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Biomedical subjects

G Das

Publications and source records attributed to G Das.

At least 109 records · Page 6Linked to original sources

Correlation of urine cytology with ABO(H) antigenicity in transitional cell carcinoma of the bladder.

Cell surface ABO(H) antigenicity of superficial bladder tumours was assessed by the indirect immunoperoxidase test in 49 patients. Good correlation was obtained between surface antigenicity of tumours and the results of urine cytology. Malignant cells were detected cytologically in 22(56%) of cases with ABO(H) antigen negative tumours which are known to behave more aggressively than ABO(H) antigen positive ones. In contrast, malignant cells were found in the urine cytology of only one (10%) of patients with ABO(H) antigen positive tumours.

ABO Blood-Group System↗

Generalized convulsions in a patient receiving ultrashort-acting beta-blocker infusion.

Beta-receptor blocking agents are commonly used to treat patients with heart disease, and generalized seizures due to therapy with these agents are rare. All reported cases of seizures due to beta blocking agents have occurred only in those subjects who ingested large doses of the drugs. We observed generalized convulsions in a patient who was receiving therapeutic doses of an ultrashort-acting beta-blocking agent (esmolol hydrochloride) intravenously. A literature survey and possible mechanisms by which these agents induce seizures are presented.

Adrenergic beta-Antagonists↗

Esmolol in the treatment of supraventricular tachyarrhythmias.

Infusion of esmolol, an ultra short acting beta-blocker was used in the acute management of 48 patients with supraventricular tachyarrhythmias. Following acute control of the heart rate, patients received maintenance of esmolol infusion for 6 h when they were transferred to alternate oral antiarrhythmic agents. Prompt control of heart rate (mean +/- SD, 15 +/- 8.8 mins) was achieved in 85% of patients with esmolol at a dose rate of 80 +/- 59 micrograms/kg/min. Ninety percent of these subjects were successfully transferred to alternate oral therapy. Five subjects experienced transient side effects. Esmolol was highly effective and particularly suitable for the acute management of patients with supraventricular tachyarrhythmias.

Adrenergic beta-Antagonists↗

Fundamentals of calcium channel blockers.

The important role calcium ions play in cellular function and specifically in muscular contraction has been well established. The details of the calcium migration into the cell and its specific mechanism of action however have only recently been elucidated. Still, our current understanding of these issues represents only a tip of the iceberg. The introduction of the calcium channel blockers have heralded to some extent a new revolution in the management of many cellular disfunctions (disease states) which are, in part, related to and are dependent on the migration of calcium ions across the cell membrane. In this article, an overview of the current understanding of the role of calcium ions in cellular function with special attention to the cardiovascular system is presented. In addition, the mechanism of action of the calcium channel blockers is discussed. Finally, the usefulness of these agents in clinical medicine is mentioned, and a review of several major studies demonstrating beneficial effects of calcium channel blockers in various disorders is presented.

Angina Pectoris↗

Extracorporeal shockwave lithotripsy: first 1000 cases at the London Stone Clinic.

One thousand patients underwent extracorporeal shockwave lithotripsy for renal and ureteric calculi at this clinic. An overall success rate of 91.8% was achieved (stone free or less than 2 mm fragments at three months) and for stones measuring 1 cm 96.3%. Lithotripsy produced extremely low morbidity, and no deaths have occurred at the clinic. Patients who had lithotripsy alone had a mean hospital stay of three days and in most instances were able to perform their full range of activities on discharge. Planned combination of lithotripsy with minimally invasive endourological procedures such as percutaneous nephrolithotomy and ureterorenoscopy has allowed us to extend the range of treatable cases to include large stones. Prophylactic use of Double-J ureteric stents in selected cases has reduced the incidence of obstruction by stone fragments after lithotripsy, thereby decreasing morbidity and hospital stay.

Adolescent↗

Structure, organization, and transcription of Drosophila U6 small nuclear RNA genes.

