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Teruaki Iwamoto

Publications and source records attributed to Teruaki Iwamoto.

At least 19 recordsLinked to original sources

Urinary prostate-specific antigen is a noninvasive indicator of sexual development in male children.

Testicular androgen induces the synthesis of prostate specific antigen (PSA) in acinar epithelial cells of the prostate. We examined PSA activity in urine from 136 male children from birth up to 17 years of age. We detected PSA at various intervals in early infant urine over a period of 1-4 months. During this period, urinary secretion of testosterone (T) gradually declined, accompanied by 1 or more surges of T prior to a transient increase in PSA in urine from full- and preterm infants (67%, n = 6). Although mean urinary T concentrations during elevations of PSA in preterm infants were 3.1 and 5.6 times greater than in full-term infants and adults, the overall mean urinary PSA concentration of full and preterm infants was just 45% and 18% that of adults, respectively. PSA was not detected in children aged 0.3 to 9 years, after which a gradual increase in urinary PSA activity was observed after 10 years of age. Urinary PSA activity was markedly persistent after Tanner stage III pubertal development. To our knowledge, this is the first study to demonstrate an induction of PSA during early infancy by bioactive T in normally developing human males. We conclude that urinary PSA is a non-invasive, useful indicator for developmental studies from neonatal and adolescent males, which can be measured with a confirmatory semiquantitative PSA assay.

Adolescent↗

Hormone profiles after intramuscular injection of testosterone enanthate in patients with hypogonadism.

To examine hormone levels after androgen replacement therapy (ART) in Japanese male patients with hypogonadism, nine Japanese male patients with hypogonadism (serum total testosterone (tT) or free testosterone (fT) levels of < or = 2.7 ng/mL or < or = 10 pg/mL, respectively; average age, 59 years) were enrolled. They were treated with 125 mg of testosterone enanthate by single intramuscular injection. Blood samples were collected on the morning of the day of treatment, pre-ART, as well as on days 1 to 7 and day 14 after administration. Serum levels of tT, fT, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were determined. On day 1 after administration, the mean serum levels of tT and fT were 7.62 ng/mL and 23.22 pg/mL, respectively. Serum levels of tT and fT on day 14 after administration were lower than their pre-ART values. One patient exhibited abnormally high serum tT and fT levels of 19.6 ng/mL and 44.4 pg/mL, respectively. Serum levels of LH and FSH began to decrease gradually on day 5 after administration. Serum levels of SHBG did not change throughout the observation period. Serum levels of E2 increased 1.7 times on day 1 after administration but returned to its pre-ART value by day 14 after administration. The dose of testosterone enanthate for male patients with hypogonadism requiring ART should be determined carefully because some patients exhibited high serum levels of androgen beyond the physiological range and gonadotropin was suppressed in all treated patients.

Aged↗

Applicability of Nanotrap Sg as a semen detection kit before male-specific DNA profiling in sexual assaults.

A commercially available semen detection kit, Nanotrap Sg, which employs a one-step detection test based on immunochromatographic assay for the semenogelin protein, was evaluated for profiling male-specific DNA in sexual assault casework samples. While semen diluted with phosphate-buffered saline held and kept at 4 degrees C for 1 week showed a relatively strong signal intensity with Nanotrap Sg, the signal intensity was decreased by dilution after storage at 4 degrees C or freezing and thawing repeated more than three times. The reproducibility of Nanotrap Sg was tested on a total of 174 sexual assault casework samples from three forensic laboratories using intra- and interassay and no variation was observed in the semenogelin (Sg) signal. The positive signal ratio was 12.6% higher for prostate-specific antigen immunochromatographic membrane tests than Nanotrap Sg. Although spermatozoa were not confirmed in 61 (35%) out of 174 samples, Sg-positive signals could be detected from 41 (67%) of the 61 samples. Female genetic profiles could be observed in 95% of the samples, which tested negative for Sg on the Nanotrap Sg test, but no male genetic profiles could be observed. These results suggest that Nanotrap Sg can positively identify samples containing male DNA even in the absence of detectable intact spermatozoa. Further, Sg-positive signals identified samples for which male-specific DNA profiling could be performed, even if no sperm could be detected from the sample. The potential of Nanotrap Sg for identifying forensic samples with male-specific DNA was clearly demonstrated.

Antibodies↗

Altered expression pattern of heat shock transcription factor, Y chromosome (HSFY) may be related to altered differentiation of spermatogenic cells in testes with deteriorated spermatogenesis.

