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Biomedical subjects

A Gupta

Publications and source records attributed to A Gupta.

At least 523 records · Page 29Linked to original sources
PubMed1996

Altered expression of glomerular heat shock protein 27 in experimental nephrotic syndrome.

Although nephrotic syndrome is a very common kidney disease, little is known about the molecular changes occurring within glomerular capillary loops during development of disease. The characteristic histologic change is retraction (effacement) of the distal "foot" processes of glomerular epithelial cells (GEC) which surround the capillary loops. The GEC foot processes are an essential part of the kidney's filtration barrier, and their structure is regulated primarily by actin microfilaments, cytoskeletal proteins present in high concentrations in foot processes. Actin polymerization has been reported to be regulated via phosphorylation of the low molecular weight heat shock protein, hsp27. We localized hsp27 within normal rat GECs using immunofluorescence and immunoelectron microscopy. Induction of nephrotic syndrome and GEC foot process effacement using the puromycin aminonucleoside rat model resulted in significant increases in: (a) renal cortical hsp27 mRNA expression (826 +/- 233%, x +/- SEM, P < 0.01 vs. control); (b) glomerular hsp27 protein expression (87 +/- 2%, P < 0.001 vs. control); and (c) glomerular hsp27 phosphorylation (101 +/- 32%, P < 0.05 vs. control). These findings support the hypothesis that hsp27, by regulating GEC foot process actin polymerization, may be important in maintaining normal foot process structure, and regulating pathophysiologic GEC cytoskeletal changes during development of nephrotic syndrome.

Animals↗
PubMed1996

Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene.

BACKGROUND: 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the interconversion of hormonally active cortisol to inactive cortisone and is vital for dictating specificity for the mineralocorticoid receptor. Thus, in patients with congenital deficiency of 11 beta-HSD (the syndrome of apparent mineralocorticoid excess, AME), cortisol and not aldosterone acts as a mineralocorticoid, resulting in hypertension and hypokalaemia with suppression of the renin-angiotensin-aldosterone axis. Two isoforms of human 11 beta-HSD have been described, but it is the NAD-dependent type 2 isoform (11 beta-HSD2), first characterised in placental tissue, that is expressed in the mineralocorticoid target tissues, kidney and colon. We have analysed the 11 beta-HSD2 gene as a candidate gene in explaining the molecular basis of AME. METHODS: By exon-specific PCR-amplification of the 11 beta-HSD2 gene in a consanguineous kindred with AME, we found a point mutation (C1228T) in two affected siblings, and also in placental DNA obtained from a stillbirth pregnancy. FINDINGS: The mutation in exon 5 of the 11 beta-HSD2 gene resulted in a premature stop site at codon 374 instead of a normal arginine (R374X), with the deletion of 32 aminoacids from the C-terminus of the 11 beta-HSD2 enzyme protein. Both parents, who are phenotypically normal, are heterozygote for the C1228T mutation in keeping with an autosomal recessive form of inheritance. NAD-dependent 11 beta-HSD activity was severely attenuated in the stillbirth placenta compared with control placental tissue, and no 11 beta-HSD immunostaining was observed in this placenta with antisera derived against a C-terminal 11 beta-HSD2 peptide sequence. INTERPRETATION: AME is due to a mutation in the 11 beta-HSD2 gene, and is an example of human hypertension arising from a single gene defect.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Effect of lung surfactant liposomes on the rabbit fetal lung type II cell antioxidant enzymes following prenatal dexamethasone treatment.

Prematurely born infants are at a high risk of developing neonatal respiratory distress syndrome (RDS), and it is believed that besides an insufficient surfactant (SF) system the initial breathing of O2-enriched air may in some way be responsible for this syndrome. Hyperventilation is a dominant stimulator for SF secretion but it may lead to oxidant-mediated cellular injury to type II cells. Since type II cells are the sole source of SF synthesis, the effect of ventilation support on these cells becomes important. In the present study, the changes in the antioxidant enzymes (AOEs) such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) in the type II cells of fetal rabbit lungs resulting from exogenous SF liposomes and steroid intervention have been investigated. The specific activities of the AOEs were found to be higher in the presence of SF liposomes in prematurely born pups whose mothers were not steroid treated (control), while such an increase was more pronounced in dexamethasone-treated groups. The results indicate that the exogenous surfactant and steroid intervention may favourably alter the AOE defences in the type II cells of fetal rabbits.

