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H Yoshimura

Publications and source records attributed to H Yoshimura.

828 records · Page 46Linked to original sources

The tumor-preventing effect of a mixture of several lactic acid bacteria on 1,2-dimethylhydrazine-induced colon carcinogenesis in mice.

The anti-tumor effect of a dietary supplement obtained from mixed cultures of several lactic acid bacteria was examined in the colon of tumor-inducing ICR male mice by use of a carcinogen, 1,2-dimethylhydrazine (DMH, 20 mg/kg body weight, 1 intra-muscular injection per week for 10 weeks). The animals were sacrificed either 15 weeks or 24-26 weeks after the first carcinogen injection. Macroscopically, the incidence of colon tumors at a 24-26 week period of tumor induction was apparently lower in mice treated with both the DMH and dietary supplement (76%) than in those treated with DMH alone (100%). Histologically, microadenomas were induced predominantly in the anal half of the total colon, and large lymphoid aggregates were often associated with dysplastic crypts in the distal colon. Apoptotic cell masses were shed into the distended lumen of the involved crypts. The statistical analysis at a 15-week period of tumor induction indicated that the incidence of microadenomas per tumor-induced mouse was lowered significantly by use of the dietary supplement. From the present results, it is suggested that the intake of the dietary supplement inhibits the early development of colon adenomas, and the inhibition of microadenomas results in a reduction of subsequent polyp and tumor yield in the mouse colon.

1,2-Dimethylhydrazine↗

Disappearance of gastric antral vascular ectasia after percutaneous transhepatic obliteration.

We report on a patient with severe iron deficiency anemia due to gastric antral vascular ectasia (GAVE), complicating hepatocellular carcinoma (HCC) and esophageal varices. Esophago-gastro-duodenoscopy (EGDS) 6 months after transarterial embolization (TAE) for the HCC and percutaneous transhepatic obliteration (PTO) for esophageal varices, showed the absence of GAVE. As GAVE did not recur in spite of the recurrence of the tumor thrombus later, lowered antral congestion by PTO might be the main cause of disappearance of GAVE. This case suggests that PTO may be an effective treatment against GAVE with portal hypertension with uncontrollable bleeding.

Aged↗

Pharmacokinetics of isolated hepatic perfusion with high dose tumor necrosis factor in rat model.

BACKGROUND: Although the application of an isolation procedure with tumor necrosis factor (TNF) to the liver is quite attractive, an animal model is not yet available to evaluate antitumor effects by TNF in isolated hepatic perfusion (IHP). To establish the rat model in IHP, the pharmacokinetics of TNF, both in a perfusate and in a systemic circuit should be examined. METHODS: All rats underwent IHP with TNF. After a 10 min perfusion, a washout procedure was performed for 5 min, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the systemic blood and concentrations of TNF were assayed by L-929 cytotoxicity. RESULTS: After the administration of 240 micrograms of TNF in the circuit, TNF reached a plateau at about 12.7 micrograms/ml of perfusion fluid, lasting until the end of IHP. As a result of the washout procedure, regional TNF concentrations declined from 12.7 micrograms/ml to 1.5 micrograms/ml. At the beginning of the IHP, all rats exhibited no detectable level of TNF activity in the systemic circulation (< 100 pg/ml). With time, TNF plasma levels quickly increased to reach a plateau of about 0.2 microgram/ml at 15 min. Systemic leakage of TNF is calculated as less than 2% of the total TNF in perfusate during perfusion. CONCLUSION: Rat IHP models with TNF showed that systemic leakage of TNF was higher than that of pig models, although a large enough amount of TNF in perfusate was achieved without death. Rat models might be feasible to evaluate antitumor effect of IHP against liver metastatic tumors.

Animals↗

Reduction of hepatotoxicity of tumor necrosis factor in isolated hepatic perfusion by administration of glucocorticoid as well as lipopolysaccharide.

BACKGROUND: The application of an isolation procedure with tumor necrosis factor (TNF) to the liver is quit attractive, however, one of problems to overcome is reducing the toxicity to the liver caused by high doses of TNF. MATERIALS AND METHODS: Rats underwent isolated hepatic perfusion (IHP) with TNF and pre-treatment of subcutaneous administration of dexamethasone (4 mg/kg) and/or intradermal administration of LPS (50 micrograms/rat). After a 10 min perfusion, a washout procedure was performed for 5 min, after which isolation was terminated. RESULTS: SD or Wister rats and F344 rats tolerated up to 120 mg/rat or 4 micrograms/rat, respectively. Dexamethasone and/or LPS was tolerated at 40 micrograms/rat of TNF in F344 rat and showed a significant reduction of hepatotoxicity, and indicated histologically the suppression of ballooning and of necrosis during and after perfusion by TNF. CONCLUSION: We propose new a protocol for IHP as follows: 1. the intradermal administration of LPS for protection against toxicity of TNF, 2. IHP with TNF-SAM2, a mutain of TNF-alpha, having less toxicity than conventional TNF-alpha, and 3. simultaneous perfusion with chemotherapeutic agents such as 5-fluorouracil (5-FU).

