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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 883 records · Page 49Linked to original sources
PubMed1994

Plasma levels of antioxidant vitamins and oxidative stress in patients with acute myocardial infarction.

Of 138 patients with suspected acute myocardial infarction (AMI), 29 were excluded. Remaining 109 patients and 182 healthy controls of similar age and sex and same population were studied in detail for demographic variables, clinical and biochemical data for comparison. Mean age, sex, body weight, body mass index and blood pressures were comparable in the two groups whereas blood lipids, blood glucose and cardiac enzymes were raised in AMI patients compared to controls. Mean levels of vitamin C, E, A and beta-carotene were significantly less in AMI patients than controls whereas the lipid peroxides were significantly higher in AMI patients. The reduction in vitamin C and beta-carotene was more marked than decrease in other vitamins. With in AMI patients, those 28 patients who had cardiac arrhythmias showed greater decrease in vitamins compared to rest of the patients. Within both groups, smokers and diabetes patients had greater reduction in vitamin C and beta-carotene than other patients and subjects without confounding factors. Smokers also had higher lipid peroxides level than non-smokers. The inverse relation between AMI and low plasma vitamin levels remained significant after exclusion of patients with smoking and diabetes. These findings suggest that vitamin deficiency may be a risk factor of AMI and these patients may benefit by administration of these antioxidant vitamins for primary and secondary prevention of coronary artery disease.

Antioxidants↗
PubMed1994

Low grade pyrexia: is it chronic fatigue syndrome?

Eighty seven consecutive patients presenting with prolonged low grade pyrexia (99 degrees-101 +/- F) during 1984-93 were followed up for a mean duration of 2.9 years. Mean age was 37.55 years (SD + 10.16) and 66 (75.8%) were females. Onset of pyrexia was acute in 57 patients and was associated with chilly sensation (42), Fatigue (69), Arthralgias (61), myalgias (55) and several other non specific symptoms. Clinical examination showed paucity of physical signs with 7 patients showing tender lymphadenopathy, 7 showing splenomegaly, 5 hepatomegaly, and 1 phylctenular conjunctivitis. Psychiatric examination was within normal limits. Extensive investigations for any viral or other infection, autoimmune disorder or malignancy were unrewarding. Patients were followed up for an average of 2.9 (2 to 5 years). Thirteen patients had become asymptomatic within one year of onset of symptoms, 38 by two years and 45 by the end of three years. This syndrome may be a variant of chronic fatigue syndrome.

Adolescent↗
PubMed1994

Anterior fontanel size.

Anterior fontanel size was determined in a cross-sectional study of 445 infants ranging in age from newborn period to 2 years. The mean anterior fontanel size in neonates was 3.37 +/- 0.61 cm which decreased to 0.37 +/- 0.06 cm in 24 months age group. The age of closure of anterior fontanel was 12, 18 and 24 months in 40%, 70.4% and 91.3%, respectively.

Child, Preschool↗
PubMed1994

The influence of fibrinogen and fibrin on thrombin generation--evidence for feedback activation of the clotting system by clot bound thrombin.

In plasma the bulk of thrombin generation takes place after a clot has formed. We therefore investigated in what way the clot influences thrombin generation in plasma. The forming clot withdraws thrombin from free solution. Consequently less thrombin activity is found and less thrombin-inhibitor complexes are formed. The thrombin that is adsorbed to the clot reduces the lag time before thrombin generation in intrinsically or extrinsically triggered platelet poor plasma as well as in platelet rich plasma. We investigated the mechanism of this activation. Clots were obtained by recalcification of plasma or by the addition of thrombin-like enzymes (Reptilase, Agihal) from snake venoms. They were thoroughly washed until the washing fluid was devoid of any detectable clotting enzyme activity. In platelet poor plasma (PPP), thrombin-induced clots shorten the factor Va-dependent lag-time of thrombin generation in the extrinsic system as well as the factor VIIIa-dependent thrombin generation in the intrinsic system. Factor V or factor VII preparations that in itself hardly influence thrombin generation patterns acquire the capacity to shorten these lag-times when incubated with clot. The last washing fluid of the clot is inactive. Snake venom induced clots are not active either. Clots that are incubated in heparinised plasma for 1 h or more are as active as clots from normal plasma are. A role of factor Xa can not be excluded but must be minor because a clot made by addition of thrombin to plasma from which the factors II, VII, IX and X have been removed is as active as a clot from normal plasma is.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1994

Role of serum ferritin in assessment of disease activity in acute & chronic leukemia.

