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Biomedical subjects

M Mathur

Publications and source records attributed to M Mathur.

At least 73 records · Page 4Linked to original sources
PubMed1997

Loss of heterozygosity of a locus on 17p13.3, independent of p53, is associated with higher grades of astrocytic tumours.

Amongst the human astrocytic tumours, the commonest of primary brain tumours, the clinical outcome of astrocytoma (AS) is significantly better than anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Often, low grade tumours can progress to or recur with a more malignant phenotype. Recent loss of heterozygosity (LOH) reports suspect the involvement of a tumour suppressor gene, different from p53, in the 17p13.3 region of the human chromosome. However, the effect of LOH of 17p13.3 region on tumour histology at presentation and prognosis is as yet undefined. As a first step to define the role of this putative oncogene in astrocytic tumour progression, we correlated the LOH of a locus, D17S379, in 17p13.3 region and the p53 locus in 17p13.1 region with the histopathology of astrocytic tumours by PCR based microsatellite and restriction fragment length polymorphism of DNA extracted from microdissected paraffin sections of 45 astrocytic tumours of different histopathological grades. LOH of D17S379 was significantly associated (P=0.02) with AA and GBM (high grade malignancy), while no such preferential association was found with LOH of p53. There were no mutations in the exons 5 to 9 of p53 gene in the five tumours with LOH of D17S379 but not of p53 region. In a case of AA with a heterogenous microscopic appearance, heterozygosity of D17S379 was lost only in the area with a more malignant histology while both areas had no LOH or mutation of p53. A locus at the 17p13.3 region, independent of the p53 locus, is involved in a large subset of astrocytic tumours during transformation into a more malignant phenotype, and thus may be a link in the chain of genetic events occurring in astrocytic tumour progression.

Astrocytoma↗
PubMed1997

Phosphorylation within the amino-terminal acidic domain I of the phosphoprotein of vesicular stomatitis virus is required for transcription but not for replication.

Phosphorylation by casein kinase II at three specific residues (S-60, T-62, and S-64) within the acidic domain I of the P protein of Indiana serotype vesicular stomatitis virus has been shown to be critical for in vitro transcription activity of the viral RNA polymerase (P-L) complex. To examine the role of phosphorylation of P protein in transcription as well as replication in vivo, we used a panel of mutant P proteins in which the phosphate acceptor sites in domain I were substituted with alanines or other amino acids. Analyses of the alanine-substituted mutant P proteins for the ability to support defective interfering RNA replication in vivo suggest that phosphorylation of these residues does not play a significant role in the replicative function of the P protein since these mutant P proteins supported replication at levels > or = 70% of the wild-type P-protein level. However, the transcription function of most of the mutant proteins in vivo was severely impaired (2 to 10% of the wild-type P-protein level). The level of transcription supported by the mutant P protein (P(60/62/64)) in which all phosphate acceptor sites have been mutated to alanines was at best 2 to 3% of that of the wild-type P protein. Increasing the amount of P(60/62/64) expression in transfected cells did not rescue significant levels of transcription. Substitution with other amino acids at these sites had various effects on replication and transcription. While substitution with threonine residues (P(TTT)) had no apparent effect on transcription (113% of the wild-type level) or replication (81% of the wild-type level), substitution with phenylalanine (P(FFF)) rendered the protein much less active in transcription (< 5%). Substitution with arginine residues led to significantly reduced activity in replication (6%), whereas glutamic acid substituted P protein (P(EEE)) supported replication (42%) and transcription (86%) well. In addition, the mutant P proteins that were defective in replication (P(RRR)) or transcription (P(60/62/64)) did not behave as transdominant repressors of replication or transcription when coexpressed with wild-type P protein. From these results, we conclude that phosphorylation of domain I residues plays a major role in in vivo transcription activity of the P protein, whereas in vivo replicative function of the protein does not require phosphorylation. These findings support the contention that different phosphorylated states of the P protein regulate the transcriptase and replicase functions of the polymerase protein, L.

