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Biomedical subjects

H Egawa

Publications and source records attributed to H Egawa.

At least 19 recordsLinked to original sources

Purification of factor XIa inhibitor from human platelets.

An inhibitor of activated factor XI (FXIa) in human platelets was recently identified as an amyloid beta-protein precursor (APP). We purified an FXIa inhibitor (XIaI) from the supernatant of activated human platelets, and assessed its inhibitor activity toward FXIa amidolytic activity. Approximately 90 micrograms of XIaI that cross-reacted with anti-APP antibody was obtained from two hundred units of platelet suspension by employing a six-step column chromatography procedure. The molecular weight of the purified XIaI was 94,000. The Ki value of XIaI to factor XIa was 526 +/- 120 pM, and the inhibition was enhanced by the addition of ZnCl2. The amino-terminal sequence of XIaI was L-E-V-P-T-D-G-N-A-, which is identical to that for the leucine (N18) to alanine (N26) sequence of APP751 and the amino-terminal sequence of protease nexin-2.

Amino Acid Sequence

A prolongation of hepatic vascular exclusion by in situ hypothermic perfusion in dogs.

In situ hypothermic hepatic perfusion was performed in dogs to explore whether the time limit of hepatic vascular exclusion could be prolonged. During hepatic vascular exclusion, hepatic hypothermic perfusion was performed via portal vein using various perfusates under active bypass from the portal vein and infrahepatic inferior vena cava area to the superior vena cava system. Dogs receiving hepatic hypothermic perfusion for 1 hour died when given Ringer's solution but survived more than 7 days when given Euro-Collins' and University of Wisconsin solutions. Although dogs tolerated 2 hours of hepatic hypothermic perfusion when give University of Wisconsin solution, all dogs died by 2 hours of hepatic hypothermic perfusion when given Euro-Collins' solution. The hepatic energy charge and arterial ketone body ratio of dogs that died were significantly lower than for those that survived. This suggests that the regimen of hepatic hypothermic perfusion with University of Wisconsin solution is able to maintain the energy metabolism of the liver under hepatic vascular exclusion for prolonged periods, hence, its possible clinical application.

Adenosine

Impaired energy metabolism of lymphocytes in cirrhotics after hepatectomy.

To clarify the mechanism of high susceptibility to infection in cirrhotics, the changes in adenylate energy charge and MTT assay in peripheral blood lymphocytes were studied in cirrhotic and noncirrhotic patients in the early postoperative period after hepatectomy. The adenylate energy charge measured by radioactive labeling of the lymphocyte adenine nucleotide pool showed no significant difference preoperatively between cirrhotics and noncirrhotics, but a significant difference was observed in the pre- and postoperative distribution of adenine nucleotide metabolites (P less than 0.01). In the cirrhotic group, the adenylate energy charge of lymphocytes decreased significantly to 0.807 +/- 0.011 on the third postoperative day compared with preoperative value (0.891 +/- 0.006, P less than 0.01) and was restored to the normal range on the fifth and tenth postoperative days (0.886 +/- 0.006, 0.899 +/- 0.014), while no significant decrease was observed in the noncirrhotic group. MTT assay revealed that lymphocyte cell function decreased significantly in cirrhotics after hepatectomy. These results indicate that, in cirrhotic patients, the energy metabolism of lymphocytes is already impaired to some extent preoperatively, and that it undergoes further deterioration when surgical stress is applied. It is suggested that the decreased energy metabolism in the lymphocyte may be responsible for the increased susceptibility to infection in postoperative cirrhotics.

Adenosine Diphosphate

Correlation of hepatic injury, synthetic function, and mitochondria energy level in orthotopic liver transplantation.

