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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 145 records · Page 8Linked to original sources
PubMed1990

Macromolecular lactate dehydrogenase: an innocent bystander.

Lactate dehydrogenase (LD) activity is often increased in malignancy, and may occasionally be a useful tumor marker. In the case reported here, a persistently increased LD activity led to an extensive search for a neoplasm. Results of routine investigations were normal, but LD electrophoresis followed by gel filtration and immunofixation confirmed the presence of a circulating macromolecular LD, comprising IgAK bound to LD. Altogether it may provoke unnecessary investigations, the LD-IgA complex currently has no diagnostic significance.

Adult↗
PubMed1990

Assessment of physicians' office pathology testing: organisational considerations.

In this paper we consider organizational and design aspects of an assessment of physicians' office pathology testing, and discuss difficulties in measuring the level of performance and effectiveness of such diagnostic services. A major consideration is the trade-off between compliance with a well-defined protocol, and use of the technology in a way which resembles normal operating practice.

Australia↗
PubMed1990

Relationships between weight change and blood lipids in men and women: 'the Adelaide 1000'.

Relationships between changes in weight and blood lipids were examined in 655 subjects who had enrolled for a fitness programme. At entry data were obtained on weight, fitness, lipids, physical activity, diet, and smoking. On re-examination 2 years later approximately half the sample had maintained stable weight (+/- 2 kg), a quarter had lost (- greater than 2 kg), and a quarter had gained weight (+ greater than 2 kg). Analyses of weight change/lipid change relationships included comparisons of lipid changes in weight 'stable', 'losers', and 'gainers' groups, and multiple regression analyses controlling for the effects of age, diet, and fitness. It was found that changes in weight and lipids were significantly related, the relationship was stronger than between any other independent variable and changes in lipids, and it was stronger for men than for women. It was concluded that there is an independent cause and effect relationship between weight and lipids to an extent useful for clinical and public health purposes.

Adult↗
PubMed1989

Identification of I-A beta-chain residues critical for T cell recognition of peptide antigens.

Major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes involves the formation of a complex composed of the T cell receptor, antigen, and restricting MHC molecule. To elucidate the interactions occurring within the antigen recognition complex, we have evaluated the ability of a panel of cell lines expressing mutated I-Ak molecules to function in the recognition by T hybridoma cells of two distinct peptide antigens. Our results indicate that while alterations along the entire length of the proposed helical structure in the carboxyterminal half of the beta 1 domain interfere with the I-Ak-restricted recognition of human fibrinopeptide B, mutations which affect recognition of hen egg lysozyme/I-Ak fall almost exclusively in the central portion of the helix. On the basis of these and previous results, we propose a "T cell receptor-mediated peptide exchange model" for formation of the antigen recognition complex.

Amino Acid Sequence↗
PubMed1989

Clonotypic heterogeneity of Lewis rat T cells specific for the encephalitogenic 68-86 region of myelin basic protein.

Experimental autoimmune encephalomyelitis was induced in a Lewis rat by sensitization with synthetic peptide GP68-86, representing the 68-86 sequence of guinea pig myelin basic protein (GPMBP). To delineate T cell determinants of GP68-86, lymph node cells from this rat were activated in culture with GP68-86 and were fused with cells of the mouse thymoma BW5147. The resultant hybrids were cloned by limiting dilution and screened for GP68-86-evoked secretion of IL2 in the presence of rat splenocytes. Twelve T cell hybrids derived in this manner were tested for reactivity to different heterologous species of MBP as well as to substituted or truncated analogs of GP68-86. The hybrids generally exhibited potent reactivity to GPMBP but differed markedly in their reactivity to autologous rat MBP (RMBP). A few exceptional hybrids exhibited crossreactivity with peptides in which native serine75 or serine80 residues of GPMBP were substituted with either alanine75 (A75) or proline80 (P80) residues. These cross-reactive hybrids also possessed high levels of anti-RMBP reactivity. The remaining hybrids were unresponsive to the A75 and P80 substituted peptides and, with one exception, had relatively low levels of anti-RMBP reactivity. Unique reactivity patterns were also revealed by hybrid responses to peptides having modified C-terminal 84-86 residues. In summary, the contrasting fine specificities of different hybrids indicated that several distinct clones of T cells mediate the immune response of Lewis rats against the 68-86 region of GPMBP. Furthermore, heterogeneity in the hybrid response to "self" RMBP may reflect substantial differences in encephalitogenic potency of the T cell clones from which these hybrids were derived.

Amino Acid Sequence↗
PubMed1989

Cross-sectional and longitudinal relationships between physical fitness and risk factors for coronary heart disease in men and women: "the Adelaide 1000".

