RESUMO
Certified reference material (CRM) for natural (40K,210Pb,210Po,226Ra,228Ra,228Th,230Th,232Th,234U,235U, and238U) and anthropogenic (137Cs,239+240Pu, and241Am) radionuclides in marine sediment from the Baltic Sea (IAEA-465) has been developed. Information values are given for 238Pu,239Pu and240Pu. Altogether 27 laboratories participated in this exercise. Radiometric (alpha-spectrometry, gamma-spectrometry and beta counting, as well as mass spectrometry (ICP-MS and AMS) techniques were applied in measurements. The CRM is intended to be used for Quality Assurance/Quality Control of radionuclide analyses, for the development and validation of analytical methods, for the development of reference methods and for training purposes.
Assuntos
Sedimentos Geológicos , Monitoramento de Radiação , Poluentes Radioativos da Água , Sedimentos Geológicos/química , Poluentes Radioativos da Água/análise , Plutônio/análise , Padrões de Referência , Radioisótopos/análise , Radioisótopos de Césio/análise , Tório/análiseRESUMO
OBJECTIVE: To perform a temporal and geographical validation of a prognostic model, considered of highest methodological quality in a recently published systematic review, for predicting survival in very preterm infants admitted to the neonatal intensive care unit. The original model was developed in the UK and included gestational age, birthweight and gender. DESIGN: External validation study in a population-based cohort. SETTING: Dutch neonatal wards. POPULATION OR SAMPLE: All admitted white, singleton infants born between 23+0 and 32+6 weeks of gestation between 1 January 2015 and 31 December 2019. Additionally, the model's performance was assessed in four populations of admitted infants born between 24+0 and 31+6 weeks of gestation: white singletons, non-white singletons, all singletons and all multiples. METHODS: The original model was applied in all five validation sets. Model performance was assessed in terms of calibration and discrimination and, if indicated, it was updated. MAIN OUTCOME MEASURES: Calibration (calibration-in-the-large and calibration slope) and discrimination (c statistic). RESULTS: Out of 6092 infants, 5659 (92.9%) survived. The model showed good external validity as indicated by good discrimination (c statistic 0.82, 95% CI 0.79-0.84) and calibration (calibration-in-the-large 0.003, calibration slope 0.92, 95% CI 0.84-1.00). The model also showed good external validity in the other singleton populations, but required a small intercept update in the multiples population. CONCLUSIONS: A high-quality prognostic model predicting survival in very preterm infants had good external validity in an independent, nationwide cohort. The accurate performance of the model indicates that after impact assessment, implementation of the model in clinical practice in the neonatal intensive care unit could be considered. TWEETABLE ABSTRACT: A high-quality model predicting survival in very preterm infants is externally valid in an independent cohort.
Assuntos
Mortalidade Infantil , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Modelos Estatísticos , Países Baixos/epidemiologia , Sistema de RegistrosRESUMO
The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: (40)K, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (234)U, (238)U, (239)Pu, (239+240)Pu and (241)Am for IAEA-410 and (40)K, (137)Cs, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (235)U, (238)U, (239)Pu, (240)Pu and (239+240)Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training.
Assuntos
Sedimentos Geológicos/análise , Radioisótopos/análise , Radioisótopos/normas , Radiometria/normas , Poluentes Radioativos do Solo/análise , Poluentes Radioativos do Solo/normas , Certificação/normas , Sedimentos Geológicos/química , Micronésia , Oceano Pacífico , Radioisótopos/química , Valores de Referência , Poluentes Radioativos do Solo/químicaRESUMO
This study combines in situ gamma spectrometry performed at different scales, in order to accurately locate the contamination pools, to identify the concerned radionuclides and to determine the distribution of the contaminants from soil to bearing phase scale. The potential mobility of several radionuclides is also evaluated using sequential extraction. Using this procedure, an accumulation area located downstream of a former French uranium mine and concentrating a significant fraction of radioactivity is highlighted. We report disequilibria in the U-decay chains, which are likely related to the processes implemented on the mining area. Coupling of mineralogical analyzes with sequential extraction allow us to highlight the presence of barium sulfate, which may be the carrier of the Ra-226 activities found in the residual phase (Ba(Ra)SO4). In contrast, uranium is essentially in the reducible fraction and potentially trapped in clay-iron coatings located on the surface of minerals.