UNLABELLED: The arterial ketone blood ratio (AKBR) of acetoacetate to b-hydroxybutyrate was previously shown to reflect hepatic mitochondria oxidation/reduction (redox) state and energy level. In this study we correlated AKBR to the degree of liver injury immediately following orthotopic liver transplantation (OLT). Serial measurements of AKBR in 209 patients undergoing OLT, during the anhepatic phase, and up to 60 hr following reperfusion demonstrated direct correlation between mitochondria Redox state (AKBR), hepatocyte injury (SGOT), and hepatic synthetic function (prothrombin time). AKBR levels less than 0.7 were seen in primary nonfunction grafts and were associated with raising SGOT (greater than 1000) and prolonged PT (greater than 18). Acute occlusion of arterial blood supply to the graft was seen in conjunction with low AKBR (less than 0.7). However, hepatic synthetic function and serum enzyme were stabilized or returned to normal within 24-48 hr postreperfusion. IN CONCLUSION: (1) AKBR measurements are useful in predicting graft survival, (2) reduction in liver mitochondria Redox state is seen in primary hepatocyte dysfunction and correlates well to synthetic function, and (3) acute occlusion of the arterial supply to the liver graft is associated with decreased redox state. However, with intact portal blood flow, it is still possible to preserve adequate hepatic synthetic function.

Adult

Eicosanoids production in endometriosis.

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.

6-Ketoprostaglandin F1 alpha

Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis.

The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed.

6-Ketoprostaglandin F1 alpha

Extent of ischaemia caused by hepatic vascular exclusion as evaluated in a canine model.

1. The difference in the extent of liver ischaemia between a hepatic vascular exclusion model and an inflow occlusion model were investigated by determining Indocyanine Green retention and hepatic mitochondrial redox state during 2 h of ischaemia in 10 mongrel dogs. The splanchnic venous bed and/or the infra-hepatic inferior vena cava were decompressed by pump-driven veno-venous bypass. 2. The Indocyanine Green retention test revealed that there was no hepatic blood flow in the hepatic vascular exclusion model during ischaemia (96.8 +/- 0.73% retention of the dye after 20 min), whereas hepatic blood perfusion was still present significantly in the inflow occlusion model (78.1 +/- 1.19% retention of the dye after 20 min) (P less than 0.01). 3. The mitochondrial redox potential of the liver in the dogs with hepatic vascular exclusion decreased immediately after the induction of ischaemia and remained fixed at extremely low levels. By contrast, in the dogs with inflow occlusion the redox potential decreased gradually after induction and was maintained significantly higher than that in dogs with hepatic vascular exclusion during 2 h of ischaemia (P less than 0.01). 4. It is concluded that the extent of liver ischaemia in the hepatic vascular exclusion model with pump-driven shunt is significantly different from that in the inflow occlusion model with shunt.

Animals

A role of cytoplasmic free adenosine diphosphate in regenerating rabbit liver.

Cytosolic free adenosine diphosphate (ADP) concentration in remnant rabbit liver 24 hours after 70% hepatectomy was calculated from the measured components of the glyceraldehyde-3-phosphate dehydrogenase:3-phosphoglycerate kinase/lactate dehydrogenase reaction. The concentration of free cytoplasmic ADP of the remnant liver increased from the control value of 76.9 +/- 6.0 mumol/L to 208.8 +/- 31.9 mumol/L (mean +/- SEM) at 24 hours after hepatectomy. The calculated free ADP provides the following three interpretations with respect to mitochondrial respiration acceleration as a result of liver regeneration. First, the Michaelis-Menten equation for physiologic respiration relative to maximal respiration gave 1.16 as the value of acceleration. Next, the classical thermodynamic theory showed that the logarithm of [adenosine triphosphate]/[free ADP] [free inorganic phosphate], which is reciprocally correlated with mitochondrial respiration, was decreased by a factor of 0.78 after hepatectomy. Finally, the irreversible thermodynamic theory indicated that chemical affinity, which is linearly correlated to mitochondrial respiration, was increased 1.36 times. These interpretations suggest that the rate of mitochondrial respiration is accelerated after major hepatectomy.

Adenosine Diphosphate

Meningeal involvement in Bence Jones multiple myeloma.

