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Biomedical subjects

A Chatterjee

Publications and source records attributed to A Chatterjee.

At least 109 records · Page 6Linked to original sources
PubMed1998

Induction of lethal mutations in experimental tumours after single and fractionated irradiations in vivo.

PURPOSE: To investigate the prolonged reduction in cellular viability (lethal mutations) of surviving cells following irradiation of tumours in vivo and to test the effects of fractionation on the expression of lethal mutations. MATERIALS AND METHODS: A mouse mammary carcinoma (CaNT) was treated with single dose or fractionated X-ray treatments in vivo and survival quantified with an in vitro excision assay soon after irradiation and at various times up to 35 days after in vitro propagation of the surviving cells. RESULTS: A dose-dependent reduction in the plating efficiency was observed in cells isolated from irradiated tumours up to 35 days and many cell generations after irradiation. Considerable heterogeneity in plating efficiency was observed in clonal cell lines isolated from individual colonies grown from irradiated tumours. Delayed expression of lethal damage was observed after fractionated irradiation, although recovery of cellular fitness was greater than after irradiation with single doses (reported previously) suggesting that this form of damage is affected by inter-fraction repair. At equi-toxic doses, delayed expression of lethal damage was similar after three compared with two fractions of radiation per day (reported previously). CONCLUSIONS: These effects indicate that conventional excision assays of tumour cell viability under-estimate the total lethal damage caused by irradiation and have implications for modelling of the response of tumours to radiotherapy. The effect of fractionation on expression of this type of damage implies the involvement of repair processes. Therefore the repair proficiency may affect the balance between the immediate and delayed reduction of viability in irradiated cells.

Animals↗
PubMed1998

Statistical modelling and phylogenetic analysis of a deaminase domain.

Deamination reactions are catalyzed by a variety of enzymes including those involved in nucleoside/nucleotide metabolism and cytosine to uracil (C-->U) and adenosine to inosine (A-->I) mRNA editing. The active site of the deaminase (DM) domain in these enzymes contains a conserved histidine (or rarely cysteine), two cysteines and a glutamate proposed to act as a proton shuttle during deamination. Here, a statistical model, a hidden Markov model (HMM), of the DM domain has been created which identifies currently known DM domains and suggests new DM domains in viral, bacterial and eucaryotic proteins. However, no DM domains were identified in the currently predicted proteins from the archaeon Methanococcus jannaschii and possible causes for, and a potential means to ameliorate this situation are discussed. In some of the newly identified DM domains, the glutamate is changed to a residue that could not function as a proton shuttle and in one instance (Mus musculus spermatid protein TENR) the cysteines are also changed to lysine and serine. These may be non-competent DM domains able to bind but not act upon their substrate. Phylogenetic analysis using an HMM-generated alignment of DM domains reveals three branches with clear substructure in each branch. The results suggest DM domains that are candidates for yeast, platyhelminth, plant and mammalian C-->U and A-->I mRNA editing enzymes. Some bacterial and eucaryotic DM domains form distinct branches in the phylogenetic tree suggesting the existence of common, novel substrates.

Amino Acid Sequence↗
PubMed1998

Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced chromosomal damage and sister chromatid exchange in mouse bone marrow cells in vivo.

Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major ingredient of betel quid. The carcinogenic potentiality as well as its cell transformation ability has already been reported. Reduced glutathione (GSH), a major non-protein thiol substance plays an important role in protection of cells against the toxic effect of exogenous compounds. In order to understand the role of factors which affect ARC sensitivity, we have made an attempt to establish a relationship between ARC-induced DNA damage and the endogenous GSH status of the cells. ARC was administered to untreated and buthionine sulfoximine (BSO) (a GSH-depleting agent)-treated mice. Exogenous GSH was also added to ARC-administered mice. Cells were fixed at 20 h and both chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) were scored. Both CAs and SCEs were significantly induced by ARC and the frequency of both these parameters were increased further when ARC was given to BSO-treated mice. However, GSH reduced the frequency of CAs induced by ARC but failed to do so for SCEs. The data indicate that ARC-induced DNA damage is influenced by endogenous GSH level. The failure of GSH to reduce the frequency of SCEs indicates that the mechanism of induction of CAs and SCEs by ARC are different.

Animals↗
PubMed1998

Reversal of resistance against doxorubicin by a newly developed compound, oxalyl bis(N-phenyl)hydroxamic acid in vitro.

