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Biomedical subjects

P Murphy

Publications and source records attributed to P Murphy.

At least 91 records · Page 5Linked to original sources
PubMed1999

New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families.

Genetic linkage of schizophrenia to markers at 5q11.2-13.3 had been reported previously in five Icelandic and two British families, but attempts at replication in independent samples have been unsuccessful. We report here an update on the diagnoses and results of linkage analyses using newer highly polymorphic microsatellite markers at or near the loci D5S76 and D5S39 in the original sample of pedigrees and in two new family samples from Iceland and from Britain. The new results show a reduction in evidence for linkage in the original sample and evidence against linkage in the two new family samples. Although it is possible that a rare locus is present, perhaps in the region 5p14.1-13.1 rather than 5q11.2-13.3, it appears most likely that the original positive lod scores represent an exaggeration of the 'true' lod scores due to random effects and that the small lod scores we now obtain could have arisen by chance.

Chromosomes, Human, Pair 5↗
PubMed1999

Molecular-based approach to the differentiation of mealybug (Hemiptera: Pseudococcidae) species.

The rDNA internal transcribed spacer (ITS) region of 4 mealybug species, Pseudococcus viburni (Signoret), P. longispinus (Targiono-Tozzetti), P. calceolariae (Maskell), and P. similans (Lidgett), was isolated by polymerase chain reaction (PCR) amplification, cloned, and sequenced. In this region of the genome there were numerous differences, including nucleotide substitutions, insertions, or deletions between P. viburni, P. longispinus, and P. calceolariae, whereas P. calceolariae and P. similans were very similar. Based on sequence differences between the ITS regions, we designed PCR primers that were able to differentiate the 4 mealybug species and that correlated with morphological differences found between adult females of these species. The PCR amplification by using the species-specific primers enabled the differentiation of not only adult females but also eggs, juveniles, and adult males, which was not previously possible by using conventional identification methods.

Animals↗
PubMed1999

No evidence for linkage of schizophrenia to DXS7 at chromosome Xp11.

There have been claims that a gene on the X chromosome may contribute to susceptibility to schizophrenia. Crow (1988) initially proposed that such a gene might lie in the pseudoautosomal region, but when evidence that weakened this hypothesis accumulated, he proposed that a susceptibility locus might be present elsewhere on the sex chromosomes instead. DeLisi et al. (1994) found a small nonsignificant positive lod score between the marker DXS7 and schizophrenia, but other failed to replicate this finding. Another study reported by Crow and DeLisi's group was also weakly positive for this marker (Dann et al., 1997). This locus was then investigated in a collaborative study by Laval et al. (1997), which produced a nonparametric lod score of 2.44. Using a sample of 17 pedigrees from Britain and Iceland, we have also tested the hypothesis of linkage between DXS7 and schizophrenia. The 17 families were selected from a larger sample on the basis of an absence of male-to-male transmission for schizophrenia. These families were originally selected for having multiple cases of schizophrenia within them and for having no cases of bipolar affective disorder. We genotyped subjects for a marker at DXS7 and performed classical lod score and model-free linkage analysis using broad and narrow definitions of affection with schizophrenia. We found strongly negative lod scores and no evidence for linkage using model-free analysis. Therefore, this study does not support the hypothesis of linkage of schizophrenia to DXS7, and the evidence for a susceptibility locus on this part of the X chromosome is weakened.

Chromosome Mapping↗
PubMed1999

Vascular surgical intervention for complications of cardiovascular radiology: 13 years' experience in a single centre.

This study investigates incidence and outcome of iatrogenic vascular complications needing surgery in a single vascular unit serving interventional vascular radiology and interventional cardiology. Evolution of diagnostic and interventional cardiovascular radiology, along with the introduction of non-surgical therapies for such complications, may have influenced the number of vascular complications requiring emergency surgery. Vascular surgical data were collected from information prospectively entered on computerised database and case note review. Radiology data were collated from prospective entries in logbooks and computerised database. In all 24,033 cardiovascular radiological procedures were performed between 1984 and 1996 (61% cardiac), numbers increasing annually. During this period, 62 patients (40 peripheral; 22 cardiac) required emergency surgical intervention after radiological procedures. Mean age was 61.9 years (range 1-92 years), male to female ratio was 1:1. The absolute number of cases requiring surgical intervention peaked in 1989, subsequently reducing annually. Sites of vascular injury included common femoral artery (40), brachial artery (6), iliac artery (6), popliteal artery (5), other (5). A total of 87 vascular surgical operations was performed (range 1-6 operations per patient). Interventions included thrombectomy/embolectomy (29), bypass grafting (16), direct repair (27). Seven major amputations were performed (two bilateral). Mortality after surgery was 9.7%. Mean inpatient hospital stay was 11.3 days (range 0-75 days). A Poisson regression model indicates a 5% reduction in risk for each successive year of observation; however, this did not reach statistical significance (P = 0.16, 95% CI 12% decreased risk to 2% increased risk). The risk of surgical intervention after diagnostic or interventional cardiovascular radiology is diminishing but still requires vigilance. Necessity for surgical intervention is associated with a high risk of morbidity and mortality.

