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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 649 records · Page 36Linked to original sources
PubMed1994

Effect on central obesity and associated disturbances of low-energy, fruit- and vegetable-enriched prudent diet in north Indians.

The effects of fruit and vegetables in conjunction with low-energy diet as adjuncts to a prudent diet were compared for 6 months in a randomized, single blind trial in the management of 202 group A and 204 group B patients with acute myocardial infarction. Dietary intakes were obtained based on weighing of fruit, vegetable and legume intake and weekly diet diaries. After 6 months of follow-up, mean body weight, waist/hip ratio and glucose intolerance fell significantly in patients in group A compared with those in group B. Body weight declined by 5.3 kg in group A versus 2.2 kg in group B (95% confidence interval of difference (CI) 1.28-4.92), waist/hip ratio decreased by 0.05 in group A and 0.02 in group B (95% CI 0.01-0.10), and glucose intolerance decreased by 0.85 mmol/l in group A versus 0.19 mmol/l in group B (95% CI 0.19-1.21). There was a significant net decrease in serum triglycerides (0.18 mmol/l), systolic and diastolic blood pressures (7.9/4.7 mmHg), and a net increase in high-density lipoprotein cholesterol (0.10 mmol/l). Underlying these changes, group A patients had 393 g/day net increase in the consumption of fruit and vegetables and 1,160 kJ/day net decrease in energy intake compared to these changes in groups. Those who made greater changes in diet also had greater improvements in central obesity, glucose intolerance and in other associated disturbances.

Blood Glucose↗
PubMed1994

Augmented arterial pressure responses to cyclosporine in spontaneously hypertensive rats. Role of cytochrome P-450 3A.

Evidence to support a hypertensinogenic role of family 3A cytochrome P-450 (CYP3A) activity is that troleandomycin, a selective inhibitor of CYP3A, decreases both blood pressure and in vivo corticosterone 6 beta-hydroxylation in spontaneously hypertensive rats (SHR). Renal CYP3A activity is markedly increased in SHR compared with Wistar-Kyoto (WKY) rats. Cyclosporine acutely increases both systolic blood pressure and renal total cytochrome P-450 in SHR. We tested the hypothesis that the augmentation of blood pressure by cyclosporine is mediated by a further increase in renal CYP3A activity. Accordingly, we assessed the effect of troleandomycin administration on cyclosporine-induced systolic blood pressure increase and renal and hepatic microsomal CYP3A activity in SHR. Cyclosporine (5 mg/kg SC) given daily in 11-week-old SHR resulted in substantial augmentation of blood pressure after 6 days. This blood pressure increase was attenuated by troleandomycin (40 mg/kg) given either during or after development of hypertension. Cyclosporine increased renal (60%) but decreased hepatic (25%) microsomal CYP3A activity in SHR. In contrast, cyclosporine failed to produce any detectable increase in either blood pressure or renal CYP3A activity in WKY rats. Troleandomycin completely inhibited renal CYP3A activity measured after cyclosporine treatment of SHR, which correlated with its attenuation of the cyclosporine-induced blood pressure increase. These findings suggest that renal CYP3A could play an important role in acute cyclosporine-induced hypertension.

Animals↗
PubMed1994

Implementation of the rhesus prevention programme: a prospective study.

All rhesus-negative women who completed a pregnancy between January and August 1992 in two Scottish regions were studied to assess whether the administration of the rhesus prevention programme was complete: 671 rhesus positive (or rhesus type unknown) pregnancies were completed in 1120 Rh D negative women. For eight pregnancies no record of Rh D administration at birth was available. For recorded antenatal events that should have resulted in its administration anti-D was given in 195/280 (69.6%). Kleihauer testing was carried out in 9 of 98 instances of antepartum haemorrhage occurring after 20 weeks gestation. No cases of antenatal immunisation were identified. The study identified a need to increase awareness of the necessity for anti-D administration after potentially immunising events during pregnancy, and for increasing compliance with administration of postnatal anti-D in one of the study regions. Re-evaluation is also required of the recommendation that Kleihauer testing should be done when antenatal anti-D is given following an obstetric event after 20 weeks.

