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Biomedical subjects

A S Acharya

Publications and source records attributed to A S Acharya.

At least 19 recordsLinked to original sources
PubMed2005

Precontrol observations on lymphatic filariasis & geo-helminthiases in two coastal districts of rural Orrisa.

BACKGROUND & OBJECTIVE: Lymphatic filariasis (LF) is a major public health problem in India, accounting for 40 per cent of the global burden. The World Health Organization has launched a global programme to eliminate LF by 2020 and India is a signatory to it. Orissa, an eastern Indian State has long been known to be endemic for LF. Prior to implementation of mass drug administration programme it is important to collect baseline data on filariasis and geo-helminthiases in the State. The present cross-sectional survey was therefore carried out between February and December 2001 to obtain baseline information on both LF and geo-helminthiases before application of the control measures. METHODS: The study was carried out in rural areas of Puri and Ganjam districts in two phases. In phase I, the distribution of microfilaraemia in two district was mapped out in randomly selected primary health centres (PHCs), and 12 microfilaraemic villages were identified in each district by cluster analysis for the phase II study. In phase II, detailed clinical and parasitological survey for LF and geo-helminthiases was carried out following the standard procedures. RESULTS: Wuchereria bancrofti was found to be widely prevalent in Puri district with certain pockets of Brugia malayi while W. bancrofti was the only species in Ganjam district. The microfilaraemia (Mf) rate was found to be 9.5 and 11.1 per cent; and circulating filarial antigenaemia (CFA) was 16.8 and 17.8 per cent in Puri and Ganjam respectively. The geometric mean intensity (GMI) of Mf per ml of blood among positive individuals was 387 in Puri and 454 in Ganjam. The overall disease rate in Puri was 7.9 and 8.9 per cent in Ganjam. The prevalence of chronic manifestations was found to be significantly higher (P<0.001) than the acute manifestations in both the districts. The prevalence of geo-helminthiases was 31.8 per cent in Puri and 42.1 per cent in Ganjam; and the heavy infection was found to be significantly higher (P<0.001) in Ganjam compared to Puri district. INTERPRETATION & CONCLUSION: The present study identified LF and geo-helminthiases as widely distributed health problem in rural areas of coastal Orissa which warrants intervention measures along the lines recommended by the global programme for elimination of LF and geo-helminthiases to reduce the disease burden.

Adolescent↗
PubMed2004

The PfCRT (K76T) point mutation favours clone multiplicity and disease severity in Plasmodium falciparum infection.

In Orissa, a malaria-hyperendemic area of India, we assessed the relationship between the PfCRT (K76T) point mutation of Plasmodium falciparum and the clinical severity of malaria. Forty uncomplicated and 36 severe malaria cases were selected, and parasite species, density and schizontaemia determined by examination of Giemsa-stained thick or thin blood films. The PfCRT point mutation was analysed by PCR-RFLP and genotypes of the parasite isolates investigated by nested PCR using the polymorphic region of the merozoite surface protein-2. We found that (i) the prevalence of the PfCRT point mutation was significantly higher (P < 0.01) in severe malaria cases and that (ii) heavy parasitaemia along with clone multiplicity was statistically more common (P < 0.01) in severe cases. These associations may be due to progression of uncomplicated to severe disease after chloroquine treatment failure and/or increased virulence of chloroquine-resistant parasites. The implications for antimalarial treatment policy are discussed.

Adult↗
PubMed2002

The economic loss due to treatment costs and work loss to individuals with chronic lymphatic filariasis in rural communities of Orissa, India.

