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Biomedical subjects

V Murphy

Publications and source records attributed to V Murphy.

14 recordsLinked to original sources
PubMed1999

No evidence to support the association of the potassium channel gene hSKCa3 CAG repeat with schizophrenia or bipolar disorder in the Irish population.

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study.1 In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population.

Bipolar Disorder↗
PubMed1999

Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1).

Two subtypes of the cannabinoid receptor (CB1 and CB2) are expressed in mammalian tissues. Although selective antagonists are available for each of the subtypes, most of the available cannabinoid agonists bind to both CB1 and CB2 with similar affinities. We have synthesized two analogs of N-arachidonylethanolamine (AEA), arachidonylcyclopropylamide (ACPA) and arachidonyl-2-chloroethylamide (ACEA), that bind to the CB1 receptor with very high affinity (KI values of 2.2 +/- 0.4 nM and 1.4 +/- 0.3 nM, respectively) and to the CB2 receptor with low affinity (KI values of 0.7 +/- 0.01 microM and 3.1 +/- 1.0 microM, respectively). Both ACPA and ACEA have the characteristics of agonists at the CB1 receptor; both inhibit forskolin-induced accumulation of cAMP in Chinese hamster ovary cells expressing the human CB1 receptor, and both analogs increase the binding of [35S]GTPgammaS to cerebellar membranes and inhibit electrically evoked contractions of the mouse vas deferens. ACPA and ACEA produce hypothermia in mice, and this effect is inhibited by coadministration of the CB1 receptor antagonist SR141716A. Therefore, ACPA and ACEA are high-affinity agonists of the CB1 receptor but do not bind the CB2 receptor, suggesting that structural analogs of AEA can be designed with considerable selectivity for the CB1 receptor over the CB2 receptor.

Adenylyl Cyclases↗
PubMed1999

Pseudoautosomal gene: possible association with bipolar males but not with schizophrenia.

The phenomenon of anticipation has been demonstrated in several neuropsychiatric disorders and suggested for schizophrenia and bipolar affective disorder. Many conditions exhibiting anticipation have been shown to be caused by trinucleotide repeat (CAG/CTG) expansions. Some evidence suggests that these expansions also exist in individuals with schizophrenia and bipolar affective disorder. In this investigation, we analysed a polymorphic CAG repeat in the interleukin receptor gene (IL9R), mapped to the pseudoautosomal region Xq28 and Yq21 (a candidate region for schizophrenia and affective disorder). Two common alleles, differing by one repeat unit and two rare alleles were found in cases and controls. Allele frequencies of this repeat were investigated in Irish schizophrenic, bipolar disorder and ethnically matched control samples. We found no evidence of an increased frequency of larger CAG repeats in either the schizophrenic or bipolar affective disorder samples as a whole when compared to the controls. However, dividing the samples by sex demonstrated a significant association between bipolar affective disorder males and the larger allele (allele 2) (patients 54.8% vs controls 40.1%, chi2 = 6.7, P = 0.009). In addition, a decreased frequency of this allele has been observed in the female patients, but did not attain statistical significance (patients 37% vs controls 46%, chi2 = 2.1, P = 0.14). This provides preliminary evidence that this locus or a closely mapped DNA variant (in linkage disequilibrium with the CAG repeat) may be involved in the genetic susceptibility to bipolar affective disorder in males.

Bipolar Disorder↗
PubMed1998

Evidence for an allelic association between bipolar disorder and a Na+, K+ adenosine triphosphatase alpha subunit gene (ATP1A3).

BACKGROUND: Disturbances in central nervous system Na+, K+ adenosine triphosphatase (ATPase) activity have previously been proposed as being involved in the pathophysiology of bipolar mood disorder. METHODS: We have examined one particular alpha subunit of this enzyme for allelic association in a sample of 85 Irish bipolar patients and 85 matched controls. RESULTS: There was evidence for an overall allelic association between the disease and a dinucleotide polymorphism within the ATP1A3 gene (p = .022). Subjects were then analyzed on the basis of a number of criteria, and the significance of the association increased when cases were divided based on the nature of the first episode. Patients who presented with a depressive episode first showed a significant association (p = .001) with this polymorphism. CONCLUSIONS: The results presented here provide preliminary evidence of an association between bipolar disorder and an alpha subunit of Na+, K+ ATPase, the expression of which predominates in the brain.

