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Y Fukabori

Publications and source records attributed to Y Fukabori.

At least 19 recordsLinked to original sources
PubMed2001

Long term follow-up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4.0 ng/ml or less.

BACKGROUND: Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. METHODS: Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. RESULTS: Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. CONCLUSIONS: It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0-4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL.

Aged↗
PubMed2001

Developmental changes in cyclooxygenase mRNA expression in the kidney of rats.

Prostaglandins, synthesized by cyclooxygenase (COX), regulate renal hemodynamics and also epithelial water and solute transport. To determine whether COX mRNA expression changes with age, we studied expression in renal medulla and in cortex in developing rats at various ages. We also examined age-related changes in COX mRNA expression induced by lipopolysaccharide (LPS). COX mRNA was quantitatively analyzed in a real-time polymerase chain reaction (PCR) with dual-labeled fluorogenic probes. COX-1 mRNA expression did not change with age in cortex or medulla. COX-2 mRNA expression was highest in 1-week-old rats and lowest in 4- and 8-week-old rats. Lipopolysaccharide treatment did not alter COX-1 mRNA expression in infantile or adult rats. In adults, LPS at 1, 5, and 10 mg/kg induced COX-2 mRNA expression in renal medulla; the higher doses, 5 and 10 mg/kg, induced COX-2 expression in cortex. In infantile rats, COX-2 mRNA, already high in the unmanipulated state, was further increased by only 1 mg/kg LPS in both renal cortex and medulla. Age-related changes in the expression of COX-2 mRNA might be responsible for changing physiologic characteristics of renal function during postnatal development in rats, and may be important in renal cortical development.

Aging↗
PubMed2001

Novel amino acid substitutional mutation, tyrosine-739-aspartic acid, in the androgen receptor gene in complete androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder. The molecular mechanism of AIS is reduction or absence of androgen signalling caused by androgen receptor (AR) malfunction or absence. The phenotype of AIS varies from a complete female phenotype (complete AIS, CAIS) to male genitalia with mild hypospadias (partial AIS, PAIS). In the current study, we characterize a novel point mutation in the ligand binding domain of the AR gene in a 50-year-old Japanese CAIS patient. Sequence analysis showed a single point mutation at nucleotide 3359 (Genbank, NM 000044), T to C, in exon E in the AR gene. This mutation led to the conversion of codon 739 tyrosine into aspartic acid in the ligand binding domain. No specific androgen binding was detected in genital fibroblasts isolated from the patient. Transcriptional activating activity of the mutant AR was examined by transient DNA transfection into COS-1 cells. Wild-type AR successfully activated androgen inducible MMTV promoter dose-dependently. In contrast, the mutant AR did not activate MMTV promoter. Thus, we demonstrated the molecular characteristics of the novel point mutation in the ligand binding domain of the AR gene associated with CAIS. This information will provide a further understanding of the structure and function of the AR gene.

Amino Acid Substitution↗
PubMed2001

A simple and reliable monitoring system to confirm the preservation of the cavernous nerves.

BACKGROUND: It is important to establish a procedure with which to confirm the preservation of the cavernous nerves during nerve-sparing radical surgery. For this purpose, we examined changes in intracavernous pressure (ICP) following electrical stimulation of the neurovascular bundle (NVB) with respect to the continuity of the cavernous nerves. METHODS: Six cases of radical prostatectomy and eight cases of radical cystoprostatectomy were examined. In all cases, prior to prostate removal, electrical stimulation of the site where the NVB was determined to run was performed and the changes in ICP measured. In eight cases, ICP changes were also measured following prostate removal. RESULTS: Prior to prostate removal, ICP changes could be measured in all 28 sides of 14 cases. These changes were classified into two patterns: stimulation-related increases of convex waveform (t1) were observed in 24 sides (85.7%); and waveforms with reversed type (t2), which was thought to be an incomplete type t1, were observed in four sides (14.3%). There were no ICP changes following non-sparing or incomplete sparing of NVB macroanatomically. Of five sides where the NVB was supposedly completely preserved macroanatomically, ICP changes consisted of type t1 on three sides, t2 on one side and type t2 or no change on a single side. All measurements were obtained within 10 min. Neither electrical stimulation nor measurement of ICP caused any adverse effects. CONCLUSION: Intraoperative stimulation of the NVB while monitoring ICP changes provides a simple and reliable method of accurately evaluating the preservation of the cavernous nerves.

