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V Srinivas

Publications and source records attributed to V Srinivas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Discrepancies in Epstein-Barr virus association at presentation and relapse of classical Hodgkin's disease: impact on pathogenesis.

BACKGROUND: Though Epstein-Barr virus (EBV) has been linked to classical Hodgkin's disease (cHD), only a proportion of cHD cases show EBV-association. While there has been evidence to suggest a crucial role for EBV in the early phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this issue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse. MATERIALS AND METHODS: We have analysed lymph node biopsy samples from 23 cases of cHD at presentation and relapse. In situ hybridization with EBER-1 probe and immunostaining with anti latent membrane protein-1 (LMP-1) antibody was performed on the paraffin sections. PCR for EBNA 3C gene was performed for EBV subtype analysis on the DNA extracted from paraffin sections. RESULTS: EBV-association was documented in both the presentation and relapse samples of 14 cases. One case showed loss of EBV-association at relapse. PCR analysable DNA was obtained from both presentation and relapse samples in four of the EBV-associated cases. The EBNA 3C amplimer corresponded to type A strain of EBV in all the samples. CONCLUSION: Loss of EBV-association between presentation and relapse seen in one case implies a hit and run mechanism in EBV-induced lymphomagenesis. Though EBV may be essential early in the evolution of cHD, it may not be required for maintenance of the neoplastic clone. Our study also brings out a speculation that a proportion of EBV-negative cHD could represent loss of EBV in the tumour prior to clinical presentation. Alternatively, an unidentified lymphotropic virus other than EBV might play a pathogenetic role in EBV-negative cHD.

Burkitt Lymphoma↗
PubMed2000

Distribution of various subtypes of non-Hodgkin's lymphoma in India: a study of 2773 lymphomas using R.E.A.L. and WHO Classifications.

INTRODUCTION: The distribution of the major subtypes of non-Hodgkin's lymphoma (NHL) differs across geographic regions. This is the first study from India that has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes. PATIENTS AND METHODS: All cases diagnosed as NHL between January 1995 and June 1998 in the Department of Pathology and in the Lymphoma Registry, Tata Memorial Hospital, Bombay, were selected for the study. The cases were reviewed by three pathologists and diagnostic problems were discussed by a panel of pathologists with a special interest in lymph node pathology. Of a total of 2831 cases, the diagnosis of NHL was accepted in 2773 cases. RESULTS: B-cell lymphomas formed 79.1% of the NHLs, whereas T-cell lymphomas formed 16.2% of the total. Diffuse large B-cell lymphoma was the most common subtype (34% of all NHLs). Follicular centre-cell lymphomas, B-cell small lymphocytic lymphoma, mantle-cell lymphoma, and marginal zone B-cell lymphomas (including MALT lymphomas) amounted to 12.6%, 5.7%, 3.4%, and 8.2%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and other nodal peripheral T-cell lymphomas accounted for 6%, 4.3%, and 2.9% of all cases, respectively. CONCLUSIONS: The distribution of NHL subtypes in India shows important differences with those from the rest of the world. Follicular lymphoma and mantle-cell lymphoma are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.

Europe↗
PubMed2000

Endosulfan poisoning--a clinical profile.

OBJECTIVES: The objective of the study is to identify the clinical profile of endosulfan poisoning and also to recognise any biochemical parameters which indicate clinical or subclinical dysfunction of organs so that the offending agent can be easily identified in a given case of poisoning and appropriate treatment instituted promptly. METHODS: Forty four individuals who consumed food which was accidentally contaminated by endosulfan in a rural area were the subjects of the present study. Except the one who died, rest 43 were examined by the authors. A details history, regarding the item of food taken and quantity consumed was noted. Routine bio-chemical parameters like CBC, blood urea, serum creatinine, serum electrolytes, LFT, S Calcium, S Phosporus, were estimated, in fourteen of the patients who were admitted into this hospital. In seven of the patients who were available for follow up, laboratory parameters which were abnormal initially were repeated. RESULTS: Examination revealed that vital signs were stable. There was no jaundice, central nervous system examination showed varying grades of altered sensorium, normal sized pupils briskly reacting to light, normal oculocephalic reflex. There were no lateralising signs like hemiparesis. Plantars were bilateral extensor. There were no signs of meningeal irritation. Complete blood counts, blood sugar, urea, serum creatinine, serum electrolytes were all normal. Liver function tests in the form of SGPT, SGOT were abnormal. Serum bilirubin levels were normal. The values of SGOT and SGPT returned to normal at the end of six weeks. All patients were treated symptomatically. A postmortem examination carried out on the individual who died due to status epilepticus confirmed that the death was due to asphyxia. CONCLUSIONS: Endosulfan poisoning can be suspected by the primary CNS manifestations with or without clinical or laboratory evidence of other organ dysfunction like liver, kidney and muscle.

Adolescent↗
PubMed2000

Chilaiditi syndrome with hypertension.

