Otolaryngologists, Plastic Surgery Specialist
9 years of experience
Video profile
Accepting new patients
LM Otolaryngology
88 McMillen Dr
Newark, OH 43055
740-348-4270
Locations and availability (2)

Education ?

Medical School Score Rankings
University of Cincinnati (2001)
  • Currently 3 of 4 apples
Top 50%

Awards & Distinctions ?

Awards  
Patients' Choice Award (2011 - 2012)
Compassionate Doctor Recognition (2011 - 2012)
Associations
American Academy of Otolaryngology: Head and Neck Surgery
American Board of Otolaryngology

Affiliations ?

Dr. Parker is affiliated with 1 hospitals.

Hospital Affilations

Score

Rankings

  • Licking Memorial Hospital
    Otolaryngology
    1320 W Main St, Newark, OH 43055
    • Currently 4 of 4 crosses
    Top 25%
  • Publications & Research

    Dr. Parker has contributed to 67 publications.
    Title Evaluating the Utility of Microsatellites for Investigations of Autopolyploid Taxa.
    Date October 2011
    Journal The Journal of Heredity
    Excerpt

    Autopolyploid taxa present numerous challenges for population genetic analyses due to difficulties determining allele dosage. Dosage ambiguity hinders accurate assessment of allele frequencies, multilocus genotypes (MLGTs), as well as levels and patterns of clonality. The pervasiveness of polyploidy in the evolutionary history of plant taxa makes this a recurring problem. Whereas diploidization of loci may occur over time, duplication of at least some loci is still frequently evident. Fortunately, with high-quality allozyme gels, it is possible to accurately infer allele dosage and, thus, determine exact MLGTs. However, accurately assessing dosage of microsatellite peaks is nearly impossible when studying wild populations with a large number of alleles per locus. Even if precise knowledge of genotypes is not required, for comparable numbers of alleles per locus and loci, the number of "phenotypes" is always lower with microsatellites than allozymes due to the inability to assess allele dosage. Microsatellite loci typically have more alleles per locus relative to allozymes although fewer loci are generally employed. Here, we present a mathematical model for comparing the relative utility of simple sequence repeat (SSR) versus allozyme markers to discriminate MLGTs. For example, the average plant allozyme study (2.6 alleles per locus, 10 polymorphic loci) has better discriminating power than SSR markers with 10 alleles at each of 3 loci, 9 alleles at 4 loci, 6 alleles at 5 loci, 5 alleles at 6 loci, and 4 alleles at 8 loci, demonstrating the value of assessing the relative discriminating power of these markers.

    Title The Better Beginnings, Better Futures Project: Findings from Grade 3 to Grade 9.
    Date April 2011
    Journal Monographs of the Society for Research in Child Development
    Excerpt

    Although comprehensive and ecological approaches to early childhood prevention are commonly advocated, there are few examples of long-term follow-up of such programs. In this monograph, we investigate the medium- and long-term effects of an ecological, community-based prevention project for primary school children and families living in three economically disadvantaged neighborhoods in Ontario, Canada. The Better Beginnings, Better Futures (BBBF) project is one of the most ambitious Canadian research projects on the long-term impacts of early childhood prevention programming to date. Bronfenbrenner's ecological model of human development informed program planning, implementation, and evaluation. Using a quasi-experimental design, the BBBF longitudinal research study involved 601 children and their families who participated in BBBF programs when children were between 4 and 8 years old and 358 children and their families from sociodemographically matched comparison communities. We collected extensive child, parent, family, and community outcome data when children were in Grade 3 (age 8–9), Grade 6 (age 11–12), and Grade 9 (age 14–15). The BBBF mandate was to develop programs that would positively impact all areas of child's development; our findings reflect this ecological approach. We found marked positive effects in social and school functioning domains in Grades 6 and 9 and evidence of fewer emotional and behavioral problems in school across the three grades. Parents from BBBF sites reported greater feelings of social support and more positive ratings of marital satisfaction and general family functioning, especially at the Grade 9 follow-up. Positive neighborhood-level effects were also evident. Economic analyses at Grade 9 showed BBBF participation was associated with government savings of $912 per child. These findings provide evidence that an affordable, ecological, community-based prevention program can promote long-term development of children living in disadvantaged neighborhoods and produce monetary benefits to government as soon as 7 years after program completion.

    Title Inferring Ancient Agave Cultivation Practices from Contemporary Genetic Patterns.
    Date July 2010
    Journal Molecular Ecology
    Excerpt

    Several Agave species have played an important ethnobotanical role since prehistory in Mesoamerica and semiarid areas to the north, including central Arizona. We examined genetic variation in relict Agave parryi populations northeast of the Mogollon Rim in Arizona, remnants from anthropogenic manipulation over 600 years ago. We used both allozymes and microsatellites to compare genetic variability and structure in anthropogenically manipulated populations with putative wild populations, to assess whether they were actively cultivated or the result of inadvertent manipulation, and to determine probable source locations for anthropogenic populations. Wild populations were more genetically diverse than anthropogenic populations, with greater expected heterozygosity, polymorphic loci, effective number of alleles and allelic richness. Anthropogenic populations exhibited many traits indicative of past active cultivation: fixed heterozygosity for several loci in all populations (nonexistent in wild populations); fewer multilocus genotypes, which differed by fewer alleles; and greater differentiation among populations than was characteristic of wild populations. Furthermore, manipulated populations date from a period when changes in the cultural context may have favoured active cultivation near dwellings. Patterns of genetic similarity among populations suggest a complex anthropogenic history. Anthropogenic populations were not simply derived from the closest wild A. parryi stock; instead they evidently came from more distant, often more diverse, wild populations, perhaps obtained through trade networks in existence at the time of cultivation.

    Title An Investigation of Methods to Detect Feigned Reading Disabilities.
    Date May 2010
    Journal Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists
    Excerpt

    No clinically proven method currently exists to determine if a test taker is feigning or exaggerating symptoms of a specific reading disability (RD) for potential secondary gain (i.e., extra time on examinations, access to bursary funds, or tax benefits). Our objective was to examine the utility of previously proposed symptom validity measures (i.e., the Dyslexia Assessment of Simulation or Honesty [DASH] and the resulting Feigning Index [FI]) in discriminating students with genuine RDs from sophisticated simulators given ample time to prepare, who were warned that noncredible performance could be detected. The DASH correctly classified almost 83% of coached simulators with no false positives. The FI accurately classified 86% of post-secondary students feigning RD without misidentifying any students with a genuine RD, resulting in 91.8% overall classification accuracy. These two methods show promise as a means of detecting noncredible performance in the assessment of RD.

    Title Interferon-stimulated Gene 15 (isg15) Conjugates Proteins in Dermatomyositis Muscle with Perifascicular Atrophy.
    Date March 2010
    Journal Annals of Neurology
    Excerpt

    We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin.

    Title Memory T-cell Responses to Vibrio Cholerae O1 Infection.
    Date November 2009
    Journal Infection and Immunity
    Excerpt

    Vibrio cholerae O1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. cholerae infection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. cholerae infection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. cholerae antigens, including the toxin-coregulated pilus (TcpA), a V. cholerae membrane preparation, and the V. cholerae cytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses to V. cholerae antigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. cholerae antigens.

    Title Nature of "tau" Immunoreactivity in Normal Myonuclei and Inclusion Body Myositis.
    Date November 2009
    Journal Muscle & Nerve
    Excerpt

    Sarcoplasmic accumulation of phosphorylated-tau has been widely stated to occur in and contribute to the pathogenesis of muscle disease in inclusion body myositis. Twenty inflammatory myopathy and 10 normal muscle samples along with a range of other tissues were stained with anti-"tau" antibodies (tau-5, pS422, and SMI-31). Myonuclear and sarcoplasmic fractions were prepared using differential solubilization and laser-capture microdissection, and immunoblots were performed using pS422 and SMI-31 antibodies. All three antibodies demonstrated anti-tau immunoreactivity in myonuclei from normal and diseased muscle, but not in nuclei from other tissues. Western blots showed pS422 and SMI-31 immunoreactivity against nuclear proteins outside the region expected for phosphorylated-tau. Antibodies previously reported to indicate abnormal accumulation of phosphorylated-tau in IBM myofibers react to normal myonuclei and recognize proteins other than tau. Normal myonuclei contain neurofilament H or other unidentified 200 kDa proteins with similar phosphorylated motifs accounting for SMI-31 immunoreactivity.

    Title Characterization of Human Skeletal Muscle Biopsy Samples Using Shotgun Proteomics.
    Date September 2009
    Journal Journal of Proteome Research
    Excerpt

    We characterized the human muscle proteome by studying muscle biopsy specimens through four different workflows, using 1 or 2D peptide separation, SDS gels, or differential solubilization. By performing MS/MS analyses of 178 4-h LC separations derived from 31 patients, we identified more than 2000 proteins, and determined how 370 very abundant proteins behave upon differential solubilization. The resulting semiquantitative database should serve as a resource for muscle biochemistry.