Aged↗
PubMed2001

Comparison of histological compositions and apoptosis in canine spontaneous benign prostatic hyperplasia treated with androgen suppressive agents chlormadinone acetate and finasteride.

PURPOSE: Chlormadinone acetate and finasteride are androgen suppressive agents clinically used for benign prostatic hyperplasia but their mechanism for inducing prostatic atrophy differs. We investigated the effect of these androgen suppressive agents on prostatic histology and apoptosis using the spontaneous canine benign prostatic hyperplasia model. MATERIALS AND METHODS: Animals were treated with oral chlormadinone acetate or finasteride for 25 weeks. The prostatic volumes were analyzed every 5 weeks. Prostatic androgen and estrogen concentrations, histological composition and apoptosis were determined at the end of treatment. Apoptosis was measured by in situ labeling of 3' hydroxy ends of the DNA breaks using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method. RESULTS: There was a similar volume reduction effect with 0.3 mg./kg. chlormadinone acetate daily and 1 mg./kg. finasteride daily. Chlormadinone acetate decreased testosterone and dihydrotestosterone but finasteride decreased only dihydrotestosterone in the prostate gland. The concentration ratio of estradiol-to-total androgen in the prostate was significantly increased in finasteride treated canines. Chlormadinone acetate and finasteride decreased the epithelial and stromal components. The extent of apoptosis observed in the prostate was significantly higher in the chlormadinone acetate group compared to that of the control and finasteride groups. CONCLUSIONS: Although a similar effect of chlormadinone acetate and finasteride was observed in the induction of prostatic regression and composition of the histological components, the sustained increase in apoptosis was observed only in chlormadinone acetate treated canines. We suggest that different intraprostatic endocrine environments created by chlormadinone acetate or finasteride, which have different intraprostatic testosterone levels and estradiol-to-androgen ratios, may be responsible for the different outcomes in the extent of apoptosis.

Androgen Antagonists↗
PubMed2001

[Suppressive effects of the antiandrogen flutamide on adrenal androgens in advanced prostate cancer patients].

PURPOSE AND METHODS: We investigated the influence of flutamide on plasma adrenal androgens in advanced prostate cancer patients treated with dietylstilbestrol diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist (LH-RH agonist). Nine patients were enrolled in this study and they were divided into the following two treatment groups; group A: LHRH agonist mono-therapy (n = 4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up, all patients were treated with DES-DP. RESULTS: Two-week DES-DP administration led to reduction of plasma adrenal androgen levels. These levels were kept lower for 16 weeks in group B in contrast with group A in which the levels returned to the pretreatment levels. Basal ACTH levels in group B were significantly lower than those in group A. CONCLUSION: From our observations, we found that flutamide reduced adrenal androgen levels in prostate cancer patients treated with LH-RH agonist. ACTH suppression might be related to this phenomenon.

Adrenocorticotropic Hormone↗
PubMed2001

NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer.

Interleukin (IL)-15 is a pleiotropic cytokine that is important for innate and adaptive immune cell homeostasis. The expression of IL-15 protein is controlled by posttranscriptional mechanisms. Here, we constructed a human IL-15 expression vector consisting of the human IL-2 signal peptide, the human IL-15 mature peptide-coding sequences, and an out-of-frame human growth hormone gene. Human prostate cancer cells, PC-3, transfected with this highly secretable form of the IL-15 gene, successfully secreted abundant bioactive IL-15 protein. In nude mice, the growth of PC-3 cells producing IL-15 was remarkably retarded. NK cell-depletion using anti-asialo GM1 antibody restored tumorigenicity. Histologically, tumors derived from IL-15-producing PC-3 cells contained necrotic areas with high apoptotic index. Splenocytes incubated with supernatant of transfectants killed target PC-3 cells and expressed a significantly high level of mIFN-gamma mRNA. These observations suggest that NK cell-mediated, anti-tumor effects of IL-15 could provide a potential rationale for gene therapy of prostate cancer.

