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Biomedical subjects

B Kannan

Publications and source records attributed to B Kannan.

10 recordsLinked to original sources
PubMed2006

Hyperekplexia in two siblings.

Hyperekplexia is a rare, hereditary, non-epileptic disorder characterized by an exaggerated startle reaction to unexpected auditory, somatosensory and visual stimuli. The authors describe a one-day-old term neonate, who presented with jitteriness and episodic tonic spasms, and his elder sister with hyperekplexia. Hyperekplexia though is a rare disorder is one of the differential diagnoses for refractory tonic spasms in infancy. The prognosis is generally good in hereditary hyperekplexia. Recent molecular studies have revealed many associated mutations in the glycine receptor alpha and beta subunit genes.

Anticonvulsants↗
PubMed2005

Jeune thoracic dystrophy with right sided diaphragmatic hernia.

Jeune thoracic dystrophy is a rare autosomal recessive chondrodysplasia, first described by Jeune et al in 1955. Early death is usually the consequence of asphyxia with or without pneumonia. Here is reported a newborn with Jeune thoracic dystrophy and a right-sided diaphragmatic hernia.

Abnormalities, Multiple↗
PubMed1999

ErbB receptor expression and growth response to heregulin beta 1 in five ovarian carcinoma lines.

SKOV-3, NIH:OVCAR-3, NIH:OVCAR-8, Ovca 429 and Ovca 433 ovarian carcinoma cell lines were examined to correlate biological behavior (growth in monolayer and soft agar) with erbB family receptor expression levels and response to recombinant Heregulin beta1 (Hrg). While all lines expressed variable amounts of each receptor, erbB-3 and to a lesser extent erbB-2 were constitutively tyrosine phosphorylated in all lines. Hrg beta1 treatment enhanced only erbB-3 tyrosine phosphorylation; however, the addition of Hrg in low serum did not stimulate ovarian cell growth, unlike all three breast cancer cell lines examined. In addition, all five of the ovarian carcinoma cell lines expressed Hrg mRNA by RT-PCR, unlike two of the three breast cancer cell lines. These results suggest the apparent importance of erbB-3 and endogenous Hrg in ovarian carcinoma cell growth in vitro.

Breast Neoplasms↗
PubMed1995

mRNA phenotyping of the major ligands and receptors of the EGF supergene family in human ovarian epithelial cells.

mRNA amplification phenotyping (MAPPing) was used to determine the level of mRNA expression of the major EGF-related ligands (EGF, TGF-alpha, and Amphiregulin) and receptors (EGF-receptor and erbB-2) of the EGF supergene family in three ovarian carcinoma lines (OVCA 429 and 433, and NIH:OVCAR-8) under serum-supplemented and reduced serum (minimal medium with 2% fetuin) growth conditions. mRNA levels of TGF-alpha, EGF-R, and erbB-2 were particularly high, and increased approximately 2-3 orders of magnitude when grown in serum, consistent with an autocrine involvement of these genes in ovarian epithelial growth in vitro. Moreover, even when grown without serum, OVCA 429 and NIH:OVCAR-8 expressed elevated levels of mRNA for erbB-2.

Amphiregulin↗
PubMed1995

Changes in tyrosine-phosphorylated p190 and its association with p120 type I and p100 type II rasGAPs during myelomonocytic differentiation of human leukemic cells.

A M(r) 190,000 protein (p190) functions as a GTPase-activating protein (GAP) for Rho and Rac family proteins, which are involved in regulating cytoskeletal actin and membrane ruffling. Tyrosine-phosphorylated p190 also complexes with rasGAP, a regulator of Ras activity, thus possibly linking Ras and Rho pathways. Leukemic cells induced to differentiate along myelomonocytic lineages have increased filamentous actin (as evidenced by phalloidin staining) and extended pseudopodia, and become irregularly shaped and flattened, suggesting altered Rho and Rac function. We, therefore, hypothesized that changes in p190 and its association with rasGAP are an integral part of these shape changes. During phorbol 13-myristate 25-acetate-induced monocytic differentiation of HL60 promyelocytic and RWLeu4 chronic myelogenous leukemic cells, the total amount of p190 decreases rapidly but returns to initial levels by 12 h. In RWLeu4, this was accompanied by commensurate changes in p190 tyrosine phosphorylation and association with p120 type I rasGAP. Association of p190 and type I rasGAP was demonstrated by immunoprecipitation with antibodies to either protein. An additional band at M(r) 100,000 (p100) was detected in immunoprecipitates after 12 h of phorbol 13-myristate 25-acetate treatment. Reverse transcription-PCR and immunoblot analyses suggest that p100 is type II rasGAP, an alternatively spliced product of p120 type I rasGAP. p100 was expressed only in response to direct protein kinase C activators, but all classes of differentiation agents increased tyrosine-phosphorylated p190. Rho and Rac are known to be involved in regulating actin polymerization. The results presented here show that the association of p190 with type I rasGAP parallels increases in actin polymerization and cell adhesion. This suggests a role for p190-rasGAP interactions in phorbol 13-myristate 25-acetate-induced cytoskeletal reorganization.

