Fiery entrance for the HIV co-receptor.
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Antigens, Differentiation, T-Lymphocyte↗
Biomedical subjects
C Thompson
Publications and source records attributed to C Thompson.
Costimulation of superantigen-activated T lymphocytes by autologous dendritic cells is dependent on B7.
Highly purified populations of dendritic cells (DCs) can be isolated from various tissues such as skin and blood. These sites are likely to encounter secreted toxins of bacteria such as superantigens. In vivo, DCs express the cell surface molecule B7, a counterreceptor for CD28 which provides costimulation to resting T cells. Highly purified preparations of DCs obtained from the epidermis and dermis of normal skin as well as blood were used to study the role of B7 in superantigen presentation to autologous T cells, as well as in alloantigen responses. We compared these results to those obtained with nondendritic antigen presenting cells (APCs) such as mononuclear cells derived from the Ficoll-Hypaque interface (PBMCs). All DC populations strongly express B7, and in a purely autologous system staphylococcal enterotoxin B (SEB)-mediated T cell proliferation was inhibited by 55-85% using a soluble chimeric fusion protein (i.e., CTLA4Ig), a potent inhibitor of CD28:B7 interaction. In contrast, while T cells also proliferated vigorously when stimulated by SEB in the presence of autologous PBMC (which only weakly express B7), costimulation was not inhibited by CTLA4Ig. In allogeneic responses, DCs were also more potent stimulators compared to PBMC, but both types of APC:T cell reactions were almost completely inhibited by CTLA4Ig (> 90%). For both SEB-mediated reactions and alloantigen reactions, the relative importance of LFA-1 and HLA-DR was similar between DCs and PBMCs. The data indicate that these DCs express B7, which can function in the SEB-driven response of autologous T cells, as well as in allogeneic T cell reactions. Overall, when comparing the relative costimulatory capabilities of different types of APCs, it appears the relatively low level of B7 expressed by PBMC functioned effectively in allogeneic reactions, whereas only the higher levels of B7 expressed by these DC populations functioned in SEB-mediated T cell responses.
Abatacept↗
Vaccination of sheep with purified cysteine proteinases of Fasciola hepatica decreases worm fecundity.
There has been some evidence from several parasite systems that proteinases might have potential as protective antigens against parasitic infection. A cysteine proteinase complex identified in the regurgitant of adult F. hepatica was examined in this context. The thiol-cathepsin-related proteinases of M(r) 28,000 were purified and tested in vaccine trials of sheep infected with liver fluke. Ten animals were immunised with the purified proteinases and developed antibodies to the cysteine proteinases prior to challenge with F. hepatica metacercariae. Infection appeared to cause a boost in antibody response by Week 4 into infection, and antibody levels were generally sustained throughout infection. The cysteine proteinases are not novel antigens, since low-level antibody titres were also detected in nonimmunised controls by late infection. On completion of the trial, there was no difference in worm burden between the two groups. However, faecal egg counts and therefore worm fecundity were significantly decreased.
Animals↗
Human endothelial stimulation of allogeneic T cells via a CTLA-4 independent pathway.
It is accepted that T cells require at least two signals to undergo proliferation and cytokine release: an antigen dependent signal mediated via the the TCR (T cell receptor) and an antigen independent signal mediated via one or more accessory or adhesion molecules. Interaction between CD28 or CTLA-4 and the B7 co-receptors found on many antigen presenting cells (APC) is known to be essential for antigen specific (including alloantigen) expansion of T cells in vitro and in vivo. CTLA-4-Ig is a fusion protein with very high affinity for B7. It has been used in vivo to block both allograft and xenograft rejection. Most of the work investigating second signal requirement has used 'professional' APC. In view of the observations that class II positive human endothelial cells can cause direct allostimulation of resting CD4+ and CD8+ T cells, we have investigated the requirement of CTLA-4 in this response. The current studies show that the proliferative response of allogeneic CD4+ and CD8+ T cells to interferon-gamma treated HUVEC (human umbilical vein endothelial cells) is inhibited by monoclonal antibodies (mAbs) against MHC class II and class I antigens, respectively, but not by CTLA-4-Ig. In contrast, lymphocytes proliferating in response to allogeneic splenocytes are inhibited by CTLA-4-Ig. Cell surface binding studies using flow cytometry demonstrated failure of endothelial cells to bind either CTLA-4-Ig or mAbs against B7 receptors. In conclusion, different APC use different co-stimulatory signals. The possibility that this leads to different cytokine profiles needs to be investigated to further understand the role of endothelial cells in transplant rejection.
