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Biomedical subjects

P Moran

Publications and source records attributed to P Moran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Multiple paternity increases effective size of southern Atlantic salmon populations.

Genetic analyses were performed on the progeny of Atlantic salmon (Salmo salar L.) sampled in natural redds of three rivers flowing into the Bay of Biscay, the Nivelle, the Mandeo and the Sella. These rivers are at the southern limit of the European distribution of the species and their populations are small and endangered by human activities. Nine variable number of tandem repeat (VNTR) loci (five minisatellites and four microsatellites) were used for parentage analysis. Multiple male participation was recognized in the fertilization of eggs. A large proportion was fertilized by precociously mature parr. We demonstrate that multiple paternity derived from mature parr is crucial for the conservation of genetic variability in small populations of Atlantic salmon.

Animals↗
PubMed2000

Anti-E in pregnancy.

Since the introduction of anti-Rhesus (Rh) D prophylaxis for RhD-negative women, other Rh and non-Rh red cell alloantibodies have become relatively more important and are now responsible for the greater proportion of haemolytic disease of the newborn. Anti-C and anti-E are the most commonly implicated non-D Rh antibodies in the pathogenesis of haemolytic disease of the newborn'. In 1977 Pepperell et al. reported the outcome of 44 women with anti-E. This is the only published series that investigates the implications of anti-E during pregnancy. The present report presents a retrospective study of the outcome of 122 pregnancies in which anti-E was the sole alloantibody detected.

Erythroblastosis, Fetal↗
PubMed2000

Isolation, characterization, and chromosomal location of the tRNA(Met) genes in Atlantic salmon (Salmo salar) and brown trout (Salmo trutta).

This work describes the isolation, characterization, and physical location of the methionine tRNA in the genome of Atlantic salmon (Salmo salar L.) and brown trout (Salmo trutta L.). An Atlantic salmon genomic library was screened using a tRNA(Met) probe from Xenopus laevis. Two cosmid clones containing the Atlantic salmon tRNA(Met) gene were isolated, subcloned and sequenced. The tRNA(Met) was mapped to metaphase chromosomes by fluorescence in situ hybridization (FISH). Chromosomal data indicated that the tDNA of methionine is tandemly repeated in a single locus in both species. Analysis of genomic DNA by Southern hybridization confirmed the tandem organization of this gene.

Animals↗
PubMed2000

Use of phage display for the generation of human antibodies that neutralize factor IXa function.

The use of libraries of phage-displayed human single-chain antibody fragments (scFv) has become a new, powerful tool in rapidly obtaining therapeutically useful antibodies. Here, we describe the generation of human scFv and F(ab')2 directed against the gamma-carboxyglutamic acid (Gla) domain of coagulation factor IX. A large library of human scFv, displayed either on M13 phage or expressed as soluble proteins, was screened for binding to human Gla-domain peptide (Tyr1-Lys43). Among a panel of scFv that bound to the factor IX-Gla domain, six scFv clones recognized full-length factor IX and exhibited strong inhibitory activity of factor IX in vitro. After reformatting as F(ab')2, the affinity for factor IX of three selected clones was determined: 10C12 Kd = 1.6 nmol/l, 13D1 Kd = 2.9 nmol/l, and 13H6 Kd = 0.46 nmol/l. The antibodies specifically bound to factor IX and not to other coagulation factors, as assessed by enzyme-linked immunosorbent-type and human plasma clotting assays. The complementarity determining region amino acid sequences of clones 10C12 and 13D1 only differed at a single residue, whereas 13H6 showed little homology, suggesting that 13H6 binds to a different epitope within the factor IX-Gla domain. Despite the slightly lower affinity of 10C12 F(ab')2 versus 13H6 F(ab')2, 10C12 was consistently more potent than 13H6 in prolonging the activated partial thromboplastin time (APTT), in inhibiting platelet-mediated plasma clotting, and in inhibiting factor X activation by the intrinsic Xase complex. Finally, 10C12 F(ab')2 also recognized and neutralized factor IX/factor IXa of different species, as demonstrated by the specific APTT prolongation of dog, mouse, baboon and rabbit plasma. In summary, the results validate the usefulness of scFv phage-displayed libraries to rapidly generate fully human antibodies as potential new therapeutics for thrombotic disorders.

Amino Acid Sequence↗
PubMed2000

Epitope location on tissue factor determines the anticoagulant potency of monoclonal anti-tissue factor antibodies.

