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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 343 records · Page 19Linked to original sources

Rat liver DT-diaphorase as a nitroso-reductase.

Reduction of several nitroso-compounds by purified DT-diaphorase from rat liver cytosol was investigated. Among nitroso-compounds tested, 1-nitroso-2-naphthol and p-nitrosophenol were reduced in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) at rates much faster than that of nitrosobenzene. On the contrary, none of the N-nitroso-compounds tested was reduced by this enzyme. Experiments on the identification of reduction products and on the inhibition with dicoumarol and the antiserum indicated that DT-diaphorase catalyzes 4-electron reduction of C-nitroso-compounds and plays a major role in the reduction of these compounds by rat liver cytosol.

Animals↗

Inhibition of hepatic microsomal cytochrome P450 by cannabidiol in adult male rats.

The mechanism of inhibitory effect of cannabidiol (CBD) on the hepatic drug-metabolizing enzyme system was studied in adult male rats in vivo. Time course studies revealed that microsomal d-benzphetamine N-demethylation and testosterone 2 alpha-, 16 alpha- and 17-oxidation were markedly suppressed 6 to 48 h after the single administration of CBD (10 mg/kg, intraperitoneally). Decreases in activities of aniline hydroxylation and p-nitroanisole O-demethylation and in content of total cytochrome P450 were intermittent and moderate. On the other hand, no change was observed in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase activity or cytochrome b5 content in the hepatic microsomes of the CBD-treated rats. Western blotting analysis showed a marked decrease in the male-specific cytochrome P450 UT-2 in the hepatic microsomes, especially 24 to 48 h after pretreatment with CBD. It is possible that CBD given 6 to 12 h before the sacrifice might interact with cytochrome P450 as a substrate, resulting in inhibition of the drug-metabolizing enzyme activities in the earlier stages. In the later stages from 24 to 48 h after CBD treatment, the reduction in content of the male-specific cytochrome P450 UT-2 may play a major role in the inhibitory effect of CBD on the hepatic drug-metabolizing enzyme system in the adult male rat in vivo.

Animals↗

In vivo and in vitro metabolism of cannabidiol monomethyl ether and cannabidiol dimethyl ether in the guinea pig: on the formation mechanism of cannabielsoin-type metabolite from cannabidiol.

Oxidative metabolism of cannabidiol monomethyl ether (CBDM), one of the components of marihuana, was studied in the guinea pig. Cannabielsoin monomethyl ether (CBEM) was found to be formed with hepatic microsomes by gas chromatography-mass spectrometry (GC-MS). Experiments using various modifiers of enzymatic reaction suggested that, as in the case of cannabielsoin (CBE) formation from canabidiol (CBD), CBEM was formed from CBDM by the monooxygenase system including cytochrome P450. When cannabidiol dimethyl ether (CBDD), in which phenolic hydroxyl groups of CBD are masked with methyl groups, was incubated with liver microsomes and an reduced nicotinamide adenine dinucleotide phosphate-generating system, 1S,2R-epoxy-CBDD was identified by GC-MS. The epoxy metabolite was also found in the liver of a guinea pig pretreated with CBDD (100 mg/kg, intraperitoneally) 1 h before sacrifice. Rate of 1S,2R-epoxide metabolism was slower than that of 1R,2S-epoxy-CBDD under the conditions, as in the microsomal oxidation of CBDD described above. These results indicate that 1S,2R-epoxides are formed from CBD, CBDM and CBDD and that the epoxides are quickly converted to elsoin-type metabolites in the cases of CBD and CBDM.

Animals↗

Comparison of pharmacological effects of tetrahydrocannabinols and their 11-hydroxy-metabolites in mice.

Pharmacological effects (catalepsy, hypothermia, pentobarbital-induced sleep prolongation, anticonvulsant and analgesic effects) of delta 8- and delta 9-tetrahydrocannabinols, and their 11-hydroxy-metabolites were evaluated and compared in mice. delta 9-Tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol exhibited somewhat greater effects than did delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol, respectively, in all pharmacological indices tested. Greater effects of 11-hydroxy-metabolites than those of tetrahydrocannabinols were also demonstrated.

