Destruction of the platelet aggregating activity of ristocetin A

Summary Hydrolysis of ristocetin A in 0.1 N HCl at 37°C for 2 h resulted in the loss of its ability to induce platelet aggregation in platelet-rich plasma derived from guinea-pigs and humans. However its antibiotic activity againstStaph. aureus was not lost.This work was supported, in part, by a contract from the National Heart, Lung, and Blood Institute (USPHS).     

Defective ristocetin and bovine factor VIII-induced platelet aggregation in normal rats

Riassunto Le piastrine di 3 diversi ceppi di ratti, contrariamente alle piastrine umane e di cavia, non sono aggregate (sia in vitro che in vivo) nè dalla ristocetine nè dal fattore von Willebrand bovino, porcino o umano, quest'ultimo reso aggregante previo trattamento enzimatico. Tale insensibilità, di cui si è potuta escludere l'origine plasmatica, potrebbe derivare dall'assenza, sulle piastrine di ratto, di un recettore per il fattore von Willebrand (acido sialico?); potrebbe essere cosi spiegata anche la mancata risposta delle piastrine alla ristocetina. Questi risultati suggeriscono che le piastrine di ratto possono essere un utile modello sperimentale per lo studio della sindrome di Bernard-Soulier nell'uomo.

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This work was supported by Contract No. 73-00400-04 of the C.N.R., Roma, Italy. The skilful technical assistance of MissAnnalisa Cavenaghi is appreciated.     

Comparative platelet anti-aggregant activity of D-cysteinolic acid analogues

D-Cysteinolic acid (1) analogues with an S-C-C-N skeleton showed increased platelet anti-aggregant activity in the following order: 2-aminoethanesulfonic acids, thiazolidines, 2-aminoethanethiols and 2-aminoethyl disulfides. Methyl substitutions at the 2-position potentiated the activity. Of these analogues, bis [(R)-2-aminopropyl] disulfide was the most potent inhibitor of platelet aggregation, with about 600-fold the activity of (1).     

A calcium-sensitizing system from human platelets and its activity on muscle and platelet actomyosin

Zusammenfassung Die Mg-ATPase des kontraktilen Systems von Blutplättchen, Thrombosthenin, wird durch Spuren von Calciumionen reguliert. Eine Regulationseiweisse enthaltende Franktion kann von Thrombosthenin abgetrennt werden. Zugabe dieser Eiweissfraktion zu sogenanntem «desensibilisierten» Thrombosthenin aber auch zu «desensibilisiertem» Actomyosin aus Skelettmuskel vermag die Mg-ATPase beider Systeme wieder von Spuren von Calciumionen abhängig zu machen. Die Regulationseiweisse, d. h. der Tropomyosin-Troponin-Komplex aus Skelettmuskeln, vermögen ebenfalls «desensibilisiertes» Thrombosthenin wieder Calcium-abhängig zu machen.     

Use of aggregating cell cultures for toxicological studies

Relatively simple techniques are now available which allow the preparation of large quantities of highly reproducible aggregate cultures from fetal rat brain or liver cells, and to grow them in a chemically defined medium. Since these cultures exhibit extensive histotypic cellular reorganization and maturation, they offer unique possibilities for developmental studies. Therefore, the purpose of the present study was to investigate the usefulness of these cultures in developmental toxicology. Aggregating brain cell cultures were exposed at different developmental stages to model drugs (i.e., antimitotic, neurotoxic, and teratogenic agents) and assayed for their responsiveness by measuring a set of biochemical parameters (i.e., total protein and DNA content, cell type-specific enzyme activities) which permit a monitoring of cellular growth and maturation. It was found that each test compound elicited a distinct, dose-dependent response pattern, which may ultimately serve to screen and classify toxic drugs by using mechanistic criteria. In addition, it could be shown that aggregating liver cell cultures are capable of toxic drug activation, and that they can be used in co-culture with brain cell aggregates, providing a potential model for complementary toxicological and metabolic studies.     

Use of aggregating cell cultures for toxicological studies

Summary Relatively simple techniques are now available which allow the preparation of large quantities of highly reproducible aggregate cultures from fetal rat brain or liver cells, and to grow them in a chemically defined medium. Since these cultures exhibit extensive histotypic cellular reorganization and maturation, they offer unique possibilities for developmental studies. Therefore, the purpose of the present study was to investigate the usefulness of these cultures in developmental toxicology. Aggregating brain cell cultures were exposed at different developmental stages to model drugs (i.e., antimitotic, neurotoxic, and teratogenic agents) and assayed for their responsiveness by measuring a set of biochemical parameters (i.e., total protein and DNA content, cell type-specific enzyme activities) which permit a monitoring of cellular growth and maturation. It was found that each test compound elicited a distinct, dose-dependent response pattern, which may ultimately serve to screen and classify toxic drugs by using mechanistic criteria. In addition, it could be shown that aggregating liver cell cultures are capable of toxic drug activation, and that they can be used in co-culture with brain cell aggregates, providing a potential model for complementary toxicological and metabolic studies.     

