Masao Kikuchi

A family with hereditary factor X deficiency with a point mutation Gla32 to Gln in the Gla domain (factor X Tokyo).

We report a new family with hereditary factor X deficiency. The propositus had a markedly prolonged prothrombin time, a mild prolongation of activated partial thromboplastin time and a clotting time activated by Russells viper venom. Factor X activity in plasma was 3 u/dl (normal range 56–138 u/dl). Factor X antigen level was 61 u/dl. Molecular analysis revealed a homozygous mutation, Glu (GAG) to Gln (CAG) at residue 32 which normally undergoes γ‐carboxylation within the γ‐carboxyglutamic acid rich domain. The genotypes of family members completely correlated with their factor X activities. It is suggested that the Glu32 to Gln mutation is the molecular basis for the abnormal factor X in this family.

The role of calcium in platelet microtubule assembly-disassembly

Abstract The role of calcium in the equilibrium between assembled and disassembled microtubules was investigated in human platelets. The two pools of microtubule protein was “frozen” by addition of a glycerol-dimethyl sulfoxide-containing medium and were estimated by measuring the colchicine binding activities of total and polymerized tubulin. Addition of A23187 to platelet rich plasma produced a transient decrease in the pool of polymerized tubulin within 30 sec., followed by a return to base-line values within 2 min.. Total content of platelet tubulin remained unchanged during the course of aggregation. TMB-8, a known intracellular calcium antagonist, abolished this transient decrease in polymerized tubulin induced by A23187, while indomethacin did not. These findings strongly suggest the important role of intracellular calcium in microtubule assembly-disassembly.

Inhibition of Platelet Function by Sulbenicillin and Its Metabolite

The effect of sulbenicillin and its major metabolite, α-sulfobenzylpenicilloic acid, on platelet function was investigated. Sulbenicillin caused inhibition of platelet aggregation and release reaction in the same manner as carbenicillin. α-Sulfobenzylpenicilloic acid was found to cause much stronger inhibition of platelet function. The results indicate that the strong inhibitory action of α-sulfobenzylpenicilloic acid may also take part in impaired platelet functions following administration of sulbenicillin to humans.

Combination Antibiotic/rhG-CSF Therapy for Bacterially Infected Granulocytopenic Patients

A clinical efficacy rate of 80.8% was obtained in 26 severely infected patients, neutropenic as a result of hematologic disease, following three-drug combination therapy with sulbactam/cefoperazone (SBT/CPZ), piperacillin (PIPC), and human recombinant granulocyte colony stimulating factor (rhG-CSF). By day 4 of treatment, patients average body temperature decreased from 38.6±0.8°C to 37.1±0.7°C and their neutrophil counts increased from 298±347/μL to 1757±2239/μL. When compared with 31 similar patients previously treated with SBT/CPZ and PIPC but without rhG-CSF, the efficacy rate in this study was somewhat higher but the difference was not statistically significant. However, there were statistically significant differences in body temperature on day 4 (37.1±0.7°C vs. 37.8±1.0°C) and in duration of fever in responding cases (3.1±1.7 vs. 4.8±2.4 days). These results suggest that addition of rhG-CSF provides a more rapid response and that the three-drug combination therapy can be selected as empiric therapy for infections in neutropenic patients.