Biomedical subjects

M R Reddy

Publications and source records attributed to M R Reddy.

33 records · Page 2Linked to original sources

PubMed1993

Outcome of pregnant diabetic patients in Benghazi (Libya) from 1984 to 1991.

During the period from 1 June 1984 to 1 June 1991, 988 pregnant diabetic patients were treated by a team of physicians and obstetricians in Benghazi Diabetic Clinic. Twelve patients were insulin-dependent (type 1) and 976 patients were non-insulin-dependent (type 2). Ninety patients were diagnosed for the first time during pregnancy. Thirty-nine patients defaulted. Eight hundred and seventy-six patients were treated with insulin and 112 patients were controlled by diet. The average daily insulin dose was 40.12 units. The majority, 64.5%, delivered vaginally and 35.5% by caesarean section. Rates of abortion, intra-uterine death and still birth were 7.99%, 3.28% and 2.6%, respectively. The mean birth weight was 3.78 +/- 0.89 kg. Congenital anomalies of infants were 3.4%. Perinatal morality was 11.44%. Poor metabolic control has been associated with increased rates of abortion, intra-uterine death and congenital anomalies. It was concluded that team approach and multiple insulin injections could improve the outcome of pregnancy in developing countries to near current western standards.

Abortion, Spontaneous↗

PubMed1991

Relative differences in the binding free energies of human immunodeficiency virus 1 protease inhibitors: a thermodynamic cycle-perturbation approach.

Peptidomimetic inhibitors of the human immunodeficiency virus 1 protease show considerable promise for treatment of AIDS. We have, therefore, been seeking computer-assisted drug design methods to aid in the systematic design of such inhibitors from a lead compound. Here we report thermodynamic cycle-perturbation calculations (using molecular dynamics simulations) to compute the relative difference in free energy of binding that results when one entire residue (valine) is deleted from one such inhibitor. In particular, we studied the "alchemic" mutation of the inhibitor Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-Val-OMe (S1) to Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-OMe (S2), where Hea is hydroxyethylamine, in two different (R and S) diastereomeric configurations of the hydroxyethylene group. The calculated (averaged for R and S) difference in binding free energy [3.3 +/- 1.1 kcal/mol (mean +/- SD); 1 cal = 4.184 J] is in good agreement with the experimental value of 3.8 +/- 1.3 kcal/mol, obtained from the measured Ki values for an equilibrium mixture of R and S configurations. Precise testing of our predictions will be possible when binding data become available for the two disastereomers separately. The observed binding preference for S1 is explained by the stronger ligand-protein interaction, which dominates an opposing contribution arising from the large desolvation penalty of S1 relative to S2. This calculation suggests that the thermodynamic cycle-perturbation approach can be useful even when a relatively large change in the ligand is simulated and supports the use of the thermodynamic cycle-perturbation algorithm for screening proposed derivatives of a lead inhibitor/drug prior to their synthesis.

Amino Acid Sequence↗

PubMed1990

Activity of synthetic tat peptides in human immunodeficiency virus type 1 long terminal repeat-promoted transcription in a cell-free system.

The tat protein encoded by the human immunodeficiency virus type 1 is a potent trans-activator of gene expression from the viral long terminal repeat. The domains that are essential for trans-activation, a Pro-Xaa3-Pro triad, a cysteine-rich metal-binding sequence motif, and a cluster of basic residues, are present within the N-terminal 57 residues of tat. To determine the structural requirements for tat function and the role of metal binding at the transcription level alone, tat-(1-86) (full-length tat peptide), tat-(1-57), and tat-(1-47) were chemically synthesized. These peptides as well as the Cd2+ and Zn2+ complexes of tat-(1-86) and tat-(1-57) were evaluated for stimulation of transcription from the human immunodeficiency virus type 1 long terminal repeat by using cell-free in vitro methods. All three peptides produced a 7- to 9-fold increase over the basal level of transcription at a peptide concentration of 0.4 microM. Interestingly, at 4 microM, both tat-(1-57) and tat-(1-86) inhibited even the basal level of transcription. In contrast, tat-(1-47), which lacks the basic domain (residues 49-57), exhibited full stimulatory activity at 4 microM. Our data suggest, therefore, that the basic region may be responsible for the observed inhibitory activity of tat-(1-86) and tat-(1-57). Furthermore, binding to Zn2+ and not to Cd2+ ions only slightly augments (approximately 2-fold) the activity of the tat peptides.

Amino Acid Sequence↗

PubMed1989

Hydration forces between parallel DNA double helices: computer simulations.

We have performed two molecular dynamics computer simulations of two 10-base-pair segments of DNA molecules immersed in water. The goal of these simulations is to study the structural and dynamical properties of water between the DNA molecules. We have observed water ordering next to DNA surfaces. Existence of such ordering was proposed earlier by Marcelja and Radic [Marcelja, S. & Radic, N. (1976) Chem. Phys. Lett. 42, 129-130] to explain strong hydration forces between macromolecular surfaces.

Chemical Phenomena↗

PubMed1984