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Biomedical subjects

M Giordano

Publications and source records attributed to M Giordano.

At least 235 records · Page 13Linked to original sources
PubMed1987

Neutrophil-mediated cytotoxicity triggered by immune complexes: the role of reactive oxygen metabolites.

Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC (sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towards nonsensitized target cells. Catalase, but not heated catalase, completely impaired this nonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Superoxide dismutase (SOD) and certain HO. and 1O2 scavengers were unable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedly enhanced it. This data suggest that the mechanism involved was not dependent upon myeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates that oxygen-dependent but MPO-independent mechanisms appeared to be operative in this system. It was also found that the microfilament disrupting agents, cytochalasin B (CB) and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), significantly enhanced NSC. In contrast, these compounds partially inhibited ADCC. This cytotoxic system provides a suitable model to study events that may occur during the course of immune complex diseases and also permits the evaluation of alternative lytic mechanisms triggered through neutrophil Fc gamma receptors.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes.

Normal human monocytes were induced to lyse nonsensitized target cells when triggered by precipitating immune complexes (IC) or soluble heat-aggregated IgG (HAIgG). Catalase, azide, cyanide and three aminoacids employed as quenchers of ClO, significantly inhibited this nonspecific cytotoxicity (NSC), suggesting an important role for the myeloperoxidase (MPO) system. However, HO and/or 1O2 may also be involved in the lysis, since certain scavengers of these species such as mannitol, benzoate, ethanol and histidine, as well as superoxide dismutase (SOD), partially inhibited NSC. Moreover, cyanide and azide were unable to completely abrogate this lytic activity. When NSC was compared to antibody dependent cellular cytotoxicity (ADCC), it was found that neither catalase nor oxygen-species scavengers affected ADCC while azide and cyanide significantly enhanced it. Antibody-coated target cells were also destroyed by IC-triggered monocytes. However, kinetic analysis and studies on the capacity of catalase to inhibit the lysis demonstrated that it was mediated through a NSC-like mechanism. The cytotoxic system described in this report offers a suitable model to study in vitro alternative lytic mechanisms triggered through monocyte receptors for the Fc portion of IgG (Fc gamma R).

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Multicenter double-blind randomized clinical trial of imidazole salicylate versus ibuprofen in patients with rheumatoid arthritis.

In a 24-week multicenter double-blind clinical trial, efficacy and safety of the novel nonsteroidal anti-inflammatory drug imidazole salicylate (750 mg t.i.d. per os) and ibuprofen (600 mg t.i.d. per os) were compared in 60 patients with classical or definite rheumatoid arthritis, randomly assigned to one of the two treatment groups. The patients improved significantly with both treatments in all the clinical parameters examined such as the duration of morning stiffness, grip strength of both hands, Ritchie's articular index and severity of joint pain. The systemic tolerability, assessed by hematological, liver and kidney function tests was excellent with both treatments. The incidence of side effects was overall fairly low with both drugs, and lower in the group treated with imidazole salicylate (23% vs. 33%).

Adult↗
PubMed1986

Interaction between actin and HMM.

It is shown that the interaction between actin and HMM results in a rapid precipitation of acto-HMM gel upon addition of MgATP. This is a simple demonstration of the idea that the formation of myosin filaments is not essential for mechanochemical reaction (muscle contraction) to occur and that the soluble myosin heads are competent to interact with actin to produce mechanical effect. Our findings also strongly support earlier suggestion that each head of one HMM molecule is able to bind to a different actin filament.

Actins↗
PubMed1986

Retrograde amnesia induced by post-trial injection of atropine into the caudate-putamen. Protective effect of the negative reinforcer.

A series of experiments was performed to test the reliability of previous reports which indicated that cholinergic blockade of the caudate-putamen produces memory deficits of passive avoidance, and to determine whether overtraining of this task protects against such deficits. In the first experiment the effects of different doses of atropine injected into the caudate-putamen of rats shortly after training were assessed, and a dose-dependent retention deficit was found. In two additional experiments it was observed that by increasing the magnitude of the negative reinforcer used in training, a protection against such retention deficit was produced. These results support the hypotheses that (a) cholinergic activity of the caudate-putamen is critically involved in memory processes that mediate passive avoidance behavior, and (b) after overtraining the control of this behavior is transferred from the striatal cholinergic system to other neurochemical systems within, or outside, the striatum.

Amnesia↗
PubMed1986

Immunomodulation exerted by cyclophosphamide is not interfered by N-acetyl cysteine.

Metabolism of cyclophosphamide (Cy) by liver enzymes results in cytostatic products and acrolein, which exerts urotoxicity. Experiments were designed to determine which metabolites are responsible for Cy-induced immunomodulation. For this purpose, mice were treated simultaneously with Cy and N-acetyl-cysteine (NAC), a thiol compound which reacts with acrolein, and different immunological functions were assayed. Results show that NAC did not interfere with Cy effects on antibody-dependent cellular cytotoxicity (ADCC), NK activity, delayed-type hypersensitivity (DTH) or antibody production, indicating that modulation of these functions by Cy is mediated by its cytostatic metabolites.

Acetylcysteine↗
PubMed1986

Adult acute non-lymphoblastic leukaemia: reliability and prognostic significance of pretreatment bone marrow S-phase size determined by flow cytofluorometry.

46 adult patients with non-lymphoblastic acute leukaemia (AnLL) had pretreatment proliferative activity of bone marrow (BM) blasts determined simultaneously with propidium iodide DNA flow cytofluorometry (as the percentage of cells with DNA content intermediate between the diploid and the tetraploid values, 2n-4n cell %) and in vitro tritiated thymidine cytoautoradiography (as the labelling index, LI). They were then treated with the same chemotherapy regimen, including 2-3 courses of sequential vincristine, arabinosylcytosine and adriamycin, for response induction, and monthly courses of different cytostatics for maintenance. Median 2n-4n cell % was 9.9 and median LI was 5.9. A close linear relationship (r = 0.913, p less than 0.001) between the two parameters was found. Patients having a 2n-4n cell % greater than 15.6 responded more often to chemotherapy than patients having a lower percentage (p less than 0.05) but also experienced a shorter duration of first response (p less than 0.05). Overall survival was longer in patients with 2n-4n cell % greater than 15.6 (p less than 0.02). Multiple regression analysis indicates that 2n-4n cell % is a statistically significant (p less than 0.05) independent factor correlating with duration of response in adult AnLL.

Acute Disease↗