Search PubMed⌕ Search

Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 163 records · Page 9Linked to original sources
PubMed1994

Differentiating major depression and panic disorders by self-report and clinical rating scales: ROC analysis and information theory.

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

Adult↗
PubMed1994

Balloon angioplasty results in increased segmental coronary distensibility: a likely mechanism of percutaneous transluminal coronary angioplasty.

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

Adult↗
PubMed1994

Identification of a transforming growth factor alpha-like molecule in human seminal plasma.

OBJECTIVE: To characterize the putative seminal growth promoting factor serendipitously observed when human seminal plasma was analyzed for bioactive FSH. DESIGN: A pool of human seminal plasma was subjected to sequential Sephadex G-75 (superfine) chromatography and high-performance size exclusion liquid chromatography. The fractions were tested for mitogenic activity using a rat granulosa cell assay and normal rat kidney (NRK) cells. Properties of the factor were established and characterization by gel electrophoresis and neutralization with antibody were accomplished. SETTING: Reproductive Biology Research Laboratory at McMaster University Medical Centre. MAIN OUTCOME MEASURES: Ability of purified fractions of human seminal plasma to augment the uptake of tritiated thymidine into cell DNA. RESULTS: Mitogenic activity of human seminal plasma was augmented in the presence of FSH but not hCG, PRL, E2, T, P, or dihydrotestosterone. The putative growth factor synergized with insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) but not with TGF-alpha. Mitogenic activity was neutralized by a specific TGF-alpha antibody in a dose-dependent manner. The molecular weight of the factor as assessed by gel electrophoresis is 6 kd. CONCLUSIONS: Human seminal plasma contains a mitogen that is similar to TGF-alpha.

Animals↗
PubMed1994

Intelligent Systems for Molecular Biology: review of the first international conference.

This review provides a description of the background to the first international conference on Intelligent Systems for Molecular Biology and a problem-oriented overview of the papers presented. It focuses on genome analysis, gene identification, protein and RNA structure prediction and function, the modelling of biochemical pathways and data and knowledge bases. The range and quality of papers indicates that intelligent systems is emerging as an important sub-field of computational applications in the biological sciences.

Artificial Intelligence↗
PubMed1994

CD56+ lymphoid cells in human first trimester pregnancy decidua as a source of novel transforming growth factor-beta 2-related immunosuppressive factors.

The lymphomyeloid cells isolated from normal first trimester pregnancy decidua may be separated into a CD56+ population of natural killer (NK)-lineage cells with the morphology of granulated lymphocytes, and a CD56- population which includes other cell types. Unlike CD56+ NK cells in peripheral blood, decidual CD56+ cells lack type III Fc receptors (CD16) and did not express significant levels of either type I FcR (CD64) or type II FcR (CDw32). By contrast to the decidual CD56- cells, CD56+ cells could release biologically active transforming growth factor (TGF)-beta in vitro, detectable using an normal rat kidney fibroblast colony-forming assay. The CD56+ cells could be stained using an antibody specific for TGF-beta 2, and similarly staining cells could be detected in intact biopsies of normal pregnancy decidua. Bioactive TGF-beta is known to suppress the generation of cytotoxic cells in vitro, and high performance liquid chromatography fractionation of supernatants conditioned by CD56+ but not CD56- cells contained reproducible peaks of immunosuppressive activity at 40-45 and 15-20 kDa, similar to the TGF-beta 2 immunosuppressive activity in supernatants conditioned by unfractionated decidua.

Antigens, CD↗
PubMed1994

On the use of machine learning to identify topological rules in the packing of beta-strands.

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

Amino Acid Sequence↗
PubMed1994

Spontaneous abortion in immunodeficient SCID mice.

PROBLEM: Immunodeficient SCID mice on the CB-17 have been used to test the role of "rejection" in a xenogeneic blastocyst transfer model of recurrent miscarriage, but interpretation of the data requires knowing syngeneic within-species matings have a high success rate and do not require immunotrophic factors expected only in immunocompetent non-T-cell deficient mice. METHOD: Resorption rates were studied in a SCID CB-17 barrier facility that provided the mice used to test the role of immunology in the resorption model. RESULTS: Spontaneous resorption in syngeneically mated immunodeficient SCID mice on the CB-17 background occurred at an unexpectedly high rate and could not be prevented by treatment with anti-asialo GM1 antibody or GM-CSF, both of which are effective in ameliorating abortion in DBA/2J-mated CBA/J mice. Immunocompetent CB-17 +/+ mice showed an even higher rate of loss. The latter was also not affected by treatment with antiasialo GM1 antibody or by GM-CSF and was not prevented by tetracycline (which is effective in the DBA/2-CBA/J system) or progesterone treatment. Mating experiments showed a scid/+ x scid@+ cross gave the highest rate of loss, and it appeared that the presence of +/(+)-type embryos in the uterus could be augmenting abortion with selective discrimination against scid/scid embryos. High abortion rates were associated both with appearance of a coagulase-negative Staphylococcus sp. in feces and with loss of one component of the SPF flora. Decidual tissue from mated CB-17 +/+ mice showed premature release of TNF-alpha in absence of TGF-beta 2-related suppressor activity, and vascular lesions (fibrinoid necrosis), varying in extent, were associated with both scid/scid x scid/scid and +/+ x +/+ pregnancies. TNF-alpha also appeared prematurely in pregnant scid/scid mice, but the levels were lower (and areas of necrosis smaller than in +/+ x +/+ pregnancies). Outcrossing onto a C57B1/6 background dramatically reduced the abortion rate, indicating an important genetic effect on susceptibility with heterogeneity protecting against abortion. CONCLUSIONS: SCID mice on the CB-17 background do not have a high rate of successful syngeneic pregnancies, and a TNF-alpha induced vasculopathy may be responsible. Abortion was not caused by immunodeficiency leading to loss of immunotrophism because immunocompetent non-SCID CB-17 mice had a higher rate of loss. Factors augmenting the abortion rate included the presence of embryos of the +/+ genotype in the uterus and treatment with anti-asialo GM1 antibody. Abortion rates were not reduced by treatments effective in the DBA/2-mated CBA/J mouse model but were reduced by re-establishing a new colony with defined flora (a temporary effect) and by outcrossing mice with a different (C57B1/6) background. Together, the data suggest an infectious trigger (identity uncertain) of the vasculopathy and an important genetic influence on susceptibility with heterozygosity and a SCID mouse mutation providing against abortion a degree of protection.

