Dietary deficiency of cystine and methionine in rats alters thiol homeostasis required for cyanide detoxification

Nutritional status is an important factor in modulating the metabolic fate of xenobiotics. Sulfur amino acid (SAA) deficiency has been proposed as a risk factor for human neurological diseases among protein-poor populations subsisting on the cyanophoric plant cassava. Female Sprague-Dawley rats were used to develop and define a model of SAA deficiency for use in future studies examining cassava-related neurotoxicity. Rats were kept in metabolic cages for 7-21 d and fed a balanced diet (BD) of known composition or a comparable diet selectively deficient in methionine and cystine (SAA-free diet). Animals fed the SAA-free diet failed to thrive, lost body weight, excreted porphyrinic materials, and showed a steep and persistent reduction of urinary inorganic sulfate. In contrast, animals on the BD gained body weight and maintained baseline output of urinary inorganic sulfate. Urinary thiocyanate excretion did not differ between groups, but plasma thiocyanate concentrations reached double that in SAA-deficient rats. Increased plasma thiocyanate suggests mobilization of sulfur amino acids from endogenous sources. Liver glutathione and blood cyanide concentrations were similar in animals on the BD and the SAA-deficient diet. In summary, a diet free of methionine and cystine results in increased retention of inorganic sulfur as thiocyanate and a near absence of inorganic sulfur excretion in urine.     

Formation of topoisomerase II alpha complexes with nascent DNA is related to VM-26-induced cytotoxicity

Several clinically active anticancer drugs are known to interfere with DNA topoisomerase II activity. However, the importance of the individual alpha (170 kDa) and beta (180 kDa) isozymes as targets of topoisomerase II-active drugs is not clear. To address this question, human CCRF-CEM leukemia cells were incubated with bromodeoxyuridine, and either the nascent DNA or bulk DNA not undergoing replication was purified by immunoprecipitation with an anti-bromodeoxyuridine antibody. The topoisomerase II isozymes that coprecipitated with either the nascent DNA or bulk DNA were analyzed by Western blotting. The alpha isozyme formed complexes with nascent DNA in cells pretreated with either VM-26 or mitoxantrone, while the beta isozyme was only bound to bulk DNA. At moderately cytotoxic concentrations, VM-26 enhanced the binding of topoisomerase II alpha to nascent DNA at least 5.2-fold compared to bulk DNA. However, in VM-26 resistant CEM/VM-1 cells incubated with equitoxic concentrations of VM-26, topoisomerase II alpha complex formation with nascent DNA was decreased at least 5.5-fold compared to bulk DNA. Drug-induced binding of topoisomerase II beta with bulk DNA in CEM/VM-1 cells did not correlate with cytotoxicity. Collectively, these results indicate that the formation of VM-26 stabilized complexes of topoisomerase II alpha with nascent DNA are critical to the development of cytotoxicity, and that resistance of CEM/VM-1 cells to VM-26 is related to impaired formation of these complexes. The results also provide indirect evidence that topoisomerase II alpha is involved in DNA, replication.     