This paper is based on 1 year round case control study to investigate the economic burden, in terms of treatment costs and loss of work to people affected with chronic lymphatic filariasis in rural communities of Orissa, Eastern India. Around three-fourths of the chronic patients have sought treatment for their condition and spent, on average an amount of INR 396 (approximately US$ 8.7) per year. The major component of the expenditure is the cost of medicines. The data on loss of work time due to chronic condition reveal that the total absenteeism to the work is significantly higher among chronic filariasis patients than controls. The total number of working hours spent per day by patients and controls are 4.94 and 6.06, respectively with a significant difference. The total absenteeism and the total number of working hours per day are influenced significantly by disease condition and other personal characteristics, namely age, sex and family type. The chronic patients lose a total of 68 days of work per year, which is equivalent to 19% of the total working time of the year. The present results show that the chronic conditions of lymphatic filariasis pose considerable burden on the patient, family and community.

Absenteeism↗
PubMed2002

Bancroftian filariasis: a 13-year follow-up study of asymptomatic microfilariae carriers and endemic normals in Orissa, India.

The natural history of human filarial infections leading to development of disease has been a subject of intense debate. The models proposed so far have largely been based on cross-sectional data on microfilariae (Mf) and disease prevalence in filariasis endemic areas. In an attempt to study the parasitological and clinical consequences of filarial infection in Beldal (Orissa, India), an area endemic for Bancroftian filariasis, cohorts of 59 asymptomatic Mf carriers (AS) and 187 asymptomatic and amicrofilaraemic subjects or 'endemic normals' ('EN'), were followed-up and a fraction (73% and 46% respectively) re-examined after 13 years to monitor (a) Mf prevalence, (b) Mf density, (c) circulating filarial antigen (CFA) and (d) chronic disease manifestations. The Mf prevalence and density were also monitored in Mf carriers after 1 and 4 years. Both Mf prevalence and density decreased progressively in the cohort of Mf carriers over a period of 13 years in Beldal. Only 37% of them continued to be microfilaraemic and the Mf density in these subjects was only 10% of the original level. However, loss of circulating Mf in this cohort did not result in loss of CFA and 95% remained CFA positive regardless of Mf status. About 23% of males in the 'EN' cohort developed hydrocoele while only 5.7% of male Mf carriers, who were not treated with DEC, had developed hydrocoele after 13 years. A cohort of Mf carriers in another area, Jatni, was also examined after 10 years to study the parasitological and clinical outcome. In this area, about 59% of the Mf carriers continued to be microfilaraemic after 10 years. These results reveal that in Mf carriers adult filarial worms persist for several years and that loss of circulating Mf with or without chemotherapy with DEC (single 12-day course) does not influence adult worm survival. The findings have been discussed in the context of 'static' and 'dynamic' models describing the relationship between infection and disease in human filariasis.

Adolescent↗
PubMed2001

Reduced activity of bamhi variants c54i, c64w, and c54d/c64r is consistent with the substrate-assisted catalysis model.

Three specific mutants, C54I, C54W, and a double-mutant C54D:C64R of restriction endonuclease BamHI, were generated and studied to investigate the role, if any, of the 54th and 64th cysteine residues in the catalysis of BamHI. The mutation was achieved using the megaprimer approach for PCR. The mutant genes were cloned and characterized by sequencing. The mutant and the wild-type proteins were expressed and purified and their kinetic parameters were determined using short synthetic oligonucleotides as substrates. All mutants had higher K(m) values than that of the wild-type enzyme suggesting a decrease in the affinity of the enzyme for its substrate. The mutant protein C54W showed significant changes in the CD spectra vis-a-vis wild-type enzyme and had the lowest K(m)/K(cat) value among the mutants indicative of changes in the secondary structure of the protein. The melting curves of the mutant proteins overlapped that of the wild-type enzyme. Analysis of the K(cat) values in the context of cocrystal structure suggests that the effect of Cys54 mutation is probably through the perturbation of the local structure whereas reduced activity of the double mutant is consistent with the substrate-assisted catalysis mechanism.

Amino Acid Substitution↗
PubMed2001

Elimination of iodine deficiency disorders by 2000 and its bearing on the people in a district of Orissa, India: a knowledge-attitude-practices study.

