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G Singh

Publications and source records attributed to G Singh.

At least 433 records · Page 24Linked to original sources
PubMed1993

Secretory product expression during Clara cell differentiation in the rabbit and rat.

One function of the nonciliated (Clara) cells of bronchiolar epithelium is to synthesize, store, and release small-molecular-mass (6-12 kDa) secretory proteins or Clara cell secretory protein (CCSP). This study compares the emergence of this secretory function during Clara cell differentiation in rabbits and rats. Lungs of fetal and postnatal animals were evaluated by ultrastructural morphometry and immunohistochemistry. Secretory granules were rarely seen in perinatal animals and increased to adult levels of abundance earlier in rats (1 wk postnatal) than in rabbits (3-4 wk). In contrast, rough endoplasmic reticulum was abundant in perinatal animals and decreased with age. Antibodies raised against CCSP revealed little CCSP in fetal animals; however, after birth CCSP increased to adult levels earlier in rats (1 wk postnatal) than in rabbits (3 wk). We conclude that the maturation of Clara cell secretory function 1) occurs postnatally, 2) involves a decrease in biosynthetic organelles, 3) shows close association between CCSP expression and secretory granule abundance, and 4) varies by species in timing and cellular abundance of biosynthetic machinery.

Animals↗
PubMed1993

Chemically induced hypotension increases PGE2 release and depresses macrophage antigen presentation.

Hemorrhagic shock causes severe depression of macrophage functions and is associated with increased susceptibility to sepsis. Because hemorrhagic shock and resuscitation encompasses several pathophysiological conditions, such as hypotension, low-flow conditions, hypoxia, and reperfusion injury, it remains unknown whether severe hypotension in the absence of blood loss has any adverse effects on macrophage functions. To study this, systemic arterial hypotension was induced in C3H/HeN mice for 15 min by intravenous infusion of sodium nitroprusside or ATP-MgCl2. Peritoneal macrophages (PM) was harvested 20 h later with lavage. Antigen presentation was measured by coculturing PM with the D10.G4.1 Th cell clone. Tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, and prostaglandin (PG) E2 levels in supernatants of PM stimulated with lipopolysaccharide were measured with bioassays or radioimmunoassay. Systemic arterial hypotension resulted in a significant decrease of PM capacity to present antigen. Although the release of TNF, IL-6, and IL-1 by PM was unaltered after hypotension, PGE2 release by PM was significantly elevated compared with the control group. These data indicate that chemically induced systemic arterial hypotension without blood loss leads to a depression of antigen presentation, which may be caused by elevated release of the immunosuppressive eicosanoid PGE2.

Adenosine Triphosphate↗
PubMed1993

ATP-MgCl2 restores gut absorptive capacity early after trauma-hemorrhagic shock.

The aim of this study was to determine whether ATP-MgCl2 as an adjunct to resuscitation has any beneficial effect on the depressed gut absorptive capacity (GAC) after hemorrhage and, if so, whether alterations in whole blood viscosity (WBV) are, in part, responsible for those effects. Rats were anesthetized, a laparotomy was performed (i.e., trauma induced), and blood vessels were cannulated. The animals then underwent fixed pressure (40 mmHg) hemorrhage, followed by resuscitation with lactated Ringer solution. One group received 50 mumol/kg ATP-MgCl2 and another received saline during resuscitation. At 2 and 4 h after the end of hemorrhage, a 1-h D-xylose absorption test was performed. Viscosity determinations were made at corresponding time points in another set of rats subjected to sham hemorrhage, acute hemodilution, or hemorrhage and resuscitation. Results show that xylose absorption is depressed after hemorrhage and resuscitation and that ATP-MgCl2 restored it to normal. D-Xylose absorption was inhibited by glucose, indicating a facilitated transport process. Furthermore, WBV was reduced by the administration of ATP-MgCl2. Thus ATP-MgCl2 improves GAC early after hemorrhage and resuscitation, possibly by reducing WBV, and may be a useful adjunct to resuscitation, allowing for early enteral nutrition.

Adenosine Triphosphate↗
PubMed1993

Quantitative comparison of intracellular concentration and volume of Clara cell 10 KD protein in rat bronchi and bronchioles based on laser scanning confocal microscopy.

