarrhoeal illness. We describe the histological features of this enteropathy and define the effector mechanisms involved in T cell induced mucosal injury in this in vivo model.

    Title Lung Deposition of Budesonide from the Novel Dry Powder Inhaler Airmax.
    Date August 2002
    Journal Respiratory Medicine
    Excerpt

    The deposition of budesonide at fast (60 l min(-1)) and slow (301 min(-1)) inspiratory flow rates from Airmax, a new multi-dose dry powder inhaler, was compared with that from Turbuhaler and a standard pressurized metered dose inhaler (pMDI). Twelve patients with mild to moderate asthma took part in a five-way randomized crossover study, and inhaled a single nominal dose of 200 microg budesonide, labelled with 99mTc, on each study day. Deposition was determined by gamma scintigraphy. At the fast flow rate, Airmax and Turbuhaler deposited 25.8+/-6.5% (mean +/- sD) and 29.8+/-6.9%, respectively of the delivered dose in the whole lung (P = 0.080). At the slow flow rate, Airmax deposited 28.3+/-5.6%, Turbuhaler 22.7+/-5.6% and pMDI 12.1+/-3.4%. Using data on emitted doses determined in vitro, it was estimated that Airmax deposited 53.1+/-13.3 microg and 43.6+/-8-6 microg budesonide in the lungs at 60 l min(-1) and 30 l min(-1) respectively whilst Turbuhaler deposited 48.3+/-11.2 microg at 60 l min -and 24.2+/-6.0 microg at 30 l min(-1). In conclusion, lung deposition of budesonide from Airmax was comparable to that of Turbuhaler at a high flow rate but was markedly superior to Turbuhaler and pMDI at a lower flow rate. Unlike Turbuhaler, Airmax performs with relative flow-rate independence.

    Title Novel Homozygous Splice Acceptor Site Gnrh Receptor (gnrhr) Mutation: Human Gnrhr "knockout".
    Date July 2002
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Mutations in the GnRH receptor (GnRHR) have been shown to be responsible for a significant number of autosomic recessive and, less commonly, sporadic cases of idiopathic hypogonadotropic hypogonadism. We describe a woman with complete GnRH resistance secondary to a novel homozygous GnRHR gene mutation, transmitted as an autosomal recessive trait. The propositus presented with primary amenorrhea and absent thelarche and pubarche. Dynamic tests demonstrated absent spontaneous gonadotropin pulsatility, and no response to either exogenous pulsatile (10 microg/pulse at 90-min intervals over 6 h) or acute (100 microg) GnRH administration. However, she responded to exogenous gonadotropin administration, with a resulting normal pregnancy. Genomic DNA extracted from peripheral blood was PCR amplified using amplimers spanning intron-exon boundaries for the three exons of GnRHR and revealed a homozygous splice junction mutation (G to A transversion) at the intron 1-exon 2 boundary. Her unaffected sister, with a totally normal phenotype, was heterozygous for this mutation. After lymphocyte Epstein-Barr virus transformation, RNA was extracted and subjected to RT-PCR, using primers located in the first and third exons. Results showed a transcript lacking all of exon 2 (exon 2 skipping), with splicing of exon 1 to exon 3. This created a frame shift, generating a coding sequence for three new amino acids, followed by a stop codon. Although it is not clear whether the mutant receptor is actually expressed, the resultant mRNA sequence was presumed to produce a truncated receptor with no binding or signaling capacity.

    Title Orientation of Bound Ligands in Mannose-binding Proteins. Implications for Multivalent Ligand Recognition.
    Date July 2002
    Journal The Journal of Biological Chemistry
    Excerpt

    Mannose-binding proteins (MBPs) are C-type animal lectins that recognize high mannose oligosaccharides on pathogenic cell surfaces. MBPs bind to their carbohydrate ligands by forming a series of Ca(2+) coordination and hydrogen bonds with two hydroxyl groups equivalent to the 3- and 4-OH of mannose. In this work, the determinants of the orientation of sugars bound to rat serum and liver MBPs (MBP-A and MBP-C) have been systematically investigated. The crystal structures of MBP-A soaked with monosaccharides and disaccharides and also the structure of the MBP-A trimer cross-linked by a high mannose asparaginyl oligosaccharide reveal that monosaccharides or alpha1-6-linked mannose bind to MBP-A in one orientation, whereas alpha1-2- or alpha1-3-linked mannose binds in an orientation rotated 180 degrees around a local symmetry axis relating the 3- and 4-OH groups. In contrast, a similar set of ligands all bind to MBP-C in a single orientation. The mutation of MBP-A His(189) to its MBP-C equivalent, valine, causes Man alpha 1-3Man to bind in a mixture of orientations. These data combined with modeling indicate that the residue at this position influences the orientation of bound ligands in MBP. We propose that the control of binding orientation can influence the recognition of multivalent ligands. A lateral association of trimers in the cross-linked crystals may reflect interactions within higher oligomers of MBP-A that are stabilized by multivalent ligands.

    Title Kinetic Analysis of a Unique Direct Prothrombinase, Fgl2, and Identification of a Serine Residue Critical for the Prothrombinase Activity.
    Date June 2002
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    fgl2 prothrombinase, by its ability to generate thrombin, has been shown to be pivotal to the pathogenesis of viral-induced hepatitis, cytokine-induced fetal loss syndrome, and xeno- and allograft rejection. In this study, the molecular basis of fgl2 prothrombinase activity was examined in detail. Purified fgl2 protein generated in a baculovirus expression system had no measurable prothrombinase activity, whereas the activity was restored when the purified protein was reconstituted into phosphatidyl-L-serine-containing vesicles. Reconstituted fgl2 catalyzed the cleavage of human prothrombin to thrombin with kinetics consistent with a first order reaction, with an apparent V(max) value of 6 mol/min/mol fgl2 and an apparent K(m) value for prothrombin of 8.3 microM. The catalytic activity was totally dependent on calcium, and factor Va (500 nM) enhanced the catalytic efficiency of fgl2 by increasing the apparent V(max) value to 3670 mol/min/mol fgl2 and decreasing the apparent K(m) value for prothrombin to 7.2 microM. By a combination of site-directed mutagenesis and production of truncated proteins, it was clearly shown that residue Ser(89) was critical for the prothrombinase activity of fgl2. Furthermore, fgl2 prothrombinase activity was not inhibited by antithrombin III, soybean trypsin inhibitor, 4-aminobenzamidine, aprotinin, or phenylmethylsulfonyl fluoride, whereas diisopropylfluorophosphate completely abrogated the activity. In this work we provide direct evidence that fgl2 cleaves prothrombin to thrombin consistent with serine protease activity and requires calcium, phospholipids, and factor Va for its full activity.

    Title Activation of the Novel Prothrombinase, Fg12, As a Basis for the Pregnancy Complications Spontaneous Abortion and Pre-eclampsia.
    Date March 2002
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Impaired trophoblast invasion during the first trimester of pregnancy is linked to spontaneous abortion, and defective invasion in the second trimester to hypertension + proteinuria (pre-eclampsia). Hypertension developing during the third trimester of human pregnancy represents, in part, a corrective response in the mother to provide adequate placental perfusion for fetal growth when trophoblast has not to invaded and converted the myometrial porprtion of maternal spiral arteries into to low resistance-high capacitance conduits. Deportation of vesicles from hypoxemic trophoblast is thought to cause hypertension plus proteinuria, vascular damage and a systemic coagulopathy. Trophoblast invasion may be inhibited by local cytokines, such as TGF-betas but Thl-type cytokines associated with pre-eclapmsia and spontaneous abortions (e.g., IL-1, TNF-alpha, IFN-gamma) are not known to inhibit migration at in situ concentrations. Trophoblast invasion is also inhibited by the binding of surface integrins to fibronectin and fibrin, and fibrin production is stimulated by these Th1 cytokines via up-regulation of prothrombinases(s) such as fg12 which directly and via TNF-alpha-facilitated inflamation compromise trophoblast cell integrity. We, therefore, asked if fg12 expression and TNF-alpha are increased in first trimester human miscarriage and in third trimester pre-eclampsia.

    Title Suppression of Obsession-like Thoughts in Nonclinical Individuals: Impact on Thought Frequency, Appraisal and Mood State.
    Date January 2002
    Journal Behaviour Research and Therapy
    Excerpt

    Wegner's (1994, Psychological Review, 101, 34-52) research on the paradoxical effect of thought suppression has been incorporated into contemporary cognitive-behavioural models of obsessive-compulsive disorder. However, findings on the effects of thought suppression on thought frequency have been inconsistent and few studies have actually examined the suppression of thoughts that are obsessional in nature. In the present study 219 nonclinical participants were randomly assigned to suppress or not suppress a neutral, obsessional or positive thought during an initial monitoring interval. In a second thought monitoring interval, all participants received instructions not to suppress their target thought. No paradoxical effect of suppression on frequency was observed for any type of thought, although suppression of obsessional thoughts was associated with greater subsequent discomfort and a more negative mood state than suppression of positive or neutral target thoughts.

    Title American College of Cardiology/society for Cardiac Angiography and Interventions Clinical Expert Consensus Document on Cardiac Catheterization Laboratory Standards: Summary of a Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.
    Date August 2001
    Journal Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions
    Title Quantitation of Porcine Cytomegalovirus in Pig Tissues by Pcr.
    Date July 2001
    Journal Journal of Clinical Microbiology
    Excerpt

    A quantitative-competitive PCR for the quantification of porcine cytomegalovirus (PCMV) was developed. The virus was detected in a variety of pig organs (including potential xenotransplant donations), with viral loads ranging from <10 to 97 genome copies/microg of DNA. This assay will have significant utility for studying the activation and replication of PCMV and in swine models for allo- and xenotransplantation.

    Title Chemical Image Fusion. The Synergy of Ft-nir and Raman Mapping Microscopy to Enable a More Complete Visualization of Pharmaceutical Formulations.
    Date July 2001
    Journal Analytical Chemistry
    Excerpt

    The pharmaceutical industry uses successfully both FT-NIR and Raman microscopy to produce chemical images of solid dosage forms, typically in troubleshooting roles. However, due to the chemical composition of the formulations, it is not always possible to describe the entire chemical formulation by using a single spectroscopic method. As Raman and NIR spectroscopies are complementary in nature, their combined usage offers the opportunity to describe heterogeneous mixtures in more detail. A novel sample referencing approach has been developed that allows data to be acquired from exactly the same area of the sample using both Raman and FT-NIR microscopies. The optimum images for the components are then overlaid, which gives rise to a combined chemical image that visually describes the entire formulation. We have named this approach chemical image fusion (CIF). CIF has been applied to two examples. The first shows how a simple formulation was used to validate the CIF approach. In the second, CIF allowed an entire formulation to be visualized and the cause of tabletting problems determined. CIF provides increased confidence in the results generated by each individual technique and offers a more powerful method for the evaluation of pharmaceutical formulations.

    Title American College of Cardiology/society for Cardiac Angiography and Interventions Clinical Expert Consensus Document on Cardiac Catheterization Laboratory Standards. A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.
    Date July 2001
    Journal Journal of the American College of Cardiology
    Title Castanospermine, an Oligosaccharide Processing Inhibitor, Reduces Both Lymphocyte-endothelial Cell Binding and Lfa-1alpha Membrane Expression.
    Date June 2001
    Journal Transplantation Proceedings
    Title Fas/fas Ligand Interaction at the Placental Interface is Not Required for the Success of Allogeneic Pregnancy in Anti-paternal Mhc Preimmunized Mice.
    Date April 2001
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    FAS ligand (FASL) induces apoptosis in FAS+ T cells. FAS-FASL interaction can explain tolerance of some types of allografts. Do similar interactions prevent rejection of the fetal allograft and transplacental passage of maternal T cells capable of causing GvH leading to runting?

    Title Ly-49d Transfected Nk Cells Show Reduced Interleukin-10 Production in Response to H-2d and Increased Lytic Activity: Implication by Interaction Using Class I Mhc Alloantigen+ Target Cells in Pregnancy.
    Date January 2001
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    Mating of CBA/J (H-2k) with DBA/2 (H-2d) males leads to a high rate of spontaneous resorption (about 40%), which is not seen in other mating combinations, such as CBA/J X BALB/c. The activation of natural killer cells (NK cells) seems to be a key mechanism for the maternal-fetal intolerance in allogeneic pregnancy, and recurrent spontaneous abortion. The effect of expression of the NK cell activating receptor Ly49D recognizing BALB/c or DBA/2 class I MHC was investigated.

    Title Antiphospholipid Antibody Status and Ivf--debate.
    Date November 2000
    Journal Fertility and Sterility
    Title White Bears and Other Elusive Intrusions. Assessing the Relevance of Thought Suppression for Obsessional Phenomena.
    Date July 2000
    Journal Behavior Modification
    Excerpt

    According to recent research, deliberate suppression of unwanted thoughts may result in a paradoxical increase in their frequency. Recent cognitive-behavioral theories of obsessive-compulsive disorder now consider active thought suppression to be a crucial factor in the pathogenesis of obsessions. However, there are considerable inconsistencies in the results of studies investigating the thought suppression paradox that make it difficult to apply findings to obsessional problems. Furthermore, many studies have low ecological validity for obsessional problems. This article reviews the thought suppression research, discusses methodological issues relevant to application of the thought suppression paradox to obsessional problems, and offers recommendations for future research.

    Title Appraisal and Control of Sexual and Non-sexual Intrusive Thoughts in University Students.
    Date June 2000
    Journal Behaviour Research and Therapy
    Excerpt

    This study examined differences in the appraisal and thought control strategies associated with the perceived control of unwanted sexual and non-sexual intrusive thoughts. Eleven appraisal dimensions, subjective physiological arousal and 10 thought control strategies were measured in 171 university students who were administered the Revised Obsessive Intrusions Inventory-Sex Version, a self-report measure of unwanted intrusive thoughts. Thought-action fusion (TAF) likelihood was a significant unique predictor of the perceived controllability of respondents' most upsetting sexual and non-sexual intrusive thought. Moreover greater subjective physiological arousal was a significant predictor of reduced control over sexual intrusions, whereas worry that one might act on an intrusive thought and greater effort to control the intrusion were significant unique predictors of the control of non-sexual intrusive thoughts. Various thought control strategies were more often used in response to non-sexual than sexual cognitions. The results are discussed in terms of the differential role of various appraisal processes in the control of unwanted sexual and non-sexual thoughts.

    Title The Relationship Between Health Care Reform and Nurses' Interest in Union Representation: the Role of Workplace Climate.
    Date April 2000
    Journal Journal of Professional Nursing : Official Journal of the American Association of Colleges of Nursing
    Excerpt

    Market-based reforms are rapidly changing the landscape of the American health care system. Over the last decade, a great deal of attention has been paid to these reforms, particularly the advent and rapid growth of managed care and the vertical and horizontal integration of provider institutions. The ramifications of these changes on both individual and institutional consumers has also been widely considered by scholars and policymakers. Yet, although these market reforms are driving the massive restructuring of work in hospitals and other health care organizations, comparatively little attention has been paid to the impact these changes have on health care employees and the environment in which they work. This article reports the results of an exploratory study examining the relationship between health care market reforms, nurses' perceptions of the climate for patient care in hospital settings, and nurses' interest in union representation. A model is proposed to help explain nurses' support for union representation in the presence of market-based reforms.

    Title Hard Science Versus Phenomenology in Reproductive Immunology.
    Date February 2000
    Journal Critical Reviews in Immunology
    Excerpt

    It has been suggested that studies of immunological aspects of reproduction have recently changed from the phenomenological (e.g., speculative/descriptive) to hard science (e.g., precise molecular description/ explanation). The significance of this development is explored by analysis of the contribution made by hard science that has led to a number of assertions. Does HLA-G determine maternal tolerance of her semi-allogeneic fetus? Do differences in placentation between humans, rodents, and other species make direct comparisons largely meaningless? Does membrane cofactor protein (CD46) contribute to pregnancy success by protecting sperm and fetal trophoblast from complement-mediated lysis? Does a low frequency in mice of maternal T cells specific for paternal alloantigens occur, and if so, does phenomenon explain specific maternal tolerance in pregnancy? Do placental and decidual macrophage components provide an important immediate antigen-nonspecific host defense to infection? Does the mix of bioactive molecules make the uterus an immunologically privileged site, and does the molecular melange have a pivotal role in promoting growth and development of the placenta and embryo? Does prolactin acting on receptors on lymphocytes suppress function and thereby account for remission of autoimmune disease in pregnant women? Is the efficacy and safety of immunotherapy for recurrent spontaneous abortion a thorny issue that will be resolved by an ongoing funded national trial? What is a scientifically correct timeline of important discoveries and developments in reproductive immunology? It is argued that it is unprofitable to divorce phenomenology from hard science and that the timeline for developments in reproductive immunology begin with Darwin. Irrespective of whether one is dealing with phenomena or hard science data, Hippocrates was correct in his aphorism that "description is infinite and easy; explanation is limited and difficult".