A knowledge-attitude-practices (KAP) study was conducted along with a prevalence study of iodine deficiency disorders (IDD) between 1998-99 in the district of Bargarh, Orissa state, India. A total of 635 people were interviewed by a pretested structured questionnaire, adopting the probability proportional to size cluster sampling method. The aim was to assess the baseline information on the KAP of the people regarding IDD. Only 37% of the males and 29.3% of the females perceived goitre as a disease. Less than 5% of both sexes knew how goitre is caused. Only 16.4% used iodised salt regularly. The awareness and perception of IDD does not correspond with the time and effort we have spent in education of this disease. The implications of this poor knowledge about IDD and consequent poor use of iodised salt is contrasted to the optimistic target of elimination of IDD. This aspect is discussed in this paper, at a time when we are at the beginning of the new millennium.

Adult↗
PubMed2001

Activation of the low oxygen affinity-inducing potential of the Asn108(beta)-->Lys mutation of Hb-Presbyterian on intramolecular alpha alpha-fumaryl cross-bridging.

The Asn108 beta-->Lys mutation in hemoglobin (HbPresbyterian mutation) endows a low O(2) affinity-inducing propensity to the protein. Introduction of a fumaryl cross-bridge between its two alpha 99 lysine residues also induces a low O(2) affinity into HbA. We have now engineered an alpha alpha-fumaryl cross-bridge into Hb-Presbyterian to determine the synergy or additivity, if any, that can be achieved between these two low O(2) affinity-inducing structural perturbations. Despite the presence of the additional epsilon-amino group of Lys108(beta) within the central cavity, the epsilon-amino group of Lys99(alpha alpha) of deoxy Hb-Presbyterian retained high selectivity for alpha alpha-fumaryl cross-bridging, with an overall efficiency comparable to that with HbA. The alpha alpha-fumaryl cross-linking of Hb-Presbyterian reduced its O(2) affinity much more significantly than that observed with HbA, indicating a synergy between the two low O(2) affinity-inducing structural perturbations. Apparently, the alpha alpha-fumaryl cross-bridge in Hb-Presbyterian activates part of the latent low O(2) affinity-inducing potential of Lys108(beta) that is generally activated in the presence of chloride. The synergy between the Asn108(beta)-->Lys mutation and the alpha alpha-fumaryl cross-bridging was conserved in the presence of chloride, but not in the presence of DPG. Furthermore, in the presence of chloride and DPG, alpha alpha-fumaryl Hb-Presbyterian accessed a low O(2) affinity T-state that is accessed by HbA, alpha alpha-HbA and Hb-Presbyterian only in the presence of IHP. Isoelectric focusing analysis suggested that the alpha alpha-fumaryl cross-linking of Hb-Presbyterian induces changes in the ionization behavior of one or more of the functional groups neighboring Lys99(alpha) and Lys108(beta) [presumably His103(alpha) and/or Glu101(beta)] to compensate for the extra positive charge of Lys108(beta). Molecular modeling studies identified two potential chloride binding sites per alpha beta dimer within the middle of the central cavity of alphaalpha-fumaryl HbA involving residues His103(alpha), Arg104(beta) and Asn108(beta). The affinity of these sites is increased in alpha alpha-fumaryl Hb-Presbyterian as a result of the Asn108(beta)-->Lys mutation. Thus, the results of the present study suggest that the enhanced neutralization of the positive charges in the middle of the central cavity of Hb achieved by these two electrostatic modifications, one (the alpha alpha-fumaryl cross-bridge) acting directly and the other (the Presbyterian mutation) acting indirectly through the mediation of chloride ion binding, facilitates the alpha alpha- fumaryl-Hb Presbyterian to access a low O(2) affinity T-state structure much more readily than either Hb-Presbyterian or alpha alpha-fumaryl HbA.

Allosteric Regulation↗
PubMed2001

Lymphatic filariasis in Khurda district of Orissa, India: an epidemiological study.

