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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 505 records · Page 28Linked to original sources
PubMed1991

Mouse bronchiolar cell carcinogenesis. Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2-chloroethyl) ureas.

Female Swiss mice (Cr:NIH(S)) developed bronchiolar cell hyperplasia, dysplasia, metaplasia, and various morphologic types of bronchiolar cell tumors after topical (skin) application of N-nitroso-methyl-bis-chloroethylurea (NMBCU) or N-nitroso-tris-chloroethylurea (NTCU). These compounds are the first found to induce systemically bronchiolar cell tumors in mice in high incidence. Twice a week, with a 3-day interval, a 25-microliter drop of 0.04 mol/l (molar) NMBCU or NTCU in acetone was applied to the shaved interscapular integument for a maximum of 35 to 40 weeks. The earliest lung neoplasms were seen in mice that died after 23 weeks of treatment and affected 11 of 19 with NMBCU and 14 of 19 with NTCU treatment. Tumor growth pattern was nodular or the neoplastic tissue was frequently disseminated throughout the parenchyma, starting from multicentric peribronchiolar foci. The most common tumor types were squamous cell carcinomas and adenosquamous carcinomas, followed by adenocarcinomas with or without secretory cells, and a single ciliated-cell tumor. Histochemical and immunohistochemical studies were carried out on paraffin-embedded lungs using the avidin-biotin immunoperoxidase complex procedure and antisera against keratin, Clara cell antigen, surfactant apoprotein, neuron-specific enolase, bombesin, and chromogranin A. In several mice from both groups, hyperplasias and tumors were composed of cells expressing Clara cell antigen. No tumor cells were found expressing alveolar type II or neuroendocrine cell markers. It appeared that bronchiolar cells, in particular Clara cells, had migrated from terminal bronchioles or invaded bronchiolar walls to extend into the alveolar parenchyma. Squamous cell metaplasia with keratin expression was seen within airways or associated with glandular tumors, especially at the periphery. A unique cell type, with large eosinophilic globules and associated eosinophilic crystals, was seen lining airways or forming hyperplastic and neoplastic lesions. N-nitroso-methyl-bis-chloroethylurea- and NTCU-induced mouse bronchiolar cell alterations could be an interesting new model to study mechanisms of bronchiolar cell differentiation and tumor formation.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1991

Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis.

The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Use of Chronogest implants and Folltropin for estrus synchronization and superovulation in goats.

Six Barbari goats each were assigned randomly to treatments 1,2 or 3, comprising im injections of FSH (folltropin) at 12, 14 or 16 mg dose level respectively. Estrus was synchronized with intravaginal sponge impregnated with flugestone acetate (30 mg; chronogest) inserted for 12 days and cloprostenol (125 micrograms) im at the insertion as well as at removal of sponge. FSH treatment started 48 hr before the sponge removal as 4-day declining dose scheme. Estrus could be effectively synchronized in all goats under the study, with significant difference (P less than 0.05) in the onset of estrus between the treatment groups. All goats were administered with 750 IU hCG i.v. at estrus. Recording of ovarian response and embryo recovery was done 45 hr after the onset of estrus. The prime aim of superovulation was effectively achieved in Barbari goats with the use of chronogest implants and folltropin. There was no difference (P greater than 0.05) between the treatment groups in recovery of transferable embryos, however, 14 mg folltropin appeared to be near optimal dose. There was no adverse effect on the quality of recovered embryos with high doses of folltropin.

Animals↗
PubMed1991

Statistical study of the socio-economic factors affecting child immunisation in rural areas.

A sample survey of immunisation coverages in children in the rural areas of Varanasi was undertaken to study how the socio-economic status of parents affects immunisation of their children. The present state of affairs in immunisation programme in India inspite of its established utility and added attempts towards its implementation, seems to be unsatisfactory. The entire problem is very closely linked with education and socio-economic uplift of the people.

Child, Preschool↗
PubMed1991

Resistant falciparum malaria in an endemic area of Allahabad (U.P.).

