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Biomedical subjects

G Steinhoff

Publications and source records attributed to G Steinhoff.

At least 73 records · Page 4Linked to original sources
PubMed1996

Do long-term results justify bridging to heart transplantation in patients with multi-organ dysfunction?

This retrospective study was performed to determine the influence of multi-organ dysfunction and the type of preoperative hemodynamic support on mortality after heart transplantation. All patients undergoing heart transplantation during a 6 year period were divided into 3 groups: group A patients (n = 110) had stable hemodynamics on oral medication, group B recipients (n = 41) received continuous i.v. catecholamine application, and in group C (n = 21) mechanical hemodynamic support was necessary. In groups B and C elevated serum creatinine and transaminase levels-reflecting renal and hepatic dysfunction-were detected more often and the survival rate was worse during the first six months (A: 85%, B: 71%, C: 52%, p < 0.01). In group C the prognosis of patients with multi-organ dysfunction was significantly worse compared to patients with normal renal and hepatic function (38% vs. 75%; p < 0.01). In recipients surviving for six months, there was no difference in long-term prognosis between the groups studied. It is concluded that heart transplantation in patients with multi-organ dysfunction on invasive hemodynamic support bears a significantly increased risk in the early postoperative period. In view of the current donor shortage the condition of other organs should be improved before transplantation as far as possible, even using long-term mechanical support.

Adult↗
PubMed1996

Cytomegalovirus induces interstitial lung disease in allogeneic bone marrow transplant recipient rats independent of acute graft-versus-host response.

Interstitial lung disease (ILD) after allogeneic bone marrow transplantation (BMTx) is an important clinical problem in terms of diagnosis, therapy, and pathogenesis. Graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection seem to be major risk factors for ILD, but their role in the pathogenesis is not well established. We previously reported CMV-induced ILD in allogeneic bone marrow recipient rats, which was prevented by antiviral drug treatment. In this paper, we describe the pathology of ILD in allogeneic bone marrow transplant recipient rats and the relation of ILD with CMV infection and GvHD. Brown Norway rats received an allogeneic (Lewis) BMTx and rat CMV infection, after an allogeneic (Lewis) lung transplantation and immunosuppression. CMV infection was recorded by the amount of infectious virus and viral antigens in the lung. ILD was monitored by the presence of diffuse histopathologic changes in the alveolar septal wall. GvHD was scored by the relative splenic weights and the presence of perivascular infiltrates in the lung. Cells expressing CMV antigens were more numerous in the alveolar septa of the allogeneic recipient lungs than in the syngeneic donor lungs (p < 0.05). The high viral load in the recipient lung of allogeneic BMTx recipient rats was accompanied by diffuse ILD, marked by extensive microvascular damage and congestion of the alveolar septa. ILD was observed neither in the syngeneic donor lung nor in both lungs of mock-infected animals. GvHD was not observed in rat-CMV-infected or in mock-infected animals. Our results indicate that CMV induces microvascular damage, resulting in ILD. This process is independent of GvHD.

Animals↗
PubMed1996

Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens.

BACKGROUND: Cytomegalovirus infection is considered a major complication after lung and heart-lung transplantation because it can trigger acute and chronic rejection. The potential mechanisms of lung transplant rejection induced by viral infection include the upregulation of expression of major histocompatibility complex antigens. To address this question, a model of rat cytomegalovirus infection and acute lung transplant rejection was established. METHODS: Lewis inbred strain rats received syngeneic (n = 25) or allogeneic (Brown-Norway inbred rat strain, n = 38) orthotopic left-side lung transplants. Triple-drug immunosuppression with cyclosporin A, methylprednisolone, and azathioprine was given from postoperative days 1 through 10. Rat cytomegalovirus was inoculated intraperitoneally on postoperative day 3. Two control groups, those infected with cytomegalovirus (n = 15) and those without rat cytomegalovirus infection (n = 6) were treated with identical immunosuppressive regimens. Animals were sacrificed on postoperative days 11, 15, 18, 20, and 25. The salivary glands and both lungs were removed for pathologic and immunohistochemical investigations. RESULTS: All animals inoculated with rat cytomegalovirus developed systemic viral infection on or after postoperative day 11, as confirmed by an assay of plaque-forming units and immunohistologic examination. Cytomegalovirus-induced expression of major histocompatibility complex class II antigens on vascular endothelial cells was seen in the nontransplanted lungs of rats, but no major histocompatibility complex class II antigens were detected on noninfected, nontransplanted lungs. Cytomegalovirus infection also was found to enhance major histocompatibility complex class II antigen expression on pneumocytes and leukocytes in rats. Acute rejection occurred in allogeneic transplants from postoperative days 15 through 25. The expression of class II antigens on endothelial cells, pneumocytes, and leukocytes was further enhanced during the course of allograft rejection in the cytomegalovirus-infected rats compared with the noninfected controls. In cytomegalovirus-positive rats, the rejection grade was higher than that in cytomegalovirus-negative rats on postoperative days 15 through 18. CONCLUSIONS: Our results indicate that cytomegalovirus induces and enhances the expression of major histocompatibility complex class II antigens on endothelial cells, pneumocytes and leukocytes. Upregulation by cytomegalovirus infection may trigger or promote acute rejection by alloantigenic T-lymphocyte stimulation after lung transplantation. By this mechanism it may strongly influence the long-term course of lung transplant rejection.