A case of Bence Jones kappa multiple myeloma with meningeal involvement in a 64-year-old woman is presented. Three years after the diagnosis of multiple myeloma, gait disturbances developed followed by visual disorders and impaired consciousness. A lumbar puncture revealed numerous atypical plasma cells in the cerebrospinal fluid. Craniospinal irradiation and intrathecal injections of methotrexate, cytarabine, and prednisolone were effective for a short period. At autopsy, the leptomeninges were infiltrated diffusely with atypical plasma cells. A review of the literature showed that multiple myeloma with meningeal involvement is accompanied frequently by circulating atypical plasma cells or plasma cell leukemia. Meningeal involvement is a rare complication and shows poor prognosis in cases of multiple myeloma.

Female

Hepatic vascular exclusion as a model for complete and stable hepatic ischemia in dogs.

In order to confirm a complete ischemia model, 1-hour warm hepatic ischemia by hepatic vascular exclusion (HVE) was studied in dogs, in comparison with that by inflow occlusion (IOC) only. The splanchnic venous bed and/or infrahepatic inferior vena cava were decompressed by a centripetal pump-driven venovenous bypass. Indocyanine green retention test revealed no hepatic blood flow in the HVE model during ischemia, while hepatic blood perfusion was still present in the IOC model. All 5 of the IOC dogs survived more than 7 days after revascularization, while 4 of the 5 HVE dogs died within 9 h. After the induction of hepatic ischemia, lactate increased in both HVE and IOC dogs. After revascularization, transaminases and guanase were elevated, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate) decreased and the serum lactate accumulated more in HVE dogs than in IOC dogs. The hepatic redox state of IOC dogs was significantly decreased by additional clamping of the inferior vena cava. It is concluded that the HVE model with a pump-driven active bypass provides complete and stable hepatic ischemia, resulting in greater deterioration of hepatic cellular functions; hence it is more suitable as a model of complete hepatic ischemia than the IOC one.

Animals

Temporary portal vein arterialization as an attractive option in canine orthotopic partial liver transplantation.

We performed 22 canine orthotopic partial liver transplantations (PLTs) with three different revascularization methods; portal vein arterialization (PVA group, n = 11), hepatic arterial shunt (HAS group, n = 5), and conventional portal vein reperfusion (control group, n = 6). Our purpose was to evaluate the feasibility of PVA as a revascularization technique in PLT assessing the changes in arterial ketone body ratio (KBR) as an index of hepatic energy status. After the first anastomosis (left hepatic vein), the ischemic partial liver graft was revascularized with arterial blood flow shunted from the external iliac artery to the hepatic side of the portal vein (PVA group) or the proper hepatic artery (HAS group). Both anhepatic period and ischemia time were significantly shortened in groups PVA and HAS as compared with those in control. In the PVA group, 10 out of 11 recipients survived for at least 5 days (14.2 +/- 3.8 days, mean +/- SEM), while 3 out of 5 (5.2 +/- 1.0) survived in the HAS group and 4 out of 6 (6.2 +/- 1.3) in the controls. Although portal blood flow during PVA was only about 25% of the total hepatic blood flow at preclamping, the KBR was rapidly restored after PVA and showed almost the same values at preclamping. The KBR values during the arterialization time and initial velocity of KBR recovery in the PVA group were significantly higher than those in the HAS and control groups. These results suggest that PVA presents an attractive option in PLT.

Animals

[Malfunctioning of infusion pumps due to interference from an electrosurgical unit].