    Title Fast-twitch Sarcomeric and Glycolytic Enzyme Protein Loss in Inclusion Body Myositis.
    Date August 2009
    Journal Muscle & Nerve
    Excerpt

    Inclusion body myositis (IBM) is an inflammatory disease of skeletal muscle of unknown cause. To further understand the nature of the tissue injury in this disease, we developed methods for large-scale detection and quantitation of proteins in muscle biopsy samples and analyzed proteomic data produced by these methods together with histochemical, immunohistochemical, and microarray data. Twenty muscle biopsy samples from patients with inflammatory myopathies (n = 17) or elderly subjects without neuromuscular disease (n = 3) were profiled by proteomic studies using liquid chromatographic separation of peptides followed by mass spectrometry. Thirteen of the diseased samples additionally underwent microarray studies. Seventy muscle specimens from patients with a range of neuromuscular disorders were examined by ATPase histochemical methods. Smaller numbers of samples underwent immunohistochemical and immunoblot studies. Mass spectrometric studies identified and quantified approximately 300 total distinct proteins in each muscle sample. In IBM and to a lesser extent in polymyositis, proteomic studies confirmed by histochemical, immunohistochemical, and immunoblot studies showed loss of many fast-twitch specific structural proteins and glycolytic enzymes despite relative preservation of transcript levels. Increased abundance of a nuclear membrane protein, immunoglobulins, and two calpain-3 substrates were present. The atrophy present in IBM muscle is accompanied by preferential loss of fast-twitch structural proteins and glycolytic enzymes, particularly glycogen debranching enzyme, with relative preservation of the abundance of their respective transcripts. Although muscle atrophy has long been recognized in IBM, these studies are the first to report specific proteins which are reduced in quantity in IBM muscle.

    Title Identifying Students Feigning Dyslexia: Preliminary Findings and Strategies for Detection.
    Date March 2009
    Journal Dyslexia (chichester, England)
    Excerpt

    When conducting psychological evaluations, clinicians typically assume that individuals being evaluated are putting forth maximal effort and are not exaggerating or magnifying symptom complaints. Recent research, however, suggests that students undergoing post-secondary-level assessments to document learning difficulties may not always put forth their best effort, and may even be motivated to exaggerate or magnify symptoms. This paper presents evidence indicating that symptom exaggeration in this context is not only possible, but is indistinguishable from valid symptomatology when it occurs. We argue that symptom validity assessment should be included in all higher-education assessments for dyslexia and other specific learning disorders, and suggest some preliminary strategies for detection.

    Title Robust Prediction of the Mascot Score for an Improved Quality Assessment in Mass Spectrometric Proteomics.
    Date November 2008
    Journal Journal of Proteome Research
    Excerpt

    Protein identification by tandem mass spectrometry is based on the reliable processing of the acquired data. Unfortunately, the generation of a large number of poor quality spectra is commonly observed in LC-MS/MS, and the processing of these mostly noninformative spectra with its associated costs should be avoided. We present a continuous quality score that can be computed very quickly and that can be considered an approximation of the MASCOT score in case of a correct identification. This score can be used to reject low quality spectra prior to database identification, or to draw attention to those spectra that exhibit a (supposedly) high information content, but could not be identified. The proposed quality score can be calibrated automatically on site without the need for a manually generated training set. When this score is turned into a classifier and when features are used that are independent of the instrument, the proposed approach performs equally to previously published classifiers and feature sets and also gives insights into the behavior of the MASCOT score.

    Title Proteomic Analysis of Vibrio Cholerae in Human Stool.
    Date September 2008
    Journal Infection and Immunity
    Excerpt

    An effective vaccine for Vibrio cholerae is not yet available for use in the developing world, where the burden of cholera disease is highest. Characterizing the proteins that are expressed by V. cholerae in the human host environment may provide insight into the pathogenesis of cholera and assist with the development of an improved vaccine. We analyzed the V. cholerae proteins present in the stools of 32 patients with clinical cholera. The V. cholerae outer membrane porin, OmpU, was identified in all of the human stool samples, and many V. cholerae proteins were repeatedly identified in separate patient samples. The majority of V. cholerae proteins identified in human stool are involved in protein synthesis and energy metabolism. A number of proteins involved in the pathogenesis of cholera, including the A and B subunits of cholera toxin and the toxin-coregulated pilus, were identified in human stool. In a subset of stool specimens, we also assessed which in vivo expressed V. cholerae proteins were recognized uniquely by convalescent-phase as opposed to acute-phase serum from cholera patients. We identified a number of these in vivo expressed proteins as immunogenic during human infection. To our knowledge, this is the first characterization of the proteome of a pathogenic bacteria recovered from a natural host.

    Title Identifying Students Faking Adhd: Preliminary Findings and Strategies for Detection.
    Date October 2007
    Journal Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists
    Excerpt

    When conducting psychological evaluations, clinicians typically assume that the subject being evaluated is putting forth maximal effort and is not exaggerating or magnifying symptom complaints. While the field of neuropsychology has identified that factors, such as effort and motivation, can significantly interfere with correct interpretation of self-reported symptoms and test scores, evaluation methods for other psychological conditions, such as attention deficit hyperactivity disorder (ADHD) have not addressed effort and motivation as potential factors influencing accurate diagnosis. In analyzing the performance of students simulating ADHD, and comparing it to performance of both non-ADHD and genuine ADHD students, this study clearly demonstrated that the symptoms of ADHD are easily fabricated, and that simulators would be indistinguishable from those with true ADHD. In addition, students motivated to feign ADHD could easily perform poorly on tests of reading and processing speed, thus allowing them access to academic accommodations. Implications of these findings are discussed.

    Title Methodology Utilizing Ms Signal Intensity and Lc Retention Time for Quantitative Analysis and Precursor Ion Selection in Proteomic Lc-maldi Analyses.
    Date February 2007
    Journal Analytical Chemistry
    Excerpt

    This study describes a methodology for performing relative quantitation in large-scale proteomic sample comparisons using an LC-MALDI mass spectrometry analytical platform without the use of isotope tagging reagents. The method utilizes replicate analyses of a sample to create a profile of constituent components that are aligned based on LC elution time and mass. Once components from individual runs have been grouped as common "features", the Student's t test is used to determine which components are systematically different between samples. In this study, five HPLC runs of human plasma were compared to five HPLC runs of human serum. About 3889 components were detected in all 10 runs. Of these, 1831 corresponded to approximately 100 known serum proteins, based on MS/MS analysis of one run each from serum and plasma. As expected, fibrinogen alpha, beta, and gamma chains accounted for many of the most significant differences. Therefore, using MALDI, samples containing thousands of peptides can be compared in a minimal amount of time. Moreover, the results of the comparison can be used to guide further MS/MS mode sample interrogation in a result dependent manner.

    Title Peer and Parenting Characteristics of Boys and Girls with Subclinical Attention Problems.
    Date November 2006
    Journal Journal of Attention Disorders
    Excerpt

    This study examines peer and parenting characteristics of 149 boys and girls with and without subclinical attention problems.

    Title Depth of Proteome Issues: a Yeast Isotope-coded Affinity Tag Reagent Study.
    Date March 2005
    Journal Molecular & Cellular Proteomics : Mcp
    Excerpt

    As a test case for optimizing how to perform proteomics experiments, we chose a yeast model system in which the UPF1 gene, a protein involved in nonsense-mediated mRNA decay, was knocked out by homologous recombination. The results from five complete isotope-coded affinity tag (ICAT) experiments were combined, two using matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry (MS/MS) and three using electrospray MS/MS. We sought to assess the reproducibility of peptide identification and to develop an informatics structure that characterizes the identification process as well as possible, especially with regard to tenuous identifications. The cleavable form of the ICAT reagent system was used for quantification. Most proteins did not change significantly in expression as a consequence of the upf1 knockout. As expected, the Upf1 protein itself was down-regulated, and there were reproducible increases in expression of proteins involved in arginine biosynthesis. Initially, it seemed that about 10% of the proteins had changed in expression level, but after more thorough examination of the data it turned out that most of these apparent changes could be explained by artifacts of quantification caused by overlapping heavy/light pairs. About 700 proteins altogether were identified with high confidence and quantified. Many peptides with chemical modifications were identified, as well as peptides with noncanonical tryptic termini. Nearly all of these modified peptides corresponded to the most abundant yeast proteins, and some would otherwise have been attributed to "single hit" proteins at low confidence. To improve our confidence in the identifications, in MALDI experiments, the parent masses for the peptides were calibrated against nearby components. In addition, five novel parameters reflecting different aspects of identification were collected for each spectrum in addition to the Mascot score that was originally used. The interrelationship between these scoring parameters and confidence in protein identification is discussed.

    Title Electronic Western Blot of Matrix-assisted Laser Desorption/ionization Mass Spectrometric-identified Polypeptides from Parallel Processed Gel-separated Proteins.
    Date February 2005
    Journal Analytical Biochemistry
    Excerpt

    Identification of proteins previously separated by one-dimensional (1-D) or two-dimensional gel electrophoresis requires significant manipulations to digest the proteins into their respective peptides and to extract them from the gel prior to mass analysis. This article describes the simultaneous transfer and digestion of proteins directly from 1-D gels onto a membrane ready for matrix-assisted laser desorption/ionization (MALDI) mass spectrometric (MS) analysis. Protein transfer and digestion efficiencies are estimated to be more than 95%. The effectiveness of this procedure is demonstrated by identifying 110 unique proteins derived from a lysate of Escherichia coli and 149 proteins derived from a mouse liver homogenate separated by 1-D sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Using crude mouse liver homogenates, four distinct glutathione S-transferase classes, ranging from 23 to 27 kDa, are identified from a separating gel, indicating the discriminating potential for this method. A Visual Basic program allowed visualization of the identified proteins according to their respective positions on the 1-D gels. In many cases, two or more proteins could be identified within a single band of the SDS gel. The "digital" images generated resemble Western blots without the use of antibodies or signal amplification techniques.

