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Biomedical subjects

S Mathew

Publications and source records attributed to S Mathew.

At least 37 records · Page 2Linked to original sources
PubMed1998

Modulation of biochemical activity of hepatocytes in culture by matrix substratum.

The influence of extra cellular matrix on the biochemical activity of hepatocytes was studied by maintaining rat hepatocytes in primary culture in a serum free medium on different matrix protein substrata or biomatrices prepared from liver, aorta or mammary gland. There was significant difference in the individual protein synthesis and distribution by cells maintained on different substrata. Comparison of the kinetics of synthesis and secretion of albumin by cells maintained on different tissue biomatrix showed that those maintained on hepatic biomatrix synthesized more albumin and retained more of albumin synthetic capacity, when compared to those maintained on aortic and mammary gland biomatrix. Similarly, hepatocytes maintained on hepatic biomatrix synthesized significantly more apo B, the major apo protein of VLDL, than those maintained on heterologous tissue matrix. Induction of tyrosine aminotransferase by dexamethasone and the uptake of [14C]-amino isobutyric acid were found to be maximum in cells maintained on liver biomatrix than the heterologous biomatrix. But cells maintained on hepatic biomatrix incorporated less amounts of radioactivity into total cytoskeletal proteins as well as the individual proteins such as actin and the cytokeratins C8 and C18 while that by cells maintained on aortic biomatrix was significantly high. Quantitative analysis of the relative incorporation of radioactivity into individual cytoskeletal proteins and albumin in pulse labelling studies with cells maintained in culture on different matrix for different lengths of time revealed a reciprocal relationship between these two activities. These results indicate that the substrata with which the cells are in contact influence on a selective basis, the biochemical activity of hepatocytes in primary culture.

Albumins↗
PubMed1997

12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia.

Although abnormalities involving the short arm of chromosome 12 (12p) are one of the most frequently observed rearrangements in childhood acute lymphoblastic leukemia (ALL), little is known about the frequency of different structural abnormalities and their relationship to the status of the ETV6 (also named TEL) gene in this region. Of 815 children with newly diagnosed ALL, 94 (11.5%) had a total of 104 cytogenetic 12p abnormalities. Loss of genetic material was observed in 67 (64%) of these abnormalities. Cases with 12p alterations had a much lower frequency of hyperdiploidy greater than 50 (7%) than did the ALL population in general, but these cases had a similar distribution of immunophenotype and similar 5-year event-free survival (70% +/- 5% SE v 64% +/- 2%, P = .64). Rearrangement of the ETV6 gene was identified in 36 (56%) of 64 cases evaluated. The ETV6-CBFA2 (TEL-AML1) fusion transcript was found in 25 (66%) of 38 cases evaluated, and all but one of these showed ETV6 rearrangement. Importantly, ETV6 rearrangement was associated with a favorable prognosis (5-year event-free survival: 89% +/- 6% v 60% +/- 1%, P < .01). We conclude that most but not all 12p cytogenetic abnormalities in childhood ALL involve ETV6, and that rearrangement of ETV6 is associated with a favorable treatment outcome.

Adolescent↗
PubMed1997

Pulmonary sequestration--a diagnostic pitfall: a case report.

Pulmonary sequestration is defined as a congenital malformation of abnormal lung tissue that does not communicate with the airway system and that receives blood supply from anomalous arteries. The majority of these sequestrations are encountered in the pediatric population. Surgical excision is the treatment of choice, with excellent prognosis. We studied a case of an extralobar pulmonary sequestration in a young adult, presenting as an intrathoracic mass; it was aspirated twice, final diagnosis being rendered after surgical resection. The cytologic findings and the accompanying diagnostic difficulties to our knowledge have never been reported.

Adult↗
PubMed1997

Parotid fine-needle aspiration: a cytologic study of pediatric lesions.

Fine-needle aspiration (FNA) of parotid lesions in the pediatric age group presents interesting diagnostic problems. There is limited cytologic literature available on the subject. We studied the cytologic findings on FNA of parotid masses in seven such cases. Patients ranged in age from 1 to 17 years (mean = 10.4). Diagnoses included lymphoepithelial cyst (n = 1), mucoepidermoid carcinoma (n = 2), pilomatrixoma (n = 1), acinic-cell carcinoma (n = 1), rhabdomyosarcoma (n = 1), and Ewing's sarcoma (n = 1). Six cases were confirmed by subsequent histologic examination. The study elaborates on the cytologic features of each lesion and discusses the differential diagnosis of closely related entities peculiar to this age group. It highlights the role of FNA as the diagnostic modality of choice in dealing with pediatric parotid masses.

