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Biomedical subjects

S Ashok

Publications and source records attributed to S Ashok.

14 recordsLinked to original sources

Malignant fibrous histiocytoma of the spermatic cord.

Malignant fibrous histiocytoma (MFH) of the spermatic cord is rare. However, owing to its location it is diagnosed early and has a better prognosis. A case of MFH of the spermatic cord is reported in a 50-year-old male along with review of the literature, discussing the recommended management and prognosis of this condition and emphasising upon its clinical recognition since the prognosis and management are different from the MFH, in general.

Genital Neoplasms, Male↗

Prevalence of neuropathy in type 2 diabetic patients attending a diabetes centre in South India.

OBJECTIVE: The aim of this study was to determine the prevalence and risk factors for neuropathy among South Indian type 2 diabetic patients attending a diabetes centre. METHODS: One thousand consecutive type 2 diabetic patients attending a diabetes centre in South India were recruited for the study. Biothesiometry studies were performed by a single observer using a biothesiometer. Neuropathy was diagnosed if the vibratory threshold of the great toe exceeded twenty five. RESULTS: Overall, 19.1% of the patients had evidence of neuropathy. The prevalence of neuropathy increased with increase in age (p < 0.001) and duration of diabetes (p < 0.001). Multiple logistic regression analysis revealed age (OR--3.2, 95% confidence interval--2.7-4.1, p < 0.001) and duration of diabetes (OR--1.4, 95% confidence interval--1.2-64, p = 0.001) as the risk factors for neuropathy. CONCLUSION: The overall prevalence of neuropathy in this South Indian type 2 diabetic subjects is 19.1% and age and duration of diabetes are the risk factors for neuropathy.

Adult↗

Pitfalls in the diagnosis of epithelioid sarcoma presenting in an unusual site: a case report.

The cytologic appearance of epithelioid sarcoma in fine-needle aspiration biopsy cytology (FNABC) smears has not been extensively described. We report a case of epithelioid sarcoma in a 55-year-old male who presented with nodular swellings in the abdominal wall and scrotum. The scrotal swelling was subsequently demonstrated to arise from the vas deferens. We highlight the cytomorphologic, immunocytochemical, and histopathologic features of this rare lesion in an unusual site, with particular emphasis on the dilemma encountered in the cytodiagnosis of this lesion.

Abdominal Neoplasms↗

Histopathology and immunohistochemistry of pancreatic islets in fibrocalculous pancreatic diabetes.

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Adolescent↗

Lipid peroxidation, free radical production and antioxidant status in breast cancer.

Reactive oxygen metabolites (ROMs), including superoxide anion (O2*-), hydrogen peroxide (H2O2) and hydroxyl radical (*OH), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O2*- and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls. The rate of O2*- production was significantly higher (p < 0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p < 0.001), stage III (p < 0.01), postmenopausal (p < 0.005), and premenopausal (p < 0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p < 0.001), except the GPx activity was found a smaller alteration in stage IV (p < 0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (-61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O2*- and *OH. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous *OH radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.

Adult↗

Ca2+-induced increases in steady-state concentrations of intracellular calcium are not required for inhibition of parathyroid hormone secretion.

It has been well established that increases in extracellular calcium concentration ([Ca2+]) inhibit parathyroid hormone (PTH) secretion. The effects of [Ca2+] are mediated through a G-protein-coupled receptor that has been cloned and characterized. Additionally, it has been demonstrated in parathyroid cells that an increase in [Ca2+] results in an increase in steady-state levels of intracellular calcium ([Ca2+]i). At present, it has not been fully resolved whether changes in [Ca2+]i are related to changes in PTH secretion. In the current study, the effect of increased [Ca2+] on PTH secretion and the connection regarding changes in concentrations of intracellular calcium [Ca2+]i have been examined in primary cultures of bovine parathyroid cells. PTH secretion was measured by radioimmunoassay and intracellular calcium was determined by single cell calcium imaging. Bovine parathyroid cells pre-incubated with either 0.5 or 1 mM calcium responded to rapid increases in [Ca2+] (> or = 0.5 mM) with an immediate and sustained increase in steady-state levels of [Ca2+]i that persisted for time intervals greater than 15 minutes. Although the magnitude of the sustained increase in [Ca2+]i varied among individual cells (approximately 40% to > 300%), the overall pattern and course of time were similar in all cells examined (n = 142). In all trials, [Ca2+]i immediately returned to baseline levels following the addition of the calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Additional control studies, however, suggest that sustained increases in [Ca2+]i do not correlate with regulation of parathyroid hormone secretion. Sustained elevations of [Ca2+]i were not observed when [Ca2+] was gradually increased by the addition of 0.1 mM increments at 1 minute intervals. Furthermore, the effect on inhibition of PTH secretion was the same regardless of whether [Ca2+] was increased by gradual or rapid addition.

Animals↗

Turning a negative into a positive: vitamin D receptor interactions with the avian parathyroid hormone response element.

