RESUMO
The aim of this study is to give an overview of the concentrations of persistent organic pollutants like the polychlorinated dibenzo- P-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), polychlorinated biphenyls (PCB), polybrominated diphenyl ether (PBDE), perfluorinated compounds (PFC) and of phthalates in breast milk. On the basis of median and 95 (th) percentile values an "average" and a "high" intake were calculated for a 3-month-old infant exclusively breast-fed. Moreover, the actual daily intake was compared with tolerable daily intakes (TDI) recommended by scientific institutions. On this basis, we found an "average" ("high") daily intake of 70 (140) pg TEQ/kg body weight (b. w.) for PCDD/F and dioxin-like PCB (dl-PCB), 10 (20) ng/kg b. w. for PFOS (perfluorooctanesulfonate), 20 (50) ng/kg b. w. for PFOA (perfluorooctanoate), 1.7 (7.5) ng/kg b. w. for BDE 47, and 0.6 (2.1) ng/kg b. w. for BDE 99. For di-2-ethylhexyl phthalate (DEHP) and di- N-butyl phthalate (DnBP) an "average" and "high" intake of 400 ng/kg b. w. and 2,000 ng/kg b. w. and of 100 and 500 ng/kg b.w. were assumed, respectively. For all of these substances we found a daily intake via breast milk below the TDI, established on a livelong basis. On contrary, the daily intake for the sum of the PCDD/F and dl-PCB considerably exceeded the recommended TDI value. Even with regard to the "high" daily intake values the share of PBDE, PFC, and phthalates on the TDI was only in the lower percentage. Scientific organisations assume that an exceeding of the PCDD/F and dl-PCB intake in relation to the TDI value is acceptable only on the basis of the still declining levels in breast milk and the fact that this high exposure only occurs during some months of the entire life when breast milk is consumed. On the basis of the recent exposure situation mothers can exclusively breast-feed their infants for 6 months without any hesitation. The well established health benefits for mothers and infants when exclusively breast-feeding should be utilised. There is also no health concern if the mother decides to breast-feed the baby for longer than 6 months when the infant also receives additional food.
Assuntos
Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Leite Humano/química , Compostos Orgânicos/análise , Ácidos Ftálicos/análise , Carga Corporal (Radioterapia) , Análise de Alimentos , Alemanha/epidemiologia , Humanos , Recém-Nascido , Masculino , Medição de Risco , Fatores de RiscoRESUMO
Alarming reports have been published about hearing loss in adolescents, and increasing leisure time noise exposure has been blamed. If the exposure limits from the Noise at Work Regulations are applied, discotheque music as well as music from portable music players are associated with the risk of hearing loss. The empirical evidence for this association, however, is not sufficient. Not even an increase in the prevalence of noise-induced hearing loss among adolescents can be documented. OHRKAN is a prospective cohort study aimed to produce information on the prevalence of hearing loss as well as its risk factors in adolescents. Currently, a total of 2,240 pupils in grade 9 at schools in the city of Regensburg, Germany, have been recruited. Data on noise exposure were collected using standardized questionnaires. In addition, hearing status was assessed by medical examination including tympanometry, audiometry, and distortion-product otoacoustic emissions. Developments in noise exposure as well as hearing status will be assessed in follow-up data collections. Independent of this empirical assessment preventive measures are already needed now to reduce the risk of hearing loss in adolescents and young adults.