Animals↗

Angioplasty of stenoses adjacent to aneurysmal coronary artery disease.

We examined the effectiveness and safety of performing angioplasty on stenoses adjacent to aneurysmal coronary artery disease. Out of 386 consecutive lesions (270 patients) on which we performed angioplasty, 13 lesions (13 patients) were within one balloon length of aneurysmal disease (group A) and 373 lesions (257 patients) were not (group NA). Angioplasty had previously been performed on 10 lesions (77%) in group A but only on 112 lesions (30%) in group NA (p less than 0.01). In group A the angioplasty success rate was 100% (13/13). The maximum inflation pressure was 6.5 +/- 1.1 atm, the frequency of inflation was 6.1 +/- 2.8, the average inflation duration was 60 +/- 0 sec, and the balloon/artery ratio was 1.20 +/- 0.11. There were no major complications. Restenosis occurred in only one lesion. There were no significant differences in the angioplasty results, procedures, complications and the incidence of restenosis between both groups. The ratio of the diameter of the aneurysmal disease to the mean diameter of the normal adjacent segments remained unchanged throughout the follow-up period. These data suggest that angioplasty may be an effective and safe treatment for those stenoses that are adjacent to aneurysmal coronary artery disease.

Angioplasty, Balloon, Coronary↗

Species differences in metabolism of codeine: urinary excretion of codeine glucuronide, morphine-3-glucuronide and morphine-6-glucuronide in mice, rats, guinea pigs and rabbits.

1. Metabolites of codeine were determined by use of h.p.l.c. in urine of male mice, rats, guinea pigs and rabbits injected with 10 mg codeine/kg subcutaneously. 2. In 24 h urines of these species, unchanged codeine, codeine glucuronide, free morphine, and morphine-3-glucuronide were as follows: mice, 6.8, 1.6, 0.8 and 7.6% dose; rats, 1.6, 0.2, 4.3 and 23.9% dose; guinea pigs, 1.6, 39.8, 0.2 and 1.6% dose; rabbits, 2.2, 24.5, 1.3 and 17.9% dose. Urinary excretion of morphine-6-glucuronide was 0.7% dose in guinea pigs, 1.9% in rabbits, and not detectable in mice and rats. Norcodeine was found only in the urine of mice. 3. These results indicate that codeine is metabolized in all four species by glucuronidation and by oxidative N- and O-demethylation, but the quantitative excretions of metabolites were quite different in different species.

Animals↗

[Effects of crude soybean trypsin inhibitor on pancreatic atrophy induced by BOP treatment in hamsters].

Experiment I: Female Syrian golden hamsters were given 5 weekly sc injections of N-nitrosobis (2-oxopropyl)amine (BOP) while simultaneously being treated with SBTI diet for 5 weeks (BOP+ SBTI). Other two groups were treated with BOP or SBTI alone. Sacrificed at week 30, the numbers of both adenocarcinomas and dysplastic lesions were decreased in the BOP+SBTI group relative to the BOP alone group. Experiment II: Female hamsters were given 3 weekly sc injections of BOP and then fed a SBTI diet for 40 weeks. The numbers of dysplastic lesions was decreased in the BOP and SBTI group relative to the BOP alone group. An inhibitory effect was observed for the pancreas in hamsters fed SBTI after BOP treatment. In experiments I and II, atrophic changes of pancreatic exocrine tissues and fatty tissue infiltration were observed in hamsters treated with BOP. The ratios of exocrine atrophy in pancreas sections were measured with the aid of an image processor. Areas (2.4 mm2) of splenic and gastric lobes were selected randomly, and the included exocrine tissue measured to allow calculation of percentage area of exocrine tissue atrophy. In hamsters simultaneously treated with BOP and SBTI, the percent areas of intact exocrine tissues in both splenic and gastric lobes were significantly higher (87% and 83%) as compared to the BOP group values (61% and 61%), at the level of p < 0.01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Early histopathological changes in trachea, bronchus and lung, and changes in lipid peroxidation in hamsters, due to inhaled cigarette smoke].