Animals↗
PubMed1996

The kerosene tragedy of 1994, an unusual epidemic of burns: epidemiological aspects and management of patients.

An unusual and perhaps the first epidemic of burns occurred between 15 February 1994 and mid April 1994 in four districts of the State of Rajasthan in India. The cause of this epidemic was the accidental mixing of petrol in kerosene oil which was inadvertently overlooked. This mixture of kerosene and petrol was used mainly by people of low-income groups for lighting lamps. Most of the accidents occurred while pouring this highly inflammable petrol-kerosene mixture into ignited lamps. A total of 303 cases were reported: 118 of these patients sustained severe burns of whom 37 died. Small numbers of fresh cases kept occurring over a period of 2 months in spite of all efforts by the administration, because poor people kept using the fatal mixture due to ignorance and illiteracy. Most of the patients were managed at district hospitals with the help of plastic surgeons called for the purpose from Jaipur, the capital city of the affected State. A total of 40 out of 303 patients were transferred to SMS Hospital where a medical ward was vacated to manage these patients, as the 10-bed burn unit already had 300 per cent best occupancy. Most of these patients were not willing to be sent to a burn unit situated far away from their homes, but they had to be transferred because the general surgeons working at district hospitals were hesitant to manage them, not so much due to lack of training in the management of burns, but more due to lack of willingness to manage burns. This indicates the need for renewed emphasis not only of the necessity of training general surgeons, nursing and paramedical staff at district level in the management of burns, but also of the need to manage these cases at district level. This idea needs serious consideration and sincere efforts to implement it at the national level. The paper has been split into two parts: epidemiological aspects and management of patients.

Accidents, Home↗
PubMed1996

Cellular distribution and regulation of NHE-1 isoform of the NA-H exchanger in the avian osteoclast.

The sodium-hydrogen exchanger (NHE) has been implicated in bone resorption by osteoclasts. We have studied expression of NHE-1, an isoform of the NHE, in chicken bone marrow mononuclear phagocyte precursors during differentiation into the osteoclast phenotype in culture. A monoclonal anti-body raised against the carboxy-terminus of NHE-1 detected the presence of a 100 kDa protein (similar to the mammalian form of NHE-1) in the osteoclasts. Laser scanning confocal microscopy revealed association with the alpha(v)beta(3) integrin and focal adhesion kinase (pp(125)FAK) at the basolateral membrane (BLM) of the osteoclast in addition to a more generalized cellular distribution. A fragment of avian NHE-1 cDNA was obtained by polymerase chain reaction cloning, and it was used to characterize expression of NHE-1 transcripts in cultured chicken osteoclast precursors. The avian NHE-1 message was a 3.9 kB band on Northern analysis, which differed from the mammalian message. Retinoic acid (RA) elicited an increase in the steady-state intracellular pH (pH(1)) from 6.87 to 7.10 in the absence of bicarbonate and was inhibited by ethylisopropylamiloride, an inhibitor of Na-H exchange. Using ribonuclease protection assays, we found that NHE-1 transcripts are induced as cells differentiate in vitro and in response to 13-cis-RA. Western blot analysis indicated that protein levels also increased in response to 13-cis-RA. Our results demonstrate expression of NHE-1 in avian osteoclasts with a complex cellular distribution in culture, and NHE-1 expression is induced as cells differentiate into mature osteoclasts in response to 13-cis-RA.

Amino Acid Sequence↗
PubMed1996

Intestinal intraepithelial lymphocytes influence the production of somatostatin.

