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Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis.

Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may be attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean +/- 2 S.D.: 19.1 +/- 13.5 nmol/L) were significantly higher than those of a normal population (n = 40; mean +/- 2 S.D.: 5.5 +/- 3.2 nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may not, however, be explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.

Adolescent↗
PubMed1997

Lichen planus and carcinoid tumour.

Lichen planus is not usually associated with malignancy and an association with carcinoid tumour has not been previously described. We now describe a patient in whom lichen planus and a carcinoid tumour presented simultaneously. In this case report, gastrointestinal symptoms of a small intestinal carcinoid tumour coincided with the appearance of a rash which progressed from a generalized exfoliative dermatitis to extensive lichen planus.

Female↗
PubMed1997

Petrified ears.

Explore the source record for details and available documents.

Aged↗
PubMed1996

Rate of cognitive decline in Alzheimer's disease is not affected by the alpha-1-antichymotrypsin A allele or the CYP2D6 B mutant.

Patients with Alzheimer's disease (AD) show considerable heterogeneity in the rate at which they decline cognitively. The biological basis for this heterogeneity is unknown. We genotyped 86 subjects with diagnoses of probable AD to determine if they carried the alpha-1-antichymotrypsin (ACT) A allele, which has been associated with AD, or the CYP2D6 B mutant, found at increased frequency in the Lewy body variant (LBV) of AD. We then examined longitudinally-collected cognitive data to determine if these genetic markers were associated with rate of cognitive decline. Our results indicate that neither the ACT A allele nor the CYP2D6 B allele have a significant association with rate of decline on the Folstein Mini Mental State examination. Further, subjects with both the ACT A allele and the apolipoprotein epsilon 4 allele showed no evidence of accelerated decline. These findings suggest that any increased risk of developing AD or LBV conferred by these markers is not necessarily accompanied by a more rapid rate of decline.

Aged↗
PubMed1996

Beta-amyloid peptide secretion by a microglial cell line is induced by beta-amyloid-(25-35) and lipopolysaccharide.

beta-Amyloid protein (betaAP) deposition is a neuropathologic hallmark of Alzheimer's disease (AD). Yet, the source of cerebral betaAP in AD is controversial. We examined the production of betaAP by the BV-2 immortalized microglial cell line using a sensitive enzyme immunoassay. Constitutive production of betaAP was detected in conditioned media from unstimulated BV-2 cells. Further, production of betaAP was induced by treatment of cultures by lipopolysaccharide (LPS) or betaAP-(25-35) and was inhibited by the calpain protease inhibitor MDL 28170. Treatment of BV-2 cells with LPS or betaAP-(25-35) did not affect cell-associated beta-amyloid precursor protein levels. These findings suggest that microglia may be an important source of betaAP in AD, and that microglial production of betaAP may be augmented by proinflammatory stimuli or by betaAP itself.

Alzheimer Disease↗
PubMed1996

Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to treatment.

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids--the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4 (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/- 0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and 'spill' into the plasma.

Acute Disease↗
PubMed1996

Porphyrin metabolism in hepatitis C infection.

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.

Adolescent↗
PubMed1996

Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones.

BACKGROUND: Octreotide treatment of acromegalic patients increases the % deoxycholic acid conjugates and the cholesterol saturation of gall bladder bile, and induces gall stone formation. AIMS: To study the roles of gall bladder emptying and intestinal transit in these phenomena. METHODS AND PATIENTS: Gall bladder emptying and mouth to caecum transit was measured in (a) control subjects and acromegalic patients given saline or 50 micrograms of octreotide, and (b) acromegalic patients taking long term octreotide. In the second group, large bowel transit was also measured. RESULTS: A single dose of octreotide inhibited meal stimulated gall bladder emptying, the ejection fraction falling from mean (SEM) 66.0 (2.3)% to 7.0 (5.3)% in controls (p < 0.001); from 72.5 (2.1) to 16.6 (5.1)% in untreated acromegalic patients (p < 0.001), and to 30.4 (9.5)% in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic group). Octreotide prolonged mouth to caecum transit time, from 112 (15) min to 237 (13) min in controls (p < 0.001), from 170 (13) min to 282 (11) min in untreated acromegalic patients (p < 0.001), and to 247 (10) min in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic patients). The mean large bowel transit in octreotide untreated compared with treated acromegalic patients remained unchanged (40 (6) h v 47 (6) h). CONCLUSIONS: Prolongation of intestinal transit and impaired gall bladder emptying may contribute to lithogenic changes in bile composition and gall stone formation in patients receiving long term octreotide.