Chilaiditi syndrome is interposition of the intestine between liver and diaphragm. It is often asymptomatic but there were cases presented as acute pain in the abdomen, needing corrective surgical procedure; or as mistaken renal colic, or as suspected subphrenic abscess, or as pneumoperitonium. The interposition of proximal transverse colon was found to be more common than the small intestine. Chilaiditi syndrome was associated with colonic volvulus. The colonic interposition then progressed from mild abdominal discomfort to intermittent bowel obstruction. Some patients needed surgical operation like hepatic extraperitonealization, after replacement of the dislocated gastroenteric tract, bringing the superior surface of the liver again into direct contact with the related diaphragmatic dome. A rare case of Chilaiditi syndrome incidentally associated with hypertension and ischaemic heart disease, in a male aged 50 years is reported.

Colon↗
PubMed1999

Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins.

Hypoxia-inducible factors are heterodimeric DNA-binding complexes that control the hypoxia responses of several genes and regulate the adaptive responses to the lack of oxygen. The complex is composed of two b-HLH protein subunits, HIF-1beta (ARNT), that is constitutively expressed, and a HIF-alpha subunit, that is present only in hypoxic cells. HIF-alpha proteins are continuously synthesized, but are rapidly degraded by the ubiquitin-proteasome system under oxic conditions. Hypoxia, transition metals, iron chelators, and several antioxidants stabilize the HIF-alpha proteins, allowing the formation of the transcriptionally active HIF complex. However, the sequences and mechanisms involved in the regulated degradation of the alpha protein subunits are poorly understood. Analysis of the available cloned sequences of human and mouse members of the HIF-alpha family of proteins revealed an area of about 15 amino acids with strong sequence conservation between all the members. This area corresponds to the region encompassing amino acids 557-571 of the hHIF-1alpha subunit. Fragments of HIF-1alpha and HIF-3alpha proteins containing this conserved sequence were able to confer hypoxia regulation when expressed as fusion proteins in Hep-3B cells. Regulation was observed with all the known hypoxia "mimics," including the reducing thiol donor N-mercaptopropionylglycine (NMPG). Selective alanine substitutions of amino acids 561-568 stabilized the protein in normoxic conditions. Furthermore, transfection with an expression vector containing a fragment of hHIF-1alpha comprising amino acids 540-580 enhanced transactivation activity of the full-length hHIF-1alpha protein. These results suggest that the above-mentioned conserved sequences are likely involved in the hypoxic stabilization of HIF-alpha proteins. The mechanisms and the interacting ubiquitin-ligases involved in the selective degradation process remain unknown.

Amino Acid Sequence↗
PubMed1999

General applicability of chicken egg yolk antibodies: the performance of IgY immunoglobulins raised against the hypoxia-inducible factor 1alpha.

Avian embryos and neonates acquire passive immunity by transferring maternal immunoglobulins from serum to egg yolk. Despite being a convenient source of antibodies, egg yolk immunoglobulins (IgY) from immunized hens have so far received scant attention in research. Here we report the generation and rapid isolation of IgY from the egg yolk of hens immunized against the alpha subunit of the human hypoxia-inducible factor 1 (HIF-1alpha). Anti-HIF-1alpha IgY antibodies were affinity purified and tested for their performance in various applications. Abundant HIF-1alpha protein was detected by Western blot analysis in nuclear extracts derived from hypoxic cells of human, mouse, monkey, swine, and dog origin whereas in hypoxic quail and frog cells, the HIF-1alpha signal was weak or absent, respectively. In electrophoretic mobility shift assays, affinity-purified IgY antibody was shown to recognize the native HIF-1 (but not the related HIF-2) complex that specifically binds an oligonucleotide containing the HIF-1 DNA binding site. Furthermore, IgY antibody immunoprecipitated HIF-1alpha from hypoxic cell extracts. Immunofluorescence experiments using IgY antibody allowed the detection of HIF-1alpha in the nucleus of hypoxic COS-7 cells. For comparison, the application of a mouse monoclonal antibody raised against the identical HIF-1alpha fragment was more restricted. Because chicken housing is inexpensive, egg collection is noninvasive, isolation and affinity purification of IgY antibodies are fast and simple, and the applicability of IgY is widespread, immunization of hens represents an excellent alternative for the generation of polyclonal antibodies.

Animals↗
PubMed1998

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a non-heme iron protein. Implications for oxygen sensing.

The hypoxia-inducible factor 1 complex (HIF-1) is involved in the transcriptional activation of several genes, like erythropoietin and vascular endothelial growth factor, that are responsive to the lack of oxygen. The HIF-1 complex is composed of two b-HLH proteins: HIF-1beta that is constitutively expressed, and HIF-1alpha, that is present only in hypoxic cells. The HIF-1alpha subunit is continuously synthesized and degraded by the ubiquitin-proteasome under oxic conditions. Hypoxia, transition metals, iron chelators, and several antioxidants stabilize the HIF-1alpha protein, allowing the formation of the transcriptionally active HIF-1 complex. The mechanisms of oxygen sensing and the pathways leading to HIF-1alpha stabilization are unclear. Because the involvement of a heme protein oxygen sensor has been postulated, we tested the heme sensor hypothesis by using a luciferase-expressing cell line (B-1), that is highly responsive to hypoxia. Exposure of B-1 cells to carbon monoxide and heme synthesis inhibitors failed to show any effect on the hypoxia responsiveness of these cells, suggesting that heme proteins are not involved in hypoxia sensing. Measurement of iron in recombinantly expressed HIF-1alpha protein revealed that this protein binds iron in vivo. Iron binding was localized to a 129-amino acid peptide between sequences 529 and 658 of the HIF-1alpha protein. Although the exact structure of the iron center has not been yet defined, a 2:1 metal/protein molar ratio suggests a di-iron center, probably similar to the one found in hemerythrin. This finding is compatible with a model where redox reaction may occur directly in the iron center of the HIF-1alpha subunit, affecting its survival in oxic conditions.

