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Biomedical subjects

R Balasubramanian

Publications and source records attributed to R Balasubramanian.

At least 55 records · Page 3Linked to original sources

Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.

A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.

Adolescent↗

A new technique in computer modeling of molecules with transparency effect, due to partially stripped surfaces.

Conventional space filling molecular modeling in computers, using the scan method, takes considerable computer time and effort. In depicting the CPK-image on a computer screen, the hidden-point removal is the main task and on such an image, the front-line atoms hide the back-benchers and their whereabouts become completely unknown, in a given view of the picture. While in search of a simple and faster algorithm for producing surface graphics of molecules, we have developed a novel method, which is considerably faster than the conventional one and it has an interesting transparency-effect which would be useful in the various fields of molecular designs.

Algorithms↗

Effect of wheat bran on bowel function and fecal calcium in older adults.

Seven healthy older volunteers participated in a 33-day study consisting of three sample collection periods, a 10-day control, and two 10-day experimental periods. Subjects consumed their usual self-selected diets throughout and a daily wheat bran supplement (30 g) during the two experimental periods. Food intake was recorded daily by subjects and accuracy and completeness checked daily by personal interview. Apparent calcium absorption decreased significantly from 22.1 +/- 5.6% (mean +/- SD) during the control to 8.6 +/- 5.2% during the second bran period. The wheat bran supplement significantly increased wet and dry stool weights but had no effect on stool moisture or defecation frequency. Gastrointestinal transit time of a dose of chromium decreased significantly, from 75 +/- 33 to 54 +/- 19 hr; of a dose of polyethylene glycol insignificantly, from 98 +/- 59 to 69 +/- 46 hr. Mean recovery of 21 doses of chromium of 98.7 +/- 5.0% verified that stool collection was complete. The results suggest that the ability of wheat bran to regulate bowel function in the apparently healthy older adult may be accompanied by increased fecal calcium losses similar to what has been reported for younger adults.

Aged↗

Name that beat.

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Electrocardiography↗

Mutagenicity of benzylic acetates, sulfates and bromides of polycyclic aromatic hydrocarbons.

Studies were performed to determine the direct mutagenicity of the acetates and some bromides and sulfates of hydroxymethyl polycyclic aromatic hydrocarbons in S. typhimurium strains TA98 and TA100. Benzylic acetates, bromides and sulfates were synthesized and characterized. The compounds tested were benzyl alcohol, 5-hydroxymethylchrysene, 1-hydroxymethylpyrene, 6-hydroxymethylbenzo[a]pyrene, 6-(2-hydroxyethyl)benzo[a]pyrene, 6-hydroxymethylanthanthrene, 9-hydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene, 7-hydroxymethylbenz[a]anthracene, 7-(2-hydroxyethyl)benz[a]anthracene, 12-hydroxymethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 12-hydroxymethyl-7-methylbenz[a]anthracene, 1-hydroxy-3-methylcholanthrene, 2-hydroxy-3-methylcholanthrene, 3-hydroxy-3, 4-dihydrocyclopental[cd]pyrene and 4-hydroxy-3, 4-dihydrocyclopental[cd]pyrene. The benzylic sulfate esters of 6-hydroxymethylbenzo[a]pyrene and 7-hydroxymethylbenz[a]anthracene were the most mutagenic compounds, whereas the aliphatic sulfate ester of 7-hydroxyethylbenz[a]anthracene did not cause an increase in mutations above background. All meso-anthracenic benzylic acetate esters were mutagenic in both strains with various degrees of activity, whereas the corresponding non-benzylic esters were inactive, as expected. Of the non-meso-benzylic acetate esters, only the 3-acetoxy-3, 4-dihydrocyclopenta[cd]pyrene was mutagenic. In the benzylic bromide series, only the eight mesoanthracenic were mutagenic, whereas benzyl bromide and 5-bromomethylchrysene were inactive. The aliphatic bromides, 6-(2-bromoethyl)benzo[a]pyrene and 7-(2-bromoethyl)benz[a]anthracene did not display significant activity. The potencies of the acetate esters more accurately reflect the mutagenicity because the rate of solvolysis did not compete with the reactivity of the esters with bacterial DNA. In the case of benzylic sulfates and bromides, the rate of solvolysis was very rapid and could have diminished the level of mutagenicity, depending on the assay conditions. These results demonstrate that meso-anthracenic benzylic acetates, sulfates and bromides are mutagenic, whereas benzylic acetate esters attached to other carbon atoms are inactive.

Acetates↗

Determining compliance with a dietary fiber supplement.

