Female sexual dysfunction and lower urinary tract symptoms associated with vulvovaginal atrophy symptoms: Results of the GENJA study.

OBJECTIVES: To investigate the main symptoms of female sexual dysfunction (FSD) and lower urinary tract symptoms associated with vulvovaginal atrophy (VVA) symptoms as the core symptoms of genitourinary syndrome of menopause. METHODS: We extracted the data of 4134 Japanese women aged 40-79 years who participated in the GENitourinary syndrome of menopause in JApanese women (GENJA) study. All participants responded to web-based questionnaires assessing their health situation, including the Vulvovaginal Symptoms Questionnaire, the Female Sexual Function Index (FSFI), and the Core Lower Urinary Tract Symptom Score. Multivariable regression and multivariable logistic regression analyses were applied to analyze the association between VVA symptoms and FSD, and between VVA symptoms and lower urinary tract symptoms. RESULTS: Multivariable regression analysis revealed that VVA symptoms were associated with lower scores for arousal, lubrication, orgasm, satisfaction, and pain domains in the FSFI in sexually active women (p < 0.01). Regression coefficients were higher for lubrication and pain domains than for the other domains. Multivariable logistic regression analysis revealed that women reporting VVA symptoms were more likely to have increased daytime urinary frequency, nocturia, urgency, slow stream, straining to void, feeling of incomplete emptying, bladder pain, and feeling a bulge/lump from or in the vagina (p < 0.05). Adjusted odds ratios were particularly high for straining to void, feeling of incomplete emptying, and bladder pain. CONCLUSIONS: Vulvovaginal atrophy symptoms were significantly associated with decreased lubrication and dyspareunia in FSD, and urinary symptoms of straining to void, feeling of incomplete emptying, and bladder pain.

Identification of transgene integration site and anatomical properties of fluorescence intensity in a EGFP transgenic chicken line.

Transgenic birds are commonly used for time-lapse imaging and fate mapping studies in developmental biology. When researchers use transgenic birds expressing fluorescent protein, they need to understand the integration site of the transgene in the genome and the intensity of fluorescence in the tissues of interest. In this study, we determined the integration site of the transgene and fluorescence property of developing organs in our transgenic chicken line generated by lentivirus infection. The transgene was localized between exons 3 and 4 of MED27. Some homozygotes and heterozygotes appeared to be lethal at early embryonic stages. We performed histological analysis of EGFP expression in transgenic embryos at St. 14, 17, and 24 by immunohistochemistry with anti-GFP antibody on paraffin sections. Next, we cut cryosections and quantified direct EGFP intensity from the transgene in each tissue without performing immunohistochemistry. These results revealed that EGFP intensity in each tissue was unique in developing embryos and changed according to developmental stages. Finally, we demonstrated that EGFP-expressing cells in a micromass culture with co-culturing wild-type cells were clearly distinguishable via live cell imaging. These results provide essential information on the potential of our transgenic line and indicate that these transgenic chicken lines are useful for research associated with developmental biology.

The oncogenic role of GASC1 in chemically induced mouse skin cancer.

Gene amplified in squamous cell carcinoma (SCC) 1 (GASC1), also known as KDM4C/JMJD2C, encodes a histone demethylase that specifically demethylates lysine residues (H3K9, H3K36, and H1.4K26) and plays a crucial role in the regulation of gene expression as well as in heterochromatin formation. GASC1 is located at human chromosome 9p23-24, where frequent genomic amplification is observed in human esophageal cancer, and its aberrant expression is detected in a variety of human cancers, such as breast, colon, and prostate. Therefore, it is highly likely that GASC1 contributes to the genesis and/or development of cancer. However, there is a lack of direct evidence of GASC1 having an oncogenic function. In this study, we aimed to clarify the role of GASC1 in the skin SCC carcinogenesis. For this purpose, we generated Gasc1-heterozygous mice (Gasc1+/-) with reduced expression of Gasc1. On the basis of our results, Gasc1+/- mice displayed a significantly lower incidence and multiplicity of both benign and malignant tumors induced by the two-stage skin carcinogenesis protocol than wild-type mice. In addition, the volume of carcinoma was significantly lower in Gasc1+/- mice. Consistent with these observations, knocking down of Gasc1 resulted in reduced cell viability of SCC cells in vitro. Our findings clearly demonstrated that GASC1 has an oncogenic role in skin carcinogenesis.

