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Biomedical subjects

J Price

Publications and source records attributed to J Price.

At least 235 records · Page 13Linked to original sources

Desialylated transferrin and mitochondrial aspartate aminotransferase compared as laboratory markers of excessive alcohol consumption.

Concentrations of both desialylated transferrin (dTf) and the mitochondrial isoenzyme of aspartate aminotransferase (EC 2.6.1.1, mAST) have been claimed to be increased in sera of alcoholic subjects. To investigate the diagnostic usefulness of these new biochemical markers of alcoholism and to compare them with more conventional markers, we measured dTf and mAST in the sera of controls, alcoholic subjects, and patients with nonalcoholic liver diseases (NALD). Alcoholic subjects had significantly (P less than 0.001) higher ratios of dTf to total transferrin than did either healthy controls or patients with NALD (sensitivity 81%, specificity 97%). The mAST was increased in 92% of alcoholic subjects but also in 48% of patients with NALD. The mAST/total AST ratio differentiated the alcoholic subjects from those with NALD (P less than 0.001) with a sensitivity of 92%, but the specificity was only 70%. In contrast, the conventional markers were less sensitive and less specific. We conclude that the best available single laboratory marker for current heavy alcohol consumption is the ratio dTf/total transferrin.

Adult↗

Transgenic HLA-DR alpha faithfully reconstitutes IE-controlled immune functions and induces cross-tolerance to E alpha in E alpha 0 mutant mice.

We have constructed transgenic mice that express the human class II MHC molecule HLA-DR alpha on a genetic background in which the equivalent endogenous gene, H-2 IE alpha, is not expressed. In these mice, DR alpha complemented the E beta chain such that tissue-specific expression of an interspecies hybrid DR alpha-E beta heterodimer was obtained. Despite 25% amino acid differences between DR alpha and E alpha, immune responsiveness to IE-controlled antigens, clonal deletion of IE-reactive T cells, and alloantigenicity were quantitatively and qualitatively indistinguishable in IE-positive mice and in mice that had integrated at least four copies of the transgene. These results demonstrate a remarkable degree of structural, regulatory, and functional conservation. They also suggest that tolerance induction involves only discrete portions of MHC molecules.

Animals↗

Interactions with hemoglobin: a source of error in measurements of transketolase activity in hemolysates.

Measurements of the activity of transketolase in human erythrocyte lysates by an assay coupled to NADH oxidation indicate that interactions of assay substrates with hemoglobin can give rise to overestimations of transketolase activity. Three potential sources of error are identified. Thus, in lysates containing methemoglobin, NADH oxidation can be due firstly to methemoglobin reductase activity or secondly to the monooxygenase activity of methemoglobin, for which the substrate can be ribose 5-phosphate, a substrate also of transketolase. Thirdly, the addition of high concentrations of the transketolase cofactor, TDP, to an insufficiently buffered reaction mixture can cause the aggregation and precipitation of hemoglobin: a phenomenon that may be misconstrued as an enhanced increase in absorbance at 340 nm and hence as additional transketolase activity. Although the present study concentrates on these potential artefacts in assays of transketolase activity, the findings may well be relevant to the measurement of other enzyme activities in hemolysates by procedures based ultimately on the rate of consumption or production of NAD(P)H.

Chromatography, Gel↗

Altered biodistribution of indium-111-labeled monoclonal antibody 96.5 to tumors and normal tissues of nude mice bearing human melanoma xenografts in visceral organs.

