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Biomedical subjects

A Bhattacharyya

Publications and source records attributed to A Bhattacharyya.

At least 91 records · Page 5Linked to original sources

A risk based methodology for assessing the efficacy and priorities for the control of various radiation sources.

There is increasing concern as to whether our limited radiation protection resources are being directed to those radiation sources that produce the greatest return as measured by the cost/risk avoided. Major contributors to this problem include public perception and the lack of an accepted methodology for assigning priorities. Described in this report is a new methodology for assigning these priorities on the basis of cost per risk avoided. This methodology provides several different approaches for comparing the cost effectiveness and priority of these sources, as well as insight into the efficacy of regulatory programs. To demonstrate its application, various radiation sources, selected on the basis of providing insight into problem areas, are evaluated and compared. These resulting assessments show that the current funding and prioritization for the control of radiation sources are, in general, exactly opposite to the risk based efficacy for their control. It is hopeful that the insights resulting from these assessments will assist decision-makers in correcting this situation.

Cost-Benefit Analysis↗

Squamous islands in Barrett's esophagus: what lies underneath?

OBJECTIVE: Squamous islands are frequently visualized at the time of upper endoscopy in patients with Barrett's esophagus, especially those on proton pump inhibitor therapy (PPI). The significance of these islands is not clearly understood. The aim of this study was to systematically biopsy macroscopic squamous islands and to examine their histologic characteristics. METHODS: Patients with Barrett's esophagus undergoing surveillance had squamous islands documented and biopsied at the time of endoscopy. Barrett's esophagus was defined as the presence of a columnar lined esophagus on endoscopy with intestinal metaplasia on biopsy. All biopsies were obtained by a single senior endoscopist and were stained with alcian blue at pH 2.5. Biopsy samples with inadequate tissue quantity were not included in the study. RESULTS: A total of 39 biopsies were obtained from 22 patients. Twenty of the 22 patients were male, with a mean age of 65.4 yr (range 47-80 yr). The mean length of Barrett's mucosa was 5.6 cm (range 1-11 cm). Eleven of 22 patients were on omeprazole (mean dose 29.1 mg/day), whereas seven patients were on lansoprazole (60 mg/day). The mean duration of PPI therapy was 2.3 yr (range 9-71 months) at the time of biopsy of the squamous islands. Three patients were on H2-blocker therapy whereas the remaining patient had not been started on acid suppression therapy. On histology, 24 biopsy specimens (61.5%) revealed only squamous epithelium, whereas 15 (38.5%) showed the presence of intestinal metaplasia underlying the squamous epithelium. There was no significant difference between the patients with and without underlying intestinal metaplasia in regard to age, Barrett's length, dose, and duration of PPI therapy. CONCLUSION: In more than one-third of biopsies of macroscopic squamous islands within Barrett's esophagus, microscopic intestinal metaplasia is detected. The presence of squamous islands should not be equated with regression of Barrett's esophagus or with decreased cancer risk.

Aged↗

Autoimmune thrombocytopenic purpura in a splenectomised patient.

Splenectomy remains a treatment in patients with autoimmune thrombocytopenic purpura (ATP) who fail to respond adequately to conservative treatment. We report on a 78-year-old man who developed ATP after splenectomy performed six years earlier for iatrogenic injury to the spleen during hemicolectomy. Incidentally, he suffered from colonic and prostatic malignancies. To our knowledge, such a case has not been reported before. We discuss the mechanism of thrombocytopenia in ATP and its association with various malignancies.

Aged↗

Activation of ErbB2 during wallerian degeneration of sciatic nerve.

We used anti-phosphopeptide-immunodetecting antibodies as immunohistochemical reagents to define the location and activity state of p185(erbB2) during Wallerian degeneration. Nerve damage induces a phosphorylation event at Y1248, a site that couples p185(erbB2) to the Ras-Raf-MAP kinase signal transduction pathway. Phosphorylation of p185(erbB2) occurs within Schwann cells and coincides in time and space with Schwann cell mitotic activity, as measured by bromodeoxyuridine uptake. These visual images of receptor autophosphorylation link activation of p185(erbB2) to the Schwann cell proliferation that accompanies nerve regeneration.

Animals↗

Trk receptors function as rapid retrograde signal carriers in the adult nervous system.

