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1.
Bioinformatics ; 35(19): 3779-3785, 2019 10 01.
Article de Anglais | MEDLINE | ID: mdl-30793173

RÉSUMÉ

MOTIVATION: Combining multiple layers of information underlying biological complexity into a structured framework represent a challenge in systems biology. A key task is the formalization of such information in models describing how biological entities interact to mediate the response to external and internal signals. Several databases with signalling information, focus on capturing, organizing and displaying signalling interactions by representing them as binary, causal relationships between biological entities. The curation efforts that build these individual databases demand a concerted effort to ensure interoperability among resources. RESULTS: Aware of the enormous benefits of standardization efforts in the molecular interaction research field, representatives of the signalling network community agreed to extend the PSI-MI controlled vocabulary to include additional terms representing aspects of causal interactions. Here, we present a common standard for the representation and dissemination of signalling information: the PSI Causal Interaction tabular format (CausalTAB) which is an extension of the existing PSI-MI tab-delimited format, now designated PSI-MITAB 2.8. We define the new term 'causal interaction', and related child terms, which are children of the PSI-MI 'molecular interaction' term. The new vocabulary terms in this extended PSI-MI format will enable systems biologists to model large-scale signalling networks more precisely and with higher coverage than before. AVAILABILITY AND IMPLEMENTATION: PSI-MITAB 2.8 format and the new reference implementation of PSICQUIC are available online (https://psicquic.github.io/ and https://psicquic.github.io/MITAB28Format.html). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Sujet(s)
Protéomique , Biologie des systèmes , Enfant , Bases de données factuelles , Humains , Transduction du signal , Logiciel
2.
Rev Sci Instrum ; 83(10): 10D530, 2012 Oct.
Article de Anglais | MEDLINE | ID: mdl-23130793

RÉSUMÉ

For the new ITER-like wall at JET, two new infrared diagnostics (KL9B, KL3B) have been installed. These diagnostics can operate between 3.5 and 5 µm and up to sampling frequencies of ∼20 kHz. KL9B and KL3B image the horizontal and vertical tiles of the divertor. The divertor tiles are tungsten coated carbon fiber composite except the central tile which is bulk tungsten and consists of lamella segments. The thermal emission between lamellae affects the surface temperature measurement and therefore KL9A has been upgraded to achieve a higher spatial resolution (by a factor of 2). A technical description of KL9A, KL9B, and KL3B and cross correlation with a near infrared camera and a two-color pyrometer is presented.

3.
Rev Sci Instrum ; 83(10): 10D727, 2012 Oct.
Article de Anglais | MEDLINE | ID: mdl-23130796

RÉSUMÉ

The new JET ITER-like wall (made of beryllium and tungsten) is more fragile than the former carbon fiber composite wall and requires active protection to prevent excessive heat loads on the plasma facing components (PFC). Analog CCD cameras operating in the near infrared wavelength are used to measure surface temperature of the PFCs. Region of interest (ROI) analysis is performed in real time and the maximum temperature measured in each ROI is sent to the vessel thermal map. The protection of the ITER-like wall system started in October 2011 and has already successfully led to a safe landing of the plasma when hot spots were observed on the Be main chamber PFCs. Divertor protection is more of a challenge due to dust deposits that often generate false hot spots. In this contribution we describe the camera, data capture and real time processing systems. We discuss the calibration strategy for the temperature measurements with cross validation with thermal IR cameras and bi-color pyrometers. Most importantly, we demonstrate that a protection system based on CCD cameras can work and show examples of hot spot detections that stop the plasma pulse. The limits of such a design and the associated constraints on the operations are also presented.

