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Biomedical subjects

A Dutta

Publications and source records attributed to A Dutta.

At least 19 recordsLinked to original sources
PubMed1992

DNA replication and the cell cycle.

The replication of DNA in the eukaryotic cell cycle is one of the most highly regulated events in cell growth and division. Biochemical studies on the replication of the genome of the small DNA virus simian virus 40 (SV40) have resulted in the identification of a number of DNA replication proteins from human cells. One of these, Replication Protein A (RPA), was phosphorylated in a cell cycle-dependent manner, beginning at the onset of DNA replication. RPA was phosphorylated in vitro by the cell cycle-regulated cdc2 protein kinase. This kinase also stimulated the unwinding of the SV40 origin of DNA replication during initiation of DNA replication in vitro, suggesting a mechanism by which cdc2 kinase may regulate DNA replication. Functional homologues of the DNA replication factors have been identified in extracts from the yeast Saccharomyces cerevisiae, enabling a genetic characterization of the role of these proteins in the replication of cellular DNA. A cellular origin binding protein had not been characterized. To identify proteins that function like T antigen at cellular origins of DNA replication, we examined the structure of a yeast origin of DNA replication in detail. This origin consists of four separate functional elements, one of which is essential. A multiprotein complex that binds to the essential element has been identified and purified. This protein complex binds to all known cellular origins from S. cerevisiae and may function as an origin recognition complex.

Animals↗
PubMed1992

cdc2 family kinases phosphorylate a human cell DNA replication factor, RPA, and activate DNA replication.

RPA is a single-stranded DNA binding protein complex purified from human cells and is essential for the initiation and elongation stages of SV40 DNA replication in vitro. In both human and yeast cells, the 34 kDa polypeptide subunit of RPA is phosphorylated in the S and G2 phases of the cell cycle and not in G1. One of the major RPA kinases present in extracts of human cells was purified and shown to be the cyclin B-cdc2 complex. This purified kinase, and a closely related cyclin A associated cdc2-like kinase, phosphorylated RPA p34 on a subset of the chymotryptic peptides that were phosphorylated in vivo at the G1-S transition. Two serines near the N-terminus of RPA p34 were identified as possible sites of phosphorylation by cdc2 kinase. These same serines were necessary for RPA phosphorylation in vivo. The purified cdc2 kinase stimulated SV40 DNA replication in vitro when added to G1 cell extracts. The kinase also stimulated unwinding at the origin of replication, one of the earliest steps in DNA replication requiring RPA, but only in the presence of an additional factor present in G1 cell extracts. Thus, one or more members of the cyclin-cdc2 kinase family may be required for the initiation and maintenance of S phase, in part due to their ability to phosphorylate and activate a cellular DNA replication factor, RPA.

Adenovirus Early Proteins↗
PubMed1992

Persistence of stimulus-response compatibility effects with extended practice.

The influence of extended practice on stimulus-response (S-R) compatibility effects was investigated. Three experiments, each extending over a period of 8 sessions, were conducted. The nature and degree of compatibility was manipulated across experiments. In all experiments, a persistent effect of S-R compatibility on reaction times was observed. Thus, the lower bound for reaction times appears to be less for compatible assignments than for incompatible assignments. This persistence of S-R compatibility indicates that the initial codings used to perform a novel task continue to exert an influence on later performance.

Adult↗
PubMed1992

Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.

Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.

Adult↗
PubMed1992

Numerical analysis of flow in an elastic artery model.

Oscillatory and pulsatile flows of Newtonian fluids in straight elastic tubes are simulated numerically with the aid of Ling and Atabek's "local flow" assumption for the nonlinear convective acceleration terms. For the first time, a theoretical assessment of the local flow assumption is presented, and the range of validity of the assumption is estimated by comparison with perturbation solutions of the complete flow problem. Subsequent simulations with the local flow model indicate that the flow field and associated wall shear stress are extremely sensitive to the phase angle between oscillatory pressure and flow waves (impedance phase angle). This phase angle, which is a measure of the wave reflection present in the system, is known to be altered by arterial disease (e.g., hypertension) and vasoactive drugs. Thus, the paper elucidates a mechanism by which subtle changes in systemic hemodynamics (i.e., phase angles) can markedly influence local wall shear stress values.

Aorta↗
PubMed1992

Who commits matricide?

The authors studied sixteen men who committed matricide. Fifteen out of sixteen cases had a diagnosis of schizophrenia and the remaining patient had a diagnosis of schizophrenia with personality disorder. All were single at the time of the matricide. Data indicate an intense conflict-laden and ambivalent relationship between the majority of patients with their mothers. Thirteen out of sixteen cases described their mothers as quite domineering and demanding but the EMBU inventory revealed that the Matricidal group differed from the Control group in how tolerant they saw their parents. The sample as a whole saw mothers were more over-involved, overprotective, tolerant, affectionate, stimulating, performance-orientated and shaming. The matricidal group differed from the control group in the way they viewed the difference between mother and father on various scales, like over-involved, tolerant, affectionate and performance-orientated. The matricidal groups' mothers were found to be more over-involved, tolerant, affectionate, and fathers more abusive. Mothers in the control group were more performance-orientated.

