Gastric mucosal biopsy via a nasogastric tube: a nonendoscopic method for diagnosing fundic and antral mucosal gastritis and Helicobacter pylori infection in man

Synthesis of poly(gamma-glutamate) metabolites of natural folates and antifolates is a critical process. Folypolyglutamates are essential for cell proliferation. Polyglutamates of glutamate (Glu)-containing antifolates are often critical for their cytotoxic action and are relevant to antifolate resistance. However, the role of polyglutamate synthesis in selectivity is less clear. We have undertaken a research program to further define the significance of polyglutamate metabolism and to devise ways to exploit this metabolism to achieve greater therapeutic selectivity in cancer chemotherapy. This article briefly reviews several approaches tested thus far. Inhibition of folypolyglutamate synthesis should lead to cell death. Current ornithine (Orn)-containing folate-based inhibitors of the enzyme responsible for their synthesis, folypolyglutamate synthetase (FPGS), are poorly transported, apparently because of interference by the protonated delta-amine. Replacement of Orn with 4, 4-difluoroOrn, the delta-amine of which has a much lower pKa and is thus less protonated at physiological pH, was explored. Since it is unclear how polyglutamylation contributes to selectivity, we explored generic means either to eliminate or to enhance polyglutamylation. The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced. Substitution of 3,3-difluoroGlu for Glu leads to enhanced polyglutamylation (although probably only to the diglutamate), retention of target specificity, and at least equal uptake. Comparative studies of the same antifolate containing different replacements for Glu, such as gamma-tetrazole-Glu (no polyglutamylation) or 3,3-difluoroGlu (enhanced polyglutamylation), will be useful in exploring the role and significance of polyglutamylation.     

Mental health supplement to the Ontario Health Survey: methodology

OBJECTIVE: To describe the methodology of a province-wide, cross-sectional, epidemiologic study of psychiatric disorder among those aged 15 years and over living in household dwellings in Ontario. METHOD: Respondents for the survey were drawn from households (N = 13002) participating in a province-wide health survey. One person per household was selected, and 9953 (76.5%) participated. RESULTS: Participants and nonparticipants were similar to each other. An extensive array of data, including measures of psychiatric disorder classified using a revised version of the Composite International Diagnostic Interview (CIDI), are available for all respondents. CONCLUSIONS: The Ontario Health Supplement is contained in a public-use data file at the Ontario Ministry of Health and is available to investigators for study. A strong survey design, careful measurement, and acceptable levels of response provide the rationale for our inviting researchers to access and use the Ontario Health Supplement data base.     

Cardiovascular effects of conventional sulfonylureas and glimepiride

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activated KATP channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly all animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.     

Management of E. coli dependent factorial diseases in weaning piglets

The most important postweaning factorial diseases are at least partly caused by E. coli. The term postweaning coli complex can be subcategorized into the following manifestations: postweaning diarrhoea, edema disease, postweaning wasting and hemorrhagic gastroenteritis. In the presented study the effect of prophylactic zootechnique alone and zoo- and biotechnique in combination was evaluated during the first weeks postweaning. The results showed that combined zoo- and biotechnique is superior to simple zootechnique regarding food conversion (1.41 kg versus 1.73 kg), average daily weight gain (390 g versus 325 g) and postweaning piglet mortality (3.1% versus 4.9%). It is the opinion of the authors that combined postweaning zoo- and biotechnique should be performed in such pig production units where ETEC and/or SLTEC are present.     

On the selective counting of third-order products

A practical and efficient method is presented for the counting of third-order products generated by an arbitrary number of carriers with arbitrary power spectral shapes. In particular, three selective counting procedures (i.e. sorting by position, sorting by position and group, and sorting by position, group, and kind) are introduced in a systemic way, based upon a discrete third-order Volterra model. The advantage of the counting algorithm is that (1) the algorithm provides the exact counting of third-order products of all eleven possible groups; (2) the counting process requires only two multiplications for the selective counting of third-order products at each position, and the algorithm, which is thus efficient, can be easily implemented     

Mechanical behavior of double-aged AA8090

The short-transverse fracture toughness of AA8090 is dramatically improved by double aging treatments, which produce a transition from coarse planar slip to homogeneous deformation. Although the fracture mode remains intergranular, stress concentrations across the weak, highangle boundaries are reduced by homogeneous deformation, ultimately increasing fracture toughness. This behavior is attributed to dissolution of the shearable phase(δ’) and growth of the strong precipitate (S’). Predictions of slip distribution agree fairly well with observed deformation behavior. A number of tempers with improved strength-toughness relationships were developed, and fatigue crack growth behavior in laboratory air was not affected by double aging.     

Evaluation of Qbd for electrons tunneling fromthe Si/SiO2 interface compared to electron tunneling from thepoly-Si/SiO2 interface

Electrical time-to-breakdown (TTB) measurements have shown the charge to breakdown Q_bd of gate oxide capacitors fabricated on n-type well (n-well) substrates always to be higher than that of capacitors on p-type well (p-well) substrates on the same wafer when both are biased into accumulation under normal test conditions. Here the authors correlate the higher n-well Q_bd to smooth capacitor oxide/substrate interfaces and minimized grain boundary cusps at the poly-Si gate/oxide interfaces, confirming that Fowler-Nordheim tunneling is the dominant current conduction mechanisms through the oxide. They correlate higher Q_bd to higher barrier height for a given substrate type and observe that the slope of the barrier height versus temperature plot is lower for both p-well and n-well cases with electrons tunneling from the silicon substrate. This is attributed to surface roughness at the poly-Si gate/SiO₂ interface. A poly-Si gate deposition and annealing process with clean, smooth oxide/substrate interfaces will improve the p-well breakdown characteristics and allow higher Q_bd to be achieved     

Study of Desorption and Adsorption During Grain Aeration

One requirement in designing and operating and operating system is to minimize the moisture change in stored grain. Moisture transfer during the aeration process is generally believed to be caused by the partial pressure difference between water in grain and water in air (P₃-P₄). A mathematical model was developed for rough rice, which predicts the partial pressure difference under various grain and ambient conditions. Observations of moisture change over 10 aeration tests confirmed the good correlation between sorption phenomena and partial pressure differences. Studies indicated that air relative humidity, air temperature, grain temperature and grain moisture are significant factors influencing the partial pressure differences and, thus, affecting     

Aromatic nitrations by mixed acid. Slow liquid-liquid reaction regime

Aromatic nitrations by mixed acid have been selected as a specific case of a heterogeneous liquid-liquid reaction. An extensive experimental programme has been followed using adiabatic and heat-flow calorimetry and pilot reactor experiments, supported by chemical analysis. A series of nitration experiments has been carried out to study the influences of different initial and operating conditions such as temperature, stirring speed and sulphuric acid concentration. In parallel, a mathematical model to predict the overall conversion rate has been developed. In this paper the mathematical modelling and the implementation and experimental validation for benzene, toluene and chlorobenzene mononitration in the kinetic control regime (slow liquid-liquid reaction) are presented and discussed.