Gaps between actual and desired sex life: web survey of 5,665 Japanese women.

To explore issues that heterosexual women have concerning their sex life and desire toward their male partner, the authors conducted an online survey on actual sex life and sexual quality of life. Survey participants included 5,665 women who were 20 years of age and older who (a) lived in or near Tokyo, (b) had a male sex partner, and (c) intended to have sexual activity. Participants were asked to respond to a wide range of questions regarding their sexual fulfillment and desires. Differences between actual and desired duration of sexual activities (foreplay, intercourse, and afterplay) and number of sexual positions were calculated. The authors performed subgroup analyses regarding pain during sexual intercourse and by degree of partner's unilateral action. In addition, the authors investigated the relation between sexual quality of life and each subgroup. Women who participated in this survey tended to desire a longer duration of foreplay and afterplay than was experienced. The greater the pain during sexual intercourse, the percentage of respondents who desired a shorter duration of intercourse and fewer numbers of sexual positions increased and the sexual quality of life decreased. The degree of partner's unilateral action during sexual activity negatively affected the woman's sexual quality of life. The present study suggests the importance of establishing good communication between sex partners.

[In two patients with economic and social issues stage I giant seminoma].

The first case was in a 39-year-old man who complained of painless, left hemiscrotal swelling. The patient's serum ß human chorionic gonadotropin (ß-hCG) was elevated. A chest X-ray and computerized tomography (CT) did not reveal any abnormal findings. The patient underwent left high orchiectomy. The tumor weighed 440 g, and was pathologically diagnosed as a seminoma. The patient chose surveillance as the management strategy. Five months after the operation, the patient stopped attending his periodic checkups. After 21 months, the patient complained of abdominal distention. A CT showed a para-aortic lymph node mass. The patient achieved a complete response following chemotherapy with etoposide and cisplatin for 4 cycles. Three months after the adjuvant chemotherapy, hospital visits stopped again due to financial difficulties. The second case was in a 36-year-old man who complained of painless, right hemiscrotal swelling and difficulty in walking. Clinical examination revealed an adult-head-sized testicular tumor with elevation of serum lactic dehydrogenase (LDH) and ß-hCG. A chest X-ray and abdominal CT did not reveal any abnormal findings. Despite a recommendation that the patient undergo immediate orchiectomy, the patient did not undergo surgery due to his unstable lifestyle. After 1 month, the patient presented with more difficulty in walking. The patient underwent right high orchiectomy. The tumor weighed 1,926 g, and was pathologically diagnosed as a seminoma. The patient chose surveillance. There has been no recurrence for 19 months postoperatively.

Epidemiological study of genitourinary syndrome of menopause in Japan (GENJA study).

OBJECTIVE: This study aimed to investigate the prevalence of genitourinary syndrome of menopause (GSM) in Japan using the Japanese translation of the Vulvovaginal Symptoms Questionnaire (VSQ) with online survey. In addition, we examined the relationship between sexual activity and GSM symptoms. METHODS: An online survey on GSM was conducted with 4,134 women aged 40 to 79 years, who were registered in an online survey company. Several questionnaires with Japanese translations of linguistic validity were used in this study. GSM was defined as a condition in women older than 40 years with vulvovaginal symptoms on the VSQ. RESULTS: The percentage of postmenopausal women 40 years and older was 69.6%. The percentage of women with sexual activity was 22%. The prevalence of GSM with vulvovaginal symptoms was 11.6%, and 31.7% in sexually active women. The prevalence of GSM was associated with age and was significantly lower in the 70s age group than in other age groups. Vulvar hurting and dryness were both age-related only in the sexual activity group, with a statistically significantly higher prevalence in the 70s group than in the 40s group. The prevalence of vulvar dryness during sexual activity was significantly lower in the 40s age group. CONCLUSIONS: An online epidemiological survey of GSM was conducted for the first time in Japan using the linguistically validated Japanese translation of the VSQ. The prevalence of GSM with genital or sexual symptoms was 11.6% in Japanese women 40 years and older, and 31.7% in sexually active women.

