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Biomedical subjects

U Fink

Publications and source records attributed to U Fink.

At least 199 records · Page 11Linked to original sources

Cytotoxicity of thioether-lysophospholipids in leukemias and tumors of human origin.

Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning electron microscopy revealed severe membrane destruction after incubation with thioether-lysophospholipids. Cytostatic and cytotoxic effects of thioether-lysophospholipids were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with greater than or equal to 5 micrograms/ml after an incubation of greater than or equal to 48 hr, but 10 to 20 micrograms/ml were necessary in solid tumors. Ester-linked 2-lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety in SN1 of the molecule for the antineoplastic properties of lysophospholipid analogues.

Adenocarcinoma↗

[Comparison of conventional radiology, ultrasound and computer tomography in the preoperative localization of intraocular foreign bodies].

Three methods complementing each other are available for the preoperative intraocular localisation of foreign bodies. Basing on the results obtained, it is recommended, first of all, to localise the site of the foreign body by means of conventional x-ray film, followed by fine diagnosis via ultrasound and, finally, in problematic or doubtful cases, by means of computed tomography.

Diagnosis, Differential↗

[Results of serial CT in the evaluation of the sellar region].

The article reports on the methodology and results of serial CT in differential diagnosis of intrasellar and parasellar structures, based on 32 examinations. Whereas the normal pituitary gland displays an approximately equal contrast medium performance as the pituitary adenomas and recurrent tumours, different types of tissue such as those of tumours, vascular structures and postoperative scans can be well differentiated from each other by means of serial CT. Aneurysms can be safely differentiated from intracranial tumours, such as meningiomas, only via serial CT.

Adenoma↗

Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells.

Alkyl-lysophospholipids (ALP) and related derivatives inhibited the in vitro incorporation of [3H]thymidine into seven different permanent cell lines derived from rat brain tumors. The cytostatic effect of ALP was dependent on dosage and incubation time. Naturally occurring 2-lysophosphatidylcholine did not exhibit cytostatic effects; under these conditions, the incorporation rates of [3H]thymidine were generally more than 100% of the controls. The trypan blue dye exclusion test, which was used to assess severe cell damage, correlated with the extent that [3H]thymidine incorporation was inhibited by ALP. Preincubation of ALP (rac-1-octadecyl-lyso-glycero-3-phosphocholine) for more than 8 min with a tetrahydropteridine-dependent O-alkyl cleavage enzyme preparation from rat liver microsomes destroyed almost all of the cytotoxic properties of ALP when tested at a concentration that previously inhibited tumor growth by more than 50%. [3H]Thymidine incorporation rates were greater than 100% for astrocytoma cells incubated with ALP after exposure to the alkyl cleavage enzyme. Comparison of the microsomal activities of the tetrahydropteridine-dependent alkyl-cleavage enzyme present in astrocytoma 78-FR-G-299 cells and the pleomorphic glioma 78-FR-G-219/S4 cells to that found in normal skin fibroblasts and rat livers revealed a markedly reduced activity in the neoplastic cell lines. Moreover, those tumor cells that were more resistant to ALP cytotoxicity (pleomorphic glioma, 78-FR-G-219/S4) had a 3-fold higher tetrahydropteridine-dependent cleavage activity than a more cytotoxic sensitive line (astrocytoma cells, 78-FR-G-299). Our results indicate that the low-alkyl-cleavage enzyme activities in these neoplastic cells in comparison to normal cells might be a factor in explaining the relatively high cytotoxicity of ALP in tumor cells.

Animals↗

Early tumor and leukemia response to alkyllysophospholipids in a phase I study.

In a phase I study on the toxicity and toleration of alkyllysophospholipids, tumor and leukemia responses have been noted in the first treated patients. Six patients with solid malignomas of different histologic types and one patient with acute myeloid leukemia are evaluable so far. All of them suffered from metastatic or wide-spread disease, were refractory to adequate polychemotherapy or other treatment modalities, or have been found untreatable because of poor general condition. Four cases revealed objective tumor and leukemia response with a minor response in a hypernephroma, two partial remissions in nonsmall cell bronchogenic carcinomas and reduction of leukemic blasts to less than 10% in acute myeloid leukemia. Limiting toxicity started with doses of 20 mg/kg given daily showing transient injury of renal and liver functions.

Adolescent↗

Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants adsorbed to antigen-presenting cells during rosette formation with sheep erythrocytes.

We present evidence that most T cells proliferating in response to autologous sheep erythrocyte (SRBC)-separated non-T cells (NT) cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations. First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. Because this weak proliferation could not be expanded in restimulation experiments, its significance as an immune recognitive event remains questionable. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or fetal calf serum. Second, restimulation of T memory cells generated in 1 degree autologous mixed lymphocyte reaction (AMLR) against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Third, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells that had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results that indicated an absolute requirement of HLA-DR+-adherent NT cells (8), we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response that is genetically restricted by the HLA-DR type of the antigen-presenting cell.

Animals↗

Response of acute myelomonocytic leukemia to alkyl-lysophospholipids. A case report.

