Biomedical subjects

C Wiltschke

Publications and source records attributed to C Wiltschke.

48 records · Page 3Linked to original sources

PubMed1994

[Emergency intubation with the Combitube in a patient with persistent vomiting].

Prompt establishment of a patient airway and effective ventilation are the major goals during initiation of cardiopulmonary resuscitation in patients with cardiac arrest. Endotracheal intubation is the definitive method to maintain an optimal airway. However, endotracheal intubation is not always possible, even for the skilled physician. The Combitube has been developed to overcome this disadvantage. Studies have proved the effectivity of ventilation with this device. A case is reported where a patient suffered from acute respiratory failure and attempts at endotracheal intubation failed due to continued vomiting rendering fibre-optical visualisation of the vocal cords impossible. Blind insertion of the Combitube led to successful ventilation, and hence replacement by an endotracheal airway could be performed without danger of aspiration.

Adult↗

PubMed1993

IL-1 alpha induced, TNF alpha mediated HLA class II (DR) antigen up-regulation in a human ductal breast carcinoma cell line ZR-75-1.

The IL-1 alpha induced up-regulation of HLA class I and HLA class II (DR) antigen expression on the cell surface of the human breast cancer cell line ZR-75-1 was demonstrated. This was associated with a concomitant increase in TNF alpha production. Coincubation with an anti-TNF alpha neutralizing antibody partially inhibited the IL-1 alpha induced up-regulation of HLA DR antigen but had no effect on IL-1 alpha induced HLA class I up-regulation. These data indicate that IL-1 alpha induced HLA class II (DR) antigen up-regulation in ZR-75-1 cells is partially mediated by TNF alpha and that IL-1 alpha induced HLA class I and class II (DR) antigen up-regulation in ZR-75-1 human breast cancer cells in vitro are mediated by different mechanisms.

Breast Neoplasms↗

PubMed1992

A phase II trial of 5-fluorouracil, leucovorin, and recombinant alpha-2b-interferon in advanced adenocarcinoma of the pancreas.

BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.

Adenocarcinoma↗

PubMed1992

Cytokine (IFN-alpha, IFN-gamma, IL-1-alpha, TNF-alpha)-induced modulation of HLA cell surface expression in human breast cancer cell lines.

Cytokine-induced modulation of HLA expression on the cell surface of four human breast cancer cell lines was determined by continuous flow immunocytofluorometry with the aid of monoclonal antibodies directed to a non-polymorphic determinant of HLA class I and class II (DR) antigen. IFN-gamma and IFN-alpha were potent inducers of HLA class I in all examined cell lines, with decreasing inducibility as follows: BT-20, ZR-75-1, MCF-7 and MDA-MB-468 cells. HLA class II (DR) antigen was highly inducible by IFN-gamma in ZR-75-1 cells, followed by BT-20, MDA-MB-468 and MCF-7 cells. IFN-alpha increased the cell surface expression of DR antigen only in ZR-75-1 cells. IL-1-alpha induced a moderate level of HLA class I antigen in ZR-75-1, BT-20 and MDA-MB-468 cells, and HLA class II (DR) expression only in ZR-75-1 cells. This pattern of cell line inducibility by IL-1-alpha was similar to that induced by TNF-alpha. Differences in inducibility of HLA antigens on human breast cancer cell lines induced by different cytokines may reflect the differences in cytokine inducibility of the original tumor cells.

Breast Neoplasms↗

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

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↗

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↗

PubMedDate not supplied

Arterial hepatic embolization of unresectable hepatocellular carcinoma using a cyanoacrylate/lipiodol mixture.

PURPOSE: A survival analysis in 16 patients with unresectable hepatocellular carcinoma (HCC) undergoing transcatheter arterial embolization (TAE) using a combination of lipiodol and N-butyl-2-cyanoacrylate (5:1) was performed in a retrospective study. METHODS: A combination of lipiodol and N-butyl-2-cyanoacrylate (5:1) was used for TAE. All patients had disease compatible with Okuda stages I and II. RESULTS: Twenty-four embolizations were done; five patients had more than one embolization. Median alpha-fetoprotein levels declined from 116 to 48.6 ng/ml. A median of 0.3 ml cyanoacrylate was administered per patient. Median survival was 8.5 months (range 2-49 months). After a median follow-up of 4 years, 12 patients have died (75%). Okuda stage I and II patients had a median survival time of 34.4 and 5.5 months respectively. Few side effects (19%) were seen. CONCLUSION: We conclude that the TAE procedure used [lipiodol and N-butyl-2-cyanoacrylate (5:1)] is safe and produced only few side effects, thus constituting a valuable therapeutic option for patients with Okuda stage I and II HCC.

Aged↗

PubMedDate not supplied

Tissue expression and serum levels of HER-2/neu in patients with breast cancer.

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.

Biomarkers, Tumor↗