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Biomedical subjects

A Mazzone

Publications and source records attributed to A Mazzone.

At least 19 recordsLinked to original sources
PubMed1995

Clinical and angiographic correlates of leukocyte activation in unstable angina.

OBJECTIVES: This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated. BACKGROUND: Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition. METHODS: Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers. RESULTS: In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood. CONCLUSION: These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Adult↗
PubMed1994

Granulocyte defects and opioid receptors in chronic exposure to heroin or methadone in humans.

In order to elucidate better the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in three groups of HIV-negative subjects, including 20 active parenteral heroin abusers (H), 20 long-term methadone-maintained former opiate abusers (M) and 20 healthy controls (C). Chemotaxis to N-formyl methionyl-leucyl-phenylalanine (fMLP), casein and activated plasma were markedly and similarly reduced (approx. 50%) in both H and M groups, as was true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. Polymorphonuclear (PMN) of H and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment, with values that were less than 10% of those in controls, as observed by flow cytometry. In parallel, PMN of H and M individuals presented an approximately four-fold increase in opioid receptors numbers compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism underlying the observed changes in PMN of H and M individuals is discussed.

Adolescent↗
PubMed1993

The role of integrins in granulocyte dysfunction in myelodysplastic syndrome.

The aim of the present study was to evaluate the function of granulocytes in 20 patients affected by myelodysplastic syndrome (MDS) and correlate this with the expression of surface membrane integrins. The granulocytes showed a deficit in chemotaxis (34 +/- 12 vs 84 +/- 10, p < 0.01) in superoxide release (12 +/- 7 vs 30 +/- 10, p < 0.01) and in aggregation 12 +/- 6 vs 36 +/- 9, p < 0.01 using fMLP as stimulus. We also demonstrated with cytofluorimetric and alkaline phosphatase immunoenzymatic analysis (APAAP), decreased expression of CD11b/CD18 receptor detected by OKM1 (p < 0.001) and CD18 detected by MoAb IOT-18 (p < 0.001). PMNs CD11b/CD18 up-regulation and APAAP image analysis studies showed a lower level of expression of CD11b/CD18 in granulocytes from MDS patients compared to controls (p < 0.001). We concluded that granulocyte dysfunction in MDS may be correlated with modification of leukocyte integrins.

Adult↗
PubMed1993

Clinical efficacy of dirithromycin versus miocamycin in tonsillopharyngitis.

A single-blind, randomized, parallel-group study was conducted to compare the efficacy and safety of dirithromycin with miocamycin in the treatment of streptococcal pharyngitis/tonsillitis caused by Group A streptococci. The study population consisted of 60 patients: 30 were randomized to receive 500 mg dirithromycin od and 30 to receive 600 mg miocamycin bd. All 30 dirithromycin-treated patients were eligible for efficacy analysis. A favourable clinical response was observed in 100% of these patients at the post-therapy visit. In the miocamycin-treated group, 28 of 30 (93.3%) patients were eligible for efficacy analysis; a favourable clinical response was observed in 100%. Bacteriological cure of evaluable dirithromycin- and miocamycin-treated patients was 96.7% and 92.9%, respectively. No statistically significant post-therapy differences in clinical or bacteriological response rates were noted between the two groups. Adverse event analysis showed no significant differences between treatment groups. There were no serious adverse events during the study. Two miocamycin-treated patients were prematurely withdrawn from the study due to adverse events (diarrhoea). Analysis of clinical laboratory data revealed no statistically significant differences between the treatment groups that were considered to be drug related. The results of this study suggest that dirithromycin has comparable safety and efficacy to miocamycin in the treatment of streptococcal pharyngitis/tonsillitis infections caused by Group A streptococci.

Adolescent↗
PubMed1993

The CD11/CD18 granulocyte adhesion molecules in myelodysplastic syndromes.

