Ferritin enhances production of DNA strand breaks by 6-hydroxydopamine,ascorbic acid and H2O2 in CCC PM2 bacteriophage DNA

Damage of CCC PM2 DNA by 6-hydroxydopamine (6-OHDA) and ascorbic acid (AA), compounds that are both able to release iron from ferritin, was significantly enhanced in the presence of ferritin. H₂O₂, a product of 6-OHDA autoxidation, did not induce DNA strand breaks in the absence of ferritin and only to a minor extent in the presence of ferritin. DNA damage by 6-OHDA and AA could be reduced by the hydroxyl radical scavenger mannitol, the iron chelator desferrioxamine, and, partly, by a combination of superoxide dismutase and catalase. These inhibitory effects were clearly less pronounced in the presence of ferritin. Ferritin obviously played an important role as a source of iron in the pro-oxidative processes of 6-OHDA and AA. These features might be of importance in cancer therapy since many tumor cells contain elevated ferritin levels.     

Retino-fugal projections in congenitally monophthalmic fish and anurans

Summary Intra-ocular deposition of horseradish peroxidase was used to visualize optic tract projections in normal and congenitally monophthalmic catfish and Xenopus. In neither species was evidence for an increased ipsilateral visual component found in congenitally one-eyed specimens. This indicates that competition between axons from both eyes is not an important mechanism for fiber distribution in the chiasm during ontogeny. Furthermore, it suggests that enhanced ipsilateral components, previously noted in unilaterally enucleated fish and anurans, are caused by debris of degenerated axons.     

The influence of hypotonic treatment on the morphology of meiotic stages II. Prophase of the first meiotic division of female mice up to dictyotene

The copy number of the mdg-1 mobile element was determined by biotinylated-DNA hybridization, in salivary gland chromosomes of inbred Drosophila melanogaster larvae from sib progenies. It appears that the lower the egg-to-adult survival (viability), the higher the mdg-1 copy number in the surviving larvae. This suggests a common regulation of the mdg-1 copy number and the viability under inbreeding.     

Genetic control of the mitochondrial form of superoxide dismutase in hexaploid wheat

Extracts of mature grains of a large number of aneuploid derivatives of Triticum aestivum cv. Chinese Spring and of the members of five wheat-alien chromosome addition series were subjected to isoelectric focusing in polyacrylamide gels in order to study the genetic control of superoxide dismutase (SOD). Evidence was obtained that homologous structural genes for the mitochondrial form of SOD are located in the long arms of the homoeologous group 2 chromosomes of Chinese Spring and in chromosome 2R of Secale cereale cv. Imperial. The SOD gene loci located in chromosomes 2A, 2B, 2D, and 2R were designated Sod-A1, Sod-B1, Sod-D1, and Sod-R1, respectively. Chromosome-arm pairing data indicate that 2DL is not homoeologous to either 2AS or 2BL. The results of this study suggest, however, that 2BL is partially homoeologous to both 2AL and 2DL.Technical article No. 21074 of the Texas Agricultural Experiment Station. This work was supported by USDA Grant 83-CRCR-1-1322 to GEH.     

Identification of the major endogenous leukotriene metabolite in the bile of rats as N-acetyl leukotrience E4

Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats after endotoxin treatment. The mercapturate N-acetyl-leukotriene E₄ (N-acetyl-LTE₄) represented a major metabolite eliminated into bile after injection of [³H]LTC₄ as shown by cochromatography with synthetic N-acetyl-LTE₄ in four different HPLC solvent systems. The identity of endogenoud N-acetyl-LTE₄ elicited by endotoxin was additionally verified by enzymatic deacetylation followed by chemical N-acetylation. The deacetylation was catalyzed by penicillin amidase. Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation. A N-acetyl-LTE₄ concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection. Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE₄. The mercapturic acid pathway, leading from the glutathione conjugate LTC₄ to N-acetyl-LTE₄, thus plays an important role in the deactivation and elimination of these potent endogenous mediators.     