During development target-derived neurotrophins promote the survival of neurons. However, mature neurons no longer depend on the target for survival. Do target-derived neurotrophins retain retrograde signaling functions in mature neurons, and, if so, how are they executed? We addressed this question by using a phosphotyrosine-directed antibody to locate activated Trk receptors in adult rat sciatic nerve. We show that catalytically active Trk receptors are located within the axon of adult rat sciatic nerve and that they are distributed throughout the length of the axons. These catalytically active receptors are phosphorylated on tyrosine at a position that couples them to the signal-generating proteins Ras and PI3 kinase. Neurotrophin applied at sciatic nerve terminals increases both catalytic activity and phosphorylation state of Trk receptors at distant points within the axons. Trk activation initiated at the nerve terminals propagates through the axon toward the nerve cell body at an initial rate that exceeds that of conventional vesicular transport. However, our data suggest that this rapid signal is nevertheless vesicle-associated. Thus, in mature nerves, activated Trk receptors function as rapid retrograde signal carriers to execute remote responses to target-derived neurotrophins.

3T3 Cells↗

A functional telomerase RNA swap in vivo reveals the importance of nontemplate RNA domains.

The ribonucleoprotein (RNP) enzyme telomerase is required for replication of eukaryotic chromosomal termini. The RNA moiety of telomerase is essential for enzyme function and provides the template for telomeric DNA synthesis. However, the roles of its nontemplate domains have not been explored. Here we demonstrate that a novel interspecies telomerase RNA swap in vivo creates a functional but aberrant telomerase. Telomerase RNA from the ciliate Glaucoma chattoni was expressed in Tetrahymena thermophila cells. The telomerase RNAs from these two species have almost superimposable secondary structures. The template region base sequence is identical in the two RNAs, but elsewhere their sequences differ by 49%. This hybrid telomerase RNP was enzymatically active but added only short stretches of telomeric repeat tracts in vivo and in vitro. This new enzyme also had a strong, aberrant DNA cleavage activity in vitro. Thus, molecular interactions in the RNP involving nontemplate RNA domains affect specific aspects of telomerase enzyme function, raising the possibility that they may regulate telomerase activity.

Animals↗

Aspergillus nidulans maintains short telomeres throughout development.

We report the identification and cloning of the telomeres of the filamentous fungus,Aspergillus nidulans. We have identified three classes of cloned chromosomal ends based on the telomere-associated sequences (TASs) and demonstrated that the telomeric repeat sequence is TTAGGG, identical to that found in vertebrates, including humans, and some lower eukaryotes. One category of telomere clones was found to contain internal, variant TAAGGG repeats. The A.nidulans telomeric tract length is strikingly short (4-22 repeats). We demonstrate that telomere length is remarkably stable in different cell types and at altered growth temperatures, suggesting a highly regulated mechanism for length control.

Aspergillus nidulans↗

The telomere and telomerase: how do they interact?

The tandemly repeated DNA sequence of telomeres is typically specified by the ribonucleoprotein enzyme telomerase. Telomerase copies part of its intrinsic RNA moiety to make one strand of the telomeric repeat DNA. Recent work has led to the concept of a telomere homeostasis system. We have been studying two key physical components of this system: the telomere itself and telomerase. Mutating the template sequence of telomerase RNA caused various phenotypes: (1) mutating specific residues in the ciliate Tetrahymena and two yeasts showed that they are required for critical aspects of telomerase action; (2) certain mutated telomeric sequences caused a previously unreported phenotype, i.e. a strong anaphase block in Tetrahymena micronuclei; and (3) certain template mutations in the telomerase RNA gene of the yeast Kluyveromyces lactis led to unregulated telomere elongation, which in some cases was directly related to loss of binding to K. lactis Rap1p. Using K. lactis carrying alterations in the genes for Rap1p and other silencing components, we proposed a general model for telomere length homeostasis: namely, that the structure and DNA length of the DNA-protein complex that comprises the telomere are key determinants of telomerase access, and hence the frequency of action of telomerase, at the telomere.

Anaphase↗

Intestinal metaplasia of the gastric cardia.