Adolescent↗
PubMed1997

Classically conditioned changes in plasma cortisol levels induced by dexamethasone in healthy men.

Animal research has indicated that the activity of the hypothalamic-pituitary-adrenal axis can be influenced by classical (Pavlovian) conditioning procedures. To test the hypothesis that alterations in plasma cortisol levels can be conditioned in humans, the present study used a prospective, randomized, double-blind, placebo-controlled design in which a distinctively flavored beverage was paired with p.o. administration of dexamethasone. Twenty-five healthy men were randomly assigned to one of two groups. During the conditioning phase of the study, subjects in the experimental group received three conditioning trials (pairings of a distinctively flavored beverage with a capsule containing 5 mg dexamethasone) separated by 1 wk recovery periods. Subjects in the control group were treated identically, except that the capsule contained a placebo. During the test phase, all subjects underwent a test day (reexposure to the distinctively flavored beverage before receiving a placebo capsule) and a comparison day (no exposure to the beverage or the capsule). Plasma cortisol was assessed repetitively before and after administration of the beverage and capsule, as were possible confounding factors, including: behavioral variables, psychological distress, aversive reactions to the beverage, and expectations of treatment. After reexposure to the beverage and administration of a placebo capsule (conditioned stimuli), the experimental group had significantly higher levels of plasma cortisol than the control group, after controlling for variability in baseline levels of cortisol (F(5,60)=3.09; P=0.015) that could not be explained by differences in other study variables. No differences in cortisol levels were found on the comparison day. These results support the study hypothesis that changes in plasma cortisol levels can be classically conditioned in humans by pairing a distinctive beverage with p.o. administration of dexamethasone.

Adult↗
PubMed1997

Significance of peritoneal washings in gynecologic oncology. The experience with 901 intraoperative washings at an academic medical center.

OBJECTIVE: Peritoneal washings are routinely performed during gynecologic surgery. The presence or absence of malignant cells in washings helps determine the stage of the malignancy. However, the efficacy of this procedure has not been studied recently. DESIGN: All intraoperative washings for gynecologic disease at our hospital from 1992 through 1994 (901 cases) were reviewed. Of these, 380 were gynecologic malignancies that were reviewed for changes in staging based on the presence of malignant cells. RESULTS: Histologically, 380 cases were gynecologic malignancies, 521 benign, 79 nongynecologic, and 25 had no accompanying surgical pathology. Of the malignancies, 125 had a diagnosis of cancer on washings. In 12 cases (3.1%), a change in stage resulted. CONCLUSIONS: In a small but significant number of cases, malignant cells in the washings changed postoperative staging, impacting therapeutic measures and prognosis for these patients greatly. Peritoneal washings remain a simple yet effective tool in the evaluation and management of gynecologic malignancies.

Ascitic Fluid↗
PubMed1997

Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity.

Extract of Tinospora cordifolia has been shown to inhibit the lipid peroxidation and superoxide and hydroxyl radicals in vitro. Concentration needed for 50% inhibition was 6 mg and 12.5 mg/ml, respectively. The extract was also found to reduce the toxic side effects of cyclophosphamide administration (25 mg/kg b.wt, 10 days) in mice hematological system by the free radical formation as seen from total white blood cell count, bone marrow cellularity and alpha-esterase positive cells. Moreover, administration of the extract partially reduced the elevated lipid peroxides in serum and liver as well as alkaline phosphatase and glutamine pyruvate transaminase. This indicates the use of Tinospora extract in reducing the chemotoxicity induced by free radical forming chemicals.

Animals↗
PubMed1996

Synthesis of sulphated proteoglycans by primary cultures of rat hepatocytes--modulation by matrix substratum.