BACKGROUND: We have previously demonstrated that intestinal intraepithelial lymphocytes (iIELs) inhibit lymphocyte proliferation. Because somatostatin also prevents lymphocyte proliferation, we hypothesized that iIELs may influence production of somatostatin. METHODS: Isolates of intestinal epithelium that were obtained from Brown Norway (BN) rats and contained an iIEL-enriched population (defined as CD45+) were incubated with irradiated Lewis splenocytes for allogeneic stimulation. BN rat splenocytes incubated with irradiated Lewis splenocytes served as a control. Supernatants were harvested after 4 days and assayed for somatostatin by using a radioimmunoassay. RESULTS: The somatostatin level in the intestinal epithelium-conditioned supernatant was significantly higher than that of the control group (176 +/- 60 versus 10 +/- 2 fmol/ml; p < 0.05). Removal of the CD45+ cell subset resulted in a fifteenfold reduction in somatostatin levels. The CD45+ cell lysates had significantly higher levels of somatostatin than did CD45+ depleted cells (1304 +/- 531 versus 128 +/- 41 fmol/ml; p < 0.05). CONCLUSIONS: The isolates of intestinal epithelium produced significant amounts of somatostatin. Removal of the CD45+ cells caused a significant loss of somatostatin production. Intracellular levels of somatostatin appeared to be highest in the CD45+ subpopulation. These data suggest that iIELs (that is, CD45+ cells) may have a significant influence on the production of somatostatin and may be a source of somatostatin production. Production of somatostatin by iIELs may help modulate immune responses in gut-associated lymphoid tissue.

Animals↗
PubMed1996

Corrective osteotomy for post-traumatic malunion of the phalanges in the hand.

Rotation, angulation, deviation, shortening or a combination of deformities can occur due to phalangeal malunion and can lead to impairment of hand function. A historical cohort study of 57 patients who had phalangeal corrective osteotomies for posttraumatic malunion between 1978 and 1990 was undertaken. 59 rotational, radial/ulnar deviation, flexion/extension, length adjustment procedures, and combinations thereof were performed, using rigid internal fixation. Concurrent tenocapsulolysis was done in 50% of the cases. Satisfactory correction was obtained in 76% of the patients. Bony union was obtained in all cases. A net gain in active range of motion was achieved in 89% of the patients. Excellent and good results were obtained in 96% of the patients who had corrective osteotomies for malunion involving only the bone and in 64% of the patients who had corrections for malunion with involvement of multiple structures (P < 0.01).

Adult↗
PubMed1996

Phosphate transport in osteoclasts: a functional and immunochemical characterization.

Osteoclasts are polarized cells involved in bone resorption. They are exposed to high ambient concentrations of inorganic phosphate (Pi) during the active process of bone resorption. We hypothesize that osteoclasts may possess specific Pi-transport system(s) for transcellular movement of Pi released from bone into the resorption cavity. We have previously reported the existence of a Na-dependent Pi cotransporter in the avian osteoclast, which provides a model culture system for the fully differentiated phenotype capable of bone resorption. In whole cell Pi-uptake studies, the rate of Pi transport was sensitive to both ouabain and 2,4-DNP, an inhibitor of aerobic ATP production. When these osteoclasts were exposed to bone particles, there was an immediate stimulation of Pi transport, independent of de novo protein synthesis. The stimulatory effect of bone particles was inhibited by peptides with the Arg-Gly-Asp-Ser (RGDS) motif, an effect which implicates integrins and cell-matrix interaction in the regulation of Pi transport. We performed Western blots on both whole cell lysates and membrane fractions using a polyclonal antibody to the N-terminal of NaPi-2 (the rat variant) and found a single approximately 100 kDa protein; the non-immune serum was used as control. Immunofluorescence studies using the same N-terminal antibody to NaPi-2 detected the protein in discrete vesicles. There was an induction of the protein in membrane fractions isolated from osteoclasts cultured in the presence of bone particles. Our preliminary studies indicate that a Na-Pi cotransporter may exist in the avian osteoclast, immunologically related to the NaPi-2 family, and which may be regulated through integrin-mediated pathways in the presence of bone. We also hypothesize that there may be a redistribution of vesicular pools containing the Na-Pi cotransporter toward discrete plasma membrane sites on the polarized osteoclast for transcellular movement of Pi during active bone resorption.