[Hyaline vascula type Castleman's disease in the pelvic cavity : a case report].

A 48-year-old man was admitted to our hospital in order to treat a right lower abdominal tumor which was detected by ultrasonography in a general health check. The tumor was considered to be a pelvic sarcoma from computed tomography and magnetic resonance imaging findings, then, resection of the tumor was performed. Pathological diagnosis was a hyaline vascular type of Castleman's disease. The patient remained well without any evidence of local recurrence 12 months after surgery. The hyaline vascular type of Castleman' s disease is characterized by a solitary hypervascular tumor which is prone to adhere to neighboring great vessels. This tendency makes dissection from great vessels difficult and should be kept in mind when surgery is planned.

[A case of giant hemorrhagic adrenal pseudocystectomy with a flank incision].

The patient was a 43-year-old woman who underwent detailed examinations for a retroperitoneal cystic lesion that was incidentally found during orthopedic treatment. Although the tumor was a non-functioning tumor, and diagnostic imaging was negative for malignancy, the tumor was surgically resected with a flank incision. The histopathological diagnosis was adrenal pseudocyst.

[LINGUISTIC VALIDATION OF JAPANESE VERSION OF THE VULVOVAGINAL SYMPTOMS QUESTIONNAIRE (VSQ)].

(Purpose) To translate the Vulvovaginal Symptoms Questionnaire (VSQ) into Japanese and evaluate the linguistic validation of the translated VSQ. (Methods) The translation and evaluation of the VSQ were performed through 3 steps: forward translation based on 2 urologists and discussed by another 3 urologists; the community review process, which consisted of one-on-one cognitive interviews with 20 patients by professional interviewers; backward translation by a native English speaker, which was discussed with the original author of the VSQ. (Results) The original author of the VSQ generally approved our translation. (Conclusion) The Japanese version of the VSQ was translated in a linguistically valid manner. It is equivalent to the original English questionnaire. It may provide a tool to assess sexual function for Japanese women with genitourinary syndrome of menopause.

An angiotensin II receptor blocker increases sexual behavior in type 2 diabetic mice.

The present study was conducted to examine the effects of olmersartan, angiotensin (ANG) II type 1 (AT(1)) receptor antagonist, on the sexual function in type 2 diabetes model mice. Twenty-week-old KK/Ta mice were used as a model of type 2 diabetes. Age-matched ICR and BALB/C mice were used as non-diabetic controls. The animals were fed powder chow either with or without olmesartan (7.5 microg/g in chow) for 4 weeks. The levels of sexual behavior, activity, and anxiety were then examined between the groups treated with and without olmesartan. The KK/Ta mice treated with olmesartan exhibited a significant increase in the number of mounts and intromission and a decrease in the latency to the first mount in comparison to the KK/Ta mice treated without olmesartan. These effects of olmesartan were not observed in the non-diabetic BALB/C and ICR mice. In addition, the olmesartan treatment did not affect the activity and anxiety regardless of the mouse strain. These findings suggest that the interaction between ANG II and AT(1) receptor may be involved in the pathogenesis of the sexual dysfunction associated with type 2 diabetes and a blockade of ANG II may therefore be a potentially useful treatment for male sexual dysfunction in type 2 diabetes.

Induction of galanin-like peptide gene expression in the arcuate nucleus of the rat after acute but not chronic inflammatory stress.

