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Biomedical subjects

K Hiraoka

Publications and source records attributed to K Hiraoka.

At least 19 recordsLinked to original sources

Heart preservation using a cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

To reduce cold ischemic injury of the heart by supplying sufficient oxygen to the heart during preservation, we have developed a new cavitary, two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. The oxygenation of the heart during preservation by this method allows ATP production within the graft and makes it possible to extend preservation time up to 48 hr in the heterotopic rat heart transplant model.

Adenosine

[Chylomicron and VLDL metabolism in daunomycin-induced nephrotic rats].

Lipid metabolism in chylomicron and VLDL were examined in daunomycin-induced nephrotic rats. 1) There was no difference in intestinal cholesterogenesis between the control rats and daunomycin-induced nephrotic rats. 2) The apoprotein content of chylomicron and VLDL increased in daunomycin-induced nephrotic rats. 3) Daunomycin-induced nephrotic rats showed increases in the content of apo B-48 and C-III, and a decrease in that of apo E in chylomicron. The apoprotein composition of VLDL in daunomycin-induced nephrotic rats showed increased apo B and decreased apo E. These results suggest that increased chylomicron-cholesterol is not due to increased intestinal cholesterogenesis, but to decreased chylomicron catabolism in daunomycin-induced nephrotic rats. Increased apoprotein in VLDL may contribute to the decreased catabolism by reducing LPL activity in the plasma and increased secretion from the liver of daunomycin induced nephrotic rats.

Animals

[A case of remission of recurrent carcinosarcoma of the uterus with massive ascites by carboplatin].

A case of remission of recurrent carcinosarcoma of the uterus with massive ascites by chemotherapy using carboplatin (CBDCA) is reported. A 75-year-old female was diagnosed with cancer of the uterine body. She underwent abdominal total hysterectomy with bilateral salpingo-oophorectomy, which revealed carcinosarcoma of the uterus penetrating the myometrium and reaching the serosa of the uterus. Eight weeks after, she developed abdominal distension, obstruction of bilateral ureters and bleeding tumor measuring 5 cm in diameter at the vaginal cuff ending. Acute retention of bloody ascites of more than 2500 ml was demonstrated. Abdominal centesis, aspiration of ascites and intraperitoneal administration of 600 mg of CBDCA were performed. Two weeks after single use of CBDCA, the ascites completely disappeared and there was recovery from anuria. The remission has lasted more than 4 months, which has suggested the efficacy of CBDCA for uterine carcinosarcoma.

Aged

Role of adenosine in preservation by the two-layer method of ischemically damaged canine pancreas.

The purpose of this study was to clarify the role of adenosine in preservation of ischemically damaged pancreas by the two-layer (Euro-Collins solution [EC]/perfluorochemical [PFC]) method using a canine model. Twenty-four-hour preservation of the pancreas graft subjected to 60-min warm ischemia was successful by the two-layer (EC with adenosine/PFC) method (4/5, 80%), but neither simple cold storage in EC (0/5, 0%), nor EC with adenosine (1/5, 20%), nor the two-layer (EC/PFC) method (0/3, 0%) was successful. Tissue ATP concentrations at the end of preservation by the two-layer (EC with adenosine/PFC) method were significantly higher compared with the two-layer (EC/PFC) method (7.23 +/- 2.17 vs. 1.56 +/- 0.40 mumol/g dry weight, P < 0.01). Studies with [2-3H]adenosine demonstrated that only part of adenosine was converted to inosine, hypoxanthine, and adenine, whereas the remainder was incorporated into adenine nucleotides in the pancreas graft. In addition, hypoxanthine, inosine, and adenine did not substitute for adenosine. We conclude that provision of adenosine to ischemically damaged pancreas during preservation by the two-layer (EC/PFC) method allows ATP synthesis within the graft via direct phosphorylation of adenosine. Metabolic processes vital to repair damaged cells and maintain cellular integrity can be maintained, which makes it possible to preserve ischemically damaged pancreas.

Adenosine

Protective effect of preservation of canine pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) method against rewarming ischemic injury during implantation.

Rewarming ischemia during implantation severely compromises posttransplant pancreas graft survival because the graft has already been subjected to warm and cold ischemia before implantation. The purpose of this study was to examine whether preservation of the pancreas graft by the two-layer method ameliorates rewarming ischemic injury of the graft during implantation using a canine model. After flushing with cold University of Wisconsin solution (UW), the pancreas grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group 1) or simple cold storage in UW (group 2) for 24 hr and then autotransplanted. In control, the pancreas grafts were flushed out with cold UW and immediately autotransplanted without preservation (group 3). After completion of vascular anastomosis, vascular clamp was not released until 90, 120, or 150 min of rewarming ischemia, including anastomosis time, had elapsed. After 90 min of rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5, 100%, in groups 1, 2, and 3, respectively. After 120 min, all the grafts in groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively); however, all the grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in group 1 survived (1/3, 33%). After 24 hr preservation, tissue ATP levels of the grafts in group 1 were about 2-fold the reference values before harvesting (8.23 +/- 0.72 vs. 4.44 +/- 0.49 mumol/g dry weight, P < 0.05) and significantly higher compared with group 2 (8.23 +/- 0.72 vs. 1.76 +/- 0.52 mumol/g dry weight, P < 0.01). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84% of the reference values and significantly higher compared with group 2 (3.75 +/- 0.25 vs. 1.57 +/- 0.48 mumol/g dry weight, P < 0.05). Two hours after reperfusion, ATP levels in group 1 were 42% of reference values but significantly higher compared with group 2 (1.86 +/- 0.36 vs. 1.03 +/- 0.18 mumol/g dry weight, P < 0.05). We conclude that the two-layer (UW/PFC) method ameliorates rewarming ischemic injury of the pancreas graft during implantation by increasing tissue ATP contents during preservation and consequently maintaining tissue ATP levels during implantation.