Acromegaly↗
PubMed1996

P3 beta-amyloid peptide has a unique and potentially pathogenic immunohistochemical profile in Alzheimer's disease brain.

The presence of beta-amyloid in brain tissue is characteristic of Alzheimer's disease (AD). A naturally occurring derivative of the beta-amyloid peptide, p3, possesses all of the structural determinants required for fibril assembly and neurotoxicity. p3-specific antibodies were used to examine the distribution of this peptide in brain. p3 reactivity was absent or sparse in aged non-AD brains but was prevalent in selected areas of AD brain in diffuse deposits and in a subset of dystrophic neurites. p3-reactive dystrophic neurites were found both independent in the neuropil and associated with plaques. Little or no reactivity was observed to amyloid cores in classical plaques or to amyloid in the cerebral vasculature. The exclusive appearance of p3 reactivity in AD brain plus the selective localization of p3 reactivity to abnormal structures in the temporal lobe limbic system suggests that p3 may be a contributing factor to AD pathology.

Alzheimer Disease↗
PubMed1996

Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease.

Mutations in the presenilin (PS)-1 and PS-2 genes have been shown to be linked with the development of Alzheimer's disease (AD). We examined Alzheimer's brain tissue by immunohistochemistry using a set of antibodies raised to sequences shared between PS-1 and PS-2 proteins. These antibodies reacted exclusively with a subset of neurofibrillary tangles and not with neuropil threads or dystrophic neurites. Detection of the presenilin epitope in neurofibrillary tangles was observed in sporadic Alzheimer's disease brain samples and in samples from individuals carrying PS-1 and PS-2 mutations with no qualitative difference. These data indicate that both wild-type and mutant PS proteins are involved in a common pathogenic pathway in AD.

Alzheimer Disease↗
PubMed1996

Porphyrin abnormalities in acquired immunodeficiency syndrome.

OBJECTIVE: To examine prospectively porphyrin metabolism in a human immunodeficiency virus (HIV)-positive population. SETTING: Specialist referral unit at the Department of Genitourinary Medicine, St James's Hospital, Dublin, Ireland. PATIENTS: Twenty-eight men and 5 women (age range, 18-35 years). Twenty-nine were current or previous intravenous drug abusers. Four were thought to have sexually acquired HIV infection. All had a history of acquired immunodeficiency syndrome-defining illnesses. The patients were selected as a consecutive sample from the inpatient department. Eligibility criteria were cooperation with urine and stool collection and confirmed HIV seropositivity. The patients were matched to 2 groups: 1 with normal results of porphyrin studies and the other with abnormal findings from porphyrin studies. INTERVENTION: None. MAIN OUTCOME MEASURES: Plasma, urine, and stool porphyrin excretion patterns. RESULTS: Of the 33 patients in the study, 13 (40%) had increased urinary porphyrin excretion. All but 2 of these patients were seropositive for hepatitis C virus. No study patient had clinical evidence of porphyria. Four patients (12%), however, had urine and stool porphyrin excretion patterns that were classic for porphyria cutanea tarda. All 4 of these patients were hepatitis C virus-positive. Patients with porphyrinuria had a greater degree of immunosuppression (P = .002) than those with normal porphyrin metabolism, and they were more likely to be taking zidovudine (P = .009). CONCLUSIONS: Commonly, porphyrin metabolism is abnormal in persons with established HIV infection. Hepatitis C may contribute to abnormal porphyrin metabolism. An unexpected number of patients studied had porphyrin excretion patterns that were characteristic of porphyria cutanea tarda, and all of these were hepatitis C virus-positive. A diagnosis of porphyria cutanea tarda, especially in a young patient, should prompt investigation for underlying HIV and hepatitis C virus infections. Dermatologists should be aware of the infectious risk associated with the vesicles and erosions in these patients. Porphyrin studies should be performed in any patient with HIV and photosensitivity.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Expression of interleukin-11 and its encoding mRNA by glioblastoma cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine with important effects on hematopoietic and other cells. IL-11 was originally described as a product of stromal cell lines and fibroblasts. Using RT-PCR, Northern blotting, and ELISA we demonstrated that the human U373 and U87 glioblastoma cell lines expressed IL-11 and its encoding mRNA when stimulated with IL-1 beta, phorbol ester, and calcium ionophore. The neuroblastoma cell line SH-SY5Y did not express IL-11 mRNA in response to these agents. Cerebral expression of IL-11 by glial cells is important because IL-11 has been shown to have effects on neuronal electrophysiology, has overlapping functions with the neuroactive cytokine interleukin-6, and is part of the gp130-associated neuropoietic family of cytokines.

