Ophthalmologists
44 years of experience
Video profile
Accepting new patients
Kessler Park And Stevens Park
1330 N Beckley Ave
Ste 104
Dallas, TX 75203
214-941-3933
Locations and availability (2)

Education ?

Medical School Score Rankings
The University of Texas Southwestern (1966)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Academy of Ophthalmology
American Board of Ophthalmology

Affiliations ?

Dr. Harris is affiliated with 3 hospitals.

Hospital Affilations

Score

Rankings

  • Methodist Dallas Medical Center
    3500 W Wheatland Rd, Dallas, TX 75237
    • Currently 4 of 4 crosses
    Top 25%
  • Methodist Medical Center
    1441 N Beckley Ave, Dallas, TX 75203
    • Currently 3 of 4 crosses
    Top 50%
  • Dallas Methodist Physicians Network
  • Publications & Research

    Dr. Harris has contributed to 83 publications.
    Title Escherichia Coli Expression, Purification and Characterization of Functional Full-length Recombinant Alpha2beta2gamma3 Heterotrimeric Complex of Human Amp-activated Protein Kinase.
    Date January 2011
    Journal Protein Expression and Purification
    Excerpt

    AMP-activated protein kinase (AMPK) is an energy-sensing serine/threonine protein kinase that plays a central role in whole-body energy homeostasis. AMPK is a heterotrimeric enzyme with a catalytic (alpha) subunit and two regulatory (beta and gamma) subunits. The muscle-specific AMPK heterotrimeric complex (alpha2beta2gamma3) is involved in glucose and fat metabolism in skeletal muscle and therefore has emerged as an attractive target for drug development for diabetes and metabolic syndrome. To date, expression of recombinant full-length human AMPK alpha2beta2gamma3 has not been reported. Here we describe the expression, purification and biochemical characterization of functional full-length AMPK alpha2beta2gamma3 heterotrimeric complex using an Escherichia coli expression system. All three subunits of AMPK alpha2beta2gamma3 were transcribed as a single tricistronic transcript driven by the T7 RNA polymerase promoter, allowing spontaneous formation of the heterotrimeric complex in the bacterial cytosol. The self-assembled trimeric complex was purified from the cell lysate by nickel-ion chromatography using the hexahistidine tag fused exclusively at the N-terminus of the alpha 2 domain. The un-assembled beta 2 and gamma 3 domains were removed by extensive washing of the column. Further purification of the heterotrimer was performed using size exclusion chromatography. The final yield of the recombinant AMPK alpha2beta2gamma3 complex was 1.1mg/L culture in shaker flasks. The E. coli expressed enzyme was catalytically inactive after purification, but was activated in vitro by upstream kinases such as CaMKKbeta and LKB1. The kinase activity of activated AMPK alpha2beta2gamma3 complex was significantly enhanced by AMP (an allosteric activator) but not by thienopyridone A-769662, a known small molecule activator of AMPK. Mass spectrometric characterization of recombinant AMPK alpha2beta2gamma3 showed significant heterogeneity before and after activation that could potentially hamper crystallographic studies of this complex.

    Title An Analysis of Hearing Aid Fittings in Adults Using Cochlear Implants and Contralateral Hearing Aids.
    Date January 2011
    Journal The Laryngoscope
    Excerpt

    The objective of this study was to assess the appropriateness of hearing aid fittings within a sample of adult cochlear implant recipients who use a hearing aid in the contralateral ear (i.e., bimodal stimulation).

    Title A Short-term, Quasi-experimental Evaluation of D.a.r.e.'s Revised Elementary School Curriculum.
    Date December 2010
    Journal Journal of Drug Education
    Excerpt

    We present the short-term results of a quasi-experimental evaluation of the revised D.A.R.E. (Drug Abuse Resistance Education) curriculum. Study outcomes examined were D.A.R.E.'s effects on three substances, namely students' lifetime and 30-day use of tobacco, alcohol, and marijuana, as well as their school attendance and academic performance. The study comprised students in 17 urban schools, each of which served as its own control; 5th graders in the 2006-2007 school year constituted the comparison group (n = 1490), and those enrolled as 5th graders in the 2007-2008 school year constituted the intervention group (n= 1450). We found no intervention effect on students' substance use for any of the substance use outcomes assessed. We did find that students were more likely to attend school on days they received D.A.R.E. lessons and that students in the intervention group were more likely to have been suspended. Study findings provide little support for the implementation and dissemination of the revised D.A.R.E. curriculum.

    Title Kinetic and Structural Characterization of Caspase-3 and Caspase-8 Inhibition by a Novel Class of Irreversible Inhibitors.
    Date October 2010
    Journal Biochimica Et Biophysica Acta
    Excerpt

    Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of information linking their functions to diseases. Through a structure-based drug design approach, a number of novel beta-strand peptidomimetic compounds were synthesized. Kinetic studies of caspase-3 and caspase-8 inhibition were carried out with these urazole ring-containing irreversible peptidomimetics and a known irreversible caspase inhibitor, Z-VAD-fmk. Using a stopped-flow fluorescence assay, we were able to determine individual kinetic parameters of caspase-3 and caspase-8 inhibition by these inhibitors. Z-VAD-fmk and the peptidomimetic inhibitors inhibit caspase-3 and caspase-8 via a three-step kinetic mechanism. Inhibition of both caspase-3 and caspase-8 by Z-VAD-fmk and of caspase-3 by the peptidomimetic inhibitors proceeds via two rapid equilibrium steps followed by a relatively fast inactivation step. However, caspase-8 inhibition by the peptidomimetics goes through a rapid equilibrium step, a slow-binding reversible step, and an extremely slow inactivation step. The crystal structures of inhibitor complexes of caspases-3 and -8 validate the design of the inhibitors by illustrating in detail how they mimic peptide substrates. One of the caspase-8 structures also shows binding at a secondary, allosteric site, providing a possible route to the development of noncovalent small molecule modulators of caspase activity.

    Title Discovering Expectant Mothers' Beliefs About Oral Health: an Application of the Centering Pregnancy Smiles Program.
    Date September 2010
    Journal International Quarterly of Community Health Education
    Excerpt

    Research shows expectant mothers with oral infections may have an increased risk for delivering preterm, low birth weight babies. Difficulty accessing dental services, limited resources, and beliefs about dental care put expectant mothers from rural communities at a greater risk for oral health problems, which can have adverse health consequences for themselves and their unborn children. There is a need to better educate these women on proper oral health practices to decrease oral infections and increase the likelihood of delivering healthy babies. Using the Extended Parallel Process Model (EPPM) [1], this study examines the impact of a prenatal program, Centering Pregnancy Smiles (CPS), on changing rural expectant mothers' attitudes and beliefs about maintaining good oral health during pregnancy. Results showed the CPS program had a primarily positive impact on changing expectant mothers' attitudes and beliefs regarding oral health. Implications for educational prenatal programs on oral health in rural areas are discussed.

    Title Sensorimotor Transformation Deficits for Smooth Pursuit in First-episode Affective Psychoses and Schizophrenia.
    Date February 2010
    Journal Biological Psychiatry
    Excerpt

    Smooth pursuit deficits are an intermediate phenotype for schizophrenia that may result from disturbances in visual motion perception, sensorimotor transformation, predictive mechanisms, or alterations in basic oculomotor control. Which of these components are the primary causes of smooth pursuit impairments and whether they are impaired similarly across psychotic disorders remain to be established.

    Title Seronegative Wegener Granulomatosis.
    Date February 2010
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Expression, Purification, Characterization and Crystallization of Non- and Phosphorylated States of Jak2 and Jak3 Kinase Domain.
    Date January 2010
    Journal Protein Expression and Purification
    Excerpt

    Janus-associated kinases (JAKs) play critical roles in cytokine signaling, and have emerged as viable therapeutic targets in inflammation and oncology related diseases. To date, targeting JAK proteins with highly selective inhibitor compounds have remained elusive. We have expressed the active kinase domains for both JAK2 and JAK3 and devised purification protocols to resolve the non-, mono- (Y1007) and diphosphorylated (Y1007 and Y1008) states of JAK2 and non- and monophosphorylated states of JAK3 (Y980). An optimal purified protein yield of 20, 29 and 69mg per 20L cell culture was obtained for the three JAK2 forms, respectively, and 12.2 and 2.3mg per 10L fermentation for the two JAK3 forms allowing detailed biochemical and biophysical studies. To monitor the purification process we developed a novel HPLC activity assay where a sequential order of phosphorylation was observed whereby the first tyrosine residue was completely phosphorylated prior to phosphorylation of the tandem tyrosine residue. A Caliper-based microfluidics assay was used to determine the kinetic parameters (K(m) and k(cat)) for each phosphorylated state, showing that monophosphorylated (Y1007) JAK2 enzyme activity increased 9-fold over that of the nonphosphorylated species, and increased an additional 6-fold for the diphosphorylated (Y1007/Y1008) species, while phosphorylation of JAK3 resulted in a negligible increase in activity. Moreover, crystal structures have been generated for each isolated state of JAK2 and JAK3 with resolutions better than 2.4A. The generation of these reagents has enabled kinetic and structural characterization to inform the design of potent and selective inhibitors of the JAK family.

    Title Response Suppression Deficits in Treatment-naïve First-episode Patients with Schizophrenia, Psychotic Bipolar Disorder and Psychotic Major Depression.
    Date January 2010
    Journal Psychiatry Research
    Excerpt

    Recent evidence indicates common genetic, neurobiological, and psychopharmacological aspects of schizophrenia and psychotic affective disorders. Some similarities in neurocognitive deficits associated with these disorders have also been reported. We investigated performance on antisaccade and visually-guided saccade tasks in treatment-naïve first-episode psychosis patients (schizophrenia n=59, major depression n=15, bipolar disorder n=9), matched non-psychotic major depression patients (n=40), and matched healthy individuals (n=106). All psychosis groups displayed elevated antisaccade error rates relative to healthy individuals. Antisaccade latencies were elevated in schizophrenia, but no significant error rate or latency differences were observed among psychosis groups. For schizophrenia only, shorter visually guided saccade latencies were associated with higher antisaccade error rates. Schizophrenia was also the only group without a significant relationship between visually guided and antisaccade latencies. Reflexive saccades were unimpaired except in psychotic unipolar depression, where saccades were hypometric. As in schizophrenia, antisaccade abnormalities are present in affective psychoses, even early in the course of illness and prior to treatment. Disturbances in frontostriatal systems are believed to occur in both affective psychoses and schizophrenia, potentially causing some similar cognitive abnormalities across psychotic disorders. However, the distinct pattern of dysfunction in schizophrenia across oculomotor paradigms suggests possible unique causes of their observed oculomotor performance deficits.

