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Biomedical subjects

J Das

Publications and source records attributed to J Das.

At least 73 records · Page 4Linked to original sources
PubMed1993

Phage psi 92: a new choleraphage infecting Vibrio cholerae cells belonging to serovars 01 and non-01.

A new choleraphage, psi 92, with an icosahedral head and no tail structure has been described. This phage has a wide host range. It infects and lyses strains belonging to different serovars and biotypes of Vibrio cholerae. The phage utilises host DNA degradation products for its own DNA synthesis. psi 92 contains a linear double-stranded DNA of 56 kbp. A physical map of the phage genome has been constructed using the restriction enzyme KpnI. Intracellular development of phage psi 92 following infection was examined by thin-section electron microscopy.

Bacteriophages↗
PubMed1992

Mathematical characterization of Chaos Game Representation. New algorithms for nucleotide sequence analysis.

Chaos Game Representation (CGR) can recognize patterns in the nucleotide sequences, obtained from databases, of a class of genes using the techniques of fractal structures and by considering DNA sequences as strings composed of four units, G, A, T and C. Such recognition of patterns relies only on visual identification and no mathematical characterization of CGR is known. The present report describes two algorithms that can predict the presence or absence of a stretch of nucleotides in any gene family. The first algorithm can be used to generate DNA sequences represented by any point in the CGR. The second algorithm can simulate known CGR patterns for different gene families by setting the probabilities of occurrence of different di- or trinucleotides by a trial and error process using some guidelines and approximate rules-of-thumb. The validity of the second algorithm has been tested by simulating sequences that can mimic the CGRs of vertebrate non-oncogenes, proto-oncogenes and oncogenes. These algorithms can provide a mathematical basis of the CGR patterns obtained using nucleotide sequences from databases.

Algorithms↗
PubMed1992

Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents.

We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (N1) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino)ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the increased antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.

Animals↗
PubMed1992

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).

Acetylation↗
PubMed1992

Benzazepinone calcium channel blockers. 3. Synthesis and structure-activity studies of 3-alkylbenzazepinones.

As part of a program aimed at identifying novel analogues of diltiazem, we developed several synthetic routes for 3-alkylbenzazepinones, both in racemic and nonracemic form. Structure-activity relationship studies in this series have led to identification of several analogues as potent calcium channel blocking agents, both in vitro and in vivo. Analogues containing a 6-trifluoromethyl substituent (17a and 17b) are the most potent vasorelaxants in vitro. The oral antihypertensive activity of these compounds is comparable to its 3-acetoxy derivative 1 (X = 6-CF3) and 8-chlorodiltiazem (2b). The 3-allyl analogue 17c is a more potent antihypertensive agent than 17a, 17b, or 8-chlorodiltiazem (2b), and has a longer duration of action in vivo.

Animals↗
PubMed1992

Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site.

We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pKa in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers.

Benzazepines↗
PubMed1992

Leiomyosarcoma of the orbit: diagnosis of its recurrence by fine-needle aspiration cytology.

An 8 1/2-yr-old boy with proptosis was diagnosed to have low-grade leiomyosarcoma of the orbit following lateral orbitotomy and histology of an incompletely excised intraconal mass. He received chemotherapy but had recurrence of proptosis at the age of 12 yr. Ultrasonography revealed a solid mass and its fine-needle aspiration cytology features were consistent with recurrence of leiomyosarcoma. A year later, the cytodiagnosis was confirmed by histology of the excised tumor from a second lateral orbitotomy. Masson's trichrome stain confirmed the smooth muscle nature of the neoplasm and ultrastructural features were in favor of leiomyosarcoma. The patient received intermittent chemotherapy, and is clinically free from disease at the age of 17 yr.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Presence of exposed phospholipids in the outer membrane of Vibrio cholerae.

Vibrio cholerae 569B was found to be highly sensitive to a wide range of chemicals, particularly hydrophobic compounds and neutral and anionic detergents. The phospholipid profile of the outer membrane was similar to that reported for other Gram-negative bacteria. The lipopolysaccharide (LPS) contained O-antigenic sugars and exhibited heterogeneity. In addition, the LPS moiety was characterized by a relatively low negative charge. Analysis by topological probes revealed the presence of a significant amount of exposed phospholipids in the outer membrane. The reduced negative charge of LPS molecules and the exposed phospholipids present in the outer membrane could be important in the increased permeation of exogenous compounds in V. cholerae.

Binding Sites↗
PubMed1992

Interaction of Vibrio cholerae cells with beta-lactam antibiotics: emergence of resistant cells at a high frequency.

