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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 559 records · Page 31Linked to original sources
PubMed1998

Down-regulation of protein kinase C isoforms in irritant contact dermatitis.

Protein kinase C (PKC) isoforms are important in cell signal transduction associated with regulation of cell proliferation and differentiation. In this study, alterations of PKC isoform levels in irritant patch test reactions were detected by Western immunoblots. 4 chemically and structurally different irritants, 4% and 8% hydrochloric acid (HCl); 1% and 2% sodium hydroxide (NaOH); 20% and 40% nonanoic acid (NON) in 1-propanol; and 5% and 10% sodium dodecyl sulfate (SDS) were applied on the backs of mice in Finn Chambers and fixed with surgical dressings. The patches were kept on the skin for 24 h and removed. 24 h after removal, mild erythema with thickening of skin without vesicles was observed in all irritated skin, except that 4% HCl and 1% NaOH treated skin showed unremarkable skin reaction. No visible skin reaction was detected in vehicle-treated skin. PKC isoform alpha, beta, gamma, and delta levels in irritated skin revealed a 10% to 65% decrease compared to vehicle treated skin. These results indicate that in HCl, NaOH, NON and SDS-induced irritation, activation of the PKC related cell signal transduction cascade may be involved, and that PKC mediated events may be a common phenomenon in irritant contact dermatitis.

Animals↗
PubMed1998

Lack of maternal antibodies to P serotypes may predispose neonates to infections with unusual rotavirus strains.

Rotavirus (RV) strains infecting newborns often have unique neutralization antigens (P serotypes) on their outer capsids that are distinct from those found on RV strains that cause diarrhea in older children. We examined the hypothesis that unusual RV strains preferentially infect newborns because the newborns lack maternal neutralizing antibodies to these strains. To test this hypothesis, sera and saliva samples collected from neonates infected with 116E-like (P[11]G9) strains in the maternity ward of the All India Institute of Medical Sciences (AIIMS) hospital in New Delhi were tested for neutralizing antibodies against common RV strains and those infecting newborns and these titers were compared with those of newborns who did not become infected (controls). The infected neonates had significantly lower levels of cord blood neutralizing antibodies to 116E than the controls, suggesting that immunity to neonatal RV infection is acquired transplacentally through maternal antibodies. Further, this study confirmed the immunogenicity of the AIIMS neonatal strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4).

Antibodies, Viral↗
PubMed1998

Determinants of action potential initiation in isolated rabbit atrial and ventricular myocytes.

Action potential conduction through the atrium and the ventricle of the heart depends on the membrane properties of the atrial and ventricular cells, particularly with respect to the determinants of the initiation of action potentials in each cell type. We have utilized both current- and voltage-clamp techniques on isolated cells to examine biophysical properties of the two cell types at physiological temperature. The resting membrane potential, action potential amplitude, current threshold, voltage threshold, and maximum rate of rise measured from atrial cells (-80 +/- 1 mV, 109 +/- 3 mV, 0.69 +/- 0.05 nA, -59 +/- 1 mV, and 206 +/- 17 V/s, respectively; means +/- SE) differed significantly (P < 0.05) from those values measured from ventricular cells (-82.7 +/- 0.4 mV, 127 +/- 1 mV, 2.45 +/- 0.13 nA, -46 +/- 2 mV, and 395 +/- 21 V/s, respectively). Input impedance, capacitance, time constant, and critical depolarization for activation also were significantly different between atrial (341 +/- 41 M omega, 70 +/- 4 pF, 23.8 +/- 2. 3 ms, and 19 +/- 1 mV, respectively) and ventricular (16.5 +/- 5.4 M omega, 99 +/- 4.3 pF, 1.56 +/- 0.32 ms, and 36 +/- 1 mV, respectively) cells. The major mechanism of these differences is the much greater magnitude of the inward rectifying potassium current in ventricular cells compared with that in atrial cells, with an additional difference of an apparently lower availability of inward Na current in atrial cells. These differences in the two cell types may be important in allowing the atrial cells to be driven successfully by normal regions of automaticity (e.g., the sinoatrial node), whereas ventricular cells would suppress action potential initiation from a region of automaticity (e.g., an ectopic focus).

