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K Gupta

Publications and source records attributed to K Gupta.

At least 91 records · Page 5Linked to original sources
PubMed1997

Practical application of non-whole animal alternatives: summary of IRAG workshop on eye irritation testing. Interagency Regulatory Alternatives Group.

In November 1993, the Interagency Regulatory Alternatives Group (IRAG) sponsored a workshop to examine the current scientific status of alternatives to the Draize eye irritation test by assessing the current practical application of methods used to predict in vivo eye irritation. Laboratories from around the world were invited to submit detailed in vitro and in vivo data in parallel according to a specific set of guidelines in a consistent format. In vitro scores were compared with individual tissue scores. Over 60 data sets from 41 laboratories were received for 29 different test methods. Methods were grouped into five categories: organotypic models, chorioallantoic membrane-based assays, cell function-based assays, cytotoxicity assays and other systems. Data submissions and correlation analyses have been used to demonstrate the application of guidelines in method evaluations. Findings are summarized and future directions are indicated. A significant outcome of the workshop was the co-operation demonstrated among representatives of industry, academia and government in sharing test data on more than 2000 chemicals, products and product formulations for evaluation by their peers. Information obtained from this workshop will add to the weight of scientific evidence and scientific consensus about in vitro test methods and will establish credibility for regulatory acceptance of non-whole animal alternatives for ocular irritation.

Animal Testing Alternatives↗
PubMed1997

A role for phospholipase C activity in GLUT4-mediated glucose transport.

Overexpression of surrogate receptors [epidermal growth factor (EGF) receptor (EGFR) and platelet-derived growth factor receptor] in adipocytes has demonstrated that multiple signaling pathways may lead to GLUT4-mediated glucose uptake. These implicated pathways function independently of IRS-1 phosphorylation and PI3-kinase activation. In addition, we previously demonstrated that EGFR tyrosyl autophosphorylation is required to stimulate GLUT4-mediated glucose transport in 3T3-L1 adipocytes. This observation suggests that signaling molecules that are dependent on EGFR autophosphorylation, such as phospholipase C (PLC), may lie in the signaling pathway to glucose transport. As PLC has been implicated in glucose transport by several clinical and basic mechanistic studies, we investigated whether EGFR signaling may promote glucose transport via modulation of PLC activity. Activation of EGFR overexpressing 3T3-L1 adipocytes leads to a 3.4 +/- 1.2-fold stimulation of PLC activity over basal levels vs. only 1.06 +/- 0.01-fold stimulation by insulin. Pharmacological inhibition of PLC by 50 microM U73122 reduced phosphoinositide accumulation by 79.2 +/- 16.9% and resulted in a concomitant 56.0 +/- 12.7% decrease in EGF-induced glucose transport. This inhibition of glucose transport by U73122 was specific, because the inactive congener, U73343, failed to block EGF-induced glucose transport. Despite the low levels of insulin-induced PLC activity, insulin-stimulated glucose transport activity was similarly inhibited by U73122 (55.9 +/- 13.1% inhibition). Inhibition of PLC activation did not impair either EGF- or insulin-induced activation of glycogen synthase or incorporation of glucose into lipid, supporting the hypothesis that both EGF- and insulin-induced glucose disposal can be independent of GLUT4-mediated glucose transport. The diminution of glucose transport secondary to inhibition of PLC activity was reflected by a decrease in GLUT4 translocation to the plasma membrane upon either EGF or insulin stimulation. These results are consistent with either a permissive or an active role for PLC activity in the translocation of GLUT4 to the plasma membrane.

3T3 Cells↗
PubMed1996

Human natural killer cell expansion is regulated by thrombospondin-mediated activation of transforming growth factor-beta 1 and independent accessory cell-derived contact and soluble factors.

