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Biomedical subjects

J C Cohen

Publications and source records attributed to J C Cohen.

At least 73 records · Page 4Linked to original sources

Reassessing the effects of simple carbohydrates on the serum triglyceride responses to fat meals.

The effects of glucose, sucrose, and fructose ingestion on the serum triglyceride responses to meals containing 40 g fat were studied in 21 normolipidemic, nonobese medical students (9 men, 12 women). Mean postprandial lipemia was not significantly lower after meals containing 50 g glucose and 40 g fat than after meals containing 40 g fat alone (2.11 vs 2.42 mmol.L-1.7 h-1, p greater than 0.45) despite a substantial increase in plasma insulin concentrations after the glucose-containing meal. Ingestion of 50 g fructose and 40 g fat (4.23 mmol.L-1.7 h-1, p less than 0.0001) and 100 g sucrose and 40 g fat (3.77 mmol.L-1.7 h-1, p less than 0.001) resulted in significantly greater lipemia than did the ingestion of fat alone. These findings suggest that the ingestion of insulinogenic carbohydrates does not reduce postprandial lipemia in normolipidemic subjects and that the ingestion of fructose and fructose-containing carbohydrates may augment the postprandial lipemia induced by a fat-containing meal.

Adult↗

Hepatic prolactin binding is rapidly altered by endotoxin in lactating mice.

Endotoxin or lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, produces profound physiologic changes in most mammals. The effects of LPS on ovine prolactin (oPRL) binding by hepatic membranes of lactating mice is explored in this report. Specific 125I-oPRL binding by liver membranes from LPS-responder C3HfB/HeN mice increased two-fold within fifteen minutes of the injection of LPS, while no change was observed in the non-responder C3H/HeJ mice. Specific 125I-insulin binding did not change. Scatchard analysis of equilibrium binding of oPRL to C3HfB/HeN liver membranes indicated that within fifteen minutes of LPS injection, a receptor of differing binding affinity appears and then disappears by one hour post-injection. We propose that these rapid alterations in the specific binding of oPRL by liver membranes from LPS-injected, lactating C3HfB/HeN mice are due to the transient creation or unmasking of a novel class of PRL receptor.

Animals↗

Mammary preneoplasia and tumorigenesis in the BALB/c mouse: structure and modification of mouse mammary tumor virus DNA sequences.

Mouse mammary tumor virus (MMTV) DNA sequences were examined in mammary tissues from BALB/c mice, including both preneoplastic hyperplastic alveolar nodule (HAN) outgrowth lines, tumors derived from those preneoplastic tissues, and DMBA-induced mammary tumors. Over 60 different HAN and tumors samples were analyzed. The D2 HAN line contained one additional provirus, whereas Cv-2 and Cv-4 HAN lines that are infected with exogenous virus exhibited multiple virus integration events. D2 tumors showed the same provirus pattern as D2 HANs, whereas Cv-2 and Cv-4 tumors exhibited a subset of the acquired proviruses found in the parental HAN populations. Differential methylation patterns of virus-specific sequences were observed that resembled those described for other tissues in which viral DNA replication and integration has occurred, i.e., acquired proviruses were hypomethylated and endogenous proviruses were methylated. In tumors that arose from HAN lines and exhibited only endogenous proviruses, demethylation of the subgenomic Mtv-6 locus was observed. Demethylation of Mtv-6 was not detected in any of the preneoplastic tissues. Altered methylation of Mtv-8 and -9 was observed in both Cv-2 and Cv-4 tumors. Finally, mammary tumors induced by DMBA carried no acquired proviruses and demethylation of endogenous MMTV proviruses was demonstrated.

5-Methylcytosine↗

A DNA probe for detecting Mycoplasma genitalium in clinical specimens.

