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Biomedical subjects

S Acharya

Publications and source records attributed to S Acharya.

At least 19 recordsLinked to original sources

Evaluation of a Skilled Birth Attendant pilot training program in Bangladesh.

OBJECTIVES: An evaluation of the pilot project of the Skilled Birth Attendant (SBA) training program has been undertaken to assess the strengths and weaknesses of the training program, the after training performances of the selected SBAs and to ascertain the sustainability of the program. METHODS: The study was conducted in three phases adopting both qualitative and quantitative methods: assessment of training program; evaluation of after training performances of SBAs; and evaluation of performance of providers in non-SBA areas. RESULTS: During the post-training period it was observed that on an average the SBAs performed 3-4 deliveries per month. They were able to perform different life saving skills. In the areas served by the SBAs, they performed 29% deliveries and 47% were performed by the TBAs. In control areas TBAs performed 61% deliveries. CONCLUSION: Overall, the study points to the efficacy of SBAs over traditional hands and the societal need for SBAs.

Adult↗

Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern.

The structural preorganization of isosequential ssDNA and ssRNA hexamers d/r(GAAAAC)(1) [J. Am. Chem. Soc. 2003, 125, 9948] have been investigated by NMR and molecular dynamics simulations. Analysis of the nuclear Overhauser effect spectrometry (NOESY) footprints in the aqueous solution has shown that there is a substantial population of ordered right-handed helical structure in both hexameric single-stranded DNA and RNA, which are reminiscent of their respective right-handed helical duplex form, despite the fact these single-stranded molecules are devoid of any intermolecular hydrogen bonds. The NMR-constrained molecular dynamics (1.5 ns) derived geometries of the adenine-adenine overlaps at each dinucleotide step of the hexameric ssDNA (1a) and ssRNA (1b) show that the relatively electron-rich imidazole stacks above the electron-deficient pyrimidine in 5' to 3' direction in ssDNA (1a) while, in contradistinction, the pyrimidine stacks above the imidazole in the 5' to 3' direction in ssRNA (1b). This also means that the pi-frame of the 5'-pyrimidine can interact with the relatively positively charged imino and amino protons in the 3' direction in ssRNA and in the 5' direction in ssDNA, thereby stabilizing the twist and slide observed in the stacked oligonucleotides. The differently preferred stacking geometries in ssDNA and ssRNA have direct physicochemical implications for self-assembly and pK(a) modulation by the nearest-neighbor interactions, as well as for the dangling-end stabilization effects and imino-proton reactivity.

Adenine↗

Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes.

To understand why the RNA-RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA-DNA duplexes, we have measured the pK(a) values of both nucleoside 3',5'-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3'-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3',5'-bis-phosphates, Etp(d/rN)pEt, mimic the internucleotidic monomeric units of DNA and RNA, in which the stacking contribution is completely absent, the 3'-ethyl phosphates, (d/rN)pEt, mimic the nucleotide at the 5'-end. The pK(a) values of the nucleobase in each of these model nucleoside phosphates have been determined with low pK(a) error (sigma = +/-0.01 to 0.02) by (1)H NMR (at 500 MHz) with 20-33 different pH measurements for each compound. This study has led us to show the following: (1) All monomeric DNA nucleobases are more basic than the corresponding RNA nucleobases in their respective Etp(d/rN)pEt and (d/rN)pEt. (2) The pK(a) values of the monomeric nucleotide blocks as well as Delta pK(a) values between the donor and acceptor can be used to understand the relative base-pairing strength in the oligomeric duplexes in the RNA and DNA series. (3) The Delta G*(pKa) of the donor and acceptor of the base pair in duplexes enables a qualitative dissection of the relative strength of the base-pairing and stacking in the RNA-RNA over the DNA-DNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNA-RNA over DNA-DNA is mutually compensating as the % A-T/U content increases or decreases. This interdependency of stacking and hydrogen bonding can be potentially important in the molecular design of the base-pair mimics to expand the alphabet of the genetic code.

DNA↗

Humoral defence factors in Indian river prawn, Macrobrachium malcolmsonii.

A preliminary study on humoral defence factors of Indian river prawn, Macrobrachium malcolmsonii was carried out. The serum of animals collected from intermoult stage had an average total protein content of 9.65 g dl(-1) and lysozyme-like activity of 0.04 unit ml(-1). The phenoloxidase activity in haemocyte lysate supernatant was triggered significantly (P < 0.05) by chitosan, Gram-positive and Gram-negative bacterial cells in comparison to other elicitors viz., levamisole, trypsin and glucan. The serum contained an agglutinin against Gram-negative bacteria and a haemagglutinin against a wide range of vertebrate erythrocytes. The haemagglutinin was stable over a wide range of pH (3.0-7.0) and temperatures (-30 degrees C to 60 degrees C). A 413 kDa N-acetyl galactosamine-specific haemagglutinin was purified by single step affinity chromatography and the protein was found to be calcium ion-dependent in nature and made up of five different subunits of varied molecular weights on denaturing SDS-PAGE.

