PubMed Health⌕ Search

Biomedical subjects

S Mathew

Publications and source records attributed to S Mathew.

At least 73 records · Page 4Linked to original sources
PubMed1994

Replication error-type genetic instability at 1q42-43 in human male germ cell tumors.

The replication error phenotype, recognized as microsatellite sequence alterations, has recently been suggested to be associated with hereditary nonpolyposis colorectal cancer and other types of sporadic tumors. We examined paired tumor-normal DNAs from 69 human male germ cell tumors for somatic instability at the 1q42-43 region. Analysis of a variable number of tandem repeats marker (D1S74) and 3 (CA)n type microsatellite loci (D1S235, D1S180, and angiotensinogen) revealed genetic alterations in tumor DNAs of 26 (38.2%) cases. The changes observed comprised rearrangements with D1S74 detected by Southern blot analysis in 4 of 55 (7%) cases; replication error-type alterations with D1S235, D1S180, and angiotensinogen in 12 of 66 (18.2%) cases; and loss of heterozygosity in 12 of 67 (17.9%) cases with the same probes. The microsatellite sequence alterations were more common in histological subsets other than teratomas, while the loss of heterozygosity was significantly more frequent in teratomas compared to other histologies. These results suggest that microsatellite instability and loss of heterozygosity at 1q42-43 may be unrelated genetic events which may play a role in germ cell tumor development.

Chromosomes, Human, Pair 1↗
PubMed1994

Origin of adult male mediastinal germ-cell tumours.

The origin of primary extragonadal germ-cell tumours, especially mediastinal and pineal germ-cell tumours in adult males remains uncertain, although the predominant view is that they originate in misplaced primordial germ cells retained in extra-gonadal sites, in contrast to gonadal germ-cell tumours which are considered to arise in premeiotic spermatocytes. We hypothesised that if mediastinal germ-cell tumours and gonadal germ-cell tumours were derived from precursor cells in different developmental states and in different cellular environments, non-random genetic changes in the two groups would be significantly different. To test this hypothesis, we compared non-random chromosomal abnormalities in mediastinal germ-cell tumours with those in gonadal germ-cell tumours. Our results show that although the two groups differed in the composition of histological subsets, their non-random chromosomal changes were essentially the same. These data suggest gonadal origin of all germ-cell tumours with occasional migration of precursors early in development to extragonadal sites to become established as primary extragonadal germ-cell tumours. Based on a review of cytogenetic data on carcinoma in situ, primary mediastinal and gonadal germ-cell tumours, embryonal migration of primordial germ-cells, and meiotic behaviour of spermatocytes, a model of origin of all germ-cell tumours in males is suggested.

Adult↗
PubMed1994

Transforming growth factor receptor gene TGFBR2 maps to human chromosome band 3p22.

In this study, we map the chromosomal position of the gene that encodes the type II receptor of TGF-beta (HGM symbol TGFBR2), a multifunctional regulator of cell proliferation and differentiation. Using a full-length cDNA and a genomic probe in Southern blot analysis of a human x rodent somatic cell hybrid panel and by direct fluorescence in situ hybridization to normal metaphase chromosomes, we show that the TGFBR2 gene maps to 3p22.

Animals↗
PubMed1994

Pancreatic lesions and modifications of pancreatic juice in tropical chronic pancreatitis (tropical calcific diabetes).

