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P Pradhan

Publications and source records attributed to P Pradhan.

At least 19 recordsLinked to original sources
PubMed2001

Solution structure of a trans-opened (10S)-dA adduct of (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a fully complementary DNA duplex: evidence for a major syn conformation.

Two-dimensional NMR was used to determine the solution structure of an undecanucleotide duplex, d(CGGTCACGAGG).d(CCTCGTGACCG), in which (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene is covalently bonded to the exocyclic N(6)() amino group of the central deoxyadenosine, dA(6), through trans addition at C10 of the epoxide (to give a 10S adduct). The present study represents the first NMR structure of a benzo[a]pyrene (10S)-dA adduct in DNA with a complementary T opposite the modified dA. Exchangeable and nonexchangeable protons of the modified duplex were assigned by the use of TOCSY (in D(2)O) and NOESY spectra (in H(2)O and D(2)O). Sequential NOEs expected for a B-type DNA conformation with typical Watson-Crick base pairing are observed along the duplex, except at the lesion site. We observed a strong intraresidue NOE cross-peak between H1' and H8 of the modified dA(6). The sugar H2' and H2' ' of dC(5) lacked NOE cross-peaks with H8 of dA(6) but showed weak interactions with H2 of dA(6) instead. In addition, the chemical shift of the H8 proton (7.51 ppm) of dA(6) appears at a higher field than that of H2 (8.48 ppm). These NOE and chemical shift data for the dA(6) base protons are typical of a syn glycosidic bond at the modified base. Restrained molecular dynamics/energy minimization calculations show that the hydrocarbon is intercalated from the major groove on the 3'-side of the modified base between base pairs A(6)-T(17) and C(7)-G(16) and confirm the syn glycosidic angle (58 degrees ) of the modified dA(6). In the syn structure, a weak A-T hydrogen bond is possible between the N3-H proton of T(17) and N7 of dA(6) (at a distance of 3.11 A), whereas N1, the usual hydrogen bonding partner for N3-H of T when dA is in the anti conformation, is 6.31 A away from this proton. The 10(S)-dA modified DNA duplex remains in a right-handed helix, which bends in the direction of the aliphatic ring of BaP at about 42 degrees from the helical axis. ROESY experiments provided evidence for interconversion between the major, syn conformer and a minor, possibly anti, conformer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2000

Correlations due to localization in quantum eigenfunctions of disordered microwave cavities

Statistical properties of experimental eigenfunctions of quantum chaotic and disordered microwave cavities are shown to demonstrate nonuniversal correlations due to localization. Varying energy E and mean free path l enable us to experimentally tune from localized to delocalized states. Large level-to-level inverse participation ratio ( I2) fluctuations are observed for the disordered billiards, whose distribution is strongly asymmetric about . The spatial density autocorrelations of eigenfunctions are shown to spatially decay exponentially and the decay lengths are experimentally determined. All the results are quantitatively consistent with calculations based upon nonlinear sigma models.

Journal Article↗
PubMed1999

Studies on the adduct heterogeneity of benzo[a]pyrene 7, 8-dihydrodiol 9,10-epoxide stereoisomers covalently bound to deoxyribooligonucleotides by induced circular dichroism and light absorption spectroscopy.

The binding conformations of single anti- and syn-BPDE-N2-dG adducts in oligonucleotides of varying base composition have been studied by induced circular dichroism (ICD) and light absorption spectroscopy. The sign of the ICD in single-stranded oligonucleotide adducts correlates with the absolute configuration of the cyclohexyl moiety of the BPDE. Adducts in oligonucleotide duplexes with UV lambdamax <350 nm exhibiting a significant duplex-induced positive ICD should have a minor groove location as the predominant conformation. Those with UV lambdamax >350 nm exhibiting either positive or negative contributions to the ICD should have intercalated binding as the predominant conformation. The magnitude of the ICD is dependent on the sequence context of the adducted strand and the particular BPDE-adduct isomer under study. In some cases, the results suggest structural heterogeneity. For instance, the (+)- and the (-)-trans-anti-BPDE-N2-dG adducts in duplexes where a dT flanks the lesion site exhibit weak positive ICD or negative ICD. These results reflect a bimodal conformational adduct distribution with contributions from both externally and internally located adducts. A key observation for the (+)-cis-syn-BPDE-N2-dG complexes in 5'-d(TGC) and 5'-d(CGC) sequence contexts is that the near-UV absorption spectra showed distinct bands corresponding to minor groove binding (lambdamax congruent with 346 nm) as well as intercalative binding (lambdamax congruent with 354 nm). Evidence for an equilibrium between the different modes of localization is provided by the results from the temperature dependence of the near-UV absorption and ICD characteristics of (+)-cis-syn-BPDE-N2-dG complexes in 5'-d(TGC) and 5'-d(CGC) sequence contexts, respectively.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Implications of cytosine methylation on (+)-anti-Benzo[a]pyrene 7, 8-dihydrodiol 9,10-epoxide N(2)-dG adduct formation in 5'-d(CGT), 5'-d(CGA), and 5'-d(CGC) sequence contexts of single- and double-stranded oligonucleotides.