OBJECTIVE: To evaluate the expression patterns of heat shock transcription factor, Y chromosome (HSFY), in the testes showing deteriorated spermatogenesis. DESIGN: Prospective study. SETTING: University hospital, its branch hospital, and academic laboratory. PATIENT(S): Men undergoing testicular biopsy for the investigation of infertility and men undergoing orchiectomy for testicular cancer. INTERVENTION(S): After pathologic evaluation, specimens were subdivided into three groups: normal spermatogenesis (n = 8), maturation arrest (n = 5), and Sertoli cell-only syndrome (n = 4). Immunostaining and Western blotting techniques determined the expression of HSFY. MAIN OUTCOME MEASURE(S): Expression of HSFY in testes. RESULT(S): Western blotting data revealed HSFY in the testicular tissues with normal spermatogenesis, maturation arrest, and Sertoli cell-only syndrome, but the amount of the protein in the maturation arrest and Sertoli cell-only syndrome samples was altered. The immunohistochemical data demonstrated that HSFY was expressed in spermatogenic cells and Sertoli cells in all specimens. However, the expression of HSFY was low or absent in spermatogenic cells of maturation arrest specimens, and the ratio of HSFY expressed in Sertoli cells was different in the specimens with maturation arrest and with Sertoli cell-only syndrome. CONCLUSION(S): Altered expression of the HSFY in the testis showing deteriorated spermatogenesis may be associated with alteration of spermatogenic cell differentiation.

Adult↗

Inter/intra investigator variation in orchidometric measurements of testicular volume by ten investigators from five institutions.

AIM: To perform quality control studies on testicular volume measurements for a multi-center epidemiological study of male reproductive function. METHODS: We constructed a data matrix with a balanced assignment for 2 consecutive days by ten investigators (andrological career: 4-21 years) from five institutions and 12 male volunteers aged 20-26 years. Testicular volume was measured by Prader's orchidometer. A skilled technician also performed an ultrasound estimate of testicular volume. RESULTS: A statistically significant inter-investigator variation was found for both testes (P < 0.05). In addition, there was a statistically significant investigator-by-volunteer interaction in testicular volume measurement (P < 0.01). However, there was no statistically significant difference in the two measurements performed on consecutive days for either testis. The testicular volumes for both the right and left testes as estimated by ultrasonography were smaller than results using the orchidometer. However, there was no statistical significance (P > 0.05). The difference in experiences of the investigators did not significantly correlate with accuracy of measurements in either testis. CONCLUSION: The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.

Adult↗

DNA damage caused by bisphenol A and estradiol through estrogenic activity.

Evidence exists that raises concern about genotoxic effects induced by estrogen: oxidative stress caused by estrogen-derived oxidants, DNA adducts formed by estrogen metabolites and estrogen-induced chromosomal aberration. Estrogen receptors (ER) participate in some of these genotoxic effects by estrogen. In this study, we showed the effects of bisphenol A (BPA), an endocrine-disrupting chemical eliciting weak estrogenic activity, and of 17beta-estradiol (E2), on DNA damage in ER-positive MCF-7 cells by Comet assay. Higher concentrations of BPA, more than 1000 times of E2, were needed to induce the same levels of effects by E2. Immunofluorescence microscopy showed that gammaH2AX, an early marker of DNA breaks, increased after treatment with E2 or BPA in MCF-7 cells. gammaH2AX foci colocalized with Bloom helicase, which is considered to be responsible for the repair of DNA damage after treatment with E2 or BPA. Interestingly, DNA damage was not as severe in ER-negative MDA-MB-231 cells as in MCF-7 cells. The ER antagonist ICI182780 blocked E2 and BPA genotoxic effects on MCF-7 cells. These results together suggest that BPA causes genotoxicity ER dependently in the same way as E2.

Benzhydryl Compounds↗

[Effects of endocrine disrupting chemicals on male reproductive function--epidemiological views].

Numerous medical studies have recently focused on the adverse trends in human male reproductive health including possible decline in semen quality and increasing incidences of reproductive anomalies such as testicular cancer, cryptorchidism and hypospadias, which have been reported from many counties during past decades. We have no sufficient evidence on the basis of which we could determine whether human male reproductive health is really declining and whether endocrine disrupting chemicals are responsible for this observed decline. However, Skakkebaek's group has currently proposed a hypothesis that the male reproductive problems are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. According to this hypothesis, TDS is a result of the disruption of embryonal programming and gonadal development during the fetal stage and the recent rise in the prevalence of TDS may be causally linked to endocrine disrupting chemicals affecting genetically susceptible individuals. This review aims to give a brief overview of the suspected adverse trend in human male reproductive health and current data associated with TDS.

