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1.
Vaccine ; 41(2): 504-510, 2023 01 09.
Article de Anglais | MEDLINE | ID: mdl-36496283

RÉSUMÉ

BACKGROUND: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. METHODS: In total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. RESULTS: Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. CONCLUSION: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.


Sujet(s)
Antirhumatismaux , Polyarthrite rhumatoïde , Infections à pneumocoques , Adulte , Humains , Femelle , Mâle , Vaccins conjugués/usage thérapeutique , Inhibiteurs du facteur de nécrose tumorale/usage thérapeutique , Antirhumatismaux/usage thérapeutique , Infections à pneumocoques/épidémiologie , Infections à pneumocoques/prévention et contrôle , Infections à pneumocoques/complications , Polyarthrite rhumatoïde/traitement médicamenteux , Polyarthrite rhumatoïde/complications , Vaccins antipneumococciques
2.
Langmuir ; 35(36): 11836-11842, 2019 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-31430161

RÉSUMÉ

A dramatic improvement is reported in the stability of colloidal particles when stabilizing surface grafts are systematically shortened from small polymers to single monomers. The colloidal dispersions consist of fluorinated latex particles, exhibiting a weak van der Waals attraction, with grafted steric layers of poly(ethylene glycol) (PEG) of different chain lengths. Using an effective salting-out electrolyte, Na2CO3, particle aggregates are detected above a threshold salt concentration that is independent of the particle concentration. The results are interpreted in terms of a sudden onset of nondispersibility of single particles, triggered by the solvent not completely wetting particle surfaces. By decreasing the PEG chain length, the threshold salt concentration is found to increase sharply. For grafts with just a single ethylene glycol group, dispersions remain stable up to exceedingly high concentrations of Na2CO3. However, on removal of the surface coverage altogether, the classical stability behavior of charge-stabilized dispersions is recovered. The behavior can be captured by a simple model that incorporates effective polymer-solvent interactions in the presence of an electrolyte.

3.
Arch Dermatol Res ; 311(4): 299-308, 2019 May.
Article de Anglais | MEDLINE | ID: mdl-30830309

RÉSUMÉ

This study investigated oxidative stress in patients with psoriasis of low and medium disease activity. We measured advanced oxidation protein products (AOPP) and malondialdehyde (MDA) in plasma using UV-spectrophotometry and high performance liquid chromatography connected to a fluorescence detector in 84 patients and 84 matched healthy subjects. AOPP is a marker of protein oxidation due to inflammation, whereas MDA is a hydroxyl radical initiated lipid peroxidation product. Clinico-demographic variables including age, gender, disease severity, and fatigue were assessed in relation to AOPP and MDA. Disease severity was evaluated with the Psoriasis Area and Severity Index and the Dermatology Life Quality Index. Median (interquartile range, IQR) AOPP concentrations were 66 µmol/l (IQR 54-102) in patients and 69 µmol/l (IQR 55-87) in healthy subjects (P = 0.75). Median plasma MDA concentrations were significantly lower in patients than in healthy subjects (0.68 µM, IQR 0.54-0.85 vs. 0.76 µM, IQR 0.60-0.97; P = 0.03). Plasma levels of AOPP and MDA did not indicate oxidative stress in patients with mild psoriasis. Higher AOPP concentrations were associated with male gender, high body mass index, and high hemoglobin values. Elevated MDA concentrations were associated with advanced age and male gender. No associations with disease severity were detected. Although, the two selected biomarkers do not provide a complete measure of oxidative damage, our study demonstrates that a number of physiological and methodological factors influence the levels of MDA and AOPP. Such methodological issues are important to consider when interpreting results using these biomarkers in patients with psoriasis.


