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Biomedical subjects

V S Chauhan

Publications and source records attributed to V S Chauhan.

At least 19 recordsLinked to original sources
PubMed2005

The prevalence of pressure ulcers in hospitalised patients in a university hospital in India.

OBJECTIVE: To estimate the prevalence of pressure ulcers in hospitalised patients and any underlying or predisposing factors to ulceration. METHOD: This cross-sectional study took place in a university hospital in Varanasi, India. A total of 445 patients hospitalised in medical and surgical wards were examined in a single day for the number, site and grade of pressure ulcers. Haemoglobin, serum albumin and blood sugar levels of patients with pressure ulcers were recorded. RESULTS: The prevalence of pressure ulcers was high (4.94%). Anaemia, malnutrition and diabetes were important risk factors, while morbidity due to pressure ulcers in long-stay wards, such as neurology, was exceptionally high (40.9%). CONCLUSION: Pressure ulcers remain one of the most neglected aspects of health-care provision in India and identifying their associated risk factors at an early stage may go a long way in preventing their occurrence.

Adult↗
PubMed2004

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures.

Amino Acid Sequence↗
PubMed2004

Enteric perforation--single-layer closure.

A hundred cases of enteric perforation, treated surgically by single- or double-layer closure, were studied prospectively. Mortality and morbidity rates were 10-18 and 37-42% and comparable in the two groups. The presence of preoperative shock was the single most important prognostic indicator observed in this study. Hence it is good closure of the perforation rather than single- or double-layer closure that determines the outcome in patients with enteric perforation.

Adolescent↗
PubMed2004

Comparison of immunogenicities of recombinant Plasmodium vivax merozoite surface protein 1 19- and 42-kiloDalton fragments expressed in Escherichia coli.

The 42- and 19-kDa C-terminal fragments of merozoite surface protein 1 (MSP-1(42) and MSP-1(19), respectively) are both promising blood-stage vaccine candidate antigens. At present, it is not clear which of the two antigens will be more suitable for inclusion in a cocktail malaria vaccine. In the present study, we expressed the two C-terminal fragments of Plasmodium vivax MSP-1 (PvMSP-1) in an Escherichia coli expression system and purified them by using a rapid two-step protocol. Both of the products were recognized by monoclonal antibodies against PvMSP-1 as well as by immune sera from several individuals exposed to P. vivax. We analyzed and compared the immunological responses to recombinant PvMSP-1(19) and PvMSP-1(42) in mice by using six different adjuvant formulations. Moderate to high antibody responses were observed with both of the antigens in different adjuvant formulations. Surprisingly, alum, which is generally considered to be a poor adjuvant for recombinant malaria antigens, was found to be as good an adjuvant as Montanide ISA 720, ASO2A, and other adjuvant formulations. Most adjuvant formulations induced high levels of immunoglobulin G1 (IgG1), followed by IgG3 and IgG2. Lymphocytes from animals in the PvMSP-1(42)- and PvMSP-1(19)-immunized groups showed proliferative responses upon stimulation with the respective antigens, and high levels of interleukin-4 (IL-4), IL-5, and gamma interferon were detected in the culture supernatants. Immunodepletion studies with sera from mice immunized with these two antigens showed that while immunization with PvMSP-1(42) does produce a PvMSP-1(19)-specific response, a substantial portion is also focused on structures in PvMSP-1(42) not represented by the epidermal growth factor-like domains of PvMSP-1(19). These findings may have implications for the design of MSP-1-based vaccine constructs.

Adjuvants, Immunologic↗
PubMed2003

Role of a two-residue spacer in an alpha,beta-Didehydrophenylalanine containing hexapeptide: crystal and solution structure of Boc-val-deltaPhe-Leu-Ala-deltaPhe-Ala-OMe.

The peptide Boc-Val1-deltaPhe2-Leu3-Ala4-deltaPhe5-Ala6-OMe has been examined for the structural consequence of placing a two-residue segment between the deltaPhe residues. The peptide is stabilized by four consecutive beta-turns. The overall conformation of the molecule is a right-handed 3(10)-helix, with average (phi, psi) values (-67.7 degrees, -22.7 degrees), unwound at the C-terminus. The 1H NMR results also suggest that the peptide maintains its 3(10)-helical structure in solution as observed in the crystal state. The crystal structure is stabilized through head-to-tail hydrogen bonds and a repertoire of aromatic interactions laterally directed between adjacent helices, which are antiparallel to each other. The aromatic ring of deltaPhe5 forms the hub of multicentred interactions, namely as a donor in aromatic C-H...pi and aromatic C-H...O=C interactions and as an acceptor in a CH3...pi interaction. The present structure uniquely illustrates the unusual capability of a deltaPhe ring to host such concerted interactions and suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures.

Circular Dichroism↗
PubMed2002

Development of molecular markers for screening of Alnus nepalensis (D. Don) genotypes for the nitrogenase activity of actinorhizal root nodules.