Amino Acid Substitution↗
PubMed1997

Changing patterns of Vibrio cholerae isolation over three consecutive cholera seasons (1992-1994) in east Delhi.

The emergence of new strains of Vibrio Cholerae has added a new dimension to the variability in pathogenicity and potential virulence of the organisms precipitating diarrhoeal diseases. Considering the shifting patterns of V. cholerae 01 there is a continuous need to monitor the strain characteristics. In this study total 541 stool specimens of acute secretory diarrhoea were investigated between May 1992 and November 1994 for strains of Vibrio Cholerae and anti-microbial susceptibility testing of all the confirmed V. Cholerae strains. In 1992, 50 of the 125 strains (40%) were positive for V. cholerae 01 predominantly biotype El Tor serotype ogawa, and 10 (80%) of non 01 type, with most strains susceptible to tetracycline (100%), chloramphenicol (98%) and Cotrimoxazole (98%), but all resistant to polymyxin B and furazolidine. In 1993, 44 (43.6%) of the 010 strains were positive for V. cholerae 0139 and the rest V. cholerae 01. In 1994, another sero group of V. cholerae 010 emerged, with 42 (13.3%) being positive. Isolates did not agglutinate with any of these antisera and have been labelled as 'other than non-01 vibrio cholerae'.

Case-Control Studies↗
PubMed1997

Display of disparate transcription phenotype by the phosphorylation negative P protein mutants of vesicular stomatitis virus, Indiana serotype, expressed in E. coli and eucaryotic cells.

The phosphoprotein (P) of vesicular stomatitis virus (VSV) is a subunit of the RNA polymerase (L) that transcribes the negative strand genome RNA into mRNAs both in vitro and in vivo. We have recently shown that the P protein of VSV, New Jersey serotype (PNJ), expressed in E. coli, is biologically inactive unless phosphorylated at specific serine residues by cellular casein kinase II (CKII). In the present work, we are studying the role of phosphorylation in the activation of the P protein of Indiana serotype (PIND), which is highly nonhomologous in amino acid sequence yet structurally similar to its New Jersey counterpart. Despite the fact that E. coli-expressed PIND required phosphorylation by CKII for activation, the phosphorylation negative P protein mutants generated by altering the phosphate acceptors S and T to alanine, surprisingly, showed transcription activity similar to wild-type in vitro. Alteration of S and T residues to phenylalanine, similarly, supported substantial transcription activity (approx. 60% of wild-type), whereas substitution with arginine residue abrogated transcription (approx. 5% of wild-type). In contrast, the same mutants, when expressed in eucaryotic cells, exhibited greatly reduced transcription activity in vitro. This disparate display of transcription phenotype by the PIND mutants expressed in bacteria and eucaryotic cells suggests that these mutants are unique in assuming different secondary structure or conformation when synthesized in two different cellular milieu. The findings that, unless phosphorylated by CKII, the bacterially expressed unphosphorylated (P0) form of PIND, as well as the phosphorylation negative mutants expressed in eucaryotic cells, demonstrates transcription negative phenotype indicate that, like PNJ, phosphorylation of PIND is essential for its activity.

Animals↗
PubMed1997

High prevalence of p53 gene alterations and protein overexpression in human esophageal cancer: correlation with dietary risk factors in India.

Epidemiological studies have demonstrated an association between human esophageal cancer and dietary/nutritional risk factors in developing countries. We examined the expression of p53 protein in 51 cases of esophageal squamous cell carcinomas (ESCCs) and paired normal esophageal tissues by immunohistochemistry. Alterations in the tumor suppressor gene p53 (exons 5-8) were analyzed in 51 cases of ESCC and paired normal tissues by PCR and single-strand conformation polymorphism. p53 protein expression was correlated with major dietary risk factors and common carcinogens identified in India. Immunohistochemical analysis of frozen esophageal tissue sections using anti-p53 monoclonal antibody (D0-1) showed overexpression of the protein in the nuclei of epithelial cells in 39 of 51 (76%) cases. The histopathologically proven normal esophageal tissue sections taken from a distant site from esophageal cancer patients did not show any detectable level of p53 immunoreactivity. The PCR-single-strand conformation polymorphism analysis showed a mobility shift in 37 of 51 (72%) ESCCs. Intake of chilies was positively associated with p53 protein expression (P < 0. 01) in the esophageal cancerous lesions. Our results suggest that p53 alterations are frequent events in esophageal oncogenesis in the Indian population, which has dietary habits that are considerably different from those of the Western population.

