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Biomedical subjects

C R King

Publications and source records attributed to C R King.

At least 73 records · Page 4Linked to original sources
PubMed1990

Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.

In order to investigate the prognostic significance of erbB-2 overexpression, immunohistochemical staining for the erbB-2 protein was performed on sections from paraffin blocks of 292 primary invasive breast cancers obtained from women enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-06. Positive reaction indicative of erbB-2 overexpression was observed on tumor cells in 62 (21%) samples. Women whose cancers were judged to have erbB-2 overexpression had a significantly worse overall survival (P = .0012) with twice the mortality rate of women without detectable erbB-2 expression. No statistically significant effect was evident for disease-free survival (P = .22). In multivariate analysis, detection of erbB-2 overexpression was the second most predictive independent variable for survival after nodal status. Overexpression of erbB-2 was more common among tumors of poor nuclear grade (29%) than those of good nuclear grade (12%). The association of erbB-2 overexpression with decreased survival was evident only among women with tumors of good nuclear grade. In this subgroup, erbB-2 overexpression was associated with an approximately fivefold increase in mortality rate (P = .00001). The combined predictive value of erbB-2 overexpression and nuclear grade was evident regardless of their lymph node status. These results provide evidence that detection of erbB-2 overexpression may be an independent prognostic variable for patient survival. Moreover, when combined with evaluation of nuclear grade, it may be possible to use immunostaining for erbB-2 protein to identify patients at increased risk from within a relatively low-risk group.

Antibodies, Monoclonal↗
PubMed1990

The normal erbB-2 product is an atypical receptor-like tyrosine kinase with constitutive activity in the absence of ligand.

Overexpression of the erbB-2/neu gene is frequently detected in human cancers. When overexpressed in NIH 3T3 cells, the normal erbB-2 product, gp185erbB-2, displays potent transforming ability as well as constitutively elevated levels of tyrosine kinase activity in the absence of exogenously added ligand. To investigate the basis for its chronic activation we sought evidence of a ligand for gp185erbB-2 either in serum or produced by NIH 3T3 cells in an autocrine manner. We demonstrate that a putative ligand for gp185erbB-2 is not contained in serum. Chimeric molecules composed of the extracellular domain of gp185erbB-2 and the intracellular portion of the epidermal growth factor receptor (EGFR) did not show any transforming ability or constitutive autophosphorylation when they were expressed in NIH 3T3 cells. However, they were able to transduce a mitogenic signal when triggered by a monoclonal antibody directed against the extracellular domain of erbB-2. These results provide evidence against the idea that an erbB-2 ligand is produced by NIH 3T3 cells. Furthermore, we obtained direct evidence of the constitutive enzymative activity of gp185erbB-2 by demonstrating that the erbB-2 kinase remained active in a chimeric configuration with the extracellular domain of the EGFR, in the absence of any detectable ligand for the EGFR. Thus, under conditions of overexpression, the normal gp185erbB-2 is a constitutively active kinase able to transform NIH 3T3 cells in the absence of ligand.

Animals↗
PubMed1990

Implications of erbB-2 overexpression for basic science and clinical medicine.

Overexpression of the Epidermal Growth Factor (EGF) Receptor gene and the related erbB-2 gene has been identified in human cancers derived from a variety of tissues. The overexpression of the encoded growth factor receptor proteins is functionally related to the development of the tumor. This observation has important potential consequences for the improved diagnosis and treatment of cancer. Overexpression of these proteins also provides experimental systems that facilitate the study of growth factor signal transduction.

Animals↗
PubMed1989

Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development.

Tumour metastasis is the principal cause of death for cancer patients. We have identified the nm23 gene, for which RNA levels are reduced in tumour cells of high metastatic potential. In this report we identify the cytoplasmic and nuclear Nm23 protein, and show that it also is differentially expressed in metastatic tumour cells. We also find that the human Nm23 protein has sequence homology over the entire translated region with a recently described developmentally regulated protein in Drosophila, encoded by the abnormal wing discs (awd) gene. Mutations in awd cause abnormal tissue morphology and necrosis and widespread aberrant differentiation in Drosophila, analogous to changes in malignant progression. The metastatic state may therefore be determined by the loss of genes such as nm23/awd which normally regulate development.

Amino Acid Sequence↗
PubMed1989

Heterogeneous expression of erbB-2 messenger RNA in human breast cancer.

Amplification and mRNA expression of the erbB-2 gene was analyzed in 61 samples of primary human breast carcinoma. In the 57 samples where RNA could be isolated four different expression level groups were identified. Comparison of hybridization signal with that for beta-actin revealed that erbB-2 mRNA could not be detected in 6 of 57 samples (11%), was detected at normal levels in 32 of 57 samples (56%), showed 4- to 8-fold overexpression in 8 of 57 samples (14%), and showed 16- to 128-fold overexpression in 11 of 57 samples (19%). Examination of the DNA of the same set of samples revealed 6 of 61 samples (10%) with distinct gene amplification and 6 of 61 samples (10%) with possible gene amplification. The highest levels of erbB-2 overexpression were associated with gene amplification. Samples with 4- to 16-fold overexpression of the erbB-2 mRNA occurred without evident gene abnormalities. There was no association of erbB-2 expression or gene amplification with clinical stage of breast carcinoma or axillary lymph node involvement. The clear amplification of the erbB-2 gene may be associated with a significantly shorter time to treatment failure.

