Search PubMed⌕ Search

Biomedical subjects

P Murphy

Publications and source records attributed to P Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2002

Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera.

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272-4760), 306 (range, 111-408) and 143 (range, 91-282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10(6) platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2-14.3) raised in secondary polycythemia (range, 26-104) compared with normal controls (range, 9.7-31.1), P<0.01. In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.

Adult↗
PubMed2002

Molecular epidemiology of cystic fibrosis-linked Burkholderia cepacia complex isolates from three national referral centres in Ireland.

AIMS: Burkholderia cepacia is a Gram-negative bacterium associated with increasing morbidity and mortality and is readily transmitted among infected cystic fibrosis (CF) patients. The B. cepacia complex consists of five distinct subgroups, termed genomovars. A collection of 17 presumptive B. cepacia isolates, obtained from three national CF referral centres located in different geographical regions in Ireland, was studied. The aim of this study was to investigate these isolates using molecular subtyping protocols for evidence of genetic relationships and for the presence of antibiotic resistance-encoding class 1 integron structures. METHODS AND RESULTS: Genomovar classifications were assigned to each isolate based on HaeIII enzyme profiles of their recA locus. Genetic relationships among this collection were also assessed after restriction fragment length polymorphism (RFLP)-mediated analysis of the 16S rDNA locus and DNA amplification fingerprinting (DAF). The surface expression of the cable pilus gene (cblA) may facilitate an early step in the infection process. All isolates were tested by amplification strategies for this marker. Burkholderia cepacia is known to be resistant to several antimicrobial agents. Resistance typing showed that the majority were resistant to three or more common antimicrobial agents. Five of the 17 isolates were resistant to sulphonamide, a characteristic linked with the presence of class 1 integrons. Gene cassettes containing beta-lactamase (oxa) and aminoglycoside acetyltransferase (aac(6')-1a) encoding genes were identified by polymerase chain reaction amplification. CONCLUSIONS: Most of the isolates in this study were classified as genomovar III and were indistinguishable based on their corresponding 16S rDNA-RFLP profiles, whilst DAF further subtyped the collection. The cblA marker was identified in 47% of the isolates, many of which clustered in the genomovar III group. Class 1 integrons with recombined gene cassettes containing bla-OXA and aac(6')-1a genes were identified. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the application of molecular methods to investigate B. cepacia, a well-recognized human pathogen, cultured from Irish CF patients. Genomovar III was the most common genomic type identified. DNA fingerprinting further subtyped the latter isolates, facilitating a more detailed description of the molecular epidemiology. Drug resistance in these organisms can be explained, at least in part, by the presence of class 1 integrons. Development of targeted infection control strategies could be facilitated using these applied methods.

Amino Acid Sequence↗
PubMed2002

Application of wavelet transform to uterine electromyographic signals recorded using abdominal surface electrodes.

OBJECTIVE: The aim of this study was to explore the use of the wavelet transform technique to extract and display simultaneously the time, frequency and amplitude information corresponding to electromyographic (EMG) activity of the uterus during labor recorded using abdominal electrodes. METHODS: Uterine EMG signals were recorded from patients in labor using three pairs of electrodes placed across the maternal abdomen. In all the patients uterine activity was also recorded either from an intrauterine pressure catheter (IUPC) or a tocodynamometer. The EMG signals were analyzed using spectral analysis and wavelet analysis. RESULTS: Uterine EMG bursts corresponded with uterine activity measured with either the IUPC or the tocodynamometer. Using wavelet analysis a time-frequency-amplitude plot was obtained to separate out the frequency components relating to uterine EMG activity. CONCLUSION: This study showed that the wavelet transform could be a useful tool to study the uterine EMG activity. Continued studies on frequency content, amplitude and origin of uterine EMG activity could be helpful in understanding uterine contraction.

Algorithms↗
PubMed2001

Developmental regulation of leptin gene expression in rat brain and pituitary.