    Title Result-driven Strategies for Protein Identification and Quantitation--a Way to Optimize Experimental Design and Derive Reliable Results.
    Date September 2004
    Journal Proteomics
    Excerpt

    Uni- or multidimensional microcapillary liquid chromatography (microLC) matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry (MS/MS) approaches have gained significant attention for quantifying and identifying proteins in complex biological samples. The off-line coupling of microLC with MS quantitation and MS/MS identification methods makes new result-dependent workflows possible. A relational database is used to store the results from multiple high performance liquid chromatography runs, including information about MALDI plate positions, and both peptide and protein quantitations, and identifications. Unlike electrospray methodology, where all the decisions about which peptide to fragment, must be made during peptide fractionations, in the MALDI experiments the samples are effectively "frozen in time". Therefore, additional MS and MS/MS spectra can be acquired, to promote more accurate quantitation or additional identifications until reliable results are derived that meet experimental design criteria. In the case of what can be designated the expression-dependent workflow, quantitation can be detached from identification and only peak pairs with biological relevant expression changes can be selected for further MS/MS analyses. Alternatively, additional MS/MS data can be acquired to confirm tentative peptide mass fingerprint hits in what is designated a search result-dependent workflow. In the MS data-dependent workflow, the goal is to collect as many meaningful spectra as possible by judiciously adjusting the acquisition parameters based on characteristics of the parent masses. This level of sophistication requires the development of innovative algorithms for these three result-dependent workflows that make MS and MS/MS analysis more efficient and also add confidence to experimental results.

    Title Urgent Adolescent Psychiatric Consultation: from the Accident and Emergency Department to Inpatient Adolescent Psychiatry.
    Date October 2003
    Journal Journal of Adolescence
    Excerpt

    The Rapid Response Model (RRM) provides psychiatric services to children and adolescents seen at the Accident and Emergency (A&E) department or at the Urgent Consultation Clinic of the Child and Adolescent Psychiatry Division the next day. In a naturally occurring experiment, the RRM was introduced, withdrawn and restarted. When RRM was withdrawn at one site, it was implemented at another. The RRM reduced nighttime Emergency Consultations and inpatient admissions from A&E, while it increased daytime consultations and daytime admissions. The RRM provided timely, organized emergency psychiatric services. A&E staff expressed satisfaction with the service.

    Title Toward a High-throughput Approach to Quantitative Proteomic Analysis: Expression-dependent Protein Identification by Mass Spectrometry.
    Date January 2002
    Journal Journal of the American Society for Mass Spectrometry
    Excerpt

    The isotope-coded affinity tag (ICAT) technology enables the concurrent identification and comparative quantitative analysis of proteins present in biological samples such as cell and tissue extracts and biological fluids by mass spectrometry. The initial implementation of this technology was based on microcapillary chromatography coupled on-line with electrospray ionization tandem mass spectrometry. This implementation lacked the ability to select proteins for identification based on their relative abundance and therefore to focus on differentially expressed proteins. In order to improve the sample throughput of this technology, we have developed a two-step approach that is focused on those proteins for which the abundance changes between samples: First, a new software program for the automated quantification of ICAT reagent labeled peptides analyzed by microcapillary electrospray ionization time-of-flight mass spectrometry determines those peptides that differ in their abundance and second, these peptides are identified by tandem mass spectrometry using an electrospray quadrupole time-of flight mass spectrometer and sequence database searching. Results from the application of this approach to the analysis of differentially expressed proteins secreted from nontumorigenic human prostate epithelial cells and metastatic cancerous human prostate epithelial cells are shown.

    Title Scoring Methods in Maldi Peptide Mass Fingerprinting: Chemscore, and the Chemapplex Program.
    Date January 2002
    Journal Journal of the American Society for Mass Spectrometry
    Excerpt

    No universally accepted score is currently available to determine when a matrix-assisted laser desorption ionization (MALDI) peptide mass fingerprint (PMF) experiment has been successfully carried out. We describe a software program (ChemApplex) based on a calculated parameter (Combined Protein Score) that takes into account (1) peak intensity, (2) the mass accuracy of the match, and (3) ChemScore, a theoretical intensity factor that estimates the probability of observing a particular peptide based on a combination of chemical considerations, in particular the amino acid composition of the peptide and the amino acid sequence of the amino acids that span the cleavage site. When these three factors are taken into account both at the level of individual peptides and at the protein level, protein components in mixtures whose peptides contribute less than 1% of the total intensity can often be correctly identified, as is demonstrated for mixtures of standard proteins. Moreover, it is possible to make robust database identifications that are nearly independent of the number of masses submitted and the mass error threshold used for matching. Protein scoring based on Combined Protein Score is orthogonal to many of the commonly used probability-based scoring schemes, and makes it possible to archive a more complete set of parameters that more thoroughly characterize the validity of the database match, which increases the confidence in the identifications.

    Title Fine-scale Genetic Structure in Pinus Clausa (pinaceae) Populations: Effects of Disturbance History.
    Date December 2001
    Journal Heredity
    Excerpt

    Spatial autocorrelation analyses of 12 allozyme loci were used to compare genetic structure within populations of two varieties of Pinus clausa. P. clausa var. immuginata populations tend to be uneven-aged, with continuous recruitment in small gaps created by wind damage, whereas P. clausa var. clausa populations are more even-aged, with recruitment postdating periodic canopy fires. Three var. immuginata populations and three matched pairs of var. clausa populations, including both a mature and a nearby recently burned population, were examined. Aggregation of multilocus genotypes at small distances was evident in all young var. clausa populations. Little inbreeding was apparent among juveniles or adults in these populations; their genetic structure is likely to have resulted from limited seed dispersal. Genotypes were not significantly spatially structured in nearby matched mature populations. Genetic structure was less evident in var. immuginata populations. Aggregated genotypes were only apparent in the population where patches included juveniles of similar ages; dense juvenile clumps in the other two var. immuginata populations comprised a variety of ages. Interannual variability in allele frequencies of surviving seedlings may account for the absence of genetic structure in these populations.

    Title Eye Movement Desensitization and Reprocessing (emdr): a Meta-analysis.
    Date July 2001
    Journal Journal of Consulting and Clinical Psychology
    Excerpt

    Eye movement desensitization and reprocessing (EMDR), a controversial treatment suggested for posttraumatic stress disorder (PTSD) and other conditions, was evaluated in a meta-analysis of 34 studies that examined EMDR with a variety of populations and measures. Process and outcome measures were examined separately. and EMDR showed an effect on both when compared with no treatment and with therapies not using exposure to anxiety-provoking stimuli and in pre post EMDR comparisons. However, no significant effect was found when EMDR was compared with other exposure techniques. No incremental effect of eye movements was noted when EMDR was compared with the same procedure without them. R. J. DeRubeis and P. Crits-Christoph (1998) noted that EMDR is a potentially effective treatment for noncombat PTSD. but studies that examined such patient groups did not give clear support to this. In sum, EMDR appears to be no more effective than other exposure techniques, and evidence suggests that the eye movements integral to the treatment, and to its name, are unnecessary.

    Title Attachment Security: a Meta-analysis of Maternal Mental Health Correlates.
    Date May 2001
    Journal Clinical Psychology Review
    Excerpt

    This meta-analysis addresses the association between attachment security and each of three maternal mental health correlates. The meta-analysis is based on 35 studies, 39 samples, and 2,064 mother-child pairs. Social-marital support (r = .14; based on 16 studies involving 17 samples and 902 dyads), stress (r = .19; 13 studies, 14 samples, and 768 dyads), and depression (r = .18; 15 studies, 19 samples, and 953 dyads) each proved significantly related to attachment security. All constructs showed substantial variance in effect size. Ecological factors and approach to measuring support may explain the heterogeneity of effect sizes within the social-marital support literature. Effect sizes for stress varied according to the time between assessment of stress and assessment of attachment security. Among studies of depression, clinical samples yielded significantly larger effect sizes than community samples. We discuss these results in terms of measurement issues (specifically, overreliance on self-report inventories) and in terms of the need to study the correlates of change in attachment security, rather than just the correlates of attachment security per se.

