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Biomedical subjects

T Kinugasa

Publications and source records attributed to T Kinugasa.

At least 37 records · Page 2Linked to original sources

Influence of timing of administration of liposome-encapsulated superoxide dismutase on its prevention of acetaminophen-induced liver cell necrosis in rats.

The possible participation of acute oxidative stress in the in vivo mechanism by which acetaminophen (APAP) induces hepatocellular injury was examined. Male Sprague-Dawley rats were administered 3-methylcholanthrene, fasted for 18 h, then given APAP and sacrificed after a further 6 h of fasting. Extensive centrilobular liver cell necrosis along with markedly elevated serum activity of aminotransferases was observed. Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) administered 1 or 0.5 h prior to APAP or simultaneously with the toxin completely prevented APAP-induced hepatocellular injury. In contrast, LSOD administered 5 or 2.5 h before or 1, 2.5 or 5 h after the toxin treatment did not prevent APAP toxicity. Incomplete protection against APAP-induced injury was obtained when LSOD was administered 0.5 h after the toxin. These results support the proposal of an oxidative mechanism for APAP hepatotoxicity.

Acetaminophen↗

[A case report of advanced gastric cancer remarkably responding to mitomycin C, aclacinomycin A, SF-SP and lentinan combination therapy].

A 63-year-old female diagnosed as inoperable gastric cancer was treated with combination immunochemotherapy of Mitomycin C, Aclacinomycin A, SF-SP and Lentinan. In this case, the tumor directly invaded the pancreas and the peritoneal dissemination, metastasis to the para-aortic lymph nodes and Virchow's metastasis were identified. As the result of this therapy, the primary tumor was remarkably reduced in size. The subjective symptoms and the metastasis of the para-aortic lymph nodes and Virchow's metastasis disappeared. The side effect was only mild thrombocytopenia.

Aclarubicin↗

Liposome-encapsulated superoxide dismutase prevents liver necrosis induced by acetaminophen.

Liposome-encapsulated human recombinant superoxide dismutase (LSOD) protected male rats that were pretreated with 3-methylcholanthrene from the liver necrosis produced by acetaminophen. By contrast, SOD-free liposomes, free SOD, or heat-denatured LSOD had no protective effect. Liposome-encapsulated SOD did not simply delay the onset of liver necrosis. A second dose of LSOD at 12 hours prevented the necrosis of the liver as assessed 24 hours after treatment with 500 mg/kg body weight of acetaminophen. Liposome-encapsulated human recombinant superoxide dismutase did not alter the metabolism of acetaminophen as assessed by either the rate or extent of the depletion of hepatic stores of glutathione or by the extent of the covalent binding of the metabolites of [3H]acetaminophen to total liver cell proteins. Evidence of the peroxidation of lipids in the accumulation of malondialdehyde in the livers was detected within 3 hours of the administration of acetaminophen and before the appearance of liver necrosis. Liposome-encapsulated human recombinant superoxide dismutase prevented the accumulation of malondialdehyde in parallel with the prevention of liver necrosis. Finally, LSOD also prevented the potentiation by 1,3-bis(2-chloroethyl)-1-nitrosourea of the hepatotoxicity of acetaminophen. These data document the participation of superoxide anions in the hepatotoxicity of acetaminophen in intact rats.

Acetaminophen↗

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis.

The effects of inhibitors of arachidonic acid metabolism and antioxidants on the rat liver tumor promotion activity of phenobarbital (PB) were assessed using the enzyme-altered focus as the end-point lesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and then divided into five groups placed on basal diet, diet containing 0.05% PB, diet containing 0.05% PB plus 0.75%, 1% or 1.5% levels of various inhibitors of arachidonic acid metabolism or antioxidants, or diet containing 1% or 1.5% inhibitors or antioxidants alone for 10 weeks, and then killed. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, significantly inhibited the promotion activity of PB at dose levels of 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin, an inhibitor of lipoxygenase, and morin, a dual inhibitor of lipoxygenase-cyclooxygenase, significantly reduced the promotion activity of PB at the 1.5% but not 0.75% dose levels. Moreover, acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependently inhibited the promotion activity of PB. Among the antioxidants investigated, vitamin E did not affect, but n-propyl gallate and ethoxyquin exerted a dose-dependent inhibition of PB promotion. These results are strongly suggestive of an involvement of phospholipase A2, lipoxygenase and cyclooxygenase arachidonic acid metabolic pathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.

