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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 325 records · Page 18Linked to original sources
PubMed1996

Is seminal prostatic acid phosphatase a reliable marker for male infertility?

This project was undertaken to determine whether there is any correlation between sperm counts and motility and the level of prostatic acid phosphatase (PAcP). Fifty-six patients were studied in this series-those with normospermia (Group A,n = 19); mild oligospermia (Group B,n = 18) and very severe oligospermia (Group C,n = 19). Each group was further subdivided into 2 groups-those who were 25-35 years old and those 36 years old and above. The results in this age group are discussed and it was found that individuals with very severe oligospermia (sperm counts 1-20x10(5)/mL) showed a positive correlation (p = 0.009) in the age group 36 years and above. The results have to be treated with caution since a statistically significant result was only displayed in one group, ie, individuals over the age of 35 years and very low sperm counts.

Acid Phosphatase↗
PubMed1995

Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints.

Agents that disrupt mitochondrial function were used to monitor the contribution of ATP to cell cycle progression. Following nontoxic exposure to these agents, flow cytometric analysis of the cell population showed a significant increase in the proportion of cells in G1 at low doses of the agent and in G2-M at higher doses, in accordance with the degree of ATP reduction induced by the compound. These data indicate that cycling cells must maintain a minimal ATP content to satisfy the energy requirement of the checkpoint that allows passage through G1 into S phase. Once committed, successful passage through G2 into mitosis is also conditional upon maintenance of a critical ATP content sufficient to satisfy the second energy-sensitive checkpoint that exists at this transition. These data establish a foundation for future investigations into the energy dependence of cell cycle events and propose novel means for cell cycle intervention.

Adenosine Triphosphate↗
PubMed1995

Detection of the lipid peroxidation product malonaldehyde in rat brain in vivo.

The extracellular concentrations of the lipid peroxidation product malonaldehyde (MDA) and the antioxidants ascorbic and uric acid were measured in rat brain in vivo using microdialysis coupled to HPLC with ultra violet spectrophotometry. Treatment with kainic acid at pH 4.1 (50 nmol) caused a significant increase in the sampled concentration of MDA but no significant changes in the antioxidants. Treatment with the same dose of kainic acid at pH 7.2 did not cause a significant increase in MDA, although some changes were noted in the antioxidants. The paper demonstrates the ability to monitor changes of a lipid peroxidation breakdown product as a measure of oxidative stress in vivo. Furthermore, the data suggests that the toxic action of kainic acid in acute preparations may be due to the elevation of hydrogen ions.

Animals↗
PubMed1995

The effect of lethal acid stress on Na+/H+ exchanger isoforms in cultured inner medullary collecting duct cells: deletion of NHE-2 and over expression of NHE-1.

Cultured inner medullary collecting duct (mIMCD-3) cells express Na+/H+ exchanger isoforms NHE-2 and NHE-1 (Soleimani et al. (1994) J. Biol. Chem. 269, 27973-27978). In the present studies we examined the effect of lethal acid stress on Na+/H+ exchanger activity and isoform expression in mIMCD-3 cells. mIMCD-3 cells were incubated for 10 min with 20 mM ammonium, and exposed to an ammonium-free acidic solution (pH 6.0) for 120 min. Thereafter, cells were recovered and grown in normal culture media. The surviving clones were isolated and subjected to two additional cycles of acid stress. A mutant clone was isolated and characterized for Na+/H+ exchange activity and isoform expression. The mutant mIMCD-3 clone demonstrated significant over-expression of Na+/H+ exchange activity as assessed by acid-stimulated 22Na influx (11.56 nmol/mg protein in mutant vs. 4.06 nmol/mg in parent cells, P < 0.001, n = 4) and sodium-dependent pHi recovery from an acid load (0.55 pH/min in mutant vs. 0.28 pH/min in parent cells, P < 0.01, n = 6). A dose-response inhibition of the exchanger showed that the mutant cells were very sensitive to dimethylamiloride (IC50 158 nM in mutant vs. 889 nM in parent mIMCD-3 cells, P < 0.001). To compare the Na+/H+ exchanger isoforms in mutant and parent mIMCD-3 cells, poly(A)+ RNA was isolated from each group and probed with radiolabeled NHE-1 or NHE-2 cDNA. The expression of NHE-1 mRNA was increased by approximately 100% in mutant cells. The NHE-2 mRNA, on the other hand, was found to be absent in mutant mIMCD-3 cells. Examination of the regulatory mechanisms of the Na+/H+ exchanger isoforms in parent mIMCD-3 cells, which express NHE-2 and NHE-1, and mutant mIMCD-3 cells, which only express NHE-1, would be helpful in elucidating the roles of NHE-2 and NHE-1 in inner medullary collecting duct cells.

