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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 55 records · Page 3Linked to original sources

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Administration, Oral↗

Case report. First isolation of Trichosporon domesticum from a cat.

The present study deals with the first isolation of Trichosporon domesticum from the urine of a cat with chronic cystitis. A 5-year-old domestic short hair cat weighing 5.6 kg was referred to an animal hospital with the chief complaint of haematuria having persisted for 3 weeks. The isolate was identified as T. domesticum, confirming the result of mycological examination by molecular analysis.

Animals↗

Higher intracerebral concentration of tacrolimus after intermittent than continuous administration to rats.

Neurotoxicity associated with tacrolimus after liver transplantation is a serious problem. The optimal way to administer tacrolimus to reduce neurotoxicity remains to be clarified. Three groups of rats were administered tacrolimus for 2 weeks: group C, continuous intravenous infusion (0.25, 0.5, and 1.0 mg/kg/d); group I, intermittent intravenous bolus injection twice daily (0.25, 0.5, and 1.0 mg/kg/d); and group O, oral administration twice daily (5 mg/kg/d; n = 12 each). Rats were killed either day 7 or 14 to measure whole-blood and intracerebral trough concentrations of tacrolimus. The area under the whole-blood concentration-time curve (AUC) was determined day 7. The relative risk ratio of neurotoxicity was evaluated on the basis of the brain to blood concentration ratio (Kp) and intracerebral concentration to AUC ratio (R(AUC)). The whole-blood concentration of tacrolimus and AUC value were greater in group C than group I. Conversely, the intracerebral concentration and Kp and R(AUC) values were significantly greater in group I than group C. The difference in Kp values between groups C and I significantly increased with the dose and duration of administration. Whole-blood and intracerebral concentrations in group O were similar to those at the 0.25-mg/kg/d dose in group I. In conclusion, the intracerebral concentration of tacrolimus was greater after intermittent than continuous administration of the drug. Continuous administration of tacrolimus might be more advantageous than the intermittent method to reduce the intracerebral concentration and neurotoxicity.

Administration, Oral↗

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in rats.

The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (rh-EPO; CAS for EPO: 11096-26-7) after repeated intravenous and subcutaneous administrations in rats were studied. Administration of rh-EPO by both routes caused significant increases in hematocrit. The pharmacokinetics of rh-EPO after intravenous and subcutaneous administration exhibited nonlinearity. The pharmacodynamics of rh-EPO was analyzed using the maximum effect (Emax) and sigmoid maximum effect (sigmoid Emax) models. Both models involved the assumption that rh-EPO in plasma would stimulate the proliferation of erythroid progenitor cells. Akaike's information criterion for the Emax model was lower than that for the sigmoid Emax model, suggesting that the Emax model might be an optimal model. The rh-EPO concentration at which the effect is half of the maximum was 0.383 ng/ml. This pharmacodynamic analysis suggests that the maintenance of effective plasma concentration might be important for the efficacy of rh-EPO.

Animals↗

[Characteristics and frequency of cortical cataracts at an early stage (Reykjavik Eye Study in Iceland)].

BACKGROUND: The frequency and characteristics of cortical cataract localization within a dilated pupillary area were investigated in a population-based cataract epidemiological survey performed in the city of Reykjavik in Iceland. MATERIALS AND METHODS: Among 1045 randomly selected individuals, the right eyes of 277 persons with mild cortical lens opacification (Grade I) were selected for our study. The localization of cortical cataracts was examined using retroillumination images, which were divided into 56 circular and radial sections, and calculations were made of the percentages for each opacified area. A questionnaire was used to record the number of hours spent outdoors during week days, the time of the day and whether the subjects wore spectacles, sunglasses or hats when outside. RESULTS: The percentage of cortical opacification was significantly higher in the lower nasal quadrant than in all other quadrants (p < 0.05). Furthermore, the percentage of opacification localized in the lower nasal quadrant was higher in individuals with a longer history of outdoor activity than those without (p < 0.05). The percentage of opacification in individuals, who have had the habit of wearing sunglasses for outdoor activities lasting longer than half an hour during weekdays in their 20's and 30's was lower in all quadrants and statistically significantly lower in the upper temporal quadrant (p < 0.05) compared to those not wearing sunglasses. CONCLUSION: This suggests that wearing sunglasses is effective in preventing the development and/or progression of cortical cataracts.

Aged↗

External doses in the environment from the Tokai-mura criticality accident.