Human melanoma xenografts were produced in the subcutis, kidney, cecum and liver of different nude mice. An 111In-labeled anti-(human melanoma) monoclonal antibody (96.5) or an 111In-labeled nonspecific control monoclonal antibody (ZCE-025) was injected intravenously in separate groups of mice. Radioactive antibody accumulation was measured in tumor, blood, viscera, and carcasses. mAb 96.5 targeted specifically to tumor tissue regardless of site of growth. Tumors in the liver exhibited significantly (P less than 0.05) higher tumor-to-blood ratios (45 +/- 6, mean +/- SEM) than xenografts at other visceral organs, the lowest value being found for subcutaneous melanoma (2.6 +/- 0.5). The differences in tumor-to-blood ratio were due to significant alterations of antibody biodistribution, since the actual antibody concentration in the different tumor sites was similar. The percentage of recovered anti-melanoma antibody per milliliter of blood in mice with visceral lesions (4.6 +/- 1.1% ml) was significantly lower than that found in mice with subcutaneous tumors (9.5 +/- 1.4%/ml, P less than 0.05). Moreover, significantly higher levels (18.2 +/- 3.2%/g, 31.0 +/- 5.1%/g, respectively) of the melanoma mAb 96.5 were found in normal liver and spleen tissue recovered from mice with visceral tumors as compared to tissue from mice with subcutaneous tumors (9.2 +/- 0.9%/g, 13.5 +/- 1.9%/g, respectively; P less than 0.05). These results demonstrate that the presence of visceral tumor can significantly affect tumor-to-blood ratios, blood levels, and biodistribution of 111In-labeled mAb 96.5.

Animals↗

Closed loop obstruction: diagnosis by enteroclysis.

The diagnosis of closed loop obstruction was made by enteroclysis in 5 patients. In each case barium outlined the involved loop, and related segments of marked narrowing were identified as the neck of the closed loop. The findings prompted early surgical intervention, and adhesive bands causing closed loop obstruction were confirmed in all 5 patients.

Adult↗

Checklists for measuring response style in hypertensives.

The need for more clearly identifying the reporting behaviour of hypertensives was addressed. An objective method of measuring reporting behaviour was developed: the Life Concerns checklist. This checklist was able to discriminate subjects defined as introspective self-doubters from those who reported either psychosomatic disorders or who blamed the environment for their problems. This checklist was also able to verify that hypertensives do have lower report rates than normotensives. The Perception of Social Acceptability of Reporting Concerns Checklist (Persolac) measured the number of specific concerns perceived to be socially acceptable to report, of which there were less for males and which in all cases varied according to whom the concerns were to be disclosed. The two checklists are presented as adjuncts to other questionnaires for use in exploring the response of individuals with essential hypertension.

Adult↗

Understanding hypertensive behaviour--I. Preference not to disclose.

Preference not to disclose information was investigated as a likely explanation for low rates of report of concerns in hypertensives. The research was designed to explore alternative explanations that have been provided by others. Two studies investigated the effect of situational contexts which provided low or high social pressure to reveal personal life concerns. Results showed that degree of disclosure by hypertensives was determined by a response style: disclosure was flexible and increased when situational pressure for accurate response increased. Thus, hypertensives prefer to withhold information. Normotensives had high levels of report whatever the situational context. The request to disclose was shown to have a potent dysregulatory effect on blood pressure for hypertensives only. Need for social approval was a possible underlying explanation for group differences. There are implications in these findings both for personality theory and therapy development.

Adult↗

The diet of steady drinkers with special reference to social variables.

The influence of a number of variables on the diets of 65 steady drinkers from alcohol rehabilitation units on Merseyside, United Kingdom was investigated. All drank principally beer or spirits. Social variables studied included age, sex, living alone or with others, employment status and socio-economic status. Alcohol-related variables included quantity consumed and preferred beverage. Dietary outcome was assessed in terms of the variety of foods and the number of meals eaten per week. Living alone proved by far the most important determinant of reduced diet. Spirit drinkers ate more meals than beer drinkers, but only if living with others. Increased alcohol consumption related modestly to fewer foods and meals being consumed. Drinkers living alone constitute a much larger proportion of those entering rehabilitation programmes in Queensland, Australia than in the United Kingdom. The present findings may help to explain the high incidence in Queensland of thiamin deficiency syndromes including the Wernicke-Korsakoff syndrome.

Adult↗

Biology of family systems and mood disorders.

Ethology offers psychiatry and family therapy an alternative perspective for understanding hierarchical dysfunction and individual psychopathology and the relation between them. Dominance and submission behaviors--descriptions from ethology--represent communicational mechanisms that play pivotal roles in maintaining the stability of the family group. When conflict becomes acute, dominant and submissive states are experienced as euphoria and mild depression respectively. Smooth functioning of these communicational mechanisms at the individual level enhances cohesion at the group level. Feelings of inadequacy and inferiority may be manifestations of submissive patterns and may function to maintain negative or corrective feedback loops, which preserve group stability. However, these communicational mechanisms may exhibit positive feedback runaway effects such that family crises result. These and other clinical implications of the model are explored.

