Search PubMed⌕ Search

Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 361 records · Page 20Linked to original sources
PubMed1995

Changes in the concentration of endothelin-1 during development of hypertensive rats.

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 +/- 43 pg/g tissue) rats was lower than that of WKY (452 +/- 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 +/- 33 pg/g tissue) rats were higher compared to WKY (439 +/- 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 +/- 33 pg/g tissue) compared to WKY rats (260 +/- 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY rats.

Animals↗
PubMed1995

Polyarteritis nodosa presenting as perirenal hemorrhage.

Though renal involvement with microaneurysm formation is common in polyarteritis nodosa (PAN), spontaneous perirenal hematoma (SPH) is rare. We report a patient in whom SPH was the presenting manifestation of PAN. SPH is a potential life-threatening complication of PAN and its early recognition is emphasized.

Adult↗
PubMed1995

Long-term high osmolality activates Na(+)-H+ exchange and protein kinase C in aortic smooth muscle cells.

The effect of long-term exposure to hypertonic medium on Na(+)-H+ exchange activity was studied in cultured vascular smooth muscle (VSM) cells by using a combination of 22Na+ influx and pH measurement with the pH-sensitive dye BCECF. Incubation of VSM cells in high-osmolality medium (510 mOsm/L) for 48 hours significantly increased the acid-stimulated 22Na+ influx (control, 3.16 +/- 0.41 nmol/mg protein per minute; high osmolality, 6.40 +/- 0.66 nmol/mg protein per minute; P < .01) and Na(+)-dependent pHi recovery (control, 0.29 +/- 0.06 pH/min; high osmolality, 0.65 +/- 0.13 pH/min; P < .03). Activation of Na(+)-H+ exchange was osmolality dependent and reached maximal stimulation at approximately 700 mOsm/L. Na(+)-H+ exchanger stimulation was independent of serum in the culture media. Na(+)-H+ exchanger isoform (NHE-1) mRNA in VSM cells cultured in high-osmolality medium was unchanged from that in VSM cells cultured in control medium, indicating an absence of transcriptional regulation by high osmolality. Long-term high osmolality significantly increased protein kinase C (PKC) activity in cultured VSM cells, as assessed by phosphorylation of a PKC-specific substrate (control, 20.9 +/- 2.1 pmol phosphorylation/mg protein per minute; high osmolality, 33.6 +/- 2.9 pmol phosphorylation/mg protein per minute; P < .01). Downregulation of PKC by preincubation of VSM cells with 0.1 mumol/L phorbol 12-myristate 13-acetate (PMA) prevented osmolality-induced stimulation of the Na(+)-H+ exchanger (control plus PMA, 0.27 +/- 0.05 pH/min; high osmolality plus PMA, 0.33 +/- 0.08 pH/min; P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hepatocyte growth factor stimulates DNA synthesis in alveolar epithelial type II cells in vitro.

Hepatocyte growth factor (HGF) and its receptor, the product of c-MET proto-oncogene, are highly expressed in both fetal and adult lung, though their physiologic functions in the lung are largely unknown. In the present study, we examined whether alveolar type II cells in the lung are the target of HGF and whether HGF has any effects on growth of these cells. The alveolar epithelial type II cells were isolated from the lungs of adult male Sprague-Dawley rats by elastase digestion, and the cells were used to determine whether they express HGF and c-MET mRNAs and whether recombinant HGF has any effect on their DNA synthesis in primary culture. The effects were further compared with those induced by epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta 1 (TGF-beta 1). Northern blot analysis and in situ hybridization revealed that type II cells express c-MET mRNA but not HGF mRNA. HGF stimulated [3H]thymidine incorporation into type II cells in primary cultures. An increase was also seen in labeling index as determined by nuclear immunostaining of bromodeoxyuridine-incorporated DNA. While aFGF (200 ng/ml) exerted an effect comparable to HGF (25 ng/ml) on DNA synthesis in type II cells, EGF (20 ng/ml) and TGF-alpha (100 ng/ml) had lesser effects. TGF-beta 1, a potent inhibitor of epithelial cell proliferation, at 0.25 to 2 ng/ml, did not inhibit HGF-induced [3H]thymidine incorporation into type II cells. The results indicate that HGF exerts its effects on type II cells as a potent mitogen by a paracrine mode of action.

Animals↗
PubMed1995

Comparative evaluation of anti-heat shock protein antibodies in SLE and healthy controls.