Primary cultures of rat hepatocytes maintained on different matrix proteins such as collagen (Co IV) fibronectin (Fn), Laminin (Ln) or different tissue biomatrices were metabolically labelled with 35[S]-SO4 and the synthesis of sulphated proteoglycans was studied. The incorporation of the label into total glycosaminoglycan (GAG) was significantly higher in cells maintained on Co IV compared to those maintained on Fn or Ln. Similarly the incorporation of label was maximum in those cells maintained on the aortic biomatrix compared to liver or mammary gland biomatrix. About 80-95% of the GAG synthesised and secreted by cells maintained on individual matrix proteins and liver biomatrix was heparan sulphate (HS). But in the case of cells maintained on collagen IV aortic or mammary biomatrix in addition to HS, significant amount of chondroitin sulphate (CS) was also found. Nearly 50% of the total 35[S]-GAG was associated with the cell layer after 24 h in culture in the case of cells maintained on individual matrix protein while those maintained on tissue biomatrix, retained about 70% of the 35[S]-labelled proteoglycans (PG) with the cell layer. Analysis of the cell surface 35[S]-labelled proteoglycans isolated from cells maintained on different biomatrix showed that it is a hybrid proteoglycan consisting of CS and HS. While the PG isolated from cells maintained on liver biomatrix consists of HS and CS in the ratio of 3:2 that from cells maintained on aorta or mammary gland matrix was about 2:3 indicating an alteration in the nature of the cell surface PGs produced by cells maintained on different tissue biomatrix. These results indicate that depending on the nature of the matrix substratum with which the cells are in contact, the nature and quantity of sulphated proteoglycans produced by hepatocytes vary.

Animals↗
PubMed1996

REL proto-oncogene is frequently amplified in extranodal diffuse large cell lymphoma.

Comparative genomic hybridization (CGH) analysis of DNA extracted from a diffuse lymphoma with a large cell component (DLLC) that displayed double minute chromosomes upon conventional karyotypic analysis indicated overt amplification of DNA sequences derived from the 2p13-15 region. Southern blot analysis of this tumor DNA with a cDNA probe for the proto-oncogene REL, previously mapped to 2p14-15, indicated a greater than 35-fold amplification of REL. To determine the incidence of REL amplification and possible clinical or histologic association with DLLC, a panel of 111 tumor DNAs from DLLC specimens was screened for REL amplification by Southern blot analysis. A copy number of > or = 4 was noted in 26 cases (23%). Southern blot analysis of these 26 tumor DNAs with a cDNA probe for TGFA, mapped to 2p13, indicated lack of coamplification except in one case. Another member of the Rel/NF-kappa B family of transcriptional activators, RELA/p65 mapped to 11q13, was amplified in five cases as determined by Southern blot analysis using a cDNA probe. Nineteen of the 26 DLLC (73%) with REL amplification were primary extranodal lymphomas. As a group, the tumors with REL amplification demonstrated an increased frequency of chromosomal aberrations previously associated with tumor progression, suggesting an oncogenic effect of amplified REL in B-lymphoid cells that already contained a transforming genetic lesion. Thus, REL amplification is a frequent event in DLLC, and probably constitutes a progression-associated marker of primary extranodal lymphomas. This study shows the usefulness of the CGH technique in identifying chromosomal regions overrepresented in tumors that can point to amplified genes and may be correlated with clinical features of the disease.

Aneuploidy↗
PubMed1996

Promoter of the canine tracheobronchial mucin gene.

The mucin gene is up-regulated in diseases such as cystic fibrosis (CF) and asthma. To understand the mechanisms involved in transcriptional regulation of mucin gene expression we have characterized the region of the mucin gene up-stream of the transcriptional start site and analysed the cis-acting elements required for mucin promoter activity. We isolated clones from a dog genomic library containing the promoter region for the tracheobronchial mucin gene (TBM). The authenticity of the promoter was tested by nucleotide sequencing, primer extension analysis, electrophoretic mobility shift assay (EMSA) and reporter gene expression analysis. The canine TBM promoter is different from housekeeping gene promoters (as it is not rich in GC content and contains TATA- and CAAT-like sequences) and different from that of regulatory genes (because it contains many TATA- and CAAT-like sequences and multiple transcriptional initiation sites). Reporter gene analysis using canine TBM promoter-chloramphenicol acetyltransferase (CAT) fusion plasmids established the regions responsible for promoter activity and verified the positions of the major mucin transcriptional initiation sites. Reporter gene analysis also established that a region of the canine TBM promoter and first exon containing all of the transcriptional initiation sites is more active in mucin expressing cells (e.g. CT1 cells-immortalized canine tracheal epithelial cells, human CFT1 cells-immortalized tracheal epithelial cells from a CF subject, or HBE1 cells-immortalized tracheal epithelial cells from non-CF subject) than in mucin non-expressing cells (COS7, 3T3), suggesting cell specificity. The promoter region contained cAMP response element (CRE) sequences, and the TBM gene transcription was enhanced when cAMP analogs were added to transfected cells. EMSA indicated the presence of at least two DNA binding proteins in CT1 cells. This is the first report describing the characterization of a TBM gene promoter. The information obtained in the present studies will be valuable in understanding mucin gene regulation in normal and pathological conditions.

