Biomedical subjects

M E Beckner

Publications and source records attributed to M E Beckner.

9 recordsLinked to original sources

PubMed1995

Identification of a new immunoglobulin superfamily protein expressed in blood vessels with a heparin-binding consensus sequence.

A novel immunoglobulin-type protein expressed in blood vessels has been identified. The cDNA for AAMP (angio-associated, migratory cell protein) was first isolated from a human melanoma cell line during a search for motility-associated cell surface proteins. Upon analysis of the tissue distribution of AAMP, it was found to be expressed strongly in endothelial cells, cytotrophoblasts, and poorly differentiated colon adenocarcinoma cells found in lymphatics. The sequence of AAMP predicts a protein (M(r) 49,000) with distant identity (25%) to known proteins. It contains immunoglobulin-like domains [one with multiple homologies to deleted in colon carcinoma (DCC) protein], the WD40 repeat motif, and a heparin-binding consensus sequence. A 1.6-kilobase mRNA transcript of AAMP is detected in tissue culture cell lines and tissues. Affinity-purified polyclonal antibodies, anti-recombinant AAMP, and anti-peptide 189 (AAMP derived) recognize a M(r) 52,000 protein in human tissue and cellular extracts. The protein size is in keeping with the mRNA and predicted sequence. The AAMP-derived peptide, P189, contains a heparin-binding domain (dissociation constant, 14 pmol) and mediates heparin-sensitive cell adhesion. The shared expression of AAMP in endothelial cells, trophoblasts, and tumor cells implies a common function in migrating cells.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Oxyphilic papillary thyroid carcinomas.

Oxyphilic papillary carcinomas of the thyroid have not been extensively studied because they are rare. The morphology and behavior of 34 cases were described. The average age was 44.1 years, the female-to-male ratio was 3.9:1, and the average diameter of the tumors was 2.3 cm. All had papillary structures present. In 31 cases, there was capsular or parenchymal invasion. Six cancers had local lymph node metastases. The average follow-up for 29 patients was 8.1 years. Tumors reappeared in four patients; one patient died from recurrent disease, one patient with disease died due to an unrelated carcinoma, and two patients were treated successfully. Twenty-seven patients at the end of follow-up were alive with no detectable thyroid cancer. The majority of patients remained free of tumor, especially those younger than 50 years.

Adenoma, Oxyphilic↗

PubMed1991

Cell motility, a principal requirement for metastasis.

In studying the role of motility in the metastasis of tumor cells, we have described an autocrine motility factor. This agent, which stimulates random motility, probably contributes to the initial dissociation of the cells from the primary tumor mass. Extracellular matrix components, via several different mechanisms, may facilitate the crossing of biological barriers by the cells prior to the entry into the circulation. In locating at new sites, the tumor cells may be induced to exit from the circulation in response to attractants such as IGFs that could emanate from the target organ. These same growth factors could then stimulate cellular proliferation for another metastatic cycle. It is quite probable that detection of AMF may provide a new tool in cancer diagnosis. The complete characterization of AMF may also yield valuable therapeutic approaches: design of low molecular size antagonists of the attractants and antibodies that might be effective therapeutically as well as diagnostically. It seems clear, in any event, that immobilizing the tumor cell may be a crucial step in inhibiting metastasis.

Cell Line↗

PubMed1991

Tumor cell motility.

Tumor cell motility is required for invasion and metastasis. The locomotory machinery of the cell includes cell projections called pseudopodia which are regulated by a complicated linkage between cell surface receptors or sensors and the internal cytoskeleton. Recently a new class of motility stimulating cytokines have been identified. These cytokines can function as autocrine motility factors and require a pertussis toxin sensitive G protein pathway to transduce a random motile response.

Biomarkers, Tumor↗

PubMed1990

Glycolysis as primary energy source in tumor cell chemotaxis.

The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF-I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose-free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose-dose dependence of glycolytic CO2 production correlated directly with motility. In contrast, mitochondrial CO2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF-I receptor inhibited both motility and glycolytic CO2 production, indicating that both processes are receptor mediated.

Antibodies, Monoclonal↗

PubMed1990

Mitochondrial adenosine triphosphatase in the oxyphil cells of a renal oncocytoma.