Affective Disorders, Psychotic↗

Na+ electrochemical gradient and Na+-Ca2+ exchange in rat proximal tubule.

The basolateral cell membrane of the rat proximal tubule contains a Na+-Ca2+ exchanger that may participate in the regulation of cytosolic calcium (Cai) and Ca2+ transport. In this work, the activity and orientation of the Na+-Ca2+ exchanger was studied in rat proximal tubules. The experiments were based on the thermodynamic notion that the exchanger is driven by the prevalence of either of two electrochemical gradients, that for Na+ (delta mu Na+) or for Ca2+ (delta mu Ca2+). Reductions in delta mu Na+, achieved by lowering extracellular Na+ (Nao) from 150 to 15 mM, increased Cai, decreased 45Ca efflux, and increased 45Ca influx. These changes occurred concurrently. When delta mu Na+ was reduced by increasing intracellular Na+ (Nai) with 10(-3) M oubain, Cai also increased. The effect of ouabain was probably dependent on Nai accumulation because the surge in Cai was prevented by exposure of the tubules to 5 mM Nao before ouabain exposure. On the other hand, when delta mu Na+ was lowered mM Nao and then by reducing Nao to 15 mM, Cai rose in two additive stages. We conclude from these data that in the rat proximal tubule the basal state of the Na+-Ca2+ exchanger is in forward mode, Nao-Cai. Moreover, the function of the Na+-Ca2+ exchanger is in accord with predictions derived from a thermodynamic analysis of its function.

Aequorin↗

Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor: a histological, immunocytochemical, and electron microscopic investigation.

The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed, and the markedly enlarged pituitaries were studied by histology, immunocytochemistry, electron microscopy, and immunogold method, using double labeling at ultrastructural level. In all pituitaries, a massive hyperplasia, chiefly of mammosomatotrophs, was found. These bihormonal cells, containing GH and PRL, were demonstrated by light microscopy and ultrastructural immunocytochemistry. Electron microscopy revealed the presence of cells with characteristics of GH cells in three pituitaries and cells resembling human adenomatous mammosomatotrophs in the other three glands. All of these cells, regardless of their ultrastructural features, contained secretory granules heavily labeled for GH by immunogold technique; PRL labeling varied from cell to cell, with the predominance of a weak immunostaining and was colocalized with GH in secretory granules. These results indicate that chronic exposure to GRF excess leads to mammosomatotroph hyperplasia. It is suggested that GH cells proliferate and transform to mammosomatotrophs in response to GRF stimulation. Focal PRL cell hyperplasia noted in three pituitaries could also be due to a GRF effect. Longer exposure to GRF is needed to clarify whether GRF can cause adenoma.

Animals↗

Antiproliferative activity of liposome-encapsulated transforming growth factor-beta against MDA-MB-435 human breast carcinoma cells.

We determined whether transforming growth factor-beta (TGF-beta) could be encapsulated in phospholipid liposomes and then would mediate antiproliferative activity against the sensitive, human breast cancer cell line, MDA-MB-435. TGF-beta was encapsulated in multilamellar liposomes consisting of phosphatidylcholine (PC) or PC and phosphatidylserine (PS) at a 7:3 molar ratio. It was captured in both the aqueous phase and the bilayer lipid (hydrophilic and lipophilic association) and was stable for at least 24 hr of incubation at 37 degrees C in medium that contained 5% fetal bovine serum. In calcium- and magnesium-free Hanks' balanced salt solution, TGF-beta in the internal aqueous compartment was stable for at least five days, even in the presence of trypsin and ethylenediamine tetraacetic acid. TGF-beta (type 1 or 2) in liposomes was active as free-form TGF-beta in mediation of antiproliferative effects. The lipophilic nature of TGF-beta, which resulted in a high capture ratio in liposomes, coupled with exceptional stability, suggested that liposomes could be a carrier for the in vivo use of TGF-beta.

Breast Neoplasms↗