Adenocarcinoma↗
PubMed2000

Usefulness of age-specific reference range of prostate-specific antigen for Japanese men older than 60 years in mass screening for prostate cancer.

OBJECTIVES: To investigate the age-specific reference range of prostate-specific antigen (PSA) in Japanese men older than 60 years of age by analyzing the receiver operating characteristic (ROC) curve. Several reports have noted that many clinically serious cancers are missed by raising the cutoff value of the age-specific PSA reference range for men older than 60 years. METHODS: We studied 6744 individuals who had undergone mass screening for prostate cancer in Gunma Prefecture from 1994 to 1998. PSA determination was the first step of the mass screening in all subjects. Digital rectal examination and transrectal ultrasonography (TRUS) were performed in all except in a fraction of patients. Subjects with an abnormal PSA level or abnormal digital rectal examination or TRUS findings underwent TRUS-guided systematic sextant biopsies. Patients older than 60 years of age were grouped according to their age at 5-year intervals, and the cutoff value of the age-specific PSA reference range was calculated for each age group by analyzing the ROC curve. RESULTS: The diagnostic efficiency of the age-specific PSA reference range was optimal with cutoff values of 3.0, 3.5, 4.0, 4.0, and 7.0 ng/mL in subjects 60 to 64, 65 to 69, 70 to 74, 75 to 79, and older than 80 years of age, respectively. By using the age-specific PSA reference range as determined by the ROC curve, the sensitivity, specificity, and efficiency increased to 92.4%, 91.2%, and 84.3%, respectively. When the standard PSA reference range was used for the diagnosis, the sensitivity, specificity, and efficiency was 89.1%, 92.4%, and 82.3%, respectively. All of the cases of prostate cancer detected by using the age-specific PSA reference range with the cutoff point based on the ROC curves were clinically significant. CONCLUSIONS: The age-specific PSA reference range cutoff value in this setting demonstrated better diagnostic efficiency than the standard cutoff value of PSA and the age-specific PSA reference range determined by the 95% confidence interval. It appears likely to be a useful diagnostic index for the first step of mass screening in Japanese men.

Age Distribution↗
PubMed2000

Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition.

BACKGROUND: It is well-known that the incidence of benign prostatic hyperplasia (BPH) increases with aging. The age-dependent changes in the ratio of serum sex steroid concentrations may play a role in BPH development. To clarify the relationship between the prostatic tissue concentrations of these steroids and age, we established a precise method of simultaneous quantitative analysis for prostatic sex steroids and used this method to investigate the tissue concentrations of three major sex steroids (testosterone, dihydrotestosterone, and estradiol) in the human prostate. METHODS: The methodology for the simultaneous quantitative analysis of prostatic sex steroids was established using castrated rat prostatic tissue, coupled with internal standards, for androgen-deprived medium, and the validation of the method was examined. Human prostatic tissues were collected during surgery and immediately frozen at -70 degrees C. Using our method, the steroidal fractions were extracted, purified, and quantified. The proportions of stroma, epithelium, and glandular lumen were measured on each histological specimen, using an image analyzer. RESULTS: The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of testosterone, dihydrotestosterone, and estradiol in the prostate. In humans, the prostatic dihydrotestosterone concentration decreased with age, but the concentrations of testosterone and estradiol showed no relation with age. Therefore, the ratio of estradiol to dihydrotestosterone concentration (E2/DHT) in prostate increased with age. The E2/DHT ratio showed a significant positive correlation with the proportion of stroma. CONCLUSIONS: The age-dependent decrease in prostatic dihydrotestosterone and constant estradiol concentration lead to a relatively estrogen-dominant environment compared to that at younger ages. We assume that this relatively estrogen-dominant status induces stromal proliferation by some mechanism and leads to the development of BPH.

Aged↗
PubMed2000

Correlation of prostate-specific antigen before prostate cancer detection and clinicopathologic features: evaluation of mass screening populations.

