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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 55 records · Page 3Linked to original sources
PubMed2000

Ly-49D transfected NK cells show reduced interleukin-10 production in response to H-2d and increased lytic activity: implication by interaction using class I MHC alloantigen+ target cells in pregnancy.

PROBLEM: Mating of CBA/J (H-2k) with DBA/2 (H-2d) males leads to a high rate of spontaneous resorption (about 40%), which is not seen in other mating combinations, such as CBA/J X BALB/c. The activation of natural killer cells (NK cells) seems to be a key mechanism for the maternal-fetal intolerance in allogeneic pregnancy, and recurrent spontaneous abortion. The effect of expression of the NK cell activating receptor Ly49D recognizing BALB/c or DBA/2 class I MHC was investigated. METHOD OF STUDY: Intracellular interleukin (IL)-100 production was detected and target cell survival rates were calculated after 22 hr coincubation of rat NK cells transfected, or not. with a murine Ly49D receptor, with either male BALB/c or male DBA/2 splenocytes, by using flow cytometry. RESULTS: Ly49D negative rat NK cells produced 13.7% more IL-10 than Ly49D positive rat NK cells, and more splenocytes were killed by Ly49D transfected rat NK cells (survival rate 2.45%) than by Ly49D negative rat NK cells (survival rate 4.36%). CONCLUSION: After physiological stimulation with BALB/c or DBA/2 splenocytes, rat NK cells are able to synthesize IL-10. Recognition of mouse splenocyte major histocompatibility complex (MHC) by Ly49D mice receptor decreased IL-10 production. The observed increase in killing activity might be a result of this phenomenon. NK cell activation via the Ly49D receptor might play an important role in pregnancy failure, but cannot explain why CBA/J X DBA/2 matings are abortion prone, and CBA/J X BALB/c matings are abortion resistant.

Abortion, Spontaneous↗
PubMed2000

Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7.

BACKGROUND: Cytomegalovirus (CMV) is the prototype member of the beta-herpesvirinae, which can cause multiple organ dysfunction in the immunocompromised host. Human herpesvirus 6 (HHV-6) and HHV-7 are newer members of the beta-herpesvirinae that can cause febrile illness in young children and are also possible pathogens in the immunocompromised patient. AIM: CMV is detected in histopathological sections by visualisation of owl's eye inclusion bodies. The aim of this study was to quantify the relation between CMV, HHV-6, and HHV-7 viral loads and the presence of owl's eye inclusions in histological sections. METHODS: Histopathological examination of postmortem material and recording of owl's eye inclusion bodies were performed. CMV, HHV-6, and HHV-7 were detected by qualitative and quantitative polymerase chain reaction (PCR) from the same postmortem samples. Statistical analysis of the histopathological and PCR results was performed. RESULTS: There was a significant association between the detection of owl's eye inclusion bodies and positive CMV PCR (p < 0.001); the median CMV viral load was significantly higher in samples that were positive for owl's eye inclusions (p < 0.001). No association was found between the presence of owl's eye inclusions and HHV-6 or HHV-7 positivity. CONCLUSION: Histological detection of owl's eye inclusion bodies is an insensitive but highly specific method for detecting CMV organ involvement. Owl's eye inclusion bodies are not associated with HHV-6 or HHV-7 infection.

Cytomegalovirus↗
PubMed2000

White bears and other elusive intrusions. Assessing the relevance of thought suppression for obsessional phenomena.

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

Affect↗
PubMed2000

High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients.

The aim of this study was to correlate human herpesvirus (HHV)-6 viral load with clinical symptoms in allogeneic stem cell transplant (SCT) patients. Seventy-four patients were monitored during the first 3 months after SCT using a qualitative polymerase chain reaction (PCR) for HHV-6 DNA. HHV-6 was detected in 181 out of 494 samples (36%) from 58 (78%) patients. These 181 samples were analysed using a quantitative competitive PCR. DNA could be quantified from 146 out of 181 samples (80.6%). The HHV-6 viral load was highest at 4 weeks compared with 8 weeks (P < 0.001) and 12 weeks (P = 0.01) after SCT. Three patients had HHV-6 encephalitis and one patient had hepatitis. The HHV-6 DNA levels were higher in patients with HHV-6 than in those without HHV-6 (P = 0.01). Patients who received grafts from unrelated or HLA-mismatched family donors had significantly higher HHV-6 DNA levels than patients who received grafts from matched sibling donors (P < 0.001). In a multiple regression model, unrelated donor grafts (P < 0.001) and use of intravenous immunoglobulin prophylaxis (P = 0.04) influenced HHV-6 DNA levels. HHV-6 viral load was significantly correlated with delayed platelet engraftment in both univariate (P < 0.01) and multivariate analysis, and to the number of platelet transfusions.

Acyclovir↗
PubMed1999

Murine T cell determination of pregnancy outcome.

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

Abortion, Spontaneous↗
PubMed1999

Interactions between beta-herpesviruses and human immunodeficiency virus in vivo: evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6.

