Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Scand J Immunol ; 58(5): 533-40, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14629625

RESUMO

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder with a presumed autoimmune aetiopathogenesis. We have recently described a novel organ-specific rat model of fibrosing cholangitis induced by intrabiliary administration of the hapten-reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS) with similarities to human PSC. In the present report, we have evaluated the long-term outcome of TNBS-induced cholangitis in this model. Mild stenosis of the common bile duct of female Lewis rats (n = 18) was achieved by subtotal ligation and cholangitis induced by TNBS injection (50 mg/kg) into the dilated bile duct after a second laparotomy. After 8 and 12 months, we found no evidence of cholangitis in serum chemistry or histology or retrograde cholangiography of TNBS-treated rats. Antineutrophil cytoplasmic antibodies were positive in 75% of animals but were not predictive of liver damage. Tumour necrosis factor-alpha levels were not elevated in serum or in mononuclear spleen cell supernatants. Our findings suggest that a single initial insult is not sufficient to trigger chronic progressive inflammation. Rather, perpetuation of inflammation probably requires additional stimuli.


Assuntos
Colangite Esclerosante/patologia , Modelos Animais de Doenças , Alanina Transaminase/sangue , Animais , Anticorpos Anticitoplasma de Neutrófilos/análise , Proteína C-Reativa/análise , Doença Crônica , Progressão da Doença , Feminino , Humanos , Fígado/patologia , Ratos , Ratos Endogâmicos Lew , Ácido Trinitrobenzenossulfônico/toxicidade
2.
Am J Gastroenterol ; 97(8): 1978-85, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12190164

RESUMO

OBJECTIVES: Detection of disease activity in Crohn's disease (CD) is of crucial importance for diagnosis and management of the disease. Noninvasive methods for monitoring are desirable and comprise hydromagnetic resonance imaging (hydro-MRI) and leukocyte scintigraphy. In addition, a recent case report indicated the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to assess CD activity. However, comparative prospective studies are lacking. METHODS: Between February, 1999 and August, 2000, 59 patients with CD were enrolled in a prospective study to assess disease activity by FDG-PET, hydro-MRI, and immunoscintigraphy with anti-nonspecific cross-reacting antigen 95 antigranulocyte antibodies. In 28 of these patients, colonoscopy could be performed. Twelve patients with irritable bowel syndrome and 20 tumor patients without gut inflammation served as controls. Results were compared by statistical analysis. RESULTS: FDG-PET detected 127 pathological findings (average maximum standardized uptake value = 4.4 +/- 1.1) in the terminal/neoterminal ileum (37), small bowel (24), and colon (66) of 54 patients with CD, whereas no pathological findings were seen in five patients with CD, the control patients with irritable bowel syndrome, and the tumor patients without gut inflammation. In contrast, examination with hydro-MRI or granulocyte antibodies detected less pathological findings in CD patients. Forty-five of the detected foci were accessible to endoscopic verification. The correlation of the foci with endoscopic findings showed a high specificity (>89%) of all three methods to detect inflamed areas in the terminal ileum and colon of patients with CD, although analyses by hydro-MRI and granulocyte antibody scan had strikingly lower sensitivities (40.9% and 66.7%) than FDG-PET analysis (85.4%). CONCLUSIONS: FDG-PET appears to be a reliable noninvasive tool for simultaneous detection of inflamed areas in the small and large bowel of patients with CD. FDG-PET can be used to detect disease activity in the terminal ileum and colon of CD patients with high sensitivity and specificity.