Agglutinins↗

Vaginal prostaglandin E2 gel versus tablet in the induction of labour at term--a retrospective analysis.

Our aim in this retrospective analysis was to compare labour outcomes between 145 consecutive women with unfavourable cervices, who received prostaglandin E2 vaginal gel (1-2 mg) for labour induction over a 3-month period, and 149 women receiving a prostaglandin E2 vaginal tablet (3 mg) over the following 3 months. Our results showed that cervical dilatation in the gel group was significantly more than in the tablet group at transfer to labour ward [4 cm (SD 2.5 cm) versus 3.3 cm (SD 2 cm), mean difference -0.7, 95% CI -1.2 to -0.2, P=0.01), with fewer women requiring oxytocin augmentation, but this was not statistically significant (41.4% versus 50%, RR 0.8, 95% CI 0.7-1.1). There were no significant differences in the mode of delivery in the number delivering vaginally within 24 hours of the induction (60.4% in the gel group versus 56.2% in the tablet group, RR1.1, 95% CI 0.9-1.4), in the number of doses of PGE2 administered, or in the neonatal outcomes between the two groups. In conclusion, there were no significant differences in labour or neonatal outcomes between prostaglandin E2 gel or tablet use in the induction of labour in this retrospective analysis.

Administration, Intravaginal↗

Nutritional changes among premenopausal women undertaking a soya based dietary intervention study in Hawaii.

BACKGROUND: We conducted a 2-year nutritional intervention among premenopausal women. The goal was to incorporate two daily servings of soya into the regular diet. This report describes the dietary modifications and assesses their nutritional adequacy with regard to major nutrients. METHODS: In this analysis of 100 intervention and 106 control subjects, women completed a validated food-frequency questionnaire at baseline; throughout the study, they participated in at least three unannounced 24-h recalls. RESULTS: At randomization, both groups were similar in age and body weight, reported low soya intake, and did not differ by intake of major nutrients and foods. According to the 24-h recalls, women in the intervention group consumed nearly two servings of soya per day, while the control women remained at 0.2 servings. In comparison with the control group, the intervention group consumed fewer dairy products, primarily milk, but also less meat, nuts and seeds. As a result of the dietary modification, the intervention women consumed less-saturated fat and cholesterol and more protein, dietary fibre, calcium and vitamins than the control group. CONCLUSION: These results suggest that women in the intervention group improved the overall quality of their diet by adding two servings of soya per day.

Adult↗

A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term.

OBJECTIVE: To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level, teaching Scottish Hospital. POPULATION: Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. METHODS: The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). MAIN OUTCOME MEASURE: The number delivering vaginally within 24 hours of the induction. RESULTS: Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group. CONCLUSIONS: Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.

Administration, Intravaginal↗

Thermodynamics and phase equilibria involving nano phases in the Cu-Ag system.

The surface tensions of the Cu-Ag system have been evaluated using Butler's equations. Since the evaluation is dependent on the thermodynamic properties of the surface phases, they are calculated based on the first and second order differentials of the surface tension at infinite dilution. The present study establishes significant differences in the properties between the surface phase and bulk phases of the system. The study of the adsorption behaviour finds silver to be surface active relative to copper, which results in the preferential adsorption of silver in the alloys. Furthermore, in view of the differences in terms of fundamental thermodynamic properties between the two phases coupled with the volume-to-radius ratio as depicted by the Thomson-Freundlich concept, the nano phases of the system exhibit a pronounced increase in the adsorption behaviour relative to that of the planar interface of the system. As expected based on the above combined effect of the surface properties, present research shows a considerable decrease in the melting points of the metals, solid-solid, solid-liquid transition and eutectic temperature with a consequent increase in the solubilities of the terminal phases of the system.

Adsorption↗

Serum prolactin in human immunodeficiency virus infection.

