Subjective and objective risk of breast cancer in Ashkenazi Jewish individuals at risk for BRCA1/2 mutations

The aims of the study were to (1) examine the differences between subjective and objective estimates of the risk of breast cancer in those being tested for BRCA1/2 mutations, (2) explore new ways to conceptualize risk, and (3) examine the change in subjective risk of developing breast cancer throughout the process of genetic counseling and testing. Participants were 86 Ashkenazi Jewish women with a family or personal history indicating risk for BRCA1/2 mutations. Surveys to assess subjective risk of breast cancer (percentage risk, projected age of onset, and survival time) were administered before counseling, after counseling, and after receipt of test results. Subjective percentage risk of breast cancer was compared to estimated objective risk to determine accuracy. Those with no personal history of cancer receiving positive results became more accurate from post-counseling to post-result. Those receiving positive results increased their estimate of their percentage risk, and those receiving uninformative negative results decreased their estimate of their percentage risk from post-counseling to post-result. Those without a personal history of cancer decreased in perceived risk from post-counseling to post-result. No change in projected age of onset of breast cancer or survival time with breast cancer was seen from pre- to post-counseling or from post-counseling to post-result, and no change in accuracy or in percentage risk of breast cancer was seen from pre- to post-counseling. Individuals use information from genetic counseling to form estimates of percentage risk following receipt of test results; however, projected age of onset and survival time with breast cancer, areas not targeted by genetic counseling that may be more closely linked to health behavior, do not change.     

Abriß über den derzeitigen Stand der Virusforschung

Ohne ZusammenfassungMit 7 Textabbildungen.     

Disturbance-driven changes in fish assemblages caused by a sudden increase in salinity in a perennial desert stream

Disturbance is a key factor in structuring fish assemblages in rivers; characterizing reactions to disturbance is especially important in systems containing endangered species due to their vulnerability to extinction. A natural disturbance event occurred in the Virgin River in 1985, when normal flow patterns changed due to the appearance of a sinkhole upstream of the hot saline Pah Tempe Springs. This led to abnormally elevated levels of temperature and salinity that propagated downstream. We examined changes in fish assemblages at five sites in a 21 km reach downstream from the hot springs in the mainstem Virgin River, which were monitored monthly (with the exception of 1 site monitored biannually) between 1984 and 1987. Specifically, we compared the responses of the different fish species in space and time. Of the six native species investigated, speckled dace, spinedace, and the endangered woundfin experienced declines in abundance at sites closest to the disturbance. In contrast, Virgin River chub, another endangered species, experienced increases in abundance in sites nearest the disturbance, and desert sucker and flannelmouth sucker showed no change. Redundancy analysis confirmed that changes in assemblage structure were significant. Differential responses to the disturbance appeared to correlate with differences in feeding ecology, with insectivores being the most affected group. In terms of recovery, species with higher abundances in neighboring sites experienced faster recoveries than those with lower abundances. This study characterizes disturbance reactions in the Virgin River, and emphasizes the susceptibility of rare species to natural disturbances and subsequent depression of recolonization rates.     

Cell wall metabolism during fruiting of the basidiomycete Schizophyllum commune

During the development of fruit bodies of the basidiomycete Schizophyllum commune, the alkali-insoluble (R glucan) and alkali-soluble (S glucan) cell wall fractions are synthesized during the entire course of morphogenesis. The water soluble glucan (WSG) is not synthesized after an early stage. There is also a relative increase in the proportion of S glucan during development which appears related to a change in the proportion of the components synthesized. Data are also presented to show that several fruiting mutants also have specific cell wall differences, and that there is a significant contribution to cell wall structure by genes which do not cause a macroscopically observable change in phenotype.     

MORPHOGENESIS OF SCHIZOPHYLLUM COMMUNE I. MORPHOLOGICAL VARIATION AND MATING BEHAVIOR OF THE THIN MUTATION

A single gene, recessive mutation of Schizophyllum commune, designated as thin, is characterized by its sparse growth on agar and unusual hyphal morphology. Many hyphae exhibit various degrees of “waviness,” although some branches of these wavy hyphae appear normal. Differences in cell size and branch development between normal and thin strains are also noted. Most of the characteristics attributed to thin vary quantitatively between strains. In addition, considerable variability in hyphal characteristics can be found in a single strain. Thin mutants behave as bilateral maters. In matings where the normal allele is present, genetic complementation occurs and normal clamped cells are produced. Fruit bodies with viable spores are formed on both the thin and normal sides of the mating. Thin X thin matings give a stable dikaryon, but they retain the thin morphology and do not produce fruit bodies. Evidence that there is only one locus for the thin mutation is presented. Certain aspects of the variability of thins, the possible role of extracellular polysaccharide, and the potential uses for thin strains in studies of hyphal and fruit body development are discussed.     

Purification and characterization of pentobarbital-induced cytochrome P-450BM-1 from Bacillus megaterium ATCC 14581

When Bacillus megaterium ATCC 14581 is grown in the presence of barbiturates, a cytochrome P-450-dependent fatty acid monooxygenase (M_r 120 000) is induced (Kim, B.-H. and Fulco, A.J. (1983) Biochem. Biophys. Res. Commun. 116, 843–850). Gel filtration chromatography of a crude monooxygenase preparation from pentobarbital-induced B. megaterium indicated that not all of the induced cytochrome P-450 present in the extract was accounted for by this high-molecular-weight component. Further purification revealed the presence of two additional but smaller cytochrome P-450 species. The minor component, designated cytochrome P-450_BM-2, had a molecular mass of about 46 kDa, but has not yet been completely purified or further characterized. The major component, designated cytochrome P-450_BM-1, was obtained in pure form, exhibited fatty acid monooxygenase activity in the presence of iodosylbenzenediacetate, and has been extensively characterized. Its M_r of 38 000 makes it the smallest cytochrome P-450 yet purified to homogeneity. Although it is a soluble protein, a complete amino acid analysis indicated that it contains 42% hydrophobic residues. By the dansyl chloride procedure the NH₂-terminal amino acid is proline; the penultimate NH₂-terminal residue is alanine. The absolute absorption spectra of cytochrome P-450_BM-1 show maxima in the same general regions as do P-450 cytochromes from mammalian or other bacterial sources, but they differ in detail. The oxidized form of P-450_BM-1 has absorption maxima at 414, 533 and 567 nm, while the reduced form has peaks at 410 and 540 nm. The absorption maxima for the CO-reduced form of P-450_BM-1 are found at 415, 448 and 550 nm. Antisera from rabbits immunized with pure P-450_BM-1 strongly reacted with and precipitated this P-450, but showed no detectable affinity for either the 46 kDa P-450 or the 120 kDa fatty acid monooxygenase.     

Comparison of developmentally controlled glucoamylase from normal and mutant strains of the basidiomycete Schizophyllum commune

During the formation of fruit bodies, the basidiomycete Schizophyllum commune produces glucoamylase activity. DEAE-cellulose chromatography resolves the enzymic activity into a major peak found early in development and a minor peak which appears when the fruit bodies are mature. A mutant homokaryon has been isolated which constitutively produces glucoamylase activity without any fruiting. When purified, the mutant enzyme and the major fruit body enzyme appear to be identical by several physical and kinetic parameters including molecular weight, temperature sensitivity, and K_m.Supported in part by NIH Research Grant AI 09779-03 from the National Institute of Allergy and Infectious Diseases.