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S Barker

Publications and source records attributed to S Barker.

At least 145 records · Page 8Linked to original sources

Effects of 1,25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells.

Incubation of bovine parathyroid cells with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) decreased both preproparathyroid mRNA levels and parathyroid hormone (PTH) secretion. There was a fall to 56.6 +/- 13.7% (mean +/- S.E.M.) and 65.1 +/- 9.3% in mRNA levels and PTH secretion respectively at 1 nmol 1,25-(OH)2D3/l, and 41.1 +/- 13.6% and 42.0 +/- 12.1% at 10 nmol 1,25-(OH)2D3/l after 24 h. After 48 h in 0.1 nmol 1,25-(OH)2D3/l, mRNA levels had fallen to 35.3 +/- 12.6% and PTH secretion to 32.1 +/- 5.0%. In human adenomatous cells, however, incubation with 1,25-(OH)2D3 (10 nmol/l) had no effect on either mRNA levels or PTH secretion even after 48 h. This lack of sensitivity of adenomatous cells to 1,25-(OH)2D3 was not due to an absence of receptors (3847 +/- 39 receptors/ng cytosolic protein in adenomatous cells compared with 4068 +/- 371 in bovine cells) or receptors being of low affinity. Cortisol (1 mumol/l) caused a reduction in the number of receptors for 1,25-(OH)2D3 in bovine parathyroid cells of approximately 20% within 24 h of incubation, but no change in affinity. This decrease was accompanied by abolition of the response to 1,25-(OH)2D3 and was reversible, in that withdrawal of cortisol for the final 24 h of incubation was sufficient for the response to return, the number of receptors having returned to control values. These results suggest that only a small percentage of receptors for 1,25-(OH)2D3 in bovine parathyroid cells may be functional at any one time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible.

Acrylates↗

Autocrine regulation of 1,25-dihydroxycholecalciferol metabolism in myelomonocytic cells.

In this study the effects of vitamin D metabolites on the myelomonocytic precursor cell line U937 have been compared with those of phorbol myristate acetate (PMA). PMA was used as a cell modulating agent in order to avoid effects of binding of the exogenous vitamin D metabolites receptors within the cell, which would interfere with subsequent measurement of these receptors in studies of the vitamin D3 metabolic pathway. Both the active 1,25 DHCC form of vitamin D3 and the inactive 24,25 DHCC metabolite inhibit cell proliferation and induce 24-hydroxylase activity, but not 1 alpha-hydroxylase activity. These effects are dose-dependent and maximum enzyme activity is seen in the adherent cell population, which is induced by these compounds. PMA inhibits proliferation of U937 and increases receptors for 1,25 DHCC in these cells (like the vitamin D metabolites). However, unlike the vitamin D metabolites, PMA induces 1 alpha-hydroxylase activity rather than 24-hydroxylase activity. Thus, while PMA and 1,25 DHCC have some similar effects on monocyte precursor cell line differentiation, there is a difference between the effects of the two agents on the vitamin D metabolic pathway. The former promotes synthesis of the active metabolite, and the latter induces an enzyme which renders the metabolite inactive. If these results are considered together, they are consistent with the hypothesis that 1,25 DHCC has an autocrine role within the mononuclear phagocyte system.

Calcitriol↗

Contrasting effects of autonomic agents and prostaglandins on 22Na uptake in rat submandibular salivary acini.

Uptake of this isotopic tracer by the acini occurred in a time-dependent manner and was increased by 1 microM concentrations of acetylcholine and of isoproterenol, but not of prostaglandins E1, E2 and F2 alpha. The lack of effect of prostaglandins on Na transport in salivary acini contrasts with their inhibitory effect on salivation in vivo, suggesting that in vivo the effects are independent of the ion-transport mechanisms underlying saliva formation.

Acetylcholine↗

PGI2 attenuates baroreflex control of renal nerve activity by a vagal mechanism.

