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Biomedical subjects

S Banerjee

Publications and source records attributed to S Banerjee.

At least 289 records · Page 16Linked to original sources

Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat prostate.

We showed previously that exogenously administered testosterone caused age- and lobe-specific overgrowth of the prostate in Brown Norway rats. A common feature observed in testosterone-treated animals was cell hypertrophy in each of the ventral, dorsal, and lateral lobes of both young (6 mo old) and old (24 mo old) rats. By contrast, hyperplasia was seen only in the dorsal and lateral lobes of old rats treated with testosterone. These observations prompted us to examine whether age- and lobe-specific overgrowth might also occur in untreated rats as a consequence of the endogenous hormonal milieu. To this end, blood and prostates were collected from a large number (25-30 rats per group) of 4- to 6-mo-old (young) and 21- to 24-mo-old (old) Brown Norway rats. Both serum testosterone (-45%) and estradiol (-22%) concentrations decreased significantly with age, but the greater magnitude of the decrement in testosterone relative to estradiol led to a reduction in the serum testosterone:estradiol ratio. Paradoxically, although the prostate is androgen dependent, the wet weight, protein, and DNA contents increased significantly with age in the dorsal and lateral lobes of old rats despite the decrease in testosterone level. Histologic examination revealed that the increased weights and DNA contents of the dorsal and lateral lobes in old rats coincided with an increased number of epithelial cells in the distal and intermediate segments of these lobes, indicative of hyperplasia but independent of change in cell size. Taken together, these results show a spontaneous age-related overgrowth of cells in the dorsal and lateral prostatic lobes of old Brown Norway rats despite diminished serum testosterone concentrations. The aging Brown Norway rat, therefore, may be a useful model for studies of some aspects of the pathogenesis underlying spontaneous age-related prostatic hyperplasia.

Aging↗

A PC-based Braille library system for the sightless.

This paper presents a novel multiclient braille reading system developed around a single low cost personal computer. The system primarily addresses the needs of the Braille libraries, where different texts are needed to be read by different users simultaneously. Moreover, the system can simultaneously cater to different texts written in different languages. This feature makes it specially suitable for use by multilingual nationalities. The major advantage of this system is its low cost, compared to the other systems available and is specially attractive for the developing or underdeveloped countries. The paper describes the system, first from the user point of view and then presents the hardware and software design details. The system performance has been evaluated by the sightless users and has shown encouraging results.

Blindness↗

Refractory status epilepticus in children: role of continuous diazepam infusion.

To determine efficacy of continuous diazepam infusion in the treatment of refractory status epilepticus in a retrospective study, we analyzed data of 62 children admitted consecutively to our Pediatric Intensive Care Unit with a diagnosis of refractory status epilepticus. The unit followed a standard treatment protocol for diazepam infusion; if it failed, thiopental infusion was used. The mean age of patients was 2.80 years (range, 1.5 to 11.5 yr). Thirty-six patients (60%) had acute infections of the central nervous system and 10 (16%) had idiopathic epilepsy. Diazepam infusion was used in 57 patients. This treatment controlled seizures in 86% of patients (49/57), on average within 40 minutes (median, 30 min; range, 10-120 min), at a mean infusion rate of 0.017 mg/kg/min (range, 0.01-0.03 mg/kg/min). The mean total duration of infusion was 68 hours (range, 12-220 hr). Diazepam infusion was associated with hypotension in one patient, respiratory depression requiring ventilatory support in 12% of patients (6/49), and death in 14% of patients (7/49). Thiopental infusion was used in nine patients, including eight in whom diazepam infusion had failed. Thiopental infusion controlled seizures in all nine patients, but all of them needed mechanical ventilation, and seven needed vasopressor support for hypotension; four patients (44%) died. We conclude that continuous diazepam infusion is a reasonably effective modality to control refractory status epilepticus in children and is associated with reduced need for ventilatory and vasopressor support.

Anticonvulsants↗

Culturally sensitive validation of screening questionnaires for depression in older African-Caribbean people living in south London.