Serum ferritin (SF) was estimated using double antibody sandwich ELISA in 83 patients of acute and chronic leukemia at various stages of the disease. In 35 patients of acute lymphoblastic leukemia (ALL) in remission, the SF levels fell significantly from 550.63 ng/ml at presentation to 319.56 ng/ml but remained significantly higher than the control values of 46.14 ng/ml. In 28 patients of acute myeloid leukemia (AML), the SF values at 775.0 ng/ml were much higher than those in ALL patients and showed no decline with remission. This pattern was also seen in patients of chronic myeloid leukemia in blast crisis (CML-BC) with SF levels of 804.03 ng/ml at presentation and 717.43 ng/ml at partial remission. The values of SF were lowest in patients of CML in chronic phase ranging from 271.5 ng/ml to 332.12 ng/ml and showed no relationship with variation in total leucocyte count. No correlation was found between SF values and various clinical and laboratory parameters such as age, sex, fever, organomegaly, haemoglobin and total leucocyte count. Thus, while there appeared to be a correlation between remission and SF values in ALL, no such correlation existed between the activity of the disease and SF in other types of leukemia.

Acute Disease↗
PubMed1994

Molecular biology of vasopressin receptors.

Despite the numerous studies that have been spawned by the cloning of more than 240 G-protein-coupled receptors, the molecular basis for receptor discrimination of receptor-ligand interactions remains a central issue in membrane receptor biology. The receptor's criteria for agonists and antagonists allow these types of ligands to compete for the same binding site on the receptor, but only agonists are able to stimulate intracellular signaling. Various vasopressin agonists and antagonists, which are known to have different binding affinities for the V1a and V2 vasopressin receptors, can be exploited in the search for the conformational changes that precede and accompany receptor activation. Because the V1a and V2 vasopressin receptors are coupled to different intracellular signaling systems, it should be possible to assay the functional components of binding and G-protein coupling in a series of chimeric receptors. With the ever-increasing database on the structural determinants of G-protein-coupled receptor function, at least some of the underlying mechanisms of transmembrane signal transduction should be better understood in the next few years.

Amino Acid Sequence↗
PubMed1994

Anomalous origin of right coronary artery from left aortic sinus.

Saphenous vein bypass grafting relieved myocardial ischemia caused by the anomalous origin of the right coronary artery from the left aortic sinus in a premenopausal woman. Contrary to the conventional impression, the anomaly is associated with sudden death, aborted death, angina, vasospasm, arrhythmia and cardiac dysfunction and is diagnosed more frequently on angiography. The literature is reviewed and the guidelines for diagnosis and surgical management of this not-so-rare but potentially serious anomaly are presented.

Adult↗
PubMed1994

Renal and intestinal calcium transport: roles of vitamin D and vitamin D-dependent calcium binding proteins.

A model has been presented here for vitamin D-dependent Ca transport, based on observations of the intestinal Ca absorption process. In this model of vitamin D-dependent Ca transport, processes that occur in different areas of the intestinal epithelial cell combine to result in active transport of Ca2+ from the intestinal lumen to the bloodstream. At the brush-border membrane, 1,25(OH)2D3 causes a rapid opening of Ca2+ channels and transport of Ca2+ into the cell in a matter of seconds to minutes by a process that is independent of gene transcription. Inside the cell, 1,25(OH)2D3 stimulates transcription of the CaBP-D9k/28k mRNA and protein in 1 or more hours after 1,25(OH)2D3 treatment. The CaBP-D9k/28k has greater affinity for Ca2+ than do the brush-border membrane components, so Ca2+ movement through the cytosol is facilitated, with Ca2+ carried by CaBP-D9k/28k. At the BLM, 1,25(OH)2D3 causes an increase in concentration of the PMCA, and stimulates Ca(2+)-pumping activity. The PMCA has still greater affinity for Ca2+ than does the CaBP-D9k/28k. The combination of these vitamin D-dependent events results in active transport of Ca across the intestinal epithelia. Vitamin D sufficiency is necessary for this response to vitamin D treatment. This model may apply to renal DT cells as well as to intestinal absorptive cells. Vitamin D-regulated factors that are involved in vitamin D-dependent active Ca transport and are present in both renal DT and intestinal epithelial cells include VDR, CaBP-D9k/28k and the PMCA. The PMCA is localized to the BLM in both cell types. Both kidney and intestine respond similarly to changes in vitamin D, Ca, or P status. The many similarities between renal DT cells and intestinal epithelia strongly support the application of this model for vitamin D-dependent Ca transport in both tissues.

Animals↗
PubMed1993

Bacterial synthesis of truncated forms of the human vitamin D receptor and characterization of anti-receptor monoclonal antibodies.

