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Biomedical subjects

M Banerjee

Publications and source records attributed to M Banerjee.

At least 73 records · Page 4Linked to original sources

Tick-borne relapsing fever in British Columbia, Canada: first isolation of Borrelia hermsii.

The spirochete that causes tick-borne relapsing fever, Borrelia hermsii, was isolated in pure culture during 1995 and 1996 from three acutely ill human patients infected in southern British Columbia, Canada. The geographic area of exposure is a known focus of this disease dating back to 1930 when the first case was recognized in a human. Analyses of plasmid DNA, protein profiles, and reactivity with a species-specific monoclonal antibody identified the new isolates of spirochetes as B. hermsii, all of which were most similar to an isolate of this spirochete from northern California described previously. These are the first reported isolates of B. hermsii from Canada.

Adult↗

Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3.

Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of transpositional dormancy. We isolated a mutation, rtt100-1, that increases the transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase. In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic processing were not altered relative to those in FUS3 strains but steady-state levels of TyA, integrase, and reverse transcriptase proteins and Ty1 cDNA were all increased. These findings suggest that Fus3 suppresses Ty1 transposition by destabilizing viruslike particle-associated proteins. The Fus3 kinase is activated through the mating-pheromone response pathway by phosphorylation at basal levels in naive cells and at enhanced levels in pheromone-treated cells. We demonstrate that suppression of Ty1 transposition in naive cells requires basal levels of Fus3 activation. Substitution of conserved amino acids required for activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses revealed that components of the pheromone response pathway that act upstream of Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1 transposition by Fus3 provides a haploid-specific mechanism through which environmental signals can modulate the levels of retrotransposition.

Calcium-Calmodulin-Dependent Protein Kinases↗

Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.

We initiated a clinical trial for patients with advanced malignant melanoma treated with an anti-idiotype antibody that mimics the disialoganglioside GD2. We report the clinical and immune responses of the first 12 patients entered into this trial. Patients received 1-, 2-, 4-, or 8-mg doses of the anti-idiotype antibody mixed with 100 microg of QS-21 adjuvant every other week, four times, and then monthly. Twelve patients have been on trial for 2-23 months, and all of them have generated immune responses. Patients were removed from the study if they demonstrated disease progression. Hyperimmune sera from all 12 patients revealed an anti-anti-idiotypic Ab3 response, as demonstrated by the inhibition of Ab2 binding to Ab1 by patients' immune sera. To further test the anti-anti-idiotypic response, patients' Ab3 antibodies were affinity purified on Sepharose 4B columns containing adsorbed immunizing anti-idiotype immunoglobulin. Purified Ab3 of all patients studied inhibited binding of Ab1 to a GD2-positive cell line. Purified Ab3 also inhibited binding of Ab1 to purified GD2, in a manner comparable to equal quantities of purified Ab1. The patient Ab3 was truly an Ab1' because it specifically bound to purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody was predominantly IgG, with only minimal IgM. The predominant IgG subclass was IgG1, with approximately equal quantities of IgG2, IgG3, and IgG4. These Ab3 antibodies reacted specifically with tumor cells expressing GD2 by immune flow cytometry and immunoperoxidase assays. Five patients' Ab3 antibodies studied for antibody-dependent cellular cytotoxicity were positive. One patient had a complete clinical response, with resolution of soft tissue disease, and six patients had stable disease, ranging from 9 to 23 months, and are being continued on vaccine therapy. Toxicity consisted of local reaction at the site of the injection, including induration and pain that generally resolved within a few days. Mild fever and chills were observed in 75% of the patients but rarely required acetaminophen. There was no additional toxicity, including abdominal pain that was previously seen with infusion of murine monoclonal anti-GD2 antibody. Current trials include patients with stage III melanoma and small cell lung cancer. Future trials will attempt to enhance the antitumor response by the addition of interleukin 2, granulocyte macrophage colony-stimulating factor, and other cytokines, together with the 1A7 vaccine.

Adult↗

A similar pattern of chromosomal alterations in prostate cancers from African-Americans and Caucasian Americans.

