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Biomedical subjects

K Toyoda

Publications and source records attributed to K Toyoda.

At least 91 records · Page 5Linked to original sources

[CD26/dipeptidyl peptidase IV and thyroid peroxidase as molecular markers for differentiated thyroid carcinoma].

Differential expression of two enzymes, dipeptidyl peptidase IV (CD26/DPP IV) and thyroid peroxidase (TPO), in neoplastic thyroid tissues was studied by Northern blot analysis and histochemical analysis using 31 thyroid tissue specimens of various thyroid diseases. On Northern blot analysis, all 16 differentiated carcinomas (12 papillary and 4 follicular carcinomas) overexpressed CD26/DPP IV mRNA, whereas all 14 benign tissue specimens (4 normal thyroid, 4 Graves' disease, 2 adenomatous goiters and 4 follicular adenomas) showed faint expression of CD26/DPP IV mRNA. All 14 benign tissues expressed high levels of TPO mRNA, whereas all 12 papillary carcinomas strongly underexpressed TPO mRNA. A medullary carcinoma did not show any mRNA expression of either enzyme. TPO mRNA expression in differentiated carcinomas did not always correlate with mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor-1. Northern blot analysis also revealed that CD26/DPP IV is a more specific marker of differentiated carcinoma than three proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2, and EGF-R. Histochemically, all 14 benign tissues were CD26/DPP IV negative and strongly TPO positive, while all 12 papillary carcinomas were strongly CD26/DPP IV positive and TPO negative. Three of 4 follicular carcinomas were histochemically positive for the two enzymes. These findings suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.

Adenocarcinoma, Follicular↗

[Systemic vascular change associated with moyamoya-like cerebrovascular disease and microvascular coronary artery disease].

A 34-year-old man with hypertension and diabetes mellitus developed dizziness and visited our institute. He had history of headache with numbness of the right hand since age 15 years and left occipital lobe infarction at age 28 years. The cerebral angiogram showed several changes peculiar to advanced stage of moyamoya disease (spontaneous occlusion of the circle of Willis), i.e. segmental stenoses or occlusions of bilateral internal carotid arteries, left vertebral artery and left posterior cerebral artery with abnormal vascular networks at the bilateral basal ganglia. He was also diagnosed to have asymptomatic ischemic heart disease. The coronary angiogram showed diffuse sclerotic lesions of left anterior descending and right coronary arteries without significant stenosis, which suggested the presence of microvascular lesion as a cause of myocardial ischemia. Coronary disease has been rarely reported as a complication of moyamoya disease, and microvascular coronary artery disease has never been described. Moyamoya disease should be regarded as a part of systemic vascular disorders, and the evaluation of extracerebral cardiovascular system is necessary to clarify pathophysiology of this disease.

Adult↗

[Recurrent aseptic meningitis caused by rupture of a pineal cyst].

A 40-year-old woman experienced three attacks of aseptic meningitis in 19 months. Each attack was characterized by sudden onset of meningeal irritation followed by spontaneous remission in several days. The patient was free of neurological symptoms between the attacks. In the acute phase of each attack, her cerebrospinal fluid (CSF) showed mononuclear pleocytosis and increased protein concentration. Epithelial cell clusters in the CSF were evident during the third episode. No pathogenic microorganisms were identified in CSF or blood cultures. Brain imaging revealed a pineal cyst, 1 cm in diameter, and we suspected that the epithelial cell clusters represented the ruptured cystic wall and that the recurrent aseptic meningitis was triggered by spontaneous rupture of the cyst. Recently several new etiologies for the benign recurrent aseptic meningitis (Mollaret's meningitis) have been reported, but its existence as a clinical entity is still in dispute. Our case appears to support "spontaneous rupture of central nervous system epidermoid cysts" as one of the etiologies of recurrent aseptic meningitis.

Adult↗

Suppression of Na+ influx in ATP-depleted hepatocytes.

The change of cytosolic Na+ concentration was examined in ATP-depleted cultured rat hepatocytes. Cytosolic Na+ concentration was increased in the hepatocytes where ATP was more than 95% depleted by chemical hypoxia with 2.5 mM KCN and 0.5 mM iodoacetate as reported in J. Biol. Chem. 266 20062-20069 (1991). However, the effect was due to the iodoacetate-treatment rather than the ATP-depletion, because the Na+ concentration was increased not by KCN but by iodoacetate, while KCN decreased ATP more than iodoacetate. Although oligomycin (10 micrograms/ml) decreased ATP to less than 5%, it did not increase cytosolic Na+ concentration much within 50 min. Ouabain (1.0 mM), an inhibitor of Na(+)-K+ pump, increased the Na+ concentration, and the increase was suppressed by oligomycin These results suggest that Na+ influx was suppressed in ATP-depleted hepatocytes.