A cross-sectional survey was undertaken to determine the prevalence of disease due to lymphatic filariasis in Khurda district of Orissa, India. The total disease attributable to filariasis was significantly higher in males (14.79%) than females (10.04%). However, elephantiasis is more prevalent in females, and adenolymphangitis is more prevalent in males than their counterparts. The prevalences of various forms of the disease are age dependent in both sexes. About one-seventh of men and women of higher age groups suffered from chronic debilitation forms of the disease. The study suggests that overt clinical forms of lymphatic filariasis constitute a major public health problem in the study area.

Adolescent↗
PubMed2001

A clinico-epidemiological perspective of lymphatic filariasis in Satyabadi block of Puri district, Orissa.

BACKGROUND & OBJECTIVES: Lymphatic filariasis is a major public health problem in the coastal district of Orissa. However, no systematic studies have been done to document the prevalence of microfilaraemia/disease in different regions of the State. Therefore, the present cross sectional study was undertaken during 1996-97 to obtain information on the clinical and epidemiological status of the disease in Satyabadi block area of Puri district, known to be endemic for filariasis. METHODS: Night blood smear survey and clinical examinations were performed on 4646 individuals aged 0-> or = 60 yr from systematically selected households of 17 randomly selected villages of the Block. Microfilaraemia was detected by thick drop technique using 20 microliters of peripheral blood and microfilariae (mf) density by nucleopore filtration technique collected during 1900-2300 h. RESULTS: The prevalence of microfilaraemia was observed to be 14.8 per cent; 13.3 per cent Wuchereria bancrofti, 1.4 per cent Brugia malayi and 0.09 per cent had mixed infections. Geometric mean microfilaraemia density (infected persons only) was found to be 1288 per ml in case of W. bancrofti and 204 per ml in case of B. malayi. The disease rate was observed to be 19.8 per cent; 12.85 per cent had acute manifestations and 6.97 per cent had chronic manifestations. INTERPRETATION & CONCLUSION: The rate of acute disease manifestations was observed to be significantly higher (P < 0.001) than chronic manifestations. There was a male preponderence among the affected individuals (P < 0.001). The interesting observations of the study were the occurrence of occult filarial manifestations viz., tropical pulmonary eosinophilia (TPE) in 0.47 per cent cases and other associated manifestations like asymptomatic microscopic haematuria, monoarticular arthritis and filarial associated respiratory diseases in 0.50, 0.24 and 0.19 per cent of cases respectively. The present study indicates that the area is highly endemic for lymphatic filariasis with active transmission.

Adolescent↗
PubMed2001

An alternative approach for screening active bam HI variants: overexpression in T-7 RNA polymerase based system.

The type II restriction endonuclease, Bam HI, has been overexpressed in E. coli by cloning the Bam HI gene in frame with an E. coli Ribosome Binding Site (RBS) under the T7 promoter of an E. coli expression vector pRSET A. The expression level of Bam HI endonuclease using this construct was found to be higher than that reported of the overexpressing clone pAEK14. Our overexpressing clone, pAABRw in BL21 cells in presence of Bam HI methylase in pMAP6 following induction with IPTG yields about 9.2 x 10(6) units per gram wet cell paste. In vivo activity of the recombinant endonuclease could be confirmed by the SOS induction assay in JH139 cells even in the absence of T7 polymerase and cognate Bam HI methylase because of leaky expression in E. coli. This provides an alternate way to screen the active endonuclease and its variants.

Binding Sites↗
PubMed2000

Interspecies hybrid HbS: complete neutralization of Val6(beta)-dependent polymerization of human beta-chain by pig alpha-chains.