We have previously reported the expression of leptin mRNA and protein in adult rat brain and pituitary gland. We report here the presence of leptin and leptin receptor mRNA in neonatal female rat brain and pituitary using RT-PCR as well as leptin and leptin receptor immunoreactivity in neonatal rat brain. In addition, we describe age-related changes in leptin mRNA expression in female rat brain and pituitary from postnatal day 2 to 28, evaluated using semi-quantitative RT-PCR analysis. Age-related differences in leptin (ob) mRNA levels were tissue-dependent. The most striking developmental changes were noted in the pituitary and cerebral cortex. In the pituitary, ob mRNA levels were maximal during postnatal days 7-14 and fell sharply by postnatal day 22. In cortex, ob mRNA levels were low in neonatal pups (day 2-7) but increased significantly between postnatal days 14 and 28. Leptin mRNA was detectable at postnatal day 2 in hypothalamus and subcutaneous fat. No significant differences in the level of expression were observed between postnatal day 2 and 28. Serum leptin levels were highest at day 7-14 and decreased significantly by day 21-28, coincident with the fall in pituitary leptin expression. The high levels of leptin expression in the neonatal pituitary suggest that this gland may contribute to the circulating leptin levels during early postnatal development, when adipose deposits are minimal. These data indicate that regulation of leptin gene expression in the postnatal period is tissue-dependent, a finding, which suggests that local leptin expression may have important functional significance in the development of the brain-pituitary system.

Age Factors↗
PubMed2001

Detection of DNA adducts of benzo[a]pyrene using immunoelectrophoresis with laser-induced fluorescence. Analysis of A549 cells.

Detection of benzo[a]pyrene diol epoxide (BPDE)-damaged DNA in a human lung carcinoma cell line (A549) has been performed using free zone affinity capillary electrophoresis with laser-induced fluorescence (LIF). Using BPDE as a model carcinogenic compound, the speed, sensitivity and specificity of this technique was demonstrated. Under free zone conditions, an antibody bound adduct was baseline-resolved from an unbound adduct in less than 2 min. The efficiencies of separation were in excess of 6 x 10(5) and 1 x 10(6) plates per meter for the antibody-bound and unbound adducts, respectively. Separation using a low ionic strength buffer permitted the use of a high electric field (830 V/cm) without the loss of resolving power. Using LIF detection, a concentration detection limit of roughly 3 x 10(-10) M was achieved for a 90-mer oligonuleotide containing a single BDPE. The use of formamide in the incubation buffer to enhance denaturing of DNA did not affect the stability of the complex between the antibody and the adducts. Using a fluorescently labeled BPDE-modified DNA adduct probe, a competitive assay was established to determine the levels of BPDE-DNA adducts in A549 cells.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2001

Is reduced dermatoglyphic a-b ridge count a reliable marker of developmental impairment in schizophrenia?

BACKGROUND: Finger and hand prints are formed during the late first and second trimester of foetal development, after which they remain unchanged. Their expression may be influenced by both genetic and environmental factors. Some studies have suggested that a reduced total finger ridge count (TFRC) and, in particular, a reduce total a-b ridge count (TABRC), may be associated with schizophrenia. AIM: To study these two variables in a large, ethnically homogenous sample and to compare our findings with those of other recent studies. METHOD: Finger and hand prints of 150 people with DSM-III-R schizophrenia were compared with those of 92 healthy controls. RESULTS: Patients had a reduced mean TABRC (P = 0.03) compared with controls. There was a significant (P=0.02) linear trend for lower TABRC and increasing incidence of schizophrenia (ORlineartrend = 1.3; 95%CI1.1-1.7), implying a continuous increase in the risk for schizophrenia with reduction in TABRC. No significant difference between groups was observed for TFRC. CONCLUSION: These results provide further evidence that dermatoglyphic abnormalities exist in at least some patients with schizophrenia and that the a-b ridge count may be a marker of disruption, probably environmental, that occurs when the developing brain may also be particularly vulnerable to such insult. These findings support the concept that some cases of schizophrenia may be due to adverse intrauterine events.

Adult↗
PubMed2001

Relationship of the factor structure of psychopathology in schizophrenia to the timing of initial intervention with antipsychotics.

Timing of intervention with antipsychotic medication may influence long-term outcome in schizophrenia in a manner that is poorly understood. This study evaluated psychopathology, its factor structure, and cognitive dysfunction in older patients with chronic schizophrenia in relation to the intervals from onset of psychosis to initiation of treatment with antipsychotics, and from initiation of antipsychotic treatment to current assessments. The subjects were 129 patients with schizophrenia, many of whom became ill in the preneuroleptic era. Their current psychopathology was assessed using the Positive and Negative Syndrome Scale, and its factor structure examined using principal component analysis. Current general and executive cognitive function was evaluated using the Mini-Mental State Examination and the Executive Interview, respectively. Using multiple regression modelling, increasing duration of initially unmedicated psychosis, but not the much longer duration of subsequently treated illness, was the primary predictor of psychomotor poverty (negative symptoms) but not of reality distortion or disorganisation over the three domains of psychopathology resolved; duration of initially unmedicated psychosis marginally predicted the severity of general, but not of executive, cognitive dysfunction. Delayed intervention with antipsychotics appears associated with poorer long-term course in terms of increased severity of psychopathology in the psychomotor poverty domain.

