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S Kumar

Publications and source records attributed to S Kumar.

At least 523 records · Page 29Linked to original sources

The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site.

The gender-specific differences in body fat distribution suggest that sex steroids play an important role in regulating body fat distribution. Sex steroids may regulate adipose tissue mass by altering adipocyte number and size. The effects of various sex steroids on in vitro proliferation of preadipocytes from both sc and omental fat depots was investigated in men and women. Abdominal sc and omental preadipocytes from men (n = 14) and women (8 premenopausal and 7 postmenopausal) were cultured in the presence of 17beta-E2 (10(-7)-10(-9) M), estrone (10(-7)-10(-9) M), or dehydrotestosterone (DHT) (10(-7)-10(-9) M), and the rate of proliferation was measured over time (1-96 h) by DNA accumulation assays (micromoles per microg) and [(3)H]thymidine incorporation (disintegrations per min). In sc preadipocytes the rate of proliferation was increased between 24-48 h with E2 (10(-7) M) in both men (P = 0.028) and women (P = 0.017). Subcutaneous preadipocytes from women were more responsive to E2 in stimulating proliferation than those from men (women vs. men, DNA assay, 24 h, P = 0.014). In omental preadipocytes the increase in the rate of proliferation occurred at 24 h with E2 (10(-7) M) in women (P = 0.034) and at 48 h in men (P = 0.031). Gender appeared to influence the rate of proliferation by E2 in omental preadipocytes, with maximal stimulation of proliferation at 48 h in preadipocytes from women treated with E2 (10(-7) M; p = 0.007) compared with 72 h in preadipocyte cells from men (P = 0.048), as shown by DNA assay. Both estrone and the androgen DHT had no significant gender- or site-specific effect on the rate of proliferation at any time point. All DNA content data were further validated by thymidine incorporation analysis. In summary, E2 stimulates the rate of proliferation of preadipocytes in a dose-dependent manner, with significant gender- and site-specific differences. Neither estrone nor DHT affected adipocyte mass through proliferation of preadipocytes in this study. In conclusion, E2 may act as an important local factor influencing the proliferation of preadipocytes that may affect fat cell number in a depot- and gender-specific pattern in human abdominal sc and omental adipose tissue.

Adipocytes↗

Messenger ribonucleic acid encoding interferon-inducible guanylate binding protein 1 is induced in human endometrium within the putative window of implantation.

The putative window of embryo implantation in the human opens between days 19--24 of the menstrual cycle. During this period, the endometrium undergoes distinctive structural and functional changes orchestrated by steroid hormones, growth factors, and cytokines to attain a receptive phase in which it acquires the ability to implant the developing embryo. A major challenge in the study of human reproduction is to identify the molecular signals that participate in the establishment of this critical receptive phase in the context of the natural cycle. Toward this goal, we analyzed human endometrial biopsies at various days of the menstrual cycle by employing messenger RNA (mRNA) differential display technique. We isolated several complementary DNAs representing genes that are either up- or down-regulated within the putative window of implantation. We identified one of these genes as that encoding interferon (IFN)-inducible guanylate-binding protein 1 (or GBP1), which possesses GTPase activity. Analysis of endometrial biopsies by Northern blotting and RT-PCR demonstrated that GBP1 mRNA is specifically induced at the midsecretory phase of the menstrual cycle. In situ hybridization analysis revealed that GBP1 mRNA expression is localized in the glandular epithelial cells as well as in the stroma in the immediate vicinity of the glands. We observed that treatment of human endometrial adenocarcinoma cell, Ishikawa, with IFN-gamma or IFN-alpha markedly induced the expression of GBP1 mRNA. IFN-gamma was, however, a more potent inducer of GBP1 than IFN-alpha. Consistent with this finding, the temporal profile of GBP1 expression during the menstrual cycle resembled that of IFN-gamma mRNA more closely than that of IFN-alpha, predicting a regulatory role of IFN-gamma in GBP1 expression in midsecretory human endometrium. Although the precise function of GBP1 in the receptive human uterus remains unclear, its unique expression overlapping the putative window of implantation suggests that it might serve as a useful marker of uterine receptivity in the human.