GFA expression in aggregating cultures of rat C6 glioma

Summary Few C6 glioma cells synthesize the astroglia-specific GFA protein in monolayer culture. A uniform population of GFA-positive cells was obtained by aggregating C6 cells in suspension culture, as previously reported for C6 glioma maintained on sponge foam matrices. These results strongly suggest that cell-to-cell interactions promote GFA expression.Acknowledgments. This work was supported by USPHS grant No. 13034 and by the Veterans Administration.     

Production of the lymphokine,macrophage aggregating factor,is not inhibited by histamine

Summary Unlike the previously reported inhibitory effect of histamine on the production of the lymphokine, migration inhibitory factor, histamine did not inhibit the production of macrophage aggregating factor (MAgF). By contrast, both prostaglandin E₂ and hydrocortisone inhibited MAgF production, in a dose-dependant manner.     

Destruction of triplet nitrenium ion by ascorbic acid

Zusammenfassung Die Reaktion des Karzinogens N-acetoxy-2-acetamidofluoren mit Guanosin wird durch Ascorbinsäure, jedoch nicht durch Zitronensäure gehemmt. Diese Hemmung bewirkt eine vermehrte Bildung von 2-Acetamidofluoren. Anscheinend reagiert Ascorbinsäure mit dem N-2-Fluorenyl-N-acetylnitreniumtriplett unter Bildung von Acetamidofluoren und oxidierter Ascorbinsäure.     

Effect of platelet membranes on the electrophoretic pattern of 6-phosphogluconic dehydrogenase from platelet lysates

Riassunto L'incubazione di lisati piastrinici con NADP provoca inattivazione della 6PGD e ne modifica la migrazione elettroforetica. Non si osserva invece attivazione della GSSG-R.

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Supported by a grant from the Consiglio Nazionale delle Ricerche Contratto No 70.00378/18/115.3565. Roma (Italy).     

Destruction of virus infected cells by neutrophils and complement

The paper describes an antibody independent mechanism of cytotoxicity whereby virus infected but not uninfected cells are destroyed by the combined presence of neutrophils and complement.     

Destruction of virus infected cells by neutrophils and complement

Summary The paper describes an antibody independent mechanism of cytotoxicity whereby virus infected but not uninfected cells are destroyed by the combined presence of neutrophils and complement.Supported by A.I. 14981 and by the MRC of Canada.Acknowledgment. We thank C.J. Wust for invaluable discussions.     

Destruction of afferent nerve terminals in the inner ear of frog by aminooxyacetic acid

Summary The drug aminooxyacetic acid, which inhibits GABA-transaminase, destroys the afferent nerve endings in the inner ear of the frog. The efferent nerve endings and the sensory cells are not affected.     

Glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity

The present study investigated the mechanisms underlying the inhibition of platelet phosphatidylserine (PS) exposure by GPIIb/IIIa blockade. Platelet PS exposure induced by thrombin stimulation was cell-cell contact dependent. GPIIb/IIIa blockade by c7E3 or SR121566 inhibited thrombin-induced platelet PS exposure. Thrombin stimulation induced mild, while A23187 induced extensive platelet-derived microparticle (PDMP) generation. Thrombin-induced PDMP generation was not inhibited by GPIIb/IIIa blockade. Aminophospholipid translocase activity was reduced upon platelet activation by thrombin. The reduction of non-PS-exposing platelets was attenuated by GPIIb/IIIa blockade, while little translocase activity was seen in PS-exposing platelets. Thrombin increased scramblase activity slightly in non-PS-exposing platelets, which was inhibited by GPIIb/IIIa blockade, and markedly enhanced scramblase activity in PS-exposing platelets. Activation of platelet calpain and caspase-3 or cytosolic calcium mobilization were not altered by GPIIb/IIIa inhibition. Thus, GPIIb/IIIa blockade inhibits platelet PS exposure by enhancing translocase activity and attenuating scramblase activity, but does not inhibit PDMP generation. Received 13 December 2006; received after revision 5 February 2007; accepted 9 March 2007     

The release of platelet factor 4 during platelet aggregation and the possible significance of this reaction in hemostasis

Résumé Nous avons constaté que le facteur plaquettaire 4 est libéré au début de l'aggrégation des plaquettes par l'ADP et l'adrénaline. Ce phénomène a pu être mis en évidence en étudiant l'activité antihéparinique et l'activité paracoagulante (coagulation non enzymatique de complexes solubles de monomères de fibrine) du facteur plaquettaire 4.     

Destruction of afferent nerve terminals in the inner ear of frog by aminooxyactic acid.

The drug aminooxyacetic acid, which inhibits GABA-transaminase, destroys the afferent nerve ending in the inner ear of the frog. The efferent nerve endings and the sensory cells are not affected.