Female↗
PubMed1994

Analysis of disease distribution, activity and complications in the patient with inflammatory bowel disease.

Management strategies in Crohn's disease and ulcerative colitis should be based on up-to-date information on disease distribution, extent, activity and complications. A system of structured analysis is suggested, with separate consideration of destructive ulceration, inflammatory activity and other factors. Direct investigation of gut immunity by using whole gut lavage fluid (WGLF) is a valuable new technique of clinical investigation in IBD and related disorders. Recent studies have shown that the concentrations of plasma-derived proteins in WGLF provide objective measures of disease activity; and that this activity is a separate phenomenon from destructive ulceration and fibrosis. Neutrophils in the lumen can be in- investigated by cytology, or by assay of neutrophil elastase in WGLF. Cytokines and other immuno-regulatory mediators can also be detected. These new techniques can provide a description of intestinal immunity and inflammation, based on a non-invasive test of 2-4 h duration. Work in progress shows that patients who respond clinically to elemental diet treatment have unusually high concentrations of soluble IL2 receptor in WGLF; cytokine profiles may facilitate the selection of patients suitable for other new treatment modalities.

Child↗
PubMed1994

Monoclonal antibodies against antigenic epitopes common between Setaria cervi and Brugia malayi.

Several common antigens between the bovine (Setaria cervi) and human (Brugia malayi) filarial parasites have been demonstrated [Immunol Investig, 16 (1987) 139]. Hybridoma cell lines producing monoclonal antibodies against such common antigenic epitopes were obtained by immunizing the BALB/c mice with S. cervi antigen, fusing the spleen cells with Sp2/0 myeloma cells and screening the culture supernatants for antibody against both S. cervi and B. malayi antigens by ELISA. Nine monoclonal antibodies directed against antigenic epitopes common between the bovine and human filarial parasites were identified. Two monoclonal antibodies (I3B4 and I5D6) showed reactivity with the antigen(s) present in filariasis patients serum and thus may have potential for detecting circulating antigen in filaria infected individuals.

Animals↗
PubMed1994

Regenerative capability of upper and lower jaws in the newt.

The regenerating amphibian jaw represents an important model for studying pattern formation and the mechanisms underlying regeneration of facial structures. We have studied regeneration of upper and lower jaws in the urodele amphibian, Notophthalmus viridescens, using whole mount preparations stained for bone and cartilage, scanning electron microscopy and immunocytochemistry to further characterize these regenerating systems. In addition, we have investigated whether lower jaws of adults and larvae display similar regenerative ability. Although in adult animals the original shape of both the lower and upper jaws is rather faithfully reproduced following amputation, and the teeth and oral mucosa with its specialized sensory organs fully regenerate, significant differences in the regenerative ability of the various skeletal elements are observed. In fact, only tooth-bearing skeletal elements ossify, while the other elements of the regenerated skeleton remain cartilaginous for as long as 5 months after amputation. In contrast, a regenerated lower jaw in the larva is indistinguishable from an unamputated one at the same stage of development. Interestingly, regenerating adult jaws form directly bicuspid teeth, which are the type of teeth normally found in the adult, rather than the monocuspid teeth characteristic of larval jaws, indicating that jaw regeneration is not a recapitulation of development, in that an adult jaw blastema directly regenerates an adult jaw. Finally, we have studied the expression of tissue specific markers in normal and regenerating upper and lower jaws to establish whether the blastemal cells, which will form the missing part of the jaw, express any of these markers of the differentiated state, or are undifferentiated as suggested by their morphological appearance. Under our experimental conditions, no expression of markers of the differentiated state, such as those for muscle, cartilage and glands is detectable in early regenerates. On the contrary, the mesenchymal marker 22/31, whose expression in normal jaws is restricted to dermal fibroblasts and the dental pulp, is expressed in at least a half of the blastemal cells. The significance of these observations in relation to the origin of blastemal cells in the jaw will be discussed.

Animals↗
PubMed1994

Recycling and buffering of intracellular calcium in vascular smooth muscle from genetically hypertensive rats.