    Title Acrosomal Integrity, Viability, and Dna Damage of Sperm from Dasyurid Marsupials After Freezing or Freeze Drying.
    Date January 2010
    Journal Theriogenology
    Excerpt

    Dasyurids are a diverse group of Australian native carnivores and insectivores that contains several threatened species. Despite successful cryopreservation of sperm from several marsupials, only 3% postthaw motility is reported for dasyurid marsupials. This study examined sperm preservation in the fat-tailed dunnart (Sminthopsis crassicaudata), an experimental model, with supplementary observations on the eastern quoll (Dasyurus viverrinus) and northern quoll (Dasyurus hallucatus). In S. crassicaudata, a toxicity trial demonstrated that incubation with up to 40% glycerol did not reduce sperm viability, suggesting that glycerol is not toxic to dasyurids. On the basis of this finding, S. crassicaudata, D. viverrinus, and D. hallucatus sperm were extended to a final concentration of 20% or 40% glycerol in Tris-citrate fructose and frozen in liquid nitrogen vapor. Postthaw sperm from all three species were nonmotile, and vital staining (SYBR14 and propidium iodide) indicated that sperm were nonviable. However, there was no evidence suggesting disruption of normal gross morphology or loss of acrosomal integrity when assessed by Bryan's staining. After freeze drying, Bryan's staining indicated that approximately 80% of S. crassicaudata sperm had normal acrosomes and no head loss. Despite being nonviable, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that S. crassicaudata sperm frozen in 40% glycerol or freeze-dried had no DNA damage compared with fresh controls. This study has described a method for preservation of the dasyurid sperm nuclei, but continued studies are required to achieve viable motile sperm and establish tools for the long-term storage of dasyurid sperm.

    Title A Comparison of Neuropsychological Dysfunction in First-episode Psychosis Patients with Unipolar Depression, Bipolar Disorder, and Schizophrenia.
    Date October 2009
    Journal Schizophrenia Research
    Excerpt

    The severity and profile of cognitive dysfunction in first episode schizophrenia and psychotic affective disorders were compared before and after antipsychotic treatment. Parallel recruitment of consecutively admitted study-eligible first-episode psychotic patients (30 schizophrenia, 22 bipolar with psychosis, and 21 psychotic depression) reduced confounds of acute and chronic disease/medication effects as well as differential treatment and course. Patient groups completed a neuropsychological battery and were demographically similar to healthy controls (n=41) studied in parallel. Prior to treatment, schizophrenia patients displayed significant deficits in all cognitive domains. The two psychotic affective groups were also impaired overall, generally performing intermediate between the schizophrenia and healthy comparison groups. No profile differences in neuropsychological deficits were observed across patient groups. Following 6 weeks of treatment, no patient group improved more than practice effects seen in healthy individuals, and level of performance improvement was similar for affective psychosis and schizophrenia groups. Although less severe in psychotic affective disorders, similar profiles of generalized neuropsychological deficits were observed across patient groups. Recovery of cognitive function after clinical stabilization was similar in mood disorders and schizophrenia. To the extent that these findings are generalizable, neuropsychological deficits in psychotic affective disorders, like schizophrenia, may be trait-like deficits with persistent functional implications.

    Title Dissociation and Preservation of Preantral Follicles and Immature Oocytes from Female Dasyurid Marsupials.
    Date August 2009
    Journal Reproduction, Fertility, and Development
    Excerpt

    The mammalian ovary contains numerous immature preantral follicles that are not dependent on endocrine support, unlike the more mature hormone-dependent antral follicles. Preantral follicles can be enzymatically dissociated to yield immature oocytes that survive sub-zero preservation better as they lack a temperature-sensitive meiotic spindle. These techniques are highly applicable to gamete banking, which is an urgent requirement for Australian carnivorous marsupials as several species have rapidly declining populations and risk extinction. The present study developed protocols for the transport, dissociation, preservation and culture of granulosa cell-oocyte complexes (GOC) from the ovaries of dasyurid marsupials. High viability of GOC following enzymatic dissociation is reported and it was demonstrated that GOC are of significantly better quality following refrigerated storage for 24 h compared with storage at room temperature. Oocytes from primary follicles were not damaged by cold shock or the toxicity of vitrification media and following vitrification in liquid nitrogen 69.42+/-2.44% of oocytes were viable. However, the surrounding granulosa cells demonstrated significant damage post-thaw. These granulosa cells proliferated during a 48-h culture period resulting in significant improvements in GOC quality. The present study is a valuable step towards cryostorage of dasyurid gametes and represents fundamentally important methods by which we can contribute to the conservation of Australia's native predators.

    Title The Efficacy and Tolerability of Ast-120 (spherical Carbon Adsorbent) in Active Pouchitis.
    Date June 2009
    Journal The American Journal of Gastroenterology
    Excerpt

    Although a majority of patients with pouchitis respond favorably to antibiotic therapy, many relapse frequently, and nonabsorbable and non-antibiotic-based agents are desirable for reducing bacterial resistance and the systemic adverse effects associated with long-term antibiotic exposure. AST-120 (a spherical carbon adsorbent) comprises highly adsorptive, porous carbon microspheres with the ability to adsorb small-molecular-weight toxins, inflammatory mediators,and harmful bile acids. The aim of this pilot trial was to evaluate the efficacy and tolerability of AST-120 in the treatment of active pouchitis.

    Title Artificial Insemination in Marsupials.
    Date March 2009
    Journal Theriogenology
    Excerpt

    Assisted breeding technology (ART), including artificial insemination (AI), has the potential to advance the conservation and welfare of marsupials. Many of the challenges facing AI and ART for marsupials are shared with other wild species. However, the marsupial mode of reproduction and development also poses unique challenges and opportunities. For the vast majority of marsupials, there is a dearth of knowledge regarding basic reproductive biology to guide an AI strategy. For threatened or endangered species, only the most basic reproductive information is available in most cases, if at all. Artificial insemination has been used to produce viable young in two marsupial species, the koala and tammar wallaby. However, in these species the timing of ovulation can be predicted with considerably more confidence than in any other marsupial. In a limited number of other marsupials, such precise timing of ovulation has only been achieved using hormonal treatment leading to conception but not live young. A unique marsupial ART strategy which has been shown to have promise is cross-fostering; the transfer of pouch young of a threatened species to the pouches of foster mothers of a common related species as a means to increase productivity. For the foreseeable future, except for a few highly iconic or well studied species, there is unlikely to be sufficient reproductive information on which to base AI. However, if more generic approaches can be developed; such as ICSI (to generate embryos) and female synchronization (to provide oocyte donors or embryo recipients), then the prospects for broader application of AI/ART to marsupials are promising.

    Title Recurrent Petrous Apex Cholesteatoma in a Patient with Basal Cell Nevus Syndrome.
    Date October 2008
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder.
    Date September 2008
    Journal Schizophrenia Bulletin
    Excerpt

    Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed.

    Title Oculomotor and Neuropsychological Effects of Antipsychotic Treatment for Schizophrenia.
    Date August 2008
    Journal Schizophrenia Bulletin
    Excerpt

    Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.

    Title Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase.
    Date August 2008
    Journal Journal of Medicinal Chemistry
    Excerpt

    Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC 50 = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a Delta H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

    Title Reduced Attentional Engagement Contributes to Deficits in Prefrontal Inhibitory Control in Schizophrenia.
    Date April 2008
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Problems with the voluntary control of behavior, such as those leading to increased antisaccade errors, are accepted as evidence of prefrontal dysfunction in schizophrenia. We previously reported that speeded prosaccade responses, i.e., shorter response latencies for automatic shifts of attention to visual targets, were associated with higher antisaccade error rates in schizophrenia. This suggests that dysregulation of automatic attentional processes may contribute to disturbances in prefrontally mediated control of voluntary behavior. METHODS: Twenty-four antipsychotic-naïve schizophrenia patients and 30 healthy individuals completed three tasks: a no-gap prosaccade task in which subjects shifted gaze toward a peripheral target that appeared coincident with the disappearance of a central fixation target and separate prosaccade and antisaccade tasks in which a temporal gap or overlap of the central target offset and peripheral target onset occurred. Sixteen patients were retested after 6 weeks of antipsychotic treatment. RESULTS: Patients' prosaccade latencies in the no-gap task were speeded compared with healthy individuals. While patients were not atypical in the degree to which response latencies were speeded or slowed by the gap and overlap manipulations, those patients with diminished attentional engagement on the prosaccade task (i.e., reduced overlap effect) had significantly elevated antisaccade error rates. This effect persisted in patients evaluated after antipsychotic treatment. CONCLUSIONS: This study provides evidence that a reduced ability to engage attention may render patients more distracted by sensory inputs, thereby further compromising impaired executive control during antisaccade tasks. Thus, alterations in attentional and executive control functions can synergistically disrupt voluntary behavioral responses in schizophrenia.

    Title Substituted Pyrazoles As Hepatoselective Hmg-coa Reductase Inhibitors: Discovery of (3r,5r)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2h-pyrazol-3-yl]-3,5-dihydroxyheptanoic Acid (pf-3052334) As a Candidate for the Treatment of Hypercholesterolemia.
    Date February 2008
    Journal Journal of Medicinal Chemistry
    Excerpt

    In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

    Title Massive Extraocular Extension and Parotid Lymph Node Metastasis of Uveal Melanoma.
    Date January 2008
    Journal Ophthalmic Plastic and Reconstructive Surgery
    Excerpt

    A 22-year-old man, diagnosed with unilateral glaucoma and treated with trabeculectomy 6 years earlier, presented with an epibulbar nodule of 6 months' duration. MRI displayed intra- and extraocular tumor, and gross invasion of the medial rectus muscle. Biopsy demonstrated uveal melanoma, and staging revealed enhancing ipsilateral parotid lymph nodes. Orbital exenteration and parotidectomy with selective neck dissection were performed. The tumor infiltrated superficial parotid nodes and extended into the parotid gland. The site of tumor origin is speculative, but a ring melanoma of the anterior chamber angle is suspected. Lymph node metastasis of uveal melanoma is rare; to our knowledge, this is the most advanced of the few reported cases.