OBJECTIVE: Although the incidence of gastric adenocarcinoma in the U. S. is declining, the incidence of cancer localized to the gastric cardia has risen dramatically. It is not yet clear whether cancer of the gastric cardia arises from a premalignant lesion such as intestinal metaplasia (IM). The purpose of this study was to determine the prevalence of IM involving the cardia in patients presenting for elective EGD, and evaluate potential associated factors. METHODS: During a 7 month period patients referred for elective EGD at the Tucson VA Medical Center were invited to participate in the study. Prior to EGD each patient was surveyed with regard to GERD symptoms and smoking and alcohol history. During EGD note was made of the presence of esophagitis, hiatus hernia, and Barrett's-appearing mucosa. The esophagogastric junction (EGJ) was defined as the end of the tubular esophagus coinciding with the proximal heads of the gastric folds. Seven biopsies were taken from specific sites in the antrum, angularis, cardia, and EGJ. Biopsy specimens were stained with a combination of H & E and Alcian blue at a pH of 2.5. Histologic evidence of IM was defined as columnar-type epithelium including goblet cells staining with Alcian blue. Patients were also evaluated for H. pylori infection by histologic and serologic examinations. RESULTS: There were 104 patients (99 male, 5 female) with a mean age of 61.6 years. Twenty-four (23%) were found to have IM involving the gastric cardia, although none of these had dysplasia. Eleven patients (11%) had Barrett's esophagus; however, only 2 of these had concomitant IM of the cardia. On the other hand, 9 of the 24 with IM of the cardia had concomitant IM elsewhere in the stomach. Forty-nine patients (47%) were found to be positive for H. pylori infection and there was a significant association between H. pylori infection and IM of the gastric cardia (p = 0.03). CONCLUSIONS: These data show that IM of the gastric cardia is a relatively common finding and is associated with H. pylori infection. Although dysplasia was not identified, long-term follow-up studies will be necessary to determine the incidence of dysplasia or adenocarcinoma developing from IM of the cardia.

Adenocarcinoma↗

Effect of short-term dermal toxicity of fenvalerate on residue, cell architecture and biochemical profiles in broiler chicks.

Effect of fenvalerate on cell architecture, tissue biochemical parameters and its residual concentration was studied in broiler chicks following dermal application at 0.1 and 1% in ethanol once daily for 31 days. It did neither produce loss of body weight nor clinical signs of toxicity. Kidney contained maximal residue followed by heart, fat, liver and brain after 0.1%; and fat contained maximal residue followed by kidney, heart, liver and brain after 1% application. Fenvalerate (0.1%) increased the aspartate aminotransferase (AST) (except brain), alanine aminotransferase (ALT), alkaline phosphatase (AP), acid phosphatase (AcP) (only brain) activities, glycogen level (only liver) in liver, kidney, heart and brain tissues; and 1% increased the AST (except brain), ALT, AcP (except liver and kidney), AP (only heart), glycogen (only liver) and decreased AP (except heart), AcP (only kidney), cholesterol (except liver and heart), and acetylcholinesterase (AChE) (liver and brain) of liver, kidney, heart and brain tissue homogenates respectively. Histopathological examination in general showed aggregation of mononuclear cells in liver, around the kidney tubules and cardiac muscle fibre. In addition, fibrosis in the periportal area of liver, proliferation of ureter and tubular degeneration, and congestion of endocardial vessels were also observed. The intensity of cellular changes was more marked after 1% dermal application.

Animals↗

Dysplasia in short-segment Barrett's esophagus: a prospective 3-year follow-up.

OBJECTIVE: Short segments of intestinal metaplasia in the distal esophagus are being recognized with increasing frequency. Both long and short segments of Barrett's esophagus can progress to dysplasia and cancer. However, the risk of short-segment Barrett's esophagus (SSBE) for the development of dysplasia and adenocarcinoma of the esophagus is not yet known. Our purpose, therefore, was to determine the frequency with which dysplasia occurs in patients with SSBE. METHODS: Patients with SSBE were followed prospectively for the development of dysplasia. SSBE was defined as <3 cm of Barrett's-appearing epithelium above the gastroesophageal junction at endoscopy, with intestinal metaplasia on biopsy as documented by alcian blue stain at pH 2.5 on at least two endoscopic biopsies 6 months apart. Patients had interval upper endoscopy with systematic biopsy of the Barrett's segment. RESULTS: Fifty-nine SSBE patients were identified. The mean length of Barrett's mucosa was 1.5 +/- 0.1 cm; the mean age of the patients was 63.1 +/- 1.3 yr. Five patients had low-grade dysplasia (LGD) at initial endoscopy, for a prevalence of 8.5%; none had high grade dysplasia (HGD). Thirty-two patients had follow-up endoscopy over a mean period of 36.9 +/- 5.4 months. Five of these patients developed dysplasia on follow-up, three with LGD and two with HGD, the incidence of any dysplasia being 5.7% per year. One patient with HGD that developed during surveillance progressed to adenocarcinoma of the esophagus over a 2-yr period. The other patient with HGD had LGD on follow-up endoscopy. Six patients with initial LGD had no evidence of dysplasia on follow-up. CONCLUSIONS: The prevalence of dysplasia was 8.5% with an incidence of 5.7% per year in this group of SSBE patients, followed prospectively. Although dysplastic changes may not be identified on follow-up examination, some patients progress to adenocarcinoma. Therefore, we recommend surveillance endoscopy and biopsy in patients with SSBE just as in those with long-segment Barrett's esophagus.