Over the last three decades the problems of resistance in P. falciparum malaria to chloroquine have emerged in many parts of the world including India. The present study was carried out at PHC, Jasra, an endemic area for malaria in Allahabad distt. to ascertain the level of resistance to chloroquine in P. falciparum in selected villages according to WHO extended 28-day field test. One hundred one (58.4%) cases were positive for malaria. Amongst the positive cases, 92 (91.1%) showed P. falciparum and 9 (8.9%) P. vivax infection. Of the 92 cases, 31 (33.7%) showed resistance to chloroquine and 61 (66.3%) were sensitive to the standard dose of chloroquine. Out of the 31 resistant cases, 19 (61.3%) showed resistance at RI level and 12 (38.7%) at RII level.

Animals↗
PubMed1990

Clara cell 10 kDa protein (CC10): comparison of structure and function to uteroglobin.

The cellular localization, functional activities and structures of rat and human Clara cell 10 kDa proteins (CC10) are compared to rabbit uteroglobin. CC10 is present exclusively in the non-ciliated cells of the surface epithelium of the pulmonary airways, whereas uteroglobin is reported to be present in the lung and reproductive organs. There is about 55% identity between the amino acid sequences of rat CC10 and either rabbit uteroglobin or human CC10. The latter two have 61% identity. Using the known structure of uteroglobin as the model, correlations between the structure and function for this group of proteins are made. Substitution of the residues for the rat and human CC10 into the structure of uteroglobin suggests that these proteins may be members of a structurally homologous family. Some of the functional differences may be due to distortion of the hydrophobic pocket in the dimeric protein and a surface hypervariability located on one contiguous helix and beta turn. Rat CC10 and rabbit uteroglobin both, nearly equally, inhibit papain and bind progesterone. Human CC10 does not inhibit papain and has markedly lower progesterone binding (4.6% of rabbit uteroglobin). Antiinflammatory activity of synthetic peptides corresponding to a homologous sequence region of uteroglobin and the two Clara cell proteins was tested. The region chosen has sequence similarity to lipocortin I. The peptides not only failed to inhibit carrageenan-induced foot pad swelling but exacerbated it. All three proteins inhibit pancreatic phospholipase A2. The phospholipase A2 inhibitory effect of CC10 may be important in regulating the inflammatory responses in the lung.

Amino Acid Sequence↗
PubMed1990

Tissue-specific expression, hormonal regulation and 5'-flanking gene region of the rat Clara cell 10 kDa protein: comparison to rabbit uteroglobin.

The amino acid sequence of rat Clara Cell 10 kDa secretory protein (CC10) shows 55% identity to rabbit uteroglobin. In order to define the relationship between rat CC10 and rabbit uteroglobin in detail, the tissue-specific expression and hormonal regulation of rat CC10 mRNA was analyzed. We report that like rabbit uteroglobin, rat CC10 mRNA is expressed in lung and esophagus, as well as in uteri of estrogen- and progesterone-treated females. Expression of CC10 mRNA in lung is regulated by glucocorticoids. The similarity in expression pattern of rat CC10 mRNA and rabbit uteroglobin mRNA is reflected by a striking similarity in the 5'-flanking regions of the two genes. Despite this overall similarity, two regions of 0.3 kb and 2.1 kb are absent in the rat CC10 upstream gene region. The larger region includes a cluster of hormone receptor binding sites, believed to be responsible for differential regulation of rabbit uteroglobin by glucocorticoids and progesterone. Thus, while the sequence identities in the coding and 5'-flanking regions point towards a common ancestor for the uteroglobin and CC10 gene, later events (deletions/insertions) might have caused species-specific differences in their regulation.

Animals↗
PubMed1990

Differential effects of cisplatin on mouse hepatic and renal mitochondrial DNA.

The objective of this study was to determine if the nephrotoxic effects induced by cisplatin were correlated to mitochondrial DNA damage. Comparisons were made with the liver since hepatotoxicity is rarely observed. Cisplatin doses of 10, 20 and 40 mg/kg were administered intraperitoneally to C57BL/6J mice. Mitochondrial DNA was isolated from both the hepatic and renal tissues and quantitated by hybridization with a specific mitochondrial probe. Cisplatin caused differential effects on mouse hepatic and renal mitochondrial DNA. The 10 and 20 mg/kg dose caused an elevation in mitochondrial DNA levels in the hepatic, but no increase in the renal tissue was observed. This is the first study demonstrating an organ specific effect of cisplatin at the DNA level.