Adult↗
PubMed1996

c-myc oncogene expression and cell proliferation in mixed oligo-astrocytoma.

Mixed gliomas (oligo-astrocytomas) are brain tumours with an admixture of 2 different cell populations: astrocytes and oligodendroglia. On the basis of histological features and behaviour, these tumours are classified as low-grade mixed gliomas (MG) and malignant mixed gliomas (MMG). We have studied the relationship between c-myc protein expression and cellular proliferation in this class of tumours. Using antibody c-33 for c-myc and PC-10 for the proliferating cell nuclear antigen (PCNA), immunohistochemistry was performed on 14 MG and 9 MMG. PCNA was increased in MMG as compared to MG in both astrocytic and oligodendroglial areas. However, more c-myc-positive cells were seen only in the astrocyte areas of MMG. Analysis of the relationship of c-myc and PCNA suggests that the correlation of c-myc with cellular proliferation is dependent on tissue type and differentiation status.

Antibodies, Monoclonal↗
PubMed1996

The nature and significance of liver cell vacuolation following hepatocellular injury--an analysis based on observations on rats rendered tolerant to hepatotoxic damage.

Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.

Adaptation, Physiological↗
PubMed1996

Microscopic colitis is a cause of large bowel diarrhea in Northern India.

Chronic diarrhea is a common clinical problem. To determine the possible causes in North India, we studied prospectively 71 patients with chronic diarrhea of the large bowel type. A definite diagnosis could be established in 70 patients. Ulcerative colitis was found in 18 patients, colorectal malignancies in three, colonic polyps in three, and irritable bowel syndrome in 32. In addition, seven patients with seronegative polyarthritis and chronic diarrhea were found to have chronic inflammation of the colon on histology. Two patients had pseudodiarrhea, and no diagnosis could be established in one patient. The remaining five patients with chronic diarrhea showed histologic evidence of chronic colonic inflammation with predominantly mononuclear cell infiltration of the lamina propria and increased intraepithelial lymphocytes, but results of their radiologic and endoscopic studies were normal. These five patients were classified as having microscopic (lymphocytic) colitis. We conclude that the causes of chronic diarrhea in North India patients are similar to a large extent to those seen in Western populations. Microscopic (lymphocytic) colitis is a definite clinicopathologic entity that should be considered in the differential diagnosis of chronic diarrhea.

Adolescent↗
PubMed1996

Recurrent pyogenic cholangitis or "oriental cholangiohepatitis' in occidentals: case reports of four patients.

The first description of recurrent pyogenic cholangitis occurring in four occidentals is presented. While recurrent pyogenic cholangitis is a common syndrome of uncertain aetiology among orientals (also known as oriental cholangiohepatitis), it has not previously been described in occidentals. Four such patients are described. They presented with recurrent attacks of ascending cholangitis and associated hepatolithiasis, biliary stricturing and dilation. Focal hepatic involvement was treated by segmental liver resection and recurrent disease by interventional endoscopy or radiology.

Adult↗
PubMed1996

Expression of L protein of vesicular stomatitis virus Indiana serotype from recombinant baculovirus in insect cells: requirement of a host factor(s) for its biological activity in vitro.

