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Biomedical subjects

U Spengler

Publications and source records attributed to U Spengler.

168 records · Page 10Linked to original sources
PubMed1983

Platelet function, thromboxane formation and blood pressure control during supplementation of the Western diet with cod liver oil.

Epidemiologic and experimental data suggest an antiatherothrombotic potential of omega-3 polyunsaturated fatty acids. Therefore, the Western diet, which supplies predominantly omega-6 polyunsaturated fatty acids, was supplemented with 40 ml/day of cod liver oil, which provides about 10 g of omega-3 polyunsaturated fatty acids daily, for 25 days in eight volunteers. The omega-3 polyunsaturated fatty acids were incorporated in platelet and erythrocyte membrane phospholipids at the expense of omega-6 polyunsaturated fatty acids. Bleeding time increased (p less than 0.01) and platelet count (p less than 0.05), platelet aggregation upon ADP and collagen (p less than 0.01-0.05), and associated thromboxane B2 formation (p less than 0.01) decreased. Blood pressure (p less than 0.05) and blood pressure response to norepinephrine (p less than 0.01) and angiotensin II (NS) fell, without major changes in plasma catecholamines, renin, urinary aldosterone, kallikrein, prostaglandins E2 and F2 alpha and red cell cation fluxes. Biochemical and functional changes were reversed 4 weeks after cod liver oil was discontinued. Formation of prostaglandins derived from eicosapentaenoic acid and interference of eicosapentaenoic acid with formation and action of prostaglandins derived from arachidonic acid were evident in vitro. Whatever the mechanism, this moderate supplement of omega-3 polyunsaturated fatty acids markedly changed membrane phospholipids, which was associated with a shift toward less reactive platelets and a blunted circulatory response to pressure hormones.

Adult↗
PubMedDate not supplied

Differential expression of MHC class II subregion products on bile duct epithelial cells and hepatocytes in patients with primary biliary cirrhosis.

To study the expression of MHC Class II subregion gene products on biliary epithelial cells in primary biliary cirrhosis, frozen sections from liver biopsies of 15 patients with primary biliary cirrhosis were studied immunohistochemically using HLA-D subregion specific monoclonal antibodies L243 (HLA-DR), Leu10 (HLA-DQ) and B7/21 (HLA-DP). Patients with early stages of primary biliary cirrhosis showed expression of HLA-DP, HLA-DR and HLA-DQ subregion gene products on bile duct epithelial cells. In advanced stages of disease, no MHC Class II antigens or only HLA-DR and HLA-DP were expressed on bile duct cells. While normal hepatocytes did not express detectable amounts of MHC Class II antigens, hepatocytes from liver biopsies of four patients with primary biliary cirrhosis showed a distinct staining exclusively with monoclonal antibodies specific for HLA-DR. The expression of MHC Class II antigens on parenchymal cells was independent of a lymphocytic infiltration into the tissue. This study demonstrates that bile ductular cells, but not hepatocytes, express a full set of MHC Class II molecules at least during the early stages of primary biliary cirrhosis. We propose, therefore, that the expression of both HLA-DR and HLA-DQ subregion products on bile duct epithelial cells may be a necessary, although not sufficient, condition for the initiation of an autoimmune process leading to the destruction of intrahepatic bile ducts in primary biliary cirrhosis.

Antibodies, Monoclonal↗
PubMedDate not supplied

Augmentation of 17-1A-induced antibody-dependent cellular cytotoxicity by the triple cytokine combination of interferon-alpha, interleukin-2, and interleukin-12.

Previously, interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and interleukin-12 (IL-12) were shown to increase the antibody-dependent cellular cytotoxicity (ADCC) induced by the murine monoclonal antibody 17-1A, which recognizes the tumor-associated antigen EpCAM. In this study, the authors wanted to determine whether the combination of these three cytokines would yield greater cytotoxicity than the single cytokines. For cytotoxicity assessment, a new flow cytometric assay was used that allows the analysis of long-term ADCC exerted by macrophages. Peripheral blood mononuclear cells from healthy donors were used as effector cells against the colorectal carcinoma cell line HT29 at a low effector-to-target ratio of 4.5:1. With this test, the effectiveness of the combinations IL-2 and IFN-alpha, IL-2 and IL-12, and IL-12 and IFN-alpha were compared with each other. The combinations IL-2 plus IL-12 and IFN-alpha plus IL-12 were more potent at the concentrations tested. Furthermore, the triple cytokine combination of IFN-alpha, IL-2, and IL-12 revealed significantly greater ADCC than dual cytokine combinations. Next, CD14+, CD4+, and CD4- cells were isolated by paramagnetic beads and magnetic activated cell sorter (MACS) columns. The CD14+ and CD4- cell populations contained the ADCC effectors. The addition of CD4+ cells to CD14+ or CD4- cells resulted in augmented ADCC, indicating that cooperation between immune cells occurs. These results suggest that multiple cytokine combinations with monoclonal antibodies may be more effective for cancer immunotherapy.

Adenocarcinoma↗
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↗