Duration of smoking cessation is negatively associated with the magnitude of chronic prostatic inflammation and storage dysfunction in patients with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the impact of smoking and the benefit of smoking cessation on lower urinary tract function and prostatic inflammation in patients with benign prostatic hyperplasia. METHODS: The medical records of 118 benign prostatic hyperplasia patients who underwent transurethral prostatic surgery between 2006 and 2016 were analyzed. Their smoking history was confirmed. The relationship between smoking and main clinical parameters, International Prostate Symptom Scores, uroflowmetry, pressure flow study, magnitude of prostatic inflammation and the level of serum C-reactive protein was investigated. Furthermore, the relationships between smoking cessation and these clinical parameters were assessed. RESULTS: The International Prostate Symptom Scores for straining among the non-smokers were significantly lower than those of the smokers (1.71 vs 2.60, P = 0.029). In the pressure flow study, there were negative correlations between the duration of smoking and strong desire to void (correlation coefficient -0.314, P = 0.013), urgency (correlation coefficient -0.349, P = 0.008) and bladder volume at initial detrusor overactivity (correlation coefficient -0.417, P = 0.021). The duration of smoking cessation was negatively correlated with the magnitude of chronic prostatic inflammation (correlation coefficient -0.253, P = 0.027). In the pressure flow study, the duration of smoking cessation was positively correlated with urgency (correlation coefficient 0.286, P = 0.030) and maximum cystometric capacity (correlation coefficient 0.241, P = 0.050). CONCLUSIONS: Smoking could be a risk factor for the exacerbation of storage dysfunction in benign prostatic hyperplasia patients. Smoking cessation is effective in improving chronic prostatic inflammation and storage dysfunction.

The usefulness of vibration perception threshold as a significant indicator for erectile dysfunction in patients with diabetes mellitus at a primary diabetes mellitus clinic.

INTRODUCTION: The aim of this study is to clarify the relationship of erectile dysfunction (ED) and diabetes mellitus (DM) parameters (referred to with '1'), including peripheral neuropathy (referred to with '2'). METHODS: (1) The DM parameters including age, serum levels of blood sugar, hemoglobin A1c, duration of DM and number of DM complications were obtained from 145 patients at a general DM clinic. (2) The peripheral neuropathy examinations by vibration perception threshold (VPT) and Achilles tendon reflex were performed in 97 DM patients. Erectile functions in DM patients were evaluated by the International Index of Erectile Function (IIEF 5). The DM patients' parameters were compared with the IIEF 5 scores. RESULTS: (1) The data showed IIEF 5 scores were significantly correlated with patient age, duration of DM and number of DM complications. (2) IIEF 5 scores were significantly correlated with VPT time. Furthermore, multiple regression analysis revealed that patient age and VPT time were independent risk factors for predicting ED in DM patients. CONCLUSIONS: The severity of ED in DM patients depended on age, duration of DM, number of DM complications and VPT. Significantly, the age of DM patients and the measurement of VPT are considered to be simple and useful indicators to diagnose ED in DM patients.

Frozen human cells can record radiation damage accumulated during space flight: mutation induction and radioadaptation.

To estimate the space-radiation effects separately from other space-environmental effects such as microgravity, frozen human lymphoblastoid TK6 cells were sent to the "Kibo" module of the International Space Station (ISS), preserved under frozen condition during the mission and finally recovered to Earth (after a total of 134 days flight, 72 mSv). Biological assays were performed on the cells recovered to Earth. We observed a tendency of increase (2.3-fold) in thymidine kinase deficient (TK(-)) mutations over the ground control. Loss of heterozygosity (LOH) analysis on the mutants also demonstrated a tendency of increase in proportion of the large deletion (beyond the TK locus) events, 6/41 in the in-flight samples and 1/17 in the ground control. Furthermore, in-flight samples exhibited 48% of the ground-control level in TK(-) mutation frequency upon exposure to a subsequent 2 Gy dose of X-rays, suggesting a tendency of radioadaptation when compared with the ground-control samples. The tendency of radioadaptation was also supported by the post-flight assays on DNA double-strand break repair: a 1.8- and 1.7-fold higher efficiency of in-flight samples compared to ground control via non-homologous end-joining and homologous recombination, respectively. These observations suggest that this system can be used as a biodosimeter, because DNA damage generated by space radiation is considered to be accumulated in the cells preserved frozen during the mission, Furthermore, this system is also suggested to be applicable for evaluating various cellular responses to low-dose space radiation, providing a better understanding of biological space-radiation effects as well as estimation of health influences of future space explores.

