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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 577 records · Page 32Linked to original sources

Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the postinitiation phase.

The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks and then they were fed the diets containing AX or CX at concentrations of 100 and 500 p.p.m. for 34 weeks. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 37), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM and followed by AX or CX containing diet at a high dose (500 p.p.m.) were significantly smaller than those of rats given AOM alone (P < 0.001). In addition, AX or CX feeding significantly inhibited the development of aberrant crypt foci induced by AOM. Dietary exposure to AX or CX also decreased cell proliferation activity as revealed by measuring 5'-bromodeoxyuridine-labeling index as crypt cells, colonic mucosal ornithine decarboxylase activity and blood polyamine levels. These results indicate that AX and CX are possible chemopreventers for carcinogenesis of colon in addition to urinary bladder and oral cavity and such effects may be partly due to suppression of cell proliferation.

Animals↗

Lack of correlated expression between the glutathione S-transferase P-form and the oncogene products c-Jun and c-Fos in rat tissues and preneoplastic hepatic foci.

Since the expression of glutathione S-transferase P-form (GST-P) has been suggested from in vitro studies to be partly regulated by the oncogene product, c-Jun and c-Fos, their distributions were compared in normal rat tissues and preneoplastic hepatic lesions induced by the Solt-Farber protocol. Immunohistochemically demonstrated GST-P protein was positively correlated with expression of both c-Jun and c-Fos in the epidermis of the skin and the smooth muscle of adult lung and with either c-Jun or c-Fos respectively in the bile ducts and bronchial epithelium. However, GST-P expression was also observed in proximal and distal straight segments of the kidney and other tissues negative for c-Jun and c-Fos and both c-Jun and c-Fos were present in the renal proximal and distal convoluted tubules, where GST-P was lacking. Thus, the localization of GST-P was in some cases clearly separable from those of c-Jun or c-Fos. GST-P was found to be focally expressed from an early stage of hepatocarcinogenesis, when c-Jun was not detectable. At later stages, this oncogene product was stained in 35.7% of GST-P-positive foci, with a clear relation to the degree of GST-P staining. Since GST-P is not always accompanied by appreciable c-Jun or c-Fos, these oncogene products are apparently not prerequisites for its expression. However, c-Jun may be partly responsible for maintaining high levels of GST-P in hepatic foci at later stages of hepatocarcinogenesis.

Animals↗

Formation of 8-hydroxydeoxyguanosine in calf thymus DNA treated in vitro with phenylhydroquinone, the major metabolite of O-phenylphenol.

The generation of 8-hydroxydeoxyguanosine (8OHdG) in calf thymus DNA treated with O-phenylphenol (OPP) or its major metabolites, phenylhydroquinone (PHQ) and phenylbenzoquinone (PBQ), was studied. The content of 8OHdG residues was increased in DNA treated with PHQ, and the generation of 8OHdG was highly dependent on PHQ concentration. PBQ had little effect on the formation of 8OHdG, and OPP had no effect. The formation of 8OHdG by PHQ was reduced by oxygen radical scavengers such as catalase, sodium benzoate and sodium azide. The PHQ-induced 8OHdG formation was accelerated by the addition of CuCl or CuCl2 to the reaction mixture, but was decreased by the addition of chelating agents such as EDTA, bathocuproinedisulfonic acid disodium salt (bathocuproine disulfonate) and O-phenanthroline. These results demonstrate that hydroxyl radicals generated in the process of oxidation of PHQ contribute to the formation of 8OHdG in DNA, and copper ions facilitate the oxidative DNA damage. Copper ions greatly accelerated the PHQ-induced DNA cleavage in vitro, although they had no effect on cleavage without PHQ. On the other hand, DNA cleavage occurred by the addition of FeCl2 in the absence and presence of PHQ. FeCl2 stimulates 8OHdG formation only slightly with or without PHQ. Furthermore, the stimulatory effect of FeCl2 on 8OHdG formation was observed even in the presence of EDTA. The formation of 8OHdG in bladder DNA is likely to be one of a series of events leading to bladder tumors seen in rats fed OPP-containing diet.

8-Hydroxy-2'-Deoxyguanosine↗

The high non-enzymatic conjugation rates of some glutathione S-transferase (GST) substrates at high glutathione concentrations.