We observed the incidence of pump errors by the interference from the electrosurgical unit (Vallylab, Force 4B) set at coagulation or cut mode, with three infusion pumps: Terumo STC-523, STC-525 and STC-525-01. The STC-525-01 painted with electrically conductive paint inside was used during electrosurgery on experimental basis. Malfunctioning of the STC-523 pump occurred frequently by using electrosurgical unit set at coagulation mode and placed close to the pump. The STC-525-01 showed markedly lower incidence of malfunctioning. Therefore, the STC-252-01 pump can be used safely during electrosurgery. Additionally, we discovered, through an estimation of radiated electrical field around the electrosurgical unit, the cable of an active electrode was important as an interference source. To minimize electrosurgical interferences, we propose the following recommendations; 1) keeping the infusion pump and its AC line as far as possible from the active electrode cable, 2) keeping the output of electrosurgical unit as low as possible, 3) operating the pump with its internal battery power supply, and 4) monitoring the operation of the pump while using electrosurgery.

Electricity

[Factor XIa-alpha 1 antitrypsin complex].

We developed a new rapid assay for the factor XIa-alpha 1 antitrypsin complex (FXIa-alpha 1AT) in plasma using an anti FXI monoclonal antibody (KMXI-1). In 20-fold diluted plasma samples, this assay was not affected by co-existing FXI or non specific color development of the plasma. Normal level of FXIa-alpha 1AT (11 +/- 4.1 ng/ml plasma) increased with the aging of healthy adults. The FXIa-alpha 1AT levels of patients with disseminated intravascular coagulation (DIC) rose along with the progression of the disease, and the appearance of high levels and the peak of FXIa-alpha 1AT developed faster than FDP-E or alpha 2plasmin inhibitor-plasmin complex (alpha 2PI-PmC) in most patients. These results indicate that, in addition of FDP and alpha 2PI-PmC, FXIa-alpha 1AT is a useful molecular marker for DIC.

Adult

The experimental study on the temporary portal vein arterialization in the canine liver transplantation: preliminary report.

To evaluate the feasibility of temporary portal vein arterialization (PVA) in orthotopic partial liver transplantation (PLT), we performed 5 canine PLTs with PVA assessing the changes in arterial ketone body ratio (AKBR) as an index of hepatic energy status, and measuring portal pressure and flow. After anastomosis of hepatic vein, the graft liver was revascularized with arterial blood shunted from the external iliac artery to the hepatic side of the portal vein. By using this technique, both anhepatic period of the recipient and ischemic time, especially warm ischemic time, of the allograft were markedly shortened (31.0 +/- 4.5 min: Mean +/- SEM). Four out of 5 recipients survived for at least 5 days (13 days in average). The AKBR was restored immediately after PVA and showed almost the same values as those at preclamping and after completion of anastomoses of both portal vein and hepatic artery. No significant difference in portal venous pressure was observed between during PVA and after vascular reconstruction. Portal blood flow during PVA was about one fourth of the total hepatic blood flow at preclamping. These results suggest that PVA can be used as an alternative procedure in PLT.

Anastomosis, Surgical

Increased accumulation of nonenzymatically glycated fibrinogen in the renal cortex in rats.

We have determined that the nonenzymatic glycation of fibrinogen altered its biological functions in vitro. Thrombin clottability of rat fibrinogen incubated with glucose decreased with increasing incubation time, but was not affected by the glucose concentration. Fibrin prepared from glycated fibrinogen showed a significant resistance in susceptibility to plasmin degradation. We also examined the in vivo distribution of glycated fibrinogen in renal cortex. Iodine labeled rat glycated or unglycated fibrinogen was injected into streptozocin-induced diabetic and control rats. No appreciable difference in the plasma disappearance rate in control rats was observed (half-lives in hours for glycated, 25.6 +/- 0.37; unglycated, 26.1 +/- 0.74). The radioactivity of fibrinogen retained to the renal cortex was calculated 24-hours after injection. In both control and diabetic rats, the retention rate of glycated fibrinogen in renal cortex was significantly higher than that of the unglycated. These results suggest that glycated fibrinogen may occur in a more resistant form to plasmin digestion with fibrin deposition as confirmed in in vitro studies. Therefore, we suggest that glycated fibrinogen may partly contribute to the development of diabetic microangiopathic lesions such as glomerulosclerosis.

Animals