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Biomedical subjects

M Bansal

Publications and source records attributed to M Bansal.

At least 55 records · Page 3Linked to original sources

The kerosene tragedy of 1994, an unusual epidemic of burns: epidemiological aspects and management of patients.

An unusual and perhaps the first epidemic of burns occurred between 15 February 1994 and mid April 1994 in four districts of the State of Rajasthan in India. The cause of this epidemic was the accidental mixing of petrol in kerosene oil which was inadvertently overlooked. This mixture of kerosene and petrol was used mainly by people of low-income groups for lighting lamps. Most of the accidents occurred while pouring this highly inflammable petrol-kerosene mixture into ignited lamps. A total of 303 cases were reported: 118 of these patients sustained severe burns of whom 37 died. Small numbers of fresh cases kept occurring over a period of 2 months in spite of all efforts by the administration, because poor people kept using the fatal mixture due to ignorance and illiteracy. Most of the patients were managed at district hospitals with the help of plastic surgeons called for the purpose from Jaipur, the capital city of the affected State. A total of 40 out of 303 patients were transferred to SMS Hospital where a medical ward was vacated to manage these patients, as the 10-bed burn unit already had 300 per cent best occupancy. Most of these patients were not willing to be sent to a burn unit situated far away from their homes, but they had to be transferred because the general surgeons working at district hospitals were hesitant to manage them, not so much due to lack of training in the management of burns, but more due to lack of willingness to manage burns. This indicates the need for renewed emphasis not only of the necessity of training general surgeons, nursing and paramedical staff at district level in the management of burns, but also of the need to manage these cases at district level. This idea needs serious consideration and sincere efforts to implement it at the national level. The paper has been split into two parts: epidemiological aspects and management of patients.

Accidents, Home↗

Structural and sequence characteristics of long alpha helices in globular proteins.

Elucidation of the detailed structural features and sequence requirements for alpha helices of various lengths could be very important in understanding secondary structure formation in proteins and, hence, in the protein folding mechanism. An algorithm to characterize the geometry of an alpha helix from its C(alpha) coordinates has been developed and used to analyze the structures of long alpha helices (number of residues > or = 25) found in globular proteins, the crystal structure coordinates of which are available from the Brookhaven Protein Data Bank. All long alpha helices can be unambiguously characterized as belonging to one of three classes: linear, curved, or kinked, with a majority being curved. Analysis of the sequences of these helices reveals that the long alpha helices have unique sequence characteristics that distinguish them from the short alpha helices in globular proteins. The distribution and statistical propensities of individual amino acids to occur in long alpha helices are different from those found in short alpha helices, with amino acids having longer side chains and/or having a greater number of functional groups occurring more frequently in these helices. The sequences of the long alpha helices can be correlated with their gross structural features, i.e., whether they are curved, linear, or kinked, and in case of the curved helices, with their curvature.

Amino Acid Sequence↗

Amyloidosis and silicone synovitis: updated classification, updated pathophysiology, and synovial articular abnormalities.

Amyloidosis is a heterogeneous group of disorders characterized by the extracellular deposition of protein fibrils in organs or tissues. Silicone synovitis, like amyloid arthropathy, is characterized radiographically by multiple subchondral cysts in the absence of cartilage space narrowing. This article examines and compares the classification, pathophysiology, and synovial articular abnormalities associated with amyloidosis and silicone synovitis.

Amyloid↗

Effect of long-term zidovudine exposure on salvage and de novo purine and pyrimidine nucleotide syntheses.

Salvage and de novo purine and pyrimidine nucleotide syntheses were studied in H9 (a human lymphoid cell line) and H9-AZT cells (chronically zidovudine-exposed H9 cells). H9-AZT cells incorporated 18% and 27% more hypoxanthine and uridine, respectively, than H9 cells. The incorporation of the formate and bicarbonate was similar in both cell lines. Purine and pyrimidine de novo synthesis was inhibited by hypoxanthine and uridine, respectively. Hypoxanthine and uridine salvage pathways, however, were not affected by formate or bicarbonate. Short-term AZT exposure of cells had no effect on nucleotide synthesis. Some of the problems encountered in the studies of purine and pyrimidine synthesis are also discussed.