Adult↗

Dexamethasone inhibits tumor necrosis factor-alpha-induced apoptosis and interleukin-1 beta release in human subcutaneous adipocytes and preadipocytes.

Tumor necrosis factor-alpha (TNF alpha) can decrease adipose tissue mass, but in obesity, adipose tissue hypertrophy persists despite increased TNF alpha expression. The hormonal milieu of obesity may antagonize the adipostat effects of TNF alpha. We examined the effects of insulin and the synthetic glucocorticoid, dexamethasone (Dex), on TNF alpha-induced apoptosis and gene expression in human adipocytes and preadipocytes. Using RT multiplex PCR, the expression of the proapoptotic genes interleukin-1 beta (IL-1 beta)-converting enzyme (ICE) and TNF alpha and the antiapoptotic genes bcl-2, nuclear factor-kappa B (NF kappa B), and NF kappa B inhibitory subunit, I kappa B, were examined. The expression and release of IL-1 beta, a postulated downstream effector of ICE-mediated apoptosis, were also determined. TNF alpha increased the messenger ribonucleic acid levels of ICE, TNF alpha, IL-1 beta, bcl-2, and NF kappa B in preadipocytes and adipocytes (P < 0.01). Dex inhibited TNFalpha-induced messenger ribonucleic acid expression of ICE, TNF alpha, and IL-1 beta (P < 0.01), but not that of bcl-2 and NF kappa B. TNF alpha stimulated IL-1 beta release from preadipocytes and adipocytes up to 20-fold, but the effect was abrogated by Dex. Apoptosis induced by TNF alpha was reduced to control levels (P < 0.01) by Dex. Insulin had no significant effect on TNF alpha-induced apoptosis and gene expression. In obesity, glucocorticoids may reduce TNF alpha actions in adipose tissue by inhibiting TNF alpha-induced apoptosis, IL-1 beta release, and TNF alpha expression.

Adipocytes↗

Rhinophycomycosis.

Rhinophycomycosis, a subcutaneous fungal infection, is less uncommon than many other frequently cited granulomatous lesions of the paranasal sinuses. Four illustrative cases are presented with their characteristic clinical, radiological and histopathological features. The initial origin of the swelling was always in the region of the nasal vestibule and ala. The therapeutic response to potassium iodide, ketaconazole and fluconazole was dramatic and sustained.

Adult↗

Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation.

A 12-week, double-blind, randomized, placebo-controlled trial of oral clonidine in three fixed doses (4, 6, and 8 mcg/kg/day) using a crossover design was conducted with 10 children who had hyperkinetic disorder (mean age 7.6 years +/-.54). All had comorbid mental retardation. Both parents' ratings on the Parent Symptom Questionnaire and clinicians' ratings on the Hillside Behaviour Rating Scale showed a marked dose-related response to clonidine in hyperactivity, impulsivity, and inattention. Drowsiness was a common side effect of clonidine. It wore off by the 2nd to 4th week in most cases. Thus, clonidine is a safe and effective medication in young hyperkinetic children with comorbid mental retardation.

Adolescent↗

Nateglinide: a new rapid-acting insulinotropic agent.

The United Kingdom Prospective Diabetes Study has shown that tight glycaemic control significantly reduces microvascular complications in Type 2 diabetes, but the effects on macrovascular complications were less impressive and did not reach statistical significance. Epidemiological studies have shown that post-prandial hyperglycaemia, rather than fasting hyperglycaemia, is more closely related to cardiovascular complications. It is, therefore, possible that previous studies may have overlooked the possible benefits of tight control of post-prandial hyperglycaemia as an important factor in reducing the cardiovascular mortality. Nateglinide is a novel D-phenylalanine derivative that inhibits ATP-sensitive K+ channels in pancreatic beta-cells in the presence of glucose and thereby restores first phase insulin response in patients with Type 2 diabetes. This helps in reducing post-prandial glucose excursion. Combination studies with metformin have shown it to be effective in controlling hyperglycaemia. While metformin reduces the basal plasma glucose, nateglinide helps in controlling post-prandial peaks. Nateglinide provides a new therapeutic option for treating Type 2 diabetes by specifically targeting post-prandial hyperglycaemia.