    Title Cytokines and the Regulation of Apoptosis in Reproductive Tissues: a Review.
    Date January 2000
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    To determine the role of apoptosis-regulating genes bax and bcl-2 in reproduction.

    Title Achilles Tendon Ruptures Stratified by Age, Race, and Cause of Injury Among Active Duty U.s. Military Members.
    Date January 2000
    Journal Military Medicine
    Excerpt

    A total of 865 members of the U.S. military underwent repair of Achilles tendon ruptures at U.S. military hospitals during calendar years 1994, 1995, and 1996. The discharge summaries of these patients were analyzed for patient demographic information, including age, race, and causative activity. Patients were then stratified by age, race, and cause of injury. Blacks were at increased risk for undergoing repair of the Achilles tendon compared with nonblacks (overall relative risk = 4.15, 95% confidence interval [CI] = 3.63, 4.74; summary odds ratio controlling for age = 3.69, CI = 3.25, 4.19). Participation in the game of basketball accounted for 64.9% of all injuries in black patients and 34.0% of all injuries in nonblack patients. Among those injured, blacks had a significantly increased risk for injury related to playing basketball than nonblacks (relative risk = 1.82, CI = 1.58, 2.10). This finding suggests that there may be other predisposing factor(s) that result in a higher risk of Achilles tendon ruptures in black individuals.

    Title Human Herpesviruses 6 and 7 As Potential Pathogens After Liver Transplant: Prospective Comparison with the Effect of Cytomegalovirus.
    Date January 2000
    Journal Journal of Medical Virology
    Excerpt

    Because cytomegalovirus (CMV) is an important opportunistic infection after liver transplant, we conducted a prospective study to see if the same applied to human herpesviruses (HHV)-6 and -7. We used polymerase chain reaction (PCR) methods optimised to detect active, not latent, infection and studied patients not receiving antiviral prophylaxis for CMV. Post-transplant, 536 blood samples were tested by PCR (median 7; range 4-50). Active infection with CMV was detected in 28/60 (47%), HHV-6 in 19/60 (32%), and HHV-7 in 29/60 (48%) of patients. The PCR-positive samples were tested by quantitative-competitive PCR to measure the virus load of each betaherpesvirus. The median peak virus load for CMV was significantly greater than that for HHV-6 or HHV-7. Detailed clinicopathological analyses for the whole population showed that CMV and HHV-6 were each significantly associated with biopsy-proven graft rejection. Individual case histories suggested that HHV-6 and HHV-7 may be the cause of some episodes of hepatitis and pyrexia. It is concluded that HHV-6 is a previously unrecognized contributor to the morbidity of liver transplantation, that HHV-7 may also be important and that both viruses should be included in the differential diagnosis of graft dysfunction.

    Title Critical Analysis of Intravenous Immunoglobulin Therapy for Recurrent Miscarriage.
    Date December 1999
    Journal Human Reproduction Update
    Excerpt

    Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.

    Title Murine T Cell Determination of Pregnancy Outcome.
    Date November 1999
    Journal Cellular Immunology
    Excerpt

    At the fetomaternal interface, maternal effector cells come in intimate contact with fetal trophoblast cells which express paternal antigens. Failure of fetal trophoblast cells to activate maternal Th1 immune responses has been attributed in part to the absence of classical Class I and Class II major histocompatibilty complex (MHC) antigen expression and elaboration of factors which reduce TcR expression and shift any immune responses which may occur to Th2. Classical TcR alphabeta(+) T cells have not been found to be able to respond to trophoblasts. Recently, TcR gammadelta(+) T cells have been characterized in the low-abortion-rate pregnant C57Bl/10 mouse decidua, and the Vgamma1(+) subset may be able to respond to trophoblasts in a non-MHC-dependent manner. Trophoblast-recognizing T cells with Vgamma1 receptors are also present in the decidua of CBA/J mice pregnant by DBA/2, an abortion-prone mating combination. To test the role of the Vgamma1 subset of decidual gammadelta T cells in abortion-prone pregnancies, we altered this subset by injecting monoclonal anti-Vgamma1.1 antibody on gestation day 5.5, 1 day after implantation. This reduced detectability of a Vgammadelta subset producing TNF-alpha and reduced the abortion rate. Anti-Vgamma2, which reacts with a similar proportion of decidual gammadelta T cells as anti-Vgamma1.1, failed to prevent abortions. Vdelta6.3(+) cells are prominent at the fetomaternal interface, and anti-Vdelta6 antibody injected on day 5.5 prevented abortions. TGF-beta2(+) gammadelta cells first appear on day 8.5 of pregnancy; anti-Vgamma1.1 antibody injection on day 8.5 depleted these cells and boosted abortions; anti-Vdelta6.3 given on day 8.5 boosted abortions to the same level. These results suggest that two populations of Vgamma1.1(+)delta6.3(+) T cells may arise in the decidua: an early population that is Th1, abortogenic, and present during the time of implantation, and a Th2/3 cell subset that is present in the decidua later during pregnancy and which is pregnancy-protective.

    Title Laparoscopic Orchidopexy for the Intra-abdominal Testis.
    Date November 1999
    Journal Pediatric Surgery International
    Excerpt

    The role of laparoscopy in the management of the impalpable testis has been largely as a diagnostic tool only. Its therapeutic application as a single or two-stage Fowler-Stephens procedure for the intra-abdominal testis is assessed and a management algorithm derived. A retrospective review was performed of 26 children with 33 intra-abdominal testes (IAT) who were operated upon between 1992 and 1997; 5 had a single-stage (6 testes) and 21 had a staged approach. All children had the operated testis located in an acceptable scrotal position on review. Six operations were performed as a single-stage procedure. Four testes were palpably smaller at follow-up: 2 in the single-stage (33.3%) and 2 in the two-stage group (7%). Of the 26 children, 24 were day-case admissions. Minor self-limiting complications were observed in 5 cases. Laparoscopic localisation and Fowler-Stephens orchidopexy can be safely employed in the definitive management of the IAT.

    Title Optimized Dairy Grazing Systems in the Northeast United States and New Zealand. I. Model Description and Evaluation.
    Date October 1999
    Journal Journal of Dairy Science
    Excerpt

    Parallels exist in the recent developments of dairy systems in the Northeast United States and New Zealand because of greater use of pasture grazing and feed supplements, respectively. Lessons can be learned from each system. However, major differences exist between the regions in the patterns of pasture production, the costs of supplementary feed, and milk prices. These differences affect the optimum use of feed. In this paper, a linear programming model developed to determine optimum feeding strategies for dairy systems in each country is presented. The model optimizes grazing management (rotation lengths) and the conservation of pasture subject to constraints on their use. Other feed resources include N fertilizer, grain, corn silage, and alfalfa silage. All feeds are represented in energy terms. The substitution of pasture intake by grain and forage supplements is included, and cow performance can be optimized by choosing from 73 seasonal calving herds that vary in calving date, lactation length, and daily milk production. The model predicts that marginal responses to grain feeding are between 1.35 and 1.8 kg of milk/kg of grain dry matter supplement, well within the range of responses reported in the literature. Evaluation of the model against data from nine grazing system treatments in New Zealand and two in Pennsylvania showed that model predictions averaged +3% (New Zealand) and +0.04% (Northeast) of measured milk production. The model could be used with confidence to study systems in both the Northeast United States and New Zealand.

    Title Optimized Dairy Grazing Systems in the Northeast United States and New Zealand. Ii. System Analysis.
    Date October 1999
    Journal Journal of Dairy Science
    Excerpt

    Factors that optimize milk production from Northeast United States and New Zealand grazing systems are compared using a linear programming model. The objective function maximized gross margin per hectare of land farmed. The experimental design compared the optimum characteristics of each system over a range of milk prices. The Northeast has a shorter grazing season and lower cropping costs than New Zealand. The optimum pasture area was 49% of the farm for Northeast systems. Gross margins declined rapidly above 55% or below 36% pasture area. The optimum stocking rate was 1.13 cows/ha, or 2.3 cows/ha of pasture. Optimum per cow production was higher for Northeast [7105 kg of fat-corrected milk (FCM)] than New Zealand (5710 kg of FCM) systems. This was related to lower grain relative to milk prices in the Northeast. New Zealand, all-pasture systems gave the lowest cost per unit of milk but also gave the lowest gross margin across all milk price scenarios. The best use of purchased feed in New Zealand systems was to support increased stocking rate rather than per cow production. Optimum grazing management practices were similar for supplemented New Zealand and Northeast systems. All-pasture New Zealand systems are characterized by short lactations and long autumn rotations to transfer pasture in situ for winter feeding. Higher costs per unit of milk produced will be an inevitable consequence of maximizing gross margin at high milk prices in New Zealand systems.

    Title T Cells in Pregnancy: Illusion and Reality.
    Date August 1999
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Title Signaling at the Fetomaternal Interface.
    Date July 1999
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Title American Society for Reproductive Immunology Report of the Committee for Establishing Criteria for Diagnosis of Reproductive Autoimmune Syndrome.
    Date July 1999
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Title Antiinflammatory Actions of Cat's Claw: the Role of Nf-kappab.
    Date April 1999
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Uncaria tomentosa is a vine commonly known as cat's claw or 'uña de gato' (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. PURPOSE: The aim of this study was to determine the proposed anti-inflammatory properties of cat's claw. Specifically: (i) does a bark extract of cat's claw protect against oxidant-induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. METHODS: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). RESULTS: The administration of UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat's claw inhibited lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF-kappaB. Cat's claw markedly attenuated indomethacin-enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. CONCLUSIONS: Cat's claw protects cells against oxidative stress and negated the activation of NF-kappaB. These studies provide a mechanistic evidence for the widely held belief that cat's claw is an effective anti-inflammatory agent.

    Title Common and Specific Dimensions of Self-reported Anxiety and Depression: the Bdi-ii Versus the Bdi-ia.
    Date March 1999
    Journal Behaviour Research and Therapy
    Excerpt

    The Beck Depression Inventory-II (BDI-II) [Beck, A. T., Steer, R. A. & Brown, G. K. (1996). Manual for Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.] and Anxiety Inventory (BAI) [Beck, A. T. & Steer, R. A. (1993a). Manual for the Beck Anxiety Inventory. San Antonio, TX: Psychological Corporation.] were administered to 840 outpatients who were diagnosed with various types of psychiatric disorders to determine whether the general symptom compositions and relative amounts of variance of the common and specific dimensions of self-reported anxiety and depression for these instruments would be comparable to those that had been found by Steer et al. [Steer, R. A., Clark, D. A., Beck, A. T. & Ranieri, W. F. (1995). Common and specific dimensions of self-reported anxiety and depression: A replication. Journal of Abnormal Psychology, 104, 542-545.] with the BAI and amended Beck Depression Inventory (BDI-IA) [Beck, A. T. & Steer, R. A. (1993b). Manual for the Beck Depression Inventory. San Antonio, TX: Psychological Corporation.]. A Schmid-Leiman transformation was used with the iterated-principal-factor pattern matrix of the BAI and the BDI-II loadings and indicated that the overall symptom compositions and relative amounts of variance that were explained by the one common and two specific anxiety and depression dimensions were comparable to those previously found with the BDI-IA.

    Title Phase I Trial of Simultaneous Administration of Interleukin 2 and Interleukin 4 Subcutaneously.
    Date February 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Interleukin (IL) 2 plays an important role in enhancing the immune response, whereas IL-4 has pluripotent activities which include affecting immune function. Preclinical data suggest that the combination might have enhanced immunomodulatory activity. In this Phase I trial in patients with advanced solid tumors, both IL-2 and IL-4 were given by separate s.c. injections simultaneously daily, 5 days in a row, Monday through Friday, for 3 consecutive weeks, followed by a 1-week break from treatment. Cycles could be repeated. The dose of IL-2 was kept constant at 9 x 10(6) IU/m2/injection while the dose of IL-4 was escalated beginning at 100 microgram/m2/injection and increasing by 100-microgram/m2 increments to a planned level of 400 microgram/m2/injection. Sixteen patients were entered in this study, with one patient being ineligible because of the presence of brain metastases. Of the 15 eligible patients, there were 14 males and 1 female, with a median age of 54 (range, 38-67) years and initial performance status of 0 in 5 patients and 1 in 10 patients. Patients were treated at levels of up to 300 microgram/m2/injection of IL-4 before the study was closed due to withdrawal of the drug by the manufacturer. The most commonly observed toxicities were fatigue, fever and chills, local reaction, nausea/vomiting and anorexia, headache and nasal stuffiness, and coughing, sometimes with the production of clear white sputum, more common in smokers. Duodenal ulcers occurred in one patient and one patient had grade 4 cardiac toxicity consisting of an asymptomatic minimal elevation of the creatinine phosphokinase MB isoenzyme (CPK-MB). Grade 3 hyponatremia occurred in two patients, and elevated liver function tests and creatinine occurred but were not dose limiting. Eosinophilia of unknown significance occurred in all patients. There were statistically significant elevations in absolute numbers of most T-cell subsets examined, without changes in circulating B cells. No antibodies to the IL-4 were found after one cycle. One patient with renal cell carcinoma showed a significant decrease in tumor burden after one cycle of treatment. Because of the IL-4 withdrawal, the maximum tolerated dose for this combination of drugs given by the route and schedule used here was not determined and will require additional testing. Subcutaneous IL-2 and IL-4 given simultaneously show important immunomodulatory and antitumor effects and should be tested further in cancer patients.

    Title Genistein and Gut Inflammation: Role of Nitric Oxide.
    Date March 1998
    Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
    Excerpt

    Genistein, a principal soy isoflavone, has been identified as a protein kinase inhibitor that possesses immunosuppressive and anti-inflammatory properties. The aim of the study was to determine if genistein modified chronic ileitis in guinea pigs induced by the hapten trinitrobenzene sulfonic acid (TNBS), and the activity index of cultured macrophages (RAW 264.7 cells) stimulated with lipopolysaccharide (LPS). Genistein at low doses (0.1 mg/kg, s.c.) had mild anti-inflammatory effects in TNBS ileitis. Therapeutic benefit included a reduction in nitric oxide production, granulocyte infiltration and improved mucosal architecture. Genistein, at low doses, also appeared to attenuate immunohistochemical staining for inducible nitric oxide synthase (iNOS) and nitrotyrosine. The beneficial effects of genistein were not apparent at doses above 0.1 mg/kg. We found that genistein also inhibited LPS-induced nitrite production by cultured macrophages and protected against LPS-induced necrosis despite its ability to cause apoptosis. These results indicate that genistein displayed mild anti-inflammatory properties which may, in part, involve an attenuation of nitric oxide release via inducible nitric oxide synthase, and the formation of peroxynitrite.

