CD4+ T cells: specificity and function.
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Biomedical subjects
Publications and source records attributed to J West.
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Isolated human and mouse pancreatic islet cells and the rat insulinoma cell line RIN-m5F were used to examine the ability of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to regulate the expression of the class I and class II major histocompatibility (MHC) surface proteins and mRNA in beta-cells. Each cytokine increased significantly the expression of class I MHC proteins as determined by double indirect immunofluorescence microscopy and flow cytofluorimetric analysis. In the RIN-m5F cells, this increase in surface expressed class I MHC proteins was mirrored by an increase in the level of class I MHC mRNA. The order of potency of the cytokines on class I MHC expression was TNF-alpha plus IFN-gamma greater than or equal to IFN-gamma greater than or equal to TNF-alpha. While IFN-gamma or TNF-alpha alone were without effect, in combination they were found to induce class II MHC proteins on 30-40% of human or murine beta-cells. In contrast, IFN-gamma plus TNF-alpha did not induce detectable class II MHC proteins or mRNA in the RIN-m5F cells. These findings indicate that 1) TNF-alpha, in addition to IFN-gamma, upregulates the expression of beta-cell class I MHC proteins and mRNA, and 2) more than one signal is required for the induction of class II MHC proteins on beta-cells. The ability of IFN-gamma plus TNF-alpha to induce class II MHC proteins on only a fraction of the normal beta-cell population and not on RIN-m5F cells suggests that this response is related to the differentiation state of the beta-cell.
This solid-phase colorimetric microtiter-plate clotting assay is much more sensitive than standard clotting tests. In enzyme-linked coagulation assay (ELCA), enzyme-labeled fibrinogen and solid-phase fibrinogen are the substrate for thrombin generated in the clotting cascade. We used this assay to measure the factors of the extrinsic pathway by an extrinsic pathway-specific assay (EP-ELCA) and to determine the individual factors of the extrinsic pathway (VII, X, V, II) in plasmas of coumadin-treated and heparin-treated patients, with prothrombin time (PT) values used as a reference. In the ELCA method, samples and controls are incubated on the same plate, eliminating the requirement for pre-standardization of the substrate "plasma" before the factor assay is done. Concentrations of factors are determined by serially diluting sample and control plasmas to yield equivalent activity at given dilutions, a more direct approach for measuring specific factors than determining log concentrations vs log clotting time. Changes in the concentrations of clotting factors are seen before changes are apparent by PT. For coumadin-treated patients, all vitamin K-dependent factors were significantly (P less than or equal to 0.001) less than in normal controls, whereas factor V concentrations were normal, as expected. For patients treated with heparin, concentrations of factors X and VII were less than in normal controls (P less than 0.01) and results for EP-ELCA, II, and V assays were normal. This methodology can readily be automated.
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Cloned L3T4a+ antigen-specific, class II-restricted T cells can be subdivided by function and by cytokine production. All cloned T cell lines produce T cell growth factors that can be distinguished by the ability of monoclonal antibodies to inhibit the proliferation of cytokine-dependent T cell lines induced by these T cell growth factors. From these types of analyses, it has been shown that all cloned T cells that help hapten-specific B cells secrete immunoglobulin, produce interleukin 4 (IL 4). Those cloned T cells that fail to help for anti-hapten responses produce neither IL 4 nor interleukin 2 (IL 2), yet release an activity that induces the proliferation of the cytokine-dependent T cell line, HT-2. Additional analysis of the HT-2 stimulating activity has shown that it is indistinguishable from granulocyte macrophage-colony stimulating factor (GM-CSF)--this activity being produced by all cloned T cells tested. Thus GM-CSF is a product of all cloned L3T4a+ T cell lines tested thus far, and can serve as a T cell growth factor for HT-2, as well as a co-factor for in vivo derived T cells.
T cells can be subdivided based on cell surface markers, MHC restriction, function, and production of soluble factors. Analysis of the ability of cloned, Ia-restricted, L3T4+ T cells to induce an in vitro anti-hapten antibody response to hapten-carrier conjugates allowed the definition of three functional subtypes. To examine whether these functional subtypes also differed in the production of soluble mediators, supernatants of the cloned lines were examined for the production of T cell growth factors and factors inducing increased expression of Ia glycoproteins on small resting B cells. All of the cloned lines produced T cell growth factors that could be further differentiated by inhibition with monoclonal antibodies. None of the Ia-restricted, L3T4+ cloned T cell lines that failed to produce IL 4/BSF-1 could provide helper function. Thus, the activation of antigen-specific B cells by helper T cells appears to require IL 4/BSF-1 as a necessary but not sufficient signal for differentiation into antibody-forming cells.
In a study of wound healing at high altitude, subcutaneously implanted PTFE tubes were used to stimulate and measure accumulation of wound hydroxyproline (an index of collagen) in 26 patients who had appendectomy and in 38 patients who had cholecystectomy. Patient age, length of surgery, and postoperative recovery seemed to predict better healing in patients who had appendectomy, but there was a difference in the preoperative illness of the two groups: acute cholecystitis was treated medically and cholecystectomy performed after resolution of the acute phase of illness, whereas patients who had appendectomy were taken to surgery as soon as a diagnosis was made. It was observed that patients who had appendectomy accumulated 20% less hydroxyproline than patients who had cholecystectomy (p less than 0.02), and that the depression of hydroxyproline accumulation was significantly related to length of preoperative illness (p = 0.008). This decrease in wound hydroxyproline accumulation is attributed to the acute preoperative illness. Conceptually, this is a unique situation since the brief illness did not produce lasting debility, and the source of illness, the inflamed appendix, was not present during healing. This indicates that even a brief preoperative illness has a more prolonged influence on postoperative healing than usually anticipated.
