PubMed Health⌕ Search

Biomedical subjects

C Holzinger

Publications and source records attributed to C Holzinger.

36 records · Page 2Linked to original sources
PubMed1989

Expression of a binding structure for sialic acid-containing glycoconjugates on rat bone marrow-derived macrophages and its modulation by IFN, TNF-alpha, and dexamethasone.

Rat macrophages express a binding structure for sialic acid-containing glycoconjugates (sialic acid-binding receptor, SAR) which can be detected by a rosette assay utilizing SRBC coated with bovine brain gangliosides (E-G). Freshly isolated rat bone marrow cells (BMC) contain about 5% SAR-positive cells. Rat BMC cultured for 1 wk with tissue culture media containing CSF-1 differentiate into a virtually pure population of bone marrow-derived macrophages (BMDM phi). All BMDM phi bound E-G coated with an optimal concentration of gangliosides (100 micrograms/ml). When BMC were cultured for 1 wk with murine recombinant granulocyte-macrophage CSF, irrespective of the dose of GM-CSF, approximately 90% of the cells were identified as rat macrophages, and practically all expressed SAR. Only about 50% of BMDM phi bound SRBC coated with a suboptimal concentration of gangliosides (20 micrograms/ml). However, this percentage increased markedly after 8 to 72 h incubation with 1 to 10,000 U/ml purified murine IFN-alpha or IFN-beta, whereas murine or rat rIFN-gamma at doses above 10 U/ml led to a decrease of E-G binding. Human and murine rTNF-alpha enhanced rosette formation in a dose-dependent manner. These effects could be blocked by the respective anti-cytokine antibodies. Treatment of BMDM phi with dexamethasone also augmented E-G rosetting. The enhancement of E-G binding was abolished by pretreatment of BMDM phi with cycloheximide and actinomycin D but not with mitomycin C, suggesting that de novo synthesis of protein and RNA, but not DNA, is required. Our results demonstrate that all rat BMDM phi constitutively bear SAR, and that murine IFN-alpha, IFN-beta, and TNF-alpha, as well as dexamethasone, may augment SAR expression.

Adjuvants, Immunologic↗
PubMed1989

[Orthotopic heart transplantation at the 2d Surgical Department of the University of Vienna: 4-year experience].

Between March 1984 and August 1988, 89 orthotopic cardiac transplants were performed in 87 patients at the Second Department of Surgery, University of Vienna. 2 patients underwent retransplantation and 3 patients received previously a total artificial heart bridge. Recipients were immunosuppressed with low dose cyclosporine, azathioprine and since May 1986 with additional low dose prednisolone; all patients were supplemented perioperatively with either ATG or OKT3. 1-year survival rates continuously increased from 33% in 1984 to 88% in 1987 (p = 0.07). The one-year survival rate in recipients given double drug therapy (cyclosporine and azathioprine) was 43% as compared with 77% on triple therapy (cyclosporine, azathioprine and prednisolone, p = 0.003). Acute rejection was the leading cause of death. These data indicate that the substantial improvement in survival rates is attributable to augmented immunosuppression and to improved patient management and recipient selection.

Adolescent↗
PubMed1989

[Development of a physiological pacing concept at the 2d Surgical Department of the University of Vienna].

With the transvenous approach of atrial leads in 1978 a progressive physiological pacing concept was developed at the Second Surgical Department of the University of Vienna. Using multiprogrammable fully-automatic double-chamber pacers and the technology of biological sensors, the most suitable treatment for any individual patient can be chosen. Our recommendations are DDD stimulation for complete AV block and rate-responsive pacing of the atrium or the ventricle for the Sick-Sinus-Syndrome or atrial fibrillation, respectively. Second choices for AV block are rate-responsive single-chamber pacemakers or simple programmable pacemakers generally.

Atrial Fibrillation↗
PubMed1989

[Infrarenal aortic aneurysm: results of surgical treatment].