Assuntos
Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Atividades de Lazer , Ruído/efeitos adversos , Testes de Impedância Acústica , Adolescente , Audiometria de Tons Puros , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Alemanha , Inquéritos Epidemiológicos , Perda Auditiva Provocada por Ruído/prevenção & controle , Humanos , MP3-Player , Masculino , Música , Emissões Otoacústicas Espontâneas , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
Endoglin is a homodimeric membrane glycoprotein which can bind the beta 1 and beta 3 isoforms of transforming growth factor-beta (TGF-beta). We reported previously that endoglin is upregulated during monocyte differentiation. We have now observed that TGF-beta itself can stimulate the expression of endoglin in cultured human monocytes and in the U-937 monocytic line. To study the functional role of endoglin, stable transfectants of U-937 cells were generated which overexpress L- or S- endoglin isoforms, differing in their cytoplasmic domain. Inhibition of cellular proliferation and downregulation of c-myc mRNA which are normally induced by TGF-beta 1 in U-937 cells were totally abrogated in L-endoglin transfectants and much reduced in the S-endoglin transfectants. Inhibition of proliferation by TGF-beta 2 was not altered in the transfectants, in agreement with the isoform specificity of endoglin. Additional responses of U-937 cells to TGF-beta 1, including stimulation of fibronectin synthesis, cellular adhesion, platelet/endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation, and homotypic aggregation were also inhibited in the endoglin transfectants. However, modulation of integrin and PECAM-1 levels and stimulation of mRNA levels for TGF-beta 1 and its receptors R-I, R-II, and betaglycan occurred normally in the endoglin transfectants. No changes in total ligand binding were observed in L-endoglin transfectants relative to mock, while a 1.5-fold increase was seen in S-endoglin transfectants. The degradation rate of the ligand was the same in all transfectants. Elucidating the mechanism by which endoglin modulates several cellular responses to TGF-beta 1 without interfering with ligand binding or degradation should increase our understanding of the complex pathways which mediate the effects of this factor.
Assuntos
Fator de Crescimento Transformador beta/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Antígenos CD , Antígenos de Diferenciação Mielomonocítica/metabolismo , Sequência de Bases , Moléculas de Adesão Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Primers do DNA/genética , DNA Complementar/genética , Endoglina , Fibronectinas/biossíntese , Genes myc/efeitos dos fármacos , Humanos , Integrinas/metabolismo , Dados de Sequência Molecular , Fosforilação , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Receptores de Superfície Celular , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transfecção , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
Perfluorinated compounds (PFC) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence and their potential to bioaccumulate in organisms they are of toxicological and public concern. In the present study, perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) were quantified in 70 breast milk samples. Samples were obtained from Leipzig, Germany (38 archived samples), Munich, Germany (19 fresh samples) and Gyor, Hungary (13 frozen samples). PFOS could be quantified in all 70 samples. The concentration in samples from Germany ranged between 28 and 309 ng/l (median: 119 ng/l). Samples from Hungary showed significantly higher PFOS concentrations (median 330 ng/l, range 96-639 ng/l). In only 11 of 70 samples (16%) PFOA reached the LOQ (200 ng/l); values ranged from 201 to 460 ng/l. If only those samples with PFOA values above the LOQ were considered, we found a significant correlation between the PFOS and PFOA concentrations (r=0.75, p=0.008). Based on the results of the German sample, we estimated an intake of 0.10 microg PFOS/day (using median) or 0.27 PFOS microg/day (using maximum value) via breast milk for an infant of 5 kg bodyweight. Our data suggest that fully breastfed infants are unlikely to exceed the recommended tolerable daily intake of PFC. However, more target-oriented studies are needed to identify the amount and time-trend of PFOS and PFOA in maternal blood during pregnancy, after delivery, as well as in the growing infant and in its diet (e.g., breast milk and formula).
Assuntos
Ácidos Alcanossulfônicos/análise , Caprilatos/análise , Fluorocarbonos/análise , Leite Humano/química , Cromatografia Líquida , Feminino , Alemanha , Humanos , Hungria , Espectrometria de Massas , Projetos Piloto , UniversidadesRESUMO
Up to now breast milk analyses of the Bavarian Health and Food Safety Authority are limited to organochlorine pesticides, polychlorinated biphenyls (PCB) and nitro musks. These chemicals have revealed decreasing background levels in breast milk over the past two decades. To implement a monitoring program with an extended spectrum of substances suspected to be of concern a new concept for breast milk monitoring in Bavaria has been developed.
Assuntos
Poluentes Ambientais/análise , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Leite Humano/química , Alemanha , HumanosRESUMO
We report the largest documented healthcare-associated outbreak of Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL(+) MRSA) in Europe. Six index patients from three long-term care facilities (LTCFs) were screened positive for PVL(+) MRSA in 2004 on admission to a community hospital in Germany. The purpose of this prospective study was to describe the prevalence of PVL(+) MRSA in the LTCFs before and after infection control interventions. Screening for MRSA with or without PVL was performed in all three LTCFs in 2004 [453 residents, 240 healthcare workers (HCWs)] and 2005 (440 residents, 192 HCWs). Swabs from anterior nares and wounds, if applicable, were collected. Colonised residents and staff were treated with mupirocin nasal ointment and topical antiseptics, and staff were provided with hygiene education. Total MRSA carrier rate of residents and HCWs in 2004 was 11.3% (PVL(+) MRSA 9.1%, PVL(-) MRSA 2.2%). There were comparable carrier rates between residents and HCWs in each LTCF. All PVL(+) MRSA isolates were of clonal origin (MLST 22) representing a novel spa sequence type t310. A decrease in total MRSA prevalence (from 11.3 to 5.5%) and PVL(+) MRSA (from 9.1 to 3.3%) was observed in 2005. The rate of PVL(-) MRSA remained unaffected. No symptomatic skin infections were noted among residents or HCWs. In this outbreak incomplete control of PVL(+) MRSA presumably resulted from difficult and delayed detection and decolonisation of carriers, incomplete compliance with control measures and lack of enforcement by public health authorities.