4.
J Clin Endocrinol Metab ; 91(1): 105-14, 2006 Jan.
Article de Anglais | MEDLINE | ID: mdl-16263835

RÉSUMÉ

CONTEXT: Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI). HYPOTHESIS: Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S). DESIGN: This was a prospective study. SETTING: This study took place in a tertiary teaching hospital. PATIENTS: Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10). AIM: The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens' method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and convalescence. RESULTS: Comparing SS, S, and HC subjects, free cortisol levels reflected illness severity more closely than total cortisol (basal free cortisol, SS, 186 vs. S, 29 vs. HC, 13 nmol/liter, P < 0.001 compared with basal total cortisol, SS, 880 vs. S, 417 vs. HC, 352 nmol/liter, P < 0.001). Stimulated free cortisol increments varied greatly with illness category (SS, 192 vs. S, 115 vs. HC, 59 nmol/liter, P = 0.004), whereas total cortisol increments did not (SS, 474 vs. S, 576 vs. HC, 524 nmol/liter, P = 0.013). The lack of increase in total cortisol with illness severity is due to lower CBG and albumin. One third of patients with SS (15 of 45) but no S patients met a recently described criterion for RAI (total cortisol increment after tetracosactrin < or = 248 nmol/liter). RAI patients had higher basal total cortisol (1157 vs. 756 nmol/liter; P = 0.028) and basal free cortisol (287 vs. 140 nmol/liter; P = 0.017) than non-RAI patients. Mean cortisol increments in RAI were lower (total, 99 vs. 648 nmol/liter, P < 0.001; free, 59 vs. 252 nmol/liter, P < 0.001). These differences were not due to altered CBG or albumin levels. Free cortisol levels normalized more promptly than total cortisol in convalescence. Calculated free cortisol by Coolens' method compared closely with measured free cortisol. CONCLUSIONS: Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity. The attenuated cortisol increment after tetracosactrin in RAI is not due to low cortisol-binding proteins. Free cortisol levels can be determined reliably using total cortisol and CBG levels.


Sujet(s)
Hydrocortisone/sang , Sepsie/sang , Choc septique/sang , Insuffisance surrénale/sang , Insuffisance surrénale/complications , Sujet âgé , Tétracosactide , Femelle , Humains , Mâle , Microdialyse , Adulte d'âge moyen , Études prospectives , Reproductibilité des résultats , Sérumalbumine/métabolisme , Transcortine/métabolisme
6.
Commun Dis Public Health ; 5(2): 114-8, 2002 Jun.
Article de Anglais | MEDLINE | ID: mdl-12166296

RÉSUMÉ

To discover laboratory ascertainment and reporting practice for cases of cryptosporidiosis in two health authority regions, we surveyed laboratories serving Wales and the North West of England for faecal screening policies and methods for detection of Cryptosporidium. Forty-eight of the 49 laboratories responded, of which 39 (81%) screen all stool specimens from symptomatic individuals for Cryptosporidium and 9 (19%) screen selected specimens. Although laboratory screening is more complete than has been reported in other regions, we identified discrepancies where patient age was used as a selection criterion, and we make suggestions to amend this. Forty-two (88%) responding laboratories report confirmed cases to the regional Communicable Disease Surveillance Centre (CDSC) and 45 (94%) report to the local authority environmental health department. We also surveyed local authorities in both regions for policy and practice concerning the investigation of reported cases of cryptosporidiosis in the same regions. All 59 local authorities responded, of which 57 (97%) investigate cases by completion of an exposure questionnaire as well as providing advice on the prevention of spread of infection. Variation in case ascertainment may influence perception of incidence, clusters and outbreaks of cases of cryptosporidiosis.


Sujet(s)
Techniques de laboratoire clinique/normes , Cryptosporidiose/épidémiologie , Cryptosporidium/isolement et purification , Administration de la santé publique , Animaux , Biais (épidémiologie) , Cryptosporidiose/diagnostic , Collecte de données , Notification des maladies , Humains , Dépistage de masse , Politique organisationnelle , Surveillance de la population , Enquêtes et questionnaires , Royaume-Uni/épidémiologie
7.
Eur J Gastroenterol Hepatol ; 14(2): 137-44, 2002 Feb.
Article de Anglais | MEDLINE | ID: mdl-11981337