Sujet(s)
Produits d'oxydation avancée des protéines/sang , Marqueurs biologiques/sang , Malonaldéhyde/sang , Psoriasis/métabolisme , Adulte , Facteurs âges , Indice de masse corporelle , Études cas-témoins , Évolution de la maladie , Fatigue , Femelle , Humains , Peroxydation lipidique , Mâle , Adulte d'âge moyen , Oxydoréduction , Psoriasis/diagnostic , Qualité de vie , Facteurs sexuels
4.
J Neurosci Methods ; 310: 24-32, 2018 12 01.
Article de Anglais | MEDLINE | ID: mdl-29935197

RÉSUMÉ

BACKGROUND: The behaviour of all living beings consists of hidden patterns in time; consequently, its nature and its underlying dynamics are intrinsically difficult to be perceived and detected by the unaided observer. METHOD: Such a scientific challenge calls for improved means of detection, data handling and analysis. By using a powerful and versatile technique known as T-pattern detection and analysis (TPA) it is possible to unveil hidden relationships among the behavioural events in time. RESULTS: TPA is demonstrated to be a solid and versatile tool to study the deep structure of behaviour in different experimental contexts, both in human and non human subjects. CONCLUSION: This review deepens and extends contents recently published by adding new concepts and examples concerning the applications of TPA in the study of behaviour both in human and non-human subjects.


Sujet(s)
Comportement/physiologie , Modèles théoriques , Reconnaissance automatique des formes/méthodes , Animaux , Humains , Logiciel
5.
Colloid Polym Sci ; 295(10): 1983-1991, 2017.
Article de Anglais | MEDLINE | ID: mdl-28989224

RÉSUMÉ

Fluorinated spheres with grafted poly(ethylene glycol) (PEG) have been synthesized using a semi-batch emulsion polymerization in which the initiator is fed slowly to the reaction. In this way, PEG-grafted colloidal spheres can be fabricated with varying PEG chain length, different cores and varying degrees of crosslinking. The resulting batches have been characterized using disc centrifuge photosedimentometry and small-angle X-ray scattering. The size distribution is shown to be a sensitive function of the molar ratio of the reactive PEG macromonomer to fluorinated monomer, and with some optimization latices of very low polydispersity can be obtained with this simple synthesis method. For short PEG grafts too high a molar ratio results in a build up of smaller size particles and a broadening of the size distribution, whereas for longer grafts the mean particle size increases with decreasing molar ratio.

6.
Br J Dermatol ; 177(2): 505-512, 2017 Aug.
Article de Anglais | MEDLINE | ID: mdl-28182255

RÉSUMÉ

BACKGROUND: Fatigue is associated with various chronic inflammatory diseases, but few studies have focused on its occurrence in psoriasis. OBJECTIVES: To describe fatigue prevalence and degree among patients with chronic plaque psoriasis vs. age- and sex-matched healthy subjects, and to examine how fatigue is influenced by essential clinical and demographic factors. METHODS: In 84 patients and 84 healthy subjects, fatigue severity was assessed using three different generic fatigue instruments: the fatigue Visual Analogue Scale (fVAS), the Fatigue Severity Scale (FSS) and the Short Form 36 (SF-36) Vitality scale. Cut-off scores for clinically important fatigue were defined as ≥ 4 for FSS, ≥ 50 for fVAS and ≤ 35 for the SF-36 Vitality scale. Disease activity was evaluated using the Psoriasis Area and Severity Index (PASI), and the impact on quality of life with the Dermatology Life Quality Index (DLQI). RESULTS: Patients and healthy control subjects, respectively, showed median fVAS scores of 51 [interquartile range (IQR) 21-67] and 11 (IQR 3-20); FSS scores of 4 (IQR 2·5-5·3) and 1·6 (IQR 1·1-2·2); and SF-36 Vitality scores of 43 (IQR 25-85) and 73 (IQR 65-85). The rates of clinically important fatigue among patients vs. healthy controls, respectively, were 51% vs. 4% (fVAS); 52% vs. 4% (FSS); and 42% vs. 2% (SF-36 Vitality) (P < 0·001 for all differences). Fatigue was associated with DLQI scores, but not PASI scores, in univariate analysis but not in multivariate analysis. CONCLUSIONS: Nearly 50% of patients with psoriasis suffered from substantial fatigue. Fatigue severity was associated with smoking, pain and depression, but not with psoriasis severity.


