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Biomedical subjects

B Murphy

Publications and source records attributed to B Murphy.

At least 109 records · Page 6Linked to original sources

The response of human dermal microvascular endothelial cells to hypoxia.

Dermal microvascular endothelial cells (DMEC) exposed to hypoxic conditions show a rapid induction of several proteins that do not increase in other cell types placed in a similar environment. These DMEC proteins differ from the well-characterized stress proteins that have been observed in a wide variety of cultured cell types. The DMEC proteins are induced rapidly, within 2-4 h, and are expressed transiently. They include a group of acidic proteins (pI approximately 5-5.2) with molecular weights in the range 100,000-120,000 and at least one glycoprotein (pI 5.1, M(r) 57,000) that is probably expressed on the cell surface. In some primary DMEC cell strains, this response is accompanied by a transient overall increase in protein synthesis. The oxygen-regulated proteins (ORP) that are induced in most other cell types under hypoxic conditions show little variation in their rate of synthesis in DMEC within the first 24 h. The response of DMEC differs from that of umbilical vein endothelial cells (UVEC) and from spindle-shaped cells derived from DMEC, that show a response to hypoxia that is similar to most other cell types. The changes seen in DMEC proteins take place in the same time scale as ischemia-reperfusion injury and may reflect the specialized change of functions of the microvasculature observed under conditions of hypoxic stress in vivo.

Cell Hypoxia↗

The relations of emotionality and regulation to dispositional and situational empathy-related responding.

The purpose of the present study was to examine the prediction of adults' situational and dispositional empathy-related responses from measures of emotionality (emotional intensity and positive and negative affect) and regulation. A multimethod approach including self-reported, facial, and heart rate (HR) responses was used to assess situational vicarious emotional responding; Ss' (and sometimes friends') reports were used to assess the dispositional characteristics. In general, dispositional sympathy, personal distress, and perspective taking exhibited different, conceptually logical patterns of association with indexes of emotionality and regulation. The relations of situational measures of vicarious emotional responding to dispositional emotionality and regulation varied somewhat by type of measure and gender. Findings for facial and HR (for men) measures were primarily for the more evocative empathy-inducing stimulus. In general, the findings provided support for the role of individual differences in emotionality and regulation in empathy-related responding.

Adolescent↗

Primary Sjögren's syndrome and gamma heavy chain disease.

We describe a patient who has primary Sjögren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis. Sjögren's syndrome is known to be complicated by lymphoproliferative disorders and tubulointerstitial nephritis but gamma heavy chain disease is rare (approximately 100 cases described). There is one previously reported case of gamma heavy chain disease associated with primary Sjögren's syndrome and 2 cases associated with secondary Sjögren's syndrome. Our patient and the 3 other patients described in the literature did not have evidence of an underlying lymphoproliferative disorder.

Aged↗

Patient drug education. Improving the working relationship between general practitioners and pharmacists.

Qualitative research with GPs, pharmacists and consumers explored their views of patients' needs for drug information, and perceived difficulties in communication between GPs, patients and pharmacists. Strategies suggested by participants for improving patient drug education were: guidelines for giving information on medication; conventions for writing the prescription; a referral mechanism from the pharmacist to the GP; distribution of patient education materials; professional bodies to reduce ethical and organisational barriers to inter professional communication; and the development of local networks and education programs.

Drug Information Services↗

Exclusion of linkage between schizophrenia and the D2 dopamine receptor gene region of chromosome 11q in 112 Irish multiplex families.

A leading theory hypothesizes that schizophrenia arises from dysregulation of the dopamine system in certain brain regions. As this dysregulation could arise from abnormal expression of D2 dopamine receptors, the D2 receptor gene (DRD2) on chromosome 11q is a candidate locus for schizophrenia. We tested whether allelic variation at DRD2 and five surrounding loci cosegregated with schizophrenia in 112 small- to moderate-size Irish families containing two or more members affected with schizophrenia or schizoaffective disorder, defined by DSM-III-R. Evidence of linkage was assessed using varying definitions of illness and modes of transmission. Assuming genetic homogeneity, linkage between schizophrenia and large regions of 11q around DRD2 could be strongly excluded. Assuming genetic heterogeneity, variation at the DRD2 locus could be rejected as a major risk factor for schizophrenia in more than 50% of these families for all models tested and in as few as 25% of the families for certain models. The DRD2 linkage in fewer than 25% of these families could not be excluded under any of the models tested. Our results suggest that the major component of genetic susceptibility to schizophrenia is not due to allelic variation at the DRD2 locus or other genes in the surrounding chromosomal region.

