Biomedical subjects

M Finiasz

Publications and source records attributed to M Finiasz.

13 recordsLinked to original sources

PubMed1995

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients.

Cytotoxic T cells play an important role in host defence mechanisms, as well as in the immunopathology of leprosy. In this study, we evaluated whether Mycobacterium leprae hsp18, hsp65 and Myco. tuberculosis hsp71 could induce cytotoxic T cell activity against autologous macrophages pulsed with these hsp. Paucibacillary (PB) patients and normal controls generated more effector cells than multibacillary (MB) patients with all three hsp tested. There was no cross-reactivity between any of the hsp tested. Mycobacterium leprae hsp65 induced cytotoxic responses only in those MB patients undergoing an erythema nodosum leprosum (ENL) episode. Although hsp65 and hsp18 induced similar proliferation in MB patients, a high proportion of these patients did not generate cytotoxic effector cells in response to hsp65. Hence, those T cells reacting to hsp65 may play an important role in the control of Myco. leprae infection.

Adolescent↗

PubMed1991

Active alpha 2 and beta adrenoceptors in lymphocytes from patients with chronic lymphocytic leukemia.

A single population of alpha 2 adrenoceptors was characterized in intact B lymphocytes from patients with chronic lymphocytic leukemia (B-CLL) by binding and saturation studies with 3H labelled yohimbine and by competition studies with alpha adrenergic antagonists. While the affinity of B-CLL alpha 2 adrenoceptors was low (KD: 9.81 nM-20.98 nM), each cell expressed a large number of receptors. No binding of the alpha 1 adrenoceptor antagonist prazosin was observed and the binding properties of beta adrenergic receptors (assayed with 3H-labelled dihydroalprenolol), were similar to those described for normal lymphocytes. Reaction of B-CLL with the beta adrenergic agonist isoproterenol raised the levels of cAMP in 11/13 patients tested, and in 8 of these, incubation with the alpha 2 adrenergic agonist clonidine prevented the effect and reduced the basal cAMP levels. The presence of active alpha 2 adrenoceptors on B-CLL lymphocytes may be involved in the regulation of metabolic pathways that affect cell functions and favor neoplastic growth.

Aged↗

PubMed1989

Stimulation of heart contractility by supernatants from lectin-activated lymphocytes. Role of IL-2.

The positive inotropic effect of cell-free supernatants from lectin-activated lymphocytes is lost by dialysis and can be partially restored by addition of arachidonic acid (AA). Interleukin-2 (IL-2) in the presence of AA could stimulate the response of the heart while the interferons (alpha-IFN or gamma-IFN) were ineffective. The activity of PHA-L-SN and that of IL-2 + AA was neutralized by anti-IL-2 MAb. These results suggest a key role for IL-2 in the stimulation of heart contractility by supernatants from activated lymphocytes.

Animals↗

PubMed1989

[The effect of activated lymphocytes on cardiac contractility].

Activated lymphocytes may have potent biologic effects outside the frame of the immune system. In these studies we analyzed the interaction of activated normal human lymphocytes and/or soluble products of lymphocyte activation on the contractile activity of isolated rat atria. The results indicate that phytohemagglutinin activated lymphocytes of the CD4 phenotype exert a positive inotropic effect on spontaneously beating atria. This effect is linked to steps of lymphocyte activation that precede cell division. Soluble factors released to the supernatant of stimulated lymphocytes can substitute for the intact cells. Interleukin-2 (IL-2) appears to be an important component of the active supernatants, as their activity can be reduced by monoclonal anti-IL-2 or by preincubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-Tac). Highly purified IL-2 was active at 10 units/ml. In order to induce a positive inotropic effect at lower doses of natural or recombinant IL-2 (2-3 units/ml), synergic factors were required (2 x 10(-6) M arachidonic acid, AA, or Ca ionophore A 23187). Indirect evidence indicates that IL-2 exerts its biologic effect by turning on the phosphoinositide cycle and activating protein kinase C in the heart tissue target. It is postulated that similar mechanisms may be activated in inflammatory myocardiopathies or during the treatment of cancer with massive doses of IL-2.

Animals↗

PubMed1988

Interleukin 2 stimulates heart contractility in the presence of exogenous arachidonate or the calcium ionophore A 23187.