Role of endoscopic injection therapy in the treatment of bleeding peptic ulcer

Transforming growth factor beta (TGF beta) was examined regarding its regulation of the mitogen EGF. A431 human epidermoid carcinoma cells were treated with TGF beta and epidermal growth factor (EGF) (10 ng/ml each) to determine if TGF beta modulates EGF-induced Ca2+ signaling and c-Fos oncoprotein levels. Changes in [Ca2+]i were determined by digital imaging analysis or photon counting. In HBSS + Ca2+ (1.37 mM), EGF treatment resulted in a transient increase in [Ca2+]i from 75 to 150 nM, which lasted approximately 3.5 min and re-equilibrated to 90 nM. In nominally Ca(2+)-free (2-5 muM) HBSS, EGF caused a [Ca2+]i elevation that peaked at 140 nM and returned to baseline. TGF beta in HBSS + Ca2+ did not elicit a [Ca2+]i increase, although affinity labeling revealed types I, II, and III TGF beta receptors. TGF beta added simultaneously with EGF in HBSS + Ca2+ caused a gradual rise in [Ca2+]i from 50 to 100 nM over 16 min. Pretreatment with TGF beta (3 h; 10 ng/ml) abolished the EGF-induced [Ca2+]i elevation. EGF or TGF beta treatments increased c-Fos immunoreactivity by around 1 h. In summary, EGF elevated [Ca2+]i in the presence or absence of [Ca2+]e, resulting in high [Ca2+]n, associated with tyrosine and threonine phosphorylation, and increased c-Fos oncoprotein immunoreactivity. TGF beta did not increase [Ca2+]i but did increase c-Fos; TGF beta + EGF added simultaneously altered the EGF-induced [Ca2+]i elevation, and TGF beta pretreatment eliminated EGF-induced [Ca2+]i elevation. This suggests that TGF beta can regulate EGF in A431 cells and that increased c-Fos may not be mediated by Ca2+.     

Pioneer Venus Sounder Probe Solar Flux Radiometer

The Solar Flux Radiometer aboard the Pioneer Venus Sounder Probe operated successfully during its descent through the atmosphere of Venus. The instrument measured atmospheric radiance over the spectral range from 400 to 1800 nm as a function of altitude. Elevation and azimuthal measurements on the radiation field were made with five optical channels. Twelve filtered Si and Ge photovoltaic detectors were maintained near 30°C with a phase-change material. The detector output currents were processed with logarithmic transimpedance converters and digitized with an 11-bit A/D converter. Atmosphetic sampling in both elevation and azimuth was done according to a Gaussian integration scheme. The serial output data averaged 20 b/s, included housekeeping (sync, spin period, sample timing and mode). The data were used to determine the deposition of solar energy in the atmosphere of Venus between 67 km and the surface along with upward and downward fluxes and radiances with an altitude resolution of several hundred meters. The results allow for more accurate modelling of the radiation balance of the atmosphere than previously possible.     

Electrical properties of laser-annealed donor-implanted GaAs

A Q-switched ruby laser has been used to anneal GaAs implanted with selenium or tellurium ions. Electron concentrations in the range 1?2 × 1019 cm?3 were measured for samples implanted at room temperature or 200°C with a dose of 1?5 × 1015 ions cm?2. High electrical activities were obtained both with and without Si3N4 coatings.     

The design and evaluation of online help for Unix EMACS: capturingthe user in menu design

The card-sort technique and cluster analysis were used for determining an effective organization for a help menu in Unix EMACS. Similarity data were gathered for with a card-sorting task using EMACS commands, and a hierarchical cluster analysis of the data was performed. The results indicate that differences among novices, intermediates, and experts appear with computer-based concepts such as windows and buffers, but that the sorts are more similar than they are different. It is argued that cluster analysis may aid designers in determining a functional organization, but that in the domain of this study, this organization may not help users bridge the mapping from real world tasks to computer tasks     

THE EMBRYO OF BARLEY IN RELATION TO MODIFICATION OF THE ENDOSPERM

Differential dissection of the embryo of barley grains, followed by observation of the extent of modification and assessment of α-amylase production in the endosperm, has shown that the various organs of the embryo make the following different contributions to modification. The isolated scutellum has a very limited ability to produce α-amylase and its powers of enzyme secretion are largely restricted to the peripheral region where aleurone cells are present. The stimulus which initiates enzyme formation in the aleurone is largely derived from the nodal region of the embryo, especially from the base of the node where subsidiary rootlets are formed; the scutellum apparently lacks the means of producing this stimulus. Translocation of the enzyme-inducing hormone from embryo to aleurone takes place through the apical half of the scutellum in which vascular tissue develops; this preferred route of translocation partially accounts for the asymmetric pattern of modification normally observed. Removal of the first foliar leaf from within the coleoptile allows increased production of α-amylase in the endosperm: this leaf can be regarded as a natural consumer of gibberellin.