Acetophenones↗

Sequence of preparatory set for response movement.

Electromyographic reaction times (EMG-RTs) of the right biceps brachii muscle were examined for two movement patterns, elbow flexion and forearm supination, in 8 healthy male subjects under simple and complex RT conditions with varied preparatory intervals (PIs): 0, 200, 400, 600, and 800 msec. In the simple RT condition, the subject was informed of the movement patterns to be performed prior to beginning the trials. In the complex RT condition the subject had to choose one of the two movement patterns at the time of the presentation of a warning signal. The results indicated that: (1) compared with the simple RT condition a delay of about 100 msec. in over-all mean EMG-RT was observed at PI = 0 msec. in the complex RT condition; (2) the difference of over-all mean EMG-RT between the two RT conditions disappeared when PI = 400 msec.; and (3) the difference in EMG-RTs between flexion and supination in the complex RT condition became the same as that in the simple RT condition when PI = 700 msec. It is assumed that the preparatory set for response movements is organized in an order, resulting in the differentiation of RT.

Arousal↗

Persistent effect of a low dose of preadministered diethylnitrosamine on the induction of enzyme-altered foci in rat liver.

The effect of a low dose of preadministered diethylnitrosamine (DEN) on the induction of enzyme-altered foci in the livers of male full-grown Fischer 344 rats was studied. As a pretreatment, DEN at a dose of 10 mg/kg body wt was injected i.p. At various times after DEN pretreatment a complete initiation, consisting of administration of the same dose of DEN by the same route in rats subjected to partial hepatectomy (PH), was performed, followed by application of selection pressure. Enzyme-altered foci stained with gamma-glutamyltranspeptidase (gamma-GTP) and glutathione S-transferase placental form (GST-P) were then assayed. Decreases in the numbers and areas of foci in the rats which received saline + PH 14 or 28 days after DEN pretreatment were observed in comparison with rats which received saline + PH immediately after DEN. On the other hand, the numbers and areas of foci were not decreased in rats which received the complete initiation, consisting of DEN + PH, at various times after DEN pretreatment when compared with rats which received these at the same time as the DEN pretreatment. This persistent effect of DEN pretreatment on the complete initiation lasted up to 182 days after the time of DEN pretreatment. In this experiment, GST-P was found to be a more sensitive marker for the detection of putative preneoplastic liver-cell foci than gamma-GTP.

Animals↗

Changes in activity of motor units preceding a rapid voluntary movement.

Motor unit activity was studied during slightly sustained contraction of the erector spinal muscle before a rapid trunk extension from a moderately bent position, with special reference to a change of the surface EMG to a rhythmic slower wave with a periodicity of 20-30 msec preceding the movement. Synchronous discharge of a few motor units appeared at regular intervals of 20-30 msec during the slower wave. EMG peaks in the slower wave corresponded to synchronous discharges at the regular intervals.

Electromyography↗

Comparative histochemical investigation of the glutathione S-transferase placental form and gamma-glutamyltranspeptidase during N-nitrosobis(2-hydroxypropyl)amine-induced pancreatic carcinogenesis in hamsters.

Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for gamma-glutamyltranspeptidase (gamma-GT) were investigated in putative preneoplastic lesions and adenocarcinomas in the pancreas of Syrian golden hamsters treated with N-nitrosobis(2-hydroxypropyl)amine (BHP). Areas with ductular proliferation, ductal hyperplasia, and intraductal carcinoma were strongly positive for GST-P binding and negative for gamma-GT. Cystic adenoma, microcarcinoma, and carcinomas were constantly positively stained by GST-P and partially positive for gamma-GT. GST-P appears to be useful as a positive marker for putative preneoplastic lesions in pancreatic carcinogenesis. Since normal acinar cells are strongly positive for gamma-GT, the findings might suggest that acinar cells contribute to the development of cystic adenoma, microcarcinoma, and carcinomas.

Animals↗

Effects of phenobarbital and secondary bile acids on liver, gallbladder, and pancreas carcinogenesis initiated by N-nitrosobis (2-hydroxypropyl)amine in hamsters.

The effects of dietary administration of phenobarbital [(PB) CAS: 50-06-6] or the secondary bile acids, deoxycholic acid [(DCA) CAS: 83-44-3] and lithocholic acid [(LCA) CAS: 434-13-9], on tumorigenesis in the liver, gallbladder, and pancreas were investigated in male Syrian golden hamsters after carcinogenic initiation by N-nitrosobis(2-hydroxypropyl)amine [(BHP) CAS: 53609-64-6]. BHP [500 mg/kg (body wt)] was injected sc once weekly for 5 weeks. The animals were then maintained on a basal diet or a diet containing either 0.05% PB, 0.1% DCA, 0.5% DCA, or 0.5% LCA for 30 weeks. DCA enhanced the development of cholangiocarcinomas without influencing that of hepatocellular lesions. PB promoted the induction of hepatocellular carcinomas but not that of cholangiocarcinomas. LCA was without effect on the induction of either hepatocellular carcinomas or cholangiocarcinomas. DCA at a dose of 0.5% enhanced the induction of polyps in the gallbladder. Both DCA, at a dose of 0.1%, and LCA significantly enhanced the induction of pancreas carcinomas. PB had no effect on the induction of polyps in the gallbladder or of pancreas carcinomas. These data document that different tumors may be differentially promoted following initiation with a common carcinogen.

Adenoma, Bile Duct↗

Combined effects of cholecystectomy and lithocholic acid on pancreatic carcinogenesis of N-nitrosobis(2-hydroxypropyl)amine in Syrian golden hamsters.

The effects of cholecystectomy and/or lithocholic acid (LCA) on the composition of biliary bile acid and on pancreatic carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) were examined in male Syrian golden hamsters. Cholecystectomy was performed 1 wk before BHP initiation. BHP (250 mg/kg of body weight) was injected s.c. once a wk for 5 wk. A diet containing 0.5% LCA was begun 1 wk after the final BHP injection. All hamsters were sacrificed 36 wk after cholecystectomy, and the pancreas was examined histologically. Only the LCA treatment but no other treatment influenced the bile acid composition, i.e., the increase in LCA and decrease in cholic acid. The incidence of pancreatic carcinoma was 23 of 30 (76.7%) in hamsters receiving cholecystectomy plus BHP followed by LCA diet. The tumor incidence was five of 18 (27.8%) with BHP followed by basal diet, ten of 18 (55.6%) with cholecystectomy plus BHP followed by basal diet, and six of 18 (33.3%) with BHP followed by LCA diet, respectively. The total number of pancreatic carcinomas in hamsters receiving cholecystectomy and BHP followed by LCA diet also increased significantly. These results indicate that combined treatments of cholecystectomy and dietary LCA enhanced BHP-inducing pancreatic carcinogenesis in hamsters.

Adenocarcinoma↗

The double-eyelid operation in Japan: its evolution as related to cultural changes.

Of the many aspects of aesthetic surgery, the double-eyelid operation generates the most interest for Japanese surgeons, as there has been an enormous demand for it by patients who are fashion-conscious. It has been possible to locate 32 operative procedures that have been published in the Japanese literature over the past ninety years. Some of these procedures have been reviewed here in relation to the cultural and social changes which are important factors determining the extent of the demand for the operation and which correlate with various changes in surgical technique. This study chronologically describes each of the principal methods related to these social changes and also considers the influence of cultural fads and fashions.

