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Biomedical subjects

R R Joshi

Publications and source records attributed to R R Joshi.

17 recordsLinked to original sources
PubMed1998

Molecular dynamics simulation of a 13-mer duplex DNA: a PvuII substrate.

Parallel version of AMBER 4.1 was ported and optimised on the Indian parallel supercomputer PARAM OpenFrame built around Sun Ultra Sparc processors. This version of AMBER program was then used to carry out molecular dynamics (MD) simulations on 5'-TGACCAGCTGGTC-3', a substrate for PvuII enzyme. MD simulations in water are carried out under following conditions: (i) unconstrained at 300 K (230 ps); (ii) unconstrained at 283 K (500 ps); (iii) Watson-Crick basepair constrained at 283 K (1 ns); and (iv) Watson-Crick basepair constrained with ions at 283 K (1.2 ns). In all these simulation studies, the molecule was observed to be bending and maximum distortions in the double helix around was seen around the G7:C7' basepair, which is the phosphodiester bond that is cleaved by PvuII. Analysis of MD simulation with ions carried out for 1.2 ns also pointed out that the conformation of double helix alternates between a conformation close to B-form and close to A-form. It is argued that a bent non-standard conformation is recognised by the PvuII enzyme. The maximum bend occurs at the G7:C7' region, weakening the phosphodiester bond and allows His48 to get placed in such a fashion to permit the scission through a general base mechanism. The bending and distortion observed is a property of the sequence which acts as a substrate for PvuII enzyme. This is confirmed by carrying out MD studies on the Dickerson's sequence d(CGCGAATTCGCG)2 as a reference molecule, which practically does not bend or get deformed.

Base Composition↗
PubMed1996

Calcification of polyurethanes implanted subdermally in rats is enhanced by calciphylaxis.

Calcification complicates the use of the polymer polyurethane in cardiovascular implants. To date only costly experimental circulatory animal models have been useful for investigating this disease process. In this paper we report that polyurethane calcification in rat subdermal implants is enhanced by overdosing with a vitamin-D analog. The calcification-prone state, known as calciphylaxis, was induced in 4-week old rats by oral administration of a vitamin-D analog, dihydrotachysterol. We studied two commercially available polyurethanes (Biomer and Mitrathane) and two proprietary polyurethanes (PEU-2000 and PEU-100). PEU-100 is unique because it is derivatized with ethanehydroxy-bisphosphonate (EHBP) for calcification resistance. Polyurethane calcium and phosphate levels and morphological changes due to calciphylaxis were compared with those of control rat subdermal explants in 60-day studies. Increased polyurethane mineralization was observed due to calciphylaxis with 60-day rat subdermal explants of Biomer, Mitrathane, and PEU-2000 (calcium levels, respectively, 4.13 +/- 0.56, 18.61 +/- 2.73, and 3.37 +/- 0.22 microgram/mg, mean +/- standard error) as compared to control explants (calcium levels, respectively, 1.22 +/- 0.1, 12.57 +/- 0.86, and 0.20 +/- 0.86 microgram/mg). The study also demonstrated that with 60-day implants calciphylaxis had no side effects on somatic growth and serum calcium levels. Explant surface morphology of these polyurethane explants examined by scanning electron microscopy, back scattering electron imaging coupled with energy dispersive X-ray spectroscopy, and light microscopy demonstrated the presence of predominantly surface-oriented calcification. PEU-100, derivatized with 100 n.moles/ mg of EHBP, resisted calcification with explant calcium levels 0.51 +/- 0.01 (calciphylaxis) and 0.38 +/- 0.01 (control) microgram/mg. It is concluded that calciphylaxis enhances superficial polyurethane calcification in rat subdermal implants and that an EHBP-modified polyurethane resists calcification despite calciphylaxis. Rat subdermal implants using calciphylaxis may be generally useful for evaluating the calcification potential of various biomedical polymers.

Animals↗
PubMed1996

Chemoenzymatic synthesis of D(-)phenylglycine using hydantoinase of Pseudomonas desmolyticum resting cells.

