Chemistry of the pyrrolo[1,2-alpha]benzimidazole antitumor agents: influence of the 7-substituent on the ability to alkylate DNA and inhibit topoisomerase II

This study addresses the influence the 7-substituent on the cytotoxicity of pyrrolo[1,2-alpha]-benzimidazole quinones possessing a 6-aziridinyl group (PBIs) and a 6-acetamido group (APBIs). Reduction of a PBI to the aziridinyl hydroquinone results in both nucleophile trapping (alkylation) and 1,5-sigmatropic shift reactions. The latter process is essentially an internal redox reaction wherein the hydroquinone causes reductive opening of the aziridinyl ring. The 7-substituent controls the fate of the aziridinyl ring by means of steric and electronic effects. An electron-rich 7-substituent favors the 1,5-sigmatropic shift reaction. If the 7-substituent distorts the 6-aziridinyl group from the conformation required for the 1,5-sigmatropic shift, then nucleophile trapping occurs. The 7-methyl substituent results in significant nucleophilic trapping, and the 7-unsubstituted and 7-methoxy substituents favor the 1,5-sigmatropic reaction. Thus, the 7-methyl PBIs show the most cytotoxicity of the analogues studied. The APBIs are cytotoxic only as quinones, and reduction to the hydroquinone results in loss of activity. Consistent with this observation, the change from 7-methyl to the more electron-rich 7-methoxy results in a substantial loss of APBI cytotoxicity as well as decreased topoisomerase II inhibition. The mechanism of inhibition is thought to involve the interacalation of only electron deficient APBIs into DNA.     

The effects of growth hormone in children with a GH deficiency: a report of 5 cases

The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone deficiency in prepubertal age, treated with human growth hormone. In four of five cases the response to treatment with GH was relevant. Only in one case (F1) the response was negative. The results of this study confirm that rhGH is a safe and effective therapy in children with GHD.     

Low-temperature phase transformation in Li-10 at. % Mg

It is not known whether impaired hematopoiesis noted during human immunodeficiency virus (HIV) infection results from infection of stem/progenitor cells or of cells of the bone marrow microenvironment. Normal adherent primary stromal layers were exposed to HIV to determine which of this mixture of endothelial cells, fibroblasts, and macrophages are susceptible to the virus. Viral p24 in supernatants was noted with monocytotropic HIV-1Ada, HIV-1Ba-L, and HIV-1JR-FL but not with lymphotropic HIV-1LAI nor HIV-1MN strain, and only stromal macrophages expressed the viral antigens. Coculture of the layers with PHA-activated normal lymphocytes failed to rescue lymphotropic virus. No p24 was produced when macrophage-depleted stromal cells were exposed to either HIV-1Ba-L or HIV-1LAI; proviral DNA was then amplified by PCR in cells exposed to either virus, though coculture with lymphocytes rescued only HIV-1Ba-L. Altogether, these data indicate that macrophages are the major targets of HIV in cultured stromal layers. As virus replication in macrophages did not affect the profile of major cytokines involved in regulating hematopoiesis, HIV infection could alter hematopoiesis by other as yet unspecified mechanisms.     

Nitric oxide reduction and carbon monoxide oxidation over carbon-supported copper-chromium catalysts

Carbon supported copper-chromium catalysts are shown to be very active for both the reduction of nitric oxide with carbon monoxide and the oxidation of carbon monoxide with oxygen. Mixed copper-chromium oxide active phases have good activity in the simultaneous removal of nitric oxide and carbon monoxide from exhaust gases. The influence of several catalyst variables has been investigated. The activity per volume of catalyst increases with increasing loading, while the intrinsic activity shows a maximum around C/M=100−50. An optimum catalyst for nitric oxide reduction and carbon monoxide oxidation has a copper/chromium ratio of 2/1. The apparent activation energy for the carbon monoxide oxidation over carbon supported copper-chromium catalysts is 77 kJ/mol, suggesting that the Cu---O bond rupture is the rate-limiting process. The reduction of nitric oxide takes place at higher temperatures. Since all catalysts have a low selectivity for molecular nitrogen formation at lower temperatures, the dissociation of nitric oxide is probably rate determining, resulting in a slightly reduced catalyst system. In an excess of carbon monoxide the reaction is first-order in nitric oxide and zero-order in carbon monoxide. Moisture inhibits the reaction by reversible competitive adsorption, whereas carbon dioxide does not. Oxygen completely inhibits the reduction of nitric oxide due to the more rapid reoxidation of the catalytic sites compared to nitric oxide. Therefore, the reduction of nitric oxide takes place only when all oxygen has been converted and, hence, is shifted to higher temperatures. As a possible consequence, the production of nitrous oxide is reduced. Nitric oxide and molecular oxygen react preferentially with carbon monoxide, so, in an excess of oxidizing component, gasification of the carbon support occurs at higher temperatures after carbon monoxide has been completely consumed.     

