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Biomedical subjects

I Fisher

Publications and source records attributed to I Fisher.

At least 19 recordsLinked to original sources
PubMed2002

Occurrence of Salmonella enterica serovar Dublin in Austria.

In Austria, Salmonella enterica subsp. enterica serovar Dublin, a bovine-adapted serovar, rarely causes infections in humans. In 2000, Austria was within the European mean with an incidence of 0.1 per million inhabitants. Our data show that the vast majority of all serovar Dublin infections (human and non-human) can be traced epidemiologically to two districts in the Tyrol. This concentration of cases can be explained by a particularly traditional aspect of cattle farming in this area, the alpine pasture. There is an increased risk of cross infection due to the communal keeping of animals from various farms. Infected cattle are a source of infection for humans, and transmission usually occurs from eating beef and drinking cows milk. Using pulsed field gel electrophoresis and automated ribotyping, three out of five isolates from human infections could be traced to characteristic Tyrolean Dublin clones. Bacteriological screening for faecal carriage before the transfer of cattle from risk-herds to the alpine pastures and before the return from risk-pastures to the farms would be a possible starting point to prevent cross-contamination of large mixed herds and contamination of pasture through latently infected cattle. Appropriate research is necessary.

Animals↗
PubMed2001

Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance.

OBJECTIVES: This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina. BACKGROUND: The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions. METHODS: Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period. RESULTS: Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups. CONCLUSIONS: In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

Administration, Oral↗
PubMed2000

beta(2)-adrenoceptors activate nitric oxide synthase in human platelets.

Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L-citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to 0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively (P<0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca(2+). In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2% respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through beta(2)ARs, as determined by coincubation with betaAR subtype-selective antagonists. We conclude that beta(2)ARs activate platelet NOS by increasing cAMP, and that this activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the L-arginine/NO system mediates the effects of beta(2)ARs on adhesion but not aggregation.

Blood Platelets↗
PubMed2000

A novel family of S-nitrosothiols: chemical synthesis and biological actions.

S-Nitrosothiols are a class of chemical compounds that decompose to release nitric oxide and show promise in the treatment of a variety of cardiovascular diseases. Some of these are present in vivo and others have been synthesized in vitro. However, those discovered or synthesized to date have very little tissue selectivity or specificity. We synthesized a number of novel S-nitrosated dipeptides of high purity and examined their effects on vasorelaxation using rat mesenteric arteries and on inhibition of platelet aggregation using platelets from healthyhuman subjects. For comparison, we also tested the effects of S-nitroso-l-glutathione (GSNO, an S-nitrosothiol present in vivo) and S-nitroso-N-acetyl-d-beta,beta-dimethylcysteine (SNAP(D), the d-isomer of SNAP, a commonly used S-nitrosothiol previously synthesized in vitro) in these biological systems. Satisfactory elemental analyses were obtained for all compounds synthesized (less than +/- 0.3%), and all accurate mass measurements were within 1-5 ppm of the expected mass. The novel S-nitrosated dipeptides all elicited vasorelaxation with significantly higher potency, of the order of one log molar unit, than either GSNO or SNAP(D). However, all compounds inhibited U46619-induced platelet aggregation with similar potency to GSNO and SNAP(D). These findings indicate a degree of tissue selectivity which may prove to be of therapeutic usefulness.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network.

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.

Adolescent↗
PubMed1999

Platelet glycoprotein IIb/IIIa blockade with tirofiban: effect on aggregation caused by P256, an antibody to human IIb/IIIa receptors.

AIMS: P256 is a divalent antibody which aggregates human platelets by interaction with glycoprotein (GP) IIb/IIIa receptors. We investigated the effect of tirofiban, an antagonist of the GP IIb/IIIa receptor, on P256-mediated platelet aggregation. METHODS: Responses to agonists were measured turbidometrically at 37 degrees C in stirred citrated platelet-rich plasma from venous blood samples from healthy human volunteers. Inhibitory effects were determined by comparison with aggregation to the same concentration of agonist in a vehicle treated sample. RESULTS: Tirofiban inhibited a near maximally effective dose of P256 (10-7 mol l-1 ) with an IC50 of 9. 3x10-8 mol l-1. Tirofiban (10-7 mol l-1 ) inhibited responses to arachidonic acid, U46619 and P256 similarly, whereas aspirin (1. 1x10-4 mol l-1 ) inhibited arachidonic acid more effectively than P256 (P<0.007 by anova ). CONCLUSIONS: Tirofiban potently and selectively inhibits P256-stimulated aggregation of human platelets.

Abciximab↗
PubMed1998

Differential regulation of formyl peptide and platelet-activating factor receptors. Role of phospholipase Cbeta3 phosphorylation by protein kinase A.