Presence of anti-heat shock protein (anti-hsp) antibodies have earlier been demonstrated in children as well as adult patients with systemic lupus erythmatosus (SLE). Since hsp share homology across several species, it is presumed that anti-E. coli antibodies could in fact be autoantibodies. Surface expression of hsps has also been shown to play a role in the generation of antibodies. In the present study antibodies to a recombinant hsp70 of Leishmania dnonvani origin have been investigated in patients with SLE and data compared with the incidence in control sera. One clone from the cDNA library of Leishmania donovani confirmed previously to be expressing hsp70, cloned in pBluescript and antibodies to the expressed protein were checked by ELISA and western blot assays. The results indicate the presence of anti-hsp70 antibodies in 22/26 (85%) SLE patients and 12/20 (60%) control sera. Our observations reconfirm the presence of antibodies to hsp in normal controls and therefore they may not bear any direct relation to the pathogenesis of SLE.

Adult↗
PubMed1995

Epithelial lung cell marker: current tools for cell typing.

This review discusses current immunohistochemical and lectin histochemical approaches to identify and to distinguish the different epithelial cell populations of the pulmonary tissue. Special emphasis is given to the characterization of pulmonary alveolar and bronchial epithelial cells and mesothelial cells. Structural proteins, membrane molecules and secretory products of the alveolar epithelium, which have already been characterized and which may be useful for monitoring the developmental or pathological processes, are listed and briefly described.

Animals↗
PubMed1995

Expression of a 130-kDa mesothelial and ciliated cell Ag (MCp130) in normal and developing human and rat lung and its role as a diagnostic marker for mesotheliomas and tumors of the female reproductive system.

BACKGROUND: Proteins in human lung lavage were analyzed to identify cell-specific markers for potential use in the study of the biology and pathology of pulmonary cells. EXPERIMENTAL DESIGN: Proteins associated with pulmonary surfactant were used to raise mAb. An Ab to a 130-kDa protein (MCp130) was reactive with ciliated and mesothelial cells. Expression of this Ag in normal organs, developing lung, and tumors was investigated. RESULTS: By Western blotting, the Ab stained a protein of about 130 kDa. In formalin-fixed, paraffin-embedded tissues from adult human and rat organs, the Ab specifically stained the luminal/apical surfaces of pulmonary and nonpulmonary ciliated and mesothelial cells. Staining of fetal airway cells was independent of ciliation. Airway cell staining was detectable in human fetal lungs at 12 weeks of gestation and at Day 18 of gestation in fetal rat. The Ab reacted with human and rat fetal mesothelial cells at the gestational ages of 15 weeks and 17 days, respectively. It also stained ciliated cells in endosalpinx and endometrium. Human epithelial mesotheliomas and ovarian and endometrial carcinomas stained selectively, whereas other pulmonary tumors and tumors of other organs did not react with the Ab. CONCLUSIONS: This 130-kDa mesothelial and ciliated cell plasma membrane protein appears in developing lung at an earlier age than secretory proteins. The marker is of potential use in the study of development of the different cell lineages in the lung and female reproductive tract. The Ab is expected to be useful in the diagnosis of epithelial mesotheliomas and ovarian/endometrial carcinomas, because it selectively stains these tumors and is reactive with formalin-fixed, paraffin-embedded tissues.

Adult↗
PubMed1995

Tumor-bone interactions in skeletal metastasis.

Bone metastases are a frequent clinical problem in patients with breast, prostate, and other cancers. Formation of these lesions is a site-specific process determined by multiple cellular and molecular interactions between the cancer cells and the bone microenvironment. Clinical studies, and in vivo and in vitro experimental approaches, have been useful to dissect different stages of this process. Mechanisms identified as relevant to cancer spreading and tumoral growth in the bones include (a) early vascular spread of cancer cells to bones; (b) adhesion of cancer cells to the bone microvasculature and matrix components; (c) presence of growth factors and chemo-attractants in bone; (d) osteolysis by osteoclasts, tumor associated macrophages, and cancer cells; and (e) tumor-induced local osteoblastic proliferation. Although none of these mechanisms alone are responsible for the development of bone metastases, their investigation may lead to novel therapeutic approaches that specifically block these stages and, thus, may hinder development of bone metastasis. The use of bisphosphonates and other experimental strategies already is being tested in clinical trials.

Animals↗
PubMed1995

Effect of intraperitoneal zinc on the haematological profiles of C57/6J mice.

Zinc is included in a number of medications and haematotoxic effects due to zinc excess have been reported. In this study, the haematological profiles (haematocrit, haemoglobin, total white blood cell count, differential white blood cell count and platelets) of mice treated with zinc were evaluated. Intraperitoneal zinc chloride was administered to C57/6J mice in varying dosages from 1.4-14 micrograms/g body weight, four times a week for a period of three weeks. Zinc chloride had no effect on the haematological profiles of these mice since the blood cell counts of treated mice were not significantly different from the controls (p < 0.05), with the exception that at half LD50 of zinc chloride (14 micrograms/g body weight) a reactive thrombocytosis resulted. (The platelet counts between the control and experimental group of mice were significantly different, exceeding 95% confidence limits; p = 0.016). We postulate that the specific effect on platelets was due to zinc being a potent inhibitor of phenol sulfotransferase (PST), an enzyme which is involved in many metabolic pathways. Platelets are a rich source of PST and the thrombocytosis observed was probably a compensatory mechanism to raise the levels of PST in the body.