Animals↗

Mastocytosis.

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Adult↗

Toxicity, feeding deterrence, and effect of activity of 1,8-cineole from Artemisia annua on progeny production of Tribolium castanaeum (Coleoptera: Tenebrionidae).

1,8-Cineole isolated from Artemisia annua was tested against Tribolium castaneum (Herbst) for contact toxicity, fumigant toxicity, and antifeedant activity. The adults of T. castaneum were more susceptible than larvae to both contact and fumigant toxicity of 1,8-cineole, and LD50 and LC50 values of 108.4 microg/mg body weight of adult insect and 1.52 mg/liter air were found, respectively. Furthermore, 14-d-old T. castaneum larvae were more tolerant than 16- and 18-d-old larvae and adults to the contact toxicity of 1,8-cineole, but the 16- and 18-d-old larvae have similar susceptibility. In contrast, all the larvae (14-18 d old) of T. castaneum were much more tolerant than the adults to the fumigant action, but larvae of different ages had similar susceptibility. The compound 1,8-ciineole applied to filter paper at a concentration of 3.22-16.10 mg/cm2 significantly (P < 0.05) reduced the hatching of T. castaneum eggs and the subsequent survival rate of the larvae. Adult emergence was also reduced by 1,8-cineole. Feeding deterrence of 81.9% was achieved in T. castateum adults by using a concentration of 121.9 mg/g food, whereas larvae showed 68.8% at the same concentration.

Animals↗

Amyloidoma of the thoracic spine. Case report.

The authors report the case of a patient with amyloidoma of the thoracic spine. A 34-year-old man presented with a 2-month history of upper-back pain, bilateral lower-extremity weakness, and numbness below the nipple. A computerized tomography study revealed an extradural mass with destruction of the T-2 lamina and pedicle. Intraoperatively, there was a pinkish, partially suctionable mass infiltrating the muscle plane and causing destruction of the T-2 lamina. Histological examination showed typical amyloid masses that demonstrated apple-green double refraction on examination of the Congo red-stained section under polarized light. Amyloidomas are rare benign lesions that, unlike other forms of amyloidosis, have an excellent prognosis. A cure is possible with complete resection of the mass.

Adult↗

Intramedullary Ewing sarcoma of the spinal cord: consequences of molecular diagnostics. Case report.

Molecular biological techniques have begun to transform modern medicine. These techniques have shown promise in the pathological diagnosis of difficult or uncommon tumors. Accurate molecular diagnosis of the small round-cell tumors, for example, is especially important because divergent therapies may be required to eradicate such disparate lesions as neuroblastoma, lymphoma, rhabdomyosarcoma, central primitive neuroectodermal tumors/medulloblastoma, or Ewing sarcoma (ES). The authors present an unusual case of a primary, extraosseous ES arising from the intramedullary spinal cord, in which molecular studies were required for specific diagnosis and therapeutic guidance.

Adult↗

Fine needle aspiration cytology (FNAC) of nerves in leprosy.