    Title Bipolar Disorder in Adhd Children Grown Up.
    Date June 2000
    Journal Journal of the American Academy of Child and Adolescent Psychiatry
    Title The Murine Liver-specific Nonclassical Mhc Class I Molecule Q10 Binds a Classical Peptide Repertoire.
    Date March 2000
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    The biological properties of the nonclassical class I MHC molecules secreted into blood and tissue fluids are not currently understood. To address this issue, we studied the murine Q10 molecule, one of the most abundant, soluble class Ib molecules. Mass spectrometry analyses of hybrid Q10 polypeptides revealed that alpha1alpha2 domains of Q10 associate with 8-9 long peptides similar to the classical class I MHC ligands. Several of the sequenced peptides matched intracellularly synthesized murine proteins. This finding and the observation that the Q10 hybrid assembly is TAP2-dependent supports the notion that Q10 groove is loaded by the classical class I Ag presentation pathway. Peptides eluted from Q10 displayed a binding motif typical of H-2K, D, and L ligands. They carried conserved residues at P2 (Gly), P6 (Leu), and Pomega (Phe/Leu). The role of these residues as anchors/auxiliary anchors was confirmed by Ala substitution experiments. The Q10 peptide repertoire was heterogeneous, with 75% of the groove occupied by a multitude of diverse peptides; however, 25% of the molecules bound a single peptide identical to a region of a TCR V beta-chain. Since this peptide did not display enhanced binding affinity for Q10 nor does its origin and sequence suggest that it is functionally significant, we propose that the nonclassical class I groove of Q10 resembles H-2K, D, and L grooves more than the highly specialized clefts of nonclassical class I Ags such as Qa-1, HLA-E, and M3.

    Title Maldi-tof Based Mutation Detection Using Tagged in Vitro Synthesized Peptides.
    Date February 2000
    Journal Nature Biotechnology
    Excerpt

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) is a powerful method to quickly and accurately determine the masses of peptides. Most genetic analyses, however, begin with PCR amplification of a test sequence to generate DNA, which is more difficult than peptides to analyze by MALDI-TOF. We describe a method that produces a PCR product of any continuous region of coding sequence which can then be used to encode an N-terminally tagged test peptide in a coupled in vitro transcription/translation reaction. The test peptide is purified using the tag, and its mass is measured by MALDI-TOF. Truncations and amino acid substitutions in peptides coded for by the breast cancer susceptibility gene BRCA1 were readily identified using this method. The process can be multiplexed and is amenable to automation, providing an efficient, high-throughput means for mutation discovery and genetic profiling.

    Title Relational V-code Conditions in a Child and Adolescent Population Do Warrant Treatment.
    Date September 1999
    Journal Journal of Marital and Family Therapy
    Excerpt

    It is often argued that relational V-code conditions are less serious than classical psychiatric disorders, and that they should therefore receive lower clinical priority or diminished levels of treatment funding. Despite these common assertions, there have been virtually no studies that have used actual case data to evaluate whether such problems are in fact less serious and less worthy of treatment funding. We used actual case data from a universally funded child and family clinic to evaluate these questions. Results showed that both classical diagnoses and relational problems were significantly related to markers of clinical severity. As with previous research, family therapy was not differentially associated with a larger number of treatment sessions.

    Title Identification of Yeast Proteins from Two-dimensional Gels: Working out Spot Cross-contamination.
    Date January 1999
    Journal Electrophoresis
    Excerpt

    With the complete sequence of the yeast genome now available, efforts by many laboratories are underway to identify each of the spots on two-dimensional (2-D) gels corresponding to the most abundant yeast proteins. The high mass accuracy now attainable using matrix assisted laser desorption/ionization (MALDI)-mass spectrometry equipped with delayed extraction simplifies the process of identification, such that many spots can be unambiguously identified in a short period of time merely by using peptide mass fingerprinting and generally available database matching programs. Although it is not always possible to match spots between gels run by different laboratories, proteins generally yield the same abundant proteolytic fragments when tryptic digestions are performed. Databases containing these signature peptides not only simplify the task of reidentifying proteins from different gels, but also make it possible to identify small amounts of cross-contaminating proteins from different spots, as well as common extraneous contaminants such as human keratins. In this paper, we present data on the identification of > 20 previously unreported yeast proteins from 2-D gels. Some novel proteins were identified from randomly analyzed spots. Focusing on 14 spots in a narrow-pH-range gel, we demonstrate how organizing peak-table data and peptide match-list data into databases enables the identification of a larger percentage of the peaks.

    Title Plasmodium Falciparum Pfs40, Renamed Pf39, is Localized to an Intracellular Membrane-bound Compartment and is Not Sexual Stage-specific.
    Date April 1998
    Journal Molecular and Biochemical Parasitology
    Title Genetic Analysis on the Nifw by Utilizing the Yeast Two-hybrid System Revealed That the Nifw of Azotobacter Vinelandii Interacts with the Nifz to Form Higher-order Complexes.
    Date April 1998
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Nitrogenase is a complex metalloenzyme composed of two separately purified proteins designated the Fe-protein and the MoFe-protein. Apart from these two proteins, a number of accessory proteins are essential for the maturation and assembly of nitrogenase. Even though experimental evidence suggests that these accessory proteins are required for nitrogenase activity, the exact roles played by many of these proteins in the functions of nitrogenase are unclear. Our studies were directed to understand the role of two nif accessory proteins, the NifW and the NifZ in the biological nitrogen fixation. To accomplish this, we have utilized a genetic method, the Yeast based Two-Hybrid protein-protein interaction assay. This analysis showed that the NifW could interact with itself to make a multimeric complex. In contrast, the NifZ could not interact with itself. However, the NifZ could interact with the NifW. Previously it was shown that mutating either the NifW or the NifZ have similar effects on the activity of nitrogenase. This observation indicated that both these proteins may exert their regulation on the nitrogenase by a common pathway. Furthermore, it was suggested that the NifW plays a role in the oxygen-protection of the MoFe-protein by direct physical interaction. Our observation that the NifW can interact with itself as well as with the NifZ, suggests that the NifW and the NifZ may form a higher order complex and such a complex may be needed to exert the effects of the NifW or the NifZ on the nitrogenase activity.

    Title Mothers' Representations of Their Infants Assessed Prenatally: Stability and Association with Infants' Attachment Classifications.
    Date September 1997
    Journal Journal of Child Psychology and Psychiatry, and Allied Disciplines
    Excerpt

    The stability and predictive validity of classifications of mothers' representations of their infants as determined by the Working Model of the Child Interview (WMCI) were examined. Concordance between mothers' representations of their infants assessed prenatally and again one year later and infant Strange Situation (SS) attachment classifications at 12 months was also examined. WMCI classifications were stable over 12 months in 80% of mothers, compared to 51% expected by chance alone. Pregnancy WMCIs predicted infant SS classifications in 74% of cases, compared to 54% expected by chance. Concordance between 11-month WMCI and 12-months SS classifications was 73% (vs. 55% expected by chance). Problems with the skewed distribution of the sample, the low concordance between pregnancy and 11 months for one of the three classifications, and future directions for research are discussed.

    Title Peptides Isolated from Hla-cw*0304 Confer Different Degrees of Protection from Natural Killer Cell-mediated Lysis.
    Date July 1997
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    HLA class I molecules bind peptides derived from proteins degraded in the cytoplasm and display them for surveillance by the immune system. The recognition of HLA class I molecules by natural killer (NK) cells generally inhibits the lytic process. To investigate the role of peptides in the interaction between HLA class I molecules and NK receptors, we first had to identify representative endogenous peptides. Individual peptides bound to HLA-Cw*0304 were isolated and sequenced by tandem mass spectrometry. These peptides ranged in length from 8 to 11 residues and shared an alanine at position 2 and a C-terminal leucine. The murine transporters associated with antigen processing (TAP)-deficient cell line RMA-S was transfected with HLA-Cw*0304 to test whether HLA molecules loaded with a single peptide could deliver the inhibitory signal to NK cells expressing p58.2, which is a killer cell inhibitory receptor known to interact with HLA molecules bearing the HLA-Cw3 public epitope. We found that, in the absence of exogenous peptides, the HLA-Cw*0304 transfectants were killed at levels comparable to untransfected RMA-S cells whereas protection from lysis required both HLA-Cw*0304 heavy chain expression and an exogenously added HLA-Cw*0304-binding peptide. Importantly, not only were HLA-Cw*0304-binding peptides required for protection, but the ability of individual peptides to provide protection differed widely. These studies indicate that the ability to distinguish between subsets of peptides may be a general feature of HLA class I recognition by NK cells.

    Title Identification of an Epitope Derived from Human Proteolipid Protein That Can Induce Autoreactive Cd8+ Cytotoxic T Lymphocytes Restricted by Hla-a3: Evidence for Cross-reactivity with an Environmental Microorganism.
    Date April 1997
    Journal Journal of Neuroimmunology
    Excerpt

    The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-A3-restricted CD8+ CTL response from HLA-A3+ donors. These PLP peptide-specific CTL could lyse HLA-A3+ target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8+ CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism.

