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Biomedical subjects

A Mukherjee

Publications and source records attributed to A Mukherjee.

At least 145 records · Page 8Linked to original sources
PubMed1994

Mutations in ftsZ that confer resistance to SulA affect the interaction of FtsZ with GTP.

Mutations in the essential cell division gene ftsZ confer resistance to SulA, a cell division inhibitor that is induced as part of the SOS response. In this study we have purified and characterized the gene products of six of these mutant ftsZ alleles, ftsZ1, ftsZ2, ftsZ3, ftsZ9, ftsZ100, and ftsZ114, and compared their properties to those of the wild-type gene product. The binding of GTP was differentially affected by these mutations. FtsZ3 exhibited no detectable GTP binding, and FtsZ9 and FtsZ100 exhibited markedly reduced GTP binding. In contrast, FtsZ1 and FtsZ2 bound GTP almost as well as the wild type, and FtsZ114 displayed increased GTP binding. Furthermore, we observed that all mutant FtsZ proteins exhibited markedly reduced intrinsic GTPase activity. It is likely that mutations in ftsZ that confer sulA resistance alter the conformation of the protein such that it assumes the active form.

Alleles↗
PubMed1994

Molecular cloning and sequencing of an operon, carRS of Azospirillum brasilense, that codes for a novel two-component regulatory system: demonstration of a positive regulatory role of carR for global control of carbohydrate catabolism.

A pleiotropic carbohydrate mutant, CR17, of Azospirillum brasilense RG (wild type) that assimilates C4 dicarboxylates (succinate and malate) but not carbohydrate (fructose, arabinose, galactose, glycerol, and gluconate) as C sources for growth was used to identify the car (carbohydrate regulation) locus by complementation analysis. The 2.8-kb genomic fragment that complemented the Car- defect of CR17 and overlapped the fru operon (S. Chattopadhyay, A. Mukherjee, and S. Ghosh, J. Bacteriol. 175:3240-3243, 1993) has now been completely sequenced. The sequence contains an operon, carRS, coding for two proteins, CARR and CARS, having 236 and 352 amino acid residues, respectively. The 3'-flanking region of the carRS operon showed sequence homology with the 5' terminus of the fruB gene of a related bacterium, Rhodobacter capsulatus. A complementation study with carRS deletion clones showed that only the carR+ gene was required to complement the Car- defect of CR17, signifying that the carbohydrate pleiotropy was due to a lesion within this gene. Although the 2.8-kb DNA containing the carRS operon when introduced by conjugation into CR17 also complemented the Car- defect, the complemented transconjugant was unable to utilize succinate as a C source. The reason for this is not clear. A sequence analysis of the two protein products strongly suggests that the protein pair may constitute a novel two-component regulatory system for global expression of carbohydrate catabolic pathways in A. brasilense.

Amino Acid Sequence↗
PubMed1994

Guanine nucleotide-dependent assembly of FtsZ into filaments.

FtsZ is an essential cell division protein that is localized to the leading edge of the bacterial septum in a cytokinetic ring. It contains the tubulin signature motif and is a GTP binding protein with a GTPase activity. Further comparison of FtsZ with eukaryotic tubulins revealed some additional sequence similarities, perhaps indicating a similar GTP binding site. Examination of FtsZ incubated in vitro by electron microscopy revealed a guanine nucleotide-dependent assembly into protein filaments, supporting the hypothesis that the FtsZ ring is formed through self-assembly. FtsZ3, which is unable to bind GTP, does not polymerize, whereas FtsZ2, which binds GTP but is deficient in GTP hydrolysis, is capable of polymerization.

Amino Acid Sequence↗
PubMed1994

Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice.

Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose- and duration-dependent clastogenicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2 h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es). The study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.

Administration, Oral↗
PubMed1993

Escherichia coli cell division protein FtsZ is a guanine nucleotide binding protein.

FtsZ is an essential cell division protein in Escherichia coli that forms a ring structure at the division site under cell cycle control. The dynamic nature of the FtsZ ring suggests possible similarities to eukaryotic filament forming proteins such as tubulin. In this study we have determined that FtsZ is a GTP/GDP binding protein with GTPase activity. A short segment of FtsZ is homologous to a segment in tubulin believed to be involved in the interaction between tubulin and guanine nucleotides. A lethal ftsZ mutation, ftsZ3 (Rsa), that leads to an amino acid alteration in this homologous segment decreased GTP binding and hydrolysis, suggesting that interaction with GTP is essential for ftsZ function.

Bacterial Proteins↗
PubMed1993

Statistical mechanics of membrane channels.

Voltage-sensitive membrane channels show co-operative behaviour as evident from electrophysiological experiments. A statistical mechanical approach is suggested for a microscopic analysis of the system. A model of the Zimm-Bragg type is developed for a membrane with a large number of channels behaving co-operatively. The model is tested with voltage-dependent conductance data for gap-junction channels in embryonic cells.

Electrophysiology↗
PubMed1993

Ciprofloxacin: mammalian DNA topoisomerase type II poison in vivo.

