PubMed Health⌕ Search

Biomedical subjects

G N Shah

Publications and source records attributed to G N Shah.

At least 37 records · Page 2Linked to original sources
PubMed1996

Age-related changes in the responsiveness of apolipoprotein A1 to thyroid hormone.

To determine the age-related changes in the effect of thyroid hormone on apolipoprotein A1 (ApoA1) gene expression, male Fischer 344 rats at 4 (young) and 26 (aged) mo of age were studied. Hyperthyroidism was induced with daily intraperitoneal injections of 3,5,3'-triiodothyronine (15 micrograms/100 g body wt) for 10 days. Hypothyroidism was induced with 0.025% methimazole in drinking water for 4 wk. Hyperthyroidism was associated with increased serum ApoA1 levels in young rats [7.52 +/- 0.41 vs. 3.67 +/- 0.30 optical density (OD); P < 0.01]. The increase in aged rats (6.5 +/- 0.87 vs. 5.14 +/- 0.09 OD) did not reach statistical significance. Hypothyroidism was not associated with significant changes in serum ApoA1 levels in either young or aged rats. Hyperthyroidism was associated with a 2.5-fold increase in ApoA1 mRNA in young rats and a 1.7-fold increase in aged rats. Hypothyroidism was associated with a 3.6-fold reduction in ApoA1 mRNA in young rats, but there was no significant change in aged hypothyroid rats. Mobility shift assays indicated that the binding of transacting factors to ApoA1 promoter increased in hyperthyroid young rats but not in hyperthyroid aged rats. It is concluded that aging in rats is associated with reduced ApoA1 responsiveness to thyroid hormones. This altered responsiveness could partly be the result of changes in the binding activity of nuclear factors to the ApoA1 promoter.

Aging↗
PubMed1995

Age-related changes in apolipoprotein A-I expression.

To determine the age-related changes in apolipoprotein A-I (ApoA1) expression, male Fischer 344 rats at 4 (young), 12 (intermediate age), and 24-26 (aged) months of age were studied. Immunoblot analysis of plasma proteins indicated that 26-month-old rats (1.79 +/- 0.16 mg/ml) and 12-month-old rats (2.23 +/- 0.11 mg/ml) have significantly higher plasma ApoA1 concentrations compared to 4-month-old rats (1.14 +/- 0.15 mg/ml) P < 0.001. Hepatic ApoA1 mRNA was approx. 2-fold higher in aged rats compared to 12-month-old and 4-month-old rats. This increase in hepatic ApoA1 mRNA in aged rats was also reflected in the increased translation of ApoA1 mRNA in vitro. Reduced mRNA turnover may account for the increased hepatic ApoA1 mRNA content in 26-month-old rats, since the rate of ApoA1 gene transcription as measured with nuclear run off assays was significantly reduced with age. The ApoA1 synthesis in vivo, as measured by [14C]leucine incorporation at 30 min, was reduced in aged rats compared to young rats (170.5 +/- 10.2 vs. 253.9 +/- 7.7 cpm per liver) P < 0.001 probably as a result of changes related to cellular metabolism rather than an alteration inherent to the ApoA1 mRNA translatability. The age-related increase in plasma ApoA1 protein is probably secondary to reduced metabolic clearance rate of ApoA1 protein or is the result of increased intestinal synthesis of ApoA1.

Aging↗
PubMed1995

Age-related shortening of poly(A) tail of albumin mRNA.

To determine the molecular mechanisms of age-related changes in hepatic albumin gene expression, male Fisher 344 rats at 4, 12, and 24 months of age were studied. The hepatic albumin content was modestly increased by 20% and plasma albumin concentration was not altered with age. There were no age-related changes in albumin mRNA content of the liver. The in vivo synthetic rate of albumin as measured with [14C]-leucin incorporation in 4-month-old rats (350 +/- 24.5 cpm) was not significantly different from that in 24-month-old rats (393 +/- 30.3 cpm). However, in vitro translational efficiency of albumin mRNA from 24-month-old rats was only 49% of that in 4-month-old rats. This was correlated with shortening of the poly(A) tail of albumin mRNA from approximately 300-450 bases in 4-month-old rats to only 50-100 bases in 24-month-old rats. The reduced albumin mRNA translational efficiency in vitro along with shortening of the poly(A) tail with age is probably an adaptive response since hepatic albumin content was increased and plasma albumin concentrations were not altered with age. The age-related shortening of the poly(A) tail is yet another mechanism of age-related alterations in the expression of specific genes where the changes seen with age are mostly translational.