Seventeen Indian patients from Kerala State and 13 Indian controls were submitted to a dietary inquiry. Indian patients and controls had a low fat intake (40.8 g +/- 12.1 and 34.5 g +/- 11.0 per day, respectively) and a moderately low protein intake (52.8 +/- 9.5 and 47.8 +/- 11.3 g per day); 11 patients and 6 controls did not consume cassava. Pure nonactivated pancreatic juice was collected at endoscopy in 10 Indian patients who presented with tropical calcific diabetes, 12 apparently normal controls from the same area, and 23 apparently normal French controls. The only significant differences between Indian and French controls was a decreased pancreatic protein response to cerulein and an increased calcium concentration in the Indian subjects. The pancreatic juice of Indian patients was characterized by decreased volume, normal bicarbonate concentration, increased protein concentration when the acinar cells were not stimulated, with no response to cerulein, increased calcium concentration, and normal citrate concentration. These changes are very similar to the changes observed in French patients with chronic alcoholic pancreatitis. The lesions of 14 surgical resection pancreatic specimens from South Indian patients presenting with tropical pancreatitis were compared to pancreata from French patients presenting with chronic alcoholic pancreatitis. The only difference was that intraductal plugs, lesions of the duct epithelium, and retention cysts or pseudocysts were less frequent in Indians. These results show that the two nutritional forms of pancreatic lithiasis, alcoholic and tropical, have similar histological lesions and biochemical modifications of pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Stress causes alteration in attachment of rat hepatocytes to matrix protein substratum.

The effect of different types of stress on the attachment of rat hepatocytes to various matrix protein substrata, such as collagen IV, fibronectin and laminin, was investigated. Study of the kinetics of attachment of adult hepatocytes subjected to heat-shock at 45 degrees C for 30 min showed significantly lower attachment to collagen IV, fibronectin and laminin substrata when compared to untreated controls. The alteration in attachment was observed after heat-treatment for 10 min and the extent of alteration appeared to increase with duration of the heat-treatment, as well as with increase in temperature. Foetal rat hepatocytes, which appeared to attach much more readily than adult rat hepatocytes to these substrata, particularly to laminin, also showed significantly lower attachment to all three substrata after heat-treatment at 45 degrees C for 30 min. This alteration in attachment appeared to be specific for matrix proteins as there was no significant effect on interaction of cells with non-matrix proteins, such as Con A and asialoglycoproteins. While the attachment of adult hepatocytes appeared to attain near control levels in about 4 h, the foetal cells recovered in about 2 h after heat-shock, indicating that the heat-shock effect is reversible and the recovery is faster in foetal hepatocytes. Other stress-causing agents, such as heavy metals, also caused an alteration in attachment of hepatocytes to these matrix proteins. Attachment of adult and foetal hepatocytes to collagen substratum was reduced by 100-microM concentrations of heavy metals in the order Zn > Cd > La > As > Cu for adult cells and La > Zn > As/Cu > Cd for foetal cells. These heavy metals also caused significant reduction in attachment of adult hepatocytes to fibronectin and laminin, although the extent of inhibition was less than that for collagen substrata. However, these heavy metals did not significantly affect the attachment of foetal hepatocytes to laminin substratum indicating that the effect of heavy metals appeared to vary with the nature of the matrix protein substratum. On heat-shock, incorporation of [3H]leucine into cytoskeletal proteins such as cytokeratins CK8 and CK18 was reduced and significant amounts of two new proteins having an average molecular mass of 80 kDa and 90 kDa were found to be tightly associated with cytoskeletal proteins.

Aging↗
PubMed1993

Interphase cytogenetics of gastric and esophageal adenocarcinomas.

Numerical changes affecting chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 16, 17, 18, and the X and Y chromosomes have been analyzed using chromosome-specific centromeric alpha-satellite repeat DNA probes in a panel of biopsies of six gastric and three esophageal adenocarcinoma and one epidermoid carcinoma of esophagus obtained at surgery. For each case, with each probe, the number of hybridization signals were determined in 200 nuclei. Hybridization of each probe to phytohemagglutinin-stimulated normal peripheral blood lymphocytes served as controls. Monosomy was defined by loss of one signal in 15% or more cells and trisomy or tetrasomy was defined by the presence of 3 or 4 signals in 7% or more cells, respectively. The Y chromosome was lost in 6 of 8 cases and monosomy 10 was seen in 5 of 10 cases. Trisomy for chromosomes 17, 8, 7, 12, 11, and 1 was seen in 4 of 10, 4 of 10, 4 of 10, 2 of 10, 2 of 8, and 2 of 10 cases, respectively, and tetrasomy for chromosome 7 was seen in 1 of 10 cases. These data show that the Y chromosome and chromosomes 10, 8, 7, 17, and 12 are most frequently involved in nondisjunctional changes in these tumors. They also document the feasibility and utility of interphase cytogenetics of gastric adenocarcinomas.

