Yoshitomo Kobori

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis

Objectives:  To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis.

Free-to-total prostate-specific antigen (PSA) ratio contributes to an increased rate of prostate cancer detection in a Japanese population screened using a PSA level of 2.1–10.0 ng/ml as a criterion

BackgroundAlthough the free-to-total prostate-specific antigen (PSA) ratio (f/t ratio) is low in prostate cancer, its usefulness in mass screening remains unclear. We examined the clinical usefulness of the f/t ratio for screening in a Japanese population.MethodsSince 2000, we have performed PSA screening in Japanese men aged 55–69 years. From 2000 to 2002, patients with total PSA (tPSA) levels over 2.1 ng/ml were referred to the urological clinic for secondary screening, regardless of the f/t ratio. We analyzed both the tPSA level and the f/t ratio in prostate cancer patients, and since 2003, subjects with tPSA levels ranging from 2.1–10.0ng/ml and f/t ratios higher than 0.22 have not been referred for secondary screening. Here, we report the results of tPSA screening, comparing findings in the two periods (2000–2002 and 2003–2005).ResultsBetween 2000 and 2005, we performed the tPSA screening test in 27 730 men, and detected 214 cases of prostate cancer. Sixty patients (28.0%) showed tPSA levels between 2.1 and 4.0ng/ml. There were no differences in cancer detection rates between the two periods in the populations referred for an initial screening. However, the percentage of individuals referred for secondary screening decreased from 17.0% to 13.0% during the later period (P < 0.001). The cancer detection rate in all patients with biopsies rose from 13.5% in the earlier period to 22.7% in the later period for the group with tPSA between 2.1 and 10.0ng/ml (P < 0.001).ConclusionThe f/t ratio may be a useful additional screening parameter for patients showing tPSA levels between 2.1 and 10.0ng/ml on their initial screening examination.

Etiological role of human papillomavirus infection for inverted papilloma of the bladder

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin‐fixed and paraffin‐embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV‐DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri‐Max HPV genotyping kit. Immunohistochemical analysis for p16‐INK4a, mcm7, HPV‐E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV‐18 was detected in two cases, including one inverted papilloma with atypia, and HPV‐16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High‐risk HPV was present in all HPV‐positive cases. Cellular proteins, p16‐INK4a and mcm7, which are surrogate markers for HPV‐E7 expression, were detected in all HPV‐positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV‐E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High‐risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. J. Med. Virol. 83:277–285, 2011.

Tissue-specific differentially methylated regions of the human VASA gene are potentially associated with maturation arrest phenotype in the testis

Numerous CpG islands containing tissue-specific differentially methylated regions (TDMRs) are potential methylation sites in normal cells and tissues. The VASA (also known as DDX4) gene is believed to be under the control of TDMRs. A total of 131 male patients with idiopathic azoospermia or severe oligospermia were evaluated histologically, and the methylation status of CpG islands in the VASA gene was screened. Genome DNAs were obtained from testicular biopsy and modified with sodium bisulfite, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied. This system is capable of analyzing both the methylated and unmethylated CpG island in the genome. The methylation analysis is conducted by an epigram as graphic data. On histological assessment, 17 of 131 patients revealed maturation arrest (MA).In all, 6 of the 17 patients showed particularly high VASA TDMR methylation rates, whereas the remaining 11 patients and controls had low methylation rates. This study may imply that the VASA TDMR methylation is significantly higher among patients with MA, in whom the VASA gene expression was silenced. This finding represents an important contribution to the molecular basis of meiotic arrest as one possible cause of idiopathic infertility.

Antioxidant cosupplementation therapy with vitamin C, vitamin E, and coenzyme Q10 in patients with oligoasthenozoospermia

OBJECTIVE Overproduction of reactive oxygen species results in oxidative stress, a deleterious process that damages cell structure as well as lipids, proteins, and DNA. Oxidative stress plays a major role in various human diseases, such as oligoasthenozoospermia syndrome. MATERIALS AND METHODS We evaluated the effectiveness of antioxidant co-supplementation therapy using vitamin C, vitamin E, and coenzyme Q10 in men with oligoasthenozoospermia. Overall, 169 infertile men with oligoasthenozoospermia received antioxidant therapy with 80 mg/day vitamin C, 40 mg/day vitamin E, and 120 mg/day coenzyme Q10. We evaluated spermiogram parameters at baseline and at 3 and 6 months of follow-up. RESULTS Significant improvements were evident in sperm concentration and motility following coenzyme Q10 therapy. Treatment resulted in 48 (28.4%) partner pregnancies, of which 16 (9.5%) were spontaneous. Significant improvements in sperm cell concentration and sperm motility were observed after 3 and 6 months of treatment. CONCLUSIONS Vitamin C, vitamin E, and coenzyme Q10 supplementation resulted in a significant improvement in certain semen parameters. However, further studies are needed to empirically determine the effect of supplementation on pregnancy rate.

The relationship of serum and salivary cortisol levels to male sexual dysfunction as measured by the International Index of Erectile Function.

To evaluate the biomarkers of sexual function, we investigated the relationship between questionnaire responses and biological hormones such as testosterone (T) and cortisol (F) in serum and saliva. The study population included 105 men aged 30–72 years (mean: 49±4.5, median: 49). Levels of all serum hormones (Total-T, Free-T, Bioavailable-T, Total-F and Bioavailable-F) and salivary hormones (Saliva-T and Saliva-F) were measured directly by liquid chromatography/tandem mass spectrometry. The International Index of Erectile Function (IIEF) was used as a questionnaire to evaluate sexual dysfunction. Free-T and Bioavailable-T showed significant inverse correlations with age (P<0.01). In the group not taking antidepressants, the levels of Bioavailable-F and Saliva-F showed significant inverse correlations with a portion of the IIEF score (P<0.05). However, reductions in Bioavailable-T and Saliva-T showed no association with the IIEF score. In the group taking antidepressants, these hormone levels showed no correlation with IIEF.