The main objective of this work was to determine the influence of cigarette smoke exposure on the mechanisms which promote respiratory tumors. And another aim was the accumulation of basic data regarding the effect of cigarette smoke exposure in hamsters in the Hamburg II smoking machine. Male Syrian golden hamsters were caused to inhale cigarette smoke in the Hamburg II smoking machine. The hamsters inhaled cigarette smoke twice a day, for 9 minutes, 5 times a week. The administration period were 1,2,4,8 and 12 weeks. For each inhalation, the rotating disk was fitted with 30 cigarettes. Each puff, 35 ml in volume, was diluted seven times with room air. At the completion of administration, subjects were examined histopathologically, and lung and serum lipid peroxidation levels were also measured. Histopathological examination of the respiratory tract and alveolar epithelium disclosed no cigarette smoke-related hyperplastic lesion in any animal. And in the hamsters which inhaled cigarette smoke, "smoke cells" accumulation were observed in the alveolar space after 8 and 12 weeks exposure. Significant increase in the number of BrdU positive cells were not observed following cigarette smoke exposure, but a tendency for lung malondialdehyde (MDA) levels to increase was evident. On the other hand, serum lipid peroxide (LPO) levels showed a marked decrease in the animals exposed to cigarette smoke for 2,4 and 8 weeks in comparison with the identically handled control animals. But serum LPO levels showed a tendency to increase with cigarette smoking during all experimental periods. The above results suggested that cigarette smoking may cause a change in lipid peroxidation levels such as lung MDA and serum LPO levels.

Animals↗

[67Ga-citrate scintigraphy in patients with fever of unknown origin].

67Ga scintigraphy was performed in 49 patients with fever of unknown origin (FUO). Positive findings were observed in 25 patients out of 49 (51%). Occult focal lesions were demonstrated in 4 patients and useful information for the diagnosis was provided in 4 patients. In short, the examination showed diagnostic usefulness in 8 (32%) out of positive cases. 67Ga scintigraphy may be recommended as a further examination for patients with strongly suspected focal lesion in FUO.

Adult↗

Two cases of dilated cardiomyopathy associated with incessant supraventricular tachycardia who showed a favorable response to beta-blockade.

Two cases of dilated cardiomyopathy with incessant supraventricular tachycardia were treated with beta-blockade. Propranolol at a dose of 30 mg per day in combination with diuretics and digitalis decreased atrial rate of tachycardia and the cardiac size in both cases. The careful administration of beta-blockade seems to be one of the choices for the treatment for atrial tachycardia associated with dilated cardiomyopathy.

Adult↗

[Efficacy of combined therapy using coronary reperfusion and elective percutaneous transluminal coronary angioplasty for acute myocardial infarction].

The effects of elective percutaneous transluminal coronary angioplasty (PTCA) performed one month after coronary reperfusion therapy in patients with acute myocardial infarction (AMI) were observed using exercise Tl-201 myocardial scintigraphy performed before and after PTCA. Myocardial perfusion in Tl-201 scintigraphy was significantly greater in the early (less than 4 hours) and late (4-9 hours) reperfusion groups than in the total occlusion group one month after the onset of AMI. Both reperfusion groups showed significant improvement in myocardial perfusion after elective PTCA; whereas, the total occlusion group showed no significant improvement. In the early reperfusion group, there were no significant differences in myocardial perfusion between those with well developed and those with poorly developed collateral circulations one month after the onset of AMI. However, in the late reperfusion group, myocardial perfusion was greater in those with well developed collateral circulations compared to those with poorly developed collateral circulations. The grade of myocardial perfusion in the late reperfusion group with poorly developed collateral circulations did not differ significantly from that of the total occlusion group. There was significant improvement of myocardial perfusion in the early and late reperfusion groups with well developed collateral circulations after elective PTCA; whereas, no significant improvement was observed in the late reperfusion group with poorly developed collateral circulations. These findings indicate that the time interval from the onset of AMI to reperfusion and the grade of development of collateral circulations are the major determinants of myocardial perfusion after elective PTCA and after reperfusion therapy.

