Biomedical subjects

Hiroyuki Takahashi

Publications and source records attributed to Hiroyuki Takahashi.

13 recordsLinked to original sources

PubMed2003

Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men.

The HPC2/ELAC2 gene may be associated with hereditary/familial prostate cancer (PCa). Two common missense variants (Ser217Leu and Ala541Thr) have been reported in the gene. We performed mutational, allelotyping and expression analyses and a molecular epidemiological study to clarify the relations between this gene and prostatic diseases, including PCa and benign prostatic hyperplasia (BPH) in Japanese men. We screened for mutations in 109 patients with PCa including 11 patients from 1 hereditary and 9 familial PCa. Loss of heterozygosity and expression were analyzed. An epidemiological study was done in sporadic PCa (n=98) and BPH (n=143) using 1 novel (Ser627Leu) and 2 previously described polymorphisms of the HPC2/ELAC2 gene. Somatic or germline mutations were not confirmed in any cases of PCa. Loss of heterozygosity at 2 microsatellites, D17S1289 and D17S520, was detected in 1 of 38 and 1 of 35 cases, respectively. Expression analysis revealed decreased or absent mRNA expression in 6 of 38 tumors. Epidemiologic analysis showed that a Leu allele at codon 217 was significantly more frequent in patients with PCa than in controls (10.2% vs. 3.5%, odds ratio = 3.11; 95% confidence interval, 1.22-7.90). At codon 541, all patients with PCa or BPH and all control subjects had the Ala/Ala genotype. At codon 627, the incidence of the Leu variant was slightly, but not significantly, higher in patients with BPH than in controls (7.0% vs. 2.8%, odds ratio = 2.59, 95% confidence interval, 0.94-7.13, not statistically significant). We concluded that germline/somatic mutations of HPC2/ELAC2 are uncommon in PCa. Similarly, allelic imbalances at the gene locus and changes in expression are rare. Although no difference in allele frequency at Ser217Leu between patients with PCa and controls has been reported in a Western population, this polymorphism is a potential indicator of PCa risk in Japanese men and it should be examined in other ethnic groups.

Aged↗

PubMed2003

Altered methylation of multiple genes in carcinogenesis of the prostate.

The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation-specific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RARbeta2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O(6)-methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARbeta2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RARbeta2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARbeta2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancer-related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARbeta2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.

Aged↗

PubMed2003

Estrous cyclicity and ovarian follicles in female rats after prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl.

Alterations of estrous cyclicity and ovarian follicles following prenatal exposure to PCB126 were examined. Female SD rats were given (i.g.) 25 pg, 2.5, 250 ng and 7.5 microg of PCB126/kg or the vehicle on days 13-19 postconception. Vaginal opening (VO) in the 250 ng and 7.5 microg offspring was significantly delayed. All groups showed irregular estrous cyclicity following VO, but it became normal after a few days. However, the start of normal estrous cyclicity following VO in the 2.5, 250 ng and 7.5 microg groups was significantly delayed. At 30 and 50 days old, the 2.5, 250 ng and 7.5 microg groups showed significantly fewer antral follicles and a higher number of atretic follicles. The 7.5 microg group at 50 days old revealed significantly fewer corpus luteums. In 50-day-old offspring, the 2.5, 250 ng and 7.5 microg groups showed a significant reduction in serum 17beta-estradiol and progesterone levels and significantly higher levels of PCB126 in the fatty tissue compared with the vehicle group. Thus, while the prenatal dose of PCB126 used in this study did not induce malformation of the external genitalia or persistent ovarian disruption, disruption of ovarian function at puberty was found in the 2.5 ng group of pups born to dams exposed to 17.5 ng/kg PCB126. The present study suggests that PCB126, at least in part, exerted direct effects on the ovary as shown by the disruption of estrous cyclicity.

Animals↗

PubMed2003

A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells.

