Biomedical subjects

G Wolff-Vorbeck

Publications and source records attributed to G Wolff-Vorbeck.

29 records · Page 2Linked to original sources

PubMed1992

[Alterations in lymphocyte subsets in variable immunodeficiency syndrome].

Besides functional defects, different phenotypical alterations of lymphocytes have been described in patients with CVID. A decrease in LAM-1- (= Leu8) and CD21 expression was observed on B cells. Some patients with CVID show alterations in their T-cell subpopulations: The most striking features of this subgroup are low CD4/CD8-ratio, an increase in CD57/CD8 double-positive lymphocytes, and a strong enhancement of HLA-DR and "memory" markers such as CD29 and LFA-3 on T cells.

B-Lymphocytes↗

PubMed1989

Autoreactive T cells in rheumatic disease (1). Analysis of growth frequencies and autoreactivity of T cells in patients with rheumatoid arthritis and Lyme disease.

A limiting dilution system was established in order to estimate frequencies of interleukin-2 (IL-2)-responsive, autoreactive and alloreactive T cells in samples of peripheral blood (PBL) and synovial fluid lymphocytes (SFL), from patients with rheumatoid arthritis (RA) and lyme disease, as well as from healthy donors and a patient with osteoarthrosis. The frequencies of IL-2-dependent T-cell colony formation were significantly higher in patients with RA and lyme disease (median: 1/287) as compared to controls (median: 1/1,313) indicating a preactivation of T cells in these patients in vivo. Autoreactivity was measured by the proliferative response of T-cell lines to autologous irradiated PBL as stimulating cells. The frequencies of autoreactive T cells in blood were significantly higher in patients (median: 1/2,615) as compared to controls (median: 1/19,607). There was no significant difference in autoreactive T-cell frequencies between the patients' SFL (median: 1/3,185) and PBL (median: 1/2,615). In every case the frequency of alloreactive T cells exceeded the frequency of autoreactive T cells. Most autoreactive T-cell lines were also alloreactive and were shown to be MHC Class II-restricted. There is evidence of a down regulation of autoreactive T cells by suppressor cells in peripheral blood in two cases with elevated autoreactive T-cell frequencies (one RA patient and one control patient suffering from a viral infection). In contrast, no suppression of autoreactive T cells was observed in the RA patients' SFL or in PBL and SFL from patients with lyme disease. These results suggest that the chronic inflammation observed in RA and lyme disease may be supported by an elevated number of autoreactive T cells in the absence of suppressive mechanisms.

Arthritis, Rheumatoid↗

PubMed1987

Chemiluminescence response of human B-cell lines.

Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cells share certain properties with monocytes: they are capable of presenting protein antigens to antigen-specific T-lymphocytes and of releasing an Interleukin 1-like factor. It was our interest to study whether transformed B-cells resemble monocytes by generating toxic oxygen radicals. Human B-cell lines were developed from human peripheral blood lymphocytes by EBV-transformation. The induction of the respiratory burst in the B-cells was assessed by chemiluminescence (CL) in the presence of lucigenin. B-cells were stimulated with phorbol-myristate-acetate (PMA), zymosan particles, the chemotactic peptide f-met-phe, the complement split product C5a and with a recently described granulocyte activating cytokine (GRAM). Stimulation with PMA elicited a distinct CL-response in the tested B-cell lines. The CL-signal was significantly reduced by superoxide dismutase, but not by D-mannitol and catalase. No significant response to any of the other stimuli was detected. Furthermore, none of the stimuli induced a luminol-enhanced CL signal, which, in contrast to lucigenin, is dependent on the presence of peroxidase. Our results indicate that EBV infected B-cells were able to generate significant amounts of reactive oxygen species, particularly superoxide. It appears that virus transformation uncovers genetic information which is usually not expressed in non-transformed B-cells.

B-Lymphocytes↗

PubMed1986

[Acquired immunodeficiency syndrome with chronic granulomatous inflammation. Clinically definable special form of the variable immunodeficiency syndrome].