Abatacept↗
A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. I. Neuropsychological performance and neurological status at baseline and at 12-month follow-up.
The aim of this study was to determine whether HIV infection is associated with neurological or neuropsychological impairment in the asymptomatic and early symptomatic stages of disease. Subjects included 61 gay men (41 HIV-, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. The assessments at baseline were conducted double-blind to HIV serostatus. Measures included a neuropsychological battery, neurological examination and full psychiatric assessment. There were no differences between the asymptomatic HIV+ and HIV- groups at baseline or at follow-up in terms of mean scores on neuropsychological tests. Mean scores were within the normal range for all neuropsychological tests for both groups. Multiple regression analysis was used to predict each individual's performance at follow-up on the basis of their baseline performance, psychiatric state, neurological history and drug use for each of the neuropsychological tests. HIV+ subjects were more likely than control subjects to perform at a significantly lower level at follow-up on one or more tests than predicted on the basis of their baseline performance.
AIDS Dementia Complex↗
A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. II. Psychological and health status at baseline and at 12-month follow-up.
The aim of this study was to determine whether HIV infection is associated with increased psychosocial distress in the asymptomatic and early symptomatic stages of disease and to determine the factors associated with reporting health symptoms. Subjects included 61 gay men (41 HIV--, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. Measures included a detailed standardized psychiatric interview (Present State Examination, PSE), a range of psychosocial self-report measures and a physical symptom checklist. There were no differences between the HIV+ and HIV-- groups in terms of self-reported symptoms. Multiple regression analysis showed that the symptom reporting was not associated with clinical or immunological markers of disease progression but was associated with measures of psychosocial distress. Although both groups showed elevated levels of psychosocial distress at the time of HIV testing, there were no differences between serostatus groups at follow-up. Multiple regression analysis indicated that the best predictors of PSE scores at follow-up were baseline PSE score and a history of psychiatric illness. Early HIV disease is not associated with increased psychosocial distress and symptom reporting is more closely related to psychological measures than to clinical or immunological markers of disease.
AIDS Dementia Complex↗
A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition. In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined. Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance. After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).
Activities of Daily Living↗
Effect of a recombinant endotoxin-neutralizing protein on endotoxin shock in rabbits.
OBJECTIVES: Limulus anti-lipopolysaccharide factor, an 11.8-kilodalton peptide isolated from amebocytes of Limulus polyphemus inhibits the biologic activities of endotoxin in vitro, including gelation of Limulus amebocyte lysate. A recombinant version of Limulus anti-lipopolysaccharide factor, termed endotoxin neutralizing protein, has now been expressed in yeast. Endotoxin-neutralizing protein was evaluated for its potential prophylactic and therapeutic effects in rabbits challenged with Escherichia coli endotoxin. DESIGN: Controlled animal trial. SETTING: Animal research laboratory. SUBJECTS: A total of 112 New Zealand white rabbits were studied. INTERVENTIONS: Rabbits were challenged with an LD80 dose of E. coli endotoxin (100 micrograms/kg); control animals (n = 52) were treated with saline solution at the time of endotoxin challenge; experimental animals received endotoxin-neutralizing protein 2.5 mg/kg prechallenge (n = 20), 5.0 mg/kg prechallenge (n = 20), or 5.0 mg/kg 30 mins postchallenge (n = 20).
