Galactose utilization by the rat tapeworm, Hymenolepis diminuta.

1. Hymenolepis diminuta incorporated label from 14C-galactose into glycogen, but the sugar would not support net glycogen synthesis. Glucose stimulated the incorporation of label from 14C-galactose into glycogen, while glycerol did not. 2. During incubations in galactose, large internal pools of galactose and galactose 1-P accumulated, while the concentration of glucose 6-phosphate remained unchanged. 3. In vitro culture experiments indicated that galactose would not support worm growth. Therefore, while galactose can be metabolized to a limited extent, it cannot substitute for glucose as a nutrient source.     

Progress in treatment of ANCA-associated vasculitis

Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, considerable progress has been made refining immunosuppressive regimens with a focus on minimising toxicity. There is, however, a high unmet need in the treatment of AAV. A proportion of patients are refractory to current therapies; 50% experience a relapse within 5 years and treatment toxicity contributes to mortality and chronic disability. As knowledge of the pathogenesis of vasculitis grows, it is mirrored by the availability of biological agents, which herald a revolution in the treatment of vasculitis. Lymphocyte-targeted and cytokine-targeted agents have been evaluated for the treatment of AAV and are entering the routine therapeutic arena with the potential to improve patient outcomes. As rare diseases, treatment advances in vasculitis depend on international collaborative research networks both to establish an evidence base for newer agents and to develop recommendations for patient management.     

2-Methylvalerate formation in mitochondria ofAscaris suum and its relationship to anaerobic energy generation

Summary Anaerobic incubation of intactAscaris suum mitochondria with pyruvate and propionate results in the formation of acetate, 2-methylvalerate, and 2-methylpentenoate and involves a rotenone sensitive, electron-transport associated phosphorylation. Malate inhibits 2-methylvalerate formation in these incubations, apparently by dissipating reducing power necessary for 2-methylvalerate formation. Indeed, malonate, an inhibitor of NADH-dependent fumarate reduction, dramatically stimulates 2-methylvalerate formation in incubations containing malate/propionate and malate/pyruvate/propionate but not pyruvate/propionate. In addition, malonate stimulates both 2-methylbutyrate and 2-methylvalerate formation in incubations with malate alone. The results of the present study suggest that branched-chain fatty acid synthesis inA. suum mitochondria is energy linked and that the inability of isolated, intact mitochondria to form branched-chain fatty acids from malate, their presumed physiological substrate, may result from an imbalance in the initial malate dismutation.Abbreviations BFA branched-chain fatty acid - 2-MB 2-methylbutyrate - 2-MC 2-methylcrotonate - 2-MP 2-methylpentenoate - 2-MV 2-methylvalerate Supported in part by NIH grant No. AI 18427     

ADP phosphorylation and glutamate oxidation in mitochondria isolated from Dictyostelium discoideum amoebae

Mitochondria have been isolated from $\text{D.}\text{discoideum}$ amoebae in which respiration is coupled to ADP phosphorylation. P:O ratios and respiratory control ratios have been obtained for a number of metabolites. In rat liver mitochondria, glutamate is oxidized almost exclusively by a respiration-dependent cyclic transamination pathway, in which glutamate is converted to aspartate. When $\text{D.}\text{discoideum}$ amoebae are incubated with glutamate alone, aspartate does not accumulate appreciably. Furthermore, when the mitochondria are incubated with glutamate plus malonate at a concentration sufficient to inhibit respiration, their utilization of glutamate is depressed only slightly. Thus, it appears that glutamate oxidation within the mitochondria of $\text{D.}\text{discoideum}$ amoebae does not, for the most part, proceed by the cyclic transamination pathway.     

The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus

Recombinant DNA clones have been isolated that contain 80 kb of the beta-globin complex from the deer mouse, Peromyscus maniculatus. Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged. Unlike other mammals studied thus far, the deer mouse possesses three adult genes. Partial sequence analysis indicates that each of the three adult genes is intact and hence may be functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to genomic blots from Peromyscus reveals that it has a homologous counterpart in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO and Hbb-bhl, are also found in Peromyscus. The strong hybridization between the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO genes suggest that both pairs are important for the ontogeny of these mice although no known product has been identified for the Hbb-bhO genes. The presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication that created this related gene set occurred before the two lineages diverged. A single gene for Hbb-y has been isolated from Peromyscus. The adult region in Peromyscus has undergone significant divergence from the same region in Mus, having three rather than two adult genes, the acquisition of at least 15 kb of extra DNA relative to Mus, and possibly the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in contrast, contains the same set of genes apparently distributed over the same amount of DNA as in the Mus beta- globin complex. This observation suggests that the embryonic region of the complex is more evolutionarily stable than the adult region.