    Title Towards a Zp-based Contraceptive for Marsupials: Comparative Analysis and Developmental Expression of Marsupial Zp Genes.
    Date January 2008
    Journal Molecular Reproduction and Development
    Excerpt

    Fertility control in the form of a zona pellucida (ZP)-based immunocontraceptive has shown potential as a humane form of control for overabundant marsupials including the brushtail possum and macropods. Further refinement and development of a ZP-based vaccine requires detailed knowledge of the protein structure and expression in order to ensure maximum efficacy and specificity. Sequencing and comparative analysis of the ZP3 protein from three marsupial orders in this study found a high overall level of conservation; within order Diprotodontia, the ZP3 protein is 86.9-98.9% identical. ZP3 identity falls to 56.6-57.2%, when the grey, short-tailed opossum (a Didelphimorphian) is compared to dasyurid and diprotodontan marsupials. This is similar to its amino acid identity with ZP3 from eutherian species (50.7-52.8%). Comparison of a 21 amino acid epitope in marsupial ZP3 that has shown contraceptive effects, reveals 95-100% identity between the four macropodid species, 81-86% amino acid identity between brushtail possum and the macropods and 67-71% identity between the diprotodontans and the fat-tailed dunnart (a dasyurid). This is comparable to the level of identity between related eutherian mammals. The expression pattern of three ZP genes during brushtail possum and tammar wallaby pouch young development was examined by RT-PCR. This analysis of ZP gene expression has confirmed that ZP mRNA transcription begins in the ovary during pouch young development by about 51 days of age. The presence of ZP transcripts at this stage in pouch young development suggests that marsupial ZP gene transcription begins before the onset of follicular development.

    Title Design and Synthesis of Novel, Conformationally Restricted Hmg-coa Reductase Inhibitors.
    Date November 2007
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

    Title Design and Synthesis of Hepatoselective, Pyrrole-based Hmg-coa Reductase Inhibitors.
    Date November 2007
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

    Title Antipsychotic Drugs Exacerbate Impairment on a Working Memory Task in First-episode Schizophrenia.
    Date October 2007
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: This study sought to replicate previous findings of worsened performance on a translational spatial working memory task among antipsychotic-naïve first-episode schizophrenia patients after antipsychotic treatment and to extend these findings by examining whether changes in the allocation of covert attention contribute to this effect. METHODS: Fourteen antipsychotic-naïve schizophrenia patients performed an oculomotor delayed response task before and 6 weeks after antipsychotic treatment (risperidone n = 11; olanzapine n = 3). Fifteen matched healthy individuals were studied in parallel. RESULTS: Patients' pretreatment deficit in accurately remembering spatial locations was exacerbated by antipsychotic treatment, consistent with previous findings; however, this occurred only when covert attention was directed away from remembered locations during delay periods. CONCLUSIONS: Disruption in the allocation of covert attention might contribute to patients' decline in spatial working memory after antipsychotic treatment. Alterations in prefrontal dopaminergic systems or reduced thalamocortical drive might account for this apparent adverse cognitive effect of antipsychotic treatment.

    Title Randomized Controlled Trial of Yoga Among a Multiethnic Sample of Breast Cancer Patients: Effects on Quality of Life.
    Date October 2007
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients. PATIENTS AND METHODS: One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment. RESULTS: Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02). CONCLUSION: Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.

    Title Effects of Cardiogenic Edema Fluid on Ion and Fluid Transport in the Adult Lung.
    Date October 2007
    Journal American Journal of Physiology. Lung Cellular and Molecular Physiology
    Excerpt

    We have previously shown that cardiogenic pulmonary edema fluid (EF) increases Na(+) and fluid transport by fetal distal lung epithelia (FDLE) (Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM and O'Brodovich H. J Physiol 544: 537-548, 2002). We now report the effect of EF on Na(+) and fluid transport by the adult lung. We first studied primary cultures of adult type II (ATII) epithelium and found that overnight exposure to EF increased Na(+) transport, and this effect was mainly due to factors other than catecholamines. Plasma did not stimulate Na(+) transport in ATII. Purification of EF demonstrated that at least some agent(s) responsible for the amiloride-insensitive component resided within the globulin fraction. ATII exposed to globulins demonstrated a conversion of amiloride-sensitive short-circuit current (I(sc)) to amiloride-insensitive I(sc) with no increase in total I(sc). Patch-clamp studies showed that ATII exposed to EF for 18 h had increased the number of highly selective Na(+) channels in their apical membrane. In situ acute exposure to EF increased the open probability of Na(+)-permeant ion channels in ATII within rat lung slices. EF did increase, by amiloride-sensitive pathways, the alveolar fluid clearance from the lungs of adult rats. We conclude that cardiogenic EF increases Na(+) transport by adult lung epithelia in primary cell culture, in situ and in vivo.

    Title Does Tailoring Matter? Meta-analytic Review of Tailored Print Health Behavior Change Interventions.
    Date September 2007
    Journal Psychological Bulletin
    Excerpt

    Although there is a large and growing literature on tailored print health behavior change interventions, it is currently not known if or to what extent tailoring works. The current study provides a meta-analytic review of this literature, with a primary focus on the effects of tailoring. A comprehensive search strategy yielded 57 studies that met inclusion criteria. Those studies-which contained a cumulative N = 58,454-were subsequently meta-analyzed. The sample size-weighted mean effect size of the effects of tailoring on health behavior change was found to be r = .074. Variables that were found to significantly moderate the effect included (a) type of comparison condition, (b) health behavior, (c) type of participant population (both type of recruitment and country of sample), (d) type of print material, (e) number of intervention contacts, (f) length of follow-up, (g) number and type of theoretical concepts tailored on, and (h) whether demographics and/or behavior were tailored on. Implications of these results are discussed and future directions for research on tailored health messages and interventions are offered.

    Title Adverse Effects of Risperidone on Spatial Working Memory in First-episode Schizophrenia.
    Date December 2006
    Journal Archives of General Psychiatry
    Excerpt

    CONTEXT: Working memory impairments are a central neurocognitive feature of schizophrenia. The nature of these impairments early in the course of illness and the impact of antipsychotic drug treatment on these deficits are not well understood. The oculomotor delayed response task is a translational spatial working memory paradigm used to characterize the neurophysiologic and neurochemical aspects of working memory in the primate brain. OBJECTIVE: To examine oculomotor delayed response task performance in patients with first-episode schizophrenia before and after antipsychotic drug treatment. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five antipsychotic drug-naive, acutely ill patients with first-episode schizophrenia performed an oculomotor delayed response task at baseline before any drug treatment and again after 6 weeks of risperidone treatment. Twenty-five matched healthy controls were studied in parallel. MAIN OUTCOME MEASURE: Accuracy for remembered spatial locations on an oculomotor delayed response task. RESULTS: Before treatment, patients demonstrated baseline impairment in the ability to maintain spatial location information in working memory at longer delay-period durations (8 seconds), when maintenance demands on working memory were greatest. After 6 weeks of risperidone treatment and significant clinical improvement, this pretreatment impairment worsened such that patients were uniformly impaired across all delay period durations (1-8 seconds). This occurred in the absence of any generalized adverse effect on oculomotor systems or significant extrapyramidal adverse effects. CONCLUSIONS: Deficits in the maintenance of spatial information in working memory are present early in the course of illness. Risperidone treatment exacerbated these deficits, perhaps by impairing the encoding of information into working memory. Studies with nonhuman primates performing oculomotor delayed response tasks suggest that the apparent adverse effect of risperidone might result from treatment-related changes in modulatory functions of prefrontal D1 receptor systems.

    Title Longitudinal Studies of Antisaccades in Antipsychotic-naive First-episode Schizophrenia.
    Date August 2006
    Journal Psychological Medicine
    Excerpt

    BACKGROUND: Prefrontal cortical dysfunctions, including disturbances in adaptive context-specific behavior, have been reported in neuropsychological and brain imaging studies of schizophrenia. Some data suggest that treatment with antipsychotic medications may ameliorate these deficits. METHOD: We investigated antisaccade performance in 39 antipsychotic-naive, first-episode schizophrenia patients who were re-evaluated 6 weeks after treatment initiation. A group of matched healthy subjects were examined at similar time-points. Patients and healthy individuals available for longer-term testing were re-assessed 26 and 52 weeks after initial testing. RESULTS: Before treatment, patients showed elevated rates of response suppression errors and prolonged latencies of correct antisaccades. Increased rates of antisaccade errors were associated with faster response latencies during a separate, visually guided saccade task, but only prior to treatment. Throughout the 1-year follow-up, patients progressively improved in their ability to voluntarily suppress context-inappropriate behavior. Although treatment assignment was by clinician choice, results of exploratory analyses revealed that patients treated with risperidone progressively planned and initiated correct antisaccades more quickly than patients receiving haloperidol. CONCLUSIONS: Deficits in the voluntary control of spatial attention are exaggerated during acute episodes of illness, but remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. During acute illness, speeded sensorimotor transformations may compound these deficits and contribute to the heightened distractibility associated with acute psychosis. Continued improvement in task performance throughout the 1-year follow-up suggests that partial normalization of prefrontal cognitive functions resulting from antipsychotic treatment may have a longer and more gradual time course than the reduction of acute psychotic symptoms.

    Title Inhibitors of Hcv Ns5b Polymerase. Part 2: Evaluation of the Northern Region of (2z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic Acid.
    Date October 2005
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    A novel series of non-nucleoside HCV NS5B polymerase inhibitors was prepared from a (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid template. Solution and solid phase analog synthesis focused on the northern region of the template combined with structure based design led to the discovery of several potent and orally bioavailable lead compounds.

    Title Inhibitors of Hcv Ns5b Polymerase. Part 1: Evaluation of the Southern Region of (2z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic Acid.
    Date October 2005
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    A novel series of nonnucleoside HCV NS5B polymerase inhibitors were prepared from (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid, a high throughput screening lead. SAR studies combined with structure based drug design focusing on the southern heterobiaryl region of the template led to the synthesis of several potent and orally bioavailable lead compounds. X-ray crystallography studies were also performed to understand the interaction of these inhibitors with HCV NS5B polymerase.