Enzymatic properties of five human glutathione S-transferases (GSTs) and non-enzymatic conjugation rates of GST substrates were examined as a function of glutathione (GSH) concentration and pH. GSTP1-1 showed a broad substrate specificity with both low and high GSH (10 mM) concentrations at pH 7.0, and the inhibitor insensitivity was then prominent. Among the GST substrates tested, ethacrynic acid, p-nitrophenylacetate, 1-chloro-2,4-dinitrobenzene and trans-4-phenyl-3-buten-2-one conjugated nonenzymatically with half-times of 0.39, 3.1, 9.4 and 10.0 min respectively at 10 mM GSH, pH 7.0 and 35 degrees C. The half-time for acrolein estimated by extrapolation was approximately 0.5 s. While the enzymatic reaction rates were independent of GSH at concentrations larger than Km values according to Michaelis-Menten kinetics and relatively insensitive to a pH change from 6.5 to 7.0, the non-enzymatic ones were linearly proportional to the GSH concentration and sensitive to pH. The enhanced non-enzymatic conjugation of various electrophiles at high GSH concentrations may in part account for the physiological significance of GSH elevation in preneoplastic and neoplastic cells.

Female↗

Decreased expression of glutathione S-transferases and increased fatty change in peroxisomal enzyme-negative foci induced by clofibrate in rat livers.

Alteration in glutathione S-transferase (GST) isoenzymes was compared with that of a peroxisomal enzyme, enoyl-CoA hydratase (ECH), during hepatocarcinogenesis caused by clofibrate (CF) administration in male Sprague-Dawley rats. The amount of alpha class GST forms, determined by single radial immunodiffusion using anti-GST 1-2 antibody, was inversely correlated with that of ECH and was decreased at week 2 of CF administration to approximately 50% of the value prior to treatment and then slightly increased to 70% of the control value by week 15, without change thereafter up to 93 weeks. Resolution of GST subunits by high performance liquid chromatography revealed an approximately 60% decrease in the amounts of subunits 1 and 3 at week 93 and a 25% decrease in the amounts of subunits 2 and 4. Immunohistochemical staining of rat livers revealed hepatic foci and minifoci negative for ECH at week 60 and thereafter. Almost all ECH-negative foci (95.1-97.9%) were clear cell in character, along with a somewhat lower proportion (68.0-73.8%) of ECH-negative minifoci. Numerous fat-positive granules were detected in 78.3% of those lesions exhibiting a clear cell change. Although the amounts of GST and ECH exhibited contrasting patterns of alteration in whole livers following CF administration, the expression of both alpha and mu class GST forms was decreased in the majority of ECH-negative foci at week 93, but were not altered in minifoci. The repression of GST forms appeared to be a later event than the loss of ECH or the clear cell change in CF-associated hepatic lesions and was in clear contrast to the enhanced expression reported for preneoplastic lesions induced by mutagenic carcinogens.

Animals↗

Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats.

The chemopreventive effect of dietary administration of a new arotinoid, mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats. Also, modulatory effects of this compound on polyamine levels (biomarkers of proliferation), the 5-bromodeoxyuridine-labeling index and the number of silver stained nucleolar organizer region proteins (AgNORs)/nucleus were assessed in the target epithelium. Rats were fed Ro 40-8757 at concentrations of 250 and 500 p.p.m. for 10 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 8 weeks. Feeding of Ro 40-8757 at both doses caused a 78% reduction in the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) by 32 weeks when compared with rats treated with 4-NQO alone (P < 0.05). Similarly, in rats treated with 4-NQO together with Ro 40-8757 the incidence of preneoplastic lesions (hyperplasia and dysplasia) was significantly less than the 4-NQO alone group (P < 0.05). Expression of three biomarkers was also decreased significantly by dietary treatment with Ro 40-8757. Thus a new arotinoid, Ro 40-8757, inhibited the oral carcinogenesis induced by 4-NQO when it was administered concurrently with the carcinogen. These results might suggest the possible application of Ro 40-8757 for cancer chemoprevention in the oral cavity, in addition to the breast.

Animals↗

Inhibition of 4-nitroquinoline-1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide, KYN-54, during the initiation and post-initiation phases.

