Journal of The Showa Medical Association
Online ISSN : 2185-0976
Print ISSN : 0037-4342
ISSN-L : 0037-4342
Volume 46, Issue 3
Displaying 1-16 of 16 articles from this issue
  • Koji SAKAMOTO, Sadao NAKAYAMA, Kenichi USAMI, Tadashi KURIMOTO, Hiroo ...
    1986 Volume 46 Issue 3 Pages 315-321
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Effects of alminoprofen, (±) -2- [p- [ (2-methylallyl) amino] phenyl] propionic acid, a new analgesic anti-inflammatory drug, on drug-metabolizing enzymes and fine-structure in rat liver were investigated compared with ibuprofen, ketoprofen and flurbiprofen. Aminopyrine N-demethylase and aniline hydroxylase activities and cytochrome P-450 contens were decreased from 6hr to 48hr after a single administration of alminoprofen (35mg/kg and 50mg/kg p. o.) . In fine-structure of liver, alminoprofen caused the morphological changes such as disarrangement and enlargement of rough endoplasmic reticulum (rER), detachment of ribosome from the rER and increase in smooth endoplasmic reticulum (sER) . Nevertheless, the decreases in drug-metabolizing enzyme activities and morphological changes induced by alminoprofen were reversible. The drug-metabolizing enzyme activities were increased transiently by administration of ibuprofen, ketoprofen and flurbiprofen. Morphological changes for endoplasmic reticulum (ER) prolonged until 96hr after administration of ibuprofen (50mg/kg p.o.) . From these results, the inhibition of hepatic drug-metabolizing enzyme activity by alminoprofen was thought a reversible response with the morphological changes in the liver. It is suggested that these changes on drug-metabolizing enzyme activity and fine-structure of liver was an adaptive reaction of liver induced by after a single administration of alminoprofen.
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  • Koji SAKAMOTO, Sadao NAKAYAMA, Taiki TSUJI, Tadashi KURIMOTO, Hiroko N ...
    1986 Volume 46 Issue 3 Pages 323-331
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Effect of repeated oral administration of alminoprofen, a new analgesic anti-inflammatory drug, on drug-metabolizing enzyme activity and fine-structure in rat liver were investigated compared with ibuprofen, flurbiprofen and ketoprofen. The drug-metabolizing enzyme activity was not affected by alminoprofen at doses of 20, 35 and 50mg/kg daily for 3days. Aminopyrine N-demethylase and aniline hydroxylase activities were inhibited by the administration of alminoprofen for 7days or 14days. Furthermore, when administered for 14days at dose of 50mg/kg, alminoprofen caused the decrease of cytochrome P-450 contents, too. After washing out for lOdays, these changes returned to the control level. On repeated oral administration of alminoprofen (35 and 50mg/kg) for 3 days or 7 days to rats, the morphological changes of fine-structure showed the decrease and enlargement of rough endoplasmic reticulum (rER), the detachment of ribosome from rER and the increase in smooth endoplasmic reticulum (sER) . On the other hand, trimethadione metabolic rate was not reduced by the repeated oral administration of alminoprofen for 14 days. From these results, the repeated oral administration of alminoprofen showed the reversible inhibition of drug-metabolizing enzyme activity and a transitory response with the morphological changes for ER in rat liver. These morphological changes for ER did not correlated with the drug-metabolizing enzyme activity. It was suggested that the changes caused by almino profen were physiological adaptive response, and alminoprofen did not induced a hindrance to hepatic functions.
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  • —FATTY LIVER AND EXPERIMENTAL HEPATIC PORPHYRIA EXAMINATIONS—
    Koji SAKAMOTO, Masako OKAZAKI, Junichi SUZUKI, Tadashi KURIMOTO, Hiroo ...