Aging↗
PubMed1994

Direct demonstration of three different states of the pancreatic cholecystokinin receptor.

We used rat pancreatic acini as well as COS-7 cells transfected with the cloned pancreatic cholecystokinin (CCK) receptor and measured the abilities of CCK octapeptide (CCK-8) and L-364,718 (a CCK receptor antagonist) to inhibit binding of 125I-labeled CCK-8 (125I-CCK-8) and [3H]L-364,718. With pancreatic acini 125I-CCK-8 bound to two different states of the CCK receptor. The high-affinity state (1% of the receptors) had a Kd for CCK-8 of 985 pM and the low-affinity state (19% of the receptors) had a Kd for CCK-8 of 30 nM. [3H]L-364,718 bound to low-affinity receptors and to a previously unrecognized very-low-affinity state (80% of the receptors) having a Kd for CCK-8 of 13 microM. L-364,718 had the same affinity (Kd 3 nM) for each of the three different states of the CCK receptor. Similar measurements using transfected COS cells also identified three different states of the CCK receptor, with the very-low-affinity state being the most abundant. Thus, the ability of the CCK receptor to exist in three different states is an intrinsic property of the CCK receptor molecule itself.

Animals↗
PubMed1993

Epidemiological trend in the distribution of cancer in Kashmir Valley.

STUDY OBJECTIVE: To study the distribution of cancers, with particular emphasis on oesophageal cancer. DESIGN: Patient records for 1986-88 in the Department of Oncology, SK Institute of Medical Sciences, were searched to identify cases and types of cancer. SETTING: The Valley of Kashmir, India. SUBJECTS: Patients with cancer resident in the valley. MAIN RESULTS: The seven most common types of cancer in men were those of the oesophagus, lungs, stomach, skin, upper respiratory tract, and urinary tract. In women the most common types of cancer were those affecting the oesophagus, breast, cervix, stomach, skin, colon/rectum, and lungs. Cancer of the oesophagus was the most frequent type in both sexes, accounting for 42.9% of all types of cancer in the valley. This distribution of cancer types is strikingly different from that in the rest of India where oropharyngeal cancer is the most common form. Again, contrary to the trend in India as a whole, cervical cancer is not a leading type of cancer in the valley and is less frequent even than cancer of the breast in the women. CONCLUSIONS: The preponderance of oesophageal cancer was attributable to the local practice of drinking boiling hot salt tea. Universal male circumcision in the majority community in the valley was considered to be partly responsible for low cervical cancer frequency.

Circumcision, Male↗
PubMed1991

Differential binding and biological activities of epidermal growth factor and transforming growth factor alpha in a human pancreatic cancer cell line.

The binding characteristics and biological activities of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) were studied in T3M4 human pancreatic cancer cells. Scatchard analysis of 125I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites: a high-affinity site (Kd = 0.58 nM; 25,300 sites/cell) and a low-affinity site (Kd = 7.0 nM; 484,000 sites/cell). At pH 8.5, there was a decrease in the number of high-affinity sites. In contrast, only a single order of high-affinity sites was detected with 125I-TGF-alpha at either pH 7.4 (Kd = 0.57 nM; 100,200 sites/cell) or pH 8.5 (Kd = 0.70 nM; 230,400 sites/cell). The two ligands bound to the same receptor, as determined in cross-linking experiments and in competitive binding assays performed in the presence of an anti-EGF receptor antibody that allows for EGF binding. Phosphoamino acid analysis of the immunoprecipitated EGF receptor indicated that EGF exerted a greater effect than TGF-alpha on tyrosine phosphorylation of the receptor. EGF and TGF-alpha also exhibited different potencies with respect to their effects on inositol 1,4,5-trisphosphate generation and exerted divergent effects on the kinetics of inositol 1,4,5-trisphosphate formation. These findings point to dissimilar interactions of EGF and TGF-alpha with the EGF receptor in T3M4 cells, which may lead to differential activation of signal transduction pathways by these ligands.