RÉSUMÉ

INTRODUCTION: Endothelial-bound cell adhesion molecules are important in recruiting inflammatory cells to the mucosa in inflammatory bowel disease (IBD). Little is known of the expression of these molecules in relation to the recruitment of particular cell subtypes in the early course of mucosal inflammation. We therefore studied the expression of several adhesion molecules to examine their potential correlation with the cellular infiltrate in the inflamed ileal pouch, a possible disease model for ulcerative colitis. METHODS: Eleven patients (group 1) with familial adenomatous polyposis (FAP) with no evidence of ileal pouch inflammation and 14 patients (group 2) with ileal pouch inflammation (all with a prior diagnosis of ulcerative colitis) underwent pouch endoscopy with biopsy. Cryostat sections of biopsies were immunostained using a three-stage immunoperoxidase method for the adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1), E-selectin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). These results were correlated with immunostaining for the cell markers CD3, CD4, CD8, CD45RO, CD14 and CD15, which were quantified by computer image analysis. RESULTS: MAdCAM-1, ICAM-1 and VCAM-1 were expressed to similar degrees on the endothelia of groups 1 and 2. In contrast, E-selectin was significantly increased in group 2 (P = 0.003) and correlated with immunostaining for CD15 (r = 0.72), CD4 (r = 0.55) and CD14 (r = 0.53). MAdCAM-1 expression did not correlate with any cell subset. CD15 was the only cell marker to be altered significantly, being increased in group 2 (P = 0.002). CONCLUSIONS: The inflammatory process seen in ileal pouch inflammation is characterized by up-regulation of E-selectin and recruitment of CD15-positive cells, emphasizing the role of neutrophil recruitment and migration to the epithelium in the pathogenesis of this condition.


Sujet(s)
Polypose adénomateuse colique/métabolisme , Immunoglobulines/analyse , Molécule-1 d'adhérence intercellulaire/métabolisme , Mucoprotéines/analyse , Récepteurs d'écotaxie des lymphocytes/métabolisme , Molécule-1 d'adhérence des cellules vasculaires/métabolisme , Adulte , Sujet âgé , Molécules d'adhérence cellulaire , Mouvement cellulaire , Sélectine E/métabolisme , Femelle , Humains , Techniques immunoenzymatiques , Muqueuse intestinale , Antigènes CD15 , Mâle , Adulte d'âge moyen , Infiltration par les neutrophiles , Régulation positive
8.
Scand J Gastroenterol ; 36(3): 258-64, 2001 Mar.
Article de Anglais | MEDLINE | ID: mdl-11305512

RÉSUMÉ

BACKGROUND: The mechanism underlying the development of ileal pouch inflammation in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is unclear. Persistent systemic T cell activation or expansion of specific memory cell populations could predispose certain patients to develop local inflammation within the neo-rectum. Therefore, the aim was to study the expression of the lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30 levels and mucosal CD30 expression in patients with pouchitis and in controls. METHODS: Flow cytometry was performed on PBMC isolated from patients with pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26) and normal controls (n = 20) by ELISA. CD30 expression was quantified in pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage immunoperoxidase method. RESULTS: Naive CD45RO-CD27+ PBMC were significantly decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03). CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1-290) U/ml, P=0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the mucosa, the numbers of CD30+ cells were increased in pouchitis compared to non-inflamed pouches (P = 0.02). CONCLUSIONS: Increased sCD30 in pouchitis is associated with elevated mucosal expression. Of the activation markers studied, only the circulating naïve CD27+ population differed in pouchitis patients compared with controls. The observed decrease in this cell type may reflect antigen priming and subsequent loss of CD27 implying that antigen driven activation of specific T cell subsets may occur in pouchitis.


