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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 91 records · Page 5Linked to original sources

Vasopressin receptor-mediated endocytosis: current view.

A number of peptide hormones have been shown to undergo receptor-mediated endocytosis (RME). RME involves the internalization of receptor-ligand complexes followed by delivery to an intracellular compartment, the endosome, from which ligands or receptors can be delivered to lysosomes or other cellular destinations. Vasopressin, a peptide hormone that plays a role in kidney and vascular physiology, has recently been demonstrated to undergo RME in LLC-PK1 and A10 cells, which express V2- and V1-type vasopressin receptors, respectively. Fluorescent vasopressin analogues are internalized by RME from the basolateral surface of polarized LLC-PK1 cells. The precise role of RME in vasopressin action is uncertain, but it is likely that it is involved in the desensitization of target cells by altering the number of cell surface vasopressin receptors. Alterations in the rate of RME may alter the response of the cell to vasopressin. Fluorescent and biotinylated vasopressins are useful tools for the study of this process.

Animals

Widespread distribution of calcium pump in calcium-transporting tissues. Immunohistochemical studies.

We examined the distribution of the plasma membrane calcium pump in several calcium-transporting tissues. Epitopes of the pump were found in the human kidney, specifically in the basolateral membrane of the distal tubule. The 28-kD calcium-binding protein co-localized with the calcium pump in cells of the distal tubule. Other human tissues that contain calcium pump epitopes include the basal surface of the syncytiotrophoblast of the placenta, human osteoblast-like cells and human choroid plexus. In the rat, calcium pump epitopes were found in the distal tubule of the kidney, the duodenum, the ileum, jejunum, placenta and in the choroid plexus. The pump is widely distributed in various calcium-transporting tissues and probably plays an important role in the translocation of calcium.

Adenosine Triphosphate

Role of membrane phosphotyrosine proteins in human spermatozoal function.

The monoclonal anti-phosphotyrosine antibody (PTA) recognized proteins related to relative molecular mass regions of 94,000 +/- 3000 and 46,000 +/- 3000 Mr on Western blots of detergent-solubilized non-capacitated human sperm extract (HSE). The pattern of phosphorylation at tyrosine residues depended upon the physiological state of the sperm cells. At least six protein bands corresponding to four molecular regions of 94,000 +/- 3000, 46,000 +/- 3000, 25,000 +/- 7000 and 12,000 +/- 2000 Mr, respectively, were labeled with 32P when human sperm were capacitated in vitro; the proteins belonging to the former three regions were phosphotyrosine proteins as they were precipitable by PTA. In vitro kinase assay performed directly on HSE indicated autophosphorylation of proteins of the same four molecular regions, with the capacitated sperm preparations having 30% higher 32P incorporation into 94,000 +/- 3000 Mr proteins and 17% less incorporation into 12,000 +/- 2000 Mr proteins as compared to the non-capacitated sperm preparations. Both of these protein regions were also autophosphorylated at tyrosine residues when immunoprecipitated phosphotyrosine proteins were used for the kinase assay. Phosphorylation of tyrosine residues of 94,000 +/- 3000 Mr proteins was further stimulated by 1.38- to 1.46-fold in response to exposure to zona pellucida proteins, namely the porcine ZP3 and human zona proteins (HZP); the HZP induced the highest response. Immunofluorescence observations on fixed human sperm demonstrated that capacitation as well as exposure to zona proteins increased the degree of tyrosine-specific fluorescence per sperm cell as well as the number of sperm cells that showed fluorescence at the acrosomal region of the spermhead.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens

Cardiotoxicity and hypertension in rats after oral lead exposure.

The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.

Administration, Oral

Myoglobinuric acute renal failure following electrical injury.

