Enhancement of ethanol-induced sedation and hypothermia by centrally administered neurotensin, β-endorphin and bombesin

Intracisternal administration of three endogenous neuropeptides (neurotensin, β-endorphin, or bombesin) potentiated the duration of sedation induced by a fixed dose of ethanol (5.2 g/kg) in mice. The minimally effective dose of each peptide that enhanced ethanol-induced sedation was: neurotensin, 0.18 nmoles; β-endorphin, 1.79 nmoles; and bombesin, 0.06 nmoles. The enhancement of ethanol-induced sedation was correlated with the potentiation of ethanol-induced hypothermia for all three peptides. None of the neuropeptides studied significantly altered blood or brain ethanol concentrations, suggesting that the observed effects were not due to differences in ethanol metabolism

The role of alternative splicing patterns of BCR/ABL transcripts in the generation of the blast crisis of chronic myeloid leukaemia

Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase.Journal ArticleResearch Support, Non-U.S. Gov'tFLWNAinfo:eu-repo/semantics/publishe

Supplementary Material for: A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation

<p>Mitochondrial DNA mutations have been reported to be associated with bipolar disorder (BD). In this study, we performed genome-wide analyses to assess mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early-onset BD (EOBD) among BD patients, focusing on interaction effects between nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European American BD cases (<i>n</i> = 1,001) and controls (<i>n</i> = 1,034) from the Genetic Association Information Network BD study were analyzed to assess the joint effect of nSNP and nSNP-mtSNP interaction on the risk of BD and EOBD. The effect of nSNP-mtSNP interactions was also assessed. For BD risk, the strongest evidence of an association was obtained for nSNP rs1880924 in <i>MGAM</i> and mtSNP rs3088309 in <i>CytB</i> (<i>p</i>_joint = 8.2 × 10^-8, <i>p</i>_int = 1.4 × 10^-4). Our results also suggest that the minor allele of the nSNP rs583990 in <i>CTNNA2</i> increases the risk of EOBD among carriers of the mtSNP rs3088309 minor allele, while the nSNP has no effect among those carrying the mtSNP major allele (OR = 4.53 vs. 1.05, <i>p</i>_joint = 2.1 × 10^-7, <i>p</i>_int = 1.16 × 10^-6). While our results are not statistically significant after multiple testing correction and a large-sample replication is required, our exploratory study demonstrates the potential importance of considering the mitochondrial genome for identifying genetic factors associated with BD.</p