    Title Molecular Analysis of Presentation by Hla-a2.1 of a Promiscuously Binding V3 Loop Peptide from the Hiv-envelope Protein to Human Cytotoxic T Lymphocytes.
    Date March 1997
    Journal International Immunology
    Excerpt

    P18(IIIB) is a highly immunogenic peptide from the V3 loop of the HIV-1 gp160 envelope protein that is presented promiscuously by multiple class I MHC molecules. Understanding the molecular basis for promiscuous presentation may have many practical applications. As the highly prevalent HLA-A2.1 class I molecule is known to present P18(IIIB) for recognition by cytotoxic T lymphocytes (CTL) found in peripheral blood mononuclear cells of HIV+ donors, a P18(IIIB)-specific CTL line was generated from and HLA-A2(+), HIV- donor in order to define the molecular basis for, and ultimately improve upon the binding of, this peptide to HLA-A2.1. The minimal epitope recognized by the line was a decamer, I10, with the sequence RGPGRAFVTI. Interestingly, this decamer is identical to the minimal epitope from P18(IIIB) seen by murine CTL restricted by H-2Dd. A panel of Ala-substituted peptides was employed in MHC-binding and T cell response studies to identify MHC- and TCR-binding residues. Notably, many of the agretopic and epitopic residues identified were identical to those involved in the corresponding interactions of I10 with the H-2Dd MHC molecule and murine I10-specific CTL. The I10 peptide does not contain the described HLA-A2.1 binding motif. Instead a Pro at P3, a Phe at P7 and an Ile at P10 are utilized for MHC binding. Agretopic residue similarities with the hepatitis B nucleocapsid decamer suggest that these residues may comprise an alternative motif of anchors utilized by decamers for binding to HLA-A2.1.

    Title Peptide Sequence Requirements for the Recognition of Hla-b*2705 by Specific Natural Killer Cells.
    Date December 1996
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    NK clones that were inhibited by target cell expression of HLA-B*2705 displayed peptide-specific recognition of HLA-B*2705. To evaluate the specificity of this recognition, synthetic versions of 14 endogenous ligands of HLA-B*2705 were tested for their ability to provide protection from NK-mediated lysis by binding to surface HLA-B*2705 molecules on RMA-S cells deficient in the transporter for Ag presentation. Several unrelated peptides inhibited lysis by the same NK clones. Despite similar capacities to stabilize HLA-B*2705 molecules on RMA-S cells, the 14 peptides differed widely in their abilities to provide protection. Single amino acid substitutions in both a protective and a nonprotective peptide revealed the importance of residues 7 and 8 in the peptide for recognition by NK clones, thus localizing the peptide influence to a polymorphic region of the alpha-helix of HLA class I molecules known to control discrimination among allelic variants of HLA-B and HLA-C by NK cells.

    Title Irradiated Sporozoite Vaccine Induces Hla-b8-restricted Cytotoxic T Lymphocyte Responses Against Two Overlapping Epitopes of the Plasmodium Falciparum Sporozoite Surface Protein 2.
    Date December 1995
    Journal The Journal of Experimental Medicine
    Excerpt

    Vaccines designed to protect against malaria by inducing CD8+ cytotoxic T lymphocytes (CTL) in individuals of diverse HLA backgrounds must contain multiple conserved epitopes from various preerythrocytic-stage antigens. Plasmodium falciparum sporozoite surface protein 2 (PfSSP2) is considered an important antigen for inclusion in such vaccines, because CD8+ CTL against the P. yoelii SSP2 protect mice against malaria by eliminating infected hepatocytes. To develop PfSSP2 as a component of malaria vaccines, we investigated the presence of anti-PfSSP2 CTL in two HLA-B8+ volunteers immunized with irradiated P. falciparum sporozoites and characterized their CTL responses using PfSSP2-derived 15-amino acid peptides bearing the HLA-B8-binding motif. Peripheral blood mononuclear cells from both volunteers stimulated with recombinant vaccinia expressing PfSSP2 displayed antigen-specific, genetically restricted, CD8+ T cell-dependent CTL activity against autologous target cells expressing PfSSP2. Of the five HLA-B8 motif-bearing 15-mers identified in the PfSSP2 sequence, two peptides sharing a 10-amino acid overlap sensitized HLA-B8-matched target cells from both volunteers for lysis by peptide-stimulated effectors. The CTL activity was HLA-B8 restricted and dependent on CD8+ T cells. Analysis of the three shorter peptides representing HLA-B8 motif-bearing sequences within the two positive peptides for their ability to bind to HLA-B8 in vitro, and to sensitize target cells for lysis by effectors stimulated with the 15-mers, identified two overlapping HLA-B8-restricted CTL epitopes. Available data indicate that the sequence of one CTL epitope is conserved and the other is variant among P. falciparum isolates. Circulating activated CTL against the conserved epitope could be directly identified in one of the two volunteers. The identification of two HLA-B8-restricted CTL epitopes on PfSSP2 provides data critical to developing an epitope-based anti-liver stage malaria vaccine.

    Title Peptide Binding to Mhc Class I Molecules: Implications for Antigenic Peptide Prediction.
    Date November 1995
    Journal Immunologic Research
    Excerpt

    The human mayor histocompatibility complex class I molecule HLA-A2 preferentially binds peptides that contain Leu at P2 and Val or Leu at the C terminus. The other amino acids in the peptide also contribute to binding positively or negatively. It is possible to estimate the binding stability of HLA-A2 complexes containing particular peptides by applying coefficients, deduced from a large amount of binding data, that quantify the relative contribution of each amino acid at each position. In this review, we describe the molecular basis for these coefficients and demonstrate that estimates of binding stability based on the coefficients are generally concordant with experimental measurements of binding affinities. Peptides that contained cysteine were predicted less well, possibly because of complications resulting from peptide dimerization and oxidation. Apparently, peptide binding affinity is largely controlled by the rate of dissociation of the HLA/peptide/beta 2-microglobulin complex, whereas the rate of formation of the complex has less impact on peptide affinity. Although peptides that bind tightly to HLA-A2, including many antigenic peptides bind much more weakly. Therefore, a full understanding of why certain peptides are immunodominant will require further research.

    Title Interleukin-2 Diphtheria Fusion Protein (dab486il-2) in Refractory Rheumatoid Arthritis. A Double-blind, Placebo-controlled Trial with Open-label Extension.
    Date October 1995
    Journal Arthritis and Rheumatism
    Excerpt

    OBJECTIVE. This pilot phase II, double-blind, placebo-controlled trial of 1 month duration, with a 2-3-month open-label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis (RA). METHODS. Forty-five RA patients were enrolled in the trial, and were randomized, after a 3-4-week disease-modifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486IL-2 or placebo (saline) for 5 days. A blinded, third-party observer evaluated arthritis activity. Clinical response was defined as > or = 25% improvement in swollen and tender joints and > or = 25% improvement in at least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo patients could cross over to receive open-label treatment for a maximum of 3 monthly DAB486IL-2 cycles. RESULTS. In the double-blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open-label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL-2, respectively. Adverse events included transient fever/chills (45%), nausea/vomiting (50%), elevated (< or = 3 x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL-2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL-2-treated versus placebo-treated patients. CONCLUSION. Clinical responses were noted in patients treated with DAB486IL-2 (18%) compared with placebo (0%) in the double-blind phase. In the open-label phase, 33% of patients completing 3 monthly DAB486IL-2 cycles had improvement in arthritis activity. Further studies of IL-2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.

    Title Identification of the Peptide Binding Motif for Hla-b44, One of the Most Common Hla-b Alleles in the Caucasian Population.
    Date September 1995
    Journal Biochemistry
    Excerpt

    Most peptides that bind to a particular MHC class I molecule share amino acid residues that are thought to physically "anchor" the peptide to polymorphic pockets within the class I binding site. Sequence analysis of endogenous peptides bound to HLA-B44 revealed two potential dominant anchor residues: Glu at P2 and Tyr, or occasionally Phe, at P9. In vitro assembly assays employing synthetic peptides and recombinant HLA-B44 produced by Escherichia coli revealed that an acidic amino acid at P2 was necessary for promoting stable peptide binding to HLA-B44. Surprisingly, although Tyr was almost exclusively found at P9 of the endogenous peptide sequences, a wide variety of amino acid residues such as Leu, Ala, Arg, Lys, His, and Phe could be tolerated at this position. Using this information, we identified antigenic peptides from the influenza virus components nonstructural protein 1 and nucleoprotein that are presented by HLA-B44 to antiinfluenza type A cytotoxic T lymphocytes. In addition, cytotoxic T lymphocytes induced by these antigenic peptides were shown to be capable of recognizing endogenously processed peptides from influenza-infected cells, indicating a potential use for these peptides in vaccine development. Finally, molecular models were created to investigate the possible ways in which the anchor residues might function to stabilize the binding of peptides to HLA-B44, and these models indicate that the acidic residue at P2 most likely interacts primarily with Lys 45 of the HLA-B44 heavy chain and makes additional contacts with Ser 67 and Tyr 9.

    Title Peptide Fingerprints After Partial Acid Hydrolysis: Analysis by Matrix-assisted Laser Desorption/ionization Mass Spectrometry.
    Date April 1995
    Journal Rapid Communications in Mass Spectrometry : Rcm
    Excerpt

    A method is described by which a sequence-dependent peptide fingerprint can be rapidly obtained upon partial hydrolysis of peptides with hydrochloric acid and subsequent analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). When synthetic peptides are treated with 3M HCI for 5 min at 110 degrees C, amino acids are released in turn from the C-terminus or, depending on the peptide, from the N-terminus. Sequence information can be deduced by identifying the amino acid whose mass corresponds to the difference in MW between the major hydrolysis products, beginning from the MW of the starting peptide. A similar pattern exclusively from the C-terminus has been obtained using pentafluoropropionic acid as a hydrolyzing agent (Tsugita et al. Eur. J. Biochem. 206, 691 (1992)), but required longer hydrolysis time and more handling prior to analysis. The technique we have developed could be used to obtain a sequence-dependent 'fingerprint' for a peptide cheaply and rapidly, starting with picomole amounts of peptide, because the hydrolysate can be directly analyzed by MALDI. This methodology might be especially useful for confirming the identity of peptides during peptide mapping.