1 ,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] negatively regulates expression of the avian PTH (aPTH) gene transcript, and a vitamin D response element (VDRE) near the promoter of the aPTH gene had previously been identified. The present report assessed whether the negative activity imparted by the aPTH VDRE could be converted to a positive transcriptional response through selective mutations introduced into the element. The tested sequences were derived from individual and combined mutations to 2 bp in the 3'-half of the direct repeat element, GGGTCAggaGGGTGT. Cold competition experiments using mutant and wild-type oligonucleotides in the mobility shift assay revealed minor differences in the ability of any of these sequences to compete for binding to a heterodimer complex comprised of recombinant proteins. Ethylation interference footprint analysis for each of the mutants produced unique patterns over the 3'-half-sites that were distinct from the weak, wild-type footprint. Transcriptional outcomes evaluated from a chloramphenicol acetyltransferase reporter construct utilizing the aPTH promoter found that the individual T-->A mutant produced an attenuated negative transcriptional response while the G-->C mutant resulted in a reproducibly weak positive transcriptional outcome. The double mutant, however, yielded a 4-fold increase in transcription, similar to the 7-fold increase observed from an analogous construct using the human osteocalcin VDRE. UV light crosslinking to gapped oligonucleotides assessed the polarity of heterodimer binding to the wild-type and double mutant sequences and was consistent with the vitamin D receptor preferentially binding to the 5'-half of both elements. Finally, DNA affinity chromatography was used to immobilize heterodimer complexes bound to the wild-type and double mutant sequences as bait to identify proteins that may preferentially interact with these DNA-bound heterodimers. This analysis revealed the presence of a p160 protein that specifically interacted with the heterodimer bound to the wild-type VDRE, but was absent from complexes bound to response elements associated with positive transcriptional activity. Thus, the sequence of the individual VDRE appears to play an active role in dictating transcriptional responses that may be mediated by altering the ability of a vitamin D receptor heterodimer to interact with accessory factor proteins.

Animals↗

Vitamin D receptor interactions with the rat parathyroid hormone gene: synergistic effects between two negative vitamin D response elements.

Vitamin D response elements (VDREs) that are required for negative regulation of rat parathyroid hormone (rPTH) gene expression have been characterized. Gel mobility shift assays using DNA restriction enzyme fragments and recombinant proteins for vitamin D and retinoic acid X receptors (VDR/RXR) revealed a sequence between -793 and -779 that bound a VDR/RXR heterodimer with high affinity (VDRE1). Furthermore, a lower affinity site (VDRE2) was detected that acted in combination with VDRE1 to bind a second VDR/RXR complex. As determined by ethylation interference analysis, the nucleotide sequence of VDRE1 consisted of GGTTCA GTG AGGTAC, which is remarkably similar to the sequence of the negative VDRE found in the chicken PTH (cPTH) gene. Using the same technique, VDRE2 was identified between positions -760 and -746 and contained the sequence AGGCTA GCC AGTTCA. Functional analysis was determined by transfection studies with plasmid constructs that expressed the gene for chloramphenicol acetyl transferase (CAT). The ability of the VDREs to regulate gene expression was tested in their native context with the rPTH promoter as well as when positioned immediately upstream from the cPTH promoter. With either plasmid construct, exposure to 10(-8)M 1,25(OH)2D3 resulted in a 60-70% decrease in CAT gene expression when both VDRE1 and VDRE2 were present. Examination of the individual VDREs showed that inhibition by 10(-8) M 1,25(OH)2D3 was only 35-40% when just VDRE1 was present. By itself, VDRE2 was even less effective, as significant inhibition of CAT activity (20%) was observed only in the presence of higher concentrations of 1, 25(OH)2D3 (10(-7)M) or when a plasmid vector that overexpressed the VDR protein was cotransfected. In conclusion, the rPTH gene contains two negative VDREs that act in concert to bind two RXR/VDR heterodimer complexes and that both VDREs are required for maximal inhibition by 1,25(OH)2D3.

Animals↗

The chemokine interleukin-8 regulates parathyroid secretion.

Interleukin-8 (IL-8) is a chemokine important in inflammatory processes. Homology cloning experiments performed using bovine parathyroid cDNA and degenerate primers encoding transmembrane regions III and VI of peptide and protein hormone G-protein coupled receptors identified a set of known receptors not previously identified in the parathyroid. Among these was the IL-8 type B receptor. Incubation of freshly isolated bovine parathyroid cells with recombinant IL-8 for 6-48 h produced an increase in the levels of mRNA for parathyroid hormone (PTH). The levels of PTH secreted in response to nanomolar amounts of IL-8 were also elevated in cells incubated for 1 h with IL-8. Differential display analysis of mRNA from parathyroid cells, incubated in the presence and absence of IL-8, permitted the identification of cDNA clones for RNA species whose expression was either elevated or suppressed. These experiments suggest that IL-8 and inflammatory events play a role in bone homeostasis through actions on the parathyroid gland.

Animals↗

Recurrent osteoid osteoma: a case report with imaging features.

We present a case of a 14-year-old boy, who presented with pain in the left thigh region for 1 year. The pain exacerbated at night, waking up the child and was relieved by salicylates. On the basis of clinical history, conventional radiography, computerized tomography and bone scintigraphy, a diagnosis of osteoid osteoma was made. The tumor was completely excised, and there was complete remission of symptoms. Six months following surgery, the pain recurred in the same region. Conventional radiography revealed dense sclerosis at the surgical site. Three-phase skeletal scintigraphy showed a focal area of increased blood pool activity followed by intense focal uptake in delayed images, characteristic of osteoid osteoma. Computerized tomography confirmed the findings of skeletal scintigraphy.

Adolescent↗

Fine needle aspiration cytology of well-differentiated papillary peritoneal mesothelioma. Report of a case.

The fine needle aspiration cytologic findings in a well-differentiated multifocal papillary peritoneal mesothelioma in a young man presenting with abdominal pain and mass are described. The patient is alive and well 50 months after the onset of symptomatology. The cytologic and histologic appearance as well as the clinical course of the patient point to a benign multifocal mesothelioma.

Adult↗