BACKGROUND: We tested the validity of two screens for depression in older African-Caribbean adults, the 15-item Geriatric Depression Scale (GDS) and a new Caribbean Culture-Specific Screen for emotional distress (CCSS). Two independent criteria were used for validity: (a) a psychiatric diagnosis derived from GMS-AGECAT, and (b) a culturally sensitive assessment of mental disorder, derived from a tool developed with local African-Caribbean religious healers. METHOD: One hundred and sixty-four consecutive African-Caribbean primary care users, aged 60 years or older, were screened with the GDS and the CCSS. Diagnostic interviews were carried out on 80% of high scorers and 20% of low scorers. RESULTS: The number of cases detected by the two separate diagnostic approaches was similar. However, the agreement between who was and who was not a case was only modest. At a cut-off of > or = 5, the GDS was an adequate case detector for psychiatric depression, and, at a cut-off of > or = 4, for 'depressed/lost spirit', as defined by culture-specific criteria. It performed as well as the new CCSS. CONCLUSIONS: At a cut-off of > or = 4 the 15-item GDS can be recommended as a case detector for significant forms of depression in older African-Caribbean people living in south London.

Aged↗

Lobe-specific telomerase activity in the intact adult brown Norway rat prostate and its regional distribution within the prostatic ducts.

It is generally established that telomerase activity is present in most cancer cells, germ line cells, and established cell lines but typically is not present in normal somatic cells. Among the few exceptions, telomerase activity has been detected in hematopoietic stem cells and in physiologically renewable epithelial cell populations (e.g. skin, small intestine). The adult rat prostate gland is a tissue that has the ability to regenerate in response to androgen. We hypothesized, therefore, that telomerase activity should be present in the normal adult rat prostate. In this study, using a highly sensitive PCR-based telomerase assay [the telomerase repeat amplification protocol (TRAP) assay], we tested this hypothesis by measuring telomerase activity in the ventral, dorsal, lateral, and anterior lobes of the adult rat prostate. We show herein that telomerase activity indeed is present in whole tissue extracts of the ventral, dorsal, and anterior lobes, though at differing levels, but not the lateral lobe. However, lateral lobe prostatic fluid was found to contain one or more factors inhibitory for the TRAP reaction, and therefore, telomerase activity was detected after removal of this fluid. Telomerase activities were not uniform within the prostatic ducts, but rather telomerase positive cells are regionally distributed within the distal, intermediate, and proximal ducts of the microdissected segments of each of the lobes. We speculate from these results that androgen-stimulated regeneration of rat prostate following androgen ablation may depend upon the telomerase-positive regenerating pool of cells present within specific regions of the ductal network.

Animals↗

Telomerase activity in normal adult Brown Norway rat seminal vesicle: regional distribution and age-dependent changes.

Telomerase activity is essential for protection of cells against the telomere erosion that occurs with each round of cell replication, and thus appears to play a role in the indefinite replication potential of some, but not all, eukaryotic cells. In this regard, some tissues contain stem cells that have a long proliferative life-span and are capable of regenerating or renewing the somatic epithelial cell population within the tissue. Because the adult seminal vesicle exhibits the ability to regenerate during androgen-replacement after castration, we hypothesized that a pool of cells with regenerating potential is present in the adult seminal vesicle, which expresses telomerase activity. In this study, we used a highly sensitive PCR-based telomerase assay [the telomeric repeat amplification protocol (TRAP) assay] to detect telomerase activity in rat seminal vesicle. Our results show that telomerase activity is, indeed, present in the normal adult rat seminal vesicle, but that, in the presence of seminal vesicle fluid, telomerase activity cannot be detected. In fact, seminal vesicle fluid was found to contain some factor(s) that is inhibitory for the TRAP assay. In addition, we found that telomerase activity in the seminal vesicle changes with age and is regionally distributed within the distal, intermediate, and proximal segments of the duct. These results suggest that as is the case for the rat prostate, a population of telomerase-positive cells is present within the adult rat seminal vesicle, and thereby, this organ retains throughout life the potential to regenerate in response to androgen replacement following castration-induced apoptotic cell death.