We screened 125 Pseudomonas strains from our culture collection for the production of hydantoinase activity using DL-phenylhydantoin as a substrate. Pseudomonas desmolyticum NCIM 2112 was found to be the best hydantoinase (dihydropyrimidinase E.C. 3.5.2.2) producer. The enzymatic reactions were carried out using 18-20-h grown cells in nutrient broth and 5-phenylhydantoin as the substrate. Optimization studies for the biotransformation reaction were performed to increase product yield. The optimum pH and temperature for D(-)N-carbamoylphenylglycine production were 9.5 and 30 degrees C, respectively. Biotransformation under these alkaline conditions allowed the complete conversion of 27.0 g l-1 of DL-phenylhydantoin to 26.5 g l-1 of N-carbamoylphenylglycine within 24 h, with a molar yield of 90%. The hydantoinase involved in this biotransformation process was strictly D-stereospecific, because the product isolated was pure D(-)N-carbamoylphenylglycine. This pure product was further chemically converted to D(-)phenylglycine using nitrous acid with an 80% chemical yield. Thus, the overall conversion efficiency of DL-5-phenylhydantoin to D(-)phenylglycine was found to be 65-68%.

Amidohydrolases↗
PubMed1996

Probabilistic learning in immune network: weighted tree matching model.

Adaptive learning properties (of clonal selection and affinity maturation) in the immune network model are investigated in this paper under a nonlinear data structural representation of the involved molecules. Weighted trees are constructed to model the multiple paratopes/epitopes on the antibodies/antigens. Parallel computing experiments are carried out for the canonical coding of these trees and the corresponding multiple matching interactions. Our experiments on real data have shown significant results on the cognitive properties of the immune network. These and other computational results are presented along with a discussion of future applications.

Amino Acid Sequence↗
PubMed1996

A self-organizing cognitive network of antibody repertoire development.

A self-organizing cognitive network is mapped here onto the Id network model. The weight-vectors in this network represent some important topographical and biophysical parameters in the antibody-antigen affinity landscape. The Kohonen layers in the network correspond to affinity clones and the involved algorithm simulates the operations of clonal selection, hypermutation, differentiation, diversity, and affinity maturation. Two significant features of this model are: (i) a computationally feasible and biophysically informative representation of the para/epitopes, and (ii) the ability to perform simultaneous (parallel) and associative computations in a multidimensional shape-space. Computational experiments with real data have shown cognitive properties of this network. The results also indicate scope in quantitative characterization of the metadynamics of the above operations/weights in the adaptive development of the antibody repertoire.

Algorithms↗
PubMed1994

Duplex and triplex directed DNA cleavage by oligonucleotide-Cu(II)/Co(III) metallodesferal conjugates.

Cu(II) desferal conjugated to d(T)10 at 5'-end is shown to direct the cleavage of single stranded 19-mer target DNA d(TA1GCCCGGCG), with a base preference G > C >> A. In contrast, the corresponding Co(II)-desferal conjugate directed the cleavage specific to only G sites (G12, G16, G17 and G19). Triplex targetting on the duplex 5'-TCCTGATAAAGGAGGAGATGAAGAAAAAATGA-3': 3'-AGGACTATTTCCTCCTCTACTTCTTTTTTACT-5', using Cu(II) desferal conjugated to 5'-end of 3'-TTTCCTCCTCT-5' directed the cleavage at G5.

Base Sequence↗
PubMed1994

DNA cleavage by Cu(II)-desferal: identification of C1'-hydroxylation as the initial event for DNA damage.

Desferal, a siderophore of microbial origin is the only drug currently used for clinical treatment of a genetic disorder, thalassemia. By using a combination of HPLC and 31P-NMR, it is demonstrated that the Cu complex of desferal cleaves DNA, the primary site of hydroxyl radical attack being the sugar C1' in the minor groove, which leads to production of 5-methylene furanone. While no C5'-oxidation was observed, a minor process involving C4'-attack accompanies the above cleavage path. The oxidative cleavage of DNA observed with CuDFO may have implications in the emerging applications of desferal as a drug delivery agent and an antimalarial.

Animals↗
PubMed1994

Ab-Ag affinity thresholds in inventory optimization.

The role of antibody-antigen affinity and concentrations in adaptive antibody response is analyzed in a framework of probabilistic inventory model for antibody production. Our results indicate significant differences in optimal behaviours of low, moderate and high affinity groups and offer important implications. Interestingly, the involved approach is also of relevance in other production systems. Directions for its applications in industries and information sciences are also presented.

Animals↗
PubMed1989

On antigen-antibody binding distribution.

The probability distributions for the number of bound antigens and antibodies during immune response are obtained in this paper. Biological significance of this work and directions for further application are discussed along with some illustrative numerical results.

Antibodies↗