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Biomedical subjects

Y Hsu

Publications and source records attributed to Y Hsu.

16 recordsLinked to original sources

A negative regulatory element in a prespore-specific promoter of dictyostelium discoideum(1).

We previously isolated several 'promoter-trap' transformants in which insertion of a promoterless beta-galactosidase gene into the genome caused expression of beta-galactosidase in specific cell types. The upstream flanking region was rescued from one transformant specifically expressing beta-galactosidase in prespore cells. We sequenced the promoter of the gene that is fused in-frame with lacZ and characterised a negative element that inhibits expression in pstO cells (a subtype of prestalk cells). Gel-retardation assays show that a developmentally regulated factor(s) recognises and binds to this element.

Amino Acid Sequence

Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations.

Release of proteins through the outer mitochondrial membrane can be a critical step in apoptosis, and the localization of apoptosis-regulating Bcl-2 family members there suggests they control this process. We used planar phospholipid membranes to test the effect of full-length Bax and Bcl-xL synthesized in vitro and native Bax purified from bovine thymocytes. Instead of forming pores with reproducible conductance levels expected for ionic channels, Bax, but not Bcl-xL, created arbitrary and continuously variable changes in membrane permeability and decreased the stability of the membrane, regardless of whether the source of the protein was synthetic or native. This breakdown of the membrane permeability barrier and destabilization of the bilayer was quantified by using membrane lifetime measurements. Bax decreased membrane lifetime in a voltage- and concentration-dependent manner. Bcl-xL did not protect against Bax-induced membrane destabilization, supporting the idea that these two proteins function independently. Corresponding to a physical theory for lipidic pore formation, Bax potently diminished the linear tension of the membrane (i.e., the energy required to form the edge of a new pore). We suggest that Bax acts directly by destabilizing the lipid bilayer structure of the outer mitochondrial membrane, promoting the formation of a pore-the apoptotic pore-large enough to allow mitochondrial proteins such as cytochrome c to be released into the cytosol. Bax could then enter and permeabilize the inner mitochondrial membrane through the same hole.

Animals

The winner and loser effect: integrating multiple experiences.

An important question in state-dependent behaviour is how multiple influences on state are integrated to determine current behaviour. Aggressive behaviour is known to be affected by a prior contest experience. Nevertheless, whether and how multiple prior fighting experiences are integrated into a fighting decision remain unexplored. In this study, individuals of Rivulus marmoratus (Cyprinodontidae), a hermaphroditic fish, were given different combinations of two prior fighting experiences to investigate: (1) the effect of penultimate experiences on the probability of winning a subsequent contest; (2) the relative effect of a recent win and loss; and (3) whether the effect of a winning experience was as short lived as observed in other species. Penultimate and recent fighting experiences were given to the test fish approximately 48 and 24 h prior to the dyadic contests, respectively. From the results of the five types of contests staged, we conclude that: (1) penultimate fighting experiences had a significant effect on the probability of winning a subsequent contest; (2) a more recent experience had a more pronounced effect than an earlier experience, which suggested that the effect of a fighting experience would decay and/or the effect of a recent experience would interfere with the effect of an earlier experience; (3) no asymmetric effect between a winning experience and a losing experience was detected; and (4) the effect of both a winning and a losing experience lasted for at least 48 h in R. marmoratus which was the maximum time tested in these experiments. The possible reasons for the differences in results among studies of experience effects on contest outcomes are discussed. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article

Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype.

Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1-hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.

Adult

Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: implications for quantitative cancer risk assessment.

Biomarkers such as DNA adducts have significant potential to improve quantitative risk assessment by characterizing individual differences in metabolism of genotoxins and DNA repair and accounting for some of the factors that could affect interindividual variation in cancer risk. Inherent uncertainty in laboratory measurements and within-person variability of DNA adduct levels over time are putatively unrelated to cancer risk and should be subtracted from observed variation to better estimate interindividual variability of response to carcinogen exposure. A total of 41 volunteers, both smokers and nonsmokers, were asked to provide a peripheral blood sample every 3 weeks for several months in order to specifically assess intraindividual variability of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels. The intraindividual variance in PAH-DNA adduct levels, together with measurement uncertainty (laboratory variability and unaccounted for differences in exposure), constituted roughly 30% of the overall variance. An estimated 70% of the total variance was contributed by interindividual variability and is probably representative of the true biologic variability of response to carcinogenic exposure in lymphocytes. The estimated interindividual variability in DNA damage after subtracting intraindividual variability and measurement uncertainty was 24-fold. Inter-individual variance was higher (52-fold) in persons who constitutively lack the Glutathione S-Transferase M1 (GSTM1) gene which is important in the detoxification pathway of PAH. Risk assessment models that do not consider the variability of susceptibility to DNA damage following carcinogen exposure may underestimate risks to the general population, especially for those people who are most vulnerable.