Five cases (3 men, 2 women) of late-onset variable immunodeficiency syndrome (CVID), characterized by similar clinical and immunological findings as well as histological demonstration of chronic granulomatous infection, are reported. All patients had frequent attacks of respiratory infections with recurrent bronchitis and pneumonia. In addition to predominating basally localized streaky-nodular lung changes all patients had hepatosplenomegaly and granulomatous infections of other organs. Immunologically, marked hypogammaglobulinaemia of all Ig classes, lymphopenia, and absence of terminal B-cell maturation were predominant. In-vitro tests under pokeweed-mitogen failed to demonstrate terminal plasma-cell differentiation of B-lymphocytes and thus Ig synthesis. Without pokeweed-mitogen there were largely nonsecretory B-blasts with abnormal granulated cytoplasmic Ig formation. Skin testing with Multitest application revealed almost complete anergy, both in the Arthus (24 h) and the late reactions (48 and 72 h). Nonetheless, T-cell reaction in-vitro was much less affected than B-cell function. "Natural killing" and antibody-dependent cytotoxicity were normal or slightly increased.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Characterization of T8 epitopes by enzymatic digestion, crossblocking, and involvement in cell-mediated lympholysis.

Eleven monoclonal antibodies, directed versus the T8 glycoprotein, were compared using enzyme digestion, phylogenetic comparisons, cross-blocking of antibody binding, and blocking of specific cell-mediated lympholysis (CML). It was found that none of the 11 anti-T8 antibodies tested define the same epitope on the T8 glycoprotein. Some of these antibodies react, however, with closely related structures, as shown by cross-blocking of antibody binding and similar enzyme sensitivity of the epitopes. Moreover, these structural related epitopes show a similar involvement in the effector phase of CML reactions, since the antibodies to these neighboring epitopes inhibit the same CML reactions. Thus, it is possible to apply structural and functional criteria to define "regions" on the T8 glycoprotein, some of which are consistently involved in CML reactions, some never, and some of these regions appear to be involved in specific effector-target cell combinations only.

Animals↗

PubMed1984

Comparison of the inhibitory activity of seven anti-T8 antibodies on specific cellular cytotoxicity.

To evaluate the functional significance of the T-cell membrane structure recognized by OKT8 or Leu2a, seven different monoclonal antibodies, reacting with different epitopes of this 76 KD big membrane structure, were evaluated for their ability to alter specific cell mediated lympholysis after a mixed leukocyte reaction. The stimulated effector cells were first incubated with a monoclonal antibody, washed and then tested for their cytotoxicity. Those antibodies, which react with a highly trypsin-sensitive region of the T8 glycoprotein, were the most effective inhibitors of the cytotoxicity (T811, FK18). Those antibodies, which react with a relative trypsin-resistant region (OKT8, Leu2a, WT82, WT85) or with a trypsin-sensitive epitope (WT81), which is in a close neighborhood to WT82 or WT85, appear to be able to block the cytotoxicity only in certain effector/target cell combinations. The data suggest that different regions of the T8 glycoprotein are involved in the specific cytotoxic reactions, and that the involvement of certain epitopes may depend on the effector/target cell combination.

Antibodies, Monoclonal↗

PubMedDate not supplied

Influence of cytokines on the expression of fas ligand and CD44 splice variants in colon carcinoma cells.

The expression of Fas ligand (FasL) by malignant cells might be a mechanism for tumor immune escape. We investigated FasL expression by LS 174T colon carcinoma cells. Furthermore, the effects of in vitro stimulation with rIL-2, rIFN-gamma and rTNF-alpha were investigated with regard to a possible regulation of the FasL expression by cytokines. FasL expression was detected by flow cytometry and RT-PCR. We observed a spontaneous expression of FasL by LS 174T cells. Incubation with high-dose rTNF-alpha induced an upregulation of FasL of 23%. rIL-2 and rIFN-gamma did not significantly affect FasL expression. To control whether our cytokine stimulation experiments were suitable to prove an upregulation of membrane proteins by tumor cells, we investigated the expression of ICAM-1, N-CAM, CD44s, CD44v6 and CD44v10. These adhesion molecules were spontaneously expressed by LS 174T cells. Only ICAM-1 and CD44v10 were significantly upregulated by rIFN-gamma and rTNF-alpha, respectively. These results could indicate that cytokines, released by tumor-infiltrating leukocytes, may induce the FasL-dependent apoptotic signal by which tumors downregulate an immunological host response.