Acute Disease↗
PubMed1996

[Simultaneous operations of the carotid bifurcation and coronary vessels in moderate systemic hypothermia].

Comorbidity of coronary heart disease and carotid stenosis raises the question of surgical stratification. A simultaneous approach of carotid endarterectomy and coronary revascularization, both under conditions of moderate hypothermic extracorporeal circulation, was applied in 48 patients. Considering the complexity of the procedures required the 30-day mortality (2.1%) and perioperative incidence of permanent stroke (2.1%) or myocardial infarction (0%) appeared to be comparably low.

Aged↗
PubMed1995

In vivo distribution of integrins in renal cell carcinoma: integrin-phenotype alteration in different degrees of tumor differentiation and VLA-2 involvement in tumor metastasis.

We studied 23 renal cell carcinomas and two normal kidney tissues by immunohistochemistry using monoclonal antibodies against subunits of the VLA integrins (VLA-1 to VLA-6) and CD51. All integrins investigated in our study, except VLA-4 (ubiquitous negative), were distributed in different patterns in tumors assayed. We found a correlation between VLA-2 expression and site of tissue; primary tumor cells expressed no VLA-2 integrin, whereas tumor cells from metastatic tissues exhibited VLA-2 positivity (P < .009). Additionally, the expression of VLA-3 and VLA-5 correlated with tumor grading; both integrins were undetectable in G1 tumors but widely expressed in G2 and G3 tumors (VLA-3, p < .000; VLA-5, p < .005). Our results suggest that VLA-2 integrin is involved in metastasis of RCC and that poorly differentiated tumor cells have a different integrin phenotype when compared to normal or highly differentiated tumor cells.

Adult↗
PubMed1995

Induction of endothelial adhesion molecules by rat cytomegalovirus in allogeneic lung transplantation in the rat.

Cytomegalovirus (CMV) infection is known to be a major risk factor for the development of chronic transplant rejection in heart and lung transplantation. A possible mechanism for the induction of lung transplant rejection by CMV infection is the inflammatory upregulation of adhesion ligand molecules by the viral infection leading to an increased endothelial-leucocyte interaction. To study this question, an experimental model was established in the rat using a rat cytomegalovirus (RCMV) infection and acute lung transplant rejection in left single lung transplantation. The distribution of RCMV, intercellular adhesion molecule-1 (ICAM-1) and its leucocyte receptor CD11a (LFA-1) were investigated by immunohistochemistry. The viral infection was observed in transplant lungs of infected hosts as early as day 11. The expression of ICAM-1 on endothelial cells was induced and enhanced by RCMV infection, and infiltration of CD11a-positive leucocytes found to be increased in infected recipients. An acceleration of the rejection of the allografts by the hosts was found.

Animals↗
PubMed1994

Expression of cell-matrix molecules and integrin receptors in human liver grafts during chronic rejection.

The inflammatory response of immune cells to target cells and cell-matrix molecules is regulated by several receptor-ligand molecules. As fibrosis develops in ongoing chronic rejection after liver transplantation, it is of interest to analyze patterns of integrin receptors and cell-matrix molecules in order to study the relation between immune cells and the stromal and parenchymal cells. In the present study, we demonstrated the expression of these molecules in chronic rejected human liver grafts using immunohistochemical techniques. The results showed a differential expression and induction of integrin receptors and cell-matrix molecules on resident liver cells, especially on sinusoids, reflecting a state of chronic inflammation and a specific interaction between integrin receptors and cell-matrix molecules. The patterns of induced integrin receptors on graft-infiltrating cells was closely related to the local production of cell-matrix molecules and reflected the final sequence of a stepwise progress of the inflammatory reaction.

