Biomedical subjects
Publications and source records attributed to Y Shiraki.
Tinea capitis caused by Trichophyton tonsurans is currently an epidemic in the United States, Europe, and Japan, and the cultivation of this microorganism is necessary for a definitive diagnosis. We recently developed a real-time PCR TaqMan assay as a culture-independent method for the rapid detection of T. tonsurans from hairbrushes.
Cathepsin B, which was originally found to be a lysosomal cysteine protease, is also an important matrix protease. In this study, we investigated the expression of cathepsin B and cystatin C, the strongest inhibitor of cathepsin B, and measured the relative amounts of each in human breast cancer tissues. Cystatin C expression relative to cathepsin B expression was found to be decreased. This finding could be associated with the looseness of cancerous interstitial tissue, which might play a role in cancer invasion and metastasis. This report documents the first simultaneous investigation of cathepsin B and cystatin C in breast cancer tissues.
We attempted to investigate whether vitamin K2 (menatetrenone) treatment effectively prevents the incidence of new fractures in osteoporosis. A total of 241 osteoporotic patients were enrolled in a 24-month randomized open label study. The control group (without treatment; n = 121) and the vitamin K2-treated group (n = 120), which received 45 mg/day orally vitamin K2, were followed for lumbar bone mineral density (LBMD; measured by dual-energy X-ray absorptiometry [DXA]) and occurrence of new clinical fractures. Serum level of Glu-osteocalcin (Glu-OC) and menaquinone-4 levels were measured at the end of the follow-up period. Serum level of OC and urinary excretion of deoxypyridinoline (DPD) were measured before and after the treatment. The background data of these two groups were identical. The incidence of clinical fractures during the 2 years of treatment in the control was higher than the vitamin K2-treated group (chi2 = 10.935; p = 0.0273). The percentages of change from the initial value of LBMD at 6, 12, and 24 months after the initiation of the study were -1.8 +/- 0.6%, -2.4 +/- 0.7%, and -3.3 +/- 0.8% for the control group, and 1.4 +/- 0.7%, -0.1 +/- 0.6%, and -0.5 +/- 1.0% for the vitamin K2-treated group, respectively. The changes in LBMD at each time point were significantly different between the control and the treated group (p = 0.0010 for 6 months, p = 0.0153 for 12 months, and p = 0.0339 for 24 months). The serum levels of Glu-OC at the end of the observation period in the control and the treated group were 3.0 +/- 0.3 ng/ml and 1.6 +/- 0.1 ng/ml, respectively (p < 0.0001), while the serum level of OC measured by the conventional radioimmunoassay (RIA) showed a significant rise (42.4 +/-6.9% from the basal value) in the treated group at 24 months (18.2 +/- 6.1% for the controls;p = 0.0081). There was no significant change in urinary DPD excretion in the treated group. These findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures, although the vitamin K2-treated group failed to increase in LBMD. Furthermore, vitamin K2 treatment enhances gamma-carboxylation of the OC molecule.
The integral roles of heat shock proteins (hsps) in the cell cycle and in multistep processes leading to tumorigenesis have been implied. We examined the expression of hsp90alpha, hsp90beta and cyclin D1 in human breast cancer. Levels of mRNAs coding for hsp90alpha and cyclin D1 were significantly higher in cancer tissues than in non-cancer tissues. Moreover, there was a close relationship between the extent of the two mRNA levels, suggesting that increased expression of hsp90alpha, an isoform of the hsp90 family, is associated with the proliferation of human breast cancer. Hsp90beta was expressed in cancer cells, but not associated with cell proliferation.
Raw vegetables cut for salad, cooked salad, cooked rice, boiled noodles, bean curd, and cooked Japanese foods were purchased in 27 retail shops in Tokyo. Intact vegetables before being processed and ready-to-eat fresh salad products were obtained from two food factories located in the suburbs of Tokyo. Two hundred thirty-eight retail samples, 137 samples of intact vegetables, and 159 samples of fresh products were examined for aerobic plate count (APC), coliforms, Escherichia coli, Listeria spp., Staphylococcus aureus, and Bacillus cereus. The APC of retail foods were 2.1 to 5.7 log CFU/g, and the range for the coliforms was 0.1 to 2.3 log CFU/g. The APC and coliform values showed that the raw vegetables cut for salad were the most heavily contaminated among the six kinds of ready-to-eat foods examined. Although L. monocytogenes was not detected, two samples of raw vegetables and five kinds of cooked foods yielded Listeria spp. S. aureus was detected in one sample of Japanese cooked food. The APC of the intact vegetables were 2.9 to 7.3 log CFU/g upon arrival and 2.2 to 7.2 log CFU/g after 3 days storage at 10 degrees C. The APC of the fresh products were 3.4 to 7.6 log CFU/g upon arrival and 4.7 to 8.7 log CFU/g after 3 days storage at 10 degrees C. The isolation rates for coliforms were 6.1 to 50% for intact vegetables and 50 to 66.7% for fresh products. E. coli was detected only in the fresh products. B. cereus was isolated from 20.1% (17 of 81) of the intact vegetables and 9.2% (8 of 87) of the fresh products.
