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Biomedical subjects

K Toyoda

Publications and source records attributed to K Toyoda.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Evaluation of a newly developed broth microdilution test method to determine minimum inhibitory concentrations (MICs) of antimicrobial agents for mycobacteria].

We developed a new broth microdilution antimycobacterial susceptibility test for determination of minimum inhibitory concentration (MICs) using an air-dried microplate containing serially diluted antimicrobial agents and the modified Middlebrook 7H9 broth. The eight agents included were streptomycin (SM), isoniazid (INH), rifampicin (RFP), ethambutol (EB), kanamycin (KM), levofloxacin (LVFX), sparfloxacin (SPFX) and clarithromycin (CAM). Serial dilutions of the agents (128 micrograms/ml to 0.125 micrograms/ml) were prepared in microplates, and were reconstituted by inoculation of 0.2ml of cell suspensions (approximately 3 x 10(5) cells/ml). The test plates were incubated at 36 degrees C in 5% CO2, and the growth endpoints were read visually after 5-day, 7-day and 10-day incubations. Four ATCC reference strains, Mycobacterium tuberculosis, M. avium, M. kansasii and M. intracellulare, were repeatedly tested at three sites. Of 480 determination against eight agents, 455 (94.8%), 470 (97.9%) and 455 (94.8%) of the MICs read after 5-day, 7-day and 10-day incubations fell within 3log2 dilutions, respectively. The MICs gradually elevated during the incubation, however those of 7-day incubation were highly precise and easily determined. A total of 160 clinical isolates of M. tuberculosis and 114 of nontuberculous mycobacteria were tested against eight agents. As for the primary drugs (SM, INH, RFP and EB), most isolates of M. tuberculosis were highly susceptible with MIC90, < or = micrograms/ml. Both LVFX and SPFX were also active. The MICs against nontuberculous mycobacteria distributed in a wide range, and the activities of RFP, LVFX, SPFX and CAM were more potent. These results demonstrate this newly developed test method to be a practical, rapid, quantitative and nonradiometric alternative for the determination of MICs in clinical mycobacteriology laboratories.

Antitubercular Agents↗
PubMed1997

Assessment of the carcinogenicity of stevioside in F344 rats.

The carcinogenic potential of stevioside, a compound that is used as a sweetener for food and drink, was examined in F344 rats of both sexes. Stevioside was added to powdered diet at concentrations of 0 (control), 2.5 and 5%. The doses were selected on the basis of results from a 13-wk subchronic toxicity study and administered to groups of 50 male and 50 female rats ad lib. for 104 wk. All surviving rats were killed at wk 108. Body weight gains were slightly depressed in line with the dose of stevioside, in both sexes, and a significant decrease in the final survival rate was observed for the 5% treated males. Histopathologically, however, there was no significantly altered development of neoplastic or non-neoplastic lesions attributable to the stevioside treatment in any organ or tissue, except for a decreased incidence of mammary adenomas in females and a reduced severity of chronic nephropathy in males. It is concluded that stevioside is not carcinogenic in F344 rats under the experimental conditions described.

Administration, Oral↗
PubMed1997

Lack of carcinogenicity of medium-viscosity liquid paraffin given in the diet to F344 rats.

The carcinogenicity of medium-viscosity liquid paraffin was examined in Fischer 344 rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 wk. Slight increases in food consumption and body weight were observed in both sexes of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematology findings. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumour type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, does not have any carcinogenic potential in F344 rats. Furthermore, granulomatous inflammation observed in mesenteric lymph nodes were not associated with any development of neoplastic lesions.

Administration, Oral↗
PubMed1997

Association between ion fluxes and defense responses in pea and cowpea tissues.

The glycopeptide elicitor from a pea pathogen, Mycosphaerella pinodes, induced rapid alkalinization and increases in levels of Na+ and K+ ions in the extracellular solution upon contact with pea and cowpea tissues. The presence of monensin, nigericin, lidocaine, quinidine or phenytoin together with the elicitor markedly inhibited these changes, whereas the presence of valinomycin, gramicidin D, tetraethylammonium, CsCl and aminopyridine did not. The production of phytoalexins in pea and cowpea tissues was also strongly inhibited by the simultaneous presence of the former reagents but not of the latter reagents. Inhibitory effects on the production of phytoalexins were diminished when monensin, nigericin or a Na(+)-channel blocker was applied 3 h after the start of treatment with elicitor. Furthermore, orthovanadate and neomycin, which suppress defense responses in both tissues, also inhibited the above mentioned changes. By contrast, the species-specific suppressor from M. pinodes inhibited the elicitor-induced release of Na+ and K+ ions from pea tissues, but, conversely, by itself it elicited either the defense response or the release of Na+ and K+ ions from cowpea tissues. The results indicate that these ion-related changes, in particular the efflux of Na+ and K+ ions, might be closely associated with the signal transduction system for defense responses at the tissue level.

