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B L Cohen

Publications and source records attributed to B L Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1990

A test of the linear-no threshold theory of radiation carcinogenesis.

It has been pointed out that, while an ecological study cannot determine whether radon causes lung cancer, it can test the validity of a linear-no threshold relationship between them. The linear-no threshold theory predicts a substantial positive correlation between the average radon exposure in various counties and their lung cancer mortality rates. Data on living areas of houses in 411 counties from all parts of the United States exhibit, rather, a substantial negative correlation with the slopes of the lines of regression differing from zero by 10 and 7 standard deviations for males and females, respectively, and from the positive slope predicted by the theory by at least 16 and 12 standard deviations. When the data are segmented into 23 groups of states or into 7 regions of the country, the predominantly negative slopes and correlations persist, applying to 18 of the 23 state groups and 6 of the 7 regions. Five state-sponsored studies are analyzed, and four of these give a strong negative slope (the other gives a weak positive slope, in agreement with our data for that state). A strong negative slope is also obtained in our data on basements in 253 counties. A random selection-no charge study of 39 high and low lung cancer counties (+4 low population states) gives a much stronger negative correlation. When nine potential confounding factors are included in a multiple linear regression analysis, the discrepancy with theory is reduced only to 12 and 8.5 standard deviations for males and females, respectively. When the data are segmented into four groups by population, the multiple regression vs radon level gives a strong negative slope for each of the four groups. Other considerations are introduced to reduce the discrepancy, but it remains very substantial. Since cigarette sales data are available only on a statewide basis, mean radon data for states are analyzed. The linear regression for lung cancer rates vs radon levels is also negative and has a much steeper slope than that for the county data. When cigarette sales per capita is introduced into the regression, the negative slope for dependence on radon level is essentially unchanged.

Environmental Exposure↗
PubMed1990

Ecological versus case-control studies for testing a linear-no threshold dose-response relationship.

The two basic problems with ecological studies are (A) individuals studied are not necessarily the individuals who are at risk, and (B) they are very vulnerable to confounding factors. It is shown that where the study is designed to test a linear-no threshold dose-response theory, (A) does not apply. Where the ecological study deals with the average dose and response in a large number of US counties, the available data and computer capability for reducing effects of confounders are so powerful that (B) may be no more important for the ecological than for a case-control study. The migration problem is treated and found to be relatively unimportant.

Bias↗
PubMed1990

Hyperphosphorylation of the retinoblastoma gene product is determined by domains outside the simian virus 40 large-T-antigen-binding regions.

With the murine retinoblastoma (RB) cDNA, a series of RB mutants were expressed in COS-1 cells and the pRB products were assessed for their ability (i) to bind to large T antigen (large T), (ii) to become modified by phosphorylation, and (iii) to localize in the nucleus. All point mutations and deletions introduced into regions previously defined as contributing to binding to large T abolished pRB-large T complex formation and prevented hyperphosphorylation of the RB protein. In contrast, a series of deletions 5' to these sites did not interfere with binding to large T. While some of the 5' deletion mutants were clearly phosphorylated in a cell cycle-dependent manner, one, delta Pvu, failed to be phosphorylated depsite binding to large T. pRB with mutations created at three putative p34cdc2 phosphorylation sites in the N-terminal region behaved similarly to wild-type pRB, whereas the construct delta P5-6-7-8, mutated at four serine residues C terminal to the large T-binding site, failed to become hyperphosphorylated despite retaining the ability to bind large T. All of the mutants described were also found to localize in the nucleus. These results demonstrate that the domains in pRB responsible for binding to large T are distinct from those recognized by the relevant pRB-specific kinase(s) and/or those which contain cell cycle-dependent phosphorylation sites. Furthermore, these data are consistent with a model in which cell cycle-dependent phosphorylation of pRB requires complex formation with other cellular proteins.

Animals↗
PubMed1989

Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus.

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.

Animals↗
PubMed1989

Expected indoor 222Rn levels in counties with very high and very low lung cancer rates.

Counties in the U.S. with high lung cancer rates should have higher average 222Rn levels than counties with low lung cancer rates, assuming the average 222Rn level in a county is not correlated with other factors that cause lung cancer. The magnitude of this effect was calculated, using the absolute risk model, the relative risk model, and an intermediate model, for females who died in 1950-1969. The results were similar for all three models. We concluded that, ignoring migration, the average Rn level in the highest lung cancer counties should be about three times higher than in the lowest lung cancer counties according to the theory. Preliminary data are presented indicating that the situation is quite the opposite: The average Rn level in the highest lung cancer counties was only about one-half that in the lowest lung cancer counties.

Cohort Studies↗
PubMed1988

Gamete intrafallopian tube transfer (GIFT): making laparoscopy more than "diagnostic".

Diagnostic laparoscopy is commonly performed on patients as part of a complete infertility investigation. Recently published protocols have investigated the efficacy of using empiric ovulation induction, intrauterine insemination, or both before beginning in vitro fertilization. Because many patients enrolled in these protocols will be exposed to both ovulation induction and diagnostic laparoscopy, the authors reasoned that it would be more effective to begin ovulation induction at the time of the proposed diagnostic laparoscopy in order to allow gamete intrafallopian tube transfer (GIFT) at the same time. Twenty-five nulliparous patients underwent diagnostic GIFT. There were eight continuing pregnancies in this group (32%). Diagnostic GIFT is a more effective use of the opportunity provided by laparoscopy than diagnostic laparoscopy alone.

Adult↗
PubMed1987

Alternatives to the BEIR relative risk model for explaining atomic-bomb survivor cancer mortality.

The apparent failure of the BEIR absolute risk model to explain the data on the Japanese atomic-bomb survivors does not imply that the BEIR relative risk model (RRM) is correct. RRM is objectionable in that it fits the data only in conjunction with an assumption not in accord with current knowledge and thinking. Contrary to what is widely believed, RRM is not a consequence of, or consistent with, initiator-promoter theories; models derived from initiator-promoter theories fit the data with fewer adjustable parameters and without requiring unpalatable assumptions. The preferable models give substantially lower radiation risks.

Age Factors↗
PubMed1987

Tests of the linear, no-threshold dose-response relationship for high-LET radiation.

It is pointed out that induction of lung cancer by exposure to Rn daughters, applied at high doses to miners and at low doses to exposures in homes, provides a very stringent and sensitive test of the linear, no-threshold dose-response relationship for high-LET radiation, because this relationship predicts that a substantial fraction of lung cancer among non-smokers is due to average Rn levels. Therefore, it predicts an easily observable elevation of lung cancer rates in areas where Rn levels are many times greater than the average, especially at times before cigarette smoking began to have important effects on lung cancer statistics. While more data are needed (and will be forthcoming), some of the early indications of these studies are reviewed here. Several cases are now known where average Rn levels are very high, and in all of these cases lung cancer rates are well below average. Methods for analyzing these data are discussed, and it is concluded that, based on current evidence, they indicate at least a factor of 4 disagreement with linear, no-threshold predictions.

Air Pollutants↗