Measurements of aerobic fitness, weight, blood pressure, and lipids were made in 1000 sedentary men and women entering a fitness programme, and were repeated 2 years later in 733 subjects. Cross-sectional analyses including (a) comparisons of CHD risk factors in subjects grouped as "low", "low/moderate", "moderate/high", and "high" fitness, and (b) multiple regression analyses of relationships between fitness and risk factors showed that fitter subjects had better risk profiles than less fit. Longitudinal analyses including (a) comparisons of risk factor changes in subjects grouped as fitness "losers", "stable", "small gain", and "large gain", and (b) multiple regression analyses of relationships between fitness change and risk factor changes showed that fitness change was largely unrelated to risk factor changes. The study supported the existence of beneficial associations between fitness and risk factors but not cause and effect relationships.

Adult↗
PubMed1989

Bloody diarrhea in children.

Bloody diarrhea is a common problem in children. It is important to distinguish bloody diarrhea from other causes of rectal bleeding. Bacterial infections and parasitic infestations are responsible for most of the cases. Milk allergy is a frequent cause in young infants. Chronic inflammatory bowel disease occurs in older children. The cause is most often apparent after a thorough history and physical assessment is performed and the stool is examined for pathogens. Proctosigmoidoscopy with biopsy is the procedure of choice if the stool tests for pathogens are negative. A few children require further diagnostic evaluation by colonoscopy and/or radiographic procedures.

Child↗
PubMed1989

Screening laboratory tests for Crohn's disease.

The prevalence of abnormal values of initial screening laboratory tests was assessed for 24 children who eventually proved to have Crohn's disease. The screening tests included in this analysis were fecal alpha 1-antitrypsin (FA) concentration, erythrocyte sedimentation rate (ESR), total leukocyte count, serum albumin level, hemoglobin concentration, and qualitative testing of stool for the presence of blood. Of the 24 patients, 21 had abnormal FA values, 17 had anemia, 19 had an increased ESR, 14 had hypoalbuminemia, rectal bleeding was found in 8, and none had leukocytosis. All 24 patients had at least one abnormal screening test value; the most frequently abnormal result was the FA concentration. Pediatric patients without elevated FA values, anemia, a high ESR, bloody stools, or hypoalbuminemia are unlikely to have active Crohn's disease.

Adolescent↗
PubMed1989

Improved method for calculating calcium fractions in plasma: reference values and effect of menopause.

Multiple linear regression analysis showed that total calcium was significantly and positively related to albumin, globulin, anion gap, and bicarbonate in plasma from 556 normal postmenopausal women. The residual constant of 1.21 mmol/L approximated the normal mean for ionized calcium in plasma. The coefficients derived from the multiple regression analysis were used to calculate ionized calcium from total calcium and ligand concentrations in a series of 105 clinical cases in whom ionized calcium was measured with the calcium electrode. The regression equation was y = 1.00x -0.0039 mmol/L, where x is measured and y calculated Ca2+ (r = 0.78, P less than 0.001). The protein-bound, ultrafiltrable, and complexed fractions of the calcium were also calculated for plasma from 69 normal young men, 66 normal young women, and 305 normal postmenopausal women. The increased plasma calcium in the postmenopausal group was accounted for by an increase in the complexed fraction, due to increases in plasma bicarbonate and anion gap.

Adult↗
PubMed1988

Molecular associations of IA antigens after T-B cell interactions. I. Identification of new molecular associations.

In this report we report the identification of novel molecular associations involving the MHC class II (Ia) Ag expressed on the surface of Ag-presenting B lymphocytes. Biosynthetically radiolabeled murine B cells were incubated for 2 h in the presence or absence of T lymphocytes before treatment with the cleavable cross-linking reagent dimethyl-3,3'-dithiobispropionimidate. Anti-Ia immunoprecipitates of solubilized cell extracts revealed novel cross-linked products of Mr 90,000 to 95,000 which, upon cleavage of the cross-linker, could in part be resolved into native Ia and other structures of approximately Mr 67,000. The detection of the cross-linked products was significantly enhanced in B cells that had been co-cultured with T lymphocytes, but not with other cell types, and co-culture with various monoclonal T cell lines resulted in different levels of enhancement. Detection of the 90- to 95-kDa cross-linked products appeared to be independent of the foreign Ag for which the T cells were specific and could be enhanced when either cell type was replaced by a plasma membrane fraction, indicating that it resulted from direct cell-cell contact. These results suggest that some proportion of the Ia glycoproteins expressed on the surface of B cells become associated with other structures of Mr 67,000 upon Ag-non-specific interactions between T and B lymphocytes.

Animals↗
PubMed1988

Two roles for Ia in antigen-specific T cell activation. II. Toward a Velcro model of antigen recognition.