We have evaluated the function of granulocytes in 14 patients suffering from myelodysplastic syndrome (MDS). We also evaluated the functional and immunochemical activities of five monoclonal antibodies (MoAbs) reactive with the CD11/CD18 leucocyte adhesion molecules of granulocytes. Granulocytes showed a decrease in chemotaxis (P < 0.001) and in aggregation (P < 0.01) using various agents as a stimulus. Cytofluorimetric and immunoenzymatic assays with alkaline phosphatase (APAAP) analysis showed decreased expression of the CD11b/CD18 receptor detected by OKM1 (P < 0.001). Despite LFA-1 and-CD11a/CD18 was expressed in normal amounts. The studies of upregulation of granulocytes CD11b/CD18 and image analysis of immunochemical preparation (APAAP) demonstrated decreased expression of CD11b/CD18 in granulocytes from MDS compared to controls (P < 0.001). We conclude that granulocyte dysfunction in MDS may be correlated with decreased expression of surface CD11b/CD18 leucocyte adhesion molecules or their structural modification.

Adult↗
PubMed1993

Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease.

BACKGROUND: A rapid increase in leukocyte adhesion to endothelial cells is one of the first events in the acute inflammatory response and in the pathogenesis of vascular diseases. A subgroup of cell surface glycoproteins (the CD11/CD18 complex) play a major role in the leukocyte adhesion process; in particular, the CD11b/CD18 receptor can be upregulated severalfold in response to chemotactic factors. The purpose of this study was to assess whether upmodulation of granulocyte and monocyte CD11b/CD18 receptors takes place during the passage of blood through the coronary tree of patients with clinical manifestations of ischemic heart disease. METHODS AND RESULTS: Thirty-nine patients who underwent diagnostic coronary arteriography were studied. Group 1 (15 patients) had a clinical diagnosis of unstable angina, group 2 (14 patients) had stable exertional angina, and group 3 (10 patients) had atypical chest pain. Simultaneous sampling from the coronary sinus and aorta was obtained before coronary arteriography. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Leukocytes were stained in unseparated blood to avoid in vitro manipulation that could activate phagocytes. Group 1 and 2 patients had significant coronary artery disease (> 50% coronary narrowing in at least one major coronary vessel), whereas group 3 patients had normal coronary arteries. In group 1, granulocytes and monocytes showed a significantly higher expression of the CD11b/CD18 adhesion receptor in the coronary sinus than in the aorta (both P < .01), whereas no difference in CD11b/CD18 expression was seen in groups 2 and 3. CONCLUSIONS: Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.

Adult↗
PubMed1993

[Correlations between membrane integrins and granulocyte defects in myelodysplastic syndromes].

The aim of the present study was to evaluate some functions of neutrophil granulocytes (PMNs), such as aggregation, superoxide production, chemotaxis and adhesion molecules involved in these processes, in 22 patients suffering from Myelodysplastic Syndrome (MDS), to clarify if granulocytes alterations described in this syndrome is really correlated with the expression of surface membrane integrins. Several patients suffering from MDS present granulocytopenia and/or absolute monocytoses; neutrophil granulocytes can have typical nuclear and cytoplasmatic alterations. These granulocytic anomalies are valuable in about 90% of patients suffering from MDS. The granulocytes showed a significant deficit in chemotaxis stimulated by serum activated with E. Coli, casein and formyl-methionyl-leucylphenylalanine (fMLP) (p < 0.01) and in superoxide production stimulated by phorbol-myristate-acetate (PMA). We also studied the role of membrane integrin CD11/CD18 using specific monoclonal antibodies (MoAb). The cytofluorimetric analysis demonstrated a significant inhibition in expression of CD11b/CD18 receptors in patients suffering from MDS (p < 0.001), while the expression of CD11a/CD18 and CD11c/CD18 receptors was normal. In conclusion we found specific alterations in PMNs functions in MDS and a correlation of these anomalies with membrane integrins of PMNs is therefore possible.

Adult↗
PubMed1993

Assay of phagocytic cell functions.

