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Biomedical subjects

M Ruggiero

Publications and source records attributed to M Ruggiero.

At least 91 records · Page 5Linked to original sources
PubMed1986

Sustained proteolysis is required for human platelet activation by thrombin.

A maximally effective dose of indomethacin does not prevent serotonin release and aggregation in human platelets stimulated with thrombin. Thrombin induces rapid activation of inositol phospholipids-specific phospholipase C, which is reflected by the degradation of inositides and the phosphorylation of the resultant 1,2-diacylglycerol to phosphatidic acid. Thrombin also activates protein kinase C and myosin light chain kinase as indicated by phosphorylation of the 40,000 and 20,000 dalton proteins, respectively. Leupeptin, a protease inhibitor that does not inhibit thrombin's proteolytic activity or its binding to platelet surface, is able to reverse platelet activation by thrombin when it is administered after the addition of the agonist and indomethacin. The results suggest a proteolytic-mediated pathway in transmembrane signalling involved in platelet activation by thrombin.

Blood Platelets↗
PubMed1986

Protease and cyclooxygenase inhibitors synergistically prevent activation of human platelets.

Thrombin induces platelet aggregation and formation of a fibrin clot in platelet-rich plasma; leupeptin, a protease inhibitor, partially inhibits platelet aggregation, but it does not inhibit fibrin clot formation. Indomethacin does not inhibit either thrombin-induced platelet aggregation or fibrin clot formation. However, when the two drugs are given together, a synergistic inhibition of thrombin-induced platelet aggregation occurs, while fibrin clot formation remains unaffected. Thrombin-induced stimulation of the release of serotonin in washed human platelets is also synergistically inhibited by the combined actions of leupeptin and indomethacin. Thrombin and collagen, added simultaneously, induce full platelet aggregation and release of serotonin. Neither leupeptin nor indomethacin inhibits platelet responses elicited by both agonists; however, when leupeptin and indomethacin are given together, a synergistic inhibition of thrombin- and collagen-induced response is observed. These findings might be relevant in prophylaxis and treatment of thromboembolic disease.

Blood Platelets↗
PubMed1986

Cooperation of heparin with other angiogenetic effectors.

The heterogeneous variety of factors involved in the induction of vessels to proliferate is briefly reviewed in connection with the possible cooperative role of heparin, a compound indicated by many kinds of evidence to be basically involved in angiogenesis.

Adenosine Diphosphate↗
PubMed1985

Leupeptin selectively inhibits human platelet responses induced by thrombin and trypsin; a role for proteolytic activation of phospholipase C.

Thrombin and trypsin induce serotonin release and aggregation in human platelets. Both proteases induce activation of phospholipase C as reflected by formation of inositol phosphates and phosphorylation of the resultant 1,2-diacylglycerol to phosphatidic acid. Also, thrombin and trypsin activate protein kinase C and myosin light chain kinase as indicated, respectively, by phosphorylation of the 40,000 and 20,000 dalton proteins. Leupeptin, a known inhibitor of serine proteases, blocks all the observed responses of human platelets to trypsin and thrombin. Leupeptin does not inhibit serotonin release and aggregation induced by other platelet stimuli such as collagen, platelet-activating factor, ionophore A23187, and arachidonic acid. The implication of a proteolytic-mediated pathway in the transmembrane signalling involved in platelet activation is discussed.

Adult↗
PubMed1985

ATP depletion in human platelets caused by permeabilization with saponin does not prevent serotonin secretion induced by collagen.

Saponin (5 to 25 micrograms/ml) produced a concentration-dependent decrease in the cellular content of total ATP and [32P]ATP in 32P-labeled human platelets. In platelets whose ATP had been profoundly decreased by saponin, Ca2+ produced phosphomonoesteratic cleavage of the polyphosphoinositides with a concomitant accumulation of phosphatidylinositol. Collagen still induced secretion of serotonin in platelets that had been treated with saponin in the presence or absence of Ca2+. This effect of collagen occurred in the absence of the formation of cyclooxygenase metabolites. In platelet permeabilized with saponin, agonist-induced secretion and aggregation seems to be unrelated to protein phosphorylation, breakdown of the inositol phospholipids by phospholipase C and formation of cyclooxygenase metabolites.

Adenosine Triphosphate↗
PubMed1985

Thrombin induces serotonin secretion and aggregation independently of inositol phospholipids hydrolysis and protein phosphorylation in human platelets permeabilized with saponin.

