Studies on the vasoactive toxins of the black widow spider Latrodectus hesperus.
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Biomedical subjects
Publications and source records attributed to H Gonzalez.
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In order to determine whether a deficiency in immunologic response predisposes certain children to recurrent infections of the urinary tract, four groups of children were investigated: a control group; children with extraurinary infections; children with urinary tract infections; and a group of children treated with trimethoprim-sulfamethoxazole (TMP-SMX). In none of the groups were there changes in humoral immunoglobulins, peripheral neutrophil counts, serum complement concentrations or urinary excretion of IgG, IgA, or IgM that might might predispose to infection. However, children with urinary tract infections were more likely to belong to blood group A (66.6%; expected frequency, 45%) and had a blunted thymidine uptake of their stimulated lymphocytes (RLB) when compared with children with extraurinary infection. As well, their nitroblue tetrazolium reduction (NBT) was significantly lowered and this paralleled their RLB response. We postulated a shared antigenic feature of either their renal-urinary tissue or bacterial antigen with blood group A antigen; this prevents the mounting of an effective immunologic defence. If TMP-SMX further depresses the lymphocyte response, it may be considered contraindicated in urinary tract infection. In 11 children treated with this drug we found no significant difference between their RLB and NBT responses and those of children with infections of the urinary system treated with other drugs. We conclude that TMP-SMX does not alter the immune responses in children.
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Cationic polymers show promise for the in vitro and in vivo delivery of macromolecular therapeutics. Known cationic polymers, e.g., poly(L)lysine (PLL) and polyethylenimine (PEI), have been employed in native and modified forms for the delivery of plasmid DNA (pDNA) and reveal varying levels of toxicity. Here, we report the preparation of a new class of cationic polymers that are specifically designed to deliver macromolecular therapeutics. Linear, cationic, beta-cyclodextrin (beta-CD)-containing polymers (CD-polymers) are synthesized by copolymerizing difunctionalized beta-CD monomers (AA) with other difunctionalized comonomers (BB) such that an AABBAABB product is formed. The beta-CD polymers are able to bind approximately 5 kbp pDNA above polymer to DNA (+/-) charge ratios of 1.5, compact the bound pDNA into particles of approximately 100-150 nm in size at charge ratios above 5+/-, and transfect cultured cells at charge ratios above 10+/-. In vitro transfections with the new beta-CD-polymers are comparable to the best results obtained in our hands with PEI and Lipofectamine. Some cell line-dependent toxicities are observed for serum-free transfections; however, no toxicity is revealed at charge ratios as high as 70+/- in transfections conducted in 10% serum. Single IV and IP doses as high as 200 mg/kg in mice showed no mortalities.
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