Aged↗
PubMed2001

A three-part bilateral swinglock design denture revisited.

This case was first reported by one of the authors in 1987, subsequent to the patient being treated using a combination of a hinge and split pin sectional denture. The same patient attended for review some 14 years later for assessment of this denture at which stage a replacement was made.

Aged↗
PubMed2001

Vulnerability to involuntary movements over a lifetime trajectory of schizophrenia approaches 100%, in association with executive (frontal) dysfunction.

This study assessed the prevalence of involuntary movements among older inpatients with severe schizophrenia, many of whom had experienced a lifetime of illness and its treatment, and examined their neuropsychological correlates. The subjects of this study were 128 inpatients with a DSM-IV diagnosis of schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale, the Mini-Mental State Examination for general cognitive impairment and the Executive Interview for executive dyscontrol; additionally, their medical records were reviewed in detail for treatment histories. Prevalence of involuntary movements was examined and their clinical correlates determined in relation to topography of movement disorder using logistic regression. In schizophrenia, prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%; >75years, 93%. The primary correlate both of overall and of orofacial movements was poor executive function, whereas the primary correlate of limb-trunkal movements was poor general cognitive function. On approaching the limits of human longevity following a lifetime trajectory of illness and its treatment, essentially 'all' patients with schizophrenia appear inherently vulnerable to the emergence of involuntary movements in topographically specific association with cognitive deficits.

Adult↗
PubMed2001

Identification of genes regulated by prolonged acid exposure in Helicobacter pylori.

To investigate the influence of prolonged acid exposure on the gene expression, transcripts of Helicobacter pylori, grown under pH 5.5 and pH 7.4 for five successive passages, were analysed by differential display PCR. Eight genes were regulated by prolonged acid exposure. These genes included topA, tufB, ureB, flaA, atoE in the H. pylori genome and a cDNA fragment with 54% identity of the predicted amino acid sequence to a Bacillus cereus YkoW protein. The remaining two cDNA fragments had no significant homology to known sequences. Our data suggest that most of these genes might be required for the resistance of H. pylori to prolonged acid exposure.

Acids↗
PubMed2001

Two domains of the human bZIP transcription factor TCF11 are necessary for transactivation.

TCF11 is a bZIP transcription factor of the CNC subfamily. It has been implicated in the regulation of the antioxidant response and is vital during embryonic development, but its precise biological functions have not yet been fully worked out. Structural characterization of the gene and several of its products indicates that complex regulatory mechanisms are employed. To investigate how altering the structure of the gene products might influence their activity we have mapped functional domains within the protein. We show that two separate domains are required for transactivation by full-length TCF11: an N-terminal acidic domain and a serine-rich stretch adjacent to the CNC-bZIP domains. A naturally occurring shorter isoform (identical to LCR-F1) produced by internal initiation of translation is unable to transactivate in our assay. However, the shorter form could interfere with the transactivating ability of the longer form, which indicates a control mechanism for keeping the activity of TCF11 at a desired level. We show that TCF11 and the closely related CNC-bZIP factor p45 NF-E2 show different cell type-specific activation patterns with full-length TCF11 being active in COS-1 cells but silent in erythroid cells (K562), whereas p45 NF-E2 is active in K562 cells and silent in COS-1 cells. Domain swapping experiments show that cell type-specific activity is not fully determined by dimerization/DNA binding domains or transactivation domains alone. The resulting profile of activity is most likely achieved by interaction of the domains and their cell-specific environment.

Humans↗
PubMed2001

TCF11/Nrf1 overexpression increases the intracellular glutathione level and can transactivate the gamma-glutamylcysteine synthetase (GCS) heavy subunit promoter.

