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C Bernstein

Publications and source records attributed to C Bernstein.

62 records · Page 4Linked to original sources
PubMed1974

Coiled rings of DNA released from cells infected with bacteriophages T7 or T4 or from uninfected Escherichia coli.

The replicating intracellular DNA of phage T7 was labeled at high specific activity with tritiated thymidine. The DNA of uninfected Escherichia coli was similarly labeled. Portions of cells which contained replicating phage T7 or E. coli DNA were lysed by a lysozyme, freeze-thaw, sodium lauryl sulfate procedure, and the DNA was spread on Millipore membranes for visualization by autoradiography. The DNA of phage T7 appeared to be highly concatenated reaching lengths of up to 721 mum. Much of the DNA of phage T7 and E. coli was retained in compact globular structures. In addition, orderly coiled rings of varying diameter up to about 43 mum were regularly observed. Similar coiled ring structures were also observed in autoradiographs of replicating phage T4 DNA which had been prepared in previous experiments. Worcel and Burgi (27) have presented evidence that E. coli chromosomes, when gently extracted from cells, are in a multilooped and superhelically twisted configuration. The coiled rings which we have observed may correspond to the relaxed, multilooped configurations which they find when the superhelical twists have been relieved by one or more nicks in each loop.

Autoradiography↗
PubMed1970

A comparison of the number of nucleotides per unit length in Escherichia coli and phage T4 chromosomes.

The grain density produced in radioautographs by fully labeled bacteriophage T(4) chromosomes was compared with the grain densities produced by fully labeled and half-labeled exponential phase Escherichia coli chromosomes. Taking into account the differing molar proportions of thymidine in E. coli and T(4) chromosomes, it was seen that the two types of chromosomes have approximately equal numbers of nucleotides per unit length, indicating that their structures are the same. Using molecular weight estimates in the literature for the T(4) and related T(2) chromosomes, and the lengths obtained in the radioautographs, the T(4) chromosome was estimated to have between 1.9 and 3.6 nucleotides/3.4 A. On the basis of these values alone, the E. coli and T(4) chromosomes could be either one Watson-Crick helix in a form about equal to or more condensed than the B form, or two helices more stretched out than the B form. The length of the T(4) chromosome was 48.7 +/- 4.1 mu when dried on the dull side of Millipore membranes and 42.3 +/- 4.8 mu on the shiny side, under the conditions used. Thus, the supporting surface apparently affects the configuration of a chromosome. Further evidence is also presented in support of the conclusion that the E. coli chromosome undergoes semi-conservative replication.

Autoradiography↗
PubMedDate not supplied

Mitochondrial perturbation attenuates bile acid-induced cytotoxicity.

Hydrophobic bile acids such as deoxycholate (DOC) are known to damage liver cells during cholestasis and promote colon cancer. Cellular stresses induced by bile acids, which include mitochondrial and endoplasmic reticulum (ER) stresses, can result in apoptosis. We found that inhibition of mitochondrial complexes I-V with rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, myxothiazol or oligomycin strongly protected against DOC-induced apoptosis of HCT-116 cells. To understand the mechanism of this protection, we explored the ability of these specific inhibitors to reduce DOC-induced mitochondrial and ER stresses. Different inhibitors markedly reduced DOC-induction of mitochondrial condensation, the DOC-induced decrease in mitochondrial membrane potential and the DOC-induced dilatation of the ER (evidence of ER stress). A dramatic induction of nucleolar segregation by antimycin A and myxothiazol, two distinct complex III inhibitors, was also observed. These findings strongly implicate mitochondrial crosstalk with apoptotic signaling pathways and mitochondrial-nucleolar crosstalk in the development of apoptosis resistance in the colon.

Antimycin A↗
PubMedDate not supplied

Role of apoptosis in biology and pathology: resistance to apoptosis in colon carcinogenesis.

The overview of apoptosis presented here emphasizes cell deletion in the immune system, with particular reference to T- and B-lymphocyte development, and the in vivo and in vitro senescence of human neutrophils. Some biochemical criteria that are used to identify apoptotic cells are described. Pitfalls in using agarose gel electrophoresis as the sole method for the identification of apoptotic cells are discussed. There are multiple modes of cell death that can be identified at the morphologic level. Thus the central role of microscopic methods, and in particular, electron microscopy, as an important tool in the study of cell death mechanisms, is presented. Apoptosis has a protective role against disease and could, a priori, have an important role in either the initiation or progression of cancer. Two paradoxes concerning the relationship of tumor aggressiveness at the clinical level to mitotic activity have been explained by an evaluation of apoptotic index. In the first case, basal cell carcinomas grow slowly but show a high rate of mitosis. Here, the apoptotic rate is quite high, but just below the mitotic rate, thereby accounting for the slow rate of growth. A second instance is follicular lymphoma, which has a low rate of mitosis that is less than that described for reactive germinal centers. However, apoptosis is markedly reduced in follicular lymphomas compared with that seen in reactive germinal centers, thus providing an explanation for the progressive growth of the follicle. We present a brief description of recent work from our laboratory that indicates that apoptosis may play an important role in colon carcinogenesis. We have shown that sodium deoxycholate, the particular bile salt present in highest concentration in the colon, induces apoptosis in the goblet cells of the human colonic mucosa in an in vitro assay. The intriguing finding is that cells of the normal-appearing mucosa of colon cancer patients are resistant to bile salt-induced apoptosis. This suggests a novel hypothesis about the etiologic role of bile salts in colon cancer. The chronic presence of bile salts that accompany a high-fat diet could select for apoptosis-resistant epithelial cells in the colon over time. Thus, a resistance-to-apoptosis bioassay may prove useful as an intermediate biomarker for determining which individuals are at high risk for colon cancer.

Apoptosis↗