Early detection of abdominal pregnancy by maternal serum AFP+ screening.
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Biomedical subjects
Publications and source records attributed to B L Cohen.
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The linear theory used to extrapolate the cancer risk of radon exposure from high levels where direct data are available to low levels encountered in homes is tested by comparing lung cancer rates, m, and average radon levels, r, in numerous U.S. states and counties. It is shown that most problems normally associated with ecological studies do not apply here. The data show a very strong tendency for lung cancer rates, corrected for smoking prevalence (S), to decrease with increasing r, in sharp contrast to the opposite behavior predicted by the theory. It is shown that even a perfect negative r-S correlation cannot explain this discrepancy. Actual r-S correlations are only a few percent. Several other possible explanations for the discrepancy are explored, but none can reduce it by more than about 25%.
Evidence that low-level radiation substantially enhances the effectiveness of repair mechanisms is summarized. This finding destroys the theoretical basis (there is no other basis) for use of a linear-no threshold dose-response relationship to estimate the cancer risk of exposure to low-level radiation. Such a methodology will exaggerate the risk. This conclusion is further supported by epidemiological evidence and by studies of the effects of radon exposure in the home, which are reviewed.
A recently published compilation of average radon levels in 1,729 U.S. counties with standard errors of approximately 20% is used to generate maps exhibiting these results and showing correlations over multicounty areas. Several large areas and numerous smaller areas with high radon levels are identified.
If a life insurance company provided free radon tests to clients, clients' life expectancies would be extended and profits would thereby be increased. This effect is quantified and it is found that the direct monetary benefits to the company could be substantial. Several subsidiary advantages are also discussed.
Correlations are studied between average radon levels in 1600 U.S. counties and mortality rates in them from various types of cancer. By far the strongest correlation is with lung cancer, but the sign of the correlation is negative. When smoking prevalence is included in a multiple regression, the large negative correlation between radon and lung cancer is essentially unaffected.
Since retroviruses integrate preferentially into transcriptionally active loci, the provirus may come under the control of regulatory elements of the gene into which it integrated and thus become a functional tag for that gene. In order to determine the frequency of retroviral integration near active endogenous enhancer elements, a retroviral enhancer trap vector was constructed. Lacking the long terminal repeat enhancer, expression of the neomycin resistance (neo) gene, used as a reporter, is dependent upon endogenous enhancer elements able to activate the long terminal repeat promoter. Infection of murine fibroblast cells indicated that a high proportion of the proviral copies expressed the neo gene. Infection of hematopoietic lines confirmed this high frequency of expression of integrated proviruses. Overall, between 43 and 74% of proviruses integrated into several different cell lines expressed the neo gene. These data suggest that retroviral integration is not only dependent upon transcriptional activity of the genomic target sites, but, more specifically, retroviruses preferentially integrate near active enhancer elements which are often associated with developmentally regulated genes.
In addition to retinoblastoma and osteosarcoma, mutation of both alleles of the RB1 gene occurs frequently in several other types of tumors. In order to evaluate the role of RB1 in cancer, the wild type RB1 gene was introduced into the RB1-deleted breast cancer cell line MDA-468-S4 and retinoblastoma cell lines WERI-Rb1 and Y-79. The RB1 complementary DNA was under control of the inducible murine metallothionein promoter in MDA-468-S4 and the thymidine kinase promoter in the retinoblastoma lines. The protein, p110RB1, produced from the exogenously introduced gene appeared normal by immunoprecipitation, Western blot analysis, and nuclear localization and also showed normal cell cycle-dependent phosphorylation and an ability to bind to E1a protein. No changes in growth rate or morphology were observed in either of the reconstituted cell types. Expression of p110RB1 in MDA-468-S4 did not affect anchorage-independent growth when measured by colony formation in soft agar. Although the ability of WERI-Rb1 cells expressing p110RB1 to form colonies in methylcellulose was reduced, the reconstituted retinoblastoma cell lines formed intraocular tumors in immunodeficient mice with the same efficiency as the RB1-negative parent cell lines and the tumors produced by the RB1-reconstituted cells continued to express p110RB1. These experimental results suggest that the malignant phenotype is little affected by the replacement of p110RB1 and that RB1 is a relatively weak tumor suppressor gene.