Despite decades of careful study, the etiologies of all cases of pelvic inflammatory disease (PID) and non-gonococcal urethritis (NGU) have yet to be described. Mycoplasma genitalium is a newly described organism which has been implicated as a cause of both PID and NGU. Because of fastidious growth requirements, prolonged incubation time and frequent overgrowth in clinical specimens by Mycoplasma hominis, non-culture methods need to be developed for its detection. We have cloned M. genitalium DNA by transfection into Escherichia coli using M13 as the vector. Using these segments as templates, we synthesized radiolabelled cDNAs that were tested for specific hybridization with M. genitalium, and clinically isolated genital mycoplasmas presumptively identified as M. hominis, and Ureaplasma urealyticum. A 256 base-pair segment was found to hybridize with M. genitalium with a sensitivity of 10(2) colour-changing units (CCUs). No cross-hybridization was observed with M. hominis, and cross-hybridization was observed only with large concentrations (greater than 10(6) CCUs) of U. urealyticum. Because of our choice of M13 as the vector, which contains the Lac Operon of E. coli, slight hybridization occurred with E. coli as well. This cDNA can be used against clinical specimens to determine the ecologic niche and spectrum of disease caused by M. genitalium.

DNA, Bacterial↗

Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids.

To examine the effects of anabolic steroid use on glucose homeostasis, we determined oral glucose tolerance and serum insulin response to glucose in 15 male powerlifters, 6 obese men, and 10 sedentary nonobese men. Eight of the powerlifters had self-administered large doses (200 mg/day) of anabolic steroids for periods of up to 7 yr, whereas 7 had never used anabolic steroids. Powerlifters who ingested anabolic steroids had diminished glucose tolerance compared to the nonsteroid-using group, despite having substantially higher postglucose serum insulin concentrations. Postglucose insulin responses were also higher in steroid users than in the sedentary nonobese and sedentary obese reference groups. These results indicate that powerlifters who ingest anabolic steroids have diminished glucose tolerance, which is likely to be secondary to insulin resistance.

Adult↗

Relation of scores on the Open Middle Test to self-control and academic achievement of inner-city fourth-grade children.

The construct validity of the Open Middle Test, a measure of children's social problem-solving ability, was investigated by assessing its relationship to self-control (Self-control Rating Scale) and academic achievement (Wide-Range Achievement Test). Subjects were 113 minority fourth graders from two urban parochial schools. A significant correlation was obtained between Open Middle Test effectiveness scores of first responses and WRAT Reading scores. No other correlations were significant. However, mean differences were significant for Open Middle Test effectiveness ratings of first responses and chosen responses, suggesting possible deficits in the evaluation of self-generated problem solutions. Implications of the results for training programs and for the use of the Open Middle Test as an outcome measure are discussed.

Achievement↗

Mouse mammary tumor virus gene expression regulated in trans by Lps locus.

Expression of mouse mammary tumor virus (MMTV) in the lactating mammary glands of uninfected mice varies between strains of mice in a manner largely independent of the proviral content. Previous linkage analysis in the mouse suggested that the Lps locus was associated with steady-state levels of MMTV RNA. The Lps locus mediates the mouse's response to the injection of lipopolysaccharide (LPS) in the responder mouse while mice with the deficient allele are incapable of responding. Injecting LPS-responder mice, C3HfB/HeN, and nonresponder mice, C3Hf/HeJ, with LPS resulted in a threefold increase in the level of MMTV RNA in responder mice but had no effect on nonresponders. The increased level was due to only one of the possible MMTV transcripts: the 1.7-kb transcript containing the open reading frame (orf) of the long terminal repeat (LTR). The level of MMTV-specific transcripts, then, is regulated by the Lps locus, a cellular gene which is not linked to any viral coding sequences and therefore must act in trans.

Animals↗

Cellular genes in the mouse regulate in trans the expression of endogenous mouse mammary tumor viruses.

The transcriptional activities of the eleven mouse mammary tumor virus (MMTV) proviruses endogenous to two sets of recombinant inbred (RI) mouse strains, BXD and BXH, were characterized. Comparison of the levels of virus-specific RNA quantitated in each strain showed no direct relationship between the presence of a particular endogenous provirus or with increasing numbers of proviruses. Association of specific genetic markers with the level of MMTV-specific RNA was examined by using multiple regression analysis. Several cellular loci as well as proviral loci were identified that were significantly associated with viral expression. Importantly, these cellular loci associated with MMTV expression segregated independently of viral sequences.

Alleles↗

Mouse mammary tumor virus DNA methylation: tissue-specific variation.

