Influence of Threshold Stress on the Estimation of the Weibull Statistics

The influence of threshold stress on the estimation of the Weibull statistics is discussed in terms of the Akaike information criterion. Numerical simulations show that, if sample data are limited in number and threshold stress is not too large, the two-parameter Weibull distribution is still a preferred choice. For example, the fit of strength data of glass and ceramics to the two- and three-parameter Weibull distributions is compared.     

Induction of c-fos and c-jun proto-oncogene expression by asbestos is ameliorated by N-acetyl-L-cysteine in mesothelial cells

Asbestos fibers cause dose-dependent, persistent increases in mRNA levels of c-jun and c-fos proto-oncogenes in rat pleural mesothelial (RPM) cells, the progenitor cells of asbestos-induced mesothelioma (N. Heintz, Y. M. W. Janssen, and B. T. Mossman. Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Here we report that addition of N-acetyl-L-cysteine decreases asbestos-mediated induction of c-fos and c-jun mRNA levels in a dose-dependent fashion. Exposure of RPM cells to asbestos causes depletion of total cellular glutathione, a response that can be abolished by pretreatment with N-acetyl-L-cysteine. Pretreatment of cells with buthionine sulfoximine, an agent which diminishes glutathione pools, increases the magnitude of induction of c-fos and c-jun mRNA by asbestos. To determine whether asbestos-induced effects on proto-oncogene expression could be attributed to extracellular generation of active oxygen species (AOS), RPM cells were exposed to H2O2 or xanthine and xanthine oxidase, a generating system of AOS. These oxidant stresses did not decrease cellular glutathione levels nor alter mRNA levels of c-fos or c-jun. However, increased mRNA levels of manganese-containing superoxide dismutase and heme oxygenase were observed, indicating that RPM cells respond to AOS by increased expression of genes encoding antioxidant enzymes. These data indicate that the signaling pathways leading to c-fos/c-jun proto-oncogene induction by asbestos are not triggered directly by formation of extracellular AOS. However, intracellular thiol levels appear to influence the expression of c-fos and c-jun, suggesting a redox-sensitive component in the signaling cascade which modulates gene expression of c-fos and c-jun by asbestos.     

A comparison of gene organization in the zwf region of the genomes of the cyanobacteria Synechococcus sp. PCC 7942 and Anabaena sp. PCC 7120

The region of the genome encoding the glucose-6-phosphate dehydrogenase gene zwf was analysed in a unicellular cyanobacterium, Synechococcus sp. PCC 7942, and a filamentous, heterocystous cyanobacterium, Anabaena sp. PCC 7120. Comparison of cyanobacterial zwf sequences revealed the presence of two absolutely conserved cysteine residues which may be implicated in the light/dark control of enzyme activity. The presence in both strains of a gene fbp, encoding fructose-1,6-bisphosphatase, upstream from zwf strongly suggests that the oxidative pentose phosphate pathway in these organisms may function to completely oxidize glucose 6-phosphate to CO2. The amino acid sequence of fructose-1,6-bisphosphatase does not support the idea of its light activation by a thiol/disulfide exchange mechanism. In the case of Anabaena sp. PCC 7120, the tal gene, encoding transaldolase, lies between zwf and fbp.     

Rail-to-rail amplifier input stage with constant g/sub m/ and commonmode elimination

A new scheme for achieving rail-to-rail input to an amplifier is introduced. Constant g/sub m/ and common mode removal is obtained by using a single input differential pair and tunable DC level shifters via multiple input floating gate transistors. The feedback circuitry basically fixes the common mode of the amplifier, resulting in consistent and stable operation for rail-to-rail inputs and a high common mode rejection ratio.     

Does Physiological Blood Glucose Control Require an Adaptive Control Strategy?