Fabaceae↗
PubMed1997

Effect of aging on regulation of brain stem circulation during hypotension.

This study was designed to determine age related changes in autoregulatory responses of the brain stem circulation in vivo. In anesthetized adult (4 to 6 months, n = 8) and aged (24 to 26 months, n = 7) Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. In aged rats, the lower limit of CBF autoregulation shifted upward to 60 to 75 mm Hg from 30 to 45 mm Hg in adult rats. Dilator responses of the basilar artery (baseline diameter: 254 +/- 15 microns), large branch (109 +/- 23 microns), and small branch (44 +/- 10 microns) to hypotension were much smaller in aged rats than in adult rats. The maximum change in diameter of the basilar artery during profound hypotension was significantly smaller in aged rats (11 +/- 8%) than that in adult ones (23 +/- 12%, P < 0.05); that of the large branch was 12 +/- 8% versus 33 +/- 17% (P < 0.005); and that of the small branch was 17 +/- 7% versus 40 +/- 13% (P < 0.0005), suggesting greater attenuation of the responses in the smaller vessels. Thus, this study provides direct evidence that aging diminishes the compensatory dilatation of brain stem arterioles and arteries during hypotension and modifies the autoregulatory plateau of CBF, which seems to increase the risk of the brain stem ischemia during hypotensive conditions.

Acetylcholine↗
PubMed1997

Role of nitric oxide in regulation of brain stem circulation during hypotension.

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-5) mol/L and 10(-4) mol/L N(omega)-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

Animals↗
PubMed1997

Role of ATP-sensitive potassium channels in brain stem circulation during hypotension.

The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.

ATP-Binding Cassette Transporters↗
PubMed1997

Age-related changes in response of brain stem vessels to opening of ATP-sensitive potassium channels.

BACKGROUND AND PURPOSE: This study was designed to determine regional differences and age-related changes in the contribution of ATP-sensitive potassium (KATP) channels to vasodilator responses in the brain stem circulation in vivo. METHODS: Changes in diameter of the basilar artery (baseline diameter, 270 +/- 5 microns [mean +/- SEM]), its large branch (112 +/- 5 microns), and its small branch (49 +/- 2 microns) in response to KATP channel openers levcromakalim and Y-26763 were measured through a cranial window in anesthetized adult (4 to 6 months) and aged (24 to 26 months) Sprague-Dawley rats. RESULTS: Topical application of levcromakalim and Y-26763 produced concentration-dependent vasodilation that was similar among the three vessel groups in adult rats. In aged rats, dilator responses of the branches, but not of the basilar artery, to the KATP channel openers were smaller than those in adult rats (P < .05). Glibenclamide, a selective KATP channel blocker, almost abolished this vasodilation in both groups of rats. Vasodilator responses to sodium nitroprusside were preserved in aged rats. CONCLUSIONS: In adult rats, there is no regional heterogeneity in vasodilator response to KATP channel openers in the brain stem circulation in vivo. In aged rats, although KATP channels are also functional in the brain stem circulation, dilator response of the microvessels but not of the large arteries to direct activation of KATP channels is impaired.

Aging↗
PubMed1997

[One-stage-bilateral adrenalectomy by thoracoabdominal approach for bilateral large pheochromocytomas in men type IIa. A case report].

We experienced a case of MEN type 2a with bilateral and large pheochromocytomas. A 39-year-old man was admitted to the previous hospital with complaints of paroxysmal headache. hypertension and diabetes mellitus. Radiographic imagings showed thyroid tumors in both lobes and bilateral adrenal tumors. Thyroid tumors were histologically proved to be medullary thyroid carcinoma by needle biopsy and systemic investigations revealed an excessive secretion of plasma and urinary cathecholamines which suggested the presence of pheochromocytoma. The patient was diagnosed as MEN type 2a. He was admitted to our hospital for the treatment of bilateral adrenal tumors for which we performed one-stage bilateral adrenalectomy by thoracoabdmonal approach. Both adrenal tumors were histologically confirmed as pheochromocytoma. The patient's postoperative course was uneventful. He underwent uneventful total thyroidectomy approximately 2 months after bilateral adrenalectomy. Even in bilateral and large pheochromocytomas, one-stage bilateral adrenarectomyenables safe postoperative managements. We concluded that the thoracoabdominal approach is feasible in the patients with huge and cranially spreading adrenal tumor, which gives us a wide operative field for easy vascular control.