Ciprofloxacin (CF), a fluoroquinolone widely used as a potent antimicrobial drug, was evaluated in vivo in mouse bone marrow cells for its ability to induce clastogenicity and DNA damage in terms of increased sister-chromatid exchange (SCE) frequencies. Doses of 0.6, 6 and 20 mg/kg body weight of CF given intraperitoneally induced a positive dose-dependent significant clastogenicity (trend test alpha < or = 0.05), though the effects were not specific for specific phases of the cell cycle. The DNA-damaging effect observed as increased SCE frequencies using doses of 0.15, 0.30, 0.60, 1.2 and 6 mg/kg body weight showed a significant dose-dependent increase (trend test alpha < or = 0.05; lowest effective concentration 1.2 mg/kg of body weight). Compared to a potent eukaryotic DNA topoisomerase type II poison, etoposide (VP-16, 0.5, 1 and 5 mg/kg body weight, given intraperitoneally), ciprofloxacin produced comparable dose-dependent SCE frequency increases. Ciprofloxacin was postulated to be specific for the target DNA gyrase, the prokaryotic homologue of DNA topoisomerase type II enzyme. The present paper along with the existing earlier data strongly suggest that topoisomerase type II and DNA gyrase are physiological targets for the drug action. In view of the present significant in vivo mammalian DNA topoisomerase type II-mediated genotoxicity and clastogenicity data, ciprofloxacin should be administered with caution.

Analysis of Variance↗
PubMed1993

Combined multidrug and Mycobacterium w vaccine therapy in patients with multibacillary leprosy.

Immunotherapy with Mycobacterium w vaccine was attempted in patients with borderline-borderline, borderline lepromatous (BL), or lepromatous leprosy (LL) to determine whether immunization can hasten recovery and reduce treatment time by invigorating cell-mediated immunity. Mycobacterium w, a nonpathogenic, rapidly growing, atypical mycobacterium, shares a number of common B and T cell determinants with Mycobacterium leprae and Mycobacterium tuberculosis. Patients receiving the vaccine had rapid clinical improvement and accelerated bacteriologic clearance. After treatment with vaccine for 2 years, 13 of 31 BL and LL patients were bacteriologically negative as were 5 of 25 controls. Vaccinated patients had one of two distinct histologic features, either an upgrading in the disease spectrum or complete clearance of granuloma. Some 80% of lepromin conversions were in BL and LL patients who received vaccine versus none and 14.3% of BL and LL controls, respectively. Thirteen of 17 vaccinated LL patients were released from treatment after 2 years in contrast to 2 of 15 controls.

Bacterial Vaccines↗
PubMed1993

Post-kala-azar dermal leishmaniasis: a clinical and therapeutic study.

BACKGROUND: Post-kala-azar dermal leishmaniasis is a condition peculiarly confined to the Indian subcontinent. METHODS: The clinical features and investigations in 18 patients of post-kala-azar dermal leishmaniasis were studied. RESULTS: There was a polymorphic picture from hypopigmented macules to nodules and plaques. Mucous membranes were affected in five, the lips and glans penis being the most frequent sites. Histopathologically, a rich dermal infiltrate was seen in indurated lesions and in macules; it was confined to perivascular foci in the upper dermis. Leishman-Donovan bodies were seen in 16. CONCLUSIONS: The lesions cleared in 4 to 5 months after treatment with sodium antimony gluconate intramuscularly 20 mg/kg/day up to a maximum of 1 g/day. The drug was well tolerated.

Adolescent↗
PubMed1993

Post-kala-azar dermal leishmaniasis: a light and electron microscopic study of 18 cases.

Post-kala-azar dermal leishmaniasis (PKDL) is caused by the protozoan parasite, Leishmania donovani, and is seen in patients with history of having been treated earlier for the visceral disease form, kala-azar, caused by the same organism. The findings from 18 patients with PKDL are described in this study. The skin manifestations ranged from hypopigmented macules to infiltrated plaques and nodules. Histopathologic examination revealed a cellular infiltrate of lymphocytes, plasma cells, and macrophages. The macrophages were scattered amidst the infiltrate without any localization. In hypopigmented lesions, the infiltrate was confined to the perivascular region in the superficial dermis and was composed mainly of lymphocytes and few plasma cells. In the nodular lesions, the infiltrate occupied the entire thickness of the dermis. Leishman-Donovan bodies were scarce and identified in 16 cases after a prolonged search of Weigert's iron hematoxylin-stained sections. In 2 cases, Leishman-Donovan bodies were not demonstrable. Electronmicroscopic study revealed parasitized macrophages which showed no structural evidence of activation despite the active cellular response around them. The fine structure of the parasites in the histiocytes was also well maintained. This unusual tropical dermatosis is a unique example of change in organotropism of a parasite associated with a change in the host response.

Adolescent↗
PubMed1993

Azospirillum brasilense locus coding for phosphoenolpyruvate:fructose phosphotransferase system and global regulation of carbohydrate metabolism.

Mutants of Azospirillum brasilense unable to grow on fructose include ones affected only on fructose (Fru-) and others impaired on many or all carbohydrates through interference with induction of their specific pathways (Car-). Both types of mutants could be complemented by a cosmid in broad-host-range vector pLAFR1 containing a 27.5-kb genomic insert, Car(-)-complementing activity depending on a 2.2-kb fragment, and Fru(-)-complementing activity depending on an overlapping 9.6-kb fragment.

