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C Bernstein

Publications and source records attributed to C Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of nitric oxide and peroxynitrite in bile salt-induced apoptosis: relevance to colon carcinogenesis.

Previous work from our laboratory indicated that the bile salt sodium deoxycholate (NaDOC) induced apoptosis in cultured cells and in normal goblet cells of the colonic mucosa. We also reported that the normal-appearing flat mucosa of patients with colon cancer exhibited apoptosis resistance. Using immunofluorescence in conjunction with confocal microscopy, we now report that high physiological concentrations (0.5 mM) of NaDOC result in the formation of nitrotyrosine residues, a footprint for the formation of reactive nitrogen species, including peroxynitrite, in plasma membrane-associated proteins of HT-29 cells. Because peroxynitrite is formed from the reaction between nitric oxide and superoxide anion, we specifically looked at the role of nitric oxide and superoxide anion in NaDOC-induced apoptosis. Pretreatment of cells with the inhibitor/antioxidants, N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, copper (II) 3,5-diisopropyl salicylate hydrate, a superoxide dismutase mimetic compound, and Trolox, a water-soluble analog of alpha-tocopherol, alone or in combination, sensitized cells to apoptosis induced by 0.5 mM NaDOC. These results suggest that nitric oxide may be part of a signaling pathway that is responsible for apoptosis resistance. The results also indicate that nitric oxide does not appear to protect cells against NaDOC-induced apoptosis by scavenging superoxide anion.

Apoptosis↗
PubMed1998

The stress-response proteins poly(ADP-ribose) polymerase and NF-kappaB protect against bile salt-induced apoptosis.

Bile salts induce apoptosis and are implicated as promoters of colon cancer. The mechanisms by which bile salts produce these effects are poorly understood. We report that the cytotoxic bile salt, sodium deoxycholate (NaDOC), activates the key stress response proteins, NF-kappaB and poly(ADP-ribose) polymerase (PARP). The activation of NF-kappaB and PARP, respectively, indicates that bile salts induce oxidative stress and DNA damage. The pre-treatment of cells with specific inhibitors of these proteins [pyrrolidine dithiocarbamate (NF-kappaB inhibitor) and 3-aminobenzamide (PARP inhibitor)] sensitizes cells to the induction of apoptosis by NaDOC, indicating that these stress response pathways are protective in nature. Colon cancer risk has been reported to be associated with resistance to apoptosis. We found an increase in activated NF-kappaB at the base of human colon crypts that exhibit apoptosis resistance. This provides a link between an increased stress response and colon cancer risk. The implications of these findings with respect to apoptosis and to colon carcinogenesis are discussed.

Apoptosis↗
PubMed1997

Sexual communication.

Sexual communication refers to the use of signals to promote or modulate sexual interaction. We suggest that these signals operate at three levels: (a) a primary level at which signals are used to increase the likelihood of sexual interaction between two individuals; (b) a secondary level at which signals inhibit inbreeding or facilitate outbreeding; and (c) a tertiary level at which signals allow selection among potential mates. Evidence is cited that the selective advantage of the primary, secondary and tertiary levels are, respectively, repair of DNA damage, masking of mutation, and selection for fitness in the mating partner. We illustrate how these advantageous processes are facilitated by sexual communication in bacteria, fungi, protozoa, insects, plants and vertebrates.

Adaptation, Physiological↗
PubMed1997

Expression of N-acetyl-D-galactosamine associated epitope in synovium: a potential marker of glycoprotein production.

OBJECTIVE: To investigate synovial glycoprotein production in situ, a novel monoclonal antibody (Mab), A13D8, was used to evaluate the expression of an epitope containing N-acetyl-D-galactosamine (GalNAc) in normal and pathological synovium. METHODS: Immunohistological and cytochemical analysis of synovial tissue samples was undertaken with single and double staining techniques using the A13D8 Mab, anti-CD68, vascular cell adhesion molecule-1 (VCAM-1), the hyaluronan associated enzyme uridine diphosphoglucose dehydrogenase (UDPGD), and the anti-Golgi Mab SSN/HR-1992. The specificity of the A13D8 Mab was established through blocking studies using carbohydrate residues, including GalNAc and N-acetylglucosamine (GlcNAc). RESULTS: A13D8 is expressed intensely in the cytoplasm of normal type B lining cells, which coexpress VCAM-1 and UDPGD, and is not expressed by CD68+ type A lining cells. In the lining layer of RA synovium, there is a negative correlation between A13D8 expression and the level of lymphocytic infiltration in the sublining areas (r = -0.43, p < 0.001). The endothelium of a subset of venules, typically in lymphocyte-rich aggregates, also stains intensely for A13D8. Pretreatment of the Mab with GalNAc completely eliminates the tissue staining, as well as the 110 kDa band seen on immunoblot, whereas pretreatment of A13D8 with GlcNAc and lactose has no effect. Double staining of HEp-2 cells with A13D8 and the anti-Golgi Mab SSN/HR-1992 reveals co-localization of the A13D8 epitope to the Golgi apparatus. CONCLUSION: Type B synovial lining cells and selected synovial endothelium express GalNAc containing epitope identified by Mab A13D8. Marked reduction in the expression of this epitope in the lining layer of inflamed RA synovium suggests that the synovial production of GalNAc containing glycoproteins, such as mucins, may be altered in this disorder.