Mouse mammary tumor virus-specific DNA sequences endogenous to the BALB/c mouse are shown to exhibit variable levels of methylation in a tissue-specific manner. In DNA from both lactating mammary gland and spleen, MMTV-specific sequences were hypomethylated at specific HpaII and HhaI sites. These variably methylated sites were found in the terminal repetitive sequences of the endogenous viral genomes. The specific hypomethylation of a HpaII site in Mtv-9 is associated with expression of a 1.6 kb transcript in the lactating mammary gland.

5-Methylcytosine↗

[Prediction of new outbreaks of myocardial infarction, based on a multivariate meteorological analysis].

In a previous paper, meteorological circumstances of myocardial infarctions, cerebrovascular attacks, and suicidal attempts were studied by a univariate method. The present work used the same clinical reports, collected by the Medical Emergency Assistance System (SAMU) in the Paris area from 1975 to 1977, but with multivariate calculations. 150 potential predictive indicators were submitted to "progressive ascending selection". Selected indicators were then combined into a composite index by "linear canonic discrimination". This index was tested in terms of successful prediction. The 150 indicators were: 1) meteorological variables, recorded at ground level, such as wind and temperature (expressed respectively in 28 and 24 ways), airpressure, moisture; 2) variables computed from data recorded in altitude; 3) pollutants; 4) non-meteorological indicators, such as day of the week, season, solar activity; 5) the "past of the predictand", i.e. the frequency of infarctions during the previous days; 6) types of weather, defined after confronting meteorological maps with clinical data. The coding of qualitative data required a new procedure. The event to be predicted, which occurred only one day a week, was an incidence of infarctions of at least twice the average. The percentage of successful prediction was 78.7%. The type of weather was by far the best indicator. Detrimental circumstances were changing weathers, with in the order of decreasing correlations, atmosphere fluxes coming from S-SE, E, SW, and NW. These results complete those of univariate analysis. They validate a simple and efficient predictive method, similar in its principle to that used in Germany.

Epidemiologic Methods↗

Targeted integration of baboon endogenous virus in the BEVI locus on human chromosome 6.

The infection of cultured human cells with baboon endogenous virus (BEV) frequently leads to an association of viral DNA with a specific genetic locus (termed BEVI, for baboon endogenous virus infection) on chromosome 6. Restriction endonuclease digestion of DNA from BEV-infected human cells and their derived somatic cell clones frequently revealed a common cellular DNA sequence in the proximity of one of the junctions between cellular DNA and the integrated virus. We propose that a short cellular DNA sequence, repeated on chromosome 6 and separated by unique DNA sequences, presents a high-affinity target for the integration of BEV in human cells.

Animals↗

Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis.

All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA integrated as proviral sequences. This complicates efforts to define viral-induced mammary carcinogenesis. Here we report the use of surgical nonlethal splenectomy in tissue typing mice and the development of an MMTV-negative mouse strain. The MMTV-negative strain allows study of the involvement of non-MMTV genes in mammary carcinogenesis. In addition, it can be used as a sterile background into which MMTV variants can be introduced. Through the techniques described here, mice containing single MMTV loci or specific combinations can be specially chosen and rapidly developed. In this manner, the oncogenecity of particular MMTV variants may be assessed.

Animals↗

Genetic mapping of endogenous mouse mammary tumor viruses: locus characterization, segregation, and chromosomal distribution.

The restriction endonuclease EcoRI has been used to study the inheritance of strain difference in endogenous mouse mammary tumor virus DNA sequences. This enzyme, which cleaves at only one site within the nondefective viral genome, generates DNA fragments containing mouse mammary tumor virus sequences which vary in size according to the locations of EcoRI restriction sites in the flanking mouse sequences, thereby defining unique integration sites of the viral genome. Recombinant inbred strains of mice have been used to study the inheritance of these DNA fragments which hybridize to mouse mammary tumor virus cDNA sequences. The results define 11 segregating units consisting of 1 or 2 fragments. These units were shown to segregate among the recombinant inbred strains, and in some instances linkage was established. Two units were shown to be linked on chromosome 1. Another unit was mapped to chromosome 7, which is presumably identical to the previously defined genetic locus Mtv- 1. One other mouse mammary tumor virus locus was tentatively assigned to chromosome 6. The results are consistent with the view that integration of mouse mammary tumor virus can take place at numerous sites within the genome, and once inserted, these proviruses appear to be relatively stable genetic entities.

Animals↗