Interspecies hybrid HbS (alpha(2)(P)beta(2)(S)), has been assembled in vitro from pig alpha-globin and human beta(S)-chain. The alpha(2)(P)beta(2)(S) retains normal tetrameric structure (alpha(2)beta(2)) of human Hb and an O(2) affinity comparable to that of HbS in 50 mM Hepes buffer; but, its O(2) affinity is slightly higher than that of HbS in the presence of allosteric effectors (chloride, DPG and phosphate). The (1)H-NMR spectroscopy detected distinct differences between the heme environments and alpha(1)beta(1) interfaces of pig Hb and HbS, while their alpha(1)beta(2) interfaces appear very similar. The interspecies hybrid alpha(2)(H)beta(2)(P) resembles pig Hb; the pig beta-chain dictated the conformation of the heme environment of the human alpha-subunit, and to the alpha(1)beta(1) interfaces of the hybrid. In the alpha(2)(P)beta(2)(S) hybrid, beta(S)-chain dictated the conformation of human heme environment to the pig alpha-chain in the hybrid; but the conformation of alpha(1)beta(1) interface of this hybrid is close to, but not identical to that of HbS. On the other hand, the alpha(1)beta(2) interface conformation is identical to that of HbS. More important, the alpha(2)(P)beta(2)(S) does not polymerize when deoxygenated; pig alpha-chain completely neutralizes the beta(S)-chain dependent polymerization. The polymerization inhibitory propensity of pig alpha-chain is higher when it is present in the cis alpha(P)beta(S) dimer relative to that in a trans alpha(P)beta(A) dimer. The semisynthetically generated chimeric pig-human and human-pig alpha-chains by exchanging the alpha(1-30) segments of human and pig alpha-chains have established that the sequence differences of pig alpha(31-141) segment can also completely neutralize the polymerization. Comparison of the electrostatic potential energy landscape of the alpha-chain surfaces of HbS and alpha(2)(P)beta(2)(S) suggests that the differences in electrostatic potential energy surfaces on the alpha-chain of alpha(2)(P)beta(2)(S) relative to that in HbS, particularly the ones involving CD region, E-helix and EF-corner of pig alpha-chain are responsible for the polymerization neutralization activity. The pig and human-pig chimeric alpha-chains can serve as blueprints for the design of a new generation of variants of alpha-chain(s) suitable for the gene therapy of sickle cell disease.

Allosteric Regulation↗
PubMed2000

Cys-93-betabeta-succinimidophenyl polyethylene glycol 2000 hemoglobin A. Intramolecular cross-bridging of hemoglobin outside the central cavity.

Bis(maleidophenyl)-PEG2000 (Bis-Mal-PEG2000), a new bifunctional protein cross-linker targeted to sulfhydryl groups, introduces intra-tetrameric cross-links into oxy-HbA in nearly quantitative yields. Structural as well as crystallographic analyses of the cross-linked species, Bis-Mal-PEG2000 HbA, identified Cys-93(beta) as the site of intramolecular cross-linking. The cross-bridging had only a limited influence on the O(2) affinity and cooperativity of HbA in 50 mM BisTris acetate, pH 7.4. However, the Bohr effect was reduced by approximately 60%. Bis-Mal-PEG2000 HbA retained sensitivity to the presence of allosteric effectors 2, 3-diphosphoglycerate, IHP, and chloride, albeit to a lesser degree compared with HbA. Crystallographic analysis revealed the overall structure of deoxy-Bis-Mal-PEG2000 HbA to be similar to deoxy-HbA but for the loss of the salt bridge between Asp-94(beta) and His-146(beta). The large influence of the cross-bridging on the alkaline Bohr effect of HbA is consistent with the loss of this salt bridge. Unlike the "central cavity cross-bridges" described previously, the cross-link introduced by Bis-Mal-PEG2000 into HbA is an "outside the central cavity cross-bridge." In view of its oxy-conformational specificity and limited influence on O(2) affinity, this new cross-linking strategy holds promise for the stabilization of new designer low O(2) affinity Hbs generated by recombinant DNA technology for applications as Hb based therapeutics.

Buffers↗
PubMed2000

Perturbation of the intermolecular contact regions (molecular surface) of hemoglobin S by intramolecular low-O2-affinity-inducing central cavity cross-bridges.