    Title Interleukin-10 Attenuates Experimental Fetal Growth Restriction and Demise.
    Date February 1998
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
    Excerpt

    Premature labor, fetal demise, and fetal growth restriction are accompanied by indices of inflammation or infection of the uteroplacental unit. To understand whether these events are causally related, we established an animal model of fetal demise and growth restriction and evaluated the potential utility of the anti-inflammatory cytokine interleukin-10 (IL-10). We administered low-dose endotoxin (lipopolysaccharide, or LPS, 100 microg/kg, i.p.) to third trimester rats (gestational days 14-20). Control rats received normal saline. A third group received IL-10 (100 microg/kg; s.c.) concomitantly with LPS for 7 prenatal days. Cytokine gene expression (IL-10 and TNF-alpha) was evaluated by RT-PCR and tissue levels (TNF-alpha) were determined by ELISA. Apoptosis was evaluated by TdT-mediated dUTP nick end labeling immunohistochemistry, and nitric oxide (NO) levels were quantified by microelectrode electrochemical detection in explants in culture media. LPS exposure resulted in 43% fetal demise and reduced the size of the surviving fetuses. Placental weight was not altered by LPS. IL-10 attenuated the LPS-induced fetal death rate (to 22%) and growth restriction (P<0.05). In normal rats, IL-10 did not affect fetus size or the incidence of resorptions, although placental size was marginally smaller. Increased uterine TNF-alpha content and NO release and apoptosis of uterine epithelia and muscularis were hallmarks of the LPS model. All were normalized by IL-10. IL-10 may represent a new therapeutic option for the treatment of a variety of perinatal complications. Benefit may result from the suppression of TNF-alpha- and NO-mediated cell death.

    Title Prospective Study of Human Herpesvirus 6, Human Herpesvirus 7, and Cytomegalovirus Infections in Human Immunodeficiency Virus-positive Patients.
    Date November 1997
    Journal Journal of Clinical Microbiology
    Excerpt

    Blood samples from human immunodeficiency virus (HIV)-positive patients were monitored for cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 by PCR. We detected CMV in 17% of the patients, HHV-6 in 6%, and HHV-7 in 3%. The viral loads of CMV were significantly higher than those of HHV-6 (P = 0.007) or HHV-7 (P = 0.01). Detection of CMV and HHV-6 was associated with low and high CD4 counts, respectively.

    Title Peroxynitrite-induced Apoptosis in Human Intestinal Epithelial Cells is Attenuated by Mesalamine.
    Date November 1997
    Journal Gastroenterology
    Excerpt

    Peroxynitrite (PN), a potent oxidant, has been implicated in the pathogenesis of gut inflammation and epithelial cell apoptosis. The aim of this study was to investigate mesalamine, a standard therapy for inflammatory bowel disease, to see if it attenuates PN-induced cytotoxicity in human intestinal epithelial cells and if mesalamine directly interacts with PN or its precursor, nitric oxide.

    Title Current Clinical Options for Diagnosis and Treatment of Recurrent Spontaneous Abortion. Clinical Guidelines Recommendation Committee for Diagnosis and Treatment of Recurrent Spontaneous Abortion.
    Date October 1997
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Title Anti-inflammatory Properties of Interleukin-10 Administration in Hapten-induced Colitis.
    Date June 1997
    Journal European Journal of Pharmacology
    Excerpt

    Therapeutic efficacy of interleukin-10 administration in colonic inflammation was assessed in rats. Following intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS), subcutaneous administration of 1-1000 micrograms/kg per day interleukin-10, or a placebo (0.9% NaCl) was commenced and continued for 5 days. Interleukin-10 administered at 1, 10 and 100 micrograms/kg per day significantly reduced myeloperoxidase activity by 34, 57, and 28%, respectively, compared to the placebo-treated group, which was paralleled by an attenuation of colonic tumor necrosis factor alpha (TNF-alpha) content. In contrast, the severity of mucosal necrosis was not affected by interleukin-10 administration at the dose range used. In addition, the 10-fold elevation in nitric oxide release, 5-fold rise in colonic nitrite production and enhanced expression of inducible nitric oxide synthase, associated with TNBS colitis, was not suppressed by interleukin-10. Interleukin-10 gene expression was elevated during the first 14 days of TNBS colitis. We conclude that 5 days administration of interleukin-10 in TNBS colitis displays mild anti-inflammatory properties which were not mediated via a nitric oxide-dependent pathway, but may involve TNF-alpha.

    Title Peroxynitrite-induced Apoptosis in T84 and Raw 264.7 Cells: Attenuation by L-ascorbic Acid.
    Date June 1997
    Journal Free Radical Biology & Medicine
    Excerpt

    The free radicals nitric oxide and superoxide react to form peroxynitrite (ONOO-), a potent cytotoxic oxidant. This study was designed to evaluate whether addition of L-Ascorbic acid (AsC) into the culture medium decreases peroxynitrite-induced apoptosis in human intestinal epithelial (T84) and murine macrophage (RAW 264.7) cell lines. In Experiment 1, T84 and RAW 264.7 cells were divided in two protocols: (1) treated with 100-300 microM ONOO- and incubated for 4 h, and (2) treated with 10-100 microM ONOO- and incubated overnight (14 h). In Experiment 2, T84 and RAW 264.7 cells were treated with 300 microM ONOO- and 500 microM AsC and incubated for 4 h. In Experiment 3, T84 and RAW 264.7 cells were preincubated for 2 h with 500 microM AsC then exposed to 300 microM ONOO- for 4 h. Cell viability (necrosis) was assessed by trypan blue dye exclusion. Apoptosis was quantified with a cell death detection ELISA assay. In the 4 h protocol, ONOO- induced apoptosis in T84 and RAW 264.7 cells, at levels of 100-300 microM. Concentrations of ONOO- greater than 300 microM caused necrosis. In contrast, extension of the protocol to 14 h indicated that ONOO- induced apoptosis at lower concentrations (50;-75 microM), with concentrations > 75 microM resulting in necrosis. AsC administered to the media or with preincubation plus washout, decreased peroxynitrite-induced apoptosis in T84 and RAW 264.7 cells. These results indicate that ONOO- may contribute to the pathophysiology of gut inflammation by promoting cell death and ascorbic acid may protect against peroxynitrie-induced damage.

    Title An Information Processing Model of Anxiety: Automatic and Strategic Processes.
    Date April 1997
    Journal Behaviour Research and Therapy
    Excerpt

    A three-stage schema-based information processing model of anxiety is described that involves: (a) the initial registration of a threat stimulus; (b) the activation of a primal threat mode; and (c) the secondary activation of more elaborative and reflective modes of thinking. The defining elements of automatic and strategic processing are discussed with the cognitive bias in anxiety reconceptualized in terms of a mixture of automatic and strategic processing characteristics depending on which stage of the information processing model is under consideration. The goal in the treatment of anxiety is to deactivate the more automatic primal threat mode and to strengthen more constructive reflective modes of thinking. Arguments are presented for the inclusion of verbal mediation as a necessary but not sufficient component in the cognitive and behavioral treatment of anxiety.

    Title Immunotherapy for Recurrent Pregnancy Loss: Analysis of Results from Clinical Trials.
    Date March 1997
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RSA) are thought to have an immunologic mechanism. Yet clinical trials using immunotherapy to treat women experiencing RSA have low treatment effects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyte immunization and intravenous (IV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on frequency of karyotype abnormalities in trophoblast of failing pregnancies. RESULTS: Results of two independent analyses using allogeneic leukocyte immunization as immunotherapy for all women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysis was limited to primary aborters, the live birth ratio increased to 1.46 (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88 (P = 0.04). Because of low treatment effects, confounders to treatment success of maternal age and number of previous abortions were studied. Chromosomal abnormalities have been identified in 55% of concepti from RSA. The frequency of chromosomal abnormalities remained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypically abnormal concepti (chi 2 = 4.54, P < 0.05). Risk factors for RSA also include number of previous losses. CONCLUSION: Chromosomal abnormalities are a significant confounder when evaluating efficacy of immunotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.

    Title Fetal Growth Retardation in Rats May Result from Apoptosis: Role of Peroxynitrite.
    Date March 1997
    Journal Free Radical Biology & Medicine
    Excerpt

    Administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) results in fetal growth retardation. This study was designed to further examine the influence of NO on fetal growth, specifically, the potential role of inducible NOS and to evaluate the possibility that apoptosis contributed to uteroplacental dysfunction. L-NAME administration caused a paradoxical increase in NO synthesis determined by direct detection of NO by electrochemistry, nitrite accumulation, and cGMP levels, indicating that a lack of NO was not the cause of the fetal growth retardation. Additionally, supplemental L-arginine or NO donors failed to reverse the effects of L-NAME on fetal and placental size. Administration of low dose endotoxin (30 micrograms/kg IP daily for 6 d) also caused significant reductions in fetal and placental size and increased NO synthesis comparable to that seen with L-NAME. Inducible NOS was constitutively expressed in the pregnant uterus (smooth muscle and epithelia) and placenta (sinusoids and macrophages) but was absent in the nonpregnant state as determined by RT-PCR and immunohistochemistry. Neither L-NAME nor endotoxin modified the expression of iNOS. In situ evidence for apoptosis (DNA fragmentation) was minimal to absent in control pregnant rats, but markedly evident in the placenta (decidua) and uterus of rats treated with L-NAME or endotoxin. Immunohistochemical evidence for nitrotyrosine, a marker for peroxynitrite formation, was absent in control rats but colocalized with apoptosis in the L-NAME and LPS groups. We conclude that L-NAME-induced fetal growth retardation is not due to a lack of NO, but as for endotoxin, results from a net reduction in cellular proliferation due to the induction of apoptosis, possibly in response to peroxynitrite formation.

    Title Failure of L-name to Cause Inhibition of Nitric Oxide Synthesis: Role of Inducible Nitric Oxide Synthase.
    Date December 1996
    Journal Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
    Excerpt

    We addressed the hypothesis that administration of nitric oxide synthase inhibitor, NG -nitro-L-arginine methyl ester (L-NAME) does not result in a sustained suppression of nitric oxide (NO) synthesis, because of a compensatory expression of inducible nitric oxide synthase (iNOS). L-NAME was administered in the drinking water (0.1-1.0 mg/ml) for 7 days to guinea pigs and rats. Nitric oxide synthesis was assessed by [1] ex vivo formation of nitrite in blood vessels and intestine [2] tissue levels of cGMP [3] iNOS gene expression by RT-PCR [4] NADPH diaphorase staining [5] direct assessment of NO release in tissue explants using a microelectrode/electrochemical detection system. Chronic L-NAME administration elevated intestinal cGMP and nitrite levels in guinea pigs (p < 0.05). In rats, intestinal nitrite levels were comparable in control and L-NAME treatment groups, whereas direct assessment of NO release defined a marked increase in the L-NAME group. Chronic L-NAME resulted in an induction of iNOS gene expression in rats and guinea pigs and novel sites of NADPH diaphorase staining in the intestine. We conclude that iNOS expression is responsible for a compensatory increase or normalization of NO synthesis during sustained administration of L-NAME.

    Title Hypoglycemic Activity of a Series of Alpha-alkylthio and Alpha-alkoxy Carboxylic Acids Related to Ciglitazone.
    Date November 1996
    Journal Journal of Medicinal Chemistry
    Excerpt

    The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an alpha-alkoxy or alpha-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.

    Title Endometrial Lymphomyeloid Cells in Abnormal Uterine Bleeding Due to Levonorgestrel (norplant).
    Date November 1996
    Journal Human Reproduction (oxford, England)
    Excerpt

    Endometrial lymphomyeloid cell subsets were evaluated in samples from normal women and from women with abnormal uterine bleeding due to subcutaneous levonorgestrel implants (Norplant) or an intrauterine device (IUD). The frequency of CD3(+), CD68(+), CD43(+) and endometrial granulated lymphoid cells was evaluated by immunohistochemical or phloxine-tartrazine staining of formalin-fixed paraffin-embedded samples. In normal women, cyclic variation in lymphomyeloid subsets was seen. In women using Norplant for contraception, the frequency of CD3(+), CD68(+) and CD43(+) cells was dramatically decreased, compatible with endometrial atrophy. When Norplant users with abnormal bleeding were compared to women without bleeding, however, the number of CD68(+) cells was significantly increased and the number of CD3(+) and CD43(+) cells was preserved, contrary to the hypothesis that this group would show a greater degree of atrophy and hence, tissue fragility. A similar pattern was seen in a preliminary study of women with bleeding associated with use of copper-only IUD contraception, and in samples taken from late secretory and menstrual biopsies from normal cycling women. Whether these changes in endometrial lymphomyeloid cells represent a result of bleeding arising from a common mechanism or rather cause the uterine bleeding is discussed.

    Title Inductive Logic Programming Used to Discover Topological Constraints in Protein Structures.
    Date December 1995
    Journal Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; Ismb. International Conference on Intelligent Systems for Molecular Biology
    Excerpt

    This paper describes the application of the Inductive Logic Programming (ILP) program GOLEM to the discovery of constraints in the packing of beta-sheets in alpha/beta proteins. These constraints (rules) have a role in understanding the protein folding problem. Constraints were learnt for four features of beta-sheet packing: the winding direction of two sequential strands, whether two consecutive strands pack parallel or anti-parallel, whether two strands pack adjacently, and whether a beta-strand is at an edge. Investigation of the learnt constraints revealed interesting patterns, some of which were previously known, others that were novel. Novel features include the discovery: that the relationship between pairs of sequential strands is in general one of decreasing size, and that more sequential pairs of strands wind in the direction out than the direction in. We conclude that machine learning has a useful place in molecular biology as a pattern discovery tool.

    Title Common and Specific Dimensions of Self-reported Anxiety and Depression: a Replication.
    Date October 1995
    Journal Journal of Abnormal Psychology
    Excerpt

    To investigate the generalizability of D. A. Clark, R. A. Steer, and A. T. Beck's (1994) findings about the common and specific dimensions of self-reported anxiety and depression, the authors administered the Beck Depression and Anxiety Inventories to 1,000 outpatients diagnosed with various types of psychiatric disorders. Iterated principal-factor analyses with oblique rotation, followed by a Schmid-Leiman transformation, indicated that the amounts of extracted variance and symptom compositions of the resultant factors were comparable to those found in the previous study. The results from both studies are discussed as supporting the tripartite (L. A. Clark & D. Watson, 1991) and cognitive-specificity (A. T. Beck, 1976, 1987) models of anxiety and depression.

    Title Amphotericin B Toxicity Reduced by Administration in Fat Emulsion.
    Date September 1995
    Journal The Annals of Pharmacotherapy
    Excerpt

    OBJECTIVE: To report a patient with intolerance to amphotericin B reversed by preparing the antifungal in fat emulsion 20% and to review the medical literature on innovative formulations of amphotericin B. CASE SUMMARY: A 51-year-old man diagnosed with acute myelogenous leukemia was treated with standard induction chemotherapy. Empiric antibiotic therapy was initiated 2 days postchemotherapy; however, the patient continued to be febrile until day 7. At this time amphotericin B 35 mg/250 mL D5W over 4 hours was administered. Despite premedication, the patient experienced severe rigors, chills, and fever. As the result of continuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusion-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsion 20% was administered over 2 hours after patient consent was obtained. Premedication was administered and the patient tolerated therapy without adverse events. Amphotericin B dosage escalations to 50 and 70 mg were tolerated similarly. During this treatment the patient became afebrile and the serum creatinine concentration decreased to normal. DISCUSSION: Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the empiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents characteristically prescribed in these patients. Furthermore, infusion-related events, if not intolerable, can dramatically reduce the patient's quality of life. For these reasons, novel means of amphotericin B administration are being explored. CONCLUSIONS: The delivery of amphotericin B in a lipid diluent may have substantial benefit in reducing the nephrotoxicity and infusion-related events associated with the antifungal. Prospective clinical trial comparing lipid-complexed amphotericin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.