Epidermal Growth Factor↗
PubMed1991

Identification and characterization of a prolactin-like polypeptide synthesized by mitogen-stimulated murine lymphocytes.

Previously, we have reported that concanavalin A (Con A)-stimulated murine splenocytes synthesize and secrete into the medium a substance with prolactin (PRL)-like properties. Western blot analysis of the culture medium of Con A-stimulated murine splenocytes identified a PRL-like polypeptide (Ly-PLP) with an apparent molecular weight (Mr) of 46 kd. Rabbit anti-rat PRL antibody (S-9, NIDDK) was used for immunostaining. Specificity was proved by the absence of a band in properly preabsorbed primary and secondary antibodies. Electroeluted Ly-PLP enhanced the mitogenic response of lymphocytes to Con A. In situ hybridization analysis of dispersed lymphocyte smears demonstrated the presence of an mRNA that hybridized with a rat PRL cDNA probe. The size of the mRNA species was 1.4 kb on Northern blot analysis. Two-dimensional peptide map analysis of pituitary PRL and Ly-PLP showed three peptides with identical migration characteristics. Western blot analysis of lymphocyte culture medium following Con-A-affinity column treatment provided evidence that the Ly-PLP was a non-glycoprotein. Therefore, we conclude that Ly-PLP represents a structural variant of pituitary-PRL (Pit-PRL), and provide evidence to strongly suggest that it is a novel lymphokine.

Animals↗
PubMed1989

Prolactin variants in the rat adenohypophysis.

Prolactin (PRL) heterogeneity in the rat pituitary gland was first reported in 1978. Since then, multiple forms of the hormone in the rat pituitary gland have been reported by other investigators. Some of these variants have been ascribed to posttranslational modifications, while the origin of the others is as yet undefined. In this study, the nature, distribution and origin(s) of PRL size variants in the rat adenohypophysis were defined by Western blotting, Northern blot hybridization analysis and pulse-chase approaches. Thirteen structurally related variants, grouped into species with apparent molecular weights (Mr) 97-34,000, 31,000, 24,000 and 22-17,000, were consistently obtained on the basis of their electrophoretic mobilities in nonreducing polyacrylamide gels. Many of the Mr forms were disulphide-linked aggregates. Northern blot analysis suggested that the 24,000 monomeric PRL was encoded by the 0.9 kb mRNA species, while the 45,000 variant could be encoded by the 1.9 kb mRNA. Four PRL variants in the Mr range of 25-46,000 were synthesized concurrently by the mammotrophs in culture. Newly synthesized high Mr variants were also released into the medium and could be detected as early as 1 min after synthesis. Collectively these results suggest that structurally related PRL variants in the rat pituitary gland are due to a combination of posttranscriptional and posttranslational modification of a single gene product. In addition high Mr variants are preferentially secreted over low Mr forms, probably through an alternative secretory pathway.

Animals↗
PubMed1989

Prevalence of hepatitis B surface antigen in Kashmiri blood donors.

Eighty eight of 7900 healthy blood donors screened for hepatitis B surface antigen (HBs Ag) carrier state by reversed passive haemagglutination assay were found to be positive. The positivity was significantly more in rural donors (P less than 0.001) as compared to urban donors. False positive results are seen only with 1.13 per cent of the sera tested.