BACKGROUND: Umbilical cord blood (CB) is being used as a source of alternative HPCs for transplantation with increasing frequency. The goal of CB banks for unrelated transplantation is to provide good quality-controlled CB units that can be transplanted for HPCs into the largest possible number of patients. STUDY DESIGN AND METHODS: Large CB samples in freezing bags wrapped with insulators and small samples in cryotubes placed into double styrene-foam boxes were cryopreserved at -85 degrees C without a rate-controlled freezing machine, followed by storage in the liquid phase of nitrogen. After thawing these cells, the viability and recovery of cells, as well as the recovery rate of HPCs such as CD34+ cells, CFU-GM, and total CFU were evaluated. RESULTS: Measurement of the freezing rate in CB bags and cryotubes demonstrated that this simple method for cryopreservation of CB cells provided optimal conditions for both large-scale and small-scale cryopreservation. Recovery of CB progenitor cells after cryopreservation was also shown to be potentially acceptable when evaluated with CD34+ cells, CFU-GM, and total CFU. These results were comparable to the method using a rate-controlled programmed freezer. CONCLUSIONS: A simple method for cryopreservation of CB cells without a rate-controlled programmed freezer could provide a sufficient-enough potential for the transplantability of HPCs after thawing.

Blood Banks↗

PubMed2003

The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors.

Retrospective analysis was conducted in 51 autologous peripheral blood progenitor cell (PBPC) collections using the Spectra AutoPBSC System from patients with hematologic malignancies and solid tumors to study the predictive value of CD34+ cell counts in the peripheral blood for the yield of CD34+ cells in the apheresis product. The correlation coefficients for CD34+ cells microL(-1) of peripheral blood with CD34+ cell yield (x 10(6) kg(-1) of body weight and x 10(5) kg(-1) of body weight L(-1) of blood processed) were 0.903 and 0.778 (n=51 collections), respectively. Products collected from patients with CD34+ cell counts below 15 microL(-1) in the peripheral blood contained a median of 0.49 x 10(6) CD34+ cells kg(-1) (range: 0.05-2.55), whereas those with CD34+ cell counts more than 15 microL(-1) contained a median of 3.72 x 10(6) CD34+ cells kg(-1) (range: 1.06-37.57). From these results, a number of at least 15 CD34+ cells microL(-1) in the peripheral blood ensured a minimum yield of 1 x 10(6) CD34+ cells kg(-1) as obtained by a single apheresis procedure. The number of CD34+ cells in the peripheral blood can be used as a good predictor for timing of apheresis and estimating PBPC yield. With regard to our results, apheresis with a possibly poor efficiency should be avoided because the collection procedure is time-consuming and expensive.

Adolescent↗

PubMed2003

[Papillary adenocarcinoma of the prostate: report of 4 cases].

Papillary adenocarcinoma of the prostate, previously referred to as endometrioid carcinoma, is a variant of prostatic adenocarcinoma. Clinical and pathological evidence of involvement of the periurethral prostatic duct or verumontanum is usually required for definitive diagnosis of papillary adenocarcinoma. However, significant histologic and clinical features of papillary adenocarcinoma overlap with typical acinar carcinoma. Four cases of papillary adenocarcinoma were studied for the clinical features, histologic characteristics and immunohistochemical nature of prostatic specific antigen. In two cases, there were papillary regions, near the verumontanum, but in the other two cases, there were no papillary regions in the urethra. In two cases, acinar adenocarcinoma coexisted with papillary adenocarcinoma. All cases displayed positive immunohistochemical staining for prostatic specific antigen. In accordance with the observations of others, we suggest that papillary adenocarcinoma is one aspect of growth pattern of acinar adenocarcinoma, not a concept of a unique clinical and pathological entity.

Adenocarcinoma, Papillary↗

PubMed2002

Mammary gland differentiation in female rats after prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl.