Adenosine Triphosphate↗

Hepatocyte growth factor-induced calcium waves in hepatocytes as revealed with rapid scanning confocal microscopy.

Cytosolic Ca2+ transients induced by hepatocyte growth factor (HGF) were imaged in primary cultured rat hepatocytes using newly developed rapid scanning confocal microscopes and indo-1. HGF (40 ng/ml) increased cytosolic free Ca2+ concentration ([Ca2+]i) in about 60% of hepatocytes, in 45% of which the increases were oscillatory. In each of the oscillatory hepatocytes, the repetitive increases in [Ca2+]i originated from a specific same region adjacent to the cell membrane and propagated across the cell like waves. Phenylephrine (10 microM) also induced Ca2+ waves. The locus where HGF-induced Ca2+ waves and phenylephrine-induced Ca2+ waves were originated was the same, and there was a correlation in the peak height between HGF-induced Ca2+ waves and phenylephrine-induced Ca2+ waves in each cell, although the mechanisms of inositol 1,4,5-trisphosphate (ins(1,4,5)P3) formation induced by HGF should be different from those by phenylephrine. On the other hand, there was no correlation between sensitivity of each cell to HGF and that to phenylephrine which were measured as latent periods prior to Ca2+ rises after an addition of the agonists. These results suggested the following: the spatial patterns of Ca2+ waves were decided by a common mechanism, probably not the propagation of ins(1,4,5)P3 but the distribution of ins(1,4,5)P3-sensitive Ca2+ pools; sensitivities of each cell to the agonists did not mainly depend on the common mechanism.

Adrenergic alpha-Agonists↗

Urinary bladder carcinogenesis induced by melamine in F344 male rats: correlation between carcinogenicity and urolith formation.

Urinary bladder carcinogenesis associated with melamine treatment was examined with concomitant use of NaCl to allow assessment of the relationship between uroliths and lesion development. Analysis of the chemical composition of calculi was also performed. F344/DuCrj male rats received diets containing 3 or 1% melamine alone or in combination with either 10 or 5 % NaCl, or 10% NaCl alone for 36 weeks, and then diet without NaCl supplement for a further 4 weeks. The water intake, used as an index of urinary output, was increased by NaCl treatment. The incidences of bladder transitional cell carcinomas and papillomas were 90 and 55% in the group treated with 3% melamine alone; 0 and 15% in the group treated with 3% melamine and 10% NaCl; and 21 and 42% in group treated with 1% melamine alone; and zero in the other groups. Calculus formation resulting from melamine administration was suppressed dose-dependently by the simultaneous NaCl treatment, along with the occurrence of hyperplasia of the papilla in the kidneys. The main constituent of calculi were melamine itself and uric acid (total contents 61.1-81.2%), contained in equal molar ratio. The results indicate that melamine-induced proliferative lesions of the urinary tract of rats were directly due to the irritative stimulation of calculi, and not molecular interactions between melamine itself or its metabolites with the bladder epithelium.

Animals↗

Pathogenicity of the Streptococcus milleri group in pulmonary infections--effect on phagocytic killing by human polymorphonuclear neutrophils.

The pathogenicity of Streptococcus constellatus in pulmonary infections was investigated in mice in correlation with the phagocytic killing of the microorganisms by human polymorphonuclear neutrophils (PMNs). The histological inflammation score of the lungs in mice inoculated intratracheally with 10(8) cfu/mouse of the virulent strain S. constellatus RZYK001 obtained from bronchoalveolar fluid of a patient with pneumonia, was significantly higher than in mice inoculated with the avirulent strains S. constellatus RT4303 and RT6002 obtained from saliva of healthy adults (p < 0.001). The bactericidal activity of human PMNs against Staphylococcus aureus ATCC 25923 was not inhibited at all by the culture filtrate of the virulent strain, but the killing index against RZYK001 was 36.4% after 90-min incubation whereas that against RT4303 and RT6002 was 94.7% and 99.4%, respectively (p < 0.001). Therefore, these results suggest a possible pathogenic mechanism of S. constellatus apparently mediated by a structural component of the organisms so that a virulent strain is less likely to be killed than an avirulent one, predisposing it to survive in the infection sites.