Tissue factor (TF), the cellular cofactor for the serine protease factor VIIa (F.VIIa), triggers blood coagulation and is involved in the pathogenesis of various thrombosis-related disorders. Therefore, agents which specifically target tissue factor, such as monoclonal antibodies, may provide promising new antithrombotic therapy. We mapped the epitopes of several anti-TF antibodies using a panel of soluble TF mutants. They bound to three distinct TF regions. The epitope of the 7G11 antibody included Phe50 and overlapped with a TF-F.VIIa light chain contact area. The common epitope of the antibodies 6B4 and HTF1 included residues Tyr94 and Phe76 both of which make critical contacts to the catalytic domain of F.VIIa. The antibodies D3 and 5G6 had a common epitope outside the TF-F.VIIa contact region. It included residues Lys 165, Lys 166, Asn199, Arg200 and Lys201 and thus overlapped with the substrate interaction region of tissue factor. The antibodies 5G6 and D3 were potent anticoagulants when infused to flowing human blood in an ex-vivo thrombosis model. Plasma fibrinopeptide A levels and fibrin deposition were completely inhibited. In contrast, 6B4 was a weak inhibitor in this ex-vivo thrombosis model, and HTF1 displayed no inhibition at all. These disparate activities were also reflected in TF-dependent F.X activation assays performed with human plasma. The potency differences could neither be explained by the determined binding affinities nor by the on-rates of antibodies. Therefore, the results suggest that antibody binding epitope and hence the particular mechanism of inhibition, is the main determinative factor of anticoagulant potency of anti-TF antibodies.

Antibodies, Monoclonal↗
PubMed1999

The epidemiology of antisocial personality disorder.

This paper reviews the current state of knowledge about the frequency, natural history, risk factors and associations of antisocial personality disorder. Important recent developments are discussed, and where possible, findings have been tabulated Epidemiological surveys have shown that antisocial personality disorder is a common disorder, with a prevalence rate of between 2 and 3% among community samples, rising to 60% among male prisoners. Antisocial personality disorder is a chronic condition, and is associated with a multitude of medical and social problems. These include substance abuse, deliberate self harm and crime. Genetic and environmental factors have been implicated in the aetiology of the disorder. However, despite the large amount of research into antisocial personality disorder, longitudinal data are missing and the validity of the diagnosis, therefore, remains questionable. The paper concludes with recommendations for future research.

Antisocial Personality Disorder↗
PubMed1999

Micropuncture laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) significantly reduces the discomfort and disability typically associated with open cholecystectomy, but there is still room for improvement. METHODS: In order to further reduce the trauma of access, we have introduced a technique of micropuncture laparoscopic cholecystectomy (MPLC) that utilizes three 3-mm cannulae in addition to the standard 10-mm cannula at the umbilicus. MPLC was performed in 25 patients (median age, 52 years; m/f, three of 22) with symptomatic cholelithiasis. RESULTS: The operation was completed in all patients. The median duration of surgery was 75 min (range, 45-180). Sixteen patients were discharged the same day and nine patients the next day. All the patients had an uncomplicated recovery. Only eight patients requested postoperative analgesia while in hospital. Micropuncture exploration of the bile duct was carried out in one patient. CONCLUSIONS: MPLC is a feasible and safe technique that appears to improve on the benefits of LC; it makes the operation even more feasible as a day-surgery procedure.

Ambulatory Surgical Procedures↗
PubMed1999

Seasonal influences on admissions for affective disorder and schizophrenia in Ireland: a comparison of first and readmissions.

Although genetic and environmental factors operating before or around the time of birth have been demonstrated to be relevant to the aetiology of the major psychoses, a seasonal variation in the rates of admission of such patients has long been recognised. Few studies have compared first and readmissions. This study examined for seasonal variation of admission in the major psychoses, and compared diagnostic categories by admission status. Patients admitted to Irish psychiatric inpatient facilities between 1989 and 1994 with an ICD-9/10 diagnosis of schizophrenia or affective disorder were identified from the National Psychiatric Inpatient Reporting System (NPIRS). The data were analysed using a hierarchical log linear model, the chi-square test, a Kolmogorov-Smirnov (KS) type statistic, and the method of Walter and Elwood. The hierarchical log linear model demonstrated significant interactions between the month of admission and admission order (change in scaled deviance 28.77, df = 11, P < 0.003). Both first admissions with mania, and readmissions with bipolar affective disorder exhibited significant seasonality. In contrast, only first admissions with schizophrenia showed significant seasonal effects. Although first admissions with mania and readmissions with bipolar disorder both show seasonality, seasonal influences appear to be more relevant to onset of schizophrenia than subsequent relapse.