    1986 Volume 46 Issue 3 Pages 333-344
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    It was investigated whether drug-induced lipidosis and porphyria of liver were caused by alminoprofen in rats, compared with chloroquine diphosphate (chloroquine), 4, 4'-bis (diethylaminoethoxy) α, β-diethyldiphenylethane (DH), carbon tetrachloride (CCl4) and 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) . Phospholipids (PL) and total cholesterol (TC) in lysosomal fraction and tissue of liver were increased significantly by chloroquine and DH. CCl4caused the remarkable increase of TC, triglyceride (TG) and non-esterified fatty acid (NEFA) in rat liver tissue. Furthermore, chloroqine, DH and CCl4showed the marked rise of GOT, mitochondria-GOT (m-GOT) and GPT in blood biochemical examinations, and also observed the cloudy swelling, fatty degeneration and necrosis of liver in pathological findings. On the other hand, PL in lysosomal fraction and tissue of liver was increased slightly by alminoprofen, ibuprofen, ketoprofen and flurbiprofen. Ibuprofen caused the slight rise of GOT and m-GOT, however, the significant changes in blood biochemical and pathological findings were not observed by repeated oral administration of alminoprofen. In experimental hepatic porphyria studies, δ-aminolevulinic acid (ALA) in urine and porphyrine (coproporphyrine and protoporphyrine) contents in rat liver were increased markedly by repeated oral administration of phenobarbital or DDC. On the contrary, alminoprofen did not show the significant changes on ALA synthetase and ALA dehydrase activities, ALA and porphobilinogen in urine, and porphyrine contents in liver. These results suggested that lipidosis and porphyria of liver were not induced by alminoprofen.
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  • Koji SAKAMOTO, Mayumi TONOOKA, Takako KASAHARA, Tadashi KURIMOTO, Hide ...
    1986 Volume 46 Issue 3 Pages 345-350
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    It was investigated that effects of alminoprofen, as an analgesic anti-inflammatory drug, on the enzyme leakage and14C-leucine uptake in primary cultures of rat hepatocytes, and on the hemolysis in rat erythrocytes. In primary culture of rat hepatocytes, carbon tetrachloride (CCl4) increased significantly the leakages of GOT, GPT, LDH and OCT into the medium. However, the leakages of GOT and OCT were inhibited by alminoprofen, as well as phenylpropionic acid derivatives, ibuprofen, ketoprofen and flurbiprofen. Also, alminoprofen and ibuprofen (1×10-6-1×10-3M) did not affect on the14C-leucine uptake into the protein. And, CCl4at the concentration of 1×10-2M caused the significant decrease of14C-leucine uptake into the protein in primary culture of rat hepatocytes. Furthermore, alminoprofen showed a membrane stabilizing effect on the hypotonic hemolysis using the rat erythrocytes, similar to ibuprofen, ketoprofen and flurbiprofen. From these results, it seems that alminoprofen, ibuprofen, ketoprofen and flurbiprofen do not have a direct damaging effect on hepatocytes.
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  • Koji SAKAMOTO, Mayumi TONOOKA, Koichiro ABE, Takako KASAHARA
    1986 Volume 46 Issue 3 Pages 351-358
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Laennec (LAE), which contains many components, is the hydrolyte of the human placenta. LAE effects a decrease of transaminase activity for liver disease. In the present study, the effect of LAE in the enzyme leakage (GOT, GPT, LDH, OCT) from hepatocytes and the incorporation of14C-leucine into intra-and extra-cellular protein, which was analysed using freshly isolated and primary cultured hepatocytes which were treated with CCl4. The enzyme leakage from freshly isolated hepatocytes significantly decreased by incubation in LAE. However, by treatment of LAE with CCl4, the enzyme leakage from freshly isolated hepatocytes increased significantly compared to those incubated only in CCl4. On the other hand, the enzyme leakage from primary cultured hepatocytes significantly decreased by incubation in LAE and LAE with CCl4. The incorporation of14C-leucine into intracellular protein decreased by treatment of LAE and CCl4. The present study shows a difference between freshly isolated and cultured hepatocytes by incubation in LAE. It suggests that LAE has a membrane stabilizing action.
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  • Sadao NAKAYAMA, Hideyuki KURISHIMA, Kenji KOBAYASHI, Taiki TSUJI
    1986 Volume 46 Issue 3 Pages 359-364
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    The changes of serum lipids at 8, 24 and 43 hour after administration of triton WR-1339 (Triton) were investigated, and the effects of γ-oryzanol (γ-OZ) and its new sterol compositions (N-γ-OZ) and cycloartenol ferulic acid ester (CAF) on this hyperlipidemic model were examined by the oral and intravenous administrations. The marked increase of total cholesterol (TC), free cholesterol (FC), triglyceride (TG) and phospholipid (PL) and the significant decrease of TC and PL in high density lipoprotein were found by the intravenous administration of Triton, and reached a peak at 24 hour after administration. In the investigations of lipid synthesis, the animals at 8 to 24 hour after administration of Triton 250mg/kg were good model. In contrast, the animals at 43 hour after administration of Triton 300mg/kg were good model on the investigations of lipid excretion. γ-OZ, N-γ-OZ and CAF were not inhibited the increases of TC, FC, TG and PL in the serum at 8 to 24 hour after administration of Triton 250 and 300mg/kg. The excretion of lipids at 43 hour after administration of Triton 300mg/kg was accelerated by the intravenous administrations of γ-OZ, N-γ-OZ and CAF. The order of effects on the lipid excretion in Triton induced hyperlipidemia was γ-OZ<CAF≤N-γ-OZ.