To test the hypothesis that only an adaptive algorithm would guarantee optimal feedback control of glycemia in insulin-dependent diabetes, fasting chronically diabetic dogs at rest were subjected to short-term artificial beta cell treatment. Insulin was applied intravenously and an oral glucose load was given during the experiment. Employing the same dosing algorithm, three different control strategies were employed in a random order on different days: adaptive control (minimum variance controller, Test A), fixed command control using on-line parameter estimates (Test B), and fixed command control using off-line individually optimized dosage constants (Test C). Comparison was made to nondiabetic control animals. The glycemic profiles were entirely normal in Test A and C, but were distinctly elevated in Test B. The peripheral hyperinsulinaemia could, however, not be avoided by adaptive control. It is concluded that the restoration of physiological blood glucose control in insulin-dependent diabetes requires dosage parameters which are either continually adapted to the actual situation (adaptive control) or are optimized to meet the individual's needs. In the latter case, fixed command control may be employed. Peripheral hyperinsulinaemia cannot be avoided as long as insulin is administered by a posthepatic route.     

Protein phosphorylation: technologies for the identification of phosphoamino acids

Protein phosphorylation plays a central role in many biological and biomedical phenomena. In this review, while a brief overview of the occurrence and function of protein phosphorylation is given, the primary focus is on studies related to the detection and analysis of phosphorylation both in vivo and in vitro. We focus on phosphorylation of serine, threonine and tyrosine, the most commonly phosphorylated amino acids in eukaryotes. Technologies such as radiolabelling, antibody recognition, chromatographic methods (HPLC, TLC), electrophoresis, Edman sequencing and mass spectrometry are reviewed. We consider the speed, simplicity and sensitivity of tools for detection and identification of protein phosphorylation, as well as quantitation and site characterisation. The limitations of currently available methods are summarised.     

Culture and characterization of sinusoidal endothelial cells isolated from human liver

BACKGROUND: Epidemiologic data concerning skin diseases in many rural areas in sub-Saharan Africa are not available. Little is known about the effect of regular treatment schedules by paramedical staff (especially community health workers) in the primary healthcare system on the severity and prevalence of dermatoses. METHODS: 5780 school and pre-school children from 13 primary schools in four sublocations in rural western Kenya (Kisumu District) were examined for dermatoses by the author, together with community health workers in 1993. On-the-spot training and weekend seminars about important and common dermatoses were also given. In 1994 a dermatology program was started within the primary healthcare system. Twelve trained community health workers carried out regular school visits once a week and diagnosed and treated pupils with dermatoses. Treatment was performed with gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses, benzylbenzoate emulsion 25% for scabies, and hydrocortisone acetate 1% cream for eczemas. All schools were visited again in 1995 to evaluate the long-term effects of the program. RESULTS: In 1993, the prevalence rate for dermatoses was 32.4%. Most of the skin diseases found were of infective origin (27.1% were caused by bacteria, 21.6% by fungi, and 17.6% by arthropods, mainly scabies mites). Dermatitis accounted for 3.5%. In 1995, the prevalence of dermatoses declined to 29.6% (p<0.05), and this reduction was most strongly observed for tropical ulcers and tinea capitis. Additionally, there was an improvement in the extent and severity of skin diseases. CONCLUSIONS: This study defines, for the first time, the number and extent of skin diseases in children in rural Kisumu District; most dermatoses were of infective origin. The study demonstrates that community health workers in the primary healthcare system are capable of dealing successfully with the most common dermatoses in children following a short training period.     

Does carbohydrate-deficient transferrin predict the severity of alcohol withdrawal syndrome?

Alcohol withdrawal often causes severe complications. However, many addicts deny any abuse. Thus, the diagnosis of alcohol abuse frequently becomes difficult. Laboratory parameters are often used to support the diagnosis of alcohol abuse. Furthermore, laboratory parameters should facilitate the prediction of the severity of alcohol withdrawal syndrome (AWS). The most promising laboratory parameter indicating a recent elevated alcohol consumption is carbohydrate-deficient transferrin (CDT). The aim of this study was to examine whether the measurement of CDT at admission can indicate a higher risk for the development of a complicated AWS. The severity of AWS was assessed by the AWS scale, consisting of two subscales for somatic and mental symptoms. CDT was measured by different methods (radioimmunoassay and HPLC). The radioimmunoassay for CDT (CDTect) yielded the best prediction. Our results showed a weak correlation between CDTect and the severity of AWS. However, there were great gender differences. In men, CDTect had the highest positive predictive value for a severe AWS (86.7%), whereas in women mean corpuscular volume was the best predictor (77.8%). However, the sensitivity of CDTect in men (25.5%), as well as mean corpuscular volume in females (29.2%), was too low for a screening test in a general hospital.     

Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium

Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.