PubMed Health⌕ Search

Biomedical subjects

P Murphy

Publications and source records attributed to P Murphy.

At least 19 recordsLinked to original sources
PubMed1992

Human HuH-7 hepatoma cells express urokinase and plasminogen activator inhibitor-1: identification, characterization and regulation by inflammatory mediators.

The human hepatoma HuH-7 cell line was shown to constitutively express both a plasminogen activator (PA) and a plasminogen activator inhibitor (PAI). Four sublines of the HuH-7 cell line were analyzed and found to express differing amounts of both PA and PAI. The plasminogen activator produced by these cells was identified as urokinase based upon molecular weight, inhibition of activity with anti-UK but not anti-t-PA antibodies, adherence to an anti-UK affinity column and by Northern blotting demonstrating positive hybridization with the cDNA for UK, but not with the t-PA cDNA. The inhibitor produced by HuH-7 cells was identified as PAI-1 by molecular weight, immunoblotting techniques, adherence to an anti-PAI-1 affinity column, and by Northern blotting demonstrating positive hybridization with the cDNA for PAI-1, but not with the PAI-2 cDNA. The expression of both UK and PAI-1 by HuH-7 cells could be modulated by cytokines known to influence the acute phase response. The addition of interleukin-1 (IL-1) induced the expression of both UK and PAI-1. The increase of PAI-1 was due to an increase in amount of the PAI-1 mRNA. The presence of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) also increased UK and PAI-1 levels, although not as dramatically as IL-1. The addition of IL-1 together with IL-6 produced a slight synergistic response with respect to PAI-1 expression. This suggests that PAI-1 is able to respond to mediators which aid in the induction of the acute phase response. These studies demonstrate that cells of liver origin are able to produce components of the fibrinolytic system. The synthesis of these components can be altered by inflammatory mediators and thus may be involved in hepatic regulation of fibrinolysis in both normal and diseased states.

Blotting, Northern↗
PubMed1992

Duplex ultrasonography and pulse-generated run-off in selecting claudicants for femoropopliteal angioplasty.

Non-invasive assessment of lower limb vasculature may avoid unnecessary angiography in claudicants. Colour duplex ultrasonography of the femoral and popliteal arteries was performed to assess patency and the presence of any stenoses, and pulse-generated run-off (PGR) was used to assess the distal vasculature. In 65 legs colour duplex scanning was successful, compared with angiography, in identifying the site and type of disease in the femoropopliteal segment and 23 lesions were correctly identified as suitable for angioplasty. More patent distal vessels were demonstrated by PGR than by angiography; no vessels patent on angiography were missed by PGR. The estimated cost of diagnostic angiography was 330 pounds per test compared with 52 pounds for non-invasive assessment. By using duplex examination as a screening test, a potential saving of 8062 pounds could have been made in this series. Duplex ultrasonography offers a non-invasive and cost-effective alternative to diagnostic angiography for clinically suspected infrainguinal arterial disease presenting as claudication. PGR was not of clinical value in assessing suitability for angioplasty.

Aged↗
PubMed1992

Concentration of ondansetron in cerebrospinal fluid following oral dosing in volunteers.

This study measured the concentrations of ondansetron in plasma and cerebrospinal fluid (CSF) in six volunteers after oral dosing to steady state. Ondansetron concentrations ranged from 39.5-147 ng ml-1 in plasma and from 2.6-15.4 ng ml-1 in CSF. There was good correlation between plasma and CSF concentrations (r = 0.89, p = 0.017). CSF concentrations were less than 15% of plasma concentrations in all cases, indicating that the rate of penetration of the blood brain barrier by ondansetron is low.

Aged↗
PubMed1992

Modulation of plasminogen activator and plasminogen activator inhibitor expression in the human U373 glioblastoma/astrocytoma cell line by inflammatory mediators.