Sujet(s)
Fatigue/étiologie , Psoriasis/complications , Études cas-témoins , Maladie chronique , Dépression/étiologie , Femelle , Humains , Mâle , Adulte d'âge moyen , Douleur musculosquelettique/étiologie , Mesure de la douleur , Psoriasis/psychologie , Qualité de vie , Indice de gravité de la maladie , Fumer/effets indésirables
7.
Ann Oncol ; 27(8): 1532-8, 2016 08.
Article de Anglais | MEDLINE | ID: mdl-27194814

RÉSUMÉ

BACKGROUND: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear. PATIENTS AND METHODS: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden. RESULTS: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years). CONCLUSIONS: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.


Sujet(s)
Protéine BRCA1/génétique , Protéine BRCA2/génétique , Tumeurs du sein/génétique , Adulte , Sujet âgé , Tumeurs du sein/épidémiologie , Tumeurs du sein/anatomopathologie , Femelle , Prédisposition génétique à une maladie , Mutation germinale , Humains , Adulte d'âge moyen , Mutation , Suède/épidémiologie
8.
Scand J Rheumatol ; 44(4): 271-9, 2015.
Article de Anglais | MEDLINE | ID: mdl-25656734

RÉSUMÉ

OBJECTIVES: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. METHOD: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagnostic codes. The following infections were considered as serious cases: pneumonia, other lower respiratory infections, meningitis, sepsis, and septic arthritis. The relative risk (RR) of infection was calculated as the number of events after/number of events before vaccination. Ratios of relative risk (RRRs) were calculated between vaccinated and non-vaccinated groups of patients. A generalized estimating equation (GEE) was used to handle correlated data for several events in the same individual. RESULTS: Although statistically non-significant, the point estimate of the RRR [0.55, 95% confidence interval (CI) 0.25-1.22] suggested a reduced risk of serious pneumococcal infections in vaccinated patients compared to the unexposed group. CONCLUSIONS: Vaccination with PCV7 tended to reduce the risk of putative serious pneumococcal infections by about 45% compared to non-vaccinated patients in this observational cohort study.


Sujet(s)
Polyarthrite rhumatoïde/immunologie , Infections à pneumocoques/épidémiologie , Vaccins antipneumococciques/usage thérapeutique , Spondylarthropathies/immunologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antirhumatismaux/usage thérapeutique , Polyarthrite rhumatoïde/complications , Polyarthrite rhumatoïde/traitement médicamenteux , Études cas-témoins , Femelle , Études de suivi , Humains , Incidence , Mâle , Adulte d'âge moyen , Infections à pneumocoques/immunologie , Infections à pneumocoques/prévention et contrôle , Facteurs de risque , Spondylarthropathies/complications , Spondylarthropathies/traitement médicamenteux , Suède , Vaccins conjugués/usage thérapeutique
9.
Br J Dermatol ; 172(5): 1196-203, 2015.
Article de Anglais | MEDLINE | ID: mdl-25557165

RÉSUMÉ

Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given.


Sujet(s)
Fatigue/étiologie , Psoriasis/complications , Facteurs biologiques/usage thérapeutique , Maladie chronique , Dépression/complications , Fatigue/diagnostic , Fatigue/traitement médicamenteux , Syndrome de fatigue chronique/étiologie , Humains , Troubles de la veille et du sommeil/complications
10.
J Neurosci Methods ; 239: 34-46, 2015 Jan 15.
Article de Anglais | MEDLINE | ID: mdl-25280983

