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Biomedical subjects

P Moran

Publications and source records attributed to P Moran.

At least 19 recordsLinked to original sources
PubMed1998

Predicting depression in women: the role of past and present vulnerability.

BACKGROUND: A prospective study, covering just over a 1-year period, sought to confirm an earlier finding that around 40% of women who experience a severe life event in the presence of two ongoing psychosocial vulnerability factors, (negative close relationships and low self-esteem) will develop a major depressive episode. Distal risk factors were examined to see if they improved prediction. METHODS: A population sample of 105 mainly working-class mothers with vulnerability and without depression were interviewed three times over a 14-month period to date the occurrence of severe life events and onset of major depression. Degree of vulnerability was assessed at first contact together with distal risk in terms of childhood neglect/abuse and any earlier episodes of depression. RESULTS: Thirty-seven per cent of these vulnerable women became depressed in the study period. The majority experienced a severe life event, and of these, 48% had onsets. Contrary to expectation, risk was only a little less among those with just one of the two vulnerability factors. Two-thirds of women with an onset had been depressed in previous years. Although this was associated with increased risk, the effect was greatest for those who had experienced an episode before age 20. A relationship between childhood neglect/abuse and onset was entirely accounted for by such early depression. CONCLUSION: An aetiological model of depression outlined in earlier research was confined with a new factor of teenage depression shown to increase risk of onset.

Adolescent↗
PubMed1997

Physical localization and characterization of the BglI element in the genomes of Atlantic salmon (Salmo salar L.) and brown trout (S. trutta L.).

This work describes chromosomal localization, fine physical mapping, and population variation of the BglI element in the genome of Atlantic salmon (Salmo salar L.) and a similar sequence in the genome of brown trout (S. trutta L.). Results from a variety of complementary approaches, clearly demonstrate that the BglI element does not occur as a satellite-like repetitive DNA in these species but is part of the rDNA cistron as suggested by Goodier and Davidson (1993). Coincident hybridization of BglI clones with rDNA loci in both single and double-probe fluorescence in situ hybridization (FISH) experiments demonstrated physical linkage between the BglI element and rDNA loci. Fine physical mapping by Southern analysis and PCR amplification showed the BglI element to be located approximately 1.6 kb upstream of the 18S gene. The BglI element was used to screen for population-specific markers by Southern analysis. Population-specific banding patterns were only observed in brown trout, allowing identification of individual populations of this species. Sequence comparisons revealed sequences similar to the BglI element present in the rDNA cistron of other salmonids. This result suggests the presence of this sequence in the genome of the salmonid tetraploid ancestor.

Animals↗
PubMed1997

Lerk2 (ephrin-B1) is a collapsing factor for a subset of cortical growth cones and acts by a mechanism different from AL-1 (ephrin-A5).

The transmembrane (TM) subfamily of Eph ligands and their receptors have been implicated in axon pathfinding and in pattern formation during embryogenesis. These functions are thought to involve repulsive interactions but this has not been demonstrated directly. In this study we used a growth cone collapse assay to determine if the TM ligands Lerk2 and HtkL have repellant guidance activity. We show that Lerk2, but not HtkL, is a collapsing factor for a subset of embryonic cortical neurons. Analysis of the effects of Lerk2 on both the morphology and the cytoskeleton of cortical neurons suggests a mechanism of action different from that of AL-1, a GPI-linked Eph ligand having similar repellant activity. Treatment with Lerk2 disrupts the organization of both the actin cytoskeleton and the microtubules and induces the formation of swellings in the center of the growth cone and along the axon. Measurement of the relative F-actin concentrations in the neurites and soma indicated that F-actin levels in the neurites decrease while those in the soma increase, with the net F-actin content of the neuron remaining unchanged. In contrast, we show that prolonged treatment with AL-1 leads to a net loss of F-actin, consistent with the hypothesis that AL-1 acts by perturbing actin polymerization. These results provide evidence that the ectodomain of Lerk2 functions as a repellant guidance cue and show that, despite overlapping specificities in vitro, the biological activities of related ligands are not necessarily overlapping. Further, TM and GPI-linked Eph ligands appear to exert repellant activity by different mechanisms, opening up the possibility that they may have different effects on growth cones in vivo.

