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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 127 records · Page 7Linked to original sources
PubMed1996

Measurement of human herpesvirus 7 load in peripheral blood and saliva of healthy subjects by quantitative polymerase chain reaction.

Qualitative and competitive-quantitative nested polymerase chain reaction (PCR) assays were developed for human herpesvirus 7 (HHV-7). These assays amplify a DNA sequence encoding part of the HHV-7 homologue of the human herpesvirus 6 (HHV-6) U42 gene. The PCR assays were used to analyze peripheral blood DNA (pbDNA) and saliva from 24 healthy volunteers. The prevalence of HHV-7 in saliva was 96%, with a median virus load of 1.1 x 10(6) copies/mL. Longitudinal analysis revealed sustained virus load, suggesting continued active viral replication. Analysis of 1 microgram of pbDNA showed the prevalence of HHV-7 to be 83%, with a median virus load of 40 copies (267 copies/10(6) cells). Analysis of sequential pbDNA samples showed individuals to have stable levels of HHV-7 virus load. These data demonstrate persistence of HHV-7 at two distinct sites and provide baseline data allowing comparisons with HHV-7 load in immunocompromised patients.

Base Sequence↗
PubMed1996

Endometrial lymphomyeloid cells in abnormal uterine bleeding due to levonorgestrel (Norplant).

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

Adult↗
PubMed1996

Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR.

A quantitative competitive PCR assay for human herpesvirus 6 (HHV-6) was developed. Firstly, viral burden was determined in the blood of 25 healthy persons. Using 1 microgram of DNA, the prevalence of HHV-6 was 36% (9/25). Eight persons had viral loads of < or = 32 HHV-6 genomes/microgram DNA. The viral burden in the ninth individual was 1.2 x 10(6) HHV-6 genome copies/microgram DNA, which remained constant over a period of 10 months. This demonstrates the persistence of a high HHV-6 load in the absence of apparent disease. Secondly, HHV-6 burden was determined in 100 post-mortem tissues from seven AIDS patients and three controls. For all tissues combined, there was a statistically significant higher median viral load in AIDS patients (56 copies/microgram DNA, range 0-43321) compared to controls (10 copies/microgram DNA, range 0-423) (P = 0.04). The precision and reproducibility of this assay will allow hypotheses concerning the pathogenic potential of HHV-6 to be tested quantitatively.

AIDS-Related Opportunistic Infections↗
PubMed1996

Immunosuppressive properties of monoclonal antibodies and human polyclonal alloantibodies to the R80K protein of trophoblast.

PROBLEM: The R80K protein on human trophoblast is antigenically polymorphic, and in all placentae of successful pregnancies, the protein is covered by maternal alloantibody. Alloantibody eluted from human placenta has been shown to inhibit killing by human NK cells. Do those antibodies to R80K that inhibit NK killing also affect the murine abortion models? METHODS: We made three murine monoclonal antibodies to conserved epitopes, on human R80K, all of which also reacted with the homologous murine molecule. One antibody only, BA11, suppressed NK cytotoxicity to K562 and of mouse spleen NK cells to murine trophoblast. All three were tested in mouse models of abortion: the CBA x DBA/2 model with a high resorption rate of F1 embryos compared with the parental strains, an endotoxin induced abortion/resorption model and a third model in which the pregnant mouse is subject to sonic stress. CONCLUSION: Those IgG antibodies eluted from microvesicles which bound to K562, and one of the three monoclonals, BA11, inhibited NK killing. The antibodies react with the murine molecule, and BA11 inhibited abortion in all three mouse abortion models. This reinforces the thesis that interference with NK killing can influence abortion/resorption in mice, and the BA11 antibody may effect similar results in analogous human situations.

Animals↗
PubMed1996

Psycho-neuro-cytokine/endocrine pathways in immunoregulation during pregnancy.

PROBLEM: Some mammalian pregnancy failure is thought to occur by immunological or immunologically modifiable mechanisms. The original model wherein spontaneous abortion was proposed to represent rejection of the conceptus as an allograft has been supplanted by a model of maternal paraimmunological natural effector cell toxicity to fetal trophoblast more closely related to tumor rejection. The problem is to integrate current information concerning the role of immunological, paraimmunological, endocrinological, and stress-triggered neural factors that determine whether or not abortion will occur. METHODS: Review of existing data. RESULTS: An integrated model is proposed. CONCLUSION: Immunological factors play an important role in abortion processes and prevention of abortions. The existence of abortogenic mechanisms and their regulation appears to be based upon optimizing survival of the species. Two new conceptual models provide a useful framework for further investigation of human pregnancy failure and its treatment.