Adult↗
PubMed1988

Hypothalamic site of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Administration of TCDD produced a significant decrease in the serum concentration of prolactin (PRL) detected in rats after 4 hr compared to pair-fed vehicle controls and noninjected controls. This effect of TCDD was reversed by pimozide, a dopamine receptor antagonist. These data suggest that TCDD decreased the release of PRL from the adenohypophysis either by a direct effect on the gland or by altering the dopamine concentration in the median eminence (ME). Concentrations of TCDD from 5 to 500 ng/ml had no direct effect on the ability of the adenohypophysis to secrete PRL in vitro. However, the dopamine concentration increased to 3.24 +/- 0.07 ng per ME in TCDD-treated rats compared to 2.81 +/- 0.08 ng in vehicle controls. This is a dramatic alteration in the dopamine concentration, since the dopamine is being measured in the portal circulation which exhibits a rapid turnover. The rate constant of dopamine depletion after alpha-methyl-p-tyrosine and the turnover rate were also significantly elevated in the ME of TCDD-treated rats. These data provide the first biochemical evidence for a hypothalamic site of action of TCDD. Since dopamine is inhibitory to PRL release from the adenohypophysis, increased ME steady-state concentrations and turnover of this catecholamine may be responsible for the decreased concentration of serum PRL detected within 4 hr of TCDD injection. Thus, one of the early modes and sites of action of TCDD is to elevate the dopaminergic activity of the tuberoinfundibular nucleus. A hypothalamic site of action for TCDD may result in a number of the endocrinological effects known to be produced by exposure to TCDD.

Animals↗
PubMed1987

Hepatic protein kinase C: translocation stimulated by prolactin and partial hepatectomy.

Prolactin stimulates a hepatotrophic response similar to that caused by phorbol esters or partial hepatectomy in rats. Since phorbol esters, which activate protein kinase C, mimic prolactin action in liver, the relationship between prolactin administration and subsequent hepatic protein kinase C translocation was assessed. Prolactin administration rapidly stimulated a 4-fold elevation of membrane protein kinase C activity. The effect of prolactin on hepatic protein kinase C was specific for lactogenic hormones but could be duplicated by phorbol esters. Further, an increase in serum prolactin was demonstrated subsequent to partial hepatectomy and preceding hepatic protein kinase C translocation. Therefore, translocation of hepatic protein kinase C appears important for hepatic proliferation in response to prolactin administration and to partial hepatectomy.

Animals↗
PubMed1987

Concanavalin A-stimulated murine splenocytes produce a factor with prolactin-like bioactivity and immunoreactivity.

Culture supernatants from concanavalin A activated murine splenic mononuclear cells (splenocytes) were assayed for prolactin-like molecules using the Nb2 node lymphoma bioassay and immunostaining procedures. Con A stimulated splenocytes produced a factor with prolactin-like immunoreactivity that was mitogenic for Nb2 lymphoma cells. This factor first appeared in culture supernatants with the onset of lymphocyte mitogenesis and its activity was proportional to the number of cells cultured. In addition, splenocyte proliferation was inhibited by antiserum to rat prolactin, and this inhibition was partially reversed by added hormone. These findings show that murine splenocytes produce a substance with prolactin-like activity and suggest that this factor is essential for lymphocyte proliferation.

Animals↗
PubMedDate not supplied

GLUT-1 expression in the cerebra of patients with Alzheimer's disease.

To investigate the molecular basis of reduced GLUT-1 concentration of the blood-brain barrier in patients with Alzheimer's disease (AD), the GLUT-1 mass, mRNA content, and structure were studied in eight patients with AD and seven age-matched controls. The results indicate that the 55-kDa GLUT-1 is significantly reduced in AD without a significant change in GLUT-1 mRNA concentrations. Because in some animal models changes in GLUT-1 expression is associated with changes in GLUT-1 mRNA structure, the length of the poly(A) tail of the GLUT-1 mRNA was estimated with a reverse transcription-polymerase chain reaction technique. The length of poly(A) tail of GLUT-1 mRNA in AD subjects was not significantly different from the controls. It is concluded that the AD-related change in GLUT-1 expression is not the result of altered poly(A) length of GLUT-1 mRNA.

Aged↗
PubMedDate not supplied

Age-related changes in the blood-brain barrier.

Aging of the cerebral microcirculation results in significant alteration in the blood-brain barrier (BBB). The barrier function appears to remain intact in older animals, although it may be more susceptible to disruption by external factors (hypertension) and drugs (haloperidol). While overall transport processes do not change with age, aging animals and humans have altered BBB function of select carrier mediated transport systems including the transport of choline, glucose, butyrate and triiodothyronine. These age-related changes are the result of either alteration in the carrier molecules or the physiochemical properties of the cerebral microvessels. At the present time, it is not known whether changes in the BBB contribute to the age-related neurodegenerative diseases or are merely epiphenomena of aging.

Aging↗