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Biomedical subjects

R Misra

Publications and source records attributed to R Misra.

At least 145 records · Page 8Linked to original sources
PubMed1986

Magnetic resonance studies of fredericamycin A: evidence for O2-dependent free-radical formation.

Fredericamycin A, a newly described potent antitumor antibiotic, exhibits unusual spectroscopic and physical properties. The drug shows a striking color change from red to blue on exposure to O2, with the appearance of an optical absorption band at 675 nm; on addition of acid these changes are readily reversed. 1H and 13C NMR spectra of fredericamycin A show that the resonances from the quininoid half of the molecule disappear after exposure to O2 but reappear on acidification in parallel with the observed optical spectral shift. These unusual NMR data are explained by electron spin resonance studies which demonstrate that fredericamycin A spontaneously forms an oxidized free radical with electron transfer to O2. The observed hyperfine structure of this radical is consistent with one-electron oxidation of the quininoid group. After fredericamycin A is exposed to O2, an EPR signal is observed with axial symmetry with temperature and power saturation behavior suggestive of .O2-. Spin-trapping EPR studies demonstrate that the drug reduces O2 to .O2- and H2O2 to .OH. This spontaneous mechanism of O2 reduction with the generation of oxidized drug free radicals and reduced oxygen free radicals is unprecedented among anticancer drugs, suggesting that fredericamycin A could be the forerunner of a new class of anticancer drug.

Antibiotics, Antineoplastic↗
PubMed1986

Systemic lupus erythematosus in North Indian Asians. A prospective analysis of clinical and immunological features.

One hundred and one patients with systemic lupus erythematosus (SLE) from North Indian stock are presented. The clinical manifestations, laboratory parameters, causes of death, and survival are compared and contrasted with the other major reported series. SLE of North Indian Asians has several features comparable to those reported from the West, but other features are more similar to the SLE seen in Mongoloid races.

Antibodies, Antinuclear↗
PubMed1986

Neuromyelitis optica: a case report from India.

A young Indian male was admitted for paraplegia of acute onset and with bilateral optic neuritis. The diagnosis of neuromyelitis optica was made. This is possibly the first case report of its kind from India.

Adult↗
PubMed1985

Intermediates in the synthesis of TolC protein include an incomplete peptide stalled at a rare Arg codon.

TolC is a minor outer membrane protein of Escherichia coli K 12 and is initially synthesized as a precursor. A distinct intermediate polypeptide of Mr about 46 000 was consistently observed at the initial stages of biosynthesis. The further elongation of this peptide can be blocked by chloramphenicol. We have investigated the cause of the temporary accumulation of the 46 000-Mr intermediate and we postulate that the presence of a rare codon AGA (Arg) at codon 402 of the tolC mRNA halts translating ribosomes owing to a limiting amount of the tRNAArg (AGA) species in the cell. The translation of tolC mRNA can be increased by providing T4 tRNAArg (AGA), encoded on a plasmid.

Arginine↗
PubMed1985

Biosynthesis of fredericamycin A, a new antitumor antibiotic.

Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented.

Acetates↗
PubMed1985

Extrachromosomal DNA in eucaryotes.

Eucaryotic extrachromosomal DNAs have been organized into four major classes: (1) Organelle DNAs, (2) plasmid DNAs, (3) amplified genes, and (4) intermediates and/or by-products of DNA transpositions and rearrangements. In this review some of the relatively well-characterized members of each class are described; it is suggested that many of them reflect the complexity and plasticity of eucaryotic genomes.

Animals↗
PubMed1985

Molecular characterisation of the Stc- mutation of Escherichia coli K-12.

The previously described Stc- (suppressor of TolC) mutation modifies the phenotype of tolC mutants from OmpF- to OmpF+. Restriction mapping of chromosomal DNA from Stc+ and Stc- strains was performed to investigate the nature of the mutation which was shown to be a deletion, upstream of the ompC gene. DNA from the region of the deletion was cloned into pUC18 and a 650-bp PstI-EcoRI fragment was sequenced. The deletion started 49 bp upstream of the AUG start codon of the ompC gene, thus removing part of the ompC promoter and the whole of the micF gene. We suggest that the deletion of micF gives rise to the Stc- phenotype since the effect of micF expression is assumed to reduce ompF expression, and the Stc- phenotype involves increase in ompF expression.

Bacterial Outer Membrane Proteins↗
PubMed1983

The TolC protein of Escherichia coli K12 is synthesised in a precursor form.

We examined the biosynthesis of the TolC protein of Escherichia coli K12 in a pulse-chase experiment, followed by immunoprecipitation with anti-TolC antibody and SDS-PAGE of the immunoprecipitate. This showed that TolC protein was originally synthesised in a precursor form (Mr 54 500) which could be chased into the mature form (Mr 52 000). DNA sequencing of a portion of the cloned tolC gene showed that the N-terminus of the mature rotein was preceded by a typical signal sequence of 22 residues (Mr 2542). The initiator Met was preceded by a Shine-Dalgarno sequence, with the correct spacing.

Bacterial Proteins↗
PubMed1983

Kpn I family of long-dispersed repeated DNA sequences of man: evidence for entry into genomic DNA of DNA copies of poly(A)-terminated Kpn I RNAs.

We have isolated eight cDNA clones complementary to the human Kpn I repeat and determined the base sequence of three. We have also determined a portion of the base sequences of three human Kpn I family members. The three cDNA sequences are extensively homologous with the 3' ends of the three genomic Kpn I family members and with a simian Kpn I family member recently described [Thayer, R. E. & Singer, M. F. (1983) Mol. Cell. Biol. 6, 967-973]. The genomic repeats terminate in regions of sequence rich in dAMP residues close to sequences at the 3' ends of the cDNA clones; a precise 3'-terminal nucleotide cannot be distinguished. These structural features are consistent with the dispersal of at least some Kpn I family members by entry into genomic DNA of copies of Kpn I RNA transcripts. Each cDNA contains a long poly(dAMP) homopolymer at its 3' end and either one or two A-A-T-A-A-A polyadenylylation signal sequences upstream from it, suggesting that Kpn I family members may be transcribed by RNA polymerase II.

Base Sequence↗