A nationwide study by random-digit-dialing telephone interviews was used to estimate f, the average percentage of people's lifetimes, f, spent within 25 miles of their residence at time of death. The result is f approximately 70%, much larger than expected from census data on migration. Except for deaths in Florida, California, and Arizona, f greater than 50% in all areas of the United States. For over half the U.S. population, f greater than 90%.
The causes of retinoblastoma (RB) can now be described with considerable accuracy, although many details are still unclear. Understanding the genetic changes leading to RB has provided an awareness of general mechanisms of cancer development and progression, previously only suspected. From the basic understanding have come new diagnostic technologies that are now ready to be applied directly to RB patients and their families, and a rational approach, based on this understanding, will help us to develop new therapies that avoid the severe complications of conventional treatment.
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Results of 175,000 purchased Rn levels are presented by county and by state. Bias elimination techniques are described, and correlations with random selection-no charge studies are presented.
Data are analyzed on measurements of Rn levels in numerous U.S. homes, accompanied by responses to questionnaires. Substantial (but far from complete) bias reduction was accomplished using questionnaire responses, leaving 37,000 measurements in living areas and 33,000 in basements for the analysis. Variables studied included: level with respect to ground where measurement was made, room type, age of house, recent weatherization actions, draftiness, location (urban, suburban, rural), air pollution, market value of house, annual household income, educational attainment of head of household, cigarette smoking, whether the house is rented or owner occupied, and geographic section of U.S. Geometric mean Rn levels were determined for each response to questionnaire items (correlations) and for each pair of responses (cross correlations). Many interesting correlations and cross correlations were found, and their explanation and consequences are discussed.
A large variety of risks are quantified in terms of the loss of life expectancy they cause in the United States. Risks considered include the following: diseases; accidents of various types at home, at work, in public, and in motor vehicles; unemployment; poor social connections; use of small cars; smoking; air pollution; other environmental pollutants leading to cancer and non-cancer effects; purposely ingested substances; sports participation; geography; medical care; epidemics; natural hazards; socioeconomic factors; Rn and other radiation; and energy conservation. A few suggestions for applications of this catalog of risks are offered.
Results are presented from approximately 9000 Rn measurements made in New York state, North Carolina, and South Carolina. The estimated statewide geometric mean concentrations were 28.1 Bq m-3 and 55.8 Bq m-3 for basements in New York state, 27.5 Bq m-3 for living rooms and 108.9 Bq m-3 for basements in North Carolina, and 25.0 Bq m-3 for living rooms in South Carolina.
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A rapid and reliable purification procedure is described that is useful for both analytical detection and quantitative recovery of milligram amounts of individual molecular variants of mouse alpha-fetoprotein (AFP). The appropriate separation conditions were developed with an analytical-size Mono Q anion-exchange column linked to an automated Fast Protein Liquid Chromatography system. Effective separations of fetal-derived AFP variants was accomplished within 20 min under mild conditions with an L-histidine buffer. Employing the optimal separation conditions established on the Mono Q HR 5/5 column we upscaled the procedure by using a preparative Mono Q HR 16/10 column in order to obtain milligram quantities of each molecular variant of AFP. Seven distinct isomeric forms of AFP could be recovered on the preparative anion exchanger in a highly reproducible manner. Each of the seven protein peaks eluted from the Mono Q column were confirmed to be distinct isoforms of AFP by isoelectric focusing and Western blotting developed with monospecific anti-AFP antisera. This method in its scaled up version offers the benefit of providing milligram quantities of immunochemically pure AFP isomers for structure and function studies.