A combination of genetic and epigenetic factors may explain the disproportionate incidence and mortality of prostate cancer among African-American males (AAMs) as compared with Caucasian American males (CAMs). We wished to determine whether primary prostate cancers from AAMs and CAMs harbor different patterns or frequencies of chromosomal alterations. Comparative genomic hybridization (CGH) was performed on clinically localized, untreated primary prostate cancers from 16 AAMs and 16 CAMs. Detailed statistical analysis was used to delineate gains and deletions with high sensitivity and specificity and to compare the frequency and pattern of alterations between the two groups of tumors. The two groups of patients had indistinguishable preoperative serum prostate-specific antigen levels, and the two groups of tumors had similar pathological stages and grades. Chromosomal gains and deletions occurred in regions known to be frequently altered in prostate cancer. Specifically, the most frequent alterations were deletions of regions on chromosomes 13q, 5q, 16q, and 8p and gains of regions on 8q and 5q. When tumors from AAMs and CAMs were compared, the frequencies of alteration (deletion, gain, or no alteration) were similar across 98.9% of the length of the genome. The patterns of alterations of the most frequently altered chromosomes were also similar between tumors from AAMs and CAMs. We concluded that primary prostate cancers from AAMs and CAMs harbor a similar pattern and frequency of chromosomal alterations. These data support the notion that sporadic prostate cancers from AAMs and CAMs develop by similar chromosomal mechanisms. Biological differences, if present, do not occur on the chromosomal level.

Black People↗

A clinicobacteriological study on leucorrhoea.

The pathogens like Trichomonas vaginalis (4.5%), N gonorrhoeae (2.7%) and C albicans (6.7%) were exclusively present in leucorrhoea. The other potential agents with their respective percentages in normal women and cases of leucorrhoea were U urealyticum (21.2% and 50.2%), actinomyces (29.7% and 41.6%), Chlamydia trachomatis (17% and 48.8%), candida-like organisms (CLO) (1.2% and 9.5%) and non-group B streptococci (4.2% and 16.7%). The percentages of urethral syndrome (65.8%), vaginal irritation (63.4%), sore vulva (17%), cervicitis (13.4%), cervical erosion (11%) of the STD clinic were more than those of gynaecological cases. The latter group more often revealed infertility (15.8%) and pelvic inflammatory disease (13.6%). The exclusive isolation rate of N gonorrhoeae (7.3%) and prevalence of G vaginalis (19.5%) and Trichomonas vaginalis (8.5%) in the STD clinic were notable. The cases of gynaecological clinic more commonly showed C albicans (8%) and CLO (13.6%). Significant differences pertaining to U urealyticum (leucorrhoea and inapparent group p < 0.01; leucorrhoea and normal cases p < 0.01), M hominis (leucorrhoea and inapparent group p < 0.05; leucorrhoea and normal cases p < 0.01), Chlamydia trachomatis (leucorrhoea and normal cases p < 0.01) and also actinomyces (leucorrhoea and normal cases p < 0.01; inapparent and normal cases p < 0.05) were recorded. There was conspicuous association of U urealyticum, M hominis, G vaginalis, Chlamydia trachomatis, CLO and actinomyces with leucorrhoea. An almost exclusive presence of Staph aureus, Esch coli and Klebsiella in cases of leucorrhoea appeared meaningful.

Cervix Uteri↗

Effect of neoadjuvant androgen deprivation on circulating prostate cells in the bone marrow of men undergoing radical prostatectomy.

Our objective was to determine the effect of neoadjuvant hormonal therapy on the presence of circulating prostate cells in patients undergoing radical prostatectomy for prostate cancer. A total of 60 patients at high risk for extraprostatic disease were analyzed for the presence of circulating prostate cells using reverse transcriptase PCR (RTPCR) amplification of the prostate-specific antigen mRNA. Twenty-nine patients underwent radical prostatectomy for a clinical T2b-c tumor or a stage T1c-T2a tumor and a serum prostate-specific antigen level > or =10ng/ml (radical prostatectomy alone), and 31 similarly staged patients received neoadjuvant hormonal therapy before radical prostatectomy (neoadjuvant). Bone marrow samples were used for RTPCR analysis. Twenty-four percent and 58% of the radical-prostatectomy-alone patients and neoadjuvant patients had organ-confined disease, respectively (P = 0.007). In the radical-prostatectomy-alone group, 77% and 14% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.03). However, in the neoadjuvant group, 46% and 28% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.29). For patients that were RTPCR positive, 45 % of the neoadjuvant patients had organ-confined disease compared with 6% in the radical-prostatectomy-alone patients (P = 0.018). These data suggest that a subset of the neoadjuvant patients are converted to organ confined disease without eliminating the prostate cells in the bone marrow. Our data suggest that hormonal therapy before radical prostatectomy decreases the occurrence of extraprostatic disease but, to a lesser degree, the incidence of circulating prostate cells. This may partially explain why hormonal therapy before radical prostatectomy has not improved disease-free survival.

Androgen Antagonists↗

Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy.