A drug-resistant cell line (EAC/Dox) was developed by repeated exposure of Ehrlich ascites carcinoma cells to Doxorubicin (Dox) in vivo in male albino Swiss mice (6-8 weeks old). The weekly i.p. injections of Dox to mice (2 or 4 mg/kg/week for 4 months) gave rise to Dox-resistant cell line EAC/Dox, which displayed typical multidrug resistant (MDR) features of cross-resistance to a number of structurally and functionally unrelated drugs like doxorubicin, vinblastine and cisplatin. Moreover, the EAC/Dox cell line had lower drug accumulation than drug-sensitive (EAC/S) cells. Study of Western blots and immunofluorescence revealed that P-glycoprotein 170 kDa (P-gp) was absent in EAC/Dox cells. The drug resistance appeared to be due to the presence of a higher level of reduced glutathione (GSH) and glutathione S-transferase (GST) in EAC/Dox cells than in drug-sensitive (EAC/S) cells. The two structurally similar hydroxamic acid derivatives, i.e. oxalyl bis(N-phenyl)hydroxamic acid (X1) and succinyl bis(N-phenyl)hydroxamic acid (X2), having very low in vitro toxicity (IC50 value 250 microg/ ml), were investigated for their efficacy to reverse MDR. The compound X1 was able to reverse the effect of MDR and reduce GST in EAC/Dox cells. The compound X2 had no ability to reverse the effect of MDR. Further study on the mechanism of glutathione depletion and the resistance modifying property of X1 on other cell lines is warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Disseminated candidosis in premature twins.

A unique case of disseminated candidosis in premature twins is presented where twin A developed disease soon after birth and died prior to the administration of antifungal therapy. On the other hand, twin B developed infection on the 26th day of birth but survived, though with sequelae (hydrocephalus), since he was promptly and accurately diagnosed and treated.

Candida albicans↗
PubMed1998

The simplest walking model: stability, complexity, and scaling.

We demonstrate that an irreducibly simple, uncontrolled, two-dimensional, two-link model, vaguely resembling human legs, can walk down a shallow slope, powered only by gravity. This model is the simplest special case of the passive-dynamic models pioneered by McGeer (1990a). It has two rigid massless legs hinged at the hip, a point-mass at the hip, and infinitesimal point-masses at the feet. The feet have plastic (no-slip, no-bounce) collisions with the slope surface, except during forward swinging, when geometric interference (foot scuffing) is ignored. After nondimensionalizing the governing equations, the model has only one free parameter, the ramp slope gamma. This model shows stable walking modes similar to more elaborate models, but allows some use of analytic methods to study its dynamics. The analytic calculations find initial conditions and stability estimates for period-one gait limit cycles. The model exhibits two period-one gait cycles, one of which is stable when 0 < gamma < 0.015 rad. With increasing gamma, stable cycles of higher periods appear, and the walking-like motions apparently become chaotic through a sequence of period doublings. Scaling laws for the model predict that walking speed is proportional to stance angle, stance angle is proportional to gamma 1/3, and that the gravitational power used is proportional to v4 where v is the velocity along the slope.

Algorithms↗
PubMed1998

Serine 257 phosphorylation regulates association of polyomavirus middle T antigen with 14-3-3 proteins.

Polyomavirus middle T antigen (MT) is phosphorylated on serine residues. Partial proteolytic mapping and Edman degradation identified serine 257 as a major site of phosphorylation. This was confirmed by site-directed mutagenesis. Isoelectric focusing of immunoprecipitated MT from transfected 293T cells showed that phosphorylation on wild-type MT occurred at near molar stoichiometry at S257. MT was previously shown to be associated with 14-3-3 proteins, which have been connected to cell cycle regulation and signaling. The association of 14-3-3 proteins with MT depended on the serine 257 phosphorylation site. This has been demonstrated by comparing wild-type and S257A mutant MTs expressed with transfected 293T cells or with Sf9 cells infected with recombinant baculoviruses. The 257 site is not critical for transformation of fibroblasts in vitro, since S257A and S257C mutant MTs retained the ability to form foci or colonies in agar. The tumor profile of a virus expressing S257C MT showed a striking deficiency in the induction of salivary gland tumors. The basis for this defect is uncertain. However, differences in activity for the wild type and mutant MT lacking the 14-3-3 binding site have been observed in transient reporter assays.

14-3-3 Proteins↗
PubMed1998

HIV, hepatitis B and sexual practices in the street-recruited injecting drug users of Calcutta: risk perception versus observed risks.