    Title Characterisation of an Epitope Shared by an Acrosomal Acrosin-like Protein and the Surface of Tammar Wallaby (macropus Eugenii) Spermatozoa.
    Date September 2005
    Journal Journal of Experimental Zoology. Part A, Comparative Experimental Biology
    Excerpt

    Monoclonal antibodies (mAb) have been raised against marsupial sperm proteins to provide insights into the molecular nature of marsupial spermatozoa, and the proteins that mediate sperm maturation and interaction with the oocyte. This study reports the production of a mAb, designated WSA-1, which bound acrosomal and surface determinants on tammar wallaby spermatozoa. The acrosomal antigen was first detected in the wallaby testis; however, ejaculated spermatozoa demonstrated whole cell WSA-1 immunoreactivity as a result of binding an epididymal protein. Ultrastructural and agglutination analyses localised the WSA-1 epitope to the acrosomal matrix and the whole sperm plasmalemma. The WSA-1 mAb bound three polypeptides with relative molecular weights of 35, 31 and 15 kDa on western blots under reducing conditions. The N-terminal amino acid sequence obtained for the 35 kDa wallaby sperm polypeptide demonstrated identity with the eutherian acrosomal protein acrosin. The 31 kDa polypeptide was of epididymal origin and will be the subject of a separate study. Further studies of the WSA-1 antigens are likely to provide useful insights into the function and maturation of marsupial sperm since proacrosin has a number of putative roles in eutherian fertilisation, and epididymal proteins are thought to mediate sperm maturation and storage.

    Title Co-crystal Structure and Inhibition of Factor Xa by Pd0313052 Identifies Structurally Stabilized Active Site Residues of Factor Xa and Prothrombinase.
    Date August 2005
    Journal Biochemistry
    Excerpt

    The enzyme complex prothrombinase plays a pivotal role in fibrin clot development through the production of thrombin, making this enzyme complex an attractive target for therapeutic regulation. This study both functionally and structurally characterizes a potent, highly selective, active site directed inhibitor of human factor Xa and prothrombinase, PD0313052, and identifies structurally conserved residues in factor Xa and prothrombinase. Analyses of the association and dissociation of PD0313052 with human factor Xa identified a reversible, slow-onset mechanism of inhibition and a simple, single-step bimolecular association between factor Xa and PD0313052. This interaction was governed by association (k(on)) and dissociation (k(off)) rate constants of (1.0 +/- 0.1) x 10(7) M(-1) s(-1) and (1.9 +/- 0.5) x 10(-3) s(-1), respectively. The inhibition of human factor Xa by PD0313052 displayed significant tight-binding character described by a Ki* = 0.29 +/- 0.08 nM. Similar analyses of the inhibition of human prothrombinase by PD0313052 also identified a slow-onset mechanism with a Ki* = 0.17 +/- 0.03 nM and a k(on) and k(off) of (0.7 +/- 0.1) x 10(7) M(-1) s(-1) and (1.7 +/- 0.8) x 10(-3) s(-1), respectively. Crystals of factor Xa and PD0313052 demonstrated hydrogen bonding contacts within the S1-S4 pocket at residues Ser195, Asp189, Gly219, and Gly216, as well as interactions with aromatic residues within the S4 pocket. Overall, these data demonstrate that the inhibition of human factor Xa by PD0313052 occurs via a slow, tight-binding mechanism and indicate that active site residues of human factor Xa, including the catalytic Ser195, are effectively unaltered following assembly into prothrombinase.

    Title Abnormalities in Visually Guided Saccades Suggest Corticofugal Dysregulation in Never-treated Schizophrenia.
    Date May 2005
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Previous studies have reported intact visually guided saccades in schizophrenia, but these are limited by potential acute and long-term pharmacological treatment effects, small sample sizes, and a failure to follow patients over time. METHODS: Visually guided saccades were examined in 44 antipsychotic-naive patients experiencing their first episode of schizophrenia prior to treatment and again after 6, 26, and 52 weeks of antipsychotic treatment. Thirty-nine matched healthy individuals were followed over the same period. RESULTS: Before treatment, patients showed faster saccade latencies to unpredictable visual targets, suggesting reduced inhibitory regulation of brainstem saccade generators by neocortical attentional systems. Risperidone treatment reduced this deficit, suggesting a facilitation of attentional function, but haloperidol treatment did not. However, there was also a modest decline in saccade accuracy after risperidone treatment. The ability to sustain fixation of static central and peripheral targets was unimpaired before and after treatment. CONCLUSIONS: These findings provide evidence for impairments in neocortical attentional systems that cause reduced corticofugal regulation of brainstem systems in schizophrenia. This dysfunction appears to be minimized by the atypical antipsychotic risperidone but at the cost of a subtle reduction in saccade accuracy, possibly mediated via adverse effects on cerebellar vermis function.

    Title Co-crystallization of Staphylococcus Aureus Peptide Deformylase (pdf) with Potent Inhibitors.
    Date June 2003
    Journal Acta Crystallographica. Section D, Biological Crystallography
    Excerpt

    In bacteria the biosynthesis of all nascent polypeptides begins with N-formylmethionine. The post-translational removal of the N-formyl group is carried out by peptide deformylase (PDF). Processing of the N-formyl group from critical bacterial proteins is required for cell survival. This formylation/deformylation cycle is unique to eubacteria and is not utilized in eucaryotic cytosolic protein biosynthesis. Thus, inhibition of PDF would halt bacterial growth, spare host cell-function, and would be a novel mechanism for a new class of antibiotic. Diffraction-quality Se-met crystals of S. aureus PDF were prepared that belong to space group C222(1) with unit cell parameters of a = 94.1 b = 121.9 c = 47.6 A. Multiple anomalous dispersion data were collected at the Advanced Photon Source 17-ID beamline and used to solve the PDF structure to 1.9 A resolution. Crystals were also prepared with three PDF inhibitors: thiorphan, actinonin and PNU-172550. The thiorphan and actinonin co-crystals belong to space group C222(1) with similar unit-cell dimensions. Repeated attempts to generate a complex structure of PDF with PNU-172550 from the orthorhombic space group were unsuccessful. Crystallization screening identified an alternate C2 crystal form with unit-cell dimensions of a = 93.4 b = 42.5 c = 104.1 A, beta = 93 degrees.

    Title Physical Methods to Determine the Binding Mode of Putative Ligands for Hepatitis C Virus Ns3 Helicase.
    Date May 2003
    Journal Analytical Biochemistry
    Excerpt

    Several small molecules identified by high-throughput screening (HTS) were evaluated for their ability to bind to a nonstructural protein 3 (NS3) helicase from hepatitis C virus (HCV). Equilibrium dissociation constants (K(d)'s) of the compounds for this helicase were determined using several techniques including an assay measuring the kinetics of isothermal enzyme denaturation at several concentrations of the test molecule. Effects of two nonhydrolyzable ATP analogs on helicase denaturation were measured as controls using the isothermal denaturation (ITD) assay. Two compounds, 4-(2,4-dimethylphenyl)-2,7,8-trimethyl-4,5-quinolinediamine and 2-phenyl-N-(5-piperazin-1-ylpentyl)quinazolin-4-amine, were identified from screening that inhibited the enzyme and had low micromolar dissociation constants for NS3 helicase in the ITD assay. Low micromolar affinity of the quinolinediamine to helicase was also confirmed by nuclear magnetic resonance experiments. Unfortunately, isothermal titration calorimetry (ITC) experiments indicated that a more water-soluble analog bound to the 47/23-mer oligonucleotide helicase substrate with low micromolar affinity as did the substituted quinazolinamine. There was no further interest in these templates as helicase inhibitors due to the nonspecific binding to enzyme and substrate. A combination of physical methods was required to discern the mode of action of compounds identified by HTS and remove undesirable lead templates from further consideration.

    Title Commentary: Eye Movement Research with Clinical Populations.
    Date January 2003
    Journal Progress in Brain Research
    Excerpt

    The preceding set of chapters span the disciplines of neurology and psychiatry, and provide a diverse introduction to clinical eye movement research. They illustrate how oculomotor paradigms can be used to learn about acute and chronic perturbations in brain function, disturbances in brain development, disturbances in sensorimotor as well as cognitive systems, and the effects of therapeutic and illicit drugs on brain function. This commentary discusses these contributions, provides an overview of broad methodological issues involved in applying eye movement studies to psychiatric populations using the antisaccade task as an exemplar, and considers the potential of collaborations between eye movement and brain imaging researchers to advance understanding of clinical eye movement abnormalities and of what they reveal about the organization of the oculomotor system.

    Title Relevance, Writing Style, and Synthesis: Key Elements in a Focused Review of the Literature.
    Date December 2002
    Journal Orthopaedic Nursing / National Association of Orthopaedic Nurses
    Excerpt

    Have the major points of the topic been covered? Did the slant of the article reflect the major theme being investigated by the author(s)? Were the strengths of the focused literature review emphasized? In this article, the authors were able to address a major gap in the existing body of knowledge impacting patient care. As a result, patients recovering from hip fractures in nursing home settings will have more effective pain management.

    Title Crystallization and Preliminary X-ray Analysis of Udp-n-acetylenolpyruvylglucosamine Reductase (murb) from Staphylococcus Aureus.
    Date September 2002
    Journal Acta Crystallographica. Section D, Biological Crystallography
    Excerpt

    UDP-N-acetylenolpyruvylglucosamine reductase (MurB) is an essential enzyme in the bacterial cell-wall biosynthetic pathway, making it a potential therapeutic target for novel antibiotics. Diffraction-quality crystals of both the native and Se-methionine-expressed MurB from Staphylococcus aureus have been prepared by sitting-drop vapour diffusion from solutions containing polyethylene glycol (PEG) 8000, ammonium sulfate, sodium cacodylate pH 6.5 and dimethyl sulfoxide (DMSO). Crystals belong to the cubic space group I2(1)3, with unit-cell parameters a = b = c = 178.99 A. X-ray data from these crystals were collected at the Advanced Photon Source 17-ID beamline and were used to solve the MurB structure to 2.3 A resolution.

    Title Crystal Structure of Type Ii Peptide Deformylase from Staphylococcus Aureus.
    Date September 2002
    Journal The Journal of Biological Chemistry
    Excerpt

    The first crystal structure of Class II peptide deformylase has been determined. The enzyme from Staphylococcus aureus has been overexpressed and purified in Escherichia coli and the structure determined by x-ray crystallography to 1.9 A resolution. The purified iron-enriched form of S. aureus peptide deformylase enzyme retained high activity over many months. In contrast, the iron-enriched form of the E. coli enzyme is very labile. Comparison of the two structures details many differences; however, there is no structural explanation for the dramatic activity differences we observed. The protein structure of the S. aureus enzyme reveals a fold similar, but not identical to, the well characterized E. coli enzyme. The most striking deviation of the S. aureus from the E. coli structure is the unique conformation of the C-terminal amino acids. The distinctive C-terminal helix of the latter is replaced by a strand in S. aureus which wraps around the enzyme, terminating near the active site. Although there are no differences at the amino acid level near the active site metal ion, significant changes are noted in the peptide binding cleft which may play a role in the design of general peptide deformylase inhibitors.

