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Biomedical subjects

V A Patel

Publications and source records attributed to V A Patel.

12 recordsLinked to original sources
PubMed2001

Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling.

Apoptosis of vascular smooth muscle cells (VSMCs) is increased in atherosclerosis compared with normal vessels, where it may contribute to plaque rupture. We have previously found that human plaque-derived VSMCs (pVSMCs) are intrinsically sensitive to apoptosis and not responsive to the protective effects of insulin-like growth factor-1 (IGF-1). We therefore examined the mechanism underlying this defect. Human pVSMCs showed <25% (125)I-IGF-1 surface binding, <20% IGF-1 receptor (IGF-1R) expression than that of normal medial VSMCs, and <40% Akt kinase activity in response to IGF-1. pVSMCs expressed and secreted high levels of IGF-1 binding proteins (IGFBPs), and the IGF-1 analogues, long R3 and Des 1,3 IGF-1, which do not bind to IGFBPs, were able to increase pVSMC survival to normal medial VSMC levels. The long R3 survival effect was phosphatidylinositol 3-kinase-mediated, but it was not dependent on Akt activity alone. Intimal pVSMCs in vivo showed reduced IGF-1R expression compared with medial VSMCs, in particular at the shoulder regions of plaques. We conclude that human pVSMCs show an intrinsic sensitivity to apoptosis caused in part by defective expression of IGF-1R, impaired IGF-1-mediated survival signaling and increased IGFBP secretion. This impaired IGF-1 protection against apoptosis may promote VSMC loss and plaque instability in atherosclerosis.

Androstadienes↗
PubMed2000

Apoptosis during goitre involution - the role of Bcl-2.

Goitrogenesis is accompanied by hyperplasia and hypertrophy and involves tissue remodelling and angiogenesis. During the involution of the goitre there must be removal of this increased thyroid volume, in addition to further remodelling, which may involve apoptosis. We investigated apoptosis in the involuting rat thyroid using male Fisher rats that were on a goitrogenic regimen for 14 days and then returned to a normal diet. Thyroid weights increased fourfold with the goitrogenic regimen. During involution, the largest decrease in weight was between day 2 and day 4 after withdrawal of treatment. After 34 days of involution, the thyroid weight plateaued, but had not returned to control values. High levels of Bcl-2 immunoreactivity were observed in normal and goitrous rat thyroids. These high levels were significantly reduced at 2 days of involution, after which high levels of Bcl-2 immunoreactivity returned. In situ end-labelling of apoptotic cells showed that there was an increase in the number of cells undergoing DNA fragmentation during goitrogenesis (1.0+/-0.8 cells/100 cells, n=9) compared with controls, in which no positive staining was observed. After 2 days of goitrogen withdrawal, there was a further fourfold increase in the number of in situ end-labelled cells (day 16: 4.1+/-1.7, n=9). Numbers of positive cells returned to low levels after 4 days of involution (day 18: 0.3+/-0.8, n=9). Using antiserum to apoptosis-specific protein, we found increased immunoreactivity during goitrogenesis and after 2 days of involution that was localised predominantly with the stromal and vascular tissue at both time points. The data show that rapid downregulation of Bcl-2 accompanies thyroid involution, which involves increased levels of apoptosis within the stromal compartment.

Animals↗
PubMed1996

Changes in the immunohistochemical localisation of fibroblast growth factor-2, transforming growth factor-beta 1 and thrombospondin-1 are associated with early angiogenic events in the hyperplastic rat thyroid.

Administration of a goitrogen (methimazole) and a low iodine diet to rats over a two-week period resulted in hypothyroidism and thyroid hyperplasia compared with controls (control: total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight; experimental: T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment; mean +/- S.D., n = 10). Immunohistochemistry carried out using a specific endothelial cell marker, CD31, and morphometric analysis (point counting of immunopositive cells) revealed that the progression of goitre in the rat thyroid is accompanied by an increase in capillary endothelial cell growth (neovascularisation). Fibroblast growth factor-2 (FGF-2) immunohistochemistry revealed widespread staining for the protein in the follicular cells of control glands. Less intense staining was found in the stroma and follicular cell nuclei. During hyperplasia and subsequent neovascularisation there was a progressive increase in the FGF-2 immunoreactivity at all locations during the two-week treatment period. Thrombospondin-1 (TSP1) immunoreactivity in the control rat thyroid was found in the stroma and in the endothelial cells, while weak follicular cell staining was also present. In the goitrous rat thyroid the TSP immunoreactivity was present after 1 week of treatment in the endothelial cells and most follicular cells, whilst stroma localisation was weak. After week 2 of treatment the endothelial cell and stromal localisation was no longer apparent, although a follicular localisation was still present. Transforming growth factor-beta 1 (TGF beta 1) immunoreactivity was present in the cytoplasm of a minority of the follicular cells in control rat thyroids, while their nuclei were unstained. In the goitrous rat thyroid an increase intensity of staining for TGF beta 1 was seen in all follicular cells, many of which now also demonstrated immuno-positive nuclei, within one week of goitrogen administration. These results show that in the hyperplastic thyroid increases in FGF-2 and TGF beta 1, and decreases in TSP1 accompany angiogenesis. These factors may interact in an autocrine/paracrine relationship to stimulate the neovascularisation that occurs during goitre formation.