Adult↗

[Significance of residual coronary artery stenosis after reperfusion therapy in acute myocardial infarction].

We evaluated the efficacy of reperfusion therapy in acute myocardial infarction in terms of postinfarction angina (PIA), reinfarction and coronary reocclusion. In 99 hospitalized patients with acute myocardial infarction within 6 hours after the onset of symptoms, 67 were treated using intracoronary thrombolysis (ICT) alone (Group T) and the remaining 32 using ICT followed by percutaneous transluminal coronary angioplasty (PTCA) (Group T + A). PTCA was performed for the arteries with high grade residual stenosis (TIMI grade 0, 1, 2) after ICT. Recatheterization was performed 28 +/- 12 days after hospitalization in 93% (62/67) of Group T and in all of Group T + A. There were no significant differences in age, sex, time interval from the onset to reperfusion, the extents of coronary artery disease and the Cohn grade of collaterals. However, anteroseptal infarction was more frequent in Group T than in Group T + A (p less than 0.05). Residual stenosis (diameter) at the end of intervention was 81 +/- 14% in Group T, and 48 +/- 15% in Group T + A, (p less than 0.01). Residual stenosis at recatheterization was 70 +/- 23% in Group T, and 55 +/- 22% in Group T + A (p less than NS). The incidence of PIA did not differ between the two groups (20.1% vs 6.2%). However, the incidence was higher in patients with residual stenosis of 70% or more than in those with residual stenosis of less than 70% (23.8% vs 2.9%, p less than 0.05). The incidence of reinfarction (re-elevation of CPK) did not differ between the two groups (7.4% in Group T, 6.2% in Group T + A); and neither did the incidence of coronary reocclusion at the time of recatheterization (14.5% vs 3.1%). We concluded that higher degree of residual stenosis at the end of intervention has a greater risk of PIA and reocclusion. Although differences were not statistically significant, the patients treated with ICT followed by PTCA seemed to have lower incidence of PIA and reocclusion compared with those treated with ICT alone, thus having better hospital prognosis.

Aged↗

[A clinicopathological study of signet-ring cell carcinomas of the stomach].

Surgically resected signet-ring cell carcinomas of the stomach have been clinicopathologically investigated. Although this type of carcinoma was found to be widely spread in the propria mucosa, a deeper invasion beyond the submucosa appeared more slowly than in other types of carcinomas. For example, the larger the early carcinoma in which the invasion was restricted to within the submucosa, the greater the incidence of a signet-ring cell carcinoma increase, especially in cases involving the mucosa. The incidence of a nodal metastasis was found to be lower than in cases of a moderately and poorly-differentiated adenocarcinoma in the early stage. However, when the signet-ring cell carcinomas invaded beyond the submucosa, the tumor cells spread rapidly and widely in the wall with a subsequent abdominal implantation, causing ascites and peritonitis carcinomatosa. It seemed likely that this deep invasion was accelerated by cellular change, such as the enlargement of nucleus, cellular atypy, and a decreased mucin production. As signet-ring cell carcinoma arise from the neck of glands and infiltrate the propria mucosae under the superficial epithelium, diagnosis by the barium enema and an endoscopic examination is very difficult in the case of small-size lesions. In lesions greater than 1 cm in diameter, these carcinomas usually showed an erosive and/or ulcerated appearance.

Adenocarcinoma, Mucinous↗

[Behavior of anti-cancer drug of transcatheter hepatic segmental arterial chemoembolization using lipiodol mixed with an anti-cancer drug followed by gelatin sponge assessed by Tc-99m pertechnetate].