In addition to handling urgent emergency calls for advice about major poisonings, the NSW Poisons Information Centre handles calls from the general community about poisonings of a much more minor nature. Although these poisonings may be perceived by the callers to be significant, the only action required is either reassurance that there is, in fact, no problem or simple treatment that does not require further intervention. The study demonstrates that callers in this category would have sought professional advice elsewhere had the Centre not existed and the subsequent cost effectiveness of the Centre's role in taking these calls.
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This study compares the responses to a self-report depression inventory administered to a sample of 243 Saudi and American expatriate psychiatric outpatients of a large Eastern Province medical centre in Saudi Arabia. The inventory was developed by Beck et al. (1961), and the Arabic language form was validated by West and Al-Kaisi (1982). A Kruskal-Wallis statistical analysis revealed that American male patients tended to be more depressed than American female patients, Saudi female patients reported "depression scores" higher than those of Saudi male patients, and Saudi patients overall reported higher "depression scores" than American patients participating in the same study. The highest and lowest significant response frequencies for Saudis were: Pessimism (H = 74.26) and Hypochondria (H = 17.13); for Americans: Indecisiveness (H = 25.57) and Self-Image (H = 7.85). (Statistical significance when H = 7.82, p less than .05; H = 16.27, p less than .001; df = 3). Although explanations are offered, the appearance of psychopathology as designated by this cross-cultural scale requires further cultural examination.
The present study describes an Arabic cross-cultural validation of the Beck Depression Inventory. An Arab sample of 53 cases was subjected to the original validation procedures which involved a preliminary exercise and a translation from English to Arabic. Acceptable equivalent meanings of Beck's depth-of-depression criteria were established by the Arab clinicians so that independent and valid clinical ratings could be made. Statistical analyses of the internal consistency and stability of the Arabic-BDI indicated a high degree of reliability. Correlations between Arabic-BDI scores and Arab clinicians' ratings indicated a high degree of validity. The results of the cross-cultural validation study agree favorably with those of the original American validation. Although the Arabic inventory makes possible an assessment of the level and intensity of a reactive type depression suffered by Saudi Arab psychiatric outpatients living in the Eastern Province, it must be adapted dialectically for other Arab-speaking regions.
Paraplegia can lead to social stigmatisation, sexual difficulties, and emotional maladjustment. The specific nature of problems experienced in these areas were investigated in an interview study of 22 male and female paraplegics. These interviews were followed up by a postal questionnaire and both qualitative and quantitative data are presented in this report. Effective counselling can only be offered on the basis of an understanding of problems as they are subjectively experienced, and with an acknowledgement of the wide differences that exist between individuals in the way that they view and react to their situation.
Paraplegia creates social, sexual and emotional problems, and the impact of these was investigated in an interview study of 22 male and female paraplegics. Of particular concern was the way in which individuals were coping with the difficulties confronting them. People used a number of strategies for dealing with other people and their attitudes, and for readjusting sexually. In dealing with their own personal feelings about their disability, ways of coping were varied and included suppression, denial and repression, resignation and acceptance, positive thinking and independence and assertiveness. No specific recommendations can be made about ways of coping that will be most adaptive, since these will depend upon the individual and his or her circumstances. What is important for counselling, however, is to recognise the range of coping strategies that are available, and to be able to guide the individual toward those which effect the best match between their needs and the demands of the situation.
Two improvements that greatly enhance the rate of phosphotriester oligonucleotide synthesis are described: 1) use of hindered primary amines, e.g. t-butyl amine for decyanoethylation of oligonucleotide triester intermediates, and 2) a simplified isolation procedure that eliminates the tedious bicarbonate extraction after each condensing reaction. Using the improved procedures, oligonucleotide fragments can be synthesized as rapidly as using solid phase chemistry. The final products are purer than those obtained by solid phase chemistry since each intermediate block is purified by chromatography. The technique has been used to synthesize five oligonucleotide fragments (size 15 to 20) for the purpose of performing guided site-specific mutagenesis on a cloned E. coli lipoprotein gene.
Plasma antidiuretic hormone concentrations were measured in a group of children with acute asthma and in a control group. Very high levels of antidiuretic hormone were found in the asthmatic group. There were no changes in other biochemical indices. If overproduction of antidiuretic hormone is sustained then fluid administration to children with severe acute asthma is potentially dangerous.
Although hydralazine improves cardiac performance in patients with chronic left ventricular failure, its long-term clinical efficacy has not been established in controlled trials. We carried out a double-blind randomized trial of hydralazine (200 mg daily in 16 patients) versus placebo (16 patients) in patients with class III and IV symptoms while they were taking digitalis and diuretics. Maximal treadmill exercise time was determined prior to and at 4, 10, 18, and 26 weeks of hydralazine or placebo treatment; average follow-up was 20 weeks. We found no change in body weight, clinical class, resting heart rate and blood pressure, or heart size (by chest x-ray examination and echocardiogram) during treatment in either group. The total number of complicating clinical events was insignificantly fewer in the hydralazine treated group (8 vs 13). Control exercise duration in the hydralazine group averaged 259 +/- 21 seconds (SEM), and increased to 347 +/- 35 seconds at 4 weeks (p less than 0.01) and 421 +/- 38 seconds at 26 weeks (p less than 0.001). Exercise duration also increased significantly in the placebo group, from 271 +/- 30 seconds at control to 340 +/- 44 seconds at 4 weeks (p less than 0.02) and 339 +/- 46 seconds at 26 weeks (p less than 0.02). No differences between groups were significant. Left ventricular ejection fraction remained depressed and unchanged in both groups. Thus long-term vasodilator treatment with hydralazine alone is not significantly more effective than placebo in chronic heart failure.