Assuntos
Sedimentos Geológicos/análise , Monitoramento de Radiação/métodos , Poluentes Radioativos do Solo/análise , Urânio/análise , França , Mineração , Espectrometria gamaRESUMO
On 15 August 2012, an increase in the number of Salmonella Thompson cases was noticed by the Salmonella surveillance in the Netherlands. A casecontrol study was performed, followed by a food investigation. In total 1,149 cases were laboratory-confirmed between August and December 2012 of which four elderly (7691 years) were reported to have died due to the infection. The cause of the outbreak was smoked salmon processed at a single site. The smoked salmon had been continuously contaminated in the processing lines through reusable dishes, which turned out to be porous and had become loaded with bacteria. This is the largest outbreak of salmonellosis ever recorded in the Netherlands. The temporary closure of the processing site and recall of the smoked salmon stopped the outbreak. An estimated four to six million Dutch residents were possibly exposed to the contaminated smoked salmon and an estimated 23,000 persons would have had acute gastroenteritis with S. Thompson during this outbreak. This outbreak showed that close collaboration between diagnostic laboratories, regional public health services, the national institute for public health and the food safety authorities is essential in outbreak investigations.
Assuntos
Surtos de Doenças , Produtos Pesqueiros/microbiologia , Salmão/microbiologia , Intoxicação Alimentar por Salmonella/mortalidade , Infecções por Salmonella/mortalidade , Salmonella enterica/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Diarreia/epidemiologia , Produtos Pesqueiros/análise , Manipulação de Alimentos/métodos , Gastroenterite/epidemiologia , Humanos , Masculino , Países Baixos/epidemiologia , Vigilância da População , Intoxicação Alimentar por Salmonella/diagnóstico , Intoxicação Alimentar por Salmonella/microbiologia , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/microbiologia , Salmonella enterica/classificação , Inquéritos e QuestionáriosRESUMO
We describe a new underground laboratory, namely LAFARA (for "LAboratoire de mesure des FAibles RAdioactivités"), that was recently created in the French Pyrénées. This laboratory is primarily designed to analyze environmental samples that display low radioactivity levels using gamma-ray spectrometry. Two high-purity germanium detectors were placed under 85 m of rock (ca. 215 m water equivalent) in the tunnel of Ferrières (Ariège, France). The background is thus reduced by a factor of â¼20 in comparison to above-ground laboratories. Both detectors are fully equipped so that the samples can be analyzed in an automatic mode without requiring permanent presence of a technician in the laboratory. Auto-samplers (twenty positions) and systems to fill liquid nitrogen automatically provide one month of autonomy to the spectrometers. The LAFARA facility allows us to develop new applications in the field of environmental sciences based on the use of natural radionuclides present at low levels in the environment. As an illustration, we present two of these applications: i) dating of marine sediments using the decay of (226)Ra in sedimentary barite (BaSO(4)), ii) determination of (227)Ac ((231)Pa) activities in marine sediment cores.
Assuntos
Laboratórios , Espectrometria gama/métodos , Actínio/análise , Contaminação Radioativa do Ar/prevenção & controle , Radiação de Fundo , Sulfato de Bário/química , França , Sedimentos Geológicos/análise , Protoactínio/análise , Monitoramento de Radiação , Poluentes Radioativos/análise , Rádio (Elemento)/análise , Água do Mar , Espectrometria gama/instrumentaçãoRESUMO
Two Dutch travellers were infected with oseltamivir-resistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely.
Assuntos
Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Oseltamivir/farmacologia , Viagem , Adolescente , Farmacorresistência Viral/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Dados de Sequência Molecular , Mutação , Países Baixos , Neuraminidase/genética , Vigilância de Evento Sentinela , Espanha , Resultado do Tratamento , Adulto JovemRESUMO
Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.