Normal delivery following resection of an androgen-secreting adrenal carcinoma.

A 31-year-old female presented to a gynecological clinic complaining of amenorrhea and virilism over a 2-month period. Blood tests revealed high serum total testosterone and free testosterone levels. A left adrenal tumor was identified following computed tomography and she was referred to our clinic where a laparoscopic left adrenalectomy was performed. The tumor weighed 98 g and the pathological diagnosis according to Weiss' criteria was adrenocortical carcinoma. The post-operative course was uneventful; her serum free testosterone level normalized and regular menstruation was observed 1 month post-operatively. The patient became pregnant 1 year later, resulting in the normal delivery of a girl.

[Adrenalectomy for metastatic adrenal tumor from uterine leiomyosarcoma: a case report].

A 63-year-female was referred to our department for close examination and treatment of a left adrenal tumor found by positron emission tomography and computed tomography. She underwent abdominal total hysterectomy and bilateral salpingo-oophorectomy for uterine leiomyosarcoma 19 years ago. After the operation, she received 2 resections for peritoneal recurrence and 7 resections for pulmonary metastases. Magnetic resonance imaging showed a heterogeneous mass with a diameter of 7 cm at the left adrenal grand. We carried out open adrenalectomy and pathological findings were a metastatic adrenal tumor from uterine leiomyosarcoma. No signs of recurrence or metastasis have been observed for 6 months after the operation.

[Laparoscopic resection of retroperitoneal schwannoma : report of three cases and review of 22 cases in Japanese literature].

Retroperitoneal schwannoma is a rare tumor. Only 19 cases have been reported to be treated by laparoscopic surgery. We performed successful laparoscopic excision of retroperitoneal schwannoma using the four-trocar in three patients who had a left retroperitoneal mass. The patients were two women and one man. They were 62, 60 and 57 years old. The tumor was 70, 45 and 50 mm in greatest diameter and operative time was 204, 243 and 254 min. respectively. The pathological diagnosis of the tumor was schwannoma. There was no morbidity or mortality. Preoperative diagnosis of schwannoma is very difficult. However schwannoma is a benign tumor with a good prognosis. This laparoscopic excision for retroperitoneal schwannoma is effective and rather safe.

[Laparoscopic nephrectomy for patients with infected nonfunctioning kidney due to ureteropelvic junction stenosis : report of two cases].

We report two cases of infected nonfunctioning kidney due to ureteropelvic junction (UPJ) stenosis treated by laparoscopic surgery. Patient 1 : A 78-year-old woman was referred to our clinic complaining of left flank pain and high fever up. Asymptomatic UPJ stenosis with mild hydronephrosis was diagnosed 9 years ago at our clinic. Therefore we followed her up with no treatment. Computed tomography (CT) scan revealed left severe hydronephrosis. Antibiotic chemotherapy was performed without percutaneous nephrostomy. Laparoscopic nephrectomy was performed with the resected renal size of 10 cm in greatest diameter and the operative time of 262 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Patient 2 : A 28-year-old man was referred to our clinic complaining of left flank pain and high fever up. CT scan revealed a left severe hydronephrosis due to UPJ stenosis. Following percutaneous nephrostomy,antibiotic chemotherapy was performed. Laparoscopic nephrectomy was performed with the resected renal size of 6 cm in greatest diameter and the operative time of 140 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Laparoscopic nephrectomy for infected nonfunctioning kidney due to UPJ stenosis is feasible and safe. With dense perinephric adhesions and failure to progress,we should consider early open conversion to reduce morbidity.