Bile Ducts↗
PubMed1994

Transmission of donor lymphocytes in clinical lung transplantation.

Passenger mononuclear cells in organ grafts are known to influence the alloimmune response to the graft. To assess their relevance in clinical lung transplantation, we studied the amount, distribution, cell types, and surface marker expression of mononuclear cells in human donor lungs. Two major compartments of mononuclear cells could be differentiated: lymph nodes containing resting T and B lymphocytes, and the lung tissue itself, containing mainly activated lymphocytes as well as monocytes/macrophages. Tissue-associated mononuclear cells make up 20-40 x 10(9) cells per lung, about 30-50% of which are lymphocytes. Tissue-associated lymphocytes are predominantly T and NK cells; most of the T cells are CD8+ CD45R0+ and express HLA-DR. Strong expression of the adhesion molecules LFA-1 and ICAM-1 is present on infiltrating cells as well as on resident cells of the organ. Moreover, the lymphocytes inside the lung tissue are functionally highly active, with a strong stimulatory as well as alloreactive potency. Thus, large numbers of allogeneic mononuclear cells and particularly large numbers of functionally active lymphocytes are obviously transmitted by human lung allografts. The immunological in vivo relevance of these cells after lung transplantation may include allostimulation and graft-versus-host activity, but also beneficial immunomodulatory effects.

Antigens, CD↗
PubMed1993

Production of cytokines (TNF-alpha, IL-1-beta) and endothelial cell activation in human liver allograft rejection.

Intragraft production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1-beta) was determined in rejecting human liver grafts during acute rejection and in chronic graft dysfunction. The localization of cytokine-producing cells was then correlated with the distribution of monocytes and macrophages as their main producers, as well as with effector functions such as endothelial cell activation. In selected patients collateral TNF-alpha plasma levels were measured. In normal liver and biopsies taken during an uncomplicated course, few TNF-alpha and even fewer IL-1-beta positive macrophages were found. During acute rejection episodes of all degrees of severity liver grafts were infiltrated by large numbers of TNF-alpha-positive monocytes, and concomitant TNF-alpha plasma levels were elevated compared with uncomplicated controls. In marked contrast IL-1-beta production by macrophages and vascular and sinus endothelial cells was restricted to the most severe, irreversible rejection episodes. The localization of cytokine-positive cells coincided with areas of maximum induction of ICAM-1 and von Willebrand Factor. In chronic graft dysfunction increased numbers of mature macrophages were found. A large proportion of these were positive for TNF-alpha as well as IL-1-beta. Distinct from acute rejection episodes, however, parallel TNF-alpha plasma levels were not elevated, suggesting cytokine storage rather than secretion. The present results indicate an important local role of TNF-alpha and IL-1-beta in the early phase of the rejection process. They presumably activate endothelial cells to upregulate the expression of adhesion molecules, thereby facilitating mononuclear cell adhesion and extravasation. Therefore, specific inactivation of cytokines or of their actions may prove to be a powerful tool in the prevention and treatment of allograft rejection in the future.

Cell Adhesion Molecules↗
PubMed1993

Passenger lymphocytes in human liver allografts and their potential role after transplantation.

Rare cases of graft-versus-host disease after liver transplantation indicate that donor lymphocytes may be transferred to the recipient by human liver grafts. In this study, we have analyzed the number and subpopulations of donor lymphocytes transferred by liver grafts in order to evaluate the potential relevance of these cells after transplantation. Therefore, mononuclear cells were isolated from the tissue of perfused human donor livers and from the associated lymph nodes. The number of lymphocytes, their location, and surface marker expression were determined by immunostaining. The majority of lymphocytes transferred by the grafts were found within the liver tissue (5.3 +/- 2.9 x 10(9) cells). These lymphocytes are mainly T and NK cells, predominantly CD8+, are partially activated (28% HLA-DR+), and show strong adhesion molecule expression (88% LFA-1(3+)). In addition, 20-500 x 10(6) of resting lymphocytes, predominantly T and B cells, are transmitted by lymph nodes. These findings demonstrate that considerable numbers of donor lymphocytes of distinct phenotype are regularly transmitted to the recipient by human liver grafts and may be of functional relevance after transplantation.

Antigens, CD↗
PubMed1993

Persistence of donor lymphocytes in liver allograft recipients.