Assuntos
Rádio (Elemento)/análise , Água do Mar/química , Poluentes Radioativos da Água/análise , Brasil , Guiana Francesa , Limite de Detecção , Rádio (Elemento)/química , Espectrometria gama , Fatores de Tempo , Poluentes Radioativos da Água/químicaRESUMO
Improved housing for laying hens may start from the translation of their behavioral needs into welfare-based design parameters for laying hen houses. The objective of our research was to gain insights into the facility usage and behavioral needs of the hen over 24 h when there are no obvious restraints. Twenty ISA Brown commercial laying hens (Gallus domesticus) that were 18 wk old and not beak trimmed, were accommodated in a pen (4 x 6 m) at 19 + 2 degrees C on a light-dark cycle of 10L:14D. The pen providing nest boxes, drinkers, feeders, perches, sand, and wood shaving was designed to accommodate the hens for the experimental period. Video recordings were made for 10 d. Behavioral analyses were conducted on 5 birds for 5 d. Time spent on each behavior, log survivor analysis of events and inter-event intervals, bout analysis, diurnal pattern in events and bouts, occurrence of behavior in different segments and the corridor of the pen, and sequence analysis were performed to gain insights into the temporal and sequential structures of behavior. Hens spent 97% of the day on nest use, preening, drinking, feeding, still, walking, perching, and resting; 43% on commodity-dependent behavior; and 57% not on commodity-oriented behaviors. Behavioral events were short (around 70% event <2 min) and frequent (around 70% inter-event intervals <40s). The pen corridor was the preferred place for attack, escape, flying, resting, walking, and wing flapping. Feeding-drinking-feeding, preening-resting-preening, scratching-resting-scratching, dust bathing-resting-preening, or dust bathing-resting-wing stretching-dust bathing were the preferred sequences of behavior. Although hens interrupted ongoing behaviors and changed behaviors frequently, they nonetheless clustered behavioral events.
Assuntos
Comportamento Animal , Galinhas/fisiologia , Abrigo para Animais , Oviposição , Animais , Ritmo Circadiano , Ingestão de Líquidos , Ingestão de Alimentos , Feminino , Fotoperíodo , Fatores de TempoRESUMO
The immune system is called into action by alarm signals generated from injured tissues. We examined the nature of these alarm signals after exposure of skin residential cells to contact allergens (nickel sulfate and potassium dichromate) and a contact irritant [sodium dodecyl sulfate (SDS)]. Nickel sulfate, potassium dichromate, and SDS were applied topically to the stratum corneum of human skin equivalents. A similar concentration-dependent increase in chemokine (CCL20, CCL27, and CXCL8) secretion was observed for all three chemicals. Exposure to nickel sulfate and SDS was investigated in more detail: similar to chemokine secretion, no difference was observed in the time- and concentration-dependent increase in pro-inflammatory cytokine [interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha)] secretion. Maximal increase in IL-1alpha secretion occurred within 2 h after exposure to both nickel sulfate and SDS and prior to increased chemokine secretion. TNF-alpha secretion was detectable 8 h after chemical exposure. After allergen or irritant exposure, increased CCL20 and CXCL8, but not CCL27, secretion was inhibited by neutralizing human antibodies to either IL-1alpha or TNF-alpha. Our data show that alarm signals consist of primary and secondary signals. IL-1alpha and TNF-alpha are released as primary alarm signals, which trigger the release of secondary chemokine (CCL20 and CXCL8) alarm signals. However, some chemokines, for example, CCL27 can be secreted in an IL-1alpha and TNF-alpha independent manner. Our data suggest that skin residential cells respond to both allergen and irritant exposure by releasing mediators that initiate infiltration of immune responsive cells into the skin.
