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M Giordano

Publications and source records attributed to M Giordano.

At least 217 records · Page 12Linked to original sources
PubMed1988

Cyclophosphamide modulates arachidonic acid metabolism by peritoneal macrophages.

The treatment of mice with a single dose of cyclophosphamide (Cy) (200 mg/kg) enhanced the chemiluminescence (CL) response of peritoneal macrophages (PM) triggered with opsonized zymosan (OpZ). The enhanced CL response could not be attributed to the stimulation of the cyanide-insensitive respiratory burst, since neither superoxide anion release nor immune complex-triggered cytotoxicity, an oxygen-dependent lytic mechanism, were increased in Cy-PM. Then, products of the oxidative metabolism of arachidonic acid were measured. It was found that Cy-PM exhibited increased release of prostaglandin E2 and leukotriene C4 in response to OpZ when compared with resident PM. In contrast, similar levels of thromboxane B2 production were observed in both populations. The activation of macrophage arachidonic acid metabolism reported here may contribute to the immunomodulating action of Cy.

Animals↗
PubMed1988

Opposite effects of amines on lymphocyte- and monocyte-mediated ADCC.

The effect of different amines on antibody-dependent cellular cytotoxicity (ADCC) activity of human mononuclear cells was tested. Whereas monocyte cytotoxic capacity was significantly stimulated in the presence of methylamine (MA), dansylcadaverine (DC) and glycine ethylester (GEE), lymphocyte ADCC was markedly suppressed by these agents. The pharmacological actions of these compounds in our system are not related to their ability to inhibit transglutaminase (TGase) enzymes, since tertiary amines such as sarcosine ethylester (SEE) and chloroquine (CQ) elicited identical responses to MA, DC and GEE. The calmodulin (CAM) inhibitors trifluoperazine (TFP) and the more specific N-(6-aminohexyl)-5-chloro-1-naphtalene sulfonamide (W-7) [Hidaka, Sasaki, Tanaka, Endo, Ohno, Fujii & Nagata (1981) Proc. natn. Acad. Sci. U.S.A., 78, 4353-4357] mimicked the effects of amines on ADCC, suggesting the possibility that a CAM-regulated process might be involved in the functional changes provoked by amines on ADCC. Finally, binding of 125I-immune complexes to the effector cells in the presence of amines showed lack of correlation between alterations in ADCC capacity and Fc gamma R expression.

Amines↗
PubMed1988

Cell cycle-related proteins: a flow cytofluorometric study in human tumors.

We used 2-parameter flow cytometry (FCM) to investigate the relationship between the cell cycle phases and 3 proteins whose expression is known to increase in proliferating cells: the surface antigen transferrin receptor (Trf-r), the "cyclin" (a proliferating cell nuclear antigen, PCNA), and the nuclear antigen recognized by the monoclonal antibody (MoAb) Ki-67. FITC-labeled antibodies against Trf-r, PCNA, and the Ki-67-reactive antigen, as well as propidium iodide-DNA distribution, were simultaneously measured on human leukemia HL-60 and K562, and breast carcinoma MCF-7 cell lines and on fresh human leukemic and glioblastoma cells. The 70% ethanol fixation for Trf-r and PCNA and the 95% acetone fixation for Ki-67 plus permeabilization (with 0.1% and 1% Triton X100, respectively, for the surface and the nuclear antigens) produced cell suspensions with negligible cell clumping, high-quality DNA profiles, and bright specific immunofluorescent staining. The investigated proteins have different relationships with the proliferative state of the cell. Trf-r is expressed mainly at the transition from G0/G1 to S-phase. PCNA expression is prominent in late G1 and through S-phase and decreases in G2-M. The Ki-67-reactive antigen is widely distributed in G1, S, and G2-M phases. Knowledge regarding the relationships between proliferation-associated antigens and cell cycle phase in normal and neoplastic cells could improve our understanding of the mechanisms underlying growth regulation and neoplastic transformation. Bivariate FCM is an easy method for obtaining these data from large numbers of cells.