The general assumption among researchers on hemoglobin is that the intramolecular central cavity cross-bridging of Hb does not result in any generalized perturbations at the protein surface. A corollary of this is that central cavity cross-bridges are unlikely to influence the polymerization of deoxy HbS, since polymerization is a protein surface phenomenon involving the participation of multiple protein surface amino acid residues. In an attempt to evaluate this experimentally, we have introduced two low-O2-affinity-inducing central cavity cross-bridges into HbS, beta(beta)-sebacyl [between the two Lys-82(beta) residues] and alpha(alpha)-fumaryl [between the two Lys-99(alpha) residues], and investigated their influence on the polymerization of the deoxy protein. The O2 affinities of the cross-bridged HbS exhibited sensitivity toward the buffer ions and pH in a cross-link-specific fashion. The modulation of the O2 affinity of these cross-bridged HbS in the presence of allosteric effectors, DPG and L-35, is also very distinct, reflecting the differences in the conformational features these two cross-bridges induce within the central cavity at the respective effector-binding domains. In addition, the alpha(alpha)-fumaryl cross bridge inhibited the polymerization, reflecting the perturbation of the microenvironment of one or more intermolecular contact residues, protein surface residues, as a consequence of the central cavity cross-bridge. On the other hand, the beta(beta)-sebacyl cross-bridge exerted a slight potentiating effect on the polymerization of HbS. This reflects the fact that the perturbations at the protein surface are limited and favor polymerization. The results presented demonstrate that the structural changes induced by the central cavity cross-bridges are very specific and not simply restricted to the sites of modification, but are propagated to distant sites/domains, both within and outside the central cavity. It is conceivable that other surface regions that are not involved in the polymerization could also experience similar structural/conformational consequences. These results should be taken into consideration in designing intramolecularly cross-bridged asymmetric hybrid HbS for mapping the contribution of the intermolecular contact residues in the cis and trans dimers of deoxy HbS during polymerization.

Allosteric Regulation↗
PubMed2000

Nutritional status of preschool children in the drought affected Kalahandi district of Orissa.

A community-based cross-sectional study was undertaken to determine the magnitude of undernutrition and protein-energy malnutrition among young children during 1996-97 in drought affected Kalahandi district of Orissa. A total of 751 children aged 0-5 yr were studied for anthropometry and clinical signs of nutritional deficiencies from 15 Gram Panchayats selected using probability proportionate to size sampling. There was no significant difference between boys and girls for nutritional status. According to weight-for-age, 57.1 per cent of the children were suffering from underweight (< median -2SD) and 21.3 per cent of children had very low body weights which were < -3SD of standard. Height-for-age and weight-for-height data showed that 41.8 per cent of children suffered from stunting and 27.9 per cent recorded wasting. The children below one year of age had relatively lower prevalence of malnutrition than the other age groups. The prevalence of clinical PEM in the form of marasmus was found in 0.7 per cent of children, while kwashiorkor was absent. This study showed that malnutrition is still a leading problem among preschool children of Kalahandi district and this has not improved in spite of nutrition intervention programmes which are currently in operation.

Child, Preschool↗
PubMed1999

Probing the diphosphoglycerate binding pocket of HbA and HbPresbyterian (beta 108Asn --> Lys).

HbPresbyterian (beta 108Asn --> Lys, HbP) contains an additional positive charge (per alpha beta dimer) in the middle of the central cavity and exhibits a lower oxygen affinity than wild-type HbA in the presence of chloride. However, very little is known about the molecular origins of its altered functional properties. In this study, we have focused on the beta beta cleft of the Hb tetramer. Recently, we developed an approach for quantifying the ligand binding affinity to the beta-end of the Hb central cavity using fluorescent analogues of the natural allosteric effector 2, 3-diphosphoglycerate (DPG) [Gottfried, D. S., et al. (1997) J. Biol. Chem. 272, 1571-1578]. Time-correlated single-photon counting fluorescence lifetime studies were used to assess the binding of pyrenetetrasulfonate to both HbA and HbP in the deoxy and CO ligation states under acidic and neutral pH conditions. Both the native and mutant proteins bind the probe at a weak binding site and a strong binding site; in all cases, the binding to HbP was stronger than to HbA. The most striking finding was that for HbA the binding affinity varies as follows: deoxy (pH 6.35) > deoxy (pH 7.20) > CO (pH 6.35); however, the binding to HbP is independent of ligation or pH. The mutant oxy protein also hydrolyzes p-nitrophenyl acetate, through a reversible acyl-imidazole pathway linked to the His residues of the beta beta cleft, at a considerably higher rate than does HbA. This implies a perturbation of the microenvironment of these residues at the DPG binding pocket. Structural consequences due to the presence of the new positive charge in the middle of the central cavity have been transmitted to the beta beta cleft of the protein, even in its liganded conformation. This is consistent with a newly described quaternary state (B) for liganded HbPresbyterian and an associated change in the allosteric control mechanism.