    Title Peptide Specificity in the Recognition of Mhc Class I by Natural Killer Cell Clones.
    Date March 1995
    Journal Science (new York, N.y.)
    Excerpt

    Recognition by natural killer (NK) cells of major histocompatibility complex (MHC) class I molecules on target cells inhibits NK-mediated lysis. Here, inhibition of NK clones by HLA-B*2705 molecules mutated at single amino acids in the peptide binding site varied among HLA-B*2705-specific NK clones. In addition, a subset of such NK clones was inhibited by only one of several self peptides loaded onto HLA-B*2705 molecules expressed in peptide transporter-deficient cells, showing that recognition was peptide-specific. These data demonstrate that specific self peptides, complexed with MHC class I, provide protection from NK-mediated lysis.

    Title The Hla-b14 Peptide Binding Site Can Accommodate Peptides with Different Combinations of Anchor Residues.
    Date January 1995
    Journal The Journal of Biological Chemistry
    Excerpt

    Most peptides that bind to a particular major histocompatibility complex class I molecule share amino acid residues important for binding at one or two positions. Sequence analyses of peptides bound to HLA-B14 revealed at least four candidates for these so-called anchor residues: Arg at P2, Tyr at P3, Arg at P5, and Leu at P9. Combinations of any three of these amino acids sufficed for binding to HLA-B14 in vitro. Using this information, we identified an antigenic peptide critical for cytotoxic T lymphocyte recognition of virus-infected cells. Molecular models of HLA-B14 peptide complexes were constructed to investigate how the potential anchor residues might function. By using binding data to calculate the contribution to binding of each amino acid at anchor positions and predicting the stability of all possible nonapeptide complexes that could be formed from antigenic proteins, we estimate that three known antigenic nonapeptides are in the highest affinity cohort of peptides. Thus, even when multiple combinations of anchor residues contribute to binding, antigenic peptides are routinely identifiable.

    Title Stability and Transmission of Attachment Across Three Generations.
    Date January 1995
    Journal Child Development
    Excerpt

    Stability of adult attachment and transmission of attachment across 3 generations were examined in a longitudinal study of 96 infants, mothers, and maternal grandmothers. The Adult Attachment Interview (AAI) was used to assess attachment in mothers (during pregnancy and when infants were 11 months old) and grandmothers (any time during the study). The Strange Situation (SS) was used to assess attachment in infants at 12 months. Both the 3- and 4-category classification systems of the AAI and SS were used. Mothers' AAI classifications were stable over 12 months in 90% (3-category) and 77% (4-category) of mothers. Mothers' AAI classifications during pregnancy predicted infants' SS classifications in 81% (3-category) and 68% (4-category) of cases, and grandmothers' AAI classifications in 75% (3-category) and 49% (4-category) of cases. Using log-linear analysis, we show that a simple parent-to-child model accounts for transmission of attachment.

    Title Autoreactive Cd8+ T-cell Responses to Human Myelin Protein-derived Peptides.
    Date December 1994
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Identification of the targets of autoreactive T cells is important for understanding the pathogenesis of many autoimmune diseases. In multiple sclerosis, myelin proteins are thought to be the targets of autoreactive T-cell responses. To date only major histocompatibility complex class II-restricted CD4+ T-cell responses to myelin proteins have been investigated. In the present study, the ability of self peptides derived from human myelin proteins to induce autoreactive CD8+ T-cell responses has been assessed. Peptide sequences from human myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein have been identified that bind to and form stable complexes with HLA-A2. MBP 110-118, PLP 80-88, MAG 287-295, MAG 509-517, and MAG 556-564 were all able to induce peptide-specific HLA-A2-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro in HLA-A2+ individuals. CTLs specific for MBP 110-118 and MAG 556-564 could recognize endogenously processed antigens presented by HLA-A2. CTL clones reactive to MBP 110-118 and MAG 556-564 produced tumor necrosis factor alpha and a subset of these clones also produced interferon gamma. These results demonstrate that (i) self peptides derived from human myelin proteins can induce autoreactive CD8+ CTLs and (ii) these CD8+ T cells produce cytokines thought to be important in mediating demyelinating disease. These studies provide an experimental approach for the assessment of CD8+ T-cell responses in such autoimmune diseases.

    Title Pocket Mutations of Hla-b27 Show That Anchor Residues Act Cumulatively to Stabilize Peptide Binding.
    Date July 1994
    Journal Biochemistry
    Excerpt

    Major histocompatibility complex (MHC) class I molecules bind endogenously synthesized peptides for presentation to cytotoxic T-cells. The human class I molecule HLA-B27 consists of a trimolecular complex containing the HLA-B27 heavy chain, a peptide that is usually nine amino acid residues (aa) long, and beta 2-microglobulin (beta 2m). The key interactions for peptide selectivity are between Glu-45, which forms a salt bridge with the Arg at P2 of the peptide, and Asp-116 which favors the binding of peptides containing a Lys or Arg at P9. The t1/2 of dissociation of [125I]beta 2m was measured for peptide-specific HLA-B27 wild-type (wt) and mutant complexes. HLA-B27 wt and HLA-B27 D116F formed relatively stable complexes, with a t1/2 of dissociation on the scale of hours, with appropriate peptides that contained Arg at P2, whereas HLA-B27 E45T required a Gln at P2. Similarly, kinetically stable D116F complexes were formed only with peptides that contained a Leu or Val at P9 instead of Arg or Lys. The [125I]beta 2m dissociation rate data were fit to a set of equations in order to calculate relative binding coefficients for each anchor residue at P2 and P9. The P2 coefficients were sensitive to the E45T mutation but not the D116F mutation, whereas the P9 coefficients were sensitive only to the D116F mutation. Thus, drastic structural changes in one subsite do not affect the other subsite, indicating that the dominant anchor residues at P2 and P9 independently contribute to stabilizing the class I/peptide complex.

    Title Endogenous Peptides with Distinct Amino Acid Anchor Residue Motifs Bind to Hla-a1 and Hla-b8.
    Date February 1994
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8 were identified by sequence analyses of reversed-phase HPLC fractions containing endogenous peptides derived from these HLA molecules. Fifteen different primary sequences were determined for HLA-A1-associated peptides, 12 of which were nine aa in length. Common features among these peptide sequences were Tyr at the COOH-terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at P4. Twenty-seven different primary sequence assignments were made for HLA-B8-associated peptides, most of which were eight aa in length. Lys, and in a few cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was the preferred COOH-terminal residue. Unlike all other human class I molecules whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8 endogenous peptide sequences have a dominant anchor residue at P3, and these aa are opposite in charge to the aa at position 156 of the peptide-binding site. Synthetic peptides corresponding to endogenous peptide sequences bound to their respective HLA molecules in vitro, indicating that they derive from peptides bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA-B8 endogenous peptide sequences matched intracellularly expressed proteins found in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to identify potential antigenic peptides from influenza A viral proteins that bound to HLA-A1 in vitro.

    Title Scheme for Ranking Potential Hla-a2 Binding Peptides Based on Independent Binding of Individual Peptide Side-chains.
    Date January 1994
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    A method to predict the relative binding strengths of all possible nonapeptides to the MHC class I molecule HLA-A2 has been developed based on experimental peptide binding data. These data indicate that, for most peptides, each side-chain of the peptide contributes a certain amount to the stability of the HLA-A2 complex that is independent of the sequence of the peptide. To quantify these contributions, the binding data from a set of 154 peptides were combined together to generate a table containing 180 coefficients (20 amino acids x 9 positions), each of which represents the contribution of one particular amino acid residue at a specified position within the peptide to binding to HLA-A2. Eighty peptides formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation of beta 2m. The remaining 74 peptides formed complexes that had a half-life of beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA-A2, and were included because they could be used to constrain the values of some of the coefficients. The "theoretical" binding stability (calculated by multiplying together the corresponding coefficients) matched the experimental binding stability to within a factor of 5. The coefficients were then used to calculate the theoretical binding stability for all the previously identified self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability for all other nonamer peptides that could be generated from the proteins from which these peptides were derived was also predicted. In every case, the previously described HLA-A2 binding peptides were ranked in the top 2% of all possible nonamers for each source protein. Therefore, most biologically relevant nonamer peptides should be identifiable using the table of coefficients. We conclude that the side-chains of most nonamer peptides to the first approximation bind independently of one another to the HLA-A2 molecule.

    Title Hla-a1 and Hla-a3 T Cell Epitopes Derived from Influenza Virus Proteins Predicted from Peptide Binding Motifs.
    Date January 1994
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses.