Bicarbonates↗

An unusual case of acute renal failure in burns.

Nowadays acute renal failure in burns is not a common occurrence, at least not when most of the wounds have already healed. We report a case of a 6-year-old child with 45 per cent flame burns, who suffered acute renal shutdown 43 days after burns when all except 1 per cent of the raw areas had already been grafted with autologous skin. There was no identifiable focus of infection and no evidence of septicemia. The patient was not receiving any nephrotoxic drugs. The child responded well to peritoneal dialysis and recovered fully.

Acute Kidney Injury↗

Chain folding and A:T pairing in human telomeric DNA: a model-building and molecular dynamics study.

The various types of chain folding and possible intraloop as well as interloop base pairing in human telomeric DNA containing d(TTAG3) repeats have been investigated by model-building, molecular mechanics, and molecular dynamics techniques. Model-building and molecular mechanics studies indicate that it is possible to build a variety of energetically favorable folded-back structures with the two TTA loops on same side and the 5' end thymines in the two loops forming TATA tetrads involving a number of different intraloop as well as interloop A:T pairing schemes. In these folded-back structures, although both intraloop and interloop Watson-Crick pairing is feasible, no structure is possible with interloop Hoogsteen pairing. MD studies of representative structures indicate that the guanine-tetraplex stem is very rigid and, while the loop regions are relatively much more flexible, most of the hydrogen bonds remain intact throughout the 350-ps in vacuo simulation. The various possible TTA loop structures, although they are energetically similar, have characteristic inter proton distances, which could give rise to unique cross-peaks in two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments. These folded-back structures with A:T pairings in the loop region help in rationalizing the data from chemical probing and other biochemical studies on human telomeric DNA.

Adenine↗

Structural polymorphism in d(T)12.d(A)12*d(T)12 triple helices.

DNA triple helices containing two thymine strands and one adenine strand have been studied, using model building followed by energy minimisation, for different orientations of the third strand resulting from variation in the hydrogen bonding between the Watson-Crick duplex and the third strand and the glycosidic torsion angle in the third strand. Our results show that the structure with a parallel orientation of the third strand, in which the third strand base forms Hoogsteen hydrogen bonds with the adenine base in the Watson-Crick duplex, is energetically the most favourable. An antiparallel orientation of the third strand is also possible, in which the third strand base hydrogen bonds to both the bases in the Watson-Crick duplex. This structure is energetically comparable to the parallel structure. For the parallel triplex a 200ps molecular dynamics simulation starting from two different starting structures indicates that at 300K significant structural heterogeneity exists in this triplex structure. The results are compared with existing structural data on this class of triplexes derived from theoretical and NMR techniques.

Base Composition↗

NUPARM and NUCGEN: software for analysis and generation of sequence dependent nucleic acid structures.

Software packages NUPARM and NUCGEN, are described, which can be used to understand sequence directed structural variations in nucleic acids, by analysis and generation of non-uniform structures. A set of local inter basepair parameters (viz. tilt, roll, twist, shift, slide and rise) have been defined, which use geometry and coordinates of two successive basepairs only and can be used to generate polymeric structures with varying geometries for each of the 16 possible dinucleotide steps. Intra basepair parameters, propeller, buckle, opening and the C6...C8 distance can also be varied, if required, while the sugar phosphate backbone atoms are fixed in some standard conformation in each of the nucleotides. NUPARM can be used to analyse both DNA and RNA structures, with single as well as double stranded helices. The NUCGEN software generates double helical models with the backbone fixed in B-form DNA, but with appropriate modifications in the input data, it can also generate A-form DNA and RNA duplex structures.