Hospitalization↗
PubMed1999

Cloning and physical mapping of Atlantic salmon (Salmo salar L.) telomeric sequences.

We cloned and sequenced DNA containing telomeric sequences from Atlantic salmon (Salmo salar L.). At both low and high stringency conditions, a cloned probe containing (TTAGGG)n sequences binds only at the extreme termini of the chromosomes, not at interstitial sites. Blocks of interstitial telomere-like sequences were expected from the chromosome polymorphism because of Robertsonian translocations that exist in Atlantic salmon. Our results support the hypothesis that telomeric sequences were almost entirely lost during chromosome fusion events.

Animals↗
PubMed1999

Physical distribution of SINE elements in the chromosomes of Atlantic salmon and rainbow trout.

SINE sequences are interspersed throughout virtually all eukaryotic genomes. In the family Salmonidae three families of SINEs have been identified. In this work we have attempted to characterize and locate by means of fluorescent in situ hybridization (FISH) one of these families (HpaI) in the genome of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Our results show that these SINEs are interspersed throughout all the chromosome pairs except for the heterochromatin-positive areas, generating a banding pattern that could be useful for chromosome identification in both species.

Animals↗
PubMed1999

Macrogeographical population differentiation in oceanic environments: a case study of European hake (Merluccius merluccius), a commercially important fish.

Polymorphism at six microsatellite loci was used to study genetic variability and population structure in six geographically distant natural populations of European hake (Merluccius merluccius L.). Four hundred and eighty-three individuals were sampled from Trondheimsfjord in Norway, the Celtic Sea, the southern Bay of Biscay, Faro off Portugal, the Mediterranean Sea north of the coast of Tunisia and the Adriatic Sea. Population subdivision was found between Mediterranean and Atlantic samples, theta = 0.029 (P < 0. 001). No substructuring was found between samples within the Mediterranean Sea, theta = 0.003 and RST = 0.007 (P > 0.05). The Atlantic population structure appears to be more complex than previously suggested by the placement of stock boundaries by the International Council for the Exploration of the Seas (ICES). Analyses based on various models of microsatellite evolution all suggest that differentiation exists between Bay of Biscay and Portugese samples, theta = 0.013 (P < 0.001), RST = 0.036 (P < 0. 001) which are currently managed as one stock. By contrast, fixation indices indicated no differentiation between southern Bay of Biscay samples and Celtic Sea samples, theta = 0.003 (P = 0.02), phiST = 0. 007 (P = 0.10) which are managed as separate stocks. These results suggest that if the observed trends are stable through time, current management policy of European hake may need revision.

Animals↗
PubMed1999

Clinical management of established pre-eclampsia.

This chapter summarizes the identification, assessment and management of women with established pre-eclampsia. Guidelines for out-patient management and in-patient treatment are given and are based on clinical experience and published reports. Drug treatment options are briefly reviewed and the timing of delivery is discussed. A comprehensive regimen for the intrapartum management of severe pre-eclampsia is provided founded on protocols used in the Royal Victoria Infirmary, Newcastle upon Tyne, over recent years. The chapter emphasizes the importance of medical history, clinical examination and investigations when arriving at what are often difficult clinical decisions. Controversial areas are highlighted with reference to recent published reports.

Anticonvulsants↗
PubMed1999

Burch colposuspension for the treatment of coital urinary leakage secondary to genuine stress incontinence.

The efficacy of Burch colposuspension in treating the symptom of coital urinary leakage in women with genuine stress incontinence has to date never been reported. Women who presented to our clinic with regular coital urinary leakage and urodynamically proven genuine stress incontinence between 1993 and 1997, and who proceeded to a Burch colposuspension procedure, were reviewed to determine the outcome of surgery. Fifty-five women were identified (mean age 46.1 years) with a mean follow-up interval after surgery of 18 months (range 3-42 months). All 55 women had symptoms of stress, urge and coital incontinence preoperatively. Following colposuspension, the subjective cure rates for stress and urge incontinence were 84% and 85%, respectively. Of 52 women that were sexually active after surgery, 81% described no further coital incontinence. The success or failure of surgery was not influenced by whether leakage occurred with penetration or orgasm preoperatively.

Journal Article↗