Animals↗

Effects of efonidipine hydrochloride on cholesterol esterification mediated by beta-very low density lipoprotein in J774 macrophages.

The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774 macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the binding and association in macrophages without pretreatment. beta-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level.

Animals↗

[A diabetic patient with bilateral carotid stenosis who developed neovascular glaucoma following cataract surgery].

A 67-year-old diabetic man suffered from right neovascular glaucoma following the ipsilateral cataract surgery. Three years later, he underwent left cataract surgery and again developed left neovascular glaucoma after the operation. Fluorescein angiogram showed a marked delay in retinal circulation. Moreover, severe stenosis of bilateral carotid origins and reflux of bilateral ophthalmic arteries were ascertained by neurosonographical examination such as duplex cervical echography and transcranial Doppler, as well as an angiogram. Brain imaging demonstrated asymptomatic watershed infarction in the left parieto-occipital cortex. Chronic ocular ischemia caused by carotid stenosis is one of the decisive risk factors for secondary glaucoma after cataract surgery. Preoperative neurosonographical screening tests are required to decrease ocular surgery complications, especially in the aged, and diabetic patients.

Aged↗

[Hepatic lesions in F344 rats treated orally with beta-cyclodextrin for 13 weeks].

A 13-week oral toxicity study of beta-cyclodextrin was carried out in F344 rats at the dose levels of 10, 5, 2.5, 1.25, 0.6 and 0% in powdered diet. Each group consisted of 10 males and 10 females. All animals survived at the end of the experiment, while a slight decrease in body-weight gain was observed in males of the 10%- and 5%-groups. Dose-dependent increases in serum levels of GOT, GPT and alkaline phosphatase were observed in treated animals of both sexes, and increases in serum levels of urea nitrogen and relative liver weights in treated males. Histopathologically, a dose-dependent increase in the severity of inflammatory cell infiltration was seen in the liver of treated animals, focal hepatocellular necrosis being detected in both sexes of the 10%-group and females of the 5%-group. These findings indicate that beta-cyclodextrin causes hepatocellular injury to rats when it is orally administered.

Alanine Transaminase↗

[Clinical application of magnetoencephalography for brain infarction].

Magnetoencephalography (MEG) is a noninvasive functional imaging technique that provides information regarding neuronal activity with high spatial resolution. Analyses of spikes and slow waves in various brain disorder have performed using spontaneous magnetic field, and functional mapping studies have performed using evoked magnetic field. The goal of this study was to determine the characteristics of MEG findings in these two magnetic fields for ischemic stroke patients. In the first examination, we recorded the spontaneous magnetic activity with a 37-channel neuromagnetometer and counted the number of equivalent current dipoles (neuromagnetic sources) which were divided into 6 groups with different frequencies of every 4 Hz. There were much more dipoles below 8 Hz in stroke patients than in normal controls, which tended to distribute in the hypoperfusion area near the infarct. In the second examination, we recorded auditory evoked responses for tone burst stimuli and analyzed the localization of dipoles for the 100-m.sec. component after the onset of the stimuli. The dipoles lay near the Heschl gyrus in most of control group. On the contrary, they often distributed apart from the Heschl gyrus in stroke patients with severely damaged regional oxygen metabolism measured by positron emission tomography, indicating an inappropriate response for auditory stimuli. In conclusion, MEG brought interesting informations for the brain function of stroke patients.

Brain↗

[Transient achromatopsia caused by cardioembolic brain ischemia].

A 51-year-old right-handed man with dilated cardiomyopathy, sleep apnea and atrial fibrillation suddenly suffered from transient color imperception, which completely recovered next morning. During the attack, both color naming and color pointing were severely disturbed, while he could correctly state the colors of named objects. There were no additional neuropsychological disturbances such as aphasia, alexia and prosopagnosia. Brain MRI revealed a new ischemic change, i.e. laminar cortical necrosis, in the right fusiform gyrus as a causative lesion as well as old asymptomatic infarcts in the left middle cerebral arterial territory. Cardioembolism was considered to be responsible for the development of brain ischemia. The transient achromatopsia is a rarely reported disease and this case appears to support 'ischemia' as its etiology.

Brain Ischemia↗

Cell proliferation induced by laxatives and related compounds in the rat intestine.