Adult↗

Relationship between microvessel quantification and inducibility of endogenous tumor necrosis factor in colorectal adenocarcinoma.

BACKGROUND: Although we have reported that the inducibility of endogenous tumor necrosis factor (en-TNF) by tumor cells is an independent prognostic factor in Dukes stage C colorectal cancer patients, the mechanism by which the patients having high inducibility of en-TNF show better prognosis is still unclear. We hypothesize that the inducibility of en-TNF by colorectal tumor cells affects the prognosis of patients through the modulation of angiogenesis. Thus, the aim of this study is to clarify the relationship between inducibility of en-TNF and tumor vascularity in colorectal cancer. PATIENTS AND METHODS: Histological sections from 62 Dukes stage C colorectal cancer patients who received curative operation were immunostained for CD34 antigen. Microvessels were counted in the photograph of x200 fields (0.298 mm2). The average count of five most vascular areas was determined as a microvessel density of each case. RESULTS: Two of 62 cases were excluded from the analysis, because of insufficient staining. A total of 60 patients were dichotomized by a median vessel count of 34 into two groups: 30 patients with lower microvessel density (Low MVD group) and 30 patients with higher microvessel density (High MVD group). There was no significance in the distribution of all clinicopathological factors among these two groups. Regarding en-TNF inducibility, no difference was shown between the two groups. The five year survival rate of Low MVD group and High MVD group were 58.7% and 68.0%, respectively. And, the 5 year relapse-free survival rate of Low MVD group and High MVD group were 59.7% and 52.2%, respectively. No significant difference was demonstrated between Low MVD group and High MVD group. CONCLUSION: Intratumoral microvessel density did not influence on the prognosis of colorectal cancer patients in Dukes stage C after curative operation. The inducibility of en-TNF showed no correlation with intratumoral microvessel density in Dukes stage C patients after curative operation.

Adenocarcinoma↗

Cytochrome P-450 isozymes involved in the oxidative metabolism of delta 9-tetrahydrocannabinol by liver microsomes of adult female rats.

Oxidative metabolism of delta 9-tetrahydrocannabinol (THC) by liver microsomes was studied in female rats. Delta 9-THC was mainly biotransformed to 11-hydroxy-delta 9-THC (11-OH-delta 9-THC) and 9 alpha,10 alpha-epoxy-hexahydrocannabinol (EHHC) by liver microsomal fraction of adult female rat. Two isozymes of cytochrome P-450 (P-450) [F-1 (IIC6) and F-2 (IIC12)] were purified from liver microsomes of female rats and oxidation activities toward delta 9-THC were assessed in the reconstituted system containing NADH-P-450 reductase and cytochrome b5. P-450 F-1 showed considerable activity toward 11-OH-delta 9-THC formation (10.62 nmol/min/nmol of P-450), whereas P-450 F-2 did not show any activity toward delta 9-THC oxidation under the conditions used. Preincubation of microsomes with antiserum against P-450 F-1 obtained from rabbits caused a marked decrease in 11-OH-delta 9-THC formation, whereas antiserum against P-450 F-2 did not exhibit any inhibitory effect on the oxidation of delta 9-THC by liver microsomes of adult female rats. Further, antiserum against P-450 F-1 or F-2 did not affect the microsomal formation of 9 alpha,10 alpha-EHHC from delta 9-THC. These results indicate that P-450 F-1 and its immunochemically related P-450 isozyme(s) play important roles in the formation of an active metabolite, 11-OH-delta 9-THC, from delta 9-THC by liver microsomes of adult female rats.

Animals↗

Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-delta 8-tetrahydrocannabinol to delta 8-tetrahydrocannabinol-11-oic acid.