Sujet(s)
Antigènes CD30/analyse , Pochite/sang , Pochite/anatomopathologie , Proctocolectomie restauratrice/effets indésirables , Antigènes CD27/analyse , Adulte , Marqueurs biologiques/analyse , Ponction-biopsie à l'aiguille , Rectocolite hémorragique/anatomopathologie , Rectocolite hémorragique/chirurgie , Femelle , Cytométrie en flux , Humains , Immunohistochimie , Mâle , Adulte d'âge moyen , Monocytes , Photomicrographie , Pochite/étiologie , Probabilité , Proctocolectomie restauratrice/méthodes , Valeurs de référence , Sensibilité et spécificité , Statistique non paramétrique
9.
Br J Dermatol ; 144(1): 55-65, 2001 Jan.
Article de Anglais | MEDLINE | ID: mdl-11167683

RÉSUMÉ

BACKGROUND: Vitiligo is a depigmenting disease of the skin, which may derive from programmed melanocyte death or destruction due to inherent sensitivity to oxidative stress arising from either toxic intermediates of melanin, a melanocyte-specific protein, or other sources. Tyrosinase-related protein (TRP) -1 has been shown to be involved not only in melanin biosynthesis but also in the prevention of premature melanocyte death in animals. OBJECTIVES: To clarify the biological role of human TRP-1 in melanocyte survival. METHODS: Cultured melanocyte strains from an active advancing border of vitiligo were established and studied. RESULTS: The established 'vitiligo melanocytes' showed large perikaryon and stubby dendrites. They showed early cell death when exposed to oxidative stress (ultraviolet B) and increased and abnormal immunostaining and immunoprecipitation by antibodies against human and mouse TRP-1, indicating an altered synthesis and processing of TRP-1. In pulse-chase and sequential immunoprecipitation experiments, vitiligo melanocytes revealed abnormal protein-protein interaction with calnexin, a melanogenesis-associated chaperone, suggesting altered folding and maturation of nascent TRP-1 polypeptides. Northern blot analysis indicated a decreased expression of TRP-1 mRNA, but heteroduplex analysis and verification of the mutation at the carboxy terminus of TRP-1 by restriction enzyme analysis did not show any abnormality. CONCLUSIONS: Our study suggests that the early cell death of vitiligo melanocytes is related to their increased sensitivity to oxidative stress, which may arise from complex processes of abnormal synthesis and processing of TRP-1 and its interaction with calnexin.


Sujet(s)
Mélanocytes/physiologie , Glycoprotéines membranaires , Stress oxydatif/physiologie , Protéines/métabolisme , Vitiligo/métabolisme , Adulte , Technique de Northern , Protéines de liaison au calcium/métabolisme , Calnexine , Techniques de culture cellulaire , Mort cellulaire/effets des radiations , Enfant , Technique d'immunofluorescence indirecte , Expression des gènes , Analyse d'hétéroduplex , Humains , Mâle , Mélanocytes/anatomopathologie , Mélanocytes/effets des radiations , Protéines membranaires/métabolisme , Chaperons moléculaires/métabolisme , Oxidoreductases/métabolisme , Protéines/génétique , ARN messager/génétique , Rayons ultraviolets , Vitiligo/anatomopathologie
10.
Science ; 291(5507): 1304-51, 2001 02 16.
Article de Anglais | MEDLINE | ID: mdl-11181995

RÉSUMÉ

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.


Sujet(s)
Génome humain , Projet génome humain , Analyse de séquence d'ADN , Algorithmes , Animaux , Zébrage chromosomique , Cartographie chromosomique , Chromosomes artificiels de bactérie , Biologie informatique , Séquence consensus , Ilots CpG , ADN intergénique , Bases de données factuelles , Évolution moléculaire , Exons , Femelle , Duplication de gène , Gènes , Variation génétique , Humains , Introns , Mâle , Phénotype , Cartographie physique de chromosome , Polymorphisme de nucléotide simple , Protéines/génétique , Protéines/physiologie , Pseudogènes , Séquences répétées d'acides nucléiques , Rétroéléments , Analyse de séquence d'ADN/méthodes , Spécificité d'espèce
12.
Biochem J ; 350 Pt 2: 599-608, 2000 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-10947976

