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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 577 records · Page 32Linked to original sources

Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants.

The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospective double-blind randomized controlled trial among "high risk" infants with family history of atopy among first-degree relatives. The incidence of atopic eczema, wheezing, rhinitis, gastrointestinal symptoms, and colic was noted and serum IgE antibodies to milk were estimated. Seventy-two infants were recruited into each of the following groups: cow milk whey hydrolysate formula (NAN/HA), conventional cow milk formula (Similac), soy-based formula (Isomil), and exclusive breast feeding for greater than or equal to 4 months. The number of infants who exited for reasons other than atopy and were excluded from analysis were 4, 5, 4, and 12 in the four groups, respectively. The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA, 24 of 67 infants fed Similac, 25 of 68 infants fed Isomil, and 12 of 60 breast-fed infants. Among symptomatic infants, skin prick test to milk proteins was positive in four out of five infants fed NAN/HA, 16 of 24 fed Similac, 2 of 25 fed Isomil, and 7 of 12 breast-fed. IgE antibodies to milk were found in 2 of 68, 9 of 67, 0 of 68, and 6 of 60 infants in the four groups, respectively. It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toxic effects of azathioprine in rheumatoid arthritis. A national post-marketing perspective.

Concerns about the short-term and long-term toxic effects of azathioprine (AZA) have limited its use. Accordingly, we surveyed 393 AZA-treated rheumatoid arthritis (RA) patients, who were recruited and enrolled through a nationwide call to rheumatologists. Findings in these patients were compared with the findings, retrieved from the databank of the American Rheumatism Association Medical Information System, on 153 similarly treated RA patients. All 546 patients were surveyed prospectively, using the Health Assessment Questionnaire and information abstracted from hospital records. The 2 groups were closely similar in clinical characteristics. The most frequently reported side effects of AZA treatment were nausea, vomiting, and leukopenia. Gastrointestinal intolerance accounted for nearly 60% of therapy interruptions in 95 patients. Of 81 hospitalizations for all causes, only 8 may have been related in part to AZA, and no deaths were attributed to AZA therapy. No lymphomas or leukemias were encountered and the overall frequency of neoplasms was not significantly different from that seen in RA patients receiving conventional therapy. As used in the treatment of RA, AZA has a surprisingly benign profile with relatively few serious therapeutic mishaps.

Arthritis, Rheumatoid↗

Role of intrathecal tetanus antitoxin (equine) in tetanus neonatorum.

The present study includes 50 cases of tetanus neonatorum who were given 200 IU of tetanus antitoxin (equine) intrathecally once only and 500 IU intravenously daily for 3 consecutive days. Nutrition was provided with intravenous drip containing dextrose and other electrolytes. The overall mortality was 78%. It appears that the course of the disease remains unaltered with intrathecal tetanus antitoxin in tetanus neonatorum.

Humans↗

Gross factors in treatment of nonhealing corneal ulcers and recurrent erosions.

Epidermal growth factor (EGF) is known to promote corneal epithelial wound healing in experimental scrape and keratectomy models. We studied its efficacy in treating alkali-burned epithelial ulceration. EGF induced hyperplasia and cell proliferation to resurface the denuded and denatured corneal stroma, but it did not prevent recurrent erosions. A combination of EGF with fibronectin (Fn) was noted to enhance epithelial defect closure after alkali burns of the cornea and was seen to prevent recurrent erosions. Histopathologic examination of these corneas revealed marked leukocytic infiltration of the alkali-burned corneal stroma. To find ways to retard this inflammatory response, we studied the role of topical steroids and their efficacy when used with EGF, Fn, and laminin (Ln) in the management of alkali-burned corneas. Use of steroids decreased the incidence of recurrent erosions and corneal perforations. Histologically, steroids markedly decreased the leukocytic infiltration of stromal tissue, thereby retarding the collagenolysis. Topical steroids used with EGF and fibronectin were seen to promote epithelial wound closure and to prevent recurrent erosions in alkali-burned corneas. Combinations of EGF, fibronectin, and steroids may have a place in the treatment of clinical corneal alkali burns.