Injecting drug users (IDUs) were recruited from the streets of Calcutta to obtain a baseline biological and behavioural data on risk practices. One-fifth of them (mostly using buprenorphine) tested positive for hepatitis B surface antigen (HBsAg); 4% were reactive to serologic test for syphilis (VDRL: Venereal Disease Research Laboratory). Condom use was insignificant while 74% reported sex with female sex workers and 15% of male IDUs also reported having sex with men. Although, sharing of injecting equipment ('works') was perceived as dangerous by the IDUs, majority of them (90/103) reportedly shared it; cleaning of works before sharing was a concern for intravenous but not for intramuscular drug injecting. Half of the IDUs reported suffering ever from abscess; a proportion (12%) of which had had superadded attack of maggots in it. They were also found to be infected with HIV (1%, 95% CI 0.028-5.97%) at a low prevalence that prompted subsequent launching of needle syringe exchange programme, establishment of cleaning norms before sharing of works, cleaning of injecting site on the body and condom promotion.

Abscess↗
PubMed1998

Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arsenic-contaminated subsoil water.

INTRODUCTION: Chronic arsenic toxicity producing various clinical manifestations is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. Animal studies have indicated that 2,3-dimercaptosuccinic acid can be used as an oral chelating agent. A prospective, double-blind, randomized controlled trial was carried out to evaluate the efficacy and safety of 2,3-dimercaptosuccinic acid for chronic arsenicosis due to drinking arsenic-contaminated (> or = 50 micrograms/L) subsoil water in West Bengal. METHOD: Twenty-one consecutive patients with chronic arsenicosis were individually randomized (random number; assignment made by individual not evaluating patients) into 2 groups: 11 patients (10 male, age 25.5 +/- 8 years) received 2,3-dimercaptosuccinic acid 1400 mg/d (1000 mg/m2) in the first week and 1050 mg/d (750 mg/m2) during the next 2 weeks with a repeat course 3 weeks later. The other 10 patients (all male, age 32.2 +/- 9.7 years) were given placebo capsules for the same schedule. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigations including liver function tests, arsenic concentrations in urine, hair, and nails, and skin biopsy evaluations were also completed. RESULTS: Though there was improvement in the clinical score of 2,3-dimercaptosuccinic acid-treated patients, similar improvement was observed in the placebo-treated group. There were no statistical differences in the clinical scores between the 2 groups at the beginning and at the end of treatment. Similarly, no differences were found for the other investigated parameters. CONCLUSION: Under the conditions of this study, 2,3-dimercaptosuccinic acid was not effective in producing any clinical or biochemical benefit or any histopathological improvement of skin lesions in patients with chronic arsenicosis.

Adolescent↗
PubMed1998

Efficacy of topical nonsteroidal drops as pain relief after excimer laser photorefractive keratectomy.

PURPOSE: To compare the efficacy of topical aqueous indomethacin and ketorolac for pain relief following excimer laser photorefractive keratectomy (PRK). METHODS: We conducted a double masked, randomized trial involving 120 patients. All patients received a standard regimen of one of the trial drugs and chloramphenicol ointment to be used four times daily for 2 days. Pain levels and quality were assessed on a 10 cm linear analogue scale prior to each instillation of the topical medication with the McGill pain questionnaire. Pain threshold was evaluated using a modified State Trait Anxiety Inventory questionnaire. Patients were advised to use paracetomol for additional pain relief but were allowed to use any oral analgesic (except nonsteroidal agents) which they documented (type and quantity). RESULTS: There was no significant difference in pain scores between the groups using indomethacin and ketoralac. CONCLUSION: We found no significant difference between topical ketoralac and aqueous indomethacin as pain relief following excimer laser PRK. Both drugs seemed to significantly reduce pain.

Administration, Topical↗
PubMed1998

Comparison of 18% ethanol and mechanical debridement for epithelial removal before photorefractive keratectomy.

PURPOSE: To assess the safety of alcohol compared to mechanical debridement for epithelial removal prior to photorefractive keratectomy (PRK). METHODS: Forty-one second eyes of 41 patients underwent epithelial removal using alcohol prior to PRK with a Nidek EC-5000 excimer laser. The results were compared with the results of the 41 first eyes of the same patients that had mechanical debridement. RESULTS: Initial results showed that the alcohol treated group tended to stay slightly hyperopic but had less haze compared to the mechanical debridement group. The treating surgeons favored alcohol as the preferred method of epithelium removal. CONCLUSION: Alcohol debridement is an effective procedure although algorithms may have to be altered to take into account the slightly different healing process postoperatively.

Debridement↗
PubMed1998

Satisfaction after photorefractive keratectomy.