Acetylgalactosamine↗
PubMed1996

Reduced bile acid-induced apoptosis in "normal" colorectal mucosa: a potential biological marker for cancer risk.

Dietary factors, including bile acids, are important in the causation of colorectal cancer (CRC). We have previously shown that in vitro exposure of colorectal mucosal biopsies to low concentrations of bile acids produces apoptosis selectively in goblet cells. Apoptosis is an important mechanism for clearing DNA-damaged cells. Inhibition of apoptosis would result in increasing accumulation of DNA-damaged cells, resulting in increased cancer risk. We compared the percentage of apoptosis induced by bile acids in mucosal biopsies from CRC patients with that of noncancer subjects. Mucosal biopsies from 15 to 20 cm from the anal verge were incubated in 1 mM sodium deoxycholate, and the percentage of goblet cells undergoing apoptosis was quantitated. Seven patients with a history of CRC within the previous 5 years were compared with 18 noncancer subjects [4 neoplasia free and 14 with small (< or = 9 mm) polyps only]. The CRC patients had a significantly lower percentage of apoptosis than noncancer subjects; the mean for CRC was 10.7% (range, 0.9-26%) and for noncancer subjects was 55.9% (range, 20.3-71%; P < or = 0.001). Two other noncancer patients had very high-risk lesions, i.e., large villous adenomas and multiple large polyps during several colonoscopies over the previous 6 years. Their percentage of apoptosis was in the cancer range, i.e., 6.2 and 10.7%. Reduced apoptotic ability may imply increased cancer risk. By applying a quantitative bile acid-induced apoptosis assay to colorectal mucosal biopsies, the percentage of apoptosis was found to be significantly reduced in CRC patients. This assay may prove to be a useful intermediate biological marker for identifying subjects at increased risk of cancer.

Aged↗
PubMed1996

The angry pope.

Explore the source record for details and available documents.

Catholicism↗
PubMed1996

Bile acid activation of the gadd153 promoter and of p53-independent apoptosis: relevance to colon cancer.

Bile acids are strongly implicated in the etiology of colon cancer. Bile acids also induce apoptosis, and this action may be a key to understanding their role in colon cancer. However the mechanism of bile acid induction of apoptosis is not known. We present evidence of bile acid activation of the gadd153 promoter (a promoter activated by DNA damaging agents). We also show that bile acid induction of apoptosis is p53-independent. In addition, bile salts were found to induce blebbing preceding the actual morphological onset of apoptosis, which indicates early cytoskeletal alterations.

Journal Article↗
PubMed1995

Apoptosis overview emphasizing the role of oxidative stress, DNA damage and signal-transduction pathways.

Apoptosis (programmed cell death) is a central protective response to excess oxidative damage (especially DNA damage), and is also essential to embryogenesis, morphogenesis and normal immune function. An understanding of the cellular events leading to apoptosis is important for the design of new chemotherapeutic agents directed against the types of leukemias and lymphomas that are resistant to currently used chemotherapeutic protocols. We present here a review of the characteristic features of apoptosis, the cell types and situations in which it occurs, the types of oxidative stress that induce apoptosis, the signal-transduction pathways that either induce or prevent apoptosis, the biologic significance of apoptosis, the role of apoptosis in cancer, and an evaluation of the methodologies used to identify apoptotic cells. Two accompanying articles, demonstrating classic apoptosis and non-classic apoptosis in the same Epstein-Barr virus-transformed lymphoid cell line, are used to illustrate the value of employing multiple criteria to determine the type of cell death occurring in a given experimental system. Aspects of apoptosis and programmed cell death that are not covered in this review include histochemistry, details of cell deletion processes in the sculpting of tissues and organs in embryogenesis and morphogenesis, and the specific pathways leading to apoptosis in specific cell types. The readers should refer to the excellent books and reviews on the morphology, biochemistry and molecular biology of apoptosis already published on these topics. Emphasis is placed, in this review, on a proposed common pathway of apoptosis that may be relevant to all cell types.