Action Potentials↗
PubMed1998

Electrical interactions between a rabbit atrial cell and a nodal cell model.

Atrial activation involves interactions between cells with automaticity and slow-response action potentials with cells that are intrinsically quiescent with fast-response action potentials. Understanding normal and abnormal atrial activity requires an understanding of this process. We studied interactions of a cell with spontaneous activity, represented by a "real-time" simulation of a model of the rabbit sinoatrial (SA) node cell, simultaneously being electrically coupled via our "coupling clamp" circuit to a real, isolated atrial myocyte with variations in coupling conductance (Gc) or stimulus frequency. The atrial cells were able to be driven at a regular rate by a single SA node model (SAN model) cell. Critical Gc for entrainment of the SAN model cell to a nonstimulated atrial cell was 0.55 +/- 0.05 nS (n = 7), and the critical Gc that allowed entrainment when the atrial cell was directly paced at a basic cycle length of 300 ms was 0.32 +/- 0.01 nS (n = 7). For each atrial cell we found periodic phenomena of synchronization other than 1:1 entrainment when Gc was between 0.1 and 0.3 nS, below the value required for frequency entrainment, when the atrial cell was directly driven at a basic cycle length of either 300 or 600 ms. In conclusion, the high input resistance of the atrial cells allows successful entrainment of nodal and atrial cells at low values of Gc, but further uncoupling produces arrhythmic interactions.

Action Potentials↗
PubMed1998

Endoscopic correction of vesicoureteric reflux in failed reimplanted ureters.

PURPOSE: Persistent vesicoureteral reflux (VUR) after reimplantation of ureters requiring reoperation has been reported in up to 7.5% of cases. We report our experience with endoscopic subureteric Teflon injection (STING) in the treatment of VUR after failure of reimplantation of ureters. MATERIALS AND METHODS: Between 1985 and 1995, 31 children (18 male, 13 female) with persistent high-grade VUR after failure of reimplantation of ureters were referred to our hospital for endoscopic correction of VUR. The reflux was unilateral in 22 and bilateral in 9 (40 refluxing units). The ages at the time of STING ranged from 2 to 14 years. Ultrasound and voiding cystourethrography was performed in all patients at 3 months, 1 year and 3 years after STING procedure. Patients were followed-up for periods ranging from 1 to 11 years. RESULTS: VUR was successfully corrected in 27 ureters after a single injection. Seven ureters required two injections and 4 ureters three injections for the correction of reflux. Failure to correct reflux was noted in 2 ureters and these were corrected by reoperation. CONCLUSIONS: STING is a simple and effective day care procedure for the correction of VUR after failure of reimplantation of ureters.

Adolescent↗
PubMed1998

Ectopic expression of wnt-5a in human renal cell carcinoma cells suppresses in vitro growth and telomerase activity.

Loss of genes located on chromosome 3p has been reported in many different types of human cancers, including renal cell carcinoma. Previous studies using a nontumorigenic human renal cell carcinoma cell line (RCC23) established from a stage III nonpapillary carcinoma with a loss of heterozygosity on 3p showed that microcell hybrids containing an introduced intact chromosome 3 resulted in a more differentiated phenotype including restored cellular senescence and repression of telomerase activity. Human wnt-5a has been cloned and mapped to chromosome 3p14-21. We have stably transfected human wnt-5a into RCC23 cells which results in in vitro growth suppression and repression of telomerase activity in a manner similar to that found in microcell hybrids containing an introduced intact chromosome 3.

Carcinoma, Renal Cell↗
PubMed1998

Reliability and acceptability of psychiatric diagnosis via telecommunication and audiovisual technology.

The reliability of psychiatric diagnoses made remotely by telecommunication was examined. Two trained interviewers each interviewed the same 30 psychiatric inpatients using the Structured Clinical Interview for DSM-III-R. Fifteen subjects had two in-person interviews, and 15 subjects had one in-person and one remote interview via telecommunication. Interrater reliability was calculated for the four most common diagnoses: major depression, bipolar disorder, panic disorder, and alcohol dependence. For each diagnosis, interrater reliability (kappa statistic) was identical or almost identical for the patients who had two in-person interviews and those who had an in-person and a remote interview, suggesting that reliable psychiatric diagnoses can be made via telecommunication.

