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I Blazsek

Publications and source records attributed to I Blazsek.

At least 37 records · Page 2Linked to original sources
PubMed1986

From experimental to clinical attempts in immunorestoration with bestatin and zinc.

Severe impairment of the lymphopoietic cell renewal system is an important etiological factor of cancer development and it may be the consequence of massive radio and/or chemotherapeutic regimens. In a comparative study, we analysed the potential, systemic immunorestoratory capacity of bestatin, a microbial leucil-aminopeptidase inhibitor and of the ubiquitous trace element zinc. In vivo administration of bestatin in mice stimulated both Interleukin 1 and Interleukin 2 production, and enhanced T cell, B cell as well as macrophage mediated immunoreactions. In a phase II clinical trial on 41 patients with non-Hodgkin lymphoma, Hodgkin disease and solid tumors, bestatin treatment corrected the pathological frequency of both OKT4 and OKT8 lymphocyte subpopulations. Zinc-saturated transferrin had a significative stimulatory effect on the ongoing DNA synthesis of antigen activated human lymphocytes in culture. Oral administration of zinc-gluconate to patients who manifested a severe T cell subpopulation defect corrected preferentially the OKT8 suppressor/cytotoxic T cell unbalances. The clinical results obtained by both bestatin and zinc were observed only on a short-term, so further studies are needed to elaborate long lasting regiments and to establish whether these treatments have determinant influence on the underlying disease.

AIDS-Related Complex↗
PubMed1986

Excess of lympho-reticular cell complexes in the bone marrow linked to T cell mediated dysmyelopoiesis.

The term dysmyelopoietic syndrome (DMPS) covers a variety of closely related disorders with various etiological factors, and characterized by chronic (pan) cytopenias whose prognosis and treatment are still controversial. Despite the recent efforts to identify pathogens, effector cells and soluble cell products involved in the development of this syndrome only a few comprehensive experimental data are available, useful for elaboration of therapeutic regimens. We describe here a patient with DMPS who was refractory to inductive chemotherapy. Initial agar gel culture studies revealed the activity of hematopoiesis inhibitory T cells within the bone marrow that could be suppressed by prednisone both in vitro and in vivo. However another pathological cell features, the excess of an unusual lympho-reticular cell complexes was identified in long-term liquid cultures. These symbiotic cell complexes persisted throughout the disease, despite the prednisone induced hematological remission, suggesting their causative role in the disease, that more recently progressed towards acute myeloid leukemia.

Adult↗
PubMed1985

The effect of zinc on normal and neoplastic T-lymphocyte proliferation.

After 24-72 h of PHA-stimulation, T-cells expressed the transferrin receptor. This receptor facilitates zinc uptake. Zinc transferrin stimulated DNA synthesis in pre-activated or activated, but not in resting T-cells. The regulatory nuclear protein matrix fraction increased from 5 to 40% of the total nuclear protein material in lymphocytes simultaneously with the initiation of DNA synthesis. In contrast, optimal concentration (0.1-0.4 mM) of zinc salts induced a mitogenic response in transferrin-receptor negative resting, but not in PHA-activated or leukemic T-cells. Higher concentrations were toxic. These findings can explain earlier reports on the effect of zinc on immunocompetence in zinc deficient mice and enteropathic acrodermatitis as well as present findings of a normalization of the T-suppressor-cell number in immunosuppressed patients.

DNA Replication↗
PubMed1984

In vivo acute hematotoxicity of N,N'-bis[N-(2-chloroethyl)-N-nitrosocarbamoyl]cystamine (CNCC), a new nitrosourea analog.

The in vivo hematotoxic effects on different hemopoietic cell compartments of a new nitrosourea analog CNCC were compared to another glycosidyl derivative, RFCNU. Bone marrow microenvironment in liquid culture, bone marrow and splenic colony-forming units in agar culture (GM-CFUc), relative spleen index, and spleen and bone marrow cellularity were evaluated in young adult (DBA/2 X C57B1/6)F1 mice. The drugs, dissolved in olive oil, were injected ip at either the minimal or the median or the maximal dose of the "maximally efficient dose range." A single administration of CNCC induced a dramatic depopulation of bone marrow and spleen within 12 and 24 hr and significantly reduced the GM-CFUc in both organs. A rapid recovery of both the total cell number and GM-CFUc was observed between Days 2 and 5 (kinetic experiment). The comparison of toxicity of 20 to 50 mg/kg CNCC and 15 to 30 mg/kg (2-chloroethyl)ribopyranosyl-3-nitrosourea RFCNU at Day 1 and Day 5 showed that the bone marrow microenvironment was modified by the effect of oil and was further impaired by CNCC in a concentration-dependent fashion. In contrast RFCNU had less effect on the microenvironment. Similarly, the bone marrow GM-CFUc population was reversibly impaired by CNCC in a dose-dependent fashion, and again RFCNU had less effect. In the spleen both drugs provoked a higher toxic effect than in the bone marrow; on Day 1 they decreased the GM-CFUc population by 1 to 2 log. On Day 5 a compensatory regeneration was obtained in all cases except the highest tolerable CNCC dose, whose effect was more delayed.

