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Biomedical subjects

R Dutta

Publications and source records attributed to R Dutta.

At least 37 records · Page 2Linked to original sources
PubMed1998

Binding of the modified daunorubicin WP401 adjacent to a T-G base pair induces the reverse Watson-Crick conformation: crystal structures of the WP401-TGGCCG and WP401-CGG[br5C]CG complexes.

2'-Bromo-4'-epi-daunorubicin (alpha-manno configuration, denoted WP401) is a new anthracycline drug that exhibits promising activity toward multidrug-resistant cancer cells. We carried out X-ray diffraction analyses of the complexes formed in the presence of formaldehyde between WP401 and two DNA hexamers, TGGCCG and CGG[br5C]CG. The two complexes crystallized in different crystal lattices with respective crystal data of space group P4322, a = b = 37.20 A, c = 70.53 A and space group P43212, a = b = 37.23 A, c = 61. 96 A. These new crystal forms are different from the P41212 form of other daunorubicin/doxorubicin complexes studied previously. The refined crystal structures at approximately 2.0 A resolution revealed that the entire 2:1 drug-DNA complex is in the asymmetrical unit. Two WP401 drug molecules bind to the duplex, with the aglycones intercalated between the CpG or TpG steps and their modified daunosamines in the minor groove. As observed earlier, in the presence of formaldehyde, WP401 more readily forms a covalent adduct with (C/T)GG*:CCG than with (C/T)GC:G*CG (G* is the crosslink site), the opposite of what is seen for daunorubicin and doxorubicin. Surprisingly, the two T-G mismatched base pairs in the WP401-TGGCCG complex adopt the reverse Watson-Crick conformation, instead of the wobble conformation. The unusual T-G reverse Watson-Crick conformation may be required in order to maintain favorable stacking interactions between the base pair and the aglycone of WP401. Our results show that chemical modifications like bromo or iodo substitution on anthracycline drugs have significant effects on their DNA binding properties.

Antibiotics, Antineoplastic↗
PubMed1998

Protein tyrosine phosphatases and neural development.

During neural development, cells interact dynamically with each other and with the extracellular matrix, using cell signaling to control differentiation, axonogenesis, and survival. Enzymes that regulate protein tyrosine phosphorylation often lie at the core of such cell signaling. Protein tyrosine phosphatases (PTPases) are recognized as being of central importance here, and a growing family of PTPases are now known to be expressed in embryonic neurons and glia. Both receptor-like and cytoplasmic enzymes have been identified. The receptor family includes immunoglobulin superfamily members that influence cell-cell adhesion, proteoglycans that control neurite growth, and enzymes in Drosophila that regulate axon guidance and target cell recognition. Cytoplasmic PTPases are implicated in nerve cell commitment and potentially in the regulation of cell survival. This review outlines what we currently know about PTPases in the nervous system and presents concepts concerning their possible modes of action.

Animals↗
PubMed1996

Reverse phosphotransfer from OmpR to EnvZ in a kinase-/phosphatase+ mutant of EnvZ (EnvZ.N347D), a bifunctional signal transducer of Escherichia coli.

EnvZ of Escherichia coli is a transmembrane histidine kinase belonging to the family of two-component signal transducing systems prevalent in prokaryotes and recently discovered in eukaryotes. In response to changes in medium osmolarity EnvZ regulates the level of phosphorylated OmpR, its conjugate response-regulating transcription factor for ompF and ompC genes. EnvZ has dual opposing enzymatic activities; OmpR-phosphorylase (kinase) and phospho-OmpR-dephosphorylase (phosphatase). The osmotic signal is proposed to regulate the ratio of the kinase to the phosphatase activities of EnvZ to modulate the level of OmpR phosphorylation. In this work we used a COOH-terminal fragment of a previously identified kinase-/phosphatase+ EnvZ mutant (EnvZ-N347D) to demonstrate that the phosphoryl group on phospho-OmpR is transferred back to EnvZ to the same histidine residue (His243) that is utilized for the autokinase reaction by the wild type protein. Phospho-EnvZ-N347D thus formed could also transfer its phosphoryl group back to OmpR. The phosphotransfer reaction from phospho-OmpR to EnvZ.N347D was inhibited by ADP while Mg2+ ions stimulated the dephosphorylation reaction, resulting in release of inorganic phosphate. These results indicate that the energy levels of phosphoryl groups on OmpR and EnvZ are very similar and that the phosphatase reaction in the EnvZ.N347D mutant involves a reversal of the phosphotransfer reaction from EnvZ to OmpR using the identical His243 residue.

Bacterial Outer Membrane Proteins↗
PubMed1994

Paddy field dermatitis in Assam: a cercarial dermatitis.