Adrenal Cortex Hormones↗

Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

Animals↗

Amino-acid and cDNA nucleotide sequences of human Clara cell 10 kDa protein.

A human lung cDNA expression library was screened by using a rabbit antiserum specific for a human Clara cell 10 kDa protein. The cDNA from two positive clones was sequenced by the dideoxy chain termination method. The nucleotide and primary amino-acid sequence deduced therefrom are presented. The N-terminal amino-acid sequence of the Clara cell 10 kDa protein, purified from bronchoalveolar lavage, was also determined. The deduced and experimentally determined sequences were identical where data for both were available. From the amino-acid composition, deduced and experimentally determined amino-acid sequences, it was determined that the 10 kDa protein in bronchoalveolar lavage consists of two identical 70-amino-acid long polypeptide chains joined by two cystine residues. The size of mRNA for the protein was found to be about 0.6 kb and the monomeric nascent protein, obtained by in vitro translation of lung mRNA was about 7.3 kDa in size. The 10 kDa protein recovered from bronchoalveolar lavage has 61% sequence identity with rabbit uteroglobin, the two proteins have common predicted secondary structures with marked surface differences when comparing predicted and actual structure determined by X-ray diffraction. The differences imply similarity of structure but, not identity of function.

Amino Acid Sequence↗

Mouse papillary lung tumors transplacentally induced by N-nitrosoethylurea: evidence for alveolar type II cell origin by comparative light microscopic, ultrastructural, and immunohistochemical studies.

A histogenetic study was designed to evaluate controversial findings on the cell of origin of tubular/papillary lung tumors in mice, i.e., bronchiolar Clara cell versus alveolar type II cell. N-Nitrosoethylurea (0.5 mmol or 0.74 mmol/kg) was given to pregnant C3H (C3H/HeNCr MTV-) and Swiss Webster [Tac:(SW)fBR] mice as a single i.p. injection on Day 14, 15, 16, or 18 of gestation. The offspring were studied at various ages ranging from 7 days to 52 wk. Serial sections of the whole lung (100 to 200 sections per mouse) showed that solid/alveolar and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. Furthermore, a mixture of solid and papillary patterns within a single module did not represent a merging of two tumors but a progression from the solid to the papillary form. By use of two rabbit antisera against mouse lung surfactant apoproteins found in normal alveolar type II cells, it was shown by the avidin-biotin peroxidase complex procedure, by the peroxidase-antiperoxidase technique, and by indirect immunofluorescence that both solid and papillary tumors contained these proteins that are specific markers for alveolar type II cells. With a rabbit anti-rat Clara cell antiserum, none of the tumors studied was immunoreactive while normal Clara cells were reactive. The nitroblue tetrazolium formazan stain for dehydrogenase enzymes, found particularly in Clara cells, did not reveal these enzymes in any lung tumors from either strain. Ultrastructurally, no typical features of the mature Clara cell were detected in papillary or other pulmonary neoplasms. However, all tumors showed characteristic alveolar type II cell structures such as various stages of lamellar body formation, although these features were less well differentiated in the papillary tumors. Argentaffin dense bodies, representing lysosomes and immature forms of lamellar bodies, were commonly observed in papillary tumors. Some features of the papillary tumors such as cell shape, high glycogen content, and primary cilia were equivalent to those seen in pulmonary epithelial precursor cells during fetal development. With age, the papillary tumors became invasive, accumulated neutral lipids, and developed bizarre cleaved nuclei and lamellated nuclear pseudoinclusions. In conclusion, the papillary lung tumors of the mouse, at least those induced transplacentally by N-nitrosoethylurea, constitute less well-differentiated or poorly differentiated alveolar type II cell adenomas or carcinomas with fetal morphological and biochemical properties.

Age Factors↗

Tubercular fistula in ano.

Of 122 patients with fistulae in ano operated upon in a 5-year period, 19 (15.6 per cent) were found to have tubercular fistulae on histopathological examination. There was no characteristic clinical picture and concomitant pulmonary tuberculosis was present in only three patients. Histological examination of the excised fistula is mandatory for the diagnosis of anal tuberculosis. There were no cases of Crohn's disease of the anal region.