Mouse hepatic microsomes oxidized 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC, aldehyde) to delta 8-THC-11-oic-acid (carboxylic acid). The reaction required NADPH and molecular oxygen and showed an optimal pH around 7.5. The activity of NADPH-dependent carboxylic acid formation was mainly localized in microsomes. The reaction was inhibited by various inhibitors of cytochrome P-450-dependent oxidation such as SKF 525-A, alpha-naphthoflavone, and metyrapone. Disulfiram and menadione also inhibited the microsomal oxidation of the aldehyde to the carboxylic acid, but pyrazole did not inhibit the reaction. The pretreatment of mice with phenobarbital significantly increased the oxidation activity on the basis of microsomal protein, but did not affect it on the basis of cytochrome P-450 content. The mechanism for the oxidation of the aldehyde to the carboxylic acid was confirmed to be oxygenation, since oxygen-18 was incorporated into delta 8-THC-11-oic acid from molecular oxygen during the hepatic microsomal oxidation of 11-oxo-delta 8-THC.

Animals↗

Cytochrome P-450 isozymes in metabolic activation of delta 9-tetrahydrocannabinol by rat liver microsomes.

delta 9-Tetrahydrocannabinol (THC) was incubated with a reconstituted system consisting of dilauroylphosphatidylcholine, NADPH-cytochrome c reductase, cytochrome b5, and cytochrome P-450 (P-450) isozyme UT-2, UT-4, or UT-5, which was purified from liver microsomes of adult male rats. It was biotransformed by UT-2 to 11-OH-delta 9-THC and 3'-OH-delta 9-THC, and by UT-4 to 8 beta-OH-delta 9-THC and 11-OH-delta 9-THC. UT-5, however, showed only a little activity for 11-OH-delta 9-THC formation. Activity of the isozyme UT-2 for 11-OH-delta 9-THC formation from delta 9-THC was calculated to be 4.07 nmol/min/nmol P-450 while those of UT-2 for the formations of 16 alpha-OH-testosterone (16 alpha-OH-T), 2 alpha-OH-T, and androstenedione from testosterone were 14.7, 6.6, and 2.2 nmol/min/nmol P-450, respectively. Anti-P-450 UT-2 IgG fraction obtained from rabbit serum dose-dependently suppressed formations of 16 alpha-OH-T, 2 alpha-OH-T, and androstenedione from testosterone with liver microsomes of adult male rats. The antibody, in the amount that inhibited above 90% of 16 alpha-OH-T and 2 alpha-OH-T formations from testosterone, also reduced 80% of the microsomal formations of 11-OH-delta 9-THC and 3'-OH-delta 9-THC from delta 9-THC, as compared with control experiments using preimmune IgG fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Afterloading intracavitary irradiation and expanding stent for malignant biliary obstruction.

A double lumen catheter was developed as an applicator for the remote afterloading (RALS) of 60Co source for the intracavitary irradiation of an obstructed common bile duct caused by carcinoma of the gallbladder. This was followed by the placement of nylon-covered expandable metallic stents to maintain patency. This combination effectively provided palliation.

Brachytherapy↗

Metabolism of strychnine in vitro.

The in vitro metabolism of strychnine was studied in the 9000g supernatant fractions from rat and rabbit livers. The metabolism was markedly inhibited by cytochrome P-450 inhibitors, SKF-525A and n-octylamine, but only slightly by a microsomal FAD-containing monooxygenase inhibitor, methimazole. Five metabolites formed in vitro with rabbit liver were isolated and purified by Sep-Pak C18 cartridge chromatography and preparative TLC. Three of them were identified as 2-hydroxystrychnine, strychnine N-oxide, and 21 alpha, 22 alpha-dihydroxy-22-hydrostrychnine by comparison with their authentic samples by means of UV, NMR, and mass spectrometries. An additional two metabolites were tentatively identified as strychnine 21,22-epoxide and 11,12-dehydrostrychnine by spectral measurements. Four of these metabolites, with the exception of 2-hydroxystrychnine, were novel metabolites of strychnine. The in vitro formation of these metabolites by rabbit liver was determined by HPLC after partial purification. The major identified metabolite was strychnine N-oxide, which accounted for approximately 15% of the metabolized strychnine. All the other metabolites accounted for less than 1%. The presence of a larger quantity of other metabolites which have been neither isolated nor identified was also suggested.

Animals↗

Enzymatic oxidation of 7-hydroxylated delta 8-tetrahydrocannabinol to 7-oxo-delta 8-tetrahydrocannabinol by hepatic microsomes of the guinea pig.