Gamma-glutamylcysteinylglycine or glutathione (GSH) performs important protective functions in the cell through maintenance of the intracellular redox balance and elimination of xenobiotics and free radicals. The production of GSH involves a number of enzymes and enzyme subunits offering multiple opportunities for regulation. Two members of the CNC subfamily of bZIP transcription factors (TCF11/Nrf1 and Nrf2) have been implicated in the regulation of detoxification enzymes and the oxidative stress response. Here we investigate the potential role of one of these factors, TCF11/Nrf1, in the regulation of GSH levels in the cell and particularly its influence on the expression of one of the enzymatic components necessary for the synthesis of GSH, the heavy subunit of gamma-glutamylcysteine synthetase (GCS(h)). Using overexpression of the transcription factor in COS-1 cells we show that TCF11/Nrf1 stimulates GSH accumulation. Using co-transfection with reporter constructs where reporter expression is driven through the GCS(h) promoter we show that this increase may be mediated in part by induced expression of the GCS(h) gene by TCF11/Nrf1. We further show that a distal portion of the promoter including two antioxidant-response elements (AREs) predominantly mediates the TCF11/Nrf1 transactivation and an electromobility shift assay showed that just one of these AREs specifically binds TCF11/Nrf1 as heterodimers with small Maf proteins. We suggest that TCF11/Nrf1 can operate through a subset of AREs to modulate the expression of GCS(h) together with other components of the pathway and in this way play a role in regulating cellular glutathione levels.

Aminoacyltransferases↗
PubMed2001

Reaction of fumonisin with glucose prevents promotion of hepatocarcinogenesis in female F344/N rats while maintaining normal hepatic sphinganine/sphingosine ratios.

The reaction of the primary amine of fumonisin B(1) (FB(1)) with glucose was hypothesized to detoxify this mycotoxin. Eighty 10-day-old female F344/N rats were injected intraperitoneally with diethylnitrosamine (DEN; 15 mg/kg of body weight). At 4 weeks of age, the weaned rats were randomly assigned to one of four treatment groups with 20 rats each. At 9 weeks of age, four rats from each treatment group were killed. At 12 weeks, another five rats from each group were killed. At 20 weeks of age, the remaining rats were killed. In comparison with the rats fed basal diet or FB(1)-glucose (containing 25 ppm of FB(1)), rats fed 8 ppm (residual amount of free FB(1) in the FB(1)-glucose mixture) or 25 ppm of FB(1) had greater alanine aminotransferase activity at 9 and 20 weeks of age (P < 0.001), greater endogenous hepatic prostaglandin E(2) production at 20 weeks of age (P < 0.05), and significantly lower plasma cholesterol at 20 weeks of age (P < 0.01). Placental glutathione S-transferase (PGST)-positive and gamma-glutamyltransferase (GGT)-positive altered hepatic foci (AHF) occurred only in rats fed 25 ppm of FB(1) at 20 weeks of age. Hepatic natural killer (NK) cell activities were similar among the four groups, but the percentage of total liver-associated mononuclear cells exhibiting the NKR-P1(bright) marker was significantly greater in rats fed FB(1)-glucose, FB(1) (8 ppm) and FB(1) (25 ppm) than in control rats at 9 weeks of age, and FB(1)-glucose-treated rats had significantly lower NKR-P1(bright) cells as a percentage of total liver-associated mononuclear cells than rats fed 25 ppm of FB(1) at 20 weeks of age (P < 0.05). PGST- or GGT-positive AHF were not detected in any treatment group at 9 or 12 weeks of age. At 20 weeks of age, half of the rats fed 25 ppm of FB(1) had PGST- and GGT-positive AHF. The sphinganine (Sa) concentration and the Sa/sphingosine (So) ratio were significantly greater in the rats fed 25 ppm of FB(1) diet as compared with the control groups at, respectively, 12 or 20 weeks of age. Therefore, modifying FB(1) with glucose seems to prevent FB(1)-induced hepatotoxicity and promotion of hepatocarcinogenesis. The Sa/So ratio was not the most sensitive biomarker of FB(1) toxicity.

Alkylating Agents↗
PubMed2001

The heat shock response reduces myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in mice.