Adrenal Gland Neoplasms↗
PubMed1997

[Gamma knife radiosurgery for metastatic brain tumors: neuropathological report of two autopsy cases and review of literatures].

More than 40,000 cases have been treated with gamma knife radiosurgery, but few neuropathological reports are available. This paper describes two autopsy cases in which the patients had been treated with gamma knife. As these patients died 67 and 24 days after therapy, early neuropathological changes are reported. The first case was a 58-year-old woman diagnosed with multiple brain metastases from breast cancer. One of these lesions, in the medullaoblongata, was irradiated with a gamma knife. Sixty-seven days later, she died from heart failure. The second case was a 69-year-old man diagnosed with multiple brain metastases from lung cancer. One of these lesions, in the pons, was irradiated with a gamma knife. Twenty-four days later, he died from acute renal failure caused by hepatorenal syndrome. In both cases, the irradiated lesions were well demarcated from the undamaged surrounding tissues on light microscopy. Histologically, the tumor cells showed a variety of degenerative changes, such as pyknosis, multinuclear cells, and vacuolar degeneration in the cytoplasm. Fibrosis, more prominent in the first case, was observed spreading in the irradiation field, adhering to the hyalinized and thickened vessel walls. Demyelination was also observed in the first case. As far as we know, this report is the first published description of fibrosis in the radiosurgical irradiation field.

Aged↗
PubMed1997

Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Pharmacological properties of NK-104 ((+)-monocalcium bis¿(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl++ +]-3,5-dihydroxy-6- heptenoate¿, CAS 147526-32-7), a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, were investigated. The kinetic study, using rat liver microsomal HMG-CoA reductase, revealed that NK-104 is a competitive inhibitor of HMG-CoA reductase with a Ki of 1.7 nmol/l. To examine the inhibitory effect on sterol synthesis in vivo, de novo synthesis of sterols from [14C]acetate 3 h after oral administration of NK-104 was measured in rats. NK-104 showed marked inhibition in liver (ED50 0.13 mg/kg) and in ileum (ED50 0.20 mg/kg), but much weaker in the other tissues. The inhibitory effect of NK-104 on liver sterol synthesis lasted over 6 h, while that of pravastatin and simvastatin disappeared 6 h after administration of the drugs twice the ED50s. Due to induction of HMG-CoA reductase, initial suppression of hepatic sterol synthesis by pravastatin and simvastatin was compensated, and the cumulative change in hepatic sterol synthesis during 12 h after drug administration was remarkably negative only with long-acting NK-104. Hypolipidemic effects of NK-104 (0.03, 0.1, 0.3 and 1 mg/kg p.o. for 2 weeks) were examined in beagle dogs. NK-104 reduced plasma total cholesterol dose-dependently (13.1, 18.5 and 20.2% at doses of 0.1, 0.3 and 1 mg/kg, respectively), and also plasma triglycerides by 0.1 mg/kg or more. Pravastatin (1 and 3 mg/kg) and simvastatin (3 mg/kg) lowered plasma total cholesterol (14.0, 15.4 and 17.4%, respectively), but did not significantly affect plasma triglyceride levels. These results indicate that NK-104 is a potent, liver-selective, long-acting HMG-CoA reductase inhibitor with a high cholesterol- and triglyceride-lowering potency.

Animals↗
PubMed1997

[A case of sarcomatoid carcinoma of the bladder: immunohistochemical study on histogenesis of sarcomatoid elements].

An 82-year-old man with microhematuria and class V cells in his urinary cytologic specimen was referred to our clinic. Cystoscopy revealed a solid, broad-based tumor of 1 cm in diameter in the bladder diverticulum. A partial cystectomy was performed. The tumor was composed of transitional cell carcinoma (TCC), sarcomatous spindle cells and the area of transition between TCC and spindle cells. The histopathological diagnosis was sarcomatoid carcinoma. Immunohistochemical examination showed that the spindle cells and the area of transition were positive for keratin, cytokeratin, vimentin and muscle actin. The histopathological and immunohistochemical transitions between the TCC and the spindle cells suggested that the sarcomatous elements originated from the TCC during tumor progression.

Actins↗
PubMed1997

[A 13-week subchronic oral toxicity study of carob germ colour in F344 rats].