Asian People↗

[Time-dependent measurement of differential digital plethysmogram in bicycle ergometer exercise].

Time-dependent measurements of differential digital plethysmogram during exercise were made on five male subjects. The results obtained were as follows; Differential digital plethysmogram (delta DPG) was obtained by using biophysical amplifier with the time constant of 0.03 seconds which minimized the fluctuation of the baseline in digital plethysmogram (DPG). A linear relationship was shown in P wave amplitude of both delta DPG and DPG. The decrease in delta DPG-P waves was observed in visual concentrations, mental learning and arithmetic, initial inspiratory phase with tachycardia, maximal inspiratory and/or expiratory breath holding, and head-up tilt at 60 degrees or over. The increase in delta DPG-P waves was obtained at the expiratory phase with bradycardia and in the effect of alcohol intake. During 15 minutes of bicycle ergometer exercise at 750 kpm/min, the P wave amplitude in delta DPG decreased to 77% of the control in the first one minute of exercise, and then gradually increased to 218% at the final stage of exercise (p less than 0.01). Heart rate measured simultaneously increased, as compared from the beginning of exercise. P wave amplitude and heart rate after exercise decreased progressively to the control level. It is suggested that the initial decrease in P wave amplitude of delta DPG couples with the dominant activity of the sympathetic vasoconstrictor, and the final increase in P waves is due to the compound factors of the increased cardiac output and arteriolar vasodilation.

Adult↗

Effect of bile duct ligation on bile acid metabolism in rats.

The effect of bile duct ligation on the quantitative and qualitative changes of bile acids in serum, liver, urine, and feces, and the concentration of cholesterol and phospholipids in serum and liver were examined in male rats. The concentration of bile acids in serum increased over 100-fold on day 5 but was lower than the 5-day level on days 10 and 15. The concentration in the liver also increased about 10-fold. beta-Muricholic acid predominantly increased but the secondary bile acids, deoxycholic acid and hyodeoxycholic acid, decreased. The urinary excretion of bile acids increased to about 40 mg/day per rat on the first day of bile duct ligation but this increase was reduced on day 2 to about half and remained at that level until day 24. These values exceeded that of fecal bile acids, 12 mg/day per rat, before bile duct ligation. The amount of bile acid sulfates in the urine was as low as 1% of the total. The urinary non-sulfated bile acids consisted mainly of beta-muricholic acid (60%) and cholic acid (20%), while the sulfates contained a considerable amount of unidentified acidic substances (40%) in addition to cholic acid and beta-muricholic acid. The concentration of cholesterol and phospholipids in serum markedly increased on day 5 but declined gradually thereafter. The liver cholesterol concentration did not change but the phospholipid concentration decreased. Fecal sterols did not change in both the total amount and composition. These data indicated that daily synthesis of bile acids, especially beta-muricholic acid, was accelerated in bile duct-ligated rats.

Animals↗

Suppression of serum levels of luteinizing hormone by short- and long-loop negative feedback in ovariectomized women.

The suppressive effects of short- and long-loop negative feedback on serum levels of LH were assessed after administration of human chorionic gonadotrophin (HCG) and conjugated oestrogens. Fourteen ovariectomized women were injected intravenously with 5 mg conjugated oestrogens, eight of these patients were also given an intramuscular injection of 10,000 i.u. HCG 8 h later, while the other six patients were given a control injection of 0.9% saline. The serum levels of LH decreased by similar amounts in both groups of women. Thirteen other ovariectomized women were initially injected with 10,000 i.u. HCG, i.m., seven of these patients were also given an i.v. ijection of 5 mg conjugated oestrogens 8 h later, while the remaining six patients received a control injection of 0.9% saline. The results showed that conjugated estrogens could further supress the serum level of LH which had been reduced by prior HCG treatment. In six ovariectomized women who received i.m. saline injections at the start of the experiment and 8 h later, the serum levels of LH did not change significantly. It is concluded that the suppression of the serum concentrations of LH by long-loop negative feedback after administration of 5 mg conjugated oestrogens is greater than that by short-loop negative feedback after treatment with 10,000 i.u. HCG.

