Biomedical subjects
Publications and source records attributed to Yoshihiro Ono.
An interdisciplinary approach was used to treat a patient with pathologic migration of teeth, with severe anterior proclination and molar mesial inclination due to localized aggressive periodontitis. The combination of regenerative periodontal therapy, prosthodontic rehabilitation, and orthodontic treatment greatly improved function and esthetics.
OBJECTIVES: To clarify the effect of androgen concentration on blood flow regulation in seminal vesicles and to identify the androgen most responsible for this effect. METHODS: The androgen concentrations in the seminal vesicles and the seminal vesicle blood flow were measured at 0, 3, 6, 12, 24, 48, and 72 hours after castration. The androgen concentration was measured with a newly developed highly sensitive simultaneous androgen quantification method that uses liquid chromatography-tandem mass spectrometry. The blood flow was measured with the radioactive microsphere injection method. The change in seminal vesicle blood flow in 6-hour castrated rats after administration of 3 mg/kg testosterone, 3 mg/kg dihydrotestosterone (DHT), 3 mg/kg dehydroepiandrosterone, or 3 mg/kg testosterone plus 20 mg/kg finasteride was evaluated. RESULTS: A correlation was observed between the DHT concentration and blood flow in the rat seminal vesicle after castration. The DHT concentration and blood flow decreased after castration to 31.6% and 37.9%, respectively, of the normal level at 6 hours. The decline in DHT concentration and blood flow decreased further thereafter to 2.2% and 18.1%, respectively, of the normal level at 72 hours. Both testosterone and DHT fully restored the organ blood flow in castrated rat seminal vesicles. However, the blood-flow-increasing effect of testosterone was attenuated by more than 50% when administered in combination with finasteride. Dehydroepiandrosterone did not increase seminal vesicle blood flow. CONCLUSIONS: The results of our study showed a strong correlation between the organ DHT concentration and blood flow in rat seminal vesicles. Of the various androgens, the most active androgen in the regulation of seminal vesicle blood flow was DHT.
To clarify the effect of androgens on the microcirculation of the prostate, organ blood flow and ultrastructural features of the capillaries were investigated. In the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured using a laser Doppler flowmetry, and the morphological features of the subepithelial capillaries were investigated and their luminal area was measured using transmission electron microscopy and a computed image analyzer at 1, 2, 3, and 7 days after castration, and 2 days after castration and gradational testosterone supplementation. The capillaries of the VP were classified into three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3). Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2 days after castration. These reductions of the blood flow and the luminal area were gradationally prevented by testosterone supplementation. In the morphological features of the capillary, type 1 had rapidly shifted to types 2 and 3 after castration, and the shift of the capillary type was significantly prevented by the testosterone supplementation. These results clearly demonstrated that the androgen-dependent ultrastructural and morphological features in subepithelial capillaries revealed local microcirculatory conditions correlating the organ blood flow changes in VP.
To clarify the effect of androgen on the microcirculation in seminal vesicles of adult Wistar rats, we investigated the organ blood flow and morphological features in the capillaries after castration and subsequent testosterone supplementation. Testosterone (T) was subcutaneously injected every 12 hours after castration and its doses were set to 10(-2), 10(-1), 10(0) and 10(1) mg/kg-body weight (T10(-2), T10(-1), T10(0) and T10(1) groups, respectively). Organ blood flow was measured using laser Doppler flowmetry, and the subepithelial capillaries were analyzed using transmission electron microscopy. The capillaries were morphologically classified into 3 types; oval opened (type 1), intermediate (type 2) and collapsed (type 3), and their luminal areas were measured using a computed image analyzer. The organ blood flow was significantly reduced from 36.3+/-5.1 to 21.9+/-2.7 ml x min(-1)/100 g tissue, and the luminal area of the capillaries was significantly reduced from 9.02+/-1.28 to 4.85+/-0.82 microm2 with the shift of the type 1 and type 2 to type 3 after castration. The reduction of the luminal area and the blood flow reduction, and shift of the capillary type were significantly protected by gradated testosterone supplementation. These results indicate that the maintenance of the blood flow and morphological profiles in capillaries depend on androgen-supplementation levels in seminal vesicles.