The present study was undertaken to determine whether left circumflex coronary artery (ic) administration of prostacyclin (PGI2) caused an inhibition of the baroreflex control of renal sympathetic nerve activity (RSNA). RSNA was recorded in 12 dogs. Baroreflex sensitivity of RSNA was assessed by infusion of either sodium nitroprusside or phenylephrine and by determining the slope of the mean arterial pressure-RSNA relationship. During nitroprusside infusion, intracoronary PGI2 depressed the baroreflex sensitivity by nearly 90% compared with intracoronary tris(hydroxymethyl)aminomethane (Tris) (P less than 0.002). In addition, the peak increase in RSNA during nitroprusside infusion was significantly inhibited during intracoronary PGI2 (57.9 +/- 6.4 vs. 21.2 +/- 3.0 spikes/s, P less than 0.05). There was no significant difference in the inhibition of RSNA during phenylephrine infusion when intracoronary PGI2 was compared with Tris. Both bilateral vagotomy and pericoronary lidocaine blocked the inhibitory effects of PGI2 on the baroreflex increase in RSNA. It is concluded from these data that exogenously administered PGI2 stimulates or sensitizes afferent endings within the supply of the left circumflex coronary artery to inhibit the baroreflex control of RSNA during evoked hypotension. These afferents traverse vagal pathways via the pericoronary nerves. The role of endogenous prostaglandins in modulation of baroreflex function via a cardiac reflex remains to be elucidated.

Animals↗

The effect of hemodialysis on whole blood, plasma and erythrocyte viscosity.

The effect of hemodialysis (HD) on blood viscosity has not been adequately investigated. We studied blood viscosity during HD employing coneplate viscometry. Ten patients with end-stage renal disease were studied before and immediately after HD. To dissect the possible effects of HD on plasma and red blood cell (RBC) determinants, we measured whole blood, plasma, and reconstituted erythrocyte viscosities. The latter consisted of RBC's suspended in a buffered saline solution (pH = 7.4 units). In addition, serum, electrolytes and hematocrit (HCT) were measured. The results revealed a significant rise in whole blood viscosity after dialysis. Likewise, plasma viscosity rose considerably with dialysis. However, when the RBC's were reconstituted to a constant HCT, no significant difference was noted before and after HD. As expected, body weight, blood urea nitrogen (BUN) and creatinine concentrations fell while HCT and protein concentration rose with HD. A significant correlation was found between the observed rise in HCT, and dialysis-induced rise in whole blood viscosity. Likewise, the observed rises in plasma viscosity after dialysis significantly correlated with the rise in protein concentration. In addition, the change in whole blood and plasma viscosity values correlated with the degree of ultrafiltration (weight loss). In conclusion, whole blood and plasma viscosity rises with hemodialysis. The observed rise in viscosity is primarily due to hemoconcentration.

Acid-Base Equilibrium↗

Characterization of the acute clinical illness associated with human immunodeficiency virus infection.

The clinical and serologic features and immune status of 39 homosexual men who had seroconversion to human immunodeficiency virus positivity were compared with 26 homosexual men who remained seronegative during a six-month period. An acute clinical illness occurred in 92.3% of seroconverted subjects and 40% of controls. The duration of illness was significantly greater in the seroconverters than the controls (10 + 4.4 days). A general practitioner was consulted by 87.2% of the seroconverters because of the illness, including 12.8% who were admitted to hospital, compared with 20% of controls. The most frequently reported symptoms in the seroconversion group were fever (76.9%); lethargy and malaise (66.7%); anorexia, sore throat, and myalgias (56.4% each); headaches and arthralgias (48.7% each); weight loss (46.2%); swollen glands (43.5%); retro-orbital pain (38.5%); and dehydration and nausea (30.8% each). Lymphadenopathy developed in 75% of seroconverters compared with 4% of controls. Changes in T-cell subsets were not found in controls, but the number of T4+ cells and the T4+/T8+ ratio decreased significantly in seroconverters.

Acquired Immunodeficiency Syndrome↗

Effect of prostaglandins on Cl and K transport in rat submandibular salivary acini.

Dispersed acini were used to investigate the effects of prostaglandins (PG) on transmembrane Cl and K transport with the aid of radioactive tracers. Neither PGE1, PG2, PGF2 alpha, arachidonic acid or phosphatidic acid (all in 1 microM final concentrations) modified the time-dependent uptake of 36Cl. Steady-state isotope content reached 6-7 nmol/mg protein with or without these substances. PG did not alter the inhibitory effect of 1 mM furosemide on 36Cl uptake, and failed to induce a net efflux of 36Cl from tracer-preloaded cells or to modify the efflux of tracer induced by 1 microM acetylcholine. PG had no significant effect on K uptake, as measured with 86Rb, and did not modify the effect of 1 mM ouabain, which inhibited K uptake or accumulation by 60 per cent. PG did not induce K (86Rb) efflux from acini preloaded with tracer, and did not prevent or enhance the K efflux induced by acetylcholine. Thus PG do not influence the major ion-transport systems that may be involved in saliva secretion by acinar cells. Any inhibitory effects of PGE1 on salivary-fluid secretion in vivo are therefore likely to be the result of extra-acinar PG actions, and not of a direct effect on ion-transport mechanisms.