Animals↗
Modelling the integration of myocardial regional perfusion and function.
The purpose of the study is to describe a method for the investigation of myocardial kinetics (wall motion or wall thickening) to define myocardial perfusion characteristics further. The data are myocardial perfusion single photon emission computed tomographic images gated in eight time bins, following the administration of a 99Tcm-labelled perfusion agent. Wall motion is defined by the phase and amplitude of the centripetal motion of the first moment of the myocardial count rate density distribution along a radius originating in the centre of the left ventricular cavity. Wall thickening is defined by phase and amplitude of the changes in the second moment of the density distribution along the radius multiplied by the maximum density. Wall motion amplitude was abnormal in 28% of transient and 43% of fixed perfusion abnormalities, phase delays were present in 28 and 57%, respectively. Wall thickening was abnormal in amplitude in 14% of transient and 86% of fixed perfusion abnormalities. We conclude that the positive predictive value of wall-thickening abnormalities relative to fixed perfusion abnormalities is high (86%). Whether fixed perfusion defects with normal wall thickening represent viable myocardium remains to be investigated.
Aged↗
Interphase cytogenetics of melanocytic neoplasms: numerical aberrations of chromosomes can be detected in interphase nuclei using centromeric DNA probes.
This study shows that fluorescence in situ hybridization (FISH) to thin sections cut from paraffin-embedded material can be used to distinguish between groups of melanocytic neoplasms and thus may be useful as an investigational and diagnostic tool. FISH with a probe for a repeated, alpha satellite sequence specific to chromosome 17 was used to investigate the chromosomal composition of dysplastic (or Clark's nevus) and Spitz's nevi and malignant melanomas. Hybridization was to thin (approximately 6 microns) sections cut from paraffin blocks. The number of signals per nucleus in normal diploid cells is expected to be less than 2 since the sections are thinner than one nuclear diameter. Keratinocytes and lymphocytes in these same sections showed 1-2 signals per nucleus with a mean of 1.2. Dysplastic nevi showed 1-4 hybridization signals per nucleus with a mean of 1.5. Spitz's nevi showed 1-2 signals per nucleus with a mean of 1.3. Melanomas showed 1-6 signals per nucleus with a mean of 2.1. We were thus able to use FISH to demonstrate differences in chromosome numbers between groups of benign and malignant melanocytic neoplasms. Technical improvements in the near future can be expected to result in more precise estimates of chromosomal number.
Centromere↗
Influence of socioeconomic status, ethnicity and an educational brochure on compliance with a postal faecal occult blood test.
The study aimed to determine if socioeconomic status and ethnicity affect compliance with postal faecal occult blood test screening, and if compliance can be increased by adding an educational brochure. A pilot intervention study was used in socioeconomically defined postcodes and defined census collection districts of the Southern Sydney Area Health Service. The study population of men and women aged 45 to 75 years was selected from general practice lists in the defined postcodes. Samples were comparable for age, sex, and socioeconomic indices. Compliance, using a general practitioner letter alone, was: for the Australian middle-socioeconomic status sample, 65.8 per cent (95 per cent confidence interval (CI) 59.5 to 72.1), the Australian low-socioeconomic status sample, 63.9 per cent (CI 57.3 to 70.5), the Arabic low-socioeconomic status sample, 33.3 per cent (CI 27.2 to 39.4). With the general practitioner letter plus brochure, compliance was: Australian middle-socioeconomic status sample, 67.0 per cent (CI 60.5 to 73.5), Australian low-socioeconomic status sample, 62.1 per cent (CI 55.3 to 68.9) and Arabic low-socioeconomic status sample, 36.8 per cent (CI 30.6 to 43.0). Compliance was higher in all Australian samples than in Arabic samples. A brochure, designed to increase compliance with testing, had no significant effect in Australian samples. Australian samples of different socioeconomic status complied almost equally. Results suggest that advice from the local doctor is very effective in motivating patients to screen with faecal occult blood testing.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Evaluation of a microdot immunofluorescent antigen detection test for Chlamydia trachomatis.