Endocrine Disruptors↗

A rapid and simple system of detecting deletions on the Y chromosome related with male infertility using multiplex PCR.

Around 10% of males with idiopathic azoospermia or oligozoospermia, which are important causes of male infertility, have partial deletions on the long arm of the Y chromosome. To develop a rapid and accurate detection system for screening major Y deletions found in infertile men, we developed a multiplex PCR system that can simultaneously amplify five loci on the Y chromosome, SRY, AMELY, DBY, RBMY, DAZ and one locus on the X chromosome, AMELX. The size of the PCR products was designed to increase gradually from the distal Yp to the distal Yq. Our system could detect deletions of three major candidate regions for the azoospermic factor, AZFa, AZFb and AZFc on the Y chromosome together with sex. The gradual increase in the size of the PCR products was convenient for imaging the location of deletions on the Y chromosome. Moreover, the multiplex PCR system was combined with microchip-based electrophoresis, and the PCR products derived from each locus were separated within 4 min. Our system is useful for screening Y chromosomes bearing the structural anomalies including three major AZF deletions found among azoospermic or oligozoospermic males.

Base Sequence↗

Molecular analysis of TBL1Y, a Y-linked homologue of TBL1X related with X-linked late-onset sensorineural deafness.

Recent progress in sequencing the human Y chromosome has unveiled a series of X-Y homologous genes. In the present study, we focused on Transducin beta-like 1Y (TBL1Y), which is a Y-linked homologue of TBL1X that is related with X-linked late-onset sensorineural deafness. Recently, it has been shown that TBLR1, another homologue whose gene resides on chromosome 3, and TBL1X act as a corepressor/coactivator exchanger for several nuclear receptors and transcription factors. However, the expression pattern and function of TBL1Y remain unknown. The RT-PCR analysis of the TBL1 family revealed that TBL1Y was expressed in all 13 tissues examined but not in leukocytes. Among the cell lines tested, however, it was only expressed in NT2/D1 cells and in lymphoblasts transformed with Epstein Barr (EB) virus. To compare the functions of the TBL1 family, we generated a series of expression plasmids for GAL4DBD-fused proteins of the TBL1 family. We carried out dual luciferase assays using these plasmids in combination with a plasmid having a luciferase reporter gene harboring 5xGAL4 binding sites. Unlike the other constructs, GAL4DBD-fused TBL1Y did not repress the promoter activity. Moreover, we found three novel polymorphisms in the TBL1Y gene, IVS7+9G>A, G268C, and IVS7+1G>C, which is presumed to cause splicing error. These polymorphisms are found in males within Y-haplogroup O3 (XO3e), which is defined as the Y-haplogroup O3 excluding O3e, a branch of O3. The results show that TBL1Y differs from other members of the TBL1 family in expression and function, suggesting other roles in maleness.

Age of Onset↗

Morphological abnormalities in the spermatozoa of fertile and infertile men.

The morphological analysis of the spermatozoa from fertile and infertile men was performed using light and electron microscopy to clarify the relationship between sperm morphology and fertility. Semen samples obtained from 22 partners of pregnant women were prepared according to the protocol standardized in an international collaborative study. Semen samples from 17 patients with asthenozoospermia or varicocele were collected in a hospital. Abnormalities in the spermatozoa were classified into three types for the tails, two for the midpieces, and six for the heads according to the criteria adapted from WHO guidelines (World Health Organization, 1999: WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction (4th edition)). Approximately 14% of the spermatozoa from the fertile men had abnormal tails at the light microscopic level while approximately 44% had abnormal heads. Most types of abnormalities found in the spermatozoa from the asthenozoospermic and varicocele patients were encountered in those from the fertile men, although the semen from the fertile men contained a higher percentage of normal spermatozoa than that from the patients. These results were also confirmed at the ultrastructural level. Most abnormal cell types are encountered in semen from fertile men, although the incidence of abnormalities is low.

Case-Control Studies↗

Survey of the two polymorphisms in DAZL, an autosomal candidate for the azoospermic factor, in Japanese infertile men and implications for male infertility.