Alleles↗

Elevation of human cerebrospinal fluid clusterin concentration is associated with acute neuropathology.

Clusterin is a serum glycoprotein which is an inhibitor of complement and is expressed in many tissues in cell injury and death. It has been identified normal and pathological brain tissue and is a component of normal human cerebrospinal fluid (CSF). We have measured the clusterin concentration of 115 abnormal and normal human CSF samples and related these data to the patient's clinical diagnoses. CSF clusterin levels in patients with neurodegenerative and meningeal disease were within the normal range. Twelve of 15 patients with demyelination, however, had significant elevation of CSF clusterin concentration. This was not a specific finding for multiple sclerosis as elevated clusterin levels were also seen in patients with other acute neuropathology. Determination of CSF clusterin concentration may be of clinical value in neurological diagnosis.

Acute Disease↗

Fish-hook injuries.

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Eye Foreign Bodies↗

Cocaine and cocaethylene: microdialysis comparison of brain drug levels and effects on dopamine and serotonin.

Cocaethylene is a pharmacologically active metabolite resulting from concurrent cocaine and ethanol consumption. The effects of cocaine and cocaethylene on extracellular levels of dopamine in the nucleus accumbens, and serotonin in the striatum were characterized in vivo in the anesthetized rat. Both intravenous (3 mumol/kg) and intraperitoneal (44 mumol/kg) routes of administration were used. In addition to monitoring neurotransmitter levels, microdialysate levels of cocaine and cocaethylene were determined at 4-min intervals after intravenous administration, and at 20-min intervals after intraperitoneal administration. Extracellular levels of dopamine in the nucleus accumbens were increased to approximately 400% of preinjection value by both cocaine and cocaethylene when administered intravenously. Cocaine caused a significant increase of striatal serotonin to 200% preinjection value, whereas cocaethylene had no effect. Brain levels of cocaine and cocaethylene after intravenous administration did not differ. After intraperitoneal administration, extracellular levels of dopamine in the nucleus accumbens were increased to 400% of preinjection levels by cocaine, but were only increased to 200% of preinjection levels by cocaethylene, the difference being statistically significant. Serotonin levels were increased to 360% of preinjection levels by cocaine, but only to 175% of preinjection value by cocaethylene. Levels of cocaine attained in brain were significantly higher than those for cocaethylene, suggesting pharmacokinetic differences with the intraperitoneal route. These results confirm in vivo that cocaethylene is more selective in its actions than cocaine with respect to dopamine and serotonin uptake. In addition, route-dependent differences in attainment of brain drug levels have been observed that may impact on interpretations of the relative potency of the reinforcement value of these compounds.

Animals↗

The reliability and validity of echocardiographic measurement of left ventricular mass index in hemodialysis patients.

We assessed the reliability and validity of a formula, based on echocardiographically derived parameters, to calculate left ventricular mass index (LVMI) in a group of 15 chronic hemodialysis patients. All patients had M-mode echocardiography before and after a hemodialysis session. Echocardiograms were interpreted by 2 observers blind to each other's measurements. Interobserver reliability for LVMI was high (r = 0.94, p < 0.0007). LVMI decreased in 11 of 15 patients during dialysis and increased in 4. The mean difference in LVMI between pre- and posthemodialysis was 26.2 +/- 15 g/m2 (p < 0.0001). End-diastolic diameter decreased from 53.5 +/- 5.9 to 49.5 +/- 7.5 mm (p = 0.0016). These data indicate that measurement of LVMI is highly reproducible in hemodialysis patients but that it changes significantly over the course of a hemodialysis session. Its use as an outcome measure in clinical trials in hemodialysis patients should be interpreted with caution.

Adult↗

The role of radiography and computed tomography in the diagnosis of acute dislocation of the proximal tibiofibular joint.

A cadaveric study was undertaken to determine the best radiographic method of diagnosing dislocation of the proximal tibio-fibular (PTFJ) joint. Three pairs of cadaver knees were used, the right side serving as a control in each case. Plain radiographs, antero-posterior (AP) lateral and 45 degrees oblique films, and axial computed tomography (CT) scans were obtained with the joints in each of three positions: (1) anatomical, (2) dislocated anteriorly and (3) dislocated posteriorly. Similar views were obtained in the control joints with the PTFJ undisturbed. The radiographs were assessed by eight independent observers and the results were analysed. The diagnostic accuracy with plain AP and lateral radiographs was 72.5%. This was unchanged with the addition of oblique views, but improved to 82% with the control films and 86% with the axial CT scans. The authors conclude that in the diagnosis of suspected dislocation of the PTFJ, axial CT scanning is the investigation of choice. Plain AP, lateral and comparison views are useful but less accurate, while oblique views are unhelpful and unnecessary.