Adenocarcinoma↗

PubMedDate not supplied

Kupffer cells infiltrate liver tissue early after ischemia-reperfusion and partial hepatectomy.

Kupffer cells, ED2+macrophages of the liver, play an important role in liver damage and regeneration. It is proposed that Kupffer cells are stationary and regenerate after acute liver trauma by local proliferation. We analyzed their kinetics in three surgically relevant murine models of acute liver injury: partial liver resection, ischemia with reperfusion and sepsis. We found an early increase in ED2+cells after 0.5 h and a maximum after 12 h. These results suggest an infiltration of the cells early after the injury and a later local proliferation. These ED2+macrophages are localized predominantly periportally; nearly no macrophages are found pericentrally, except in the sepsis model. Therefore, a shifting of macrophages from portal to central seems to be unlikely, suggesting a hepatic zonation of homing factors.

Animals↗

PubMedDate not supplied

Chemokines in human colorectal carcinoma.

BACKGROUND: Chemokines (CKs) may promote antitumor immunity in cancer, act as tumor growth factors, influence metastatic spreading or angiogenesis. The purpose of this study was to investigate whether CK expression is altered in colorectal carcinomas compared to normal mucosa and to elucidate its possible clinico-pathological implications. MATERIALS AND METHODS: The levels of CCL2 (MCP-1), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL 1 (GRO-alpha), CXCL 5 (ENA-78) and CXCL 8 (IL-8) were investigated in 10 colorectal carcinomas and their corresponding normal mucosa by the use of ELISA. RESULTS: All CK analyzed, with the exception of CCL5 (RANTES), were expressed at a significantly higher level in malignant tissue. CONCLUSION: Therapeutic studies in colon carcinomas should, therefore, focus more on the neutralization of CKs than on their application.

Adenocarcinoma↗

PubMedDate not supplied

Hepatocyte proliferation and apoptosis in rat liver after liver injury.

BACKGROUND/AIMS: In this paper the early phase of proliferate response and apoptosis of hepatocytes after partial liver resection, during reperfusion after ischemia and during sepsis is demonstrated. METHODOLOGY: Experiments were conducted in a rat model with regeneration times of 0.5-24 hours after injury. Proliferation was analyzed by Ki-67 immunohistochemistry and confirmed by double staining with CK18 in FACS. Apoptosis was analyzed by TUNEL technique. RESULTS: Periportal hepatocytes enter the cell cycle already 0.5-2 hours after injury in all three models. This early proliferative response is predominant periportally localized. During reperfusion and during sepsis there was a strict pericentral apoptosis of hepatocytes found. CONCLUSIONS: An early periportal proliferation of hepatocytes is a common reaction of the liver to injury. This proliferation takes place much earlier then the main proliferative response 24-72 h after partial resection. This predominant periportal proliferation together with the pericentral apoptosis fit to the concept of the "streaming liver" in liver regeneration.

Animals↗

PubMedDate not supplied

Expression of CD44, ICAM-1 and N-CAM in colorectal cancer. Correlation with the tumor stage and the phenotypical characteristics of tumor-infiltrating lymphocytes.

The cellular adhesion molecules (CAMs) CD44s, CD44v6, CD44v10, ICAM-1 and N-CAM were immunohistologically detected in colorectal cancers using the APAAP method. The expression of CD44s and CD44v6 was associated with the presence of lymph node metastases in the examined tumors. The pattern of ICAM-1 expression was inversely related to that of CD44, i.e. lower numbers of ICAM-1 positive cells were observed in metastasizing tumors. An intense focal staining of N-CAM was observed in the majority of the metastasizing tumors. The expression of CD44v, ICAM-1 or N-CAM on tumor cells did not correlate with the density of the tumor-infiltrating lymphocytes (TIL) within the tumors. The flowcytometric analysis of TIL showed a significant accumulation of CD25+ and HLA-DR+ cells and a reduced number of CD45RA+ cells as compared to autologous peripheral blood lymphocytes (PBL) or intraepithelial lymphocytes of the colon mucosa (IEL). These phenotypic characteristics of TIL did not correlate with the CAMexpression on tumor cells.

Adenocarcinoma↗