Adult↗

Endocrine and androgen-receptor studies in a patient with XY gonadal agenesis.

A 19-year-old phenotypic female with gonadal agenesis and XY karyotype underwent an endocrinologic study. She lacked secondary sexual characteristics and there was posterior labial fusion, absence of vagina, and no gonadal or gonadal duct tissues present at laparotomy. Elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responded well to intravenous injection of LH-releasing hormone (LH-RH) but did not respond to clomiphene citrate. Both OH and FSH levels were suppressed by administration of testosterone or estrogen. Low serum concentration of testosterone did not respond to human chorionic gonadotropin (hCG) injection. Dihydrotestosterone binding by cultured skin fibroblast revealed the existence of a binding component with low capacity and high affinity. This is the first report of a patient with XY gonadal agenesis in whom androgen receptors in the target cells are demonstrated.

Adult↗

Afferent fiber connections from lower brain stem to hypothalamus studied by the horseradish peroxidase method with special reference to noradrenaline innervation.

Attempts were made to determine the afferent projections to the anterior hypothalamus including the preoptic area from the lower brain stem by means of the horseradish peroxidase method combined with monoamine oxidase staining to identify noradrenaline (NA) neurons. In addition to this technique, a histofluorescence analysis was performed. NA fibers in the medial part of the anterior hypothalamus were mainly supplied by A1 and A2 NA neuron groups, while the lateral part and periventricular zone received NA terminals from both pontine and medulla oblongata NA neuron groups. Furthermore, the present study indicated that there were direct projections to the anterior hypothalamus from non-noradrenergic neurons in the lower brain stem: nuclei raphe dorsalis, centralis superior, cells in the mesencephalic and pontine central gray matter, nuclei parabrachialis lateralis and medialis, cells around fasciculus longitudinalis medialis.

Afferent Pathways↗

Clinical and endocrinological analyses of patients with galactorrhea and menstrual disorders due to sulpiride or metoclopramide.

The clinical courses of galactorrhea and menstrual disorders were studied in 18 women with galactorrhea induced by sulpiride (SLP) or metoclopramide (MCP) given for the treatment of gastrointestinal diseases. The response of PRL and TSH to 500 micrograms iv TRH and the response of LH and FSH to 100 micrograms LRH were assessed by retrospective analysis during treatment in nine patients (six, SLP; three, MCP) and shortly after the end of treatment in nine patients (seven, SLP; two, MCP). The average time from the initiation of treatment to the onset of galactorrhea was 27.2 +/- 4.7 (mean +/- SE) days in the 13 SLP-treated patients and 23.2 +/- 5.8 days in the 5 MCP-treated patients. Five of the SLP-treated patients experienced amenorrhea, four had oligomenorrhea, and one had dysfunctional bleeding. In the MCP-treated patients, oligomenorrhea and dysfunctional bleeding occurred in one each. The average length of time from the end of treatment to disappearance of galactorrhea was 50.0 +/- 7.3 days in the SLP-treated patients and 56.6 +/- 12.1 days in the MCP-treated patients. Cyclic uterine bleeding returned within 2 months after treatment was stopped. Elevated PRL levels with good response to TRH were observed in four of six patients during SLP treatment, and in two of three patients during MCP treatment. Basal PRL levels and response to TRH were normal in almost all patients after the drugs were withdrawn. Normal HL and FSH levels with exaggerated responses of LH to LRH were observed in most patients during treatment, whereas the response of LH to LRH was normal in about half of the patients after treatment. Our findings suggest that hyperprolactinemia in patients treated with SLP or MCP may be in part the cause of both galactorrhea and menstrual abnormalities, and that these symptoms can be reversed by stopping treatment, provided the patients have not taken the drugs for longer than a year.

Adult↗