Base Composition↗

NUVIEW: software for display and interactive manipulation of nucleic acid models.

The NUVIEW software package allows skeletal models of any double helical nucleic acid molecule to be displayed on a graphics monitor and to apply various rotations, translations and scaling transformations interactively, through the keyboard. The skeletal model is generated by connecting any pair of representative points, one from each of the bases in the basepair. In addition to the above mentioned manipulations, the base residues can be identified by using a locator and the distance between any pair of residues can be obtained. A sequence based color coded display allows easy identification of sequence repeats, such as runs of Adenines. The real time interactive manipulation of such skeletal models for large DNA/RNA double helices, can be used to trace the path of the nucleic acid chain in three dimensions and hence get a better idea of its topology, location of linear or curved regions, distances between far off regions in the sequence etc. A physical picture of these features will assist in understanding the relationship between base sequence, structure and biological function in nucleic acids.

Animals↗

Molecular mechanics studies of homopolymeric and mixed sequence Py.Pu*Pu triple helices.

DNA triple helices containing two purine strands and one pyrimidine strand (C.G*G and T.A*A) have been studied, using model building followed by energy minimisation, for different orientations of the third strand resulting from variation in the hydrogen bonding between the Watson-Crick duplex and the third strand and the glycosidic torsion angle in the third strand. Our results show that in the C.G*G case the structure with a parallel orientation of the third strand, resulting from Hoogsteen hydrogen bonds between the third strand and the Watson-Crick duplex, is energetically the most favourable while in the T.A*A case the antiparallel orientation of the third strand, resulting from reverse Hoogsteen hydrogen bonds, is energetically the most favourable. These studies when extended to the mixed sequence triplexes, in which the second strand is a mixture of G and A, correspondingly the third strand is a mixture of G and A/T, show that though the parallel orientation is still energetically more favourable, the antiparallel orientation becomes energetically comparable with an increasing number of thymines in the third strand. Structurally, for the mixed triplexes containing G and T in the third strand, it is seen that the basepair non-isomorphism between the C.G*G and the T.A*T triplets can be overcome with some changes in the base pair parameters without much distortion of either the backbone or the hydrogen bonds.

Base Sequence↗

CA/TG sequence at the 5' end of oligo(A)-tracts strongly modulates DNA curvature.

An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAAC-CCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.

Base Sequence↗

Conformational polymorphism in telomeric structures: loop orientation and interloop pairing in d(G4TnG4).

Sequence repeats constituting the telomeric regions of chromosomes are known to adopt a variety of unusual structures, consisting of a G tetraplex stem and short stretches of thymines or thymines and adenines forming loops over the stem. Detailed model building and molecular mechanics studies have been carried out for these telomeric sequences to elucidate different types of loop orientations and possible conformations of thymines in the loop. The model building studies indicate that a minimum of two thymines have to be interspersed between guanine stretches to form folded-back structures with loops across adjacent strands in a G tetraplex (both over the small as well as large groove), while the minimum number of thymines required to build a loop across the diagonal strands in a G tetraplex is three. For two repeat sequences, these hairpins, resulting from different types of folding, can dimerize in three distinct ways--i.e., with loops across adjacent strands and on same side, with loops across adjacent strands and on opposite sides, and with loops across diagonal strands and on opposite sides--to form hairpin dimer structures. Energy minimization studies indicate that all possible hairpin dimers have very similar total energy values, though different structures are stabilized by different types of interactions. When the two loops are on the same side, in the hairpin dimer structures of d(G4TnG4), the thymines form favorably stacked tetrads in the loop region and there is interloop hydrogen bonding involving two hydrogen bonds for each thymine-thymine pair. Our molecular mechanics calculations on various folded-back as well as parallel tetraplex structures of these telomeric sequences provide a theoretical rationale for the experimentally observed feature that the presence of intervening thymine stretches stabilizes folded-back structures, while isolated stretches of guanines adopt a parallel tetraplex structure.