    Title Dab486il-2 Fusion Toxin in Refractory Rheumatoid Arthritis.
    Date November 1993
    Journal Arthritis and Rheumatism
    Excerpt

    To evaluate the safety and antiarthritic effects of DAB486IL-2. This agent is a fusion toxin and the product of a synthetic gene, engineered by replacing the codons for the receptor-binding domain of diphtheria toxin (DT) with the codons for human interleukin-2 (IL-2). DAB486IL-2 targets cells expressing the 2-chain, high-affinity form of the IL-2 receptor (IL-2R), and achieves selective diphtheria toxin-mediated cytotoxicity of activated T cells by inhibition of protein synthesis.

    Title Endogenous Peptides Bound to Hla-a3 Possess a Specific Combination of Anchor Residues That Permit Identification of Potential Antigenic Peptides.
    Date March 1993
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    A motif specific to peptides that bind to the human class I major histocompatibility complex molecule HLA-A3 was identified by sequence analysis of HPLC fractions containing endogenous peptides. Twenty-six different sequences were obtained, 19 of which were nonamers. The majority of these endogenous peptide sequences contained Leu at position (P)2, while most sequences contained Tyr or Lys at P9. In addition, Phe was shared by 16 sequences at P3. Synthetic peptides corresponding to endogenous peptide sequences were shown to bind to HLA-A3. The importance of Leu at P2 and Tyr or Lys at P9 ("anchor" residues) for peptide binding to HLA-A3 was demonstrated by the following results: (i) peptides GLFGGGGGY, GLFGGGGGK, and GLGGGGFGY, but not GLFGGGGGV, specifically bound to HLA-A3 and (ii) six nonapeptides from within the influenza A nucleoprotein, matrix, and polymerase proteins, selected for synthesis based upon their possession of P2 and P9 anchor residues, were shown to bind HLA-A3. In contrast, none of a set of eight peptides that bound to HLA-A2, or six that bound to HLA-B27, bound detectably to HLA-A3. These findings provide a rationale for the design and selection of peptides that can be recognized by HLA-A3-restricted T cells.

    Title Sequence Motifs Important for Peptide Binding to the Human Mhc Class I Molecule, Hla-a2.
    Date December 1992
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    Previous studies have indicated that most HLA-A2-binding peptides are 9 amino acid (aa) residues long, with a Leu at position 2 (P2), and a Val or Leu at P9. We compared the binding properties of different peptides by measuring the rate of dissociation of beta 2-microglobulin from peptide-specific HLA-A2 complexes. The simplest peptide that we identified that could form HLA-A2 complexes had the sequence (in single letter aa code) GLFGGGGGV, indicating that three nonglycine aa are sufficient for binding to HLA-A2. To determine whether most nonapeptides that contained Leu at P2 and Val or Leu at P9 could bind to HLA-A2, we tested the binding of nonapeptides selected from published HIV and melanoma protein sequences, and found that six of seven tested formed stable HLA-A2 complexes. We identified an optimal antigenic undecapeptide from the cytomegalovirus gB protein that could form stable HLA-A2 complexes that contained apparent anchor residues at P2 and P11 (sequence FIAGN-SAYEYV), indicating that the spacing between anchor residues can be somewhat variable. Finally, we tested the importance of every aa in the influenza A matrix peptide 58-66 (sequence GILGFVFTL) for binding to HLA-A2, by using Ala-substituted and Lys-substituted peptides. We found that multiple positions were important for stable binding, including P2, P3, P5-P7, and P9. We conclude that the P2 and P9 anchor residues are of prime importance for peptide binding to HLA-A2. However, other peptide side chains (especially at P3) contribute to the stability of the interaction. In certain cases, the optimal length for peptide binding can be longer than 9 residues.

    Title Waiting List Information Strategies for Child Psychiatry: an Intervention and Measurement Approach.
    Date November 1992
    Journal Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
    Excerpt

    This paper describes a number of steps we have initiated to study our chronic waiting list problems. We describe a program involving monthly data collection which has enabled us to document the effectiveness of some strategies and predictive variables. During 1989 the data were supplemented with information collected by a questionnaire mailed to every other referral. We found that an initial response to the questionnaire was a powerful predictor of successfully kept first appointments six to 12 months later. The significance of these differences, the impact of our tracking procedures and the issues and causes, along with some strategies, are discussed.

    Title The Beta 2-microglobulin Dissociation Rate is an Accurate Measure of the Stability of Mhc Class I Heterotrimers and Depends on Which Peptide is Bound.
    Date October 1992
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    Stable, recombinant, water-soluble complexes of HLA-A2 and HLA-B27 were reconstituted from 125I-labeled beta 2-microglobulin (beta 2m), a synthetic peptide, and HLA H chain fragments expressed as inclusion bodies in the Escherichia coli cytoplasm. Using this system, we were able to show: 1) the t1/2 of beta 2m dissociation from HLA complexes at 37 degrees C varied from approximately 40 h to less than 1 h, depending on the peptide employed for reconstitution. Peptide length and composition were found to be critical factors in determining the beta 2m dissociation rate. Endogenous peptides form complexes that are about as stable as those formed with typical antigenic peptides. 2) Peptide exchange reactions, in which an exogenous peptide replaces the peptide that is already bound by the class I molecule, proceed readily for complexes that have rapid beta 2m dissociation rates. Thus, difficulties in demonstrating peptide binding to complexes that contain endogenous peptides can be attributed to the stability of the endogenous peptide/class I molecule complex. 3) The peptide exchange reaction does not require concomitant beta 2m dissociation. 4) Distal parts of the class I molecule, which are not directly involved in peptide binding or beta 2m binding, have a major impact on the stability of class I molecules. Thus, these studies show that the dissociation rate of beta 2m is an excellent measure of how tightly a given peptide binds to class I MHC molecules, that the ability to bind peptide is tightly coupled to the binding of beta 2m and vice versa, and that regions of the molecule distal from the binding site influence the stability of peptide binding.

    Title An Hla-a2/beta 2-microglobulin/peptide Complex Assembled from Subunits Expressed Separately in Escherichia Coli.
    Date May 1992
    Journal Molecular Immunology
    Excerpt

    The human class I histocompatibility antigen HLA-A2 has been assembled from subunits expressed separately in E. coli. A peptide that is known to be recognized by human cytotoxic T lymphocytes (CTLs) in association with HLA-A2 is a necessary component of the reconstitution mixture. The N-terminal extracellular fragment of the HLA-A2 heavy chain is initially synthesised as an insoluble aggregate. The aggregate is solubilized in denaturant, mixed with the influenza nucleoprotein 85-94 decapeptide (NP peptide), and diluted into a solution containing human beta 2-microglobulin (beta 2 m) isolated from the E. coli periplasm. The HLA-A2 heavy chain becomes soluble in physiological solutions if both beta 2m and the NP peptide are present. The reconstituted HLA-A2 complex is recognised by a monoclonal antibody that is specific for the native HLA-A2/beta 2m heterodimer, and is also recognised by a monoclonal antibody that recognises beta 2m. When other peptides known from CTL studies to associate with HLA-A2 are used, a significantly lower yield of reconstituted complex is obtained. The isoelectric point of the reconstituted complex depends on which peptide is used, confirming that the peptide is a component of the reconstituted complex.

    Title Peptide Binding to Hla-a2 and Hla-b27 Isolated from Escherichia Coli. Reconstitution of Hla-a2 and Hla-b27 Heavy Chain/beta 2-microglobulin Complexes Requires Specific Peptides.
    Date April 1992
    Journal The Journal of Biological Chemistry
    Excerpt

    The specificity of peptide binding by human leukocyte antigen (HLA) class I molecules was investigated in a cell-free direct-binding assay. Peptides were assessed for binding to HLA-A2 and HLA-B27 by measuring the formation of heterotrimeric HLA complexes that consisted of iodinated beta 2-microglobulin, HLA heavy chain fragments isolated from the Escherichia coli cytoplasm, and peptide. In this system, no detectable HLA heavy chain-beta 2-microglobulin complexes were formed unless appropriate peptides were intentionally added to the reconstitution solution. Analysis with monoclonal antibodies demonstrated that these heterotrimeric complexes were correctly folded. Five nonhomologous peptides, known to form complexes with HLA-A2 or HLA-B27 from T-cell functional studies, were tested for their capacity to bind to HLA-A2 and HLA-B27 using the reconstitution assay. Four of the peptides bound to the appropriate class I molecule only. One peptide and some (but not all) substitution analogs of it bound to both HLA-A2 and HLA-B27. The effect of peptide length on binding to HLA-B27 was studied, and it was found that the optimal length was 9 or 10 amino acid residues; however, one peptide that bound to HLA-B27 was 15 amino acids long. All peptides that bound to HLA-B27 in the direct-binding assay also competed with antigenic peptides for binding to HLA-B27 on the surface of intact cells, as determined by a standard cytotoxic T-lymphocyte functional assay. Thus, we conclude that HLA-A2 and HLA-B27 bind distinct but partially overlapping sets of peptides and that, at least in vitro, the assembly of HLA heavy chain-beta 2-microglobulin complexes requires specific peptides.