Adult↗
PubMed1992

Initial intensive therapy for multibacillary leprosy patients--in retrospect.

We analysed the results of 4845 multibacillary (MB) patients being treated with multidrug treatment (MDT) in the Srikakulam District of Andhra Pradesh, India. Of these, 2309 (47.7%) patients were given an initial 14-day intensive therapy with rifampicin, clofazimine and dapsone, followed by the WHO recommended pulse therapy. The rest of the cases were given only pulse therapy. The improvement in terms of bacteriological clearance and the proportion of cases declared released from treatment (RFT) was found to be significantly higher among patients treated with only pulse therapy. Clinic attendance was found to be better and more regular in patients treated with intensive therapy, and no relapses were seen with either therapy. The implications of these findings on the operational aspects of programme implementation are discussed.

Humans↗
PubMed1991

Is bacteriological examination by skin smear necessary in all paucibacillary leprosy patients in mass control programmes?

Skin smear bacteriological examination results of 11,255 paucibacillary leprosy patients from 8 leprosy control units under the National Leprosy Eradication Programme (NLEP) in South India and the Outpatient Department (OPD) of the Central Leprosy Teaching & Research Institute (CLT&RI), Chengalpattu, between 1987 and 1989 were collected and analysed. Only 0.05% of the smears from leprosy control units and 2.49% from the OPD of CLT&RI were found to be positive. Not a single smear from indeterminate, tuberculoid and pure neuritic types of leprosy out of 8263 examined was found positive under field conditions. The relevance of carrying out routine bacteriological examination in mass leprosy control programmes is discussed.

Humans↗
PubMed1991

Seroepidemiological study of leprosy in a highly endemic population of south India based on an ELISA using synthetic PGL-I.

As part of a continuing longitudinal immuno-epidemiological study, blood samples were collected by finger prick from 4243 individuals living in a highly endemic area for leprosy in South India. The samples were tested for IgM antibodies against phenolic glycolipid-I using an ELISA. Seropositivity defined as optical density greater than or equal to 0.2000 was marginally higher in the age group 10-30 years and in females. There was no evidence for a higher level in contacts than in non-contacts. The future prospect for the large scale use of this ELISA in high-endemic populations in special epidemiological investigations or routine control programs as a serological tool to detect leprosy infection appears questionable.

Adolescent↗
PubMed1990

Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia.

The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6-tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Serum independence of transcription from the promoter of an avian retrovirus in v-src-transformed cells is a primary, intracellular effect of increased tyrosine phosphorylation.

We found that transcription from the promoter in the long terminal repeat of Rous sarcoma virus in rat 3Y1 cells is dependent on the presence of serum in the culture. However, this serum dependence of transcription was relieved when 3Y1 cells were transformed by the oncogene v-src. Crossfeeding experiments showed no evidence for the production of a serum-substituting extracellular growth factor by the transformed cells. Using 3Y1 cells transformed with temperature-sensitive Rous sarcoma virus, we showed that the tyrosine kinase activity of pp60v-src was responsible for the serum-sparing effect on the level of RNA expressed from the viral promoter. Sodium orthovanadate, an inhibitor of phosphotyrosine phosphatases that nonspecifically elevates the level of phosphotyrosine-containing proteins in cells, stimulated transcription from the viral promoter. The effects of both pp60v-src and orthovanadate were resistant to cycloheximide. These results suggest that the serum independence of transcription from the viral promoter in v-src-transformed cells was probably due to the constitutive activation of intracellular growth-factor pathways by the tyrosine kinase activity of pp60v-src.

Animals↗
PubMed1990

Serum and v-src increase the level of a CCAAT-binding factor required for transcription from a retroviral long terminal repeat.

Transcription from the long terminal repeat (LTR) of Rous sarcoma virus (RSV) in rat 3Y1 fibroblasts was dependent on the presence of serum. Within 1 hr after addition of serum to a serum-deprived culture, there was a fivefold increase in the level of transcripts initiated at the LTR. This stimulation did not require synthesis of new proteins. The induction of transcription by serum was mostly dependent on two CCAAT boxes in the LTR. Within 1 hr after addition of serum, there was also an increase in the level of a nuclear protein that bound to the two CCAAT boxes, even in the presence of cycloheximide. This serum-induced CCAAT factor also bound CCAAT sequences from other promoters, for example, those of human heat shock protein 70, human c-Ha-ras, and human histone 1, but not to the adenovirus origin of replication or the SV40 enhancer core sequence, suggesting that it was related to CP1 or CP2. Expression from the RSV LTR was not dependent on serum in v-src-transformed cells. Using temperature-sensitive v-src, it was shown that the tyrosine kinase activity of the oncogene increased the amount of CCAAT factor that was present in the nucleus. These findings demonstrate that a basal transcription factor, the CCAAT-binding factor, could be a second messenger for transducing a primary signal from serum to the cellular transcriptional apparatus. This also suggests a pathway by which a tyrosine kinase oncogene could influence the transcription of several genes in the nucleus.

