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Biomedical subjects

A Mukherjee

Publications and source records attributed to A Mukherjee.

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

Kaposi's sarcoma of the parotid gland in acquired immunodeficiency syndrome.

Parotid gland enlargement is common in patients infected with the human immunodeficiency virus. Although parotitis is the usual histopathological feature in such cases, patients with acquired immunodeficiency syndrome are at high risk of developing both lymphoma and Kaposi's sarcoma of the parotid gland. Human immunodeficiency virus, however, is not detected within the parotid parenchyma even in the presence of Kaposi's sarcoma. The pathway of the virus' entry into the saliva remains unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda reactive: lessons form Convit's experiment on bacteria-clearing capacity of lepromin-induced granuloma.

It is amazing how after years of scientific research and therapeutic progress many simple and basic questions about protective immunity against Mycobacterium leprae remain unanswered. Although the World Health Organization (WHO) has recommended short-term multidrug therapy (WHO/MDT) for the treatment of paucibacillary (PB) leprosy patients, from time to time several workers from different parts of the globe have reported inadequate clinical responses in a few tuberculoid and indeterminate leprosy patients following adequate WHO/MDT despite the fact that they are Mitsuda responsive. A few borderline tuberculoid patients harbor acid-fast bacilli (AFB) in their nerves for many years even though they become clinically inactive following MDT, a fact which has been ignored by many leprosy field workers. Keeping these patients in mind, we have attempted to investigate the cause of the persistence of AFB in PB cases and have looked into the question of why Mitsuda positivity in tuberculoid and indeterminate leprosy patients, as well as in healthy contacts, is not invariably a guarantee for protectivity against the leprosy bacilli. We have: a) analyzed the histological features of lepromin-induced granulomas, b) studied the bacteria-clearing capacity of the macrophages within such granulomas, and c) studied the in vitro leukocyte migration inhibition factor released by the blood leukocytes of these subjects when M. leprae sonicates have been used as an elicitor. The results of these three tests in the three groups of subjects have been compared and led us to conclude that the bacteria-clearing capacity of the macrophages within lepromin-induced granuloma (positive CCB test) may be taken as an indicator of the capability of elimination of leprosy bacilli and protective immunity against the disease. This important macrophage function is not invariably present in all tuberculoid and indeterminate leprosy patients or in all contacts even though they are Mitsuda responsive and are able to show a positive leukocyte migration inhibition (LMI) test. It is likely but not certain that this deficit of the macrophage is genetically predetermined and persists after completion of short-term WHO/MDT. Thus, after discontinuation of treatment slow-growing, persisting M. leprae multiply within macrophages leading to relapse.

Adolescent↗
PubMed1997

The founding mitochondrial DNA lineages of Tristan da Cunha Islanders.

Genealogical histories show that the inhabitants of Tristan da Cunha are derived from a known number of founders. Using the transmission of mitochondrial DNA (mtDNA) from mother to offspring pairs, we traced the mtDNA types found in 161 extant individuals to five female founders. Although the historical data claimed that two pairs of sisters were among the founding females, mtDNA data showed support for only one pair of sisters. We also studied the fidelity of mtDNA transmission in conjunction with the genealogical data. We did not detect any mutations from 698 base pairs of sequence data from 75 individuals, which together accounted for 108 independent transmissions of mtDNA from mother to offspring. Based on this observation, we estimate that the mtDNA mutation rate is no more than one new mutation every 36 transmissions. These results indicate a high fidelity of maternal mtDNA transmission and support the utility of mtDNA in evolutionary and forensic studies.

DNA, Mitochondrial↗
PubMed1997

In vivo cytogenetic studies on mice exposed to acesulfame-K--a non-nutritive sweetener.

Acesulfame-K, a sweetening agent, was evaluated in vivo for its genotoxic and clastogenic potentials. Swiss albino male mice were exposed to the compound by gavage. Bone marrow cells isolated from femora were analysed for chromosome aberrations. Doses of 15, 30, 60, 450, 1500 and 2250 mg of acesulfame-K/kg body weight induced a positive dose-dependent significant clastogenicity (trend test alpha < 0.05). These doses were within the no-toxic-effect levels (1.5-3 g/kg body weight in rats) reported by the Joint Expert Committee for Food Additives of the World Health Organization and the Food and Agriculture Organization of the United Nations. In view of the present significant in vivo mammalian genotoxicity data, acesulfame-K should be used with caution.