Alcoholism↗
PubMed1998

Body temperatures of home delivered newborns in north India.

In this prospective study, axillary temperature of newborns delivered at home were recorded by a field worker once within a period of 24 h after the birth in 10 villages of Haryana, India, during 1992-1993. Room air temperature was measured at the same time. Family members were interviewed to record newborn care practices. Of the 189 babies, 11.1% were found to be hypothermic (temperature < 35.6 degrees C) and 22.8% were hyperthermic (temperature > 37.3 degrees C). During winter months 19.1% were hypothermic as compared to only 3.1% in summer whereas 8.5% were hyperthermic in winter compared to 36.8% in summer. Room air temperature of < 24 degrees C was recorded in 41%. A strong correlation was observed between room air temperature and neonatal temperature. At the time of birth, 13.2% of the delivery rooms in summer and 73.6% in winter were reported to have heat source: 58.2% babies were reported to be wiped soon after birth; 97.3% were wrapped in cloth; the head was covered in 59.1% cases in winter and 10.5% in summer; 97.3% babies were kept with mother in same bed but not in skin-to-skin contact; and 65% were bathed within 24 h after delivery. Neonatal hypothermia is a common problem in developing countries. It is important that information, education and communication strategy about appropriate technologies for prevention and management of neonatal hypothermia is provided at domiciliary level. A significant proportion of babies are likely to suffer from hyperthermia in warm countries, specially in summer. Therefore, guidelines for thermal control in home births should be tailored to the specific environmental situation.

Fever↗
PubMed1998

Systemic lupus erythematosus in Kuwait--hospital based study.

The present study describes the clinical characteristics of patients with systemic lupus erythematosus (SLE), from the rheumatology service of the two main teaching hospitals in Kuwait. It was a retrospective-cum-prospective clinical study of 108 SLE patients. There were 98 females and 10 males, with a median age of 31.5y. Kuwaitis constituted 69%, while 31% were expatriates. The mean disease duration was 62 months. The main clinical features were: musculoskeletal involvement (87%), photosensitivity (48%), malar rash (43%), discoid lesions (10%), oral ulcers (33%), vasculitic skin lesions (10%), haematological features (53%), constitutional symptoms (51.4%), neuropsychiatric manifestations (23%), renal involvement (37%), serositis (29%), clinical manifestations of antiphospholipid syndrome (21%), cardiac involvement (10%) and pulmonary manifestations (19%). In conclusion, the clinical features of SLE in Kuwait were similar to most major studies from developed countries. Main differences included prominent haematological and mucocutaneous manifestations and possibly a low prevalence of anti-Sm antibodies. Whether these differences are due to the environment or genetic factors, remains to be studied.

Adult↗
PubMed1998

Estrogen receptor expression and function in long-term estrogen-deprived human breast cancer cells.

Hormone-dependent breast cancer responds to primary therapies that block estrogen production or action, but tumor regrowth often occurs 12-18 months later. Additional hormonal treatments that further reduce estrogen synthesis or more effectively block its action cause additional remissions, but the mechanisms responsible for these secondary responses are not well understood. As a working hypothesis, we postulated that primary hormonal therapy induces adaptive changes, resulting in enhanced estrogen receptor (ER) expression and target gene activation and, further, that secondary treatment modalities interfere with these receptor-mediated transcriptional pathways. To test this hypothesis, we used an MCF-7 breast cancer model system involving deprivation of estradiol in culture for a prolonged period. These long-term estradiol-deprived (LTED) cells adapt by acquiring the ability to regrow in the absence of added estradiol. The experimental paradigm involved the comparison of wild-type cells with LTED cells. As endpoints, we directly assessed ER expression at the messenger RNA-, protein-, and ligand-binding levels and ER functionality by quantitating reporter gene activation and expression of endogenous estrogen target gene messenger RNA, as well as ER coactivator levels. Our data demonstrated an adaptive increase in ER expression and in basal ER functionality, as assessed by read-out of three different transfected reporters in LTED, as opposed to wild-type MCF-7 cells. Increased reporter gene read-out was dramatically inhibited by the pure antiestrogen ICI 182,780. As verification that endogenous (as well as transfected) estrogen target genes had enhanced transcription, we found that the basal levels of c-myb and c-myc message were substantially increased in LTED cells and could be inhibited by antiestrogen. Interestingly, the levels of c-myb and c-myc message in the LTED cells seemed to be increased out of proportion to the degree of ER reporter gene activation and were similar to those in wild-type cells maximally stimulated with estradiol. In addition, not all estrogen-responsive genes were activated, because transforming growth factor-alpha message level was not increased in LTED cells. Up-regulation of the steroid receptor coactivator SRC-1 did not seem to mediate the process of enhanced ER-induced transcription. Considering these observations together, we suggest that long-term estradiol deprivation causes adaptive processes that not only involve up-regulation of the ER but also influence the specificity and magnitude of activation of estrogen-responsive genes.