The fundamental role of the immune system is recognition of the self from the non-self; in this way the principal functions of the immune system can be summarized as: resistance against the cells and foreign substances which are potentially damaging the tissues; identification of neoplastic cells to be destroyed. The cells which have this role are essentially lymphocyte, neutrophils and macrophages: extracellular and cellular humoral factors also play their role into the inflammatory process. In fact, we define the normal responses of phagocyte as the capacity of the specific phagocytic cell to respond to various stimuli and to migrate to the location of the damage. This complex cellular defense mechanism comprises several steps that can be summarized as following: opsonization of particles to be ingested, adhesion and aggregation of phagocytes to vascular endothelium, migration of phagocytes through the vessel walls, chemotaxis of phagocytes towards pathogenic agents, recognition of the particles/antigens by the phagocytes which subsequently adhere to their surface, ingestion of the particles with formation of a phagosome. This process is completed with the fusion of the phagosome with cellular granules (lysosomes) and formation of phagolysosomes, degranulation and release of the enzyme laden granules into the phagolysosome, lysis and killing of ingested particles and bacteria. It is clear from this schematic summary, that the response to pathogens can be very complex and each of the processes involved in the above described steps could be deranged leading to various pathological changes. We analyze the most classical and new methods to study the physiopathology of granulocytes, which are important for clinical diagnosis of phagocyte diseases or for phagocytic dysfunction in various syndromes and in neoplastic patients.

Cell Adhesion↗
PubMed1992

Correlation between CD11b/CD18 and increase of aggregability of granulocytes in coronary artery disease.

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Rabbit-derived antiserum-dependent reduction of circulating PMNs in the dog or using monoclonal antibody anti-CD11b/CD18 of PMNs resulted in smaller myocardial infarcts. Experience in humans shows the modification of PMN function in angina and during myocardial ischemia. In our studies, patients affected by coronary artery disease presented an increase in granulocyte aggregability in coronary sinus and showed a related higher expression of CD11b/CD18 in coronary sinus with respect to aorta leukocytes. The potential role of this modification of PMNs was analyzed.

Adult↗
PubMed1992

Phagocyte activation in coronary artery disease.

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Granulocytes can release a variety of molecules mediating tissue injury which act synergistically with other molecules and cells. The aim of our investigation was to evaluate the granulocyte function in patients affected by coronary artery disease (CAD) and during coronary angioplasty (PTCA). We studied 20 patients suffering from CAD. The PMN's aggregating activity was greater in the coronary sinus than in the aorta (P < 0.01). The increase in aggregating activity was evident in patients who were smokers: their cells release significantly lower quantities of leukotriene C4 (P < 0.025). In the 20 patients who underwent coronary angioplasty we analyzed superoxide release after stimulation with phorbol-myristate-acetate (PMA). The results showed a greater decrease of PMN's superoxide production in the coronary sinus than in the aorta (P < 0.05). In all patients affected by CAD we evaluated the PMN's expression of CD11b/CD18 membrane integrins. In these patients the increase in expression of CD11b/CD18 was statistically significant in comparison with the controls (P < 0.01). This increase in expression correlates with a higher aggregation (r = 0.87, P < 0.001). The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in the pathophysiology of myocardial injury due to regional ischemia and reperfusion is an area of intense investigation. This paper presents studies carried out in vivo which have been instrumental in demonstrating the role of granulocytes as mediators of myocardial ischemia.

Angioplasty, Balloon, Coronary↗
PubMed1992

Interaction between (-)naloxone and morphine in modifying superoxide generation from human granulocytes.

The effect of the opioid agonist morphine and of the (-) and (+) stereoisomers of the antagonist naloxone were studied on superoxide generation from human granulocytes. Morphine or naloxone had no effect on basal or phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide generation. Combined equimolar (-)naloxone and morphine concentrations (0.1 pM-0.1 microM) inhibited PMA-stimulated superoxide generation, while combined (+)naloxone and morphine had no effect. The stereospecific effect of naloxone suggests the involvement of opioid receptors. Thus, inhibition of superoxide generation by combined (-)naloxone and morphine could result from the unmasking of non opioid effects of morphine. It is suggested that the opioid control of oxidative metabolism in human granulocytes could involve multiple receptors mediating opposite effects.