Administration, Oral↗
PubMed1997

Molecular characterization and expression of the Erwinia carotovora hrpNEcc gene, which encodes an elicitor of the hypersensitive reaction.

The nucleotide sequence of hrpNEcc DNA, cloned from Erwinia carotovora subsp. carotovora strain Ecc71, reveals a coding region of 1,068 bp which matches the size of hrpNEcc transcripts. hrpNEcc is predicted to encode a glycine-rich protein of approximately 36 kDa. Like the elicitors of the hypersensitive reaction (HR) produced by E. chrysanthemi (HarpinEch) and E. amylovora (HarpinEa), the deduced 36-kDa protein does not possess a typical signal sequence, but it contains a putative membrane-spanning domain. In Escherichia coli strains overexpressing hrpNEcc, the 36-kDa protein has been identified as the hrpNEcc product by Western blot analysis using anti-HarpinEch antibodies. The 36-kDa protein fractionated from E. coli elicits the HR in tobacco leaves. Moreover, a HrpN- and RsmA- double mutant (RsmA = regulator of secondary metabolites) does not produce this 36-kDa protein or elicit the HR, although this strain, like the RsmA- and HrpN+ bacteria, overproduces extracellular enzymes and macerates celery petioles. These observations demonstrate that hrpNEcc encodes the elicitor of the HR, designated HarpinEcc. The levels of hrpNEcc transcripts are affected in both RsmA+ and RsmA- strains by media composition and carbon sources, although the mRNA levels are substantially higher in the RsmA- strains. The expression of hrpNEcc in Ecc71 is cell density dependent and is activated by the quorum-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone (OHL). By contrast, hrpNEcc expression in an RsmA- strain is independent of cell density, and substantial expression occurs in the absence of OHL. The effects of cultural conditions and the occurrence of putative cis-acting sequences, such as consensus sigma 54 promoters and an hrp promoter upstream of the transcriptional start site, indicate that the production of HarpinEcc in wild-type RsmA+ E. carotovora subsp. carotovora is tightly regulated. These observations, taken along with the finding that the HR is caused by RsmA- mutants but not by RsmA+ strains (Cui et al., 1996, Mol. Plant-Microbe Interact. 9:565-573), strongly support the idea that the inability of the wild-type pectolytic E. carotovora subsp. carotovora to elicit the HR is due to the lack of a significant level of HarpinEcc production.

4-Butyrolactone↗
PubMed1997

Analysis of the interaction of FtsZ with itself, GTP, and FtsA.

The interaction of FtsZ with itself, GTP, and FtsA was examined by analyzing the sensitivity of FtsZ to proteolysis and by using the yeast two-hybrid system. The N-terminal conserved domain consisting of 320 amino acids bound GTP, and a central region of FtsZ, encompassing slightly more than half of the protein, was cross-linked to GTP. Site-directed mutagenesis revealed that none of six highly conserved aspartic acid and asparagine residues were required for GTP binding. These results indicate that the specificity determinants for GTP binding are different than those for the GTPase superfamily. The N-terminal conserved domain of FtsZ contained a site for self-interaction that is conserved between FtsZ proteins from distantly related bacterial species. FtsZ320, which was truncated at the end of the conserved domain, was a potent inhibitor of division although it expressed normal GTPase activity and could polymerize. FtsZ was also found to interact directly with FtsA, and this interaction could also be observed between these proteins from distantly related bacterial species.

Asparagine↗
PubMed1997

Acute appendicitis in minority communities: an epidemiologic study.