Breast Neoplasms↗
PubMed1998

Vitamin D metabolism is altered in Asian Indians in the southern United States: a clinical research center study.

Asian Indians who immigrate to northern Europe have lower serum 25-hydroxyvitamin D [25(OH)D] than Caucasians, and they develop vitamin D deficiency, rickets, and osteomalacia. We investigated vitamin D metabolism, the effects of 25(OH)D3 on vitamin D metabolism and activity of 25(OH) D-24-hydroxylase, the rate-limiting enzyme for degradation of 25(OH)D, from cultured skin fibroblasts of Asian Indians and compared them with cultured skin fibroblasts of Caucasians in the southern United States. Normal subjects, ages 20-40 yr, were admitted to a metabolic ward for 2.5 days and given a daily diet containing 400 mg calcium and 900 mg phosphorus. Serum vitamin D, serum 25(OH)D, urinary calcium, and urinary phosphorus were significantly lower, whereas serum immunoreactive intact parathyroid hormone (PTH) and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] were significantly higher in Asian Indians than in Caucasians. Administration of 25(OH)D3 increased serum 25(OH)D and urinary calcium but did not change serum PTH or serum 1,25(OH)2D in Asian Indians. In cultured skin fibroblasts, Emax and Vmax of 25(OH)D-24-hydroxylase activity were significantly higher in Asian Indians. In summary, in Asian Indians serum vitamin D and 25(OH)D are markedly reduced, altered vitamin D metabolism is only partially reversed by 25(OH)D3, and 25(OH)D-24-hydroxylase activity in cultured skin fibroblasts is markedly increased. Thus, Asian Indians residing in the U.S. are at risk for developing vitamin D deficiency, rickets, and osteomalacia.

Adult↗
PubMed1998

Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease.

OBJECTIVE: To examine objectively the clinical effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in advanced PD. METHODS: Our initial seven consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic STN DBS underwent a standardized preoperative evaluation followed by a 2-day double-blind evaluation of efficacy 6 to 12 months after electrode implantation. Diaries documenting motor fluctuations and dyskinesias were also completed preoperatively and postoperatively. RESULTS: In the medication-off state, turning the stimulators on resulted in improvement in mean total Unified Parkinson's Disease Rating Scale (UPDRS) motor score by 58% including the following improvements in composite scores: akinesia 57%, rigidity 52%, tremor 82%, and gait and postural stability 49%. Additionally, the medication-off state improved 17% without stimulation, possibly as a result of electrode insertion alone or carry-over of chronic stimulation. In the medication-on, stimulation-on state, all major features of parkinsonism improved and total UPDRS motor score improved 41% compared with before surgery. Activities of daily living were improved while off medication 30%, and levodopa-induced dyskinesias were reduced 83% while total drug dosage was decreased 40%. With chronic stimulation, patients reported that the percentage of time spent in the "on" state (without dyskinesias) increased from 26% to 52% and "off" time decreased from 30% to 6%. Operative complications including cognitive worsening were not uncommon. CONCLUSIONS: STN DBS is a promising new surgical option for the treatment of advanced PD. The marked clinical benefits obtained in these severely disabled patients outweighed the adverse effects.

Aged↗
PubMed1998

Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women.