We have observed that the addition of Ca2+ to platelets, permeabilized with saponin, promotes a drastic dephosphorylation of proteins and polyphosphoinositides without inducing platelet responses. Subsequent addition of thrombin could promote secretion of serotonin and aggregation in the absence of phospholipase C-induced breakdown of the inositol phospholipids and protein phosphorylation. This information indicates that activation of saponized platelets by thrombin is independent of the formation of second messengers derived from the phospholipase C-induced breakdown of the inositol phospholipids. The implications of this result for intact platelets are discussed.

Blood Platelets↗
PubMed1985

Effects of cortisone with and without heparin on angiogenesis induced by prostaglandin E1 and by S180 cells, and on growth of murine transplantable tumours.

Cortisone acetate, locally applied in sustained-release pellets, is effective in inhibiting angiogenesis induced by prostaglandin E1 in the rabbit cornea. The inhibitory effect of cortisone is not increased by addition of heparin. Similar results were obtained with angiogenesis induced by S180 cells. The effects of cortisone with and without heparin were also studied on 5 transplantable murine tumours: 3 variants of B16 melanoma, Lewis lung carcinoma and fibrosarcoma M4. The effect of cortisone in slowing the growth rate of tumours was modestly potentiated by heparin, but no regression of the tumour mass occurred.

Alprostadil↗
PubMed1985

Complexing of heparin with phosphatidylcholine. A possible supramolecular assembly of plasma heparin.

In a series of attempts to reveal plasma heparin, we found that high ionic strength and modification of protein amino groups were not effective in extracting endogenous heparin (or, indeed, a large percentage of exogenous labelled heparin), whereas delipidation in the presence of 4M-guanidinium chloride gave high yields, indicating that plasma heparin may be assembled with compounds other than proteins, in a form making it inaccessible to water and ions. During the extraction of lipids, a paradoxical entry of heparin into the organic phase was observed. Detergents, including sodium dodecyl sulphate, did not shift heparin into the aqueous phase, whereas repeated chloroform/methanol extraction did so. Using purified compounds we were able to reproduce in vitro both the scavenging of heparin from water as well as the formation of heparin-phosphatidylcholine complexes soluble in organic solvents. Evidence for complexing of heparin with phosphatidylcholine was also obtained by electrophoretic and ultracentrifugation assays. The quaternary-ammonium-containing phosphatidylcholine was the more effective phospholipid in binding heparin; anionic phospholipids did not bind. Only heparin-like glycosaminoglycans bound phosphatidylcholine, but less-sulphated compounds (heparan sulphate and dermatan sulphate) were weaker ligands. Gel-filtration experiments showed that heparin was not bound to liposome vesicles, but that a measurable percentage of the phospholipids was stripped off from vesicles and was found in the form of a complex separable from liposomes by gel filtration. The molecular basis as well as the biological role of the interaction of heparin with major membrane phospholipids are discussed.

Chloroform↗
PubMed1984

Molecular events involved in the proaggregating effect of heparin on human platelets.

Molecular mechanisms underlying the ability of heparin to enhance the platelet-aggregating effect of various agonists were studied. Heparin potentiates the aggregating effect of adenosine diphosphate (ADP) and epinephrine, but it is uneffective on the aggregation induced by ristocetin and collagen. Heparin inhibits aggregation induced by thrombin in the presence of plasma, but it is uneffective, or sometimes stimulates aggregation, in the absence of plasma. The effects on the platelet-activating factor- (PAF-acether) induced aggregation are very variable. The late phase of the ADP-induced aggregation is sensitive to proteinase inhibitors, but heparin overcomes this inhibitory effect. Drugs which inhibit remodeling of membrane phospholipids abolish the potentiating effect of heparin, while cyclooxygenase inhibitors do not. The proaggregating effect of heparin subfractions correlates with the lipoprotein lipase activity and, slightly, with the molecular weight, but it does not correlate with the anticoagulant activity. Platelets prelabelled with phosphatidyl[U14C]inositol show a very rapid effect of heparin in triggering phosphatidylinositor breakdown and a cooperative effect with ADP, a known agonist of the 'phosphatidylinositol cycle'. Heparin is also effective in stimulating the labelling of polyphosphoinositides in platelets prelabelled with 32Pi. These results, together with the selective sensitivity to drugs, lead to the conclusion that a stimulatory effect on the very early events of remodeling of membrane phospholipids is involved in the platelet proaggregating effect of heparin.

Adenosine Diphosphate↗
PubMed1984

Cooperative effect of exogenous heparin-like compounds and secreted glucocorticoid-induced inhibitor on plasminogen activator in 3T3 cell cultures.