OBJECTIVE: To test the hypothesis that impaired Ca2+ recycling by the sarcoplasmic reticulum Ca-ATPase contributes to augmented force development in arteries from stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Force development to caffeine (0.3-30 mmol/l) in the absence of extracellular Ca2+ was compared in aortic strips from SHRSP and Wistar-Kyoto (WKY) rats. In another protocol the strips were rinsed at the peak of contraction to caffeine (20 mmol/l) and subsequently restimulated with the alkaloid. The second response, dependent on recycled Ca2+, was used as a measure of sarcoplasmic reticulum function. A third protocol evaluated caffeine-induced contractions after Ca2+ depletion and reloading. In these latter experiments the effects of thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca-ATPase, and ryanodine, an activator of sarcoplasmic reticulum Ca2+ release channels, were used to evaluate Ca2+ buffering. Finally, unidirectional 45Ca2+ influx was measured. RESULTS: Contractions to caffeine (0.3-30 mmol/l) were larger in SHRSP aortic strips than in WKY rat strips. After a rinse at the peak of the initial response to caffeine, SHRSP segments contracted more when challenged a second time. Thapsigargin (0.3-10 mumol/l) caused a concentration-dependent contraction during Ca2+ loading that was greater in SHRSP than in WKY rat strips, and a concentration-dependent inhibition of caffeine-induced contraction with similar median inhibitory concentrations in the two groups. Ryanodine did not cause contraction during Ca2+ loading, but caffeine-induced contractions were reduced after ryanodine treatment in both groups. 45Ca2+ influx was increased in SHRSP aortic segments. CONCLUSIONS: The greater force development to caffeine in SHRSP aortic strips probably reflects a greater storage of activator Ca2+ in the sarcoplasmic reticulum. On the basis of the pharmacological properties of thapsigargin and ryanodine, it appears that the larger store is caused by enhanced Ca2+ influx across the sarcolemma rather than by recycling of Ca2+ by sarcoplasmic reticulum Ca-ATPase. Experiments evaluating the secondary response to caffeine also support the interpretation that recycling of activator Ca2+ into the sarcoplasmic reticulum does not explain the augmented force development in SHRSP aortic segments.

Animals↗
PubMed1994

99Tcm-cystine, a renal function and imaging agent: a comparative study in dog with 131I-hippurate and 99Tcm-glucoheptonate to evaluate its functional and imaging characteristics.

99Tcm-cystine, which has been proposed as a renal radiopharmaceutical for evaluating renal morphology and function in a single experiment, is compared with 131I-orthoiodohippurate (OIH) with respect to its renal clearance and extraction parameters and with 99Tcm-glucoheptonate (GHA) regarding its imaging characteristics. In spite of its comparable renal accumulation with 131I-OIH, its clearance (10.1 +/- 1.0 ml min-1 kg-1) was lower than that of 131I-OIH (21.5 +/- 0.9 ml min-1 kg-1) but was higher than that of 125I-iothalamate (5.4 +/- 0.6 ml min-1 kg-1). Extraction efficiencies of 99Tcm-cystine, 131I-OIH and 125I-iothalamate were 39 +/- 5, 64 +/- 4 and 27 +/- 3, respectively. The glomerular filtration components of 99Tcm-cystine and 131I-OIH were 26 and 16% of their respective clearances. In probenecid-treated animals the clearance of both agents was affected to a similar extent and fell to half of their respective control values, whereas tubular secretory components were found to be 19 and 31% of the controls. The kidney images obtained with 99Tcm-cystine were superior to those obtained with 99Tcm-GHA at different time points. Therefore, considering both renal function and imaging properties of 99Tcm-cystine it appears that this radiopharmaceutical offers some definite advantages over the currently available renal agents and commands further study.

Animals↗
PubMed1993

Synergism between Tat and VP16 in trans-activation of HIV-1 LTR.