Animals↗
PubMed1995

Dexamethasone and phosphoramidon inhibit endothelin release by cultured nonciliated bronchiolar epithelial (Clara) cells.

The release of immunoreactive endothelin (ir-ET) by cultured Clara cells isolated from guinea pig lung was investigated. Clara cells were cultured in DMEM-F12 with 10% fetal bovine serum for 4-5 days. The basal release of ir-ET, measured by radioimmunoassay, from cultured guinea pig Clara cells incubated for 2, 6, and 10 h was 59.6 +/- 8.6, 206.0 +/- 25.0, and 291.0 +/- 16.5 pg/ml, respectively. Treatment with phosphoramidon (1 mM) for 45 min decreased the release of ir-ET by 73% and 76% in 6- and 10-h incubation periods, respectively. In addition, treatment with dexamethasone (1 microM) for 24 h significantly attenuated the release of ir-ET by 62% and 71% during 6- and 10-h incubation periods, respectively. Our results show that Clara cells isolated from guinea pig can synthesize significant amounts of ir-ET and that a phosphoramidon-sensitive metalloprotease appears to be responsible for the generation of endothelin. This basal release of ir-ET was significantly attenuated by dexamethasone.

Animals↗
PubMed1995

Multifocal micronodular pneumocyte hyperplasia: a distinctive pulmonary manifestation of tuberous sclerosis.

We report a peculiar multifocal micronodular proliferation of pneumocytes occurring in a 24-yr-old woman with tuberous sclerosis and lymphangioleiomyomatosis. A computed tomographic scan of the chest demonstrated multiple minute nodules present throughout both lung fields. Histologically, the nodules were well demarcated, measured up to 1.6 mm in diameter, and were composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II pneumocytes. Positive immunohistochemical stains for keratin, BER-EP4, and surfactant, and negative immunohistochemical staining with an antibody recognizing Clara cells support an epithelial origin from type II pneumocytes. The absence of immunohistochemical staining for HMB45 suggests a histogenesis separate than the lesions of lymphangioleiomyomatosis. We failed to detect estrogen or progesterone receptors in either the lesions of lymphangioleiomyomatosis or the micronodular proliferations. Recognition of these unique lesions facilitates their distinction from other epithelial proliferations, particularly atypical bronchioloalveolar cell hyperplasia. This lesion appears to be a distinctive manifestation of tuberous sclerosis. It is probably hamartomatous.

Adult↗
PubMed1994

Na+/H+ exchanger isoforms NHE-2 and NHE-1 in inner medullary collecting duct cells. Expression, functional localization, and differential regulation.

Recent cloning experiments have identified the existance of four distinct Na+/H+ exchanger isoforms designated as NHE-1, NHE-2, NHE-3, and NHE-4. The cellular distribution, subcellular localization, and regulation of one of these isoforms, NHE-2, in the kidney remains unknown. Northern hybridization showed that NHE-2, along with NHE-1, is expressed in cultured renal medullary collecting duct (mIMCD-3) cells. Acid-stimulated, dimethyl amiloride-sensitive 22Na+ uptake and sodium-dependent pHi recovery occurred only from the basolateral surface of the cells, indicating localization of Na+/H+ exchanger to the basolateral membrane domain. Incubation of IMCD cells in high osmolality media (510 mosm/liter) for 72 h stimulated the Na+/H+ exchanger activity by 59% (p < 0.001). NHE-1 mRNA abundance decreased, whereas NHE-2 mRNA increased in high osmolality media. Incubation of IMCD cells in acid media (pH 7.1) for 48 h did not affect the Na+/H+ exchanger activity compared with control (pH 7.4) (p > 0.05). Northern hybridization, however, indicated that NHE-1 mRNA increased, whereas NHE-2 mRNA decreased in acid media. In conclusion, mIMCD-3 cells express NHE-1 and NHE-2 mRNAs. The cell functional studies in mIMCD-3 cells strongly suggest that NHE-2, along with NHE-1, is expressed in the basolateral membrane domain. They further demonstrate differential regulation of NHE-1 and NHE-2 mRNAs in response to acidosis and high osmolality and suggest that NHE-2 may be involved in volume regulation of IMCD cells.