    Title Accumulation of Chromotrope 2r Positive Cells in Equine Endometrium During Early Pregnancy and Expression of Transforming Growth Factor-beta 2 (tgf-beta 2).
    Date August 1995
    Journal Journal of Reproduction and Fertility
    Excerpt

    Endometrial tissue from the gravid uterine horn of pregnant mares was examined by northern analysis and in situ hybridization for mRNA that hybridized to cDNA and RNA probes generated from a mouse TGF-beta 2 1.2 kb cDNA clone. The mouse cDNA probe hybridized to characteristic TGF-beta 2 mRNA transcripts on a northern blot of total RNA isolated from horse endometrium collected at day 45 of gestation. Two major 4.0 and 3.5 kb transcripts and possibly a minor 1.6 kb transcript were observed, consistent with specific hybridization to equine TGF-beta 2 mRNA. By in situ hybridization, riboprobes transcribed from the same fragment used in northern analysis hybridized to clusters of cells scattered between endometrial glands at days 38, 40, 42, 43, 78 and 81 of gestation. Positive cells were absent before day 38. From day 38 to day 43 there was marked hybridization over maternal leucocytes in the region of the developing endometrial cups, and at later stages (day 78 and day 81) clusters of cells positive for mRNA encoding TGF-beta 2 were localized within the dense band of leucocytes at the periphery of the degenerating endometrial cups. There was no hybridization to invasive or non-invasive trophoblast or to fully differentiated endometrial cup cells. Approximately 90% of the TGF-beta 2 positive cells detected in the sections taken at day 78 also stained with chromotrope 2R used to detect eosinophils and the morphology of approximately 50% of these cells was characteristic of eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Psychometric Characteristics of Revised Sociotropy and Autonomy Scales in College Students.
    Date May 1995
    Journal Behaviour Research and Therapy
    Excerpt

    Beck, Epstein, Harrison and Emery (unpublished manuscript, 1983) developed the Sociotropy-Autonomy Scale (SAS) to assess personality constructs that were considered possible vulnerability factors to reactive depression. Principal components and factor analyses of an expanded 93-item version of the SAS were performed with successive samples of undergraduates totalling 2041 Ss. Only 59 items were needed to establish the generalizabilities of one dimension of Sociotropy and two dimensions of Autonomy. Three subscales reflecting Sociotropy, Solitude and Independence were constructed from these items. The convergent and discriminant validities of the three subscales were assessed with respect to a variety of other psychological tests. The overall pattern of relationships indicated that Solitude was positively correlated with dysphoria, perfectionism, self-criticalness, and loneliness. In contrast, Independence was positively correlated with perfectionism and self-efficacy, but inversely related to concern about approval from others. Sociotropy was correlated with dependency, self criticalness, and affiliation motivation. The findings supported the construct validity of the three revised SAS subscales.

    Title On the Use of Machine Learning to Identify Topological Rules in the Packing of Beta-strands.
    Date May 1995
    Journal Protein Engineering
    Excerpt

    The machine learning program GOLEM was applied to discover topological rules in the packing of beta-sheets in alpha/beta-domain proteins. Rules (constraints) were determined for four features of beta-sheet packing: (i) whether a beta-strand is at an edge; (ii) whether two consecutive beta-strands pack parallel or anti-parallel; (iii) whether two beta-strands pack adjacently; and (iv) the winding direction of two consecutive beta-strands. Rules were found with high predictive accuracy and coverage. The errors were generally associated with complications in domain folds, especially in one doubly would domains. Investigation of the rules revealed interesting patterns, some of which were known previously, others that are novel. Novel features include (i) the relationship between pairs of sequential strands is in general one of decreasing size; (ii) more sequential pairs of strands wind in the direction out than in; and (iii) it takes a larger alteration in hydrophobicity to change a strand from winding in the direction out than in. These patterns in the data may be the result of folding pathways in the domains. The rules found are of predictive value and could be used in the combinatorial prediction of protein structure, or as a general test of model structures, e.g. those produced by threading. We conclude that machine learning has a useful role in the analysis of protein structures.

    Title Potential Role of Nitric Oxide in a Model of Chronic Colitis in Rhesus Macaques.
    Date April 1995
    Journal Gastroenterology
    Excerpt

    BACKGROUND/AIMS: Excess nitric oxide formation, via the inducible NO synthase isoform, has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease. The aim of this study was to assess the site, enzyme source, and magnitude of NO production in juvenile rhesus macaques with idiopathic colitis. METHODS: NO production was assessed systemically from plasma and urine levels of reactive nitrogen intermediates and locally by the formation of [3H]citrulline from [3H]arginine and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. Inducible NO synthase gene expression was assessed by reverse-transcription polymerase chain reaction. RESULTS: Plasma and urine levels of reactive nitrogen intermediates were greater in colitic animals than in control monkeys by 13- and 5-fold, respectively. NADPH diaphorase activity in normal animals was confined to the myenteric plexus. In colitis, staining was also apparent in crypt abscesses and superficial epithelial and mucosal bands. Gene expression for inducible NO synthase was only found in colitic specimens. Colonic [3H]citrulline formation was markedly elevated in colitic specimens, and the inducible isoform accounted for 58% of total activity. CONCLUSIONS: It is proposed that excess NO, formed via the inducible form of NO synthase, contributes to the mucosal inflammation and symptoms of this idiopathic colitis model.

    Title Common and Specific Dimensions of Self-reported Anxiety and Depression: Implications for the Cognitive and Tripartite Models.
    Date February 1995
    Journal Journal of Abnormal Psychology
    Excerpt

    The common and specific symptom dimensions of anxiety and depression proposed by the tripartite (L.A. Clark & D. Watson, 1991 c) and cognitive (A.T. Beck, 1976, 1987) models were investigated in 844 psychiatric outpatients and 420 undergraduates. Principal-factor analyses with oblique rotations performed on the 42 items of the Beck Depression Inventory and Beck Anxiety Inventory for both samples revealed that there were 2 correlated factors. Depression and Anxiety. Second-order factor analyses of the interfactor correlation matrices indicated a large general distress or negative affect factor underlying the relationship between the 2 first-order factors. Specific depression and anxiety dimensions were apparent even after we controlled for negative affect. The results were consistent with both the tripartite and cognitive models, with the cognitive and motivational symptoms specific to depression and the physiological arousal symptoms unique to anxiety.

    Title Nitric Oxide Inhibition Causes Intrauterine Growth Retardation and Hind-limb Disruptions in Rats.
    Date December 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our purpose was to determine the effects of nitric oxide synthase inhibition on maternal and fetal health in the last third of pregnancy. STUDY DESIGN: Pregnant rats were treated from gestational day 13 to day 19 or 20 with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, which was administered in the drinking water ad libitum. Control animals received the inactive enantiomer NG-nitro-D-arginine methyl ester or no treatment. Maternal blood pressure, blood chemistry studies, and placenta and pup size were determined. A separate group of rats received nitroprusside sodium in conjunction with NG-nitro-L-arginine methyl ester. RESULTS: NG-nitro-L-arginine methyl ester caused a dose-dependent reduction in placenta and pup size. Amniotic fluid levels of cyclic guanosine monophosphate were significantly reduced at 0.1 mg/ml but not at higher doses. Hemorrhagic necrosis of fetal hind limbs occurred only with treatment with NG-nitro-L-arginine methyl ester and was prevented by coadministration of nitroprusside sodium. Maternal blood pressure and blood and urine chemistry studies were unaffected by NG-nitro-L-arginine methyl ester. CONCLUSION: Chronic reductions of nitric oxide production in the last third of pregnancy result in significant intrauterine growth retardation and hemorrhagic disruptions of hind limbs. Maternal complications were minimal and did not mimic preeclampsia.

    Title Differentiating Major Depression and Panic Disorders by Self-report and Clinical Rating Scales: Roc Analysis and Information Theory.
    Date December 1994
    Journal Behaviour Research and Therapy
    Excerpt

    The revised Beck Depression Inventory, Beck Anxiety Inventory, the Cognition Checklist Depression and Anxiety subscales, revised Hamilton Psychiatric Rating Scale for Depression (HRSD-R), and the revised Hamilton Anxiety Rating Scale were administered to 92 outpatients diagnosed only with major depression disorders and 50 outpatients diagnosed only with panic disorders. A receiver operating characteristic (ROC) analysis was used to evaluate each instrument's ability to discriminate the two diagnostic groups. The optimum cut-off score for each scale was determined as a function of prevalence by maximizing information gain. The results indicated that the depression scales were better than the anxiety scales in discriminating the two groups. The HRSD-R was superior to the other depression scales, whereas all the anxiety scales displayed similar discriminating power.

    Title Symptom Dimensions of the Scl-90-r: a Test of the Tripartite Model of Anxiety and Depression.
    Date August 1994
    Journal Journal of Personality Assessment
    Excerpt

    To determine the extent to which the SCL-90-R assesses general distress or specific dimensions of psychopathology, two principal components analyses were conducted based on 900 outpatients diagnosed with mixed psychiatric disorders. The first component explained 30.5% of the total variance and was interpreted as reflecting overall symptom distress. Partialling the first component out of the correlations among the symptoms in a second principal components analysis, we found four specific residual components reflecting somatic anxiety, depression, irritability, and attention problems. The results were discussed as partially supporting Clark and Watson's (1991) tripartite model of anxiety and depression.

    Title The West Point Study: 40 Years of Follow-up.
    Date July 1994
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    Completion of cardiovascular evaluations of 387 members marked the end of 40 years of follow-up in the West Point Study. Coronary artery disease (CAD) caused 4 cases of sudden death, 14 cases of myocardial infarction (MI), 13 cases of angina, and 17 cases of silent CAD. Using risk factors (serum cholesterol, estimated HDL-cholesterol, systolic blood pressure, and smoking status) measured before age 28, we derived a multivariate regression formula for predicting which members of the study, had they been pilots, would have been grounded for CAD before age 55. This derivation used data from only those subjects with CAD or with no evidence of CAD. We then used the formula to compute a risk-related score for each member of the study. In the tertile group with the highest risk-related scores, 17% manifested CAD by age 55 and the first event occurred at age 39. In the tertile group of lowest scores, 2% experienced CAD by age 55 and the first event occurred at age 51. We conclude that it is possible to select pilot candidates with the lowest risk for CAD.

    Title Inhibition of Calcium-dependent Nitric Oxide Synthase Causes Ileitis and Leukocytosis in Guinea Pigs.
    Date July 1994
    Journal Digestive Diseases and Sciences
    Excerpt

    As nitric oxide reduces gut epithelial permeability, we designed a study to determine if chronic nitric oxide synthase inhibition predisposes the gut to inflammation. Nitric oxide synthase (NOS) inhibitors were administered in the drinking water ad libitum, for seven days: aminoguanidine (10 micrograms/ml), a selective inhibitor of the inducible form of nitric oxide synthase; and NG-nitro-L-arginine methyl ester (L-NAME, 1, 10, and 100 micrograms/ml), which inhibits both the constitutive and inducible forms. Control animals drank tap water only or water with D-NAME, the inactive enantiomer. After one week, circulating leukocyte count and tissue myeloperoxidase activity were measured. L-NAME (100 micrograms/ml), but not D-NAME or aminoguanidine, caused a twofold increase in a circulating leukocyte numbers. This increase in leukocyte numbers was time- and dose-dependent, but the differential count was unaltered. Tissue myeloperoxidase (MPO) activity as an index of granulocyte infiltration was comparable in all groups in the stomach, jejunum, colon, liver, lung, kidney, heart, and skeletal muscle. However, ileal MPO activity was elevated threefold in the L-NAME-(100 micrograms/ml) treated group (P < 0.05). Results in the D-NAME and aminoguanidine groups were similar to controls. L-NAME administration resulted in a reduction in NOS activity ([14C]citrulline formation) in the ileum but not jejunum, whereas cGMP levels were elevated in both ileum and jejunum. We conclude that chronic inhibition of the constitutive form of nitric oxide synthase predisposes the ileum to inflammation and leads to a progressive leukocytosis.

    Title Balloon Angioplasty Results in Increased Segmental Coronary Distensibility: a Likely Mechanism of Percutaneous Transluminal Coronary Angioplasty.
    Date May 1994
    Journal Journal of the American College of Cardiology
    Excerpt

    OBJECTIVES. The purpose of this study was to evaluate the hypothesis that the increase in lumen area induced by percutaneous transluminal coronary angioplasty is secondary to a change in lesion (segmental) distensibility. BACKGROUND. Despite the widespread use of coronary angioplasty, the precise mechanism (or mechanisms) of lumen area improvement remains poorly understood. METHODS. Quantitative coronary angiography was used to measure the minimal (contrast agent filled) balloon diameters at 1 to 5 atm, inclusive, during the first and final balloon inflations in 24 lesions successfully treated with coronary angioplasty. To rule out possible confounding effects due to changes in balloon material distensibility during repeated inflations, five control balloons were studied ex vivo. In parallel, intravascular ultrasound imaging was utilized to compare the segmental distensibility (change in lumen area during the cardiac cycle) of eight disease-free and seven mildly diseased coronary segments and seven segments after successful balloon angioplasty. RESULTS. Minimal balloon diameters increased significantly between the first and final inflations (46%, 33%, 26%, 14% and 10% at 1, 2, 3, 4 and 5 atm, respectively, all p < 0.0001), demonstrating an increase in arterial distensibility after successful coronary angioplasty. No significant changes in balloon diameters were observed during sequential initial inflations at 1 and 2 atm (n = 5). Minimal increases in balloon diameters were observed during repeated balloon inflations in the ex vivo studies (4.9 +/- 1% [mean +/- SEM]). A distensibility index, derived from the intravascular ultrasound data, was not different between the balloon-dilated and the normal segments but was significantly lower in mildly diseased sites (14.7 +/- 2.2 vs. 12.9 +/- 1.2 vs. 6.9 +/- 1.9, respectively, p < 0.05) despite a smaller plaque area (7.3 +/- 1 vs. 11.3 +/- 1 mm2, proximal/nondilated vs. dilated segments, respectively, p < 0.05). CONCLUSIONS. Coronary distensibility is significantly impaired in atherosclerotically diseased coronary segments and increases significantly after balloon angioplasty. This increase in segmental coronary compliance after coronary angioplasty may create a larger lumen area by allowing the vessel to distend in response to normal intraarterial pressure.

    Title Symptom Differences in Major Depression, Dysthymia, Panic Disorder, and Generalized Anxiety Disorder.
    Date February 1994
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: The authors compared symptom features of specific subtypes of depressive and anxiety disorders. METHODS: Psychiatric outpatients with moderate levels of psychopathology and DSM-III diagnoses of major depression, dysthymia, panic disorder, or generalized anxiety disorder were given five standard measures of symptoms of anxiety and depressive disorders. Most of the outpatients were white, and most were middle-class. RESULTS: Principal components analysis revealed 12 orthogonal symptom components. Discriminant function analysis indicated that anxiety was distinguished by specific autonomic arousal symptoms, threat-related cognitions, and subjective anxiety and tension. Discriminant function analysis also indicated that depression was distinguished by anhedonia, cognitions of personal loss and failure, and dysphoric mood. CONCLUSIONS: As nosological categories, major depression and panic disorder were better differentiated by specific symptom markers than dysthymia and generalized anxiety disorder.

    Title Protease Inhibitors Suppress in Vitro Growth of Human Small Cell Lung Cancer.
    Date February 1994
    Journal Peptides
    Excerpt

    The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell lines was investigated. In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI-H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated by Western blot analysis. NCI-H345 cells, when treated with BBI (100 micrograms/ml), also showed highly significant decreases of mRNA for PC1 and PC2 of about 50%. These data suggest that proteases serve an important role in the growth regulation of SCLC and that inhibitors of these proteases may be potent suppressors of SCLC growth at the level of the gene.

    Title Nitric Oxide: the Jekyll and Hyde of Gut Inflammation.
    Date January 1994
    Journal Agents and Actions
    Excerpt

    We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water (100 micrograms/ml ad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs, L-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs has a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals, L-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an anti-inflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.

    Title Amelioration of Chronic Ileitis by Nitric Oxide Synthase Inhibition.
    Date February 1993
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Guidelines for the Performance of Outpatient Catheterization and Angiographic Procedures.
    Date October 1992
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    Cardiac catheterization and angiography is a safe procedure performed on patients with suspected or potentially serious cardiovascular disorders. Complications of the procedure are related both to heart disease itself and to elements of the procedure. For a variety of social and financial reasons, the performance of cardiac catheterization and coronary angiography on an outpatient basis has increased recently. The purpose of this paper is to state the guidelines of The Society for Cardiac Angiography and Interventions regarding the performance of outpatient catheterization in a hospital setting.

    Title Mycosis Fungoides of the Larynx. Report of Two Cases and Review of the Literature.
    Date September 1992
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    Involvement of the larynx by mycosis fungoides is extremely rare with only three reported clinical cases in the English-language literature. We present two patients with laryngeal mycosis fungoides, one of whom presented with vocal cord paresis (progressing to paralysis) as the initial clinical manifestation of laryngeal involvement. Our clinical findings and the observations from the three previous case reports suggest that laryngeal mycosis fungoides has a predilection for the arytenoids, aryepiglottic folds, and the laryngeal surface of the epiglottis. Laryngeal involvement, like other forms of visceral dissemination, appears to manifest clinically in the terminal stages of the disease. The natural history, clinical features, histopathology, and treatment of mycosis fungoides are reviewed and the etiopathology of the vocal cord paralysis is described.