Between 1976 and 1987 93 patients with an infrarenal aortic aneurysm underwent surgical correction. In 62 patients the procedure was performed electively, whilst 13 displayed an unstable aneurysm and in 18 cases a ruptured aneurysm was present at operation. During the past 5 years the mortality was lowered to 2% in elective cases, whereas in cases of ongoing rupture only moderate improvement took place. The most frequent cause of a lethal outcome was pump failure of the heart (6 times), followed by renal insufficiency and haemorrhagic shock and bleeding complications. Among the non-lethal complications, relaparotomy on the basis of postoperative bleeding ranks first, followed by pulmonary insufficiency, peripheral emboli and partial ischemia of the spine. Resection of infrarenal aneurysms should be performed in the stable state of disease, since insufficiency of multiple vital organ systems increases the mortality by up to 20 fold.

Aged↗
PubMed1989

Murine recombinant GM-CSF-driven rat bone marrow cell differentiation and factors suppressing cell proliferation.

Rat or mouse bone marrow cells (BMC) cultured for one week with a crude mouse L929 cell supernatant or with purified colony stimulating factor type 1 (CSF-1) differentiate into an essentially pure population of macrophages (M phi). Surprisingly, 90 to 95% of the cells obtained by culturing rat BMC for seven days with recombinant murine granulocyte-macrophage CSF (rmGM-CSF), regardless of concentrations, were classified as M phi. The majority of the remaining cells were granulocytes. This effect is in contrast to that on mouse BMC cultures, where the percentage of granulocytes increased with higher concentrations of rmGM-CSF. The proliferative capacity of rat BMC was demonstrated by colony formation in soft-agar, enumerating total cell number in liquid cultures or measuring 3H-thymidine uptake. A crude L929 cell supernatant and rmGM-CSF induced cell proliferation in a dose-dependent manner. Maximal DNA-synthesis was observed on the fifth day of incubation when BMC were cultured at a density of greater than or equal to 1 x 10(5) cells/well. In cultures initiated with lower cell density, prolonged DNA synthesis was observed. Thereafter, the rate of proliferation declined rapidly. Simultaneous incubation of BMC with GM-CSF and indomethacin led to increased levels of DNA synthesis, suggesting that prostaglandins may suppress cell proliferation. Furthermore, the CSF-induced BMC proliferation was dose dependently inhibited by dexamethasone and 1,25-dihydroxy-vitamin D3 as well as by interferon-gamma and tumor necrosis factor-alpha. The suppressive effect of both cytokines could be abrogated by the addition of the respective anticytokine antibodies.

Animals↗
PubMed1989

Beta 2-microglobulin. A reliable parameter for differentiating between graft rejection and severe infection after cardiac transplantation.

We investigated the role of beta 2-microglobulin as a noninvasive parameter to monitor acute rejection and severe infection in 45 consecutive heart transplant recipients. Endomyocardial biopsy revealed moderate (41 patients) or severe (three patients) rejection in 44 patients. Severe infections of bacterial septicemia (11 patients), bronchopneumonia (two patients), and viral infection (seven patients) were detected by a meticulous schedule of various clinical and laboratory tests. beta 2-Microglobulin levels in serum, generally corrected for serum creatinine, were significantly elevated in patients with infections (median, 6.3 mg/l; range Q10-Q90, 3.47-10.27 mg/l) compared with levels in patients with rejection (p less than 0.0001) or in patients in obviously good condition (p less than 0.0001). At the onset of acute rejection, the median corrected beta 2-microglobulin serum level was 1.56 mg/l (range Q10-Q90, -0.05-3.46 mg/l) and was significantly different from the control group (p less than 0.01). In addition, density function and empirical quantile analyses allowed us to define ranges of beta 2-microglobulin levels that would differentiate between rejection (2.05-3.46 mg/l) and infection (greater than 3.46 mg/l). With these values, sensitivity and specificity were 0.9 and 0.938 for detection of infection and 0.23 and 0.925 for detection of rejection, respectively. By means of beta 2-microglobulin, two cases of infection were misinterpreted as rejection (10%), and four of 44 rejections were mistaken for infections (9%). We conclude that measurements of beta 2-microglobulin may improve the management of heart transplant patients.

Adult↗
PubMed1989

Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression.

To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T-cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA-A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin.

Acute Disease↗
PubMed1988

Expression of the VEP13 antigen (CD16) on native human alveolar macrophages and cultured blood monocytes.

