The interaction between heparin and plasmin on amidolysis.

The effect of the interaction between heparin and plasmin not only on fibrinolytic, caseinolytic and esterolytic activities but also on amidolytic activity, since plasmin has amidolytic or amidase activity, was investigated. Following were the results obtained from these investigations: 1. Heparin enhanced amidolytic activity of a fixed level of plasmin which was prepared by activating plasminogen with urokinase within the range from 2 to 64 units/ml of the final concentration of heparin. 2. Heparin also enhanced amidolytic activity of a fixed level of plasmin which was prepared by converting plasminogen with insolubilized urokinase. 3. Heparin did not enhance or inhibit fibrinolytic, caseinolytic and esterolytic activities of a fixed level of plasmin which was prepared by activating plasminogen with urokinase, in the fibrinolytic activity within the range from 0.032 to 125 units/ml, in the caseinolytic activity within the range from 0.0125 to 100 units/ml, and in the esterolytic activity within the range from 0.016 to 128 units/ml, of the final concentration of heparin respectively.     

Non-cardiogenic pulmonary edema induced by non-ionic radiographic contrast media during the coil embolization for a ruptured cerebral aneurysm

We describe a 48(correction of 44) year-old woman, who presents a non-cardiogenic pulmonary edema caused by non-ionic radiographic contrast medium. She suffered from subarachnoid hemorrhage due to dissecting aneurysm of right vertebral artery. Cerebral angiography followed by coil embolization for the aneurysm was performed. During the interventional procedure, saturation of blood oxygen suddenly declined and chest X-ray photography obviously revealed pulmonary edema. At first we dealt with it as neurogenic phenomenon but subsequently interpreted it to non-cardiogenic pulmonary edema induced by radiographic contrast medium, since intra-arterial injection of contrast medium at follow-up angiography led the symptoms into more fulminant status. Intensive care including endotracheal intubation and continuous positive airway pressure ventilation consequently achieved complete remission and the patient discharged without any sequelae. Although low osmolar, non-ionic contrast medium has been regarded as relatively safe, severe reaction such as dyspnea, hypotension and cardiac arrest could emerge at certain intervals. We must perceive the adverse effects of it because the usage of contrast medium will dramatically increase with development of diagnostic radiographical methodology and interventional neurosurgery.     

A method for the measurement of fibrinolytic activity based on one dimensional diffusion using small glass tubes. II. With special reference to the differences between the use of plasminogen-rich fibrinogen and that of plasminogen-free fibrinogen as the substrates

The optimal conditions for the measurement of the fibrinolytic factors of plasma were examined using human and bovine plasminogen-rich fibrinogen or plasminogen-free fibrinogen as the substrates using the one dimensional diffusion method. The results were as follows: 1. There was no essential difference found between using human or bovine fibrinogen. 2. The levels of proactivator-plasminogen and plasminogen could be measured while using either plasminogen-rich or plasminogen-free fibrinogen. But, in using the latter, the proactivator-plasminogen level could not be measured, if a final concentration of more than 2,000 Christensen units of streptokinase were employed. 3. When using plasminogen-rich fibrinogen, anti-plasmin(s) and anti-activator(s) could be measured while using urokinase and plasmin, but not while using streptokinase. However, further study should be given to the measurement of the inhibitors, when using plasminogen-free fibrinogen.     

Protective effects of SM-20302, an orally active GPIIb/IIIa antagonist, in an ADP/epinephrine-induced guinea pig model of transient cerebral ischemia

The potential benefits of SM-20302, (2S)-3-(3-(4-amidinobenzoylamino)propanoylamino)-2-(4-ethyl)benzensulfonylaminopropionic acid hydrochloride, a nonpeptide GPIIb/IIIa receptor antagonist, were compared with those of aspirin and ticlopidine in a transient cerebral ischemia model in guinea pigs. Transient cerebral ischemia was induced in guinea pigs by an infusion of ADP/epinephrine into the left internal carotid artery. Each compound was orally administered 1 h (SM-20302 and aspirin) or 3 h (ticlopidine) before the ADP/epinephrine infusion. The ischemic area in coronal brain slices was assessed 1 min after the cessation of ADP/epinephrine infusion by a carbon black perfusion method. In a separate experiment, neurological deficits and lactate contents of ipsilateral hemispheres were evaluated 60 min after the cessation of ADP/epinephrine infusion by neurological scores and the standard enzymatic method, respectively. SM-20302 (0.3 and 1 mg/kg p.o.) significantly reduced the ischemic area, neurological deficits and lactate contents in comparison with the vehicle control. Aspirin (100 mg/kg po) had no significant effect on either parameter. Ticlopidine (300 mg/kg p.o.) reduced the lactate content. Although a combination of aspirin (100 mg/kg p.o.) and ticlopidine (300 mg/kg po) also reduced the lactate content, no additive effect was observed. These results suggest that SM-20302 is of potential clinical benefit in the treatment of thromboembolic diseases.     