Amiloride↗
PubMed1995

Endothelin-1 stimulates proliferation of normal airway epithelial cells.

To investigate the influence of endothelins on airway epithelial cell growth, we measured [3H]thymidine incorporation and cell numbers of cultured porcine tracheal epithelial cells in the presence or absence of endothelin-1 or -3 with or without PD-145065 (a combined endothelin-A and -B receptor antagonist), BQ-123 (an antagonist specific for endothelin-A receptors) or phosphoramidon (an inhibitor, in part, of endothelin converting enzymes). We found that endothelin-1 stimulated the proliferation of airway epithelial cells and this response was progressively inhibited by increasing concentrations of either PD-145065 or BQ-123. In contrast to endothelin-1, airway epithelial cells were not responsive to endothelin-3. They also appeared to be producing endothelin-1 endogenously. Phosphoramidon significantly decreased basal growth of cells incubated in the absence of exogenous endothelin, and was associated with a significant diminution in their endothelin production. We conclude that endothelin-1 is mitogenic for porcine airway epithelial cells and may be involved in both autocrine and paracrine control of them.

Amino Acid Sequence↗
PubMed1995

Self tolerance to T cell receptor V beta sequences.

T cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V beta 8.1 and V beta 8.2 TCR proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V beta protein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks.

Amino Acid Sequence↗
PubMed1995

Effect of diaspirin crosslinked and stroma-reduced hemoglobin on mean arterial pressure and endothelin-1 concentration in rats.

The effect of unmodified stroma reduced (SRHb) and modified diaspirin crosslinked (DCLHb) hemoglobin solutions on the mean arterial pressure and endothelin-1 (ET-1) concentration in blood plasma and various tissues was studied. Infusion of DCLHb or SRHb increased mean arterial blood pressure by 96% and 39%, respectively. Heart rate was not significantly affected by DCLHb or SRHb. A significant increase (P < 0.003) in the ET-1 levels in blood plasma after DCLHb and SRHb infusion was observed. The increase in plasma ET-1 concentration was significantly more marked with SRHb (141%) as compared to DCLHb (78%) treated rats. The concentration of ET-1 in the heart and brain regions was not altered in DCLHb or SRHb treated rats as compared to control. However, ET-1 concentration was significantly increased in the thoracic aorta (151%) and renal medulla (272%) of DCLHb treated rats. SRHb treated rats also showed a significant increase in ET-1 concentration in the thoracic aorta (141%) and renal medulla (429%). The effect of SRHb on the renal medulla was found to be significantly greater than that of DCLHb. ET may be one of the factors responsible for the cardiovascular effects of hemoglobin solutions.

Animals↗
PubMed1995

Crystallization and preliminary analysis of two crystal forms of human clara cell 16 kDa protein (CC10).

The human Clara cell 16 kDa protein (CC10), isolated from lung lavage fluid, has been crystallized in two crystal forms. The first is in space group P1 and has cell parameters a = 43.04, b = 45.90, c = 51.29 A and alpha = 62.46, beta = 69.74, gamma = 69.43 degrees. Two molecules are present in the unit cell. The second form is in space group P222, with cell parameters a = 42.24, b = 84.06, c = 40.05 A and alpha = beta = gamma = 90 degrees, and four molecules per unit cell. Its diffraction pattern displays pseudo-body-centered symmetry. Both crystal forms diffract X-rays beyond 2.0 A.

Journal Article↗
PubMed1995

Gsh-1: a novel murine homeobox gene expressed in the central nervous system.

We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in size present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-1 homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/CA/CATTAG/A.