Adult↗
PubMed1992

[An in-vivo and in-vitro study of phagocyte migration in patients with AIDS].

Polymorphonuclear leukocytes (PMN), are considered the first line of host defense. The PMN defects were related with an increase susceptibility to infections. We studied the neutrophil chemotactic function in 20 patients suffering from AIDS. The results of in vivo study demonstrated the decrease of chemotactic activity at 6 hour (p < 0.001) in the patients respect to control. The data of in vitro studies confirmed the granulocyte chemotactic defects, statistically significant, in the patients compared to the control subjects, when we used all chemotactic factors. These results showing the profound immune disturbances characteristic of the disease can favour infective susceptibility and complicate follow-up of AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1991

Granulocyte function in coronary artery disease.

Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty.

Coronary Disease↗
PubMed1991

Role of granulocytes in endothelial injury in coronary heart disease in humans.

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. A positive correlation was also found between leukocyte count and severity of coronary artery disease. Rabbit derived antiserum dependent-reduction of circulating PMNs in the dog or using monoclonal antibody anti-CD11b/CD18 of PMNs resulted in smaller myocardial infarcts. Granulocytes can release a variety of mediators tissue injury and synergize with these different mediators and other cells resulting in amplification of neutrophil stimulation and rising to additional products with enhanced endothelial injury. This paper reviews "in vivo" studies that have been instrumental in demonstrating this role of granulocytes as a mediator of myocardial ischemia. Experience in humans shows the modification of PMNs function in angina and during myocardial ischemia, and data from our group demonstrated that their aggregability is increased in the coronary sinus of patients with angiographically documented coronary disease. Upon re-perfusion PMNs accumulate and produce an inflammatory response resulting in endothelial injury. Free radicals formed during ischemia or re-perfusion produce deleterious effects on cell membranes, endothelial cell and myocardium. On the other hand the PMNs activation occurring during coronary angioplasty (PTCA) by the release of proteolytic enzymes and the generation of oxygen-free radicals, may aggravate the endothelial damage induced by PTCA and further stimulate platelets having potential implications in subsequent development of restenosis. An other aspect of PMNs function is related to leukotriene C4 release; the vasoconstrictor effect of this leukotriene on coronary arteries is synergistic with that induced by platelet-released thromboxane A2, as well as the decrease in coronary flow produced by the combination of both substances is greater than the sum of changes caused by the two eicosanoids separately administered. The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in pathophysiology of myocardial injury due to a regional ischemia and reperfusion is an area of intense investigation. Experimental and clinical studies to elucidate these events should not only provide insights into acute and chronic pathologic tissue damage, but may also lead to the identification of important new targets of pharmacologic intervention.

Angioplasty, Balloon, Coronary↗
PubMed1991

Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease.

Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II). To assess leukotriene C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 +/- 0.69 versus 5.92 +/- 0.54 ng/ml, p less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 +/- 0.72 versus 6.4 +/- 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Flow cytometry analysis of T cell subsets in skin of patients with specific cutaneous manifestation of B non-Hodgkin lymphoma.

Cutaneous lesions may be the atypical initial manifestation of blood disorder. Monoclonal antibodies identify surface phenotype of lymphocytes present in specific cutaneous lesions. We studied cutaneous infiltrates with flow cytometry in 10 cases of non-Hodgkin lymphoma. We characterized T cell subset in skin immune system. The percentage of T cells was compared to percentage observed in healthy specimens from same patient. T4 cells predominate in cutaneous infiltrates, with an increase in T4/T8 ratio. There was also an increase in T6+ cells, Langerhans cell markers in the skin. HLA-Dr+, T6 cells increased in all cases tested, indicative of dendritic cells. These data showed a modification of T lymphocytes only in skin infiltrate of lymphoma.

CD4-Positive T-Lymphocytes↗