Oxyphil cells are characterized by cytoplasm packed with large numbers of mitochondria. Study of these unusual cells may provide information about the regulation of mitochondrial biogenesis. Although it has been suggested that this is a compensatory proliferation due to a mitochondrial dysfunction, no such dysfunction has been well documented. In this study we considered the possibility of dysfunction in the mitochondrial enzyme F1/Fo-adenosine triphosphatase(ATPase) as a stimulating factor involved in the mitochondrial proliferation of oxyphil cells. Mitochondria isolated from frozen tissue of a renal oncocytoma showing structural integrity and purity by electron microscopy were studied. Submitochondrial particles formed by sonic disruption showed the presence of the F1 component of mitochondrial ATPase with electron microscopy which was functionally active. The oligomycinsensitive ATPase activity from the renal oncocytoma was 0.133 mumol/min.mg submitochondrial particle protein which was higher than the readings obtained from normal kidney tissue (0.091 mumol/min.mg SMP protein) obtained from hamsters. Normal human renal tissue obtained at autopsy contained only nonfunctional mitochondria and therefore could not be used as control tissue. Mitochondrial ATPase dysfunction does not appear to be the inciting factor in the proliferation of mitochondria seen in oxyphil cell metaplasia and future studies should consider other possibilities. Preliminary functional studies of this nature can be performed with properly prepared frozen surgical tissue.

Adenoma↗

PubMed1990

Solid and cystic ultimobranchial body remnants in the thyroid.

In this study we determined the incidence rate (89%) and characterized the morphology of ultimobranchial body (UBB) remnants found in 18 serially sectioned neonatal thyroid glands. Although UBB remnants are often referred to as solid cell nests, we found cystic features in 55%. Ciliated columnar cells were seen in 23%. One contained a large pseudo-papilla. The UBB cells had nuclei with features reminiscent of papillary carcinoma nuclei in that they were enlarged, oval, and contained finely dispersed chromatin when compared with follicular cell nuclei. Both papillary carcinomas and UBB remnants are common, occur as tiny, solid, or cystic thyroid entities in patients of all ages, may contain papillary structures, and share some common nuclear features. Therefore, it is important to include UBB remnants in the differential diagnosis of minute thyroid entities and to recognize their morphologic features.

Animals↗

PubMed1986

Cytologic diagnosis and ultrastructure of fine-needle aspirates of ganglion cysts.

This report describes 28 ganglion cysts in 21 patients. The presence of a colorless to pale-yellow gelatinous material in the aspirate is pathognomonic of ganglion cyst. The smears are fairly monotonous, and show abundant mucoid material, single cells resembling histiocytes, a few tight clusters of cells, some collagen fibers, and some red blood cells with altered shapes. Ultrastructural studies performed on five specimens reveal the fibroblastic and/or histiocytic nature of the cells in the aspirates.

Adolescent↗

PubMed1985

Endometrial carcinoma: nontumor factors in prognosis.

The clinical records and pathologic specimens from 150 patients with endometrial carcinoma were reviewed to test the hypothesis that constitutionally predisposed patients with evidence of endogenous hyperestrinism (i.e., obesity, hypertension, diabetes, nulliparity, leiomyomata, adenomyosis) have a more benign form of carcinoma than do patients who do not fit this profile. Our results do not support this hypothesis, but do reveal certain other prognostic indicators, in addition to factors relating to the tumor itself, including stage, grade, histologic type, and extent of invasion. These indicators include: (a) age and menopausal status--women over 50 years of age, and more impressively, postmenopausal women of any age, have less favorable histology, staging, and survival; (b) race--black women have higher-grade tumors, higher-stage tumors, and poorer survival rates than white women; (c) hyperplasia--when hyperplasia is found in the biopsy, curettage, or hysterectomy specimen, the accompanying carcinoma is of a much more favorable type and extent, and survival rates are significantly better. The reasons for these correlations are not fully understood, and possible explanations are discussed. There may be two distinct patterns of endometrial carcinoma: a prognostically favorable one arising on a background of hyperplasia predominantly in premenopausal women, and a prognostically unfavorable one, occurring principally in postmenopausal women without hyperplasia. Empirically, we advise pathologists to comment on the presence or absence of hyperplasia in any specimen in which endometrial carcinoma is diagnosed.

Adult↗