Acute myelomonocytic leukemia refractory to treatment with daunomycin, cytosin arabinoside and thioguanine morphologically and clinically responded twice to therapy with alkyl-lysophospholipids (ALP). Beginning 48 h after treatment leukemic cells developed large vacuoles in cytoplasm and nucleus which disrupted the continuity of the cell membranes. Normal hematopoietic cells remained morphologically unchanged. Within 14 days of first ALP treatment leukemic cells in peripheral blood were reduced to less than 10%, but normal hematopoiesis recovered under therapy with an increase of granulocytes.

Adolescent↗

Protein synthesis in the blood lymphocytes of chronic lymphocytic leukemia and its relationship to prognosis.

Protein synthesis primed by endogenous messenger RNA (mRNA) as well as polyuridylic acid-[poly (U)] directed polyphenylalanine synthesis was measured in extracts of blood lymphocytes from a series of 50 chronic lymphocytic leukemia (CLL) patients and compared with the prognostic stage. Patients were clinically classified according to the new international workshop classification [4]. There were 23 patients at stage A, 14 at stage B and 13 at stage C. Extracts from patients of the high risk group (stage C), defined by anemia and/or thrombocytopenia, exhibited a significantly higher poly (U)-translation activity than extracts from low and intermediate risk patients-stages A and B--(P less than 0.01). This finding has a sensitivity of 62% but a specificity of 100%. During follow-up, an increase of poly (U)-translation and endogenous protein synthesis was observed after changing from stages A or B to stage C. Activity of protein synthesis could neither be correlated with proliferation activity, as measured by lymphocyte doubling time, nor with the expression of immunologic surface markers, nor with serum immunoglobulin (Ig) levels.

Acute Disease↗

Alloantigen-induced suppressor- and memory cells in chronic lymphocytic leukemia.

T cell function was evaluated in patients with B cell type of chronic lymphocytic leukemia (CLL). Unseparated peripheral blood lymphocytes (PBL) and T cells from CLL patients stimulated in a primary allogeneic MLR were able to inhibit significantly a second MLR between the original responder (CLL) and stimulator (normal PBL) cell donors. Furthermore, it is shown the T lymphocytes from patients with CLL develop immunologic memory during the course of a primary MLR as evidenced by an enhanced response in secondary MLR. These results are discussed with respect to recently described imbalances of T cell subpopulations in CLL.

B-Lymphocytes↗

Purification of human monocytes by adherence to polymeric fluorocarbon. Characterization of the monocyte-enriched cell fraction.

Human mononuclear cells were obtained from peripheral blood by density gradients. Monocytes can be purified after cultivation of 2 hours by a modified adherence procedure on membranes of gas-permeable polymeric fluorocarbon (teflon). After further cultivation of 24-48 hours, monocyte-enriched cell fraction can be easily detached from the membranes with a viability greater than 98% and a final cell yield of approximately 50% of the peripheral monocyte count. The cells showed the morphological and cytochemical characteristics of human monocytes and differentiated into dense monolayers of macrophages within 10 days of cultivation. Immune-autoradiography with iodine-125-labelled xenogeneic antimonocytic antisera and staining with several monoclonal antisera in an indirect immunofluorescence technique revealed up to 92% of these cells to carry monocytic characteristics. To show their functional integrity, monocytes obtained by this procedure were activated by 48 hours' cultivation with synthetic alkyl-lysophospholipids to inhibit the proliferation of autologous tumor cells.

Autoradiography↗

[Head and neck cancers. What's new in clinical oncology for the practicing ENT physician?].

An interdisciplinary evaluation is made of the most common forms of head and neck cancer, with emphasis on certain aspects.--In the field of x-ray diagnostics, computed tomography dominates varying importance being given to the individual organs. Nuclear medicine pays particular attention to skeletal scintigraphy and gallium scintigraphy. In radiation therapy, progress has been made especially through the use of optimal radiation planning as well as the use of the after-loading technique and neutron radiation. Antineoplastic chemotherapy is currently being used as palliative treatment, adjuvant chemotherapy and as the first step towards a curative therapy.

Antineoplastic Agents↗

[Skin metastasis of a teratocarcinoma].

Various tumors develop skin metastasis with a variable incidence. Skin metastasis is rare in teratocarcinoma of the testis [1]. This report deals with a case history in which a teratocarcinoma developed metastasis in the skin of the face and head.

Adult↗

Alkyl-lysophospholipids inhibit the growth of hypernephroid carcinomas in vitro.

Synthetic alkyl-lysophospholipids (ALPs) inhibit the proliferation of human hypernephromas in vitro. Cells of ten different tumors were incubated with 4 ALPs for periods of more than 24h. Eight of ten cell lines showed proliferation rates below 1% of the controls after cultivation. One microgram of ALPs per 10(6) tumor cells was effective, in some experiments a dose response relation was found for even lower concentrations. Equivalent concentrations of cytostatic drugs did not show reproducible higher antitumor effects in vitro. In two of the tested cell lines ALPs did not show any reproducible tumor growth inhibition, whereas at least some of the cytostatic drugs revealed slight cytostatis.

Adenocarcinoma↗