Animals↗
PubMed1994

Running and the development of disability with age.

OBJECTIVE: To determine, by longitudinal study, whether regular vigorous running activity is associated with accelerated, unchanged, or postponed development of disability with increasing age. STUDY DESIGN: 8-year prospective, longitudinal study with yearly assessments. PARTICIPANTS: 451 members of a runners' club and 330 community controls who were initially 50 to 72 years old (also characterized as "ever-runners" [n = 534] and "never-runners" [n = 247], respectively). MEASUREMENTS: The dependent variable was disability as assessed by the Health Assessment Questionnaire and separately validated in these participant cohorts. Covariates included age, sex, body mass index, comorbid conditions, education level, smoking history, alcohol intake, mean blood pressure, initial disability level, family history of arthritis, and radiologic evidence of osteoarthritis of the knee in a subsample. RESULTS: Initially, the runners were leaner, reported joint symptoms less frequently, took fewer medications, had fewer medical problems, and had fewer instances of and less severe disability, suggesting either that the average previous 12 years of running had improved health or that self-selection bias was present. After 8 years of longitudinal study, the differences in initial disability levels (0.026 compared with 0.079; P < 0.001) had steadily increased to 0.071 for runners compared with 0.242 for controls (P < 0.001). The difference was consistent for men and women. The rate of development of disability was several times lower in the runners' club members than in community controls; this difference persisted after adjusting for age, sex, body mass, baseline disability, smoking history, history of arthritis, or other comorbid conditions (slopes of progression of disability for the years 1984 to 1992, after adjusting for covariates: men in the runners' club, 0.004 [SE, 0.002]; community controls, 0.012 [SE, 0.002]; women in the runners' club, 0.009 [SE, 0.005]; community controls, 0.027 [SE, 0.004]; P < 0.002 for both sets of comparisons). In addition to differences in disability, there were significant differences in mortality between the runners' club members (1.49%) and community controls (7.09%) (P < 0.001). These differences remained significant after adjusting for age, sex, body mass, comorbid conditions, education level, smoking history, alcohol intake, and mean blood pressure (P < 0.002, conditional risk ratio for community controls compared with the runners, 4.27; 95% CI, 1.78 to 10.26). CONCLUSIONS: Older persons who engage in vigorous running and other aerobic activities have lower mortality and slower development of disability than do members of the general population. This association is probably related to increased aerobic activity, strength, fitness, and increased organ reserve rather than to an effect of postponed osteoarthritis development.

Aging↗
PubMed1994

Use of 125I-[Y39]exendin-4 to characterize exendin receptors on dispersed pancreatic acini and gastric chief cells from guinea pig.

We synthesized and iodinated an exendin-4 analogue, [Y39]exendin-4 (700 Ci/mmol), for use as a radioligand to characterize exendin receptors on dispersed pancreatic acini and gastric chief cells from guinea pig. Binding of this bioactive radioligand was rapid, temperature-dependent and specific (not inhibited by other pancreatic or gastric secretagogues). Measurement of the ability of exendin-4 to inhibit the binding of 125I-[Y39]exendin-4 indicated the presence of two classes of receptors. Pancreatic acini had 12.5.10(10) binding sites/mg acinar protein of which 6% were high affinity (Kd = 0.5 nM) and 94% were low affinity (Kd = 0.1 microM). Chief cells had 3370 binding sites/cell of which 9% were high affinity (Kd = 0.3 nM) and 91% were low affinity (Kd = 0.2 microM). Washing with 0.2 M acetic acid (pH 2.5), 0.2 M glycine (pH 10.5), or trypsin (100 micrograms/ml) after 30 min incubation at 37 degrees C, indicated that 63 and 49% of radioligand was internalized in acini and chief cells, respectively. Truncated glucagon-like peptide-1 (tGLP-1), a mammalian peptide sharing 53% homology with exendin-4, inhibited radioligand binding at the same concentrations that altered secretion from acini and chief cells. Glucagon, GLP-1 and GLP-2 inhibited 125I-[Y39]exendin-4 binding only at concentrations > or = 100 nM. Exendin(9-39)NH2, a specific exendin-receptor antagonist, potently inhibited 125I-[Y39] exendin-4 binding (IC50 = 6.1 and 3.5 nM in acini and chief cells, respectively). In pancreatic acini and gastric chief cells from guinea pig, exendin-3, exendin-4 and tGLP-1 increase cellular cAMP and modulate enzyme secretion by interacting with high-affinity exendin receptors. 125I-[Y39] exendin-4 is a useful radioligand for studying exendin receptors.

Amino Acid Sequence↗
PubMed1994

Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival.

We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.

Amino Acid Sequence↗