Adult

The reliability of the functional independence measure: a quantitative review.

OBJECTIVE: The reliability of the Functional Independence Measure (FIMSM) for adults was examined using procedures of meta-analysis. DATA SOURCES: Eleven published studies reporting estimates of reliability for the FIM were located using computer searches of Index Medicus, Psychological Abstracts, the Functional Assessment Information Service, and citation tracking. STUDY SELECTION: Studies were identified and coded based on type of reliability (interrater, test-retest, or equivalence), method of data analysis, size of sample, and training or experience of raters. DATA EXTRACTION: Information from the articles was coded by two independent raters. Interrater reliability for coding all elements included in the analysis ranged from .89 to 1.00. DATA SYNTHESIS: The 11 investigations included a total of 1,568 patients and produced 221 reliability coefficients. The majority of the reliability values (81%) were from interrater reliability studies, and the intraclass correlation coefficient (ICC) was the most commonly used statistical procedure to compute reliability. The reported reliability values were converted to a common correlation metric and aggregated across the 11 studies. The results revealed a median interrater reliability for the total FIM of .95 and median test-retest and equivalence reliability values of .95 and .92, respectively. The median reliability values for the six FIM subscales ranged from .95 for Self-Care to .78 for Social Cognition. For the individual FIM items, median reliability values varied from .90 for Toilet Transfer to .61 for Comprehension. Median and mean reliability coefficients for FIM motor items were generally higher than for items in the cognitive or communication subscales. CONCLUSIONS: Based on the 11 studies examined in this review the FIM demonstrated acceptable reliability across a wide variety of settings, raters, and patients.

Activities of Daily Living

The effect of immunostimulation on thymic innervation in the rat.

In order to test whether the thymic innervation shows morphological plasticity in response to thymic functional changes, the density of thymic innervation was determined in sterile control animals and three groups of antigenically stimulated sterile rats. Thymic function was defined from the numbers of mitotic cells present in the thymic cortex, and these were reduced by antigenic stimulation. The innervation was determined separately for the various compartments of the thymus. Nerves were present in the capsule and the septa, but could not be found in either cortex or medulla of the thymic parenchyma. A statistically significant increase in the density of innervation after antigenic stimulation was found for the vessel and the non-vessel innervation of the septa. No significant changes were found in the innervation of the capsule.

Animals

Comparison of reticuloendothelial scans with bone scans in malignant disease.

Thirty patients with histologically proven malignant disease were selected for reticuloendothelial scans and bone scans because of suspected bone or bone marrow involvement. Reticuloendothelial scans were abnormal in 83% of the patients and bone scans were abnormal in 47%. Focal defects on the reticuloendothelial marrow scan correlated better with tumor infiltration of the marrow than did diffusely abnormal scans. Focal defects were found in nine patients (30% of total), four of whom had negative or equivocal bone scans. In multiple myeloma, reticuloendothelial marrow scans were more sensitive than bone scans, but were not clearly better than bone scans in patients with solid tumors. In the interpretation of reticuloendothelial scans, consideration must be given to the effects of radiation, chemotherapy, and uremia, all of which may cause decreased reticuloendothelial uptake and falsely positive reticuloendothelial scans. Reticuloendothelial scans seem most useful for hematologic malignancies that have not been previously treated. The advantages and disadvantages of reticuloendothelial scans are discussed.

Bone Marrow

Bacillus subtilis mutant altered in spore morphology and in RNA polymerase activity.

A Bacillus subtilis mutant, that was selected for rifampin resistance produces spores with an altered morphology. The mutant spores are pleomorphic and differ both in shape and size from the wild-type spores. They frequently have an exosporium that is usually absent from wild-type spores. The mutant spores are similar to the wild-type spores in heat resistance, dipicolinic acid content, and density, but exhibit a slower rate of germination, outgrowth, and growth. In vitro studies show that the RNA polymerase of the mutant is resistant to rifampin inhibition, whereas the wild-type enzyme is completely inhibited by low concentrations of the antibiotic. Rifampin resistance and the altered spore morphology are contransformed with 100% frequency, suggesting that the altered morphology is caused by an alteration in the RNA polymerase.

Bacillus subtilis

A computerized mental patient classification system.

This paper presents the detailed logic and flow of a computerized actuarial report system based on the patient's demographic and clinical information routinely collected in a state mental health information system. Probability statements regarding the patient's diagnostic classifications, likelihood of harm to self and others, probable psychotropic drug prescription, likelihood of unauthorized absence, and prediction of length of stay are presented in the report. The multivariate linear discriminant function and linear regression are used in the calculation of the posterior probabilities and the predicted value of length of stay.

Computers