    Title How Humana Stays Profitable and Still Satisfies Patients.
    Date July 1991
    Journal Hospital Patient Relations Report
    Title Reconstitution by Mhc-restricted Peptides of Hla-a2 Heavy Chain with Beta 2-microglobulin, in Vitro.
    Date May 1991
    Journal Nature
    Excerpt

    Cytotoxic T lymphocytes kill virally infected cells when they detect antigenic fragments presented by class I major histocompatibility complex (MHC) antigens (HLA in humans). The crystal structures of HLA-A2 and HLA-Aw68 reveal that peptide-antigen forms an integral part of the HLA structure, being retained in a prominent groove even after purification and crystallization. Here we report that the heavy chain and beta 2-microglobulin of HLA-A2, after separation and fractionation in denaturants, reassemble efficiently under renaturing conditions only in the presence of MHC-restricted peptides. A complex of heavy chain, beta 2-microglobulin, and viral peptide in the ratio 1:1:1 is formed in up to 46% yield. Reconstitution is not stimulated by either of two peptides not restricted to HLA-A2. The reconstituted complex of HLA-A2 and the influenza virus (B/Lee/40) nucleoprotein peptide, Np (85-94), crystallizes under conditions previously used to crystallize HLA-A2. Peptide-linked folding and assembly suggests mechanisms for the unusual capacity of HLA to bind many peptides of diverse sequence.

    Title Overexpression of Native Human Beta 2-microglobulin in Escherichia Coli and Its Purification.
    Date January 1990
    Journal Gene
    Excerpt

    beta 2-Microglobulin (beta 2M), the small subunit of human leukocyte antigen (HLA) class-I proteins, has been synthesized in Escherichia coli and purified in mg amounts. A beta 2m cDNA clone was fused in-frame behind DNA encoding the signal sequence for the outer membrane protein, OmpA. Three different constructions were made, whose products differed by the insertion of either an extra Ala residue, the hexapeptide AEFLEA [single-letter amino acid (aa) code], or no aa between the OmpA signal sequence and beta 2M-coding sequence. All three protein products were correctly processed by bacterial signal peptidase, as determined by N-terminal sequencing, and all three were secreted as soluble proteins into the periplasmic space. However, the signal sequence of the preprotein with the inserted hexapeptide, AEFLEA, was cleaved to a much greater degree than the other two preproteins. When there was no insertion, the mature protein was identical to human beta 2M, as analyzed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, circular dichroism, and native isoelectric focusing. This 'bacterial beta 2M', radiolabeled with Bolton-Hunter reagent, was able to exchange into papain-solubilized HLA-B7, as determined by Sephadex G-75 chromatography and immune precipitation, indicating that bacterial beta 2M could complex with the heavy chain of HLA-B7.

    Title A Summary of the Reliability and Stability of Mmpi Scales.
    Date March 1988
    Journal Journal of Clinical Psychology
    Excerpt

    A sample of MMPI research published between 1970 and 1981 was analyzed to yield reliability and stability estimates for the MMPI scales. In fundamental agreement with previous research, moderately high levels of reliability and stability were found for all scales. Reliability values ranged from .71 to .84; stability values ranged from .63 to .86. These findings are based on thousands of adult subjects from college, psychiatric, medical, alcohol or drug rehabilitation, and prison populations. The present scale estimates have wide generalizability and, therefore, should be of value to clinicians and researchers in various settings.

    Title Biochemical and Functional Analyses of a Secreted H-2ld Molecule.
    Date January 1987
    Journal Molecular and Cellular Biology
    Excerpt

    A truncated H-2Ld gene was constructed by deleting the transmembrane and cytoplasmic exons. The truncated H-2Ld gene was introduced into mouse L cells using the thymidine kinase gene as a selectable marker. Transformants were isolated and screened for the presence of truncated H-2Ld antigen. The truncated H-2Ld gene product was present in both the cytoplasm and culture medium, but not on the cell surface. The truncated H-2Ld antigen was stable in culture medium for at least 9 h and was secreted into the medium at a rate similar to the kinetics with which complete H-2 antigens reach the cell surface. Transformants expressing the truncated H-2Ld molecule were not recognized by cytotoxic T lymphocytes specific for the H-2Ld antigen.

    Title Subunit Interactions of Class I Histocompatibility Antigens.
    Date February 1986
    Journal Biochemistry
    Excerpt

    The kinetics of dissociation of iodinated beta 2-microglobulin (beta 2m) from the papain-solubilized class I histocompatibility antigen HLA-B7 have been investigated. In the presence of unlabeled beta 2m, most of the HLA dissociates according to a single rate constant, whereas in the absence of unlabeled beta 2m, the system approaches an equilibrium dependent upon the initial HLA concentration. When iodinated beta 2m is incubated with unlabeled HLA-B7, the rate of incorporation of beta 2m into the complex is much less dependent on the concentration than is expected for a simple association/dissociation system; instead, the system behaves as if the "activity" (in a thermodynamic sense) of the HLA heavy-chain intermediate cannot surpass a critical concentration. The dissociation rate for each class I specificity is a function of temperature, ionic strength, pH, and the status of the heavy chain (papain solubilized vs. detergent solubilized). High temperature, high ionic strength, and extremes of pH promote dissociation. The intact molecule dissociates about 10 times more slowly than the papain-solubilized molecule. In contrast, the rate of dissociation of all papain-solubilized class I antigens tested falls within the range of about a factor of 2. The presence of the carbohydrate has no effect on the rate of dissociation. The possibility that HLA class I antigen dissociation may occur in vivo within acidic internal vesicles is discussed.

    Title Anesthesia-related Transient Aphonia and Quadriplegia.
    Date October 1985
    Journal Anesthesia and Analgesia
    Title Localization of the Sites of Iodination of Human Beta 2-microglobulin: Quaternary Structure Implications for Histocompatibility Antigens.
    Date June 1983
    Journal Biochemistry
    Excerpt

    Human urinary beta 2-microglobulin (beta 2m) and pa-pain-solubilized human histocompatibility antigen HLA-B7 were iodinated with iodogen and the sites of iodination determined. In the case of free urinary beta 2m, four of the six tyrosines were modified to some degree. Two of these were heavily iodinated (tyrosine-63 and -67) while two were lightly iodinated (tyrosine-10 and -26). In the case of beta 2m iodinated in the intact HLA-B7 complex, only one of these tyrosines was modified substantially (tyrosine-67). beta 2m iodinated at either of the two major sites exchanged into the HLA-B7 complex, whereas beta 2m iodinated at either of the two minor sites did not exchange at all. The relationship of these findings to the quaternary structure of HLA is discussed.

    Title Sequence of Human Beta 2-microglobulin: a Correction.
    Date September 1982
    Journal Molecular Immunology
    Excerpt

    A tryptic peptide isolated from human urinary beta 2-microglobulin (beta 2m++) has has a composition that does not correspond to the published sequence. Automated sequence analysis confirms that the published sequence contains an error, an additional serine residue at position 67. In fact, human beta 2m has 99 residues, like the rabbit and mouse homologues.

    Title Comparison of Clinical Diagnoses, Nimh-disc-iv Diagnoses and Scl-90-r Ratings in an Adolescent Psychiatric Inpatient Unit: A Brief Report.
    Date
    Journal The Canadian Child and Adolescent Psychiatry Review = La Revue Canadienne De Psychiatrie De L'enfant Et De L'adolescent
    Excerpt

    To compare results of clinical diagnosis, NIMH DISC-IV diagnoses and the Global Severity Index of the Symptom Check List- Revised (SCL-90-R) in an adolescent inpatient population.

    Title Genetic Consequences of Pre-columbian Cultivation for Agave Murpheyi and A. Delamateri (agavaceae).
    Date
    Journal American Journal of Botany
    Excerpt

    Pre-Columbian farmers cultivated several species of agave in central Arizona from ca. A.D. 600-1350. Because of the longevity and primarily asexual reproduction of these species, relict agave clones remain in the landscape and provide insights into pre-Columbian agricultural practices. We analyzed variation in allozyme allele frequencies to infer genetic effects of prehistoric cultivation on Agave murpheyi and A. delamateri, specifically to estimate genetic diversity and structure, to determine whether cultivated populations descended from a single clone, and to examine regional-scale genetic variation. Agave murpheyi maintained more genetic diversity at the species and population levels than A. delamateri, and A. murpheyi populations typically included more multilocus genotypes. Relict plants from prehistoric fields reflect a more complex history than descent from a single clone; A. murpheyi populations may have included more diversity initially because bulbils (produced routinely in A. murpheyi but not A. delamateri) and possibly seed would have facilitated transport of genetically diverse planting stock. Genetic variation in both cultigens was lower than in most contemporary commercial crops but similar to that observed in modern traditional agricultural systems.


    Similar doctors nearby

    Dr. Shaun Roof

    Otolaryngology
    14 years experience
    Newark, OH

    Dr. James Silone

    Neuromusculoskeletal Medicine & OMM
    18 years experience
    Newark, OH

    Dr. David Sand

    Otolaryngology
    28 years experience
    Granville, OH

    Dr. Ashish Shah

    Otolaryngology
    9 years experience
    Columbus, OH

    Dr. Evan Tobin

    Otolaryngology
    18 years experience
    Columbus, OH

    Dr. John Zulliger

    Otolaryngology
    33 years experience
    Columbus, OH
    Search All Similar Doctors