Amino Acid Sequence↗
PubMed1995

Enterocystoplasty in the neuropathic bladder.

Patients with neuropathic bladders who have intractable hyperreflexia often require cystoplasty and in patients adequately motivated and counselled, continence rates in excess of 90% can be achieved. Seventy-eight patients with neurological disease have undergone enterocystoplasty and are presented. Twenty-two patients had acquired cord lesions of which 17 were traumatic. Of the 56 patients with congenital myelodysplasia, 49 were meningomyelocele, 5 had sacral agenesis, and 2 lipoma of cauda equina. The mean age was 26 (range 13-61) years with 48 male and 30 females. Pre-operative video urodynamics showed sphincter weakness in 54 patients, all patients had intermediate type bladders; hyperreflexia in 52, reduced compliance in 17, and in 7 a combination of both. Forty-seven patients had ileal, 20 had sigmoid, and 11 had ileocaecal cystoplasty. Fifty-two patients had an artificial urinary sphincter inserted, 9 had a colposuspension, and 1 had both for concurrent sphincter weakness incontinence. Acceptable continence has been achieved in 73 (93.6%) patients, 65 claiming complete continence with no pads or incontinence episodes and the 8 others needing pharmacotherapy or pads. Two of our 5 failures have been converted to an ileal loop, 2 are awaiting further surgery, and 1 is wet despite normal urodynamics. Our threshold for initiating intermittent catheterisation is low and 63 (81%) of our patients catheterise. Complications in these patients are few and the only one of note is persistent bowel problems in 30% of our patients. Cystoplasty is recommended as safe and reliable in the treatment of neurogenic detrusor over activity with a continence rate of 93% being achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Intravesical oxybutynin in patients with posterior rhizotomies and sacral anterior root stimulators.

This report investigates the use of intravesical oxybutynin in spinal injury patients, who have had dorsal rhizotomies to abolish reflex detrusor activity and void with S2, S3, and S4 stimulation, done with the Brindley anterior root stimulator. Six male patients (age range 27 to 56, mean 36 years) who have had Brindley anterior root stimulators implanted were included in this study. Video urodynamic assessment was done and 10 mg of oxybutynin hydrochloride was instilled through the urethral catheter. This was left in the bladder for 60 minutes and video urodynamics were repeated. Voiding, both pre and post oxybutynin, was achieved with sacral root stimulation. Peak detrusor pressure (Pves) during voiding in the 6 patients before oxybutynin instillation was 89, 154, 90, 60, 56, and 80 (mean 88.2) cm of water. Post oxybutynin the pressures were 83, 163, 95, 40, 30, and 68 (mean 79.8) cm of water. The peak flow rate (Qmax) pre oxybutynin was 32, 24, 20, 20, 12, and 28 (mean 22.7) ml per second and this changed to 28, 31, 18, 24, 10, and 32 (mean 23.8) ml per second. This shows no difference in the detrusor pressure (P = 0.2) and flow rate (P = 0.54) pre and post oxybutynin instillation into the bladder. Effectiveness of oxybutynin is attributed to a combination of M3 receptor antagonism in the smooth muscle and direct spasmolytic, local anaesthetic and calcium channel blocking action. Its therapeutic benefit is limited by the anti cholinergic side effects (40-80%) and recent studies have shown the intravesical route to be effective and better tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1995

Evidence for the presence of a non-catecholamine, clonidine-displacing substance in crude, methanolic extracts of bovine brain and lung.