Hepatic microsomes of the guinea pig converted delta 8-tetrahydrocannabinol (delta 8-THC) to various oxidized metabolites, including 7 alpha-hydroxy-delta 8-THC (7 alpha-OH-delta 8-THC), 7 beta-OH-delta 8-THC, and 7-oxo-delta 8-THC. The enzyme which mediates biotransformation of 7-OH-delta 8-THCs to 7-oxo-delta 8-THC was characterized in the present study. The oxidative activity was mainly located in microsomes. The microsomal reaction required NADPH and oxygen and showed an optimal pH around 7.5. The reaction was inhibited by beta-diethylaminoethyl diphenylpropylacetate (SKF 525-A), an inhibitor of cytochrome P-450, but not by pyrazole, a specific inhibitor of alcohol dehydrogenase. However, 7-oxo-delta 8-THC formation was not affected by carbon monoxide or by pretreatment of animals with cobaltous chloride (40 mg/kg, ip, once a day for 3 days). Atmospheric oxygen was incorporated into 7-oxo-delta 8-THC formed from 7 alpha-OH-delta 8-THC, but not into that from 7 beta-OH-delta 8-THC. Further, 7-oxo-delta 8-THC formed from 7 alpha-18OH-delta 8-THC released about half of 18O at the 7-position, whereas the 7-oxo metabolite from 7 beta-18OH-delta 8-THC lost little of the isotope at the 7 beta-position during the oxidative reaction. From these results, it is likely that hepatic microsomal monooxygenase (probably cytochrome P-450) plays a main role in the oxidation. In addition, mechanisms for 7-oxo-delta 8-THC formation from 7 alpha-OH-delta 8-THC or 7 beta-OH-delta 8-THC are different.

Animals↗

Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver.

Effects of four cannabinoids [cannabidiol (CBD), delta 8-tetrahydrocannabinol, delta 9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17 beta-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 microM) competitively inhibited 2 alpha-hydroxy-testosterone (2 alpha-OH-T) and 16 alpha-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3,17-dione) and 7 alpha-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2 alpha- and 16 alpha-hydroxylations and noncompetitive inhibition for 6 alpha-hydroxylation, and of metyrapone, which inhibited only 6 beta-hydroxylation competitively. CBD also suppressed formation of 2 alpha-OH-T, 16 alpha-OH-T, and androstenedione from testosterone, catalyzed by a reconstituted system containing hepatic cytochrome P-450 purified from phenobarbital-treated rats. Pretreatment of the rat with CBD (10 mg/kg, ip, once a day for 3 days) decreased testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions and increased 7 alpha-OH-T formation, while total cytochrome P-450 content was decreased. These results suggest that CBD suppresses hepatic testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions through selective inhibition of the male-specific cytochrome P-450 in the adult male rat.

Animals↗

Isolation and identification of urinary metabolites of oxycodone in rabbits.

Metabolism of oxycodone was studied in the rabbit and found to proceed through five metabolic pathways: O-demethylation, N-demethylation, N-oxidation, 6-keto reduction, and glucuronidation. Six urinary metabolites were isolated and identified in the unconjugated form: 14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydrocodeinone N-oxide (oxycodone N-oxide), 14-hydroxydihydroisocodeine, 14-hydroxydihydrocodeine N-oxide, and noroxycodone, together with unchanged oxycodone. Identification was made by means of various chromatographic and spectral comparisons with authentic samples. Oxycodone, 14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydroisocodeine, and noroxycodone were also identified as aglycons of conjugated metabolites.

Animals↗

Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice.

Metabolic disposition of delta 8-tetrahydrocannabinol (delta 8-THC), 11-hydroxy-delta 8-THC (11-OH-delta 8-THC), and 11-oxo-delta 8-THC was studied in mouse blood, liver, and brain. After administration of these cannabinoids at a dose of 10 mg/kg iv, the concentration in blood declined biphasically. The biological half-lives of the slower phases were 32, 12, and 6 min, respectively, for delta 8-THC, 11-OH-delta 8-THC, and 11-oxo-delta 8-THC. 11-OH- and 11-oxo-delta 8-THC were also eliminated faster from brain than is delta 8-THC. The peak levels of 11-OH- and 11-oxo-delta 8-THC in brain were, however, higher (10.64 and 4.25 microgram/g, respectively) than that of delta 8-THC (3.48 microgram/g) at 0.5 min after the iv injection (10 mg/kg). These results indicate that 11-OH- and 11-oxo-delta 8-THC are distributed more readily from blood to brain in mice than is delta 8-THC, and explain the greater pharmacological activity of these metabolites, as reported previously. It was also interesting to note that a much higher level of 11-OH-delta 8-THC (3.27 microgram/g) was found in brain than in liver(0.74 microgram/g) and blood (0.29 microgram/ml) at 15 min after the injection of 11-oxo-delta 8-THC (10 microgram/kg, iv). In this case the levels of 11-OH-delta 8-THC were always higher than those of 11-oxo-delta 8-THC. The results suggest that 11-OH-delta 8-THC may play an important role in the pharmacological effects of 11-oxo-delta 8-THC. In additional experiments, SKF 525-A (25 mg/kg, ip) inhibited the metabolism of 11-OH-delta 8-THC to 11-oxo-delta 8-THC, supporting the previous suggestion that this oxidation, as well as the 11-hydroxylation of delta 8-THC, is mediated by the microsomal mono-oxygenase system.

