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Biomedical subjects

T Gotoh

Publications and source records attributed to T Gotoh.

285 records · Page 16Linked to original sources

Generation of the superoxide radical during autoxidation of oxymyoglobin.

Autoxidation of bovine oxymyoglobin to metmyoglobin induces co-oxidation of epinephrine to adrenochrome. This co-oxidation is markedly inhibited by superoxide dismutase [EC 1.15.1.1]. Electron transfer from oxymyoglobin to ferricytochrome c is partially inhibited by superoxide dismutase. These results indicate that autoxidation of oxymyoglobin results in generation of superoxide radicals. Autoxidation of oxymyoglobin is accelerated by superoxide dismutase and partially inhibited by catalase [EC 1.11.1.6].

Adrenochrome↗

Augmentation of tissue ATP level during digestion using preoxygenated perfluorocarbon results in high islet yield-new strategy for islet isolation.

BACKGROUND: Recently, preservation using oxygenated perfluorocarbon (the two-layer method) has shown beneficial effects on islet yield and viability. In this paper, we apply this concept on isolation processes to examine the effectiveness of oxygenation. METHODS: Rat pancreata were digested using four different methods: (groups 1A, 1B, 2A, and 2B) with or without oxygenated perfluorocarbon in groups 1 and 2, respectively. Adenosine was added into the collagenase solution in subgroup A whereas it is not added in subgroup B. RESULTS: Tissue oxygen tension in group 1 was about 0 during digestion; whereas it rapidly reached about 300 mm Hg and was maintained in group 2. Tissue ATP level just after laparotomy (control) was 4.2 +/- 0.7 micromol/g dry weight. The ATP levels after digestion were 0.12 +/- 0.03 in group 1A (P < 0.01 vs control); 0.70 +/- 0.10 in group 1B (P < 0.01 vs control); 0.30 +/- 0.18 in group 2A (P < 0.01 vs control); and 2.90 +/- 0.80 in group 2B (P = 0.19 vs control). Islet yields (IEQ/pancreas) were 1600 +/- 400 in group 1B; 1400 +/- 400 in group 1B; 1300 +/- 400 in group 2A; and 2400 +/- 100 in group 2B. The amount in group 2B was significantly greater than that in the other three groups. CONCLUSIONS: Oxygen provision by preoxygenated perfluorocarbon itself showed no beneficial effect on islet yield. However, if oxygen provision was associated with adenosine administration into the pancreas, tissue ATP levels after digestion were well maintained, and a greater number of islets were retrieved.

Adenosine Triphosphate↗

Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension.

Hypertension is common in patients with type 2 diabetes mellitus (DM), and contributes to the progression of its complications in patients with diabetes. Doxazosin is a selective alpha1-adrenoceptor-blocking anti-hypertensive agent and has a favorable impact upon lipid metabolism. We investigated the effect of doxazosin on the lipid metabolism in hypertensive patients with type 2 diabetes, especially low-density lipoprotein (LDL) particle size that is associated with many elements of the insulin resistance syndrome. Cross-sectional study (n=19) was designed to determine whether doxazosin, administered with an angiotensin II-converting enzyme inhibitor (ACEI) and a Ca antagonist, affects LDL particle size. As a follow-up study (n=6), lipid and glucose metabolism and LDL particle size were followed for 12 weeks before and after the initiation of doxazosin administration (1-4 mg/day). The average size of LDL particle was significantly larger in the patients treated with doxazosin (LDL-migration index (LDL-MI): 0.348+/-0.027) than those in the patient treated without doxazosin (0.378+/-0.035), although LDL cholesterol levels did not differ between the two groups. The plasma glucose and HbA1c levels remained unchanged. Lipid profile showed normolipemia throughout the period of the study. However, LDL particle size was demonstrated to become larger during the following period. Small LDL fraction (LDL3-7) diminished remarkably and large LDL (LDL1-2) increased on the polyacrylamide gel electrophoresis (PAGE) LDL system (LipoPrint). From this pilot study, it was concluded that doxazosin is a useful anti-hypertensive agent for hypertensive type 2 diabetic patients in improving the size of LDL particle.

Angiotensin-Converting Enzyme Inhibitors↗

Arginase acts as an alternative pathway of L-arginine metabolism in experimental colon anastomosis.