Balb/c 3T3 cultures grown in the absence of serum release both plasminogen activator and plasminogen activator inhibitor in the culture medium. Cellular transformation with SV-40 virus increased the level of the activator, whereas dexamethasone increased the level of the inhibitor. Heparin added to the medium potentiated the glucocorticoid-induced inhibitory activity, strongly decreasing or completely abolishing the activity of plasminogen activator. Heparin sulfate showed similar effects to heparin, although at higher concentrations. It is suggested that heparin-like compounds are involved in the regulation of plasminogen activator, acting as inhibitory cofactors.

Animals↗
PubMed1984

Chronic obstructive airways disease after bone marrow transplantation.

The clinical course, serial pulmonary function studies, lung histopathologic findings, and treatment in two patients after bone marrow transplantation for acute monoblastic leukemia or aplastic anemia are presented. The course in one patient has been slowly progressive for 2 years and characterized by chronic obstructive airways disease and recurrent pneumothoraces. Histopathologic changes were nonspecific, characterized by chronic interstitial pneumonitis and interstitial fibrosis. In the second patient there was insidious onset of disease with increasing dyspnea on exertion and rapid clinical deterioration; he died within 4 months of severe obstructive airways disease. Necrotizing bronchitis and bronchiolitis characterized the lung findings. Neither patient responded to conventional bronchodilator therapy, and prednisone was the only agent to produce subjective, though transient, improvement. Symptomatic obstructive airways disease associated with chronic graft-versus-host disease is emerging as a potentially major cause of morbidity and mortality after marrow transplantation.

Adolescent↗
PubMed1983

Stressful life change and delinquent behavior.

The study examined life change in relation to self-reported involvement in five specific types of crime and delinquency among members of a noninstitutionalized sample. A group of 531 in-school youths, age 14 to 19, were asked to report how frequently in the 6 months since school started they had performed each of 26 criminal or delinquent acts and how many of 20 potentially stressful life events they had experienced in the year preceding the start of school. Regression analyses showed that, for both males and females, life change added significantly to age and SES in predicting violence, theft, drug use, property damage, and a group of relatively nonserious delinquent acts. On the basis of social psychological theory and research, possible explanatory mechanisms in the link between life stress and specific forms of crime and delinquency are discussed as part of a proposed life stress-deviance model.

Adolescent↗
PubMed1982

Stone-Roth model of civil commitment and the California dangerousness standard: operational comparison.

Professional opposition to making "dangerousness" the primary criterion for involuntary civil commitment has galvanized in support of the proposed "new medical model." The Stone-Roth criteria for commitment were applied to patients being committed under California's version of the dangerousness standard. Results showed that 86% of the patients committed under the California statute were viewed by the examining psychiatrists as committable under the Stone-Roth procedures as well.

Adult↗
PubMed1981

Diurnal variations in plasma aminoacid concentrations. I) Effect of dietary protein intake on rhythm of neutral aminoacids.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For 3 consecutive 5-day periods, subjects consumed diet containing 0-or 75 or 150 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentration of all amino acids in the late morning and afternoon, while the 150 g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g protein tended to diminish the amplitude the daily rhythms.

Adult↗
PubMed1981

Diurnal variations in plasma concentrations of neutral amino acids. 2) Effect of dietary protein intake on amino acid ratios.

The ratios of plasma tryptophan, tyrosine and phenilanine levels to the sum of other large neutral amino acids are reported. They tended to fall as the protein content of the diet was increased. The isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma tryptophan and tyrosine ratios in animal are known to cause parallel alterations in brain tryptophan and tyrosine and levels, and thus in the rates of brain serotonin and catecholamines synthesis, out data suggest that the ingestion of carbohydrates and protein may also normally affect brain monoamine synthesis in humans.

Adult↗
PubMed1981

Plasma 1,25 hydroxycholecalciferol concentrations and net intestinal calcium, phosphate and magnesium absorption in man.

We evaluated the relationship between plasma concentrations of the renal hormone (I,25(OH)2 vitamin D and net intestinal CA,PO4 and Mg absorption in healthy volunteers eating similar diets. Net intestinal CA absorption was positively correlated to plasma I,25(OH)2D concentrations. By contrast, there was no significant correlation between PO4 and Mg absorption and plasma I,25(OH)2D concentrations. We conclude that net intestinal Ca absorption is critically dependent upon the availability of renal homone, while other factors must play a dominant role in regulating net intestinal PO4 and MG absorption.

Adult↗