Galanin-like peptide (GALP) has been recently isolated from the porcine hypothalamus. The GALP mRNA is restricted to neurons in the hypothalamic arcuate nucleus (Arc) and pituicytes in the posterior pituitary gland (PP), but physiological functions of the GALP remains unclear in both areas. We examined the effects of acute and chronic inflammatory stresses on the GALP mRNA levels in the rat Arc using in situ hybridization histochemistry. Intraperitoneal (i.p.) injection of bacterial endotoxin lipopolysaccharide (LPS) caused a marked increase of the GALP mRNA levels in the Arc. The effects of i.p. injection of LPS on the GALP mRNA levels in the Arc were significantly attenuated by pretreatment with i.p. injection of indomethacin cyclooxygenase inhibitor. Adjuvant arthritis caused by subcutaneous (s.c.) injection of heat-killed Mycobacterium butyricum as chronic inflammatory stress did not affect the GALP mRNA levels in the Arc, though the GALP mRNA levels in the pituicytes of the PP were markedly increased by two peaks at 12 h and 15 days after s.c. injection of heat-killed M. butyricum. Enzymeimmunoassay showed that the plasma concentration of GALP was not affected by these inflammatory stresses. These results suggest that acute inflammatory stress might be a potent stimulant to increase the GALP mRNA levels in the Arc of the rat via synthesis of prostaglandins.

Sexual Problems among Japanese Women: Data from an Online Helpline.

INTRODUCTION: Sexual problems have been more prevalent among East Asian women than those from other areas of the world. However, Japanese women seldom tend to consult their treating physicians as such intimate problems are socially awkward topics to share and may be considered shameful. Presently, there is little data in the literature regarding women's sexual problems in Japan. AIMS: We aimed (i) to investigate the types of sexual problems that were reported among Japanese women who had sought online consultations; and (ii) to examine whether factors such as age and family structure (marital status and presence of children) increased the likelihood of sexual problems. METHODS: An online helpline received a total of 316 messages from Japanese women related to sexual problems over a 3-year period. We evaluated 276 respondents, who provided demographic information such as age and family structure as well as their response to an open-ended question regarding their sexual problems. MAIN OUTCOME MEASURES: Main outcome measures were the types of sexual problems reported by Japanese women. RESULTS: The majority of respondents were in their 30s (53.6%). Sexual aversion accounted for 42.4% of the complaints, partners' sexual issues for 18.5%, and pain during sex for 16.7%. Family structure significantly correlated with sexual problems (P < 0.001). Women with sexual aversion were more likely to be younger (P = 0.003) and have children (P < 0.001). Women whose partners had sexual issues were more likely to be married (P < 0.001) and have no children (P < 0.001). Women who reported pain during sex were more likely to have no children (P = 0.006). CONCLUSION: Sexual aversion was the most common sexual problem among Japanese women who sought help via the online helpline. Family structure was related to sexual problems. More detailed assessments of family structure may be important in better identifying the triggering causes of the reported sexual problems. Ozaki Y, Nagao K, Saigo R, Tai T, Tanaka N, Kobayashi H, Nakajima K, and Takahashi Y. Sexual problems among Japanese women: Data from an online helpline. Sex Med 2015;3:289-295.

Centrally administered neuromedin U activates neurosecretion and induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of rat.

We examined the effects of intracerebroventricular (icv) administration of neuromedin U (NMU) on plasma arginine vasopressin (AVP), oxytocin (OXT), and ACTH in rats, using RIA. The induction of c-fos protein (Fos) was examined by immunohistochemical study, and in situ hybridization histochemistry was used to detect c-fos gene expression in the paraventricular (PVN) and supraoptic nuclei (SON). Plasma AVP, OXT, and ACTH were increased in a dose-related manner 15 min after icv administration of NMU. The icv administration of NMU caused a marked induction of Fos-like immunoreactivity (LI) in the SON and the magnocellular and parvocellular divisions of the PVN. In the SON and the magnocellular divisions of the PVN, OXT-LI cells predominantly exhibited nuclear Fos-LI in comparison with AVP-LI cells. The marked induction of the expression of c-fos gene in the PVN and SON was observed 15, 30, and 60 min after icv administration of NMU. Neurosecretion and induction of c-fos gene expression after centrally administered NMU were significantly reduced by pretreatment with anti-NMU IgG. These results suggest that centrally administered NMU activates OXTergic cells in the PVN and SON predominantly as well as hypothalamo-pituitary adrenal axis.

