Osamu Takada

Congenital antititrombin III deficiency (AT-III Kyoto) : Identification of a point mutation altering arginine-406 to methionine behind the reactive site

A Japanese patient with congenital antithrombin III (AT-III) deficiency, named AT-III Kyoto, is associated with reduced levels (60% of normal) of AT-III antigen, progressive activity and heparin cofactor activity. The antithrombin III gene of this patient was investigated by polymerase chain reaction (PCR) method followed by direct DNA sequencing analysis, which revealed a G to T transitional mutation resulting in the conversion of arginine-406 to methionine in exon 6. Arginine-406 is located at the 12th amino acid residue from the reactive site on the C-terminal side of AT-III in a core region of the molecule which has been highly conserved during evolution of serine protease inhibitor (serpin) family. It is concluded that AT-III Kyoto is a newly described mutation which is similar to AT-III Utah and lends support to the idea that the conserved region near the reactive site is important in maintaining biological function of the AT-III molecule.

Hypokalemic alkalosis with hypocalciuria and normomagnesemia: A subgroup of Gitelman's syndrome?

Abstract We report a normomagnesemic patient with low normal blood pressure, hypokalemic alkalosis, hyperreninemia, hyperaldosteronism, and hypocalciuria. In renal clearance studies, distal delivery increased well and fractional distal solute reabsorption was dramatically diminished after the administration of furosemide, whereas thiazide produced no change in distal delivery and a moderate decrease in fractional distal solute reabsorption. These findings suggested that there may have been a defective locus in some part of the thiazide-sensitive segment of the distal convoluted tubule. As the features in this patient appear to be similar to those in Gitelmans syndrome, it is appropriate to designate this case, characterized by lack of hypomagnesemia, as a subgroup of Gitelmans syndrome.

Effects of Anticoagulants on Thrombolysis Mediated by Tissue Plasminogen Activator in Experimental Thrombosis Model

Tissue plasminogen activator (t-PA) is being used as thrombolytic therapy for patients with acute myocardial infarction [1], given in combination with anticoagulants such as heparin or warfarin. We compared the effects of the new selective thrombin inhibitors, argatroban and hirudin, with those of heparin, on the thrombolysis mediated by t-PA in an experimental model of thrombosis using the hamster cheek pouch.