    Title A Crossover Study of Focused Cognitive Therapy for Panic Disorder.
    Date June 1992
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: This study sought to determine the short- and long-term effects of focused cognitive therapy for panic disorder. METHOD: Thirty-three psychiatric outpatients with the DSM-III diagnosis of panic disorder were randomly assigned to either 12 weeks of individual, focused cognitive therapy or 8 weeks of brief supportive psychotherapy based on principles of client-centered therapy. The patients who received supportive psychotherapy were subsequently given the opportunity to cross over to cognitive therapy for 12 weeks. Patients were rated for panic and depression before therapy, after 4 and 8 weeks of therapy, and at 6-month and 1-year follow-up. RESULTS: Clinician ratings and self-ratings of panic frequency and intensity indicated that the focused cognitive therapy group achieved significantly greater reductions in panic symptoms and general anxiety after 8 weeks of treatment than did the group that received brief supportive psychotherapy. At 8 weeks, 71% of the cognitive therapy group were panic free, compared to 25% of the psychotherapy group. Moreover, 94% of the psychotherapy patients elected to cross over to 12 weeks of cognitive therapy. At 1-year follow-up, 87% of the group that received cognitive therapy only and 79% of the group that crossed over into cognitive therapy remained free of panic attacks. CONCLUSIONS: Focused cognitive therapy offers a promising nonpharmacological alternative for the treatment of panic disorder.

    Title Novel Thiazolidine-2,4-diones As Potent Euglycemic Agents.
    Date June 1992
    Journal Journal of Medicinal Chemistry
    Excerpt

    A new series of thiazolidine-2,4-diones was obtained by replacing the ether function of englitazone with various functional groups, i.e., a ketone, alcohol, or olefin moiety. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Appending an oxazole-based group at the terminus of the chain provided highly potent compounds.

    Title Fine Needle Aspiration Diagnosis of Lymphomatoid Granulomatosis. A Case Report.
    Date April 1992
    Journal Acta Cytologica
    Excerpt

    The diagnosis of lymphomatoid granulomatosis (LG) of the lung depends on obtaining adequate histologic material to demonstrate the characteristic angioinvasive, polymorphous, lymphoid infiltrate and normally requires an open lung biopsy. Fine needle aspiration biopsy (FNAB), if only smeared directly, does not allow an assessment of the lymphoid infiltrate in relation to blood vessels. However, we report a case diagnosed by FNAB in which the specimen was processed by an alternative method that allows cell blocks to be made from all visible particles. Percutaneous FNAB of a nodular pulmonary infiltrate was performed after bronchoscopy and transbronchial needle biopsy failed to yield a diagnosis. The FNAB specimen was placed in 50% alcohol and submitted for processing. The specimen was then filtered through a fine sieve, and all visible tissue was embedded in bacteriologic agar and processed as a standard surgical specimen. The filtrate was processed as standard fluid cytology. The atypical, angioinvasive, lymphoid infiltrate was clearly demonstrated on the cell blocks, and the diagnosis of LG was made. This diagnosis was confirmed by subsequent open lung and skin biopsies.

    Title Cardiac Catheterization 1990: a Report of the Registry of the Society for Cardiac Angiography and Interventions (sca&i).
    Date January 1992
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    This report presents the first year's experience of a totally computerized cardiac catheterization laboratory reporting system, including the results and complications of invasive and interventional procedures. Sixty-three laboratories reported a total of 71,916 patients studied between January 1 through December 31, 1990. Two previous registry reports have been published. Compared with data acquired by previous methods, in spite of an older and sicker population, the mortality for diagnostic procedures has remained remarkably constant (0.11%). The computerized format facilitates data collection and analysis, helps resolve new issues as they arise and serves as a method of monitoring quality of laboratories and individuals.

    Title Mesenteric Vein Thrombosis Associated with a Familial Deficiency of Free Protein S.
    Date June 1991
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    Signs and symptoms of an acute intra-abdominal emergency developed in a 26-year-old man; this emergency prompted surgical exploration. It was discovered that he had a devitalized small bowel as a result of mesenteric vein thrombosis. An extensive evaluation for hypercoagulable states disclosed that he had a normal total protein S concentration, but by assay and on crossed immunoelectrophoresis studies, he had a decreased concentration of free protein S. A family study demonstrated protein S deficiency in his father and in a sister. On a subsequent determination, the propositus had a decreased concentration of total protein S. This case illustrates the association of protein S deficiency with mesenteric thrombosis and serves to caution that a single determination of total protein S is not an adequate evaluation when the index of suspicion for a hypercoagulable state is high.

    Title Benzyloxazolidine-2,4-diones As Potent Hypoglycemic Agents.
    Date June 1991
    Journal Journal of Medicinal Chemistry
    Excerpt

    A series of benzyloxazolidine-2,4-diones, containing oxazole-based side chains, were found to lower blood glucose levels in the genetically obese ob/ob mouse. Incorporation of a benzofuran structural element in these compounds provides greatly enhanced in vivo potency. The syntheses and structure-activity relationships for this series are detailed.

    Title Substituted Dihydrobenzopyran and Dihydrobenzofuran Thiazolidine-2,4-diones As Hypoglycemic Agents.
    Date March 1991
    Journal Journal of Medicinal Chemistry
    Excerpt

    A series of dihydrobenzofuran and dihydrobenzopyran thiazolidine-2,4-diones (compounds 3-26) was synthesized from the corresponding aryl aldehydes 1 in two steps. These compounds represent conformationally restricted analogues of the novel hypoglycemic ciglitazone. The series was evaluated by hypoglycemic effects in vitro by measuring stimulation of 2-deoxyglucose uptake in L6 myocytes and stimulation of expression of the glucose transporter protein in 3T3-L1 adipocytes. In vivo hypoglycemic effects were evaluated in the genetically obese ob/ob mouse, and structure-activity relationships are discussed. On the basis of this in vivo potency, we have selected the 2(R)-benzylbenzopyran derivative to be further studied in a clinical setting.

    Title Actions of Novel Antidiabetic Agent Englitazone in Hyperglycemic Hyperinsulinemic Ob/ob Mice.
    Date November 1990
    Journal Diabetes
    Excerpt

    The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM.

    Title Cognitive Specificity and Positive-negative Affectivity: Complementary or Contradictory Views on Anxiety and Depression?
    Date July 1990
    Journal Journal of Abnormal Psychology
    Excerpt

    A principal factor analysis, conducted on a mixed psychiatric outpatient sample (N = 470), identified both common and specific dimensions underlying anxiety and depression. Although an initial single-factor extraction accounted for a significant proportion of variance in cognitive and symptom measures of anxiety and depression, a two-factor solution, in which anxiety and depression formed separate dimensions, proved to be the better solution. MANOVAS performed on pure depressed, pure anxious, and mixed anxious/depressed subgroups provided evidence of a specific cognitive profile for anxiety and depression. The mixed subsample evidenced greater severity, a mixed cognitive and symptom profile, and character traits that may indicate increased vulnerability to psychological disturbance. Results are discussed in terms of Beck's (1976) cognitive content-specificity hypothesis and the positive-negative affect model (Watson & Tellegen, 1985).

    Title Trophoblast Induction of Suppressor-type Cell Activity in Human Endometrial Tissue.
    Date September 1989
    Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
    Excerpt

    First trimester (10-12 weeks gestation) human decidua contains small lymphocytic suppressor cells that release 22 and 43 kd soluble suppressor factors blocking the action of interleukin 2. Luteal phase endometrium, in contrast, contains large suppressor cells that do not release soluble immunosuppressive factors. However, if luteal phase endometrium from days 24 to 25 of the menstrual cycle is incubated with placental syncytiotrophoblast membrane vesicles, suppressor factors having the same molecular weight as those found in end of first-trimester pregnancy decidua are released into the supernatant. This generation of soluble suppressor activity is dependent on cells similar in size to the small lymphocytic suppressor cell population. When uterine decidua is obtained from women with tubal ectopic pregnancy (early in the first trimester), the decidual tissue releases soluble immunosuppressive factors with a 100-135 kd molecular mass and the suppressor cells are large rather than small in size. Supernatant conditioned by trophoblast dissected from ectopic implants was able to interact with large cells in luteal phase endometrium to generate additional soluble suppressor activity. A model is proposed wherein fetal trophoblast activates two suppressor cell populations (large and small) in endometrium via soluble long-range inducer and by direct contact with trophoblast membrane. The potential role of trophoblast-dependent suppressor cells in preventing rejection of the conceptus leading to occult or clinical abortion is discussed.

    Title Cognitive Mediation in General Psychiatric Outpatients: a Test of the Content-specificity Hypothesis.
    Date August 1989
    Journal Journal of Personality and Social Psychology
    Excerpt

    We investigated the degree of content specificity evident in the negative cognitions associated with anxiety and depression in two large samples of general psychiatric outpatients. Standardized measures of affect and cognition were analyzed in a multiple regression design. As predicted by Beck's (1967, 1976, 1987) cognitive theory of psychopathology, thoughts of loss and failure were specifically associated with depression, whereas cognitions of harm and danger were uniquely predictive of anxiety. In addition, hopelessness was specific to depression and not to anxiety. Dysfunctional beliefs showed no consistent association with either mood state. The implication of these results, as well as related findings, is discussed in terms of a cognitive perspective on the differentiation of emotional disorders. Also discussed are the methodological difficulties encountered in research on cognitive-affective relationships.

    Title Transluminal Coronary Angioplasty in the Treatment of Silent Ischemia.
    Date April 1989
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    Fifty-four asymptomatic patients with positive thallium exercise tests underwent coronary angiography followed by coronary angioplasty (PTCA), as the primary therapy for silent ischemia. The procedure was technically successful in 89% of these patients. Emergency bypass graft surgery was necessary in 2 (3.6%) and q-wave myocardial infarction occurred in 1 (1.8%) of these. All fifty-four patients have been followed for a mean of 35 months since angioplasty. Of the 48 patients with initially successful PTCA, 12 had either clinical restenosis (9/14 or 19%) or a new lesion (3/48 or 6%) during follow-up, which required a repeat PTCA. At the longest follow-up, 46 (85%) had been successfully treated with on or more PTCA procedures. Two patients (3.6%) had sustained late q-wave myocardial infarction and two additional patients reported angina pectoris. There were no deaths. Angioplasty as a primary therapy for silent ischemia appears efficacious, with success and restenosis rates comparable to those in the symptomatic population. Event-free survival is improved, compared with natural history data for patients with silent ischemia from other studies. Prudent risk/benefit analysis may help to define subgroups most likely to benefit from this intervention.

    Title The West Point Study: Occurrence of Coronary Artery Disease After 34 Years.
    Date January 1989
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    This report reviews the current status of the West Point Study and addresses the prediction of risk of coronary artery disease (CAD) based on cholesterol levels measured at various times during the study. Subjects were grouped into quintiles by their risk index score calculated from the Framingham risk equation. The number of cases of CAD among the subjects in each of the quintiles was tabulated. The cases of CAD in these quintiles increased from the lowest to the highest quintiles and produced a significant correlation between the risk score and the percent of subjects in the quintiles having CAD, even when the data used for calculating the risk scores had been collected up to 26 years earlier. The numbers of CAD cases are small; they are only approximately 50% of the expected numbers computed for U.S. males of comparable ages, despite the increases in serum cholesterol and low density lipoprotein levels recorded during the first 6 years of the study. The authors speculate about possible explanations of these findings.

    Title Sod Prevents Damage and Attenuates Eicosanoid Release in a Rabbit Model of Necrotizing Enterocolitis.
    Date December 1988
    Journal The American Journal of Physiology
    Excerpt

    Necrotizing enterocolitis (NEC) was produced in anesthetized rabbits by transmural injection of intestinal loops with an acidified solution of casein and calcium gluconate, mimicking the luminal milieu of afflicted neonates. Intravenous infusion of superoxide dismutase (SOD) 15 min after NEC induction prevented intestinal damage. In ex vivo perfused intestinal loops, we determined the sites of eicosanoid release and their contribution to the vascular effects of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) in damaged and SOD-salvaged intestine. The vascular effluent was the primary site of stimulated eicosanoid release. The vascular responses to fMLP (vasoconstriction) and PAF (vasodilation) were not altered by SOD, although vascular resistance was higher in the SOD group. SOD treatment attenuated 1) transmural fluid shifts in ex vivo perfused intestinal preparations, an index of vascular permeability, 2) fMLP-induced prostaglandin E2, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) release, and 3) PAF-induced release of 6-keto-PGF1 alpha and LTB4. Stimulated thromboxane B2 release was not altered by SOD. Thus NEC can be established by a luminal insult that causes local generation of free radicals and exaggerated release of prostaglandins and leukotrienes.

    Title Increased Sensitivity to Complement of Megakaryocyte Progenitors in Paroxysmal Nocturnal Haemoglobinuria.
    Date October 1988
    Journal British Journal of Haematology
    Excerpt

    Paroxysmal nocturnal haemoglobinuria (PNH) is a haemolytic disorder characterized by an increased sensitivity of peripheral blood cells including platelets to the lytic action of complement (C'). Previous studies have demonstrated that in PNH bone marrow erythroid colony and burst forming units, as well as granulocytic-monocytic colony forming units, have an increased sensitivity to complement-induced injury as compared with normal erythroid and myeloid progenitors. The purpose of this study was to investigate the effect of complement on PNH and normal marrow megakaryocytic progenitors (CFU-M). Bone marrow non-adherent and T-cell depleted light density mononuclear cells from three patients with PNH and six normal volunteers were exposed to fresh or heat-inactivated AB human serum in the presence of medium or isotonic aqueous sucrose solution for 30 min at 37 degrees C. After being washed the cells were assayed for CFU-M by the plasma clot method in a complement free medium containing 6% medium conditioned by T-lymphocytes stimulated by phytohaemagglutinin. The number of megakaryocytic colonies grown from PNH marrow cells exposed to isotonic sucrose and C' was reduced to one third of those grown from PNH cells exposed to isotonic sucrose and heat-inactivated C', or to medium with and without C'. In contrast, the number of megakaryocytic colonies grown from normal marrow cells exposed to isotonic sucrose and C' was unchanged. These findings indicate that PNH marrow CFU-M express an increased sensitivity to C'-mediated injury similar to that detected on PNH-erythrocytes by the sucrose haemolysis test, and support the hypothesis that the PNH defect is expressed at the level of pluripotent haematopoietic stem cell.

    Title Coronary Angiography and Angioplasty.
    Date August 1988
    Journal Catheterization and Cardiovascular Diagnosis
    Title The Balloon on a Wire Device: a New Ultra-low-profile Coronary Angioplasty System/concept.
    Date June 1988
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    A new ultra-low-profile coronary angioplasty device, a "balloon probe," is presented. This device consists of a balloon on a coronary guidewire and is the lowest profile dilatation system presently available. The balloon material is polyethylene terephthalate, a new polymer with high inflation pressure limits and very low compliance. This report discusses this device and its usage in coronary artery disease.

