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Biomedical subjects

S B Singh

Publications and source records attributed to S B Singh.

At least 19 recordsLinked to original sources
PubMed1992

Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA.

We have synthesized, separated, and purified approximately 10 mg of a deoxyundecanucleotide duplex containing a single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide and the exocyclic amino group of guanosine. Excellent proton NMR spectra are observed for the (+)-trans-anti-BP diol epoxide-N2-dG adduct positioned opposite dC and flanked by G.C pairs in the d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18-A19-T20-G 21-G22] duplex +ADdesignated (BP)G.C 11-mer+BD. We have determined the solution structure centered about the BP covalent adduct site in the (BP)G.C 11-mer duplex by incorporating intramolecular and intermolecular proton-proton distance bounds deduced from the NMR data sets as constraints in energy minimization computations. The BP ring is positioned in the minor groove and directed toward the 5' end of the modified strand. One face of the BP ring of (BP)G6 is stacked over the G18 and A19 sugar-phosphate backbone on the partner strand and the other face is exposed to solvent. A minimally perturbed B-DNA helix is observed for the d[T4-C5-(BP)G6-C7-T8].d[A15-G16-C17-G18-A19] segment centered about the adduct site with Watson-Crick alignment for both the (BP)G6.C17 pair and flanking G.C pairs. A widening of the minor groove at the adduct site is detected that accommodates the BP ring whose long axis makes an angle of approximately 45 degrees with the average direction of the DNA helix axis. Our study holds future promise for the characterization of other steroisomerically pure adducts of BP diol epoxides with DNA to elucidate the molecular basis of structure-activity relationships associated with the stereoisomer-dependent spectrum of mutational and carcinogenic activities.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Lactation failure.

Seventy five mothers with lactation failure were studied, whose less than 4-month-old babies were admitted to the hospital. Partial lactational failure (94.7%) was noted more often than complete lactational failure (5.3%). Initiation of breastfeeding was delayed for 2 to 5 days usually for traditional reasons (77.3%) and because the mothers felt that the milk output was inadequate (92%). The various causes of lactation failure were determined and the relationship to various factors was analyzed. The commonest cause of lactation failure was insufficient milk or no milk (80%). The age, parity, education, socio-economic status, religion, family structure and urban vs rural status of mother--all had a bearing on the occurrence of lactation failure. An attempt was made to relactate all these mothers. The outcome was successful in 69.3 cases and failed in only 4% cases. In 26.7% cases, we cannot predict the outcome as the mothers hospital stay was very brief with no follow up.

Adolescent↗
PubMed1992

Osteoarticular tuberculosis in children.

One hundred and four cases of osteoarticular tuberculosis were studied. There were 74 boys (71.2%) and 30 girls (28.8%). The mean age at the onset of symptoms was 7.3 years, ranging from 9 months to 18 years. Seventy four cases (71%) reported 3 months after onset of symptoms. The spine was the commonest site involved (43%) followed by hip (14.9%) and knee joints (10.3%). Evidence of active or inactive pulmonary tuberculosis was found in 16.2%. All cases were treated by three drug regimen of rifampicin, isoniazid and ethambutol; rifampicin was discontinued after 6 months, ethambutol after 12-14 months. In 12 cases (11.5%) isoniazid was continued for 18 months. Along with chemotherapy suitable braces, splints, tractions, exercises and other form of physical therapy produced satisfactory results. Seventy eight patients (75%) showed clinical and radiological improvement with one year of treatment. The follow up period ranged between 4 months to 24 months with an average of 17 months. Children because of capacity to grow, showed progressive deformity in knee in 3 cases (2.8%), hip in 98 cases (8.6%), shortening of limbs in 14 cases (13.4%) and kyphosis in 13 cases (12.5%).

Adolescent↗
PubMed1991

Structures of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyre ne adducts to guanine-N2 in a duplex dodecamer.

The structures of the mirror image (+)- and (-)-trans-anti-adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene to guanine N2 have been of great interest because the high biological activity of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in mammalian mutagenesis and tumorigenesis has been attributed to the predominant (+)-trans-anti-adduct. We have carried out new potential energy minimization studies, involving wide-scale conformational searches on small modified DNA subunits, followed by energy-minimized build-up techniques, to generate atomic resolution views of these adducts. These energy-minimized duplex dodecamers were then subjected to 100-ps molecular dynamic simulations with solvent and salt to yield animated molecular structures. The most favored computed structure for the (+)-adduct places the pyrenyl moiety in the B-DNA minor groove, with its long axis directed toward the 5' end of the modified strand, and with a pronounced bend in the helix axis. In the (-)-adduct, there are 2 favored structures. One places the pyrenyl moiety in the minor groove, whereas the other positions it in the major groove; in both cases, the pyrenyl long axis is directed more toward the 3' end of the modified strand, and with much less helix axis bend. Structures with intercalation character computed for these adducts are less preferred. The favored computed structures agree with spectroscopic data on the (+)- and (-)-trans-anti-adducts, whereas recent experimental evidence suggests that cis-adducts assume intercalation-type structures. Perhaps the conformational distinctions elucidated for the (+)- and (-)-trans anti-adducts play a role in their differential tumorigenic properties in mammalian systems.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1991

Microbial degradation of pendimethalin.