Assuntos
Quimiocinas CC/biossíntese , Interleucina-1/biossíntese , Interleucina-8/biossíntese , Proteínas Inflamatórias de Macrófagos/biossíntese , Pele/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Alérgenos/metabolismo , Cáusticos/farmacologia , Células Cultivadas , Quimiocina CCL20 , Quimiocina CCL27 , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Humanos , Interleucina-1/metabolismo , Irritantes/farmacologia , Queratinócitos/citologia , Níquel/farmacologia , Dicromato de Potássio/farmacologia , Proteínas Recombinantes/química , Pele/metabolismo , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Fatores de TempoAssuntos
Antiprotozoários/uso terapêutico , Surtos de Doenças/veterinária , Doenças das Aves Domésticas/epidemiologia , Infecções Protozoárias em Animais/epidemiologia , Perus/parasitologia , Animais , Surtos de Doenças/prevenção & controle , Europa (Continente)/epidemiologia , Países Baixos/epidemiologia , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Infecções Protozoárias em Animais/tratamento farmacológico , Infecções Protozoárias em Animais/prevenção & controleRESUMO
Recruitment of activated T-cells to the skin is a common feature in a wide variety of inflammatory skin diseases. As CXCR3 activating chemokines CXCL10 (IP-10), CXCL9 (Mig), and CXCL11 (IP-9/I-TAC) specifically attract activated T-cells, this study addressed the question of whether differences in the expression of these chemokines correlate with the site and cellular composition of the skin infiltrates in different types of inflammatory skin disease. Skin biopsies from lichen planus, chronic discoid lupus erythematosus, allergic patch test reactions, psoriasis, and Jessner's lymphocytic infiltration of the skin were investigated for chemokine expression using RNA in situ hybridization, and for the expression of CXCR3 using immunohistochemistry. The results showed differential expression of CXCL10, CXCL9, and CXCL11, which correlated with differences in the localization and cellular composition of the infiltrates. Whereas CXCL10 and CXCL11 were mainly expressed by basal keratinoctyes, CXCL9 mRNA expression was located predominantly in the dermal infiltrates. Correlation with immunohistochemical data suggested that macrophages and activated keratinocytes were the main producers of these chemokines. CXCR3 was expressed by a majority of both CD4+ and CD8+ infiltrating T-cells, suggesting a functional interaction between locally produced chemokines and CXCR3-expressing T-cells. In conclusion, these findings indicate that these CXCR3 activating chemokines play a significant role in the recruitment and maintenance of T-cell infiltrates in the inflammatory skin diseases studied.
Assuntos
Quimiocinas CXC/metabolismo , Dermatite/imunologia , Receptores de Quimiocinas/metabolismo , Quimiocina CXCL10 , Quimiocina CXCL11 , Quimiocinas CXC/genética , Expressão Gênica , Antígenos HLA-DR/metabolismo , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Molécula 1 de Adesão Intercelular/metabolismo , Líquen Plano/imunologia , Lúpus Eritematoso Discoide/imunologia , Psoríase/imunologia , RNA Mensageiro/genética , Receptores CXCR3RESUMO
Vaginal infections by Trichomonas vaginalis and Mycoplasma hominis have been shown to be associated. Since M. hominis and Ureaplasma urealyticum are similar pathogens, both belonging to the class of the mycoplasmata, we describe here a molecular study into the interdependence of U. urealyticum and T. vaginalis during infection. Susceptibility towards infection by U. urealyticum depends on genetic polymorphism in the interleukin-1 receptor antagonist (IL-1RA) gene. Now, we defined the relation between IL-1RA genotypes and infection by M. hominis and T. vaginalis. Finally, we also developed a restriction fragment length polymorphism (RFLP) tool for mapping variation in the T. vaginalis AP33 adhesin in order to define putative associations between parasite subtype and mycoplasmata or host. Studies using crudepellets from T. vaginalis culture broth clearly confirm the association between T. vaginalis and M. hominis infection. The association between IL-1RA genotype 2,2 and lack of U. urealyticum infection is corroborated as well. U. urealyticum infection and infection by T. vaginalis are independent. Furthermore, T. vaginalis and M. hominis infection are not depending on IL-1RA genotypes. Interestingly, one of the three AP33 RFLP types identified appeared to be associated with the absence of U. urealyticum infection. In conclusion, the complex interaction between bacterial and parasitic pathogens and the infected host is determined by genetic characteristics of host and microorganisms involved.