The human U373 glioblastoma/astrocytoma cell line was found to constitutively produce and secrete a plasminogen activator and a plasminogen activator inhibitor. The plasminogen activator was identified as urokinase based on apparent molecular weight, immunoblotting with anti-urokinase antibodies, and Northern blotting with a human urokinase cDNA probe. The inhibitor secreted by U373 cells was found to be related to the PAI-1 molecule based on reactivity with anti-human PAI-1 antibodies, apparent molecular weight, and Northern blot analysis with a human PAI-1 cDNA probe. The expression of both urokinase and the PAI-1-like molecule by U373 cells could be modulated by phorbol myristate acetate or by inflammatory mediators such as interferon-gamma and interleukin-1. In the case of interleukin-1, the alpha form exhibited no detectable effect while the beta form not only elevated inhibitor levels, it also appeared to induce the production of tissue plasminogen activator. Thus, in these cells interleukin-1 beta induces alterations in PA and PAI expression and interleukin-1 alpha does not, even though the two forms are reported to utilize the same cellular receptor.

Astrocytes↗
PubMed1992

Immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis A virus (HAV) peptide sequences: evidence for a neutralization domain near the amino terminus of VP1 of HAV.

We evaluated the antigenic characteristics of chimeric picornaviruses created by inserting peptide sequences from hepatitis A virus (HAV) capsid proteins into the B-C loop of VP1 of Sabin strain type 1 poliovirus (PV-1). Fifteen viable chimeras were generated. Each retained the ability to be neutralized by polyclonal PV-1 antisera. Two chimeras (H15 and H2) stimulated production of low levels of HAV neutralizing antibodies in immunized rabbits or mice, although in both cases only a small fraction of immunized animals produced this response. The H15 chimera, which contains residues 13-24 of HAV VP1, elicited HAV neutralizing antibodies in three of nine rabbits and at least one of seven immunized mice. These results indicate that a neutralization domain exists in this region of VP1. However, human sera with high titers of antibodies to HAV failed to neutralize or immunoprecipitate this chimera, suggesting the absence of a significant antibody response to this neutralization domain following natural infection. Sera from rabbits immunized with H15 that did not develop HAV neutralizing antibodies contained antibodies reactive with the HAV peptide segment expressed by the H15 virus, indicating substantial differences in the specificities of antibodies elicited by this peptide segment among individual immunized rabbits. The H15 peptide insert was an effective antigen, as indicated by a high level of sensitivity of the H15 chimera to neutralization by a related anti-peptide antibody which was itself devoid of HAV neutralizing activity. One of 16 rabbits immunized with the H2 chimera (residues 101-108 of HAV VP1) developed HAV neutralizing antibodies, confirming both the presence and the highly conformational nature of a neutralization antigenic site involving these residues of HAV.

Amino Acid Sequence↗
PubMed1992

Burns from electric fire-guards.

Nine children with burns caused by contact with electric fire-guards are presented. A method of preventing such injuries is recommended.

Burns, Electric↗
PubMed1992

Hemodynamic effects of different temporary pacing modes for the management of bradycardias complicating acute myocardial infarction.

Twelve patients requiring temporary pacing following acute myocardial infarction (AMI) (10 heart block, 2 junctional bradycardia) had hemodynamic measurements taken with ventricular demand pacing at 80 ppm (VVI80), ventricular demand pacing at the atrial rate (VVIa), physiological pacing (DDD), and spontaneous (intrinsic) rhythm. VVI80 mode did not improve any hemodynamic parameter compared with spontaneous rhythm. VVIa mode improved diastolic and mean arterial pressures only. DDD mode improved most hemodynamic parameters compared with spontaneous rhythm (cardiac output by 29% [P less than 0.0001]; blood pressure: diastolic by 24% [P less than 0.01], systolic by 19% [P less than 0.01], mean by 21% [P less than 0.005]; pulmonary wedge pressure by 10% [P = 0.057] and right atrial pressure by 24% [P less than 0.005]) and also significantly improved some parameters compared with VVIa (cardiac output by 20% [P less than 0.001], systolic blood pressure by 11% [P less than 0.01] and right atrial pressure by 15% [P less than 0.01]). Physiological pacing is hemodynamically superior both to ventricular pacing and spontaneous rhythm for patients requiring temporary pacing following AMI. Ventricular pacing at 80 ppm has little hemodynamic advantage over spontaneous rhythm.

Adult↗
PubMed1992

Mutations within the 5' nontranslated region of hepatitis A virus RNA which enhance replication in BS-C-1 cells.