Patients infected with human immunodeficiency virus (HIV) have higher serum prolactin compared to healthy controls but this is controversial. As part of a laboratory audit investigating the interference of macroprolactin in our prolactin assay, we investigated whether low biological activity macroprolactin could account for the increased serum prolactin concentrations observed in HIV infection. We, therefore, compared serum total prolactin and free prolactin in 32 subjects infected with HIV (HIV+ve) with 52 subjects not infected with HIV (HIV-ve). Serum total prolactin concentrations were similar in HIV+ve and HIV-ve patients [median (95% confidence limits); 167.0 (122.4 - 313.8) vs 206.5 (187.8 - 248.4) mU/L respectively]. Serum free prolactin concentrations were lower (p <0.005) in HIV+ve subjects than in HIV-ve subjects [112.0 (91.1-141.8) vs 171.0 (154.5 - 200.9) mU/L respectively; p<0.0005]. These results are consistent with the notion that low biological activity macroprolactin contributes to circulating prolactin concentrations in HIV+ve subjects.

Adult↗

Cross-modulation of the pKa of nucleobases in a single-stranded hexameric-RNA due to tandem electrostatic nearest-neighbor interactions.

The pH titration studies (pH 6.7-12.1) in a series of dimeric, trimeric, tetrameric, pentameric, and hexameric oligo-RNA molecules [GpA (2a), GpC (3a), GpApC (5), GpA(1)pA(2)pC (6), GpA(1)pA(2)pA(3)pC (7), GpA(1)pA(2)pA(3)pA(4)pC (8)] have shown that the pK(a) of N(1)-H of 9-guaninyl could be measured not only from its own deltaH8G, but also from the aromatic marker protons of other constituent nucleobases. The relative chemical shift differences [Deltadelta((N)(-)(D))] between the protons in various nucleotide residues in the oligo-RNAs at the neutral (N) and deprotonated (D) states of the guanine moiety show that the generation of the 5'-(9-guanylate ion) in oligo-RNAs 2-8 reduces the stability of the stacked helical RNA conformation owing to the destabilizing anion(G(-))-pi/dipole(Im(delta)(-)) interaction. This destabilizing effect in the deprotonated RNA is, however, opposed by the electrostatically attractive atom-pisigma (major) as well as the anion(G(-))-pi/dipole(Py(delta)(+)) (minor) interactions. Our studies have demonstrated that the electrostatically repulsive anion(G(-))-pi/dipole(Im(delta)(-)) interaction propagates from the first to the third nucleobase quite strongly in the oligo-RNAs 6-8, causing destacking of the helix, and then its effect is gradually reduced, although it is clearly NMR detectable along the RNA chain. Thus, such specific generation of a charge at a single nucleobase moiety allows us to explore the relative strength of stacking within a single-stranded helix. The pK(a) of 5'-Gp residue from its own deltaH8G in the hexameric RNA 8 is found to be 9.76 +/- 0.01; it, however, varies from 9.65 +/- 0.01 to 10.5 +/- 0.07 along the RNA chain as measured from the other marker protons (H2, H8, H5, and H6) of 9-adeninyl and 1-cytosinyl residues. This nucleobase-dependent modulation of pK(a)s (DeltapK(a) +/- 0.9) of 9-guaninyl obtained from other nucleobases in the hexameric RNA 8 represents a difference of ca. 5.1 kJ mol(-)(1), which has been attributed to the variable strength of electrostatic interactions between the electron densities of the involved atoms in the offset stacked nucleobases as well as with that of the phosphates. The chemical implication of this variable pK(a) for guanin-9-yl deprotonation as obtained from all other marker protons of each nucleotide residue within a ssRNA molecule is that it enables us to experimentally understand the variation of the electronic microenvironment around each constituent nucleobase along the RNA chain in a stepwise manner with very high accuracy without having to make any assumption. This means that the pseudoaromaticity of neighboring 9-adeninyl and next-neighbor nucleobases within a polyanionic sugar-phosphate backbone of a ssRNA can vary from one case to another due to cross-modulation of an electronically coupled pi system by a neighboring nucleobase. This modulation may depend on the sequence context, spatial proximity of the negatively charged phosphates, as well as whether the offset stacking is ON or OFF. The net outcome of this electrostatic interaction between the neighbors is creation of new sequence-dependent hybrid nucleobases in an oligo- or polynucleotide whose properties are unlike the monomeric counterpart, which may have considerable biological implications.

Guanosine Monophosphate↗

The pK(a) of the internucleotidic 2'-hydroxyl group in diribonucleoside (3'-->5') monophosphates.