    Title Chemotherapy Can Prolong Survival in Patients with Advanced Non-small-cell Lung Cancer--report of a Canadian Multicenter Randomized Trial.
    Date May 1988
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

    Title Current Concepts in Unstable Myocardial Ischemia.
    Date May 1988
    Journal American Heart Journal
    Title Prevention of Transfusion-associated Cytomegalovirus (cmv) Infection in Neonates by Screening Blood Donors for Igm to Cmv.
    Date April 1988
    Journal The Journal of Infectious Diseases
    Title Contribution of Oxygen-derived Free Radicals to Experimental Necrotizing Enterocolitis.
    Date April 1988
    Journal The American Journal of Pathology
    Excerpt

    Oxygen-derived free radicals, particularly superoxide anion, are considered important mediators of intestinal injury induced by ischemia/reperfusion based on the protective effects of superoxide dismutase and allopurinol. A role for free radicals was investigated in a model of necrotizing enterocolitis (NEC) which was initiated by a luminal, as opposed to a vascular, insult. Intestinal loops of weanling rabbits received either saline (control loops) or a solution of 10 mg/ml casein and 50 mg/ml calcium gluconate acidified to pH 4 with proprionic acid (treated loops). When the animals were sacrificed 3 hours later, severe damage was noted in the treated loops, which included blunting of villi and edema, with all animals surviving. At 16 hours only 5 of 8 rabbits survived, and 3 had hemorrhagic necrosis. Control loops were normal in each case. Intravenous infusion of superoxide dismutase (4 mg/kg/hr), commencing 15 minutes after NEC induction, totally prevented intestinal injury. On the other hand, pretreatment with allopurinol, an inhibitor of xanthine oxidase, for 2 days (30 and 60 mg/kg by mouth) was not protective against intestinal damage. A cellular infiltration in treated loops was not histologically evident in the majority of animals at 3 hours after treatment, a finding confirmed by the minimal accumulation of 111In-labeled leukocytes in damaged and intact intestinal tissue. These results suggest that superoxide generated locally from sources other than xanthine oxidase play a critical and early role in experimental NEC and that superoxide dismutase may prove to be an effective therapy in this devastating neonatal disease.

    Title Superiority of Alternating Non-cross-resistant Chemotherapy in Extensive Small Cell Lung Cancer. A Multicenter, Randomized Clinical Trial by the National Cancer Institute of Canada.
    Date October 1987
    Journal Annals of Internal Medicine
    Excerpt

    The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

    Title Recurrence After Coronary Angioplasty.
    Date June 1987
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    Recurrence (restenosis) after coronary angioplasty has undermined the initial success of the procedure and has compromised, to some extent, the attractiveness of the technique in the treatment of ischemic heart disease. Assessment of recurrence predictors has been problematic due to lack of coordination of angioplasty recurrence research and includes: incomplete angiographic documentation, variations in definitions of restenosis anatomically and the results of restenosis physiologically (ie, myocardial ischemia), the dirth of morphologic specifications of subsets under investigation and late outcome pathology, limitations in statistical analyses used, and minimal efforts to classify the available data on recurrence. A review of the literature suggests that all findings regarding recurrence after angioplasty can be organized in four categories: clinical, morphologic, technical (or procedural), and pharmacologic. The reported findings with high concordance as risk factors for recurrence after angioplasty include the clinical factors of diabetes mellitus, hyperlipidemia, and angina of short duration or unstable presentation. Morphologic factors which have been corroborated vis-à-vis recurrence include stenoses with diameter reduction of greater than 90% before and greater than 30% after angioplasty, residual trans-stenotic pressure gradients of greater than 20 mmHg after angioplasty, and lesions that are diffuse, long, eccentric, or calcified. Technical factors associated with recurrence include lower balloon/vessel (or graft) ratios and the absence of (uncomplicated) "intimal dissection." The category most deficient in research regarding recurrence after angioplasty is pharmacologic. Since there are statistically documented and reproducible factors predictive of restenosis, to ignore or minimize these findings or resist further evaluation (because of the ease and safety of performing repeat angioplasty) is to deny the opportunity to understand the mechanisms and favorably affect the incidence of recurrence. This review concludes with two major implications of the restenosis research: certain clinical, technical, and pharmacologic factors, if addressed, may predictably decrease the rate of restenosis and certain clinical and morphologic factors may increase the risk of restenosis; these factors may be less readily modified (eg, diabetes, lesion calcification) and thus must be considered in the decision for angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Surfactant Displacement by Meconium Free Fatty Acids: an Alternative Explanation for Atelectasis in Meconium Aspiration Syndrome.
    Date June 1987
    Journal The Journal of Pediatrics
    Excerpt

    Meconium, an ether extract of meconium, and the major free fatty acids of meconium (palmitic, stearic, and oleic acids) were all found to increase the surface tension minimum of dog lung extract in a Wilhelmy balance. Each of these fractions was instilled into the lungs of dogs (15 experimental, eight saline solution controls), and cardiac output, venous and arterial blood gases, pulmonary, atrial, and systemic pressures, airway pressure, and static lung compliance were serially monitored for 2 hours. Mean airway pressure increased and static lung compliance decreased significantly in all of the experimental groups. Although arterial pH and PaCO2 and the various hemodynamic measurements did not change during the experiment, PaO2 decreased significantly and did not return to baseline in all experimental groups. Extracts from atelectatic portions of experimental dog lung had a surface tension minimum of greater than 20 dynes/cm, whereas airway foam had a surface tension minimum of less than 10 dynes/cm, suggesting that the free fatty acids of meconium are able to strip surfactant from the alveoli.

    Title Multiple Vessel Coronary Angioplasty: Classification, Results, and Patterns of Restenosis in 494 Consecutive Patients.
    Date April 1987
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    We report the immediate results and 6 month follow-up data of 494 consecutive patients who underwent coronary angioplasty in two or more major epicardial arteries. Clinical success was achieved in 95% of the 494 patients. The technical success rate of the 1,117 vessels dilated was 89%, defined as at least a 35% reduction (mean = 53%) of the initial percent diameter stenosis and a decrease in the transstenotic gradient to less than or equal to 15 mmHg (mean = 9 mmHg). Complications of the procedure included emergency bypass surgery (2.8%), myocardial infarction (3.0%), and hospital death (0.4%) inclusive. At least one of these complications (major cardiac event) occurred in 3.8% of patients. Prior to angioplasty, 46% of patients were in Canadian Cardiovascular Society Class II, 42% in Class III, and 12% in Class IV. Follow-up clinical evaluation (mean follow-up period of 16.9 months) showed 83% of patients in Class I, 14% in Class II, and 3% in Class III. Of the 286 successful patients who have reached 6 month follow-up plateau (mean follow-up period of 20.5 months), 164 (57%) have so far had repeat coronary angiography and exhibited three different patterns: all lesions patent (N = 54), some lesions restenosed (N = 60), and all lesions restenosed (N = 32). There were 18 patients with new vessel lesions (not previously dilated). Logistic regression analyses demonstrated that clinical factors including diabetes (P less than .05), hypercholesterolemia, (P less than .01), new onset angina (P less than .05), current smoking (P less than .01), and morphologic and technical factors such as preangioplasty diameter stenosis greater than 95% (P less than .05) and higher balloon inflation pressure (P less than .05) were predictive of increased risk of recurrence. Patients were classified into two groups based on the anatomy of the target lesions. In Group A (N = 217), patients had a single lesion in each of the vessels to be dilated; Group B (N = 277) patients had a complex lesion in at least one of the vessels dilated. Group B patients were more likely to develop recurrence (P less than .05). Of the original 494 patients, 488 (99%) are alive. Coronary angioplasty (either initially or with repeat PTCA) has been the definitive treatment in 453 of the 494 patients for an overall success of 92%.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Induction of Megakaryocytic Colony-stimulating Activity in Mouse Skin by Inflammatory Agents and Tumor Promoters.
    Date March 1987
    Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
    Excerpt

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with beta-methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by beta-methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

    Title Psychologic Predictors of Psychosocial and Medical Outcomes in Patients Undergoing Coronary Angioplasty.
    Date March 1987
    Journal Psychosomatic Medicine
    Excerpt

    The relationship between psychologic variables (the match between repressive style and level of cardiac information, and anxiety level) and medical complications, re-stenosis (renarrowing), and psychosocial adjustment was studied in 97 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for treatment of narrowed coronary arteries. Three major findings emerged for outcomes measured 6 months after PTCA: repressors with a high level of cardiac information (coping style-information level mismatch) and no history of heart attack were at higher risk for late medical complications (p less than 0.001); sensitizers with a low level of cardiac information (coping style-information level mismatch) and whose PTCA was only moderately successful were at higher risk for re-stenosis of the artery previously widened during PTCA (p less than 0.01); and patients who were more anxious during hospitalization had poorer social functioning and more mood disturbance 6 months after PTCA (p less than 0.05). Thus, psychologic, information, and medical factors are important in predicting 6-month outcomes in patients undergoing PTCA.

    Title Percutaneous Transluminal Angioplasty of Stenotic Coronary Artery Bypass Grafts: 5 Years' Experience.
    Date February 1987
    Journal Journal of the American College of Cardiology
    Excerpt

    In a 60 month period (January 1981 to December 1985), 82 patients (79% male with a mean age of 60 years) had 83 saphenous vein grafts and 5 internal mammary artery grafts with a total of 101 stenotic sites treated with percutaneous transluminal coronary angioplasty. The mean time between bypass surgery and angioplasty was 51.2 months. The procedure was technically successful in 85% of patients, 86% of grafts and 85% of the sites attempted. In these cases, the mean diameter stenosis was reduced from 77 +/- 14 to 27 +/- 20% (p less than 0.001), the mean pressure gradient from 49 +/- 16 to 7 +/- 6 mm Hg (p less than 0.001). Emergency coronary artery bypass graft surgery was necessary in one patient (1.2%) whereas myocardial infarction occurred in three patients (3.6%). There were no hospital deaths. Clinical follow-up was obtained in all 82 patients. Before angioplasty, 23% were in Canadian Cardiovascular Society functional class II, 60% in class III and 17% in class IV. With a mean clinical follow-up period of 21.4 +/- 2.3 months, 71% are in class I, 17% in class II and 12% in class III. There were two deaths, 3 months or more after angioplasty, one probably due to graft closure. So far, angiographic follow-up (at 7.9 +/- 2.1 months) has been available in 26 patients. Ten patients (with 10 grafts) exhibited graft restenosis; six of them have had second successful repeat angioplasty. Among the many variables analyzed, statistically significant predictors of success were a higher measured balloon/graft ratio (p less than 0.001), smaller diameter graft (p less than 0.001), and shorter lesion length (p less than 0.01). The only predictor of complication was diffuseness of disease in the graft (p less than 0.05). The statistically significant predictors of recurrence were the residual stenosis after the initial angioplasty (p less than 0.01) and the measured balloon/graft ratio (p less than 0.01). Angioplasty of coronary artery grafts appears to be a feasible and efficacious procedure with a low complication rate. The technique is a satisfactory alternative to repeat surgery in selected patients.

    Title Effects of Ethanol on Cultured Human Megakaryocytic Progenitors.
    Date December 1986
    Journal Experimental Hematology
    Excerpt

    Ethanol intoxication may result in the suppression of platelet production in human beings through direct toxicity to the bone marrow. To determine whether this suppression is due in part to a toxic effect on megakaryocytic progenitors, human bone marrow was cultured for 15 days in plasma clots, and megakaryocytic colonies were enumerated. Addition of ethanol to cultures at the beginning of incubation resulted in a reduction in megakaryocytic colonies only when the initial ethanol concentration exceeded 1 g/dl, well above physiologically tolerated levels. However, when cultures were treated with lower concentrations of ethanol (0.5 g/dl) after seven days of incubation, a reduction of megakaryocytic colony formation also occurred. These results suggest that development of a human cell more differentiated than the megakaryocytic progenitor is sensitive to ethanol toxicity at or near concentrations observed in vivo and is in accord with clinical features of the reversible alcohol-induced thrombocytopenic syndrome.

    Title Effects of Recombinant Erythropoietin on Murine Megakaryocytic Colony Formation in Vitro.
    Date December 1986
    Journal The Journal of Laboratory and Clinical Medicine
    Excerpt

    The availability of pure recombinant erythropoietin permits the study of its effects on hematopoietic progenitors free from those of other factors that may copurify with it. Mouse bone marrow cells were cultured in plasma clots in the presence of recombinant human erythropoietin. This factor supported megakaryocytic colony formation in a dose-dependent fashion, with plateau growth at 1 U erythropoietin per milliliter of culture medium. Erythropoietin did not increase the number of granulocyte-macrophage colonies. Plasma clots per se were not essential for megakaryocytic colony formation, because recombinant erythropoietin also supported colony growth in soft agar containing 25% serum. However, little colony formation was observed in serum-free soft agar cultures containing erythropoietin. Colony formation supported by suboptimal concentrations of erythropoietin was additive to that supported by suboptimal amounts of medium conditioned by pokeweed mitogen-stimulated spleen cells or by WEHI-3 cells. Delayed addition of conditioned medium to cultures resulted in a 50% to 100% decline in the number of megakaryocytic colonies by 12 to 48 hours, which was abolished by the inclusion of erythropoietin in the original culture medium. Delayed addition of erythropoietin by 24 hours to cultures resulted in loss of its effect on colony formation. These results indicate that erythropoietin has an effect on murine megakaryocytic colony formation in vitro and show that at least a portion of this effect is exerted during the early stages of colony development.

    Title Coronary Angioplasty at the Time of Initial Cardiac Catheterization: "ad Hoc" Angioplasty Possibilities and Challenges.
    Date November 1986
    Journal Catheterization and Cardiovascular Diagnosis
    Title Balloon Angioplasty of Coronary Bifurcation Lesions: the Kissing Balloon Technique.
    Date July 1986
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    Initial experience with the technique of "kissing balloon" angioplasty is described in 52 patients undergoing coronary angioplasty. Guiding catheters employing both the femoral and brachial approach were used in all but two of the coronary angioplasties and, in addition, the bilateral femoral approach was used in the renal and peripheral angioplasties. Initial success was achieved in 51 (98%) patients. Abrupt closure requiring urgent coronary revascularization occurred in one patient six hours following the completion of the procedure. Another patient developed a new Q-wave on the electrocardiogram and moderate elevation of CPK-MB fraction following the procedure due to loss of a diagonal branch. No deaths occurred in this series. Angiographic restenosis developed in ten patients. In the recurrence group, five had repeat kissing balloon angioplasty, two had repeat single vessel angioplasty, and three patients chose elective surgical revascularization. Based on our experience, the technique of kissing balloon coronary angioplasty can be performed safely utilizing the brachio-femoral technique. The risk of major side branch occlusion can be minimized with this technique and the overall complication rate does not significantly differ from that of our experience in single vessel coronary angioplasty. Patient selection criteria are based upon the angiographic relationship of the major branch to the side branch and is important in determining the initial and long-term success of this technique.

    Title Phosphorus-31 Nuclear Magnetic Resonance Measurements of 2,3-dpg Degradation in Human Adult and Cord Blood Erythrocytes.
    Date May 1986
    Journal Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
    Excerpt

    We have measured the percent change in 2,3-diphosphoglycerate (DPG) concentration in cord blood erythrocytes and adult erythrocytes during incubation at 37 degrees C using 31P nuclear magnetic resonance spectroscopy. DPG concentrations remained unchanged during the first 4.0 +/- 0.9 h (mean + SD) for cord blood erythrocytes and 6.0 +/- 1.0 h for adult blood erythrocytes. After this plateau phase, cord blood and adult erythrocyte DPG concentrations decreased at a rate of 11.6 +/- 0.4 and 11.4 +/- 0.5% of the baseline DPG concentration per hour, respectively. There was no statistically significant difference in the percent rate of DPG degradation when comparing cord blood erythrocytes to adult erythrocytes during either the plateau phase or the decay phase. Starting at the onset of the decay phase, the neonate 3-P DPG resonance shifted downfield at a rate of 0.03 +/- 0.006 ppm per hour; the adult 3-P DPG resonance shifted downfield at a rate of 0.02 +/- 0.003 ppm per hour.

    Title Chemotactic Factor Induced Neutrophil Shape Changes in Whole Blood. A Comparison of Adults and Neonates.
    Date December 1985
    Journal Annals of Clinical and Laboratory Science
    Excerpt

    To define further the nature of the decreased responsiveness of neonatal neutrophils to chemotactic factor stimulation, neutrophil shape change induced by various concentrations of N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) was studied using a whole blood assay. Samples from 48 full term neonates and paired healthy adult controls were examined. The neutrophil response to the chemotactic peptide was assessed by the morphologic transformation from a spherical to a bipolar shape in monolayer blood smears made from fresh whole blood samples. Neonatal neutrophils were found to have increased responsiveness relative to adult controls at low concentrations of fMLP (10(-11) to 10(-9) M), resulting in a significantly lower calculated chemotactic peptide concentration necessary for a 50 percent maximal response (ED50) in neonatal cells (1.01 X 10(-9) M compared to 2.25 X 10(-9) M). The maximal response at higher concentrations of fMLP (5.0 X 10(-9) to 10(-6) M) showed no differences between neonatal and adult cells, thereby supporting the concept that the early cellular events of the chemotactic factor activation in neonatal neutrophils are functionally intact.