Acute Disease↗
PubMed1984

Zinc and immunity.

The ubiquitous trace metal zinc has been discovered since a long time as an intrinsic element in all biological systems. However, its role other than structural or catalytic in enzymes is poorly defined. Zinc plays a determinative role both in primary and secondary T lymphocyte production. Experimental data support the notion that during intrathymic maturation, non-autoreactive, immunocompetent T cell clones are selected from the excess of immature thymocytes as a result of expansion of bone marrow derived prothymocytes in response to pleiotropically acting alarmon (s) and a subsequent escape via the thymic stroma cells from nucleotide-mediated "biochemical suicide". The activity of alarmon (Ap4A), nucleotide metabolizing enzymes (TdT, DNA polymerase, thymidine kinase, 5'-nucleotidase) and some of the soluble stromal cell products (FTS) require constitutive zinc. In the peripheral lymphoid organs the magnitude and duration of antigen induced, T cell mediated immunoreactions are regulated by T-cell growth factor (IL-2). Using receptor specific monoclonal antibody probes, it has been established recently that the intracellular role of IL-2 is probably to induce the phenotypic expression of high affinity transferrin receptors, known to be the main zinc transporter system in T-lymphocytes. The coordinative role of zinc in T lymphocyte development via the inducible metallothionein system is emphasized. Some clinical aspects of zinc metabolism are discussed.

Animals↗
PubMed1983

The stimulatory effect of serum thymic factor (FTS) on spontaneous DNA synthesis of mouse thymocytes.

Synthetic serum thymic factor (FTS), a T-cell differentiating factor, was studied for its ability to modify the spontaneous DNA synthetic activity of immature or immunocompetent T cells in vitro. In serum free RPMI 1640 medium, FTS stimulated [3H]thymidine incorporation into the DNA of young adult mouse thymocytes in a time and concentration dependent manner. One to 100 pg/ml FTS were the effective concentrations, and the stimulation appeared 3 h after the treatment. A comparable stimulation was noticed, but to a lesser extent, on cultured bone marrow cells. In contrast, no effect could be detected on spleen cells whatever time or concentrations were studied. Neither thymocytes treated in vitro with hydroxyurea nor the medullary, cortisol-resistant thymocytes were sensitive to FTS treatment. In contrast, thymocytes bearing receptor to peanut agglutinin (PNA+) were significantly stimulated with FTS, which suggested that the target population of FTS belongs to the maturing, non-immunocompetent thymocyte compartment.

Aging↗
PubMed1983

Interleukins and immunosuppressive factors: a regulatory system?

On exogenous stimulus immunocompetent leucocytes produce antigen-specific factors, which essentially determine the magnitude and duration of T-lymphocyte dependent immunoreactions. Interleukin 1 (IL-1, monokin) and interleukin 2 (IL-2, lymphokine) form a bimodal amplification system which may operate in vivo at the level of peripheral lymphoid organs, which interleukin 3 (IL 3, lymphokine) may function as a positive feed-back signal at the level of multipotential stem cells. The physiological IL-2 has wider importance, since the permanent expression of Il-2 gene due to the insertion of the viral promoter sequence (HTLV in human) led to uncontrolled proliferation of T-cells and to the development of lymphomas and leukemias of mature T-cell phenotype. On the afferent arc of immunoreactions endogenous factors mediate T-cell proliferation inhibitory effect probably via interaction with the interleukin system. Some practical aspects of these two antagonistic group of factors are presented and discussed.

Animals↗
PubMed1983

Relationship between a spleen-derived immunosuppressive peptide 'SDIP' and the 'Facteur thymique sérique' (FTS): biochemical and biological comparison of the two factors.