Animals↗
PubMed1995

Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. I. Induction of classic apoptosis by the bile salt, sodium deoxycholate.

In this study, we examined the effect of different concentrations of sodium deoxycholate (NaDOC), a secondary bile salt, on an Epstein-Barr virus transformed human lymphoid cell line (NC-37). We found that NaDOC induces classic apoptosis in a dose-dependent manner at 0.1-0.4 mM doses, and necrosis at much higher concentrations (0.8-3.1 mM). This is the first demonstration that a bile salt can induce apoptosis in any cell type. The mode of cell death was determined using morphologic methods (light and electron microscopy) as the gold standard. Standard agarose gel electrophoretic techniques were applied to identify the "ladder" of DNA fragments that have been associated with apoptosis in certain cell types. Although DNA fragmentation was observed during the apoptotic death of NC-37 cells, we were not able to identify a "ladder" pattern of fragmentation. Two other types of cells, however, that previously have been reported to display a characteristic "ladder" pattern of DNA fragmentation, glucocorticoid-treated WEHI7.2 cells and isolated human neutrophils, did display the "ladder" pattern. This study emphasizes the need to examine morphology when identifying the mode of cell death induced by a new agent.

Apoptosis↗
PubMed1995

Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. II. Induction of non-classic apoptosis ("para-apoptosis") by tritiated thymidine.

There is an extensive literature dating back to the late 1950's, on the damaging biological effects of radiolabeling DNA in vivo. Nonetheless, tritiated thymidine has often been used to label DNA in studies of programmed cell death (apoptosis). In the present study, we have investigated the effects of incorporation of tritiated thymidine into the DNA of an Epstein-Barr virus-transformed cell line (NC-37) in the absence of any other apoptosis-inducing agent. Cells were incubated in media containing 1-20 microCi/ml [methyl-3H]-thymidine ([3H]-TdR). At each concentration of tritiated thymidine used, cell proliferation ceased within 12 hours of incubation. The mode of cell death caused by tritiated thymidine incorporation was evaluated using DNA degradation patterns and cellular morphology. DNA degradation, in the absence of a "ladder" pattern, was shown by agarose gel electrophoresis. Electron microscopy was used as the "gold standard" to evaluate the specific morphologic type of cell death that accompanied the DNA degradation. Although some of the features of apoptosis were present, the cells lacked the early margination of the chromatin within an intact nucleus and surface blebbing leading to apoptotic body formation, two characteristic morphological features of apoptosis. We, therefore, coined the term "para-apoptosis" to be more precise about the morphologic type of cell death. The percent of para-apoptotic cells was quantitated by light microscopy using whole mount preparations (cytospins). The morphologic criteria of chromatin condensation, nuclear fragmentation, increase in cell density and cytoplasmic vacuolization were used for the evaluation of para-apoptosis by light microscopy of cytospin preparations. In the absence of tritiated thymidine, < 2% of the cells became apoptotic/para-apoptotic after 43 hours of incubation. However, at all concentrations of tritiated thymidine used in the incubation medium (1-20 microCi/ml), the number of para-apoptotic cells increased. In addition, we detected perturbations in the timing of the cell cycle of the surviving cells and an increase in the number of micronuclei after only one division cycle. The induction of para-apoptosis and micronuclei formation represent two distinct modes of cell death caused by tritiated thymidine incorporation. These studies emphasize the necessity for morphological examination in characterizing the induction of cell death in a new experimental system.

Apoptosis↗
PubMed1994

State of the cart.

Food on wheels: it's here, there and everywhere. But while some operations rev up cart expansion plans, others have shifted into low gear. Here's an update on that '90s phenomenon: mobile merchandising.

Entrepreneurship↗
PubMed1992

Oxidative and other DNA damages as the basis of aging: a review.

DNA damages occur continuously in cells of living organisms. While most of these damages are repaired, some accumulate. In particular, there is evidence for DNA damage accumulation in non-dividing cells of mammals. These accumulated DNA damages probably interfere with RNA transcription. We consider that the decline in the ability of DNA to serve as a template for gene expression is the primary cause of aging. Oxidative DNA damages are among the best documented and prevalent DNA damages and are likely to be a prominent cause of aging.

Aging↗