Assuntos
Toxinas Bacterianas/biossíntese , Portador Sadio/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Exotoxinas/biossíntese , Leucocidinas/biossíntese , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Administração Intranasal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/microbiologia , Feminino , Alemanha/epidemiologia , Fidelidade a Diretrizes , Pessoal de Saúde , Humanos , Controle de Infecções/métodos , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Mupirocina/uso terapêutico , Nariz/microbiologia , Pacientes , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Ferimentos e Lesões/microbiologiaRESUMO
Characterization of novel cell-surface protein molecules, initially identified by cDNA cloning techniques, usually requires the generation of specific antibodies to further analyze their biochemical and/or functional properties. Here we report a simple method, using recombinant vaccinia virus, for the generation of monoclonal antibodies (mAb) to the cell-surface antigen endoglin. A recombinant vaccinia virus carrying a cDNA encoding human endoglin was inserted into the thymidine kinase locus under the control of the 7.5k vaccinia virus promoter. Infection of Balb/c mice with this recombinant virus led to the generation of specific polyclonal antibodies, as demonstrated by the antisera reactivity against human endoglin transfectants. The spleen cells of these infected animals were fused to myeloma cells, allowing efficient generation of several hybridomas which secrete mAbs to human endoglin, as evidenced by their reactivity with purified endoglin as well as with endoglin transfectants. Some of the mAbs selected seem to be specific for regions of endoglin conserved among different species as evidenced by their cross-reactivity with chicken endoglin. These results underline the utility of recombinant vaccinia virus to generate antibodies with novel properties to new cell surface proteins such as endoglin.
Assuntos
Anticorpos Monoclonais , Proteínas Recombinantes de Fusão/imunologia , Vaccinia virus/imunologia , Vacínia/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Animais , Especificidade de Anticorpos , Antígenos CD , Endoglina , Humanos , Hibridomas , Camundongos , Camundongos Endogâmicos BALB C , Receptores de Superfície Celular , Timidina Quinase/genética , Vaccinia virus/genéticaRESUMO
Endoglin is a component of the transforming growth factor beta (TGF-beta) receptor complex, highly expressed by endothelial cells. Mutations in the endoglin gene are responsible for hereditary hemorrhagic telangiectasia type 1 (HHT1), an autosomal dominant vascular disorder caused by a haploinsufficiency mechanism. Vascular lesions (telangiectasia and arteriovenous malformations) in HHT1 are associated with loss of the capillary network, suggesting the involvement of endoglin in vascular repair processes. Using the chick chorioallantoic membrane (CAM) as an angiogenic model, we have analyzed the expression and function of chicken endoglin. A pan-specific polyclonal antibody (pAb) recognized chicken endoglin as demonstrated by immunostaining and Western blot analysis. In ovo treatment of chicken embryos with this pAb resulted in a significantly increased area of CAM. This effect was likely mediated by modulation of the ligand binding to endoglin as this pAb was able to inhibit TGF-beta1 binding. These results support the involvement of endoglin in the angiogenic process.