We used an antibody to rat Clara cell 10 KD secretory protein (CC10) to compare the abundance of CC10 in non-ciliated epithelium of bronchioles and bronchi by immunohistochemistry and laser scanning confocal microscopy (LSCM) in the reflectance mode. Three zones of reflectance intensity (high, medium, low), directly related to CC10 content, were used to distinguish subcellular compartments of differing densities. Two major compartments contained CC10: granules and endoplasmic reticulum. Bronchiolar cell granules had relatively even reflectance, a high CC10 concentration (0.92 mg/ml), and occupied 7.5% of the cell volume. Bronchial cell granules were bi-zonal, lower in CC10 concentration (0.83 mg/ml), and occupied less cell volume (2.3%). Low-reflecting endoplasmic reticulum occupied a greater cell volume in bronchioles than in bronchi (32.8% and 22.1%, respectively). An intermediate-density zone consisted of endoplasmic reticulum close to granules. CC10 abundance, expressed as ng stored per unit surface area of epithelial basal lamina, was more than three times greater in bronchioles than in proximal bronchi (1.50 ng/mm2 vs 0.42 ng/mm2). These data demonstrate that the process of CC10 secretion differs markedly in non-ciliated epithelium of bronchi and bronchioles. Identifiable mucous-goblet cells did not contain CC10. The LSCM provides a method for quantifying intracellular CC10 pools in intact lung cells and has the potential for quantifying other proteins in subcellular compartments.

Animals↗
PubMed1993

Surgical treatment of induced peri-implantitis in the micro pig: clinical and histological analysis.

The purpose of this pilot study was to determine if lost osseous support adjacent to root form implants could be regenerated using a guided tissue regeneration technique. Three fixtures were placed in each edentulous mandibular bicuspid region of two micro pigs. A total of 6 fixtures were placed in each pig. Due to the presence of a pathologic condition, which was in no way related to the research, the results of one pig were not evaluated. Following osseointegration, peri-implantitis were induced by the use of ligatures and a soft diet. Three modalities of treatment were performed. Utilizing a surgical flap approach, one third of the fixtures (one per quadrant) were covered with expanded polytetrafluoroethylene (ePTFE) membrane and submerged under the soft tissue complex. The second group of fixtures were submerged under the soft tissue complex with no ePTFE membrane. The control fixtures along with their abutments were debrided and remained non-submerged. All fixtures were debrided using an air-abrasive polishing system. The osseous defects around the fixtures were measured from a fixed reference point at the time of surgery and after obtaining block sections.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗
PubMed1993

Intraoperative mitomycin C in complicated glaucomas.

Filtering surgery has been found to be less successful in certain types of glaucoma. These include young patients, those with pigmentary glaucoma, secondary glaucoma, angle recession glaucoma, aphakic or pseudophakic glaucoma, and patients requiring reoperation. This study describes the authors' attempt to evaluate the effectiveness of conventional trabeculectomy with intraoperative application of mitomycin C in such patients. Ten eyes of 8 patients were evaluated in this study. Of these cases 4 eyes (2 bilateral cases) were from the primary juvenile open angle group; 2 eyes each had pseudophakic glaucoma and previous anti-glaucoma surgery which had failed; one eye had aphakic glaucoma and the last suffered from angle recession glaucoma. The intraocular pressure was successfully controlled in all the ten eyes. The preoperative IOP ranged from 28 to 50 mm Hg and the postoperative IOP ranged from 7 to 16 mm Hg. The postoperative complications were minimal.

Adult↗
PubMed1993

Trichobezoar.

Explore the source record for details and available documents.

Adult↗
PubMed1993

Diltiazem reduces whole blood viscosity following trauma-hemorrhagic shock and resuscitation.

Although diltiazem improves function in several organs following trauma-hemorrhagic shock, the mechanism remains unknown. It is hypothesized that diltiazem maintains red blood cell calcium-to-magnesium ratio, resulting in better deformability of red blood cells. This should reduce blood viscosity, allowing red blood cells to traverse the microcirculation more efficiently and improve tissue oxygenation. To study this, rats (n = 23) underwent cannulation of various blood vessels and were divided into five groups: Group 1, control rats which had surgery only; Group 2, sham-operated rats which were not hemorrhaged but were infused with a volume of lactated Ringer's solution (LRS) equivalent to that given to the hemorrhaged animals (Groups 4 and 5); Group 3, hemodilution animals which were maintained at normal blood pressure but with the hematocrit lowered to values equivalent to hemorrhaged rats (Groups 4 and 5); Groups 4 and 5, animals which underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with LRS, 5x the shed blood volume, and were given IV saline (Group 4) or 400 micrograms diltiazem/kg (Group 5) with the resuscitation. Blood viscosity was measured at the end of resuscitation with a Brookfield DV-III viscometer. Results showed that blood viscosity was markedly reduced in the diltiazem treatment group, but was unchanged in any of the other groups versus the control. Thus, the beneficial effects of diltiazem after trauma-hemorrhage and resuscitation may be due in part to the marked decrease in blood viscosity allowing for improved oxygen delivery and removal of metabolites.

