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Biomedical subjects

M Dutta

Publications and source records attributed to M Dutta.

At least 19 recordsLinked to original sources

Adsorptive separation of beta-lactam antibiotics: technological perspectives.

An overview on adsorptive separation of cephalosporin antibiotics has been presented. The fundamental aspects on adsorption mechanism, kinetic and column dynamics have been exhaustedly discussed. The importance of molecular modelling studies on deducing implications for design of adsorbents has been highlighted. Finally, some aspects of process design and scale-up of adsorption column have been addressed and research needs of pragmatic importance have been identified.

Adsorption↗

Tunable optical properties of colloidal quantum dots in electrolytic environments.

The absorption spectra of colloidal cadmium sulfide quantum dots in electrolytic solutions are found to manifest a shift in the absorption threshold as the concentration of the electrolyte is varied. These results are consistent with a shift in the absorption threshold that would be caused by electrolytic screening of the field caused by the intrinsic spontaneous polarisation of these würtzite structured quantum dots. These electrolyte-dependent absorption properties provide a potential means of gaining insights on the variable extracellular and intracellular electrolytic concentrations that are present in biological systems.

Journal Article↗

[Psychosomatic research in primary health care--ideal concept and reality].

UNLABELLED: The cooperation between research institutions and primary care doctors can be seen as a possible model for practical research in psychosomatic medicine. Cooperation experience with a study in the field of sexual medicine are reported as well as recommendations regarding the planning and implementation of similar studies are given. 7455 Swiss physicians specialized in psychiatry, internal or general medicine were asked to fill out a survey on "sexual dysfunction and anti-depressants". They were also asked if they were willing to interview their patients on the same issue. 1100 physicians agreed to answer the doctors survey and 62 were interested in interviewing their patients. However, only 12 physicians actually did. In 55 telephone interviews doctors mentioned as their main reasons for not participating: lack of time and their hesitation to discuss sexual issues with depressive patients. CONCLUSION: The collaboration in research projects means a considerable effort on the side of primary care doctors. Therefore, their cooperation should be rewarded appropriately, e.g. time could be counted as further training.

Academies and Institutes↗

Lack of abundance of cytoplasmic cyclosporin A-binding protein renders free-living Leishmania donovani resistant to cyclosporin A.

The majority of the effects of cyclosporin A (CsA) on cells is caused by the inhibition of phosphatase activity of calcineurin (CN) by the cyclophilin A (CyPA)-CsA complex formed in the cytoplasm. Although CsA inhibits the proliferation of a large number of parasites, not all are susceptible. The presence of structurally altered CyPA with lower affinity for CsA had been suggested to be the cause of resistance. We report here the identification and cloning of a high affinity CsA-binding protein (LdCyP) from Leishmania donovani, a trypanosomatid parasite that is naturally resistant to CsA. The translated LdCyP consists of 187 amino acids with a cleavable 21-amino acid hydrophobic NH(2)-terminal extension. Modeling studies confirmed that all the residues of human CyPs responsible for interaction with CsA are sequentially and conformationally conserved in LdCyP. The purified recombinant protein displayed biochemical parameters comparable to human CyPs. Reverse transcription-polymerase chain reaction analysis confirmed that LdCyP was abundantly expressed. Immunoblot experiments and direct CsA binding studies revealed that LdCyP located in the subcellular organelles constituted the bulk of the CsA binding activity present in L. donovani, whereas the level of binding activity in the cytosol was conspicuously low. CsA selectively facilitated the secretion of LdCyP in the culture medium. Based on these results, it is concluded that the insensitivity of L. donovani to CsA is probably due to the paucity of CsA binding activity in the cytoplasm of the parasite. We suggest that LdCyP, located in the secretory pathway, may function as a chaperone by binding to membrane proteins rather than as the mediator of CN inhibition.

Amino Acid Sequence↗

Low prevalence of psychoses among the Hutterites, an isolated religious community.