Induction of cell proliferation by laxatives and related compounds in rat intestines was analysed by BrdU-labelling and compared with histopathological changes in the mucosa and findings for feces. Male F344 rats were fed a diet containing danthron, sennosid A, bisacodyl, 1-hydroxyanthraquinone (1-HAQ), magnesium sulfate (MgSO4), dextran sulfate sodium (DSS), pectin, carboxymethylcellulose sodium (CMC-Na) or sodium chloride (NaCl) for 7 days. The stimulant laxatives, danthron, sennosid A and bisacodyl, significantly induced cell proliferation in almost the entire intestinal epithelia in a clear dose-dependent manner. DSS also induced cell proliferation in some portions at high doses. Increase in BrdU-labelling indices was correlated well with the severity of inflammatory changes in the intestinal mucosa as well as with purging effects of stimulant laxatives and DSS. In contrast, the bulk-forming laxative CMC-Na did not consistently enhance cell proliferation nor cause apparent cytotoxicity in the intestine despite exerting remarkable purging effects. 1-HAQ and MgSO4 slightly induced cell proliferation in the cecum and the colorectum, although there was little or no intestinal cytotoxicity. Pectin and NaCl did not influence cell kinetics of the epithelia, nor cause any inflammatory changes in the mucosa. Our results thus indicate that diarrhea caused by laxatives is not necessarily correlated with induction of cell proliferation, as in the intestinal mucosa, and that inflammatory changes followed by regenerative process could be responsible for enhancing cell kinetics. Although the precise significance of cell proliferation in carcinogenesis remains unclear, it is crucial for setting doses of carcinogenicity testings that charges in cell kinetics caused by chemicals be taken into account.

Animals↗

Long-term changes in cerebral blood flow according to different types of ischemic stroke.

Recurrence of ischemic stroke may be related to chronic hemodynamic failure of the brain. Long-term changes in cerebral blood flow (CBF) remain undetermined for each ischemic stroke subtype. We performed the present study to clarify this issue. The study group consisted of 77 unilateral, hemispheric, ischemic stroke patients who had a single stroke episode; atherothrombotic stroke in 34, cardioembolic in 26 and lacunar in 17. We measured baseline CBF in the affected and unaffected hemispheres 1.0-3.4 months after stroke onset, then repeated the measurements 10 months to 10 years later (mean 43.7 months), with the xenon-133 inhalation method. We analyzed changes in CBF in relation to other clinical characteristics. CBF in the affected hemisphere changed differently among the stroke subtypes (P < 0.01); increased in the atherothrombotic group, particularly within 40 months of stroke; remained unchanged in the cardioembolic group; and decreased in the lacunar group, especially later than 40 months of stroke. In the atherothrombotic group, CBF increased in hypertensive patients but decreased in normotensives (7.9 +/- 2.4% and -3.6 +/- 3.9%, respectively; P < 0.05). Present results suggest that long-term changes in CBF depend on ischemic stroke subtype. Development of collateral circulation may occur after several years in atherothrombotic stroke patients. The findings raise doubts about the significance of chronic hemodynamic failure as a cause of stroke recurrence.

Adult↗

Peroxisome proliferation of hepatocytes in rats by a microbial degradation product of cholic acid, 4-(decahydro-6-methyl-3-oxocyclopenta(f)quinoline-7-yl)valeric acid.

Three-week oral administration of 4-(decahydro-6-methyl-3-oxo-cyclopenta(f)quinoline-7-yl)valeric acid (32-1328) in the diet supplemented at concentrations of 0.1% or 0.3% was associated with hepatomegaly and hypotriglyceridemia in male F344 rats. Electron microscopic examination of the liver revealed a remarkable increase of peroxisomes in hepatocytes both in number and size. Biochemically, there were increased activities of peroxisomal marker enzymes including the heat-labile enoyl-CoA hydratase and catalase while the mitochondrial enoyl-CoA hydratase activity was unchanged after feeding of 32-1328. These findings indicate that 32-1328 can exert peroxisome-proliferating activity to rat liver in a manner similar to typical peroxisome proliferators such as clofibrate or di(2-ethylhexyl)phthalate.

Animals↗

A case of giant sebaceoma on the head.

A 43-year-old Japanese woman had a giant dome-shaped tumor on her head without any other involvement. Clinically, we considered several diseases; however, the histological features matched those of sebaceoma.

Adult↗