A spleen-derived immunosuppressive peptide (SDIP) has been purified to homogeneity. Its physicochemical properties (electrophoretic mobility, u.v. spectra, absence of dansyl derivative) and its enzymatic susceptibilities (proteolytic enzymes, RNase, and DNase) were similar to those of the thymic hormone 'FTS'. SDIP and FTS were eluted with identical retention times in high performance liquid chromatography analysis in three different systems. When tested in sheep cell rosettes, and in the FTS radioimmunoassay in J.F. Bach's laboratory, SDIP presented an activity similar to FTS. In order to compare the thymic hormone to SDIP the biological activity of FTS was determined in in vivo and in in vitro humoral immunity reactions to a T-dependent antigen. As SDIP, FTS inhibited in vivo and in vitro the 19S-bearing cell formation during the last step of the differentiation of the lymphocytes, in the same range of concentration. The two factors appeared to stimulate the incorporation of [3H]-thymidine into the DNA of short-term cultures of thymocytes. The similarity of biological properties of SDIP and FTS together with the similarity observed in the physico-chemical and biochemical properties led to the conclusion that bovine spleen contains a factor similar to FTS.

Animals↗
PubMed1982

In vitro and in vivo specificities of purified thymic factors inhibiting graft-versus-host reaction.

A calf thymic factor has been prepared by extraction in distilled water, followed by selective precipitation with ethanol and ammonium sulfate. The non-dialysable fraction obtained by this method was further purified by a preparative electrofocusing technique which allows the isolation of two fractions which can specifically inhibit, in vitro, without toxicity or species specificity, spontaneous DNA synthesis in hemopoietic cell suspensions. When injected in vivo in mice, 3 days after immunization with SRBC, both these fractions exhibited immunosuppressive properties. In contrast, they were without any effect on a thymus-independent antibody response to TNP-LPS, whatever the day of administration. Still more important, in vitro pretreatment of lymphoid cells by the purified fractions inhibits their ability to elicit a graft-versus-host reaction when injected to histo-incompatible recipients.

Animals↗
PubMed1980

Regulation of T lymphocyte differentiation and proliferation by thymus hormones, Ca2+ and chalone-T.

The regulatory effect on T lymphocyte proliferation of the differentiator thymosin hormone family (thymosin fr. 5, A. L. Goldstein), Ca2+, and purified inhibitory protein fractions prepared from calf thymus was investigated in C57Bl/6 mice. 1.2 mM Ca2+ concentration was the most favourable for murine thymocyte growth in culture. Net protein synthesis was transitorily inhibited by Cu2+ concentrations higher than 2 mM. This inhibition was followed by a marked inhibition of DNA synthesis 2 hrs later. The effect of thymosin fr. 5 was slight, of short duration, and oscillatory in nature; in contrast, chalone-T preparations inhibited thymocyte DNA synthesis permanently up to 12 hrs of cultivation. When spleen cells taken from mice treated with the immunoadjuvant Bacillus Calmette-Guérin (BCG) were exposed to chalone-T in culture, then stimulated with PHA, a reduced proliferative response was measured in chalone-T pretreated cultures compared to controls or spleen cells from normal non-BCG-activated mice. This result had led us to suggest that chalone-T has a dual effect on thymocytes, viz. it inhibits cell cycle progression and induces the phenotypic conversion of suppressor T lymphocytes. The multifactorial concept of T lymphocyte production is discussed.

Animals↗
PubMed1979

Binding of benzo(a)pyrene into lung and thymocyte nuclear fractions.

Binding of (3H)benzo(a)pyrene into lung and thymocyte nuclear fractions is studied in short term cultures. DNA, RNA and protein in the subnuclear fractions is separated and tightly bound radioactivity is measured. Among the fractions, proteins of the matrix sediment fraction display the highest specific radioactivity. DNA has a low specific radioactivity as compared to that of RNA and protein in all fractions. In thymocyte matrix extract and chromatin fractions the specific radioactivity of RNA exceeds that of protein. Lung nonhistones display a 30 times higher specific radioactivity as compared to histones. The corresponding ratio of the thymocyte fractions is about 10.

Animals↗
PubMed1978

Steroid transport through the surface of the prothoracic gland cells in Galleria mellonella L.