DISSEMINATED INTRAVASGULAR COAGULATION (DIC)

Renal tissues of 208 autopsied cases were examined. Malignant neoplasm with hematological malignancies often accompanied DIG. Tissue sections were stained with hematoxylin and eosin and Mallory's phosphotungstic acid hematoxylin (PTAH), and were applied for immunoperoxidase method (IP), using antisera against human fibrinogen, FDP-D and FDP-E. Histologically in 80 cases (38%) fibrin or fibrinogen related materials (FRMs) were observed in the glomerular capillary or the intratubular area or in both. FRMs were PTAH or IP positive or both in 23 of the 26 cases (88%) clinically diagnosed as DIC. In the remaining three cases anticoagulants probably Interfered with FRMs observation. This study showed the PTAH stain was nonspecific and insensitive to FRMs, and that IP was necessary for a pathological diagnosis of DIC. The presence of FRMs in the renal tubuli is an important finding in confirming DIG. DIC may be present histologically in the absence of clinical DIC symptoms.     

RANTES -28G delays and DC-SIGN - 139C enhances AIDS progression in HIV type 1-infected Japanese hemophiliacs

The relationships between host immune factors and HIV-1 disease progression are still in dispute. Unlike CCR5Delta32, which has been found to delay disease progression of HIV-1, there still remain several factors whose effect on the clinical course is unconfirmed. To clarify the relationships, we selected seven single-nucleotide polymorphisms (SNPs) out of the previously reported factors, namely, RANTES promoter -28G/-403A, RANTES In1.1C, SDF-1 3'A, IL-4 promoter -589T, and DC-SIGN promoter -139C/-336C, and examined these in Japanese HIV-1-infected hemophiliacs (n = 102). The genotypes were examined by the direct sequencing method, and the distributions of genotype and allelic frequencies were compared between two groups, slow progressors (n = 54) who did not develop AIDS more than 10 years after intravenous infection and others (progressors) (n = 48). The allelic frequency of RANTES -28G was significantly higher in slow progressors (0.185) than in the progressor group (0.074) [p = 0.023, OR = 0.35, 95% CI (0.142, 0.880)]. DC-SIGN promoter -139C, and appeared in progressors with significantly higher allelic frequency (0.333) than slow progressors [0.204, p = 0.040, OR = 1.95, 95% CI (1.039, 3.677)]. With RANTES -403A, RANTES In1.1C, SDF-1 3' A, IL-4 -589T, and DC-SIGN -336C, no significant difference was observed in allelic frequencies between the two groups. These results suggest that RANTES -28G was associated with delayed AIDS progression, while DC-SIGN -139C was associated with accelerated AIDS progression in HIV-1-infected Japanese hemophiliacs.     

Common risk factors for changes in body weight and psychological well-being in Japanese male middle-aged workers

Objectives  

Overweight and poor psychological well-being are becoming serious health issues in the Japanese workplace. Concurrence of those physical and mental conditions has been pointed out, especially in middle-aged workers. Therefore, we tried to determine common risk factors for body weight gain and the deterioration of psychological well-being in male middle-aged office workers using a five-year follow-up study.     

铁过剩时铁在肝小叶内区域性沉积的机理

用Ｗｉｓｔａｒ大鼠通过词以缺铁词料或腹腔内反复注射铁。氨三乙酸络合物４个月制成铁缺乏或铁过剩大鼠模型。用ＡＢＣ法及铁染色法观察、分析铁缺乏（Ａ组）、铁过剩（Ｂ组）与对照（Ｃ组）大鼠肝脏转铁蛋白（Ｔｆ）及其受体（ＴｆＲ）的表达与铁沉积的关系。与Ｃ组相比，ＴｆＲ的表达在Ａ组增强、Ｂ组减弱。三组动物ＴｆＲ在肝小叶第１区表达最强，第２区次之，第３区最弱。三组动物Ｔｆ表达差异与ＴｆＲ类似。Ｂ组肝小叶内可见铁沉积。以１区分布最多，３区最少；与ＴｆＲ表达在肝小叶分布一致。作者认为体内肝细胞摄取铁主要经ＴｆＲ与Ｔｆ介导，ＴｆＲ和Ｔｆ的区域性分布可导致铁过剩时肝小叶内铁从第１区至第３区的顺序递减型区域性沉积。     

Effect of a factor VIII concentrate on type IIB von Willebrand's disease-associated thrombocytopenia presenting during pregnancy in identical twin mothers

Marked thrombocytopenia developed during pregnancy in both identical twins mothers who had systemic lupus erythematosus (SLE) and also type IIB von Willebrand's disease (vWD). The proband's platelet count decreased in the third trimester of pregnancy. Large-dose gamma-globulin and prednisolone treatments were performed because of the suspicion of immune thrombocytopenic reaction associated with SLE. These treatments were not effective. Her platelet count returned to the normal range immediately after delivery. Postpartum examinations revealed the decreased ristocetin cofactor activity and the deficiency of large von Willebrand factor (vWF) multimers in preserved plasma samples from the third trimester. These abnormal findings improved after delivery. Investigation of family members revealed that the proband had inherited type IIB vWD from her mother. The other twin, who was also under treatment for SLE, became pregnant about 1 year after delivery in the proband and followed almost the same course as that observed in the proband. As bleeding tendency was observed a few days before delivery, a factor VIII concentrate (Haemate P) was administered to compete with her variant vWF. This concentrate could prevent the further decrease in her platelet count, thereby correcting the hemorrhagic tendency. It seems evident that factor VII concentrate would be effective in treating thrombocytopenia associated with type IIB vWD.