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  • Takeo NOMURA
    1986 Volume 46 Issue 3 Pages 365-376
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    In order to see the effects of endurance training for 12 weeks, oxygen intake and cardio-respiratory parameters (mainly alveolar capillary gas exchange) were measured at rest and during submaximal and maximal work in bicycle exercise. Static lung volume, functional capacity, heart volume (HV) and body composition were also measured. Subjects were 5 male between the ages of 15-16 years. The subjects were not engaged in regular physical activity during their daily life. Comparisons were made of another 5 male track and field athletes aged 18-20 years for the determination of Alveolar-arterial O2difference (A-aDO2) at rest and during exercise up through the maximal level. There was no significant difference in total body fat %, HV and pulmonary function measurements (VC, FEV 1.0, MMF, DLco) except MVV between pre and post training. During submaximal exercise minute ventilation was significantly lower after training. Maximal oxygen intake increased significantly after training (29 %, p<0.05) . DLcoincreased liniarly with increasing VO2. There was no significant difference in DLcoduring submaximal up through maximal exercise between pre and post training. Higher PAO2 (106.1±4.6 mmHg) and lower PaO2 (77.1±4.0 mmHg) resulting in larger AaDO2 (29.0±2.6 mmHg) being present in non-athletes group than athletes during heavy exercise suggested that there was a evidence of diffusion limitation at maximal level of work.
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  • Yasuhiko KOMATSU, Sachie OKUBO, Nobuhiko KOMATSU
    1986 Volume 46 Issue 3 Pages 377-382
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Various kinds of immunopotentiators were intraperitoneally administrated into mice (BALB/c strain), and the peritoneal macrophages were collected at intervals. Subsequently the opsonized zymosan-induced and luminol-amplified chemiluminescence (CL) was measured. The CL Value of macrophages collected 24 hours after injection of 0.4-4 mg/kg of native schizophyllan (MW: 6×106) was twice higher than that of the control group. On the other hand, the macrophages from mice treated with 0.04-4 mg/kg of sonicated schizophyllan (MW: 4.5×105) showed the peak of CL one hour after the administration, the relative intensity (RI) of CL being 2-3. Mannoglucan (MG) ofMicroellobosporia griseashowed the peak (RI: 2.7) 24 hours after the injection of 4 mg/kg. The peak (RI: 3.2) was recognized 48 hours after injection of 4 mg/kg of zymosan. In the case of krestin, the peak (RI: 5) appeared 48 hours after injection of 200mg/kg. Muramyl dipeptide (MDP) showed the peak (RI: 3.2) 48 hours after the administration of 0.4mg/kg. In the case of MDP-Lys (L18), an acyl derivative of MDP, the peak was observed after 72 hours at the dose of 4 mg/kg. LPS exhibited the the highest CL value (RI: 27) 1-24 hours after injection of 0.4mg/kg.
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  • Masahiro ARIIZUMI, Noboru NAGUMO, Katsuko KIMURA, [in Japanese], Nobuh ...
    1986 Volume 46 Issue 3 Pages 383-389
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    The subcutaneous administration of muramyl dipeptide (MDP) and MDP-stearoyllysine [MDP-Lys (L18) ] proved to prolong the life-span of mice infected withMycobacterium tuberculosis. The time course for the change of viable number ofM. tuberculosisin lung revealed that the multiplication of the infected bacteria was more remarkably inhibited in MDP-Lys (L18) -treated mice than in control and MDP-treated mice. The lesions of lungs of MDP-Lys (L18) -treated mice showed tendency toward histopathological characteristics of proliferative-granulomatous type, while necrotic-exudative changes were predominant in control and MDP-treated groups. Marked enhancement of delayed-type hypersensitivity to PPD was observed in groups treated with MDP and MDP-Lys (L18) . Among bacteria other than M. tuberculosis, both substances were effective on infections ofStaphylococcus aureusand Escherichia coli. MDP and MDP-Lys (L18) were intraperitoneally injected into mice, and the opsonized zymosan-induced and luminol-amplified chemiluminescence (CL) of the peritoneal macrophages was measured. The CL values of macrophages collected 2-3 days after injection were 3-5 times higher than those of control group. Increase of candidastatic activity of peritoneal macrophages could also be demonstrated after intraperitoneal administration of MDP and MDP-Lys (L18) . The protective effect of MDP and MDP-Lys (L18) on bacterial infections is considered to be due to the activation of macrophages, as well as polymorphonu-clear leukocytes.