Induction of galanin-like peptide gene expression in the rat posterior pituitary gland during endotoxin shock and adjuvant arthritis.

Galanin-like peptide (GALP) was recently isolated from the porcine hypothalamus. The GALP mRNA is restricted in the hypothalamic arcuate nucleus and pituicytes in the posterior pituitary grand (PP) of the rat. The physiological function of the GALP is not clear in both areas. We focused on the regulation of the GALP gene expression to determine the role of GALP in the PP. We examined the effects of potent stressors to modulate a pituitary function, nociceptive stimuli and acute and chronic inflammatory stresses on the expression of the GALP gene in the PP using in situ hybridization histochemistry. Subcutaneous (s.c.) injection of 5% formalin in the bilateral hind paws caused a moderate increase of GALP gene expression in the PP. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) also caused a marked increase of GALP gene expression in the PP. Effects of i.p. injection of LPS on the expression of the GALP gene in the PP were attenuated by pretreatment with i.p. injection of indomethacin. The levels of GALP mRNA in the PP were markedly increased by two peaks at 24 h and 15 days after s.c. injection of heat-inactivated M. butyricum that induced adjuvant arthritis. These results suggested that inflammatory stresses may be a potent stimulant to induce the expression of the GALP gene in the PP.

Galanin-like peptide gene expression in the hypothalamus and posterior pituitary of the obese fa/fa rat.

We examined the galanin-like peptide (GALP) gene expression in the arcuate nucleus (ARC) and posterior pituitary (PP) in 6- and 18-week-old male obese fa/fa rats. GALP mRNA in the ARC in fa/fa rats was significantly decreased in 6- and 18-week-old and GALP mRNA in the PP in fa/fa rats was significantly increased in 18-week-old compared to lean Fa/? rats. Insulin treatment in hyperglycemic fa/fa rats partially reversed those changes. These results suggest that the GALP gene expression in fa/fa rats might be regulated in part by leptin-independent mechanisms.

Effects of restricted feeding on the activity of hypothalamic Orexin (OX)-A containing neurons and OX2 receptor mRNA level in the paraventricular nucleus of rats.

We have examined the effects of 3 weeks of food restriction on both the activity of neurons containing hypothalamic orexin (OX)-A and the level of OX receptor type 2 (OX2R) mRNA in the paraventricular nucleus (PVN) of rats. Double immunohistochemistry was used to examine the expression of OX-A and Fos in the lateral hypothalamic area (LHA), and in situ hybridization histochemistry was used to measure levels of OX2R mRNA in the PVN. After the period of restricted feeding, 20-30% of OX-A-containing neurons exhibited Fos-like immunoreactivity (LI). The distribution of OX-A-LI/Fos-LI cells in the food-restricted rats was similar to that observed in glucose-deprived rats after intracerebroventricular (icv) administration of 2-deoxy-D-glucose (2-DG). In addition, 3 weeks of food restriction caused a significant decrease in the expression of the OX2R gene in the parvocellular division of the PVN. These results suggest that the activation of OX-A-containing neurons induced by restricted feeding may be involved in neuroendocrine responses to food restriction.

Osmotic stimuli increase brain-derived neurotrophic factor mRNA level in the rat subfornical organ.

The effects of water deprivation and chronic salt loading on the expression of the brain-derived neurotrophic factor (BDNF) gene were examined in the rat subfornical organ (SFO), using immunohistochemistry for BDNF and in situ hybridization histochemistry. Increased BDNF-like immunoreactivity was observed in the SFO after water deprivation for 4 days. Water deprivation for 24 h and 2 and 4 days and salt loading for 7 days caused a significant increase in the BDNF gene transcripts in the SFO, compared with euhydrated rats. These results suggest that BDNF in the SFO may be involved in the regulatory mechanisms of body fluid balance.