OBJECTIVES: Although prostate-specific antigen (PSA) has become the reference standard for prostate cancer diagnosis, few reports have examined the long-term changes in PSA values before the diagnosis of prostate cancer in a large number of subjects. We investigated serial PSA levels and related values before prostate cancer diagnosis in a mass screening population and analyzed the values in an attempt to discover some values useful in clinical diagnostic science. METHODS: We performed mass screening for prostate cancer in 9671 subjects from 1986 to 1998. The initial screening method was measurement of prostatic acid phosphatase from 1986 to 1991 and measurement of PSA from 1992 to 1998. As a result, 303 cases of prostate cancer were diagnosed. For all the cases diagnosed before 1991, we measured the serum PSA value in preserved frozen serum. RESULTS: The prostate cancer detection rate was 3.1% among all subjects observed during the 13-year period. By measurement of the PSA level using frozen serum during the pre-PSA era, we found that 62% of patients demonstrated a PSA abnormality for more than 1 year (average 2.8) before prostate cancer diagnosis. Prostate cancer that was diagnosed within 1 year after a PSA value became abnormal was not associated with bone metastasis. Concerning the relationship between PSA velocity (PSAV) and clinical stage, the proportion of Stage B cancer was 86% in the subjects whose PSAV level before diagnosis was 0.18 ng/mL/yr or less and it was only 29% in those with PSAV levels of 4.5 ng/mL/yr or more. Only 3 (3.5%) of 86 patients with prostate cancer with PSAV levels of 4.4 ng/mL/yr or less had bone metastasis, and 2 of those 3 patients had poorly differentiated adenocarcinoma. CONCLUSIONS: Although a total of 62% of patients had an abnormal PSA level more than 1 year before prostate cancer diagnosis, no patients with prostate cancer who were diagnosed within 1 year after the PSA level became abnormal had bone metastasis. Among patients who have undergone mass screening twice or more, a clinically useful indicator of the lack of bone metastasis would be a period between the detection of PSA levels of 4.1 ng/mL or more but not more than 10 ng/mL and prostate cancer diagnosis of less than 1 year and a diagnosis of well or moderately differentiated adenocarcinoma or a PSAV of 4.4 ng/mL/yr or less and a cancer diagnosis of well or moderately differentiated adenocarcinoma.

Adult↗
PubMed2000

Clinical characteristics of prostate cancer in Gunma prefecture.

Prostate cancer clinical data from patients registered at Gunma University Urologic Oncology Study Group were compared between pre-PSA and PSA eras, dividing them between those patients diagnosed at clinical practice and those diagnosed on the Gunma mass-screening programme. In the MS, the number of incidents of prostate cancer increased from 126 out of 16750 screened cases in the pre-PSA era (0. 75%) to 227 out of 19782 screened cases in the PSA era (1.15%). The average age was lower in the PSA era. As for clinical stage, stage B and C cases increased while stage D cases decreased. For the clinical practice cases at the Gunma University Urologic Oncology Study Group, the number of registered incidents of prostate cancer increased from 1164 in the pre-PSA era to 2098 in the PSA era. The average age was similar between the pre-PSA and PSA eras. The percentage of cases who were stage D declined from 46.1 during the pre-PSA era to 37.7 in the PSA era. In the PSA era, earlier and more cases of prostate cancer are diagnosed both in clinical practice and in the mass screening program in Gunma Prefecture.

Aged↗
PubMed2000

Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia.

OBJECTIVE: It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated. METHODS: (1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X). RESULTS: Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly. CONCLUSIONS: TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.

5-alpha Reductase Inhibitors↗
PubMed1999

Regulation by interleukin-1beta of gene expression of bradykinin B1 receptor in MH-S murine alveolar macrophage cell line.