Animals↗
PubMed1993

Differentiated bronchiolar epithelium in alveolar ducts of rats exposed to ozone for 20 months.

The effects of exposure to 1.0 ppm of ozone for twenty months were studied in male Fischer 344 rats. Light microscopic, morphometric, and immunohistological approaches were used to determine the distribution and degree of differentiation of ciliated and nonciliated bronchiolar epithelial (Clara) cells lining alveolar ducts of the central acinus, a primary target of ozone-induced lung injury. Alveolar duct pathways extending beyond the level of the most proximal alveolar outpocketing of terminal bronchioles were isolated in longitudinal profile. The distance that ciliated and nonciliated bronchiolar epithelial (Clara) cells projected down each alveolar duct pathway was determined by placing concentric arcs radiating outward from a single reference point at the level of the first alveolar outpocketing. A high degree of heterogeneity in the magnitude of bronchiolar epithelial cell extension into alveolar ducts was noted for each isolation and animal. Age-matched control animals also demonstrated variation in the degree of bronchiolar epithelial cell extension down alveolar ducts. In animals exposed to ozone, a striking similarity was noted by scanning electron microscopy in the surface characteristics of cells lining both terminal bronchioles and alveolar ducts. The presence of Clara cell secretory protein in cells of bronchioles and alveolar ducts was also detected immunohistochemically and visualized using confocal laser scanning microscopy in the reflectance mode. Well-differentiated ciliated and nonciliated bronchiolar epithelial cells were found lining alveolar septal tips and alveoli up to a depth of 1,000 mu into the pulmonary acinus after 20 months of exposure to ozone. No evidence of inflammation was present in alveolar ducts, suggesting that epithelial cell transformations in alveolar ducts is a natural consequence of lifetime exposures to oxidant gases.

Animals↗
PubMed1993

Tumor necrosis factor depresses gut absorptive function.

Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-alpha) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D-xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 micrograms recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D-xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alpha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha.

Animals↗
PubMed1992

Dominant mutation of the murine Hox-2.2 gene results in developmental abnormalities.

Genes carrying the homeobox were originally identified in Drosophila, in which they are now known to play key roles in establishing segmentation patterns and in determining segment identities. A number of genes with striking homology to the Drosophila homeobox genes have now been found in the mouse genome, and mutational analysis is beginning to shed light on their function in mammalian development. To understand better the developmental significance of the murine Hox-2.2 gene, we have generated gain of function mutants by using the chicken beta-actin promoter to drive ubiquitous expression in transgenic mice. The resulting Hox-2.2 misexpression produces early postnatal lethality as well as craniofacial and axial skeletal perturbations that include open eyes at birth, cleft palate, micrognathia, microtia, skull bone deficiencies, and structural and positional alterations in the vertebral column. We repeatedly observe complete or partial absence of the supraoccipital bone and malformations of the exoccipital and the basioccipital bones. These results suggests a role for the Hox-2.2 gene in specifying positional identity along the anterior-posterior axis.

Abnormalities, Multiple↗
PubMed1992

Truncated glucagon-like peptide-1 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Identification of a mammalian analogue of the reptilian peptide exendin-4.