Actins↗
PubMed1997

AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton.

Previous experiments identified AL-1 as a glycosylphosphatidylinositol (GPI)-linked ligand for the Eph-related receptor, REK7, and showed that a REK7-IgG fusion protein blocks axon bundling in co-cultures of cortical neurons on astrocytes, suggesting a role for REK7 and AL-1 in axon fasciculation. Subsequent identification of RAGS, the chick homologue of AL-1, as a repellent axon guidance molecule in the developing chick visual system led to speculation that AL-1, expressed on astrocytes, provides a repellent stimulus for cortical axons, inducing them to bundle as an avoidance mechanism. Using a growth cone collapse assay to test this hypothesis, we show that a soluble AL-1-IgG fusion protein is a potent collapsing factor for embryonic rat cortical neurons. The response is strongly correlated with REK7 expression, implicating REK7 as a receptor mediating AL-1-induced collapse. Morphological collapse is preceded by an AL-1-IgG-induced reorganization of the actin cytoskeleton that resembles the effects of cytochalasin D. This suggests a pathway whereby REK7 activation by AL-1 leads to perturbation of the actin cytoskeleton, possibly by an effect on actin polymerization, followed by growth cone collapse. We further show that AL-1-IgG causes collapse of rat hippocampal neurons and rat retinal ganglion cells. These data suggest a role for REK7 and AL-1 in the patterning of axonal connections in the developing cortex, hippocampus and visual system.

Actins↗
PubMed1997

Increased rate of psychosis among African-Caribbeans in Britain is not due to an excess of pregnancy and birth complications.

BACKGROUND: It has been suggested that the increased rate of psychotic illness among African-Caribbeans living in Britain is due to an excess of pregnancy and birth complications (PBCs). METHOD: We therefore compared the frequency of PBCs in a group of White psychotic patients (n = 103) and a comparable group of patients of African-Caribbean origin (n = 61); the latter consisted of 30 first-generation (born in the Caribbean) and 31 second-generation (born in Britain) individuals. RESULTS: White psychotic patients were more than twice as likely to have a history of PBCs as their African-Caribbean counterparts (odds ratio = 2.34, 95% confidence interval (CI) 0.88-6.47, P = 0.062). The same trend was observed among patients with a DSM-III diagnosis of schizophrenia (odds ratio = 1.65, 95% CI 0.56-4.97, P = 0.32). The rate of PBCs was similar among the first- and second-generation Caribbean psychotic patients. CONCLUSIONS: The increased rate of psychotic illness that has been reported among the African-Caribbean population in Britain is not due to an increased prevalence of PBCs.

Adult↗
PubMed1997

Prospective study of Entamoeba dispar infection in a cohort of mothers and their infants: relationship to serum antibody response.

The sera of cohorts of newborn infants and their mothers, characterized as cyst passers of Entamoeba with nonpathogenic zymodemes (E. dispar) and seropositive for amoebic antigens, were analyzed. Both cohorts were followed for a period of 12 months by microscopic examination of feces and determination of serum anti-amoebic antibody titers using the indirect hemagglutination assay. Control groups (noncyst passer mothers and their infants) were included and followed. To characterize antigens involved in the induction of IgG and IgA antibody responses, Western blots of serum from all participants were tested and immunoplots of the frequency of antigenic recognition were constructed. Results of clinical follow-up and microscopic examination of feces showed that during the 12-month period none of the cyst passer mothers had episodes of diarrhea attributable to E. histolytica invasion; five of 21 children of cyst passer mothers became infected during the study, five of five infected children developed serum antiamebic antibodies (titers 1:64-1:128); none of the cohort of children from cyst passer mothers had diarrhea due to E. histolytica. Western blot analysis showed that there are antigenic fractions that induce serum antibodies of the IgG and IgA classes against E. dispar very early in the host-parasite relationship. Our results suggest that mechanisms of antibody induction different from intestinal invasion may be operating in amebic infection. Intestinal absorption of antigen, systemic reflection of secretory antibody response, and priming of newborns by maternal anti-idiotypic antibody transfer are discussed.