We report a 4-year randomized, double-blind, placebo-controlled clinical trial in 236 normal postmenopausal women (mean age +/- SE, 66.3+/-0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: -18.9% (p = 0.002) for parathyroid hormone (PTH), -11.9% (p = 0.026) for serum osteocalcin, and -32.2% (p = 0.003) for urine free pyridinoline. We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Aged↗
PubMed1998

Plasma insulin and growth hormone during antarctic residence.

Circulatory levels of insulin and growth hormone (GH) were estimated in nine tropical euglycemic men in New Delhi and during the first week of every month of stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not alter GH levels because mean GH values during Austral summer and Austral winter were not significantly different from the New Delhi values. Compared with GH, the insulin levels during March, April, and June were found to be significantly lower than the New Delhi values. In Antarctica, the insulin levels in March, April, May, June, July, and August were also found to be significantly lower than the December values. This decline in insulin in Antarctica might be important in increasing substrate availability for heat production by facilitating lipolysis and hepatic glucose output.

Acclimatization↗
PubMed1998

Novel inhibitors of cyclooxygenase-2: the sulfones and sulfonamides of 1,2-diaryl-4,5-difluorobenzene. Analysis of quantitative structure-activity relationship.

By a quantitative structure-activity relationship (QSAR) study, the inhibitory activity of a novel series of sulfones and sulfonamides of 1,2-diaryl-4,5-difluorobenzene, against the inducible form of cyclooxygenase (COX-2) was shown to be significantly correlated with the electronic constant (sigma) and some suitable indicator parameters. Considering the results of derived correlations, the substitutional requirement at different positions in the aromatic rings is discussed. In addition, a similar substitutional pattern for these congeners is found through a Fujita-Ban study. The latter approach also assigns higher (positive) activity contributions to those substituents that were guided by the former QSAR study.

Chemical Phenomena↗
PubMed1998

Inhibitors of the epidermal growth factor receptor protein tyrosine kinase: a quantitative structure-activity relationship analysis.

Hansch and Free-Wilson analyses are described on a data set, 4-anilinoquinazolines [the analogues of 4-(3-bromo-anilino)-6,7-dimethoxy quinazoline: PD 153035], as inhibitors of the epidermal growth factor receptor protein tyrosine kinase. These analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory activities. From both approaches, it is concluded that the combined electron-donating nature of R1- and R2-substitutions of the quinazoline ring and the electron-withdrawing nature of the X-substitution of the anilino-ring are beneficial for increasing the inhibition activity of a compound. Further, the symmetrical alkoxy substituents present at the R1- and R2-positions are also engaged in a steric interaction which was determined quantitatively through the parabolic relationship between the activity and combined molar refraction parameter, sigma MR of the substituents.

Drug Design↗
PubMed1998

Regulation of distinct steps of angiogenesis by different angiogenic molecules.

This study was designed to determine the relative activity of basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), platelet-derived growth factor (PDGF), platelet-derived endothelial cell growth factor (PD-ECGF), hepatocyte growth factor (HGF), and interleukin-8 (IL-8) in regulating endothelial cell division, migration, degradation of the extracellular matrix (ECM), morphogenesis, and survival. Human umbilical vein endothelial cells (HUVEC) were treated with different concentrations of the six cytokines. bFGF was the most potent mitogen followed by VEGF/VPF and PD-ECGF. VEGF/VPF and bFGF also enhanced the survival of the endothelial cells in serum-free medium. Interstitial collagenase (MMP-1) and urokinase plasminogen activator (uPA) were significantly upregulated only by bFGF. HGF, bFGF, and VEGF/VPF induced chemotactic migration of the endothelial cells, but only HGF (scatter factor) enhanced nondirectional motility. The organization of endothelial cells to form tubes on Matrigel was induced by bFGF and, to a lesser extent, by VEGF/VPF and IL-8. Permeability across endothelial cell monolayers was induced only by VEGF/VPF. These data demonstrate that different angiogenic molecules differentially regulate distinct steps in the process of angiogenesis, suggesting that any given molecule may be necessary but in itself insufficient for establishment of a viable vasculature.

Angiogenesis Inducing Agents↗