Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Construction and performance of a multiparameter focal plane detector for use on a QMG/2 magnetic spectrometer

The design, construction and performance of a modular, two pressure focal plane detector, 550 mm long, 1000 mm deep and with an active height of 60 mm are described. The detector has been operated with ions ranging from 50 MeV ¹H to 200 MeV ³⁶S. Typical results achieved are 0.5 mm and 0.3° for the spatial and angular resolutions, and 0.7% and 3% for the total energy and energy loss measurements. A height signal is also provided.     

Amplified primer extension assay for psoralen photoproducts provides a sensitive assay for a (CG)6TA(CG)2(TG)8 Z-DNA torsionally tuned probe: preferential psoralen photobinding to one strand of a B-Z junction

An amplified primer extension assay has been developed for quantitatively mapping the sites of psoralen photoaddition to DNA. This assay was applied to a torsionally tuned Z-DNA-probe that was specifically designed for the primer extension assay. The torsionally tuned Z-DNA forming sequence, (CG)6TA(CG)2(TG)8, forms Z-DNA in vitro at negative superhelical density: sigma = -0.05. The internal 5'-TA dinucleotide was reactive to psoralen when it existed as B-DNA. Upon the formation of Z-DNA, the internal 5'-TA no longer photobound psoralen. The torsionally tuned sequence was synthesized as an EcoRI fragment such that, when Z-DNA formed, the central 5'-AATT of the EcoRI sites was part of the B-Z junctions. The 5'-AATT sequence was not reactive with psoralen when it existed as B-DNA. When the 5'-AATT sequence existed as a B-Z junction, one strand of each junction became hyperreactive to psoralen. The TT directly 5' to the B-DNA-Z-DNA junction photobound psoralen in a strand-specific fashion. Quantitation of the relative rate of psoralen photobinding to the internal 5'-TA and the 5'-AATT at the B-Z junctions provides relationships that are characteristic of the level of supercoiling in DNA.     

Intracellular sequestration of sodium by a novel Na+/H+ exchanger in yeast is enhanced by mutations in the plasma membrane H+-ATPase. Insights into mechanisms of sodium tolerance

Sodium tolerance in yeast is disrupted by mutations in calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, which is required for modulation of Na+ uptake and efflux mechanisms. Five Na+-tolerant mutants were isolated by selecting for suppressors of calcineurin mutations, and mapped to the PMA1 gene, encoding the plasma membrane H+-ATPase. One mutant, pma1-alpha4, which has the single amino acid change Glu367 --> Lys at a highly conserved site within the catalytic domain of the ATPase, was analyzed in detail to determine the mechanism of Na+ tolerance. After exposure to Na+ in the culture medium, 22Na influx in the pma1 mutant was reduced 2-fold relative to control, consistent with a similar decrease in ATPase activity. Efflux of 22Na from intact cells was relatively unchanged in the pma1 mutant. However, selective permeabilization of the plasma membrane revealed that mutant cells retained up to 80% of intracellular Na+ within a slowly exchanging pool. We show that NHX1, a novel gene homologous to the mammalian NHE family of Na+/H+ exchangers, is required for Na+ sequestration in yeast and contributes to the Na+-tolerant phenotype of pma1-alpha4.     

Fetus-in-fetu with malignant recurrence

Fetus-in-fetu is an unusual condition in which a vertebrate fetus is enclosed within the abdomen of another fetus. These occurrences are usually benign. This report describes an instance of malignant recurrence after resection of a fetus-in-fetu.