This study examines the incidence and epidemiological factors of acute appendicitis in various ethnic groups in an urban minority community. The charts of 278 consecutive patients who underwent appendectomy at The Bronx-Lebanon Hospital Center, Bronx, New York, between January 1988 and December 1990 were reviewed. Thirty-eight patients who underwent incidental appendectomy and one patient who had an interval appendectomy were excluded. The remaining 239 patients, all of whom had acute appendicitis, constituted the study population. The incidence of appendicitis for each ethnic group was calculated as a percentage of the total emergency surgical admissions for that group. Acute appendicitis constituted 3.1% of all emergency admissions to the surgical service over the period studied and represented 4.5% of surgical service admissions from the emergency department in Hispanics, 1.9% in African Americans, 1.5% in whites, and 21% in Asians. These differences were statistically significant except some comparisons involving whites. There were no significant differences in the pathological findings regarding the diseased appendix in different racial groups. These results indicate that acute appendicitis is responsible for a higher incidence of emergency admissions among Hispanics than among African Americans. This finding was statistically significant. High white blood cell counts indicated inflammation of the appendix, but had no predictive value for the type of pathology. Surgical findings were similar in all groups.

Acute Disease↗
PubMed1996

Phenethyl isothiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo.

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p < or = 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by mitomycin C.

Animals↗
PubMed1996

Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats.

OBJECTIVE AND DESIGN: Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. MATERIAL: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanol-water partition coefficient and elimination half-life. TREATMENT: Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. METHODS: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. RESULTS: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin > yeast induced fever > pressure induced pain = adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pKa contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED50 and pKa were established that may assist in the future clinical development of NSAIDs. CONCLUSIONS: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pKa) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed.

Administration, Oral↗
PubMed1996

RecA relieves negative autoregulation of rdgA, which specifies a component of the RecA-Rdg regulatory circuit controlling pectin lyase production in Erwinia carotovora ssp. carotovora.

The production of pectin lyase (Pnl) in Erwinia carotovora ssp. carotovora strain 71 is induced by DNA-damaging agents such as mitomycin C (MC). This induction requires functions of recA, rdgA and rdgB genes. Based upon sequence homology, rdgA was predicted to encode a repressor and rdgB was presumed to specify a transcriptional activator. To elucidate the function of rdgA, the gene has been over-expressed in Escherichia coli, and the 30 kDa product purified by ammonium-sulphate precipitation, heparin-agarose chromatography and gel filtration. The results of gel mobility-shift and DNase I protection assays revealed that purified RdgA specifically binds the rdgA operator sequence located between the -10 and -35 boxes. The expression of a rdgA-lacZ gene fusion in E. coli MC4100 is suppressed upon overproduction of RdgA from a Ptac-rdgA construct induced by isopropyl-beta-D-thiogalactopyranoside (IPTG). However, the suppression of rdgA-tacZ expression is relieved by MC in the RecA+ E. coli strain MC4100, but not in its RecA- derivative, MC4160. An immunoblot analysis revealed RecA-dependent in vivo cleavage of the 30 kDa RdgA protein upon MC treatment. These results demonstrate that the transcription of rdgA is autoregulated, and strongly support the idea that proteolytic activity of RecA* is responsible for the derepression of rdgA expression.

Bacterial Proteins↗
PubMed1996

Aflatoxin B1 contamination in groundnut samples collected from different geographical regions of India: a multicentre study.

Under a multicentre study conducted by the Indian Council of Medical Research, 2062 samples of groundnut were collected from rural and urban areas of 11 states representing different geographical regions of the country. These samples were analysed for aflatoxin B1 using the AOAC method. Analytical quality assurance between various participating laboratories was ensured through analysis of check-samples. Twenty-one per cent of groundnut samples collected from 11 states exceeded the permissible Indian regulatory limit of 30 micrograms/kg. No statistically significant difference in percentage of samples contaminated (> 30 micrograms/kg) were observed between pooled rural (22.9%) and urban (19.9%) data. Amongst the 11 states, the minimum and maximum per cent contamination respectively (> 30 micrograms/kg) was observed to be 15.2 in the state of Andhra Pradesh and 28.3 in the state of Haryana. The maximum level of contamination of 833 micrograms/kg was observed in the state of Gujarat. The median level of < 5 micrograms/kg was observed in the states of Gujarat, Haryana, Punjab, Andhra Pradesh and Karnataka. In all other states studied, the median level was found to vary between 10 and 20 micrograms/kg. The 90th percentile values were high in Andhra Pradesh (125 micrograms/kg), Gujarat (111 micrograms/kg) and Haryana (110 micrograms/kg). In the remaining states the 90th percentile value ranged from 60 to 93 micrograms/kg. Analysis of pooled data showed the percentages of samples exceeding the level of contamination of 5 micrograms/kg and 15 micrograms/kg, respectively were 44.9% and 37.4% which therefore, showed a marked increase when compared with the per cent of samples exceeding 30 micrograms/kg in the overall data.