Base Sequence↗

Knotted upper end: a new complication in the use of an indwelling ureteral stent.

Use of the indwelling ureteral stent is a key factor in the management of stone disease by extracorporeal shock wave lithotripsy. We report on a knotted stent in a patient with a solitary kidney, which had to be removed percutaneously. This case demonstrates that the ureteral stent is not free of serious complications.

Combined Modality Therapy↗

Analysis of sequence dependent variations in secondary and tertiary structure of tRNA molecules.

The double helical regions of the five tRNA(Phe) and two tRNA(Asp) crystal structures have been analyzed using the local basepair step parameters. The sequence dependent effects in the mini double helices of tRNA are very similar to those observed in the crystal structures of oligonucleotides in the A-form, the purine-pyrimidine and purine-purine steps have small roll angles when compared to the fiber models of A-DNA as well as A-RNA, while the pyrimidine-purine doublet steps have large roll angles. The orientation of the basepairs in the D-stem is unusual and invariant i.e. they are different from the other three stems but are very similar in all the five tRNA(Phe) crystal structures, presumably due to tertiary interaction of the Watson-Crick basepairs with other bases, with all bases being highly conserved. The origin of the differences between the tertiary structures of tRNA(Phe) and tRNA(Asp) from yeast has also been investigated. It is found that even though the angle between the acceptor arm and the D-stem is very similar in the two structures, the angle subtended by the acceptor arm and the anticodon arm is smaller in the tRNA(Phe) structure (by more than 10 degrees). This is due to differences in the orientation of the two mini helices constituting the anticodon arm, which are inclined to each other by approximately 25 degrees in tRNA(Phe) and 16 degrees in tRNA(Asp). In addition, the acceptor arm, the D-stem and the anticodon stem are nearly coplanar in tRNA(Phe), while in tRNA(Asp) the anticodon stem projects out of the plane defined by the acceptor arm and the anticodon stem. These two features together lead to a larger separation between the acceptor and anticodon ends in tRNA(Asp) and indicate that the junction between the D-stem and the anticodon stem is quite variable, with features characteristic of a ball-and-socket type joint and determined for each tRNA molecule by the base sequence at the junction.

Anticodon↗

Opioids modulate migration, spreading and adherence of mesangial cells.

Glomerular mesangial cells are considered to be modified smooth muscle cells and seem to play a role in the maintenance of glomerular hemodynamics. The present study was carried out to determine the effect of opioids on adhesiveness, spreading and migration of mesangial cells. Morphine enhanced spreading of mesangial cells at early time periods (5 mini, control 8 +/- 2% vs. morphine 15 +/- 1%, p < 0.05; 15 min, control 21 +/- 5% vs. morphine 38 +/- 2%, p < 0.05) as well as at later time periods when compared to control cells (at 2 h, control 23 +/- 1% vs. morphine 49 +/- 1%, p < 0.001; at 3 h, control 28 +/- 3% vs. morphine 63 +/- 2%, p < 0.05). beta-Endorphin also enhanced (p < 0.001) spreading of mesangial cells (at 2 h, control 23 +/- 1% vs. beta-endorphin 48 +/- 3%; at 3 h, control 28 +/- 3% vs. beta-endorphin 65 +/- 1%). Morphine decreased adhesion of mesangial cells to the plastic substrate at 24 h as well at 48 h when compared to the control cells. Naloxone attenuated the effect of morphine on adhesion to the substrate. Morphine enhanced (p < 0.05) migration (percentage of denuded area covered by mesangial cells when compared to control cells (control 26.07 +/- 1.08% vs. morphine 37.5 +/- 2.94%; n = 9). Since the morphine-induced decreased adhesiveness could be attenuated by naloxone, this effect of morphine on mesangial cells appears to be mediated by opioid receptors.

Animals↗