Assuntos
Mycoplasma hominis/fisiologia , Trichomonas vaginalis/fisiologia , Ureaplasma urealyticum/fisiologia , Doenças Vaginais/microbiologia , Doenças Vaginais/parasitologia , Adulto , Animais , Estudos de Coortes , DNA de Protozoário/química , Feminino , Variação Genética/genética , Interações Hospedeiro-Parasita/fisiologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/parasitologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Sialoglicoproteínas/química , Sialoglicoproteínas/genética , Vaginite por Trichomonas/microbiologia , Vaginite por Trichomonas/parasitologia , Trichomonas vaginalis/classificação , Trichomonas vaginalis/genética , Infecções por Ureaplasma/microbiologia , Infecções por Ureaplasma/parasitologiaRESUMO
BACKGROUND: Fas (CD95; APO-1) is a transmembrane protein that mediates apoptosis upon cross-linking with Fas-ligand (Fas-L). Interaction of Fas-L expressed by cytotoxic T cells with Fas-expressing tumour cells plays an important part in antitumour immune responses. OBJECTIVES: We aimed to investigate Fas and Fas-L expression in frozen and paraffin-embedded material from a large group of patients with cutaneous T-cell lymphoma (CTCL). METHODS: Immunostaining with monoclonal antibodies against Fas and Fas-L was performed in material from 23 patients with mycosis fungoides (MF), 10 with lymphomatoid papulosis (LyP), 10 with CD30-positive primary cutaneous large T-cell lymphoma (LTCL) and nine with CD30-negative LTCL. The results were correlated with the type and stage of CTCL and clinical features. RESULTS: Expression of Fas by the large majority of the neoplastic T cells was observed in 15 of 15 cases of plaque-stage MF, 10 of 10 cases of LyP and 10 of 10 cases of CD30-positive LTCL, but only in four of 12 cases of tumour-stage MF and two of nine cases of CD30-negative LTCL. In three of four MF patients in whom both plaques and tumours could be studied, a significant decrease in Fas expression was observed with progression from plaque-stage to tumour-stage disease. Fas-L was expressed by > 50% of the neoplastic T cells in 46 of 56 biopsies, and no clear relationship with type of CTCL and clinical behaviour was observed. CONCLUSIONS: This study demonstrates loss of Fas expression in aggressive types of CTCL, but not in indolent types of CTCL. These data suggest that loss of Fas receptor expression may be one of the mechanisms that allow tumour cells to escape an effective immune response, and may contribute to the unfavourable prognosis of some types of CTCL.
Assuntos
Antígenos de Neoplasias/metabolismo , Linfoma Cutâneo de Células T/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Cutâneas/metabolismo , Receptor fas/metabolismo , Proteína Ligante Fas , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-1/análise , Ligantes , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/imunologia , Micose Fungoide/metabolismo , Micose Fungoide/patologia , Proteínas de Neoplasias/metabolismo , Prognóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologiaRESUMO
Differentiation between allergic and irritant contact dermatitis reactions is difficult, as both inflammatory diseases are clinically, histologically, and immunohistologically very similar. Previous studies in mice revealed that the chemokine IP-10 is exclusively expressed in allergic contact dermatitis reactions. In the present study, we investigated whether the mRNA expression of IP-10 and the related CXCR3 activating chemokines, Mig and IP-9 are also differentially expressed in human allergic contact dermatitis and irritant contact dermatitis reactions. Skin biopsies from allergic (13 cases) and sodium lauryl sulfate-induced irritant patch test reactions (13 cases), obtained 1-72 h after patch testing, were studied by means of an in situ hybridization technique. Results of chemokine mRNA expression were correlated with clinical scoring, histology, and immunohistochemical data including the proportion of inflammatory cells expressing CXCR3, the receptor for IP-10, Mig, and IP-9, and ICAM-1 and HLA-DR expression on keratinocytes. IP-10, Mig, and IP-9 mRNA were detected in seven of nine allergic contact dermatitis reactions after 24-72 h, but not in sodium lauryl sulfate-induced irritant contact dermatitis reactions. ICAM-1 expression by keratinocytes was only found in allergic contact dermatitis reactions and correlated with chemokine expression. Moreover, up to 50% of the infiltrating cells in allergic contact dermatitis expressed CXCR3, in contrast to only 20% in irritant contact dermatitis reactions. In conclusion, we have demonstrated differences in chemokine expression between allergic contact dermatitis and irritant contact dermatitis reactions, which might reflect different regulatory mechanisms operating in these diseases and may be an important clue for differentiation between allergic contact dermatitis and irritant contact dermatitis reactions.