Rice field dermatitis is an occupational health problem in Assam. The afflicted paddy field workers develop exanthema on the exposed parts of their skin mainly legs and arms when they come in contact with water in rice fields. Itching sensations start after 30 minutes to 1 1/2 hours after initial exposure. After 6-12 hours there is intensely pruritic macular eruption and in a few cases secondary skin infection may also develop. The clinical course of the disease is suggestive of cercarial dermatitis. Numerous gastropod snails belonging to families Lymnaeidae, Bulinidae and Planorbidae were collected from paddy fields and were investigated for cercarial infection. It was found that planorbid snails were infected with animal schistosome cercariae. These cercariae were able to invade human skin and caused dermatitis in human volunteers after repeated exposure.

Agricultural Workers' Diseases↗
PubMed1991

Relationship between rigidity-flexibility and cognitive abilities in adulthood.

The interrelationship of measures of rigidity-flexibility and of psychometric intelligence is examined. The latent factors of Attitudinal Flexibility, Motor-Cognitive Flexibility, and Psychomotor Speed are derived from the Test of Behavioral Rigidity, and factors of Inductive Reasoning, Spatial Orientation, Verbal Ability, Numeric Ability, Verbal Memory, and Perceptual Speed are derived from the Thurstone Primary Mental Abilities Test and the Educational Testing Service Kit of Factor-Referenced Tests. The data base in this study comes from the fifth wave of the Seattle Longitudinal Study (N = 1,628; age range, 22-95 years). The Rigidity-Flexibility factors were found to be independent of the cognitive domain. Also, longitudinal stability of the factor structure of the rigidity-flexibility domain was confirmed for 837 participants tested in both 1977 and 1984.

Adult↗
PubMed1991

Natural cohorts: family similarity in adult cognition.

We now return to the sets of hypotheses formulated in the introductory section to explore how the findings reported above bear on these propositions. Our first hypothesis dealt with whether family similarity could be observed in adulthood and whether there were differing ability patterns in such similarity. Significant family similarities were observed for our total sample for all ability measures, except Perceptual Speed, and for the cognitive style measures. The magnitude of correlations for the ability measures are comparable for those found between young adults and their children (DeFries et al., 1976). Similar to the DeFries study, we also found differences in resemblance across subsets. For example, same gender pairs showed higher correlations on Verbal Meaning, Number, and Word Fluency but opposite-gender pairs on Spatial Orientation, Inductive Reasoning, and Motor-Cognitive Flexibility. Also, greater similarity was found between mother-offspring pairs than father-offspring pairs on Inductive Reasoning and Psychomotor Speed. Moreover, higher parent-offspring correlations were found for daughters than for sons, suggesting at least the possibility that females may experience greater shared environmental influences than males. Our first hypothesis also argued for the possible effect of early shared environment upon offspring performance on Verbal Meaning and Word Fluency. After age adjustment, these were indeed the abilities that showed the highest parent-offspring similarity. Our second hypothesis proposed that if shared environmental influences are relatively unimportant in adulthood, then similarity within parent-offspring pairs should remain reasonably constant in adulthood across time and age. Our examination of this issue with a longitudinal sample ranging over a 21-year period strongly supports this proposition for all of those variables that displayed significant parent-offspring correlations. Indeed, parent-offspring correlations measured at approximately the same age of parent and offspring and when those ages were 20 years apart had similar magnitudes. The third hypothesis asked whether family similarity would decrease with age because of the increasing amount of nonnormative, nonshared environment expected as adult life progresses. Counterintuitively, no such decrease in similarity could be observed. Indeed, for two variables there was evidence for increasing similarity as a function of offspring age. This finding makes good sense for our Perceptual Speed variable. Most of our younger offspring typically have not yet experienced age-related decline on this variable, whereas some of their parents have. Both older offspring and parents may have experienced sufficient decline so that once again their observed similarity is increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Ovarian fibroma--clinical and histopathological characteristics.

Twenty-three cases of ovarian fibroma, comprising 3% of all benign tumors seen over a 20-year period, were analyzed. It was unilateral in all cases affecting more commonly the left ovary (70%). Whilst a majority of cases (77%) were encountered in the reproductive age group, the tumor was rare before the second decade. Only in 13% of cases was ascitis clinically detectable. This was not influenced by the size and weight (average of 9.3 x 10.8 x 11.1 cm and 959 g, respectively) of the tumors; a smooth-surfaced tumor was, however, associated with a greater amount of peritoneal fluid. Varying degrees of calcification in some tumors are detectable on ultrasonography and occasionally on abdominal radiography. The classical Meig's Syndrome was seldom encountered. The histopathological features, diagnostic problems and management are discussed.

Adult↗