Passage of human hepatitis A virus (HAV) in cell culture results in attenuation of the virus as well as progressive increases in the efficiency of virus replication in cell culture. Because the presence of identical mutations within the 5' nontranslated regions (5'NTRs) of several independently isolated cell culture-adapted HAV variants suggests that the 5'NTR may play a role in determining this change in virus host range, we constructed chimeric infectious cDNA clones in which portions of the 5'NTR of cell culture-adapted HM175/p35 virus were replaced with cDNA from either wild-type virus (HM175/wt) or a second independently isolated, but closely related cell culture-adapted virus (HM175/p16). Substitution of the complete 5'NTR of HM175/p35 with the 5'NTR of HM175/wt resulted in virus with very small replication foci in continuous African green monkey kidney (BS-C-1) cells, indicating that 5'NTR mutations in HM175/p35 virus are required for optimal growth in these cells. A chimera with the 5'NTR sequence of HM175/p16 retained the large foci of HM175/p35 virus, while the growth properties of other viruses having chimeric 5'NTR sequences indicated that mutations at bases 152 and/or 203 to 207 enhance replication in BS-C-1 cells. These findings were confirmed in one-step growth experiments, which also indicated that radioimmunofocus size is a valid measure of virus replication competence in cell culture. An additional mutation at base 687 of HM175/p16 had only a minor role in enhancing growth. In contrast to their effect in BS-C-1 cells, these 5'NTR mutations did not enhance replication in continuous fetal rhesus monkey kidney (FRhK-4) cells. Thus, mutations at bases 152 and/or 203 to 207 enhance the replication of HAV in a highly host cell-specific fashion.

Animals↗
PubMed1992

The effects of flosequinan on hemodynamics and oxygen delivery in cor pulmonale.

The hemodynamic effects of a new orally active vasodilator, flosequinan, were compared with placebo (single blind) over 24 h in eight patients with pulmonary hypertension secondary to severe chronic obstructive pulmonary disease. Mean pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189) dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04) and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A significant reduction in systemic vascular resistance was observed, 132 (35,230) dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial blood pressure or arterial blood gas tensions. Flosequinan favorably altered pulmonary hemodynamics relative to systemic and resulted in a significant improvement in oxygen delivery. The hemodynamic and blood gas effects of this compound suggest that it is a promising vasodilator for the treatment of pulmonary hypertension.

Adult↗
PubMed1992

Stability of parental nurturance as a salient predictor of self-esteem.

The relationship of parental nurturance to self-esteem for seven distinct adolescent and early-adulthood age groups (N = 784) was investigated. Analysis showed that even though mothers' and fathers' nurturance together were more strongly related to self-esteem during the junior high school years (R2 values greater than 50% were obtained in each of the junior high samples) than during the high school and college years (R2 values less than 40% were obtained in each of these samples), parental nurturance still remained a robust predictor of self-esteem during these latter years. These results were discussed within the context of (a) the stability at different ages of the bases upon which one's judgments of self-esteem are made, and (b) parental nurturance as a stabilizing influence during the transitional years of adolescence and early adulthood.

Adolescent↗
PubMed1991

Intra-arterial streptokinase infusion in acute lower limb ischaemia.

Between 1986 and 1988, 38 patients (29 men and nine women), median age 65 years (range 38-85 years), underwent local intra-arterial streptokinase therapy for acute lower limb ischaemia. Three patient groups were identified: 15 with acute on chronic ischaemia (group 1), 12 postangioplasty (group 2) and 11 postfemorodistal bypass (group 3). Distal arteriographic run-off was a significant discriminant between success and failure in group 1 (n = 15, chi 2 = 11.5, P = 0.001) and in the overall group (n = 38, chi 2 = 17.2, P less than 0.001). In group 2, four patients with good run-off had an unsuccessful outcome; this was due in all cases to technical problems (haemorrhage in two and intimal dissection in two). In group 3, two patients with good run-off had unsuccessful streptokinase infusions. In both cases the graft failed in the early postoperative period (less than 30 days). By contrast, the four patients whose grafts occluded after 30 days had successful streptokinase infusions and long-term graft patency was achieved by further surgery and balloon dilatation. In all groups, no patient with a poor run-off had a successful outcome following streptokinase administration. The role of local intra-arterial streptokinase therapy in the critically ischaemic limb remains controversial, but these results suggest that an adequate run-off is an important factor in the selection of patients for treatment.

Acute Disease↗
PubMed1991

Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos.