On 30 September 1999, a criticality accident occurred at a uranium processing plant operated by JCO in Tokai-mura, Japan and the criticality remained for about 20 h. Almost all doses to the neighbouring residents were brought by neutrons and gamma rays emitted from the facility rather than fission products released to the environment. External doses in the environment were evaluated using radiation monitoring data and radiation transport calculation. A pattern of the dose rate evolution was modelled based on the records of gamma ray monitors in the JCO facilities. Relations between the ambient dose equivalent rates of neutrons/gamma rays and the distance from the facility were determined from the monitoring data obtained around the accident site. Conversion from the ambient dose equivalent to the effective dose equivalent was made assuming the energy spectra calculated by the radiation transport code, ANISN. It was estimated that the people who stayed outside the 350 m zone would receive doses of less than 1 mSv.

Gamma Rays↗

An experimental study on radiation streaming through a labyrinth in a proton accelerator facility of intermediate energy.

A radiation streaming experiment has been carried out at the Takasaki Ion Accelerator Facility for Advanced Radiation Application at the Japan Atomic Energy Research Institute in a room housing a Cu target irradiated with 68 MeV protons and in a labyrinth of three-legs having a total length of 29 m. In the experiment, neutron and gamma ray energy spectra, neutron reaction rates, and neutron and gamma ray dose equivalent rates were measured using various counters and dosimeters. The experimental data show the applicability of some empirical formulas for estimating the thermal neutron flux in a room and neutrons streaming in a labyrinth designed for a proton accelerator operating in the intermediate energy region. The data suggest that it is mandatory to estimate the gamma ray dose equivalent rate in a labyrinth, which is dominated by the secondary gamma rays due to the neutron capture reaction.

Academies and Institutes↗

[Long-term observations on type distribution of clinical isolated of beta-hemolytic streptococci in Sapporo. I. T-type distribution of group A hemolytic streptococci during the thirty one-year period between 1969 and 1999].

During the thirty one-year period between 1969 and 1999, a total of 6,876 strains of group A streptococci isolated in Sapporo City General Hospital were classified by T-agglutination method. This research consisted of 5,866 strains of scarlet fever-patients (scarlet fever-strains), 450 of child-patients (child-strains), 141 of adult-patients (adult-strains) and 409 strains of the indistinct. The results were summarized as follows: 1. Total of 6,866 strains were classified to sixteen kinds of T-types such as T12 (44.1%), T4 (21.7%), T1 (9.2%), T6 (4.4%), T3 (2.8%), T22 (2.1%), T18 (1.9%), T28 (1.6%) & others. This pattern of type distribution, three prevailing types of T12/T4/T1, have been reported in other areas generally. But original increase of isolation rates of strains of some T-types as T6, for example, also appeared in Sapporo. 2. Long-term observations demonstrated that the isolation rates of individual T-type, especially T4 or T1, had been forming a small epidemic-wave having a 4 to 8 year-interval and these of type T3 or type T6 on the other hand were repeating sudden prevalence every several years. 3. The isolation rates of type T12 or type T4 in scarlet fever-strains, were significantly higher than in child-strains or adult-strains. It was shown that Type T1 was distributed widely irrespective of patient-group and age-group. It was also characteristic to be distributed to many T-types in adult-strains.

Adult↗

[Long-term observations on type distribution of clinical isolates of beta-hemolytic streptococci in Sapporo. II. Type distribution of Group B streptococci during the fifteen-year period between 1985 and 1999].

During the fifteen-year period between 1985 and 1999, a total of 1,985 strains of Group B Streptococci isolated in Sapporo City General Hospital were classified by agglutination method. The results were summarized as follows: 1. Type distribution of 1,513 isolates of group B streptococci in and after 1992 when type NT6 and type JM9 were started to be typed for the first time was as follows; according to rate isolation it was in the order of type NT6 (412 strains 27.3%), JM9 (257 17.0%), III (220 14.5%), Ia (182 12.0%), following IV, Ib, V and II. 2. As for proportion of origin-materials of isolates, vaginal discharge was 49.5%, urine 26.8%, throat swab 6.8%, sputum 6.6%, pus or exudate 4.2%, blood or spinal fluid 1.8% and stomach contents was 1.3%. A proportion of vagina-origin strains went up to 55% in the second half (1992-1999) from 23% in the first half (1985-1991). 3. In type distribution of isolates in terms of origin-materials, the proportion of type III was significant by high in the stomach contents and blood and spinal fluid. Proportion of type Ia was significant by high in the sputum or throat swab. 4. Thirteen out of 28 strains (46.4%) from newborns were type III; 3 out of 4 (75.0%) from spinal fluid, 5 out of 10 (50.0%) from blood, 5 out of 13 (35.7%) from stomach contents.