RÉSUMÉ

A basic tenet in the realm of modern behavioral sciences is that behavior consists of patterns in time. For this reason, investigations of behavior deal with sequences that are not easily perceivable by the unaided observer. This problem calls for improved means of detection, data handling and analysis. This review focuses on the analysis of the temporal structure of behavior carried out by means of a multivariate approach known as T-pattern analysis. Using this technique, recurring sequences of behavioral events, usually hard to detect, can be unveiled and carefully described. T-pattern analysis has been successfully applied in the study of various aspects of human or animal behavior such as behavioral modifications in neuro-psychiatric diseases, route-tracing stereotypy in mice, interaction between human subjects and animal or artificial agents, hormonal-behavioral interactions, patterns of behavior associated with emesis and, in our laboratories, exploration and anxiety-related behaviors in rodents. After describing the theory and concepts of T-pattern analysis, this review will focus on the application of the analysis to the study of the temporal characteristics of behavior in different species from rodents to human beings. This work could represent a useful background for researchers who intend to employ such a refined multivariate approach to the study of behavior.


Sujet(s)
Comportement/physiologie , Recherche comportementale/méthodes , Analyse multifactorielle , Animaux , Humains , Modèles statistiques , Reproductibilité des résultats
11.
Clin Genet ; 88(3): 267-72, 2015 Sep.
Article de Anglais | MEDLINE | ID: mdl-25225168

RÉSUMÉ

We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.


Sujet(s)
Carcinome basocellulaire/génétique , Prédisposition génétique à une maladie , Mutation germinale , Protéines suppresseurs de tumeurs/génétique , Ubiquitin thiolesterase/génétique , Carcinome basocellulaire/métabolisme , Analyse de mutations d'ADN , Femelle , Haplotypes , Hétérozygote , Humains , Perte d'hétérozygotie , Mâle , Pedigree , Polymorphisme de nucléotide simple , Protéines suppresseurs de tumeurs/métabolisme , Ubiquitin thiolesterase/métabolisme
12.
Br J Dermatol ; 169(5): 1049-55, 2013 Nov.
Article de Anglais | MEDLINE | ID: mdl-23855428

RÉSUMÉ

BACKGROUND: BRAF and NRAS mutations are frequently found in melanoma tumours, and recently developed BRAF-targeted therapies demonstrate significant clinical benefit. OBJECTIVES: We sought to investigate the clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort. METHODS: In total, 237 tumours, mostly metastatic lesions, from 203 patients were screened for mutations in exon 15 of BRAF and exon 2 of NRAS using Sanger sequencing. BRAF and NRAS mutation status was analysed in relation to clinical and histopathological characteristics, and outcome. RESULTS: Mutation in BRAF and NRAS was present in 43% (88% V600E, 10% V600K) and 30% (48% Q61K, 40% Q61R) of metastatic melanomas, respectively. We found consistent BRAF and NRAS mutation status in all but one of 27 patients with multiple metastases. BRAF mutation was associated with younger age at primary diagnosis (P = 0.02). Among patients with distant metastatic melanoma, patients with BRAF-mutant tumours without BRAF inhibitor treatment had inferior survival compared with patients with BRAF inhibitor treatment [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.10-5.01, P = 0.03]. We also observed a trend towards better prognosis for patients with wild-type and NRAS-mutant tumours compared with BRAF V600E-mutant tumours (HR 0.64, 95% CI 0.39-1.04, P = 0.07; and HR 0.76, 95% CI 0.48-1.21, P = 0.25, respectively). CONCLUSIONS: We were able to confirm the effect of BRAF inhibitor treatment in a single clinical institution. The results suggest further that BRAF mutation is a weak prognostic factor but a strong predictive factor and that BRAF-mutant melanoma might constitute one or more distinct subtypes of the disease with certain aetiology and clinical outcome.