Assuntos
Antígenos de Neoplasias , Moléculas de Adesão Celular , Doença de Crohn/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Anticorpos Monoclonais , Colonoscopia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Fluordesoxiglucose F18 , Granulócitos/imunologia , Humanos , Masculino , Glicoproteínas de Membrana , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
3.
Rofo ; 173(8): 731-8, 2001 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-11570244

RESUMO

PURPOSE: To compare hydro-MRI with colonoscopy and biopsy specimen regarding the assessment of inflammatory activity and the differentiation of inflammatory bowel diseases. MATERIAL AND METHODS: After an oral bowel opacification using 1000 ml of a 2.5% mannitol solution and a rectal bowel opacification using 250-500 ml of a 0.9% saline solution, axial and coronal breath-hold sequences +/- Gd-DTPA (HASTE-["half-Fourier acquisition single-shot turbo spin echo"] and dynamic FLASH-["fast low angle shot"]) were acquired in 27 patients with inflammatory bowel disease. The enhancement of the bowel wall as well as morphological MRI findings were correlated with colonoscopy and biopsy specimens. By means of the MRI findings, Crohn's disease (CD) and ulcerative colitis (UC) should be differentiated. RESULTS: In CD, a significant correlation between the contrast enhancement of the inflamed bowel wall (delta SI) and the endoscopic/histopathologic indices could be established (r = 0.52; p = 0.02 and r = 0.72; p = 0.001). In UC, no correlations between delta SI and the endoscopic/histopathologic indices could be found. The correct diagnosis of CD and UC by MRI findings was possible in 22/27 patients (81%). CONCLUSION: Hydro-MRI with dynamic studies is suitable for the assessment of disease activity in CD, but unreliable in UC. Hydro-MRI provides useful information for the differentiation of CD and UC.


Assuntos
Biópsia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Colonoscopia , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Colo/patologia , Meios de Contraste/administração & dosagem , Interpretação Estatística de Dados , Diagnóstico Diferencial , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Reto/patologia
4.
J Mol Recognit ; 13(6): 360-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11114069

RESUMO

Self carbohydrate-mediated dimerization of glycoprotein angiotensin-converting enzyme (ACE) was demonstrated. The dimerization was studied in the reverse micelle experimental system as a model of biomembrane situation. Asialo-ACE or agalacto-ACE was able to form a dimer, whereas deglycosylated ACE and sequentially desialylated and degalactosylated ACE failed to dimerize. ACE-ACE interaction was competitively inhibited by Neu5Ac- or Gal-terminated saccharides. The results have allowed us to propose the existence of carbohydrate-recognizing domain (CRD) on ACE molecule. The structural requirements of this CRD were estimated based on the ability of saccharides to inhibit ACE dimerization. The most effective monosaccharides with equal inhibition potencies were shown to be galactose (as GalbetaOMe) and N-acetylneuraminic acid (as Neu5AcalphaOMe). Among oligosaccharides, the most effective ones were found to be 3'SiaLac and, especially, the whole pool of ACE oligosaccharide chains and biantennae complex oligosaccharide chains of other glycoproteins. Bovine and human ACEs were shown to be similar in terms of recognition of carbohydrates.


Assuntos
Metabolismo dos Carboidratos , Peptidil Dipeptidase A/metabolismo , Animais , Sítios de Ligação , Configuração de Carboidratos , Bovinos , Dimerização , Galactose/química , Humanos , Monossacarídeos/metabolismo , Ácido N-Acetilneuramínico/química , Peptidil Dipeptidase A/química , Conformação Proteica , Estrutura Terciária de Proteína , Ultracentrifugação
5.
J Hepatol ; 33(6): 862-72, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11131446

RESUMO

BACKGROUND/AIM: The cholangiopathies represent hepatobiliary diseases in which bile-duct epithelial cells are targets for destructive processes, including immune-mediated damage. We describe a novel rat model of chronic fibrosing cholangitis induced by administration of the hapten reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the dilated bile duct. METHODS: The common bile duct was dilated due to a mild stenosis in 8-week-old female Lewis rats. TNBS (50 mg/kg) was injected during a second laparotomy. RESULTS: TNBS-treatment reproducibly resulted in chronic fibrosing cholangitis. In retrograde cholangiography the bile ducts showed irregularities, beading and strictures. Alkaline phosphatase levels remained abnormal throughout the study period. Immunohistochemical staining showed an increased number of macrophages, CD3+ T-lympbocytes and MHC class II antigen upregulation. The spontaneous interferon-gamma, tumor necrosis factor-alpha and interleukin-10 production of liver-derived mononuclear cells was increased. Anti-neutrophil cytoplasmic antibodies with specificity against myeloperoxidase, catalase and actin were found between 1 and 12 weeks after TNBS injection. CONCLUSIONS: We established a novel rat model of chronic fibrosing cholangitis with histologic, cholangiographic, serologic and immunologic similarities to human primary sclerosing cholangitis. This model may be used to study pathomechanisms of chronic cholangitis without concomitant inflammatory bowel disease.