Adolescent↗
PubMed1998

Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription.

We have previously shown that the widely expressed human transcription factor TCF11/LCR-F1/Nrf1 interacts with small Maf proteins and binds to a subclass of AP1-sites. Such sites are required for beta-globin 5' DNase I hypersensitive site 2 enhancer activity, erythroid porphobilinogen deaminase inducibility, hemin responsiveness by heme-oxygenase 1 and expression of the gene NAD(P)H:quinone oxidoreductase1. Here we report the optimal DNA-binding sequences for TCF11/LCR-F1/Nrf1 alone and as a heterodimer with MafG, identified by using binding-site selection. The heterodimer recognises a 5'-TGCTgaGTCAT-3' binding-site that is identical to the established NF-E2-site, the antioxidant response element and the heme-responsive element while the binding specificity of the homomer is less stringent. To investigate the activity of TCF11 through this selected site, both alone and in the presence of MafG, we have used a transient transfection assay. TCF11 alone activates transcription while MafG alone acts as a repressor. When co-expressed, MafG interferes with TCF11 transactivation in a dose dependent manner. This indicates that MafG protein, which heterodimerises efficiently with TCF11 in vitro (the heterodimer having a higher affinity for DNA than TCF11 alone), does not co-operate with TCF11 in transactivating transcription. We propose that since both these factors are widely expressed, they may act together to contribute to the negative regulation of this specific target site. Efficient positive regulation by TCF11 may require alternative partners with perhaps more restricted expression patterns.

Base Sequence↗
PubMed1998

The progression and correction of duplex detected velocity shifts in angiographically normal vein grafts.

OBJECTIVES: To review the sensitivity of duplex scanning and angiography at detecting vein graft stenoses in patients on a graft surveillance programme. DESIGN: Prospective, open, non-randomised study. PATIENTS AND METHODS: Since February 1993, 143 patients with 148 grafts (70% in situ, 30% reversed) have attended postoperative infrainguinal vein graft surveillance for a minimum of 6 weeks. Fifty-seven graft stenoses in 57 grafts were identified by duplex scanning as a localised high velocity jet. Angiography was performed in all except 12 patients. RESULTS: Angiography confirmed a duplex abnormality in all but 10 patients. Of these, five patients remain stable and asymptomatic with a persisting duplex abnormality. The remaining five patients, although asymptomatic, exhibited disease progression on duplex and surgical intervention confirmed significant stenoses, which were successfully treated. CONCLUSION: The results suggest that duplex scanning is a reliable imaging modality for detecting vein graft stenoses. Selection for surgical correction can be made, in some circumstances on the basis of clinical and ultrasound criteria alone.

Adult↗
PubMed1998

The outcome of children requiring admission to an intensive care unit following bone marrow transplantation.

We report the results of a retrospective study of the role of intensive care unit (ICU) admission in the management of 367 children who underwent bone marrow transplantation (BMT) at a tertiary referral institution. 39 patients (11%) required 44 ICU admissions for a median of 6 d. 70% received marrow from unrelated donors, half of which were mismatched; 80% had leukaemia and two-thirds were considered high-risk transplants. Respiratory failure was the major reason for admission to ICU. 75% of admissions required mechanical ventilation (for a median of 5 d) and 20 patients had lung injury as defined by the criteria of the Seattle group. None of 11 patients with proven viral pneumonitis survived (P = 0.06) and only one of 20 patients with lung injury survived (P < 0.01). Six of seven patients with a primary neurological problem survived (P < 0.001); these appear to represent a good outcome group. Age, the presence of graft-versus-host disease, the use of inotropes, isolated renal or hepatic impairment, and paediatric risk of mortality (PRISM) score were not predictive of outcome. In total, 12 patients (27% of admissions) survived and were discharged from hospital 30d or more after admission and eight (18%) survived >6 months. ICU admission can be beneficial to selected children post-BMT but it may be less useful in proven viral pneumonitis. Where mechanical ventilation is required, the duration of this support should be limited unless there is rapid improvement.