Animals↗
PubMed1989

Effects of ethanol on plasma corticosterone and rectal temperature modification by U50488H and WIN 44441-3.

Endogenous opiates are believed to subserve various behaviors and physiological functions. We have examined the effect of U50488H (0-12 mg/kg), a kappa agonist, and WIN 44441-3 (0-4.0 mg/kg), a kappa antagonist, on ethanol (ET)-induced changes in rectal temperature and in plasma corticosterone (CS) levels in rats. The 12 mg/kg dose of U50488H produced marked hypothermia, the other doses either produced hyperthermia comparable to that seen in control animals, or had no effect. The 0.5 mg/kg of WIN44441-3 had a small hypothermic effect while the 4.0 mg/kg produced hyperthermia. U50488H potentiated and the low dose of WIN 44441-3 reversed the hypothermic effect of ethanol. By contrast, neither WIN 44441-3 nor U50488H pretreatments affected the ethanol-induced elevation in plasma CS. These results indicate that kappa agonists increase plasma CS concentration and affect thermoregulatory mechanisms. Furthermore, our data indicate a possible role of endogenous kappa opioids in the hypothermic effect of ethanol, but not in the elevation of plasma CS.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Interaction of stress and ethanol: effect on beta-endorphin and catecholamines.

To examine the interaction of ethanol (ET) and stress on beta-endorphin and catecholamine (CA) levels, male rats pretreated with ET (3.0 g/kg, i.p.) or saline were immobilized for 30 min and killed 90 min after the initial injection. Stress resulted in (a) an increase in plasma levels of norepinephrine (NE, 243%), epinephrine (E, 175%), beta-endorphin (220%) and corticosterone (CS, 151%) and a decrease in dopamine (DA, 54%); (b) a decrease in hypothalamic NE (15%) and beta-endorphin (33%) levels and an increase E (23%) and DA (58%) levels; (c) a decrease in pituitary beta-endorphin levels in both the neurointermediate (23%) and anterior (131%) lobes. Treatment with ET resulted in: (a) an increase in plasma NE (81%), E (53%), CS (71%), and beta-endorphin (33%) levels and decrease in DA (54%); (b) a decrease in the hypothalamic NE (12%) levels and an increase DA (27%) and beta-endorphin (46%) levels, and (c) a decrease in beta-endorphin (15.5%) in the intermediate lobe of the pituitary. Treatment with ET of stressed animals had only a small effect: (a) in plasma NE, E, CS, and beta-endorphin levels decreased by 30, 31, 14, and 36%, respectively; (b) in the hypothalamus DA levels decreased by 40% and beta-endorphin increased by 71%; (c) in the pituitary beta-endorphin increased in both the intermediate lobe (25%) and anterior (50%) lobes. Thus when the data of the stressed ET-treated group is compared to that of the nonstressed saline injected group, none of the measures differ significantly. These results confirm our earlier work indicating a significant interaction of ET and stress.

Animals↗
PubMed1983

Linkage analysis in von Willebrand disease.

We studied a 3-generation kindred to determine whether the gene responsible for one form of von Willebrand disease (vWD) is linked to 1) the HLA locus, or 2) a polymorphic locus for a serum enzyme or red cell antigen. HLA haplotypes were determined in 12 affected family members, in 10 cases by direct analysis and in 2 cases by deduction. Seven of 12 affected individuals were A2, B7, as compared to 0 of 9 unaffected. However, the maximum lod score was only 0.41 at a recombination frequency of 0.2. Of the 17 serum red cell and plasma protein markers studied, 5 (Kell, ADA, AK1, BF, GC) did not segregate, and 12 (ABO, Rh, JK, Fy, P, PGM1, ACP1, ESD, GLO1, MN, HP, GPT) gave lod scores less than + 1.0. We conclude that there is no strong evidence for linkage between the locus for vWD and any of the markers studied.