Assuntos
Neovascularização Fisiológica/fisiologia , Molécula 1 de Adesão de Célula Vascular/biossíntese , Alantoide/irrigação sanguínea , Animais , Antígenos CD , Embrião de Galinha , Córion/irrigação sanguínea , Endoglina , Pulmão/irrigação sanguínea , Pulmão/fisiologia , Receptores de Superfície Celular , Molécula 1 de Adesão de Célula Vascular/fisiologiaRESUMO
CD105 (endoglin) is a receptor for transforming growth factor beta (TGFbeta). Although methods to measure soluble forms of TGFbeta and CD105 have been published, no assay is available to quantify the receptor-ligand complexes. We describe both an indirect enzyme-linked immunosorbent assay for the quantitation of soluble CD105-TGFbeta1 and the characterization of the complexes by immunoprecipitation and immunoblotting. Mab E9, specifically reactive with CD105, was utilised as the capture reagent in the ELISA system. Detection of complexes was achieved using chicken antibody against TGFbeta1 and the subsequent detection of bound antibody demonstrated by the addition of anti-species antiserum conjugated to horseradish peroxidase (HRP). By using enhanced chemiluminescence and optimised antibodies, the assay was made sufficiently sensitive and reproducible to detect low levels of circulating complexes. Whether the assay had any practical applications was evaluated in breast cancer patients. Plasma levels of CD105-TGFbeta1 were significantly elevated in 59 patients with breast cancer compared to 52 age matched normal women (p < 0.001). Immunoprecipitation using a rabbit anti-CD105 antibody, which reacts with both dimeric and monomeric CD105, and immunoblotting showed that three molecular forms of CD105-TGFbeta1 complexes > 200, 195, and 125 kDa existed in the plasma. We believe these represent the oligomer, dimer and probably the protease degraded form of CD105 complexed to TGFbeta1. The resistance to hypertonic solution, SDS and heat treatment suggested that the soluble CD105-TGFbeta1 complex may be linked by covalent bonds. The measurement of CD105-TGFbeta complexes in the circulation may have important clinical applications not only in cancer but also in patients with other angiogenic diseases such as rheumatoid arthritis, myocardial infarction and stroke.
Assuntos
Neoplasias da Mama/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Fator de Crescimento Transformador beta/análise , Molécula 1 de Adesão de Célula Vascular/análise , Antígenos CD , Endoglina , Feminino , Humanos , Ligantes , Testes de Precipitina , Ligação Proteica , Receptores de Superfície Celular , Sensibilidade e Especificidade , Solubilidade , Fator de Crescimento Transformador beta/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologiaRESUMO
The great variation of primary cheiloplasty procedures in Cleft Lip and Palate (CLP) patients shows that there is disagreement regarding the embryonic development of this part of the face, the macroscopic and microscopic functional anatomy of the human muscles of facial expression and their role as a functional matrix for balanced and harmonious facial development. The purpose of this study is to present results of microsurgically dissected facial muscles, several parts of the nose and the human midface in specimens with and without cleft lip and palate. The results are compared with those of other investigations. Recommendations are presented for a standardized dissection technique of the facial muscles of expression for different types of primary cheilo- and rhinoplasty techniques.
Assuntos
Fenda Labial/patologia , Fenda Labial/cirurgia , Fissura Palatina/patologia , Fissura Palatina/cirurgia , Expressão Facial , Músculos Faciais/anatomia & histologia , Fácies , Procedimentos de Cirurgia Plástica , Rinoplastia , Músculos Faciais/patologia , Músculos Faciais/cirurgia , Feminino , Humanos , Recém-Nascido , Masculino , Microcirurgia , Valores de ReferênciaRESUMO
Phthalates have long been used as plasticizers to soften plastic products and, thus, are ubiquitous in modern life. As part of the Bavarian Monitoring of Breast Milk (BAMBI), we aimed to characterize the exposure of infants to phthalates in Germany. Overall, 15 phthalates, including di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), di-isobutyl phthalate (DiBP), di-isononyl phthalate (DiNP), three primary metabolites of DEHP [mono-(2-ethylhexyl) phthalate (MEHP), mono-isobutyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP)], and two secondary metabolites of DEHP were analyzed in 78 breast milk samples. We found median concentrations of 3.9 ng/g for DEHP, 0.8 ng/g for DnBP, and 1.2 ng/g for DiBP, while other parent phthalates were found in only some or none of the samples at levels above the limit of quantitation. In infant formula (n=4) we observed mean values of 19.7 ng/g (DEHP), 3.8 ng/g (DnBP), and 3.6 ng/g (DiBP). For MEHP, MiBP, and MnBP, the median values in breast milk were 2.3 µg/l, 11.8 µg/l, and 2.1 µg/l, respectively. The secondary metabolites were not detected in any samples. Using median and 95th percentile values, we estimated an "average" and "high" daily intake for an exclusively breast-fed infant of 0.6 µg/kg body weight (b.w.) and 2.1 µg/kg b.w., respectively, for DEHP, 0.1 µg/kg b.w. and 0.5 µg/kg b.w. for DnBP, and 0.2 µg/kg b.w. and 0.7 µg/kg b.w. for DiBP. For DiNP, intake values were 3.2 µg/kg b.w. and 6.4 µg/kg b.w., respectively, if all values in milk were set half of the detection limit or the detection limit. The above-mentioned "average" and "high" intake values corresponded to only about 2% to 7%, respectively, of the recommended tolerable daily intake. Thus, it is not likely that an infant's exposure to phthalates from breast milk poses any significant health risk. Nevertheless, other sources of phthalates in this vulnerable phase have to be considered. Moreover, it should be noted that for infants nourished with formula, phthalate intake is of the same magnitude or slightly higher (DEHP) than for exclusively breast-fed infants.
Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Fórmulas Infantis/química , Leite Humano/metabolismo , Ácidos Ftálicos/metabolismo , Adulto , Exposição Ambiental/análise , Poluentes Ambientais/análise , Feminino , Alemanha , Humanos , Ácidos Ftálicos/análise , Adulto JovemRESUMO
Acute parvovirus B19 infection is a risk for pregnant women. After vertical transmission the infected fetus may develop hydrops fetalis. Since B19 infection occurs mainly during childhood, children represent a main source for virus transmission. In order to determine whether certain groups in the German population show increased risks for B19 infection we analysed the seroprevalence using 6583 sera collected from adults in former Eastern and Western Germany during the German National Health Survey and 649 sera from healthy Thuringian children and adolescents. In adults the overall seroprevalence was 72.1%, rising from 20.4% in children (1-3 years) and 66.9% in adolescents (18-19 years) to 79.1% in the elderly (65-69 years). Significant differences were observed between females (73.3%) and males (70.9%) and between inhabitants of small (74.8%) and big cities (69.0%) but not between people of the former Eastern (72.8%) and Western states (72.0%) of Germany. For women during childbearing age (18-49 years) highest values were observed in those living together with two or more children (81.6%) and in women with occupational contact with children aged <6 years (88.9%). In contrast seroprevalence was significantly lower in age-matched female singles (64.8%) and in women with occupational contact with children aged >6 years and adolescents (63.8%).
Assuntos
Infecções por Parvoviridae/epidemiologia , Parvovirus B19 Humano/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Animais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Fatores Sexuais , População UrbanaRESUMO
Severe neurological complications such as spinal cord ischemia and paraplegia can occur with acute aortic dissection in 3%. This report describes the case of a 67-year old patient with delayed onset of paraplegia 8 h after acute chest pain. Contrast enhanced computed tomography documented Stanford type B dissection confined to a short segment of the aorta. Furthermore, magnetic resonance imaging revealed intraspinal intraaxial hematoma of the myelon, which can explain the neurological complication. This case shows that even in the scenario of acute aortic dissection other mechanisms for paraplegia may be operational than dissection itself. Paraplegia in this case results from intramyelon bleeding preceding aortic dissection.
Assuntos
Aneurisma Aórtico/complicações , Dissecção Aórtica/complicações , Dor no Peito/etiologia , Hematoma Subdural Espinal/etiologia , Paraplegia/etiologia , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico , Aneurisma Aórtico/diagnóstico , Dor no Peito/diagnóstico , Diagnóstico Diferencial , Feminino , Hematoma Subdural Espinal/diagnóstico , Humanos , Paraplegia/diagnósticoRESUMO
The capsids of human parvovirus B19 consist of two structural proteins, the minor-capsid protein VP1 and the major-capsid protein VP2. The latter which constitutes for 95% of the capsid are able to form virus-like particles (VLPs) in yeast without the presence of VP1-proteins. VP2-proteins produced in Saccharomyces cerevisiae have the capacity to form VLPs in the absence of VP1-proteins. These yeast-derived VLPs resemble native virus or recombinant VP2-VLPs produced by baculovirus systems in respect of size, molecular weight and of antigenicity as shown by antigen-capture ELISA and T-cell proliferation tests. Regarding costs, yield and ease of handling particle production in yeast represents an alternative to the recombinant baculovirus expression system which is so far the source for VP2-VLPs of human parvovirus B19.