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  • Yutaka OHNO, Noboru NAGUMO, Katsuko KIMURA, Nobuhiko KOMATSU
    1986 Volume 46 Issue 3 Pages 391-397
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Effect of schizophyllan (SPG), a simple glucan produced bySchizophyllumcommune, and other immunostimulants on candidastatic activity of murine macrophage cell line J774.1 was examinedin vitro. The J774.1 cells treated with each immunostimulant were seeded in 96-multiwell tissue culture plates and infected with serially (2-fold) dilutedCandida parapsilosiscells. Fungistatic index (FI) was estimated after 24 hours incubation. (1) When J774.1 cells were cultivated in the presence of SPG at the concentrations of 10-4-102μg/ml, the candidastatic activity proved to be augmented, showing diphasic pattern. The first peak was observed at one hour cultivation (FI: 2.5-9.0), and the second between 24 and 72 hours (FI: 2.12-7.25) . (2) In the case of LPS, increase of candidastatic activity (FI: 4-8) was recognized after one hour cultivation at the concentrations of 10-5-10-1μg/ml, and maintained for 24 hours. (3) The activation of macrophage with krestin (FI: 4-32) could be observed at the higher concentrations (10-500μg/ml) . (4) Lentinan showed weak activation (FI: 2-4) at the concentrations of 10-1-10-3μg/ml after 24 hours cultivation. (5) Corynebacterium parvum, BCG-CWS and picibanil activated J774.1 cells at the very narrow range of concentrations after 48 hours cultivation. (6) No enhancement of candidastatic activity could be detected in the cases of lipid A, MDP, MDP-Lys (L18), DMG and levamisole.
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  • Haruo MIURA, Noboru NAGUMO, Katsuko KIMURA, Shizuko ABE, Sachie OKUBO, ...
    1986 Volume 46 Issue 3 Pages 399-405
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    DMG (degraded mannoglucan ; MW: about 3×105) prepared from a mannoglucan (MW: about 9×105) produced byMicroellobosporia grisea, showed a marked inhibitory effect on the growth of subcutaneously transplanted sarcoma 180. Pretreatment of mice with a single injection of 100 mg/kg of DMG 6 days before the transplantation could also induce a remarkable effect. On the other hand, DMG failed to inhibit the growth of ascites tumor of sarcoma 180. DMG proved to induce prolongation of life-span of mice infected withMycobacterium tuberculosis.The time course for the change of viable number ofM. tuberculosisin lungs revealed that the multiplication of infected bacteria was markedly suppressed, as compared to that of control mice. The lesions of lungs of DMG-treated mice exhibited tendency toward histopathological characteristics of proliferative-granulomatous type, while necrotic-exudative changes were predominant in control groups. Marked enhancement of delayed-type hypersensitivity to PPD was recognized in DMG-treated group. Among bacteria other thanM. tuberculosis, the pretreatment with DMG showed protective effect on experimental infections ofStaphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Serratia marcescens. The pretreatment of mice with DMG proved to increase the number of hemolytic plaque-forming cells of spleen after immunization with sheep red blood cells. Significant enhancement of delayed cutaneous hypersensitivity to picryl chloride could also be observed in mice treated with DMG.
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  • Fumio TANISHIMA, Masako SATOYOSHI
    1986 Volume 46 Issue 3 Pages 407-414
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Regional capillary density and capillary per fiber ratio were studied in normal and trained rat hearts. Male Wister strain rats were trained on a 22m/min treadmill for 22 weeks, 6days/week for 45 minutes each day. The animals were anesthetized and Indian ink was infused through their great vein into their heart. The hearts were frozen and sectioned, and stained with toluidine blue solution to reveal the number of capillaries with Indian ink. Measurement were made of the right ventricular subepicardial zone (LVepi.), Left ventricular subepicardial zone (LVepi.), left ventricular subendocardial zone (LVendo.), and papillary muscle zone (PM) . The following results were obtained ; When the C/F Ratio was compared in the control group, the values of RVepi. and LVepi. proved to be significantly higher than those of LVendo. and PM (RVepi. 1.17±0.022, LVepi. 1.17±0.033, LVendo. 1.12±0.023, PM 1.13±0.022) . In the exercised group, the C/F Ratio values were higher than those of the control group (RVepi. 1.21±0.035, LVepi. 1.19±0.057, LVendo. 1.15+0.023, PM 1.21±0.025) . Training caused a significant increase in the C/F Ratio of RVepi. and PM. The values of capillary density and muscle fiber per mm2in the control group were higher than those of exercised group, but not significantly. The present experiment shows that there was a regional effect on the capillary supply in the rat hearts. It is obvious that the capillary supply of the subepicardial zone was greater than that of the subendocardial zone. Exercise may cause a different effect on the capillary supply of various regions.