Age Factors↗

Regional expression of transforming growth factor-alpha in rat ventral prostate during postnatal development, after androgen ablation, and after androgen replacement.

The prostate is a highly heterogeneous organ, composed of different types of epithelial and stromal cells organized regionally along the ductal network. Although androgen-stimulated growth and maintenance of the prostate gland primarily involve epithelial cells, it is unclear whether all epithelial cells are androgen dependent. Moreover, the actions of androgens may not be direct; a number of polypeptide growth factors, including transforming growth factor-alpha (TGFalpha), are postulated to mediate androgen action in the rat prostate. In this investigation, using an immunohistochemical technique, we examined the cellular and regional expression of TGFalpha in the rat ventral prostate during postnatal development to adulthood. TGFalpha-immunopositive cells were located throughout the ductal epithelium from postnatal days 5-20. By day 45 and thereafter, regional variation in TGFalpha expression became apparent; epithelial cells in the proximal segment exhibited intense staining, whereas those in the distal segment exhibited negligible staining. These observations were coincident with increased serum testosterone concentrations at puberty. To understand the role of androgen in the expression of TGFalpha in the epithelial cells of the distal and proximal segments of the adult rat ventral prostate, androgen was withdrawn by castration, and testosterone subsequently was administered. Androgen receptor protein expression decreased after castration and reappeared after androgen replacement in both the distal and proximal segments. TGFalpha staining was negligible in epithelial cells of the distal segment of intact adult rats, became prominent by 7 days after castration, but then diminished after the administration of testosterone. Western blot analyses revealed the presence of a specific 30-kDa immunoreactive form of TGFalpha in rat ventral prostate, and its quantity reflected the staining intensities observed in the immunohistochemical studies. These results suggest that TGFalpha expression is negatively regulated by androgen in epithelial cells of the distal segment. In contrast, staining for TGFalpha in epithelial cells of the proximal segment did not change with castration or testosterone administration, suggesting that TGFalpha is not regulated by androgen in this region of the ventral prostate. In summary, TGFalpha expression is differentially regulated among epithelial cells localized in two different regions of the ventral prostate. We hypothesize that TGFalpha may function as a survival factor for epithelial cells which, as a consequence of its expression, become androgen independent and thus escape apoptotic cell death after androgen ablation.

Aging↗

Hormonal findings in African-American and Caribbean Hispanic girls with premature adrenarche: implications for polycystic ovarian syndrome.

BACKGROUND: Premature adrenarche refers to the early maturation of the adrenal zona reticularis such that the resultant modest hyperandrogenism causes the early appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The precise etiology of premature adrenarche is not known. However, recent studies indicate that certain girls with premature adrenarche are at risk of developing functional ovarian hyperandrogenism, polycystic ovarian syndrome, and hyperinsulinism. Caribbean Hispanic women in general are at increased risk of developing polycystic ovarian syndrome, and African-Americans are at increased risk of developing the complications of hyperinsulinism. Previously, girls with premature adrenarche were reported to have androgens in the range found in normal children in the early stages of puberty. We noted that many of our African-American and Caribbean Hispanic patients with premature adrenarche had androgens that were much higher than what has been reported previously. OBJECTIVE: This retrospective study was performed to characterize the adrenocorticotropin-stimulated androgen response in an African-American and Caribbean Hispanic population of girls with premature adrenarche. METHODOLOGY: The androgen response to adrenocorticotropin stimulation in 72 African-American and Caribbean Hispanic girls with premature adrenarche was compared with those reported for normal girls in early puberty (Tanner stages II and III). The mean age was 6.8 +/- 0.8 years, bone age was 8 +/- 1.5 years, pubic hair was Tanner stages II and III, and body mass index was 18.6 +/- 4. RESULTS: Of the girls, 28% were found to have elevated stimulated 17OHPregnenolone (17OHPreg) levels that were >2 SD units above the mean for normal early pubertal children. The stimulated ratio of 17OHPreg/17OHProgesterone also was elevated in 18% of the girls and showed a modest correlation with body mass index. CONCLUSION: In contrast to previous studies of girls of mixed ethnic backgrounds with premature adrenarche, 28% of the 72 African-American and Caribbean Hispanic girls with premature adrenarche had adrenocorticotropin-stimulated 17OHPreg levels that were significantly higher than those seen in early pubertal girls. Because 17OHPreg hyperresponsiveness has been described previously in women with hirsutism or polycystic ovarian syndrome, the similar finding in many African-American and Caribbean Hispanic girls with premature adrenarche suggests that the two conditions may share a common mechanism for their hyperandrogenism. Therefore, the hyperandrogenism in certain African-American and Caribbean Hispanic girls with premature adrenarche may not be benign and may be the first presentation of polycystic ovarian syndrome.