Adult↗
PubMed1997

Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction.

Leukemia inhibitory factor (LIF) induces a variety of disparate biological responses in different cell types. These responses are thought to be mediated through the functional LIF receptor (LIFR), consisting of a heterodimeric complex of LIFR alpha-chain (LIFRalpha) and gp130. The present study investigated the relative capacity of the cytoplasmic domains of each receptor subunit to signal particular responses in several cell types. To monitor the signaling potential of LIFRalpha and gp130 individually, we constructed chimeric receptors by linking the extracellular domain of granulocyte colony-stimulating factor receptor (GCSFR) to the transmembrane and cytoplasmic regions of either LIFRalpha or gp130. Both chimeric receptors and the full-length GCSFR in expressed in M1 myeloid leukemic cells to measure differentiation induction, in embryonic stem cells to measure differentiation inhibition, and in Ba/F3 cells to measure cell proliferation. Our results demonstrated that whereas GCSFR-gp130 receptor homodimer mediated a GCSF-induced signal in all three cell types, the GCSFR-LIFRalpha receptor homodimer was only functional in embryonic stem cells. These findings suggest that the signaling potential of gp130 and LIFRalpha cytoplasmic domains may differ depending upon the tissue and cellular response initiated.

Antigens, CD↗
PubMed1997

Amygdala-prefrontal interactions and conditioned bradycardia in the rabbit.

Damage to the amygdala or medial prefrontal cortex (mPFC) produces deficits in learned autonomic adjustments. Whether connections between these 2 structures are necessary for acquiring classically conditioned heart rate (HR) decelerations was studied. Connections between them were interrupted by unilateral lesions of the mPFC and amygdala, but on opposite sides of the brain. One experiment focused on the mPFC and amygdala central nucleus and a second on the mPFC and amygdala basolateral complex. Bilateral lesions of either structure disrupted the HR conditioned response. The response of the 2 crossed lesioned groups also was smaller than that of the sham-operated and unilateral lesioned groups, but significant conditioned stimulus-evoked bradycardia occurred in both, suggesting that although interactions between the amygdala and mPFC may normally occur during associative emotional responding, these connections are not necessary for the acquisition of conditioned bradycardia.

Amygdala↗
PubMed1994

Risk factors for repeatedly reactive HIV-1 EIA and indeterminate western blots. A population-based case-control study.

OBJECTIVE: Causes of indeterminate results of Western blot testing (IWB) for human immunodeficiency virus (HIV) type 1 include seroconversion, HIV-2 cross-reactivity, and autoimmune disease, but most IWB results remain unexplained. This case-control study assessed risk factors for IWB results, including early HIV infection, other retroviral infection, autoantibodies, and other medical conditions. DESIGN: Prospective study to determine HIV seroconversion rate, with a case-control design to assess other risk factors for IWB. Cases (persons with one or more repeatedly reactive HIV-1 enzyme immunoassay with IWB), their current sexual partners, and controls (persons with negative enzyme immunoassay and Western blot results) were recruited from blood banks, health department and prenatal clinics, and private providers in Washington and Oregon. RESULTS: Of 244 cases enrolled, 206 were followed up for 6 months or longer, and six (3.0%; 95% confidence interval [CI], 0.7% to 5.3%) with recent HIV risk behaviors seroconverted. The Western blot banding patterns differed among groups; cases usually had p17 or p24 bands, while controls and cases' sexual partners usually had polymerase bands. Conditional logistic regression indicated that independent risk factors for IWB among male cases and controls were a tetanus booster in the past 2 years (odds ratio, 3.2; 95% CI, 1.2 to 8.6) and sexual contact with a prostitute (odds ratio, 3.0; 95% CI, 1.0 to 9.5). Independent risk factors for women were parity (odds ratio, 1.2; 95% CI, 1.02 to 1.4) and autoantibodies, either rheumatoid factor or antinuclear antibodies (odds ratio, 2.3; 95% CI, 1.03 to 5.6). No cross-reactivity was detected with HIV-2, human T-lymphotrophic virus type 1, feline immunodeficiency or feline leukemia, or bovine immunodeficiency viruses. CONCLUSIONS: Evaluation of persons with reactive HIV-1 enzyme immunoassays and IWB should include an assessment of HIV risk and other possible risk factors, such as alloimmunization (ie, parity or recent immunization) or autoantibodies (ie, antinuclear antibodies and rheumatoid factor). The relationship of IWB among men who reported sex with prostitutes is intriguing and warrants further study.