Acute Disease↗
PubMed1998

Antioxidant activity of propofol in blood from anaesthetized patients.

The antioxidant capacity of plasma taken from 10 patients before and during propofol anaesthesia was measured. Mean total plasma antioxidant activity fell from 1.73 to 1.64 mM L-1 trolox equivalents (P = 0.047). This was caused by haemodilution since mean haemoglobin concentration fell from 13.0 to 12.5 g dL-1 (P = 0.016). The time to 50% haemolysis (H50) of 10% red blood cell suspensions induced by 2,2'azo-bis(2-amidinopropane) dihydrochloride (ABAP) was measured in blood from six patients. There was no change when red cells alone were studied, but when the patients' plasma was added to red cell suspensions (producing 10% plasma and 10% red cell suspensions), mean H50 increased from 291 to 308 min (P = 0.049). Despite there being no overall increase in plasma antioxidant activity, the lipid soluble component of blood antioxidant activity appears to be increased by propofol.

Adult↗
PubMed1997

Exclusion of linkage between schizophrenia and the gene encoding a neutral amino acid glutamate/aspartate transporter, SLC1A5.

An abnormality in glutamatergic function has been hypothesized as being of etiological importance in schizophrenia. Twenty-three multiplex English and Icelandic schizophrenia families were genotyped with a polymorphic dinucleotide repeat sequence in the 3'-untranslated region of the glutamate/aspartate transporter gene called SLC1A5. Using the lod and a model-free method of linkage analysis (MFLINK), no evidence of linkage between SLC1A5 and schizophrenia was found. Our results do not support the hypothesis that SLC1A5 gene mutations or allelic variants provide a major gene contribution to the etiology of schizophrenia. However, because of the likelihood of heterogeneity of linkage in schizophrenia, there is a case for testing other pedigrees for linkage to the SLC1A5 locus. The SLC1A5 locus is one of a complex family of genes encoding neutral amino acid transporter proteins and the genetic relation between these other loci and schizophrenia has not yet been established.

Alleles↗
PubMed1997

Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22.

Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 (theta = 0.01, alpha = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at theta = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding.

Bipolar Disorder↗
PubMed1997

Relationship of fat embolism to haemodynamic and echocardiographic changes during cemented arthroplasty.

PURPOSE: Pressurisation of the medullary cavity during cemented arthroplasty causes "intravasation" of marrow fat. The purpose of this study was to examine the relationship between the amount of pulmonary intravascular fat and the haemodynamic and echocardiographic changes. METHODS: Anaesthetised mongrel dogs (n = 16) underwent bilateral cemented arthroplasty (BCA) to create a large embolic load. Haemodynamic measurements included blood pressure (BP), pulmonary artery pressure (PAP), right atrial pressure and cardiac output as well as transoesophageal echocardiographic (TEE) assessment of right ventricular (RV) and left ventricular (LV) areas. Using quantitative morphometry on postmortem lung specimens, the proportion of lung tissue occluded by fat was measured. RESULTS: Mean BP decreased within one minute of BCA, coinciding with the appearance of echogenic material in the RV. The RV area increased by 56% (P < 0.05) and LV area decreased by 34% (P < 0.05) while PAP increased from 15 +/- 3 mmHg to 39 +/- 10 mmHg within one minute (P < 0.001). The PAP remained elevated throughout the study (30 min). Stroke volume decreased in 14/15 dogs, yet cardiac output was maintained by increased heart rate. There was a curvilinear relationship (r = 0.87) between the maximum increase in PAP and the proportion of lung occupied by fat. CONCLUSION: In this model, stroke volume decreased within one minute of BCA when fat embolism accompanied prosthesis insertion. The TEE detected an increased RV area and reduced LV area associated with decreased stroke volume. The maintenance of cardiac output after intraoperative fat embolism depends primarily on the ability to increase heart rate.

Animals↗
PubMed1997

How cancer gene testing can benefit patients.

A revolution has taken place in the past few decades in our understanding of the genetic origins of human cancer. In particular, genes implicated in inherited susceptibility to forms of cancer are increasingly being identified and their mutations characterized. Many of these genes are also involved in sporadic tumours of the same type, as well as additional tumour types. Understanding of these genes will therefore affect an even greater number of patients.

Bioethics↗