Haemostatic alterations in malaria correlate to parasitaemia

Fibrin(ogen) degradation products, platelet counts, antithrombin III, and the components of the Factor VIII complex were studied in a total of 80 patients with Plasmodium falciparum, Plasmodium vivax or Plasmodium ovale infections. The haemostatic findings were correlated to the numbers of parasitized erythrocytes and to each other. The results indicate that haemostatic changes in malaria correlate with the degree of parasitaemia. Evidence for moderate hyperfibrinolysis was found in patients with high P. falciparum parasitaemias only. Thrombocytopenia closely corresponded to parasitaemia and to von Willebrand factor levels, but appeared not to be linked to a consumption of coagulation factors. It was concluded that thrombocytopenia in malaria is not indicative of disseminated intravascular coagulation (DIC) but may relate to endothelial damage.     

Preliminary clinical observations with recombinant interleukin-2 in patients with AIDS or LAS

The toxicity of recombinant Interleukin-2 (IL-2) was studied in patients with acquired immunodeficiency syndrome (AIDS) or persistent lymphadenopathy syndrome (LAS). Increasing doses of the drug from 10(3) Units/m2 to 10(6) U/m2 were given as an intravenous bolus injection. At the high-dose levels some minor effects, such as fever up to 39.5 degrees C, chills, malaise or vomiting, were observed. The administration of 10(6) U/m2 as a 4-hour infusion showed identical results. No particular alterations of laboratory parameters were found. At the high-dose level the serum concentration of neopterin, which is released from macrophages after interferon gamma stimulation, was significantly (p less than 0.001) elevated above pretreatment levels. The clinical observation of daily infusions of 10(6)/m2 for 14 days revealed the same side effects. All patients developed lymphocytosis and eosinophilia. Two patients had suffered from severe diarrhoea for several weeks presumably due to cryptosporidiosis. In both cases diarrhoea ceased under the treatment with IL-2 and did not occur in the following two months.     

Isolation and characterization of a heparin with high anticoagulant activity from Anomalocardia brasiliana

The isolation, some structural features, physicochemical properties and pharmacological activities of a heparin from Anomalocardia brasiliana are reported. It is shown that the mollusc heparin is very similar to those present in mammalian tissues with regard to chemical composition, physicochemical properties, pharmacological activities and susceptibility to heparinase and heparitinase II from Flavobacterium heparinum, as well as to the types of products formed by the action of these enzymes. Three significant quantitative differences were observed for the mollusc heparin when compared with the ones from mammalian origin, namely, a higher degree of binding with antithrombin III (45%), higher molecular weight (27-43 kDa) and higher anticoagulant activity (320 I.U./mg). The possible biological role of heparin is discussed in view of the present findings.     

Complete complementary DNA of rat tyrosine aminotransferase messenger RNA. Deduction of the primary structure of the enzyme

The primary structure of rat tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase; EC 2.6.1.5), a liver-specific enzyme involved in gluconeogenesis, has been deduced from the nucleotide sequence of a cloned full-length cDNA. The mRNA is 2362 nucleotides long (excluding the poly(A) tail) and codes for a polypeptide of 454 amino acids with a molecular weight of 50634. Unambiguous identification was obtained by comparison of this sequence with the amino acid sequences of several peptides obtained from the purified enzyme.     

Catabolism of myo-Inositol to Precursors Utilized for De Novo Glycerolipid Biosynthesis

Systemic injection of [2-3H]myo-inositol into frogs resulted in the incorporation of more than half of the label into glycerolipid classes other than phosphoinositides in retinal rod outer segment membranes. Following methanolysis and differential extraction of isolated lipid classes, radioactivity was recovered primarily in the aqueous phase. After phospholipase C hydrolysis of the total membrane lipids, 97% of the radioactivity was extractable with organic solvents, and 70% of the label in lipids was in 1,2-diglycerides. These results indicate that the label was incorporated primarily into the glyceryl moiety of the membrane glycerolipids. Intraocular injection of frog eyes or in vitro incubation of frog retinas with [2-3H]myo-inositol resulted in the incorporation of radioactivity almost exclusively into phosphoinositides in rod outer segment membranes. Incubation of retinas with [U-14C]glucuronic acid did not result in the formation of labeled retinal lipids. These results suggest that myo-inositol can be catabolized systemically to precursors utilized for glycerolipid biosynthesis in the retina.