Occasional cases of graft-versus-host disease after liver transplantation indicate a transfer of donor lymphocytes by human liver grafts. However, little is known about the usual fate and potential function of passenger lymphocytes in clinical liver transplantation. In this study, we have analyzed liver graft recipients for the presence of donor lymphocytes in the early course after transplantation. The presence of such cells in blood, the graft, and, occasionally, the skin was studied by the use of mAb to polymorphic HLA class I determinants and double-staining techniques in flow cytometry and immunocytology. The findings were compared with the clinical courses and with the results of routine graft biopsies. Within the first week after transplantation, in all 16 patients, between 1% and 24% donor lymphocytes (T, NK, and B cells) were detectable in blood, and in 14 of 22 patients (64%), between 2% and 23% donor T cells were found in the graft. After more than 2 weeks, donor cells were still present in blood in 2 of 14 patients at very low numbers. The presence of donor lymphocytes in the graft was associated with intragraft immune activation in 5 of 15 patients, but no clinical rejection occurred in these cases; mild graft-versus-host disease was observed in one patient. These findings demonstrate that donor lymphocytes regularly persist in liver-grafted patients for some time; this transient mixed lymphoid chimerism is only rarely associated with clinical graft-versus-host disease and some evidence even suggests that these donor-derived lymphocytes may exert beneficial immunomodulatory properties.

Adult↗
PubMed1993

Intercellular immune adhesion molecules in human liver transplants: overview on expression patterns of leukocyte receptor and ligand molecules.

Recently it has become clear that the inflammatory response of immune cells to target cells and extracellular matrix is regulated by several receptor-ligand molecules. Three main classes of molecules mediating intercellular adhesion and activation processes have been identified: the integrin, immunoglobulin and selectin families. This study surveys the expression of adhesion molecules on resident and infiltrating cells in human liver grafts. The patterns of cellular expression and inducibility in different pathological conditions of the graft are described. Our results show organ-specific regulation of the different adhesion molecules during alloreactive reactions and other types of inflammatory reactions. No rejection-specific patterns were detected on comparison with reperfusion damage or infectious transplant inflammation. Major differences were noted in the composition of the portal tract and sinusoid with regard to endothelial and parenchymal cell expression of cell-cell and cell-matrix adhesion molecules. Intravascular and interstitial differences in the expression patterns of leukocyte adhesion receptors support a concept of stepwise expression. The implications for the appearance of inflammatory reactions in human liver in immunosuppressive and therapeutic interventions are discussed.

Cell Adhesion Molecules↗
PubMed1993

Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3.

Vascular expressed adhesion molecules mediate leukocyte reactivity and activation by receptor-ligand binding. A number of different ligand molecules have been identified to mediate the interaction between endothelial cells and leukocyte subpopulations. In this study, the tissue expression of ELAM-1, CD62 (PADGEM, GMP-140), VACM-1 (INCAM-110), ICAM-2, ICAM-1, and LFA-3 was analyzed on various liver endothelial cell types by immunohistology. The results reveal a differential expression of these molecules in normal liver and inflammation or rejection after liver transplantation. The selectins ELAM-1 and CD62 are basally expressed and inducible on portal tract endothelia (arterial and venous) and central vein endothelia with acute and chronic liver inflammation. Sinusoidal endothelia, however, lack this mechanism, even with severe inflammation, as in cases of irreversible rejection and sepsis. Portal and sinusoidal endothelia show a different expression and inducibility of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The differences in expression of adhesion molecules on liver endothelial cell types may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. The inability of sinusoidal endothelia to express selectins may have implications for the pathophysiology of liver graft infiltration.

Cell Adhesion Molecules↗
PubMed1992

Liver transplantation for hepatocellular carcinoma: clinical results and future aspects.

The treatment of unresectable hepatocellular carcinoma (HCC) by liver transplantation remains controversial. In our series, the 5-year survival value for 87 patients who underwent transplantations between 1972 and 1990 was 19.6%. There was no difference in the long-term survival of patients who had underlying cirrhosis and those who did not. In patients with early-stage tumors the long-term prognosis was improved, the 5-year survival in stage II disease being 55.6% according to UICC criteria. Even in some cases of more advanced tumour stage, good long-term results were obtained. In a review of the recent literature, we evaluated prognostic factors to work out criteria for a more differentiated indication for liver transplantation. Resection of increased radicality--which will keep its place as the therapy of choice--and transplantation should be performed complementarily. Further developments will reveal the value of multimodal therapeutic strategies, including chemo-embolisation, chemotherapy and immunotherapy.

Carcinoma, Hepatocellular↗