Alnus nepalensis (D. Don), an alder species, is an actinorhizal tree found in the hilly regions of Eastern and Northeastern India. It is useful in the reclamation of wastelands generated by land slips, shifting agriculture and coal mining. To maximise the soil regeneration capacity of alder plantations, it would be useful to be able to select superior alder genotypes at the nursery level. Conventional methods of genotype screening are difficult to apply to open-pollinated forest trees. It would be beneficial if molecular markers could be developed for early screening. The study reported here was conducted to assess the feasibility of developing PCR-based AFLP and RFLP screening tools for the selection of superior genotypes of this valuable tree with respect to their ability to support efficient nitrogen-fixing root nodules. It was found that a multi-site strategy, including the chloroplast rrn operon and the nuclear rRNA genes, yielded promising results. A molecular marker for genotypes that support nodules with low nitrogenase activity was also identified.

Alnus↗
PubMed2002

Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization.

A lack of molecular understanding of the targets and mechanisms of artemisinin action has impeded the improvisation of more efficient antimalarials based on this class of endoperoxide drugs. We have synthesized a heme-artemisinin adduct designated as "hemart" to discover if it mediates the ability of artemisinin to inhibit heme polymerization. Hemart mimics heme in binding to Plasmodium falciparum histidine-rich protein II (PfHRP II) but cannot self-polymerize. Instead, it inhibits all heme polymerizations, including basal and those triggered by PfHRP II, Monooleoyl glycerol (MOG), or P. yoelii extract. Hemart has an edge over heme in displacing heme from PfHRP II, and either low pH or chloroquine dissociates heme but not hemart from PfHRP II. Our results suggest that hemart, by mimicking heme, stalls all mechanisms of heme polymerization, resulting in the death of the malaria parasite.

Animals↗
PubMed2001

Flexibility in MHC and TCR recognition: degenerate specificity at the T cell level in the recognition of promiscuous Th epitopes exhibiting no primary sequence homology.

Recognition of peptide Ags by T cells through the TCR can be highly specific. In this report we show the degeneracy of Ag recognition at both MHC and TCR levels. We present evidence that unrelated promiscuous Th cell epitopes from various protein sources exhibit sufficient structural homology, despite minimal structural identity, to elicit cross-reactive proliferative responses at the bulk T cell level. This epitopic mimicry was also observed when peptide (CS.T3(378-395) and TT(830-844))-specific CD4+ T cell lines and T cell hybridoma clones were used in proliferation and Ag presentation assays. A scrambled CS.T3(378-395) peptide did not show any proliferation, indicating that the specificity of the cross-reactive responses may be linked with the primary structure of the peptides. Blocking of CS.T3(378-395)-specific CD4+ T cell proliferation by anti-MHC class II mAb showed that recognition of promiscuous T cell epitopes is largely in association with MHC class II molecules. These findings suggest that promiscuous Th epitopes may be useful in designing peptide-based vaccine constructs. At the same time these results show that at the T cell level there may be a great deal of immunological cross-reactivity between heterologous pathogens, and because of this the host's response to a pathogen may be modified by its previous experience with other unrelated pathogens.

Amino Acid Sequence↗
PubMed2001

Mechanism of malarial haem detoxification inhibition by chloroquine.

The haem detoxification pathway of the malaria parasite Plasmodium falciparum is a potential biochemical target for drug development. Free haem, released after haemoglobin degradation, is polymerized by the parasite to form haemozoin pigment. Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2) has been implicated as the catalytic scaffold for detoxification of haem in the malaria parasite. Previously we have shown that a hexapeptide repeat sequence (Ala-His-His-Ala-Ala-Asp), which appears 33 times in Pfhrp-2, may be the major haem binding site in this protein. The haem binding studies carried out by ourselves indicate that up to 18 equivalents of haem could be bound by this protein with an observed K(d) of 0.94 microM. Absorbance spectroscopy provides evidence that chloroquine is capable of extracting haem bound to Pfhrp-2. This was supported by the K(d) value, of 37 nM, observed for the haem-chloroquine complex. The native PAGE studies reveal that the formation of the haem-Pfhrp-2 complex is disrupted by chloroquine. These results indicate that chloroquine may be acting by inhibiting haem detoxification/binding to Pfhrp-2. Moreover, the higher affinity of chloroquine for haem than Pfhrp-2 suggests a possible mechanism of action for chloroquine; it may remove the haem bound to Pfhrp-2 and form a complex that is toxic to the parasite.

Amino Acid Sequence↗
PubMed2001

De novo design and characterization of an apolar helical hairpin peptide at atomic resolution: Compaction mediated by weak interactions.