Natural killer cells (NK) were studied to determine factors important in their expansion. Flourescence-activated cell sorter (FACS) purified CD56+/CD3- NK cells cultured alone for 18 days in rIL-2 containing medium (1,000 U/mL) showed enhanced cytotoxicity but only minimal expansion. NK expansion was increased (12.5 +/- 1.6-fold) by coculturing NK with soluble factors produced by irradiated peripheral blood mononuclear cells (PBMNC) in which the two populations were separated by a microporous membrane. However, maximal NK expansion was always observed when NK were cocultured in direct contact with irradiated PBMNC (49.4 +/- 5.9-fold). To determine if marrow stroma, which supports differentiation of primitive NK progenitors, was a better accessory cell population than irradiated PBMNC, NK were cocultured in direct contact with primary marrow stromal layers. NK expansion with marrow stroma was similar to PBMNC. Fibroblast cell lines (M2-10B4, NRK-49F, NIH-3T3) and human umbilical vein endothelial cells (HUVEC), all homogeneous populations and devoid of monocytes, also exhibited a similar contact-dependent increase in NK expansion. Experiments were designed using fixed M2-10B4 stromal cells to separate the contact-induced proliferative stimuli from soluble factors. NK plated directly on ethanol/acetic acid-fixed M2-10B4, which leaves stromal ligands (cell membrane components and ECM) intact, resulted in increased NK expansion compared with medium alone. We further show that the combination of independent contact and soluble factors is responsible for maximal late NK expansion (days 28 through 40) but paradoxically inhibits early NK expansion (day 7). The proliferation inhibitory effects were verified by 3H-thymidine uptake and could be detected at days 2 through 6 but no longer 14 days after the initiation of the culture. We show that both laminin and thrombospondin inhibit early NK proliferation, whereas only thrombospondin was capable of also stimulating late NK expansion. The effect of thrombospondin on early NK proliferation is related to activation of transforming growth factor-beta 1 (TGF-beta) because anti-TGF-beta neutralizing antibody completely abrogated thrombospondin-mediated inhibition of early NK proliferation. Although inhibitory early in culture, active TGF-beta added only at culture initiation increases late NK expansion similar to thrombospondin. TGF-beta was not present in the thrombospondin preparation but latent TGF-beta in serum, or TGF-beta transcripts identified in IL-2-activated NK could explain paracrine or autocrine mechanisms for the regulation of NK proliferation. Finally, anti-TGF-beta neutralizing antibody only minimally affects stroma-mediated inhibition of early NK proliferation suggesting that aside from thrombospondin/TGF-beta, additional contact factors are important for the regulation of NK proliferation.

3T3 Cells↗
PubMed1996

Biomechanics of the deconditioned left ventricle.

To determine if strain and wall motion are enhanced in the left ventricle (LV) in a chronically afterload-reduced milieu, a magnetic resonance tagging technique was used to examine 19 subjects: 11 with transposition of the great arteries who have undergone an atrial inversion operation (TGA-LV, 11.6 +/- 4.3 yr postoperative) and eight normal adults. Finite strains (E1), regional twist, and radial motion were calculated at the atrioventricular valve and apical short axis levels in four anatomic wall regions. Strain was greatest in TGA-LV patients (-0.20 +/- 0.02 at the atrioventricular valve septal wall) and was significantly greater than controls in six out of eight regions. Marked differences were noted in the distribution of strain between TGA-LV and normal subjects as well as within the TGA-LV group. Ten of 11 LV of TGA-LV patients twisted clockwise in the lateral or inferior walls and counterclockwise in other walls (more counterclockwise than control subjects), whereas control LV twisted uniformly counterclockwise. The lateral wall of TGA-LV demonstrated the greatest radial inward motion, whereas controls demonstrated uniform radial inward motion. We conclude that the biomechanics of the LV faced with a chronic afterload reduction is enhanced; a marked increase in regional strain is observed in TGA-LV patients. Abnormalities in the distribution of strain were also observed. Markedly abnormal clockwise twist and increased lateral wall motion were demonstrated in TGA-LV patients.

Adolescent↗
PubMed1996

Epidermal growth factor induces glucose storage in transgenic 3T3-L1 adipocytes overexpressing epidermal growth factor receptors.

3T3-L1 adipocytes represent an established physiological model for studying glucose uptake and storage. Overexpression of epidermal growth factor (EGF) receptors in these cells (200,000-250,000 receptors per cell) confers EGF-inducible GLUT4-mediated glucose uptake (17). We now report that EGF receptor (EGFR)-mediated signals can induce incorporation of glucose into glycogen and lipids in these cells. Incorporation into lipids was stimulated to similar levels by insulin or EGF in adipocytes expressing full-length (wild type) EGFR (2.05 +/- 0.26-fold for insulin vs. 2.28 +/- 0.15-fold for EGF). EGF induced incorporation into glycogen at roughly 60% of the level of insulin (4.53 +/- 0.57-fold for insulin vs. 2.76 +/- 0.25-fold for EGF); this corresponded with similarly lower levels of glycogen synthase activation by EGF relative to insulin stimulation. EGFR kinase activity was required for induced storage because a kinase-inactive (M721) EGFR failed to stimulate glucose incorporation into glycogen or lipids. EGFRs that lack all or part of the unique EGFR COOH-terminal tail induced glucose incorporation at levels similar to that stimulated by full-length (wild type) EGFR. Thus, domains in the COOH-terminal tail of the EGFR, which are necessary for stimulating glucose transport, are not required for signaling EGF-induced glucose storage. EGF-induced glucose storage did not require de novo protein synthesis, suggesting that EGFR signaling uses existing pathways in the adipocytes. These data demonstrate that signaling pathways for EGFR-mediated glucose storage and GLUT4-mediated glucose transport diverge at the receptor level. Thus, EGF-induced glucose storage can be achieved in the absence of induced GLUT4-mediated glucose transport.