2,3-Diphosphoglycerate↗
PubMed1999

Inhibition of beta(S)-chain dependent polymerization by synergistic complementation of contact site perturbations of alpha-chain: application of semisynthetic chimeric alpha-chains.

Mouse alpha(1-30)-horse alpha(31-141) chimeric alpha-chain, a semisynthetic super-inhibitory alpha-chain, inhibits beta(S)-chain dependent polymerization better than both parent alpha-chains. Although contact site sequence differences are absent in the alpha(1-30) region of the chimeric chain, the four sequence differences of the region alpha(17-22) could induce perturbations of the side chains at alpha(16), alpha(20) and alpha(23), the three contact sites of the region. A synergistic complementation of such contact site perturbation with that of horse alpha(31-141) probably results in the super-inhibitory activity of the chimeric alpha-chain. The inhibitory contact site sequence differences, by themselves, could also exhibit similar synergistic complementation. Accordingly, the polymerization inhibitory activity of Hb Le-Lamentin (LM) mutation [His20(alpha)-->Gln], a contact site sequence difference, engineered into human-horse chimeric alpha-chain has been investigated to map such a synergistic complementation. Gln20(alpha) has little effect on the O(2) affinity of HbS, but in human-horse chimeric alpha-chain it reduces the O(2) affinity slightly. In the chimeric alpha-chain, Gln20(alpha) increased sensitivity of the betabeta cleft for the DPG influence, reflecting a cross-talk between the alpha(1)beta(1) interface and betabeta cleft in this semisynthetic chimeric HbS. In the human alpha-chain frame, the polymerization inhibitory activity of Gln20(alpha) is higher compared with horse alpha(1-30), but lower than mouse alpha(1-30). Gln20(alpha) synergistically complements the inhibitory propensity of horse alpha(31-141). However, the inhibitory activity of LM-horse chimeric alpha-chain is still lower than that of mouse-horse chimeric alpha-chain. Therefore, perturbation of multiple contact sites in the alpha(1-30) region of the mouse-horse chimeric alpha-chain and its linkage with the inhibitory propensity of horse alpha(31-141) has been now invoked to explain the super-inhibitory activity of the chimeric alpha-chain. The 'linkage-map' of contact sites can serve as a blueprint for designing synergistic complementation of multiple contact sites into alpha-chains as a strategy for generating super-inhibitory antisickling hemoglobins for gene therapy of sickle cell disease.

Anemia, Sickle Cell↗
PubMed1999

Seroprevalence of HIV infection among jail inmates in Orissa.

Seroprevalence of human immunodeficiency virus (HIV) infection was carried out in three prisons in Orissa from March 1994 to December 1995. All the prisoners of Indian origin (300), housed in these jails tested negative for HIV infection. On the other hand, 33.8 per cent (26/77) of jail inmates from foreign countries (Thailand and Myanmar), serving short terms in Orissa jails were found positive for HIV infection. While all the 26 HIV positive prisoners had HIV-1 infection, five of them had antibodies for HIV-1 and HIV-2 viruses. Such a high prevalence of HIV infection and detection of HIV-2 virus is being reported for the first time from Orissa.

Adolescent↗