Abortion, Spontaneous↗
PubMed1996

Transforming growth factor-beta 2-related-decidual suppressor factor is not related to TJ6 protein.

Transforming growth factor (TGF)-beta 2-related-decidual suppressor factor (DSF) and TJ6 protein are both immunosuppressive molecules present in murine and human pregnancy. Treatment of mice with either anti-TJ6 or anti-TGF-beta 2 neutralizing antibodies results in increased fetal loss. Western blots of supernatants from pregnant mouse decidua probed with anti-TJ6 (soluble form) showed a doublet at a similar molecular size as when the blot was probed with anti-TGF-beta 2 antibody. The problem is to determine whether TJ6 and DSF are the same protein. In order to determine if TJ6 and DSF are the same or different proteins, we used affinity column purified TGF-beta 2-DSF and stained Western blots with anti-TJ6. The TGF-beta 2-monoclonal antibody affinity column-purified DSF that stained with anti TGF-beta 2 was not reactive with anti-TJ6 antibody. TJ6 has only a 30% gene sequence homology and a 13% amino acid homology to TGF-beta 2. TJ6 and TGF-beta 2-related DSF appear to be different immunosuppressive proteins in decidua.

Animals↗
PubMed1996

Immunotherapy for recurrent pregnancy loss: analysis of results from clinical trials.

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

Abortion, Habitual↗
PubMed1995

Psychometric characteristics of revised Sociotropy and Autonomy Scales in college students.

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

Adjustment Disorders↗
PubMed1995

Daily hassles, major and minor life events, and their interaction with sociotropy and autonomy.

A cross-sectional study investigated whether Beck's (1983; 1987) (Treatment of depression: Old controversies and new approaches. New York: Raven Press; Journal of Cognitive Psychotherapy, 1, 2-27) cognitive-personality traits of sociotropy and autonomy had a specific interaction with daily minor life events (hassles) or major life experiences within the interpersonal and autonomous domains. Ninety-four undergraduates were administered the revised Sociotropy-Autonomy Scale (SAS), Beck Depression Inventory (BDI), Negative Experiences Inventory--Student Version (NEI), List of Threatening Events and the Hassles and Uplifts Scale. Hierarchical multiple regression analysis, with the BDI as the dependent variable, revealed a specific congruent interaction between Solitude, one of the two dimensions of autonomy, and NEI negative autonomous events. Sociotropy and the other dimension of autonomy, Independence, did not interact significantly with any of the life event scales. The findings suggest that more severe life events rather than daily hassles or strains may be more relevant when investigating cognitive diathesis-stress interactions in dysphoria.

Adult↗
PubMed1995

The assessment of unwanted intrusive thoughts: a review and critique of the literature.

In this paper we review the assessment and measurement of normal unwanted intrusive thoughts, images, and impulses that are considered the basis of clinical obsessions. After highlighting some difficulties with how the definition of cognitive intrusion has been applied to the development of assessment measures, we evaluate the construct validity of a number of retrospective self-report instruments such as the Intrusive Thoughts Questionnaire, Cognitive Intrusions Questionnaire, and Obsessional Intrusions Inventory, as well as interview and diary procedures. Measures of personal responsibility and meta-cognitive beliefs, which are still in the developmental phase, are also discussed. We conclude with a number of recommendations and areas of further research which would strengthen the construct validity of measures of intrusive thoughts and related constructs.

Attention↗
PubMed1995

Potential role of nitric oxide in a model of chronic colitis in rhesus macaques.

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

Amino Acid Oxidoreductases↗
PubMed1995

Case clustering, Epstein-Barr virus Reed-Sternberg cell status and herpes virus serology in Hodgkin's disease: results of a case-control study.

The Leukaemia Research Fund Data Collection Study (DCS) is a specialist registry of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's disease (HD) registered with the DCS between 1985 and 1989. This entire data set has been tested for localised spatial clustering using an established nearest neighbour method with 18% of all cases in young people classified as clustered (P < 0.05). No clustering was found in older cases. Subsamples were selected from the registered cases for a pilot study in which case clustering, herpes virus antibody titres and Epstein-Barr virus (EBV) presence within the Reed-Sternberg (RS) cells (EBV-RS status) were investigated together. Firstly, a case-control study of HD in young people or nodular sclerosing (NS) subtype (39 HD cases and 26 healthy controls) found significant elevation of antibody titres to EBV-viral capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in HD cases compared with controls. EBV viral genome was present in 5 cases and 4 of these were in clusters of HD in young people. Elevation of antibody titres to the EBV antigens was not associated with case clustering or EBV-RS status. Antibody titres to HHV-6 differed significantly between EBV-RS+ and EBV-RS- cases (P = 0.04). Geometric mean titres for HHV-6 for EBV-RS+ and EBV-RS- cases were 11.5 and 73.7, respectively, with the former lower than the control value of 20.5. Secondly, a cluster study included all other cases (n = 14) in clusters containing known EBV-RS+ cases. 3 further cases were EBV-RS+ positive but no cluster consisted entirely of positive cases. Overall, 5/16 clustered, 2/12 peripheral and 1/25 random cases in these studies were EBV-RS+ (P = 0.017). The interpretation of these results in terms of shared aetiological exposures of cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses for testing in future studies proposed.