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  • Hiraku MORI, Sadamu OKADA, Yoshio TAKIZAWA, Shoji HAGIWARA, Haruo NIIK ...
    1986 Volume 46 Issue 3 Pages 415-421
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Clinical study of ten cases with erythroleukemia was performed. Age ranged from 19 to 77 years (average 53) . According to FAB classification, the diagnosis of each case altered during the clinical course as follows ; Case 1 RAEB, Case 2 RAEB→RAEBt, Case 3 RAEBt→M4, Case 4 RAEB→RAEBt→M4, Case 5 RA, Case 6 RAEBt→M1→RAEBt, Case 7 RAEBt→M1, Case 8 RA-RAEB→fibrosis, Case 9 RA, Case 10 RAEB→RAEBt, Cytogenetic study revealed seven cases with major karyo type abnormalities (MAKA type) . None of ten cases obtained a complete remission with chemotherapy. 50% survival was 4.5months. Improved survival was noted in cases which showed LDH revels less than 1000 WU and platelet count more than 5×104/μl. There were no significant correlation between survival and age, hemoglobin level, WBC count, chromosome abnormalities.
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  • Kenichiro OKAMOTO, Takashi ITO, Gentaro TAKAHASHI, Hitomi HIGUCHI, Nob ...
    1986 Volume 46 Issue 3 Pages 423-426
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    The delayed effect of stellate ganglion block for allergic rhinitis was studied by the quetionnaire to the patients. Concerning 3 complaints, i.e. paroxysmal sneezing, watery rhinorrhea and nasal obstruction, 77% out of 44 patients answered to the questionnaire hed either no complaints or relieved complaints compared with the previous year. The study should be continued every year in the future.
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  • Minoru SHIBATA, Shinsai AKAGI, Nobuo HIROSE, Hitoshi FUNATOMI, Yoshio ...
    1986 Volume 46 Issue 3 Pages 427-431
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    A case of liver cirrhosis with primary hyperparathyroidism and leukoderma vulgaris was reported. A 57-year-old woman with liver cirrhosis showed hypercalcemia and hypophosphatemia in her clinical course. Biochemically, both serum parathormone level and urinary excretion of nephrogenic cyclic AMP elevated and mass lesion in the posterior region of the left lobe of thyroid gland was noticed on cervical CT scanning. No malignant tumors were detected anywhere as far as we could examine. Urinary excretion of calcium did not decrease. From these findings, hypercalcemia and hypophosphatemia were seemed to be due to primary hyperparathyroidism other than pseudohyperparathyroidism and familial hypocalciuric hypercalcemia. The progression of primary hyperparathyroidism and leukoderma vulgaris are generally considered to be affected by autoimmunological factors. Although we could not show any automimmunological changes in our case, it could be possible to assume that some immunological changes based on liver cirrhosis might play some role in development of primary hyperparathyroidism and leulkoderma vulgaris.
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  • Kiyoshi KOZASA, Masazumi ISHIKAWA, Shinichi ITO, Morio FUJISAWA, Toyoh ...
    1986 Volume 46 Issue 3 Pages 433-437
    Published: June 28, 1986
    Released on J-STAGE: September 09, 2010
    JOURNAL FREE ACCESS
    Relationship between herpes zoster and upper gastrointestinal lesions were studied from 1982 to 1983. During this period of the study, 12 cases of herpes zoster with epigastralgia etc. were admitted to our hospital. Upper gastrointestinalgraphy and upper gastrointestinal endoscopic examinations were performed. Of these cases, abnormal endoscopic findings were noted in 6 cases. We evaluated abnormal endoscopic findings in relation to age, the period from the onset of skin rash to examination, the site of skin lesion and with or without analgesic theraphy. All cases had benign lesions; gastric ulcer and gastric erosion. Most of the benign lesions were found in the old aged men administrated analgesic theraphy. All of the benign lesions were found on and after 11 days when the skin rash occurred.
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