The modifying effect of dietary exposure of a newly synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54) during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) was investigated in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with KYN-54 alone and those in a control group were given 4-NQO (20 p.p.m.) in the drinking water for 8 weeks to induce oral neoplasms. Seven days after stopping 4-NQO exposure, groups of animals fed the diets containing 100 and 200 p.p.m. KYN-54 for 10 weeks starting 1 week before 4-NQO exposure were switched to the basal diet and kept on this diet until the end of the experiment. Starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets containing 100 or 200 p.p.m. KYN-54 and maintained on these diets for 22 weeks. The other group consisted of rats given 200 p.p.m. KYN-54 alone or untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine (BrdU)-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein (AgNORs) were compared among the groups. Feeding of KYN-54 during either initiation or post-initiation phase caused a significant reduction in the frequency of tongue carcinoma (48-71% reduction, P < 0.05) and such chemopreventive efficacy was dose-related. The incidences of preneoplastic lesion in rats fed the diets mixed with KYN-54 at both doses were also decreased (P < 0.05). Dietary administration of KYN-54 also significantly decreased the labeling index of BrdUrd and the number of AgNORs per cell nucleus of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats given 4-NQO and test compound when compared to those given 4-NQO alone, but no significant difference was obtained. These results indicate that the novel synthesized retinoidal butenolide KYN-54 inhibits oral carcinogenesis initiated with 4-NQO and such inhibition may be related to suppression of cell proliferation.

4-Butyrolactone↗

Efficacy of lansoprazole in eradication of Helicobacter pylori.

Fifty-eight Helicobacter pylori-positive ulcer patients received omeprazole 20 mg (n = 15), or lansoprazole 30 mg (n = 23), lansoprazole 60 mg (n = 13), or E3810 20 mg (n = 7) q.d. Another 63 H. pylori-positive ulcer patients received lansoprazole and clarithromycin for 2 weeks. Patients received lansoprazole 30 mg and clarithromycin 400 mg (group 1, n = 22), lansoprazole 30 mg and clarithromycin 800 mg (group 2, n = 12), or lansoprazole 60 mg and clarithromycin 800 mg (group 3, n = 29). Neither proton pump inhibitor (PPI) was capable of eradication by monotherapy, but the clearance rates in the lansoprazole group were 60.9 and 69.2%, which were higher than those for omeprazole (p < 0.05). In the dual therapy, eradication rates were 50, 50, and 72.4% in groups 1, 2, and 3, respectively. Minor side effects were observed in one case each in groups 1 and 3. Lansoprazole monotherapy proved more efficacious than omeprazole monotherapy, but it was unable to eradicate H. pylori. Dual therapy with lansoprazole 60 mg and clarithromycin 800 mg was an efficacious and safe regimen for H. pylori eradication in this study.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Hypersensitivity pneumonitis in a pearl nucleus worker.

A 37-year-old woman had worked for 4 years in a shell-processing factory where considerable airborne dust was produced cutting and polishing fresh water shells into pearl nuclei. She had a dry cough and dyspnea. Transbronchial lung biopsy showed noncaseating granulomas and cellular intraalveolar infiltrates. High-resolution lung computed tomography (HRCT) showed diffuse small nodules and ground-glass opacities. Hypersensitivity pneumonitis caused by shell dust should be considered in the appropriate clinical setting in a patient with the appropriate radiographic abnormalities.

Adult↗

Resurfacing the distal part of the foot with a dorsal foot skin island flap pedicled on the plantar vasculature.

The dorsal foot skin island flap pedicled on the plantar vasculature as a reconstructive entity is described. Two successful cases of resurfacing of the distal end of the foot with a dorsal foot island flap pedicled on the proximal communicating vessels and the distal communicating vessels, respectively, are reported, and this type of reconstructive procedure is proposed as an addition to existing procedures for reconstructing the distal end of the foot.

Adult↗

Clinical trial of a prefabricated secondary hypogastric flap pedicled on the deep inferior epigastric vessel with or without a tissue expander in three patients.

A newly developed prefabricated free hypogastric flap was used in three patients. Although the total clinical results were far from satisfactory, including one complete necrosis due to vascular thrombosis, we think that it is a useful free flap with a long vascular pedicle and a large diameter and that some future hopes exist in the secondary flap era.