Steroid transport through the cell surface of the giant polyploid prothoracic gland cells of Galleria mellonella L. was studied by an ultracytochemical method. The alkaloid digitonin, known to form a complex with all sterols having a free-OH radical in position 3, proved to be suitable for studying the interiorisation of moulting hormone precursors and the release of synthesized hormones. The results suggest that cholesterol uptake in the last larval instar occurs by macropinocytosis during the feeding period, while the release of the steroids produced by the gland occurs by reverse micropinocytosis mostly on days 5-7 of the instar. The two processes are not simultaneous. The intracytoplasmic localisation of the reaction product confirms the steroidogenic role of the prothoracic gland.

Animals↗
PubMed1978

Endogenous thymic factors regulating cell proliferation and analysis of their mechanism of action.

Endogenous factors inhibiting the proliferation of T-lymphocytes were investigated which may function as modulators of T-lymphocyte production within the thymus. An extract from calf thymus (T4) enriched in lymphocyte chalone arrests rat thymocytes at the G1 leads to S boundary and in the S phase of the cell cycle in short-term cultures. It also inhibits the proliferative response of human peripheral blood lymphocytes to PHA-P in a time-dependent manner, as well as the spontaneous proliferation of in vitro cultured human chronic leukaemic lymphoblasts. This crude extract contains two active moities which can be isolated by molecular filtration on Sephadex G-75 column. A species non-specific, cell line selectivity inhibitory effect is characteristic of the high molecular weight fraction (mol. wt. greater than 40,000). This activity is resistant to moderate heat treatment and trypsin but is sensitive to mild alkaline hydrolysis and to RNase A digestion. About ten protein components and a toluidine blue positive substance can be detected by analytical polyacrylamide gel electrophoresis. The active inhibitor, a proposed protein-RNA complex, might be identical with the chalone. The low molecular weight, non-dialysable factor (T4-4) inhibits [3H]thymidine incorporation into acid insoluble DNA in a cell non-specific manner. A possible relationship between the two activities is discussed.

Cell Division↗
PubMed1978

In vitro sensitivity of transplantable leukemias to endogenous granuloid (GCE, GI-2) and lymphoid (T4, T4-1) inhibitors of proliferation.

The effect on cell proliferation of crude granulocyte and thymocyte extracts (GCE, T4) and of their target-specific fractions (GI-2, T4-1) was studied in cultures with transplantable subacute myeloid and lymphoid leukemia (ML, LL). In the dose rage studied (1-500 microgram/ml) each factor reduced 3H-TdR incorporation into acid-insoluble DNA of bone marrow, thymus and spleen cells with ML or LL as a function of the dose, approximately linearly. Normal bone marrow proved to be less sensitive to GCE than the ML one: according to parallel line bioassay by a factor of mu = 0.56. The reactivity of LL spleen and thymus is also higher to medium T4-1 concentrations (50-200 microgram/ml) than that of normal lymphoid populations. T4-1 inhibits 3H-TdR incorporation into the DNA of LL spleen cells submaximally in 90': this effect lasts for greater than 7 hours. Because of its more homogeneous cell composition and higher sensitivity, subacute myeloid leukemia is more suitable for screening endogenous granuloid inhibitors than are homologous normal cell cultures.

Bone Marrow Cells↗
PubMed1975

Ultrastructural study of the prothoracic glands of Galleria mellonella L. in the penultimate last larval, and pupal stages.

The prothoracic gland (PGL) of Galleria mellonella is a Y-shaped, paired organ, consisting of 45-50 polyploid giant cells. The PGL cells are supplied by neurosecretory axons; release of neurosecretory granules (1000-1300 A in diameter) directly on the surface of PGL cells was frequently observed. Based on ultrastructure, the last two larval instars can be divided into three phases: 1) restitutive phase immediately after moulting; 2) gradual activation in mid-intermoult as indicated by the logarithmic cell growth, decrease of nucleo-cytoplasmic ratio, increase in the number of cell organelles participating in protein synthesis, and the structural changes of these organelles; 3) "release' period preceding moulting, characterized mainly by the extreme dilatation of peripheral invaginations. From the prepupal stage onward cellular activity is asynchronous. Part of the cells already show the signs of involution, while others histolyse only after the activation phase subsequent to moulting. PGL in G. mellonella is one of the larval tissues. In the course of activation its ultrastructure changes as a function of juvenile hormone (JH) cocentration, in the absence of which it histolyses. Accordingly, it has seemed to us to be a suitable model for the cytological study of JH activity.

Axons↗