Amino Acid Sequence↗
PubMed1996

Reactive oxygen species-mediated tissue injury in experimental ascending pyelonephritis.

Pyelonephritis is the most common urinary tract infection in females, but the pathogenetic mechanisms are not well understood. Reactive oxygen species (ROS) have been implicated as cause of injury in several renal diseases. In this study, we have demonstrated the role of ROS in pathogenesis of pyelonephritis in Balb/c mice. A clear correlation between extent of ROS generation and subsequent lipid peroxidation and DNA damage in kidneys was observed during the course of infection, from 2 to 14 days. Activities of brush border membrane marker enzymes were also significantly altered. Administration of antioxidants, superoxide dismutase, catalase and dimethylsulfoxide significantly reversed the histopathological changes, reduced the extent of lipid peroxidation in renal brush border membrane, and also reversed the altered enzyme activities to near normal situation. These results clearly suggest that interaction of ROS with various cellular organelles in kidneys has a significant deleterious effect, and this could be the underlying mechanism for renal dysfunction in pyelonephritis.

Animals↗
PubMed1996

Thrombin receptor-related hemostatic defect after cardiopulmonary bypass.

Platelet abnormalities have been blamed for the hemostatic defect that develops after cardiopulmonary bypass (CPB), but investigators have not been able to agree upon an intrinsic platelet abnormality responsible for the observed defect. To better define the blood components responsible for this post-operative hemostatic defect, we compared platelet function in whole blood (WB) to that in platelet-rich plasma (PRP) in 33 patients undergoing coronary artery bypass grafting. We measured platelet aggregation in response to various platelet agonists, including thrombin and TRAP-6 (a 6-amino acid peptide that activates the thrombin "tethered ligand" receptor site). In WB there was a lasting, diminished response to TRAP-6, but not to gamma-thrombin, after CPB. Control experiments showed that this diminished response to TRAP-6: (1) was not related to heparin or heparin-protamine complexes, (2) was not the result of hemodilution during CPB, (3) was not related to increased amounts of naturally occurring enzymes (aminopeptidases) that degrade TRAP, and (4) was not able to be reversed by the addition of as much as a 10-fold excess of the usual TRAP-6 aggregating dose to WB preparations. In contrast, no corresponding defect in platelet aggregation could be identified in PRP obtained from patients after CPB. These results show that, in post-operative blood samples, blood components present in WB and not in PRP (eg, red blood cells, activated white cells or platelets bound to white cells) diminish the ability of TRAP peptides to activate the thrombin receptor but do not decrease the ability of gamma-thrombin to induce platelet aggregation. This suggests that for circulating platelets after CPB: (1) interactions of platelets with other blood cell elements are the cause of altered postoperative platelet reactivity rather than any intrinsic CPB-induced platelet defect, (2) drugs, such as aprotinin, that limit activation of white cells and the fibrinolytic system may also have beneficial effects on platelet function after CPB, and (3) alternate mechanisms exist that allow thrombin, but not TRAP-6, to activate platelets normally after CPB (perhaps a second, as yet undefined, thrombin receptor).

Cardiopulmonary Bypass↗
PubMed1996

Effects of levodopa and viscosity on the velocity and accuracy of visually guided tracking in Parkinson's disease.