[Brain tumor (germinoma) diagnosed after assessment for male late-onset hypogonadism syndrome: a case report].

A 44-year-old man suffered from sleep disturbance, headache, lack of energy and appetite loss. His local doctor recommended he consult our clinic for further examination of late-onset hypogonadism. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 62 and 1, respectively. His biochemistry revealed 0.29 mIU/ml luteinizing hormone (LH), 1.36 mIU/ml follicular stimulating hormone (FSH), 0.16 ng/ml total testosterone (TT) and＜0.6 pg/ml free testosterone (FT). Male hypogonadotropic hypogonadism was suspected from these results, He was then referred to a neurosurgeon for discrimination of intracranial disease where magnetic resonance imaging (MRI) revealed multiple intracranial tumors. An open brain biopsy was performed, and germinoma was diagnosed. After 4 courses of anti-cancer chemotherapy, complete remission was achieved. He was followed up endocrinologically by administration of testosterone injections along with other endocrinology replacement treatments. However, MRI 3 months later revealed tumor recurrence in the left lateral ventricle, and he has been receiving radiation therapy.

Advanced bladder cancer with malignant psoas syndrome: A case report with a focus on physical findings and complications.

Malignant psoas syndrome (MPS) is a rare clinical condition caused by cancer invasion of the iliopsoas muscle and has very poor prognosis. We report a case involving a 58-year-old woman with bilateral MPS caused by advanced bladder cancer. Rapid progress of a severe crouching posture with multiple deep venous thromboses was an important symptom of this case. Although 4 cycles of chemotherapy were administered, the patient died 8 months following disease onset. Since, these noteworthy symptoms have never been previously reported, in this report, we present the characteristic physical findings using photographs and cancer-related events that occur in MPS.

Role of corticotropin-releasing factor on bladder function in rats with psychological stress.

Stress-related peptide corticotropin-releasing factor (CRF) and CRF-related peptides are distributed in the peripheral viscera such as the bladder. We investigated the contribution of psychological stress (PS) and CRF on bladder function. Male rats received sham stress (SS) or PS using a communication box method for 120 min every day for 7 days. One group of rats received the intraperitoneal CRF-R1 antagonist antalarmin for 7 days during stress exposure. Mean voided volume per micturition was significantly lower in PS rats compared to SS rats, which was antagonized by antalarmin treatment. Increases in plasma and bladder CRF, and mRNA expressions of bladder CRF, CRF-R1, and M2/3 muscarinic receptors, were found in PS rats. CRF did not influence bladder contraction in itself; however, stress increased the response of muscarinic contraction of bladder strips. These changes were antagonized by antalarmin treatment. In conclusion, PS reinforces M3 receptor-mediated contractions via CRF-R1, resulting in bladder storage dysfunction.

Castration increases PGE2 release from the bladder epithelium in male rats.

AIMS: Androgen deprivation therapy has been widely used for the treatment of prostate cancer. While sexual side effects including decreased sexual desire and function are well studied, there are only limited reports about its influences on lower urinary tract symptoms. The aim of this study is to clarify the influences of castration in male rats. METHODS: Ten-week-old male rats were divided into treatment group (bilateral orchiectomy) and control group (sham surgery). Two-months after the surgery, adenosine triphosphate (ATP), prostaglandin E2 (PGE2), and nerve growth factor (NGF) released from stretched bladder epithelium were measured by luciferin-luciferase assay or ELISA. The mRNA levels of bladder cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined by real-time PCR. The protein level of bladder COX-2 was analyzed by western blot analysis. Bio-Plex Pro cytokine assay was performed to quantify the level of proinflammatory cytokine interleukin (IL)-1ß in the bladder. RESULTS: The PGE2 release from stretched bladder epithelium was significantly increased after castration, which increased more than 50% compared with control. On the other hand, those of ATP and NGF were not different from those of the controls. Testosterone replacement restored the PGE2 increase. Castration significantly increased bladder IL-1ß protein level and COX-2 at both mRNA and protein levels, whereas caused no marked changes in the COX-1 mRNA level. CONCLUSIONS: These findings suggest that castration induces inflammation in the rat bladder, which causes elevated PGE2 release from bladder epithelium and may finally contribute to the disruption of bladder storage function.

