V beta-specific immunotoxin selectively kills acetylcholine receptor-reactive T lymphocytes from mice with experimental autoimmune myasthenia gravis

Immunization of C57BL/6 mice with purified acetylcholine receptor (AChR) is known to induce a T cell-dependent antibody response that results in experimental autoimmune myasthenia gravis (EAMG). Since past observations link V beta 6+ T cells with a prominent AChR epitope specificity, a V beta 6-specific immunotoxin (VIT6) was tested in vitro for its ability to selectively kill monoclonal and polyclonal T cells that demonstrate reactivity against AChR. Results described below clearly demonstrate the ability to selectively kill AChR-reactive T cells based on their expression of a particular V beta-associated antigen receptor.     

Validation of [13C]urea breath test for Helicobacter pylori using a simple gas chromatograph-mass selective detector

OBJECTIVE: Isotope ratio mass spectrometry (IRMS) is the accepted method for accurately measuring the 13CO2:12CO2 ratio in the non-invasive and non-radioactive [13C]urea breath test (13C-UBT) for Helicobactor pylori. The IRMS instrument, an expensive and highly specialized analyser, is rarely available. The objective of this project was to modify and validate the use of a simple bench-top gas chromatograph-mass selective detector (GC-MSD) for 13C-UBT. METHODS: Breath samples from 71 patients were taken at baseline and 30 min after ingestion of 100 mg [13C]urea. The breath samples were analysed using GC-MSD in the selected ion monitoring mode. The reference 13CO2:12CO2 ratio was from NBS19 obtained from the US National Institute of Standards and Technology. 13CO2:12CO2 ratios of the breath samples were determined. Excess delta per thousand (per mil, delta/thousand) of the 30 min sample over the baseline (deltadelta/thousand) of > or = 6deltadelta/thousand was considered H. pylori positive. Results from 13C-UBT and histology determined blind to each other were compared. RESULTS: The coefficient of variation of the reference 13CO2:12CO2 ratio was 0.06%. Using histology as the 'gold standard', the sensitivity (97.9%) and specificity (95.8%) of the GC-MSD 13C-UBT were comparable to those of other methods of H. pylori diagnosis. CONCLUSION: A gas chromatograph coupled to a mass selective detector that is available in many analytical and biomedical laboratories can be used for the 13C-UBT. This method will increase the availability and reduce the cost of this non-invasive, non-radioactive diagnostic test.     

Multiple risk factors in the development of externalizing behavior problems: group and individual differences

The aim of this study was to test whether individual risk factors as well as the number of risk factors (cumulative risk) predicted children's externalizing behaviors over middle childhood. A sample of 466 European American and 100 African American boys and girls from a broad range of socioeconomic levels was followed from age 5 to 10 years. Twenty risk variables from four domains (child, sociocultural, parenting, and peer-related) were measured using in-home interviews at the beginning of the study, and annual assessments of externalizing behaviors were conducted. Consistent with past research, individual differences in externalizing behavior problems were stable over time and were related to individual risk factors as well as the number of risk factors present. Particular risks accounted for 36% to 45% of the variance, and the number of risks present (cumulative risk status) accounted for 19% to 32% of the variance, in externalizing outcomes. Cumulative risk was related to subsequent externalizing even after initial levels of externalizing had been statistically controlled. All four domains of risk variables made significant unique contributions to this statistical prediction, and there were multiple clusters of risks that led to similar outcomes. There was also evidence that this prediction was moderated by ethnic group status, most of the prediction of externalizing being found for European American children. However, this moderation effect varied depending on the predictor and outcome variables included in the model.     

Features of the parasitic system of Ixodid ticks--Borrelia--small mammals in the Russian Northwest

BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. METHODS: In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. RESULTS: The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. CONCLUSIONS: Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency.     

Salt effects on ligand-DNA binding. Minor groove binding antibiotics

Salt dependent electrostatic effects play a central role in intermolecular interactions involving nucleic acids. In this paper, the finite-difference solution to the nonlinear Poisson-Boltzmann (NLPB) equation is used to evaluate the salt dependent contribution to the electrostatic binding free energy of the minor groove binding antibiotics DAPI, Hoechst 33258 and netropsin to DNA using detailed molecular structures of the complexes. For each of these systems, a treatment based on the NLPB equation accurately describes the variation of the experimentally observed binding constant with bulk salt concentration. A solvation formalism is developed in which salt effects are described in terms of three free energy contributions: the electrostatic ion-molecule interaction free energy, delta delta G degrees im; the electrostatic ion-ion interaction free energy, delta delta G degrees ii; and the entropic ion organization free energy, delta delta G degrees org. The electrostatic terms, delta delta G degrees im and delta delta G degrees ii, have both enthalpic and entropic components, while the term delta delta G degrees org is purely a cratic entropy. Each of these terms depends significantly on salt dependent changes in the counterion and coion concentrations around the DNA. In each of the systems studied, univalent ions substantially destabilize charged ligand-DNA complexes at physiological salt concentrations. This effect involves a salt dependent redistribution of counterions near the DNA. The free energy associated with the redistribution of counterions upon binding is dominated by the unfavorable change in the electrostatic ion-molecule interactions, delta delta G degrees im, rather than the change in the cratic entropy of ion organization, delta delta G degrees org. In addition, the observed slope of the salt dependence of the free energy is determined by electrostatic ion-molecule and ion-ion interactions as well as the cratic entropy of ion release. These findings are in contrast to models in which the cratic entropy of counterion release drives binding.     

Scope of word meaning activation during sentence processing by young and older adults

In a naming experiment, we examined word meaning activation on-line during sentence processing by younger and older adults. Sentences were biased to either the most or least frequently used meaning of a sentence-final ambiguous word. In order to determine the scope of initial meaning activation, targets represented either high- or low-salient semantic relationships to a single sense of the ambiguous word in context. Both age groups evidenced context-dependent activation of word meaning. In addition, context activated a wide scope of meaning that included both high- and low-salience aspects of the ambiguous words. These results contradict predictions based on the inhibition deficit hypothesis (Hasher & Zacks, 1988). However, they are compatible with an interactive activation model of language comprehension that does not discriminate among age groups.