Ionization of the internucleotidic 2'-hydroxyl group in RNA facilitates transesterification reactions in Group I and II introns (splicing), hammerhead and hairpin ribozymes, self-cleavage in lariat-RNA, and leadzymes and tRNA processing by RNase P RNA, as well as in some RNA cleavage reactions promoted by ribonucleases. Earlier, the pK(a) of 2'-OH in mono- and diribonucleoside (3'-->5') monophosphates had been measured under various nonuniform conditions, which make their comparison difficult. This work overcomes this limitation by measuring the pK(a) values for internucleotidic 2'-OH of eight different diribonucleoside (3'-->5') monophosphates under a set of uniform noninvasive conditions by 1H NMR. Thus the pK(a) is 12.31 (+/-0.02) for ApG and 12.41 (+/-0.04) for ApA, 12.73 (+/-0.04) for GpG and 12.71 (+/-0.08) for GpA, 12.77 (+/-0.03) for CpG and 12.88 (+/-0.02) for CpA, and 12.76 (+/-0.03) for UpG and 12.70 (+/-0.03) for UpA. By comparing the pK(a)s of the respective 2'-OH of monomeric nucleoside 3'-ethyl phosphates with that of internucleotidic 2'-OH in corresponding diribonucleoside (3'-->5') monophosphates, it has been confirmed that the aglycons have no significant effect on the pK(a) values of their 2'-OH under our measurement condition, except for the internucleotidic 2'-OH of 9-adeninyl nucleotide at the 5'-end (ApA and ApG), which is more acidic by 0.3-0.4 pK(a) units.

Endoribonucleases↗

Tandem electrostatic effect from the first to the third aglycon in the trimeric RNA owing to the nearest-neighbor interaction.

We here show an electrostatic polar-pi interaction from the first to the third aglycon, via the second aglycon, in the ground state in two single stranded trimeric RNAs, 5'-GpA(1)pA(2)-3' (3) and 5'-GpApC-3' (4), as a result of intramolecular nearest neighbor offset-stacking. The experimental evidence in support of this conclusion has been obtained by comparing the pK(a)s of each aglycone in the two trimers with those of guanosine 3'-ethyl phosphate, GpEt (1) and 5'-GpA-3' (2): Thus, the pK(a) of N(1)-H of guanin-9-yl of 5'-GpA(1)pA(2)-3' (3) could be measured by pH titration (pH 7.3-11.6) of its own deltaH8G (pK(a) 9.75 +/- 0.02) as well as from deltaH8A(1) (pK(a) 9.72 +/- 0.02) and deltaH2A(1) (pK(a) 9.83 +/- 0.04) of the neighboring pA(1)p moiety and the deltaH8A(2) (pK(a) 9.83 +/- 0.02) of the terminal pA(2) moiety. Similarly, the pH titration of GpApC (4) shows the pK(a) of N(1)-H of guanin-9-yl from its own deltaH8G (pK(a) 9.88 +/- 0.03) as well as from deltaH8A (pK(a) 9.87 +/- 0.01) of the neighboring pAp moiety, and deltaH5/H6C (pK(a) 9.88 +/- 0.01 and 9.90 +/- 0.01 respectively) of the 3'-terminal cytosin-1-yl. This intramolecular nearest neighbor electrostatic interaction in the single-stranded RNA modulates the pseudoaromaticity of the nearest neighbors by almost total transmission of because they constitute an extended array of offset-stacked coupled aromatic heterocycles within a polyanionic sugar-phosphate backbone at the ground state. The enhanced basicity of Gp residue by ca. 0.6 pK(a) unit in the trimers compared to that of the dimer is a result of the change in the electrostatic microenvironment owing to the nearest neighbors in the former (the nucleobases as well as the phosphates). Thus, the from the 5'-guanylate ion to the 3'-end aglycon via the central adenin-9-yl is 55 to 56 kJ mol(-)(1) in each step through a distance spanning approximately 6.8 A in an unfolded state. As a result, the pK(a) of guanin-9-yl moiety has become 9.25 +/- 0.02 in GpEt (1), 9.17 +/- 0.02 in GpA (2), 9.75 +/- 0.02 in GpApA (3), and 9.88 +/- 0.03 in GpApC (4). This means that guanin-9-yl moiety of trimers 3 and 4 is more basic than in the monomer or the dimer. The net outcome of this electrostatic cross-talk between the two neighboring heterocycles is creation of new hybrid aglycones in an oligo or polynucleotide, whose physicochemical property and the pseudoaromatic character are completely dependent both upon the nearest neighbors, and whether they are stacked or unstacked. Thus, this tunable physicochemical property of an aglycon (an array of the extended genetic code) may have considerable implication in our understanding of the specific ligand binding ability of an aptamer, the pK(a) and the hydrogen bonding ability of nucleic acids in a microenvironment, or in the triplet usage by the anticodon-codon interaction in the protein biosynthesis in the ribosome.

Hydrogen-Ion Concentration↗

Aberrant subclavian artery causing difficulty in transhiatal esophageal dissection.