To evaluate the accuracy and reliability of laser speckle blood flowmetry in the measurement of prostate blood flow, we performed a comparative study with the ordinary intra-arterial radioactive microsphere injection method using the well-known castrate-rat model. Adult male Wistar strain rats were used for the study. The rats were either only castrated or subcutaneous testosterone replenishment was followed subcutaneously 6 h after castration. The prostate blood flow was measured at different time courses after castration. The effect of a single androgen replenishment on prostate blood flow was also evaluated. The measurement of prostate blood flow was performed by both the radioactive microsphere injection method and laser speckle blood flowmetry, and then the outcomes were compared. Rapid reduction in prostate blood flow to 30% of the normal level was observed 24 h after castration in the measurements with the microsphere injection technique. The prostate blood flow decreased gradually after 24 h post-castration to 23 and 21% of the normal level at 48 and 72 h after castration, respectively. The laser speckle blood flowmetry also detected the decrease in prostate blood flow well, but in a more gradual manner. The prostate blood flow was 70, 52 and 35% of the normal level at 24, 48 and 72 h after castration, respectively. The effect of a single administration of testosterone to castrated rats had recovered the prostate blood flow to 74 and 98% of the normal level by measurement with the microsphere injection technique and laser speckle blood flowmetry, respectively. The different outcome in blood flow rate change between the methods can be explained according to their different mechanism of measurement, thus suggesting the capillary vessels are the early and most responsive portion for hormonal manipulation. In conclusion, the laser speckle blood flowmetry is a convenient and reliable method for evaluating prostate blood flow, especially when the organ is required for other biological and molecular assays, since the method does not require the excision of the organ for the measurement.
OBJECTIVES: To clarify the basic aspects of the regulation of the prostatic blood supply by antiandrogens, their effect on the prostatic blood supply was studied for both androgen content and morphology of true capillaries in the rat ventral prostate. The effectiveness of antiandrogens on the control of hemorrhagic status in prostatic diseases has been previously reported. METHODS: Androgen concentrations in the prostate were quantified after administration of chlormadinone acetate (CMA), finasteride, or flutamide. The prostatic blood supplies were measured after administration of CMA, finasteride, flutamide, or bicalutamide. The alpha-blockers, terazosin and tamsulosin, were included in the study as negative controls. The histologic changes in the capillaries of the ventral prostate were observed, and the luminal area was measured. RESULTS: The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area. CONCLUSIONS: The reduction of the prostatic blood supply was suggested to be the result of a decrease in dihydrotestosterone content and the reduction in the luminal area of capillaries. The early reductive effect of antiandrogens on the prostatic blood supply suggests an alternative use for antiandrogens independent of their typical use for prostate volume regression. The results support the basic aspects of the advantage of preoperative treatment with CMA, flutamide, and bicalutamide, similar to finasteride, in reducing perioperative hemorrhage.
We present here a hook that can be used to free both hands from holding the endoscope during endourological procedures. We made the hook from a wire hanger, and thus, it is a convenient, cheap and easy tool to make using this everyday item. As this hook makes the insertion of the endoscope into the urethra easier, it allows urologists to perform endourological procedures, which require the handling of biopsy forceps, a basket wire and lithotripsy probes, unassisted.
In order to discover whether or not a Denis Browne splint is an effective orthosis in the conservative treatment of congenital club foot, we investigated clinically and radiologically 34 congenital club feet treated with full-time splint wearing after serial manipulations and casts. We found objectively that the correction achieved by the initial treatments was not improved but was at least maintained. However, the age when the splint was applied statistically influenced the changes in radiological measurements. The Denis Browne splint with a well-molded heel is an effective orthosis to maintain clinical and radiological results after initial treatments, especially when it is applied at an early age.
The purpose of this study was to clarify the androgen-ablation-induced morphological changes in the capillaries and stroma near the epithelial cells in prostate and seminal vesicles (SV) using transmission electron microscopy (TEM). In ventral prostate (VP) and SV of immature male rats, the luminal areas of subepithelial capillaries and the width of the stromal layers between endothelia and epithelia were measured quantitatively after castration using TEM and a computed image analyzer. The luminal areas of the capillaries were significantly reduced in VP and SV in the short-term after castration. In the stromal layer, the width of the collagen layer surrounding the capillary significantly increased in VP and SV in the long-term after castration. These data suggest that the reduction of the capillaries and the thickening of collagen surrounding them are related to the involution of glandular epithelial cells in VP and SV after castration.
Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.
BACKGROUND: A study was carried out to gain extensive understanding of the disease status in patients who had suffered and died of urological neoplasms. METHODS: The subjects were 524 patients who had died at the Department of Urology of Gunma Cancer Center. The autopsy rate for each urological, neoplasm, the extent of the disease, and incidental diseases were analyzed. RESULTS: Autopsies were performed in 27.1% (142/524) of the patients. Frequent metastatic sites were the lymph nodes, bone, and lung in prostate neoplasms; the lymph nodes, liver, and lung in bladder neoplasms; and the lymph nodes, lung, and bone in kidney neoplasms. In the 116 patients with these three major urological neoplasms, the autopsy findings of all patients were compatible with progression of the disease, except for 5 cases (acute myocardial infarction in 2 and liver failure in 3). Multiple primary cancers were seen in 21.6% (25/116), and other cancers that caused death, apart from those at urological sites, were confirmed in 7 patients (pancreas in 2, and esophagus, lung, gallbladder, liver, and uterus in 1 patient each). CONCLUSION: Autopsies revealed the macroscopic and microscopic extent of the disease and the presence of incidental disease beyond the diagnosis made in the patient's lifetime.