A total of 196 samples were collected from equipment for trimming, washing, slicing, soaking, dehydrating, blending, and packaging and from the floor and air of operation rooms before and after operation in two food factories processing ready-to-eat fresh vegetables located in the suburbs of Tokyo. Heavy contamination determined by an aerobic plate count of >5.0 log CFU/cm2 or ml was observed after operation in most of the samples examined, as were samples taken before operation on the interior surfaces of equipment for washing, slicing, dehydrating, and blending, the surfaces of blades for slicing, and the floor surfaces of operation rooms. From these environmental samples, the coliform group was detected before operation. Although 67 strains of 70 coliforms isolated were nonfecal, three Escherichia coli strains were detected in the surface of the operation room floors and the gloves of employees. Bacillus cereus was isolated from 9 of 86 and 17 of 85 samples examined before and after operation with the number of 2.0 to 3.0 log CFU/cm2 or ml. Listeria spp. were not detected in the environment of the food factories.
There is accumulating evidence that some substances which are originally transmitters affect neuronal development. Though noradrenaline (NA) containing neurons in the brain-stem innervate motoneurons as well as interneurons in the spinal cord, little is known about whether or not NA may play roles other than neurotransmission during development. Therefore, we have examined the effects of NA on developing neurons in the spinal cords of chick embryos. The dissociated cells were incubated with chemicals and the number of surviving cells was counted 2 days later. It was found that NA induced cell death in a dose dependent manner (EC50, 13 microM). Phentolamine, an alpha-adrenoceptor antagonist, prevented the cell death induced by NA (KD, 1.5 nM), whereas, alprenolol, a beta-adrenoceptor antagonist, did not. Furthermore, prazosin, an alpha 1-adrenoceptor antagonist, prevented the NA-induced cell death, but yohimbine, an alpha 2-adrenoceptor antagonist, did not. Dithiothreitol, an antioxidant, did not prevent NA-induced cell death. These results indicate that NA induces cell death in the developing neurons in the chick spinal cord through alpha 1-adrenoceptors.
The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47-82 years (64.0 +/- 1.0 years, mean +/- SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217, Apo E4 +/- (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4-/- (0.91 +/- 0.01 g/cm2), E4 +/- (0.85 +/- 0.02 g/cm2), and E4+/+ (0.83 +/- 0.06 g/cm2) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 +/- 5.7 ng/ml) was higher than in E4-/- (7.7 +/- 0.3 ng/ml) or E4 +/- (7.7 +/- 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (-0.493 +/- 0.152) was not significantly different from that in the AAB of VDR (-0.616 +/- 0.225) or PPxx of ER (-0.785 +/- 0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.
To evaluate the effects of 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), a series of clinical trials, preventive and therapeutic, were performed in an open label manner in women immediately after oophorectomy. The series included a total of 121 oophorectomized subjects, whose lumbar bone mineral density (L2-4BMD) was followed by the use of dual energy X-ray absorptiometry. (1) Preventive trial: 61 women who had undergone premenopausal bilateral oophorectomy, were divided into 3 groups (Group C: control; Group L: 0.25 micrograms 1 alpha (OH)D3/day; Group H: 0.50-0.75 micrograms 1 alpha (OH)D3/day). The changes in BMD and chemical indices were followed up for one year. (2) Therapeutic trial: the trial included 60 premenopausally oophorectomized subjects having L2-4BMD lower than the normal control level minus 1SD which has been reported in age-matched normal Japanese women. These subjects were divided into 3 groups and treated in the same way as in the preventive trial. In the preventive trial, L2-4BMD decreased by 8.2%, 6.5% and 4.5% in groups C, L and H, respectively, at 12 months of treatment, whereas in the therapeutic trial, L2-4BMD decreased by 3.6%, 3.2% and 0.8% in the groups C, L and H, respectively, at 12 months of treatment. In conclusion, 1 alpha(OH)D3 was found to be effective both to prevent the bone loss subsequent to bilateral oophorectomy and improve low bone mass after oophorectomy.
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To clarify the clinical significance of the measurement of bone metabolic markers in postmenopausal subjects, a cross-sectional study of 546 healthy women (215 premenopausal, 164 bilateral oophorectomized and 167 natural menopausal) was conducted. All the subjects had their lumbar bone (L2-4 mineral density measured by means of DEXA. Bone metabolic markers (bone formation markers: serum alkaline phosphatase, osteocalcin and intact osteocalcin; bone resorption markers: urine excretion of hydroxyproline, pyridinoline and deoxypyridinoline) were also evaluated. After dividing the subjects according to the length of time after menopause, the time course changes in the Z-score values for bone metabolic markers were calculated. A triphasic pattern of lumbar bone loss was seen: there was a rapid phase in the first 5 years after menopause, a plateau phase in the second 5 years and a slow phase beginning 10 years menopause. The changes in bone metabolic markers coincided closely with the rapid phase of bone loss. In the plateau and slow phases, there were no markers which significant changed greatly. One possible clinical application of bone metabolic markers is in assessing the results of treatment for postmenopausal osteoporosis.