Acute Disease↗

Immunohistological detection of C5b-9 complement complexes in normal and pathological human livers.

The immunohistological localization of components and neoantigens of the C5b-9 human terminal complement complex was studied in 30 human liver biopsies. C5b-9, apparently in the soluble SC5b-9 form, was invariably detected in normal liver capsule and normal portal tract connective tissue. In livers with fibrosis and or cirrhosis, the pathological connective tissue contained variable amounts of SC5b-9 which was distributed in a similar way to that seen in normal livers. There was no significant C5b-9 deposition outside of the portal tract and capsule in any of the liver biopsies. In particular, in pathological livers, there was no deposition in relation to cellular infiltrates or areas of hepatic necrosis. These data support the concept that C5b-9 is a common component of connective tissue but do not indicate that C5b-9 mediated pathways are involved in the pathogenesis of hepatic injury.

Clusterin↗

Normal bone density in Irish women: is American normative data suitable for use in Ireland?

The objective of the study was to determine whether or not U.S. normal data for female Vertebral Bone Mineral Density is suitable for use in an Irish population. One hundred and fifty-six healthy Caucasian women of permanent Irish domicile had bone densitometry performed using single energy quantitative computed tomography of L2, L3 and L4 vertebrae. We found that comparison of our results to normal American data shows a slight and progressive increase in bone mineral content of postmenopausal American women with age relative to the Irish population. This difference is small and not sufficient to justify development of separate normal values for Irish women. We conclude that this discrepancy may be due to a combination of environmental and racial factors or to the more rigorous exclusion criteria applied in our study.

Adult↗

Differential expression of clusterin in inducible models of apoptosis.

Apoptosis (programmed cell death) and necrosis can be readily distinguished morphologically and biochemically. The most striking biochemical change observed in apoptotic cells is the cleavage of the genomic DNA into discrete nucleosome sized fragments, producing a laddering pattern when the DNA is examined electrophoretically. It has recently been shown that RNA and protein products of the testosterone-repressed prostate message-2 gene are induced, coordinate with the onset of cell death. This gene has been isolated from a variety of species and tissues, it is highly conserved, and collectively referred to as clusterin. We have examined a number of inducible leucocyte models of apoptosis, including glucocorticoid and calcium ionophore induced thymocyte death, 'aged' neutrophils and cytotoxic T cells, and found that in these situations that cell death is not associated with up-regulation of clusterin gene expression. The finding that clusterin is not expressed in all cells undergoing apoptosis would suggest that this molecule is not critical to the mechanism of cell death. It does, however, provide the first example of a readily detectable marker which is differentially expressed in cells undergoing apoptosis and adds further weight to the argument that apoptosis is not a uniform phenomena, but is dependent on the nature of the cells involved and the means of induction.

Animals↗

Antibodies against cortisol block suppressive effects of corticosteroids on lymphocytes in vitro.

Lymphocyte transformation assays were used to test the ability of antibodies against cortisol to reduce bioactivity of corticosteroids in vitro. Mononuclear cells were separated from whole bovine blood and cultured in the presence of PHA alone, PHA + steroid, PHA + steroid + anticortisol, or PHA + steroid + anti-bovine serum albumin. Tritiated thymidine uptake was determined for all groups during the last 24 hr of a 72-hr culture period by scintillation counting. Polyclonal anticortisol against cortisol-bovine serum albumin conjugated in the 21 position was more effective in blocking cortisol activity than monoclonal anticortisol built against conjugates in the 3 position. The steroids that suppressed PHA-induced lymphocyte proliferation in a concentration-dependent manner were: cortisol, corticosterone, dexamethasone, prednisolone, 11-deoxycortisol, and 11-deoxycorticosterone. Aldosterone, cortisone, cholesterol, estradiol, and progesterone did not exhibit concentration-dependent effects and, thus, were not considered suppressive. These concentration-independent steroids were also the least suppressive (with the exception of aldosterone). Anticortisol was able to reduce bioactivity of suppressive corticosteroids that had an 11-hydroxy group, suggesting the antibody was primarily made against this site. Anti-BSA was not effective in blocking corticosteroid activity, but it did enhance proliferation of lymphocytes if added in combination with weakly suppressive steroids. Anticortisol also had an enhancing effect when added with some weakly suppressive steroids. We conclude that antibodies against cortisol are capable of reducing bioactivity of steroids that strongly suppress lymphocyte proliferation. Additionally, the 11-hydroxy group may be an important antigenic determinant of steroid molecules.

Adrenal Cortex Hormones↗