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Biomedical subjects

U Fink

Publications and source records attributed to U Fink.

At least 217 records · Page 12Linked to original sources

Enrichment of MLR-activated human suppressor cells by discontinuous density-gradient centrifugation.

6-day allogeneic mixed lymphocyte cultures (MLR) were fractionated on a four-step discontinuous Percoll gradient. The various fractions were added as regulatory cells to freshly established micro-MLRs between the original or third-party cell donors. Unspecific suppressor activity was highly enriched in gradient fraction III (density 1.069--1.062 g/ml), consisting mainly of blast-like cells. Suppressor cells were non-adherent T cells as determined by their spontaneous rosette formation with sheep erythrocytes and their susceptibility to lysis by anti-T-cell globulin plus complement. Mitomycin C treatment diminished their inhibitory capacity. In addition, gradient fraction III was also enriched with alloantigen-activated memory cells. By contrast, unprimed alloreactive cells were recovered from gradient fraction IV (density greater than or equal to 1.070 g/ml), consisting mainly of small, resting lymphocytes.

Adult↗

Isolation of T lymphocytes in chronic lymphocytic leukaemia by depletion of mouse rosette-forming cells.

Separation of mouse rosette-forming cells (MRFC) was used as a technique to isolate T lymphocytes in patients with chronic lymphocytic leukaemia. The resulting interface fraction (non-MRFC) was highly enriched for sheep rosette-forming T cells (mean value 71.8% SRFC) as compared with unfractionated peripheral blood lymphocytes (mean value 18% SRFC). A higher degree of T-cell purity was achieved by this method than by the sheep rosette sedimentation technique in patients with leucocyte counts greater than 50 X 10(9)/l. Functional tests revealed that depletion of MRFC increased not only phytohaemagglutinin and mixed lymphocyte culture (MLC) reactivity but also the stimulatory capacity in the allogeneic MLC. In contrast, separation of MRFC in normal blood donors gave only a poor degree of separation and was not an effective means to isolate lymphocyte subpopulations.

Animals↗

The role of adherent HLA-DR+ mononuclear cells in autologous and allogeneic MLR.

The aim of this study was to define the significance of HLA-DR+ cells for the in vitro induction of human autoreactive T cell proliferation. Proliferation was induced by autologous or allogeneic non-T cells or EB virus-transformed LCL. Pretreatment of stimulator cells with low concentrations of RAHLA-DR and C and with high amounts of RAHLA-DR alone abolished the capacity to stimulate autologous or allogeneic T cells. This suggested that antigens associated with HLA-DR+ stimulator cells or HLA-DR itself are involved in the induction of this proliferation. At the responder cell level the cytotoxic elimination of HLA-DR+ cells as well as depletion of adherent cells by passage through Sephadex G-10 columns reduced both autoreactive and alloreactive responsiveness. Responses of serologically and physically depleted populations were both restored by reconstitution with mitomycin-C treated autologous adherent cells. These cells were resistant to lysis with T cell specific antibodies and preferentially cooperated with T cells of autologous deprivation. Co-cultivation experiments further revealed that such accessory cells were capable of amplifying T cell proliferation in the presence of suboptimal numbers of autologous LCL. We concluded, therefore, that an HLA-DR+-adherent cell, presumably of monocytic origin, is required for optimal proliferative responsiveness of both autoreactive and alloreactive T cells.

Animals↗

Inhibition by alkyl-lysophospholipids of tritiated thymidine uptake in cells of human malignant urologic tumors.

Alkyl-lysophospholipids (ALP) inhibited the uptake of [3H]thymidine by cells from a variety of human urologic tumors in vitro. Cells of prostate carcinomas, a seminoma, various bladder carcinomas and teratocarcinomas showed proliferation rates that were 10% of those of the controls when incubated with some ALP for longer than 24 hours. Concentrations as low as 1 microgram ALP/ml medium (10(6) tumor cells) were effective. Antitumor action increased after incubation for 2-5 days. Morphologic studies showed tumor cell death after incubation periods of this length. Equivalent concentrations of conventional cytostatic drugs used in anticancer chemotherapy protocols did not cause greater inhibition of [3H]thymidine uptake by tumor cells in vitro. Human embryonic fibroblasts were not sensitive to ALP, whereas cytostatic drugs completely inhibited their proliferation at comparable doses.

Cell Division↗

Anti-tumor action of alkyl-lysophospholipids (Review).

Alkyl-lysophospholipids (ALP) are synthetic analogs of the naturally occurring 2-lysophosphatidylcholine. Some of these compounds show significant prophylactic and therapeutic activity against the growth of various allogeneic and syngeneic mouse tumors. Furthermore, they reproducibly inhibit the development of metastases of Lewis lung carcinoma in syngeneic mice. The antitumor action of ALP is mediated by an induction of cytotoxic macrophages and by a direct, selective destruction of neoplastic cells. Among other possible mechanisms, both phenomena might be based on a disturbance of the phospholipid metabolism in the tumor cell membrane, due to a lack of a 1-0-alkyl cleavage enzyme. In preliminary studies, ALP revealed only limited toxicity.

Animals↗

[Sonographic determination of thyroid volume. Comparison with other methods (author's transl)].

Using ultrasound it is possible to determine the thyroid volume with a maximal error of 12%. The method is based on the electronic planimetry of a sequence of transverse ultrasound scans of the thyroid. Following this, the "slices" are added using a small computer. On 101 patients five commonly used methods of volume determination were compared with this reference technique. The volume estimation by palpation and interpretation of the scintigram as well as the volume calculation from the scintigram area or from an ellipsoid model gave maximal errors between plus or minus 82% and plus or minus 90%. The combination of scintigram area or scintigraphically determined length and width of a single thyroid lobe and the sonographically measured thickness reduced the maximal error to plus or minus 35% and plus or minus 37%. In 10 patients teh reproducibility of the reference technique was excellent and the absolute maximal error was 4.6%, even when the patients were differently positioned.