Human alveolar macrophages (AM phi) from thirteen patients, who were suffering from various lung diseases were harvested by bronchoalveolar lavage. Peripheral blood monocytes from eight healthy donors were isolated by Ficoll-Hypaque gradient centrifugation and adherence to plastic surface. To detect the VEP13 antigen (CD16) on these cells, a rosette assay employing ox erythrocytes coated by the CrCl3 method with purified VEP13 monoclonal antibody (Eo-VEP13) was used. A mean of 31.3% of freshly isolated AM phi and 3.9% of blood monocytes formed Eo-VEP13 rosettes. Monocytes cultured for 3 or 6 days in the presence of a supernatant from mouse L929 cells, which had been shown previously to improve long-term viability of human monocytes in culture, showed 12.5% and 25.3% Eo-VEP13 rosettes, respectively. No significant increase in VEP13 antigen expression was noted by culturing monocytes without L929 cell supernatant. The factor in L929 supernatant that induces VEP13 antigen expression has not been identified. Tunicamycin at 10 micrograms/ml inhibited significantly VEP13 antigen expression on monocytes. In contrast, IgG rosette formation was not reduced by tunicamycin. Our data show that subpopulations of native human AM phi and peripheral blood monocytes cultured in presence of a supernatant of L929 fibroblasts containing mainly murine CSF may express the CD16 antigen, which is normally found on large granular lymphocytes (LGL). Suppression by tunicamycin indicates that Fc receptor glycosylation takes place during a later differentiation step of mononuclear phagocytes.

Antibodies, Monoclonal↗
PubMed1988

Augmentation of IgE receptor expression and IgE receptor-mediated phagocytosis of rat bone marrow-derived macrophages by murine interferons.

Receptors for IgE (Fc epsilon R) on rat bone marrow-derived macrophages (BMDM phi) were demonstrated by a rosette assay employing trinitrophenyl-coated ox erythrocytes (EoTNP) sensitized with mouse IgE anti-dinitrophenyl monoclonal antibody (EoTNP-IgE). Virtually all BMDM phi emerging from bone marrow cells cultured for 1 week in the presence of mouse L929 cell supernatant, with partially purified murine CSF-1 or recombinant murine GM-CSF, formed IgE rosettes. To study the effect of interferons (IFNs) on Fc epsilon R expression, 1-week-old rat BMDM phi were incubated with murine recombinant IFN-gamma, purified IFN-alpha or IFN-beta, and were tested for their capacity to bind and ingest EoTNP sensitized suboptimally with IgE. A marked increase in the percentage of cells forming IgE rosettes or phagocytosing EoTNP-IgE was noted after 8-72 hr incubation of BMDM phi with 0.1-1000 U/ml of IFNs. At similar concentrations IFN-gamma and IFN-beta triggered EoTNP-IgE binding or ingestion more efficiently than IFN-alpha. The enhancing effect was blocked by the respective anti-IFN antibodies, cycloheximide or actinomycin D but not by mitomycin C. The IgE rosette formation and IgE-mediated phagocytosis were dose-dependently inhibited by native rat IgE but not by heat-denaturated IgE myeloma protein IR162 or monomeric rabbit IgG. Our results demonstrate that rat BMDM phi express constitutively Fc epsilon R, and that murine IFNs augment Fc epsilon R-mediated binding and ingestion in a time- and dose-dependent manner. This effect probably reflects an increase in the number of Fc epsilon R per cell, as a result of de novo synthesis of Fc epsilon R.

Animals↗
PubMed1987

Differentiation of rat bone marrow cells into macrophages under the influence of mouse L929 cell supernatant.