Animals↗
PubMed1990

Disposition of three glycol ethers administered in drinking water to male F344/N rats.

The glycol ethers 2-methoxyethanol (ME), 2-ethoxyethanol (EE), and 2-butoxyethanol (BE) are widely used solvents in industrial and consumer applications. The reproductive, teratogenic, and hematotoxic effects of the glycol ethers are due to the alkoxyacetic acid metabolites of these compounds. The effect of alkyl group length on disposition of these three glycol ethers was studied in male F344/N rats allowed access for 24 hr to 2-butoxy[U-14C]ethanol, 2-ethoxy[U-14C]ethanol, or 2-methoxy[U-14C]ethanol in drinking water at three doses (180 to 2590 ppm), resulting in absorbed doses ranging from 100 to 1450 mumols/kg body wt. Elimination of radioactivity was monitored for 72 hr. The majority of the 14C was excreted in urine or exhaled as CO2. Less than 5% of the dose was exhaled as unmetabolized glycol ether. Distinct differences in the metabolism of the glycol ethers as a function of alkyl chain length were noted. For BE 50-60% of the dose was eliminated in the urine as butoxyacetic acid and 8-10% as CO2; for EE 25-40% was eliminated as ethoxyacetic acid and 20% as CO2; for ME 34% was eliminated as methoxyacetic acid and 10-30% as CO2. Ethylene glycol, a previously unreported metabolite of these glycol ethers, was excreted in urine, representing approximately 10, 18, and 21% of the dose for BE, EE, and ME, respectively. Thus, for longer alkyl chain lengths, a smaller fraction of the administered glycol ether was metabolized to ethylene glycol and CO2. Formation of ethylene glycol suggests that dealkylation of the glycol ethers occurs prior to oxidation to alkoxyacetic acid and, as such, represents an alternate pathway in the metabolism of these compounds that does not involve formation of the toxic acid metabolite.

Alcohol Dehydrogenase↗
PubMed1990

Immunochemical localization of Clara cell protein by light and electron microscopy in conducting airways of fetal and neonatal hamster lung.

An antibody to a protein produced by Clara cells in adult Syrian golden hamsters has been used to monitor the development and functional differentiation of secretory cells in the conducting airway epithelium of this species. Lungs from fetal and neonatal hamsters at gestational day 11 and at intervals up to and including 3.5 weeks of age (as well as adults) were studied. The earliest time this Clara cell protein could be identified by immunoperoxidase labeling in the fetal conducting airways was at gestational day 15. On this day, labeling was observed in a few secretory cells lining the trachea, in many lining the lobar bronchi, and in virtually all secretory cells lining the bronchioles. Ciliated cells and endocrine cells were not labeled. Granules first appeared within the apical cytoplasm of the secretory cells on gestational day 15 at all airway levels. To identify the exact subcellular location of this protein, an ultrastructural labeling procedure using protein A gold was employed. The gold particles labeled only electron-dense granules within the secretory cells, indicating that they represent the specific site of this protein. Since secretory cells in the most distal conducting airways began to produce this protein on the same day in development as cells in the larger airways, including the trachea, this expression of functional maturation occurs simultaneously throughout the conducting respiratory tree rather than proceeding sequentially in a cranial to caudal direction. Consequently, secretory cells lining the smaller conducting airways mature more rapidly than those lining the larger airways.

Animals↗
PubMed1990

Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis.

Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued.

Alanine Transaminase↗
PubMed1990

Development and testing of a human collagen graft material.