Eight patients with acute renal failure (ARF) following electrical injury were studied. The mean area of cutaneous burns was 23 +/- 16% (range 6-60%) and extensive tissue necrosis with gangrene was uniformly present. Oliguria developed 9.3 +/- 7 h (range 3-24 h) after the injury in 7 patients (88%). Urinalysis revealed presence of myoglobin in 75% of the patients. The mean duration of oliguria among those who recovered was 16 +/- 6 days (range 11-23 days) and the mean interval between the onset of oliguria and recovery of renal function was 25 +/- 6 days (range 21-34 days). Four patients died. The cause of death was Klebsiella septicemia in 1, hyperkalemia associated with extensive myonecrosis in 2 patients, and uncertain in 1 patient. Our observations showed that myoglobinuric acute renal failure associated with electrical injury carries a high mortality. Early detection and aggressive management of hyperkalemia and sepsis are necessary to reduce mortality among these patients.

Acute Kidney Injury

Life stress and post-partum psychosis: a preliminary report.

This is a preliminary report from a prospective study of the influence of psychosocial stressors on post-natal relapse in women at high risk of psychiatric disorder after childbirth. Forty-three index subjects with a previous history of psychosis or severe depression were compared with 45 pregnant control subjects without any previous psychiatric disorder. After delivery 51% of index subjects relapsed (RDC diagnoses): 28% were categorised as psychotic and 23% non-psychotic. All psychotic relapses were in women with a previous history of bipolar or schizoaffective disorder (46% of this subgroup). Only the non-psychotic post-partum relapses (mostly depressions) were associated with an increased likelihood of a severe life event in the 12 months preceding illness onset.

Bipolar Disorder

Dietary sources of N-nitrosamines in a high-risk area for oesophageal cancer--Kashmir, India.

Samples of foods consumed frequently in Kashmir, a high-risk area for oesophageal cancer, were analysed for the presence of volatile N-nitrosamines. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were detected in smoked fish (20 micrograms/kg NDMA), sun-dried spinach (5.8 micrograms/kg NDMA; 23.8 micrograms/kg NPIP), sun-dried pumpkin (24.6 micrograms/kg NPYR) and dried, mixed vegetables (10 micrograms/kg NDMA). The possible role of N-nitrosamines in the etiology of oesophageal cancer in Kashmir is discussed.

Diet

Variations in plasma trace-elements concentration during fracture healing in dogs.

The study was conducted on healthy Mongrel dogs. Fracture of Radius Ulna was inflicted with wire-saw. Subsequently repair was carried out using bone plates. Plasma Zinc concentrations decreased significantly from control values of 317.71 to 294.92 micrograms/dl at day one post-operatively and the values reached basal levels by 21st day. The concentrations of plasma Copper, Cobalt and Iron continued to decrease during the post-operative period. However, Manganese concentration increased significantly during the corresponding post operative period. Results indicate withdrawal of minerals from body reserves during bone repair.

Animals

The transport of digoxin across the perfused human placental lobule.

The cardiac glycoside, digoxin, is clinically used to treat fetal tachyarrhythmias and congestive heart failure. The time course of digoxin transfer across the human placenta was studied by dually perfusing an isolated lobule of the human placenta in vitro. Viability of the placental preparation was validated by measuring the rates of glucose and oxygen consumption, lactate production and synthesis of the protein hormone, chorionic gonadotropin. Following administration of 5 ng/ml digoxin to the maternal circulation, digoxin appeared in the fetal circulation within 5 min. The disappearance of digoxin from the maternal circulation was biexponential and best fit a two-compartment pharmacokinetic model. Mean calculated volume of the central compartment (257 +/- 6.3 ml) was consistent with the actual volume of the in vitro maternal circulation (246 +/- 7.4 ml). The half-life of the distribution phase was 9.7 +/- 3.3 min, and half-life of the terminal elimination phase was 362 +/- 83 min. After 30 min of perfusion, the amount of digoxin leaving the maternal circulation and appearing in the fetal circulation was constant at a fetomaternal mass ratio of 0.36 +/- 0.04. This ratio was maintained through to the end of the 3-hr experiment. All of the digoxin leaving the maternal circulation could be accounted for either in the fetal circulation or bound to placental tissue. The time to achieve equal concentrations on both sides of the placenta was estimated to be 268 +/- 34 min. These data are consistent with in vivo data obtained in humans, and support the relevance of using the in vitro placental perfusion model to obtain information regarding placental drug transfer in humans.

Digoxin