PURPOSE: Bone scintigrams of patients with increasing serum prostate specific antigen (PSA) after radical prostatectomy are only rarely positive. We identify clinical parameters that would improve our ability to select patients for this imaging study. MATERIALS AND METHODS: We reviewed all bone scintigrams done at our institution between 1991 and 1996 in patients with persistently increasing serum PSA after radical prostatectomy. What prompted the clinician to obtain the bone scintigram was trigger PSA (tPSA). The rate of increase in PSA to tPSA was measured by tPSA/time from radical prostatectomy (slope 1) and tPSA/time from last undetectable PSA (slope 2). These parameters were evaluated together with standard clinicopathological data in univariate and multivariate analyses to determine the ability to predict the bone scintigram result. RESULTS: In univariate analysis tPSA (p = 0.003), slope 1 (p = 0.005) and slope 2 (p = 0.004) were useful in predicting the bone scintigram result but pathological stage, Gleason score, preoperative PSA and time to recurrence were not. In multivariate analysis the single most useful parameter in predicting the bone scintigram result was tPSA (p = 0.01). Based on a logistic regression model the probability of a positive bone scintigram was less than 5% until tPSA increased to 40 to 45 ng./ml. CONCLUSIONS: In patients with increasing serum PSA after radical prostatectomy current serum PSA is the best predictor of the bone scintigram result. Furthermore, there is limited usefulness of bone scintigraphy until PSA increases above 30 to 40 ng./ml.

Bone Neoplasms↗

Are there ethnic differences in deletions in the dystrophin gene?

We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene.

Adolescent↗

Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.

We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon.

Base Sequence↗

Interpreting kappa values for two-observer nursing diagnosis data.

Reliability of nursing observations often is estimated using Cohen's kappa, a chance-adjusted measure of agreement between observer RNs. However, use of kappa as an omnibus measure sometimes can be misleading. In a study partly designed to describe the frequency and reliability of nursing diagnoses in long-term care facilities, 360 residents each were assessed independently by two registered nurses, and kappa and observed proportion of agreement were calculated as estimates of reliability. For some diagnoses we observed high proportions of agreement, yet paradoxically low kappa values. This article presents an in-depth statistical analysis to resolve this paradox. Results from our analysis also suggest means for planning improvements in the diagnostic performance of participating RNs. Consequently, our approach can be used in similar studies of diagnosis reliability to enhance nursing research, education, and practice.

Bias↗

Genetic variation in Asiatic lions and Indian tigers.

Previous reports have suggested that Asiatic lions and tigers are highly inbred and exhibit very low levels of genetic variation. Our analyses on these species have shown much higher degrees of polymorphism than reported. Randomly amplified polymorphic DNA (RAPD) analysis of 38 Asiatic lions, which exist as a single population in the Gir Forest Sanctuary in India, shows an average heterozygosity of 25.82% with four primers. Sperm motility studies by our colleagues corroborate this data. In Indian tigers, microsatellite analysis of five CA repeat loci and multilocus fingerprinting using Bkm 2(8) probe on a population of 22 individuals revealed a heterozygosity of 22.65%. Microsatellite analysis of loci Fca 77 and Fca 126 revealed polymorphism amongst the Asiatic x African lion hybrids, which has enabled us to use these as markers to discriminate the pure Asiatic lions from the hybrids. A similar analysis was used to identify hybrids of Indian and Siberian tigers through polymerase chain reaction (PCR) amplification of hair samples. To ascertain the variation which existed before the population bottleneck at the turn of the present century, microsatellite analysis was performed on 50- to 125-year-old skin samples from museum specimens. Our results show similar levels of genetic variability as in the present population (21.01%). This suggests that low genetic variability may be the characteristic feature of these species and not the result of intensive inbreeding. DNA fingerprinting studies of Asiatic lions and tigers have helped in identifying individuals with high genetic variability which can be used for conservation breeding programs.

Animals↗

Prognostic implications of a positive apical margin in radical prostatectomy specimens.

PURPOSE: We evaluated the prognostic implication of a positive surgical margin at the prostatic apex to define the risk of failure after radical prostatectomy. MATERIALS AND METHODS: Radical prostatectomy specimens of 590 patients operated on between 1990 and 1994 were reviewed by 2 uropathologists (D. G. and W. S.) to determine the percentage of patients with a positive margin at the apex in the absence of positive margins, extraprostatic extension or involvement of seminal vesicles and pelvic lymph nodes. In this group of 33 patients, the significance of a positive apex could be determined without the influence of any other stage related prognostic factors. Treatment failure was defined as prostate specific antigen greater than 0.4. All 33 patients have been followed between 3.5 and 65.5 months (median 38.7). RESULTS: Among 590 patients 236 (40%) had disease completely confined to the prostate. A total of 217 patients (37%) had either positive surgical margins (M+) or extraprostatic extension and of these, only 33 (5.5%) had an apical positive margin in an otherwise prostate confined tumor. Of 33 apical positive margin patients only 3 in whom surgery failed had progressively detectable prostate specific antigen 3.5 to 65.5 months after surgery. CONCLUSIONS: A positive surgical margin at the prostatic apex in the absence of positive margins or extraprostatic extension elsewhere does not confer a worse prognosis than organ confined disease. In this study the recurrence rate for patients with positive apical margins was the same as for those with confined disease.