Adenosine

Adsorption of human recombinant erythropoietin on dialysis membranes in vitro.

The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of beta 2-microglobulin (beta 2-MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes.

Acrylic Resins

Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells.

BACKGROUND: It is known that extracellular matrix-degrading enzymes play an important role in tissue remodeling and that large amounts of structural proteins including types I, III, IV, and V collagens and elastin are produced by smooth muscle cells (SMC) in the arterial wall. We have recently shown that matrix metalloproteinases (MMPs) produced by human aortic medial smooth muscle cells are closely related to the proliferation of the cells, leading to the formation of atherosclerotic plaques, characteristic of intimal remodeling. For a better understanding of the mechanism of atherogenesis, therefore, it is important to clarify the relationship between the production of matrix-degrading enzymes and artery development. EXPERIMENTAL DESIGN: In vivo or in vitro synthesis of MMPs by SMC was analyzed by immunohistochemistry and immunoblotting. Elastase activity in the culture medium was also estimated. RESULTS: Production of proMMP 1, 2, and 3 was detected in cultured SMC isolated from the aortas of both neonates and fetuses; in medial SMC cultured from young individuals, production of proMMP-1 and -3 was extremely decreased, but was apparent in intimal SMC. Immunohistochemical observation indicated that in the media of fetal or neonatal aorta, SMC synthesized large amounts of the three proMMPs; in aortas from older individuals, proMMP-2, but not proMMP-1 and -3, was detected in the media, and relatively large amounts of proMMP-1, -2, and -3 were produced by SMC in the slightly thickened intima. Assay of elastase activity in the culture medium gave results similar to those for MMPs. CONCLUSIONS: We conclude that the production of proMMP-1 and -3 is associated with phenotypic modulation of SMC to a "synthetic" state, and that the ability of SMC to produce MMPs plays an important role in the development and/or aging of the human aorta through remodeling of the extracellular matrix; furthermore elastase is also involved in these processes in the arterial wall.

Adolescent

Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by human rheumatoid synovial fibroblasts.

The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhibited by linoleic acid hydroperoxide. These results indicate that lipid peroxide causes the disruption of extracellular matrix macromolecules and the inhibition of cell repair in synovial tissue. Therefore, they also suggest that an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid may play an important role in the process of rheumatoid arthritis, resulting in the disruption of the joint.

Arthritis, Rheumatoid

Effect of linoleic acid hydroperoxide on production of matrix metalloproteinases by human aortic endothelial and smooth muscle cells.

The effect of linoleic acid hydroperoxide on the production of proforms of matrix metalloproteinase-1, -2, and -3 (proMMP-1, -2, and -3) in cultured human arterial endothelial and smooth muscle cells was investigated. Upon cultivation of the endothelial cells in the absence of the hydroperoxide, only proMMP-1 was detected, and its amount was increased by cultivation with the hydroperoxide. In the cultures of the intimal smooth muscle cells in the absence of the hydroperoxide, a large amount of proMMP-2 and small amounts of proMMP-1 and -3 were detected, and the hydroperoxide treatment increased remarkably the amounts of proMMP-1 and -3, but rather decreased the amount of proMMP-2. In the cultures of the medial smooth muscle cells, the same tendency was observed. However, the amounts of these proenzymes found in the intimal smooth muscle cells exceeded those found in the medial smooth muscle cells, both in the absence and in the presence of the hydroperoxide. Possible involvement of these phenomena in atherogenesis was discussed.

Aorta, Thoracic

Analysis of a common antigenic epitope in Bacillus cereus flagellar fraction.

The strain-specific antigenicity between Bacillus cereus decreased but the common antigenicity did not change, when the flagellar antigen was treated with pH 2. Flagellar antigen of B. cereus H.1 was separated into two fractions by gel chromatography, one with a specific antigenicity (P1 fraction), and the other with a common antigenicity (P2 fraction). It was revealed that a common antigenic epitope of the P2 fraction was detected on a 61 kDa protein by further purification using a Mono Q column. This common antigenicity of flagella was increased by treatment with sodium dodecyl sulfate (SDS) and 2-mercaptoethanol, suggesting that a common antigenic epitope exists inside the flagellar component.