L-Arginine is the substrate for the nitric oxide synthase (NOS) pathway that is essential for gastrointestinal wound healing. L-Arginine is also the substrate for the enzyme arginase which metabolizes L-arginine to ornithine and subsequently to proline and polyamines both known to interact in cell proliferation and collagen synthesis. Two distinct isoforms of arginase exist. The temporal expression of the L-arginine metabolism in experimental colon anastomosis was investigated. Male Lewis rats underwent laparotomy. A left-sided colotomy was performed and the colon reanastomosed using 6-0 prolene. Sham operation was performed in controls. On days 2, 5, 10, 14, and 28 after the surgery the anastomosis was excised. The tissue at the anastomosis (ANAST) as well as above and below the anastomosis (PDC) and from sham colon was harvested and analyzed for distinct arginase isoform I (AI) and arginase isoform II (AII) activity, protein and mRNA expression as well as immunohistochemistry. iNOS protein and mRNA expression were investigated in parallel. A mean of 3 to 4 separate rats were analyzed per time point. Statistical analysis was performed by student's t-test, significance was reached when P < 0.05. AI activity, protein, and mRNA expression were significantly upregulated at the anastomosis compared to sham controls and PDC colons at all time points. The maximum was achieved at days 10 to 14 after wounding, and decreased to baseline levels thereafter. Inflammatory cells stained positive for AI. AII protein was not detectable. However RT-PCR showed low baseline expression. iNOS expression was upregulated early but for a shorter time period after wounding and reverted quickly to undetectable levels. In anastomotic healing, AI upregulation suggests a prolonged metabolism of arginine via arginase to polyamines and proline to provide substrate for collagen synthesis and cell proliferation. The functional implication of this arginase pathway further needs to be elucidated.

Anastomosis, Surgical↗

Synchronous mucinous adenocarcinoma of the endometrium and mucinous cystadenoma of bilateral ovaries presenting during fertility therapy.

We describe a very rare case of synchronous mucinous tumor of the endometrium and ovaries presenting during ovulation induction. A 31-year-old woman received ovulation induction for 5-year primary infertility. Ultrasonography revealed mucus retention in the uterine cavity and bilateral multicystic ovaries during ovulation induction. Atypical hyperplasia was diagnosed by endometrial curettage. Repeated procedures including ovarian cystectomy, endometrial curettage and in vitro fertilization combined with progestine therapy resulted in no pregnancy but rapid recurrences. She finally underwent simple hysterectomy and bilateral salpingo-oophorectomy. Microscopic examination revealed mucinous cystadenoma in the both ovaries and well differentiated mucinous adenocarcinoma of the endometrium.

Adenocarcinoma, Mucinous↗

Features of patients with influenza virus infection examined in the emergency department of a university hospital in north-western Japan.

We aimed to determine if there were any changes in the clinical features of patients infected with influenza during an influenza epidemic in north-western Japan. We retrospectively obtained data on influenza-infected patients from an electronic database set up in the emergency department. Patients were examined in the Department of Emergency Medicine, Kanazawa Medical University in 2001, 2002 or 2003. The information collected included age, sex, time of visiting the emergency department, visiting method, grade of emergency, where they were when their symptoms started to develop, influenza-related complication(s) and outcome. The retrospective data collected for the 3 years analysed (2001-2003) were similar despite the influenza epidemic in the winter of 2002/2003. These results allow us to estimate the influenza-related total medical costs and total work burden for staff in the emergency department of a university hospital during any future influenza epidemics.

Adolescent↗

Acute and late effects of tritium beta particles on rats exposed to tritiated water as infants.

Lethality and physiological disorders induced by tritium beta particles were studied in rats. Newborn CD/Crj rats received i.p. HTO saline at 0, 8.14, 16.28, 24.42 and 32.56 MBq/g body weight (BW). At four weeks of age, HTO over 24.42 MBq/g BW was fatal, especially in male rats, but it was not obvious under 16.28 MBq/g BW. Surviving female rats were weaned at four weeks of age and rats were monitored for heart rate and blood pressure (systolic, mean and diastolic) at 13, 23 and 30 weeks of age and sacrificed. The blood pressure significantly increased with the administered doses of HTO. Sclerotic kidneys were frequently observed in hypertensive rats exposed to HTO over 24.42 MBq/g BW. Thickened intermediate layer of artery, infiltrating lymphocytes and atrophic mesangiums were observed in sclerotic kidneys. These results indicate that internal exposure to HTO as infants was induced consequent hypertension in association with sclerotic kidney at sublethal doses.

Acute Disease↗

Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection.