The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats.

The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth-related hypertrophy in sham-operated muscles and attenuated atrophy in denervated muscles. In denervated muscles, the transcription of ubiquitin ligase, atrogin-1/muscle atrophy F-box (Atrogin-1), and muscle RING-finger protein-1 (MuRF-1), genes was upregulated and ubiquitination of proteins was also increased. Intermittent heat stress inhibited the upregulation of Atrogin-1, but not MuRF-1 transcription. And the denervation-caused reduction in phosphorylated protein kinase B (Akt), 70-kDa heat-shock protein (HSP70), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which are negative regulators of Atrogin-1 and MuRF-1 transcription, was mitigated. In sham-operated muscles, repeated application of heat stress did not affect Atrogin-1 and MuRF-1 transcription, but increased the level of phosphorylated Akt and HSP70, but not PGC-1α Furthermore, the phosphorylation of Akt and ribosomal protein S6, which is known to stimulate protein synthesis, was increased immediately after a single heat stress particularly in the sham-operated muscles. The effect of a heat stress was suppressed in denervated muscles. These results indicated that the beneficial effects of heat stress on the morphological properties of muscles were brought regardless of innervation. However, the responses of intracellular signaling to heat stress were distinct between the innervated and denervated muscles.

Influence of simulated microgravity on the activation of the small GTPase Rho involved in cytoskeletal formation--molecular cloning and sequencing of bovine leukemia-associated guanine nucleotide exchange factor.

BACKGROUND: The irregular formation of cytoskeletal fibers in spaceflown experimental cells has been observed, but the disorganization process of fibers is still poorly understood. It is well known that the activation of the small GTPase Rho leads to actin stress fibers assembly. This study was performed to evaluate the effect of simulated microgravity on the activation of Rho that is involved in actin fiber remodeling in cells. RESULTS: Clinorotation influences actin fiber remodeling and its related signaling pathways that involve the small GTPase Rho. Actin stress fiber remodeling was significantly inhibited to a greater extent in cells cultured under clinorotation than in static cultured cells. From the gene and protein expression analyses, we found that the expression level of leukemia-associated Rho guanine nucleotide exchange factor (LARG), which activates Rho, was downregulated under clinorotation. Moreover, we identified the full-length LARG cDNA. The amount of GTP-bound RhoA, that is, the active form of RhoA, decreased under this condition. CONCLUSION: The activation of the small GTPase Rho was influenced by simulated microgravity generated by a three-dimensional (3D) clinostat. Furthermore, the full-length cDNA of bovine LARG, a member of the Rho guanine nucleotide exchange factor (GEF) family, was identified, and its gene expression was observed to be downregulated under clinorotation. This downregulation subsequently resulted in the repression of RhoA activation. These results indicated that the disorganization of the actin fibers was caused by the inhibition of Rho activation by 3D clinorotation.

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station.

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.

Correction: Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station.

[This corrects the article DOI: 10.1371/journal.pone.0150801.].

Importance of the converter region for the motility of myosin as revealed by the studies on chimeric Chara myosins.

A long alpha-helix in myosin head constitutes a lever arm together with light chains. It is known from X-ray crystallographic studies that the first three turns of this lever arm alpha-helix are inserted into the converter region of myosin. We previously showed that chimeric Chara myosin in which the motor domain of Chara myosin was connected to the lever arm alpha-helix of Dictyostelium myosin had motility far less than that expected for the motor domain of Chara myosin. Here, we replaced the inserted three turns of alpha-helix of Dictyostelium myosin with that of the Chara myosin and found that the replacement enhanced the motility 2.6-fold without changing the ATPase activity so much. The result clearly showed the importance of interaction between the converter region and the lever arm alpha-helix for the efficient motility of myosin.