Assuntos
Autoanticorpos/análise , Colangite Esclerosante/induzido quimicamente , Colangite Esclerosante/patologia , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos Anticitoplasma de Neutrófilos/análise , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Ductos Biliares/patologia , Colangiografia , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Colangite Esclerosante/metabolismo , Doença Crônica , Epitopos , Feminino , Injeções , Interferon gama/metabolismo , Interleucina-10/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Endogâmicos BUF , Ratos Endogâmicos Lew , Ácido Trinitrobenzenossulfônico/administração & dosagem
6.
Med Klin (Munich) ; 95(7): 409-12, 2000 Jul 15.
Artigo em Alemão | MEDLINE | ID: mdl-10943103

RESUMO

BACKGROUND: The antiphospholipid-antibody syndrome (APS) is a thrombophilic disorder, in which venous and arterial thrombosis can occur. We report the rare case of a patient with mesenteric infarction due to primary APS. CASE REPORT: A 46-year-old male patient was admitted to the hospital because of severe abdominal pain. A laparotomy was performed and revealed infarction of a jejunal loop which was resected. At pathohistological examination mesenteric artery infarction was found. Preoperatively prolonged partial thromboplastin time led to coagulation analysis. Lupus anticoagulant and anticardiolipin antibodies were found. TREATMENT: The diagnosis of primary APS was made and the patient was treated with aspirin (100 mg/day) and low molecular weight heparin (2,500 IE/day) permanently. Eighteen months after mesenteric infarction the patient is free of further thromboembolic events.


Assuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/complicações , Doenças do Jejuno/etiologia , Oclusão Vascular Mesentérica/etiologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Humanos , Doenças do Jejuno/imunologia , Doenças do Jejuno/patologia , Laparotomia , Masculino , Artérias Mesentéricas , Oclusão Vascular Mesentérica/imunologia , Oclusão Vascular Mesentérica/patologia , Pessoa de Meia-Idade
7.
Invest Radiol ; 35(7): 431-7, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10901105

RESUMO

RATIONALE AND OBJECTIVES: To appraise the value of hydro-MRI in the assessment of activity in Crohn's disease. METHODS: After bowel opacification with 1000 mL of an orally administered 2.5% mannitol solution was achieved, axial and coronal breath-hold sequences (T2-weighted half-Fourier acquisition single-shot turbo spin-echo sequences with or without fat saturation, dynamic T1-weighted fast low-angle shot sequences, and contrast-enhanced T1-weighted fast low-angle shot with fat saturation sequences) were acquired in 82 patients with proved Crohn's disease at 1.0 T. Enhancement of the bowel wall was correlated with other MRI findings, with the Crohn's disease activity index (CDAI), and with levels of C-reactive protein (CRP). RESULTS: In Crohn's disease, contrast enhancement of the affected bowel wall was markedly increased in comparison with the normal bowel wall (+80% +/- 22% versus +43% +/- 12%; P = 3 x 10(-15)). Positive correlations could be established between the increase in bowel wall enhancement and many other MRI findings. Between the increase in bowel wall enhancement and the CDAI, only a poor correlation was found (r = 0.25, P = 0.02). There was no statistical correlation between the increase in bowel wall enhancement and CRP. CONCLUSIONS: Hydro-MRI seems to be superior to the CDAI and CRP for the registration of Crohn's disease activity. In particular, differentiation between an active and an inactive (scarred) stenosis, which is crucial for the choice of therapeutic procedures, seems to be more reliable by the interpretation of several morphological and functional parameters on hydro-MRI than by the use of CDAI and CRP.