Actins↗
PubMed1989

Ontogeny and distribution of cells expressing HLA-B locus-specific determinants in the placenta and extraplacental membranes.

Both the trophectoderm and the inner cell mass of the blastocyst contribute to the cell populations found in the placenta and extraplacental membranes. Previous studies have shown differences between those two embryologically distinct populations of cells in their expression of class I HLA, and further differences among trophectoderm-derived trophoblast cell subpopulations. Binding patterns for antibodies to both monomorphic and allotypic determinants on class I heavy chains have been reported. In the present study, extraembryonic cells were evaluated by immunohistology for binding of the monoclonal antibody 4E, which identifies locus-specific determinants on HLA-B. Some inner cell mass-derived cells (mesenchymal cells) acquired high levels of HLA-B as gestation progressed and other continued to express low levels at late stages of gestation (amnion cells). In contrast, throughout gestation both villous and extravillous trophoblast cells failed to express detectable HLA-B. The binding patterns for 4E followed the patterns established by a monoclonal antibody to class I HLA heavy chains (61D2), and those reported for antisera to allotypic determinants. The findings support the suggestion that trophoblast cells forming the fetal component of the maternal-fetal interface exert highly effective regulation over the expression of class I HLA.

Antibodies, Monoclonal↗
PubMed1989

Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12-21.32.

Through the use of a cDNA probe, the human erbB-2 gene was localized by in situ hybridization of normal human chromosomes at 17q11-q21. In situ hybridization of chromosomes derived from fibroblasts carrying a constitutional 15;17t(q22.3;q11.21) translocation showed that the erbB-2 gene was relocated on the rearranged chromosome 15. These results as well as grain localization on prophase chromosomes locate the erbB-2 gene at 17q12-q21.32. This localization may facilitate the search for human malignancies with chromosome changes involving the erbB-2 gene.

Base Sequence↗
PubMed1989

Parallels between neurasthenia and premenstrual syndrome.

Neurasthenia and premenstrual syndrome became medical diseases because of the historical recognition of menstruation as a medical disease. Both the nineteenth and twentieth century cultural views of women were important in the establishment of menstruation, neurasthenia and premenstrual syndrome as medical conditions. Uncertainty of diagnosis with ever expanding diagnostic criteria, therapy undertaken without an adequate physiological basis, and often adverse effects from therapy, were characteristic of the medicalization of neurasthenia and premenstrual syndrome. A recognition of the cultural basis of these conditions is essential to a better understanding of women as human beings.

Female↗
PubMed1989

Ligand-independent tyrosine phosphorylation of EGF receptor and the erbB-2/neu proto-oncogene product is induced by hyperosmotic shock.

Treatment of intact cells with media containing high concentrations of ionic and non-ionic solutes induced increased tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and the protein product of the erbB-2/neu proto-oncogene. This self phosphorylation occurred in the absence of EGF or other growth factors. High concentrations of solutes did not activate phosphorylation of either isolated EGF receptor or EGF receptor solubilized by non-ionic detergents. No evidence for receptor dimerization was found in response to hyperosmotic shock. Since receptor dimers have been implicated in the EGF-induced activation of EGF receptor, hyperosmotic shock may activate EGF receptor by a different mechanism.

Cell Line↗
PubMed1989

Obstetrics and Ernest Hemingway.

Ernest Hemingway is one of the most popular and important American writers of the 20th century. His fiction, ranging from the short story to the novel, is well known, but his medical knowledge, and in particular his knowledge of obstetrics, often is not recognized. To achieve the realistic depiction of the childbirth scenes in A Farewell to Arms required that Hemingway acquire special knowledge of obstetrics practice.

Cesarean Section↗
PubMed1989

Chorionic villus sampling: first trimester fetal diagnosis.

Chorionic villus sampling has a promising future as a method of first-trimester fetal diagnosis. Its greatest advantage, compared with amniocentesis, is the earlier diagnosis of fetal disease. Evidence from more than 20,000 pregnancies indicates the safety and reliability of this emerging method of prenatal diagnosis.

Chorionic Villi Sampling↗
PubMed1989

Innovations in human genetics education. Alternative methods of instruction in medical genetics.

A course in medical genetics for first-year medical students was developed with the use of alternative methods of instruction, including audiovisual materials and computer-assisted instruction. The use of this methodology enabled students to consider many significant areas of medical genetics, without a dependency on the traditional lecture-based instructional format. Seventy-eight percent of the students identified the alternative instructional methods as an enhancement to their education. These students performed a mean of 6% better on class examinations.

Curriculum↗
PubMed1988

Demonstration of epidermal growth factor-induced receptor dimerization in living cells using a chemical covalent cross-linking agent.

We have used the soluble covalent cross-linking agent 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDAC) to examine the capacity of epidermal growth factor (EGF) to stimulate the dimerization of purified EGF receptor, of EGF receptor in membrane preparations and in intact A431 cells. The addition of EGF either to membranes from A431 cells or to EGF receptor which was purified from A431 cells by immunoaffinity chromatography caused the appearance of a cross-linked product of Mr 340,000 which was identified using EGF receptor-specific antibodies as an EGF receptor dimer. Three independent approaches including biosynthetic labeling, surface iodination, and immunoblotting experiments were utilized to follow EGF receptor dimerization in living A431 cells. These approaches provided consistent results indicating that EGF induced rapid dimerization of EGF receptor in living cells, suggesting that this process may play a role in transmembrane signalling mediated by EGF.

Carbodiimides↗