U6 RNA is an abundant, capped small nuclear RNA (snRNA) associated with hnRNP particles (Reddy, R., and Busch, H. (1983) Prog. Nucleic Acid Res. Mol. Biol. 30, 127-162). Small nuclear ribonucleoprotein particles containing U4 and U6 RNAs are required components for splicing of pre-mRNAs (Berget and Robberson, 1986; Black and Steitz, 1986). In this study the Drosophila U6 RNA genes have been isolated and characterized. The Drosophila genome contains three U6 snRNA genes which are clustered in a 2-kilobase-pairs long DNA fragment. The U6 RNA coding regions are 100% homologous in all three genes, but the flanking sequences diverged significantly from each other. A possible secondary structure model for the Drosophila U4/U6 RNA complex is presented. Consistent with our previous observation that U6 RNA is a RNA polymerase III product (Reddy, R., Henning, D., Das, G., Harless, M., and Wright, D. (1987) J. Biol. Chem. 262, 75-81), all three genes contained a region homologous to the consensus intragenic regulatory region and a cluster of T residues on the 3'-end, characteristic of genes transcribed by RNA polymerase III. A TATA box was found between nucleotides -23 and -31, and a stretch of 28 nucleotides from -43 to -71 was conserved in the 5'-flanking region of all three U6 RNA genes. The Drosophila U6 RNA genes were transcribed in vitro by Drosophila nuclear extracts but were not transcribed by Novikoff hepatoma or HeLa cell extracts. Similarly, a mouse U6 RNA gene was transcribed in Novikoff hepatoma or HeLa cell extracts but not in Drosophila nuclear extracts. These results suggest that species-specific factor(s) are involved in the transcription of U6 snRNA genes.

Animals↗

The capped U6 small nuclear RNA is transcribed by RNA polymerase III.

U6 RNA is an abundant, capped, small nuclear RNA (snRNA) species associated with heterogeneous nuclear ribonucleoproteins in eukaryotic cells. U4 RNA and U6 RNA are hydrogen bonded in a 1:1 ratio in discrete small nuclear ribonucleoprotein particles that are required in pre-mRNA processing. Previous reports have established that the mRNAs and U1 to U5 U-snRNAs are synthesized by RNA polymerase II. Evidence is presented here for synthesis of U6 RNA by RNA polymerase III. The synthesis of U6 RNA in vitro, using Novikoff hepatoma or HeLa whole cell extracts, was not inhibited at low (1 microgram/ml) concentrations of alpha-amanitin, and only 35% inhibition occurred at 10 micrograms/ml concentration. The in vitro synthesized U6 RNA, like other RNA polymerase III transcripts, was associated with La antigen. The U6 RNA synthesized in vitro by the whole cell extracts was capped, but no other internal post-transcriptional modifications were found. Uridylic acid residues were also added post-transcriptionally to the 3'-end of U6 RNA in vitro. U6 RNA, though capped on its 5'-end, is transcribed by RNA polymerase III; this is the first report of a capped RNA molecule synthesized by RNA polymerase III.

Amanitins↗

Amino acid replacements in yeast iso-1-cytochrome c. Comparison with the phylogenetic series and the tertiary structure of related cytochromes c.

The structural and folding requirements of eukaryotic cytochromes c have been investigated by determining the appropriate DNA sequences of a collection of 46 independent cyc 1 missense mutations obtained in the yeast Saccharomyces cerevisiae and by deducing the corresponding amino acid replacements that abolish function of iso-1-cytochrome c. A total of 33 different replacements at 19 amino acid positions were uncovered in this and previous studies. Because all of these nonfunctional iso-1-cytochromes c are produced at far below the normal level and because a representative number are labile in vitro, most of the replacements appear to be affecting stability of the protein or heme attachment. By considering the tertiary structure of related cytochromes c, the loss of function of most of the mutant iso-1-cytochromes c could be attributed to either replacements of critical residues that directly interact with the heme group or to replacements that disrupt the proper folding of the protein. The replacements of residues interacting with the heme group include those required for covalent attachment (Cys-19 and Cys-22), ligand formation (His-23 and Met-85), and formation of the immediate heme environment (Leu-37, Tyr-53, Trp-64, and Leu-73). Proper folding of the protein is prevented by replacements of glycine residues at sites that cannot accommodate side chains (Gly-11 and Gly-34); by replacements of residues with proline, which limit the torsion angle (Leu-14 and His-38); and by replacements apparently unable to direct the local folding of the backbone into the proper conformation (Pro-35, Tyr-72, Asn-75, Pro-76, Lys-84, Leu-99, and Leu-103). Even though most of the missense mutations occurred at sites corresponding to evolutionarily invariant or conserved residues, a consideration of the replacements in functional revertants indicates that the requirement for residues evolutionarily preserved is less stringent than commonly assumed.

