PubMed Health⌕ Search

Biomedical subjects

A Choudhary

Publications and source records attributed to A Choudhary.

At least 19 recordsLinked to original sources

Influence of electric field on the hydrogen bond network of water.

Understanding the inherent response of water to an external electric (E)-field is useful towards decoupling the role of E-field and surface in several practically encountered situations, such as that near an ion, near a charged surface, or within a biological nanopore. While this problem has been studied in some detail through simulations in the past, it has not been very amenable for theoretical analysis owing to the complexities presented by the hydrogen (H) bond interactions in water. It is also difficult to perform experiments with water in externally imposed, high E-fields owing to dielectric breakdown problems; it is hence all the more important that theoretical progress in this area complements the progress achieved through simulations. In an attempt to fill this lacuna, we develop a theory based on relatively simple concepts of reaction equilibria and Boltzmann distribution. The results are discussed in three parts: one pertaining to a comparison of the key features of the theory vis a vis published simulation/experimental results; second pertaining to insights into the H-bond stoichiometry and molecular orientations at different field strengths and temperatures; and the third relating to a surprising but explainable finding that H-bonds can stabilize molecules whose dipoles are oriented perpendicular to the direction of field (in addition to the E-field and H-bonds both stabilizing molecules with dipoles aligned in the direction of the field).

Journal Article↗

Modified laser DCR for paediatric nasolacrimal duct obstruction.

AIMS: To evaluate the efficacy, safety, and long-term outcome of modified laser dacryocystorhinostomy (DCR) for primary nasolacrimal duct obstruction, unresponsive to probing. METHODS: Retrospective, noncomparative case-note review of all paediatric cases operated between September 2000 and November 2003. PROCEDURE: A fibre optic light, inserted through the canaliculi into the lacrimal sac was visualized endonasally. Nasal mucosa was incised using a keratome and a bony ostium was created with the Holmium : YAG laser. Bicanalicular silicone tubes were inserted. RESULTS: Five children with a mean follow-up of 25.6 months (range 21-48 months) and a mean age of 7 years were reviewed. Silicone tubes were used in four patients and were removed at a mean 6.5 months (range 3-9 months). One patient developed a mucocele 6 months after the procedure requiring excision of the membrane covering the ostium. There were no other immediate or late postoperative complications. Complete cure of symptoms was achieved in all patients and was maintained at final follow up. CONCLUSION: Modified paediatric laser DCR appears to be an encouraging technique for primary nasolacrimal duct obstruction unresponsive to probing. This may be attributable to the modification of excision of mucous membrane, which may prevent regrowth.

Child↗

Kin discrimination and sex ratios in a parasitoid wasp.

Sex ratio theory provides a clear and simple way to test if nonsocial haplodiploid wasps can discriminate between kin and nonkin. Specifically, if females can discriminate siblings from nonrelatives, then they are expected to produce a higher proportion of daughters if they mate with a sibling. This prediction arises because in haplodiploids, inbreeding (sib-mating) causes a mother to be relatively more related to her daughters than her sons. Here we formally model this prediction for when multiple females lay eggs in a patch, and test it with the parasitoid wasp Nasonia vitripennis. Our results show that females do not adjust their sex ratio behaviour dependent upon whether they mate with a sibling or nonrelative, in response to either direct genetic or a range of indirect environmental cues. This suggests that females of N. vitripennis cannot discriminate between kin and nonkin. The implications of our results for the understanding of sex ratio and social evolution are discussed.

Animals↗

Double extradural hematoma: an analysis of 46 cases.

AIMS: The authors analyze epidemiology, location, clinical profile and outcome of double extradural hematoma (EDH) or EDH at more than one site. DESIGN: A retrospective clinical study. MATERIALS AND METHODS: 46 cases of double EDH were studied. All the cases were evaluated for their mode of injury, clinical presentation, level of sensorium at the time of injury, CT scan finding and outcome after surgery, and were compared with single EDH cases. RESULTS: Out of 1025 cases 46 cases had 'double' EDH. There was bilateral EDH in 39 cases; multiple EDH in 3 cases and ipsilateral double EDH was present in 4 cases. The most common site was frontal (70%). The majority of the patients (80.3%) were in altered sensorium from the time of injury, similar situation was seen in 52.2% of cases with single EDH. The number of patients having a low GCS score was higher when first examined in the double EDH group and the mortality rate was 34.8% as compared to 9% in the single EDH group. CONCLUSION: Majority of the double EDH cases presented with a low GCS and there was a relatively quick neurological deterioration in these cases.

Adolescent↗

Periampullary gangliocytic paraganglioma.

A33-year-old man presented with features of obstructive jaundice. Enterohepatic retrograde cholangiopancreatography examination revealed a periampullary growth. After pancreatoduodenectomy, histologic examination of the growth revealed three elements: a spindle cell element, large ganglion cells, and smaller paraganglioma-like cells arranged in small nests and groups. A diagnosis of gangliocytic paraganglioma was given. Gangliocytic paraganglioma is a rare benign duodenal tumor, with uncertain histogenesis. It is possible to identify the three components that are essential for its diagnosis on routine hematoxylin and eosin sections without the use of immunohistochemical markers. Because this lesion may present clinically as a periampullary carcinoma, it is important to recognize and diagnose this rare, but benign, entity.