Antibodies, Monoclonal↗
PubMed1988

The catalepsy test: its ups and downs.

The typical catalepsy test consists of placing an animal into an unusual posture and recording the time taken to correct this posture. This time is regarded as an index of the intensity of catalepsy. Catalepsy is a robust behavior, and the lack of standardization does not usually hinder its actual detection. However, the intensity of the cataleptic effect is influenced by minor methodological differences, and thus interpretation and comparison of results across laboratories are difficult. The behavioral catalepsy test can use any of several different apparatus, including wire grids, parallel bars, platforms, or pegs, to situate the animals in unusual positions. The most common, however, is the "bar test," and despite its wide use in psychopharmacological research, even parameters of this test are not standardized. The present article reviews the wide variety of parameters chosen by investigators that measure catalepsy. The methodological issues of repeated testing, scaling of scores, apparatus, animal weight, maximal test duration, behavioral criteria, and other influences are discussed. In addition, a brief review of the neuropharmacological basis of catalepsy is also included. Finally, it is argued that a universal, standardized bar test be adopted by researchers. New data on a novel automated bar test in the Digiscan Activity Monitoring System is presented.

Animals↗
PubMed1988

Prognostic parameters in myelodysplastic syndromes: a multiple regression analysis.

The influence on survival of 21 basic clinical and hematologic parameters was evaluated in 72 patients with previously untreated myelodysplastic syndromes (MDS). Only five parameters were significant by both survival curves and multiple regression analyses: hemoglobin level, bone marrow (BM) cellularity (estimated from trephine BM biopsies), BM blast percentage, age and BM erythro/myeloid (E/M) ratio. Using these parameters, multiple regression analysis enabled us to predict 34% of the survival of all MDS patients (p less than 0.002), 38% of that of patients who had stable disease (p less than 0.04) and over 80% of that of patients who developed acute leukemia (p less than 0.02). High BM cellularity was the most predictive factor for the development of leukemia. No factor was predictive for patients who died of cytopenic or other complications.

Humans↗
PubMed1988

Different activation pathways involved in antibody-dependent and immune-complexes-triggered cytotoxicity mediated by neutrophils.

We have shown previously that normal human neutrophils triggered by immune complexes displayed significant levels of cytotoxicity towards non-sensitized target cells (non-specific cytotoxicity-NSC) (Geffner, J. R. et al. 1987). Despite the fact that NSC and antibody-dependent cellular cytotoxicity (ADCC) are both mediated through neutrophil Fc gamma R and require the activation of the respiratory burst, the cytolytic mechanisms involved in each case appear to be different. In order to analyse the pathways of activation involved in the induction of NSC and ADCC, we studied here some of the metabolic requirements associated with each cytotoxic function. Our results suggest that ADCC is dependent on Na+/H+ antiporter activity, de novo protein synthesis, availability of external Ca2+ and calmodulin activity, activation of phospholipase C and activation of protein kinase C. On the other hand, NSC appears to be dependent on availability of external Ca2+ and calmodulin activity and activation of phospholipase A2. These results indicate that different pathways of activation are involved in the induction of neutrophil-mediated ADCC and NSC.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Refractory cytopenias: clinical course according to bone marrow cytology and cellularity.