Adolescent↗

Consideration of operative procedures for zygomatic reduction in Orientals: based on a consecutive series of 28 clinical cases.

Operative procedures for reduction malar bone plasty were considered in our consecutive series of 28 Japanese cases. The patients consisted of 7 males and 21 females whose ages ranged from 21 to 57 years. The operative procedures used were either shaving the protruded zygomatic body and arch with chisels by means of an intraoral approach and/or an extraoral sideburn-lateral canthal approach or, alternatively, mobilizing the protruded zygoma en bloc medioposteriorly into reduction of the prominent zygoma by a coronal approach. In principle, the noncoronal approach was indicated for males and young females, and the coronal approach, conducted in association with forehead lifting with or without canthopexy, was indicated for females over age 40. These procedures have individual merits and demerits. In some cases, associated surgery was performed concomitantly according to the facial balance or facial rejuvenization. We believe that the optimal operative approach and operative procedure should be considered in accordance with the patient's sex, age, wishes, and/or cultural background.

Adult↗

Loss of heterozygosity on the short arm of chromosome 9 without p16 gene mutation in gastric carcinomas.

A putative tumor suppressor gene, p16 (MST1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4 inhibitor), was isolated and mapped on the short arm of chromosome 9 (9p). The significance of p16 mutations in gastric tumorigenesis was examined by assessing p16 mutations as well as loss of heterozygosity (LOH) on 9p in 13 gastric adenomas and 45 adenocarcinomas. LOH on 9p (IFNA; alpha-interferon locus) was detected in 22% (5/23 informative cases) of differentiated adenocarcinomas, 10% (1/10) of undifferentiated carcinomas and none (0/6) of the adenomas. Although we found a sequence polymorphism at the second position of codon 99 (CGC/CAC) of the p16 in one gastric adenoma patient, no somatic mutations were detected in any of the gastric adenomas or adenocarcinomas. These results suggest that p16 mutations probably do not contribute to gastric tumorigenesis. However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach.

Adenocarcinoma↗

The possibility of clinical application of the thromboxane A2 synthase inhibitor, ozagrel, for the treatment and prevention of preeclampsia: a preliminary report.

OBJECTIVES: This study was performed to investigate whether the TXA2 synthase inhibitor, ozagrel, was effective in the treatment and prevention of pre-eclampsia. STUDY DESIGN: Ozagrel was administrated therapeutically to 4 severely pre-eclamptic women, and prophylactically to 5 pregnant women with histories of severe preeclampsia and complications. RESULTS: The therapeutic administration (TA) of ozagrel improved hypertension and proteinuria. Two patients delivered appropriate-for-date (AFD) infants, whereas the other 2 patients delivered light-for-date (LFD) infants. Mean plasma concentrations of TXB2 (plasma TXB2) decreased, whereas plasma 6-keto PGF1 alpha were almost unchanged. The prophylactic administration (PA) of ozagrel prevented the occurrence of preeclampsia in 3 of the 5 patients. All delivered AFD infants. The duration of pregnancy was prolonged more than that of previous pregnancies in all patients. Plasma TXB2 decreased, whereas plasma 6-keto PGF1 alpha increased. CONCLUSIONS: PA prevented preeclampsia and intrauterine growth retardation, whereas TA improved only maternal symptoms. These results might justify a large prospective study to determine whether ozagrel is an effective prophylactic.

Adult↗

Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts.

1. Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on the myocardial level of coenzyme Q10, and on mitochondrial respiration were examined in dogs. 2. Either vehicle (control), pravastatin (4 mg kg-1 day-1), or simvastatin (2 mg kg-1 day-1) was administered orally for 3 weeks. First, the myocardial tissue level of coenzyme Q10 was determined in the 3 groups. Second, ischaemia was induced by ligating the left anterior descending coronary artery (LAD) in anaesthetized open chest dogs, pretreated with the inhibitors. After 30 min of ischaemia, nonischaemic and ischaemic myocardium were removed from the left circumflex and LAD regions, respectively, and immediately used for isolation of mitochondria. The mitochondrial respiration was determined by polarography, with glutamate and succinate used as substrates. 3. Simvastatin significantly decreased the myocardial level of coenzyme Q10, but pravastatin did not. 4. Ischaemia decreased the mitochondrial respiratory control index (RCI) in both groups. Significant differences in RCI between nonischaemic and ischaemic myocardium were observed in the control and simvastatin-treated groups. 5. Only in the simvastatin-treated group did ischaemia significantly decrease the ADP/O ratio, determined with succinate. 6. The present results indicate that simvastatin but not pravastatin may cause worsening of the myocardial mitochondrial respiration during ischaemia, probably because of reduction of the myocardial coenzyme Q10 level.