Adult↗

Surgery for stage 5 retinopathy of prematurity: the learning curve and evolving technique.

PURPOSE: To describe our experience with management of eyes with stage 5 retinopathy of prematurity (ROP). METHODS: Closed vitreoretinal surgery was done on 96 eyes of patients with stage 5 ROP. Lens was sacrificed in all but one eye. Surgery involved an attempt to clear all preretinal tissue and open the peripheral trough all round. In most instances bimanual surgery under viscoelastic was performed. RESULTS: At last follow up, anatomical success (defined as attached posterior pole) was achieved in 22.5% cases. Significant postoperative problems included reproliferation and secondary glaucoma. Only two infants obtained mobile vision. CONCLUSION: Late identification of disease, lack of prior treatment such as laser or cryo, and higher incidence of narrow-narrow funnel configuration were responsible for the poor surgical results noted in this series. The poor surgical and functional results reemphasize the need for prompt screening and management of infants at risk.

Clinical Competence↗

Mutated cytochrome b as a determinant of a new monoclonal antibody (H8.98) on renal carcinoma cell lines recognized by a Vgamma3Vdelta1(+) T-cell clone.

We generated a monoclonal antibody (MAb), H8.98, that recognizes an antigen shared by 50% of examined renal carcinoma cell (RCC) lines and is susceptible to lysis by a Vgamma3Vdelta1(+) T-cell clone derived from RCC tumor-infiltrating lymphocytes. H8.98 inhibited Vgamma3Vdelta1(+ )T-cell clone-mediated lysis of RCC lines. It did not stain normal kidney lines, melanomas, fibroblasts, Burkitt's lymphoma or Epstein-Barr virus-transformed B-cell lines but it did stain 2 of 4 tested breast cancer lines. Through screening of a renal carcinoma cDNA library using H8.98, we isolated a cDNA clone which, upon sequencing, was found to be cytochrome b with 2 point mutations.

Amino Acid Sequence↗

Role of an operative score in mitral reconstruction in dominantly stenotic lesions.

OBJECTIVE: The role of an operative score in selection and results of mitral valve reconstruction in dominantly stenotic mitral lesions was assessed. METHODS: A total of 136 patients consecutively underwent reconstruction for rheumatic mitral stenosis with or without regurgitation from December 1989 through December 1994. Mitral valve structure was scored for cuspal pliability and thickness, cuspal area loss, chordal length, papillary muscle length, annular dilatation and degree of associated regurgitation and calcification. A score of 0 indicated normal valve while a score of 24 indicated a grossly deformed valve. Age, sex, functional class, cardiac rhythm, mitral valve orifice area, left ventricular and left atrial dimensions, transmitral gradients, pulmonary artery pressures and thoroughness of repair were evaluated. RESULTS: Mitral valve architecture was disorganised moderately in 50 (37%) and severely in 69 (52%) patients. Extent of thoroughness in different operative techniques correlated with good (n = 30) or adequate (n = 60) outcome. Mean mitral valve orifice area increased from 0.77 +/- 0.2 to 2.56 +/- 0.6 cm2, peak gradient dropped from 20.3 +/- 6.2 to 8.6 +/- 3.5 torr, mean gradient from 13.5 +/- 4.9 to 4.76 +/- 2.2 torr and end-diastolic gradient from 10.1 +/- 5.0 to 3.2 +/- 1.9 torr. Lack of recognition of anatomical details and of all necessary componental measures constituted the learning curve of different operators. CONCLUSIONS: Recurrent disease, learning curve, inadequate repair and higher operative mitral valve score were the factors for poorer results in the intermediate term follow-up to 64 months. Thoroughness of repair was the most important correlate of outcome and indicative of expertise.

Adolescent↗

Identification of the complete expressed human TCR V gamma repertoire by flow cytometry.

Five of the six expressed human TCR V gamma regions (V gamma 2, 3, 4, 8 and 9) can be detected by available mAb. No mAb with specificity for the remaining V gamma 5 region has been described. In this study, we have characterized mAb 56.3, which was obtained after immunization with V gamma 2/3/4/9-negative thymic gamma delta cells. V gamma transcripts were analyzed by inverse PCR and RT-PCR in 56.3+ cell lines and clones derived from peripheral blood. mAb 56.3 recognized all cells that expressed in-frame V gamma 5 transcripts. In addition, mAb 56.3 recognized some but not all cells expressing V gamma 3, but did not react with a large panel of clones expressing V gamma 2, 4, 8 or 9. In combination with anti-V gamma 2/3/4 mAb 23D12, V gamma 5-expressing cells could be clearly identified as 56.3+23D12(-). In some donors, mAb 56.3 also recognized a small fraction of TCR alpha beta cells. At the clonal level, these cells expressed in-frame V gamma 5-J beta-C beta or V gamma 3-J beta-C beta trans-rearrangements. When mAb 56.3 was combined with V gamma 2/3/4-, V gamma 8- and V gamma 9-specific mAb, all peripheral blood gamma delta T cells were stained. Thus, mAb 56.3 supplements the panel of available TCR V gamma-specific mAb. It is now possible to analyze the complete expressed human V gamma repertoire by flow cytometry.

