Genetic influences in antisocial personality and drug use disorders

Small stress proteins protect against the cytotoxicity mediated by oxidative stress. The relationship between Hsp25 expression and the integrity of the actin network was studied in H2O2-treated murine L929 fibrosarcoma cells overexpressing endogenous wild-type (wt-) or non-phosphorylatable mutant (mt-) Hsp25. We show here that both proteins prevented actin network disruption induced by a 1 h treatment with 400 microM H2O2. In contrast, SB203580, a p38 MAPkinase inhibitor which suppresses Hsp25 phosphorylation, abolished the protective activity conferred by both wt- and mt-Hsp25. Hence, phosphorylation does not appear essential for Hsp25 protective activity against H2O2-induced actin disruption, and SB203580-sensitive events other than Hsp25 phosphorylation may be important for actin network regulation. Since, in L929 cells, wt- or mt-Hsp25 expression modulates intracellular glutathione levels, analyses were performed which revealed a direct correlation between glutathione and the integrity of the actin network. Moreover, laser scanning confocal immunofluorescences revealed that only a small fraction of wt- or mt-Hsp25 colocalized with actin microfilaments. Taken together, our results suggest that, in L929 cells, the protection against actin network disruption is probably a consequence of the redox change mediated by Hsp25 rather than a direct effect of this stress protein towards actin.     

Ocular neuromyotonia: clinical features, physiological mechanisms, and response to therapy

Ocular neuromyotonia (ONM) is a rare disorder characterized by episodic diplopia, occurring either spontaneously or following sustained eccentric gaze. Most patients have had prior radiation therapy to the sellar and parasellar region. ONM is thought to reflect impaired muscle relaxation due to inappropriate discharges from oculomotor, trochlear, or abducens neurons or axons with unstable cell membranes. Patients with ONM often benefit from membrane stabilizing agents such as carbamazepine. Here we describe a 71-year-old man, with no history of radiation therapy, who for 18 months had had transient episodic diplopia that occurred after down gaze. Clinical examination indicated ONM in muscles supplied by the right oculomotor nerve. Binocular scleral search coil eye movement recordings revealed a defect not only of muscle relaxation but also of maximal muscle contraction. The patient was treated with carbamazepine 200 mg per day with complete resolution of his symptoms. ONM may be more common than previously recognized, and patients with unexplained transient episodic diplopia should be specifically tested for diplopia and ocular misalignment following sustained eccentric gaze.     

New hepatitis viruses: are there enough letters in the alphabet?

Testing is now available for five recognised hepatitis viruses (A, B, C, D and E), and molecular technology is uncovering further hepatotropic viruses. An enteric agent isolated from human stool samples and transmitted experimentally to primates is a candidate hepatitis F virus. A provisionally designated blood-borne hepatitis G virus is associated with acute and chronic non-ABCDE hepatitis and has a worldwide distribution. A group of flavi-like viruses, the GB group, also blood borne, has also been reported. The role of two of these viruses, GBV-A and GBV-B, in human viral hepatitis has not been determined, but a third agent, GBV-C, is associated with acute and chronic hepatitis and appears to be a West African variant of hepatitis G. Our current knowledge suggests that the hepatitis alphabet may need to be extended even after inclusion of some of these new viruses.     

Comparison of sire breed solutions for growth traits adjusted by mean expected progeny differences to a 1993 base

Records on growth traits were obtained from five Midwestern agricultural experiment stations as part of a beef cattle crossbreeding project (NC-196). Records on birth weight (BWT, n =3,490), weaning weight (WWT, n = 3,237), and yearling weight (YWT, n = 1,372) were analyzed within locations and pooled across locations to obtain estimates of breed of sire differences. Solutions for breed of sire differences were adjusted to the common base year of 1993. Then, factors to use with within-breed expected progeny differences (EPD) to obtain across-breed EPD were calculated. These factors were compared with factors obtained from similar analyses of records from the U. S. Meat Animal Research Center (MARC). Progeny of Brahman sires mated to Bos taurus cows were heaviest at birth and among the lightest at weaning. Simmental and Gelbvieh sires produced the heaviest progeny at weaning. Estimates of heritability pooled across locations were .34, .19, and .07 for BWT, WWT, and YWT, respectively. Regression coefficients of progeny performance on EPD of sire were 1.25+/-.09, .98+/-.13, and .62+/-.18 for BWT, WWT, and YWT, respectively. Rankings of breeds of sire generally did not change when adjusted for sire sampling. Rankings were generally similar to those previously reported for MARC data, except for Limousin and Charolais sires, which ranked lower for BWT and WWT at NC-196 locations than at MARC. Adjustment factors used to obtain across-breed EPD were largest for Brahman for BWT and for Gelbvieh for WWT. The data for YWT allow only comparison of Angus with Simmental and of Gelbvieh with Limousin.     