    Title Quantitation of Human Megakaryocyte Progenitors (cfu-m) in Plasma Clot Culture by an Indirect Immunoperoxidase Method.
    Date November 1985
    Journal Experimental Hematology
    Excerpt

    We have developed an indirect immunoperoxidase method to detect human megakaryocytic colonies in plasma clot culture. A monoclonal antibody directed against platelet glycoprotein IIb/IIIa complex is incubated with plasma clots fixed to gelatin-coated slides with methanol. This antibody is subsequently linked to horseradish peroxidase by means of an avidin-biotin sandwich technique. Megakaryocytic colonies are identified by precipitation of benzidine by the horseradish peroxidase. This method detects growth of megakaryocytic colonies in culture, which is dependent on factors present in leukocyte-conditioned medium and is linear with respect to the concentration of human light-density nonadherent bone marrow cells plated at a concentration of 1.5-7 X 10(5) cells/ml. This method is simple to apply, uses objective criteria for recognition of megakaryocytes, and leaves cultures mounted and stained for permanent record.

    Title Necrotizing Enterocolitis: Intraluminal Biochemistry in Human Neonates and a Rabbit Model.
    Date November 1985
    Journal Pediatric Research
    Excerpt

    The intestinal contents of 17 neonates with necrotizing enterocolitis were analyzed for pH, carbohydrate, protein, and bacteria. The intraluminal pH was less than 5.0 (16/17). Sufficient carbohydrate and bacteria capable of fermenting the carbohydrate to organic acids were found. The intraluminal protein content was greater than 5 g/dl. The variables of acid and protein were then examined in a rabbit intestinal loop model. The hemorrhagic response in individual loops was measured using Cr51 tagged red blood cells such that the microliters of blood per centimeter intestine could be determined. Loops with organic acid and protein had significantly (p less than 0.01) more intramural blood than control loops. Organic acid (possibly generated by bacterial mixed acid fermentation of carbohydrate) in the presence of protein promotes intramural hemorrhage similar to that seen in neonates with necrotizing enterocolitis.

    Title Continuous Gastric Ph Measurement in Young and Older Healthy Preterm Infants Receiving Formula and Clear Liquid Feedings.
    Date September 1985
    Journal Journal of Pediatric Gastroenterology and Nutrition
    Excerpt

    Gastric pH was recorded with an intragastric pH electrode for 12 h in two groups of healthy, preterm infants with similar birth weights (range 1.4 to 2.0 kg). Group I infants (n = 13) were less than 7 days old and Group II infants (n = 10) were 7-15 days old. Infants were fed three formula feedings and one clear liquid feeding during the study. In Group I, mean gastric pH measured at 15-min intervals was above 4.0 for 3 h after either feeding. In Group II mean gastric pH was lower particularly after clear liquid feedings, where it remained below pH 4.0 for the entire 3-h postprandial period. The percent of monitored time at gastric pH less than 4.0 was low in Group I--15.2 +/- 4.2% and 20.6 +/- 6.4% after formula and clear liquid, respectively. The percent time was greater in Group II--42.7 +/- 8.0% and 61.9 +/- 7.3% after formula and clear liquid, respectively. In the younger preterm infant, gastric pH does not appear sufficiently low to support peptic activity.

    Title Anemia of Prematurity: Determinants of the Erythropoietin Response.
    Date December 1984
    Journal The Journal of Pediatrics
    Excerpt

    This study was undertaken to determine the factors that are important in determining the erythropoietin response in low-birth-weight infants during the period of so-called anemia of prematurity. In the first weeks of life oxygen consumption in a group of 21 infants gradually increased as hemoglobin level fell. The magnitude of the erythropoietin response inversely varied with the central venous oxygen tension (P-vO2) (r = -0.55, P less than 0.001). When the P-vO2 declined to less than 30 torr, erythropoietin values were uniformly increased above the "normal" range (defined as the values associated with P-vO2 greater than 38 torr). Erythropoietin values varied inversely with hemoglobin but in general did not exceed the values observed for normal adult men. The erythropoietin values in the infants were remarkably lower at any given hemoglobin level when compared with those of older children with anemia resulting from bone marrow failure. In general, elevations of erythropoietin were seen when the hemoglobin concentration declined to less than 10.0 gm/dl. Change in heart rate did not appear to be a reliable indicator of the presence of anemia; rather, it correlated best with oxygen consumption.

    Title Acquired Immune Hemolytic Anemia Associated with Iga Erythrocyte Coating: Investigation of Hemolytic Mechanisms.
    Date November 1984
    Journal Blood
    Excerpt

    We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.

    Title Differences in Thromboxane Production Between Neonatal and Adult Platelets in Response to Arachidonic Acid and Epinephrine.
    Date November 1984
    Journal Pediatric Research
    Excerpt

    In this study, we have investigated the possible role of the pro-aggregatory arachidonic acid (AA) metabolite thromboxane, in the impaired function of neonatal platelets. In platelet-rich plasma thromboxane production (measured by radioimmunoassay of thromboxane B2) was not different between neonates and adults when stimulated by thrombin (at 0.1 or 1.0 U/ml) or collagen (70 micrograms/ml) although neonatal platelets produced decreased thromboxane (TBX2) postepinephrine stimulation. In response to 1 U/ml thrombin, adult and neonatal platelet-rich plasmas produced mean values of 3.41 +/- 0.35 (SEM) and 3.11 +/- 0.49 pmol of TXB2/10(6) platelets, respectively. Production of TXB2 in response to 0.1 U/ml thrombin was not dissimilar between neonates (1.01 +/- 0.46 pmol) and adults (1.04 +/- 0.38 pmol). When collagen was used as the aggregating agent, TXB2 production was also not significantly different with values of 2.44 +/- 0.48 and 1.90 +/- 0.46 pmol/10(6) platelets produced by adult and neonatal platelet-rich plasma, respectively. In response to 200 microM epinephrine, adult platelets produced 1.03 +/- 0.39 pmol TXB2/10(6) platelets while neonatal platelet TXB2 production was significantly decreased (0.15 +/- 0.04; P less than 0.05). Thromboxane production in response to AA, however, was markedly elevated in neonatal platelet-rich plasma. When 200 and 400 microM concentrations of AA were used as the aggregating stimuli, neonatal platelet rich plasma produced 3.17 +/- 0.77 and 8.0 +/- 1.47 pmol TXB2/10(6) platelets, respectively. These values were significantly elevated P less than 0.02 and less than 0.005) when compared to mean values of 0.41 +/- 0.10 and 3.32 +/- 0.15 pmol in adult platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Weight Gain: a Response to Transfusion in Selected Preterm Infants.
    Date September 1984
    Journal American Journal of Diseases of Children (1960)
    Excerpt

    A group of low-birth-weight infants with daily weight gains that were below the expected mean for postnatal age were examined to determine the effects of RBC transfusion on their weight gain. The mean hemoglobin concentration (+/- SD) in 13 infants (birth weight less than 1,500 g) prior to transfusion was 8.5 +/- 1.6 g/dL and 11.4 +/- 2.1 g/dL after transfusion. When a comparison was made between the daily weight gain for the week prior to transfusion with the week following transfusion, the mean daily weight gain (+/- SD) increased from 20.8 +/- 4.6 g to 28.0 +/- 6.3 g. Among the six infants with pretransfusion hemogloblin concentrations of less than 7.5 g/dL, the increase in daily weight gain was greatest (a rise from 22.6 +/- 4.0 g to 34.1 +/- 4.9 g). Improvements in weight gain were associated with a decrease in metabolic rates as determined by declines in oxygen consumption.

    Title Glottic Carcinoma. The Roles of Surgery and Irradiation.
    Date July 1984
    Journal Cancer
    Excerpt

    The treatment of 336 patients with squamous cell carcinoma of the glottic larynx seen at the University of Virginia Medical Center from 1960 through 1977 was reviewed. Two hundred eighty-five patients form the basis of this report. Patients were grouped by stage and by other prognostic factors. Five-year actuarial survival, recurrences, salvage therapy, complications, second primaries, and incidence in patients younger than 45-years-old were examined. The actuarial 5-year survivals are Stage I, 96%; Stage II, 88%; Stage III, 65%; and Stage IV, 57%. Early glottic carcinoma responded equally well to radiation therapy or surgery, and mortality from intercurrent disease was more common than death from glottic carcinoma. Anterior commissure involvement was not found to significantly decrease prognosis in Stage I disease. Within Stage II, patients with impaired true cord mobility had a significantly decreased survival, 71%, versus 93% for Stage II carcinoma with mobile cords. Surgery was superior to irradiation when cord mobility was impaired or fixed. Surgical salvage was successful in 70% of cases when the cords were originally mobile but 11% when cord motion had been impaired or fixed. Patients younger than age 45 years presented with more advanced disease, but by stage, treatment response did not differ from the remaining older group. Based on this review and from data reported in the literature, the authors recommend curative radiation therapy in patients with glottic carcinoma where the vocal cords are fully mobile. When cord mobility is impaired or fixed, the inclusion of surgery in the initial management results increased survival over irradiation alone. Recognizing that glottic carcinoma is often part of a multisystem disease, individualization of treatment is especially important in these advanced tumors.

    Title Interspecific Hybrids and Chimeras in Mice.
    Date March 1984
    Journal The Journal of Experimental Zoology
    Excerpt

    Interspecific hybrids and chimeras in mammals provide unique tools for investigating problems in genetics and embryology, because of the degree of disparity between the two component genotypes. We have attempted to produce hybrids and chimeras between Mus musculus, the laboratory mouse, and Mus caroli, a wild species of mouse from Southeast Asia. M. musculus and M. caroli do not normally interbreed, although sterile hybrids can be produced at a low rate by artificial insemination. Extrinsic problems of genotypic incompatibility between the fetus and the maternal environment seem to be involved in poor hybrid survival, since M. caroli blastocysts also die when transferred to the M. musculus uterus. Death is associated with the generation of maternal T-cells which are cytotoxic to M. caroli target cells in vitro. It is not yet clear whether this immune response is the primary cause of death or is secondary to breakdown of some other components of the fetal-maternal interaction. It is clear, however, that it is the trophoblast layer that mediates survival or death of the foreign embryonic cells in the M. musculus juterus, since M. caroli inner cell mass cells can survive to term after injection into M. musculus blastocysts: Viable interspecific chimeras result. Even more convincing evidence is provided by the production of viable M. caroli offspring by trophoblast vesicle reconstitution using trophoblast of M. musculus genotype and inner-cell mass of M. caroli type. Studies of properties of isolated trophoblast tissues have indicated that M. caroli trophoblast may differ from M. musculus in both its antigenic and immunosuppressive properties. Elucidation of trophoblast-uterine interactions in these various interspecific pregnancies is being aided by the development of an in situ marker system, which can distinguish cells of the two species in sectioned material by in situ hybridization with a M. musculus satellite DNA probe. This same marker is also proving a very powerful tool for analyzing cell lineage development in chimeras.

    Title Studies on Pure Red Cell Aplasia. Xi. Results of Immunosuppressive Treatment of 37 Patients.
    Date March 1984
    Journal Blood
    Excerpt

    Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

    Title Association of Morphological Differentiation with Enhanced Surface Antigen Expression and Susceptibility to Natural Killer Cell Lysis in Theophylline-treated Human Melanoma Cells.
    Date January 1984
    Journal Journal of Biological Response Modifiers
    Excerpt

    Human and animal melanomas undergo maturation spontaneously in vivo and in vitro, and as a result of experimental manipulation in vitro. To gain a better understanding of this phenomenon, we studied the effects of theophylline on a cultured human malignant melanoma cell line (CaCL 73-36). We observed a dose-dependent inhibition of cell growth with a reduction in plating efficiency of 16, 64, and 99% at concentrations of theophylline of 0.1, 1.0, and 2.0 mM, respectively. Theophylline-treated cells showed morphological changes consistent with a more differentiated state such as increased dendrite formation and contact inhibition. Expression of surface HLA-A,B,C antigens and beta-2-microglobulin was enhanced 15- and fivefold, respectively. Finally, cells treated with theophylline for 96 h showed a five- to eightfold increase in sensitivity to lysis by natural killer cells. These findings have obvious bearing on the potential use of theophylline in the treatment of malignant melanoma.

    Title Renal Allotransplantation During Pregnancy. Successful Outcome for Mother, Child, and Kidney.
    Date October 1983
    Journal Transplantation
    Title Increased Sensitivity to Complement or Erythroid and Myeloid Progenitors in Paroxysmal Nocturnal Hemoglobinuria.
    Date October 1983
    Journal The New England Journal of Medicine
    Excerpt

    Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia characterized by a membrane defect leading to increased sensitivity of erythrocytes, granulocytes, platelets, and bone-marrow erythroid and myeloid cells to complement-mediated lysis. To determine whether the phenotype of paroxysmal nocturnal hemoglobinuria is also expressed on erythroid and myeloid progenitors, marrow cells from five patients with the disease were exposed to a sucrose hemolytic system and then assayed for colony-forming units-erythroid (CFU-E), burst-forming units-erythroid (BFU-E), and colony-forming units-granulocyte/macrophage (CFU-GM). A 50 percent or greater decrease in the numbers of erythroid and myeloid colonies was noted when marrow cells from the patients with paroxysmal nocturnal hemoglobinuria were exposed to a sucrose solution of low ionic strength in the presence of complement but not in its absence. Such a decrease was not noted in similarly treated normal marrow cells or in marrow cells from a patient with the disease in remission. These results suggest that in paroxysmal nocturnal hemoglobinuria, CFU-E, BFU-E, and CFU-GM express a membrane abnormality similar to that on erythrocytes, and that the disease is the result of a change occurring at the level of the pluripotent hematopoietic stem cell.

    Title Stage Ii Glottic Carcinoma: Prognostic Factors and Management.
    Date July 1983
    Journal The Laryngoscope
    Excerpt

    Three hundred thirty-six patients with squamous cell carcinoma of the glottic larynx treated at the University of Virginia Medical Center from 1960 through 1977 were reviewed. Seventy patients with T2N0M0 disease, grouped according to the criteria of the American Joint Committee on Cancer, 1978, form the basis of this report. The 5-year actuarial survivals, recurrences, salvages, and prognostic factors were examined. Treatment was radiation, surgery, or a combination of radiation and surgery. Impaired vocal cord mobility in Stage II glottic squamous cell carcinoma is the crucial significant prognostic factor in predicting response to therapy, survival, and response to salvage therapy for recurrences. The 90% 5-year recurrence-free rate with freely mobile cords is comparable to that achieved with Stage I lesions. Impaired mobility resulted in a 5-year recurrence-free rate of 73%, which is comparable to that of T3N0 lesions. We support the concept of reclassifying Stage II disease into Stage IIa (mobile cords) and Stage IIb (impaired mobility). Based on this review and those reported in the literature, we recommend radiation therapy for Stage IIa disease. Surgery results in fewer recurrences and in longer survival than irradiation when the vocal cords are not freely mobile (Stage IIb).

    Title Interspecific Chimeras in Mammals: a New Experimental System.
    Date February 1983
    Journal Journal of Animal Science
    Excerpt

    The first viable interspecific chimeras in mammals have been made by mixing embryonic cells from two species of mouse, Mus musculus and Mus caroli. These chimeras resemble intraspecific chimeras in M. musculus in their patterns of mosaicism. They provide an interesting experimental system for studying interactions between cells of the two species. Three separate but related areas of investigation utilizing these chimeras are described. 1) In situ DNA-DNA hybridization using a cloned repetitive DNa sequence from M. musculus has enabled M. caroli and M. musculus cells to be distinguished in bone marrow spreads from chimeras. Further refinement of this technique should allow use of this in situ marker system for detailed analysis of cell distribution in chimeras. Such a ubiquitous marker system is not yet available in M. musculus. 2) Breeding interspecific chimeras has increased production of interspecific hybrids, which are very useful for studies of genetic interactions between the two species. 3) Mus caroli embryonic cells can survive in the M. musculus uterus in a chimera, although M. caroli embryos alone die around d 11 to 16 of pregnancy in M. musculus. Investigation of this phenomenon has implicated immune effector mechanisms in death of M. caroli embryos and has revealed the importance of trophoblast genotype for survival of foreign cells in the uterine environment.

