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Biomedical subjects

Y Miyauchi

Publications and source records attributed to Y Miyauchi.

At least 127 records · Page 7Linked to original sources

Endotoxin-induced lung hemorrhages in obstructive jaundiced rats.

Endotoxemia in patients with biliary obstruction contributes to the high morbidity and mortality rates following surgery. We developed an animal model of disseminated intravascular coagulation (DIC) in rats on which bile duct ligation was performed following an injection of endotoxin (200 micrograms/kg bw). Macroscopic hemorrhages and microthrombi in the lung were found in jaundiced rats 6 hours after the injection of endotoxin and yet these phenomena were not found in non-jaundiced rats following an injection of the same amount of endotoxin. Coagulation studies also revealed characteristic findings of DIC in the jaundiced rats following the injection of endotoxin. This study confirms that obstructive jaundice is one of the main predisposing factors in the course of endotoxin-induced DIC.

Animals↗

Scale and bone type I collagens of carp (Cyprinus carpio).

1. Soluble Type I collagens were isolated from the scale and bone (skull) of lathyritic carp. Each tissue collagen was assumed to consist of two different molecular forms, (alpha 1)2 alpha 2 as a main component and alpha 1 alpha 2 alpha 3 as a minor one. 2. The possible coexistence of these two forms in soluble Type I collagen of carp was previously observed for skin and muscle, but not for the swim bladder in which only the form of (alpha 1)2 alpha 2 was found. 3. These composite results suggest the wide distribution of alpha 1 alpha 2 alpha 3 heterotrimers in collagenous tissues of carp.

Amino Acids↗

Cerebral circulation and metabolism in patients with septic encephalopathy.

Cerebral circulation and metabolism in septic encephalopathy have not been well documented. The authors measured cerebral blood flow (CBF) and metabolic rate for oxygen (CMRO2) in six patients with septic encephalopathy associated with multiple organ failure (three to five organs). They found that CBF and CMRO2 were significantly lower than awake control values of 46 +/- 2 to 28 +/- 3 mL/100g/min (mean +/- SEM) and 3.1 +/- 0.2 to 1.2 +/- 0.2 mL/100g/min, respectively. Cerebral vascular resistance (CVR) and cerebral circulatory index (CCI:CBF/CMRO2) were significantly higher than the control values of 2.0 +/- 0.1 to 3.0 +/- 0.4 mm Hg/mL/100g/min and 15.1 +/- 0.8 to 24.2 +/- 3.3, respectively. At the time of cerebral circulatory and metabolic measurements, their consciousness varied between 4 and 10 as evaluated by the Glasgow coma scale. The electroencephalogram showed diffuse slow wave activity and the latency of the auditory brain stem evoked response was prolonged in four of six patients. Computed brain tomography showed either no abnormality or mild atrophy. It is concluded that CBF and CMRO2 are disproportionally decreased during septic encephalopathy in association with dysfunction of the CNS and decreased electrical activity.

Adult↗

Metastatic potential of malignant fibrous histiocytoma of myxoid or giant-cell subtype in rats.

We have previously reported on the induction of rat malignant fibrous histiocytomas by 4-hydroxiaminoquinoline 1-oxide. The present study describes cell number- and time-related formation of metastatic lung nodules after i.v. injection of cell suspensions containing various numbers (10(3) to 10(5)/ml) of myxoid or giant-cell subtype malignant fibrous histiocytoma cells. The metastatic potential of the myxoid subtype of rat malignant fibrous histiocytoma was significantly enhanced by i.v. injection of tumor cells selected from metastatic lung nodules and was further increased by repeating the selection procedure more than 7 times. In contrast, the growth activity of subcutaneous transplants of tumor fragments obtained from metastatic lung nodules derived from myxoid subtype did not differ from that of parent malignant fibrous histiocytomas.

4-Hydroxyaminoquinoline-1-oxide↗

Enzyme-induced aggregation and disaggregation of tumor cells via the cell surface glycocalyx in association with deoxyribonucleic acid.