Sphingosine 1-phosphate inhibits activation of caspases that cleave poly(ADP-ribose) polymerase and lamins during Fas- and ceramide-mediated apoptosis in Jurkat T lymphocytes

Ceramide, a sphingolipid generated by the hydrolysis of membrane-associated sphingomyelin, appears to play a role as a gauge of apoptosis. A further metabolite of ceramide, sphingosine 1-phosphate (SPP), prevents ceramide-mediated apoptosis, and it has been suggested that the balance between intracellular ceramide and SPP levels may determine the cell fate (Cuvillier, O., Pirianov, G, Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, J. S., and Spiegel, S. (1996) Nature 381, 800-803). Here, we investigated the role of SPP and the protein kinase C activator, phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), in the caspase cascade leading to the proteolysis of poly(ADP-ribose) polymerase (PARP) and lamins. In Jurkat T cells, Fas ligation or addition of exogenous C2-ceramide induced activations of caspase-3/CPP32 and caspase-7/Mch3 followed by PARP cleavage, effects that can be blocked either by SPP or TPA. Furthermore, both SPP and TPA inhibit the activation of caspase-6/Mch2 and subsequent lamin B cleavage. Ceramide, in contrast to Fas ligation, did not induce activation of caspase-8/FLICE and neither SPP nor TPA were able to prevent this activation. Thus, SPP, likely generated via protein kinase C-mediated activation of sphingosine kinase, suppresses the apoptotic pathway downstream of FLICE but upstream of the executioner caspases, caspase-3, -6, and -7.     

Fatal rhino-orbital-cerebral zygomycosis

Rhinocerebral zygomycosis is usually an aggressive, fulminant and, at times, fatal disease most often affecting poorly controlled diabetics of all ages. We report the case of a 13-month-old white boy, a previously undiagnosed diabetic. He came to our hospital with recurrent epistaxis, decreasing consciousness, and a small visible infection at the inner canthus of the left eye. Initial evaluation revealed that the patient was in diabetic ketoacidosis. Despite aggressive medical and surgical treatment, his condition deteriorated rapidly, including the development of diabetes insipidus, and he died 4 days after admission. At autopsy, he was found to have fungal cerebritis (Rhizopus) with multiple areas of infarction and massive cerebral edema.     

Treatment of functional decline in adults with Down syndrome using selective serotonin-reuptake inhibitor drugs

Alzheimer's disease (AD) is a common cause of functional decline in Down syndrome (DS) adults. Acquired cognitive deficits may be difficult to evaluate in the context of baseline impairments. Behavioral symptoms are also common and may represent the effects of depression, AD, or both. Therefore, the objective of this study was to report a clinical case series of selected adults with DS and behavioral change who responded to treatment with selective serotonin-reuptake inhibitor (SSRI) medication. Six patients, aged 23 to 63 years, 5 women and 1 man, with the clinical diagnosis of DS presented for diagnosis and treatment of functional decline in adult life. Noncognitive symptoms were prominent and included aggression, social withdrawal, and compulsive behaviors. Memory dysfunction was reported in varying degrees. Treatment with SSRI antidepressants was instituted for depressive, apathetic, and compulsive behaviors. Treated patients showed improvement in behaviors as reported by caregivers, and on objective measures, such as workplace productivity. Noncognitive symptoms are a cardinal feature of functional decline in adults with DS and may represent either depression or AD. In some patients, the symptoms respond well to SSRI agents with concomitant improvement in daily function. Treatment trials with SSRIs may, therefore, be warranted in such cases.     

Purification of myosin translational control RNA and its interaction with myosin messenger RNA

Myosin messenger ribonucleoprotein-translational control ribonucleic acid (mRNP-tcNA) from myosin mRNPs found in embryonic chick muscle has been further purified by Dowex chromatography and, from a number of controls, it is suggested that this small RNA is not an artifact produced through the degradation of RNA during its isolation. This highly purified myosin mRNP-tcRNA is shown to have a molecular weight of 10 000 on formamide-acrylamide gels, and reacts stoichometrically (on a 1:1 mole ratio) with myosin mRNA. The stoichiometric interaction between myosin mRNA and myosin mRNP-tcRNP is demonstrated by ists ability to increase the nuclease resistance of the messenger, as well as inhibit its translation in a cell-free amino acid incorporating system.     

A novel class of antitumour agents. III. Morphological findings in treated cells

The findings of intracellular light-reflecting droplets and clotted mitoses after incubation of Walker and HeLa cells, human lymphocytes and rat fibroblasts with the synthetic amino steroid, 2beta, 16beta-dipiperidino-5alpha-androstane-3-alpha,17beta-diol dipivalate (DAP) were examined in detail. An interaction of DAP with the cellular membranes in all stages of cell life, with the exception of the Go-phase, is postulated.