    Title Hla-a2 and Chronic Lung Disease in Neonates.
    Date December 1982
    Journal Jama : the Journal of the American Medical Association
    Title Prostaglandin I2 Fails to Influence Red Cell Deformability.
    Date July 1982
    Journal Prostaglandins, Leukotrienes, and Medicine
    Title Radioimmunoassay of the Leukotrienes of Slow Reacting Substance of Anaphylaxis.
    Date May 1982
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    A rabbit immunized with a conjugate of leukotriene D4 (LTD4) and bovine albumin via the icosanoid carboxyl produced antibodies with comparable affinities for leukotrienes C4, D4, and E4 (LTC4, LTD4, and LTE4) and their 11-trans stereoisomers. The antibodies bound 3H-labeled 11-trans-LTC4 and 11-trans-LTC4 with the same average association constant (Ka) of 2.8 x 10(9) M-1 at 37 degrees C and were present at a concentration of 0.32 microgram/ml of the immune rabbit plasma. When 9.5 microliter of anti-LTD4 and 108 pmol of 11-trans-[3H]LTC4 (40 Ci/mmol) were incubated in a volume of 300 microliter with LTC4, LTD4, LTE4, or their 11-trans stereoisomers, 50% inhibition of 11-trans-[3H]LTC4 binding was achieved at levels varying between 0.3 and 0.7 ng. As assessed with synthetic analogs of the natural leukotrienes, the antibodies recognized neither those changes within the 6-sulfidopeptide unit of LTD4 produced by deamination or modest peptide lengthening nor the specific stereochemistry of the delta 14-cis double bond. However, the antibodies did recognize the triene lipid domain and the position and spatial orientation of the glutathione or cysteinylglycine function. Binding of 11-trans-[3H]LTC4 by anti-LTD4 was not inhibited by glutathione, cystinylbisglycine, arachidonic acid, or 5-hydroxy-6,8,11,14-icosatetraenoic acid, and leukotriene B4 (LTB4) was about 1/1000th as active as LTC4, LTD4, or LTE4. Mouse lymphoma (WEHI-5) and rat basophil leukemia (RBL-1) cells, when stimulated with calcium ionophore A23187, each produced immunoreactive leukotrienes; and LTC4, LTD4, and LTE4 from RBL-1 cells were individually quantitated by radioimmunoassay after resolution by high-performance liquid chromatography.

    Title Efficient Blood Use in a Neonatal Intensive Care Unit: the 'cow' Technique.
    Date February 1982
    Journal American Journal of Diseases of Children (1960)
    Title Decrease Prostacyclin Production: a Characteristic of Chronic Placental Insufficiency Syndromes.
    Date July 1981
    Journal Lancet
    Excerpt

    Prostacyclin production in neonates born at various gestational ages (28 weeks to term) was compared with that in neonates born of pregnancies complicated by various acute and chronic placental insufficiency states. Prostacyclin levels were reflected by the amount of conversion of 14C arachidonic acid to 6-keto-PGF1 alpha (the stable end-product of prostacyclin) by umbilical arteries. The uptake of 14C arachidonic acid by the umbilical arteries was also determined, and since this was similar for all groups it was not the cause of the differences noted in prostacyclin production. Neonates born of normal pregnancies had similar levels of prostacyclin production regardless of gestational age. Prostacyclin production was very low in neonates born of pregnancies complicated by chronic placental insufficiency (intrauterine growth retardation, essential hypertension, and pre-eclampsia), but normal with acute placental insufficiency (abruptio placentae). Hence the decrease in fetal prostacyclin production in pre-eclampsia is not related to gestational age; furthermore, it is also seen in other chronic placental insufficiency states.

    Title The Kidneys in Paroxysmal Nocturnal Hemoglobinuria.
    Date March 1981
    Journal Blood
    Excerpt

    Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

    Title Nurses As Health Educators with Emotionally Disturbed Children.
    Date December 1979
    Journal Perspectives in Psychiatric Care
    Title Provocation of Coronary Spasm with Ergonovine Maleate. New Test with Results in 57 Patients Undergoing Coronary Arteriography.
    Date November 1977
    Journal The American Journal of Cardiology
    Excerpt

    Ergonovine maleate (Ergotrate) was given to 57 patients undergoing coronary arteriography for investigation of angina occurring at rest or without provocation when routine study showed normal arteries or insufficient occlusive disease to explain their symptoms. This provocative test induced coronary arterial spasm in 13 patients, 10 of whom had definite Prinzmetal's angina. The spasm was easily reversed with sublingually administered nitroglycerin. The spasm was occlusive or nearly occlusive in nine patients, and there was associated reproduction of the chest pain and S-T elevation similar to the spontaneous episodes. One patient with Prinzmetal's angina had S-T depression rather than elevation in association with the chest pain. The other three patients without Prinzmetal's angina had focal narrowing without coronary occlusion, reproduction of the chest pain or electrocardiographic changes. Of the 44 patients who did not demonstrate coronary spasm in response to ergonovine, 29 had normal coronary arteries and 15 had various degrees of atherosclerotic occlusive disease. We conclude that cautious administration of ergonovine maleate during coronary arteriography can be safely used to elicit coronary spasm in some patients who have insufficient fixed occlusive disease to explain their symptoms.

    Title Coronary Artery Spasm. Medical Management, Surgical Denervation, and Autotransplantation.
    Date April 1977
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    Coronary artery spasm was induced by intravascular administration of ergonovine maleate (Ergotrate) during cardiac catheterization. In 78 patients suspected to have Prinzmetal's angina, no morbidity or death has resulted despite complete occlusive spasm in two and three coronary arteries. Typical EKG changes and akinesia of the myocardium in the distribution of the occluded vessels documented functional myocardial ischemia during spasm. The occlusive spasm is readily reversed by sublingual or intravascular nitroglycerin, and ventricular contractility returns to normal following relief of spasm. Occlusive spasm has been demonstrated in 15 patients with clinical evidence of Prinzmetal's angina. Symptoms have been effectively relieved by coronary vasodilators in 10 patients. Of the 5 patients in whom medical therapy failed, 4 were treated surgically. These 4 patients were in the intensive care unit with protracted, prolonged pain, subendocardial infarctions, and persistent failure of coronary vasodilators. Aorta-coronary bypass grafts have been combined with total cardiac denervation by autotransplantation (one patient) and total cardiac denervation by stripping of the great vessels (3 patients). Two of the patients treated by cardiac denervation died in the early postoperative period. The patient treated by autotransplantation has total relief of symptoms but persistent spasm on angiography. The angiographic demonstration of occlusive coronary spasm remains a valuable diagnostic tool to document definitively the presence of spasm. The surgical results question the value of surgical intervention in this disease.

    Title The Use of Oral Bcg in the Treatment or Metastatic Malignant Melanoma.
    Date October 1976
    Journal Medical and Pediatric Oncology
    Excerpt

    This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.

    Title Serum Urate and Cholesterol Levels in Air Force Academy Cadets.
    Date December 1975
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    Serum cholesterol and urate levels were measured in 150 young men at 2- to 4-month intervals during their first 18 months at the U.S. Air Force Academy. During the first week of cadet training, mean serum urate levels rose as high as 9.5 mg/100 m/, but decreased after a Sunday break. During this week, urate levels in excess of 8.49 mg/100 m/ were found in 44% of the subjects. Such levels, while definitely exceeding normal limits, were attributed to acute psychosocial stress rather than to an abnormal or pathological process. One month after the completion of basic military training, mean serum urate levels were within normal limits, as were all subsequent mean urate levels. Mean serum cholesterol levels were elevated at three times - during the first week of training, after the first month of the first academic year, and during a week of intense military training in the following spring. Apparently, urate and cholesterol levels were elevated by different aspects of stress. Elevations of uric acid level appeared to reflect stress that excited fear or insecurity. Elevations of cholesterol levels apeared to reflect a stress which the individual perceived as requiring a sustained increase in physical and/or mental performance.

    Title Usafam Cardiovascular Disease Followup Study: Comparisons of Serum Lipid and Lipoprotein Levels.
    Date January 1975
    Journal Aerospace Medicine
    Title Cardiac Transplantation in Man. Review of First Three Years' Experience.
    Date July 1973
    Journal The American Journal of Medicine
    Title Usafsam Cardiovascular Disease Followup Study: 1972 Progress Report.
    Date April 1973
    Journal Aerospace Medicine
    Title Effects of in Vivo Inhalation of 100 Per Cent Oxygen at Reduced Pressure on Serum and Red Cell Lipids.
    Date August 1972
    Journal Aerospace Medicine
    Title Cardiac Transplantation in Man. Vi. Prognosis of Patients Selected for Cardiac Transplantation.
    Date August 1971
    Journal Annals of Internal Medicine
    Title Pharmacology and Toxicology of Propellant Hydrazines.
    Date November 1969
    Journal Aeromedical Reviews
    Title Pharmacology and Toxicology of Propellant Hydrazines.
    Date October 1969
    Journal Aeromedical Reviews
    Title Effects of Hydrogen Peroxide on Lipoproteins and Associated Lipids.
    Date April 1969
    Journal Lipids
    Title Patterns of Change in Serum Lipid and Lipoprotein Levels in a Selected Military Population over a 14-year Period. Sam-tr-67-101.
    Date July 1968
    Journal [technical Report] Sam-tr. Usaf School of Aerospace Medicine
    Title Longitudinal Study of Serum Lipids. 12-year Report.
    Date October 1967
    Journal The American Journal of Clinical Nutrition
    Title Stability of the 1p O Shape Resonance in H- in Moderate Electric Fields.
    Date
    Journal Physical Review. A
    Title Response of the 1po Resonance Near N=3 in the H- Continuum to External Electric Fields.
    Date
    Journal Physical Review. A
    Title Muon-neutrino Carbon Charged-current Interaction Near the Muon Threshold.
    Date
    Journal Physical Review C: Nuclear Physics
    Title Comparative Analysis of Photosynthetic Light Environments Within the Crowns of Juvenile Rain Forest Trees.
    Date
    Journal Tree Physiology
    Excerpt

    Irradiances within the crowns of saplings of two tropical tree species were simultaneously compared in primary rain forest in Costa Rica. The species examined, Minquartia guianensis Aubl., a relatively slow-growing, canopy species, and Pithecellobium pedicellare (DC) Benth., a less-tolerant, emergent species, have different crown and leaf display patterns. Crown light environments were assessed by placing arrays of quantum sensors among leaves and recording at 5-s intervals for seven days with microloggers. Median total daily quantum flux densities for saplings of both species were less than 2% of full sun and did not differ significantly. More than 90% of the measurements within the crowns of these saplings were less than 25 micromol m(-2) s(-1). Spatial variability of photon flux densities within sapling crowns was similar for the two species despite differences in leaf display patterns. In saplings of both species, photon flux densities varied significantly over the relatively short distances within crowns and from day to day. Height growth of both species was significantly correlated with total daily photon flux densities and with percentage of full sun. However, only the tolerant species, Minquartia, showed a significant correlation between diameter growth and crown light environment.

    Title Inducible Nitric Oxide Synthase and Guinea-pig Ileitis Induced by Adjuvant.
    Date
    Journal Mediators of Inflammation
    Excerpt

    We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS) expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE(2) levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO) and N-acetyl-D-glucosaminidase (NAG) activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE(2) and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

    Title Nitric Oxide Synthase Inhibition Decreases Tolerance to Hyperoxia in Newborn Rats.
    Date
    Journal Mediators of Inflammation
    Excerpt

    We evaluated the effects of sustained perinatal inhibition of NO synthase (NOS) on hyperoxia induced lung injury in newborn rats. N(G)-nitro-Larginine-methyl-ester (L-NAME) or untreated water was administered to pregnant rats for the final 7 days of gestation and during lactation; followed by postnatal exposure to hyperoxia (>95% O(2)) or room air. The survival rate of L-NAME treated pups when placed in > 95% O(2) at birth was significantly lower than controls from day 4 (L-NAME, 87%; control pups, 100%, p < 0.05) to 14 (L-NAME, 0%; control pups, 53%, p < 0.05). Foetal pulmonary artery vasoconstriction was induced by L-NAME with a decrease in internal diameter from 0.88 +/- 0.03 mm to 0.64 +/- 0.01 mm in control vs. L-NAME groups (p < 0.05), respectively. We conclude that perinatal NOS inhibition results in pulmonary artery vasoconstriction and a decreased tolerance to hyperoxia induced lung injury in newborn rats.

    Title 'team Up Against Tb': Promoting Involvement in Thibela Tb, a Trial of Community-wide Tuberculosis Preventive Therapy.
    Date
    Journal Aids (london, England)
    Excerpt

    To describe a programme of community education and mobilization to promote uptake in a cluster-randomized trial of tuberculosis preventive therapy offered to all members of intervention clusters.

    Title Laparoscopic Resection of Advanced Colorectal Cancer.
    Date
    Journal The British Journal of Surgery
    Excerpt

    BACKGROUND:: Palliative resection of the primary tumour in asymptomatic patients with stage IV colorectal cancer is associated with improved survival and fewer complications. Laparoscopic surgery is widely employed in the curative treatment of colorectal cancer, but its value in advanced colorectal cancer remains unclear. METHODS:: All patients who underwent laparoscopic resection of primary colorectal cancer in this unit between June 1991 and Jan 2010 were entered into a prospective computerized database. Outcomes for patients with laparoscopic resection of stage IV colorectal cancer were compared with those of patients who had laparoscopic surgery for stage I disease. RESULTS:: Some 185 patients with stage IV colorectal cancer who underwent laparoscopic resection were compared with 310 patients who had stage I colorectal cancer. Some 94·1 and 98·4 per cent of operations respectively were completed laparoscopically. Hospital stay was slightly longer in the group with stage IV disease (mean 6·2 versus 5·3 days; P = 0·091). The 30-day mortality rate was 2·7 per cent in patients with stage IV disease and 0·6 per cent in those with stage I tumours (P = 0·061). There was no difference in complications. One-year survival rates were 77·8 and 99·0 per cent respectively (P < 0·001). CONCLUSION:: Short-term outcomes after laparoscopic surgery for stage IV colorectal cancer in selected patients are equivalent to those for stage I cancers. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

    Title Role of Cd200 Expression in Regulation of Metastasis of Emt6 Tumor Cells in Mice.
    Date
    Journal Breast Cancer Research and Treatment
    Excerpt

    Previous studies have confirmed that levels of CD200 expression on the cells of the transplantable EMT6 mouse breast cancer line are increased markedly during growth in immunocompetent mice, unlike the persistent low levels of expression observed in NOD-SCID.IL-2(γr-/-) mice or mice with generalized over-expression of a CD200 transgene (CD200(tg) mice). Faster tumor growth occurs in both of these latter mice, with decreased evidence for a host immune reaction in lymph nodes draining the tumor (DLN). We now report evidence for a role for CD200 expression (by the host and/or tumor cells) in increased seeding of tumor cells to DLN in immunocompromised (CD200(tg) or NOD-SCID.IL-2(γr-/-)) vs immunocompetent mice, by limiting dilution cloning of tumor cells from DLN (vs contralateral lymph nodes, CLN), using control and GFP-tagged EMT6 cells. Neutralization of expressed CD200 by anti-CD200mAbs decreased the tumor metastasis at the same time as increasing detection of cytotoxic anti-tumor immune cells in DLN. Infusion of either anti-CD4 to deplete T-effector cells, or anti-TGFβ antibody, increased metastasis to DLN, as did indeed the infusion of EMT6 cells selected for the loss of TGFβRII expression. It is concluded that the increased CD200 expression by breast cancer cells (and/or host tissue) may be an important variable involved in determining the risk of metastasis.

    Title Seminal Advances in Immunology of Reproduction.
    Date
    Journal Biology of Reproduction

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