3T3 Cells↗
PubMed1996

Comparative study of immunoglobulin G and immunoglobulin M among neonates in caesarean section and vaginal delivery.

The present study comprised 50 cases of normal vaginal delivery and 50 cases of caesarean section. The cord blood level of immunoglobulin G was significantly higher in normal vaginal delivery cases than in caesarean section cases (mean level is 1653.2 +/- 443.1 mg/dl and 898.3 +/- 415.6 mg/dl respectively). The immunoglobulin G was low in cord blood but had higher concentration in all the 7 cases in study group who had fever with rigor in antenatal period. Thus the babies delivered with caesarean section had lower immunoglobulin level than normal vaginal delivery.

Adult↗
PubMed1996

Congenital sulfhemoglobin and transient methemoglobinemia secondary to diarrhoea.

Sulfhemoglobinemia and Methemoglobinemia are common causes of cyanosis arising due to accumulation of abnormal heme pigment. We present an unusual case of congenital sulfhemoglobinemia along with diarrhoea induced methemo-globinemia in a neonate. A high index of suspicion and a proper diagnostic approach is needed to determine the true frequency of their occurrence together.

Diarrhea↗
PubMed1996

An epidemiological study of obesity in Shimla Town.

A cross sectional study of 888 randomly selected subjects in Shimla town was done to determine prevalence of obesity, its relation to age and physical activity. The prevalence of obesity was 21.5% using cut off levels of BMI 25. The prevalence of obesity rose significantly with age. Obesity was less in those having moderate physical activity as compared to those with low and high activity. Primary prevention is required to tackle this disease risk factor through health education focussing on promotion of moderate regular physical activity.

Adult↗
PubMed1995

Medical education.

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Clinical Competence↗
PubMed1995

Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors.

The murine Unp proto-oncogene encodes a nuclear ubiquitin protease whose overexpression leads to oncogenic transformation of NIH3T3 cells. We have cloned cDNAs originating from the human homolog of this gene, designated herein as Unph (Unp, human), and have used these cDNAs to map the gene to 3p21.3, a region frequently rearranged in human tumor cells. Unph mRNA levels are consistently elevated in small cell tumors and adenocarcinomas of the lung, suggesting a possible causative role for the gene in the neoplastic process.

3T3 Cells↗
PubMed1995

Normolipemic xanthomatosis.

A 20-year-old woman presented with tendon and tuberous xanthomas. Plasma lipid levels were normal. Xanthomatosis with normal lipid levels is rare.

Adult↗
PubMed1995

Sudden spurt of cryptococcosis at a tertiary care hospital at New Delhi between December 1994 to February 1995.

In a short span of three months, nine patients of cryptococcal infection were diagnosed at the All India Institute of Medical Sciences (AIIMS), New Delhi with varied clinical presentation. Predisposing factors could be ascertained in two patients only. The diagnosis was based on the direct demonstration of the organism followed by successful culture supported by histopathology (in one patient) and radiology. The specific antigen was also detected in the body fluids. The increased awareness and greater suspicion helped in the diagnosis of these patients. Those who were diagnosed early, responded well with specific antifungal therapy.

Adolescent↗
PubMed1994

Anorexia nervosa and tuberculosis: case reports and a review of immune mechanisms.

A pair of identical twins living together and with a long-standing history of anorexia nervosa were admitted to restore weight. In the course of their admission one of them was found to be suffering from pulmonary tuberculosis and the other developed tuberculosis after 1 year. We seek to highlight factors that can lead to a delay in case detection and discuss issues relating to the immune mechanisms in tuberculosis and anorexia nervosa.

Adult↗