RÉSUMÉ

In the liver, malonyl-CoA is central to many cellular processes, including both fatty acid biosynthesis and oxidation. Malonyl-CoA decarboxylase (MCD) is involved in the control of cellular malonyl-CoA levels, and functions to decarboxylate malonyl-CoA to acetyl-CoA. MCD may play an essential role in regulating energy utilization in the liver by regulating malonyl-CoA levels in response to various nutritional or pathological states. The purpose of the present study was to investigate the role of liver MCD in the regulation of fatty acid oxidation in situations where lipid metabolism is altered. A single MCD enzyme of molecular mass 50.7 kDa was purified from rat liver using a sequential column chromatography procedure and the cDNA was subsequently cloned and sequenced. The liver MCD cDNA was identical to rat pancreatic beta-cell MCD cDNA, and contained two potential translational start sites, producing proteins of 50.7 kDa and 54.7 kDa. Western blot analysis using polyclonal antibodies generated against rat liver MCD showed that the 50.7 kDa isoform of MCD is most abundant in heart and liver, and of relatively low abundance in skeletal muscle (despite elevated MCD transcript levels in skeletal muscle). Tissue distribution experiments demonstrated that the pancreas is the only rat tissue so far identified that contains both the 50.7 kDa and 54. 7 kDa isoforms of MCD. In addition, transfection of the full-length rat liver MCD cDNA into COS cells produced two isoforms of MCD. This indicated either that both initiating methionines are functionally active, generating two proteins, or that the 54.7 kDa isoform is the only MCD protein translated and removal of the putative mitochondrial targeting pre-sequence generates a protein of approx. 50.7 kDa in size. To address this, we transiently transfected a mutated MCD expression plasmid (second ATG to GCG) into COS-7 cells and performed Western blot analysis using our anti-MCD antibody. Western blot analysis revealed that two isoforms of MCD were still present, demonstrating that the second ATG may not be responsible for translation of the 50.7 kDa isoform of MCD. These data also suggest that the smaller isoform of MCD may originate from intracellular processing. To ascertain the functional role of the 50. 7 kDa isoform of rat liver MCD, we measured liver MCD activity and expression in rats subjected to conditions which are known to alter fatty acid metabolism. The activity of MCD was significantly elevated under conditions in which hepatic fatty acid oxidation is known to increase, such as streptozotocin-induced diabetes or following a 48 h fast. A 2-fold increase in expression was observed in the streptozotocin-diabetic rats compared with control rats. In addition, MCD activity was shown to be enhanced by alkaline phosphatase treatment, suggesting phosphorylation-related control of the enzyme. Taken together, our data demonstrate that rat liver expresses a 50.7 kDa form of MCD which does not originate from the second methionine of the cDNA sequence. This MCD is regulated by at least two mechanisms (only one of which is phosphorylation), and its activity and expression are increased under conditions where fatty acid oxidation increases.


Sujet(s)
Carboxy-lyases/composition chimique , Carboxy-lyases/physiologie , Acides gras/métabolisme , Foie/enzymologie , Oxygène/métabolisme , Phosphatase alcaline/pharmacologie , Séquence d'acides aminés , Animaux , Séquence nucléotidique , Glycémie/métabolisme , Technique de Western , Cellules COS , Chromatographie sur agarose , Clonage moléculaire , ADN complémentaire/métabolisme , Diabète expérimental/métabolisme , Acides gras/sang , Privation alimentaire , Insuline/sang , Foie/métabolisme , Mâle , Méthionine/composition chimique , Données de séquences moléculaires , Myocarde/métabolisme , Phosphorylation , Biosynthèse des protéines , Isoformes de protéines , Rats , Rat Sprague-Dawley , Analyse de séquence d'ADN , Streptozocine , Distribution tissulaire , Transfection
13.
Gut ; 46(6): 838-41, 2000 Jun.
Article de Anglais | MEDLINE | ID: mdl-10807897

