Acute pretreatment with pyrazole and ethanol: effects on glucose-induced changes in insulin and glucagon

Ethanol suppressed, in a dose-related manner, glucose-induced insulin (IRI) release and thus delayed the disappearance of glucose from the blood of rats. Pretreatment with pyrazole, an alcohol dehydrogenase inhibitor, exacerbated the effect of ethanol on IRI release, glucose tolerance and glucagon (IRG) release. These results suggest that ethanol produces glucose intolerance by inhibiting glucose-induced IRI release and by augmenting IRG release. Moreover, these findings indicate that ethanol does not have to be metabolized completely in order to produce these effects.     

Discrimination of aerobic endospore-forming bacteria via electrospray-lonization mass spectrometry of whole cell suspensions

Direct injection electrospray ionization mass spectrometry (ESI-MS) without prior analyte separation was investigated for the analysis of whole cell suspensions of bacteria. Thirty-six strains of aerobic endospore-forming bacteria, consisting of six Bacillus species and one Brevibacillus species, were studied     

Derepressed hyphal growth and reduced virulence in a VH1 family-related protein phosphatase mutant of the human pathogen Candida albicans

Mitogen-activated protein (MAP) kinases are pivotal components of eukaryotic signaling cascades. Phosphorylation of tyrosine and threonine residues activates MAP kinases, but either dual-specificity or monospecificity phosphatases can inactivate them. The Candida albicans CPP1 gene, a structural member of the VH1 family of dual- specificity phosphatases, was previously cloned by its ability to block the pheromone response MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzyme. In C. albicans a MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruption of the CPP1 gene in C. albicans derepressed the yeast to hyphal transition at ambient temperatures, on solid surfaces. A hyphal growth rate defect under physiological conditions in vitro was also observed and could explain a reduction in virulence associated with reduced fungal burden in the kidneys seen in a systemic mouse model. A hyper-hyphal pathway may thus have some detrimental effects on C. albicans cells. Disruption of the MAP kinase homologue CEK1 suppressed the morphological effects of the CPP1 disruption in C. albicans. The results presented here demonstrate the biological importance of a tyrosine phosphatase in cell-fate decisions and virulence in C. albicans.     

Measurement of α-linolenic acid in the development of edible oil flax

A thiobarbituric acid-gas liquid chromatograph combination procedure is described for rapid screening of individual or half-seeds of flax for α-linolenic acid (ALA) in the development of an edible oil flax. The thiobarbituric acid test may be used to screen as many as 1000 seeds in a single day. However, the test needs to be complemented by quantitative determination of fatty acids by gas chromatography. The latter technique has been used to analyze half-seed of flax. The combination has worked extremely well for the isolation of low ALA mutants of flax.     

Toxicity of individual naphthenic acids to Vibrio fischeri

Numerous studies have suggested that the toxicity of organic compounds containing at least one carboxylic acid group and broadly classified as "naphthenic acids", is of environmental concern. For example, the acute toxicity of the more than 1 billion m(3) of oil sands process-affected water and the hormonal activity of some offshore produced waters has been attributed to the acids. However, experimental evidence for the toxicity of the individual acids causing these effects has not been very forthcoming. Instead, most data have been gathered from assays of incompletely characterized extracts of the water, which may contain other toxic constituents. An alternative approach is to assay the individual identified toxicants. Since numerous petroleum-derived naphthenic acids and some in oil sands process water, have recently been identified, we were able to measure the toxicity of some individual acids to the bioluminescent bacterium, Vibrio fischeri. Thirty-five pure individual acids were either synthesized or purchased for this purpose. We also used the US EPA ECOSAR computer model to predict the toxicity of each acid to the water flea, Daphnia magna. Both are well-accepted toxicological screening end points. The results show how toxic some of the naphthenic acids really are (e.g., V. fischeri Effective Concentrations for 50% response (EC(50)) 0.004 to 0.7 mM) and reveal the influence of hydrophobicity and aqueous solubility on the toxicities. Comparison with measured toxicities of other known, but more minor, constituents of oil sands process water, such as polycyclic aromatic hydrocarbons and alkylphenols, helps place these toxicities into a wider context. Given the reported toxicological effects of naphthenic acids to other organisms (e.g., fish, plants), the toxicities of the acids to further end points should now be determined.     

Immunologic dysfunction in cancer

The interactions between the tumor and its host are complex, and many aspects of the immune system appear to be adversely affected directly or indirectly by the presence of the tumor. Virtually all of the processes involved in immune induction and action have been implicated in the observed deficient response in tumor-bearing patients. Improved understanding and molecular analysis of the mechanisms underlying the escape of tumors from immune surveillance may lead to the development of novel strategies for the prevention of T-cell immunosuppression in cancer patients, the development of novel immunotherapeutic strategies, and potentially prevention of tumor progression or development.     

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

The associations between serum concentrations of oestradiol, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.