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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 181 records · Page 10Linked to original sources

Inhibition of mouse skin protein kinase C by benzoyl peroxide.

Benzoyl peroxide (BP), used widely in dermatologic therapy and by the food industry, is considered a tumor promoter in chemically induced skin. Tumor promoters of both the phorbol and non-phorbol type interact with protein kinase C (PKC). This enzyme, therefore, is regarded as the intracellular receptor for a number of tumor promoters. BP bears some structural resemblance to diacylglycerol (DAG) and thus may exert its action through the PKC system. Based on these observations, we have investigated the effect of BP on PKC from mouse skin. Our data show that unlike phorbol esters, which stimulate PKC (in vivo and in vitro), BP inhibits PKC. Concentration-dependent inhibition by BP is observed when PKC is stimulated by phorbol esters, diacylglycerol, phosphatidyl serine (PS), or a combination of the latter two. BP also inhibits PKC stimulated by (-) Indolactam V, a nonphorbol compound resembling the teleocidins. 3H-phorbol ester binding experiments reveal that inhibition by BP may be due to its interference with the phorbol ester binding site and consequently diacylglycerol binding. The binding data and the inability of BP to inhibit either cyclic AMP-dependent protein kinase I or II imply that BP interacts with PKC, and not with the histone substrate. Results presented here clearly indicate that unlike phorbol and certain non-phorbol type of tumor promoters BP does not stimulate PKC in vitro.

Animals

Japanese encephalitis virus latency in peripheral blood lymphocytes and recurrence of infection in children.

In a study group of 40 children who had been admitted to hospital with acute encephalitis, the disease was due to infection with Japanese encephalitis virus (JEV). Three children developed recurrence of disease 8-9 months later. No virus had been isolated from these three patients during the acute stage of their illness, but virus was recovered from all during the recurrence phase by co-cultivation of their peripheral blood mononuclear cells in primary mouse embryo fibroblast cultures. Virus was also recovered by co-cultivation of peripheral blood mononuclear cells collected 8 months after their acute disease from three out of eight randomly selected asymptomatic children within the study group but not from similar cultures set up from JEV-seronegative children used as controls. Virus was also isolated by co-cultivation of T lymphocytes of asymptomatic children as detected by indirect immunofluorescence or by inoculation in mice.

Cells, Cultured

Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells.

Monoclonal antibody (MAb) 4D5 was used to analyze the phosphorylation of p185HER2, the gene product of c-erbB-2/HER2, in SK-BR-3 cells. Culture in the continuous presence of 4D5 reduced the in vivo steady-state levels of p185HER2 phosphorylation by 80% in a dose-dependent manner, suggesting that MAb 4D5 may have interfered with the activation of phosphorylation of p185HER2. The observed MAb-mediated reduction of p185HER2 phosphorylation could not be completely accounted for by down-regulation. When cultures were grown under serum-free conditions, the steady-state levels of p185HER2 phosphorylation were reduced by 56%, and addition of 4D5 further inhibited phosphorylation to 20% of steady-state levels. With continuous exposure to increasing concentrations of newborn calf serum in these cultures, there was a linear increase in tyrosine-specific phosphorylation of p185HER2, reaching a 5.4-fold increase with 10% newborn calf serum. Phosphorylation of p185HER2 in the presence of newborn calf serum was not attributable to stimulation of the epidermal growth factor receptor by epidermal growth factor or by transforming growth factor-alpha. Extension of these observations to two other mammary carcinoma cell lines. MDA-MB-453 and BT-474, also demonstrated a significant capacity of serum to induce p185HER2 phosphorylation. The demonstration of antibody-mediated partial inhibition of phosphorylation under serum-free conditions suggests that mammary carcinoma cells may also produce and secrete a factor or factors which may activate p185HER2. Our observation that growth-inhibitory MAb 4D5 is able to reduce the phosphorylation of p185HER2 by newborn calf serum and by a cellular-derived factor(s) suggests the existence of a growth factor(s) which uses phosphorylation of p185HER2 as a signal transduction pathway to regulate cell proliferation.

Animals

Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study.

A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. This multifactorial study has shown that hypomotility, including gastroparesis and delayed small bowel transit, is common in non-ulcer dyspepsia and may be related to other disorders of gastrointestinal function. No relation between symptoms and disorders of function, however, has been shown.

Adult

The calcaneus: normal and abnormal.

The calcaneus is the largest tarsal bone. Many congenital and acquired disorders affect the bone. Primary disorders arise in the calcaneus itself, whereas secondary disorders arising in the neighboring soft tissues extend into and affect the calcaneus indirectly. Among the primary lesions, congenital, traumatic, infectious, hematologic, neoplastic, and other miscellaneous disorders constitute the majority, whereas various arthritides and soft-tissue neoplasms that arise adjacent to the bone constitute the important secondary calcaneal disorders. Radiographic features of many disorders of the calcaneus are disease-specific and thus diagnostic. This article describes a wide spectrum of calcaneal disorders and illustrates their salient radiographic features. This knowledge should facilitate radiographic diagnosis of various calcaneal disorders encountered in clinical practice.

Bone Diseases

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