Azospirillum brasilense↗
PubMed1993

Randomized clinical trial of furazolidone for typhoid fever in children.

The efficacy of furazolidone and chloramphenicol was compared in a randomized trial involving 133 children with bacteriologically confirmed typhoid fever. Sixty-five children were randomized to receive furazolidone, 7.5 mg/kg/day, and 68 children to receive chloramphenicol, 75 mg/kg/day. Both drugs were administered orally. The clinical characteristics of the two treatment groups were comparable on admission. All the strains of Salmonella typhi isolated from the furazolidone group were susceptible to furazolidone. However, of the 68 strains of S. typhi isolated from the chloramphenicol group, 10 were susceptible and 58 were resistant to chloramphenicol. Clinical and bacteriologic cure was observed in 56 (86.2%) children treated with furazolidone and in 35 (51.5%) children given chloramphenicol who were infected with S. typhi strains, irrespective of susceptibility pattern (P = 0.00003). Cure was achieved in 86.2% of furazolidone recipients and 90.0% of chloramphenicol recipients who were infected with strains of S. typhi susceptible to both drugs (P = 0.6). The difference in cure rate was statistically significant (P = 0.000003) when the two treatment groups infected with furazolidone-susceptible but chloramphenicol-resistant strains of S. typhi were compared. There was no relapse or carriers in either of the groups. Furazolidone appears to be a satisfactory alternative to chloramphenicol in the treatment of typhoid fever caused by chloramphenicol-resistant strains of S. typhi.

Carrier State↗
PubMed1993

9 Knee arthroplasties for sickle cell disease.

Sickle cell disease sometimes presents with knee arthropathy secondary to osteonecrosis. We report our experience with 9 total knee arthroplasties in 5 patients. The joint fluid, synovium, capsule, and excised bones were sent for culture. Tissue cultures from 5 knees grew organisms. The outcome was: 6 excellent, 1 good, 1 satisfactory, and 1 poor. Infection in 1 case led to removal of the prosthesis and subsequent arthrodesis. 1 patient had persistent peroneal nerve palsy. There were no hematological complications. We suggest that osteonecrosis in sickle cell disease should be considered septic.

Adolescent↗
PubMed1993

Borderline-tuberculoid relapse in lepromatous leprosy.

We report details of 2 patients who had been treated for a long time by dapsone monotherapy and who had remained smear negative for over 10 years, but were found to have relapsed with borderline-tuberculoid (BT) leprosy.

Dapsone↗
PubMed1993

Reversal reaction in multibacillary leprosy patients following MDT with and without immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w.

Immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w, was given in addition to standard multidrug therapy (MDT) to 53 multibacillary lepromin negative patients belonging to BB, BL and LL types of leprosy (vaccine group). An equal control group received MDT and injections of micronized starch as placebo. Both the vaccine and placebo were administered intradermally every 3 months. The patients were evaluated at determined intervals by clinical, bacteriological and histopathological parameters and lepromin testing. Reactional episodes were analysed with reference to incidence, onset, frequency and severity during and after release from treatment (RFT). Incidence of reversal reaction (RR) was marginally higher in the vaccine group (22.6% vaccine group vs 15% control group). All cases with a history of downgrading type 1 reaction developed RR during therapy. Most episodes occurred within the 1st year of the commencement of therapy--50% developing within 3 months. Late reversal reaction (after RFT) were observed in 3.8% of cases in both groups, and 50% of the reactors in the control group and 33% in the vaccine group had repeated reactional episodes. Incidence of neuritis associated with RR as well as isolated neuritis was similar in both groups.

Bacterial Vaccines↗
PubMed1993

Evolution of early lesions in leprosy.

We observed 29 patients presenting with vague peripheral neurological symptoms for 6 months or more. During this period, 16 developed clinical leprosy, 3 developed borderline tuberculoid leprosy and the other 13 developed neuritic leprosy. Of these 13 cases 11 subsequently developed skin lesions similar to those seen in indeterminate and in borderline tuberculoid leprosy. Based on the above observations, an attempt has been made to explain the evolution of early lesions of leprosy.

Adolescent↗
PubMed1993

Field trials on the use of Mycobacterium w vaccine in conjunction with multidrug therapy in leprosy patients for immunotherapeutic and immunoprophylactic purposes.

A double blind field trial was started with a candidate anti-leprosy vaccine, Mycobacterium w as an immunotherapeutic and immunoprophylactic agent against leprosy in a highly endemic region with a prevalence rate of over 18 per 1000 population. By 31 August 1992, 224 villages have been surveyed, covering a population of 307,981 (1981 census). A total of 979 MB patients and 2801 PB patients have been registered. A total of 19,453 household contacts of leprosy patients have been examined for clinical signs of disease, of which 16,519 have received the initial dose while 10,434 have also received the booster dose of vaccine/placebo. The aims and objectives, study design of the trial, present status as well as the socio-cultural aspect involved are highlighted in this paper.

Bacterial Vaccines↗