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Biomedical subjects

G Gupta

Publications and source records attributed to G Gupta.

At least 199 records · Page 11Linked to original sources

Left-handed helices for DNA: studies on poly[d(I-C)].

Earlier, we showed that, for the D form (n = 8 and h = 3.03 A, where n is number of nucleotide units per turn and h is height per nucleotide unit) of poly[d(A-T)], both right- and left-handed double helical models are stereochemically satisfactory and give good agreement with the observed fiber diffraction data. It was also noted that the conformations of the right- and left-handed D-DNA models are very similar to those of the right- and left-handed B-DNA models. This observation was consistent with the D leads to B transition in the solid phase. As a continuation of our earlier studies, we have carried out similar experiments with poly[d(I-C)]. We could obtain a crystalline D-form pattern (n = 8, h = 3.13 A) of the fiber at 75% relative humidity (r.h.); the hydrated (r.h. approximately equal to 95%) form of the same fiber gave the classical B-form pattern (n = 10, h = 3.40 A). In the present report, we show that both right- and left-handed double-helical models are consistent with the fiber diffraction data of poly[d(I-C)] in the D-form. Theoretical energy calculations also suggest that the right- and left-handed B- and D-DNA models are almost equally stable. Hence, we conclude that the right- and left-handed double-helical models of poly[d(I-C)] in a given form (B or D) are equally likely and that the fiber diffraction data do not permit discrimination.

DNA↗

Hemoperfusion for chronic schizophrenia: preliminary psychiatric results.

Six patients with chronic schizophrenia unresponsive to accepted therapy were assigned randomly to receive as adjunctive therapy either (A) weekly coated-charcoal hemoperfusion (CCHP) or (B) sham hemoperfusion (Sham HP) in a double-blind study using two independent psychiatric raters. Four weeks of treatment suggested that (1) CCHP was associated with significant improvement in some psychiatric measures, (2) improvement was early in the treatment course, and (3) neither CCHP nor Sham-HP was associated with deterioration in any of the psychiatric measures. When one patient from each group was "crossed-over" to receive the opposite treatment these conclusions were supported. Further studies appear to be warranted.

Chronic Disease↗

Conformational flexibility of DNA: polymorphism and handedness.

It is shown that left-handed duplexes are possible for A, B, and D forms of DNA. These duplexes are stereochemically satisfactory and are consistent with the observed x-ray intensity data. On scrutiny the refined right-handed models of B and D DNA by Arnott and coworkers are found to be stereochemically unacceptable. It was possible to formulate a stereochemical guideline for molecular model building based on theory and analysis of single-crystal structure data of dinucleoside monophosphate and higher oligomers. This led to both right- and left-handed DNA duplexes. The right-handed B and D DNA duplexes so obtained are stereochemically superior to earlier models and agree well with the observed x-ray intensity data. The observation that DNA can exist in either handedness for all the polymorphous forms of DNA at once explained A in equilibrium B and B in equilibrium D transitions. Hence it is confirmed that polymorphism of DNA is a reflection on the conformational flexibility inherent in DNA, the same cause that ultimately allows DNA in either handedness. The possibility of various types of right- and left-handed duplexes generated by using dinucleoside monophosphate and trinucleoside diphosphate as repeating units resulted in a variety of models, called RL models. All these models have alternating right and left helical segments and inverted stacking at the bend region as suggested by us earlier. It turns out that the B-Z DNA model of Wang et al. is only an example of RL models.

DNA↗

The selection and evaluation of new chelating agents for the treatment of iron overload.

A large-scale systematic evaluation of potential iron chelators for the treatment of hemosiderosis was conducted. The compounds were identified and evaluated using a hypertransfused mouse screen in which deferrioxamine B was a standard. This screen was designed to measure iron depletion in the tissues as well as iron excretion. Groups of 10 previously hypertransfused BDF1 male mice received a single daily i.p. injection of either vehicle, standard, or test compound for 7 days. Iron in daily urine pools and individual spleen and liver homogenates was determined by atomic absorption. More than 70 chelators were evaluated, including natural and synthetic hydroxamic acids, phenols, catechols and tropolones known to have a high affinity for iron (III) in vitro. Ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) was shown to be considerably more effective than deferrioxamine B (i.p.) and, in addition, was orally active. Factors determining the efficacy of this and other chelating agents are discussed.

Animals↗

Some implications of an alternative structure for DNA.

We have constructed a space-filling (Corey-Pauling-Koltun) model of an alternative structure for DNA. This structure is not a double helix, but consists of a pair of polynucleotide strands lying side by side and held together by Watson-Crick base pairing. Each of the two strands has alternating right- and left-handed helical segments approximately five base pairs in length. Sugar residues in alternating segments along a strand point in opposite directions. A structure slightly different from the present one proposed earlier by ourselves and another group and in which sugars in a strand all point in the same direction is ruled out. The present structure yields natural solutions to the problems of supercoiling of DNA and of strand separation during DNA replication. This model is energetically more favorable than the double helix.

Chromatin↗

Theoretical calculations of base-base interactions in nucleic acids: I. Stacking interactions in free bases.

Stacking interactions in free bases were computed on the basis of molecular association. The results of the calculations were compared with the stacking patterns observed in a few single crystals of nucleic acid components as examples. The following are the conclusions: (i) there can be two types of stacking pattern classified as normal and inverted types for any two interacting bases and both can be energetically favourable (ii) in both the types the stacking interaction is a combined effect of the overlap of the interacting bases and relative positions and orientations of the atomic centres of the two bases (iii) crystal symmetry and H-bonding interaction may influence stacking patterns.

Chemical Phenomena↗

Theoretical calculations of base-base interactions in nucleic acids: II. Stacking interactions in polynucleotides.

Base-base interactions were computed for single- and double stranded poly,ucleotides, for all possible base sequences. In each case, both right and left stacking arrangements are energetically possible. The preference of one over the other depends upon the base-sequence and the orientation of the bases with respect to helix-axis. Inverted stacking arrangement is also energetically possible for both single- and double-stranded polynucleotides. Finally, interacting energies of a regular duplex and the alternative structures were compared. It was found that the type II model is energetically more favourable than the rest.

Base Sequence↗

Physiology of the epididymis and induction of functional sterility in the male.

The factors regulating the physiology of the epididymis and the induction of functional sterility by alteration of epididymal function are discussed. The threshold requirement of androgens to maintain the structural and functional integrity of the epididymis in the rat, hamster and monkey is much higher than that needed by the accessory glands. Further, the cauda epididymidis has a higher threshold requirement of androgens than the caput epididymidis and may reflect the differences in the availability and metabolism of androgens to these two segments. An inverse relationship exists between the levels of sialic acid (sialoproteins) in the epididymal luminal plasma and that bound to the spermatozoa in the cauda epididymidis. Androgen deprivation and consequent alteration of the secretory activity of the epididymis either by castration or by treatment with antiserum to LH or by the antiandrogen, cyproterone acetate, caused concurrent decrease in the levels of sialic acid in the luminal plasma and in the spermatozoa of the different regions of the epididymis. These changing patterns of sialic acid in the spermatozoa and luminal plasma may be associated with changes in the surface charge of the spermatozoa and the stabilization of the acrosome and its membranes during sperm maturation.

Androgens↗