Formylated peptides (e.g. n-formyl-Met-Leu-Phe (fMLP)) and platelet-activating factor (PAF) mediate chemotactic and cytotoxic responses in leukocytes through receptors coupled to G proteins that activate phospholipase C (PLC). In RBL-2H3 cells, fMLP utilizes a pertussis toxin (ptx)-sensitive G protein to activate PLC, whereas PAF utilizes a ptx-insensitive G protein. Here we demonstrate that fMLP, but not PAF, enhanced intracellular cAMP levels via a ptx-sensitive mechanism. Protein kinase A (PKA) inhibition by H-89 enhanced inositol phosphate formation stimulated by fMLP but not PAF. Furthermore, a membrane-permeable cAMP analog 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) inhibited phosphoinositide hydrolysis and secretion stimulated by fMLP but not PAF. Both cpt-cAMP and fMLP stimulated PLCbeta3 phosphorylation in intact RBL cells. The purified catalytic subunit of PKA phosphorylated PLCbeta3 immunoprecipitated from RBL cell lysate. Pretreatment of intact cells with cpt-cAMP and fMLP, but not PAF, resulted in an inhibition of subsequent PLCbeta3 phosphorylation by PKA in vitro. These data demonstrate that fMLP receptor, which couples to a ptx-sensitive G protein, activates both PLC and cAMP production. The resulting PKA activation phosphorylates PLCbeta3 and appears to block the ability of Gbetagamma to activate PLC. Thus, both fMLP and PAF generate stimulatory signals for PLCbeta3, but only fMLP produces a PKA-dependent inhibitory signal. This suggests a novel mechanism for the bidirectional regulation of receptors which activate PLC by ptx-sensitive G proteins.

Cell Line↗
PubMed1997

Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitization and internalization.

Members of the chemokine receptor family CCR5 and CXCR4 have recently been shown to be involved in the entry of human immunodeficiency virus (HIV) into target cells. Here, we investigated the regulation of CXCR4 in rat basophilic leukemia cells (RBL-2H3) stably transfected with wild type (Wt CXCR4) or a cytoplasmic tail deletion mutant (DeltaCyto CXCR4) of CXCR4. The ligand, stromal cell derived factor-1 (SDF-1) stimulated higher G-protein activation, inositol phosphate generation, and a more sustained calcium elevation in cells expressing DeltaCyto CXCR4 relative to Wt CXCR4. SDF-1 and phorbol 12-myristate 13-acetate (PMA), but not a membrane permeable cAMP analog induced rapid phosphorylation as well as desensitization of Wt CXCR4. Phosphorylation of DeltaCyto CXCR4 was not detected under any of these conditions. Despite lack of receptor phosphorylation, calcium mobilization by SDF-1 in DeltaCyto CXCR4 cells was partially desensitized by prior treatment with SDF-1. Of interest, the rapid release of calcium was inhibited without affecting the sustained calcium elevation, indicating independent regulatory pathways for these processes. PMA completely inhibited phosphoinositide hydrolysis and calcium mobilization in Wt CXCR4 but only partially inhibited these responses in DeltaCyto CXCR4. cAMP also partially inhibited these responses in both Wt CXCR4 and DeltaCyto CXCR4. SDF-1, PMA, and cAMP caused phosphorylation of phospholipase Cbeta3 in Wt and DeltaCyto CXCR4 cells. Both SDF-1 as well as PMA induced rapid internalization of Wt CXCR4. SDF-1 but not PMA induced internalization of DeltaCyto CXCR4 albeit at reduced levels relative to Wt CXCR4. These results indicate that signaling and internalization of CXCR4 are regulated by receptor phosphorylation dependent and independent mechanisms. Desensitization of CXCR4 signaling, independent of receptor phosphorylation, appears to be a consequence of the phosphorylation of phospholipase Cbeta3.

Amino Acid Sequence↗
PubMed1997

Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor.

Platelet-activating factor (PAF) stimulates a diverse array of cellular responses through receptors coupled to G proteins that activate phospholipase C (PLC). Truncation of the cytoplasmic tail of the receptor to remove phosphorylation sites (mutant PAF receptor, mPAFR) results in enhancement of PAF-stimulated responses. Here we demonstrate that PAF or phorbol 12-myristate 13-acetate (PMA) pretreatment inhibited wild type PAFR-induced PLC-mediated responses by approximately 90%, whereas these responses to the phosphorylation-deficient mPAFR were inhibited by approximately 50%, despite normal G protein coupling, suggesting a distal inhibitory locus. PAF and PMA, as well as a membrane permeable cyclic AMP analog, stimulated phosphorylation of PLCbeta3. A protein kinase C (PKC) inhibitor blocked phosphorylation of PLCbeta3 stimulated by PAF and PMA but not by cAMP. Activation of protein kinase A (PKA) by cAMP did not result in inhibition of Ca2+ mobilization stimulated by PAF. In contrast, cAMP did inhibit the response to formylpeptide chemoattractant receptor. These data suggest that homologous desensitization of PAF-mediated responses is regulated via phosphorylation at two levels in the signaling pathway, one at the receptor and the other at PLCbeta3 mediated by PKC but not by PKA. Phosphorylation of PLCbeta3 by PKA could explain the inhibition of formylpeptide chemoattractant receptor signaling by cAMP. As PAF and formylpeptide chemoattractant receptors activate PLC via different G proteins, phosphorylation of PLCbeta3 by PKC and PKA could provide distinct regulatory control for classes of G protein-coupled receptors.