Adult↗
PubMed1996

Sex chromosome linkage of 5S rDNA in rainbow trout (Oncorhynchus mykiss).

The karyotype of the rainbow trout is characterized by a primitive XX/XY sex-determining chromosomal system. (Thorgaard et al., 1977). In the present study using FISH we have physically linked the 5S rRNA genes to the partially undifferentiated X chromosome pair. PCR amplified 5S rDNA was used for FISH and hybridization signals indicated that the genes were duplicated, present in one acrocentric and one metacentric pair of chromosomes. After analyzing several individuals, the female metaphases showed four fluorescent signals whereas males presented only three signals. Two of the three signals obtained in males corresponded to the metacentric pair whereas the single signal was mapped to the heterochromatin that cytologically differentiates the X chromosome from the Y chromosome. Double FISH experiments demonstrated that the 5S rDNA which is not sex linked is located at the NOR bearing arm close to the major ribosomal RNA genes (5.8S, 18S and 28S), similar to the situation observed in Atlantic salmon (Pendas et al., 1994a).

Animals↗
PubMed1996

Morbid risk of schizophrenia in first-degree relatives of white and African-Caribbean patients with psychosis.

BACKGROUND: The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of White patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 White and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of White and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their White counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their White counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.

Adult↗
PubMed1995

Suppression of haloperidol-induced oral dyskinesias in rats by vigabatrin.

Acute and chronic administration of vigabatrin, a selective inactivator of GABA-T, suppresses haloperidol-induced dyskinesias at low doses without preventing the enhancement of striatal dopamine D2 receptor density or the development of vacuous chewing movements. The long-term administration of vigabatrin does not attenuate its effect. The observations presented in this work support the GABA hypothesis of haloperidol-induced vacuous chewing behavior in rats, and suggest that vigabatrin is an appropriate means to enhance nigral GABAergic activity.

4-Aminobutyrate Transaminase↗
PubMed1995

Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation.

REK7 is an Eph-related tyrosine kinase receptor expressed exclusively in the nervous system, predominantly in hippocampus and cortex. A soluble REK7-IgG fusion protein, produced to analyze the biological role of REK7, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. Using REK7-IgG as an affinity reagent, we purified and cloned a novel REK7 ligand called AL-1, a GPI-linked protein homologous to other members of an emerging ligand family. Membrane attachment of AL-1 appears necessary for receptor activation, since REK7 on cortical neurons is efficiently activated by transfected cells expressing GPI-linked AL-1, but not by soluble AL-1. Consistent with this, soluble AL-1 blocks axon bundling. Our findings, together with the observation that both molecules are expressed in the brain, suggest a role in the formation of neuronal pathways, a crucial feature of nervous system development and regeneration.

Amino Acid Sequence↗
PubMed1995

Adolescent health-threatening and health-enhancing behaviors: a study of word association and imagery.

PURPOSE: To examine the ways in which perceived risks and benefits relate to health-threatening and health-enhancing behaviors by adolescents. METHOD: The study used a word association methodology to explore adolescents' thoughts and affective feelings associated with five health-threatening behaviors (e.g., drinking beer, smoking cigarettes) and three health-enhancing behaviors (e.g., exercising, using a seat belt). RESULTS: Each behavior elicited a mix of positive and negative associations. Health-threatening behaviors had many positive associations in common, such as having fun, social facilitation, and physiological arousal. Health-enhancing behaviors had much less commonality in their positive associations. Patterns of negative associations were not highly similar across behaviors. The content and affective tone of the associations were closely linked to participation in health-threatening behaviors and health-enhancing behaviors. Participants in an activity were far more likely than nonparticipants to associate that activity with positive outcomes, concepts, and affect and less likely to produce outcomes, concepts, and affect and less likely to produce negative associations. CONCLUSIONS: The word association methodology provides a useful technique for exploring adolescents' cognitions and affective reactions with regard to health-related behaviors. The data provided by this method have implications for prevention and intervention programs, as well as for future research.

Adolescent↗