Assuntos
Quimiocinas CXC/genética , Dermatite Alérgica de Contato/imunologia , Dermatite Irritante/imunologia , Peptídeos e Proteínas de Sinalização Intercelular , Testes do Emplastro , RNA Mensageiro/análise , Quimiocina CXCL10 , Quimiocina CXCL11 , Quimiocina CXCL9 , Antígenos HLA-DR/análise , Humanos , Molécula 1 de Adesão Intercelular/análise , Interferon gama/farmacologia , Queratinócitos/química , Receptores CXCR3 , Receptores de Quimiocinas/análiseRESUMO
Primary cutaneous B-cell lymphomas (CBCLs) represent a rare, but distinct group of B-cell neoplasms with a different clinical behaviour to B-cell lymphomas secondarily involving the skin. Fas-Fas ligand (Fasl) expression was investigated in a group of primary and secondary CBCLs to gain an insight into the putative role of these apoptotic molecules in the clinical behaviour of these lymphomas. Frozen and paraffin sections from 32 patients with a CBCL were investigated for Fas and Fasl expression, using immunohistochemistry. This group included 24 primary CBCLs [14 primary cutaneous follicle centre cell lymphomas (PCFCCLs), six primary cutaneous large B-cell lymphomas (PCLBCLs) on the leg, and four primary cutaneous immunocytomas] and eight secondary CBCLs. The results were correlated with follow-up data, bcl-2, and ICAM-1 expression. High Fas expression and absent or low Fasl expression were detected in the vast majority of PCFCCLs and immunocytomas. The group of PCLBCLs on the leg, which have an intermediate prognosis, showed variable results with relatively higher Fasl expression. The highest Fasl expression was found in the more aggressive secondary CBCLs whereas in this group, Fas was undetectable in five of eight cases. Statistical analysis showed that Fas and ICAM-1 expression was strongly related to a favourable prognosis, whereas expression of Fasl and bcl-2 was related to a very poor prognosis. Although only type of CBCL and age, but not Fas, Fasl, bcl-2, and ICAM-1 expression, proved independent prognostic parameters using multivariate analysis, the results of this study suggest that differences in the expression of Fas and Fasl, as well as bcl-2 and ICAM-1, contribute to the differences in clinical behaviour between these different types of CBCL.
Assuntos
Linfoma de Células B/metabolismo , Glicoproteínas de Membrana/análise , Proteínas de Neoplasias/análise , Neoplasias Cutâneas/metabolismo , Receptor fas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Proteína Ligante Fas , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/análise , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-2/análiseRESUMO
Epidermal infiltration by neoplastic CD4+ T cells is a characteristic histologic feature of early stage mycosis fungoides, the most common type of cutaneous T cell lymphoma (CTCL). The mechanisms involved in epidermotropism are unknown. It has been suggested that the CXC chemokines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epidermis in epidermotropic CTCL is lacking. In this study skin biopsies from 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8+ CTCL, were investigated for epidermal IL-8 and IP-10 mRNA expression by RNA in situ hybridization. In addition, the expression of monokine induced by gamma-interferon (Mig) mRNA, a CXC chemokine closely related to IP-10, was studied as well. The expression of IL-8 receptors A and B (CXCR1 and CXCR2, respectively) was investigated by immunohistochemistry. The results were correlated with the number and phenotype of epidermotropic T cells. Epidermal expression of IP-10 and Mig mRNA was detected in 10 of 11 and seven of 11 epidermotropic CTCL, respectively, but not in five nonepidermotropic CTCL biopsies or normal human skin. Epidermal IP-10 and Mig mRNA expression correlated with epidermal infiltration of CD4+ T cells, but not of CD8+ T cells. IL-8 mRNA was demonstrated in the epidermis of only two of 15 CTCL biopsies, and was associated, in both cases, with accumulation of neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In conclusion, the results of this study indicate that IP-10, and to a lesser extent Mig, but not IL-8 is involved in the preferential infiltration of neoplastic CD4+ T cells in CTCL.