Adolescent↗
PubMed1991

Intussusception in cystic fibrosis.

Two cases of acute intussusception in older children with cystic fibrosis are reported. Both cases presented with symptoms and signs consistent with meconium ileus equivalent, which delayed the final diagnosis. Both cases required abdominal surgery but made full and uneventful recoveries.

Cystic Fibrosis↗
PubMed1989

Expression and characterization of the Ha-ras p21 protein produced at high levels in the insect/baculovirus system.

Normal and mutated cDNAs of Ha-ras have each been cloned into a standard (pAc373) and a novel (p36C) baculovirus transfer vector and introduced via homologous recombination into the genome of Autographa californica nuclear polyhedrosis virus immediately downstream of the polyhedrin promoter. Spodoptera frugiperda cells infected with recombinant virus containing the normal Ha-ras gene express very high levels of ras p21 protein (approximately 20% of total cell protein), whereas the mutant protein was expressed at considerably lower levels. Molecular analysis showed that this was most likely due to a post-transcriptional event. The expression vector p36C produced considerably higher levels of recombinant p21 compared to the more commonly used pAc373. The majority of the normal ras p21 protein is soluble, cytoplasmic, and appears to be nonacylated. However, about 10% of the p21 associates with the membrane fraction of infected cells and migrates as a slightly faster band on gels. Furthermore, this band is sensitive to hydroxylamine treatment and shows specific incorporation of [3H]palmitate, strongly suggesting that it is the palmitoylated form of p21, which is the biologically active form of the protein. Both the soluble and membrane-associated p21 have been purified to homogeneity under nondenaturing conditions, the latter in the presence of detergents. The isolation of native palmitoylated p21 has not been reported previously. The difference in hydrophobicity between these two proteins has been demonstrated by Triton X-114 partitioning. The use of the insect/baculovirus expression system to express relatively high levels (20 mg/liter) of palmitoylated p21 should aid experiments to resolve the structural and functional properties of this molecule.

Amino Acid Sequence↗
PubMed1989

Pentylenetetrazol kindling in mice.

Kindling with pentylenetetrazol to produce minimal and maximal convulsions was investigated in CF-1 mice. Like electrical kindling, the kindling effect was directly proportional to the dose or the intensity of the kindling stimulus. Similarly, the kindling effect was persistent, as was emphasized by the ability to kindle with an interdose interval of 3 days and by the convulsions produced by a challenge with pentylenetetrazol 30 days after withdrawal from the kindling treatment. The changes in excitability, associated with the kindling state, appeared to be relatively selective for pentylenetetrazol, because no changes in thresholds to either electroshock or administration of picrotoxin or N-methyl-DL-aspartate correlated temporally with the persistence of kindling. The influence of two anticonvulsant drugs, ethosuximide and cannabidiol, on kindling was also investigated. Both drugs blocked the development of kindling to pentylenetetrazol-induced minimal convulsions. Of these drugs, only ethosuximide raised the minimal convulsive threshold to pentylenetetrazol. Against pentylenetetrazol-induced kindling to maximal convulsions, only cannabidiol blocked kindling and only cannabidiol raised the maximal seizure threshold for pentylenetetrazol. Although the drugs modified the kindling effect, the mechanism of the interaction is not clear.

Animals↗