Hepatocellular carcinoma and focal nodular hyperplasia associated with norethandrolone-therapy: a case report

A 33-year-old woman was treated for severe aplastic anemia with norethandrolone over a period of four years, with a cumulative dose of 25 g. In the fifth year of therapy two intrahepatic tumors were detected and were classified as hepatocellular carcinoma and as focal nodular hyperplasia, respectively.     

Mechanism of triangularis sterni shortening during expiration in dogs

The triangularis sterni in the dog shortens during expiration below its in situ relaxation length (Lr) (J. Appl. Physiol. 61: 539-544, 1986). To assess the mechanism of this expiratory muscle shortening, we have measured the electromyogram and the respiratory changes in length of the canine triangularis sterni in the third and fourth right intercostal space, first before and then after selective denervation. Eleven anesthetized, spontaneously breathing animals were studied in the supine posture; five of them were also studied during postural changes from supine to head-up. Before denervation, the muscle in the supine animals shortened by -12.84 +/- 1.81% Lr. With selective denervation, the amount of expiratory muscle shortening was reduced to only -2.54 +/- 0.71% Lr (P less than 0.001). Similarly, a change from the supine to the head-up posture before denervation promoted an increase in expiratory muscle shortening from -13.58 +/- 3.62 to -21.17 +/- 4.04% Lr (P less than 0.005), but the denervation abolished this increase. Denervating the triangularis sterni, however, did not affect expiratory activation of the internal intercostals. These results demonstrate that the expiratory contraction of the canine triangularis sterni is agonistic in nature, and they suggest that this contraction is responsible for most of the active caudal displacement of the ribs in the upper half of the rib cage.     

Genetic factors and malaria in the Temuan.

The jungle habitat of the Temuan aborigines harbors a variety of infectious diseases, the most notable being malaria. Our study of 15 genetic systems in the Temuan revealed substantial polymorphism and within-population genetic diversity. The polymorphisms for Hb beta, G6PD, and El are of interest in regard to genetic adaptation to malaria. Among the polymorphisms investigated we conclude that G6PD deficiency and elliptocytosis are likely to have malaria-resistant effects as evidenced by their low association with malarial parasitemia or their higher frequency in adults than in children. These findings suggest that the malarial habitat of the Temuans is livable in the long range sense for them because of the cluster of malaria-resistant alleles in their gene pool (G6PD)-, El, and possibly, but not tested here because of its low frequency, Hb beta E). The same condition probably holds for the Semai, the nearest aborigine neighbors of the Temuan (although the Semai have not been tested for malarial parasitemia and for these polymorphisms simultaneously), since the Semai have substantial Hb betaE, G6PD-, and El. The Temuan have a cultural identity system of rituals, beliefs, and certain aspects of language which effectively isolates them genetically from Malays and other nonaborigines. This system hinders the dilution of the malaria-resistant alleles of the Temuan gene pool with the malaria-susceptible alleles of the nonaborigine gene pools.     

Abiotic stress does not magnify the deleterious effects of spontaneous mutations

Although the effects of deleterious alleles often are predicted to be greater in stressful environments, there is no theoretical basis for this prediction and the empirical evidence is mixed. Here we characterized the effects of three types of abiotic stress (thermal, oxidative and hyperosmotic) on two sets of nematode (Caenorhabditis elegans) mutation accumulation (MA) lines that differ by threefold in fitness. We compared the survival and egg-to-adult viability between environments (benign and stressful) and between fitness categories (high-fitness MA, low-fitness MA). If the environment and mutation load have synergistic effects on trait means, then the difference between the high and low-fitness MA lines should be larger in stressful environments. Although the stress treatments consistently decreased survival and/or viability, we did not detect significant interactions between fitness categories and environment types. In contrast, we did find consistent evidence for synergistic effects on (micro)environmental variation. The lack of signal in trait means likely reflects the very low starting fitness of some low-fitness MA lines, the potential for cross-stress responses and the context dependence of mutational effects. In addition, the large increases in the environmental variance in the stressful environments may have masked small changes in trait means. These results do not provide evidence for synergism between mutation and stress.     

Marine polyprenylated hydroquinones, quinones, and chromenols with inhibitory effects on leukotriene formation

A series of polyprenylated hydroquinones, quinones, and chromenols were isolated from the extracts of the marine sponge Ircinia spinosula and the brown alga Taonia atomaria, which gave rise to the constituents 1-4 and 5-8, respectively. Compounds 1, 2, 6, and 7 are new natural products, which were fully characterized. Their anti-inflammatory activities in terms of leukotriene formation were evaluated in an in vitro assay with pork leukocytes. The new hydroxylated compound, 2'-[28-hydroxy]heptaprenyl-1',4'-hydroquinone (= 2-[(2E,6E,10E,14E,18Z,22E)-19-(hydroxymethyl)-3,7,11,15,23,27-hexamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl]benzene-1,4-diol; 1), the known tetraprenyl benzoquinone sargaquinone (5), and the known polyprenyl chromenols 3 and 4 exhibited the highest anti-inflammatory activities, with IC50 values of 1.9-9.4 microM (Table 3). Potential structure-activity relationships (SAR) are discussed.     

Sterols synthesized by cultured trichomycetes

Desmosterol was synthesized by all but 2 of 14 isolates of the fungal genus Smittium (Harpellales) obtained from the hindguts of various Diptera larvae and grown axenically on a sterol-free medium. Also detected in some isolates of Smittium were cholesterol and ergosterol, and another, unidentified sterol with an apparent molecular ion of 470. Sterol content based on dry weight of fungal tissue was as high as 0.34%, but it was shown in one isolate that sterols vary both quantitatively and qualitatively during growth of the fungus. Two axenic cultures of the trichomycete Amoebidium parasiticum (Amoebidiales) isolated from the exoskeleton of a Cladocera contained cholesterol and ergosterol, but no desmosterol. Two soil fungi with possible phylogenetic affinities to Smittium, Linderina pennispora and Dipsacomyces acuminosporus (Kickxellales), produced cholesterol alone. The possible influence of the gut fungi on arthropod growth and development is discussed.Abbreviations TMS trimethylsilyl Based upon a Master of Arts thesis submitted by the senior author to the Department of Botany, University of Kansas. This research was partially supported by NSF grants BMS 72-02380-AO and DEB 77-16161 to R.W.L.