Assuntos
Baculoviridae/metabolismo , Proteínas do Capsídeo/biossíntese , Parvovirus B19 Humano/fisiologia , Saccharomyces cerevisiae/metabolismo , Vírion/metabolismo , Baculoviridae/genética , Proteínas do Capsídeo/genética , Vetores Genéticos , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Saccharomyces cerevisiae/genética , Vírion/genéticaRESUMO
In response to several isolations of methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leucocidin gene (PVL-MRSA), the present study was conducted to document the spread of infection in a small region of southeastern Germany. During a 9-month period, two healthcare-associated outbreaks with PVL-MRSA occurred, affecting 83 patients, personnel and contacts of personnel, and 34 additional cases were detected in the community. The clinical spectrum ranged from colonization to skin infection and necrotizing pneumonia. The findings represent the largest number of PVL-MRSA cases detected in Germany so far, and demonstrate the potential of this emerging pathogen to spread within the community and in healthcare institutions.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Leucocidinas/genética , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Toxinas Bacterianas , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Exotoxinas , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Resistência a Meticilina/genética , Pessoa de Meia-Idade , Staphylococcus aureus/efeitos dos fármacosRESUMO
Parvovirus B19 is the causative agent of erythema infectiosum in children, but the virus is associated with an increasing range of different diseases. These include acute and chronic arthritis, hydrops fetalis in pregnant women, aplastic anemia, and thrombocytopenia. The host's immune response is directed against the viral structural proteins VP1 and VP2. This study investigated the presence of IgG against the viral nonstructural protein NS1 using Western blot. Serum panels from healthy individuals, B19-infected pregnant women, and various disease groups were tested. The disease groups included patients with symptoms that may be linked to parvovirus B19 infection. The results showed that IgG against the NS1 protein was present in 22% of healthy individuals with past B19 infection. In cases of persistent or prolonged B19 infections, the prevalence of NS1-specific antibodies was as high as 80%. It is concluded that NS1-specific IgG may be used as an indicator of chronic or more severe courses of parvovirus B19 infections.
Assuntos
Anticorpos Antivirais/sangue , Proteínas do Capsídeo , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/imunologia , Complicações Infecciosas na Gravidez/imunologia , Proteínas não Estruturais Virais/imunologia , Adolescente , Adulto , Idoso , Western Blotting , Capsídeo/imunologia , Feminino , Doenças Hematológicas/virologia , Humanos , Imunoglobulina G/sangue , Artropatias/virologia , Pessoa de Meia-Idade , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologiaRESUMO
Endoglin (CD105) is the target gene for the hereditary hemorrhagic telangiectasia type I (HHT1), a dominantly inherited vascular disorder. It shares with betaglycan a limited amino acid sequence homology and being components of the membrane transforming growth factor-beta (TGF-beta) receptor complex. Using rat myoblasts as a model system, we found that overexpression of endoglin led to a decreased TGF-beta response to cellular growth inhibition and plasminogen activator inhibitor-1 synthesis, whereas overexpression of betaglycan resulted in an enhanced response to inhibition of cellular proliferation and plasminogen activator inhibitor-1 induced expression in the presence of TGF-beta. The regulation by endoglin of TGF-beta responses seems to reside on the extracellular domain, as evidenced by the functional analysis of two chimeric proteins containing different combinations of endoglin and betaglycan domains. Binding followed by cross-linking with 125I-TGF-beta1 demonstrated that betaglycan expressing cells displayed a clear increase (about 3. 5-fold), whereas endoglin expressing cells only displayed an slight increment (about 1.6-fold) in ligand binding with respect to mock transfectants. SDS-polyacrylamide gel electrophoresis analysis of radiolabeled receptors demonstrated that expression of endoglin or betaglycan is associated with an increased TGF-beta binding to the signaling receptor complex; however, while endoglin increased binding to types I and II receptors, betaglycan increased the binding to the type II receptor. Conversely, we found that TGF-beta binding to endoglin required the presence of receptor type II as evidenced by transient transfections experiments in COS cells. These findings suggest a role for endoglin in TGF-beta responses distinct from that of betaglycan.