Adenocarcinoma↗

Is Barrett's esophagus associated with intestinal metaplasia of the gastric cardia?

OBJECTIVE: Barrett's esophagus has been associated with adenocarcinoma of the esophagogastric junction and gastric cardia. The purpose of this study was to determine whether patients with Barrett's esophagus have a higher prevalence of intestinal metaplasia involving the gastric cardia than those without Barrett's esophagus. METHODS: Two groups of patients were compared for the prevalence of intestinal metaplasia of the gastric cardia. Group 1 included 50 patients with well-defined Barrett's esophagus who were being followed in an endoscopic surveillance program. Group 2 consisted of 104 individuals participating in a separate study identifying the prevalence of cardia intestinal metaplasia in patients undergoing elective upper endoscopy. Both groups had biopsy specimens taken from the gastric cardia. Eleven patients in group 2 were found to have Barrett's esophagus and were excluded from the analysis. Histological evidence of intestinal metaplasia was defined as specialized columnar epithelium containing goblet cells staining with Alcian blue at pH 2.5. RESULTS: The prevalence of cardia intestinal metaplasia in the 50 patients in group 1 (Barrett's esophagus) was 22%, whereas the prevalence in the 93 patients in group 2 (no Barrett's esophagus) was 24%, which was not a statistically significant difference. A significant difference between groups still could not be identified when the results were examined with regard to equal number of biopsy specimens taken. None of the patients in either group had dysplasia identified within the cardia intestinal metaplasia. CONCLUSIONS: Patients with Barrett's esophagus do not have a higher prevalence of intestinal metaplasia of the gastric cardia than those presenting for routine endoscopy. Although intestinal metaplasia of the gastric cardia is a relatively common finding, dysplasia is uncommon. Therefore, we suggest that screening biopsy specimens of the gastric cardia in patients with Barrett's esophagus be limited to study protocols at this time. In addition, we believe that these data raise the question of whether a true association exists between Barrett's esophagus and gastric cardia cancer.

Aged↗

A comparative study of silver binding nucleolar organiser regions (AgNORs) of breast lesions in histological sections and fine needle aspiration smears.

The study presents a comparative profile of AgNOR dot counting in different types of breast lesions in histopathological (HP) sections and fine needle aspiration cytology (FNAC) smears. The breast lesions chosen were non-neoplastic lesion like fibroadenosis, benign neoplastic lesion like fibroadenoma and malignant neoplastic lesion like infiltrating duct carcinoma-grade 2. The AgNOR counts of non-neoplastic lesion were significantly less in number than the neoplastic lesions--both benign and malignant, in both the HP section and FNAC smear. But the counts did not show significant difference in the two neoplastic lesions eg, fibroadenoma and infiltrating duct carcinoma-grade 2, in both the HP section and FNAC smear. The appearance of the dots, as felt by the observers, were more discriminating between the three lesions, eg, uniform small compact centrally placed in fibroadenosis; mostly uniform small compact but occasional large irregular in fibroadenoma and large irregular marginally located in infiltrating duct carcinoma. Counting was easier and the appearance of the dots more easily discernible in FNAC smear than the HP section as the smear was monolayer and the malignant cells were easily detected from macrophages and stromal cells. But the tissue fluid or secretions or blood when present in the smear gave the smear a dirty background which was disturbing to the observers. Thus this AgNOR technique, when applied in HP section or FNAC smear, appears cost ineffective, lengthy and tedious procedure; did not offer absolute histochemical discriminant for malignancy from benignancy. But the shape and size distribution and appearance of the dots showing much variability in FNAC smear than the HP section, might be of some help in the diagnosis of malignancy and discriminating from benignancy.

Biopsy, Needle↗