Biomedical subjects

W Auerbach

Publications and source records attributed to W Auerbach.

9 recordsLinked to original sources

PubMed1994

Angiogenesis inhibition: a review.

In this review we discuss the concept of anti-angiogenesis, which is the inhibition of neovascularization. Anti-angiogenic agents are viewed from the standpoint of their effect on various elements of the angiogenic process, including induction of vascular discontinuity, endothelial cell movement, endothelial cell proliferation, and three-dimensional restructuring of patent vessels. An effort is made to place the many different approaches to anti-angiogenesis research into a comprehensible structure, in order to identify problems of evaluation and interpretation, thereby providing a clearer basis for determining promising and needed directions for further investigation.

Animals↗

PubMed1992

Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.

CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco-2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1-antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP-activated C1- transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR.

Blotting, Western↗

PubMed1991

Regulation of expression of CFTR in human intestinal epithelial cells.

As a first step in our efforts to delineate the role of CFTR in cellular phenotypes we have studied its expression in cultured human intestinal epithelial cells. In particular we have examined the effect of cellular differentiation on CFTR gene expression. CFTR mRNA was measured by quantitative densitometry of Northern blots and normalized to the amounts of pyruvate dehydrogenase message. We have found that in T84 cells the levels of CFTR mRNA do not change as the cells grow to confluence. In contrast, levels of CFTR mRNA increase by a factor of 10-20 as Caco2 cells grow after subculture. This change in the levels of CFTR mRNA is correlated with the morphological differentiation that occurs in Caco2 cells during culture. The potential significance of this observation is discussed.

Cell Differentiation↗

PubMed1991

Assays for angiogenesis: a review.

Accurate, reliable quantitation of the neovascular (angiogenic) response, both in vitro and in vivo, is an essential requirement for the study of new blood vessel growth. Over many years, ingenious ways have been developed for measuring this process, and they have contributed much to our present understanding of the vasculogenesis and angiogenesis that accompany normal embryonic development, lactation and wound healing, as well as tumor growth and a variety of other disease states ranging from diabetic retinopathy to autoimmune vasculitis. In this review we describe and evaluate the methodology and specific features of some of the most frequently used of these assays.

Animals↗

PubMed1990

Effect of alcohol on lipoprotein metabolism. II. Lipolytic activities and mixed function oxidases.

The mechanism by which alcohol increases plasma total high density lipoproteins (HDLs) and HDL-cholesterol is unknown, but it may involve modulation of the lipolytic enzymes, hepatic triglyceride lipase (HTGL) and/or lipoprotein lipase (LPL) in hepatic and extrahepatic tissues. The modulation of HDL metabolism by alcohol may also be related to its potential to induce mixed function oxidases in liver microsomes. These possibilities were examined by a pair-feeding protocol in which rats were fed diets with 35% of the caloric content as ethanol; control groups received a diet with an isocaloric amount of sucrose or were fed chow ad libitum. Alcohol caused a significant decrease in HTGL activity of liver microsomes, but there was no significant effect of alcohol upon the activities of LPL in adipose tissue and heart muscle. The relative rates of mixed function oxidases, assayed in control liver microsomes using ethoxy-,pentoxy- and benzyloxy-resorufin as substrates, were benzyloxy greater than ethoxy greater than pentoxy. This order was not affected by alcohol, but the oxidation of ethoxy- and pentoxyresorufin was reduced in liver microsomes from the ethanol-fed group. HTGL synthesis and secretion were also measured using primary rat hepatocyte cultures isolated from animals on the above dietary regimes and maintained for up to 3 days in basal medium alone or supplemented with 10 mmol/l ethanol. In basal media the order of activity of extracellular HTGL, released by the addition of heparin, was sucrose-fed greater than chow-fed greater than ethanol-fed. The rate of HTGL secretion from hepatocytes was stimulated in ethanol-containing medium, and was greater in hepatocytes from the sucrose-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1990

Transformed sweat gland and nasal epithelial cell lines from control and cystic fibrosis individuals.

We undertook to extend the in vitro lifespan of epithelial cell cultures useful for the study of the cellular defect underlying cystic fibrosis (CF). Primary cultures from sweat glands of four CF and four non-CF and from nasal polyps of one non-CF and two CF individuals were transformed using a chimaeric virus, Ad5/SV40 1613 ori-. The extended lifespans ranged from 20 to more than 250 population doublings beyond that of the primary cultures. Despite some degree of aneuploidy (as assayed by total cellular DNA content) all samples tested retained at least one copy of the region of chromosome 7 containing the CF gene (as assayed by probing with flanking DNA markers). Epithelial characteristics, including an epithelioid morphology, tight junctions and desmosomes, apical microvilli, keratin networks, and dome formation were positive in the majority of cells examined, although variably expressed. All cells tested demonstrated outwardly rectifying chloride channels by patch clamp, with some from non-CF cells responsive to the catalytic subunit of cyclic AMP-dependent protein kinase. The cells were used for DNA transfection assays with selectable marker genes in appropriate vectors, in order to develop methodology for assaying the function of the CF gene product and the effects of mutations.

Cell Division↗

PubMed1982

Regional differences in the growth of normal and neoplastic cells.

This article provides a review of the literature on anteroposterior differences in the growth and functional expression of normal and neoplastic cells. Diverse studies in immunology, wound healing, carcinogenesis, transplantation biology, and developmental biology are brought together to emphasize the practical implications of regional differences for research protocols in all these areas of research. The more fundamental question of mechanisms is approached by consideration of variations in the vascular supply, pattern of nervous system development, expression of temperature differentials, and the establishment of metabolic gradients during development.

Animals↗

PubMed1982

Hematology problem.

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Diseases in Twins↗

PubMedDate not supplied

Expression of a mutant regulatory subunit of cAMP-dependent protein kinase in the Caco-2 human colonic carcinoma cell line.

Caco-2 human colonic carcinoma cells were transfected with an expression vector encoding a mutant form of RI (regulatory subunit of the type 1 cAMP-dependent protein kinase), driven by the metallothionein 1 promoter. A stable transformant was isolated that expressed the mutant RI gene in a Zn(2+)-inducible manner. The consequences of the RI mutation on cAMP-dependent protein kinase activity, cell division, and regulation of chloride efflux were examined. When grown in the absence of ZnSO4, protein kinase activity in the transformant was stimulated 2.5-fold by cAMP and approached the levels of cAMP-dependent protein kinase activity seen in parental Caco-2 cells; when treated with ZnSO4, cAMP-dependent protein kinase activity in the transformant was inhibited by 60%. In the absence of ZnSO4 the transformant grew with the same doubling time and to the same saturation density as the untransformed parent. In the presence of ZnSO4 the transformant exhibited a cAMP-reversible inhibition of cell division, indicating that a functional cAMP-dependent protein kinase was required for the growth of these cells in culture. Induction of the mutant RI gene also abolished forskolin-stimulated chloride efflux from these cells, suggesting obligatory roles for cAMP and cAMP-dependent protein kinase in forskolin's actions on chloride channel activity. We anticipate that this transformant will be useful for further studies on the roles of cAMP and cAMP-dependent protein kinase in the regulation of intestinal epithelial cells, including regulation of cell proliferation and differentiation, and regulation of chloride channel activity by neurohormones and neurotransmitters.

Carrier Proteins↗