Adolescent↗

[Functional scintigraphy of pulmonary ventilation with 133Xe in juvenile scoliosis (author's transl)].

Twenty children with severe scoliosis underwent spirometry, chest X-ray and 133Xe ventilation studies before surgical correction by the Harrington operation. By means of functional scintigraphy the relative distribution of the functional residual capacity (FRC) and the wash-out curves (3-min-retention without background correction, mean time constant, effectivity index after background correction) were analysed quantitatively. The chest X-ray and the single-breath-phase of the ventilation study remained mostly unchanged, whereas the shifting of the FRC distribution towards the lung of the concave side indicated in all cases a regional ventilation restriction of the convex side. In addition the analysis of the wash-out curves showed a regional impairment of the alveolar ventilation of the convex side which exceeded the shifting of FRC distribution. Even in the cases with normal spirometric values all scintigraphic parameters were slightly pathological, probably due to the decreased lung function caused by the scoliosis. The effectivity index taking into account the respiration frequency, the tidal volume, the FRC and the dead space, was found to be the most accurate and sensitive parameter for the evaluation of regional ventilation impairment.

Adolescent↗

Growth inhibition of malignant hypernephroma cells by autologous lysophospholipid incubated macrophages obtained by a new method.

In order to obtain pure human macrophages, mononuclear cells from peripheral blood were cultured on teflon membranes and the non-adherent lymphocytes removed. After 24 hours, all remaining adherent cells were detached from the membranes with 100% viability. They showed all the morphological and cytochemical characteristics of human monocytes. Within 10 days of cultivation they differentiated into monolayers of pure macrophages. Untreated macrophages of this origin showed only limited cytostatic effects on autologous hypernephroma cells in vitro. After preincubation with different alkyl-lysophospholipids they revealed a tumor growth inhibition capability of up to 90%.

Adenocarcinoma↗

[Primary amyloidosis with nephrotic syndrome: 5 year follow-up under polychemotherapy. A case report (author's transl)].

A patient with primary amyloidosis had infiltration of liver, bone and bone marrow and a nephrotic syndrome with massive proteinuria. In addition, there was evidence for a plasma cell dyscrasia with an increased number of plasma cells and other lymphoreticular cell elements in the bone marrow and an impairment of immunoglobulin synthesis without M-gradient. The course of disease was observed over a period of five years. The patient was treated intermittently with a combination of penicillamine, melphalan, fluocortolone and fluoxymesterone. Under treatment the nephrotic syndrome disappeared and liver size decreased. Hemopoiesis remained sufficient but bone marrow infiltration by amyloid did not respond to therapy and massive osteoporosis developed. Comparison of our with other reported cases treated with the same regime suggests that response to this treatment may be influenced by factors such as sex and clinical manifestation of the disease.

Amyloidosis↗

[CT for staging of systemic lymphatic diseases (author's transl)].

In 75 patients with lymphoma (46 Hodgkin's disease, 29 non-Hodgkin lymphomas) computed tomography was performed in order to detect neoplastic invasion of the abdominal organs (55 new cases) or to control the results of treatment (20 cases). In 30 cases enlarged retroperitoneal or mesenteric lymphnodes and/or liver or spleen enlargement were found. Neoplastic involvement of lymphnodes without enlargement was missed in two cases. CT failed also to demonstrate microscopic malignant invasion of liver and spleen. The false-negative rate in our series was 10.9%. Computed tomography is a non-invasive method which is very well suited for staging malignant lymphoma.

Hepatomegaly↗

[Chronic septic granulomatosis imitating exogenic allergic alveolitis (farmer's lung)].

A 17-year-old boy demonstrated clinical and immunological signs of exogenic allergic alveolitis (farmer's lung). The patient grew up in the country and suffered from recurrent "pneumonia." In his serum precipitins were detected against Micropolyspora faeni, Aspergillus fumigatus and hay. Transbronchially obtained lung tissue showed histologically an inflammation of the epitheloid-cell-granulomatous type with fibrosis. A congenital defect of the neutrophilic function was suspected in view of the recurrent infections with significant polyclonal hypergammaglobulinemia, accompanied by leucocytosis and neutrophilia. In vitro studies of isolated patient's neutrophils showed that he suffered from chronic granulomatous disease. CGD should be considered in adolescents and adults with a history of severe infections and unexplained pulmonary fibrosis or pulmonary fibrosis simulating exogen allergic alveolitis.

Adolescent↗

[Simultaneous occurrence of pure red cell aplasia and malignant lymphoma (author's transl)].

A case report will be given about a patient, in whom a pure red cell aplasia preceded an IgM paraprotein-aemia and the clinical manifestations of a malignant B-cell lymphoma. The discussion deals with the question of a fortituous occurrence of two different diseases or of a common pathogenetic mechanism by which the PRCA could be considered as a paraneoplastic manifestation of an immunoproliferative disease.

Anemia, Aplastic↗

K cell activity of normal and chronic lymphocytic leukaemia lymphocytes: association with lymphocytes bearing receptors for human C3b.

Blood lymphocytes of patients with chronic lymphocytic leukaemia (CLL) and of normal individuals were depleted of EAC3b- or EAC3d-rosette-forming cells (RFC), respectively and assayed for K-cell activity in a system measuring antibody-dependent-cell-mediated cytotoxicity (ADCC). K-cell activity was found to be associated with a cell population bearing receptors for C3b.

Antibody-Dependent Cell Cytotoxicity↗