Serine proteases cause aggregation of the rat ascites tumor cell lines AH-130, AH-109A and YS in vitro, and the tumor cell aggregates are dissolved by treatment with DNase I. We previously demonstrated that these events played a critical role in the augmentation or reduction of experimental blood-borne metastasis of these cell lines. In the present study, the ultrastructural features of this protease-dependent aggregation were analysed. Transmission and scanning electron microscopy revealed that after the protease treatment each tumor cell was surrounded by a thin membranous (sleeve-like) structure. This sleeve-like structure was stained with ruthenium red to an intensity similar to the cell surface of the control. Adjacent cells became attached to each other with microvilli via this fine structure. Immuno-electron microscopy revealed DNA antigen as dense patches on the sleeve-like structure or as faint and diffuse deposits on the outer surface of the cells by indirect immunoperoxidase staining using an anti-DNA monoclonal antibody. Both the sleeve-like structure and immunopositive deposits disappeared after treatment with DNase I. Neither cell viability nor the normal ultrastructure of their organelles was influenced by the enzyme treatment. These results indicate that serine protease-induced tumor cell aggregation is due to cellular contact via the sleeve-like structure, which probably originates from the cell surface glycocalyx in association with DNA molecules of unknown origin.

Animals↗

24-hour preservation of isolated rat hearts perfused with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) solution at low temperature.

We examined the effects of long-term perfusion with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) solution on cardiac function of isolated rat hearts. Hearts were perfused with oxygenated Krebs-Henseleit (K-H) solution containing 3% PHP or hydroxyethyl starch (HES) at a constant pressure of 13 mm Hg for 24 h at 15 degrees C. After 24 h preservation, hearts were rewarmed with K-H solution. Heart rate (HR) in PHP-preserved hearts was almost the same as control and cardiac contractility was maintained at 70% of control, but coronary outflow decreased to about 50% of control. No edema developed in the PHP group. Addition of a Ca2+ antagonist, diltiazem, inhibited the elevation of the end-diastolic pressure significantly. In HES-preserved hearts, HR did not recover to control levels, but there was no significant difference in cardiac contractility between PHP- and HES-perfused hearts. The results demonstrate that isolated hearts can be preserved by perfusion with PHP solution under hypothermic conditions for 24 h and suggest that PHP solution would be useful for a perfusate of isolated organs and tissues for preservation.

Animals↗

Intramedullary multiple hematomas in siblings with congenital alpha-2-plasmin inhibitor deficiency: orthopedic surgery with protection by tranexamic acid.

Congenital alpha 2-plasmin inhibitor deficiency is very rare, but causes bleeding problems similar to hemophilia. Three young Japanese sisters affected with congenital alpha 2-plasmin inhibitor deficiency have been reported by us earlier. Recently we encountered a particular form of intramedullary multiple hematomas in the long bones in all of them which was not reported previously. In 2 of the sisters orthopedic operations were successfully performed by using an antiplasmin reagent: tranexamic acid. In this paper we describe the characteristics of the hematomas and the hemostatic management with tranexamic acid.

Adolescent↗

Inhibition of posthemorrhagic transfusion-induced gastric injury by a long-acting superoxide dismutase derivative.

Although oxygen-free radicals have been postulated to play an important role in the pathogenesis of gastric mucosal injury induced by posthemorrhagic blood transfusion, direct evidence supporting this hypothesis is lacking. Superoxide dismutase (SOD) has been shown to inhibit oxygen toxicity in vitro in various types of cell injury. However, in some cases, oxidative tissue injury cannot be decreased efficiency predominantly due to its rapid elimination by renal glomerular filtration. To overcome such frustrating situations, we have synthesized a SOD derivative that circulates bound to albumin with a half-life of 6 hr. When blood was withdrawn from the rat (22 ml/kg) for 30 min followed by transfusion of the extracted blood, marked gastric mucosal lesions occurred within 30 min after transfusion. Intravenously injected SOD derivative markedly decreased gastric mucosal injury. Kinetic analysis using 125I-labeled albumin revealed that the vascular permeability of the stomach increased significantly after transfusion by a SOD derivative inhibitable mechanism. Thus, superoxide radical and/or its metabolite(s) play a critical role in the pathogenesis of posthemorrhagic transfusion-induced gastric injury.

Animals↗

Mechanism for enterohepatic injury caused by circulatory disturbance of hepatic vessels in the rat.

We reported previously that a transient occlusion followed by reperfusion of the portal vein and the hepatic artery of the rat significantly decreased the transhepatic transport of a cholephilic compound, and that this decrease was prevented by pretreating animals with poly(styrene co-maleic acid butyl ester)-conjugated superoxide dismutase (SM-SOD). To elucidate the mechanism for oxidative injury of the liver and the site for the generation of superoxide radicals, the effect of a portosystemic bypass on the liver function was examined in the rat whose hepatic vessels were temporarily occluded. A portosystemic bypass inhibited the reperfusion-induced decrease in hepatic transport of bromosulfophthalein as effectively as did SM-SOD. Kinetic analysis using 125I-labeled albumin revealed that the permeability of the small intestine markedly increased after a transient occlusion. The increase in intestinal permeability was also inhibited either by SM-SOD or by the portosystemic bypass. Xanthine oxidase activity in portal plasma markedly increased during occlusion and reperfusion, while it remained within normal ranges in the bypassed group. Thus, superoxide radical, and/or its metabolite(s), might play a critical role in increasing the intestinal permeability and in the pathogenesis of reperfusion-induced liver injury.