Animals↗
PubMed1996

Ochratoxin induced hemolysis in rabbits.

A saline suspension of RBC when incubated with an increasing concentration (1 to 10 micrograms/ml) of crude ochratoxin at 37 degrees C for 16 hr showed a marked alteration in morphological characters followed by hemolysis. The effect was more pronounced with higher concentration of toxin. The result suggests extreme cytotoxic effect of ochratoxin on RBC leading to its lysis.

Animals↗
PubMed1996

Mediastinal enterogenic cyst presenting as paraplegia--a case report.

A rare case of a mediastinal enterogenic cyst with an intraspinal extension through a anterior vertebral defect presenting with paraplegia in a 10 year boy is presented. Laminectomy and the trans-thoracic excision of the cyst resulted in the complete recovery of the neural deficit.

Abnormalities, Multiple↗
PubMed1996

Selection for high and low number of sternopleural bristles in Drosophila ananassae: correlated response in the frequency of chromosome inversions.

Directional selection for high and low number of sternopleural bristles in Drosophila ananassae was applied for 13 generations. The selection produced a rapid divergence in the mean number of sternopleural bristles in the replicates high and low lines: i-high (H1 -25.75, H2 -25.69); ii-low (L1 -14.16 L2 -13.55); iii-control (17.21) lines in G13. Regression coefficients for the high and low lines were significantly different from zero. The realized heritability over thirteen generations was 21-23 for the high lines and 14-18 for the low lines. The results suggest that the number of sternopleural bristles in D. ananassae is under polygenic control, with a substantial amount of additive genetic variation. Flies of the base population had three chromosome inversions: AL (2L), ZE (2R) and DE (3L). The comparisons of chromosome arrangement between high and low lines (the G13 generation of selection) indicates significant changes in the inversion frequency during the course of selection, providing evidence for correlation between the bristle number and particular chromosome arrangements.

Animals↗
PubMed1995

Chromosomal assignment of human ID1 and ID2 genes.

The Id (inhibitor of DNA binding) proteins regulate transcription during development by interacting with transcription factors. Three human genes, ID1, ID2, and ID3, have been identified that belong to this family of transcription regulators. We show, by somatic cell hybridization and fluorescence in situ hybridization experiments, that ID1 and ID2 are localized at 20q11 and 2p25, respectively.

Blotting, Southern↗
PubMed1995

Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2.

Thymopoietins (TMPOs, previously abbreviated TPs) alpha (75 kDa), beta (51 kDa), and gamma (39 kDa) are related nuclear proteins expressed in many or all tissues. TMPO alpha is present diffusely throughout the nucleus, while TMPOs beta and gamma are localized to the nuclear membrane. Here we report the cloning and analysis of a single TMPO gene encoding TMPOs alpha, beta, and gamma, which are produced by alternative mRNA splicing, as previously inferred from cDNA sequences. The eight exons of the TMPO gene are spread over approximately 35 kb. Exon 4, which is spliced into TMPO alpha mRNA, contains sequences that encode a putative basic nuclear localization motif. Exon 8, which is spliced into TMPO beta and gamma mRNAs, encodes a hydrophobic putative membrane-spanning domain that is thought to target TMPOs beta and gamma to the nuclear membrane. TMPO beta appears to be the human homologue of the recently described rat protein LAP2 (lamina-associated polypeptide 2), which is thought to play an important role in the regulation of nuclear architecture by binding lamin B1 and chromosomes in a manner regulated by phosphorylation during mitosis (K. Furukawa and L. Gerace, La Jolla, pers. comm., 22 Nov. 1994). The human TMPO gene maps to chromosome band 12q22.

Amino Acid Sequence↗
PubMed1995

p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors.

The p27Kip1 gene codes for a cyclin-dependent kinase inhibitor implicated in G1 arrest by transforming growth factor beta, cell-cell contact, agents that elevate cyclic AMP, and the growth-inhibitory drug rapamycin. p27 binds to and inhibits complexes formed by cyclin E-cdk2, cyclin A-cdk2, and cyclin D-cdk4. The involvement of p27 in the negative regulation of cell proliferation suggests that it may also function as a tumor suppressor gene. Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27Kip1 has been mapped to the short arm of chromosome 12 at the 12p12-12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas. In order to assess potential p27Kip1 gene alterations, we have screened a total of 147 human primary solid tumors and found no detectable cancer-specific mutations. These results argue that the often observed loss of antimitogenic transforming growth factor beta responsiveness in human cancer cells is not due to structural defects in p27Kip1.

Base Sequence↗