Aflatoxin B1↗
PubMed1996

Chemical pleurodesis for spontaneous pneumothorax in a patient with AIDS.

Persistent air leak and failure of the lung to expand completely after closed thoracostomy complicate the course of spontaneous pneumothorax in patients with AIDS. In such cases, attempts to discontinue chest tube drainage may fail. The following is a case of a patient with AIDS and spontaneous pneumothorax who responded to chemical pleurodesis with tetracycline.

AIDS-Related Opportunistic Infections↗
PubMed1996

The RsmA- mutants of Erwinia carotovora subsp. carotovora strain Ecc71 overexpress hrpNEcc and elicit a hypersensitive reaction-like response in tobacco leaves.

Erwinia carotovora subsp. carotovora wild-type strain Ecc71 does not elicit the hypersensitive reaction (HR) in tobacco leaves. By mini-Tn5-Km and chemical mutagenesis we have isolated RsmA- mutants of Ecc71 that produce high basal levels of pectate lyases, polygalacturonase, cellulase, and protease; they also are hypervirulent. The RsmA- mutants, but not their parent strains, elicit an HR-like response in tobacco leaves. This reaction is characterized by the rapid appearance of water soaking followed by tissue collapse and necrosis. The affected areas remain limited to the region infiltrated with bacterial cells, and the symptoms closely resemble a typical HR, e.g., the reactions caused by Pseudomonas syringae pv. pisi. Moreover, low concentrations of cells of the mini-Tn5-Km insertion RsmA- mutant, AC5070, infiltrated into tobacco leaf tissue prevent elicitation of the rapid necrosis by AC5070 or by P. syringae pv. pisi. Elicitation of the HR-like response by the mutants is not affected by the deficiency of N-(3-oxohexanoyl)-L-homoserine lactone, the cell density (quorum) sensing signal. Cloning and sequence analysis have disclosed that E. carotovora subsp. carotovora strain Ecc71 possesses a homolog of E. chrysanthemi hrpN known to encode an elicitor of the HR; the corresponding Ecc71 gene is designated hrpNEcc. Northern (RNA) blot data show that the level of hrpNEcc mRNA is considerably higher in the RsmA- mutants than in the RsmA+ strains. Moreover, a low copy plasmid carrying the rsmA+ allele severely reduces the level of the hrpNEcc transcripts in the RsmA- mutants. These constructs, like the RsmA+ E. carotovora subsp. carotovora strains, do not elicit the HR-like response. These data taken along with the effects of rsmA on exoenzyme production and pathogenicity (A. Chatterjee et al., 1995, Appl. Environ. Microbiol. 61:1959-1967) demonstrate that this global regulator gene plays a critical role in plant interaction of E. carotovora subsp. carotovora.

Amino Acid Sequence↗
PubMed1996

Gonadotropins induce rapid phosphorylation of the 3',5'-cyclic adenosine monophosphate response element binding protein in ovarian granulosa cells.

