Hemolytic substitution

Keywords Free radicals, antioxidants, selenium, tellurium, hemolytic substitution, chiral stannanes, enantioselective... 

Scheme 8 Generation of acyl radical by intramolecular hemolytic substitution at sulfur...

Gas phase hemolytic substitution by H at Si is fast if other Si atoms attached... 

Mlnisci, F., Porta, 0., AdvatKes in Hemolytic Substitution tf Heteroaromatic Compounds, 16,123. 

G. H. Williams, Hemolytic Aromatic Substitution. Pergamon Press, London, 1960. 

K7. Kanno, H Fujii, H and Miwa, S., Low substrate affinity of pyruvate kinase variant (PK Sapporo) due to a single amino acid substitution (426Arg- Gln) associated with hereditary hemolytic anemia. Blood 81,2439-2441 (1993). 

M2. Maeda, M and Yoshida, A., Molecular defect of a phosphoglycerate kinase variant (PGK-Mat-sue) associated with hemolytic anemia Leu - Pro substitution caused by T/A - C/G transition in exon 3. Blood 77, 1348-1352(1991). 

M14. Matsuura, S., Igarashi, M Tanizawa, Y., Yamada, M., Kishi, F Kajii, T Fujii, H., Miwa, S Sakurai, M., and Nakazawa, A., Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of cytosolic adenylate kinase. J. Biol. Chem. 264, 10148-10155 (1989). 

Addition of the silyl radical to carbon-carbon double bonds is an elementary reaction of radical hydrosilation (Scheme 1). Homolytic aromatic silationalso occurs involving silyl radicals. Silyl radicals are nucleophilic owing to the high SOMO energy, as evidenced by the directive effects in the hemolytic aromatic substitution. The intermediate cyclohexadienyl radicals have been observed by ESR. 

Koshi K, Kohyama N, Myojo, et al. 1991. Cell toxicity, hemolytic action and clastogenic activity of asbestos and its substitutes. Ind Health 29 37-56. 

Sabine, represent spontaneous mutations. The effect of the substitution can be extremely mild (Hb-Richmond, Hb-I-Toulouse) to severe (Hb-Bibba, Hb-Hammersmith). Subjects with Hb-Zurich are asymptomatic unless exposed to oxidant drugs causing an acute hemolytic episode with formation of Heinz bodies. Particularly severe is the lesion in Hb-Hammersmith because the removal of phenylalanine GDI is accompanied by the introduction of the polar OH group of serine which probably facilitates the entry of water into the heme pocket which causes the heme group to drop out (P14). Substitution of this phenylalanine by leucine, as in Hb-Louisville, results in a much less severe anemia (K9). 

Table 3A lists the residues of the a and the p chain which are involved in the aijSi contact the positions of these residues within the chains can also be found in Figs. 1 and 2. Six variants involving substitutions in this contact have been reported (Table 3A). Three (Hb-G-Chinese, Hb-Chiapas, and Hb-Khartoum) do not cause clinical symptoms in the heterozygote. Carriers of the other three variants suflfer from a mild hemolytic anemia with erythrocytosis and an increased oxygen affinity in the Hb-Tacoma heterozygote, and a decreased oxygen affinity in the carrier of the Yoshizuka variant.

In 16 renal transplant patients with suspected ciclosporin nephrotoxicity, the addition of mycophenolate allowed safe reduction in the dosage of ciclosporin, with subsequent improvement in renal function and arterial blood pressure over 6 months (1). It might allow the rapid withdrawal of glucocorticoids in patients taking ciclosporin or tacrolimus, and therefore reduce the incidence of glucocorticoid-induced post-transplant diabetes, hypercholesterolemia, and hypertension (2). There have been several reports of patients with ciclosporin-associated thrombotic micro-angiopathy/hemolytic-uremic syndrome in whom mycophenolate was successfully substituted (3,4). 

Itano HA, Hollister DW, Fogarty WM, Jr, et al. Effect of ring substitution on the hemolytic action of arylhydrazines. Proc SocExp Biol Med. 1974 147(3) 656-658. 

Both of the C4 loci are highly polymorphic, with at least 13 known alleles for C4A and at least 21 for C4B, in addition to deletions and nonexpressed genes. Most of the alleles are due to substitutions in the a-chain, although a few variants of the P-chain have also been reported. Either or both loci may be deleted, unexpressed, or duplicated as a result, a given individual may have zero to four copies of each locus. Both the total C4 level and the ratio of C4A to C4B depend on the number of copies of each locus. Most C4A variants have 25% to 35% of the hemolytic activity of the C4B alleles one, C4A6, has little if any hemolytic activity and no C5 con-vertase activity. 

Only three cases of aldolase deficiency have been described. Beutler et aF have described a boy with an unstable enzyme with mental retardation and hemolytic anemia and dysmorphic features. Kishi et al described a patient with severe hemolytic anemia, exacerbated by infection, but none of the features described by Beutler et al. Kishi identified the mutation, leading to a conversion of aspartic acid at position 128 to glycine. Kreuder et ai reported on a boy with hemolytic anemia and myopathy caused by aldolase A deficiency. They identified a mutation, causative of an amino acid substitution at position 206 (Glu to Lys). 

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