OBJECTIVE: The authors estimated the prevalence of psychoses among the Hutterites in Manitoba, Canada, who lived in 102 communal farms or colonies. The study stemmed from an earlier epidemiological survey of North American Hutterite colonies (1950-1953), in which a low prevalence of psychoses was documented. METHOD: Psychiatrically ill individuals identified during the previous survey were rediagnosed with DSM-IV criteria. A current provincial health insurance claims database was queried anonymously for the period June 1992-May 1997, and the prevalence rate of disease among Hutterites, identified by distinctive surnames and unique postal addresses, was compared with the rate in the entire population of the province of Manitoba and in a comparison group of persons with Hutterite surnames but with addresses outside the Hutterite colonies. RESULTS: The annual prevalence of schizophrenia among the communal Hutterites, estimated from the database search by using ICD-9 criteria, was consistent with the prevalence found in the prior epidemiological survey (annual mean of 1.2/1,000 population, compared with 1.3/1,000 in the prior survey). The database search yielded a significantly lower prevalence for schizophrenia and other functional psychoses among communal Hutterites as well as among the comparison group, compared to the total Manitoba population. There was also lower prevalence for affective psychoses and adjustment reaction disorders among the communal Hutterites, compared to the total Manitoba population. Rates for neurotic disorders were elevated both among the communal Hutterites and the comparison group. CONCLUSIONS: The prevalence of specific psychoses was reduced among the Hutterites, although neurotic disorders were more prevalent. These findings suggest some specificity, although possible artifacts such as ascertainment bias must be considered. Further research is needed to examine genetic and environmental factors that may contribute to reduced prevalence of specific psychoses among the Hutterites.

Age of Onset↗

Poly (DL-lactide-co-glycolide) based delivery systems for vaccines and drugs.

Current vaccination and drug delivery strategies emphasize on the development of controlled release techniques for persistent and sustained effects. In the recent years, polymer based systems for the delivery of bioactive agents have gained considerable attention due to their marked adjuvanticity, established biodegradability and biocompatibility, excellent mechanical strength and controlled release profiles. This review deals with the potential applications of synthetic polymers mainly PLG polymers in delivery of vaccines and drugs.

Drug Carriers↗

The 80s loop of the catalytic chain of Escherichia coli aspartate transcarbamoylase is critical for catalysis and homotropic cooperativity.

The X-ray structure of the Escherichia coli aspartate transcarbamoylase with the bisubstrate analog phosphonacetyl-L-aspartate (PALA) bound shows that PALA interacts with Lys84 from an adjacent catalytic chain. To probe the function of Lys84, site-specific mutagenesis was used to convert Lys84 to alanine, threonine, and asparagine. The K84N and K84T enzymes exhibited 0.08 and 0.29% of the activity of the wild-type enzyme, respectively. However, the K84A enzyme retained 12% of the activity of the wild-type enzyme. For each of these enzymes, the affinity for aspartate was reduced 5- to 10-fold, and the affinity for carbamoyl phosphate was reduced 10- to 30-fold. The enzymes K84N and K84T exhibited no appreciable cooperativity, whereas the K84A enzyme exhibited a Hill coefficient of 1.8. The residual cooperativity and enhanced activity of the K84A enzyme suggest that in this enzyme another mechanism functions to restore catalytic activity. Modeling studies as well as molecular dynamics simulations suggest that in the case of only the K84A enzyme, the lysine residue at position 83 can reorient into the active site and complement for the loss of Lys84. This hypothesis was tested by the creation and analysis of the K83A enzyme and a double mutant enzyme (DM) that has both Lys83 and Lys84 replaced by alanine. The DM enzyme has no cooperativity and exhibited 0.18% of wild-type activity, while the K83A enzyme exhibited 61% of wild-type activity. These data suggest that Lys84 is not only catalytically important, but is also essential for binding both substrates and creation of the high-activity, high-affinity active site. Since low-angle X-ray scattering demonstrated that the mutant enzymes can be converted to the R-structural state, the loss of cooperativity must be related to the inability of these mutant enzymes to form the high-activity, high-affinity active site characteristic of the R-functional state of the enzyme.

Aspartate Carbamoyltransferase↗

The influence of the regulatory chain amino acids Glu-62 and IIe-12 on the heterotropic properties of Escherichia coli aspartate transcarbamoylase.