OBJECTIVE: To evaluate a centrifuge enhanced direct immunofluorescent antigen test (MD test), compared with conventional culture and ELISA testing in the diagnosis of Chlamydia trachomatis infection. SETTING: A District General Hospital situated 30 miles from a University Department of Medical Microbiology. SUBJECT AND METHOD: A prospective study on specimens from 638 patients. Culture was performed on 348 specimens from genitourinary medicine patients and ELISA testing was carried out on 272 specimens from Gynaecology patients. RESULTS: When compared with culture the MD test had a sensitivity of 90.6%, specificity of 96.8%, positive predictive value of 74.3% and a negative predictive value of 99%. When compared with confirmed ELISA results the MD test had a sensitivity of 100%, specificity of 98.8%, positive predictive value of 78.5% and negative predictive value of 100%. CONCLUSION: The MD test compares favourably with other chlamydial diagnostic techniques and in our setting is preferable to sending specimens for chlamydial culture. It is not suitable as the sole diagnostic method for screening large numbers of specimens but is a cost effective confirmatory test for positive ELISA results.
Antigens, Bacterial↗
Neurodevelopment in pediatric HIV infection. The use of CAT/CLAMS. Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale.
Pediatric neuro-AIDS may be the first clinical manifestation of HIV infection in children born to HIV-infected mothers. As part of the neurodevelopmental examination of children, the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was investigated as a tool for pediatricians to use to monitor the development of children at risk for HIV infection. The CAT/CLAMS was found to detect neurodevelopmental differences between HIV-infected and uninfected children at 12 and 18 months of age. Good correlations were found between the CAT/CLAMS and concurrently administered Bayley Scales of Infant Development. These findings suggest that the CAT/CLAMS should be considered as a part of the neurodevelopmental examination of children at risk for pediatric neuro-AIDS.
Acquired Immunodeficiency Syndrome↗
The use of high-dose antipsychotic medication.
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Contraindications↗
Patterns of food choices among Arkansans with less than a high school education.
This study surveyed students in Adult Basic Education (ABE) Programs in Arkansas to determine their pattern of food choices. The results indicated that entire food groups, e.g. vegetables, fruits, or milk were not included in the diets of many participants. This population more frequently chose high fat than low fat foods. Regression analyses indicated that the choice of low fat products increased with age and family income level. The most dramatic trends were in changes in consumption of dairy products, fruits, and vegetables. These data support the need for nutrition education in Arkansans with less than a high school education.
Adolescent↗
Management of depression in real-life settings: knowledge gained from large-scale clinical trials.
This paper reports the results of two studies of depressed patients, evaluating the efficacy and toleration of the selective serotonin reuptake inhibitor (SSRI) sertraline in a general practice setting in the UK. In the first of these studies, 308 patients, with a DSM-III-R diagnosis of major depressive episode, were treated for 6 weeks with either sertraline 50-100 mg/day or the tricyclic antidepressant dothiepin 75-150 mg/day, or placebo. Seventy-six per cent of sertraline-treated patients were maintained on the lower dose (50 mg/day), whereas 81% of dothiepin-treated patients required the higher dose (150 mg/day). Sertraline-treated patients demonstrated a significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) severity scores compared with placebo-treated patients, while dothiepin-treated patients did not show significant improvement compared with placebo. The active drugs were well tolerated, and there were no significant differences in adverse events between the groups. The second study, "Sertraline in General Practice, A Multicenter Assessment", or SIGMA, was a large, multicentre trial with a cohort of 3396 patients recruited to receive 6 weeks of treatment. Patients started on sertraline 50 mg/day, and for 59% of patients this was the final dose; less than 10% of patients reached final doses of more than 100 mg/day. A 50% or greater reduction in MADRS scores was seen in 69% of patients across a wide range of severity of symptoms at baseline, and 87% of patients demonstrated excellent or good toleration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
1-Naphthylamine↗