Adolescent↗
PubMed1995

Common and specific dimensions of self-reported anxiety and depression: a replication.

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

Adult↗
PubMed1995

Some effects of feeding pasture silage as a supplement to pasture on reproductive performance in lactating dairy cows.

Supplementation of a ryegrass/white clover pasture diet with pasture silage is a common management practice in New Zealand dairy herds. The effect of this supplementation on reproductive performance has not been investigated. Five herds of 20 cows were formed before calving commenced on 1 June 1992. From 5 August to 4 September, two of these herds were fed 5 kg/cow/day of pasture silage in addition to the ryegrass/white clover pasture offered to all herds. Pasture silage supplementation did not alter the intervals from calving to first ovulation, first oestrus, or to conception. However, it reduced the first service conception rate (37.5% v. 53.3%; difference +/- sed = 15.8 +/- 10.0%, for pasture and silage and pasture only cows, respectively). A positive effect on reproductive performance of pasture silage supplementation was not demonstrated in this trial.

Journal Article↗
PubMed1995

Polyamines may increase the percentage of in-vitro fertilized murine oocytes that develop into blastocysts.

This study was designed to investigate whether the polyamines spermine, spermidine and putrescine can prevent the arrest of development of in-vitro fertilized murine oocytes from CD1 strain mice. Development in M16 or Brinster's medium with or without polyamine supplementation was assessed and the ability of blastocysts to attach and grow out on laminin was compared with in-vivo-generated embryo blastocysts. Oocytes from old (20 weeks) females showed lower rates of fertilization and subsequent development in comparison with oocytes from young (6-8 weeks old) females, but in both cases < 5% of in-vitro fertilized oocytes achieved the blastocyst stage. In-vitro fertilized young oocytes showed enhanced development to the blastocyst stage with the addition of the polyamine putrescine, although lesser enhancement was seen with spermine and spermidine; this effect was only evident when the oocytes were grown in Brinster's medium, reflecting the need for a particular set of culture conditions for growth-enhancing agents to be effective. Blastocysts generated in putrescine-supplemented Brinster's medium were able to implant on laminin-coated surfaces in vitro and to respond to the cytokines colony-stimulating factor-1, epidermal growth factor and platelet-derived growth factor with increased trophoblast outgrowth to a greater degree than in-vivo-generated blastocysts. Murine in-vitro fertilized embryo development was not enhanced by co-culture with Vero cells. Putrescine was the most effective polyamine, enhancing the in-vitro fertilized oocyte development to blastocysts in a permissive environment.

Animals↗
PubMed1995

Characterization of murine pregnancy decidua transforming growth factor beta. I. Transforming growth factor beta 2-like molecules of unusual molecular size released in bioactive form.

A novel type of bioactive transforming growth factor beta 2 (TGF beta 2)-related immunosuppressive activity, lower in molecular mass (20-23 kDa) than a conventional TGF beta 2 standard (25 kDa), has been shown to be released by non-T non-B suppressor cells of murine decidua into fetal bovine serum (FBS)-containing tissue culture medium during a 48-h incubation at 37 degrees C. Substitution of a serum-free medium has allowed direct PAGE-Western blotting and the demonstration in supernatant (prior to incubation at 37 degrees C) of a TGF beta 2-immunoreactive doublet at a higher molecular mass (26 and 27 kDa) than the standard but with apparent immunosuppressive activity. When decidua were incubated in serum-free medium at 37 degrees C, immunosuppressive activity in the supernatant increased to peak at 18 h in association with the appearance of the previously described lower molecular mass species of molecule. The doublet did not appear to be the result of glycosylation of a conventional 25-kDa TGF beta 2 and could be converted into the lower molecular mass form by incubation for 18 h at 37 degrees C, with pH 4.5 but not with pH 7.5 buffer; this incubation in the absence of decidual cells was not accompanied by increased immunosuppressive activity. This transformation could be blocked by a brief heating of the supernatant to 80 degrees C for 10 min to destroy enzymes present in supernatant prior to mixing with the acidic buffer, but biologic activity neutralizable by anti-TGF beta 2 was retained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