A cDNA coding for human interleukin-2 (IL-2) has been cloned from a cDNA library prepared from partially purified IL-2 mRNA. The DNA sequence codes for a polypeptide which consists of 153 amino acids including a putative signal sequence. A biologically active polypeptide, characteristic of human IL-2, was produced when the cDNA was fused to a simian virus 40 promoter sequence and used to transfect cultured monkey COS cells.

1 A murine anti-human vWF monoclonal antibody, AJvW-2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin-(IC 50 =0.7+0.1 mg ml 71 ) and botrocetin-(IC 50 =1.8+0.3 mg ml 71 ) induced aggregation of human platelets. 2 AJvW-2 inhibited the high shear stress (10.8 N m 72 ) induced aggregation of human platelets dosedependently with an IC 50 =2.4+0.3 mg ml 71 , but had no e ect on low shear stress induced platelet aggregation (1.2 N m 72 ) up to 100 mg ml 71 . 3 AJvW-2 also inhibited the high shear stress (5.0 N m 72 ) induced adhesion of human platelets to collagen I with the same e cacy (IC 50 =2.4+0.3 mg ml 71 ), but had no e ect at low shear conditions (1.5 N m 72 ). 4 AJvW-2 inhibited the botrocetin-induced aggregation of platelets from guinea-pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea-pig platelets. 5 AJvW-2 prevented arterial thrombus formation in guinea-pigs at a dose of 100 mg kg 71 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonist lami®ban mediated inhibition of thrombosis at 1000 mg kg 71 was accompanied by a signi®cant prolongation of the bleeding time. 6 These results suggest that AJvW-2 is a potent inhibitor of the GPIb-vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.

1 The inhibitory eects of cilnidipine and various organic Ca 2+ channel blockers on high voltage-activated Ba 2+ currents (HVA I Ba ) in rat sympathetic neurones were examined by means of the conventional whole-cell patch-clamp recording mode under voltage-clamped conditions. 2 HVA I Ba was classi®ed into three dierent current components with subtype selective peptide Ca 2+ channel blockers. No o-Agatoxin IVA-sensitive (P-type) or o-conotoxin MVIIC-sensitive (Q-type) current components were observed. Most (485%) I Ba was found to consist of o-conotoxin GVIAsensitive N-type components. 3 The application of cilnidipine inhibited HVA I Ba in a concentration-dependent manner. The K d value for cilnidipine was 0.8 mM. Cilnidipine did not shift the current-voltage (I-V) relationship for HVA I Ba , as regards the threshold potential and peak potential where the amplitude reached a maximum. 4 High concentrations of three hypotensive Ca 2+ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA I Ba in a concentration-dependent manner. The K d values for nifedipine, diltiazem and verapamil were 131, 151 and 47 mM, respectively. A piperazine-type Ca 2+ channel blocker,¯unarizine, showed a relatively potent blocking action on I Ba . The K d value was about 3 mM. 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca 2+ channels which predominantly consist of an o-Cg-GVIA-sensitive component. This blockade of the N-type Ca 2+ channel, as well as the L-type Ca 2+ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.

The interaction between platelet glycoprotein Ib and von Willebrand factor (vWF) plays a crucial role in platelet-mediated thrombus formation under high-shear-stress conditions. The aim of this study was to investigate the antiplatelet profile of a humanized anti-vWF monoclonal antibody, AJW200. In vitro studies were performed with a modified cone-and-plate viscometer and human platelets. AJW200 inhibited high-shear-stress-induced platelet adhesion, aggregation, and thrombin generation, but it did not have such effects under low-shear-stress conditions. Although abciximab inhibited platelet aggregation under both shear stress conditions, it did not inhibit platelet adhesion and thrombin generation. In addition, the pharmacokinetics and pharmacodynamics of AJW200 were evaluated in cynomolgus monkeys. Sustained inhibition of ristocetin-induced platelet aggregation was observed over 24 hours, 6 days, and 2 weeks after a single bolus injection of 0.3, 1, and 3 mg/kg, respectively. Moderate prolongation of the bleeding time was observed at the doses of 1 and 3 mg/kg. Abciximab markedly prolonged the bleeding time at 0.4 mg/kg, at which concentration complete inhibition of ADP-induced platelet aggregation was observed. These results suggest that glycoprotein Ib-vWF blockade with AJW200 results in a sustained antiplatelet effect without extensive prolongation of the bleeding time, probably due to a shear-stress-dependent inhibitory action.