Deficits in velocity generation and movement accuracy occur in Parkinson's disease and are postulated to contribute to the characteristic bradykinesia. In the present study, we attempted to clarify the relationship between the deficits in velocity generation and movement accuracy. Patients with Parkinson's disease and normal controls tracked visually displayed sinusoidal and step targets with the wrist. Performance was evaluated using measurements of velocity and error. Movement velocity was manipulated by two methods: (i) administration of levodopa; (ii) viscous loading. Dependencies of velocity and error on disease state, medication state and viscosity were examined. Visually guided pursuit tracking was characterized by intermittent and frequent velocity excursions in both the patients and controls. For sinusoidal tracking, levodopa significantly increased velocity in the severely affected parkinsonian patients. Prior to the administration of levodopa, step tracking velocity was significantly lower in all patients than in controls. The "on' state produced an increase in velocity to control levels. Error was significantly greater in the parkinsonian subjects than in controls, but was unchanged by levodopa for both tracking tasks. Manipulations of viscosity produced greater changes in velocity than did levodopa, yet a similar independence with respect to accuracy remained. Velocity significantly changed by 40-60% in the two tracking tasks from the viscous to antiviscous loads. Error did not change significantly in 12 out of 14 comparisons of subgroups based on disease and medication state. This contradicts the hypothesis that patients with Parkinson's disease primarily reduce velocity during tracking to maintain acceptable accuracy in the presence of a defective error correction system. Although parkinsonian subjects tracked with reduced accuracy, both normal and parkinsonian subjects were able to compensate for significant changes in velocity due to external loading. Thus a propulsion deficit exists in parkinsonism that may be alleviated with either antiviscosity or levodopa. An error correction deficit is also present in parkinsonism, but is not modified by antiviscosity or levodopa.

Adult↗
PubMed1996

Acute renal failure in falciparum malaria--increasing prevalence in some areas of India--a need for awareness.

Twenty-six cases (4.8%) from a total of 540 patients with acute renal failure (ARF) of diverse aetiology had ARF in association with falciparum malaria. Their ages ranged from 15 to 85 years (mean 31.2). Urinary sediment abnormalities and proteinuria (less than 1 g/24 h) were observed in 15 (57.7%) cases. The probable underlying factors leading to ARF were: volume depletion 17 (65.3%), intravascular haemolysis 8 (30.8%), hyperparasitaemia 8 (30.8%), cholestatic jaundice 6 (23%), and hypotension 5 (19.2%). Dialysis therapy was required in 15 patients (57.7%) as they had severe renal failure, and the remaining 11 patients improved with supportive measures. All patients received antimalarial therapy. The clinical course of ARF was consistent with acute tubular necrosis in 20 patients. Six cases were subjected to percutaneous renal biopsy. One patient showed histological features of necrotizing glomerulonephritis along with acute tubulointerstitial nephritis. The biopsies in the other five patients showed features of acute tubular necrosis in three, and acute interstitial oedema with patchy tubular necrosis in two. The mortality rate was 30.8%. Thus falciparum malaria, which has been an important cause of ARF in certain highly endemic zones of India, is showing an increasing prevalence in other parts such as Eastern Uttar Pradesh due to an imbalance between the increasing population and inadequate sanitary facilities, which further worsen during floods.

Acute Kidney Injury↗
PubMed1996

Differential expression of beta transforming growth factors (TGF beta 1, TGF beta 2, and TGF beta 3) and their receptors (type I and type II) in peri-implantation porcine conceptuses.

Beta transforming growth factors (TGF beta 1, TGF beta 2, and TGF beta 3) and type I and II TGF beta receptors were immunohistochemically localized in peri-implantation porcine conceptuses (embryos and associated membranes) collected on Day 10 through Day 14 of gestation. Our results indicate specific immunolocalization of TGF beta isoforms and their receptors in conceptuses during these gestational days. In parietal endoderm, TGF beta 1 immunoreactions were weak to undetectable, TGF beta 2 immunoreactions were intense, and TGF beta 3 immunoreactions were intermediate in intensity to TGF beta 2 and TGF beta 1. In contrast to immunoreactions in endoderm, TGF beta 1 and TGF beta 3 immunostaining in trophectoderm (Tr) was intense. Differences in TGF beta 2 immunostaining of Tr were observed from Days 10 to 14 of gestation. A drastic decrease in cytoplasmic immunostaining of ectoderm and mesoderm was detected from Days 12 to 14 for all TGF beta isoforms and type II receptor; however, type I receptor immunoreactions were consistently detected between Days 10 and 14. Concurrent expression of both type I and type II receptors in the peri-implantation conceptuses suggests that porcine conceptuses are capable of binding and responding to TGF beta s during this period. Differential expression of the three TGF beta isoforms suggests different roles for TGF beta s 1, 2, and 3 in conceptus development. Our results suggest possible roles for TGF beta s in early growth and differentiation of the embryo, differentiation of the Tr, and implantation.

Animals↗