Unlike other gram-negative enteric bacteria, Vibrio cholerae cells were equally susceptible to penicillin and ampicillin and in general more susceptible than Escherichia coli to most of the beta-lactam antibiotics. The turbidity of penicillin-treated cultures contained to increase exponentially for about 3 h, although the cell viability declined rapidly within 30 min of penicillin addition. Prolonged treatment with beta-lactam antibiotics produced cells resistant to these antibiotics. A fluctuation test indicated that this resistance might be due to adaptive mutation. Cells resistant to a beta-lactam exhibited broad cross-resistance to other beta-lactam antibiotics. A new 12,000-Da outer membrane protein was detected both in beta-lactam-resistant cells and in wild-type cells growing in medium containing beta-lactam antibiotics. While the penicillin-resistant cells had all of the penicillin-binding proteins (PBPs) present in the parental cells, significant differences in the relative proportion of low-molecular-weight PBPs were seen. The low-molecular-weight PBPs from resistant cells seemed to form more stable complexes with penicillin than those from the parental strain.

Anti-Bacterial Agents↗
PubMed1992

Cell surface characteristics of environmental and clinical isolates of Vibrio cholerae non-O1.

The cell surfaces of several toxigenic and nontoxigenic environmental and clinical isolates of Vibrio cholerae non-O1 have been examined. The environmental strains, irrespective of toxigenicity, are significantly more resistant to antibiotics and detergents than are V. cholerae O1 strains. The clinical isolates of non-O1 vibrios are as sensitive to a wide variety of chemicals as the O1 vibrios. The environmental non-O1 strains are also less susceptible to lysis when treated with protein denaturants or neutral and anionic detergents than are O1 vibrios and the clinical non-O1 strains. In contrast to O1 vibrios, the environmental non-O1 vibrios do not have exposed phospholipids in their outer membranes. These features of the cell surfaces of environmental non-O1 vibrios might have a role in the better survival of these organisms under environmental fluctuations.

Anti-Bacterial Agents↗
PubMed1992

A 14-kilodalton inner membrane protein of Vibrio cholerae biotype e1 tor confers resistance to group IV choleraphage infection to classical vibrios.

Choleraphage phi 149 differentiates the two biotypes, classical and el tor, of Vibrio cholerae. This phage cannot replicate in V. cholerae biotype el tor cells because the concatemeric DNA intermediates produced are unstable and cannot be chased to mature phage DNA. A V. cholerae biotype el tor gene coding for a 14,000-Da inner membrane protein which destabilizes the concatemeric DNA intermediates by hindering their binding to the cell membrane has been identified. Presumably, a 22,000-Da V. cholerae biotype el tor protein might also have a role in conferring phage phi 149 resistance to cells belonging to the biotype el tor. A nucleotide sequence homologous to the 1.2-kb V. cholerae biotype el tor DNA coding for both the 14,000- and 22,000-Da proteins is present in all strains of classical vibrios but is not transcribed. The nucleotide sequence of the gene coding for the 14,000-Da protein has been determined.

Amino Acid Sequence↗
PubMed1991

Transformation of Vibrio cholerae by plasmid DNA.

The lack of an efficient transformation system in Vibrio cholerae was a handicap in the genetic manipulation of this important human pathogen. Since V. cholerae cells secrete DNases, this may interfere with the uptake of DNA. The present report describes the approaches taken for transforming V. cholerae cells with plasmid DNA, by overcoming this DNase barrier. The partial success of transforming DNase-negative mutants confirmed the role of DNase in the nontransformability of the wild-type cells. Successful transformation was carried out following removal of DNases from the periplasmic space. This was achieved by treating the cells with Mg2+ and Ca2+ ions to allow the DNase to be released, and then holding them under conditions where the remaining DNase activity was minimized before adding DNA to the competent cells. Transformation efficiencies of the order of 10(-5) per recipient cell were observed.

Calcium↗
PubMed1991

Rapid high voltage isoelectric focusing of proteins in rod gels.

A rapid procedure of isoelectric focusing (IEF) of proteins in polyacrylamide rod gels (i.d., 1.1 mm; length, 7.5 cm) is described. The time required for IEF can be reduced to 0.5 h by using high voltages up to 3000 V in the presence or absence of urea in the gels. When used as the first dimension of a two-dimensional technique for IEF sodium dodecyl sulphate electrophoresis, high voltage IEF gives smaller protein spots on the second dimension gel, associated with an increase in resolution. The method has been tested by a two-dimensional separation of an eye sample of the goodeid fish Xenotoca eiseni.

Animals↗