Adenocarcinoma↗
PubMed1993

Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2.

Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells. Using somatic cell hybrid analysis and fluorescence in situ hybridization we co-localized both genes to 17q21.3. The 17q21 region carries the locus responsible for early-onset familial breast-ovarian cancer and several other genes that are involved in tumorigenesis and differentiation and undergo frequent rearrangements during neoplastic development. Thus, our mapping places the NME genes in a region that may be subjected to multiple selection pressures. NME1 and NME2 genes were expressed as soluble proteins in a T7 bacterial expression system. Both proteins are independently active nucleotide diphosphate kinases and readily form intra- and intermolecular disulfide bonds. The biochemical properties of these proteins may explain the diversity of mature eucaryotic nucleoside diphosphate kinases.

Animals↗
PubMed1993

Chromosomal localization of genes encoding the transcription factors, c-rel, NF-kappa Bp50, NF-kappa Bp65, and lyt-10 by fluorescence in situ hybridization.

We have used fluorescence in situ hybridization (FISH) to perform precise chromosomal mapping of the genes encoding the transcription factors c-rel, NF-kappa Bp50, NF-kappa Bp65, and lyt-10. The previously published assignments of c-rel and NF-kappa Bp50 have been refined to specific bands. The map position of lyt-10, inferred from its isolation from a t(10;14)(q24;q32) translocation, has been confirmed. NF-kappa Bp65 has now been mapped to 11q13, a site of frequent involvement in aberration in multiple tumor types.

Chromosome Mapping↗
PubMed1992

Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors.

We report the cytogenetic analysis of 124 adult male germ cell tumors ascertained consecutively at the Memorial Sloan-Kettering Cancer Center between 1988 and 1990. Biopsies from testicular and extragonadal primary and metastatic lesions studied included all histological subtypes of germ cell tumors and cases of malignant transformation. Nonrandom numerical and structural chromosomal abnormalities including i(12p), the previously described characteristic marker of these tumors, were determined, and their frequency was compared between histological subtypes, between gonadal and extragonadal lesions, and between primary and transformed lesions. The frequency and copy number of i(12p) were found to be higher in nonseminomas compared with seminomas. Nonrandom sites of chromosome rearrangements associated with specific histologies comprised 1p32-36 and 7q11.2 in teratomas and 1p22 in yolk sac tumors. Some tumors that underwent malignant differentiation exhibited chromosome changes previously described to be nonrandomly associated with de novo tumors with the same histological characteristics. Cytological evidence of gene amplification in the form of homogeneously staining regions and/or double minutes was detected in 24% of extragonadal lesions, mainly metastatic tumors, suggesting amplification of a gene(s) associated with metastatic progression of these tumors. While a number of previous small cytogenetic series or individual case reports of germ cell tumors identified several of the features of these tumors reported here, this series comprises analysis of the largest group of tumors ascertained consecutively at a single institution, defines the incidence of nonrandom abnormalities in tumor subsets, and addresses their biological significance.

Cell Transformation, Neoplastic↗
PubMed1992

Analysis of chromosome 12 aneuploidy in interphase cells from human male germ cell tumors by fluorescence in situ hybridization.

The i(12p) marker chromosome has been found to be a highly nonrandom chromosome abnormality associated with germ cell tumors (GCTs). We have previously shown that a chromosome 12 centromere specific alpha-satellite DNA probe detects the i(12p) by virtue of differences in the size of the signal originating from the i(12p) and normal chromosome 12 centromeres after fluorescence in situ hybridization (FISH) in metaphase and interphase cells of cultured GCT cell lines. We have now extended this analysis to 72 fresh GCT tumor biopsy specimens. Banded cytogenetic analysis was attempted on each of these tumors, 45 of which were found to be clonally abnormal. Data on i(12p) and chromosome 12 copy number obtained by FISH agreed well with those obtained by cytogenetic analysis. In addition, the FISH method made possible the detection and determination of i(12p) and the chromosome 12 copy number in cases in which conventional cytogenetic analysis was unsuccessful. We found the incidence of i(12p) in seminomas to be low (7%) compared to that in nonseminomas (75%) when tumor biopsy specimens were studied by FISH. Our results show that the FISH technique can be used reliably for detection of the diagnostically and prognostically useful i(12p) marker in GCT tumor biopsy specimens.