BACKGROUND: Tumor-associated tissue eosinophilia (TATE) occurs in many kinds of cancer. This study analyzed whether TATE improves the survival of penile cancer patients. METHODS: In 17 patients with penile cancer, survival was compared between the TATE-positive group and the TATE-negative group. Tissue eosinophils were observed by transmission electron microscopy. RESULTS: In all cases, 5-year survival was 72.9% in the TATE-positive group (n = 8) and 38.9% in the TATE-negative group (n = 9; P = 0.131). In stage III and IV, it was 60% in the TATE-positive group (n = 5) and 0% in the TATE-negative group (n = 5; P = 0.058). Transmission electron microscopy images revealed the vigorous infiltration of tissue eosinophils. CONCLUSIONS: It is suggested that TATE improves the survival of patients with advanced penile cancer. However, a greater number of subjects is needed to prove statistical significance.
BACKGROUND: We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable selection to discriminate between GR and nGR revealed that the time from sEBRT initiation to the nadir PSA was the most significant factor (P = 0.000097). Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.
Femoral distraction was done in rats to determine whether the injection of osteoblastlike cells with collagen gel into the distracted callus was useful for new bone formation. The cells were obtained from the femoral marrow of Sprague-Dawley rats and cultured for approximately 3 weeks. These rats were divided into four groups. The rats in Group A received injections of physiologic saline, those in Group B received injections of collagen gel, those in Group C received injections of cells, and those in Group D received injections containing a mixture of cells and collagen gel. The distracted areas were harvested and evaluated by histologic analysis, radiography, three-point bending testing, and the weight of femoral ash. Histologic evaluation did not show an immunoreaction between the donor and recipient. Radiographs showed that Group D had the most callus, and the fracture strength in this group as determined by the three-point bending test was higher than in Group A at 2, 4, and 6 weeks after elongation was completed. Group D showed a significant difference in the ash weight of the distracted femurs at 2 weeks. The current study showed that osteoblastlike cells with collagen gel promoted new bone formation in the distracted gap, and shortened the consolidation period.
An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.
It is known that abnormal androgen dynamics in the tissues is a cause of androgen-dependent disorders. Investigation of tissue androgen levels could provide a clue to the elucidation of disorders. However, it is difficult to measure a trace amount of androgen in the tissues. We established a highly sensitive simultaneous quantification method of testosterone and dihydrotestosterone (DHT), which play the most important roles in the body among androgenic steroids in trace amounts, and investigated time course changes in testosterone and DHT levels in male accessory sex organs, serum, and seminal fluid after castration in rat models. In addition, changes in the testosterone/DHT ratio of male accessory sex organs and seminal fluid were observed. The simultaneous testosterone and DHT measurement method established by us was validated. Intra-assay variation and interassay precision and accuracy were all within +/-20%, and the quantification limits of testosterone and DHT were both 15.6 pg/g. With the use of this method, the testosterone and DHT levels in the prostate, seminal vesicles, and serum immediately after castration were similar to those previously reported. The testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which showed dominance of DHT in seminal fluid, although it was not as marked as that in the male accessory sex organs. Androgens decreased with time after castration in the accessory sex organs, serum, and seminal fluid. In the prostate and seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the normal levels, respectively, 72 hours after castration. The serum levels were under the quantification limits 6 hours after castration and thereafter. In seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal levels, respectively, 72 hours after castration. The testosterone/DHT ratio in the male accessory sex organs was lower in the prostate (0.06) than in the seminal vesicles (0.13) immediately after castration. In the seminal fluid, changes in the ratio were small compared with those in the accessory sex organs and serum. These results showed that our method was capable of measuring testosterone and DHT in very small amounts of samples such as prostate biopsy specimens, and it might provide a clue to the elucidation of the pathology of androgen-dependent disorders.
BACKGROUND: To investigate the relationship between two common variants (Ser217 and Ala541) of the HPC2/ELAC2 gene and prostate cancer risk in a Japanese population, we performed a case-control study. MATERIALS AND METHODS: Cases and controls consisted of 81 prostate cancer patients with a family history and 106 controls. Ser217 and Ala541 polymorphisms were analyzed by the restriction fragment length polymorphism method. RESULTS: In controls, 94.5% and 100.0% had wild-type Ser217Ser and Ala541Ala genotypes, respectively. 5.7% of the controls had the Leu217 genotype. No Thr541 genotype was observed in the controls. 92.6% and 97.5% of the cases had the Ser217Ser and Ala541Ala genotypes. No significant differences were observed in the genotypic frequencies between controls and cases. We stratified prostate cancer cases according to the pathological grade (low- or high-grade) or the clinical stage (localized or metastatic). There was no statistical difference between the genotypic frequencies between the groups. CONCLUSION: The present study suggested that the common variants in the HPC2/ELAC2 gene play a limited role in the risk of prostate cancer in the Japanese population.