In vitro, beta-herpesviruses can stimulate or inhibit HIV replication under particular circumstances. In order to investigate the effects of beta-herpesvirus infection on HIV replication and vice versa at an organ level, we determined the quantitative relationships between cytomegalovirus (CMV), human herpesviruses (HHV) 6 and 7, and HIV-1 proviral DNA using quantitative competitive PCR methods in 141 organs collected at autopsy from 11 AIDS patients. The presence of HHV-6 DNA in an organ was significantly associated with elevated HIV-1 proviral DNA (difference in HIV median loads, 1.3 log10 genomes; P = 0.004). Consistent with this, there was a trend for the presence of HIV-1 proviral DNA to be associated with an elevated HHV-6 load (0.44 log10 difference; P = 0.07). In contrast, there were no significant differences between viral loads in the combinations of either CMV or HHV-7 with HIV-1 proviral DNA load. Pairwise combinations of the beta-herpesviruses revealed that the quantity of HHV-7 was increased in the presence of HHV-6 (difference in median loads, 1.3 log10; P = 0.001) and the quantity of HHV-6 was increased in the presence of HHV-7 (difference in median loads, 0.7 log10; P=0.002). These results demonstrate that the presence of HHV-6 in an organ is significantly associated with an elevated HIV-1 proviral load and have implications for understanding HIV pathogenesis in the human host and the role that beta-herpesviruses, especially HHV-6, might play as cofactors in the HIV disease process.

AIDS-Related Opportunistic Infections↗
PubMed1999

Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus.

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

Adult↗
PubMed1999

Laparoscopic orchidopexy for the intra-abdominal testis.

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

Adolescent↗
PubMed1999

Common and specific dimensions of self-reported anxiety and depression: the BDI-II versus the BDI-IA.

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

Adjustment Disorders↗
PubMed1999

Why did your mother reject you? Immunogenetic determinants of the response to environmental selective pressure expressed at the uterine level.

PROBLEM: Maternal "rejection" of the implanted conceptus is considered to account for a significant proportion of miscarriages (abortions) in both humans and animals. Our understanding of mechanisms has been limited, and hence, explanations for nonrejection have remained largely speculative. Losses, when they occur, could represent either random accidental failure of protective mechanisms or a more purposeful discrimination. METHOD OF STUDY: An analysis of the most recent data. RESULTS AND CONCLUSIONS: The embryo is most akin to a parasite, and pregnancy is most akin to a host-parasite interaction. If one excludes chromosome abnormalities in the embryo as a cause of death, activation of coagulation mechanisms, leading to vasculitis affecting the maternal blood supply to the implanted embryo, appears to represent a major loss-causing mechanisms--a form of ischemic autoamputation. Proinflammatory T-helper (Th) 1-type cytokines trigger this process via upregulation of a novel prothrombinase, fgl2. Th2/3 cytokines, such as interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-beta 2, may antagonize the processes involved. Cytokine balance is determined by the genetics of the mother, which regulate her response to stress; endotoxin (LPS); and paternal antigens, selectively expressed on the trophoblast of the embryo, via imprinting. Based on studies in abortion-prone mice, where immunity to paternal alloantigens prevents loss, three distinct gene products in the embryo are proposed to determine the cytokine response to maternal lymphomyeloid cells in the uterus.

Abortion, Spontaneous↗
PubMed1999

The emerging role of immunoregulation of fibrinogen-related procoagulant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans.

PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, and interleukin [IL]-1), which cause abortion via a novel prothrombinase, Fgl2, and polymorphonuclear leukocytes. The site of activation may be maternal vascular endothelium on arteries and veins nourishing the placenta. Activation of coagulation is also prominent in spontaneous abortion of chromosomally normal human embryos. We asked where is Fgl2 up-regulated in the uterus in murine abortions, and if similar Fgl2 expression occurs in human pregnancy failure. METHODS: Control CBA X DBA/2 pregnant mice, or from mice injected with TNF-alpha + IFN-gamma on day 7.5 of gestation, were removed on day 8.5, fixed, sectioned, and subject to in situ hybridization for Fgl2. Sections were also stained for fibrin. Elective first trimester termination samples or biopsies taken early in the course of a recurrent miscarriage were similarly fixed, sectioned, and analyzed by in situ hybridization. Control and cytokine-treated mice were anticoagulated with heparin, an activator of antithrombin III, and/or the direct anti-thrombin inhibitor hirudin. RESULTS: Low level Fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up-regulation in this area as well as in a band at the junction of decidua and myometrium. Trophoblast also became strikingly positive. Fgl2 expression was associated with increased fibrin staining. Anticoagulation significantly protected against abortions, but doses were limited by the complication of retroplacental hemorrhage. In tissue from normal first trimester pregnancy, minimal Fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua. In spontaneous abortion of normal embryo, striking Fgl2 positivity was seen in syncytiotrophoblast and extravillous cytotrophoblast, in association with areas of thrombus formation. CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible. External dangers in the form of stress, endotoxin, and antigens eliciting Th1 cytokine responses upregulate Fgl2 prothrombinase in trophoblast as well as in decidua, which results in spontaneous abortion of immunogenetically "weaker" embryos.

Abortion, Spontaneous↗
PubMed1999

Optimized dairy grazing systems in the northeast United States and New Zealand. I. Model description and evaluation.

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

Agriculture↗
PubMed1999

Optimized dairy grazing systems in the northeast United States and New Zealand. II. System analysis.

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

Agriculture↗