RÉSUMÉ

BACKGROUND: Endoscopic biliary manometry is useful in the assessment of patients with types II and III sphincter of Oddi dysfunction, but it is time consuming and invasive. AIM: To investigate the role of (99m)Tc-DISIDA scanning, with and without morphine provocation, as a non-invasive investigation in these patients compared with endoscopic biliary manometry. SUBJECTS AND METHODS: A total of 34 patients with a clinical diagnosis of type II (n = 21) or III (n = 13) sphincter of Oddi dysfunction were studied. Biliary scintigraphy with 100 MBq of (99m)Tc-DISIDA was carried out with and without morphine provocation (0.04 mg/kg intravenously) and time/activity curves were compared with the results of subsequent endoscopic biliary manometry. RESULTS: Eighteen (nine type II, nine type III) of the 34 (53%) patients had sphincter of Oddi basal pressures above the upper limit of normal (40 mm Hg). In the standard DISIDA scan without morphine, no significant differences were observed in time to maximal activity (Tmax) or percentage excretion at 45 or 60 minutes between those with normal and those with abnormal biliary manometry. However, following morphine provocation, median percentage excretion at 60 minutes was 4.9% in those with abnormal manometry and 28.2% in the normal manometry group (p = 0.002). Using a cut off value of 15% excretion at 60 minutes, the sensitivity for detecting elevated sphincter of Oddi basal pressure by the morphine augmented DISIDA scan was 83% and specificity was 81%. Also, 14 of the 18 patients with abnormal manometry complained of biliary-type pain after morphine infusion compared with only two of 16 patients in the normal manometry group (p = 0.001). CONCLUSIONS: (99m)Tc-DISIDA with morphine provocation is a useful non-invasive investigation for types II and III sphincter of Oddi dysfunction to detect those with elevated sphincter basal pressures who may respond to endoscopic sphincterotomy.


Sujet(s)
Maladies du cholédoque/imagerie diagnostique , Morphine , Radiopharmaceutiques , Muscle sphincter de l'ampoule hépatopancréatique/imagerie diagnostique , Disofénine de technétium (99mTc) , Adulte , Études de cohortes , Humains , Perfusions veineuses , Adulte d'âge moyen , Pression , Scintigraphie
14.
Melanoma Res ; 10(1): 9-15, 2000 Feb.
Article de Anglais | MEDLINE | ID: mdl-10711635

RÉSUMÉ

Our laboratory has synthesized two new phenolic thioether amines, N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) and N[2-[(4-propionyloxyphenyl)thio]ethyl] propionamide (N,O-diPr-4-S-CAP). These compounds, along with the previously described phenolic thioether amine N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) and its acetyl form (N,O-diAc-4-S-CAP), are tyrosine-amine derivative analogues. The cytotoxicity of these compounds is thought to be tyrosinase dependent, which may make them suitable for targeted anti-melanoma therapy since only melanocytes and their malignant counterparts contain this active enzyme. To further investigate this hypothesis, we performed MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assays to determine the cytotoxicity of these compounds in 10 different cell lines. Specifically, we examined to what extent cytotoxicity is related to tyrosinase and tyrosine hydroxylase activity using melanoma and neuroblastoma cells, which have a common metabolic pathway using tyrosinase and tyrosine hydroxylase, respectively. The most sensitive cell line was the highly pigmented SK-MEL-23 melanoma cell line, which shows a very high tyrosinase activity with the highest melanin pigmentation. KAN and SK-NSH (two neuroblastoma cell lines), which have no tyrosinase activity but high tyrosine hydroxylase, were also sensitive. However, C32 (a non-pigmented melanoma with a lower tyrosinase activity) was also sensitive, and MeWo (a moderately pigmented melanoma with a high tyrosinase activity) was less sensitive. This in vitro study may indicate that there is a non-tyrosinase-mediated mechanism of cytotoxicity for phenolic thioether amines in addition to the tyrosinase-mediated one described previously.


