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Biomedical subjects

F L Dumoulin

Publications and source records attributed to F L Dumoulin.

30 records · Page 2Linked to original sources
PubMed1997

Semiquantitative analysis of intrahepatic cytokine mRNAs in chronic hepatitis C.

In order to characterize intrahepatic cytokine production, the mRNA levels of interleukin (IL)-2, -4, and -10 and interferon (IFN)-gamma were semiquantitatively determined by reverse-transcription competitive polymerase chain reaction in liver specimens from patients with chronic hepatitis C (n = 23), chronic hepatitis B (n = 9), or primary biliary cirrhosis (n = 12) and normal liver (control) specimens (n = 12). IL-4 mRNA was undetectable. Similar IL-10 mRNA levels were detected in all samples studied, including the controls. Mean IFN-gamma and IL-2 mRNA levels were elevated in chronic inflammatory liver disease. IL-2 mRNA levels were similar in all 3 patient groups, but intrahepatic IFN-gamma mRNA levels were significantly higher in chronic hepatitis C than in chronic hepatitis B or primary biliary cirrhosis patients. This predominance of IFN-gamma may indicate a lower susceptibility of hepatitis C virus to the antiviral effects of this cytokine. The presence of IL-10 in normal liver may impair the induction of antiviral immune responses.

Actins↗
PubMed1997

Hepatitis C virus-associated mixed cryoglobulinaemia.

Symptomatic mixed cryoglobulinaemia may dominate the course of hepatitis C virus infection. While conventional treatment of mixed cryoglobulinaemia relied on immunosuppression, the discovery of the close association to HCV infection has prompted treatment studies with interferon-alpha. Although symptomatic improvement is achieved in most patients during therapy, the rate of sustained response is low.

Cryoglobulinemia↗
PubMed1996

Immune responses in hepatitis C virus infection.

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.

CD4-Positive T-Lymphocytes↗
PubMed1994

[Chronic hepatitis C in type-II cryoglobulinemia and cutaneous vasculitis].

Over a period of 2 years recurrent erysipelas-like skin eruptions developed over both lower legs of a 77-year-old woman. On examination there was a vasculitic purpura which histologically was like leukocytoclastic vasculitis. Further tests revealed a positive rheuma factor, a mixed type II cryoglobulinaemia of monoclonal IgM-kappa paraprotein and polyclonal IgG, as well as chronic hepatitis C with viral replication and demonstration of hepatitis C virus-RNA in the cryoprecipitates, diagnostic of chronic hepatitis C with mixed type II cryoglobulinaemia. Treatment was begun with prednisone, 25 mg/d orally, and cyclophosphamide, 100 mg/d orally. Once hepatitis C had been diagnosed, treatment was continued with interferon alpha-2b (initially 3 x 5 mill. IU, later 3 x 3 mill. IU, each weekly subcutaneously). The vasculitis quickly healed and the cryoglobulinaemia had disappeared within 5 weeks. So far, during the treatment of 9 months, the vasculitis has not recurred, but cryoglobulins have again been demonstrated. The signs and symptoms of hepatitis C were not affected by the interferon treatment.

Aged↗
PubMed1993

[Pulmonary thromboembolism in antiphospholipid syndrome].

A 37-year-old woman in acute right heart failure had experienced systemic venous thromboses for 17 years, five miscarriages and repeated pulmonary emboli. For the last 7 years she had been treated symptomatically for pulmonary hypertension. The platelet count was 62,000/microliters, thromboplastin time under phenprocoumon was 22%, partial thromboplastin time was 72 s. Despite anticoagulation with phenprocoumon and heparin (7,500 IU two times daily subcutaneously) new pulmonary emboli occurred and platelet count fell to 12,000/microliters. An increased titre for anticardiolipin antibodies (IgG > 320 GPL U/l, IgM 8 MPL U/l), antinuclear (1:640) and anti-ds-DNA antibodies (> 200 IU/ml) with simultaneous complement consumption suggested secondary antiphospholipid syndrome associated with lupus erythematodes. Treatment with prednisolone (150 mg/d), immunoglobulins (20 mg/d intravenously for 5 days) and heparin (25,000 IU/24 h intravenously) achieved an increase in platelet count to 200,000/microliters within 10 days, but fell again when the prednisolone dose was reduced, recovering under azathioprine, 150 mg/d. Four weeks later the patient died of renewed acute right heart failure.

Acute Disease↗
PubMed1993

Defect of a complement receptor 3 epitope in a patient with systemic lupus erythematosus.

Complement receptor 3 (CR3) is expressed on cells of the reticuloendothelial system and involved in the clearance of immune complexes. In this article a patient with a deficiency of the C3bi binding site of this receptor is described. Clinically this patient exhibited predominantly cutaneous manifestations of a systemic lupus erythematosus with an immune vasculitis and panniculitis. The deficiency of the CR3 epitope was demonstrated using flow cytometry. The functional relevance of this defect was demonstrated in a rosetting assay with C3bi-loaded erythrocytes. C3bi binding was found to be significantly decreased. Furthermore, there was an impairment of phagocytosis of opsonized Escherichia coli. The CR3 defect is not due to an autoantibody but is assumed to have a genetic basis. These data suggest that the defect of the CR3 may be involved in the pathogenesis of the immune vasculitis in this patient.

Adult↗
PubMed1989

Calcitonin gene-related peptide increases in rat facial motoneurons after peripheral nerve transection.

The rat facial nerve was transected and the retrograde reaction studied in the facial nucleus using light and electron microscopic immunohistochemistry and radioimmunoassay for calcitonin gene-related peptide (CGRP). An initial increase of CGRP-immunoreactivity (IR) was noted at 15 h after axotomy, thereafter CGRP-IR continued to rise to maximal levels around day 6 after which it gradually decreased and reached normal levels again after 5-6 weeks. Immunoreactive CGRP was found to fill the perikarya of facial motoneurons extending into dendrites and axons. Possible functional implications of CGRP as a neuroregulatory molecule during nerve regeneration are discussed.

Animals↗
PubMedDate not supplied

Intrahepatic mRNA levels of interferon gamma and tumor necrosis factor alpha and response to antiviral treatment of chronic hepatitis C.

OBJECTIVES: The impact of intrahepatic messenger RNA (mRNA) levels of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on the outcome of antiviral treatment of chronic hepatitis C was evaluated. METHODS: Semiquantitative mRNA determination was performed on 36 pretreatment liver biopsies by reverse transcription/competitive polymerase chain reaction. RESULTS: Sustained response (normal aminotransferase levels and negative hepatitis C virus [HCV] RNA for more than 6 months) was achieved in 13 patients, whereas 23 of 36 patients did not achieve sustained response (12 partial responders, 11 complete nonresponders). In sustained responders, pretreatment intrahepatic mRNA levels of IFN-gamma and TNF-alpha were lower than in nonsustained responders (IFN-gamma, 0.23 +/- 0.10 vs. 0.35 +/- 0.07, respectively; p = 0.024 and TNF-alpha, 1.2 +/- 0.7 vs. 2.3 +/- 1.4, respectively; p= 0.009); similarly, HCV viral load was lower in sustained responders than in nonresponders (663,424 +/- 756,389 copies/mL vs. 1,656,713 +/- 1,517,683 copies/mL, respectively; p = 0.037). In addition, TNF-alpha mRNA levels were correlated to HCV viral load and liver fibrosis scores. CONCLUSIONS: Higher intrahepatic mRNA levels of IFN-gamma and TNF-alpha may reflect interferon resistance of HCV strains and may contribute to tissue damage in patients refractory to antiviral treatment.

Adolescent↗