Assuntos
Proteoglicanas/fisiologia , Receptores de Fatores de Crescimento Transformadores beta/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Animais , Antígenos CD , Sequência de Bases , Linhagem Celular , Primers do DNA , Endoglina , Músculos/citologia , Músculos/metabolismo , Ratos , Receptores de Superfície Celular , Transdução de Sinais , Transfecção , Fator de Crescimento Transformador beta/genéticaRESUMO
In situ hybridization studies have proved that myocardial enterovirus infections are detectable in all stages of acute and chronic enterovirus-induced myocarditis as well as in some patients with end-stage dilated cardiomyopathy, suggesting the possibility of myocardial enterovirus persistence. Possible enterovirus persistence in the human heart is supported by the discovery of enterovirus persistence in different murine models of chronic myocarditis, demonstrating that coxsackievirus B3, typically a cytolytic enterovirus, is capable of evading immunological surveillance in a host-dependent fashion. Progress is currently being made in unraveling the molecular mechanisms of enterovirus persistence, the diversity of host and virus genetics and their impact on the nature and severity of the disease. Apart from providing an etiologic diagnosis, there are therapeutic implications from the in situ demonstration of myocardial enterovirus infection. Evaluation of specific antiviral agents, for example interferons, may lead to the development of new therapeutic strategies capable of providing protection against myocardial enterovirus infection.
Assuntos
Infecções por Enterovirus/microbiologia , Miocardite/microbiologia , Animais , Doença Crônica , Enterovirus/fisiologia , Coração/microbiologia , Humanos , Replicação ViralRESUMO
Endoglin is an integral membrane glycoprotein that binds transforming growth factor-beta1 (TGF-beta1) with high affinity and it is strongly expressed on syncytiotrophoblasts throughout pregnancy. Here, we describe the expression of endoglin by the choriocarcinoma cell line JAR as evidenced by flow cytometry, immunoprecipitation, Western blot and reverse transcriptase polymerase chain reaction analyses. Cross-linking experiments of [125I]-labeled TGF-beta1 to JAR cells indicated that endoglin expressed at the surface of these cells binds TGF-beta. Furthermore, staining of human choriocarcinoma tissue sections with a polyclonal antibody to endoglin demonstrated a high expression of endoglin in syncytiotrophoblast-like areas, as opposed to a negative staining of cytotrophoblast-like cells. This pattern of endoglin expression was confirmed by experiments with methotrexate, an inducer of giant, multinucleated, non-proliferative cells, morphologically indistinguishable from the naturally occurring syncytiotrophoblasts. Thus, treatment of the JAR and JEG-3 choriocarcinoma cell lines with methotrexate led to an increase in endoglin expression, as demonstrated by Western and Northern blot analyses. Taken together, our results suggest that endoglin, in addition to being involved in placental development, may also be a cellular differentiation marker.
Assuntos
Coriocarcinoma/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Antígenos CD , Northern Blotting , Técnicas de Cultura , Endoglina , Humanos , Metotrexato/farmacologia , Fosforilação , Reação em Cadeia da Polimerase , Testes de Precipitina , Receptores de Superfície Celular , Fator de Crescimento Transformador beta/metabolismo , Células Tumorais CultivadasRESUMO
Endoglin is a transmembrane glycoprotein 633 residues in length expressed at the surface of endothelial cells as a disulphide-linked homodimer; the specific cysteine residues involved in endoglin dimerization are unknown. Mutations in the coding region of the endoglin gene are responsible for hereditary haemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. Many of these mutations, if translated, would lead to truncated forms of the protein. It is therefore of interest to assess the protein expression of different truncated forms of endoglin. Infections in vitro or in vivo with recombinant vaccinia virus, as well as transient transfections with expression vectors, were used to express normal and truncated forms of endoglin. Truncated mutants could be classified into three different groups: (1) those that did not produce stable transcripts; (2) those that produced stable transcripts but did not secrete the protein; and (3) those that secreted a soluble dimeric protein. This is the first time that a recombinant truncated form of endoglin has been found to be expressed in a soluble form. Because a chimaeric construct encoding the N-terminal sequence of platelet/endothelial cell adhesion molecule (PECAM-1) antigen fused to residues Ile281-Ala658 of endoglin also yielded a dimeric surface protein, these results suggest that cysteine residues contained within the fragment Cys330-Cys412 are involved in disulphide bond formation. Infection with vaccinia recombinants encoding an HHT1 mutation did not affect the expression of the normal endoglin, and did not reveal an association of the recombinant soluble form with the transmembrane endoglin, supporting a haploinsufficiency model for HHT1.