Health promotion and empowerment: reflections on professional practice

Recent reformulations of health promotion focus on empowerment as both a means and an end in health promotion practice. Both concepts, however, are rarely examined for their assumptions about social change processes or the potential of community groups, professionals, and institutions to create healthier living situations. This article attends to some of these assumptions, expressing ideas generated during 6 years of professional training workshops with over 2,500 community health practitioners in Canada, New Zealand, and Australia. The article first argues that health promotion is not a social movement but a professional and bureaucratic response to the new knowledge challenges of social movements. As such, it has both empowering and disempowering aspects. The article analyzes empowerment as a dialectical relation in which power is simultaneously given and taken, and illustrates this in the context of health promotion programs. A model of an empowering professional (institutional) health promotion practice is presented, in which linkages among personal services, small group supports, community organizing, coalition advocacy, and political action are made explicit. Practice examples are provided to illustrate each level of the empowering relation, and the article concludes with a brief discussion of the model's educational and organizational utility.     

Predictive equation for acquisition of hepatitis B in hospital workers in a general hospital

A cross-sectional study was performed to obtain risk factors for hepatitis B disease, HBsAg carriers and immunised personnel, among 2470 workers in a general hospital in Madrid, Spain. The data obtained were analyzed with multiple logistic regression to obtain beta coefficients for variables. The results of the analysis show that being a nurse or being regularly exposed to blood are the most important risk factors for hepatitis B acquisition. The length of time working at the same job activity was also a risk factor. The resulting beta coefficients allow the construction for a hepatitis non-immunised, HBsAg carrier and immunised HBV status, which can select subjects for a hepatitis B vaccination program.     

The evolution of custom microarray manufacture

Given the enormous size of the genome and that there are potentially many other types of measurements we need to do to understand it, it has become necessary to pick and choose one's targets to measure because it is still impossible to evaluate the entire genome all at once. What has emerged is a need to have rapidly customizable microarrays. There are two dominant methods to accomplish custom microarray synthesis, Affymetrix-like microarrays manufactured using light projection rather than semiconductor-like masks used by Affymetrix to mass manufacture their GeneChip/sup TM/ arrays now, or the ink-jet printing method employed by Agilent. The manufacture of these custom Affymetrix-like microarrays can now be done on a digital optical chemistry (DOC) machine developed at the University of Texas Southwestern Medical Center, and this method offers much higher feature numbers and feature density than is possible with ink-jet printed arrays. On a microarray, each feature contains a single genetic measurement. The initial DOC prototype has been described in several publications, but that has now led to a second-generation machine. This machine reliably produces a number of arrays daily, has been deployed against a number of biomedical questions, is being used in new ways and has also led to a number of spin-off technologies.     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.     

Functional Properties and Food Applications of Rapeseed Protein Concentrate

Rapeseed protein concentrate (RC), prepared with 2% hexameta-phosphate, was tested for its functionality and performance in some foods. The RC had good nitrogen solubility, fat absorption, emulsification, and whipping capacities but poor water absorption and gelling properties. It increased the emulsion stability, and protein but lowered the fat content of wieners. It also increased the cooking yield, reduced the shrinkage and tenderized meat patties. Results were similar to soybean isolate except for the poorer color and flavor. The cooking yield of RC supplemented wieners was less than the all-meat control and soybean-supplemented wieners. A 9% RC dispersion mixed with an equal volume of eggwhite produced a meringue of comparable stability and texture to that of eggwhite alone.