In the structure of Escherichia coli aspartate transcarbamoylase with CTP bound [Kosman, R. P., Gouaux, J. E., and Lipscomb, W. N. (1993) Proteins, Struct. Funct. Genet. 15, 147-177] Lys-6 and Glu-62 form a salt-link between two regulatory chains. However, recent X-ray structural studies suggest that side chain and backbone interactions existed between Glu-62 and Ile-12. Thus the interaction between Glu-62 and Ile-12 may help to establish the correct conformation of the nucleotide binding site. The present study of two single-site mutant enzymes, Glu-62r-->Ala and Ile-12r-->Ala, was undertaken to investigate whether the role of Glu-62 is to maintain the stability of the interface between the regulatory chains in the dimer, or interacts with the side chain of Ile-12r to define the nucleotide binding site. For both the mutant enzymes, the maximal velocity, the aspartate saturation at half the maximal velocity, and Hill coefficient were close to wild-type values. The Glu-62r-->Ala enzyme showed enhanced regulatory effects with ATP, CTP, and UTP. As a result of this mutation the enzyme losses its ability to discriminate between CTP and UTP. For the Ile-12r-->Ala enzyme, the heterotropic properties were reduced or eliminated. The enhanced regulatory effects observed with the Glu-62r-->Ala enzyme do not seem to be consistent with the presence of a salt-link between Glu-62r and Lys-6r. However, based upon kinetic data of the unique but completely opposite heterotropic properties of the two mutant enzymes, it is suggested that the side chain interaction between Glu-62r and Ile-12r helps to define the conformation of the effector binding pocket. In this study, we report the properties of both the Glu-62r-->Ala and Ile-12r-->Ala enzymes and their importance for the heterotropic activation and inhibition of aspartate transcarbamoylase.

Allosteric Regulation↗

Risk of preschool asthma: incidence, hospitalization, recurrence, and readmission probability.

Asthma is one of the most common chronic illnesses in childhood. Increases in hospitalization rates have occurred in several countries. The cumulative risk of asthma requiring medical attention was 11.7% for males and 7.0% for females aged 0-4 in Manitoba, Canada, for the cohort of children born in 1984/1985. The cumulative risk of hospitalization for males was nearly twice that of females (2.1% vs. 1.1%). Disease onset was most likely at age 1 year. The risk of rehospitalization or return physician visit for asthma increased significantly with the number of prior hospitalizations and physician visits, respectively, which may reflect both the persistence of asthma and the difficulty of developing an effective disease management strategy.

Age of Onset↗

Neonatal characteristics as risk factors for preschool asthma.

Childhood asthma usually begins early in life. Neonatal characteristics are reportedly predictive of symptom onset. This investigation utilized data from a provincial health organization to evaluate the effect of several birth characteristics on asthma incidence and hospitalization for asthma during age 0-4. Using logistic regression, the odds ratios (OR) for the following variables indicate a significant (p < 0.05) association with physician-diagnosed preschool asthma: male gender (OR = 1.72), birthweight < 1500 g (OR = 2.11), prematurity (OR = 1.34), respiratory distress syndrome (RDS) in the presence (OR = 2.95) or absence (OR = 1.61) of bronchopulmonary dysplasia (BPD), and transient tachypnea of the newborn (TTN; OR = 1.36). Male gender (OR = 1.91), birthweight < 1500 g (OR = 2.56), RDS with and without BPD (OR = 3.35 and 2.50, respectively), TTN (OR = 2.08), and severe birth asphyxia (OR = 1.94) showed an important association with hospitalization due to asthma. Neonatal characteristics are important determinants for the risk of preschool asthma, even after mutual adjustment.

Asthma↗

Neoglycosylated liposomes as efficient ligands for the evaluation of specific sugar receptors on macrophages in health and in experimental leishmaniasis.

Receptors interacting with terminal sugars as ligands are involved in the binding of Leishmania donovani promastigotes to the macrophage surface and their subsequent internalization. Mannose and glucose are specifically involved in the binding process. Decreased binding occurs to macrophages already infected with L. donovani either in vivo or in vitro. When mannose- or glucose-bearing liposomes are used as ligands the binding shows similar trends and the percentage inhibition of binding with mannose-bearing liposomes increases when compared to that for the glucose-bearing ones. The decreased binding of the ligand seems to be due to a decrease in the number of receptors after infection. The affinity of the ligands for the binding sites either on the normal macrophages or on the infected macrophages apparently remains the same. The results based on the incorporation of [3H]phenyl alanine and supported by the binding of glycosylated liposomes to both infected and non-infected macrophages suggest that protein synthesis, in general, is suppressed in L. donovani-infected macrophages thus affecting also mannose/glucose receptor protein synthesis, resulting in fewer receptors on the macrophage surface.

Animals↗