The 241-kDa large (L) protein of vesicular stomatitis virus (VSV) Indiana serotype, a multifunctional catalytic subunit of the viral RNA polymerase, has been expressed in Spodoptera frugiperda cells infected with recombinant baculovirus BacPAK6-L containing the L gene under the control of a polyhedrin promoter. The recombinant L protein was biologically active and supported viral mRNA synthesis in vitro. When the expressed L protein was purified by phosphocellulose column chromatography, it eluted in two peaks, one at 0.4 M NaCl (peak I) and the second at 0.75 M NaCl (peak II). The L protein in peak I showed significant transcriptional activity in an in vitro transcription reconstitution experiment, whereas the L protein in peak II was inactive. Interestingly, the addition of cytoplasmic extract from uninfected Sf21 cells to peak II completely restored transcription in vitro, indicating the requirement of a host factor(s) for the activity of the L protein. This factor is relatively heat stable and is dissociable from the recombinant L protein. It is also present in BHK, COS, and HeLa cells in detectable levels. The role of the putative host protein(s) in the activation of the L protein is discussed.

Animals↗
PubMed1996

Constitutive activation of a single effector pathway: evidence for multiple activation states of a G protein-coupled receptor.

A cysteine-to-phenylalanine mutation in the third transmembrane domain of the alpha 1B-adrenergic receptor constitutively activates the receptor, resulting in G protein coupling in the absence of agonist and activation of only a single effector pathway (phospholipase C but not phospholipase A2). This mutant receptor displays a higher affinity for the catecholamines, norepinephrine, and epinephrine, as well as for other phenethylamines, but not for imidazolines, a class of structurally distinct alpha agonists. Dose-response studies demonstrate a higher potency and intrinsic activity of phenethylamines for polyphosphoinositide turnover but not for arachidonic acid release. Imidazolines have wild-type potencies and intrinsic activities for both pathways. These data indicate that a single receptor subtype forms multiple conformations (i.e., exhibits induced conformational pleiotropy) for G protein interactions (high affinity states) that are specific for a particular G protein/effector pathway and that multiple binding sites exist for agonists, which promote or induce these specific interactions. Pharmacological diversity may, thus, be achieved through a single receptor by the development of compounds that induce a single activated conformer. This has major ramifications for the eventual development of signaling-specific therapeutics.

Adrenergic alpha-Antagonists↗
PubMed1996

Cluster of cases of clinical cholera due to Vibrio cholerae 010 in east Delhi.

A total of 514 samples of acute diarrhoeal stools received over a period of four months yielded 315 isolates morphologically and biochemically resembling V. cholerae. Out of 315 isolates, 223 (70.8%) were identified as V. cholerae 01, 20 (6.4%) as 0139 and 42 (13.3%) as 010. Thirty (9.5%) isolates did not agglutinate with any of the available antisera. All V. cholerae 010 isolates showed complete homogeneity in their biochemical and physiological properties. This strain appears to be closely related to El Tor biotype of V. cholerae 01, since it was positive for some of the tests used for identification of El Tor. The ability of strain 010 to grow in the presence of 6 per cent salt provides it the status of an important environmental pathogen. Acquisition of some virulence genes from El Tor vibrios by this strain 010 appears to be one of the mechanisms involved in the emergence of this serogroup.

Cholera↗
PubMed1996

Management of metastatic Wilms tumor: an eleven year experience.

During the last 11 years, 101 patients of Wilms tumor were seen. Of these, 13 patients had metastatic disease at onset while 24 patients presented with relapse at a latter date. Seven patients have been cured, all had favourable histology. The risk factors associated with relapse were found to be unfavourable histology, lymph node involvement, age more than 6 years, diffuse spill, capsular and vascular invasion, and aneuploidy. Of the 18 patients who had relapsed, 14 were found to be aneuploid. Judicious use of various therapeutic options like radiotherapy to metastatic sites, second look surgery, resection of pulmonary metastasis and use of cis-platinum, VP-16 and Ifosfamide as "alternative chemotherapy protocols" were used to achieve cure in these advance cases.

Child↗
PubMed1996

Characterisation of Vibrio cholerae 0139 isolated from diarrhoeal stools.