Adolescent↗

Differential toxicity of cis and trans isomers of dichlorodiammineplatinum.

Nephrotoxicity is the dose-limiting toxic effect of cis-dichlorodiammineplatinum (cis-platin) in humans. Its stereoisomer transplatin does not have any toxicity at equimolar concentrations, and it also possesses little antitumor activity. In this study, subcellular localization of both the platinum isomers was examined in the liver and kidney of the mouse 24 hours following the drug administration. Levels of the platinum isomers were measured using flameless atomic absorption. The results showed that higher concentrations of the cis isomer were localized in the liver and kidney, while the concentration of the trans isomer was higher in blood. This indicates that trans isomer is sequestered in the central compartment, whereas cis isomer is distributed in the organs. We also measured metallothionein mRNA and protein levels in both liver and kidney following cisdichlorodiammineplatinum and transdichlorodiammine-platinum treatment to distinguish if the differential toxicity of the two stereoisomers could be related to metallothionein induction. We report here that cisplatin was capable of inducing metallothionein expression in mice in vivo and that there is an inverse relationship between metallothionein expression and the pattern of tissue toxicity induced by the drug.

Animals↗

Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and -resistant cell lines.

3-Deazaguanine (3-DG), a purine analogue, has unusual antitumor activity against experimental mammary tumor models and a number of other solid tumors. Others have shown that mutant CHO cells deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) or adenine phosphoribosyl transferase (APRTase) are resistant to 3-DG. We developed a L1210 cell line resistant to 3-DG, L1210/3-DG, by subculturing the parent L1210/0 cells in the presence of increasing concentrations of 3-DG. The IC50 was 3.5 microM and 620 microM for L1210/0 and L1210/3-DG, respectively. Cytotoxicity studies proved the resistance to be stable. Examination of the baseline-specific activity of HGPRTase and APRTase showed that the former was 118-fold lower in L1210/3-DG than in L1210/0, and the latter demonstrated no difference. A 4-h treatment of the cell lines at IC50 doses showed 48% and 23% reductions in IMP dehydrogenase in L1210/0 and L1210/3-DG, respectively. The rate of de novo purine biosynthesis was studied by using [14C]formic acid. Formate flux increased 2-fold in L1210/3DG in concert with the observed deficiency of HGPRTase in the cell line. 3-DG uptake was studied with [14C]-labelled compound. The total radioactivity was 9-fold higher in L1210/0 than in L1210/3-DG at 2 h. Subsequent chromatographic separation of radioactivity showed the 3-DG and 3-deazaguanosine pools of the drug to be equal in both lines. However, 3-DG nucleotide pools at 1 min and 2 h were 2.5-fold and 16-fold lower, respectively, in L1210/3-DG than in L1210/0. 3-DG incorporation studies with radiolabelled drug demonstrated that 3-deazaguanine is incorporated in the acid-insoluble fraction of the cell. These studies conclude that HGPRTase, and not APRTase, is required for the activation of drug. Inhibition of IMP dehydrogenase is partially responsible for antitumor activity of the drug. The incorporation of drug into nucleic acids may be a major mechanism for its antitumor activity. Further studies using a cloned cDNA probe for hypoxanthine guanine phosphoribosyltransferase (HGPRT) demonstrated no change in the DNA arrangements of the L1210/3-DG cell line, and Northern blot analysis showed approximately equal expression of mRNA in both cell lines.

Adenine Phosphoribosyltransferase↗

Effect of nutritional factors on aflatoxin B1 inhibition of growth in Escherichia coli and Salmonella typhi.

The extent of growth inhibition by aflatoxin B1 in S. typhi and E. coli was greater in the presence of sodium citrate or sodium phosphate, palmitic and stearic acid than aflatoxin B1 alone. The addition of amino acids (glycine or glutamic acid) stimulated growth in E. coli and inhibited in S. typhi in the presence of aflatoxin B1. Other nutrients, such as yeast extract, lactose, or salt addition did not alter aflatoxin B1 antibacterial activity but decreased growth was observed in the presence of peptone.

Aflatoxin B1↗