In the present study we have prepared crude, methanolic extracts of bovine lung and bovine brain and, using radioligand binding assays in conjunction with a number of simple chromatographic techniques, provided evidence for the presence of a non-catecholamine 'clonidine-displacing substance' (CDS). The level of CDS in lung extracts (9 units/g wet weight n = 11) is approximately 3 times that in the brain extracts. Furthermore, the effect of the crude, methanolic extracts are selective for non-adrenoceptor, imidazoline (labelled by [3H]-idazoxan) and alpha 2-adrenoceptor binding sites (labelled by [3H]-clonidine); both extracts are 5-10-fold more potent displacers of ligand binding to alpha 2-adrenoceptors compared with binding to opiate receptors (labelled by [3H]-etorphine) and practically inactive against alpha 1-adrenoceptor and muscarinic binding sites (labelled by [3H]-prazosin and [3H]-quinuclidinyl benzilate, respectively). With the exception of the non-adrenoceptor, imidazoline binding assay, which used rat kidney membranes labelled by [3H]-idazoxan in the presence of the alpha 2-adrenoceptor antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex membranes. Although the extracts contain catecholamines (brain only), histamine (lung only) and monovalent cations (both), which have the potential to interfere with the radioligand binding assays, their concentrations were too low to account for the effects observed. Preliminary attempts at purification of the extracts revealed that CDS activities from the two tissues are similar, i.e., practically insoluble in organic solvents at room temperature, not affected by either Sep-Pak C18 column or anion exchange resins but retained (along with the monovalent cations) by cation exchange resin. However, following chromatographic separation on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit qualitatively similar elution profiles. Future experiments will involve further purification of 'clonidine-displacing substance' to characterize its interaction with alpha 2-adrenoceptor binding sites in greater detail and establish whether it has biological activity consistent with the properties implied by its effects in radioligand binding assays.

Animals↗
PubMed1995

Differential regulation of Na+/H+ exchange and H(+)-ATPase by pH and HCO3- in kidney proximal tubules.

This study examines the effects of acute in vitro acid-base disorders on Na+/H+ and H(+)-ATPase transporters in rabbit kidney proximal tubules (PT). PT suspensions were incubated in solutions with varying acid base conditions for 45 min and utilized for brush border membrane (BBM) vesicles preparation. BBM vesicles were studied for Na+/H+ exchange activity (assayed by 22Na+ influx) or abundance (using NHE-3 specific antibody) and H(+)-ATPase transporter abundance (using antibody against the 31 kDa subunit). The Na+/H+ exchanger activity increased by 55% in metabolic acidosis (pH 6.5, HCO3- 3 mM) and decreased by 41% in metabolic alkalosis (pH 8.0, HCO3- 90 mM). The abundance of NHE-3 remained constant in acidic, control, and alkalotic groups. H(+)-ATPase abundance, however, decreased in metabolic acidosis and increased in metabolic alkalosis by 57% and 42%, respectively. In PT suspensions incubated in isohydric conditions (pH 7.4), Na+/H+ exchanger activity increased by 29% in high HCO3- group (HCO3- 96 mM) and decreased by 16% in the low HCO3- groups (HCO3- 7 mM. The NHE-3 abundance remained constant in high, normal, and low [HCO3-] tubules. The abundance of H(+)-ATPase, however, increased by 82% in high [HCO3-] and decreased by 77% in the low [HCO3-] tubules. In PT suspensions incubated in varying pCO2 and constant [HCO3-], Na+/H+ exchanger activity increased by 35% in high pCO2 (20% pCO2, respiratory acidosis) and decreased by 32% in low pCO2 (1.5% pCO2, respiratory alkalosis) tubules. The NHE-3 abundance remained unchanged in high, normal, and low pCO2 tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1995

Inhibition of plasma membrane Ca(2+)-ATPase pump activity in cultured C6 glioma cells by halothane and xenon.

We have compared the effect of two inhalational anesthetics, halothane and xenon, on Ca(2+)-ATPase (PMCA) pumping activity in plasma membrane vesicles prepared from cultured rat C6 glioma cells. Halothane, at concentrations ranging from 0.5 to 1.75 vol% (equivalent to 0.5 to 1.6 MAC), significantly inhibited Ca2+ uptake (transport) by plasma membrane vesicles in a dose-related fashion. Xenon, at partial pressures ranging from 0.5 to 1.5 atm (equivalent to 0.5 to 1.6 MAC), similarly inhibited PMCA pumping activity. Additive effects on suppression of PMCA pump activity were observed when C6 cell plasma membrane vesicles were exposed to increasing partial pressures of xenon in the presence of halothane (1 vol%). Halothane also inhibited PMCA pumping in cells from two other lines of neural origin, B104 (rat neuroblastoma) and PC12 (rat pheochromocytoma). Studies described in this report support the thesis that PMCA in cells of neural origin is inhibited by quite different inhalational anesthetics at clinically relevant concentrations.

Animals↗