Animals↗
PubMed1990

Who commits patricide?

The authors studied 10 men charged with patricide, including 2 men charged with both patricide and matricide and compared them with 10 schizophrenic patients who did not commit any crime. Eight patients who committed patricide were diagnosed as suffering from schizophrenic illness and 2 patients received a diagnosis of personality-disorder. Seven schizophrenics who committed patricide and both personality-disordered patients had a cruel and unusual relationship with their father. All were single at the time of patricide. The EMBU inventory revealed fathers to be more punitive than mothers and fathers favoured siblings more than the patients. Mothers were more overprotective and tolerant than fathers. Patricide patients' fathers were more punitive and shaming than control patients' fathers, and control patients' fathers were more stimulating and depriving than patricide patients' fathers. Patricide patients' mothers were more overinvolved and tolerant than control patients' mothers. A sense of relief was felt following the patricide rather than remorse. In contrast, the majority of patients in the control group described their father and mother as kind and affectionate. The EMBU inventory did not reveal any significant difference between father and mother.

Adult↗
PubMed1990

Double-blind, randomized, controlled clinical trial of norfloxacin for cholera.

In a double-blind, randomized clinical trial with 78 adults with acute watery diarrhea and severe dehydration, 37 subjects were positive for Vibrio cholerae. In conjunction with rehydration therapy, 13 patients received norfloxacin, 12 received trimethoprim-sulfamethoxazole (TMP-SMX), and 12 received a placebo. Norfloxacin was superior to TMP-SMX and to the placebo in reducing stool output, duration of diarrhea, fluid requirements, and vibrio excretion. TMP-SMX was no better than the placebo.

Adult↗
PubMed1989

Increased dolichol content in glucocorticoid-sensitive human T-cell leukemia line grown in the presence of dexamethasone.

Two cell lines, derived from human T-cell acute leukemia, one glucocorticoid sensitive (CEM-C7) and the other glucocorticoid resistant (CEM-C1) were grown in the presence of 1 x 10-7 M dexamethasone and were analyzed for their dolichol content. After 24 hrs of incubation, dolichols became significantly elevated in the sensitive but not in the resistant line. Lovastatin, the specific inhibitor of cholesterol synthesis did not affect dolichol levels in either of the two cell lines. The results raise the possibility that dolichol accumulation might be involved in the early stages of the glucocorticoid-induced apoptosis (directed cell killing).

Cell Line↗
PubMed1989

Numerical simulation of sinusoidal flow in a straight elastic tube: effects of phase angles.

Numerical simulations of flow in straight elastic (moving wall) tubes subjected to a sinusoidal pressure gradient were performed for conditions prevailing in large and medium sized arteries. The effects of varying the phase angle between the pressure gradient and the tube radius, the amplitude of wall motion, and the unsteadiness parameter (alpha) on flow rate and wall shear stress were investigated. Mean and peak flow rates and shear stresses were found to be strongly affected by the phase angle between the pressure gradient and the tube radius with greater sensitivity at higher diameter variation and higher alpha. In large artery simulations (alpha = 12), means flow rate was found to be 60% higher and peak flow rate to be 73% higher than corresponding rigid tube values for certain phase angles, while a threefold increase in mean wall shear stress and sevenfold increase in peak wall shear stress were observed in a sensitive phase angle range. Significant reversal in the wall shear stress direction occurred in the sensitive phase angle range even when there was negligible flow rate reversal. All effects were greatly diminished in simulations of medium sized vessels (alpha = 4). Some experimental evidence to support the predictions of a strong effect of phase angle on wall shear stress in large vessels is presented. Finally, physiological implications of the present work are discussed from a basis of aortic input impedance data, and a physical explanation for the extreme sensitivity of the flow field to small amplitude wall motion at high alpha is given.

Arteries↗
PubMed1988

Phosphorylation of serum response factor, a factor that binds to the serum response element of the c-FOS enhancer.

Serum and growth factor regulation of c-FOS protooncogene transcription is mediated by the serum response element. A factor, serum response factor, binding to this element has already been identified. We demonstrate that serum response factor is phosphorylated in vivo on serine residues and that phosphatase treatment of this factor in vitro abolishes its DNA-binding activity. These results show phosphorylation of serum response factor to be required for its DNA-binding activity. The importance of serum response factor phosphorylation for the regulation of c-FOS expression is discussed.

Animals↗