Adult↗

Eosinophil transmigration across VCAM-1-expressing endothelial cells is upregulated by antigen-stimulated mononuclear cells.

BACKGROUND: Adhesion to and transmigration across endothelial cells expressing vascular cell adhesion molecule 1 (VCAM-1) may be key steps in the development of selective eosinophil accumulation at the allergic inflammation sites. There is evidence that cytokines/chemokines produced by CD4+ T cells play a prominent role in these processes. OBJECTIVE: The objective of this study was to evaluate whether eosinophil migration across human pulmonary microvascular endothelial cells (HPMEC) expressing VCAM-1 is modulated by the supernatants of antigen-stimulated mononuclear cells obtained from atopic asthmatics. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from Dermatophagoides farinae (Df)-sensitive asthmatic subjects and cultured for 96 h at 37 degrees C in the presence or absence of 1 microg/ml Df antigen. Eosinophils were isolated from blood of healthy subjects and placed on the HPMEC monolayers cultured on a transwell filter (3-microm pore size) stimulated with IL-4 plus TNF-alpha (both at 100 pM, 24 h) The supernatants of PBMC were then applied to the lower compartment and the transmigration of eosinophils was examined. RESULTS: The supernatants of PBMC stimulated with Df significantly enhanced the eosinophil transmigration across VCAM-1-expressing HPMEC (% migration: 7.6 +/- 0.6 by the supernatants of PBMC cultured without Df vs. 12.3 +/- 1.2 by the PBMC cultured with Df, p < 0.01, n = 8). The enhanced migration, but not spontaneous migration, was blocked by the anti-alpha4 integrin antibody. Moreover, the enhanced transmigration was blocked by anti-CCR3 antibody. CONCLUSION: The antigen-stimulated PBMC from atopic asthmatics produce an activity to induce eosinophil migration across VCAM-1-expressing endothelial cells. This activity appears to involve CCR3 as an essential molecule.

Antibodies↗

Dexamethasone does not modulate eosinophil adhesion to endothelial cells.

BACKGROUND: Glucocorticoids are representative agents in the anti-inflammatory treatment of allergic airway diseases. Although they reduce the number of tissue eosinophils, its exact mechanism has not been completely established. OBJECTIVE: The present study was undertaken to evaluate whether dexamethasone modulates the adhesive property of eosinophils. The effect on the expression of endothelial adhesion molecules was also evaluated. METHODS: Blood eosinophils from healthy subjects were incubated in the presence or absence of 0.1-1 microM of dexamethasone for 6 h at 37 degrees C. Eosinophil chemotaxis and adhesion to paraformaldehyde-fixed human pulmonary vascular endothelial cells (HPMEC) were then examined. The effects of dexamethasone on the expression of VCAM-1 and ICAM-1 on HPMEC were examined by cell ELISA. RESULTS: 1 microM dexamethasone significantly inhibited the chemotactic response of eosinophils to 1 microM formyl-methionyl-leucyl-phenylalanine (FMLP). On the other hand, dexamethasone did not modify either the spontaneous or FMLP-stimulated adhesion of eosinophils to resting HPMEC. Similarly, dexamethasone did not alter either the spontaneous adhesion of eosinophils to or the expression of VCAM-1 or ICAM-1 on HPMEC stimulated with IL-4 + TNF-alpha. CONCLUSION: Dexamethasone does not modify the adhesive property of eosinophils or the expression of adhesion molecules on endothelial cells. Thus, it is unlikely that glucocorticoids directly modulate the adhesive interaction between eosinophils and endothelial cells.

Adult↗

Molecular identification of Candida parapsilosis from crop mucosa in a cockatiel.

A 2-month-old cockatiel was evaluated for diarrhea, dyspnea, and death. Histologic examination of lesions in the crop mucosa revealed hyperkeratosis and the presence of blastoconidia and hyphae. Positive immunohistochemical staining of the organisms was achieved with an antibody directed against Candida spp. Polymerase chain reaction amplification of DNA from crop lesion material with internal transcribed spacer 2 (ITS2) primers yielded fragments of approximately 300 bp, which demonstrated 95% DNA homology with the corresponding sequence from a strain of Candida parapsilosis deposited in the GenBank data base. The Candida species in the lesion of the crop mucosa was therefore identified by DNA sequence analysis as C. parapsilosis.