The right subclavian artery normally arises from the brachiocephalic artery. Anomalies in development may lead to peculiar problems during surgery. We report a patient with esophageal carcinoma who had an aberrant right subclavian artery, posing specific difficulties during a transhiatal esophagectomy, requiring conversion of the procedure into a transthoracic approach. The embryologic basis of this anomaly and the clinical significance are discussed.

Carcinoma, Squamous Cell↗

Lead acetate induced cytotoxicity in male germinal cells of Swiss mice.

Single intraperitoneal injection of lead acetate (200 mg/kg b.w) to Swiss mice stimulated testicular weight loss with a constant increase in the incidence of abnormal sperm population and decrease in the total sperm count. Testicular ascorbic acid also declined significantly during the post-treatment phase with significant rise in Lipid Peroxidation Potential (LPP) of the tissue. Elevated LPP is indicative of oxidative stress in treated mice testes. The possible role of lead-induced oxidative stress in culminating increased sperm abnormality and decreased sperm count have been discussed. Further, possible antioxidative role of testicular ascorbic acid in minimizing oxidative stress in lead-treated mice has been demonstrated.

Animals↗

Formula feeding in infancy is associated with adolescent body fat and earlier menarche.

The tempo, level of growth and maturation during adolescence may have important implications to future adult health. The purpose of the study was to examine factors associated with menarche. Three hundred and forty girls, 9 to 14 years old, were selected from all age eligible girls at Kaiser Permanente Oahu (Honolulu). Girls' age, ethnicity, menstrual status and feeding pattern during infancy were obtained by questionnaire. The mean age of girls was 11.5 +/- 1.4 yr and the mean age at menarche among 112 (33%) girls who had reached menarche was 11.6 +/- 1.1 yr. In logistic regression, achievement of menarche was positively explained by age, Asian ethnicity and formula feeding during infancy. In simple linear regression, higher body mass index (BMI) and subcutaneous fat were also positively associated with formula feeding during infancy. The study suggests that girls who were formula fed deposit more body fat than girls who were breast-fed, resulting in early attainment of menarche.

Adipose Tissue↗

Cross-modulation of physicochemical character of aglycones in dinucleoside (3'-->5') monophosphates by the nearest neighbor interaction in the stacked state.

Each nucleobase in a series of stacked dinucleoside (3'-->5') monophosphates, in both acidic and alkaline pH, shows ((1)H NMR) not only its own pK(a) but also the pK(a) of the neighboring nucleobase as a result of cross-modulation of two-coupled pi systems of neighboring aglycones. This means that the electronic character of two nearest neighbors are not like the monomeric counterparts anymore; they have simultaneously changed, almost quantitatively, to something that is a hybrid of the two due to two-way transmission of charge (i.e. 3'-->5' as well as 5'-->3'). This change is permanent due to total modulation of each others pseudoaromatic character by intramolecular stacking, which can be tuned by the nature of the medium across the whole pH range. The small difference observed in the pK(a) of the dimer compared to the monomer is a result of the change in microenvironment in the former. The charge transfer takes place between two stacked nucleobases from the negatively charged end because of the attempt to minimize the charge difference between the two neighboring pseudoaromatic aglycones. Experimental evidence points that the charge transmission in the stacked state takes place by atom-pisigma interaction between nearest neighbor nucleobases in 1-6. The net result of this cross-talk between two neighboring aglycones is a unique set of aglycones in an oligo- or polynucleotide, whose physicochemical property and the pseudoaromatic character are completely dependent both upon the sequence makeup, and whether they are stacked or unstacked. Thus, the physicochemical property of individual nucleobases in an oligonucleotide is determined in a tunable manner, depending upon who the nearest neighbors are, which may have considerable implication in the specific ligand binding ability of an aptamer, the pK(a) and the hydrogen bonding ability in a microenvironment, in the use of codon triplets in the protein biosynthesis or in the triplet usage by the anticodon-codon interaction.

Carbohydrate Conformation↗

The interaction of DNA mismatch repair proteins with human exonuclease I.

Exonucleolytic degradation of DNA is an essential part of many DNA metabolic processes including DNA mismatch repair (MMR) and recombination. Human exonuclease I (hExoI) is a member of a family of conserved 5' --> 3' exonucleases, which are implicated in these processes by genetic studies. Here, we demonstrate that hExoI binds strongly to hMLH1, and we describe interaction regions between hExoI and the MMR proteins hMSH2, hMSH3, and hMLH1. In addition, hExoI forms an immunoprecipitable complex with hMLH1/hPMS2 in vivo. The study of interaction regions suggests a biochemical mechanism of the involvement of hExoI as a downstream effector in MMR and/or DNA recombination.

Adaptor Proteins, Signal Transducing↗