A13-week subchronic oral toxicity study of carob germ colour, one of natural colour additives was carried out in F344 rats at dose levels of 5.0, 1.7, 0.6, 0.2 and 0% in the powdered diet. Rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the experiment and no changes in body weights and food intakes were observed in any dosed groups. Changes indicating obvious toxicity of carob germ colour were not observed in the organ weights, hematological, serum biochemical and histopathological examinations. These findings indicate that the treatment of 5% carob germ colour in diet for 13 weeks did not cause any significant toxicity in rat.

Administration, Oral↗
PubMed1996

[A case of tubercular liver and splenic abscesses].

A 34-years male was admitted to our hospital with a hypochondria pain and low grade fever. Abdominal CT revealed an encapsulated 8 x 3 cm low density lesion on the surface of the liver (S5, S8) and multiple low density lesions of the spleen. The patient had already been treated with anti-tuberculous drugs for the past 7 months after being diagnosed as tuberculous pleuritis. Although echo-guided percutaneous needle biopsy was tried for the hepatic lesion, no special finding was obtained. Therefore a diagnostic laparotomy was performed and the hepatic lesion was resected. Abscess formation of the resected lesion was noted. Histopathology of the lesion revealed epithelioid granuloma, but microscopy, culture and PCR for tuberculosis revealed negative results. Abdominal CT, 3 weeks after surgery, revealed enlargement of the splenic lesion. Splenectomy was carried out to avoid splenic rupture. Multiple abscess of the resected spleen was noted. Pathological finding, Ziehl-Neelsen stain and PCR for tuberculosis confirmed the diagnosis of tubercular splenic and liver abscess. Although tubercular liver and splenic abscess are very rare recently, it should be included in the differential diagnosis of unknown hepatic and splenic lesions.

Abscess↗
PubMed1996

Changes in arterioles, arteries, and local perfusion of the brain stem during hemorrhagic hypertension.

Cerebral arterioles have been regarded as the primary sites of autoregulatory responses, whereas the role of large arteries in the cerebral autoregulation is poorly understood. The goal of this study was to determine in vivo whether the basilar artery and its primary branches act as resistance vessels under hypotensive conditions by simultaneously measuring their diameters and local brain stem blood flow with laser-Doppler flowmetry. In 10 anesthetized rats, blood flow to the brain stem was well maintained during stepwise hemorrhagic hypotension when mean arterial blood pressure fell from 116 +/- 3 to 50 mmHg and decreased gradually between 50 and 30 mmHg. Diameter of the basilar artery (n = 10) and its large branches (n = 22), measured through an open cranial window, increased by 10% from the baseline value at 50 mmHg and reached their maximum at 30 mmHg (314 +/- 9 from 244 +/- 6 mum, and 149 +/- 4 from 117 +/- 3 mum, respectively). Small branches (n = 15) dilated to a larger extent compared with the larger arteries throughout hypotension and reached the maximum at 30 mmHg (69 +/- 3 from 48 +/- 2 mum). Below 30 mmHg, there was a steep fall in blood flow and reduction in diameter of all-sized arteries. Thus small vessels contribute to reductions in cerebrovascular resistance throughout the entire autoregulatory-range in the brain stem circulation. Large arteries, such as the basilar artery and its branches, also contribute to reductions in cerebrovascular resistance around the lower limits of cerebral blood flow autoregulation and may thus play a significant role in maintaining blood flow to the brain stem during severe systemic hypotension.

Animals↗
PubMed1996

Medial medullary infarction: analyses of eleven patients.

Of 2,130 consecutive patients admitted to two hospitals with acute brain infarction, we examined 11 patients (0.52%) with medial medullary infarction. The infarcts documented by MRI were unilateral in 9 patients and bilateral in 2 patients, and located in the anteromedial arterial territory of the upper or middle part of the medulla. Atherosclerosis of the vertebral arteries was the predominant vascular pathology. The vertebral artery was occluded at its terminal portion in 7 patients. Nine patients had hypertension, and 8 of these had additional risk factors. Male gender (10 patients) and smoking habits (7 patients) were more prevalent compared with patients with pontine infarction. One patient had a medial medullary infarction attributed to dissection of the vertebral arteries following blunt head injury. Limb weakness was the major symptom in all patients, and gaze-evoked nystagmus was also frequent (6 patients). Tongue weakness ipsilateral to the infarct, the classic sign of medial medullary syndrome, was evident in only 3 patients. The outcome was usually excellent.

Adult↗