PURPOSE: To evaluate patient satisfaction one year after photorefractive keratectomy (PRK) for myopia and myopia astigmatism using the Nidek EC-5000 excimer laser. METHODS: This study assessed the level of satisfaction of 6280 patients who underwent PRK after a minimum follow-up of 1 year. All patients were asked to enter their level of satisfaction as excellent, good, worthwhile, or disappointed into a networked computer database. Their responses were subsequently analyzed according to baseline and postoperative refractive data. RESULTS: Patients considered their results to be as follows: 82.3% good or excellent, 14.9% worthwhile, and 2.8% were disappointed with the outcome. CONCLUSION: A high percentage of patients were satisfied with the outcome following PRK. However, a fair number (14%) of patients considered the treatment to be worthwhile but it did not meet their expectations. Extensive counseling and inculcating realistic expectations before treatment is essential in achieving better patient satisfaction.

Astigmatism↗
PubMed1998

Photorefractive keratectomy for myopia with -8.00 diopter cylindrical correction.

PURPOSE: A colleague requested PRK. The last time the patient was seen, no spectacles or contact lenses were worn. However, subjective refraction was -7.00 -5.50 x 165 degrees. The original Nidek nomogram would have suggested setting the laser at the actual refraction. Our algorithm adjustments suggested a 40% extra correction of cylinder would be required. The laser was therefore set to -3.50 -8.00 x 165 degrees aiming for a -1.00 -2.00 x 165 degrees outcome to allow for possible retreatment. METHODS: A 165 micron depth ablation was performed. RESULTS AND CONCLUSION: At 6 weeks after surgery, visual acuity was 0.63 unaided with a refraction of +1.50 -1.75 x 170 degrees on pred forte.

Adult↗
PubMed1997

The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains.

Prior sequence analysis studies have suggested that bacterial ribonuclease (RNase) Ds comprise a complete domain that is found also in Homo sapiens polymyositis-scleroderma overlap syndrome 100 kDa autoantigen and Werner syndrome protein. This RNase D 3'-->5' exoribonuclease domain was predicted to have a structure and mechanism of action similar to the 3'-->5' exodeoxyibonuclease (proofreading) domain of DNA polymerases. Here, hidden Markov model (HMM) and phylogenetic studies have been used to identify and characterise other sequences that may possess this exonuclease domain. Results indicate that it is also present in the RNase T family; Borrelia burgdorferi P93 protein, an immunodominant antigen in Lyme disease; bacteriophage T4 dexA and Escherichia coli exonuclease I, processive 3'-->5' exodeoxyribonucleases that degrade single-stranded DNA; Bacillus subtilis dinG, a probable helicase involved in DNA repair and possibly replication, and peptide synthase 1; Saccharomyces cerevisiae Pab1p-dependent poly(A) nuclease PAN2 subunit, required for shortening mRNA poly(A) tails; Caenorhabditis elegans and Mus musculus CAF1, transcription factor CCR4-associated factor 1; Xenopus laevis XPMC2, prevention of mitotic catastrophe in fission yeast; Drosophila melanogaster egalitarian, oocyte specification and axis determination, and exuperantia, establishment of oocyte polarity; H.sapiens HEM45, expressed in tumour cell lines and uterus and regulated by oestrogen; and 31 open reading frames including one in Methanococcus jannaschii . Examination of a multiple sequence alignment and two three-dimensional structures of proofreading domains has allowed definition of the core sequence, structural and functional elements of this exonuclease domain.

Amino Acid Sequence↗
PubMed1997

Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family.

The LAGLIDADG and HNH families of site-specific DNA endonucleases encoded by viruses, bacteriophages as well as archaeal, eucaryotic nuclear and organellar genomes are characterized by the sequence motifs 'LAGLIDADG' and 'HNH', respectively. These endonucleases have been shown to occur in different environments: LAGLIDADG endonucleases are found in inteins, archaeal and group I introns and as free standing open reading frames (ORFs); HNH endonucleases occur in group I and group II introns and as ORFs. Here, statistical models (hidden Markov models, HMMs) that encompass both the conserved motifs and more variable regions of these families have been created and employed to characterize known and potential new family members. A number of new, putative LAGLIDADG and HNH endonucleases have been identified including an intein-encoded HNH sequence. Analysis of an HMM-generated multiple alignment of 130 LAGLIDADG family members and the three-dimensional structure of the I- Cre I endonuclease has enabled definition of the core elements of the repeated domain (approximately 90 residues) that is present in this family of proteins. A conserved negatively charged residue is proposed to be involved in catalysis. Phylogenetic analysis of the two families indicates a lack of exchange of endonucleases between different mobile elements (environments) and between hosts from different phylogenetic kingdoms. However, there does appear to have been considerable exchange of endonuclease domains amongst elements of the same type. Such events are suggested to be important for the formation of elements of new specficity.

Amino Acid Sequence↗