We biosynthesized full-length (amino acids 1-427) and truncated human 1,25-dihydroxyvitamin D3 receptor proteins that encompassed only the putative DNA binding domain (amino acids 1-112) or the DNA binding domain and parts of the sterol binding domain (amino acids 1-193 and 1-328) in a bacterial expression system. We also prepared monoclonal antibodies against the full-length vitamin D receptor. The binding properties of the monoclonal antibodies were characterized by their ability to bind to full-length and truncated vitamin D receptor protein constructs. Seven of twelve monoclonal antibodies recognized the full-length receptor protein. These antibodies bound to truncated hVDR proteins with decreasing affinities as successive truncations were made from the carboxy-terminal end of the receptor protein. The five remaining monoclonal antibodies recognized the full-length and truncated receptor proteins with equally low affinities. Truncated forms of the vitamin D receptor and region-specific antibodies will be useful in assessing the properties of the receptor.

Antibodies, Monoclonal↗
PubMed1993

Regulation of epidermal growth factor receptor in NIH3T3/HER14 cells by antireceptor monoclonal antibodies.

The mechanism(s) by which monoclonal antibodies (mAbs) against the epidermal growth factor (EGF) receptor regulate receptor function have been investigated with NIH3T3/HER14 fibroblasts expressing human EGF receptors. Bivalent 225 mAb or monovalent 225 Fab' inhibited transforming growth factor (TGF)-alpha-induced EGF receptor tyrosine phosphorylation and cell proliferation. Culture of HER14 cells with 225 mAb or 225 Fab' did not activate EGF receptor tyrosine kinase when assayed after lysis of cells in SDS sample buffer. However, when cells were cultured with bivalent 225 mAb, but not with monovalent 225 Fab', and were subsequently lysed and further incubated in Triton X-100 lysis buffer containing proteinase and phosphatase inhibitors, receptor phosphorylation was observed. Phosphorylation was confined to tyrosine residues and was inhibited by addition of genistein after lysis, indicating that it was due to the activation of protein tyrosine kinase. The activity of bivalent 225 mAb was unphysiologic, in contrast with TGF-alpha, in that receptor kinase activation occurred only after cell lysis and with delayed kinetics; serine and threonine phosphorylation did not occur; and down-regulation of EGF receptors was slower. Selective mAb-mediated phosphorylation of tyrosine residues on EGF receptors was sufficient to activate phosphorylation of a SH2 group-bearing substrate, phospholipase C-gamma, indicating that serine/threonine phosphorylation is not required for EGF receptor kinase activity. These studies provide novel insights into the capacity of bivalent mAb to modulate EGF receptor function.

3T3 Cells↗
PubMed1993

Synthesis and antiviral activity of novel 5-(1-azido-2-haloethyl) and 5-(1-azido-, amino-, or methoxyethyl) analogs of 2'-deoxyuridine.

A new class of 5-(1-azido-2-haloethyl)-2'-deoxyuridines 3a-c was synthesized by the regiospecific addition of XN3 (X = I, Br, Cl) to the vinyl substituent of 5-vinyl-2'-deoxyuridine. Treatment of the 5-(1-azido-2-iodoethyl) compound (3a) with H2 and 10% Pd/C yielded the 5-(1-azidoethyl) (4) and 5-(1-aminoethyl) (5) derivatives of 2'-deoxyuridine. A similar hydrogenation of 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (1f) afforded the 5-(1-methoxyethyl) analog 6. The 5-(1-azido-2-haloethyl)-2'-deoxyuridines 3a-c exhibited in vitro antiviral activity against HSV-1, HSV-2, VZV, and EBV, but they were inactive against HCMV. In this group of compounds, the activity order was Cl > or = I > Br against HSV-1 and Br > or = Cl > I against HSV-2. A halogen atom in the 5-(1-azido-2-haloethyl) moiety 3a-c is an essential requirement since the 5-(1-azidoethyl) analog 4 was inactive, except for weak antiviral activity against VZV. Although the 5-(1-aminoethyl)-2'-deoxyuridine.HI (5) was inactive against HSV-1 and HSV-2, the 5-(1-methoxyethyl) compound 6 was equiactive to 5-ethyl-2'-deoxyuridine (EDU) against both HSV-1 and HSV-2 and 7-fold and 12-fold less active against HCMV relative to EDU and ganciclovir, respectively. All compounds investigated (3-6) exhibited low host cell cytotoxicity (IC50 > 118 microM) and inhibited cell proliferation only at high concentrations (IC50 > 76 microM).

Antiviral Agents↗