    Title Effects of Fetal Bovine Serum on Ferrous Ion-induced Oxidative Stress in Pheochromocytoma (pc12) Cells.
    Date January 2002
    Journal Neurochemical Research
    Excerpt

    Ferrous ion (Fe2+) has been considered to be a cause of neuronal oxidative injury. Since body fluids contain protein and serum is an essential component of tissue culture medium, we have examined the role of serum protein on Fe2+-mediated oxidative stress using PC12 cells and rat cerebral cortices. Fe2+ or the combination of ascorbate and Fe2+ increased concentrations of thiobarbituric acid reactive substances (TBARS) in PC12 cells and cerebrocortical homogenates in medium (RPMI 1640), but did not increase TBARS when the medium was supplemented with 10% fetal bovine serum. Treatment with ascorbate/Fe2+ in serum-free medium reduced endogenous glutathione (GSH) concentration in PC12 cells. However, the medium supplemented with serum did not reduce GSH concentrations. PC12 cell death induced by ascorbate/Fe2+ was alleviated by increasing serum or bovine albumin concentrations in the medium. These observations indicated that oxidative injury caused by the transition metal ion could be lessened by adding fetal bovine serum to culture medium.

    Title A Structural Variation for Murb: X-ray Crystal Structure of Staphylococcus Aureus Udp-n-acetylenolpyruvylglucosamine Reductase (murb).
    Date May 2001
    Journal Biochemistry
    Excerpt

    The X-ray crystal structure of the substrate free form of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB) has been solved to 2.3 A resolution with an R-factor of 20.3% and a free R-factor of 22.3%. While the overall fold of the S. aureus enzyme is similar to that of the homologous Escherichia coli MurB X-ray crystal structure, notable distinctions between the S. aureus and E. coli MurB protein structures occur in residues involved in substrate binding. Analysis of available MurB sequences from other bacteria suggest that the S. aureus MurB structure is representative of a distinct structural class of UDP-N-acetylenolpyruvylglucosamine reductases including Bacillus subtilis and Helicobacter pylori that are characterized by a modified mechanism for substrate binding.

    Title Marketing Health Care to Minorities: Tapping an Emerging Market.
    Date February 2001
    Journal Marketing Health Services
    Excerpt

    A number of myths have prevented the development of a formal health care marketing strategy for the 100 million-plus racial and ethnic group members in the United States, despite their relatively greater need for health services. This market continues to grow in numbers, resources, and influence as the majority market level off. Marketers must look to minorities for new business, but traditional health care marketers have a long way to go before they are in a position to truly maximize this opportunity.

    Title Comparison Among the Perforation Rates of Maloney, Balloon, and Savary Dilation of Esophageal Strictures.
    Date May 2000
    Journal Gastrointestinal Endoscopy
    Excerpt

    BACKGROUND: Traditionally, mercury-filled rubber bougies are used for dilation of simple or mild-to-moderate esophageal strictures, whereas through-the-scope balloon dilators and wire-guided polyvinyl bougies have become standard for more complex strictures. Because few comparative trials are available, the choice of dilator and technique is largely based on the training and experience of the operator. METHODS: We reviewed 348 esophageal dilation procedures performed on a total of 142 patients over a 4-year period (January 1, 1993, to January 1, 1997). The location and cause of stricture, the maximum diameter of the instrument used per session, the rate of perforation, and the rate of fluoroscopy use were recorded. RESULTS: Maloney, balloon (hydrostatic and pneumatic type), and Savary dilations were performed in 102, 156, and 90 sessions, respectively. Perforations occurred in 4 patients. All of these perforations occurred when Maloney dilators were passed blindly into complex strictures (Fisher's exact test, p = 0.011, two-tailed). Three of these four patients had undergone endoscopy with conscious sedation immediately before the dilation. The immediate outcome of surgery was good in all 4 patients with no deaths. CONCLUSION: Perforation was most commonly associated with the blind passage of Maloney bougies into complex strictures.

    Title Characterisation of Fibrous Sheath and Midpiece Fibre Network Polypeptides of Marsupial Spermatozoa with a Monoclonal Antibody.
    Date October 1998
    Journal Molecular Reproduction and Development
    Excerpt

    In this study cytoskeletal antigens common to brushtail possum and tammar wallaby spermatozoa were characterised using a monoclonal antibody (PSA-10). Using indirect immunofluorescence, the PSA-10 antibody detected antigens predominantly associated with the midpiece and principal piece of mature, permeabilised marsupial spermatozoa. The principal piece determinant, shared by a variety of other species, was found to arise in the marsupial testis. Midpiece localisation of the PSA-10 epitope was detected only in marsupial spermatozoa and shown to arise in the epididymis. Immunogold labelling demonstrated that the PSA-10 antigens were predominantly associated with the fibrous sheath and midpiece fibre network of both possum and wallaby spermatozoa. Western blotting suggested that two major possum and wallaby sperm polypeptides of 158 and 182 kDa were associated with the midpiece fibre network, a cytoskeletal structure unique to marsupial spermatozoa. A 32 kDa polypeptide was associated with the principal piece fibre network and/or fibrous sheath. The finding that these marsupial sperm cytoskeletal proteins share a common linear epitope suggests that they share some sequence similarity. The midpiece fibre network of marsupial sperm, like the fibrous sheath, has been proposed to have a structural role in providing passive stiffening for the flagellum (Harding et al., 1975, 1979; Olsen, 1975). The PSA-10 monoclonal antibody may provide a tool for comparative studies of mammalian sperm cytoskeletal proteins, particularly the marsupial midpiece fibre network. It may also allow the formation of this unique marsupial cytoskeletal structure, and its fate during the fertilisation process, to be followed by immunological means.

    Title Hypericin Inhibits Choroidal Endothelial Cell Proliferation and Cord Formation in Vitro.
    Date November 1997
    Journal Current Eye Research
    Excerpt

    PURPOSE: To evaluate the effect of hypericin on bovine choroidal endothelial cell proliferation and cord formation and on protein kinase C activity. METHODS: The effect of hypericin (0.1-5 microM) on bovine choroidal endothelial cell proliferation was determined by cell number counting and a 3H-thymidine uptake assay in media containing 1, 5 or 10% serum. For the cord formation assay, bovine choroidal endothelial cells were seeded on basement membrane matrix, and the lengths of the capillary-like structures (cords) formed were quantified by image analysis. The effect of hypericin on cord formation was evaluated in the presence of serum or vascular endothelial growth factor. The effect of hypericin on protein kinase C activity was also measured in the presence or absence of light. RESULTS: Hypericin inhibited bovine choroidal endothelial cell proliferation in a dose-dependent manner in the presence of light but not in the dark. Serum dose-dependently masked the inhibition of DNA synthesis by hypericin. Cord formation by bovine choroidal endothelial cells was stimulated by serum or vascular endothelial growth factor and inhibited by hypericin in the presence of light. Protein kinase C activity was completely inhibited by hypericin in the presence of light but only mildly inhibited in the absence of light. CONCLUSIONS: Hypericin inhibits bovine choroidal endothelial cell proliferation and cord formation and choroidal endothelial cell protein kinase C activity. These results suggest that hypericin should be further investigated in animal models for its potential to inhibit subretinal neovascularization.

    Title Irritable Bowel Syndrome. A Cost-effective Approach for Primary Care Physicians.
    Date April 1997
    Journal Postgraduate Medicine
    Excerpt

    Recognition and appropriate treatment of IBS can be challenging. A rational approach to management focuses on a positive diagnosis based on the characteristic pattern of symptoms and the exclusion of organic disorders. Dietary modification and pharmacologic therapy may be useful for relieving symptoms. Patient education and reassurance about the benign course of the disease are important aspects of effective treatment. In severe cases, referral to a psychologist or psychiatrist may be warranted. As our understanding of the pathophysiologic processes in IBS increases, more effective therapies will likely emerge.

    Title Cis-hydroxyproline Inhibits Proliferation, Collagen Synthesis, Attachment, and Migration of Cultured Bovine Retinal Pigment Epithelial Cells.
    Date March 1997
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) and other cells into the vitreous cavity. The PVR membrane formation also is associated with collagen production by RPE. The authors examined the effect of a proline analog, cis-hydroxyproline (CHP), on proliferation, collagen synthesis, attachment, and migration of bovine RPE in vitro. METHODS: The effect of CHP on cell proliferation was determined as a function of dosage and days in culture by counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined by trichloroacetic acid precipitation of the radiolabeled samples before and after bacterial collagenase digestion. The attachment assay involved type I collagen or fibronectin substrates or both (2.5 micrograms/well). For migration experiments, RPE cells were removed from a defined area of a confluent culture, and migration was quantitated by counting the number of cells migrating into the denuded area over 30 hours. RESULTS: The addition of CHP inhibited RPE proliferation in both a dose- and a time-dependent manner; collagen synthesis, attachment, and migration also were inhibited by CHP in a dose-dependent manner. When the culture plates were coated with collagen, < 100 micrograms/ml of CHP had no effect on cell attachment. Higher doses of CHP resulted in mild inhibition of attachment on collagen-coated plates. Simultaneous addition of L-proline to the cultures resulted in blockade of these inhibitory effects on proliferation, collagen synthesis, attachment, and migration. CONCLUSIONS: The results show that RPE functions critical to the development of PVR are inhibited by CHP, suggesting the possibility that this drug may have potential clinical application.

    Title Enteroscopy. Outcomes.
    Date February 1997
    Journal Gastrointestinal Endoscopy Clinics of North America
    Excerpt

    Outcomes studies are important to determine the role of enteroscopy in the management of patients with obscure gastrointestinal bleeding. This article discusses the current available data and identifies areas for further research.

    Title Sacrospinous Colpopexy in the Management of Uterovaginal Prolapse.
    Date November 1996
    Journal The Journal of Reproductive Medicine
    Excerpt

    OBJECTIVE: To investigate the morbidity and results of vaginal hysterectomy with concomitant sacrospinous colpopexy for uterovaginal prolapse. STUDY DESIGN: An observational study was carried out from June 17, 1986, to September 22, 1992. Patients were selected if it was thought that the cardinal-uterosacral ligaments could not be relied upon for vaginal vault support. RESULT: During the study period, 265 vaginal hysterectomies were performed. Forty-five (17%) were with concomitant sacrospinous colpopexy. The mean patient age was 54 years. There was one incidental cystotomy during hysterectomy, and two patients required transfusion. Postoperatively, eight patients were treated for soft tissue infection, one developed new-onset urinary incontinence, and no apparent nerve injuries were diagnosed. The mean day of discharge was 4.4. Six patients were lost to follow-up after the early postoperative period. The mean follow-up for the remaining patients was 29 months (12-66). One patient required subsequent vaginal repair for recurrent cystocele and enterocele. Four patients had persistent stress urinary incontinence. CONCLUSION: Sacrospinous colpopexy at the time of vaginal hysterectomy is reasonably safe and effective for reestablishing upper vaginal support.