Expression of p53-regulated proteins in human cultured lymphoblastoid TSCE5 and WTK1 cell lines during spaceflight.

The aim of this study was to determine the biological effects of space radiations, microgravity, and the interaction of them on the expression of p53-regulated proteins. Space experiments were performed with two human cultured lymphoblastoid cell lines: one line (TSCE5) bears a wild-type p53 gene status, and another line (WTK1) bears a mutated p53 gene status. Under 1 gravity or microgravity conditions, the cells were grown in the cell biology experimental facility (CBEF) of the International Space Station for 8 days without experiencing the stress during launching and landing because the cells were frozen during these periods. Ground control samples were simultaneously cultured for 8 days in the CBEF on the ground for 8 days. After spaceflight, protein expression was analyzed using a Panorama(TM) Ab MicroArray protein chips. It was found that p53-dependent up-regulated proteins in response to space radiations and space environment were MeCP2 (methyl CpG binding protein 2), and Notch1 (Notch homolog 1), respectively. On the other hand, p53-dependent down-regulated proteins were TGF-ß, TWEAKR (tumor necrosis factor-like weak inducer of apoptosis receptor), phosho-Pyk2 (Proline-rich tyrosine kinase 2), and 14-3-3θ/τ which were affected by microgravity, and DR4 (death receptor 4), PRMT1 (protein arginine methyltransferase 1) and ROCK-2 (Rho-associated, coiled-coil containing protein kinase 2) in response to space radiations. ROCK-2 was also suppressed in response to the space environment. The data provides the p53-dependent regulated proteins by exposure to space radiations and/or microgravity during spaceflight. Our expression data revealed proteins that might help to advance the basic space radiation biology.

p53-dependent adaptive responses in human cells exposed to space radiations.

PURPOSE: It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. METHODS AND MATERIALS: Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. RESULTS: In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. CONCLUSION: These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low.

The expression of p53-regulated genes in human cultured lymphoblastoid TSCE5 and WTK1 cell lines during spaceflight.

PURPOSE: The space environment contains two major biologically significant influences; space radiations and microgravity. The 53 kDa tumour suppressor protein (p53) plays a role as a guardian of the genome through the activity of p53-centered signal transduction pathways. The aim of this study was to clarify the biological effects of space radiations, microgravity, and the space environment on the gene expression of p53-regulated genes. MATERIALS AND METHODS: Space experiments were performed with two human cultured lymphoblastoid cell lines; one line (TSCE5) bears a wild-type p53 gene status, and another line (WTK1) bears a mutated p53 gene status. Under one gravity or microgravity conditions, the cells were grown in the cell biology experimental facility (CBEF) of the International Space Station for 8 days without experiencing stress during launching and landing because the cells were frozen during these periods. Ground control samples also were cultured for 8 days in the CBEF on the ground during the spaceflight. Gene expression was analysed using an Agilent Technologies 44 k whole human genome microarray DNA chip. RESULTS: p53-dependent up-regulated gene expression was observed for 111, 95, and 328 genes and p53-dependent down-regulated gene expression was found for 177, 16, and 282 genes after exposure to space radiations, to microgravity, and to both, respectively. CONCLUSIONS: The data provide the p53-dependent regulated genes by exposure to radiations and/or microgravity during spaceflight. Our expression data revealed genes that might help to advance the basic space radiation biology.

Susceptibility of Chara myosin to SH reagents.

Cellular and intracellular motile events in plants are susceptible to SH reagents such as N-ethylmaleimide (NEM). It has long been believed that the target of the reagent is myosin. We compared the effect of NEM on the motile and ATPase activities of skeletal muscle myosin with that on plant myosin using characean algal myosin. It was found that the motile activity of myosin prepared from NEM-treated C. corallina decreased to a level accountable for the decrease in the velocity of cytoplasmic streaming but it was also found that Chara myosin was far less susceptible to NEM than skeletal muscle myosin.