Mouse embryos were exposed to maternally administered RA on day 8.0 or day 7 3/4 of development, i.e. at or just before the differentiation of the cranial neural plate, and before the start of segmentation. On day 9.0, the RA-treated embryos had a shorter preotic hindbrain than the controls and clear rhombomeric segmentation was absent. These morphological effects were correlated with alterations in the spatiotemporal distribution patterns of two genes, Hox-2.9 and Krox-20, which are expressed in the otic and preotic hindbrain and in specific neural crest cell populations. Hox-2.9 was expressed throughout the preotic hindbrain region, instead of being confined to rhombomere 4. Krox-20 was not expressed rostral to the Hox-2.9 domain, i.e. its normal rhombomere 3 domain was absent. The Hox-2.9/Krox-20 boundary was ill-defined, with patches of alternating expression of the two genes. In migrating neural crest cells, Hox-2.9 expression was both abnormally extensive and abnormally prolonged. Neural crest cells expressing Krox-20 remained close to the neural tube. Embryos exposed to RA on day 8 1/4 appeared to be morphologically normal. We suggest that early events leading to rhombomeric segmentation and rhombomere-specific gene expression are specifically vulnerable to raised RA levels, and may require RA levels lower than those in the region of somitic segmentation.

Animals↗
PubMed1991

Xanthine oxidase/dehydrogenase in mammary gland of mouse: relationship to mammogenesis and lactogenesis in vivo and in vitro.

Xanthine oxidase/dehydrogenase (XO/XDH) increases at mid gestation in mammary gland but not in liver of the mouse and remains elevated until the pups are weaned at 20 d post partum. The increase in enzyme activity is due neither to alteration in activators or inhibitors nor to a production of a variant enzyme with altered catalytic properties. The increase is preceded in vivo by a surge of prolactin-like activity (placental lactogen) in plasma, and prolactin is required for induction of XO/XDH in explant culture in vitro. Induction of XO/XDH in vivo and in vitro precedes the full histological differentiation of the gland. In addition, induction of XO/XDH in vitro occurs more rapidly and at lower concentrations of prolactin than does histological differentiation. Thus although XO/XDH is present in milk, increased XO/XDH activity is an early event in mammogenesis in vivo and in vitro rather than a terminal component of differentiation.

Animals↗
PubMed1991

Effect of prior administration of cold saline on pain during propofol injection. A comparison with cold propofol and propofol with lignocaine.

A single-blind, randomised, controlled study was undertaken to compare the efficacy of three methods of preventing pain during injection of propofol on induction of anaesthesia. Patients were allocated randomly to receive unmodified propofol, propofol with 0.05% lignocaine, propofol at 4 degrees C and unmodified propofol preceded by 10 ml of 0.9% saline at 4 degrees C. Prior injection of cold saline reduced the incidence of pain and discomfort significantly (22%) compared with unmodified propofol (75%; p less than 0.005) and was similar to that after cold propofol (33%) and propofol with lignocaine (44%). There was no significant difference between the treatment groups.

Adult↗
PubMed1991

Effect of atrial pacing on the frequency of tachycardia in patients with recurrent junctional tachycardia.

In order to assess whether atrial pacing reduced the frequency of tachycardia in patients with recurrent junctional tachycardias, ten patients with recurrent junctional tachycardias with atrial Intertach antitachycardia pacemakers in situ were paced in a random order in atrial demand mode at 50 ppm (AAI 50), 80 ppm (AAI 80), and 100 ppm (AAI 100) for a period of up to 1 month. The numbers of tachycardias detected by the pacemaker over this period were recorded and compared with the number seen when unpaced (000). Correct arrhythmia detection by the pacemaker was confirmed by Holter monitoring. The number of tachycardias in 000 was 44.7 +/- 19.8 (mean +/- SEM). No significant reduction in tachycardia frequency was seen in any pacing mode. Back-up atrial pacing at 50 ppm tended to reduce the frequency of tachycardias (32.3 +/- 12.8 tachycardias; P = 0.06). The higher pacing rates increased the number of tachycardias (AAI 80; 57.1 +/- 24.6 tachycardias, P = 0.20: AAI 100; 81.8 +/- 30.2 tachycardias; P = 0.31). Symptoms increased with each pacing mode and palpitations were statistically more severe in AAI 100 mode. Four patients had disabling symptoms at this rate and had to drop out. Atrial back-up pacing may be of use in some patients with junctional tachycardia, but overdrive pacing is not helpful.

Adult↗