Covalent binding of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9, 10-epoxide (anti-BPDE) to the N(2)-amino group of deoxyguanine in the oligonucleotides 5'-d(CCTATCGXTATCC) and 5'-d(CCTATm(5)CGXTATCC) (X being T, A, or C) has been studied. The extent of formation of the (+)-trans-anti-BPDE-N(2)-dG adduct in single-stranded 13-mer oligonucleotides with 5'-d(m(5)CGT) and 5'-d(m(5)CGA) sequence contexts was significantly higher (1.5- and 2.4-fold, respectively) relative to that of the nonmethylated sequences. With the 5'-d(CGC) sequence context, m(5)dC had no significant effect on adduct formation. When the reaction was allowed to proceed in the presence of oligonucleotide duplexes (composed of a 13-mer parent strand and a 9-mer complement), a significant increase in the extent of adduct formation was observed with 5'-d(m(5)CGT)/d(CGA) and 5'-d(m(5)CGA)/d(CGT), but not with 5'-d(CGC)/d(GCG), relative to those of the nonmethylated duplexes. Independent of sequence context, no clear effect of m(5)dC on diol epoxide binding to the opposite dG in the complementary strand was observed. The level of diol epoxide binding to the dG target in the 13-mer oligonucleotides is in general higher in single-stranded sequences than in the duplexes. With 5'-d(CGA) and 5'-d(m(5)CGA), for instance, adduct yields were 3- and 4-fold higher, respectively. The thermodynamic stability of the (+)-trans-anti-BPDE-N(2)-dG adduct in the 5'-d(m(5)CGT)-containing duplex (composed of a 13-mer parent strand and a full complement) was substantially higher than in the 5'-d(CGT)/d(GCA) sequence context. The stimulating effect of cytosine methylation on the formation of DNA adducts of anti-BPDE has previously been demonstrated in other experimental systems. The increase in yield could possibly be rationalized in terms of prestacking of the pyrenyl ring system with the nucleobases prior to the nucleophilic addition reaction of the exocyclic amino group. The results from induced circular dichroism studies with the (+)-trans-anti-BPDE-N(2)-dG adduct in the 5'-d(m(5)CGT)-containing duplex are consistent with substantial heterogeneity of adduct conformations, including both external minor groove-localized and intercalated structures.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Induced circular dichroism of benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide stereoisomers covalently bound to deoxyribooligonucleotides used to probe equilibrium distribution between groove binding and intercalative adduct conformations.

Binding conformations of single anti-BPDE-N2-dG adducts in oligonucleotides of varying base composition have been studied by induced circular dichroism (ICD). The sign of the ICD around 350 nm of single-stranded oligonucleotide adducts and the sign of an exciton type of CD component at 260 nm in both single strand and duplex forms of adducts correlate with the absolute configuration of the cyclohexyl moiety of the adduct. Changes in magnitude and sign of the ICD around 350 nm were observed upon duplex formation. The results show that adducts displaying external (minor groove) binding characteristics are associated with a significant positive ICD. Conversely, adducts displaying intercalation binding characteristics were found to have a positive or negative ICD. The magnitude of the ICD is dependent on the sequence context and the particular adduct isomer studied. Duplexes with (+)-trans-anti-BPDE-N2-dG in 5'-d(CCTATCGCTATCC) or 5'-d(CCTATAGATATCC) exhibit a relatively strong positive ICD. In contrast, the duplexes with (+)-trans-anti-BPDE-N2-dG in 5'-d(CCTATTGCTATCC) and 5'-d(CCTATTGTTATCC) display a small positive and negative ICD, respectively, in both cases suggesting conformational heterogeneity. Partially complementary duplexes (dA, dT, or dG) localized opposite the (+)-trans-anti-BPDE-N2-dG adduct in 5'-d(CCTATCGCTATCC) or 5'-d(CCTATAGATATCC) also demonstrated negative ICD. These results together with light absorption characteristics suggest a preferred conformation of intercalation for the mismatched duplexes. Evidence of an equilibrium between the external and intercalative adduct conformation is provided by the results from the temperature dependence of the near-UV absorption and ICD characteristics of (+)-trans-anti-BPDE-N2-dG complex in a 5'-d(CCTATAGATATCC) duplex.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Immunodiagnosis of childhood pulmonary and extrapulmonary tuberculosis using Mycobacterium tuberculosis ES antigen by penicillinase ELISA.