    Title Myoelectric Activity and Absorptive Capacity of Rat Small Intestinal Isografts.
    Date July 1996
    Journal Digestive Diseases and Sciences
    Excerpt

    The effect of transplantation on small intestinal absorption, digestive capacity, myoelectric activity, and morphology was assessed in inbred Lewis rats. Electrodes were sutured to the duodenum and isografted jejunoileum or to the native jejunoileum in controls. The frequency of migrating myoelectric complexes (MMCs) in the duodenum was 3.3 +/- 0.3/hr in controls and 1.8 +/- 0.4/hr in transplants (P < 0.05). MMC frequency in the jejunoileum was 5.1 +/- 1.3/hr in controls and 3.2 +/- 0.9/hr in transplants (P > 0.05). MMCs appeared to migrate from the duodenum to the jejunoileum 80 +/- 3% of the time in controls and 59 +/- 7% of the time in transplant rats (P < 0.05). Absorption in the transplanted jejunoileum demonstrated a 35-40% decrease in glucose and electrolytes absorption. Villus height and number of nuclei per villus was reduced. Intestinal length (dry) was 103 +/- 6 cm for controls and 51 +/- 3 cm for transplant rats (P < 0.05). Brush border sucrase activity was unchanged. We conclude that small intestinal isografts display similar myoelectric activity as controls, but the decreased absorptive capacity and villus height may require longer segments of intestine to be transplanted in order to support normal nutrition.

    Title Hypericin Inhibits Cell Growth and Induces Apoptosis in Retinal Pigment Epithelial Cells: Possible Involvement of Protein Kinase C.
    Date July 1996
    Journal Current Eye Research
    Excerpt

    Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) cells in the vitreous cavity. The drug hypericin, which is already in clinical use as an antidepressant, has shown promise as an antiviral and antineoplastic agent. To investigate the therapeutic potential of hypericin in PVR, we incubated RPE cells in standard medium with various serum concentrations containing 0.5 to 5 microM hypericin. In some experiments we studied the effects of hypericin in conjunction with the RPE growth stimulating cytokine tumor necrosis factor alpha (TNF-alpha). Dose-dependent inhibition of RPE cell proliferation with IC50 values of 0.7 microM and 3.3 microM in 1% and 5% serum respectively, was found. Even in conjunction with TNF-alpha, hypericin inhibited RPE proliferation with an IC50 value of 1.5 microM. The drug inhibited PKC activity in cells treated with a 2.5 microM dose by 72% after 30 min and by 100% after 180 min. Finally, hypericin induced RPE cells to undergo apoptotic cell death, as shown by the presence of DNA laddering. These results suggest that hypericin may have potential as a therapeutic drug for PVR and that its antiproliferative and apoptotic effects on RPE cells in vitro are in part mediated by PKC.

    Title Effect of Tecogalan Sodium on Angiogenesis in Vitro by Choroidal Endothelial Cells.
    Date May 1995
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    PURPOSE. To examine the possible inhibitory effect of tecogalan sodium, derived from bacteria, on three important components of in vitro angiogenesis (endothelial proliferation, migration, and tube formation in a collagen gel) using bovine choroidal endothelial cells (CECs). METHODS. The effects of tecogalan sodium (1, 5, 25, 125, and 250 micrograms/ml) on cultured CECs were examined when basic fibroblast growth factor (bFGF, 10 ng/ml), vascular endothelial growth factor (VEGF, 50 ng/ml), a combination of bFGF (10 ng/ml) and VEGF (50 ng/ml) (bFGF/VEGF) and 10% fetal calf serum (FCS) were used as angiogenic stimulants. For the proliferation assay, CECs were cultured and the cell numbers counted on days 1, 3, and 5. For migration assay, CECs were seeded in the upper half of a Boyden chamber while an angiogenic growth factor was loaded in the lower half. After 6 hours of incubation, cell migration was evaluated by counting the numbers of migrated cells per microscopic field on the lower side of the filter. For the tube-forming assay, CECs were seeded in a type I collagen gel, and the length of the tube-like structures (an indicator of angiogenesis) formed by CECs per microscopic field was quantified by image analysis. The effect of neutralizing antibody for bFGF also was tested in these three assays. RESULTS. All tested angiogenic stimulants induced CEC proliferation. The stimulatory effect of bFGF and bFGF/VEGF was reduced by tecogalan sodium (IC50 for bFGF effect, 26.1 micrograms/ml). However, the effect of VEGF and of 10% FCS was not altered by low doses of tecogalan sodium (< 25 micrograms/ml). Chemotaxis of CECs was stimulated by bFGF alone and by bFGF/VEGF, and this effect was inhibited by tecogalan sodium (IC50 for bFGF, 3.2 micrograms/ml). Stimulation of chemotaxis by VEGF alone and by 10% FCS was not affected by tecogalan sodium in low doses but was inhibited by high doses. Tube formation was stimulated by administration of each of the factors. Stimulation of tube formation by bFGF and by bFGF/VEGF was inhibited by tecogalan sodium (IC50 for bFGF, 18.2 micrograms/ml). High doses of tecogalan sodium (125 and 250 micrograms/ml) also inhibited 10% FCS-induced proliferation, migration, and tube formation. CONCLUSION. bFGF, VEGF, and a combination of bFGF and VEGF stimulated proliferation, migration, and tube formation by CECs in vitro. These stimulatory effects, but especially those of bFGF, were inhibited by tecogalan sodium. If tecogalan sodium can be shown to have a similar effect in vivo, it might have the potential for pharmacologic control of subretinal neovascularization.

    Title Cytogenetic and Molecular Identification of a De Novo Direct Duplication of the Long Arm of Chromosome 4(q21.3-->q31.3).
    Date June 1993
    Journal American Journal of Medical Genetics
    Excerpt

    We report on a 3-year-old boy with moderate developmental retardation, microcephaly, and malformations of ears, lids, mouth, and thumbs. Cytogenetic analysis demonstrated a direct duplication of chromosome subregion 4(q21.3-->q31.3). Confirmation of this specific rearrangement was performed by fluorescent in situ hybridization (FISH) with a chromosome painting probe and by means of quantitative Southern hybridization with DNA probes localized within the chromosome 4 region presumed to be duplicated.

    Title Seroepidemiology of Hepatitis B Infection in Children in Vanuatu. Implications for Vaccination Strategy.
    Date March 1991
    Journal The Medical Journal of Australia
    Excerpt

    Four hundred and eighty-two unvaccinated children from three different age groups (12-18 months, 30-42 months, 54-115 months) in a hepatitis B virus (HBV) endemic area were tested for markers of HBV infection. HBV seromarkers were detected in 52.3% of children and 26.9% were hepatitis B surface antigen (HBsAg) positive. Evidence of infection was related to age, with HBV seromarker rates highest (67.5%) in school children aged 56-115 months. The HBsAg positive rate was highest (30.1%) in children 30-42 months of age. However, even children in the youngest age group (12-18 months) had high seromarker (26.8%) and HBsAg positive (17.0%) rates. A high proportion of HBsAg positive children (83.8%) were also hepatitis Be antigen (HBeAg) positive. Mothers of children in the youngest age group (12-18 months) were also tested, and 24.5% were HBsAg positive. Factors associated with higher rates of infection in children included maternal HBeAg positivity (for children in the youngest age group), increasing age, and residence on the islands of Emao or Nguna. Higher rates of HBsAg positivity were associated with these factors and with being male. Crossinfection between children is probably the most important source of infection, based on the evidence of the high rate of HBeAg positivity in children and the rising infection rate with age. A possible vehicle of spread is through skin infections and skin sores which are highly prevalent in children in Vanuatu. Since this study indicates that both perinatal and early child-to-child transmission are occurring, the most practical strategy to prevent the majority of infections is to vaccinate all children, commencing at birth and completing the course early in the first year of life.

    Title Streamlining the Management of Defecation Disorders.
    Date October 1990
    Journal Diseases of the Colon and Rectum
    Excerpt

    Obstinate constipation is a frequent but elusive gastrointestinal symptom. Increased understanding of defecation physiology and recent availability of simple, ready-to-use tools have increased specificity of both diagnosis and treatment. This patient series includes over 700 severely constipated patients with over 70 percent overall therapeutic success. Cinedefecography, pelvic floor electromyography, and determination of rectoanal inhibitory reflex were performed with simple and readily available equipment to document outlet anatomy and dynamics. Colonic transit time was examined in patients whose defecography and electromyography results were nondiagnostic and/or whose response to medical management was suboptimal, using a commercially available marker capsule, followed by abdominal x-rays. Retention of markers throughout the colon suggested colonic hypomotility or "inertia"; rectosigmoid retention confirmed functional outlet obstruction. With careful history, physical examination, and exclusion of organic causes, orderly application of readily available techniques can afford rapid, objective, and anatomically specific evidence upon which treatment of disordered defecation may be based.

    Title Delorme's Transrectal Excision for Internal Rectal Prolapse. Patient Selection, Technique, and Three-year Follow-up.
    Date August 1990
    Journal Diseases of the Colon and Rectum
    Excerpt

    Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term "placebo" effect attends many therapies, this report describes results of transrectal excision only after a three-year postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.

    Title An Alui Rflp Detected in the Human Prion Protein (prp) Gene.
    Date May 1990
    Journal Nucleic Acids Research
    Title Induction of Neurally Mediated Nahco3 Secretion by Luminal Distension in Rat Ileum.
    Date September 1989
    Journal The American Journal of Physiology
    Excerpt

    Distension induces secretion in the intact intestine, but the mechanism of this secretory process remains unresolved. We sought to characterize the effect of intraluminal pressures below 20 cmH2O on water and electrolyte movements in the rat ileum and the subsequent effects of two cholinergic antagonists, hexamethonium and atropine. An increase in intraluminal pressure from 3.0 to 12.5 cmH2O led to inhibition of net H2O and Na absorption and stimulation of HCO3 secretion. However, there was no significant change in Cl absorption. Secretion occurred in the absence of changes in tissue wet weight, intercellular fluid accumulation, villus tip erosions, or mannitol flux. Alterations in fluid and electrolyte absorption were prevented by the intra-arterial administration of hexamethonium (10 mg/kg). Atropine (0.5 mg/kg) had no effect. Our studies demonstrate that distension induces the secretion of Na and HCO3 by the intact ileum. This secretory process may represent a neurally rather than passively mediated mechanism.