Bone marrow cells (BMC) flushed from femora of Lewis rats were cultured in Dulbecco's modification of Eagle's medium supplemented with mouse L929 cell supernatant as a source of colony-stimulating factor (CSF). Differentiation of macrophage progenitor cells into macrophages (M phi) and expression of various markers were kinetically assessed. The proportion of M phi increases from approximately 4% in freshly isolated BMC to 100% after 7-8 days of cell culture. These cells, termed bone marrow cell-derived macrophages (BMDM phi), adhere to and spread on plastic surface; exhibit M phi morphology; stain intensely for nonspecific esterase; are able to phagocytose latex particles, IgG-sensitized erythrocytes, and C3-coated red cells; and express receptors for IgG and C3. A subpopulation of BMDM phi expresses MHC class II antigens as demonstrated by immunofluorescence using MRC OX6 and MRC OX17 monoclonal antibodies which recognize antigens coded in the I-A or I-E subregion of the MHC, respectively. Collectively, our results show that supernatant from mouse L929 cells supports and is continuously required for proliferation and differentiation of rat BMC into typical M phi, and suggest that mouse CSF cross-reacts with the putative receptor on rat M phi.

Animals↗
PubMed1987

Surface phenotypes of human peripheral blood mononuclear cells from patients with gastrointestinal carcinoma.

Peripheral blood mononuclear cells (PBMC) from 40 patients with gastrointestinal carcinoma (GIC), 13 patients with primary carcinoma in other localizations(non-GIC), and from 57 apparently healthy donors were isolated by Ficoll-Paque gradient centrifugation. The separated cells were stained with several monoclonal antibodies and subjected to analysis on a fluorescence-activated cell sorter. A decreased percentage of PBMC expressing T cell antigens was noted amongst GIC patients, and was mainly due to a reduction of the Leu 2a subset, thus, leading to an increase in the Leu 3a/Leu 2a ratio from 1.4 to 2.1 Non-GIC patients had decreased numbers of both T helper and suppressor cells. Amongst PBMC from GIC and non-GIC patients a statistically increased percentage of cells expressed LeuM 2 (P less than 0.001), LeuM 3 (P less than 0.001), OKM 1 (P less than 0.005), VEP 9 (P less than 0.001), and HLA-DR (P less than 0.001) antigens compared to healthy controls. The percentage of cells bearing these monocyte/macrophage antigens correlated well with the number of cells having monocyte morphology, stained for non-specific esterase, phagocytosed latex particles, and expressed Fc IgG receptor. Our results demonstrate clearly that tumor-bearing patients have an increased relative number of monocytes. The data suggest that cells of the macrophage lineage may be involved in defense mechanisms and changes of the immune system evoked by various tumors.

Adolescent↗
PubMed1986

Specificity of ganglioside binding to rat macrophages.

The binding specificity of rat alveolar macrophages (AM phi) for sheep erythrocytes (E) coated with gangliosides GM1, GM2, GM3, GD1a, GD1b or GT1b was analyzed in a rosette assay by studying the inhibitory effect of gangliosides, various carbohydrates, IgG, C3b-like C3, and fibronectin in this assay. The uptake of gangliosides by E was calculated from radioactivity measurements using 3H-labeled gangliosides. The different gangliosides were taken up by E at 37 degrees C to a similar extent. Uptake of 3H-labeled GM2 correlated linearly to its concn in the incubation medium. Erythrocytes pretreated with the same molar concn of GM2, GD1a, GD1b or GT1b were bound to AM phi to the same degree reaching a maximum of about 90% rosette forming cells. A mean of 17.8% AM phi-bound GM3-coated E. Treatment of E with asialo-GM2 (GA2) or GM1 did not induce significant rosette formation. A dose-dependent inhibition of rosette formation was observed when AM phi were preincubated at 0 degree C with GM2, GM3, GD1a, GD1b or GT1b, but not with GM1 or GA2 Of the tested carbohydrates, sialyl-lactose had a strong inhibitory effect, while lactose was completely ineffective. N-acetyl-neuraminic acid, N-glycolyl-neuraminic acid and N-acetyl-galactosamine were slightly inhibitory. A series of other carbohydrates including highly negatively charged compounds, as well as fibronectin, IgG or C3b-like C3 did not show significant inhibition. Our data indicate the expression of a receptor on rat AM phi recognizing carbohydrates containing sialic acid at or near the non-reducing terminus.

Animals↗
PubMed1984

Macrophages as regulatory cells in mitogen induced spleen cell proliferation. 1. Macrophages as suppressor cells.