Microbial degradation of pendimethalin (N-(1-Ethylpropyl)-3, 4-dimethyl-2, 6-dinitroaniline) in vitro was studied. Fusarium oxysporum and Paecilomyces varioti, two soil fungi, in culture media degraded pendimethalin to two metabolites namely N-(1-Ethylpropyl)-3, 4-dimethyl-2-nitrobenzene-1, 6-diamine (II) and 3,4-Dimethyl-2, 6-dinitroaniline (IV). Rhizoctonia bataticola, another soil fungus, decomposed pendimethalin yielding only the latter metabolite (IV). Fungal decomposition of pendimethalin involved nitro reduction and dealkylation.

Aniline Compounds↗
PubMed1990

Coitus induced changes in oviductal motility & effect of progesterone.

Motility of different oviductal segments of conscious rabbits was recorded through permanently implanted sensors using the technique of impedance plethysmography. The implants were around the oviductal wall and therefore did not obstruct its lumen. Pre-ovulatory ampullary motility was always less than the isthmic motility. Coitus induced ovulation produced a characteristic oviductal motility pattern consisting of (i) initial relaxation of both isthmus and ampulla (4-12 h) followed by (ii) increased isthmic motility in the face of a continually relaxed ampulla (36-48 h), and finally phase (iii) leading to restitution of both ampullary and isthmic motility to the base-line at 72-96 h. Estimation of ova positions indicated the presence of fertilized eggs in the ampulla and ampullo-isthmic junction at 48 h and the ova could come to the end of the isthmic segment only at 72 h or after. Increased isthmic motility thus served to counter the transportation of ova and their retention in the ampulla. Rabbits in which oviducts were not taken out for ova positioning achieved normal pregnancy. Administration of progesterone (im, 2.5 mg) produced complete relaxation of both isthmus and ampulla, did not produce increased isthmic contractility on coitus, accelerated the ovum transport rate and inhibited pregnancy, again emphasising the ova retentive role of oviductal motility.

Animals↗
PubMed1989

Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4.

The African tree Combretum caffrum (Combretacae) has been found to contain a powerful inhibitor of tubulin polymerization (IC50 2-3 microM), the growth of murine lymphocytic leukemia (L 1210 and P 388 with ED50 approximately 0.003 microM and human colon cancer cell lines [(e.g. LoVo (ED50 = 0.005 microgram/ml), HT 29 (ED50 0.02 microgram/ml, Colo 205 (ED50 = 0.07 microgram/ml), DLD-1 (ED50 = 0.005 microgram/ml) and HCT-15 (ED50 = 0.0009 microgram/ml] designated combretastatin A-4 (1c). The structure assigned by spectral techniques was confirmed by synthesis.

Animals↗
PubMed1989

Tropical myositis. A clinical immunological and histopathological study.

Thirty cases of tropical myositis, (22 suppurative, 8 non-suppurative) aged 11 to 65 years were seen in a period of one year. There were 22 males and 8 females. There was a total of 78 muscular lesions in 22 suppurative cases and 19 muscular lesions in 8 non-suppurative cases. The most common presentation was localised myalgia (100%), fever (96.7%) generalized myalgia (56.7%), arthralgia (40%), pain in abdomen (33.3%) and breathlessness (30%). Extramuscular complications were present in 50% cases. Twenty four muscle biopsies were taken. Sixteen showed changes of suppurative myositis i.e. non-specific acute inflammatory reaction, muscle necrosis with myocytolysis, vacuolation of cytoplasm and loss of striations. Cell mediated immunity was found to be suppressed in patients of non-suppurative myositis in comparison with the suppurative group. IgG, IgA and IgM were significantly raised in patients in comparison to controls (p less than 0.05). The intact humoral immunity indicates good response to acute phase reaction and increased levels of IgG, IgA and IgM (specially IgG) can be taken as good prognostic parameter.

Abscess↗
PubMed1989

A SEM study of the olfactory lamellae of the catfish Heteropneustes fossilis (Bl.).