Human Type I collagen was extracted from placenta using pepsin and salt fractionation. The collagen was characterized by SDS-PAG electrophoresis dispersed in acidic medium, freeze-dried, and cross-linked in an 0.25% glutaraldehyde solution pH 4.5 for 2 days. After washing for 7 days and freeze drying the resultant collagen sponge was tested with regard to mechanical, physical, enzymatic degradation properties and biological responses. The modulus of elasticity was found to be 289 +/- 10 g/mm2 and the sponge was insoluble in water, buffered saline, or tissue culture medium over a period of 6 weeks with swelling occurring at less than 5% of volume. The sponge had a high fluid binding capacity, amounting to 56 +/- 5 mL tissue culture medium per gram of dry weight. Bacterial collagenase produced slow degradation of the sponge with complete disappearance by 24 h only when high concentrations (200 units enzyme per mg of the collagen sponge) were used. Cytotoxicity studies using human gingival and periodontal ligament fibroblasts revealed less than 5% apparent cytotoxicity or proliferation. Subcutaneous implantation was followed by resorption and vascularization over a period of 6-8 weeks. It was concluded that the collagen sponge prepared from human Type I collagen has potential as a graft material in oral surgical procedures.

Animals↗
PubMed1990

Cholinergic desensitization of pepsinogen secretion and calcium mobilization of dispersed guinea pig chief cells.

When dispersed chief cells from guinea pig stomach were first incubated with carbachol, washed, and then reincubated with carbachol in fresh incubation solution, the stimulation of pepsinogen secretion and the rise in intracellular calcium concentration during the second incubation were reduced. Carbachol did not cause residual enzyme secretion, but the same range of concentrations that causes enzyme secretion caused desensitization that was rapid, temperature dependent, and reversible with time. Preincubation with carbachol caused approximately a 65% reduction in enzyme secretion stimulated during a subsequent incubation with this agonist, but the potency of carbachol was unaffected. Prior exposure to carbachol also reduced subsequent stimulation caused by cholecystokinin (CCK-8), gastrin I, ionophore A23187, or 12-O-tetradecanoylphorbol 13-acetate but did not alter stimulation by any agonist that increases cellular cAMP. Carbachol pretreatment of Fura-loaded chief cells caused a threefold increase in the EC50 for carbachol-stimulated [Ca2+]i and approximately a 30% reduction in the maximal rise in [Ca2+]i in response to carbachol or CCK-8. Inhibition of [N-methyl-3H] scopolamine binding by carbachol following carbachol pretreatment indicated that modulation of receptor affinity or number did not account for functional desensitization. These data indicate that carbachol causes heterologous desensitization of pepsinogen secretion stimulated by agonists that mobilize cellular Ca2+ or activate protein kinase C through a postreceptor action and suggest that an attenuated rise in chief cell calcium is one mechanism mediating the desensitization of enzyme secretion.

Animals↗
PubMed1990

Distinct genomic copy number in mitochondria of different mammalian organs.

This study shows that mitochondria in liver, kidney, heart, and brain of the mouse have a distinct mitochondrial density. It also demonstrates that the mtDNA copy number per mitochondrion is organ-specific. A reliable method of determining mitochondrial density per organ is by stereological analysis of tissue sections while mtDNA quantitation is by the use of radiolabelled mtDNA probe. This is the first study in which a comprehensive examination of mitochondrial density and quantitation of mitochondrial genomes in mouse organs have been done. In summary the variability is not only in mitochondrial density but also in genomic copy number in mitochondria of various tissues.

Animals↗
PubMed1990

Effect of whole-body hyperthermia on hepatic cytochrome P450.

Currently, the combination of hyperthermia with a variety of chemotherapeutic agents and cytokines for the treatment of disseminated human malignancy is being examined. In this study we investigated the effects of 41 degrees-42 degrees C whole-body hyperthermia (WBH) and the cytokine interleukin-1 (IL-1) on cytochrome P450 in mice. At 24 h following 1 h of 41 degrees-42 degrees C WBH, IL-1 or combined treatment, hepatic microsomal cytochrome b5 and aminopyrine N-demethylation were assayed. Cytochrome b5 activity was not significantly diminished by WBH, IL-1 or WBH + IL-1, but N-demethylation was suppressed by the combination of WBH + IL-1 and, to a lesser extent, by WBH alone.

Animals↗