Involvement of novel feeding-related peptides in neuroendocrine response to stress.

Various stressors are known to cause eating disorders. However, it is not known in detail about the neural network and molecular mechanism that are involved in the stress-induced changes of feeding behavior in the central nervous system. Many novel feeding-regulated peptides such as orexins/hypocretins and ghrelin have been discovered since the discovery of leptin derived from adipocytes as a product of the ob gene. These novel peptides were identified as endogenous ligands of orphan G protein-coupled receptors. The accumulating evidence reveals that these peptides may be involved in stress responses via the central nervous system, as well as feeding behavior. The possible involvement of novel feeding-related peptides in neuroendocrine responses to stress is reviewed here.

Upregulation of CRH gene expression and downregulation of arginine vasopressin gene expression in the hypothalamus of bilateral nephrectomized rats.

The expression of the corticotropin-releasing hormone (CRH) gene and the arginine vasopressin (AVP) gene in the hypothalamus examined in bilateral nephrectomized rats by in situ hybridization histochemistry. The expression of the CRH gene was significantly increased in the parvocellular part of the paraventricular nucleus (PVN) 12 and 20 h after bilateral nephrectomy in comparison with that after sham operation. The plasma concentration of adrenocorticotropic hormone (ACTH) in nephrectomized rats was significantly higher than that in sham operated rats 20 h after surgery. In contrast, the expression of the AVP gene in both the parvocellular and magnocellular parts of the PVN and throughout the supraoptic nucleus (SON) was significantly decreased 20 h after bilateral nephrectomy in comparison with that after sham operation. These results suggest that nephrectomy-induced upregulation of the CRH gene with elevation of plasma ACTH may be due to the activation of the hypothalamo-pituitary adrenal (HPA) axis.

Two sporadic cases of infections due to Klebsiella pneumoniae resistant to expanded-spectrum cephalosporins in Japan.

TEM- or SHV-type extended-spectrum beta-lactamases (ESBLs) are of clinical concern in Europe and the United States, whereas bacterial strains producing such types of ESBLs have not been reported in Japan. We report here two cases of infection due to Klebsiella pneumoniae resistant to extended-spectrum cephalosporins in Japan. A ceftadizime-resistant K. pneumoniae strain (minimum inhibitory concentration; 32 &mgr;g/ml) was isolated transiently from the sputum of an 87-year-old woman with acute myocardial infarction and pneumonia (patient 1). Ceftadizime-susceptible and -resistant (minimum inhibitory concentration; >/=8 &mgr;g/ml) K. pneumoniae strains were isolated over a month from the blood, ascites, and feces of a 44-year-old man after bone marrow transplantation for acute lymphoblastic leukemia (patient 2); this patient died of K. pneumoniae sepsis and peritonitis followed by multiple organ failure. These isolates produced penicillinase, which was inhibited by clavulanic acid. A polymerase chain reaction (PCR) study showed that both isolates carried the SHV or LEN genes, but not the TEM, Toho-1, and IMP-1 genes. The pulsed-field gel electrophoresis profile of the strain isolated from patient 1 was genetically distinguishable from the profiles of the strains isolated from patient 2. It appeared that mutation of the beta-lactamase gene may have occurred in the body of patient 2, since the genotypes of the ceftadizime-susceptible and -resistant isolates from this patient were identical. Another 12 strains of K. pneumoniae, isolated from other patients in the same wards during the period in which the K. pneumoniae strains were isolated from patients 1 and 2, did not produce ESBLs and showed different genotypes. The results suggest that these isolates of resistant K. pneumoniae did not spread by cross transmission in the hospital and that the two cases were sporadic. Surveillance of these types of resistant bacteria is necessary, since they may well be present in other hospitals in Japan. Although the organisms are suspected to produce SHV-type ESBLs or LEN-1 variant beta-lactamases, further studies are necessary to specify the resistance genes.