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R Weinstein

Publications and source records attributed to R Weinstein.

At least 91 records · Page 5Linked to original sources
PubMed1988

Radiation-induced thyroid neoplasms: evidence for familial susceptibility factors.

To determine if there is a familial component to susceptibility to radiation-induced thyroid neoplasms, we studied 572 individuals who were members of 286 sibpairs who received childhood radiation treatment and for whom follow-up information was obtained. Of these 572 individuals, 240 (42.0%) had thyroid neoplasms (benign and malignant), and 75 (13.1%) had surgically confirmed thyroid cancer. To test the null hypothesis, that neoplasm occurred without regard to family membership, it was necessary to take into account each individual's years at risk and known risk factors. These risk factors, analyzed by the proportional hazards model of Cox, were sex, age at time of radiation treatment, and treatment dose. For each individual, we calculated the cumulative hazard that a neoplasm would occur from that individual's specific risk factors and years at risk. Each individual was also assigned an indicator, D = 1 or 0, according to whether a neoplasm had occurred. Finally, for each individual we computed a residual, D minus the cumulative hazard. In the absence of familial effects, positive and negative residuals would be distributed without regard to family membership, whereas residuals would tend to have concordant signs and magnitudes within families if familial effects were present. Permutational methods, therefore, were used to determine whether the sum among families of the products of residuals within sibpairs was too large, compared to random pairing. For all thyroid neoplasms (both benign and malignant), within-family concordance was significant (P = 0.05, the observed sum among families of the products of residuals was larger than 9468 of 9999 permutations). For thyroid cancer considered alone, the same analysis did not demonstrate familial concordance conclusively, but the results were suggestive (P = 0.18). We conclude that in addition to the previously described risk factors of female sex, younger age at radiation exposure, and higher dose, it is likely that there are independent familial risk factors for developing thyroid neoplasms. Whether these are genetic or environmental factors remains to be determined.

Age Factors↗
PubMed1987

[Bonded bridges].

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Acid Etching, Dental↗
PubMed1987

Isolation and characterization of bleomycin-sensitive Chinese hamster ovary cells.

Nineteen bleomycin-sensitive Chinese hamster ovary cell mutants have been isolated using a replica plating and photography approach. As judged by the dose which reduces cell survival to 37% of the untreated control, these mutants are from 2.5- to 32-fold more sensitive to a 16-h bleomycin treatment than the parental cell, while for chronic bleomycin exposure, the increase in sensitivity was 5 to 58 times that of the parental cell. Four bleomycin-sensitive mutants had increased sensitivities to killing by gamma-rays (2- to 3-fold), mitomycin C (2-fold), and ethyl methane sulfonate (4- to 5-fold), while six other mutants were resistant to these agents. Nine other bleomycin-sensitive mutants displayed a variable pattern of cross-sensitivities to these agents. Using the technique of alkaline elution, the relative frequency of single-strand DNA breaks introduced by varying concentrations of bleomycin was examined in one mutant and its parent cell. The elution profiles of both cells were similar, suggesting that the bleomycin sensitivity of this mutant is not due to a greater frequency of single-strand breaks introduced by bleomycin.

Aminacrine↗
PubMed1987

Delayed mutation in Chinese hamster cells.

The possibility was examined that mutational events can be delayed for more than one or two cell divisions following treatment of Chinese hamster cells with the DNA alkylating agent ethyl methane sulfonate. If mutations in mammalian cells are delayed, the proportion of mutant cells in colonies grown from single mutagen-treated cells will reflect the cell division at which the mutation is genetically fixed, i.e., a first division mutation yields a 1/2 mutant colony, a fifth division mutation produces a 1/32 mutant colony, etc. In the present study, replating of cells from single colonies grown for six to seven days after mutagen treatment resulted in the discrete ratios of glucose-6-phosphate dehydrogenase (G6PD)-deficient mutant to wild-type colonies expected for a delayed mutational process which produces mutations over at least 8-10 cell generations. Further, when cells from 7- to 10-day colonies, grown from ethyl methane sulfonate (EMS)-treated cells were replated into selective medium containing 6-thioguanine (6TG), the number of 6TG-resistant colonies obtained per flask was distributed over a very wide range, consistent with a mutational delay process. These results could not be explained by differences in the number of cells per colony or plating efficiency in selective medium. Assuming that the relative number of 6TG-resistant colonies per flask reflects the time of mutation, EMS treatment produced two groups of mutational events: one which occurred within the first five cell generations and another uniformly distributed over at least the next eight to nine divisions. These results support the conclusion that EMS induces mutants for at least 10-14 cell generations after treatment and raise the possibility that current methods to assess the mutagenic potential of an agent might lead to significant underestimation. The role of delayed mutation in the phenomenon of "mutation expression time" is also discussed.

Animals↗
PubMed1987

Adrenergic receptor hyperactivity--a cause for pseudopheochromocytoma?

Two patients with classical signs and symptoms of pheochromocytoma, are described. In these two patients the 24-hr urinary excretion of dopamine, norepinephrine, epinephrine and their metabolites were normal or low, both in basal states or after attacks (spontaneous or provoked). However, the 24-hr urinary excretion of cyclic AMP was exceedingly high in one patient (13000 nmol/gm creatinine), and elevated in the second (5920 nmol/gm creatinine). Both patients were benefited by treatment with a combination of alpha and beta adrenergic blocking drugs. The first patient, after stopping treatment, developed hypertensive crisis and died. Post-mortem examination did not detect a pheochromocytoma or any other abnormality which could explain the excessively elevated cyclic AMP. In the second patient, extensive X-ray and CT examinations were negative for pheochromocytoma. A hypothesis is developed linking the symptoms and biochemical findings of both patients to an abnormality of the adrenergic receptor.

Adrenal Gland Neoplasms↗
PubMed1987

Human vascular smooth muscle cells both express and respond to heparin-binding growth factor I (endothelial cell growth factor).

The control of vascular endothelial and smooth muscle cell proliferation is important in such processes as tumor angiogenesis, wound healing, and the pathogenesis of atherosclerosis. Class I heparin-binding growth factor (HBGF-I) is a potent mitogen and chemoattractant for human endothelial cells in vitro and will induce angiogenesis in vivo. RNA gel blot hybridization experiments demonstrate that cultured human vascular smooth muscle cells, but not human umbilical vein endothelial cells, express HBGF-I mRNA. Smooth muscle cells also synthesize an HBGF-I-like polypeptide since (i) extract prepared from smooth muscle cells will compete with 125I-labeled HBGF-I for binding to the HBGF-I cell surface receptor, and (ii) the competing ligand is eluted from heparin-Sepharose affinity resin at a NaCl concentration similar to that required by purified bovine brain HBGF-I and stimulates endothelial cell proliferation in vitro. Furthermore, like endothelial cells, smooth muscle cells possess cell-surface-associated HBGF-I receptors and respond to HBGF-I as a mitogen. These results indicate the potential for an additional autocrine component of vascular smooth muscle cell growth control and establish a vessel wall source of HBGF-I for endothelial cell division in vivo.

Animals↗