In this study the effect of alveolar (AC) or peritoneal (PC) lavage cells from Lewis rats on the mitogen induced proliferation of syngeneic spleen cells was investigated. When total spleen cells were stimulated with PHA (5 micrograms/ml) or ConA (6 micrograms/ml), the addition of AC or PC and of their adherent (A) or non-adherent (NA) fractions had dose dependent suppressive effects. After passing the spleen cells through a Sephadex G-10 column, the eluted cells responded poorly to the mitogens. Addition of low numbers (2 X 10(3) = 1%) AC or NA-AC improved this response, whereas higher concentrations (5 or 10%) of these cells or any concentration of A-AC, PC, A-PC or NA-PC showed either none or a suppressive effect. The cells which strongly suppress mitogen induced lymphocyte proliferation have macrophage morphology, are adherent, esterase positive, bear Fc receptor for IgG and bind ganglioside coated erythrocytes. NA-AC were further separated into Ia-depleted (Ia-) and Ia-enriched (Ia+) population. The Ia+ fraction contained 80 to 90% Ia bearing cells, supported the mitogen induced stimulation of Sephadex G-10 depleted spleen cells and was ineffective in suppression. Interestingly, these cells did not bind ganglioside treated sheep erythrocytes. On the other hand, the Ia-negative NA-AC fraction and particularly the A-AC population strongly expressed the "ganglioside receptor" as well as typical macrophage markers like Fc receptors, latex-phagocytosis and non-specific esterase. Therefore, the "ganglioside receptor" may be a useful marker to define suppressor macrophages.

Animals↗
PubMedDate not supplied

Quality of life after orthotopic heart transplantation.

During the last decade heart transplantation has become the chosen method to treat terminally ill patients suffering from severe cardiac illness. It was the aim of our study to retrospectively survey life quality of donor organ recipients who underwent heart transplantation during the first years of transplantation at our center (1984 through 1987). Thirty-five patients were asked to evaluate their postoperative improvement or deterioration and their satisfaction with the level reached on visual scales. Life quality was defined in nine areas: physical, emotional, mental, vocational, and sexual status, financial situation, leisure activities, partnership, and overall life quality. The following results were obtained: (1) our former patients informed us about a distinct improvement in almost all dimensions (except financial situation). We found an absolute increase in life quality after heart transplantation. (2) Although improvement was ranked best for physical status, there was also a high amelioration in psychosocial fields. (3) A significant difference was seen between changes in condition and satisfaction in the financial situation (z = 2.3) and in partnership (z = 2.9), in which the latter was ranked higher. (4) The date of transplantation (less/more than 2 years ago) had no influence on the evaluation of postoperative life quality.

Adult↗
PubMedDate not supplied

Impacts of low-dose steroids and prophylactic monoclonal versus polyclonal antibodies on acute rejection in cyclosporine- and azathioprine-immunosuppressed cardiac allografts.

The ideal combination of immunosuppressants after heart transplantation that safely prevents graft rejection and maintains a low rate of infections and toxic side effects is still a topic of discussion. Between March 1984 and March 1988, 76 patients underwent orthotopic heart transplantation. Sixty-five patients received either double-drug (cyclosporine + azathioprine) or triple-drug (cyclosporine + azathioprine + steroids) maintenance therapy. In addition all patients with double-drug protocol (group 1, n = 13) and the majority with triple-drug protocol (group 2, n = 39) received prophylactic antithymocyte globulin (ATG); 13 patients with triple-drug protocol (group 3) received prophylactic monoclonal antibody (murine antihuman mature T cell [OKT3]). Recipients with perioperative or intraoperative deaths, maintenance protocol without cyclosporine, or previous total artificial heart bridge were excluded from the study. Cyclosporine was given in low doses according to a trough whole blood high-performance liquid chromatography target level of 200 to 400 ng/ml in the first month, 150 to 250 ng/ml from the second to sixth month, and 100 to 150 ng/ml after the sixth month. Azathioprine dose was adjusted to a leukocyte count of approximately 4,000 cells/mm3. In patients with triple-drug protocol, prednisolone (0.2 mg/kg/day) was added. The mean follow-up (group 1, 12.75 months; group 2, 12.84 months) was comparable between the groups who received ATG perioperatively. The mean follow-up for group 3 was 3.46 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