The stress response (SR) can block inflammatory gene expression by preventing activation of transcription factor nuclear factor-kappa B (NF-kappaB). As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases, we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis (EAE). EAE was actively induced in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide. Whole body hyperthermia was used to induce a heat shock response (HSR) in immunized mice 2 days after the booster MOG(35-55) peptide injection. The HSR reduced the incidence of EAE by 70%, delayed disease onset by 6 days, and attenuated disease severity. The HSR attenuated leukocyte infiltration into CNS assessed by quantitation of perivascular infiltrates, and by reduced staining for CD4 and CD25 immunopositive T-cells. T-cell activation, assessed by the production of interferon gamma (IFNgamma) in response to MOG(35-55), was also decreased by the HSR. The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE, including the early increase in RANTES (regulated on activation of normal T-cell expressed and secreted) expression, and the later expression of the inducible form of nitric oxide synthase. The early activation of transcription factor NF-kappaB was also blocked by the HSR. The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases.

Animals↗
PubMed2001

Prevention of venous thromboembolism in critically ill surgery patients: a cross-sectional study.

BACKGROUND: The risk for venous thromboembolism (VTE) and the risk for bleeding among critically ill surgical patients are both important in the early postoperative period. MATERIALS AND METHODS: To record VTE prophylaxis prescribed for surgical patients in the intensive care unit (ICU) within the first postoperative week. We conducted a prospective observational cross-sectional study of Canadian university affiliated ICUs. RESULTS: Of 29 ICU Directors approached, 28 (96.6%) participated, representing 34 ICUs and 589 ICU beds across Canada. Among 89 patients, surgical procedures were 32 abdominal (36.0%), 19 vascular (21.3%), 10 orthopedic (11.2%), 9 trauma (10.1%), 8 neurologic (9.0%), 5 thoracic (5.6%), 5 gynecologic (5.6%), and 1 for necrotizing fasciitis (1.1%). VTE prophylaxis with unfractionated heparin, low molecular weight heparin, and intermittent pneumatic compression was used in 35 of 89 (39.3%), 8 of 89 (9.0%), and 9 of 89 (10.1%) patients, respectively, whereas 8 of 89 (9.0%) patients were receiving therapeutic anticoagulation. Two methods of VTE prophylaxis were prescribed for 20 of 89 (22.5%) patients. Prophylaxis with unfractionated or low molecular weight heparin was significantly less likely to be prescribed for postoperative ICU patients requiring mechanical ventilation compared with those weaned from mechanical ventilation (odds ratio [OR] 0.36, P =.03). The use of intermittent pneumatic compression devices was significantly associated with current hemorrhage (OR 13.5, P =.02), and risk for future hemorrhage (OR 19.3, P =.001). CONCLUSIONS: VTE prevention for surgical ICU patients within the first postoperative week appear to be individualized, and influenced by current and future risks of thrombosis and bleeding.

Adult↗
PubMed2001

Investigation of infection with Campylobacter jejuni in a man with hypogammaglobulinaemia using PCR-single-stranded conformational polymorphism (PCR-SSCP) typing.

This study investigated several episodes of infection of Campylobacter jejuni in an immunocompromised male with hypogammaglobulinaemia, presenting with diarrhoea and bacteraemia over a 16-month period, by employing three phenotyping and four genotyping schemes, including the single-stranded conformational polymorphism (SSCP) technique to establish if infection was reinfection or persistent infection. Four isolates from blood culture and two faecal isolates of Campylobacter jejuni were obtained from the patient by direct selective plating on Skirrow Selective agar. Isolates were characterised at the sub-species level by Penner serology, Preston biotyping, Preston phage-typing, as well as E3CJC2 restriction fragment length polymorphism (RFLP), 16S ribotyping, flagellin (flaA) RFLP and single-stranded conformational polymorphism (SSCP) analyses. Phenotyping and genotyping sub-species analyses demonstrated that the patient was infected with at least two different strains of Campylobacter jejuni, i. e. one strain that persisted throughout the 16-month period and another strain that was transient suggesting reinfection from a different source. SSCP analysis was the most discriminatory of all the typing schemes examined and demonstrated an altered genotype of the persistent strain, whereby there were subtle modifications to the hypervariable regions of the flaA gene. Overall, as SSCP examines the hypervariable region of the flaA gene and as this technique can detect point mutations, differences between SSCP banding patterns may represent markers and thus examine mutations that occur under immune selection, thereby permitting the C. jejuni to evade the host immune response. In conclusion, this study describes the novel use of SSCP genotyping of C. jejuni and demonstrated that this method is a highly discriminatory technique which may be beneficial in outbreak characterisation, but which is not suitable to examine the clonal patterns of C. jejuni over a long period of time.

Agammaglobulinemia↗