Leprosy is primarily a disease of the peripheral nerves and a technique that is simpler than nerve biopsy is required to evaluate nerve involvement, especially in pure neuritic (PN) leprosy. This study was designed to evaluate the role of FNAC of the nerve in the diagnosis and classification of leprosy. A prospective study was carried out on 25 patients with clinically active leprosy and at least one thickened peripheral sensory nerve. Nerve aspirates were evaluated by May-Grunwald-Giemsa and Fite's staining. Lepromin test, slit skin smears (SSS), skin biopsies (except PN cases) and nerve biopsies were performed and compared with FNAC. FNAC of nerve from 23 cases (92%) yielded diagnostic aspirates. Acid fast bacilli were observed in six cases by FNAC. FNAC and nerve pathology were equally comparable with the other parameters evaluated. Based on the results, cytological criteria were developed for interpreting nerve aspirates and the cases were classified as paucibacillary (18), BB (2), BL (2), LL (1) and non-diagnostic (2). All PN cases showed diagnostic paucibacillary type cytology. FNAC of the nerve yields diagnostic aspirates in leprosy comparable with nerve pathology and the proposed cytological criteria may be useful in classification of nerve aspirates.

Adult↗

SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia.

The stress-activated mitogen-activated protein kinase (MAPK) p38 has been linked to the production of inflammatory cytokines/mediators/inflammation and death/apoptosis following cell stress. In these studies, a second-generation p38 MAPK inhibitor, SB 239063 (IC(50) = 44 nM), was found to exhibit improved kinase selectivity and increased cellular (3-fold) and in vivo (3- to 10-fold) activity over first-generation inhibitors. Oral SB 239063 inhibited lipopolysaccharide-induced plasma tumor necrosis factor production (IC(50) = 2.6 mg/kg) and reduced adjuvant-induced arthritis (51% at 10 mg/kg) in rats. SB 239063 reduced infarct volume (48%) and neurological deficits (42%) when administered orally (15 mg/kg, b.i.d.) before moderate stroke. Intravenous SB 239063 exhibited a clearance of 34 ml/min/kg, a volume of distribution of 3 l/kg, and a plasma half-life of 75 min. An i.v. dosing regimen that provided effective plasma concentrations of 0.38, 0.75, or 1.5 microg/ml (i.e., begun 15 min poststroke and continuing over the initial 6-h p38 activation period) was used. Significant and dose-proportional brain penetration of SB 239063 was demonstrated during these infusion periods. In both moderate and severe stroke, intravenous SB 239063 produced a maximum reduction of infarct size by 41 and 27% and neurological deficits by 35 and 33%, respectively. No effects of the drug were observed on cerebral perfusion, hemodynamics, or body temperature. Direct neuroprotective effects from oxygen and glucose deprivation were also demonstrated in organotypic cultures of rat brain tissue. This robust in vitro and in vivo SB 239063-induced neuroprotection emphasizes the potential role of MAPK pathways in ischemic stroke and also suggests that p38 inhibition warrants further study, including protection in other models of nervous system injury and neurodegeneration.

Animals↗

Development of a novel plant system as biosensor for detecting environmental hazards and bioactive molecules through distinct responses.

Currently, chemicals are used excessively in medicine, industry, and agriculture throughout the world. Because of the current rise in environmental pollutants and hazardous exposures of human beings, there is an imperative need for monitoring the environment for biosafety. In addition, the importance of natural products with novel activity for drug or agrochemical scopes is being more and more realized. We report on a novel test system that can act as biosensors for detecting useful compounds while simultaneously monitoring or forecasting the biohazard exposure of organisms to chemicals as well as to physical factors in a given environment. Using different compounds and factors with known biological and cytotoxic activities, a detail plant test procedure has been developed that can be used in detecting and analyzing the value and/or danger of any given compound or treatment, including cell division inhibition, cytotoxicity, growth inhibition, and anticancer activities. The method provides a highly efficient single biosensor system that can replace several individual biotesting procedures. This plant assay procedure is a highly sensitive system for monitoring physical stress factors in the environment, including ionizing and nonionizing radiation. The procedure can be followed throughout the year because of the rapid growth rate of the plant used and its regeneration in ambient conditions. Therefore, the described system is highly useful to thoroughly monitor the environment and detection of new chemicals/compounds.

Biosensing Techniques↗