An increase in the isometric developed tension (IDT) of isolated rat atria was observed shortly after the addition of human interleukin 2 (IL-2) to the organ preparation with subthreshold concentrations of either arachidonate (AA, 1.98 X 10(-6)M) or the calcium ionophore A 23187 (1.9 X 10(-6)M). Both natural purified IL-2 (nIL-2) and yeast recombinant IL-2 (rIL-2) were active in this experimental system. It was determined that this lymphokine was active at 2 X 10(-11)M, considering as a reference the specific activity of rIL-2. Anti-IL-2 monoclonal antibody (anti-IL-2 MAb) abolished this reaction. Inhibition of atrial phospholipase C activity by nitrocarboxyphenyl N,N-diphenylcarbamate (NCDC, 5 X 10(-6)M) prevented the development of the inotropic positive effect of IL-2 in the presence of either AA or A 23187. The synthetic diacylglyceride 1-oleoyl, 2-acetyl-glycerol (OAG) replaced the IL-2 as stimulatory signal but NCDC had no effect on the reaction. The results suggest that IL-2 can alter the physiologic behaviour of the heart and that its mechanism of action is probably similar to the one proposed for other IL-2 targets (IL-2 receptor-positive T lymphocytes, T cell lines).

Animals↗

PubMed1988

Lymphocyte-induced stimulation of the contractile response of the heart.

In previous reports we have shown that phytohemagglutinin (PHA)-activated human lymphocytes had positive inotropic effects on spontaneously beating isolated rat atria. In this study, we demonstrated that the stimulatory effect on heart contractility induced by lymphocytes was linked to early events of lymphocyte activation by lectins. Active soluble factors were gradually released to the fluid phase. Similar results were obtained with both mitogenic (PHA) and nonmitogenic (WGA) lectins indicating that the stimulatory action of activated lymphocytes did not require cell division. Absence of Ca2+ inhibited both the generation of the stimulatory activity and lymphocyte proliferation. In contrast, verapamil, dexamethasone and low concentrations of cycloheximide eliminated only the appearance of the stimulatory effect.

Animals↗

PubMed1986

Modification of the contractile activity of isolated atria by T4 lymphocytes from patients with Chagas' disease: effect of soluble factors.

The results of this study show that peripheral blood mononuclear leukocytes of patients with Chagas' disease (Ch-PBMC) respond to challenge with homologous as well as with heterologous heart antigens releasing active soluble factors capable of increasing the contractile tension and frequency of beating rat atria. The reaction was related to T. cruzi infection rather than to the presence of cardiomyopathy. Indirect evidence suggests that supernatants of Ch-PBMC activated with heart tissue homogenates involved the generation of arachidonic acid metabolites by the lipoxygenase system of rat atria. Active effector cells were present in Ch-PBMC that had been depleted of T8-lymphocytes by lysis with OKT8 and rabbit complement (C) and not in those depleted of T4-lymphocytes with OKT4 and C. Therefore, the positive inotropic and chronotropic effects of Ch-PBMC were due to the action of cells from the T4 subset.

Animals↗

PubMed1986

Platelet aggregating substance from mononuclear leukocytes.

Human peripheral blood mononuclear leukocytes (ML) in suspension stimulated with arachidonic acid (AA) were able to induce platelet aggregation. Shape change followed by first and second wave aggregation was the pattern of the platelet response. ML not treated with AA did not induce platelet aggregation nor did AA done at the concentration employed. The aggregating activity was not due to the ML presence, since cell-free supernatants of ML stimulated with AA induced similar platelet aggregation as the whole suspension. Aspirin incubated with ML-AA produced 65% reduction of the above aggregatory activity described while 38% and 45% reduction was obtained when ML-AA was incubated with 5, 8, 11, 14 eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA). Complete platelet cyclooxygenase integrity was necessary to obtain the second wave of aggregation induced by ML-AA, while this was not required for the first wave response. We propose that ML-AA are able to produce a platelet activating substance(s) derived from AA metabolism involving cyclo and lipoxygenase actions. It is unlikely that this substance(s) is a hydroperoxyfatty acid or thromboxane A2 (TXA2) since it is active for at least two hours once generated.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1985

Modification of the contractile activity of isolated rat atria by lectin-activated T-lymphocyte subsets.