The diagnostic potential for detection of IgG to Mycobacterium tuberculosis excretory secretory (ES) antigen in childhood pulmonary and extrapulmonary tuberculosis was explored. IgG antibody to M. tuberculosis ES antigen was detected by indirect penicillinase ELISA. Twenty (80%) out of 25 pulmonary tuberculosis cases (clinically diagnosed and/or AFB-positive), five of nine tuberculous pleural effusion cases and only six of 69 cases in the control group were positive for IgG antibody to M. tuberculosis ES antigen. All CSF and sera were positive for IgG antibody in 12 cases of clinically diagnosed tuberculous meningitis (TBM). Out of 35 cases in the control group for TBM, all five cases of pyogenic meningitis but none of the 13 cases of viral encephalitis, five cases of enteric encephalopathy and 12 cases with no CNS infection were positive for anti-tubercular IgG antibody in CSF samples. Only two of them, i.e. one case of pyogenic meningitis and the other with no CNS infection, were positive for antibody in sera. The study demonstrated the potential of this assay in the diagnosis of tuberculosis in children where bacteriological confirmation is very difficult.

Antibodies, Bacterial↗
PubMed1992

A new approach in training pre-clinical medical undergraduates in community medicine in Pondicherry, South India.

Pre-clinical medical undergraduates are taught Community Medicine using a variety of teaching methods keeping the didactic lectures to the minimum in conformity with the latest recommendations of Medical Council of India. Five of the total twelve topics were taught using group discussion during 1988-89. The present paper gives the details of lesson plans for two topics. Evaluation was done based on the results of the written test, opinions expressed by the students and on the spot observation by the faculty members. Suggestions given by the students to improve the sessions have also been highlighted.

Clinical Clerkship↗
PubMed1991

Processes that mediate the relationship between a group goal and improved group performance.

The relationships between the level of a group performance goal for quantity, group process, and group performance were assessed. Forty groups of 3 people performed 3 trials of a production task. One half of the groups were assigned a low goal for Sessions 2 and 3, and one half were assigned a high goal. To measure group process, videotapes of each group were analyzed and self-reports of behavior were collected. A significant difference in performance across the high and low goal conditions was found for Session 3, and measures of group process showed that effort, group planning, changes in individual and group performance plans, and reduced concern for quality mediated the group goal effect. These results are discussed in relation to Weldon and Weingart's (1988) model of group goals and group performance.

Adult↗
PubMed1985

A multicentre prospective randomized controlled trial of induction of labour with an automatic closed-loop feedback controlled oxytocin infusion system.

A randomized prospective controlled trial of an automatic feed-back controlled oxytocin infusion system (AIS) for the induction of labour at term was carried out in three hospitals. In primiparae, a four-fold reduction in the total dose of oxytocin infused, for the same induction-delivery interval, was achieved with the AIS compared with standard labour ward protocols relying on midwife control of oxytocin infusion rate. In multiparae, the total dose of oxytocin infused was almost halved when the AIS was used, while the mean duration of labour was increased by 1.6 h to 7.5 h. There were no differences in the mode of delivery or Apgar scores. It is concluded that the AIS is a safe technique for induction of labour. Its use has demonstrated that term labour can be induced efficiently with a mean oxytocin infusion rate between 2.5 and 3 mU/min (max 8.8 mU/min) and a total oxytocin dose infused of less than 5 U.

Adult↗