The DAZL (DAZ-like) gene is suggested to be an ancestral gene of the DAZ (deleted in azoospermia) gene on the Y chromosome, which is a strong candidate for the azoospermic factor. Recently, it has been reported that the T54A (Thr54-->Ala) polymorphism in exon 3 of the DAZL gene is associated with spermatogenic failure in the Taiwanese population. In this study, to investigate whether this polymorphism is associated with spermatogenic failure in Japanese males, we analysed genomic DNA derived from 234 patients with azoospermia or oligozoospermia and 131 fertile controls. The T54A polymorphism was completely absent in both the patients and the controls. The T12A (Thr12-->Ala) polymorphism in exon 2 of the DAZL gene was found at a similar frequency in the patients and controls, 15.4% and 13.7%, respectively (P = 0.67). However, the frequency of T12A was higher for the azoospermic (20.5%) than oligozoospermic (9.6%) individuals in infertile men without DAZ deletions, although statistical difference was not so apparent (chi2 test: P = 0.037, OR = 2.413, 95% CI = 1.035-5.629; Yate's chi2 test: P = 0.058, OR = 2.319, 95% CI = 0.973-6.166). Our results show that the T54A polymorphism in DAZL has no major role in Japanese males with azoospermia or oligozoospermia. The distribution of the T54A polymorphism may be restricted to the narrow area including Taiwan.

Adult↗

Relationships between erectile dysfunction, depression, and anxiety in Japanese subjects.

AIMS: This study aimed to elucidate the relationships between erectile dysfunction (ED) and depression or anxiety. METHODS: Subjects were 1,419 Japanese men aged 40-64 years. ED was assessed by the International Index of Erectile Function 5 (IIEF-5) score (Japanese version), and depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). In this study ED cases were defined as those whose IIEF-5 value was less than 12, and a score of 8 or higher was used to classify a subject as suffering from depression or anxiety, respectively. The prevalence odds ratio (OR) of ED was calculated with confidence interval (CI) estimated by the Woolf's method by five age groups (40-44, 45-49, 50-54, 55-59, 60-64 years). To control for age, body mass index, smoking, and alcohol drinking factors, we conducted the multivariate logistic regression analysis for calculating adjusted ORs and 99% CIs. RESULTS: ED was significantly associated with depression in age groups 45-49 (OR 3.42, 99% CI 1.51-7.76) and 50-54 years (OR 2.43, 99% CI 1.11-5.35). After using multivariate analysis, adjusted OR also showed statistical significance. (OR 2.02, 99% CI 1.32-3.08). ED was significantly associated with anxiety in the 50-55-year-old age group (OR 2.48, 99% CI 1.12-5.47). After using multivariate analysis, adjusted OR also showed statistical significance (OR 1.77, 99% CI 1.15-2.72). The concomitant depression and anxiety group (A+D+) had significantly higher prevalence of ED than the control group (A-D-) in both the 45-49 and 50-54 age groups. (P < 0.01) CONCLUSION: ED associated significantly with depression and anxiety status only in late 40s to early 50s (45-55 years) in male Japanese. Furthermore, comorbidities of depression and anxiety strengthen this association. Our results might be useful in furthering understanding of ED etiology and determining a target population for prevention in ED subjects.

Adult↗

HST-1/FGF-4 plays a critical role in crypt cell survival and facilitates epithelial cell restitution and proliferation.

The fibroblast growth factor-4 (HST-1/FGF-4) is a heparin-binding growth factor that influences on epithelial and many other cells through interaction with FGF receptors. It has been demonstrated that the HST-1/FGF-4 gene protects mice from lethal irradiation by preventing bone marrow damage and intestinal tract damage. However, the radioprotective mechanism is unknown. In this study, we have investigated the expression of Hst-1/Fgf-4 in mouse small intestine after irradiation, and determined the role of HST-1/FGF-4 in mouse intestinal crypt cell survival and epithelial cell proliferation and restitution. We found the induction of endogenous Hst-1/Fgf-4 expression in intestine when mice are exposed to 9.0 Gy irradiation. Laser-captured microdissection (LCM) coupled with RT-PCR analysis revealed that expression of Hst-1/Fgf-4 was found in epithelial cell of the villi and crypt cells. Pretreatment of HST-1/FGF-4 caused an increase in the number of surviving crypt cells, and clearly suppresses the radiation-induced apoptosis of the crypt cells. Moreover, exogenous HST-1/FGF-4 enhances epithelial cell restitution and proliferation in an in vitro model. These data suggest that HST-1/FGF-4 is induced by irradiation injury, and that HST-1/FGF-4 will find a therapeutic role in the prevention of intestinal cell toxicity following intensive chemotherapy and radiation therapy protocols, and in allogenic cell transplantation.

Animals↗

Molecular characterization of heat shock-like factor encoded on the human Y chromosome, and implications for male infertility.

