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Biomedical subjects

F Porzsolt

Publications and source records attributed to F Porzsolt.

At least 109 records · Page 6Linked to original sources

Hematopoietic colony formation after allogeneic bone marrow transplantation: enhancement by cyclosporin A and anti-gamma-(immune) interferon antiserum in vitro.

Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow target with cyclosporin A (CyA; 0.5 microgram/ml) or with a monoclonal anti-gamma-(immune) interferon (IFN-gamma) antibody. Both effects were highly correlated. The data indicate that (a) endogenous elaboration of IFN-gamma may contribute to decreased colony formation in allogeneic bone marrow transplant recipients, and (b) CyA may induce a gradual release of the progenitor cell pool from IFN-gamma-mediated suppression.

Antibodies, Monoclonal↗

Platelet-adjusted IFN dosage in the treatment of advanced hairy cell leukemia.

It has been demonstrated that hairy cell leukemia (HCL) can be efficiently treated by various preparations of alpha interferons (IFN). Nevertheless, there are several open questions, such as the route, mode and dosage of IFN application. These variables of IFN treatment may be critical since a myelosuppressive effect of IFN, which is commonly seen in the initial phase of treatment, can result in further deterioration of the already impaired platelet production in advanced HCL. The present study shows that serious side effects can be avoided and the flu-like syndromes described by others almost completely reduced by s.c. application of IFN via a portable pump during a daily 8 h period. IFN is initially given five times a week and the daily dose is adjusted according to the actual platelet count. The efficiency controls show that the increase of platelets in the peripheral blood, which is most critical in advanced HCL, may be seen earlier by this than by other protocols, which usually recommend higher daily doses of IFN and only three instead of five weekly applications.

Adult↗

Impaired natural killer cell function in hemophiliacs with or without continuous substitution.

In the present study, 28 hemophiliacs substituted continuously and 5 hemophiliacs who had received almost no blood products were investigated. Cells of OKT 3+, OKT 4+, and OKT 8+ subsets were counted. Percoll separated fractions of peripheral blood mononuclear cells were examined by morphological criteria and were tested for NK cell activity. We found that the NK cell activity of both groups of hemophiliacs was decreased on testing Ficoll separated cells or low density Percoll separated cells. Normal NK cell activity was found in medium density cells of hemophiliacs. Two possible explanations are discussed: first, the NK cell activity may be suppressed in hemophiliacs and secondly, there may be a block in maturation of NK cell activity. It is unlikely that chronic substitution by blood products counts for these alterations. The possible role of chronic infections is discussed.

Acquired Immunodeficiency Syndrome↗

The relationship of lytic effects against autologous and allogeneic PHA blasts induced in human mixed lymphocyte cultures.

In addition to the cytotoxic T lymphocytes (CTL) killer cells which lyse autologous PHA lymphoblasts are also generated in mixed lymphocyte cultures (MLC). By modifying various tissue culture conditions, we demonstrate that the generation of allospecific effectors can be reduced but not the lytic activity against autologous PHA lymphoblasts. Cold target inhibition experiments showed a cross reaction between autologous and allogeneic PHA lymphoblasts. No inhibition was seen with fresh lymphocytes. It seems, therefore, that the measured lytic activity of specific CTL generated in a MLC is in fact partially mediated by cytotoxic cells which kill also autologous PHA lymphoblasts.

Cytotoxicity, Immunologic↗

Variations in the susceptibility to lysis of NK target cells.

Natural killer (NK) cell activity varied considerably from one subject to another and in the same subject tested on different occasions. In addition to the interindividual variations, considerable variation was also found in the susceptibility to lysis of cultured target cell lines. In this report it is shown that the susceptibility to lysis of NK target cells depends on the growth phase of these cells but is independent of the cell cycle. These results may be important for interpreting NK cell data, may have some implications for transplantation experiments in animals using cultured tumor cells and are in agreement with the data describing the sensitivity of tumor cells to radiation or chemotherapy.

Adult↗

The evaluation of serial measurements of the NK cell activity in man.