Assuntos
Doença de Crohn/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Meios de Contraste , Diuréticos Osmóticos , Feminino , Gadolínio DTPA , Humanos , Íleo/patologia , Masculino , Manitol , Estudos Prospectivos
9.
Am J Gastroenterol ; 95(5): 1201-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10811328

RESUMO

OBJECTIVE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology frequently requiring long-term therapy for control of symptoms and prevention of relapse. Azathioprine (AZA) has been shown to be effective and safe in the treatment of chronic active UC. However, the alternatives to treatment with AZA are limited. Our aim was to compare the efficacy and safety of treatment with mycophenolate mofetil (MMF)/prednisolone versus standard immunosuppressive treatment with azathioprine (AZA)/prednisolone in patients with chronic active UC. METHODS: The study was designed as an open comparison of MMF versus AZA. Twenty-four patients with active UC (Rachmilewitz score > or =6 points) were randomly assigned to the MMF (20 mg/kg)/prednisolone or AZA (2 mg/kg)/prednisolone group. The initial prednisolone dosage was 50 mg and was tapered according to a standard protocol. Treatment was scheduled for 1 yr. RESULTS: The rates of remission were higher in the AZA/prednisolone group (n = 12) than in the MMF/prednisolone group (n = 12) throughout the study. Remission rates were 92% versus 67% after 4 wk, 92% versus 67% after 3 months, 92% versus 67% after 6 months, 83% versus 78% after 9 months, and 100% versus 88% after 1 yr. The number of patients not requiring steroids was higher in the AZA/prednisolone group than in the MMF/prednisolone group. Moreover, in the AZA/prednisolone group no severe adverse events were recorded, whereas in the MMF/prednisolone group two severe adverse events were observed: one patient discontinued MMF after 6 months because of recurrent upper airway infections, and one patient exhibited a bacterial meningitis after 9 months. CONCLUSIONS: Treatment with AZA/prednisolone appears to be more effective and safe compared to MMF/prednisolone in patients with chronic active UC. MMF might be an alternative treatment for patients with contraindications to AZA. To further evaluate the effects of MMF in active UC, a placebo-controlled double-blinded study appears warranted.


Assuntos
Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Adulto , Idoso , Azatioprina/efeitos adversos , Doença Crônica , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Projetos Piloto , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Indução de Remissão
10.
Rofo ; 172(2): 153-60, 2000 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-10723489

RESUMO

PURPOSE: To assess the value of hydro-MRI in the assessment of the activity of Crohn's disease. MATERIALS AND METHODS: After an oral bowel opacification using 1000 ml of a 2.5% mannitol solution, axial and coronal breath-hold sequences (T2W HASTE +/- FS, contrast-enhanced T1W FLASH FS) were acquired in 63 patients with Crohn's disease at 1.0 T. The enhancement of the bowel wall was correlated with other MRI findings, with the Crohn's disease activity index (CDAI), and the C-reactive protein (CRP). RESULTS: In Crohn's disease, contrast enhancement of the affected bowel wall is markedly increased in comparison with the normal bowel wall (+80 +/- 23% vs. +43 +/- 11%; p = 8 x 10(-11)). Positive correlations could be established between the increase of bowel wall enhancement and other MRI findings. Between the increase of bowel wall enhancement and the CDAI a poor correlation was found (r = 0.25; p = 0.046). There was no statistical correlation between the increase of bowel wall enhancement and the CRP (r = 0.09; p = 0.24). CONCLUSION: Hydro-MRI allows an assessment of the activity of Crohn's disease.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Mucosa Intestinal/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Meios de Contraste , Feminino , Humanos , Inflamação/diagnóstico , Mucosa Intestinal/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Reprodutibilidade dos Testes
11.
Eur J Clin Invest ; 29(11): 929-39, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10583437