Recently we reported finding that prenatal exposure to a relatively low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) increases the rate of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma, while a high dose decreases it. One of the most important factors determining sensitivity of the mammary gland to neoplastic stimuli is its stage of differentiation at the time of exposure to the carcinogenic agent. Hence, to verify a biphasic dose-response relationship (enhancement of carcinogenesis at low dose, and inhibition at high dose), we investigated the effects of prenatal exposure to PCB126 on mammary gland differentiation. Female SD rats were injected (i.g.) with 25 pg, 2.5 ng, 250 ng, 7.5 microg of PCB126/kg, or the vehicle, on days 13-19 postconception. In 50-day-old offspring, regardless of the day of exposure to DMBA, only the 7.5 microg group showed statistically significant high levels of PCB126 in the fatty tissue of their mammary glands. Fifty-day-old female offspring of the 250 ng group showed apparent inhibition of the normal differentiation of terminal end buds (TEB) to alveolar buds and lobules (ABL), while those of the 7.5 microg group showed mammary gland hypoplasia. Expression levels of the estrogen receptor-alpha (ER) in TEBs and the ER mRNA in mammary glands were higher in the 7.5 microg, 250 ng, 2.5 ng groups. Proliferating cell nuclear antigen (PCNA) expression in TEBs of 50-day-old rats was statistically significantly higher in the 250 ng group and lower in the 7.5 microg group. In the developing mammary gland, TEBs are considered the most susceptible to mammary carcinogenesis, while ABLs are relatively protected from mammary carcinogenesis. Thus, prenatal exposure to a relatively low dose of PCB126 induced an alteration of mammary gland differentiation that might potentially increase the risk of DMBA-induced mammary carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Female reproductive parameters and fruit availability: factors determining onset of estrus in Japanese macaques.

This study examined the onset of estrus, nutritional conditions during the mating season, and female reproductive parameters in a troop of unprovisioned Japanese macaques (Macaca fuscata fuscata). The mean interbirth interval (IBI) was 25.1 mo, suggesting a 2-yr birth cycle. The mean IBI following the death of an infant before the mating season was only 19.8 mo, whereas the mean IBI was 27.8 mo when the infant survived. Estrus occurred during the time of the greatest food quality, in the autumn (i.e., mating season). A female whose infant did not survive the mating season tended to come into estrus more readily than one with a surviving infant. Only one of the 19 females whose infants survived came into estrus, whereas 43 of the 58 (74.1%) females whose infants did not survive came into estrus. Fruit conditions during the mating season each year were evaluated by the seed crop of the two species (Fagus crenata and Zelkova serrata) that constituted the main food source for the macaques; fruiting levels were classified as "high-fruit" or "low-fruit." Females came into estrus more often during high-fruit mating seasons than during low-fruit mating seasons: 36 (97.3%) of 37 females came into estrus during high-fruit mating seasons, whereas eight (20%) of 40 females came into estrus during low-fruit mating seasons. Although females came into estrus under both high- and low-fruit conditions during the mating season, estrus seldom occurred when females had a surviving infant, and it appears that the absence of a surviving infant is an almost essential variable for the onset of estrus. When females with a surviving infant were excluded from the analysis because they were unlikely to come into estrus, all 35 remaining females (100%) came into estrus during high-fruit mating seasons, whereas only eight (34.8%) of 23 females came into estrus during low-fruit mating seasons. Therefore, the onset of estrus is strongly affected not only by the survival of infants through the mating season, but also by fruiting conditions, especially the availability of high-quality food.

Animals↗

PubMed2002

Changes of dominance rank, age, and tenure of wild Japanese macaque males in the Kinkazan a troop during seven years.

Male age-rank and tenure-rank relationships were studied for seven years in unprovisioned Japanese macaque (Macaca fuscata fuscata) troop on Kinkazan Island, Japan. Males whose estimated ages were between 15 and 19 yr old monopolized the highest ranks, while older males whose estimated ages were > or = 20 yr old tended to decline in rank, resulting in a humped age-rank curve. The ranks of males tended to rise as their tenure in the troop increased. The departure of higher-ranking males was the social mechanism for changes in rank, suggesting that the disappearance of higher-ranking males plays an important role in determining rank dominance.

Aging↗

PubMed2002

Carney complex: report of a Japanese case associated with cutaneous superficial angiomyxomas, labial lentigines, and a pituitary adenoma.