Studies on the NK cell activity require extensive controls because it is known that a series of variables can influence both the quality of effector cells and of target cells. This known variation of the susceptibility to lysis in one target cell line or even in sublines requires "standards", if separately performed experiments should be compared. In some laboratories, the experiments have been controlled for the variation of the target cell's susceptibility to lysis; others control for the differences of NK cell activities among subjects or for the variation of the NK cell activity in individuals from day to day. Each of these methods concentrates the main point of control to a particular variable. To demonstrate the power of several variables in relation to an induced and expected variation of the NK cell activity, we describe in this paper the results of a factorial analysis of variance testing PB-MNC from healthy donors against two target cells. The in vitro treatment of PB-MNC by IFN was chosen as induced variation of NK cell activity. As variables of the system, we defined subjects, days, target cells, and the effect of IFN. It is shown that the induced variable (IFN-treatment) counts for the most powerful variance component (32% of the total variance). Other large variance components are the differences of NK cell activities among subjects (20%), the day to day variation of the subjects' NK cell activities (13%), and the day to day variation of the susceptibility of target cells to lysis (13%). Since it is almost impossible to control for all variables in an experiment, some variables have to be selected which should be controlled for. The quantification of the variables, which is possible by a factorial analysis of variance, is useful for that purpose. This method of data analysis allows to estimate further the relevance of a particular expected effect if several variables, as in NK cell tests, influence the result of the experiment.

Adult↗

Modulation of natural killer activity by aspirin: I. In vitro effect of aspirin.

It has been previously shown that the Natural Killer (NK) cell activity of peripheral blood mononuclear cells (NMC) from healthy donors can be augmented by in vitro coculture of MNC with melanoma cells. This augmentation was not seen when the blood donors had taken acetylsalicylic acid (ASA) 12 h before venipuncture. To examine the direct action of ASA on the NK cell activity we treated MNC in vitro by ASA and tested the cytotoxic activity on NK-sensitive target cells. Neither the spontaneous NK cell activity nor the in vitro stimulation of NK cell activity by beta-interferon (IFN) was influenced by ASA treatment in vitro.

Aspirin↗

Impaired T-cell and NK-cell function in patients with preleukemia.

The responses to the T-cell mitogens Phythemagglutinin (PHA) and Concanavalin A (Con A) and the natural killer (NK) cell activity are tested in patients with preleukemia (PL). The results are compared with those of healthy controls. The PL patients show low responses to T-cell mitogens and low NK cell activities. It is discussed that the data are not of prognostic value in PL as to development of overt leukemia. However, the results suggest that PL impaired cell functions are not limited to erythropoiesis, granulopoiesis, and thrombopoiesis but are also found in the immune system.

Adolescent↗

Stimulation of human NK cell activity by cultured cells. II Ingestion of aspirin by blood donors suppresses induced NK activity.

Incubation of mononuclear cells with a melanoma tumour cell. M4, induces a rapid increase in NK cell activity in both normal and tumour patient cells. A marked individual variation among the patient population can be attributed to the prior ingestion of aspirin. Single therapeutic doses of aspirin (two tablets, 660 mg) taken 12 hr prior to donation of the blood sample cause an 80-100% reduction in the NK cell activity induced by M4. Since many patients coming to cancer clinics take aspirin regularly, it is essential that they be questioned about their recent usage of this drug if their cells are to be used in assays for NK activity.

Antibody-Dependent Cell Cytotoxicity↗

Measurement of cell mediated cytotoxicity by post-labeling surviving target cells.

The 51Cr release assay (CRA) is the commonly accepted technique for measurement of cell mediated cytotoxicity. This assay shows some disadvantages when mononucleated cells of human peripheral blood (MNC) are used as effector and target cells. The uptake of 51Cr by PHA stimulated lymphocytes is low compared to the spontaneous release. In an attempt to develop a cytotoxicity assay suitable for human lymphocytes we used 14C-TdR to label target cells surviving after contact with effector cells. Cytotoxic lymphocytes were generated by incubation of MNC with irradiated allogeneic MNC for 6 days. On day 6 the effector cells are irradiated and co-cultured with PHA stimulated target cells. Twenty-four hours later 14C-TdR is added. After an additional 24 h the cultures are harvested and 14C-TdR taken up by target cells is measured. It is shown that the effector cells are still cytotoxic after irradiation. These cells do not take up 14C-TdR. Cell-free supernatants do not influence the uptake of 14C-TdR by target cells. The results obtained with this assay correlate very well with those obtained by the CRA, if the spontaneous release does not exceed 30%.

Adult↗

Stimulation of human NK-cell activity by cultured cells. I. Response of normals.

Natural cell-mediated cytotoxicity, observed on co-cultivation of peripheral blood lymphocytes (PBL) with malignant melanoma tumor cells (M4), is described. The activity was inhibited when PBL were cultured in autologous serum. Studies using competitive inhibition with cold targets and stimulation of PBL with other tumor cell lines failed to detect specificity.

Cell Line↗