The purpose of this pilot study was to evaluate possible ways to determine compliance with a dietary fiber supplement. A wheat bran supplement (30 g daily) significantly increased mean daily wet and dry stool weights (SW) in 7 adults, when compared to SW during an ad libitum low-fiber diet (paired t-test, P less than .01). Because unpaired data would be used during a clinical trial, distribution of the 7 ad libitum low-fiber mean SW observations was used to establish a reference distribution and an upper confidence limit against which the bran supplement SW could be compared. Only one of the seven bran supplement mean SW was above the confidence limit of the low-fiber period, independent of the number of days of collection (2-10) used to calculate the individual mean daily SW. Total fecal output over varying periods of time (2-10 days) suffered the same intersubject and intrasubject variability. Most (5-6) of the bran mean daily SW were above the group mean SW of the low-fiber period. However, this dose of bran was large enough to significantly decrease calcium absorption, and differences in SW produced by lower doses of wheat bran would probably not be as great. The bulk (greater than or equal to 80%) of a single dose of a fecal marker, chromium sesquioxide, which could be incorporated into a specific day's fiber supplement, was recovered in 5 days of excretion during the control period and in 4 days during the bran period. However, the blue color of the chromium before ingestion is clearly a negative feature. Another marker, polyethylene glycol, could not be recovered in excreta when transient time was 4 days or more. In a separate study, demonstration of very little overlap in the concentration of fecal neutral detergent fiber between the control and bran periods suggests that fecal fiber may be a marker of compliance with a fiber supplement.

Aged↗

Origins of life: conformational energy calculations on primitive tRNA nestling an amino acid.

We report conformational energy calculations on our proposal of a molecular interaction theory for the origin of the nucleic acid-directed, adaptor-mediated synthesis of proteins that links the phenomena of chemical and biological evolution. A particular conformation of a pentanucleotide turns out to be a double-sided template for a primitive decoding system. It is able to neatly nestle an amino acid via hydrogen bonds, and this complex is found to be an energetically favourable conformation. The total potential energy of the complex is calculated using semi-empirical potential energy functions. A local-minimum conformation is obtained and its features are reported. The template conformation of the pentanucleotide is found to have an energy value far lower than a regular helical conformation. When the amino acid is nestled in the cleft of the template-conformation through specific hydrogen bonds, the energy is further lowered. A D-amino acid nestled into the PIT (Primitive tRNA) is found to be less stable than its L counterpart, as revealed by energy calculations.

Amino Acids↗

Suppressed proliferation of lymphatic tissue in diabetic and adrenalectomized-diabetic rats.

One week following induction of diabetes in rats by alloxan administration, the thymus and spleen showed marked involution and a highly significant depression of in vivo incorporation of [3H]deoxycytidine into the DNA of these tissues. Adrenalectomy of diabetic rats reduced the decline of lymphatic tissue weight, but uptake of [3H]deoxycytidine into thymic and spleen DNA remained suppressed. These results indicate that in alloxan-induced diabetes, the observed depressed lymphatic tissue weight and cellular proliferation are not simply due to the elevated plasma level of corticosteroids, but are either a result of the insulin deficiency per se or due to other metabolic alterations associated with the diabetic condition.

Adrenal Glands↗

Conformational relationships between amino acids and their anticodons in the primitive decoding system.

Detailed calculations of the conformational characteristics of a primitive decoding system are presented. A penta-nucleotide serves as the primitive tRNA (PIT) with a triplet of primitive anticodon (PAC) in a helical conformation. This molecular moiety has a cleft in the middle. An amino acid can comfortably nestle into the cleft. The conformation of this molecular association is stabilised by a few hydrogen bonds. The stereochemistry of the moiety restricts the conformational possibilities and the sidechain of the amino acid gets oriented at a proper position and in the correct direction to interact intimately with the PAC in the middle of the PIT. The model favours L-amino acids for beta-D-ribonucleotides. The location of the sidechain of the amino acid in the PIT gives a raison d'être for the important features of the organisation of nucleotide triplets for amino acids in the Genetic Code. The interaction of a few key amino acids with the different combinations of bases as PAC sequences has been studied and the stereochemical basis for the selection of the anticodons for amino acids is elucidated.

Amino Acids↗

A conformational rationale for the replication of nucleic acids under prebiotic conditions.

The Watson-Crick model at once gave an explanation for the mechanism of replication of DNA. But the hydrogen-bonding forces between the bases alone are not enough for the specificity of base-pairing mechanisms, since any pair of bases can be positioned to have at least two hydrogen bonds. In the present-day biological organisms, sophisticated enzymatic machinery is supposed to constrain the ribose-phosphate backbone to have regular structure, aiding the self-templating duplication. For the prebiotic stage, whence sophisticated enzymes would not have been evolved, we propose a novel double helical conformation of DNA wherein the two sugar-phosphate backbones are pulled towards each other by (C-H - -O) hydrogen bonds conferring stereospecificity for the formation of (A:T)- and (G:C)-pairs, in the self-templating chains of DNA. Our model-building efforts and computer calculations endorse the stereochemical feasibility of the conformation. The pairing of homologous sequences of two double helices of DNA is explained by direct hydrogen-bonding interactions in our model and it is thus relevant to the present-day biological functions also, at least in some stages of the cell-cycle.