BACKGROUND/AIMS: The evaluation of portal blood flow in hepatic mass is important for the diagnosis of hepatocellular carcinoma. We have designed a new method to easily evaluate portal blood flow in hepatic mass using ultrasonography with injection of carbon dioxide into the intrahepatic portal vein by direct puncture with a fine needle. METHODOLOGY: We evaluated 29 masses in the liver of 20 patients ultrasonically with injection of carbon dioxide into the intrahepatic portal vein. RESULTS: Of 29 space-occupying lesions (SOLs), 13 were found to have portal blood flow and 16 were found to have no portal flow by this method. All 15 SOLs which had no portal flow were histologically confirmed to be hepatocellular carcinoma. Of 13 SOLs with portal flow, 5 were confirmed to be hepatocellular carcinoma. For 7 of 9 SOLs in which both this method and arterial portographic computed tomography were performed, the results were in agreement. CONCLUSIONS: Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection appears to be useful for the evaluation of portal flow in mass and may aid in the diagnosis and management of mass in patients with liver disease.

Adolescent↗

Intranasal L-threo-3,4,-dihydroxyphenylserine in treating diarrhea associated with familial amyloidotic polyneuropathy.

We evaluated the absorption disturbance of the gastrointestinal tract in patients with familial amyloidotic polyneuropathy (FAP). Ursodeoxycholic acid (UDCA) 300 mg was administered orally to 10 patients with FAP and 11 control subjects. Serum levels of total bile acid were determined as an indicator of absorption. The patients had lower serum levels of total bile acid than controls, suggesting an absorption disorder. To attempt to treat the diarrhea commonly associated with FAP, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine, was administered 100 mg/dose by the oral and 8 mg/0.4 ml by the intranasal route and their effects on the elevation of serum norepinephrine levels were compared. The 3-0-monohemiphthalate salt of glycyrrhizinic acid and sodium ascorbate were used as vehicles for the intranasal preparation to enhance drug absorption and prevent oxidation. Increased serum levels of norepinephrine, the converted metabolite of L-threo-DOPS in serum, was observed 2 hours after intranasal administration, but not after administration of the oral preparation or vehicle alone. Intranasal administration of 8 mg 3 times/day for 1 week resulted in reduction of the daily frequency of diarrhea as well as a decrease in the severe orthostatic hypotension in three patients with FAP. Thus, an intranasal delivery system for L-threo-DOPS, which acts by stimulating adrenergic receptors, may be considered in treating patients with FAP with severe diarrhea.

Administration, Intranasal↗

High level of tritium-remaining in brain of rats exposed to tritiated water as infants.

Newborn CD/Crj rats were given tritiated water (HTO) saline i.p. at the dose of 220 microCi (8.14 MBq)/g of B.W. We monitored residual tritium in the sera and organs of male rats up to 26 weeks of age. The total absorbed doses in serum, liver, spleen, testis and brain were estimated to be 3.10, 2.35, 2.43, 2.38 and 2.84 Gy, respectively. Over four weeks of age, a 3-19 times higher tritium content was noted in brain compared to the values of other organs. At 26 weeks of age, testis atrophy was predominant with 20% of control value by relative organ weight in association with decreased spermatogonia and increased Leydig cells. The serum testosterone level was 67% and relative adrenal weight was significantly increased in comparison with the control values. The results indicated that the high accumulation of tritium in brain, destruction of spermatogenesis and feedback of androgenic response were caused by exposure to HTO as infants.

Adrenal Glands↗

High sensitivity to hepato-tumorigenesis in hypocatalasemic C3H/C(s)b/Gen mice exposed to low doses of 252Cf fission neutrons and 60Co gamma-rays.

The sensitivity of hypocatalasemic C3H/C(s)b/Gen mouse (C(s)b) a mutant of the C3H/He mouse, for radiation tumorigenesis was studied following the irradiations of 252Cf fission neutrons (252Cf) and 60Co gamma-rays (60Co). Mice of both sexes at six weeks of age were irradiated once with 252Cf and 60Co at the doses of 0-200 cGy. As the control, C3H/HeN mice of both sexes (C3H) were also irradiated with 252Cf and 60Co. The mice were observed for 13 months after irradiation. The incidence of liver tumors in male C(s)b increased semilogarithmically from 1 to 50 cGy in the 252Cf-irradiated group. By 60Co irradiation, the tumor incidence of male C(s)b was highest at 6 cGy and then decreased with increasing radiation doses up to 200 cGy. In contrast, the incidence of liver tumors in male C3H steadily increased by 0-200 cGy of both 252Cf and 60Co irradiations. The glutathione peroxidase activity in the liver of the male was higher in C(s)b than that in C3H although catalase activity in C(s)b was lower than that in C3H. Significantly higher TBA value and lowered antioxidant activities were also observed in neoplastic liver foci in comparison with those of its adjacent liver in male C(s)b. Therefore, the implication of oxygen radicals in hepato-tumorigenesis was strongly suggested and high sensitivity of C(s)b to low doses of radiation would be useful to investigate the mechanism of radiation tumorigenesis.

Acatalasia↗