Acetylcholine↗

Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol.

Dendritic cells have been isolated from human tonsillar tissue and shown to act as accessory cells in a mitogenic response. The dendritic cells will induced receptors for the active metabolite of vitamin D3, 1,25(OH)2D3, in the responder E+ T cells. The dendritic cells themselves constitutively express receptors for the metabolite, and this distinguishes them from other non-T cells in lymphomedullary tissue. Expression of the 1,25(OH)2D3 receptor may be a dendritic cell property that facilitates their accessory cell role within the tissue microenvironment.

Calcitriol↗

The effect of hypoxia on the number of amine-containing cells in the lung of the adult rat.

Adult rats of Wistar and Sprague Dawley strains were exposed to a 21-day period of hypoxia (10% O2). At the end of this period, the hypoxic animals and paired controls were anaesthetised, dissected and tissues were taken for light microscopy. All the hypoxic animals had an increased haematocrit, right ventricle weight and carotid body size when compared with controls. The Grimelius method was used to demonstrate argyrophil structures in the lung. This method stained the amine-containing cells of the epithelium, mast cells and nerves. Mast cells associated with the pulmonary vasculature were increased in number in the hypoxic animals. Single epithelial argyrophil cells were more frequent than those in groups. In control animals the groups of cells only rarely contained more than 5 cells. In the Wistar strain there was no significant difference in the number of argyrophil cells between the control animals and those exposed to chronic hypoxia. However, in the Sprague Dawley rats, the numbers of cells, both single and in groups, were significantly increased following 3 weeks chronic hypoxia. The cell groups were also larger in the hypoxic animals, with up to 12 cells per section.

APUD Cells↗

Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.

Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.

Cells, Cultured↗

Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.

We have examined the effects of 1,25(OH)2D3 on T-cell populations isolated by buoyant density and E rosetting from human tonsils. Cell proliferation was assessed by measuring the incorporation of 125iododeoxyuridine; interleukin-2 (IL-2) production was measured using an IL-2-dependent cell line, and the number of 1,25(OH)2D3 receptors was measured by whole-cell nuclear association assay. At a concentration of 10(-7) M, 1,25(OH)2D3 inhibited mitogen-induced T-cell proliferation in all E+ T-cell populations. This effect was more pronounced in the cells from the intermediate and high density layers and was reflected both in cell proliferative responses and in relative IL-2 synthesis. By adding the 1,25(OH)2D3 during the course of the mitogen assay, we demonstrated that activation of the T cell precedes the 1,25(OH)2D3-mediated inhibition. Cells that had been preincubated with mitogen in the presence of the 1,25(OH)2D3 were refractory to further stimulation by mitogens. Receptors for 1,25(OH)2D3 could not be detected in unstimulated T cells. However, activation led to the expression of high-affinity receptors for 1,25(OH)2D3. Co-incubation of the cells with mitogen and 1,25(OH)2D3 increased the number of receptors compared with mitogen alone. The effects provide further evidence for the hypothesis that 1,25(OH)2D3 is an important potential modulator of the immune system through its action on T cells. Taking our observations in conjunction with the known capacity of monocytes to hydroxylate the precursor metabolite (and thus synthesize the active form of cholecalciferol), the results support the suggestion that 1,25(OH)2D3 plays a role as a local mediator of mononuclear phagocyte-T cell interaction in human lymphomedullary tissues.

Calcitriol↗

Neutralising antibody against type 1 and type 2 herpes simplex virus in cervical mucus of women with cervical intra-epithelial neoplasia.

Patients with cervical intra-epithelial neoplasia had significantly increased neutralising antibody activity to type 2 herpes simplex virus in the cervical mucus. While patients differed from control subjects with respect to their number of sexual partners and socio-economic class, there were significant differences in neutralising antibody activity for case control comparisons within the same number of sexual partners or socio-economic groupings. The results lend support to the putative association between type 2 herpes simplex virus infection and pre-invasive and invasive carcinoma of the uterine cervix.

Adult↗

Ethanol potentiates the toxic effects of 1,4-butanediol.

The simultaneous administration of ethanol increases the mortality rate and tissue damage observed in rats after 1,4-butanediol (1,4-BD). A related increase in tissue 1,4-BD concentration supported the hypothesis of an in vivo competition of the two substances for alcohol dehydrogenase. The clinical implications of the results, in light of the recent discovery of the presence of endogenous 1,4-BD in humans are discussed.

Animals↗