We had previously shown that human T-lymphocytes (ERFC) that had been activated for a short time with phytohemagglutinin (PHA) produced positive inotropic and chronotropic effects on spontaneously beating rat atria (Sterin-Borda, L., et al., Naunyn Scmiedeberg's Arch. Pharmacol. 324, 58, 1983). In this study, we first prepared T4-rich (T4) and T8-rich (T8) cells from ERFC by selective lysis with OKT4 and OKT8 monoclonal antibodies and rabbit complement. Then, we tested the effect of PHA-stimulated T4 (PHA-T4) and T8 (PHA-T8) on beating rat atria. PHA-T4 cells stimulated the tension and the frequency of contraction of isolated rat atria by a mechanism that involved the generation of the slow reacting substance of anaphylaxis (SRS-A), since both 10(-5) M nordihydroguaiaretic acid (NDGA) and 10(-7) M FPL-55712 were effective inhibitors. On the other hand, PHA-T8 cells decreased the tension of beating atria. Indomethacin (10(-6) M) could not block the depressor effect. Cell-free PHA-T4 supernatants reacted with the heart tissue similarly to whole PHA-T4 cells. Since NDGA or FPL-55712 treated organs did not respond to active PHA-T4 supernatants, the lipoxygenase system of the auricles seems to be required for the reaction and the active metabolites appear to derive mainly from the heart. Our results suggest that PHA-activated "helper/inducer" cells release soluble factors that can in turn trigger the lipoxygenase metabolic pathway of arachidonic acid in the heart, generating the active leukotrienes responsible for the positive inotropic and chronotropic effects.

Animals↗

PubMed1984

Human lymphocyte aggregation?

The purpose of the present study was to assess lymphocyte (L) aggregation. Mononuclear cells were obtained according to Boÿum. Blood was defibrinated with glass beads and laid on Ficoll-Hypaque gradients. Monocyte depletion was achieved by adherence to plastic for 18 hs. L aggregation was assayed using the turbidimetric method. When L were challenged with collagen (1-8 micrograms/ml), ADP (2.5 microM), epinephrine (1 X 10(-4) M), ristocetin (1.5 mg/ml) and bovine F VIII no aggregation could be observed. When L were stimulated by arachidonic acid (AA) (160 microM) a complete and irreversible aggregation was obtained. This effect was markedly inhibited when L were previously incubated with aspirin (40 micrograms/ml). On the other hand 5, 8, 11, 14 eicosatetraynoic acid (ETYA), a lypoxygenase inhibitor, was not able to reverse L aggregation induced by AA. Leukotriene B4, C4 and D4 were not able to induce L aggregation. When TXA2 like material from platelets and L was transferred to L preincubated with aspirin a normal aggregation response was obtained. All these results lead to the concept that the main pathway involved in L AA metabolism is probably cyclo-oxygenase. Ionophore A 23187 was not able to induce L aggregation at any concentration employed (0.1 - 100 microM) and 6 keto PGE1 could not inhibit AA induced lymphocyte aggregation.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1984

Lymphocytes sensitize rat isolated atria to the inotropic and chronotropic effects of sodium arachidonate.

Normal human lymphocytes (4 X 10(5) ml-1) incubated with sodium arachidonate (8 X 10(-7)M) (NaA-L) induced a strong enhancement of the tension and frequency of spontaneously beating rat atria. Normal human lymphocytes (L) or NaA alone at 8 X 10(-7)M did not modify this contractile activity. Between 2 X 10(-6)M to 1 X 10(-5)M NaA alone increased the tension of the atria without effect on the rate. In the presence of L (4 X 10(5) ml-1) the dose-response curve to NaA shifted to the left, the potency and the efficiency of NaA were enhanced and the chronotropic action was triggered. Inhibitors of cyclo-oxygenase (indomethacin 1 X 10(-6)M or acetylsalicylic acid (ASA) 1.8 X 10(-4)M) completely blocked the positive inotropic effect induced by NaA alone. Inhibitors of lipoxygenase/s (nordihydroguaiaretic acid (NDGA) 1 X 10(-5)M or 5,8,11,14-eicosatetraynoic acid (ETYA) 1 X 10(-7)M did not modify this effect. Indomethacin and ASA did not block the positive inotropic and chronotropic effects of the lower concentration of NaA-L and significantly reduced the inotropic effect of the higher ones. NDGA and ETYA shifted to the right the inotropic and chronotropic dose-response curve to NaA-L. FPL-55712 (1 X 10(-7)M), the slow reacting substance of anaphylaxis (SRS-A) antagonist, significantly reduced the overall inotropic and chronotropic effect of NaA-L. Direct contact of NaA-L with the atria was not necessary. Cell-free supernatants of L exposed to NaA increased the tension and the frequency of beating rat atria. 7 The stimulatory effect of NaA-L supernatants did not occur if rat atria had been previously incubated with NDGA 1 x 10-5 M. On the other hand, the generation of stimulatory products from NaA-L was not prevented by preincubating L with 1 x 10-5 M NDGA. Hence SRS-A and/or other oxidative metabolites of arachidonic acid were produced by the atria. 8 These results suggest that NaA-L react in vitro with spontaneous beating rat atria, inducing inotropic and chronotropic effects. Moreover, the stimulatory action of NaA itself was potentiated by L. These reactions involved a balance between cyclo-oxygenase and lipoxygenase oxidative products with a central role for SRS-A.