Carbon Monoxide↗
PubMed1998

Regulation of transforming growth factor-beta type II receptor expression in human breast cancer MCF-7 cells by vitamin D3 and its analogues.

In view of the tumor suppressor role of the transforming growth factor-beta (TGFbeta) type II receptor (RII), the identification and characterization of agents that can induce the expression of this receptor are of potential importance to the development of chemoprevention approaches as well as treatment of cancer. To date, the identification of exogenous agents that control RII expression has been rare. We demonstrated that proliferation of MCF-7 early passage cells (MCF-7 E), which express RII and are sensitive to TGFbeta growth inhibition activity, was significantly inhibited by vitamin D3 and its analogue EB1089. In contrast, proliferation of MCF-7 late passage cells (MCF-7 L), which have lost cell surface RII and are resistant to TGFbeta, was not affected by these two compounds. TGFbeta-neutralizing antibody was able to block the inhibitory effect on MCF-7 E cells by these compounds, indicating that treatment induced autocrine-negative TGFbeta activity. An RNase protection assay showed approximately a 3-fold induction of the RII mRNA, while a receptor cross-linking assay revealed a 3-4-fold induction of the RII protein. In contrast, there was no change in either RII mRNA or protein in the MCF-7 L cells.

Antineoplastic Agents↗
PubMed1996

A case control study of senile cataract in a hospital based population.

A case-control study (244 cases and 264 controls) was done during 1986-89 on a hospital based population to evaluate the risk factors associated with the etiology of senile cataract. Patient with age between 40-60 years, visual acuity of 6/9 or less, and presence of lenticular opacity of senile origin were included as cases. Age matched individuals with absence of lenticular opacity made up the controls. Multivariate logistic regression analysis revealed that higher systolic BP and number of meals were significantly (P < or = 0.05) associated with presence of senile cataract; whereas higher weight, education and income, and utilization of cooking water had a significant protective effect against senile cataract. The present study helps the clinician to understand the possible risk factors associated with the development of senile cataract and could be helpful in designing a intervention strategy in future.

Adult↗
PubMed1995

Carcinoma of the prostate--state at initial presentation.

In this retrospective study an attempt is made to document the stage at initial presentation of prostatic cancer. Of the 142 patients seen, 84% presented in an advanced stage and this explains why radical prostatectomies are rarely done in India. Hence efforts are required to screen the population for early diagnosis of the disease.

Humans↗
PubMed1995

Penile cancer--is lymphadenectomy necessary in all cases?

OBJECTIVES: This retrospective study examines the need for lymphadenectomy in all cases of penile cancer. METHODS: Thirty-six patients were followed up regularly by the same person between 1986 and 1992. RESULTS: Nine (25%) patients presented with positive groin lymph nodes and underwent immediate ilioinguinal node dissection. Of the 27 (75%) patients who presented with negative groin lymph nodes, 10 had a delayed lymph node dissection. Four of these patients are alive at 3.7 years. Three died within 1 year of surgery and 3 are lost to follow-up. Seventeen patients (47%) did not require lymphadenectomy and 14 (82%) of these patients are alive at 3.8 years, the other 3 being lost to follow-up. CONCLUSIONS: A careful, closely monitored, follow-up protocol can eliminate the need for lymphadenectomy in select patients with penile cancer.

Adult↗
PubMed1994

Complications in a personal series of one hundred and five radical cystectomies: specific problems in a developing country.

During the 6-year period 1986-1992, 105 patients with muscle invasive bladder cancer underwent radical cystectomy in our department. All the operations were done by the principal author using the same standard technique. Herein we analyse our perioperative complication rate and highlight some of the surgical steps which contribute to this low complication rate.

Adult↗
PubMed1994

Glycogenic effect of an alkali soluble fraction from sepia shell.

The alkali soluble fraction of the sepia shell possesses both anticonvulsant and hypoglycemic effect. The investigation regarding the fate of the blood sugar during the hypoglycemia revealed that the sepia shell extract acts as a glycogenic agent by mobilising the blood sugar towards liver glycogen reserve through the modulation of the enzymes glycogen phosphorylase a and ab in normal and streptozotocin diabetic mice. The glucose tolerance test (GTT) showed a depression in the GTT curve in experimental mice. The available literature on the biochemistry of the shell reveals that it contains glucosamines and some amino acid residues. The presence of amine group may resemble the sulfonylureas like tolbutamide which also possesses both anticonvulsant and hypoglycemic effect.

Animals↗