Astrocytes↗
PubMed1995

In vitro determination by 1H-NMR studies that bile with shorter nucleation times contain cholesterol-enriched vesicles.

Although biliary vesicles are considered to be the primary source of cholesterol found in cholesterol gallstones, difficulties in quantitatively separating the different cholesterol transport modes in bile still remain. Proton nuclear magnetic resonance spectroscopy (1H-NMR) offers an alternative approach. Investigations were carried out on both model biles and human gallbladder bile samples: (i) to follow the effect of increasing sodium glycocholate concentrations on the 1H-NMR spectra of arachidonic acid rich-phospholipid, and cholesterol-lecithin vesicles, (ii) to compare the concentrations of total phospholipids in bile determined enzymatically with those obtained by integration of the phospholipid choline head group resonance peak, and (iii) to examine the relationship between biliary cholesterol nucleation time (NT) and the areas of the biliary lipid 1H-NMR peaks. It was found that the molecular motions of vesicle phospholipid, as determined by 1H-NMR, were restricted by saturation with cholesterol. In bile from patients with cholesterol gallstones, the reduced NMR fluidity of the phospholipid choline-head group indicated that the proportion of cholesterol-phospholipid vesicles containing more than 50% cholesterol, on a molar basis, was increased. The ratios of the N+(CH3)3 and = CH proton resonance peaks showed no overlap between samples with cholesterol gallstones and shorter NT and those with either no gallstones or pigment stones and longer NT. 1H-NMR spectroscopy indicates in a non-invasive manner those biles which are prone to cholesterol crystal formation.

Arachidonic Acid↗
PubMed1995

Macrophage inflammatory protein 1-alpha mRNA expression in an immortalized microglial cell line and cortical astrocyte cultures.

Macrophage inflammatory protein 1 (MIP-1) is a recently characterized inflammatory and chemokinetic cytokine. Proinflammatory stimuli have been shown to induce expression of MIP-1 by macrophages. We hypothesized that microglia and astrocytes express MIP-1 alpha because of their many immunologic similarities to macrophages. MIP-1 alpha mRNA was examined with quantitative reverse transcription and polymerase chain reaction in an immortalized mouse microglial cell line (BV-2) and in mouse cortical astrocyte cultures. We found that in both the BV-2 microglial cell line and in astrocyte cultures, MIP-1 alpha mRNA was strongly induced by lipopolysaccharide and the phorbol ester PMA. MIP-1 alpha mRNA was reduced by dBcAMP, interferon-gamma, and PGE1. Dexamethasone decreased MIP-1 alpha mRNA levels in astrocyte cultures, but not in BV-2 microglial cells. Interleukin-1 beta, tumor necrosis factor alpha, and MIP-1 alpha had no effect on MIP-1 alpha mRNA expression. These findings demonstrate that MIP-1 alpha mRNA is expressed by cultured glial cells and is regulated by proinflammatory and anti-inflammatory stimuli. MIP-1 alpha may be expressed by microglia and astrocytes in vivo, and may help modulate cerebral inflammation.

Animals↗
PubMed1995

Leukemia inhibitory factor mRNA is expressed in cortical astrocyte cultures but not in an immortalized microglial cell line.

Leukemia inhibitory factor (LIF) is a multifunctional cytokine synthesized by a variety of cell types. In the nervous system LIF affects neuronal differentiation, and may be important during cerebral infection and inflammation. To clarify the cellular source of LIF in the brain, we examined the expression of LIF mRNA by primary cortical astrocyte cultures and an immortalized microglial cell line. The microglial cell line did not express LIF mRNA in response to pro-inflammatory agents such as lipopolysaccharide (LPS) that induced expression of other cytokine mRNAs. In contrast, primary astrocyte cultures grown in serum-containing medium expressed LIF mRNA constitutively, and this expression was regulated by pro-inflammatory and anti-inflammatory stimuli. Agents which activate the cAMP and protein kinase C second messenger systems also increased LIF mRNA in astrocyte cultures. These results suggest that astrocytes, but not microglia, may be an important source of LIF during cerebral inflammation and infection.

Animals↗