Sujet(s)
Amides/toxicité , Antinéoplasiques/toxicité , Cystamine/analogues et dérivés , Mercaptamine/analogues et dérivés , Mélanome/anatomopathologie , Monophenol monooxygenase/métabolisme , Neuroblastome/anatomopathologie , Phénols/toxicité , Tyrosine 3-monooxygenase/métabolisme , Division cellulaire/effets des médicaments et des substances chimiques , Cystamine/toxicité , Mercaptamine/toxicité , Inhibiteurs de croissance/toxicité , Cellules HeLa , Humains , Mélanome/enzymologie , Neuroblastome/enzymologie , Cellules cancéreuses en culture
15.
Crit Care Resusc ; 2(1): 34-7, 2000 Mar.
Article de Anglais | MEDLINE | ID: mdl-16597282

RÉSUMÉ

This case report describes a patient with Guillain-Barré syndrome in whom the presence of coma and absent brain stem reflexes suggested the possibility of brainstem death. A differential diagnosis of fixed dilated pupils is presented.

17.
J Invest Dermatol ; 113(6): 928-34, 1999 Dec.
Article de Anglais | MEDLINE | ID: mdl-10594732

RÉSUMÉ

Tyrosine analogs are good candidates for developing melanoma chemotherapy because melanogenesis is inherently toxic and uniquely expressed in melanocytic cells. Sulphur containing substrate (tyrosine) analogs, N-acetyl-4-S-cysteaminylphenol (NAcCAP) and N-propionyl-4-S-cysteaminylphenol (NPrCAP), have been shown to have potent antimelanoma activity in mice bearing melanoma. Both NAcCAP and NPrCAP show selective cytotoxicity towards melanoma cell lines. But the mechanism leading to selectivity is not clear as these drugs are also toxic to other cell lines to a lesser extent. Here we show that these drugs have both cytostatic and cytocidal effects, which could account for this. Cytostatic effect is suggested by DNA flow cytometry. The drug causes cell cycle changes in four human cell lines (normal skin fibroblasts, HeLa cells, and melanoma cell lines, C32 and SK-MEL-23) in a dose-dependent manner blocking cells in S phase with concomitant decrease in the number of cells in G1 phase. There is also a gradual decrease in cells in G2 + M phases. The dose-concentration curves give IC50 values in the range of 50-400 microM and the melanotic melanoma cell line SK-MEL-23 has the lowest IC50 value consistent with our hypothesis that these drugs are selective towards melanoma cells. The concentration-dependent accumulation of cells in S phase suggest a cytostatic effect as a consequence of inhibition of DNA synthesis in agreement with [3H] thymidine incorporation assay. There is a highly specific uptake of [14C]NAcCAP and irreversible damage to DNA synthesis machinery in SK-MEL-23 cells, indicating a melanotic-specific cytocidal effect as well. Trypan blue exclusion study and competitive inhibition assay indicated that visible cytocidal effect occurs slowly and oxidative stress resulting from tyrosinase mediated oxidation of the drug appears to be the underlying mechanism. The primary antimelanoma effect of cysteaminylphenols derives from a selective cytostatic effect, but is followed by a specific cytocidal action rendering the drugs useful for targeted melanoma chemotherapy.


Sujet(s)
Antinéoplasiques/pharmacologie , Cystamine/analogues et dérivés , Mercaptamine/analogues et dérivés , Mélanome/traitement médicamenteux , Phénols/pharmacologie , Animaux , Cycle cellulaire/effets des médicaments et des substances chimiques , Division cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire , Cystamine/pharmacocinétique , Cystamine/pharmacologie , Mercaptamine/pharmacocinétique , Mercaptamine/pharmacologie , ADN/biosynthèse , Relation dose-effet des médicaments , Cytométrie en flux , Cellules HeLa , Humains , Souris , Monophenol monooxygenase/physiologie , Phénols/pharmacocinétique
18.
Eur J Gastroenterol Hepatol ; 11(9): 1001-5, 1999 Sep.
Article de Anglais | MEDLINE | ID: mdl-10503837

RÉSUMÉ

BACKGROUND: Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. OBJECTIVE: To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. METHODS: One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. RESULTS: Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. CONCLUSIONS: A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.