Blood Proteins↗
PubMed1982

Hypermodal cells in amniotic fluid cultures: frequency, interpretation, and clinical significance.

Specimens of amniotic fluid were studied to assess the frequency of hypermodal cells and their significance. Multiple cultures were initiated on each specimen, and thorough cytogenetic analysis was performed routinely. Of 1,000 specimens, 59 (5.9%) contained a total of 64 hypermodal cells. However, true fetal mosaicism was not detected. An additional structurally abnormal chromosome accounted for 32 of the 64 hypermodal cells, and, in each case, cytogenetic analysis offered an explanation that obviated clinical concern. In 17 of the 32 cases, hypermodality was only apparent, the result of a single chromosome broken into two parts to produce a spuriously elevated count; in the other 15 cases, the extra chromosome was an unidentified fragment. In the 32 other hypermodal cells, an additional morphologically normal chromosome was present; however, in each case, failure to detect similar aberrations in other cultures initiated from the same specimen minimized the possibility that such cells reflected true fetal mosaicism. Indeed, clinical outcome was normal in all cases. Thus, for clinical purposes, routine banding techniques and analysis of multiple cultures seem to be adequate to exclude fetal mosaicism; laborious in situ methodology seems to be unnecessary. Future cytogenetic efforts should emphasize processing of more specimens of amniotic fluid, rather than more detailed analysis of individual specimens.

Amniocentesis↗
PubMed1979

Localization of the nucleolar organizer by computer-aided analysis of a variant no. 21 in a human isolate.

A variant chromosome no. 21 consisting of two stalks and two satellites in tandem was detected during a survey of a human isolate. The variant segregated in three generations of a large kindred. One male had the variant no. 21, a metacentric Y, and a 47,XXY complement; however, no other evidence of chromosomal nondisjunction was found. Computer-aided analysis of sequentially stained variant no. 21 chromosomes indicated that silver-stained material corresponded to the proximal stalk region (as defined by Giemsa), but often covered both the distal stalk and satellite (also as defined by Giemsa). These data support the hypothesis that human nucleolar organizers are localized to the stalks of acrocentric chromosomes.

Azure Stains↗
PubMed1979

Analysis for amniotic fluid crystallization in second-trimester amniocentesis.

A potential complication of second-trimester amniocentesis for genetic indications is inadvertent needle insertion into the maternal bladder, resulting in aspiration of urine rather than amniotic fluid. Amniotic fluid forms a characteristic crystalline arborization pattern when allowed to air dry. We utilized this property of amniotic fluid to distinguish amniotic fluid from maternal urine. In 24 of 25 cases studied in a randomized blind fashion the crystalline arborization test correctly identified amniotic fluid, whereas none of the 25 urine samples showed this pattern. Our study indicates that the crystalline arborization test is reliable in distinguishing amniotic fluid from maternal urine during the second trimester of pregnancy.

Amniocentesis↗
PubMedDate not supplied

Acute and chronic ethanol treatment on beta-endorphin and catecholamine levels.

The effect of acute (2.0 g/kg, intragastrically) and chronic (8.0-11.0 g/kg/day for 10 days, intragastrically) ethanol exposure on beta-endorphin levels in plasma, hypothalamus and pituitary were examined in rats. Hypothalamic and plasma catecholamines and plasma corticosterone were also measured in these animals. Plasma beta-endorphin, norepinephrine (NE) and corticosterone levels were significantly increased and dopamine (DA) was unchanged in acute and chronic ethanol-treated rats. Compared to controls, plasma epinephrine (E) levels were increased in acute ethanol-treated rats but no significant change was observed in chronic ethanol-treated rats. Plasma dopamine were significantly decreased following chronic ethanol treatment while no significant change was observed after acute treatment. In the hypothalamus, beta-endorphin and dopamine contents were increased and norepinephrine levels were reduced in response to ethanol exposure. Beta-endorphin levels were decreased significantly in the anterior pituitary and the neurointermediate lobe of the pituitary in ethanol-treated animals except in the neurointermediate lobe of the chronic ethanol-treated animals. These findings together suggest that there is an interaction between beta-endorphin, catecholamines, corticosterone and ethanol in response to acute and chronic ethanol exposure in rats.

Animals↗