Animals↗

PubMed1984

alpha-Adrenoceptor stimulated lymphocytes trigger the mechanical response of vas deferens: participation of arachidonic acid metabolites.

Normal human lymphocytes (L) (8 X 10(5) ml-1) incubated with methoxamine (Me) (1 X 10(-7) M) (Me-L) triggered the mechanical response of the isolated vas deferens of the rat. L or Me alone did not modify this contractile activity at the concentrations cited above. Me alone (10(-6) to 10(-3) M) increased the tension of the vas. In the presence of L (8 X 10(5) ml-1) the dose-response curve to Me shifted to the left and the efficacy of Me was enhanced. Inhibitors of alpha 1-adrenoceptors completely blocked the reaction between Me and L while drugs that block alpha 1 and alpha 2-adrenoceptors reduced the reaction between Me-L and the vas deferens. Direct contact of Me-L with the assay organ was not necessary. Cell-free supernatants of L exposed to Me (Me-L supernatants) elicited the reaction in the same way as Me-L. This effect required the continuous presence of Me since dialyzed Me-L supernatants were inactive. Inhibitors of lipoxygenase(s) completely blocked the positive inotropic effect of Me-L or of Me-L supernatants. Inhibitors of cyclo-oxygenase potentiated this effect. These results suggest that Me reacts with alpha 1-adrenoceptors of L. From this reaction, soluble factors are released that potentiate the alpha-adrenoceptor stimulatory effect of Me on the vas deferens as a consequence of the release of oxidative products of the lipoxygenase/s pathway of arachidonic acid.

Adrenergic alpha-Agonists↗

PubMed1984

Stimulatory effect of lymphocytes from Chagas' patients on spontaneously beating rat atria.

The aim of this work was to study the effect of lymphocytes from individuals infected with Trypanosoma cruzi (Chagas' patients) on the contractile behaviour of living heart tissue. Chagas' lymphocytes (ChL) reacted with isolated rat atria preparations increasing the isometric development tension (IDT) and frequency of contractions (FC) in a dose-dependent manner. The maximal stimulatory effect was reached after 30-40 min of contract. In contrast, normal lymphocytes (NL) did not alter the basal IDT and FC values. beta-adrenergic antagonists, anti-histamine agents and inhibitors of the synthesis and action of arachidonic acid (AA) products were used to study the mechanisms of the reaction. (-)-propranolol (10(-7)M) and pyrilamine (10(-6)M) had no effect ruling out the participation of beta-adrenergic agonists or histamine. However, indomethacin (10(-6)M) and acetylsalicylic acid (1.8 X 10(-4)M) enhanced the effect of ChL. Inhibitors of the lipoxygenase pathway (5,8,11,14-eicosatetraynoic acid, 10(-7)M; nordihydroguairetic acid, 10(-5)M) and FPL55712, an antagonist of one of its terminal products: the slow reacting substance of anaphilaxis (SRS-A), abolished the reaction. Therefore, a fundamental role for SRS-A in the production of the stimulatory effect is postulated. Lymphocytes of the T cell lineage (E rosette forming cells, ERFC) are the effector cells involved in this reaction, whereas non-rosetting ChL depressed IDT. T ascertain if effector cells could be replaced by soluble factors, ChL were reacted with homogenates of rat atria and the cell free supernatants were added to beating rat atria. Positive ino- and chronotropic effects were obtained, indicating that soluble factors generated during the reaction can substitute for the intact effector cells. On the other hand if the effector cells were purified from Chagas' patients that had been treated 1 month to 6 years before the assay with trypanocidal drugs (3-methyl-4-(5'-nitrofurfurylidene-amino)-tetrahydro-4H-1, 4-tiazine-1, 1-dioxide, nifurtimox or N-benzyl-2-nitro-imidazolacetamide, benznidazole) only depressor effects were found. The depressor inotropic action of lymphocytes from treated patients (tr-ChL) was abolished with indomethacin and acetyl salicylic acid indicating that products of the cyclooxygenase pathway of AA were involved. While this work provides additional evidence for the hypothesis that lymphocytes from T. cruzi infected patients may react with heart tissue and alter its contractile behaviour, the results should not be extrapolated to the in vivo situation.(ABSTRACT TRUNCATED AT 400 WORDS)

5,8,11,14-Eicosatetraynoic Acid↗