Sujet(s)
Rectocolite hémorragique/complications , Maladies articulaires/étiologie , Complications postopératoires/étiologie , Proctocolectomie restauratrice , Adulte , Sujet âgé , Arthralgie/étiologie , Rectocolite hémorragique/chirurgie , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Pochite/étiologie , Prévalence
19.
Int J STD AIDS ; 10(8): 508-13, 1999 Aug.
Article de Anglais | MEDLINE | ID: mdl-10471099

RÉSUMÉ

A previous study of infection and morbidity in 400 women attending for termination of pregnancy (TOP) had shown that 32 (8%) harboured cervical Chlamydia trachomatis and 112 (28%) had anaerobic (bacterial) vaginosis (AV). Fifty-three per cent of the women with preoperative C. trachomatis had AV. Thirty of the 32 women with chlamydial infection were followed up and 19 (63%) of these developed post-abortion upper genital tract infection, 7 of whom needed re-admission. In view of the high morbidity in women with chlamydial infection attending for TOP, anti-bacterial prophylaxis with metronidazole suppositories and oral oxytetracycline was introduced for women attending for suction termination of pregnancy (STOP). An audit of the clinical and financial benefits and/or losses was carried out. The audit of 1951 consecutive patients attending for STOP revealed that 132 (6.8%) had chlamydial infection with equivocal results reported in a further 2 patients. One hundred and eight of the 134 women responded to recall. Full genital tract infection screening was carried out in 105 of the 108 recalled patients of whom 5 had repeat positive cervical swabs for C. trachomatis, one had Trichomonas vaginalis, 24 had candidiasis and 17 had anaerobic vaginosis, none had gonorrhoea. Thirteen (12%) of the 108 women had pelvic infection as previously defined, none of whom required re-admission. At least pound sterling 20,000 has been saved each year in our Trust following the introduction of pre-abortion chlamydial screening and universal antichlamydial and anti-anaerobe prophylaxis. The introduction of universal prophylaxis against C. trachomatis and AV has profoundly reduced morbidity in patients attending for TOP and has also resulted in substantial financial savings.


PIP: This paper presents an audit of the clinical and financial benefits and/or losses of a new management protocol for Chlamydia trachomatis and anaerobic vaginosis (AV) in women requesting suction termination of pregnancy (STOP). This management protocol is known as the Singleton Regimen and involves the introduction of an antibacterial prophylaxis with metronidazole suppositories and oral oxytetracycline. The audit included 1951 patients requesting STOP at the Singleton Hospital between January 1992 and October 1993; 132 of them had chlamydial infection. A total of 108 women responded to recall. Full genital tract infection screening was carried out in 105 of the 108 recalled patients. Of the 105 patients, 5 had repeat positive cervical swabs for C. trachomatis, 1 had Trichomonas vaginalis, 24 had candidiasis, and 17 had anaerobic vaginosis. 13 of the 108 women had pelvic infection; none of them required readmission. In conclusion, the introduction of universal prophylaxis against C. trachomatis and AV has significantly reduced morbidity in patients obtaining a termination of pregnancy and has also resulted in substantial financial savings.


Sujet(s)
Avortement provoqué , Infections à Chlamydia/prévention et contrôle , Chlamydia trachomatis , Vaginose bactérienne/prévention et contrôle , Antibactériens/usage thérapeutique , Antibioprophylaxie , Infections à Chlamydia/économie , Infections à Chlamydia/épidémiologie , Femelle , Humains , Métronidazole/usage thérapeutique , Oxytétracycline/usage thérapeutique , Grossesse , Vaginose bactérienne/économie , Vaginose bactérienne/épidémiologie
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