RESUMO

BACKGROUND: In sera from patients with autoimmune liver diseases, e. g. primary sclerosing cholangitis (PSC) and autoimmune hepatitis, anti-neutrophil cytoplasmic antibodies (ANCAs) can be found. Until now, no animal model of ANCA induction in liver disease has been described. In this study, we describe a novel rat model of acute liver injury and subsequent ANCA production. MATERIALS AND METHODS: The hapten reagent 2,4,6-trinitrobenzenesulphonic acid (TNBS) was injected into the portal vein of female Lewis rats. Two experimental groups were studied: group A (TNBS/ethanol) received different TNBS concentrations; control animals of group B (ethanol) were injected with 10% (v/v) ethanol/0.9% (w/v) NaCl. RESULTS: A dose-dependent acute necrotizing liver injury occurred after injection of TNBS. Histopathological examination revealed acute hepatic injury with confluent parenchymal necrosis, mild bile duct proliferation and periportal infiltration. The periportal infiltration consisted mainly of macrophages and T lymphocytes. ANCAs were found in an allogenic test system between 1 and 8 weeks after TNBS injection in 11 out of 28 (39%) TNBS-treated rats (group A) and did not correlate with the extent of liver injury or TNBS dose. Autoantibody specificities of IgG type were directed against catalase (29%), myeloperoxidase (14%) and actin (7%), as detected by enzyme-linked immunosorbent assay and Western blotting. Moreover, autoantibodies against the asialoglycoprotein receptor were observed. Peripheral blood mononuclear cells and spleen lymphocytes from TNBS-treated rats were shown to produce ANCAs. CONCLUSION: In summary, we were able to show that intraportal administration of the hapten reagent TNBS induces an acute necrotizing liver injury with subsequent ANCA production in Lewis rats. ANCA specificities were mainly directed against catalase, an autoantigen that has recently been identified in sera from patients with primary sclerosing cholangitis and autoimmune hepatitis. This animal model offers the opportunity to study the pathomechanisms of ANCA production in necrotizing liver injury.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/análise , Fígado/efeitos dos fármacos , Ácido Trinitrobenzenossulfônico/toxicidade , Animais , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Fígado/imunologia , Fígado/patologia , Macrófagos/imunologia , Macrófagos/patologia , Necrose , Ratos , Ratos Endogâmicos Lew , Linfócitos T/imunologia , Linfócitos T/patologia
12.
Rofo ; 170(4): 338-46, 1999 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-10341791

RESUMO

PURPOSE: To compare the value of hydro-MRI with that of barium studies in patients with Crohn's disease. MATERIALS AND METHODS: After an oral bowel opacification using 1000 ml of a 2.5% mannitol solution, axial and coronal breath-hold sequences (T2W HASTE +/- FS, contrast-enhanced T1W FLASH FS) were acquired in 46 patients with Crohn's disease at 1.0 T. The findings of hydro-MRI were compared with those of barium studies. RESULTS: In the stomach and the small bowel, hydro-MRI and barium studies demonstrated similar numbers of Crohn's involvements (39 vs. 36); in the colon, hydro-MRI showed clearly more affections (23 vs. 10). Hydro-MRI showed 12.7 cm of inflamed bowel per patient, on average (barium studies: 10.4 cm; p = 0.004). There was a good agreement between the two methods regarding the assessment of the extent of Crohn's disease and the severity of bowel stenoses (r = 0.89 and 0.88, respectively). CONCLUSIONS: For the assessment of Crohn's disease, hydro-MRI is preferable to the barium study because of the superior imaging quality and the lack of radiation exposure.


Assuntos
Doença de Crohn/diagnóstico , Sistema Digestório/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Administração Oral , Adolescente , Adulto , Idoso , Sulfato de Bário/administração & dosagem , Brometo de Butilescopolamônio , Meios de Contraste/administração & dosagem , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Radiografia , Estatísticas não Paramétricas , Fatores de Tempo
14.
Scand J Rheumatol ; 27(6): 461-4, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9855219

RESUMO

During a period of more than eleven years serum samples of a patient with Systemic Lupus Erythematosus were collected and analyzed for anti-nuclear autoantibodies. High titer of anti-La/SS-B were detectable in all serum samples. The La/SS-B epitopes remained constant. Besides anti-La/SS-B antibodies all serum samples contained traces of anti-Ro/SS-A including anti-Ro52 and anti-Ro60 antibodies. During disease flares anti-Ro/SS A antibodies were upregulated and anti-dsDNA antibodies appeared, thus supporting the concept of an antigen driven intermolecular epitope spreading to Ro/SS-A and dsDNA.