Animals↗

[Studies on factors influencing the attack of subarachnoid hemorrhage during labor].

We analyzed factors affecting attacks of subarachnoid hemorrhage (SAH) retrospectively in 411 patients and studied the relation of the attacks with labor. The onset time of SAH has two peaks of the time: one is 7:00 a.m. and the other is between 16:00 and 17:00 in the afternoon. The attacks of SAH during labor were observed in 15.1% of all the patients. It was noted that 66.7% of all the attacks were observed at the time with certain external stress such as working, sporting, sexual intercourse, etc. The number of patients who suffered from attacks during labor with history of hypertension and insomnia were not significantly different compared with those suffered from attacks during other activities, but 40-59 aged men those who have a history of smoking were significantly more in number compared with those that suffered attacks during other activities. Transient increase of blood pressure due to external stress is suggested as an initiative factor of the bleeding during working. Reactivity of the individuals against physical and mental stress (external stress) might be considered to be the major problem, although it remains not to be unexplained whether labor itself participates in the onset of SAH. Regarding the prevention of SAH during labor, new methods of medical examination and health control is required.

Adult↗

[Supra-annular mitral valve replacement for a patient with prosthetic valve endocarditis].

Supraanular mitral valve replacement with a 29 mm CarboMedics prosthetic valve was performed for a 58-year-old patient of prosthetic valve endocarditis. He has received mitral valve replacement 2 years ago, and was admitted because of high fever and severe heart failure diagnosed mitral regurgitation due to valve dehiscence. An annular abscess was observed and the new 29 mm CarboMedics prosthetic valve was sutured to the left atrial wall approximately 10 mm above the original annulus in order to secure the firm suturings for valve implantation and to left the infected annulus intact. The patient, however, underwent reoperation because of valve dehiscence from atrial wall 6 months after surgery. Infectious abscess at the native mitral annulau was observed to be completely cured, and a mitral prosthesis was implanted at the annulus. The patient is discharged under satisfactory condition.

Endocarditis↗

[Evaluation by proton magnetic resonance spectroscopy of carotid-cavernous fistula with cortical venous drainage].

Cases with carotid-cavernous fistula (CCF) associated with cortical venous drainage through the sylvian veins are rather rare. However, such cases involve risk for subarachnoid hemorrhage, subcortical hemorrhage and venous infarction due to venous hypertension in the brain. Even without these symptoms, CCF under these conditions provokes disturbance in cerebral metabolism. We report two cases of CCF associated with cortical venous drainage evaluated by proton magnetic resonance spectroscopy (1H-MRS). Case 1: A 56 year-old female suffered from a right CCF associated with cortical venous drainage through the sylvian veins after trauma. Before embolization with a detachable balloon catheter, the ratios of N-acetyl-aspartate (NAA)/Choline (Cho) and NAA/Creatine (Cr) in 1H-MRS on the right temporo-basal ganglia were lower than those in normal volunteers. After curative balloon embolization of the CCF, serial 1H-MRS still demonstrated laterality (NAA/Cho and NAA/Cr ratios on the right side were lower than those on the left). Six months after embolization, these ratios on the right became closer to those on the left. Case 2: A 48 year-old female suffered from spontaneous CCF associated with cortical venous drainage. Before embolization of the CCF, ratios of NAA/Cho and NAA/Cr on the temporo-basal ganglia of the drainage side (left side) were lower than those on the contralateral side. After partial embolization of the CCF, which caused the angiographical disappearance of the cortical venous drainage, NAA/Cho and NAA/Cr ratios on the affected side increased to almost the same levels as those on the contralateral side. We consider that 1H-MRS is noninvasive and is a useful method to generate data evaluation of affected brain metabolism by venous reflux in cases of CCF associated with cortical venous drainage.

Arteriovenous Fistula↗