Animals↗
PubMed1996

Salm-Net facilitates collaborative investigation of an outbreak of Salmonella tosamanga infection in Europe.

Twenty-eight cases of Salmonella tosamanga infection were identified in six western European countries during the first half of 1995. Salm-Net, a European system for collaborative surveillance of gastrointestinal infection, detected the outbreak and coordinated its investigation. There were 28 cases, 14 of each sex, with a broad age distribution. Interviews with cases to identify common food and other exposures failed to generate a working hypothesis. The initial cluster occurred in a period of eight weeks and, since only one further case occurred in June, the investigation was closed. This incident shows that Salm-Net is effective in identifying international outbreaks of human salmonellosis. Practical difficulties in the field investigation of the outbreak are discussed.

Adult↗
PubMed1995

[Use of the Bactec TB 460 method for the bacteriological diagnosis of tuberculosis. Results of a multicenter study].

Isolation of Mycobacteria on Loewenstein-Jensen medium lasts many weeks. The use of Radiometric method (Bactec TB 460) reduces the delays. Results of 79,064 cultures are reported from a multicentric study associating 16 laboratories. The average was 4.8% of positivity and 2.51% of contamination. The comparison of the results with conventional method previously obtained shows that radiometric method is more sensitive and contaminations are less numerous. Concerning hemocultures the Bactec method is very usefull. Among 11,277 tests performed 907 were positive (8.04%). Mycobacterium avium was identified in 89% of the cases. Identification test utilizes Biochemical and NAP tests, but also more and more Nucleic probes. The antibiotic sensitivity is performed in five days. The mean delay of analysis is about 25 days, lessening by half the conventional method delays. Nevertheless, Bactec method has the following inconveniences: syringe inoculation, use of radiolabelled products, expensive cost.

Anti-Bacterial Agents↗
PubMed1980

Cicatricial pemphigoid confined to the larynx.

The main features linking and yet distinguishing bullous pemphigoid from cicatricial pemphigoid have been discussed. This report demonstrates the usefulness of direct immunofluorescence study in establishing a diagnosis of cicatricial pemphigoid when lesions are confined to a single and unusual site such as the larynx.

Aged↗
PubMed1977

Beef cattle productivity under traditional and improved management in Botswana.

A comparison of productivity over a 4-year period from indigenous type beef cattle under two production systems in Botswana is reported. The two systems are: the traditional system on unenclosed communal grazing (cattle post) and ranching within fenced paddocks. Calving percentages, 7-month old calf weight, calf mortality and post-weaning growth to 18 months of age under cattle post conditions were 46.4 per cent, 122.5 kg, 10.2 percent and 88.5 kg respectively. Corresponding figures for cattle on the fenced ranches were 74.0 per cent, 177.4 kg, 8.5 per cent and 105.8 kg. These results indicate overall productivity estimates of 51 and 120 kg of weaner calf per cow per year and 86 and 188 kg of 18-month old calf per cow per year for the cattle post and fenced ranch respectively.

Animal Husbandry↗
PubMed1977

Recurrent multiple pyogenic granuloma with multiple satellites. Features of Masson's hemangioma.

The case of a thirteen year old white girl who had multiple recurrences of pyogenic granuloma arranged in a satellite fashion is presented. The incidence and frequency of pyogenic granuloma with or without recurrences is discussed, stressing the unusual nature of the present problem. In addition to the microscopic features of pyogenic granuloma, the changes seen in Masson's hemangioma were demonstrable in some of the sections. The microscopic distinguishing feature of Masson's hemangioma is discussed, with emphasis on the importance of recognizing this as a benign structure rather than a malignant one. Opinions concerning the etiology of pyogenic granuloma as well as the reasons for the development of multiple satellites are presented, along with suggestions for therapy.

Adolescent↗
PubMed1976

Coexistence of discoid lupus erythematosus and porphyria cutanea tarda.

A case of coexistent porphyria cutanea tarda and discoid lupus erythematosus is presented. Abnormal urinary porphyrins, the presence of liver fluorescence, chronic alcoholism, fatty metamorphosis of the liver and histologically typical LE with the demonstration of basement membrane fluorescence were present in the patient. Awareness of the possible coexistence of these two conditions is of practical significance for the practicing dermatologist. The nature of the relationship between these conditions remains obscure. Is it coincidental or does it represent a common pathophysiological mechanism? Further work on this unique pair of diseases seems indicated.

Humans↗