Animals↗

Effects of constituents from the bark of Magnolia obovata on nitric oxide production in lipopolysaccharide-activated macrophages.

The methanolic extract from a Japanese herbal medicine, the bark of Magnolia obovata, was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. By bioassay-guided separation, three neolignans (magnolol, honokiol, obovatol) and three sesquiterpenes (alpha-eudesmol, beta-eudesmol, gamma-eudesmol) were obtained as active constituents. A trineolignan (magnolianin), a phenylpropanoid glycoside (syringin), lignan glycosides (liriodendrin, (+)-syringaresinol 4'-O-beta-D-glucopyranoside) and a sesquiterpene (caryophyllene oxide) did not show any activity. On the other hand, sesquiterpene-neolignans (eudesmagnolol, clovanemagnolol, caryolanemagnolol, eudeshonokiol A, eudesobovatol A) showed the strong cytotoxic effects. Active constituents (magnolol, honokiol, obovatol) showed weak inhibition for inducible NO synthase (iNOS) enzyme activity, but potent inhibition of iNOS induction and activation of nuclear factor-kappaB.

Animals↗

Methylation of CpG loci in 5'-flanking region alters steady-state expression of adenomatous polyposis coli gene in colon cancer cell lines.

The APC genetic locus has been linked to the tumorigenesis and progression of colorectal cancer, although the precise mechanism of its involvement in this disease remains unknown. We used high sensitivity mapping of the methylated cytosine, Northern blot analysis and immunocytochemical staining in six colorectal cancer cell lines (DLD-1, SW480, Colo320, HT29, WiDr, and Colo201) to examine the relationship between the methylation status of the CpG loci in the 5'-flanking region of the APC gene and its expression. APC mRNA expression levels determined by Northern blot analysis correlated well with APC protein levels visualized by immunocytochemistry. In these colorectal cancer cell lines, no major genetic alterations of the APC gene, such as amplification or deletion, were detected. Analysis of the epigenetic control of APC gene expression in these lines revealed that methylation of the CpG loci in the 5'-untranslated region of APC mRNA repressed steady-state expression of the gene. Furthermore, epigenetic alteration of the APC gene was independent of the APC protein truncation and CpG methylation of the hMLH1 promoter. Although less eminent than protein truncation by point mutation within the coding region of the APC gene, epigenetic alteration suppressing APC gene expression may significantly contribute to oncogenesis and the progression of colorectal cancer.

Adaptor Proteins, Signal Transducing↗

[Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for gastric cancer--study report of JFMTC Study No. 10].

The purpose of this study was to investigate the correlation between efficacy and dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total of 1,410 patients from 180 institutions were allocated into a low-dose group and a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months. The patients in the high-dose group received MMC at 8 mg/m2 on the day of surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600 mg in tegafur) daily for 6 months. The patients in the high-dose group tended to exhibit higher survival rates than those in the low-dose group, although the difference was not significant. For the n(+)ps(-) patients, however, the survival rates were significantly higher in the high-dose group (p = 0.043). The recurrence-free rates showed a similar tendency. The incidence rates of adverse events were significantly higher in the high-dose group than in the low-dose group. Compliance was poorer in the high-dose group. Although the number of adverse events increases, a better prognosis can be expected with a high dose. These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and UFT.

Antibiotics, Antineoplastic↗

Efficacy of nonwoven fabric bioreactor immobilized with porcine hepatocytes for ex vivo xenogeneic perfusion treatment of liver failure in dogs.

We have developed a new bioartificial liver bioreactor filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF). In this study, we investigated the efficacy of our hybrid bioartificial liver system incorporating the NWF bioreactors and an immunoglobulin adsorbent column for perfusion treatment in a canine liver failure model. Xenogeneic perfusion treatment for operative canine liver failure models were performed for 3 h, and survival time, intracranial pressure, and blood and cerebrospinal fluid data were documented. Treatment was carried out without obstruction by immunological rejection when immunoglobulin adsorbent columns were used with the NWF bioreactors in combination. Dogs treated with this system exhibited a restricted increase of intracranial pressure and significant compensatory effects on blood and cerebrospinal amino acid imbalances as shown by a significant improvement of Fischer's ratio. On the other hand, relatively low capacity for ammonia elimination was shown as compared with homologous direct hemoperfusion.

Animals↗