Base Composition↗

Possible mechanism for origin of chiral specificity during origins of life.

We have earlier (Origins of Life 10 (1980), 15-30) proposed a conformational theory for the origin of nucleic acid-directed adaptor-mediated ordered and proliferative synthesis of proteins and hence origin of life. Conjunction of L-amino acids and beta-D-ribonucleotides emerges as a natural consequence of a template fitting interaction in this theory of the origin of the genetic decoding apparatus. Here we propose an interesting new concept for the origin of chiral specificity, by showing that two autonomously developing systems of protein-synthesizing machinery, one manufacturing L-peptides (L-system) and the other, D-peptides (D-system) could have arisen and during early stages of evolution L-system could have developed a killer enzyme to destroy the D-system, causing the presently existing chiral specificity in all the evolved organisms on Earth. It would be interesting to look for such 'killer enzymes' in the present-day organisms. Of course, the existence of D-amino acid-containing antibiotics gives some credence to this theory.

Genetic Code↗

Origin of life: a hypothesis for the origin of adaptor-mediated ordered synthesis of proteins and an explanation for the choice of terminating codons in the genetic code.

Life can be defined as a system of self-sustained chemical processes springing from the ordered synthesis of proteins directed by nucleic acids. To the notoriously difficult problem of the origin of this basic process of nucleic acid-directed protein synthesis, we give a solution of molecular interactions between pentanucleotides and amino acids. A particular conformation of a pentanucleotide forms a double sided template, with its 'inside' capable of nestling an amino acid while the 'outside' acts as an adaptor to a 'codon' triplet on long-chain nucleic acids. This serves as a primitive decoding system. An important aspect of our postulate is that a dynamic interaction is triggered, by this decoding system, through which amino acids are brought to juxtaposition facilitating peptide bond formation. Almost all the important and unique features of contemporary protein-synthesizing machinery are seen to be a direct and natural consequence of our postulate. The emergence of the termination codons also fits in, as a natural consequence of this molecular mechanism.

Animals↗

Possible role of RNA-dependent DNA-polymerase in early stages of evolution.

The tDNA cistrons have permuted sequences of triplets corresponding to anti-codons in tRNA at specific regions in their sequences. We invoke reverse transcription for the generation of such sequences in the genome during early stages of evolution. Making the assumption that a single tDNA cistron, in a genome might have come into existence by an 'accident', after transcription, tRNA is expected to fold into a three-dimensional shape analogous to the contemporary tRNA, where the anti-codon triplet bases are sticking out well-exposed for chemical mutagens. The mutated tRNAs would have been reverse-transcribed into the genome by crude analogs of now-known reverse-transcriptases. The back and forth process of transcription and reverse transcription would give rise to all the tDNA cistrons with the required anti-codons. This process may act as an important feedback mechanism for the efficient progress of evolution.

Animals↗

A conformational rationale for the origin of the mechanism of nucleicacid-directed protein synthesis of 'living' organisms.

The physical basis for the natural evolution of a primitive decoding system is presented using the concepts of molecular interactions. Oligoribonucleotides of five residues having U at the 5'-end, a purine at the 3'-end and any combination of three bases in the middle is taken as a primitive tRNA (PIT). From conformational considerations PIT is expected to have U-turn conformation wherein, N3-H3 of base U hydrogen-bonds with phosphate, three residues ahead leaving triplet bases called primitive anticodons (PAC) into a helical conformation, and this creates a cleft between U and PAC. An amino acid can be comfortably nestled into the cleft with the amide hydrogens and carboxyl oxygen hydrogen-bonded to the last purine and the first uridine, while the side-chain can interact with the cleft side of PAC. The other side of PAC is free to base-pair with triplet codons on a longer RNA. Also two PACs can 'recognize' consecutive triplet codons, and this leads to a dynamic interaction in which the amino and carboxyl ends are brought into proximity, making the formation of peptide bond feasible. The cleft formed by different anticodon triplets, broadly speaking, shows preferences for the corresponding amino acids of the presently known codon assignment. Thus the nucleicacid-directed protein synthesis, which is a unique feature of all 'living' organisms is shown to be a natural consequence of a particular way of favourable interaction between nucleic acids and amino acids, and our model provides the missing link between the chemical evolution of small organic molecules and biological evolution through the process of mutations in nucleicacids and nucleicacid-directed protein synthesis.

Animals↗