Follow-Up Studies↗

Incidence of urethral involvement in female bladder cancer: an anatomic pathologic study.

OBJECTIVES: To evaluate risk factors for urethral involvement in female patients undergoing cystectomy for bladder cancer and to define potential candidates for orthotopic continent urinary diversion. METHODS: From 1990 to 1996, 43 female patients underwent cystectomy for primary bladder malignancy. Bladder mapping studies were performed with special attention to tumor location, multifocality, pathologic stage and grade, presence of carcinoma in situ (CIS), and the relationship of these factors to urethral involvement. RESULTS: Of the 43 patients evaluated, 7 (16.3%) had urethral involvement by tumor. Two patterns of urethral invasion were identified: 5 patients had tumors in the vascular or lymphatic channels of the periurethral tissue, and 2 had tumors in the mucosa or submucosa. Three of the 12 patients with tumors located at the trigone and 4 of the 26 with CIS of the bladder had tumor in the urethra. Three of the 5 patients with vaginal involvement had tumor in the urethra. Only vaginal involvement was significantly associated with urethral involvement (P = 0.02). CONCLUSIONS: Vaginal involvement was the only preoperative factor that was associated with presence of tumor in the urethra. Five patients with urethral involvement had submucosal tumors without concomitant CIS of the urethra. Before the performance of orthotopic urinary diversions, intraoperative full-thickness bladder neck biopsies are needed to accurately evaluate the female urethra.

Cystectomy↗

Localization of a 25 kDa human sperm surface protein: its role in in-vitro human sperm capacitation.

A human endometrial sialic acid-binding glycoprotein (SABP) binds specifically to a 25 kDa protein on the plasma membranes of human non-capacitated sperm heads. In-vitro labelling of the sperm surface sialoglycoconjugates and subsequent incubation with SABP, suggests removal of some sialoglycoconjugate moieties from the sperm surface upon interaction with SABP. SABP also induces the exposure of mannose ligand receptors on the sperm surface and increases the production of superoxide anion (O2-).

Binding Sites↗

Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.

PURPOSE: To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy. MATERIALS AND METHODS: We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4). RESULTS: Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival. CONCLUSION: RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.

Adenocarcinoma↗

Polymerase chain reaction-based diagnosis of del (5q) in acute myeloid leukemia and myelodysplastic syndrome identifies a minimal deletion interval.

Loss of all or part of the long arm of human chromosome 5 is a recurrent abnormality in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), especially after chemotherapy for a prior malignancy. It is one of the worst prognostic indicators in AML, associated with chemotherapy resistance and short survival. These deletions center at band 5q31, which has thus been proposed as the location of a tumor suppressor gene; this site is to be distinguished from that observed in 5q- syndrome, centering at 5q32. To define the molecular extent and the clinical prevalence of 5q31 deletions, we collected a series of AML and MDS cases of mixed karyotype, taking care to exclude MDS cases with 5q- syndrome. The samples were analyzed for loss of heterozygosity (LOH) using a panel polymerase chain reaction (PCR)-based microsatellite markers from 5q, comparing malignant cells with normal tissue derived from lymphoblastoid cell lines or buccal mucosa scrapings. Losses were detected in seven of 29 matched samples, including four of 17 with MDS, and three of 12 with AML; six of these seven also had a cytogenetically-visible del(5q) or -5. The one case without a cytogenetic deletion showed molecular loss of three contiguous markers, with retention of flanking markers interleukin-9 (IL-9) and D5S414, and thus contained a small deletion that is below cytogenetic resolution. PCR failed to detect 5q loss in two cases with large cytogenetic deletions, but both had been treated and contained low percentages of malignant cells in the samples. This study thus led to the identification of a case with a minimal deletion for the 5q31 tumor suppressor gene, specified by IL-9-D5S414, that is approximately 1 Mb (2 cM) in extent. Additionally, we demonstrate that PCR-based allelotyping is a reliable method for the detection of chromosomal deletion in myeloid malignancy, providing the specimens contain a high proportion of malignant cells. These studies will help to identify the tumor-suppressor gene at 5q31, and will help to develop molecular methods for diagnosis and monitoring of these disorders.

Acute Disease↗