One hundred and one patients with refractory cytopenia were reviewed for morphological classification (using bone marrow, BM, imprints for cytology and Jamshidi biopsies for BM cellularity) and clinical course. Final diagnoses were: moderate aplastic anemia (MAA), myelodysplastic syndromes (MDS) and hypoplastic acute leukemia (HAL). Ninety-two patients received high dose testosterone enanthate (TE) as first treatment (starting dose = 7-10 mg/week i.m. for at least three months). Median survival was significantly longer in MAA than in MDS and in HAL. Among MDS patients, those with primary acquired sideroblastic (AISA) and refractory (RA) anemia had median survival similar to those with MAA, but distinctly longer (p = 0.01) than patients with RA with an excess of blasts (RAEB), RAEB in transformation (RAEBtr) and chronic myelomonocytic leukemia (CMMoL). Acute leukemia (AL) developed more rarely (p less than 0.02) in MAA, AISA and RA than in RAEB, RAEBtr and CMMoL. Response to TE was seen in about two thirds of MAA and in a half of MDS and HAL patients. Among MDS patients, those with hypocellular BM developed leukemia less frequently, responded to androgens more often and survived longer than those with normocellular and, especially, with hypercellular BM. These data indicate that the cytohistological classification of refractory cytopenias identifies essentially two groups with different clinical behaviour, one (MAA, AISA and RA) having long life expectancy and a low probability of developing AL and the other (RAEB, RAEBtr, CMMoL) with a short survival and relatively frequent leukemic complication. Bone marrow hypocellularity seems to be a favourable prognostic factor in MDS. Patients with refractory cytopenias, especially those with a hypocellular BM, can be advantageously treated with androgens.

Acute Disease↗
PubMed1987

Amphetamine-induced on- and off-wall rearing in adult laboratory rats.

Recently, Bauer reported that amphetamine did not increase rearing behavior in adult rats. This result is at variance with many earlier reports demonstrating that amphetamine does increase rearing behavior. Because Bauer's automated measure only detected rearing when it occurred on the wall of the cage, it is possible that amphetamine only increased rearing behavior that occurred off the wall, which was not measured in his study. Bauer also included non-habituated animals in his study which might account for the discrepant results. The present experiment was performed to determine if, indeed, there was a difference between amphetamine induced on- and off-wall rearing and to determine to what extent habituation affected both types of rearing. The findings demonstrated that both types of rearing increased following d-amphetamine administration for both habituated and non-habituated animals. However, at the highest dose of d-amphetamine studied (4 mg/kg) rearing occurred mainly on the wall. Additionally, rearing behavior was found to increase following amphetamine when measured in the Digiscan Animal Activity Monitoring system which detects, but does not discriminate between, both on- and off-wall rearing.

Animals↗
PubMed1987

Inhibition of lymphocyte and monocyte antibody-dependent cellular cytotoxicity by immune complexes: effect of normal human serum.

Antibody-dependent cellular cytotoxicity (ADCC) mediated by peripheral blood mononuclear cells (PBMC) and by isolated populations of lymphocytes and monocytes was compared for susceptibility to inhibition by soluble immune complexes (IC) and by heat-aggregated IgG (HAIgG). It was found that the decrease of ADCC was significantly higher in lymphocytes than in monocytes at all IC and HAIgG concentrations employed (P less than 0.001). The degree of inhibition of PBMC-mediated ADCC was similar to that observed in monocyte ADCC. In previous reports, we demonstrated that IC inhibition of PBMC-mediated ADCC could be reversed by normal human serum (NHS) used as a source of complement (C). In this paper, we study the effects of NHS on isolated populations of monocytes and lymphocytes. It was found that NHS was unable to modify the capacity of IC-blocked monocytes to mediate ADCC. On the contrary, NHS efficiently reversed the inhibition of both ADCC and Fc gamma R expression in IC-blocked lymphocytes. We propose that the regulation of Fc gamma R-IC interactions by C may constitute a physiological way to preserve Fc gamma R expression in lymphocytes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Cyclophosphamide augments ADCC by increasing the expression of Fc-receptors.

Previous reports demonstrated that cyclophosphamide (Cy) enhances two Fc gamma receptor (Fc gamma R) mediated functions: antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. In this paper we examine the mechanisms whereby Cy modifies the cytotoxic capacity of mouse splenocytes. The results indicate that the observed augmentation of ADCC could not be attributed to a higher proportion of macrophages and/or polymorphonuclear leukocytes (PMN), but rather to an enhanced activity per effector cell. Binding studies showed that this augmentation was associated with an increased number, but not an increased avidity of Fc gamma R sites. The possibility that the enhanced Fc gamma R expression by Cy may result in the alteration of other Fc gamma R-mediated functions is discussed.

Animals↗