    Title Sodium-proton Exchange in Human Ileal Brush-border Membrane Vesicles.
    Date July 1989
    Journal Biochimica Et Biophysica Acta
    Excerpt

    This study examines the characteristics of Na+ and H+ transport as well as Na+-H+ exchange in human ileal brush-border membrane vesicles from organ donor intestine. 22Na+ uptake into vesicles and the fluorescence quenching of Acridine orange were employed to measure Na+ and H+ transport, respectively. Concentrative uptake of 22Na+ (4-fold overshoot above equilibrium) was observed under conditions of an outward proton gradient (pHi 5.5; pHo 7.5). Voltage-clamping (Ki+ = Ko+ + valinomycin) reduced the uptake of 22Na+ by 40-50% indicating the presence of Na+ conductance. Dissipation of the Acridine orange fluorescence quench in ileal vesicles with a preformed pH gradient (pHi 5.5; pHo 7.5) was accelerated by either external Na+ or voltage-clamping in the absence of Na+. The effects of Na+ and voltage-clamping were additive under the above conditions. In the absence of a pH gradient, Acridine orange quenching was induced by intravesicular Na+ as well as an interior negative K+ diffusion potential. In voltage-clamped BBMV, pH-driven Na+ uptake was inhibited by amiloride (Ki = 140 microM). The initial rate of pH-driven Na+ uptake was saturable and conformed to Michaelis-Menten kinetics with apparent Km and Vmax values of 27 +/- 1 mM and 47 +/- 1 nmol.(mg protein)-1.(3 s)-1, respectively. Li+ and NH4+, but not Cs+, K+, Rb+ or choline+ inhibited pH gradient-driven 22Na+ uptake. The results demonstrate in human ileal brush-border membrane vesicles the presence of an Na+/H+ exchanger and conductive transport pathways for Na+ and H+.

    Title Particle Size Analysis of Gelatin-acacia Coacervate and Ethylcellulose Walled Microcapsules.
    Date June 1989
    Journal Journal of Microencapsulation
    Excerpt

    The Coulter counter has become one of the methods of choice for the measurement of small particle sizes. However, many colloidal walled microcapsules are prone to hydration when dispersed in the electrolyte solution used in Coulter measurements. This hydration causes the walls to swell, producing different size analyses dependent upon the time of measurement. In the present work the change in size with time was studied for microcapsules with gelatin-acacia coacervate, or ethylcellulose, walls. The former, although rendered insoluble with formalin, still hydrated; the latter were almost unaffected by water. A sample size of 30 mg was required to prevent blocking of the orifice with larger samples, or too few particles to permit measurement in smaller samples. The coacervate coated microcapsules showed a bimodal distribution, in part due to aggregate of smaller microcapsules, and this distribution changed significantly over the time of measurement. Although the peak due to larger microcapsules did not disappear, the number of large microcapsules fell significantly, most probably because of the disintegration of aggregated microcapsules. Microcapsules with ethyl cellulose walls did not show a bimodal distribution and the particle size analysis did not alter significantly with time.

    Title Georgia's Experience with Newborn Screening: 1981 to 1985.
    Date June 1989
    Journal Pediatrics
    Title Incidental Thrombosis of Prosthetic Vascular Grafts to the Lower Extremity After Colonoscopic Polypectomy.
    Date June 1988
    Journal Gastrointestinal Endoscopy
    Title Relationship Between Distention and Absorption in Rat Intestine. I. Effect of Luminal Volume on the Morphology of the Absorbing Surface.
    Date May 1988
    Journal Gastroenterology
    Excerpt

    Previous studies in vivo have suggested that distention of the intestinal lumen may enhance intestinal absorption by augmenting absorptive surface area. The precise anatomic mechanism for this increase in surface area, however, has not been explored in detail. We developed methods for rapidly freezing and fixing intestinal segments in situ in the nondistended or distended state. Distention led to a reduction in villus height (309.2 +/- 9.9 to 230.7 +/- 11.8 micron) and a marked increase in the width of intervillus space in both the transverse (50.4 +/- 4.8 to 298.0 +/- 24.8 micron) and longitudinal (15.2 +/- 3.4 to 76.0 +/- 10.6 micron) dimensions. There was, however, no absolute change in total mucosal surface area. The changes in morphology occurred instantaneously, were entirely reversible, and were demonstrated at pressures that occur spontaneously in the mammalian intestine. These studies demonstrate that luminal distention results in marked alterations in intestinal histology that promote increased access of luminal contents to intervillus transport sites in the intestine in vivo. The resulting alterations could lead to an increase in functional rather than absolute absorptive surface area.

    Title Relationship Between Distention and Absorption in Rat Intestine. Ii. Effects of Volume and Flow Rate on Transport.
    Date May 1988
    Journal Gastroenterology
    Excerpt

    Studies in intact animals have shown that intestinal solute absorption may be enhanced with increasing intraluminal volume and flow rate, perhaps because of increases in functional absorptive surface area or perturbation of unstirred layers. We used single-pass perfusions of rat ileum, performed by simultaneously infusing and withdrawing at equal rates, to determine the separate effects of volume and flow rate on solute absorption at pressures between 3.0 and 12.5 cmH2O. Distention enhanced the absorption of passive probes (3H2O, urea), had no effect on the absorption of solutes transported by carrier mechanisms (D-glucose, L-alanine), and led to decreases in the net absorption of sodium and water whenever intraluminal pressure exceeded 10 cmH2O. Increasing flow rate enhanced the absorption of both glucose and 3H2O. However, the effects of increasing flow rate and distention on 3H2O were not additive. In the presence of higher filling volume, faster flow rate led to no further increases in 3H2O absorption; vice versa, at faster flow rate, no further increases in 3H2O absorption were noted when luminal volume was increased. We conclude that increased intraluminal volume enhances the absorption of solutes transported by passive but not carrier-mediated mechanisms, perhaps via augmentation of functional absorptive surface area. Increased flow rate and volume may increase the absorption of passively absorbed probes, in part, by a similar mechanism.

    Title Rectal Reservoir Reduction Procedures for Internal Rectal Prolapse.
    Date November 1987
    Journal Diseases of the Colon and Rectum
    Excerpt

    Forty-four patients presenting with painful outlet constipation had internal rectal intussusception documented by cinedefecography. Rectal reservoir reduction by multiple elastic ligation or staple excision of redundant mucosa effectively improved bowel function and outlet symptoms in the majority of patients. Rectal reduction procedures were performed under intravenous sedation with antibiotic coverage, no postoperative sepsis, and a single case of significant postoperative bleeding. Associated abnormalities on defecography were unaffected.

    Title Augmentation of Neutral Sodium Chloride Absorption by Increased Flow Rate in Rat Ileum in Vivo.
    Date September 1986
    Journal The Journal of Clinical Investigation
    Excerpt

    Studies in intact animals have shown that intestinal solute absorption is enhanced with increasing flow rates; the mechanism of this phenomenon has not been explored in detail. We used single pass perfusions of rat ileum to study the effect of higher flow rate on electrolyte absorption. Augmenting perfusion rate from 0.5 to 5.0 ml/min resulted in increased rates of sodium (11.0 +/- 0.9 vs. 23.5 +/- 2.7 mueq/min X g) and chloride (12.1 +/- 0.8 vs. 25.0 +/- 2.2 mueq/min X g) absorption, reduction in the estimated unstirred layer thickness (668 +/- 31 vs. 433 +/- 28 micron), minimal changes in intraluminal pressure and transmural potential difference, and a small, though significant, increase in intraluminal volume (19.4 +/- 8.4%). Removal of sodium from the perfusion medium abolished the effect of increased flow rate on chloride absorption as did removal of chloride on sodium absorption; addition of furosemide or acetazolamide to Ringer's solution also inhibited this effect. In separate experiments, stepwise increases in intraluminal volume were induced by elevating the outflow tubing; no effect on electrolyte transport was observed. These studies demonstrate that neutral sodium chloride absorption is enhanced in rat ileum at higher flow rates, perhaps as a result of a decrease in the thickness of unstirred layers.

    Title Planning a Statewide Genetic Screening Program: Defining Program Functions to Achieve Desired Outcomes.
    Date December 1985
    Journal American Journal of Medical Genetics
    Excerpt

    When responsibility for administering the Genetic Screening Program in Georgia was transferred from an academic institution to state authority in 1982, the need was identified to reassess program planning. Accordingly, a cooperative effort was initiated between the Director of the Genetic Screening Program and representatives of the Centers for Disease Control to define desired program outcomes and the functions that should be performed to achieve these outcomes. This cooperative effort resulted in the development of specific and measurable outcomes for Georgia's Genetic Screening Program. These desired outcomes indicate the degree of reduction in morbidity and mortality associated with genetic diseases the Program is expected to achieve within a specified period of time. The major actions that should be taken to achieve these outcomes were also identified and delineated in sequence using flowchart format. These explicit descriptions of desired program outcomes and the functions necessary to achieve these outcomes provide the Genetic Screening Program Director with a valuable resource to use in planning program activities and assessing the extent to which the Program is successful in achieving its overall goal of reducing morbidity and mortality associated with genetic diseases.

    Title Bifid Epiglottis, Hand Anomalies, and Congenital Hypopituitarism.
    Date October 1985
    Journal Lancet
    Title Cutaneous Autoinoculation by Mycobacterium Tuberculosis.
    Date July 1982
    Journal Archives of Dermatology
    Title Preparation and Release Characteristics of Potassium Chloride Microcapsules.
    Date July 1981
    Journal Journal of Pharmaceutical Sciences
    Excerpt

    The release characteristics of potassium chloride was studied when it was coated with a selection of polymers; from the results obtained, a suitable batch was microencapsulated using a gelatin-gum arabic coacervate system. The microencapsulated product offers better controlled release for this drug when compared to standard table and powder forms.

    Title The Induction of Cellular Dna Synthesis in G1-arrested Bkh21 Cell Infected with Adenovirus Type 2.
    Date August 1980
    Journal The Journal of General Virology
    Excerpt

    G1-arrested BHK21 cells infected with adenovirus type 2 were studied to determine the effect of infection on host DNA synthesis in a productive cycle of infection. At various intervals following infection, analysis of the intracellular DNA was carried out by zonal sedimentation centrifugation through alkaline sucrose gradients. In addition to material which sedimented to the position of the virus markers (34S), a class of high mol. wt. DNA (40 to 100S) was found to be synthesized beginning approx. 13 h p.i. and continuing up to about 35 h p.i. DNA--DNA hybridization studies on this newly synthesized DNA showed it to be cellular DNA. When this material was density labelled with 5-bromodeoxyuridine and centrifuged to equilibrium through alkaline CsCl gradients, it was found to be the product of semi-conservation replication and not of repair synthesis.