Assuntos
Quimiocinas CXC/genética , Peptídeos e Proteínas de Sinalização Intercelular , Interferon gama/farmacologia , Interleucina-8/genética , Linfoma Cutâneo de Células T/metabolismo , RNA Mensageiro/análise , Neoplasias Cutâneas/metabolismo , Antígenos CD/fisiologia , Quimiocina CXCL10 , Quimiocina CXCL9 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Receptores de Quimiocinas/fisiologia , Receptores de Interleucina/fisiologia , Receptores de Interleucina-8A , Receptores de Interleucina-8BRESUMO
BACKGROUND: Primary cutaneous follicle center cell lymphomas (PCFCCLs) of the head or trunk have a much better prognosis than morphologically similar large-cell lymphomas on the legs or follicle center cell lymphomas involving the skin secondarily (SCFCCLs). Recent studies suggest a relation between the expression of adhesion molecules and clinical behavior of malignant B-cell lymphomas. OBJECTIVE: Our purpose was to investigate a potential relation between the expression of adhesion molecules and clinical behavior of these three prognostically different groups of cutaneous B-cell lymphomas. METHODS: Immunohistochemical studies with a selected panel of monoclonal antibodies against adhesion molecules were performed on 10 PCFCCLs on the head or trunk, five PCFCCLs of the legs, and seven SCFCCLs. Expression of adhesion molecules was correlated with clinical and follow-up data. RESULTS: PCFCCLs of the head and trunk expressed ICAM-1 (80%) and LFA-1 (50%) much more frequently than PCFCCLs of the legs (40% and 20%, respectively) and SCFCCLs (14% and 14%, respectively). VLA-4 was expressed in 60% of PCFCCLs of the legs, but not by the PCFCCLs of the head or trunk. Absence of both ICAM-1 and LFA-1 on the neoplastic B cells correlated with a poor prognosis (seven of nine patients died of systemic lymphoma). In contrast, none of the patients with expression of LFA-1 or ICAM-1 have died of lymphoma thus far. CONCLUSION: Our results suggest a relation between the expression of adhesion molecules and the differences in clinical behavior between different groups of primary and secondary cutaneous follicle center cell lymphomas.
Assuntos
Moléculas de Adesão Celular/análise , Linfoma de Células B/metabolismo , Linfoma Folicular/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Integrina alfa4beta1 , Integrinas/análise , Molécula 1 de Adesão Intercelular/análise , Antígeno-1 Associado à Função Linfocitária/análise , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Retorno de Linfócitos/análise , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Molécula 1 de Adesão de Célula Vascular/análiseRESUMO
The expression of IL-8 in psoriasis has been clearly shown with the use of immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We report here a study of the expression of both IL-8 type A and B receptors by immunohistochemical techniques, using one polyclonal and four monoclonal antibodies. By this technique, we found that the neutrophilic granulocytes express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on the keratinocytes. The type B receptor on the keratinocytes was localized in the suprabasal layers of the epidermis. Following therapy, the expression of the IL-8 type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in psoriasis is involved in the disturbed differentiation rather than in proliferation, probably via an autocrine loop.
Assuntos
Antígenos CD/análise , Psoríase/metabolismo , Receptores de Interleucina/análise , Animais , Humanos , Imuno-Histoquímica , Camundongos , Psoríase/terapia , Coelhos , Receptores de Interleucina-8A , Pele/químicaRESUMO
The present experiment was done to obtain experimental evidence supporting the existence of an optimal initial contamination level of Eimeria acervulina with respect to broiler productivity, as suggested by simulation model outcomes. Three levels of initial (on Day 3) contamination of the litter were applied (low, intermediate and high). The peak of oocyst excretion during the flock cycle (grow-out) (Days 0-36) depended on the initial contamination level. Oocysts peaked at Day 15, 22 and 33 for the high, intermediate and low contamination level, respectively. Antibody titres and plasma carotenoid contents were not significantly affected by contamination levels. Average body weight at the end of the flock cycle (Day 36) and average daily body weight gain were significantly higher at the intermediate contamination level compared with the low and high contamination levels. Average body weight at Day 36 was 1681 g, 1712 g and 1674 g for the low, intermediate and high contamination level, respectively. Average daily weight gain was 45.7 g, 46.5 g and 45.5 g for the low, intermediate and high contamination level, respectively. Thus, the data from this experiment support the existence of an optimum initial contamination level for E. acervulina with respect to performance results.