Antibodies, Monoclonal

[Liver impairment in kidney transplant recipients. 1. Prevalence and clinical significance of hepatitis C].

The prevalence and the clinical significance of hepatitis C (HCV) infection in recipients of kidney transplantation was assessed using second generation anti-HCV antibody (anti-HCV-2). Out of 88 patients whose preoperative sera were available for anti-HCV-2 determination, 27 patients (30.7%) were positive. Transfusion units were significantly larger and the duration of hemodialysis was significantly longer in the patients with anti-HCV-2 than those without. In 10 patients whose preoperative sera were negative for anti-HCV-2, seroconversion was documented after the operation, so that the postoperative positive rate of anti-HCV-2 increased to 42.9% (39/91). Seroconversion from positive to negative was observed in only one patient. Out of 91 patients who were followed-up at least 3 months after operation, 66 patients (72.5%) developed liver dysfunction. According to the criteria of non-A, non-B post-transfusion hepatitis established by the Japanese Society of Digestive Disease, 31 of 66 patients (34.1%) were diagnosed as "definite", 21 patients (23.1%) as "suspicious". The anti-HCV-2 positive rate was 90.3% in the "definite" group, which was significantly higher than the other groups. Liver dysfunction in the patients with anti-HCV-2 had a tendency for a chronic or prolonged course. Out of 20 patients in whom liver dysfunction continued for more than 1 year, 18 patients were positive for anti-HCV-2. It is concluded from this study that the prevalence of hepatitis C is very high in kidney transplant recipients with HCV as the main and most important etiologic factor of liver dysfunction, especially in chronic liver impairment.

Adolescent

The importance of adenosine metabolism in ischemically damaged canine pancreas during preservation by the two-layer cold storage method.

The two-layer cold storage method using the University of Wisconsin solution (UW) allows continuous tissue adenosine triphosphate (ATP) production during the preservation period. UW contains 5mM of adenosine which has several mechanisms of action, however, its efficacy is controversial. In this study, at first, we investigated the metabolism of exogenous adenosine during preservation by the two-layer method in the canine pancreas graft subjected to 60 min warm ischemia. High concentration (> 5 mM) of adenosine in Euro-Collins' solution (EC) remarkably increased ATP and total adenine nucleotide (TAN) levels during 24 hr preservation by the two-layer method using EC. Furthermore, experiments with 5 mM of [2-3H] adenosine demonstrated that adenosine was metabolized and incorporated into adenine nucleotides (ANs). However, neither 5 mM of inosine, hypoxanthine nor adenine substituted for adenosine. It was clear that adenosine was directly phosphorylated and converted into ANs. Secondly, the effect of adenosine on the viability of the ischemically damaged pancreas graft was evaluated by graft survival following autotransplantation. The ischemically damaged pancreas grafts were preserved for 24 hours by simple cold storage in EC (group 1), EC with 5 mM of adenosine (group 2), the two-layer method using EC (group 3), EC with 5 mM of adenosine (group 4). Graft survival rates were 0/5 (0%), 1/5 (20%), 0/3 (0%) and 4/5 (80%) in groups 1, 2, 3 and 4 respectively. Adenosine was clearly effective on graft survival via recovering high tissue ATP and TAN levels only in case of the preservation by the two-layer method. We conclude that exogenous adenosine works as a substrate for ANs synthesis and is directly phosphorylated to ANs during preservation by the two-layer method. This is essential to repair damaged cells and maintain cellular integrity, making it possible to preserve ischemically damaged pancreas.

Adenine Nucleotides

Post-translational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for their activation of NADPH oxidase.

rac1 and rac2 p21s are ras p21-like small GTP-binding proteins which are implicated in the NADPH oxidase-catalyzed superoxide generation in phagocytes. rac1 and rac2 p21s have a Cys-A-A-Leu (A = aliphatic amino acid) structure in their C-terminal region which may undergo post-translational processing including prenylation, proteolysis, and carboxyl methylation. We studied the function of this post-translational processing of rac p21s in their interaction with the stimulatory and inhibitory GDP/GTP exchange proteins for rac p21s, named smg GDS and rho GDI, and in their NADPH oxidase activation. We produced human recombinant rac1 and rac2 p21s in insect cells and purified them from the membrane and soluble fractions as the post-translationally processed and unprocessed forms, respectively. Post-translationally processed rac1 and rac2 p21s were sensitive to both smg GDS and rho GDI, but post-translationally unprocessed rac1 and rac2 p21s were insensitive to them. The GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-bound form of post-translationally processed rac1 and rac2 p21s stimulated the NADPH oxidase activity, but post-translationally unprocessed rac1 and rac2 p21s were far less effective. These results indicate that both rac1 and rac2 p21s stimulate the NADPH oxidase activity and that their post-translational processing is important not only for their interaction with smg GDS and rho GDI but also for their NADPH oxidase activation.

Amino Acid Sequence