The olfactory lamellae of the catfish H. fossilis (Bl.) was studied in the scanning electron microscope. The olfactory lamellae are composed of sensory and non-sensory epithelium. The sensory epithelium contains large numbers of ciliated receptor cells, whereas the non-sensory raphe epithelium is covered with a dense mat of non-sensory cilia. It is not known whether the olfactory cilia possess receptor sites.

Animals↗
PubMed1988

Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study.

Combretastatin, an antineoplastic and antimitotic agent, was isolated from the bark of Combretum caffrum [Can. J. Chem. 60: 1374-1376 (1982); Biochem. Pharmacol. 32:3864-3867 (1983)]. Structurally, combretastatin consists of two substituted benzene rings linked by a saturated, hydroxy-substituted two-carbon bridge. A large number of combretastatin analogs have now been synthesized or obtained from C. caffrum. These vary in substituents on the phenyl rings or bridge carbons, bridge length, unsaturation of the bridge (i.e., stilbene derivatives, with the two phenyl rings oriented either cis or trans), and in precise ring structure (two major variants, with the bridge incorporated into a third six-member ring to form a phenanthrene structure or a methyl group eliminated from vicinal methoxy substituents to form a benzodioxole ring). Available analogs (17 natural products and 22 synthetic agents) were examined for antimitotic and cytotoxic activity and for effects on tubulin polymerization and colchicine binding. Nineteen compounds inhibited cell growth by 50% or more at concentrations of 1 microM or less, and 14 inhibited tubulin polymerization by at least 50% at stoichiometric drug concentrations. The most potent cytotoxic agents generally strongly inhibited both tubulin polymerization and the binding of colchicine to tubulin. The most promising compound is the (cis)-stilbene derivative (cis)-1-(3,4,5-trimethoxyphenyl)-2-(3'-hydroxy-4'-methoxyphenyl)ethene, which has been named combretastatin A-4. This compound inhibited cell growth by 50% at 7 nM, inhibited tubulin polymerization by 50% at 2.5 microM (1/4 molar equivalent), and competitively inhibited colchicine binding with an apparent Ki of 0.14 microM.

Animals↗
PubMed1985

Q fever serologic surveillance program for sheep and goats at a research animal facility.

Since Q fever is a potential risk to personnel working with small ruminants, the serologic status of sheep and goats received at a medical school animal facility for research was evaluated. A total of 104 sheep and 102 goats were subjected to blood sample-collection procedures on arrival, as well as after a 2-week quarantine period, and the sera were tested for Q fever specific antibodies by complement-fixation (CF) and microagglutination (MA) tests. The results from the 2 tests were compared and analyzed for seroconversion. On the basis of the CF test, 14 sheep and 3 goats were considered positive; these included 7 sheep and 2 goats that seroconverted during the quarantine period. In contrast, 1 sheep and 5 goats were found positive by the MA test, which also detected seroconversion of 1 sheep and 1 goat. The use of both tests for serologic surveillance of Q fever in sheep and goats increased the likelihood of detection. Management safety practices are also required to minimize the risk of disease transmission.

Agglutination Tests↗
PubMed1984

Enzyme-linked immunosorbent assay in the diagnosis of Kilham rat virus infection in rats.

An enzyme-linked immunosorbent assay (ELISA) was adapted and compared with the haemagglutination-inhibition (HAI) test for the serological diagnosis of Kilham rat virus (KRV) infection in rats. The assay is a solid phase, indirect method for the measurement of specific antibody. Test variables such as the amount of purified KRV for coating polystyrene microtitre plates, dilution of peroxidase conjugate, etc. were standardized for optimum results. Sera from both naturally and experimentally infected rats were examined, and the ELISA was found to be 5-10 times more sensitive for KRV serology. The kinetics of antibody development during experimental infection, as determined by ELISA, paralleled that of the HAI test and antibodies could be detected as early as 4 days after infection.

Animals↗
PubMed1984

Effects of Kilham rat virus on natural killer cell-mediated cytotoxicity in brown Norway and Wistar Furth rats.

Effects of Kilham rat virus (KRV) on selected aspects of the immune response of 2 strains of laboratory rats were studied. The Brown Norway rat and Wistar Furth rat were infected with KRV and serum antibody and interferon values and cytotoxic activity of natural killer cells were determined to assess the virus' effect on the rat's immune systems. Antibody values to the virus were increased in both strains after viral inoculation, and total antibody values were comparable in the 2 rat strains. Natural cytotoxicity was increased in Brown Norway rats 3 to 4 days after inoculation in contrast to a distinct depression for a period of 10 days in the Wistar Furth strain. Serum interferon was not measurable in either strain of rat. Seemingly, there is a distinct immune response to KRV in each rat strain and the cytotoxic activity response differs in these 2 strains of rats.

Animals↗