Animals↗

Three-dimensional power Doppler sonography of tumor vascularity.

PURPOSE: To assess the clinical value of three-dimensional (3D) power Doppler imaging of intratumoral blood flow. MATERIALS AND METHODS: Two hepatocellular carcinomas (HCC), one renal cell carcinoma, one hepatic focal nodular hyperplasia (FNH), and one iliac bone metastasis of HCC were used. Images were collected by power mode using the GE-Yokogawa LOGIQ 700. Power Doppler images were recorded on S-VHS videotape and fed into a workstation. Flow information was then extracted, and 3D images were constructed by surface rendering. RESULTS: Preparation of 3D images could be accomplished in one minute after feeding flow information into the workstation. Intratumoral vascular structure could be easily evaluated. This 3D imaging was useful for the differential diagnosis of hepatic tumors, especially HCC and FNH, which were confirmed in 3D imaging to have distinctly different intratumoral vascular structures. CONCLUSION: 3D imaging of intratumoral blood flow was possible by 3D processing of the power Doppler images. 3D power Doppler imaging is expected to be helpful for the differential diagnosis of tumors.

Bone Neoplasms↗

Endogenous TNF inducibility and prognosis of colorectal cancer.

BACKGROUND: We have demonstrated that the inducibility of endogenous TNF (en-TNF) by colorectal tumor cells is a factor in predicting a patient prognosis. The prognoses of colorectal tumor patients with the K-ras gene mutations in their tumors were poorer to those of patients with the wild type gene. Therefore, we analyzed the possible relationship between the inducibility of en-TNF by colorectal tumor cells during the follow-up of patients with K-ras mutations. MATERIALS AND PATIENTS: In 62 of 154 Dukes Stage C patients who received curative operation from June 1988 to June 1997, the prognoses in terms of the tumor-free rate and survival rate were compared with the inducibility of en-TNF by colorectal tumor cells, which were classified into three groups: grade 1: > or = 500 pg/ml, grade 2: 100-500 pg/ml, and grade 3: < 100 pg/ml. Regardless of the Dukes Stage of the patients, the K-ras gene was analyzed in 21 whose colorectal tumor cells were classified as grade 1: 8, grade 2: 4, and grade 3: 9. RESULTS: The tumor-free rate of the patients with grade 1 was significantly higher than that of the patients with grade 3, and the survival period of the patients with grades 1 and 2 was significantly longer than that of the patients with grade 3. Possible mutations disorder of K-ras were observed in 37.5% (grade 1), 50.0% (grade 2), and 88.9% (grade 3) of cases, respectively. CONCLUSION: The prognostic value of the inducibility of en-TNF by colorectal tumor cells from colorectal cancer patients who received curative operation at Dukes Stage C was confirmed. It is suggested that K-ras mutation may affect patient prognosis through modulation of the quality and/or quantity of cytokines such as TNF produced by tumor cells.

Colorectal Neoplasms↗

Ultrasonographic screening for arterial occlusive disease in the pelvis and lower extremities.

PURPOSE: To evaluate the accuracy of pulsed Doppler ultrasound (PDUS) and color Doppler ultrasound (CDUS) for the screening of arterial occlusive disease in the pelvis and lower extremities. METHODS: We studied 52 patients with intermittent claudication or lower extremity "coolness." Pulsed Doppler waveforms were measured in the inguinal and popliteal regions and were classified according to their pattern. Patients with abnormal waveforms underwent subsequent CDUS evaluation from the aortic bifurcation to the popliteal arteries. All patients also underwent conventional angiography. RESULTS: All stenoses (> 50%) and occlusions on angiography were detected by PDUS. The combination of PDUS and CDUS allowed detection of 78.0% of stenotic lesions (> 50% narrowing) and 96.6% of occlusive lesions in the iliofemoral regions and in 100% of stenotic lesions (> 50% narrowing) and occlusive lesions in the femoropopliteal regions. PDUS required approximately 3 min. About more 5 min are required when CDUS was added. CONCLUSION: Combined PDUS and CDUS appears to be a rapid, highly sensitive means of screening for arterial occlusive disease in the pelvis and lower extremities.

Angiography↗