The effects of recombinant murine interleukin (IL)-1beta on gene expression of murine bradykinin B1 receptor (BDKRB1) in MH-S murine alveolar macrophage cell line were evaluated. BDKRB1 mRNA expression in MH-S cells was increased by IL-1beta (1, 3, and 10 ng/ml) in a time-dependent manner, peaking at 3-4 h by 100-1000 fold. IL-1beta (5 ng/ml, 24h) also induced significant binding to [3H]-des-Arg10-kallidin with a dissociation constant (Kd) of 2.95 nM and a maximal binding density (Bmax) of 670 sites/cell. Des-Arg10-kallidin (10 microM), a BDKRB1 agonist, increased intracellular calcium ion ([Ca2+]i) in IL-1beta (5 ng/ml, 24 h)-exposed cells, an increase not observed in the cells not exposed to IL-1beta. A significant increase of tumor necrosis factor (TNF)-alpha secretion occurred in the IL-1beta (5 ng/ml, 24 h)-exposed cells following addition of des-Arg10-kallidin (the IL-1beta-exposed group: 57. 8 +/- 13.7 vs. the vehicle-exposed group: 16.7 +/- 4.3 pg/ml, p < 0.05 after a 100 nM des-Arg10-kallidin for 8 h), with an optimal effect at 3-100 nM. These data suggest that IL-1beta may up-regulate BDKRB1-mediated functions of alveolar macrophages via an induction of BDKRB1 gene expression.

Animals↗
PubMed1999

Androgen-stimulated human prostate epithelial growth mediated by stromal-derived fibroblast growth factor-10.

It has been suggested that prostate homeostasis is regulated indirectly by androgens through stromal-epithelial interactions in part by factors from the stromal cells acting on receptors in epithelial cells. In this report, the role of fibroblast growth factor (FGF)-10 in prostatic epithelial proliferation was investigated. The expression of FGF-10 mRNA was apparent in primary-cultured stromal cells, but not in epithelial cells derived from human tissue from patients with benign prostatic hyperplasia (BPH). The mitogenic activity of human recombinant FGF-10 assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation was demonstrated in isolated epithelial cells, but not in cultured stromal cells. No mitogenic activity of dihydrotestosterone (DHT) for either epithelial or stromal cells could be demonstrated, but quantitative PCR (real-time PCR) with a double-labeled fluorogenic probe demonstrated that expression of FGF-10 in stromal cells was enhanced 5.3-fold at a DHT concentration of 100 pM. Androgen receptor mRNA levels showed no significant change with DHT at concentrations less than 100 pM, but were reduced to 50% of control levels at a DHT concentration of 10 nM. These results suggest that stromal-derived FGF-10 stimulates human prostatic epithelial growth and its mRNA expression is induced by androgens, without an increase in the androgen receptor mRNA. Moreover, FGF-10 may be involved in the development or support of human BPH.

Androgens↗
PubMed1999

Immunohistochemical characteristics of estrogen receptor alpha positive cells in glandular epithelium of the rat seminal vesicle.

Epithelial cells of the rat seminal vesicle stained positively for nuclear estrogen receptor alpha (ER alpha). We studied these cells using immunohistochemical means. We demonstrated in a previous study that some glandular epithelial cells of the seminal vesicles of immature castrated rats treated with estrogen for 1-2 weeks had multilayer features. The present study shows that these glandular epithelial cells are nuclear ER and basal cell-specific cytokeratin (34betaE12) positive. These findings suggested characteristics of basal cells. Moreover, we demonstrated that these cells express transforming growth factor beta1 (TGFbeta1) as a result of castration and estrogen treatment. Our findings indicate that glandular epithelial cells with multilayer features, which stained positively for nuclear ER alpha have basal cell features and may play an important role in the expression of TGFbeta1 through an epithelial-stromal interaction.

Animals↗
PubMed1999

[Usefulness of magnetic resonance imaging for the diagnosis of superior lumbar hernia: a case report].

A 48-year-old man consulted us with the chief complaints of right flank mass. On examination, there was a soft bulge on the right superior lumbar area. Since computed tomographic scanning showed subcutaneous fatty tissue, we suspected a superior lumbar hernia. The diagnosis was confirmed by magnetic resonance imaging (MRI) that revealed a lumbar muscle defect and prolapsed fatty tissue around the kidney. During the operation, a small hernia hiatus, 2 cm in width, opened in the superior lumbar triangle. The herniated fatty tissue was excised, and the defect of fascia was closed by overlapping the adjacent fascial structure. No signs of recurrence were found at 3 months postoperatively. The usefulness of MRI for the diagnosis is discussed and previous literature is reviewed.

Hernia, Ventral↗