Animals↗

Effect of neo red cells on the canine hemorrhagic shock model.

This study evaluated the newly developed artificial red blood cells named Neo Red Cells (NRC) after hemorrhagic shock in mongrel dogs. NRC is prepared as microcapsules by a method in which stroma-free hemoglobin is encapsulated using a bimolecular lipid membrane called liposome. The particle size is 0.2 micron, methemoglobin content is less than 5% and the hemoglobin concentration is 5.6 g/dl. We analyzed blood gases and hemodynamics and carried out laboratory examinations after 59-88% blood exchange using NRC. The hemodynamic parameters returned to the normal range after NRC. Inhaling normal room air, oxygen carried by NRC was 60.40% at the exchange rate of 88%. Renal and hepatic function and other laboratory findings were normal after administration of NRC. After further study and improvement NRC could be considered suitable as artificial blood for treatment of hemorrhagic shock.

Animals↗

Surgical indication and significance of portal vein resection in biliary and pancreatic cancer.

Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection.

Adult↗

[Role of combined pulmonary resection during descending thoracic aortic aneurysmectomy].

Between April, 1982 and December 1990, five of 98 patients who underwent aneurysm repair for the thoracic aorta received combined resection of the descending thoracic aortic aneurysm and the lung because of marked adhesion between the aneurysm and the lung. Partial resection of the upper lobe of the lung was performed in all of five patients with auto-suture device. Three of the five patients needed no homologous blood transfusion during the surgery. Neither operative death nor pulmonary complication related to lung injury and bleeding was noticed. Our results indicate that partial resection of the lung is beneficial for avoiding intra-operative rupture of the aneurysm as well as lung injury in patients with descending thoracic aortic aneurysm severely adherent to the lung.

Aged↗

Inhibition of ischemia and reflow-induced liver injury by an SOD derivative that circulates bound to albumin.

Ischemia followed by reflow often results in tissue injury. Although reactive oxygens seem to play an important role in the pathogenesis of postischemic reflow-induced tissue injury, the mechanism and an efficient way to inhibit oxidative injury are not known. We studied the mechanism by which hepatic transport function was inhibited by a transient occlusion followed by reflow of the portal vein and hepatic artery by using a superoxide dismutase (SOD) derivative (SM-SOD) which circulates bound to albumin with a half-life of 6 h. Occlusion of the hepatic vessels for 20 min followed by reflow for 60 min significantly inhibited transhepatic transport of cholephilic ligands, such as bromosulfophthalein (BSP) and taurocholic acid. Intravenous administration of SM-SOD markedly inhibited the reflow-induced decrease in transhepatic transport of these ligands. Thiobarbituric acid - reactive metabolites (TBAR) in the liver and plasma remained unchanged during occlusion and reflow, while TBAR in the bile increased significantly. Intravenous injection of SM-SOD inhibited the reflow-induced increase in biliary TBAR. Xanthine oxidase activity in plasma also increased during occlusion and reflow by an SM-SOD-inhibitable mechanism. Polymorphonuclear leukocyte-dependent chemiluminescence of the peripheral blood remained unchanged during occlusion, but increased markedly with time after reflow. SM-SOD also inhibited the increase in chemiluminescence almost completely. These and other results suggested that the superoxide radical and/or its metabolite(s) might play an important role in the pathogenesis of the reflow-induced liver injury and that SM-SOD might be useful for studying the mechanism for tissue injury caused by oxygen toxicity.

Animals↗

Neuronal damage in the striatum following forebrain ischemia: lack of effect of selective lesions of mesostriatal dopamine neurons.

Transient periods of global cerebral ischemia lead to selective neuronal damage in the striatum. We investigated the effects of unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine (DA) system on the density and distribution of neuronal necrosis in the rat striatum following ischemia induced by bilateral occlusion of the common carotid arteries combined with hypotension. After both 12 and 15 min of ischemia, which caused slight and extensive striatal damage, respectively, there was no difference in the density of neuronal necrosis in the striatum between DA-lesioned and sham-operated animals. We conclude that the DA system alone does not modulate injury following complete cerebral ischemia, but may contribute significantly to damage following conditions such as during hypoglycemia and incomplete cerebral ischemia.

