Substituted ammonium ions as allergenic determinants in drug allergy

Serious, and occasionally fatal, anaphylactic-like (anaphylactoid) reactions may occur when a patient is exposed to a drug for the first time. Apart from the penicillins, nothing is known of the nature of antigenic or sensitizing drug determinants and, as yet, there is no evidence for the involvement of IgE antibodies in most drug reactions. Muscle relaxants such as alcuronium have been implicated in many life-threatening anaphylactoid reactions but the mechanisms remain unclear. We have now investigated the possibility that drug-specific IgE antibodies are involved by using an alcuronium-carrier complex in a radioimmunoassay with patients' sera. Alcuronium-reactive antibodies were found in five drug-sensitive subjects and most of the antibodies cross-reacted with other muscle relaxants and with a variety of apparently structurally unrelated drugs. Structure-activity studies designed to explore the molecular basis of the antibody binding established that quaternary and tertiary ammonium ions were the complementary allergenic sites on the reactive drugs. These structures occur widely in many drugs but also in foods, cosmetics, disinfectants and industrial materials. Hence, there would seem to be ample opportunity for sensitive individuals to come into contact with and synthesize IgE antibodies to these unusual, and previously unsuspected, antigenic determinants.     

Capture locations of two endangered rodents during a 1902 exploration of the Sacramento Mountains, New Mexico

We investigated localities from which Eutamias atristriatus Bailey, 1913 (= Tamias minimus atristriatus ) and Zapus luteus Miller, 1911 (= Zapus hudsonius luteus ) were collected during a 1902 survey in the Sacramento Mountains, New Mexico, by the United States Biological Survey. The locality from which the holotype of Eutamias atristriatus was collected is restricted to James Canyon rather than the Rio Pe?asco. Locality records indicate that the historical distribution of Zapus hudsonius luteus and its obligate wetland habitat were broader than currently realized.     

Increased rate of melanization in hemolymph of American cockroaches (Periplaneta americana) an house crickets (Acheta domesticus) intoxicated by insecticides

Summary Treatment of house crickets and American cockroaches with any one of a variety of insecticides increased the rate of melanization in hemolymph incubated with diphenol substrates.     

The effect of thyroid function on the prothrombin time response to warfarin in rats

Zusammenfassung Die Wirkung von Warfarin, einem Anticoagulans der Dicumarolgruppe, ist erhöht bei hyperthyroiden und vermindert bei hypothyroiden Ratten.

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This work was supported by a grant from the National Research Council of Canada.     

A major susceptibility locus for leprosy in India maps to chromosome 10p13

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.     

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.