Novel device for male infertility screening with single-ball lens microscope and smartphone

OBJECTIVE To investigate the usefulness of a novel semen analysis device consisting of a single-ball lens microscope paired with a state-of-the-art smartphone equipped with a camera. DESIGN Laboratory investigation. SETTING University research laboratory. PATIENT(S) A total of 50 semen samples obtained from volunteers were analyzed for count, concentration, and motility with an 0.8-mm ball lens and three types of smartphone. Comparisons were made with results obtained with a laboratory-based computer-assisted sperm analysis (CASA) system. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Sperm concentration; sperm motility. RESULT(S) Sperm concentration counted with a ball lens and each smartphone showed a very strong correlation with the CASA results. Likewise, sperm motility calculated with our device showed significant correlations to CASA. If eight spermatozoa or fewer were found on the field of view of an iPhone 6s, the semen specimens were considered to be below the lower reference limit for sperm concentration of World Health Organization 2010 guidelines (15 × 10(6) spermatozoa/mL). The sensitivity was 87.5%, and specificity was 90.9%. CONCLUSION(S) Smartphones have great potential to analyze semen because they are portable, contain excellent digital cameras, and can be easily attached to a microscope. A single-ball lens microscope is inexpensive and easy to use for acquiring digital microscopic movies. Given its small size and weight, the device can support testing for male fertility at home or in the field, making it much more convenient and economical than current practice. This single-ball lens microscope provides an easy solution for global users to rapidly screen for male infertility.

Inflammatory bowel disease in subfertile men and the effect of mesalazine on fertility

Abstract This study aimed to examine the effect of mesalazine on fertility. In this retrospective analysis of 1,225 male subfertile patients, we reviewed the cases of inflammatory bowel disease (IBD) in the medical records and evaluated the prevalence of the disease in our reproduction center. Specifically, we examined IBD patients who ceased mesalazine during male infertility treatment, and compared the seminogram of these patients before and after discontinuation of mesalazine. We also analyzed pregnancy outcome after discontinuation. The prevalence rate of Crohn’s disease and ulcerative colitis in our male infertile patients was 163 per 100,000 men and 490 per 100,000 men, respectively. Seven patients had taken mesalazine and six of them subsequently stopped the medication. The mean values of sperm concentration, sperm motility, percentage of normal formed sperm, semen volume, and total motile sperm count taken before discontinuation increased after discontinuation of mesalazine. Among these parameters, the sperm motility and total motile sperm count were significantly improved (p < 0.05) after discontinuation. Of the six patients who stopped the drug, four achieved pregnancy with their partners, with two of the four men showing significant improvement not only in the percentage of normal shaped sperm but also sperm motility and total motile sperm count. This study provides further insight into the rarely investigated relationship between male fertility and mesalazine.

A sensitive immunochromatographic assay using gold nanoparticles for the semiquantitative detection of prostate-specific antigen in serum

In prostate cancer screening, prostate-specific antigen (PSA) has been utilized as a valuable biomarker. There are routinely used procedures based on enzyme-linked immunosorbent assay (ELISA) for PSA detection. The procedures based on ELISA, however, are time consuming, complicated, and costly. We have developed a rapid, very simple, cost effective and sensitive immunochromatographic assay using gold nanoparticles and evaluated its applications for first screening of prostate cancer in serum samples. The sensitive immunochromatographic assay requires only 40 μL of the serum sample. The assay used is rapid and simple, that it totally takes approx 15 min to complete. The method for sensitive immunochromatographic assay has the other advantage of decreasing the antibody concentration that is used for the test line. In this study, we show the advantage to decrease the antibody concentration and the evaluation of our sensitive immunochromatographic assay for the semiquantitative detection of PSA in serum. The results obtained from 163 serum samples using sensitive immunochromatographic assay are compared with the results obtained using the chemiluminescent enzyme immunoassay (CLEIA) and normal immunochromatographic assay. The results obtained in the sensitive immunochromatographic assay correlated well with the values obtained in CLEIA. We concluded that our sensitive immunochromatographic assay is applicable to the first screening test for the diagnosis of prostate cancer. Our developed sensitive immunochromatographic assay is a promising candidate for diagnosis or research use, which may become commercially available in the near future.

Role of male pelvic floor muscles and anterior fibromuscular stroma in males on α1-blocker treatment: A magnetic resonance imaging study

Dynamic motion of the pelvic floor muscles during voiding was analyzed using real‐time magnetic resonance imaging. To evaluate the contraction of the pelvic floor muscles, striated urethral sphincter distance, levator ani muscle thickness and anterior fibromuscular stroma distance were measured. The percent contraction of the striated urethral sphincter from before voiding to just before initiation of voiding was 14% in the normal group and 5% in the voiding dysfunction group. The percent contraction of the anterior fibromuscular stroma from before voiding to just before initiation of voiding was 11% in the normal group and 1% in the voiding dysfunction group; the percent contraction of the muscles was significantly greater in the normal group (P < 0.05). Striated urethral sphincter and anterior fibromuscular stroma contraction at initiation of voiding open the bladder neck and urethra. This plays an important role in the smooth initiation of voiding.