Antibodies, Monoclonal↗

Negative electrostatic surface potential of protein sites specific for anionic ligands.

Determination of the crystal structure of an "open" unliganded active mutant (T141D) form of the Escherichia coli phosphate receptor for active transport has allowed calculation of the electrostatic surface potential for it and two other comparably modeled receptor structures (wild type and D137N). A discovery of considerable implication is the intensely negative potential of the phosphate-binding cleft. We report similar findings for a sulfate transport receptor, a DNA-binding protein, and, even more dramatically, redox proteins. Evidently, for proteins such as these, which rely almost exclusively on hydrogen bonding for anion interactions and electrostatic balance, a noncomplementary surface potential is not a barrier to binding. Moreover, experimental results show that the exquisite specificity and high affinity of the phosphate and sulfate receptors for unions are insensitive to modulations of charge potential, but extremely sensitive to conditions that leave a hydrogen bond donor or acceptor unpaired.

Anions↗

Modulation of a salt link does not affect binding of phosphate to its specific active transport receptor.

Electrostatic interactions are among the key forces determining the structure and function of proteins. These are exemplified in the liganded form of the receptor, a phosphate binding protein from Escherichia coli. The phosphate, completely dehydrated and buried in the receptor, is bound by 12 hydrogen bonds as well as a salt link with Arg 135. We have modulated the ionic attraction while preserving the hydrogen bonds by mutating Asp 137, also salt linked to Arg 135, to Asn, Gly or Thr. High-resolution crystallographic analysis revealed that Gly and Thr (but not Asn) mutant proteins have incorporated a more electronegative Cl- in place of the Asp carboxylate. That no dramatic effect on phosphate affinity was produced by these ionic perturbations indicates a major role for hydrogen bonds and other local dipoles in the binding and charge stabilization of ionic ligands.

Asparagine↗

Selective lysis of autologous tumor cells by recurrent gamma delta tumor-infiltrating lymphocytes from renal carcinoma.

We show here that tumor infiltrating lymphocytes (TIL) derived from three renal carcinoma (RC) tumors, which developed in the same patient over a 3-yr period, were systematically enriched in gamma delta + T cells (27-74%) after short term in vitro culture. Analysis of the repertoire of gamma delta + TIL and PBL from this patient, revealed the predominant expression of structurally diverse V delta 1 gamma delta TCR by TIL from the three tumors, contrasting with the classically dominant use of V delta 2 TCR by PBL. Functional analysis further showed that, independently of the V gamma genes expressed, all the V delta 1+ TIL clones exhibited a lytic activity apparently restricted to RC lines, while V gamma 9+V delta 2+ clones (either PBL- or TIL-derived) had a broad killing activity. Surprisingly most V delta 1+ CTL clones lysed several allogeneic, but not the autologous, RC lines. Only one V gamma 3+V delta 1+ TIL clone, identified by its specific variable TCR gene sequence, consistently killed autologous tumor cells, apparently via TCR-mediated MHC-unrestricted recognition. This clone also lysed two allogeneic RC lines out of four tested but did not kill 30 non-RC lines, except for one breast carcinoma line. Significantly, this clone was found in recurrent fashion in all three tumors analyzed, including a metastasis. The high frequency of V delta 1 expressing RC-reactive gamma delta cells among TIL from this patient suggests that this gamma delta subset was selectively trapped and/or preferentially induced to proliferate in the autologous tumors. The recurrence of a single V gamma 3+V delta 1+ gamma delta clone, reacting with autologous tumor cells, inside three tumors of different localizations additionally suggests that, for this clone, intratumor selection and/or proliferation was due to TCR-mediated recognition of a non-MHC-restricted RC-specific Ag.

Adolescent↗

Fine tuning the specificity of the periplasmic phosphate transport receptor. Site-directed mutagenesis, ligand binding, and crystallographic studies.

Phosphorous, primarily in the form of phosphate, is a critical nutrient for the life of a cell. We have previously determined the 1.7-A resolution structure of the phosphate-binding protein, an initial receptor for the high-affinity phosphate active transport system or permease in Escherichia coli (Luecke, H., and Quiocho, F.A. (1990) Nature 347, 402-406). This structure is the first to reveal the key role of hydrogen bonding interactions in conferring the high specificity of the permease, a specificity also shared by other phosphate transport systems. Both monobasic and dibasic phosphates are recognized by the phosphate-binding protein with Asp56 playing a key role. Here we report site-directed mutagenesis, ligand binding, and crystallographic studies of the binding protein which show that introduction of one additional Asp by mutagenesis of the Thr141 in the ligand-binding site restricts binding to only the monobasic phosphate.

Bacterial Proteins↗