Black or African American↗

The prevalence of Tourette syndrome in a mainstream school population.

The aim of this study was to ascertain accurately the prevalence of Tourette syndrome (TS) in a mainstream school population. All year 9 pupils (aged 13 to 14 years) in a mainstream secondary school were investigated using a two-stage procedure. Standardized questionnaires were completed by parents, teachers, and pupils. Class observations were also carried out to identify tics. Those pupils identified as having tics underwent a semistructured interview to determine whether they had TS according to DSM-III-R criteria. Data were available from at least one source (parent, teacher, or self-reports) on 166 of the 167 pupils in the year. Five subjects were identified as having TS according to DSM-III-R criteria, yielding a prevalence estimate of 299 per 10,000 pupils in this age group. The results of this study suggest that TS in the community as a whole is more common and milder than those prevalence estimates and descriptions of the disorder based on TS encountered in secondary or tertiary health-care service settings.

Adolescent↗

Autoimmunity to cartilage link protein in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) express cellular immunity to cartilage link protein (LP). METHODS: LP was purified from human fetal epiphyseal and bovine adult nasal cartilage. It was used in proliferation assays with the peripheral blood lymphocytes (PBL) isolated from 83 patients with RA, 21 patients with AS, and 30 healthy controls. RESULTS: Patients with RA (34%) and AS (71%) expressed a significantly higher prevalence of cellular immune responses to human LP compared with the healthy control group (13%). Such significant differences were not observed for bovine LP. Half the patients with RA responding to LP exhibited cellular immunity to both human and bovine protein. In the AS group, PBL from a majority of responders to LP recognized only human LP. CONCLUSION: These data suggest that LP is a potential autoantigen in the development of RA and AS and that cellular immune reactivity to common and distinct LP epitopes in patients with RA and AS may play a role in the pathogenesis of these diseases.

Adult↗

A variant of DNA polymerase beta acts as a dominant negative mutant.

In eukaryotic cells, DNA polymerase beta (polbeta) carries out base-excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. A specific deletion in one allele in the coding sequence of the polbeta gene occurs in colorectal and breast carcinomas. The 87-bp deleted region encodes amino acid residues 208-236 in the catalytic domain of the enzyme. Here, we report evidence for expression of the wild-type (WT) and the truncated polbeta proteins in colorectal tumors. To elucidate the potential functional consequences of polbeta truncation, stable HeLa cell lines were established from cloned WT and variant polbetaDelta208-236. Cells expressing the variant protein exhibited substantially decreased BER activity. To test our hypothesis that truncated polbeta may disrupt the function of the WT enzyme, we stably transfected mouse embryonic fibroblast 16.3 cells with polbetaDelta208-236 cDNA. Reverse transcription-PCR and Western blot analyses showed that the new cell line, 16.3DeltaP, expresses the WT and the truncated polbeta mRNA and proteins. BER and binding activities were undetectable in these cells. Furthermore, in vivo the 16.3DeltaP cells were more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine than the 16.3 cells. On adding increasing amounts of 16.3DeltaP protein extracts, the BER and DNA binding activities of extracts of the parent 16.3 cell line progressively declined. These results strongly suggest that truncated polbeta acts as a dominant negative mutant. The defective polbeta may facilitate accumulation of mutations, leading to the expression of a mutator phenotype in tumor cells.