The pituitary gonadotropins FSH and LH exert their effects on gonadal target cells, at least in part, through the activation of adenylyl cyclase and the production of the second messenger cAMP. To elucidate further the signal transduction pathways regulating gonadotropin-responsive genes in ovarian granulosa cells, we have investigated the expression of the cAMP response element binding protein (CREB), which mediates many of the effects of cAMP by modulating the transcription of target genes in a cAMP-dependent fashion. In situ hybridization, RNA blot analysis and RT-PCR RNA quantification demonstrated that CREB messenger RNA (mRNA) is expressed at low levels throughout the ovary, and that CREB mRNA levels do not change appreciably after gonadotropin stimulation. Similar results were obtained using immunohistochemistry and Western protein blotting to examine CREB protein in ovaries isolated from immature animals treated with gonadotropins or immunocytochemistry and Western protein blotting to examine the CREB protein in cultured granulosa cells after gonadotropin treatment. In contrast, immunocytochemistry and Western protein blotting using an antipeptide antibody specific to CREB phosphorylated at serine 133 (P-CREB), which is the activated from of the CREB protein, revealed a dramatic increase in the phosphorylated form of CREB within 20 min of gonadotropin treatment of granulosa cells that was transient and was decreased by 60 min after gonadotropin treatment. Stimulation of P-CREB was observed using granulosa cells isolated from immature animals and treated with recombinant human FSH in vitro, or using granulosa cells isolated from immature animals primed with PMSG in vivo and treated with human CG (hCG) in vitro. Stimulation of P-CREB was also observed in ovarian granulosa cells isolated from animals treated with PMSG in vivo. These results indicate that both gonadotropins can induce a rapid and transient phosphorylation of the CREB protein in granulosa cells, leading to the activation of a factor likely to play an important role in the transcription of many gonadotropin-regulated ovarian genes.

Animals↗
PubMed1996

Enantioselective binding of Casodex to the androgen receptor.

1. The biologic activity of androgens is mediated through the formation of a non-covalent androgen receptor (AR)-steroid complex. Casodex and other antiandrogens inhibit formation of this complex and thus negate the role of endogenous steroids in androgen-dependent growth of prostate. 2. Casodex is currently available as a racemic mixture. The goal of this investigation was to determine the in vitro AR binding affinities of the individual isomers of Casodex. 3. The (R) or (S) isomers of Casodex were synthesized according to the general synthetic scheme proposed by Tucker et al. for (S)-Casodex, using (R) or (S)-proline as the chiral matrix respectively. 4. ARs were isolated from rat ventral prostate tissue by homogenization and differential centrifugation, and used as the receptor source. 5. AR binding studies were conducted by incubation of the cytosol with 1 nM 3H-mibolerone (a synthetic androgen) and increasing concentrations of each isomer (10(-12) - 10(-5) M). Bound radioligand was quantitated by liquid scintillation counting. 6. Ki for (R)-Casodex (11.0 +/- 1.5 nM) was about 30 times lower than that of (S)-Casodex (364 +/- 10 nM). Ki for the racemate was 20.2 +/- 2.0 nM. 7. This study demonstrated that (R)-Casodex has a higher binding affinity than its stereoisomer and suggests that the antiandrogenic activity of racemic Casodex is almost completely due to the (R)-isomer.

Androgen Antagonists↗
PubMed1996

Ultrastructure of normal armadillo epidermis.

In view of the importance of the nine-banded armadillo (Dasypus novemcinctus) in leprosy research, we studied the ultrastructure of the normal epidermis of this species. The three basic cell types of human epidermis were identified in armadillo skin: keratinocytes, melanocytes, and Langerhans' cells. The role of Langerhans' cells in the human cell-mediated immune system and the description of changes in the number and structure of Langerhans' cells in human leprosy make detailed observations of these cells in the armadillo highly relevant. Clear cells with ultrastructural features typical of Langerhans' cells were observed in normal armadillo epidermis in all areas of skin sampled (abdomen, chin, ear, and thigh), but are fewer than in human skin. These baseline findings are valuable for further studies on Langerhans' cells and the cell-mediated immune function in armadillos with naturally acquired or experimental leprosy.

Animals↗
PubMed1996

Nuclear matrix bound DNA polymerase-beta in mouse fibrosarcoma: effect of gamma-radiation.

Nuclear matrices isolated from the mouse fibrosarcoma tumour cells contain the eukaryotic replicative enzyme DNA polymerase-alpha and the presumptive repair enzyme DNA polymerase-beta. Exposure of tumors to various doses of gamma-radiation (1.95 to 6.5 Gy) causes a 2-fold increase in the levels of only DNA polymerase-beta in the nuclear matrix. The increase in the levels of this enzyme is not discernible if the matrices are isolated 24 hr after irradiation. The rise in the levels of the repair enzyme DNA polymerase-beta could be indicative of radiation stress response of the tumour cells and their repair ability.

Animals↗