Sujet(s)
dGTPases/génétique , Gènes ras , Mélanome/génétique , Protéines membranaires/génétique , Mutation , Protéines proto-oncogènes B-raf/génétique , Tumeurs cutanées/génétique , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antinéoplasiques/usage thérapeutique , Survie sans rechute , Exons , Femelle , Humains , Indoles/usage thérapeutique , Mâle , Mélanome/traitement médicamenteux , Mélanome/chirurgie , Adulte d'âge moyen , Métastase tumorale , Récidive tumorale locale/génétique , Pronostic , Protéines proto-oncogènes B-raf/antagonistes et inhibiteurs , Tumeurs cutanées/traitement médicamenteux , Tumeurs cutanées/chirurgie , Sulfonamides/usage thérapeutique , Vémurafénib
13.
Afr J Psychiatry (Johannesbg) ; 16(2): 94-103, 2013 Mar.
Article de Anglais | MEDLINE | ID: mdl-23595528

RÉSUMÉ

OBJECTIVE: To determine the outcomes of mental health care users (MHCU's) admitted in terms of Section 40 of the South African Mental Health Care Act (No 17 of 2002) (MHCA) and the factors, if any, that are associated with these outcomes. METHOD: The study was a retrospective record review of MHCU's, 18 years and older, referred by the South African Police Service (SAPS) to Chris Hani Baragwanath Hospital (CHBH). All mental health care users handed over to CHBH by SAPS with completed MHCA form 22's during the period July 2007 to December 2007 were included in the study. The outcomes, demographics and clinical characteristics of these referrals were obtained from hospital records. RESULTS: During the six-month study period, 718 MHCU's were referred by members of SAPS to the CHBH Emergency Department. Associations were found between discharged MHCU's and i) being male, ii) being less than 35 years of age, iii) being unemployed, iv) having a lower level of education, v) having a past history of substance abuse and/or vi) a past psychiatric illness. Females were twice as likely to be unemployed and admitted to hospital (either to a psychiatric or general medical ward). MHCU's diagnosed with delirium were more likely to be admitted into a medical ward as compared to a psychiatric ward. CONCLUSION: As has been the case in most countries where police services have been incorporated into mental health acts, South Africa's new Mental Health Care Act (No 17 of 2002) has resulted in a large number of referrals by the police to mental health services. However, many of these referrals may not be necessary as most MHCU's end up not being admitted. The characteristics of police referrals suggest that the receiving facility should have the capacity to identify factors that favour outpatient care (especially substance abuse problems) and divert MHCU's presenting with such factors to appropriate treatment facilities without admitting them to the hospital.


Sujet(s)
Services des urgences psychiatriques , Hospitalisation , Troubles mentaux , Personnes handicapées mentales , Adolescent , Adulte , Facteurs âges , Soins ambulatoires/législation et jurisprudence , Soins ambulatoires/statistiques et données numériques , Services des urgences psychiatriques/législation et jurisprudence , Services des urgences psychiatriques/statistiques et données numériques , Femelle , Hospitalisation/législation et jurisprudence , Hospitalisation/statistiques et données numériques , Humains , Application de la loi/méthodes , Mâle , Dossiers médicaux basés sur les problèmes/statistiques et données numériques , Troubles mentaux/épidémiologie , Troubles mentaux/thérapie , Personnes handicapées mentales/législation et jurisprudence , Personnes handicapées mentales/statistiques et données numériques , Police , Service hospitalier de psychiatrie/législation et jurisprudence , Service hospitalier de psychiatrie/statistiques et données numériques , Orientation vers un spécialiste/statistiques et données numériques , Études rétrospectives , Facteurs sexuels , Facteurs socioéconomiques , République d'Afrique du Sud/épidémiologie
14.
Mar Pollut Bull ; 58(12): 1796-807, 2009 Dec.
Article de Anglais | MEDLINE | ID: mdl-19732912

RÉSUMÉ

Mytilus edulis and Chlamys islandica were exposed to nominal dispersed crude oil concentrations in the range 0.015-0.25 mg/l for one month. Five biomarkers (enzymatic and cellular responses) were analysed together with bioaccumulation of PAHs at the end of exposure. In both species, PAH tissue residues reflected the exposure concentration measured in the water and lipophilicity determined the bioaccumulation levels. Oil caused biomarker responses in both species but more significant alterations in exposed C. islandica were observed. The relationships between exposure levels and enzymatic responses were apparently complex. The integrated biomarker response related against the exposure levels was U-shaped in both species and no correlation with total PAH body burden was found. For the monitoring of chronic offshore discharges, dose- and time-related events should be evaluated in the selection of biomarkers to apply. From this study, cellular damages appear more fitted than enzymatic responses, transient and more complex to interpret.