To find mammalian analogues of exendin-4, a peptide from Helodermatidae venoms that interacts with newly discovered exendin receptors on dispersed acini from guinea pig pancreas, we examined the actions of recent additions to the vasoactive intestinal peptide/secretin/glucagon family of regulatory peptides. In every respect tested, the truncated form of glucagon-like peptide-1, GLP-1(7-36)NH2, mimicked the actions of exendin-4. Like exendin-4, GLP-1(7-36)NH2 caused an increase in acinar cAMP without stimulating amylase release. GLP-1(7-36)NH2-induced increases in cAMP were inhibited progressively by increasing concentrations of the specific exendin-receptor antagonist, exendin(9-39)NH2. In dispersed acini from guinea pig and rat pancreas, concentrations of GLP-1(7-36)NH2 that stimulated increases in cAMP caused potentiation of cholecystokinin-induced amylase release. Binding of 125I-[Y39]exendin-4 or 125I-GLP-1(7-36)NH2 to dispersed acini from guinea pig pancreas was inhibited by adding increasing concentrations of unlabeled exendin-4 or GLP-1(7-36)NH2. We conclude that the mammalian peptide GLP-1(7-36)NH2 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Exendin(9-39)NH2, a competitive antagonist of the actions of GLP-1(7-36)NH2 in pancreatic acini, may be a useful tool for examining the physiological actions of this peptide.

Amino Acid Sequence↗
PubMed1992

cis-acting elements that confer lung epithelial cell expression of the CC10 gene.

To define cis-acting genetic elements responsible for cell-specific transcriptional regulation of the CC10 gene, DNA sequences spanning nucleotides -2338 to +49 of the rat CC10 gene were linked to a reporter gene coding for chloramphenicol acetyltransferase (CAT). In transient expression assays, CC10 sequences were capable of restricting CAT expression to a human lung adenocarcinoma cell line similar to pulmonary Clara cells. Transgenic mice harboring the hybrid RtCC10-CAT construct expressed high levels of CAT activity specifically within protein extracts of lung and trachea. Transcripts for the CAT reporter gene colocalized with those for the endogenous murine CC10 gene within the airways of transgenic mice. Functional analysis of deletion mutants identified stimulatory, inhibitory, and cell type-specific transcriptional regulatory elements. The results of gel retention and DNaseI protection assays suggest that a transcriptional stimulatory region located between -320 and -175, and a cell type-specific regulatory element located between -175 and +49, result from a series of protein-DNA interactions occurring at -220 to -205 and -128 to -86, respectively. Lung epithelial specific transcriptional regulatory elements described herein will be useful for expression of chimeric genes within epithelial cells lining the trachea, bronchi, and bronchioles of mice.

Adenocarcinoma↗
PubMed1992

Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas.

The recent identification in Heloderma horridum venom of exendin-3, a new member of the glucagon superfamily that acts as a pancreatic secretagogue, prompted a search for a similar peptide in Heloderma suspectum venom. An amino acid sequencing assay for peptides containing an amino-terminal histidine residue (His1) was used to isolate a 39-amino acid peptide, exendin-4, from H. suspectum venom. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, but is otherwise identical. The structural differences make exendin-4 distinct from exendin-3 in its bioactivity. In dispersed acini from guinea pig pancreas, natural and synthetic exendin-4 stimulate a monophasic increase in cAMP beginning at 100 pM that plateaus at 10 nM. The exendin-4-induced increase in cAMP is inhibited progressively by increasing concentrations of the exendin receptor antagonist, exendin-(9-39) amide. Unlike exendin-3, exendin-4 does not stimulate a second rise in acinar cAMP at concentrations greater than 100 nM, does not stimulate amylase release, and does not inhibit the binding of radiolabeled vasoactive intestinal peptide to acini. This indicates that in dispersed pancreatic acini, exendin-4 interacts only with the recently described exendin receptor.

Amino Acid Sequence↗
PubMed1992

Refined structure of rat Clara cell 17 kDa protein at 3.0 A resolution.

The rat Clara cell 17 kDa protein (previously referred to as the rat Clara cell 10 kDa protein) has been reported to inhibit phospholipase A2 and papain, and to also bind progesterone. It has been isolated from rat lung lavage fluid and crystallized in the space group P6(5)22. The structure has been determined to 3.0 A resolution using the molecular replacement method. Uteroglobin, whose amino acid sequence is 55.7% identical, was used as the search model. The structure was then refined using restrained least-squares and simulated annealing methods. The R-factor is 22.5%. The protein is a covalently bound dimer. Two disulfide bonds join the monomers together in an antiparallel manner such that the dimer encloses a large internal hydrophobic cavity. The hydrophobic cavity is large enough to serve as the progesterone binding site, but access to the cavity is limited. Each monomer is composed of four alpha-helices. The main-chain structure of the Clara cell protein closely resembles that of uteroglobin, but the nature of many of the exposed side-chains differ. This is true, particularly in a hypervariable region between residues 23 and 36, and in the H1H4 pocket.

Amino Acid Sequence↗