It has been previously reported that Ia Ag on APC seems to be involved in Ag-specific T cell activation in at least two different ways: one is to associate with foreign Ag to form a neoantigenic determinant (the Ag-specific Ia function), and the second is to interact with T cells in a non-Ag-specific manner. Both Ia functions are required for T cell activation. In the present study we examined whether the T cell structures responsible for the non-Ag-specific Ia interaction were separable from the Ag-specific alpha/beta TCR. Purified protein derivative of tuberculin (PPD)-specific murine hybridoma T cells and polyclonal lymph node T cells were stimulated for IL-2 production by APC pulsed with PPD, glutaraldehyde fixed, and anti-Ia antibody treated, to provide the antigenic PPD/Ia determinant, in the presence of glutaraldehyde-fixed non-Ag-pulsed APC, to provide the non-Ag-specific Ia interactions. However, in several different approaches the T cell structures or activation signals responsible for the Ag-specific recognition and non-Ag-specific Ia interactions seemed to be associated with each other in this experimental system. First, the Ag-specific and non-Ag-specific Ia interactions with T cells were both required simultaneously to initiate T cell activation, and it was not possible to activate T cells by providing either Ia signal subsequent to the other. Second, the T cell structures responsible for the non-Ag-specific Ia interactions appeared to be clonally distributed in PPD-specific lymph node T cells. Third, another T cell hybridoma specific for bovine insulin also showed dual Ia interactions, but the specificity of the non-Ag-specific Ia function was different than that for the PPD-specific T cell response. Fourth, all subclones of PPD-specific T hybridomas that had lost Ag-specific responsiveness also lost functional non-Ag-specific Ia interactions. Taken together, these observations suggest that a single species of TCR may mediate both the Ag-specific and non-Ag-specific Ia interactions. In addition, the non-Ag-specific Ia interaction with T cells augmented the Ag-specific Ia interaction for T cell activation, indicating that both types of interactions may be involved in some T cell responses. Based on these observations, a Velcromodel depicting the synergy between the two Ia functions is proposed in which a matrix of interactions consisting of higher affinity Ag binding and lower affinity Ia-TCR associations provides cooperative sets of signals necessary for cellular activation.

Animals↗
PubMed1988

Functional and biochemical parameters of peptide antigen presentation.

To understand the mechanism by which peptide antigens are processed and presented to T cells, we examined the T-cell response to the 13-amino-acid peptide alpha-melanocyte-stimulating hormone (alpha-MSH). To determine the fine specificity of T-cell recognition, T cells specific for alpha-MSH, and genetically restricted by I-Ab/d, were challenged with different alpha-MSH analogs and homologs. It was found that intact alpha-MSH, including the blocked amino and carboxy termini of the native molecule, was required for T-cell responsiveness. Antigen-presenting cells (APC) could be briefly pulsed with alpha-MSH and then present the alpha-MSH antigenic determinant to T cells, indicating that the relevant antigen was retained by the APC. APC stimulatory capacity was dramatically reduced by aldehyde treatment of the APC, or by pulsing the APC with alpha-MSH at low temperature. Efficient alpha-MSH pulsing was also impaired by treatment of the APC with the carboxylic ionophore, monensin, but not by the lysosomotropic agents chloroquine and methylamine. In addition, isolated APC plasma membranes added to the T cells in the presence of soluble alpha-MSH were not stimulatory. However, plasma membranes isolated from APC that had been previously pulsed with alpha-MSH retained stimulatory activity for T-cell responses. The only detectable alpha-MSH contained in these pulsed APC membranes was in an acid-stable complex of higher molecular weight than native peptide. The amount of alpha-MSH detected in the cellular membrane fraction isolated by density gradient sedimentation was also reduced by treatments that reduced the APC stimulatory capacity, such as pulsing at low temperature or in the presence of monensin. Taken together, these results suggest that processing of alpha-MSH is unlike that heretofore described for other peptide antigens and seems to involve APC handling to form the stimulatory moiety presented on the APC surface.

Animals↗
PubMed1988

Vitamin E distribution in ocular tissues following long-term dietary depletion and supplementation as determined by microdissection and gas chromatography-mass spectrometry.

Vitamin E is thought to be important for protection of polyunsaturated fatty acids (PUFA) from oxidative damage. A microbiochemical procedure using microdissection and gas chromatography-mass spectrometry was developed to determine vitamin E distribution in ocular tissues in a rodent model, with the eventual goal of using it in a study of phototoxic degeneration of the retina, where PUFA oxidation is potentially the causal mechanism. Sample preparation was achieved by freeze-drying the retina followed by micro-dissection to obtain the desired structures for analysis. A deuterated alpha-tocopherol internal standard is added to the tissue sample before extraction and derivatization which are achieved in a single step. The data presented show the vitamin-E content in various structures of the retina, particularly the outer segments and retinal pigment epithelium (RPE); however, the vitamin E content of other ocular tissues is also included. Data were obtained from albino and pigmented rats receiving vitamin E-depleted, supplemented, and regular chow diets, and from rabbits and cats receiving regular chow diets formulated for each species. Within all dietary groups the highest concentration of vitamin E was located in the RPE followed by the outer segments of the photoreceptor cells. Other ocular tissues consistently contained lower amounts of vitamin E. Different tissues were depleted of vitamin E at different rates and this points out the importance of determining vitamin E levels in tissues of interest in studies on the consequences of dietary depletion.

Animals↗