We report the case of a 12-year-old female patient who manifested multiple cutaneous angiomyxomas and labial pigmented lesions. Although the familial history was not confirmed in the present case, autosomal dominant inheritance has been reported to be involved in the pathogenesis of this condition. In addition to the cutaneous complications, magnetic resonance (MR) images revealed the presence of a pituitary adenoma, which provoked an elevation of serum growth hormone (GH) level. On the other hand, no significant symptoms such as cardiac myxoma, myxoid fibroadenoma of the breast, or adrenocortical complaints suggesting Cushing syndrome, were detected. In the Japanese literature, only a few cases of this disorder have been described in the form of brief reports. There have been only a few similar cases described in the dermatological field, except for one report diagnosed as Carney complex in 1990. Therefore, the present case seems to be the first Japanese case of typical Carney complex manifesting major clinical complications, including angiomyxomas, lentigines, and a pituitary adenoma, which induced endocrine overactivity.

Adenoma↗

PubMed2002

Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method.

A novel and convenient method was established for the prediction of in vivo metabolic clearance in human liver. The present method applied the in vitro-in vivo extrapolation paradigm previously established in rats to the in vitro data obtained from cryopreserved human hepatocytes. Predicted hepatic availability and clearance were compared with the reported oral bioavailability and plasma clearance in humans for 14 clinically used drugs (naloxone, buspirone, verapamil, lidocaine, imipramine, metoprolol, timolol, antipyrine, diazepam, quinidine, caffeine, propranolol, diclofenac, and phenacetin). A large interindividual variation was observed in the intrinsic metabolic clearance among separate cryopreserved preparations from different subjects. The prediction generally resulted in a marked underestimation when the biologically based scaling factor (3.1 x 10(9) cells/kg) was used for the extrapolation of in vitro data (milliliters per minutes per cells) to in vivo value (milliliters per minutes per kilograms). Reasonably good in vitro-in vivo correlations were obtained with empirically calculated scaling factors, 8.5 x 10(9) (cells/kg) from 10 individual preparations and 10.8 x 10(9) (cells/kg) from pooled preparation of two selected lots, which were 3- to 4-fold larger than the biologically based scaling factor. These data suggested that the calibration of inherent interindividual variation of metabolic activities among different cryopreserved preparations of human hepatocytes to obtain the empirical scaling factor, which is applicable only to the preparation used, was an essential step for more reliable and quantitative prediction of in vivo metabolic activity in humans.

Administration, Oral↗

PubMed2002

[A case report of hemidiaphragmatic paresis caused by interscalene brachial plexus block].

A 76-yr-old woman was scheduled for left upper extremity orthopedic procedure. Preoperative examinations were within normal limits except forced vital capacity. Interscalene brachial plexus block with 0.25% bupivacaine 15 ml, was performed under general anesthesia. Her intraoperative course was uneventful. She, however, complained of the dyspnea after removal of a tracheal tube, and Spo2 dropped to 89%. A chest X-ray demonstrated the elevation of hemidiaphragm. She was diagnosed as ipsilateral hemidiaphragmatic paresis, treated with oxygen inhalation under deep breathing for approximately one hour, and then transferred to the common ward. We conclude that respiratory movement should be carefully observed following interscalene brachial plexus block especially in geriatric patients.

Aged↗

PubMed2002

[Relationship between self-management behavior and cognitive skills in type 2 diabetes mellitus patients].

OBJECTIVES: The relationship between general self-management skill (SMS) and specific SMS, and associations with self-management behavior were investigated in diabetes patients. METHODS: A total of 306 diabetes patients were asked to complete questionnaires and additional information was collected from medical records. The contents of the questionnaires covered attributes, the SMS scale developed by Takahashi, the specific SMS score (diabetes skills score), and self-management behavior, referring to items of Yasukata's and Kinoshita's scales. RESULTS: 1. The SMS scale correlated with the diabetes skills score, although high values were observed for the latter, and these skills influenced self-management behavior. 2. Path analysis was applied to examine association between cognitive skills and self-management behavior. The results showed direct associations between self-management behavior and the SMS scale, the diabetes skills score and the presence or absence of a job. The SMS scale, the degree of knowledge, family support, and the presence or absence of a job were indirectly associated with self-management behavior through the diabetes skills score. The standardized partial regression coefficient (beta) showed self-management behavior to be much more related to the diabetes skills score than the SMS scale. CONCLUSION: These findings suggest that support of cognitive skills related to diabetes may be effective for improvement of the self-management behavior of diabetes patients.

Behavior↗