Base Sequence↗
PubMed1994

Frequent immunohistochemical detection of EGF supergene family members in ovarian carcinogenesis.

Primary and metastatic ovarian cystadenocarcinomas, carcinomas of low malignant potential (borderline tumors), benign ovarian cystadenomas, and normal ovaries were compared for immunoperoxidase detection of the ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin (AR), cripto, and the receptors, epidermal growth factor receptor (EGF-R), and c-erbB-2. This matrix analysis of these EGF family members indicated no specific pattern of ligand or receptor expression with a specific ovarian histologic category except in the case of AR and TGF-alpha. AR was detected almost exclusively in borderline tumors, suggesting that these tumors may not arise as a pathological continuum between benign cystadenomas and invasive cystadenocarcinomas. Second, the presence of TGF-alpha immunoreactivity in the absence of coexpression of cripto or EGF appeared to be associated only with adenocarcinomas of high grade and stage.

Amphiregulin↗
PubMed1993

Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells.

The COOH-terminal half of the amphiregulin (AR) molecule has sequence homology to epidermal growth factor (EGF). The ability of AR to elicit in vivo phosphorylation of the EGF receptor (EGFR) and p185erbB2 was studied in four human epithelial cell lines which expressed either or both of the receptor tyrosine kinases. AR induced the phosphorylation of the EGFR and p185erbB2, and phosphoamino acid analysis revealed enhanced phosphorylation of tyrosine residues in both receptor proteins. A monoclonal antibody (mAb) which binds to the extracellular domain of the EGFR blocked the phosphorylation of the EGFR and p185erbB2 as well as AR-induced mitogenesis indicating that the EGFR mediated these responses. In MDA-MB-453 cells which lack EGFRs, AR did not induce phosphorylation of p185erbB2, did not affect proliferation, and had no detectable effect on the phosphorylation of cellular proteins isolated using an anti-phosphotyrosine mAb. Qualitatively, in vivo phosphorylations induced by AR and EGF were found to be indistinguishable as demonstrated by analysis of cellular 32P-labeled proteins isolated with the anti-phosphotyrosine mAb. Moreover, in the presence of the anti-EGFR mAb, AR had no effect on the proliferation of cells. These results provide strong evidence that the EGFR is the sole cell surface mediator of the action of AR in human epithelial cells.

Amphiregulin↗
PubMed1993

Tyrosine phosphorylated proteins in chronic myelogenous leukemia.

An aberrantly expressed and highly active abl tyrosine kinase (p210bcr-abl) appears critical for the development and pathogenesis of chronic myelogenous-leukemia (CML). CML cells and cell lines each displayed a similar spectrum of phosphotyrosyl proteins. Analysis of these proteins by glycerol-gradient ultracentrifugation showed that many apparently existed as multimeric complexes. Confirming this, several of these proteins co-immunoprecipitated, along with the p210bcr-abl, with antibody to abl. Included were co-precipitating proteins identified as the p120 ras GTPase-activating protein (GAP) and the p62 protein that binds both to GAP and to a number of other tyrosine-phosphorylated proteins having peptide regions homologous to the second domain of src. Because p62, ras GAP and ras are involved in growth-factor and oncogene activation of cells, this pathway may also play an important role in CML.

Fusion Proteins, bcr-abl↗
PubMed1992

Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses.

The erbB-2 oncogene encodes a 185-kDa transmembrane protein that has been suggested to be a growth factor receptor. We have previously identified and purified a 30-kDa growth factor (gp30) that is a ligand for the p185erbB-2 protein that at high concentrations induces growth inhibition of cells with erbB-2 amplification. We now report the purification and characterization of a protein from SKBr-3 human breast cancer cells with a molecular mass of 75 kDa (p75) that is a p185erbB-2 ligand. An affinity column coupled to the extracellular domain of p185erbB-2 was used for the purification. We found that p75 induced tyrosine phosphorylation of the erbB-2 oncoprotein, as determined by in vivo and in vitro phosphorylation and phosphoamino acid analysis. p75, as well as gp30, stimulated cell proliferation and colony formation of cells overexpressing erbB-2. The specificity of this effect was confirmed by showing that the antiproliferative effects of soluble erbB-2 extracellular domain were reversed by either p75 or gp30. p75 did not show binding to the epidermal growth factor receptor and had no growth effects on cells overexpressing epidermal growth factor receptor. These data show that SKBR-3 cells, which exhibit erbB-2 amplification and overexpression, secrete a growth factor that binds and activates p185erbB-2 specifically.

Breast Neoplasms↗