Design of helical super secondary structural motifs is expected to provide important scaffolds to incorporate functional sites, thus allowing the engineering of novel miniproteins with function. An alpha,beta-dehydrophenylalanine containing 21-residue apolar peptide was designed to mimic the helical hairpin motif by using a simple geometrical design strategy. The synthetic peptide folds into the desired structure as assessed crystallographically at 1.0-A resolution. The two helices of the helical-hairpin motif, connected by a flexible (Gly)(4) linker, are docked to each other by the concerted influence of weak interactions. The folding of the peptide without binary patterning of amino acids, disulfide bonds, or metal ions is a remarkable observation. The results demonstrate that preferred interactions among the hydrophobic residues selectively discriminate their putative partners in space, leading to the unique folding of the peptide, also a hallmark of the unique folding of hydrophobic core in globular proteins. We demonstrate here the engineering of molecules by using weak interactions pointing to their possible further exploitation in the de novo design of protein super secondary structural elements.

Amino Acid Sequence↗
PubMed2001

Regulation of sodium influx in the NaCl-resistant (NaCl(r)) mutant strain of the cyanobacterium Anabaena variabilis.

A NaCl(r) mutant of the diazotrophic cyanobacterium Anabaena variabilis has been isolated by NTG mutagenesis and selection for NaCl resistance. The NaCl(r) strain has been characterized with respect to its mechanism of NaCl tolerance and regulation of Na(+) influx. NaCl(r) strain exhibits low Na(+) influx, accumulated high level of glycine betaine as a compatible solute, and persistent synthesis of SSPs at a higher rate than its wild-type counterpart. DCMU, an inhibitor of PS-II, inhibited Na(+) influx, suggesting that Na(+) influx is an energy-dependent process and that the energy is derived from photophosphorylation. This contention is further supported by the inhibition of Na(+) influx under dark conditions. The inhibition of Na(+) influx by KCN, DNP, NaN(3) also supports the involvement of oxidative phosphorylation in the regulation of active Na(+) influx. Thus, it appears that the synthesis of SSPs, accumulation of compatible solutes, and exhibition of low Na(+) influx in the NaCl(r) strain made this organism NaCl tolerant.

Anabaena↗
PubMed2001

Isolation and partial characterization of Het- Fix- mutant strain of the diazotrophic cyanobacterium Anabaena variabilis showing chromatic adaptation.

We propose a model to describe the changes taking place in biochemical processes/events to explain the development of heterocyst and nitrogenase in a diazotrophic cyanobacterium Anabaena variabilis. For this purpose, a mutant strain of A. variabilis lacking heterocyst differentiation and incapable of growth with dinitrogen as the sole source of nitrogen has been isolated after nitrosoguanidine (NTG) mutagenesis and selection by penicillin enrichment. The mutant strain (Het- Fix-) thus isolated has morphological variation and was incapable of reducing acetylene under anaerobic conditions, indicating its mutational loss of the process of nitrogen fixation. The Het- Fix- mutant strain had reduced glutamine synthetase (transferase) activity compared with its wild-type counterpart, suggesting a link between nif gene expression and the expression of gln A, the structural gene of GS. The Het- Fix- mutant strain compared with its wild-type strain also had an extremely high level of phycobiliprotein and a low level of carotenoids. Furthermore, the coiling of vegetative filaments in the Het- Fix- mutant strain, which reduced the surface area to be exposed to light, was a direct indication of the chromatic adaptation, because the mutant strain was found to be photosensitive, showing bleaching of the cells under high light intensity.

Anabaena↗
PubMed2001

Supraventricular tachycardia.

Supraventricular tachycardias (SVT) comprise those tachycardias that originate above the bifurcation of the bundle of His. They can be classified broadly as AV node dependent and AV node independent. The mechanism and clinical manifestation of SVTs, which is essential to their correct diagnosis, is reviewed. The therapeutic management of SVTs, including acute and chronic drug therapy and catheter ablation, is discussed also.

Anti-Arrhythmia Agents↗
PubMed2001

Immunogenicity of recombinant fragments of Plasmodium falciparum acidic basic repeat antigen produced in Escherichia coli.

The acidic basic repeat antigen (ABRA) of Plasmodium falciparum is a potential vaccine candidate against erythrocytic stages of malaria. We report, for the first time, the immunological characteristics of recombinant ABRA constructs. The recombinant proteins representing different fragments of ABRA were expressed in Escherichia coli, either as fusions with maltose binding protein or as 6X histidine tagged molecules, and purified by affinity chromatography. Immunogenicity studies with these constructs in rabbits and mice indicated that the N-terminal region is the least immunogenic part of ABRA. T-cell proliferation experiments in mice immunized with these constructs revealed that the T-cell epitopes were localized in the middle portion of the protein. More importantly, the purified immunoglobulin G specific to middle and C-terminal fragments prevented parasite growth at levels approaching 80-90%. We found that these proteins were also recognized by sera from P. falciparum-infected patients from Rourkela, a malaria endemic zone of India. Our immunogenicity results suggest that potential of ABRA as a vaccine candidate antigen should be investigated further.

Adolescent↗