Assuntos
Anticorpos Antinucleares/imunologia , Mapeamento de Epitopos , Epitopos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Anticorpos Antinucleares/análise , Feminino , Humanos
15.
FEBS Lett ; 431(2): 255-8, 1998 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-9708914

RESUMO

To study the role of the oligosaccharide moiety in the catalytic properties of angiotensin-converting enzyme (ACE), we obtained asialo- and partially deglycosylated ACE by enzymatic treatment of two-domain somatic enzyme from bovine lung. Treated enzymes demonstrated appreciable, but different changes of catalytic properties in the reaction of the hydrolysis of N-substituted tripeptides, C-terminal analogs of angiotensin I and bradykinin among them, compared to those for native enzyme. Deglycosylation also altered the catalytic properties of a single N domain of bovine ACE. So, various patterns of glycosylation modulate substrate specificity of somatic ACE and may be the reason for functional heterogeneity of the enzyme.


Assuntos
Pulmão/enzimologia , Peptidil Dipeptidase A/metabolismo , Animais , Catálise , Bovinos , Estabilidade Enzimática , Glicosilação , Especificidade por Substrato
16.
Clin Exp Immunol ; 112(3): 507-15, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9649223

RESUMO

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Recent studies have shown that genetic factors and both cellular and humoral immunological abnormalities are important in the pathogenesis of PSC. The most prominent autoantibodies in PSC are anti-neutrophil cytoplasmic antibodies (ANCA). The autoepitopes of ANCA in PSC are not well defined. The aim of this study was to identify corresponding ANCA autoantigens in patients with PSC. A biochemical approach with enrichment and partial purification of soluble neutrophil proteins, detection of autoantibodies by Western blot and partial amino acid sequencing were used. Two new autoantigen/autoantibody systems in patients with PSC were detected: catalase and alpha-enolase. The presence of catalase autoantibodies in 9/15 (60%) and alpha-enolase autoantibodies in 4/15 (27%) was confirmed by ELISA and Western blot. Furthermore, we showed immunoreactions of PSC sera with human biliary epithelial cells, showed the reduction of fluorescence in anti-catalase absorption experiments and observed partial co-localization of anti-catalase antibodies and PSC sera in double-staining experiments on biliary epithelial cells. The anti-catalase antibody-positive PSC patients had a more severe course of disease with a significantly higher alkaline phosphatase compared with the anti-catalase-negative PSC patients (P < 0.06). All ulcerative colitis control sera were anti-catalase antibody-negative. The identified antigens catalase and alpha-enolase can partly explain the ANCA fluorescence on ethanol-fixed and formaldehyde-fixed granulocytes in patients with PSC. Catalase is an important anti-oxidant enzyme and prevents cell damage from highly reactive oxygen-derived free radicals. Catalase autoantibodies might play a pathogenic role in patients with PSC. Our findings support the hypothesis that oxidative stress is one of the pathogenic mechanisms in patients with PSC.


Assuntos
Autoanticorpos/imunologia , Catalase/imunologia , Colangite Esclerosante/imunologia , Fosfopiruvato Hidratase/imunologia , Sequência de Aminoácidos , Autoanticorpos/sangue , Autoimunidade , Western Blotting , Colangite Esclerosante/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Dados de Sequência Molecular
18.
Biochem Mol Biol Int ; 44(3): 535-42, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9556215

RESUMO

Regulation of the catalytic activity and supramolecular structure of angiotensin-converting enzyme was studied in reverse micelles of Aerosol OT in octane as biomembrane model. The kinetic experiments and the sedimentation analysis demonstrated that the enzyme can function both in monomeric and dimeric form. The degree of dimerization was strongly dependent on the concentration and structure of mono- and disaccharides added to the media, indicating the specific role of carbohydrates in forming the supramolecular structure of angiotensin-converting enzyme. The existence of carbohydrate-binding center on the enzyme molecule is proposed.