When tethered to heterologous DNA both Tat and VP16 can activate transcription from the HIV-1 LTR. To determine if they act by similar mechanisms, we constructed several hybrid effectors between Tat or VP16 and DNA-binding domains of GAL4 or LexA proteins. We tested these effectors on substituted reporter targets, which contained one to six GAL4 or LexA DNA-binding sites placed upstream of the HIV-1 promoter. Whereas Tat acted very inefficiently via DNA even with five DNA-binding sites, effects of VP16 were observed with a single DNA-binding site and increased with increasing number of sites. More importantly, effects of VP16 via DNA were synergistic with those of Tat via TAR RNA when both proteins were expressed simultaneously. We next created a tripartite fusion protein, which contained the GAL4 DNA-binding domain and activation domains of both Tat and VP16, which could be targeted to the HIV-1 LTR either via DNA or RNA. By introducing individual deleterious mutations into either Tat or VP16, we confirmed that effects of VP16 predominated via DNA whereas Tat but not VP16 acted via TAR RNA. Thus, Tat and VP16 act at different steps of the transcription process and increase expression from the HIV-1 LTR by different mechanisms.

Bacterial Proteins↗
PubMed1993

Renal corticosterone 6 beta-hydroxylase in the spontaneously hypertensive rat.

Excess 6 beta-OH-corticosterone production by family 3A cytochromes P-450 may play a role in genesis of hypertension in the spontaneously hypertensive rat (SHR), by producing a renal defect in Na+ excretion. Renal cytochromes P-450 may be a causal factor in this genetic model. Since family 3A P-450 is present in rat kidney (collecting duct), the renal family 3A catalytic (6 beta-OHase) and immunoreactive activities were compared in SHR and normotensive control (Wistar-Kyoto; WKY) rats. Corticosterone 6 beta-hydroxylation is markedly higher in SHR than in WKY renal microsomal preparations. Western blot analysis with antibodies to rat and rabbit liver family 3A isoforms demonstrated related proteins. Densitometry revealed greater relative intensity of staining in SHR compared to WKY with both antibodies. Both antibodies inhibited corticosterone 6 beta-hydroxylation by SHR renal microsomes. Increased renal 6 beta-OH-corticosterone production by increased renal family 3A cytochromes P-450 may play a role in the blood pressure elevation in SHR.

Animals↗
PubMed1993

Lack of effect of 1-desamino-8-D-arginine vasopressin on direct adhesion of platelets to collagen.

Administration of 1-desamino-8-D-arginine vasopressin (DDAVP), a synthetic vasopressin derivative, causes an increase in plasma factor VIII and von Willebrand factor (vWF). Recently, evidence has become available that intravenous infusion of DDAVP shortens the prolonged bleeding times in some patients with primary platelet defects even though their plasma levels of vWF and FVIII are normal prior to drug administration. The mechanism of this effect of DDAVP has not been well defined and it has been generally considered that the beneficial effect on the bleeding time is related to the rise in plasma vWF and its impact on platelet adhesion to subendothelial components including collagen, an important step in hemostasis. Thus, studies aimed at understanding the effect of DDAVP have focused on vWF-mediated adhesion of platelets to the subendothelium. For example, Sakariassen et al studied the platelet adherence to human arterial subendothelium and concluded that DDAVP improves hemostasis by causing enhanced vWF-mediated platelet adherence. This mechanism would explain the shortening of the bleeding time in patients with milder forms of vWD with subnormal levels of vWF. But patients with congenital platelets defects have normal plasma vWF raising the possibility that there may be other mechanisms contributing to the beneficial effect of DDAVP. It is clear that platelets can interact directly with collagen, mediated by specific platelet binding sites. Further, DDAVP binds to platelets even though by itself does not activate them. The present investigation was designed to elucidate whether DDAVP had any effect on the direct adhesion of platelets to collagen in the absence of mediation by vWF. Hashemi et al have suggested that the effect of DDAVP on endothelial cell release of vWF is mediated by an as yet uncharacterized intermediate factor(s) released from peripheral mononuclear cells. Therefore, we studied the effect also of plasma samples obtained from patients treated with DDAVP on adhesion of platelets to collagen.

Bleeding Time↗
PubMed1993

Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice.

A congenic, non-obese diabetic (NOD) mouse strain that contains a segment of chromosome 3 from the diabetes-resistant mouse strain B6.PL-Thy-1a was less susceptible to diabetes than NOD mice. A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), Fc gamma RI. The NOD Fcgr1 allele, which results in a deletion of the cytoplasmic tail, caused a 73 percent reduction in the turnover of cell surface receptor-antibody complexes. The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases.

Animals↗