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S K Arora

Publications and source records attributed to S K Arora.

At least 19 recordsLinked to original sources

Genetic nature of vitiligo.

Four hundred vitiligo patients and 100 non-vitiliginous controls were studied to find out the prevalence of vitiligo in relatives of patients and controls. The difference was found to be statistically highly significant. The data reflected that there is some genetic mechanism involved in the etiology of vitiligo. Respective relatives of all forms of the disease in the vitiligo group showed a clear preponderance compared to controls. There was clustering of affected relatives in vitiligo cases compared to controls. The ratio of affected and unaffected siblings with unaffected parents or one parent affected, the ratio in the children of probands, the ratio in children of affected paternal and maternal grandparents of probands, suggest the polygenic nature of vitiligo.

Adult

Humoral antibody response in Leishmania tropica infection.

A small epidemic of Leishmania tropica infection was detected in Rajasthan, India. Most cases were in the 21-25 years age group and were possibly related to outdoor activity. Nearly one third of the patients had more than five lesions, the maximum number of lesions being confined to the face, neck and extremities. As determined by ELISA, 90% cases had leishmania antibodies with an OD range of 0.8-1.1. The serum of 60% of patients was positive by CIEP against L. tropica promastigote soluble antigen. By immunofluorescence, 96% persons were positive when L. tropica promastigotes were used as the substrate. The prevalence of infection with L. tropica appears to be much higher than that reported earlier.

Adolescent

Detection of leishmania antigen in kala azar patients using monoclonal antibodies.

Twenty-one monoclonal antibodies were produced against promastigote antigens of Leishmania donovani. Five monoclonal antibodies (Hyb.17, 6, 5, 4 and 2) identifying molecules associated with various L. donovani antigenic determinants ranging from 42-116 kDa were selected as 'capture antibodies' and compared with specific anti-leishmania antisera for detection of circulating leishmania antigens in kala azar patients' sera in a competitive-enzyme-linked immunosorbent assay system (ELISA). The anti-leishmania antisera could detect circulating antigen in 30% of kala azar cases while out of the five monoclonals, Hyb.17 could effectively detect circulating leishmania antigen in 85.4%. The efficacy of Hyb.6 was however low (31.7%). The antigens recognized by these monoclonal antibodies in the western blot assay could possibly represent the ones circulating in sera of patients suffering from kala azar. A cocktail of these monoclonal antibodies may be more useful than the conventional polyclonal antisera in detection of circulating antigen for clinical diagnosis of kala azar.

Animals

Use of in vitro method to assess different brands of anti-leishmanial drugs.

Reports in the literature indicate the use of animal models for testing newer anti-leishmanial drugs in vivo. However, in certain established cell lines and macrophages in vitro models have the advantage over the in vivo system of simplicity and speed with which the results can be obtained. A simple in vitro system using peritoneal exudate macrophages of BALB/c mice infected with Leishmania donovani promastigotes has been tested for its use in determining the efficacy of several new drugs. Two well-established drugs, amphotericin B and sodium stibogluconate, as expected, could kill the intracellular parasites effectively. Two relatively new drugs not routinely used against leishmania, rifampicin and metronidazole at concentrations of 20 micrograms/ml and 10 micrograms/ml, respectively, were also able to kill the intracellular leishmania parasites effectively. Critical factors for drug testing in vitro have been elucidated: the most important being the temperature of incubation after infection.

Animals

Cloning of a catabolite repression control (crc) gene from Pseudomonas aeruginosa, expression of the gene in Escherichia coli, and identification of the gene product in Pseudomonas aeruginosa.

Mutants which are defective in catabolite repression control (CRC) of multiple independently regulated catabolic pathways have been previously described. The mutations were mapped at 11 min on the Pseudomonas aeruginosa chromosome and designated crc. This report describes the cloning of a gene which restores normal CRC to these Crc- mutants in trans. The gene expressing this CRC activity was subcloned on a 2-kb piece of DNA. When this 2-kb fragment was placed in a plasmid behind a phage T7 promoter and transcribed by T7 RNA polymerase, a soluble protein with a molecular weight (MW) of about 30,000 was produced in Escherichia coli. A soluble protein of identical size was overproduced in a Crc- mutant when it contained the 2-kb fragment on a multicopy plasmid. This protein could not be detected in the mutant containing the vector without the 2-kb insert or with no plasmid. When a 0.3-kb AccI fragment was removed from the crc gene and replaced with a kanamycin resistance cassette, the interrupted crc gene no longer restored CRC to the mutant, and the mutant containing the interrupted gene no longer overproduced the 30,000-MW protein. Pools of intracellular cyclic AMP and the activities of adenylate cyclase and phosphodiesterase were measured in mutant and wild-type strains with and without a plasmid containing the crc gene. No consistent differences between any strains were found in any case. These results provide original evidence for a 30,000-MW protein encoded by crc+ that is required for wild-type CRC in P. aeruginosa and confirms earlier reports that the mode of CRC is cyclic AMP independent in this bacterium.