The behavior of an anti-cancer drug consisting of transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anti-cancer drug followed by gelatin sponge (segmental Lp-TAE: Seg-Lp-TAE) was assessed in comparison to that of the non-segmental Lp-TAE to whole liver (Lp-TAE) by means of Tc-99m pertechnetate (RI). Injection of Lipiodol mixed with Adriamycin and 740 mBq of RI followed by gelatin sponge was carried out from segmental or subsegmental hepatic artery in 12 cases of hepatocellular carcinoma and from proper or right hepatic artery in 11 cases (9 with hepatocellular carcinoma and 2 with metastatic liver tumor). The distribution and retention of RI were studied from the time activity curves of ROIs in tumor and non-tumor area, and scintigrams at 4 and 24 hours after injection. The integral value ratio of tumor to non-tumor was significantly higher in Seg-Lp-TAE, indicating that es the distribution of RI after Seg-Lp-TAE is selective in the segments where tumor exists. In Seg-Lp-TAE, the T1/2 was higher and the count ratio of tumor to non-tumor was significantly higher at 4 hours and even higher at 24 hours after injection. These results suggest that an anti-cancer drug reinforces the effect on tumor with little adverse effect on normal liver in Seg-Lp-TAE, which is more advantageous to the treatment of hepatocellular carcinoma.

Antineoplastic Agents↗

[Two cases of acute coronary occlusion after successful coronary angioplasty associated with a treadmill stress testing].

We presented two cases of acute coronary occlusion after successful percutaneous transluminal coronary angioplasty (PTCA) associated with a treadmill stress testing. Case 1: A 54-year-old man with effort angina was referred to our hospital for cardiac catheterization. At the time of cardiac catheterization, the proximal RCA had a 99% diameter narrowing, and the proximal LCX had a 90% diameter narrowing. PTCA was performed and both lesions were successfully dilated. Eight days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 173/min (103% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 140 mmHg. A few minutes after the end of exercise, he developed a severe chest pain and ECG changes, which showed ST elevation in leads II, III, aVF and ST depression in leads V4-V6. Emergency coronary angiography disclosed an acute coronary occlusion of RCA at the site of PTCA. Emergency PTCA was performed and the lesion was successfully re-dilated. Case 2: A 68-year-old man was referred to our hospital for cardiac catheterization a month after subendocardial anterior myocardial infarction. At the time of cardiac catheterization, the proximal LAD have a 99% diameter narrowing. PTCA was performed and the lesion was successfully dilated. 18 days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 158/min (102% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 218 mmHg. Ten minutes after the one of 218 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Carcinogenicity of anticancer agents].

Chemotherapeutic treatment for cancer has been successful in prolonging survival but it has also been demonstrated that survivors of cancer patients who had received chemotherapy with alkylating agents have an increased risk of second malignancies, mostly acute non-lymphatic leukemia. The purpose of this paper is to show practical problems pertaining to the development and clinical use of anticancer agents in terms of prevention of second cancers.

Alkylating Agents↗

[Evaluation of combined resection of aortic wall in lung cancer invaded aorta].

Left pneumonectomy with combined resection of aortic wall was performed for three patients with lung cancer invaded aorta. In clinical and pathological examination, the following results were obtained. 1: In all three cases, metastasized subaortic lymphnodes invaded to medial wall of the descending aorta. 2: Microscopically, invasion of aortic wall was limited to the adventitia adjacent to the muscle layer. We think that the resection of whole layer of the aortic wall was preferable. 3: The resections of aortic wall were performed under partial clamp of aorta in one case, and under total clamp with the use of cardiopulmonary bypass in two cases. If the area of invasion is wide, total clamp was recommended. 4: Two patients died of recurrent disease 56 months and 20 months after surgery. In the other one, postoperative empyema was occurred. He died of bleeding from the suture line of Dacron patch to the aortic wall three months postoperatively. Covering of the bronchial stump and the patch of the aorta should be considered to prevent postoperative empyema.

Adenocarcinoma↗