Azoospermia and oligospermia are major causes of male infertility. Some genes located on the Y chromosome are suggested as candidates. Recently, HSFY, which is similar to the HSF (heat shock transcription factor) family, has been mapped on the human Y chromosome as multicopies. However, newly available sequence data deposited at NCBI shows that only the HSFY gene located on Yq has a long open reading frame containing a HSF-type DNA-binding domain. HSFY is similar to LW-1 on the human X chromosome and a murine HSFY-like sequence (mHSFYL), 4933413G11Rik, on the mouse chromosome 1. LW-1 and mHSFYL have 53% and 70% homology to HSFY for amino acid sequences of their presumed DNA-binding domains, respectively. Comparison of the presumed DNA-binding domains unveiled that the three HSF-like factors, HSFY, LW-1, and mHSFYL, belong to a different class than conventional HSFs. When we screened for deletions on the Yq of males suffering from infertility, we found that HSFY was involved in interstitial deletions on the Y chromosomes for two azoospermic males who had DBY, USP9Y, and DAZ but did not have RBMY located on the AZFb. Expression analysis of HSFY, LW-1, and mHSFYL unveiled that they are expressed predominantly in testis. Furthermore, immunhistochemistry of HSFY in testis showed that its expression is restricted to both Sertoli cells and spermatogenic cells and that it exhibits a stage-dependent translocation from the cytoplasm to the nucleus in spermatogenetic cells during spermatogenesis. These results may suggest that deletion of HSFY is involved in azoospermia or oligospermia.

Adult↗

Rapid detection of semenogelin by one-step immunochromatographic assay for semen identification.

To identify semen in forensic samples, we developed an analytical system for one-step immunoassay that has been constructed using the concept of immunochromatography and can identify semenogelin (Sg), which originates in the seminal vesicles. The system employed monoclonal antibody (mAb) and polyclonal antibody (pAb) against recombinant Sg-II (63 kDa), which has been synthesized in insect cells using baculovirus. The two antibodies bound with the seminal plasma motility inhibitor (SPMI; 14 kDa) as a final fragment peptide of Sg. The test stick is based on the sandwich technique using the above antibodies. When serial dilutions of seminal plasma were analyzed using this test stick, the intensity of a clear immunoreactive signal peaked at 2000-fold dilution. Thereafter, the signals decreased slowly but still persisted up to 400,000-fold dilution. The Sg antigen was undetectable in saliva, urine, breast milk, serum or vaginal secretions. Also, the test stick shown did not react with animal semen samples, such as those from horses, dogs, swine and bulls. When semen samples, diluted 100,000-fold from 100 men were tested, the Sg antigenic activity was detectable in all samples. In addition, the specificity and sensitivity of the test stick for identification of semen were demonstrated by comparative forensic studies. We conclude that this immunoassay method is a useful confirmatory test for the identification of semen. The immunochromatographic system for forensic testing or research use will become available commercially soon.

Animals↗

[Reference ranges of total serum and free testosterone in Japanese male adults].

PURPOSE: To establish reference range of serum Total Testosterone (T-T) and Free Testosterone (F-T) in Japanese male adults. SUBJECTS AND METHOD: Among 1,172 male adults, who daily lived their healthy life, 1,143 subjects in the year range from 20 to 77 years old, who had serum LH concentration within its reference range (For 20-70 years old: 1.1-25.9 mIU/mL), were selected. As diurnal rhythm of both T-T and F-T was observed, blood samples were collected in the morning when T-T and F-T concentration were relatively stable at their high concentration levels. The collected samples were stored at -20 degree C until they were used for assays. RESULTS: Reference range for T-T has decided to express by the mean +/- 2SD calculated from the entire test results, because influence of aging on the results was negligible, Reference range of T-T has established as 2.01-7.50 ng/mL. The other hand, reference ranges of F-T classified for every decade have decided to express by the mean +/- 2SD of each decade subgroup, because great influence of aging on F-T was observed. For each decade from 20 years on and > 70 years, reference ranges of F-T have established as: 8.5-27.9 pg/mL, 7.6-23.1 pg/mL, 7.7-21.6 pg/mL, 6.9-18.4 pg/mL, 5.4-16.7 pg/mL, and 4.5-13.8 pg/ mL, respectively. CONCLUSION: Reference ranges of serum T-T and F-T in Japanese male adults have established. And the value of Young Adult Mean (YAM) of F-T calculated for a group of the ages between 20 and 39 years have been proposed as a guideline of requirement for the Androgen Replacement Therapy (HRT). The value of 80% and 70% of YAM were 12.4 pg/mL and 10.9 pg/mL, respectively.

Adult↗