Aneuploidy↗
PubMed1992

Assignment of the human TYRP (brown) locus to chromosome region 9p23 by nonradioactive in situ hybridization.

The TYRP (brown) locus determines pigmentation and coat color in the mouse. The human homolog of the TYRP locus has been recently identified and shown to encode a 75-kDa transmembrane melanosomal glycoprotein called gp75. The gp75 glycoprotein is homologous to tyrosinase, an enzyme involved in the synthesis of melanin, forming a family of tyrosinase-related proteins. A genomic clone of human gp75 was used to map the human TYRP locus to chromosome 9, region 9p23, by nonradioactive fluorescent in situ hybridization. Specificity of hybridization was tested with a genomic fragment of human tyrosinase that mapped to a distinct site on 11q21. The 9p region has been reported to be nonrandomly altered in human melanoma, suggesting a role for the region near the TYRP locus in melanocyte transformation.

Chromosomes, Human, Pair 9↗
PubMed1992

Subregional mapping of 13 single-copy genes on the long arm of chromosome 12 by fluorescence in situ hybridization.

Subregional localization of 13 single-copy DNA sequences previously assigned to the long arm of chromosome 12 has been performed using the fluorescence in situ hybridization (FISH) technique. The following order is suggested for the 13 mapped genes: cen-->COL2A1-->(VDR-D12S15)-->(D12S17-D12S4++ +-D12S14-D12S6)-->D12S8-->(IAPP-MGF- D12S7-D12S12)-->IGF1-->qter. Eight of the mapped genes clustered at two regions, one at 12q13 (D12S17-D12S4-D12S14-D12S6) and the other at 12q22 (IAPP-MGF-D12S7-D12S12). Our results show that single-copy DNA sequences as small as 500 bp can be successfully mapped by FISH.

Chromosome Mapping↗
PubMed1992

The teaching of behavioural sciences.

Medical science over the last few decades has undergone vast changes. Technologically it has advanced at a rapid pace. There has been a realization as well that the behaviour of individuals and communities also influences the occurrence of disease. Medical schools around the globe have realized the need for incorporating behavioural sciences as an integral part of the basic sciences taught to medical students. This paper presents the experience of Christian Medical College, Vellore in teaching behavioural sciences. Students are taught sociology, psychology and medical anthropology through a community-based, problem-oriented teaching programme. The students have first-hand experience of living in a community and learn by observation and interaction. Pre- and post-assessment has shown a significant improvement of their knowledge and attitude. Feedback from students also indicates that they find this programme relevant and interesting.

Behavioral Sciences↗
PubMed1991

Cytogenetic studies in Down syndrome.

Cytogenetic studies were carried out in 645 patients with Down syndrome. Free trisomy of chromosome 21 was present in 600 cases (93%). Translocation karyotypes were observed in 26 cases (4%). Seventeen patients (2.6%) had mosaicism. Two (0.3%) patients had additional karyotypic abnormalities along with trisomy 21.

Chromosome Aberrations↗
PubMed1991

How long after being collected can blood still be cultured for chromosomal studies in the tropics.

To examine how long after their collection samples of peripheral blood could be successfully cultured for cytogenetic analysis in tropical countries, we determined the mitotic index in cultures of blood stored for up to 7 days in summer and winter. The results indicate that chromosomal analysis is successful if blood is stored for up to 2 days in summer or for up to 4 days in winter before initiating culture. Storing the blood in tissue culture medium rather than in heparin solution did not significantly improve the mitotic index.

Adult↗