3',5'-Cyclic-AMP Phosphodiesterases

Naphthyridinomycin-DNA adducts: a molecular modeling study.

Monocovalent groove binding complexes of antitumor antibiotic naphthyridinomycin and its analogs with DNA sequence d(ATGCAT)2 have been studied by molecular mechanics to understand which enantiomer of the drug and what chirality at C(7) of the drug are preferred for forming better drug-DNA adducts. The effect of hydroquinone intermediate and the substitution at C(11) on drug-DNA interactions have also been investigated. The results indicate that the enantiomer that forms the best adduct is different from the one reported earlier in the literature. The drug with an R configuration at C(7) is preferred for binding. The hydroquinone models do not necessarily provide a given analog of the drug with additional favorable DNA interactions. The substitution at C(11) by OH provides the best binding model. This finding agrees well with the results from previous biochemical studies. The sequence specific studies indicate that the sequence d(ATGCAT)2 is slightly preferred over others.

Base Sequence

Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X-ray, NMR, and molecular mechanics.

X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five-membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross-linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic.

Antibiotics, Antineoplastic

Structural and conformational analysis of pentostatin (2'-deoxycoformycin), a potent inhibitor of adenosine deaminase.

X-ray, NMR and molecular mechanics studies on pentostatin (C11H16N4O4), a potent inhibitor of the enzyme adenosine deaminase, have been carried out to study the structure and conformation. The crystals belong to the monoclinic space group P21 with the cell dimensions of a = 4.960(1), b = 10.746(3), c = 11.279(4)A, beta = 101.18(2) degrees and Z = 2. The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.047 for 997 reflections. The trihydrodiazepine ring is nonplanar and adopts a distorted sofa conformation with C(7) deviated from the mean plane by 0.66A. The deoxyribose ring adopts a C3'-endo conformation, different from coformycin where the sugar has a C2'-endo conformation. The observed glycosidic torsion angle (chi = -119.5 degrees) is in the anti range. The conformation about the C(4')-C(5') bond is gauche+. The conformation of the molecule is compared with that of coformycin and 2-azacoformycin. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. The conformation of deoxyribose in solution is approximately 70% S and 30% N. Molecular mechanics studies were performed to obtain the energy minimized conformation, which is compared with X-ray and NMR results.

Adenosine Deaminase Inhibitors

Changing phage pattern of Staphylococcus in pyoderma cases.

Staphylococcus aureus is a major pathogen for pyoderma in India. Phage pattern of bacteria gives valuable information in epidemiological studies of infection. Two hundred and two strains of Staphylococcus aureus isolated from pyoderma cases at Gorakhpur, were phage grouped and phage typed. It was found that 43.1 percent strains were not typable. Most common group was mixed phage group (23.8 percent) followed by phage group III (12.4 percent). Predominant phage types in mixed phage group was 84/81/85 and in phage group III was 84/85.

Bacteriophage Typing

Plain radiograph skull: is it really needed in epilepsy?

One hundred and three children with seizure disorder were studied. Plain radiograph skull was normal in all the cases. CT scan skull done in 34 patients, showed abnormalities in 24 cases. More than 80% children in partial seizures group had treatable lesions on CT scans, mainly CNS tuberculoma. The need for omitting plain radiograph skull as a routine investigation for epilepsy cases is emphasized.

Brain

Receptor-mediated drug delivery to macrophages in chemotherapy of leishmaniasis.

Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the "scavenger" receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.

Albumins

Identification of major antigens of Leishmania donovani using kala azar sera.

The study was conducted with the prime objective of isolating an antigen from the crude preparation of whole promastigotes (Leishmania donovani) with a view to future exploitation in serodiagnosis and production of monoclonal antibodies. Soluble antigen, prepared from promastigotes isolated from actively growing cultures, was fractionated by gel filtration chromatography over a column of Sephadex G200. Three peaks of proteins could be recovered. The antigenic reactivity of different fractions was checked against sera of kala azar patients by immunoelectrophoresis (IEP), rocket immunoelectrophoresis (RIEP) and enzyme-linked immunosorbent assay (ELISA). The first peak was found to be highly reactive in comparison with other peaks. SDS-PAGE and western blot analysis of this antigen revealed a major antigen of promastigotes in the vicinity of 65 to 66 kDa, while a weakly reactive triplet could also be detected in the low molecular weight region.

Animals

Pattern of leprosy disabilities in Gorakhpur (Uttar Pradesh).

Out of 514 leprosy cases studied, 229(44.56%) had disability. Disability was most commonly seen in lepromatous leprosy. There was an increasing trend in disability with increasing age of patient and duration of disease. Disability rate was higher in males as compared to females. Nerve thickening and reactional states were more common in disabled cases. Dapsone treated group showed a disability rate of 63.8% as compared to 30.0% in untreated group. Hand was the most commonly affected site and mobile claw hand was the single most common disability. The overall disability index-D.I. (2) of Bachelli was 1.25 and lepromatous cases had highest D.I. (1.89). Disability index was higher in males and was found to increase with increasing age of patient and duration of disease.

Adolescent