A total of 174 samples of acute diarrhoeal stools received over a period of seven months, yielded 101 isolated morphologically and biochemically resembling Vibro cholerae. Serologically, 57(56.4 per cent) of the 101 isolates were identified as V. cholerae 01 and remaining 44 (43.6 per cent) as V. cholerae 0139. Keeping in mind the unique potential of 0139 among non 01 vibrio to cause epidemics, we decided to undertake the study of biochemical characters and physiological behaviour of all the 44 V. cholerae 0139 isolates. All the stains were Voges Proskauer's test positive' haemagglutinating and grew in the presence of 6 per cent sodium chloride. 13 (29.5 per cent) strains showed haemolytic activity. Nine (20.5 per cent) were polymyxin-B sensitive and 4 (9.0 per cent) fermented lactose. All the isolates showed considerable degree of homogeneity in their biochemical and physiological properties, some characters define them to be closer to El Tor biotype.

Cholera↗
PubMed1995

Infrequent alteration of the c-myc gene in human glial tumours associated with increased numbers of c-myc positive cells.

Twenty five human glial tumours of different grades of malignancy were examined by Southern blotting and polymerase chain reaction (PCR) for alterations (rearrangements, amplification and deletions) in the c-myc gene. Number of c-myc positive cells per thousand cells were also counted in all the tumours after immunohistochemical staining for c-myc protein was done on fixed sections of the tumours. No tumours exhibited any amplification of the gene, as found by Southern blotting. One astrocytoma and one mixed glioma showed some rearrangements in the 3' end of the gene, as detected by Southern blotting and hydridization. These two tumours had higher number of c-myc positive cells than in other tumours of the same histopathological groups. Deletion in the first promoter region, as determined by PCR, was seen in only one astrocytoma. However, the number of c-myc positive cells in that tumour did not show any deviation from that found in other astrocytomas. In light of present literature, it is speculated that the 3' rearrangements may be the cause of increased number of c-myc immunopositive cells in those tumours by disrupting the 3' end of the gene leading to increased c-myc mRNA stability. Such a mechanism may play a part in small subset of glial and possibly other tumours.

Base Sequence↗
PubMed1995

A correlative study of in vivo and in vitro labeling index using bromodeoxyuridine in human brain tumors.

The labeling index (LI) of 216 cases of human brain tumors was determined by the immunohistochemical technique with monoclonal antibody to bromodeoxyuridine (BrdU). The proliferative potential of 110 cases was estimated using the intra-operative intravenous infusion of BrdU at a dose of 200 mg/sq m. In another 106 cases, the in vitro technique of incubating freshly resected tumor tissue fragments with 100 microM bromodeoxyuridine was used. The BrdU LI in these tumors was then correlated with the histological types and the data as determined by both the in vivo and in vitro BrdU incorporation were compared. The results indicate that although in vivo and in vitro techniques could possibly provide equivalent data in some histologic types, a clear statistically valid proof however is not apparent from this study.

Adolescent↗
PubMed1995

Diarrhoeal outbreak of Vibrio cholerae 0139 from north India.

Epidemics of cholera caused by Vibrio cholerae 01 occur regularly in India. Until recently, Vibrio cholerae non-01 have been the the causative agents of sporadic cases of gastroenteritis and septicaemia, especially in immunocompromised children. We describe a large outbreak of cholera-like illness from North India caused by Vibrio cholerae non-01, later serotyped as Vibrio cholerae 0139. Forty-one of a total of 391 patients with acute diarrhoea during a 2-month period (May-July 1993) were identified as having Vibrio cholerae in faecal samples. All patients were aged 1.5-12 years. Vibrio cholerae 0139 was isolated in 30 patients (73%-group I) and Vibrio cholerae 01 biotype eltor in 11 patients (27%-group II). The clinical presentation and severity of the cholera-like illness were similar to typical cholera. This strain is toxigenic with an epidemic potential and should be monitored carefully.

Acute Disease↗