Assuntos
Carboidratos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Animais , Sítios de Ligação , Metabolismo dos Carboidratos , Carboidratos/química , Bovinos , Dimerização , Pulmão/química , Micelas , Peptidil Dipeptidase A/efeitos dos fármacos , Relação Estrutura-Atividade
19.
Z Gastroenterol ; 36(11): 971-5, 1998 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-9880823

RESUMO

Portopulmonary venous anastomosis are a very rare complication of chronic liver diseases. We report on a patient with a cryptogenic liver cirrhosis and thrombosis of the portal vein who underwent antibiotic treatment because of recurrent pneumonias several times. Although treated successfully a pulmonal infiltrate persisted in further radiologic controls. By means of a velocity-encoded MRI a portopulmonary shunt of 30% of the cardiac output was assured. An operative correction with a distal splenorenal shunt was performed successfully. Former reports of portopulmonary anastomoses complicating chronic liver disease never were hemodynamically relevant. In the presented case, a portopulmonary anastomosis lead to recurrent pneumonias and a restrictive ventilatory disorder.


Assuntos
Hipertensão Pulmonar/diagnóstico , Cirrose Hepática/diagnóstico , Imageamento por Ressonância Magnética , Veia Porta/patologia , Veias Pulmonares/patologia , Trombose/diagnóstico , Tomografia Computadorizada por Raios X , Feminino , Humanos , Hipertensão Pulmonar/cirurgia , Cirrose Hepática/cirurgia , Pneumopatias Obstrutivas/etiologia , Pneumopatias Obstrutivas/cirurgia , Pessoa de Meia-Idade , Pneumonia/etiologia , Pneumonia/cirurgia , Veia Porta/cirurgia , Veias Pulmonares/cirurgia , Recidiva , Derivação Esplenorrenal Cirúrgica , Trombose/cirurgia
20.
Eur J Clin Invest ; 27(11): 893-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9395784

RESUMO

At present, the exact mechanism of the pathogenic effect of anti-PR-3 antibodies remains unknown. Interaction of anti-neutrophil cytoplasmic antibodies (ANCAs) with human umbilical vein endothelial cells (HUVECs) may play a key role. Recently we were able to show that ANCAs recognize their target antigen, PR-3, translocated into the membrane of HUVECs. The objective of this study was to investigate regulation, i.e. signal transduction pathways, of PR-3 expression in endothelial cells. HUVECs were isolated according to the method of Jaffe et al. and cultured under standard conditions. A cyto-enzyme-linked immunosorbent assay (ELISA) with unfixed cells was performed. Membrane-expressed PR-3 was detected by affinity-purified and monoclonal anti-PR-3 Ab. Tumour necrosis factor alpha (TNF-alpha)-induced membrane expression of PR-3 could be blocked with the RNA synthesis inhibitor actinomycin D, the protein kinase C (PKC) and proteinase A (PKA) inhibitor staurosporine, the specific PKA inhibitor calphostin C, the c-AMP-dependent PKA inhibitor KT5720 and the tyrosine kinase inhibitor genistein in a dose-dependent manner. The effect of calphostin C was the most significant. In addition, the effect of phorbol 12-myristate 13-acetate (PMA), a mediator of intracellular second messengers, was investigated. In our study, pretreatment of cells with PMA for 48 h led to a down-regulation of PR-3 expression. This effect, however, could be overridden by TNF-alpha stimulation, i.e. TNF-alpha-induced membrane expression of PR-3 was resistant to down-regulation of PKC. In conclusion, our data suggest that translocation of PR-3 in HUVECs is an active process depending on protein synthesis. PR-3 expression by HUVECs may involve a PKC reactive to cytokines such as TNF-alpha which induces PR-3 expression at a transcriptional level.


Assuntos
Endotélio Vascular/enzimologia , Serina Endopeptidases/metabolismo , Transdução de Sinais , Membrana Celular/enzimologia , Dactinomicina/farmacologia , Humanos , Mieloblastina , Proteína Quinase C/fisiologia , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...