Sujet(s)
Mytilus edulis/effets des médicaments et des substances chimiques , Pectinidae/effets des médicaments et des substances chimiques , Pétrole/toxicité , Hydrocarbures aromatiques polycycliques/toxicité , Polluants chimiques de l'eau/toxicité , Animaux , Océan Atlantique , Marqueurs biologiques/métabolisme , Charge corporelle , Catalase/métabolisme , Surveillance de l'environnement , Glutathione transferase/métabolisme , Mytilus edulis/enzymologie , Mer du Nord , Pectinidae/enzymologie , Pétrole/métabolisme , Hydrocarbures aromatiques polycycliques/métabolisme , Eau de mer/composition chimique , Tests de toxicité , Polluants chimiques de l'eau/analyse , Polluants chimiques de l'eau/métabolisme
15.
J Med Genet ; 45(5): 284-9, 2008 May.
Article de Anglais | MEDLINE | ID: mdl-18178632

RÉSUMÉ

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.


Sujet(s)
Gènes p16 , Mutation germinale , Mélanome/épidémiologie , Mélanome/génétique , Allèles , Australie , Études cas-témoins , Fréquence d'allèle , Génotype , Humains , Islande/épidémiologie , Amérique du Nord , Groupes de population , Facteurs de risque
16.
Br J Cancer ; 98(2): 434-42, 2008 Jan 29.
Article de Anglais | MEDLINE | ID: mdl-18071362

RÉSUMÉ

The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development.


Sujet(s)
Chordome/génétique , Aberrations des chromosomes , Délétion de gène , Gènes p16 , Hybridation d'acides nucléiques , Séquençage par oligonucléotides en batterie , Tumeurs du rachis/génétique , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Chromosomes humains de la paire 9 , Inhibiteur p15 de kinase cycline-dépendante/génétique , Femelle , Dosage génique , Humains , Hybridation fluorescente in situ , Mâle , Adulte d'âge moyen , Hybridation d'acides nucléiques/méthodes
17.
Rheumatology (Oxford) ; 46(7): 1133-9, 2007 Jul.
Article de Anglais | MEDLINE | ID: mdl-17478473

RÉSUMÉ

OBJECTIVE: To analyse rheumatological manifestations, organ damage and autoimmune responses in a large cohort of patients (n = 45) with homozygous C2 deficiency (C2D) and long-term follow-up. METHODS: Medical records were reviewed and were supplemented with a mailed questionnaire for assessment of cardiovascular disease (CVD) risk factors. Organ damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Causes for disability pensions were investigated. Autoantibodies were determined with established methods. RESULTS: Patients with rheumatological diseases had systemic lupus erythematosus (SLE, n = 12), undifferentiated connective tissue disease (n = 5) or vasculitis (n = 3). Judging from annual SLICC/ACR DI, C2D patients with SLE run a similar risk of development of severe disease as other patients with SLE. An increased rate of CVD was observed not explained by Framingham-related risk factors. Disability pensions were mainly related to rheumatological disease. The prevalence of anti-nuclear antibodies in C2D with SLE and of anti-SS-A was 25% while anti-RNP was found in 45%. Only one patient showed antibodies to dsDNA. Formation of anti-cardiolipin antibodies (aCL) appeared to be increased in C2D despite the absence of an anti-phospholipid syndrome. The prevalence of antibodies to the collagen-like region of C1q (C1qCLR) was also remarkably high and was not related to rheumatological manifestations. CONCLUSIONS: Severity of SLE in C2D is similar to that of SLE in other patients. Conventional risk factors do not explain the occurrence of CVD in C2D. The high prevalence of aCL and anti-C1qCLR indicates mechanisms through which impaired complement function promotes formation of autoantibodies.