Abortion, Veterinary↗
PubMed1994

Intralipid as treatment for recurrent unexplained abortion?

PROBLEM: Safe, effective, and inexpensive alternatives to partner leukocyte immunotherapy are being sought. Psychotherapy may be effective but it is uncertain what constitutes effective treatment and the form of treatment tested in cohort controlled trials is expensive. IVIG also appears effective, but is expensive. METHOD: A published double blind randomized controlled trial in which Intralipid (Kabi Vitrum, Toronto, Ontario) was used as a control versus trophoblast membrane vesicles was reviewed. A prediction made from this data was then tested using the DBA/2-mated CBA/J mouse model of recurrent spontaneous abortion. RESULTS: It can be hypothesized from the human clinical trial data that Intralipid even in small doses could be an effective antiabortion treatment. The number of patients in the published study is too small for the required degree of precision. Intralipid was highly effective in preventing abortion in mice, and protection was prolonged. This may be explained by previous data in the literature showing that Intralipid affects the reticuloendothelial system of the recipient. CONCLUSIONS: The evidence suggests that Intralipid might be an effective treatment for human recurrent miscarriages, and injection into women who may become pregnant has been found ethically acceptable at one university center. Comparison of Intralipid to partner leukocyte immunotherapy or IVIG would be worthwhile. For adequate statistical power, this would require a large, multicenter, prognostically stratified randomized controlled trial and could be accomplished via the Recurrent Miscarriage Immunotherapy Trialists Group network.

Abortion, Habitual↗
PubMed1994

Symptom differences in major depression, dysthymia, panic disorder, and generalized anxiety disorder.

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

Adult↗
PubMed1994

Symptom dimensions of the SCL-90-R: a test of the tripartite model of anxiety and depression.

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

Adolescent↗
PubMed1994

Use of nonsomatic symptoms to differentiate clinically depressed and nondepressed hospitalized patients with chronic medical illnesses.

The differential sensitivity of the Depression subscale scores of the Hospital Anxiety and Depression Scale and the Cognitive-Affective subscale scores of the revised Beck Depression Inventory were compared for 21 chronic medically ill hospitalized patients with DSM-III--R unipolar depressive disorders and 54 hospitalized medically ill patients without a comorbid psychiatric disorder. Both subscales significantly differentiated these two types of patients beyond the .001 level and yielded comparable effect sizes. The Cognitive-Affective subscale detected clinical depression as well as a specialized self-report measure.

Chronic Disease↗
PubMed1994

A model to study viral and cytokine involvement in Sjögren's syndrome.

To investigate mechanisms that may be important in the pathogenesis of Sjögren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La are common in SS and it has been proposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advenovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-gamma resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as an in vitro model to study mechanisms of autoimmunity in SS.

Autoantigens↗
PubMed1994

Inductive logic programming used to discover topological constraints in protein structures.

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

Animals↗
PubMed1994

Genetic map construction with constraints.

A pilot program, CME, is described for generating a physical genetic map from hybridization fingerprinting data. CME is implemented in the parallel constraint logic programming language ElipSys. The features of constraint logic programming are used to enable the integration of pre-existing mapping information (partial probe orders from cytogenetic maps and local physical maps) into the global map generation process, while parallelism enables the search space to be traversed more efficiently. CME was tested using data from chromosome 2 of Schizosaccharomyces pombe and was found able to generate maps as well as (and sometimes better than) a more traditional method. This paper illustrates the practical benefits of using a symbolic logic programming language and shows that the features of constraint handling and parallel execution bring the development of practical systems based on AI programming technologies nearer to being a reality.

Algorithms↗
PubMed1994

Common and specific dimensions of self-reported anxiety and depression: implications for the cognitive and tripartite models.

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

Adult↗