Blotting, Western↗

Probing the non-proline cis peptide bond in beta-lactamase from Staphylococcus aureus PC1 by the replacement Asn136 --> Ala.

A non-proline cis peptide is present between Glu166 and Ile167 in the active site of beta-lactamase from Staphylococcus aureus PC1. To examine the role of the interaction between the side chain of Asn136 and the main chain of Glu166, the site-directed mutant N136A was produced. The enzyme shows no measurable hydrolytic activity toward a variety of penicillins or cephalosporins except for the chromogenic cephalosporin, nitrocefin. For nitrocefin, the progress curve exhibits a fast burst with a stoichiometry of 1 mol of degraded substrate per mole of enzyme followed by a slow phase with a hydrolysis rate that is reduced by approximately 700-fold compared with that of the wild-type enzyme. Thus, the mutant enzyme is deacylation defective. Monitoring the hydrolysis of nitrocefin after preincubation with a number of beta-lactam compounds shows that cephalosporins form stable acyl complexes with the enzyme, whereas penicillins do not. The molecular weight of the mutant was determined by electrospray mass spectrometry, and the presence of the stable acyl enzyme adducts with cephaloridine and cefotaxime was confirmed by both electrospray and MALDI mass spectrometry. Therefore, in addition to impairing deacylation, the acylation machinery has been altered compared with the wild-type enzyme to act on cephalosporins and not on penicillins. Urea denaturation and thermal unfolding studies show that the N136A mutant enzyme is less stable than the wild-type enzyme. However, stability against chemical denaturation of the mutant enzyme is enhanced in the presence of cephaloridine beyond the stability of the wild-type protein. This is attributed to accumulation of favorable interactions between the cephaloridine and the protein, which play a role in the folded state and not in the unfolded state.

Alanine↗

Colchicine binding to tubulin monomers: a mechanistic study.

The kinetic and thermodynamic parameters for colchicine-tubulin and deacetamidocolchicine-tubulin interaction, under the condition where tubulin is predominantly in its dissociated state (approximately 80% monomer), have been determined. We observe that the kinetic parameters exihibit marked change when colchicine interacts with the monomeric form of tubulin rather than with the dimeric form of tubulin. The reaction of colchicine with tubulin monomers is characterized by an enhanced association rate which is a consequence of the lowering of activation energy. Colchicine-tubulin interaction, which is only poorly reversible, becomes partially reversible under this condition. Differences were also noticed in the thermodynamic parameters: the reaction of colchicine with tubulin monomers is enthalpy driven with small positive entropy, while with tubulin dimers a large positive entropy change was reported. However, no such changes in the binding parameters were observed for the reaction involving deacetamidocolchicine (a colchicine analog devoid of a side chain at the C-7 position of B-ring) with tubulin monomers. We therefore conclude that a single subunit of tubulin is capable of binding colchicine and that the unusual properties of colchicine-tubulin interactions such as the slow association rate, high activation energy, and the poor reversibility are due to the possible contact(s) of the C-7 substituent (in the B-ring) of colchicine with the other subunit of tubulin.

Animals↗

X-ray reflectivity study of semiconductor interfaces.

The results of an X-ray reflectivity study of thick AlAs-AlGaAs and thin Ge-Si-Ge multilayers grown using metal-organic vapour-phase epitaxy and ion-beam sputtering deposition techniques, respectively, are presented. Asymmetry in interfaces is observed in both of these semiconductor multilayers. It is also observed that although the Si-on-Ge interface is sharp, an Si(0.4)Ge(0.6) alloy is formed at the Ge-on-Si interface. In the case of the III-V semiconductor, the AlAs-on-AlGaAs interface shows much greater roughness than that observed in the AlGaAs-on-AlAs interface. For thin multilayers it is demonstrated that the compositional profile as a function of depth can be obtained directly from the X-ray reflectivity data.

Journal Article↗