Sujet(s)
Autoanticorps/sang , Auto-immunité , Complément C2/déficit , Lupus érythémateux disséminé/immunologie , Rhumatismes/immunologie , Adulte , Anticorps anticardiolipines/sang , Anticorps antinucléaires/sang , Anticorps antinucléaires/immunologie , Maladies cardiovasculaires/immunologie , Loi du khi-deux , Complément C1q/immunologie , Maladies du tissu conjonctif/immunologie , Évaluation de l'invalidité , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Statistique non paramétrique , Vascularite/immunologie
18.
Oncogene ; 26(32): 4738-48, 2007 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-17260012

RÉSUMÉ

Malignant melanoma is an aggressive, heterogeneous disease where new biomarkers for diagnosis and clinical outcome are needed. We searched for chromosomal aberrations that characterize its pathogenesis using 47 different melanoma cell lines and tiling-resolution bacterial artificial chromosome-arrays for comparative genomic hybridization. Major melanoma genes, including BRAF, NRAS, CDKN2A, TP53, CTNNB1, CDK4 and PTEN, were examined for mutations. Distinct copy number alterations were detected, including loss or gain of whole chromosomes but also minute amplifications and homozygous deletions. Most common overlapping regions with losses were mapped to 9p24.3-q13, 10 and 11q14.1-qter, whereas copy number gains were most frequent on chromosomes 1q, 7, 17q and 20q. Amplifications were delineated to oncogenes such as MITF (3p14), CCND1 (11q13), MDM2 (12q15), CCNE1 (19q12) and NOTCH2 (1p12). Frequent findings of homozygous deletions on 9p21 and 10q23 confirmed the importance of CDKN2A and PTEN. Pair-wise comparisons revealed distinct sets of alterations, for example, mutually exclusive mutations in BRAF and NRAS, mutual mutations in BRAF and PTEN, concomitant chromosome 7 gain and 10 loss and concomitant chromosome 15q22.2-q26.3 gain and 20 gain. Moreover, alterations of the various melanoma genes were associated with distinct chromosomal imbalances suggestive of specific genomic programs in melanoma development.


Sujet(s)
Aberrations des chromosomes , Gènes tumoraux/génétique , Mélanome/génétique , Tumeurs cutanées/génétique , Lignée cellulaire tumorale , Analyse de mutations d'ADN , Amplification de gène , Dosage génique , Génomique , Humains , Mutation , Séquençage par oligonucléotides en batterie
19.
Behav Processes ; 73(1): 92-9, 2006 Jul.
Article de Anglais | MEDLINE | ID: mdl-16678360

RÉSUMÉ

The behavioural analysis of human-robot interactions can help in developing socially interactive robots. The current study analyzes human-robot interaction with Theme software and the corresponding pattern detection algorithm. The method is based on the analysis of the temporal structure of the interactions by detecting T-patterns in the behaviour. We have compared humans' (children and adults) play behaviour interacting either with an AIBO or a living dog puppy. The analysis based on measuring latencies and frequencies of behavioural units suggested limited differences, e.g. the latency of humans touching the dog/AIBO was similar. In addition other differences could be accounted for by the limited abilities of the robot to interact with objects. Although the number of interactive T-patterns did not significantly differ among the groups but the partner's type (whether humans were playing with dog or AIBO) had a significant effect on the structure of the patterns. Both children and adults terminated T-patterns more frequently when playing with AIBO than when playing with the dog puppy, which suggest that the robot has a limited ability to engage in temporally structured behavioural interactions with humans. As other human studies suggest that the temporal complexity of the interaction is good measure of the partner's attitude, we suggest that more attention should be paid in the future to the robots' ability to engage in cooperative interaction with humans.


Sujet(s)
Robotique , Comportement social , Logiciel , Adulte , Algorithmes , Animaux , Comportement animal/physiologie , Enfant , Chiens , Femelle , Humains , Mâle , Jeu et accessoires de jeu
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