    Title Genetic Disease Programs and the Black Community.
    Date December 1979
    Journal Urban Health
    Title Virus-like Particles and Double Stranded Rna from Killer and Non-killer Strains of Saccharomyces Cerevisiae.
    Date August 1979
    Journal Microbios
    Excerpt

    Virus-like particles and DsRNA found in extracts of killer, non-killer and suppressive non-killer strains were co-precipitated from cell extracts using an antibody prepared against purified virus-like particles isolated from a non-killer strain having only the higher molecular weight L dsRNA. The relative amount of virus-like particles correlated roughly with the amount of dsRNA: those strains with high concentrations of dsRNA had the most particles. When a preparation of particles was subjected to sucrose gradient velocity centrifugation, particles containing the S and M dsRNA could be separated from those containing the L dsRNA. These experiments taken together suggest that the L, M and S dsRNAs are separately encapsulated by the same protein coat.

    Title Umbilical Artery Catheters: High, Low, or No.
    Date September 1978
    Journal Journal of Perinatal Medicine
    Title Relationship Between the Plasma Glucose Level and Glucose Uptake in the Conscious Dog.
    Date August 1978
    Journal Metabolism: Clinical and Experimental
    Excerpt

    In the absence of a change in the pancreatic hormonal milieu, elevations in the normal fasting plasma glucose level have little effect on glucose clearance. In view of these data, and the previously established responsiveness of M to hormones, glucose clearance can be considered to represent a useful index of hormone action on glucose uptake in vivo. Care should be taken, however, when interpreting clearance data obtained under hypoglycemic conditions, since there is a possibility that clearance may spontaneously increase at very low plasma glucose levels.

    Title Letter: Effect of Speaking Mode on Temporal Factors in Speech: Vowel Duration.
    Date January 1975
    Journal The Journal of the Acoustical Society of America
    Title Effects of Risperidone on Procedural Learning in Antipsychotic-naive First-episode Schizophrenia.
    Date
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    Studies of procedural learning in medicated schizophrenia patients using predictive saccade paradigms have consistently demonstrated hypometric predictive responses. Findings from antipsychotic-naive schizophrenia patients indicate fewer or no deficits. This pattern of findings suggests that antipsychotic medications might adversely affect frontostriatal systems supporting procedural learning on this task. The accuracy and latency of predictive saccades were assessed in 25 antipsychotic-naive first-episode schizophrenia patients and 22 matched healthy individuals. Patients were retested after 6 weeks of treatment with risperidone. Healthy individuals were reevaluated after a similar time period. The ability to learn to time response initiation in anticipation of target appearance (target prediction) was not impaired in patients before or after treatment. In contrast, although no deficits were evident before treatment initiation, after treatment patients showed a marked decrease in the accuracy of predictive but not sensory-guided responses. The findings from pretreatment testing indicate that procedural learning is a relatively unaffected cognitive domain in antipsychotic-naive first-episode schizophrenia. Although treatment-emergent extrapyramidal symptoms were minimal, these data suggest that D2 antagonism in striatum after risperidone treatment was sufficiently robust to disrupt the generation of planned volitional behavior guided by internalized representations.Neuropsychopharmacology advance online publication, 4 June 2008; doi:10.1038/npp.2008.79.

    Title Roots, Shoots and Reproduction: Sexual Dimorphism in Size and Costs of Reproductive Allocation in an Annual Herb.
    Date
    Journal Proceedings. Biological Sciences / The Royal Society
    Excerpt

    Females tend to be smaller than males in woody dioecious plant species, but they tend to be larger in herbs. The smaller size of females in woody species has been attributed to higher reproductive costs, yet no satisfactory explanation has been provided for their larger size in herbs. Because herbs have higher nitrogen concentrations in their tissues than woody plants, and because pollen is particularly rich in nitrogen, we predicted that male growth would be more compromised by reproduction than female growth. To test this hypothesis, we conducted three experiments on the annual dioecious herb Mercurialis annua. First, we compared the timing of reproduction between males and females and found that males started flowering earlier than females; early flowering is expected to compromise growth more than later flowering. Second, we compared plants allowed to flower with those prevented from flowering by experimental debudding and found that males incurred a higher reproductive cost than females in terms of both biomass and, particularly, nitrogen. Third, we grew plants under varying levels of nitrogen availability and found that although sexual size dimorphism was unaffected by nitrogen, females, but not males, decreased their relative allocation to both roots and reproduction under high nitrogen availability. We propose that males deal with the high cost of pollen production in terms of nitrogen by allocating biomass to nitrogen-harvesting roots, whereas females pay for carbon-rich seeds and fruits by investing in photosynthetic organs. Sexual dimorphism would thus seem to be the outcome of allocation to above- versus below-ground sinks that supply resources (carbon versus nitrogen) limiting the female and male reproduction differentially.

    Title Effects of Second-generation Antipsychotic Medication on Smooth Pursuit Performance in Antipsychotic-naive Schizophrenia.
    Date
    Journal Archives of General Psychiatry
    Excerpt

    CONTEXT: Analyses of smooth pursuit eye movement parameters in patients with schizophrenia provide information about the integrity of neural networks mediating motion perception, sensorimotor transformation, and cognitive processes such as prediction. Although pursuit eye tracking deficits have been widely reported in schizophrenia, the integrity of discrete components of pursuit responses and the effect of second-generation antipsychotic medication on them are not well established. OBJECTIVE: To examine different components of smooth pursuit performance in antipsychotic-naive patients with schizophrenia before and after treatment with second-generation antipsychotic medication. DESIGN, SETTING, AND PARTICIPANTS: Thirty-three antipsychotic-naive patients with schizophrenia performed 3 different smooth pursuit paradigms designed to evaluate specific components of the pursuit response. All of the patients were retested after 6 weeks of treatment with risperidone or olanzapine. Testing was also performed with 39 matched healthy individuals. Thirteen patients and 21 healthy participants were retested after 26 and 52 weeks. MAIN OUTCOME MEASURES: Pursuit initiation, maintenance gain (ratio of eye velocity over target velocity), and frequency of catch-up saccades during pursuit maintenance. RESULTS: Prior to treatment, pursuit gain when tracking less predictable ramp targets tended to be reduced, latency of pursuit initiation was speeded, and catch-up saccade frequency was increased during predictive pursuit. After antipsychotic treatment initiation, pursuit gain decreased with ramp targets, indicating treatment-emergent impairments in sensorimotor processing. No changes were observed for predictive pursuit. Exploratory analyses in the subgroup with follow-up to 1 year revealed that these effects continued through long-term follow-up with some partial normalization at 1 year. Deficits were unrelated to drug dosage and clinical ratings. CONCLUSIONS: Impaired sensorimotor function was observed after initiation of second-generation antipsychotic medications, which may be explained by their serotonergic antagonism of brainstem sensorimotor systems. Predictive mechanisms supported by frontostriatal-cerebellar circuitry were not affected by treatment initiation and appear able to compensate for treatment-emergent sensorimotor impairments during predictive tracking.

    Title Comparison of the Production, Quality, and in Vitro Maturation Capacity of Oocytes from Untreated Cycling and Intermediate Phase Equine Serum Gonadotropin-treated Fat-tailed Dunnarts (sminthopsis Crassicaudata).
    Date
    Journal Reproduction (cambridge, England)
    Excerpt

    This study describes ovarian changes during the natural and stimulated reproductive cycle of breeding (< or =12 month) and retired (>12 month) fat-tailed dunnarts, Sminthopsis crassicaudata. Increased urinary cornified epithelial cells and the influx of leukocytes defined day 0, at which time the naturally cycling females had already ovulated; at day 16 females had no antral follicles, but by day 20 antral follicles had begun to develop. There was no difference between naturally cycling breeding and retired females. Females were stimulated with 1 IU equine serum gonadotropin (eSG) during the intermediate phase on day 16 and killed 3, 4, or 5 days later. Stimulation resulted in a significant increase in the number of growing antral follicles but retired females demonstrated a reduced response. Upon collection from breeding females 4 days following eSG stimulation, 100% of oocytes were at the first polar body (PB1) stage, those collected from retired females were immature upon collection but within 48 h 98.2+/-1.9% were cultured to the PB1 stage. The rate of ovulation was high in breeding females 5 days following stimulation but retired females were less reliable, and in both groups all oocytes were degraded. This is the first study to describe a reliable technique, involving ovarian stimulation during the intermediate phase and segregation of age groups, allowing the collection of a large number of healthy PB1 stage oocytes from S. crassicaudata. This is important for the development of further assisted reproductive techniques for this species and threatened dasyurids.

    Title Computers and Psychosocial Treatment for Child Anxiety: Recent Advances and Ongoing Efforts.
    Date
    Journal Depression and Anxiety
    Excerpt

    Building on the empirical data supporting the efficacy of cognitive-behavioral therapy (CBT) for child anxiety, researchers are working on the development and evaluation of cost-effective and transportable CBT approaches. Related to this, a widely endorsed goal is to disseminate evidence-based treatments from research settings to community settings. Computer-assisted treatments have emerged as a means to provide cost-effective and efficient service to an increased number of anxious youth for whom a CBT treatment would be otherwise unavailable. We offer a rationale for the development and evaluation of computer-assisted psychosocial treatments for anxiety in youth, offer illustrative advances made in this area, and describe our efforts in using computers to enhance dissemination of CBT for child anxiety. Specifically, our illustrations include a description of (a) Camp-Cope-A-Lot (CCAL), a computer-assisted CBT for the treatment of anxiety disorders in youth ages 7-12, and (b) CBT4CBT: Computer-based training in CBT for anxious youth. Findings from evaluations of these programs are summarized, and further advances are proposed and discussed.


    Similar doctors nearby

    Dr. Jean Manning

    Ophthalmology
    30 years experience
    Dallas, TX

    Dr. Sylvia Hargrave

    Ophthalmology
    20 years experience
    Dallas, TX

    Dr. Tomasz Wiraszka

    Ophthalmology
    1 years experience
    Dallas, TX

    Dr. Charles Key

    Ophthalmology
    Dallas, TX

    Dr. Norman Slusher

    Ophthalmology
    36 years experience
    Dallas, TX

    Dr. Michael Milner

    Ophthalmology
    20 years experience
    Dallas, TX
    Search All Similar Doctors