Animals↗

Serine protease-induced enhancement of blood-borne metastasis of rat ascites tumour cells and its prevention with deoxyribonuclease.

Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resistant to treatment with either a calcium chelating reagent (EDTA) or neuraminidase. However, the tumour cell aggregates were redispersed by treatment with deoxyribonuclease I (DNase I). This dispersal effect was dependent upon the DNase activity. A possible relationship between the tumour cell aggregation and development of blood-borne metastasis was studied. An intravenous inoculation in rats of tumour cell aggregates performed by the alpha-chymotrypsin treatment resulted in significantly higher numbers of lung metastatic foci than an injection of single cells. When the re-separated single cells, prepared in vitro by treatment with DNase I following alpha-chymotrypsin treatment, were injected instead of the aggregates, the enhancement of metastasis was reversed. These enhancement and reversal effects were mimicked in vivo by intravenous injections of protease and nuclease following inoculation of a single cell suspension. That is, the number of metastatic foci caused by single cell inoculation followed by an intravenous alpha-chymotrypsin injection, was higher than that in a control group receiving PBS instead of alpha-chymotrypsin. Again, this augmentation was reversed by an injection of DNase I following alpha-chymotrypsin injection. Furthermore, an injection of DNase I alone itself reduced the starting number of metastases resulting from injection of the single tumour cell suspension. These data suggest that the metastatic behaviour of tumour cells may be increased by protease inducible DNA dependent cell aggregation should it occur in the blood stream.

Animals↗

Surfactant therapy for pulmonary edema due to intratracheally injected bile acid.

Intratracheally injected bile acid has been shown to produce severe pulmonary edema. We investigated the therapeutic effect of an exogenous surfactant for aspirated bile acid. Anesthetized rabbits were injected intratracheally with 1 ml/kg body weight of taurocholic acid, diluted to 0.6% with normal saline solution. After the injection of taurocholic acid, the PaO2 values decreased, the PaCO2 values increased, and abnormal shadows appeared in chest x-rays. After surfactant injection, the rabbits improved, but pulmonary edema recurred after one hour. After additional injection of the surfactant, the improved condition was sustained for 6 h. All animals in the untreated group died within 5 h and were shown to have severe pulmonary edema. Conversely, microscopic examination revealed no pulmonary edema in animals surviving 6 h after surfactant treatment. Thus, exogenous surfactant can prevent damage to the lung caused by intratracheally injected bile acid.

Animals↗

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma-free hemoglobin on cardiac function in isolated rat heart.

Effects of a newly introduced modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), and stroma-free hemoglobin (SFH) on cardiac rhythm and contractility were examined in isolated rat hearts. Hearts were perfused with HEPES-buffered Krebs solution containing 6% PHP, 6% SFH, or 6% hydroxyethylstarch (HES). Arrhythmia was not observed in PHP-perfused hearts, but marked sinus bradycardia occurred in SFH-perfused hearts. Ventricular contractility assessed by left ventricular pressure and pressure-volume relationship in both PHP and SFH-perfused hearts were well maintained during perfusion. There was no significant difference to the coronary flow resistance between hearts perfused with PHP and HES solutions, indicating that PHP has little vasoactive effect. The flow resistance in SFH-perfused hearts decreased significantly when compared with other groups. Results demonstrate that PHP solution can preserve cardiac function and have no toxic effects in isolated rat hearts.

Animals↗

Amyloid angiopathy with cerebral hemorrhage and senile plaque in aged dogs.

Amyloid angiopathy with cerebral hemorrhage and senile plaques was found in the brain of aged dogs. In all 9 cases examined, 13 to 19 years old, 6 males and 3 females, amyloid deposits were observed mostly in the wall of cerebral arterioles and capillaries showed hyaline degeneration. The accumulation of amyloid fibrils measuring about 10 nm in diameter was seen in the cerebral vessel wall by electron microscopy. The cerebral hemorrhage was observed in 6 of 9 dogs and 2 of them showed massive hemorrhage. The hemorrhagic foci were sometimes closely contact with the vessels involved in amyloid angiopathy. In addition, senile plaques being classified into 2 types were found in the cerebral cortex of 3 dogs. The first type was characterized by the accumulation of degenerative neurites and often contained granular argyrophilic material. The second type had a well-defined amyloid core with neuritic halo. Amyloid deposits were also found in or around intestinal vessel walls of 3 dogs. The amyloid deposited in the cerebral vessels, senile plaques and intestinal vessels showed characteristic green birefringence under the polarized light even after potassium permanganate treatment.

Age Factors↗