Alleles↗

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

Adrenergic beta-Antagonists↗

Mutational alterations induced in yeast by ionizing radiation.

The cycl-9 ochre (UAA) mutant and the cycl-179 amber (UAG) mutant of the yeast Saccharomyces cerevisiae were reverted with X-rays and alpha-particles. The amino acid sequence changes of iso-1-cytochromes c from 36 of the intragenic revertants were determined by amino acid analysis and peptide mapping, aided by partial amino acid sequencing of 4 revertants. In addition, the DNA segments encompassing 3 unusual mutations with complex changes were cloned and sequenced. This study and previous studies of 16 other revertants of cycl-9 and cycl-179 revealed that ionizing radiation primarily induces single base-pair substitutions; 47 of the 52 revertants arose by transversions and transitions without any apparent preference. However, the A X T----T X A substitution at the first base pair for the cycl-179 UAG codon, leading to the normal protein, was not detected, nor was it found previously in 32 revertants of cycl-179 obtained spontaneously or induced with various other mutagens; apparently, there is a prohibition of certain base-pair substitutions at certain sites in DNA. In addition, 5 of the 52 revertants arose by multiple changes within a short region of 11 base pairs. These consisted of the deletion of 6 base pairs, the substitution of 3 base pairs, and 3 different kinds of substitutions of two base pairs. Compared to other mutagens previously tested with the cycl system, ionizing radiation produces the most random types of base-pair substitutions.

Alpha Particles↗

Prognostic significance of ABH antigenicity of mucosal biopsies in superficial bladder cancer.

ABH antigenicity of mucosal biopsies was studied in 36 patients with superficial bladder cancer. Those with mucosal biopsies positive for antigen had a recurrence rate of 0.33 recurrences per year, compared to 1.97 in those negative for antigen. This difference was highly significant on statistical analysis. ABH antigenicity of mucosal biopsies proved to be a better predictor of recurrent disease than other prognostic indexes, such as number, size, histological grade and ABH antigenicity of primary tumors, as well as histological status of the mucosal biopsies.

ABO Blood-Group System↗

REV7, a new gene concerned with UV mutagenesis in yeast.

Three allelic mutations of a new yeast gene, which we have named REV7, have been isolated by testing 313 methyl methane sulfonate sensitive mutants for UV-induced reversion of a lys2 allele. Rev7 mutants are markedly deficient with respect to UV-induced reversion of lys2, are slightly sensitive to UV and appear to be in the RAD6 epistasis group for UV survival. Rev7-1, which is probably an amber mutation, does not appear to affect sporulation in homozygous diploids. The REV7 gene is located about 12 cM distal to HIS5 on chromosome IX.

Chromosome Mapping↗

Invasive potential of superficial bladder cancer. A study of the relative merits of predictive parameters.

The indirect immunoperoxidase test to detect urothelial cell surface blood group antigens was performed in an attempt to assess the loss of these antigens as a prognostic predictor. In our technique A, B and O(H) blood group specific monoclonal antibodies were used. It was possible to perform the test satisfactorily on histological material from 55 cases which were superficial on presentation; 15 subsequently became invasive. The loss of surface antigens correlated well with histological grade--44.4% of G1, 87.2% of G2 and 94.1% of G3 tumours were antigen-negative. The blood group phenotype of 114 patients was studied. In the group that subsequently became invasive, 14 of 26 (54%) were of blood group A phenotype compared with 37 of 88 (42%) in the non-invasive category. Acetylation studies were performed on 47 cases. In the group that subsequently became invasive, 5 of 10 (50%) had the slow phenotype of the enzyme N-acetyltransferase compared with 13 of 37 (35%) in the group that remained superficial.

Acetylation↗