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Introduction: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro., Methods: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability., Results: IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone., Conclusion: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function., (© 2019 S. Karger AG, Basel.)

Background/aims: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells., Methods: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone., Results: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release., Conclusions: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases., (© 2019 S. Karger AG, Basel.)

Background: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models., Methods: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles., Results: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (-) group after 48 h was significantly lower than that in the nigericin (+) group., Conclusions: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Introduction: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP)., Materials and Methods: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra- and perioperative complications were collected., Results: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors., Conclusions: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP., (© 2017 S. Karger AG, Basel.)

An inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells, accompanied by inflammatory infiltration of plasma cells, lymphocytes, and eosinophils. IMTs rarely occur in the urinary bladder. It is important to distinguish this tumor from other malignant spindle cell tumors. Herein, we report a patient with an IMT showing muscle invasion, who underwent a transurethral resection of the bladder tumor and, at a later date, partial cystectomy. The resected tumor specimen revealed a proliferation of spindle-shaped cells on a background of plasma cells and lymphocytes. Immunohistochemical staining showed the tumor to be positive for anaplastic lymphoma kinase (ALK), smooth muscle actin, and vascular endothelial growth factor (VEGF). Such histopathological findings were indicative of an IMT, suggesting the use of inhibitors of ALK and VEGF as pharmacotherapy.

Primitive neuroectodermal tumor (PNET) is a member of the Ewing's sarcoma family of tumors (ESFT). We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide) chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.

Objective: Osteoporosis is associated with the pathogenesis and risk of urolithiasis, which is higher among postmenopausal women (as opposed to premenopausal). Bisphosphonates potently inhibit bone resorption, and are used in the management of bone disease. We investigated the ability of a bisphosphonate to prevent calcium stone formation., Methods: We studied 12 postmenopausal women (63.8 +/- 7.3 years) who were not receiving osteoporosis therapy, and had stones comprised of calcium phosphate (CaP; n = 3), calcium oxalate (CaOx; n = 3) and CaP + CaOx (n = 6). We measured bone mineral density (BMD), serum and urinary values in 24-hour urine specimens before and 3 months after the oral administration of 5 mg/day of alendronate (ALN). The indexes of the ionic activity product of calcium oxalate, AP(CaOx), and of calcium phosphate, AP(CaP), were estimated using the Tiselius method., Results: ALN significantly reduced the AP(CaP) index (1.53 +/- 1.37 to 0.89 +/- 0.81, p <0.05). Urinary calcium, oxalate, phosphate and the AP(CaOx) index did not significantly change. BMD improved in 11 of the 12 patients. Urinary stones did not develop in any of the patients during the course of the study., Conclusion: The results suggested that ALN not only improves BMD and osteoporosis, but also reduces the risk of calcium phosphate stone formation in postmenopausal women., (Copyright (c) 2009 S. Karger AG, Basel.)

Background: With a westernized diet the oxygenated products of renal prostaglandin synthesis are metabolites of the n-6 series and these are known to play important roles in several pathophysiological processes involved in calcium stone formation. As eicosapentaenoic acid (EPA) administration is effective for the prevention of hyperlipidemia and atherosclerosis, we suggest the use of EPA as a possible method of preventing calcium stone formation., Methods: We administered a highly purified preparation of 1,800 mg/day EPA to 29 patients for 36.4 +/- 22.0 months after therapy for nephrolithiasis. We observed the urinary stone recurrence in these patients over the course of 8 years (before, during and after medication) and studied the preventive effect on the recurrence of nephrolithiasis. We analyzed the effect of EPA administration and compared the findings to those before and after administration., Results: The incidence rates of nephrolithiasis (times/year) before, during and after the administration of EPA were 0.2283, 0.0693 and 0.1742, respectively. The incidence rate of nephrolithiasis during the administration of EPA was significantly lower compared the findings to those before and after its administration (p < 0.05)., Conclusion: The results suggest that EPA might reduce the risk of calcium stone formation., ((c) 2008 S. Karger AG, Basel.)

Background/aim: Active ulcerative colitis (UC) is often associated with increased peripheral granulocytes and monocytes/macrophages which show activation behavior and prolonged survival time. Further, mucosal granulocyte level parallels intestinal inflammation and can predict UC relapse. Accordingly, our aim was to see if adsorptive granulocyte/monocyte apheresis (GMA) can promote remission and spare steroid in patients with steroid-dependent (SD) UC., Methods: 69 SD patients, at the time of relapse, were randomly assigned to groups I (n = 46) and II (n = 23). The mean dose of prednisolone (PSL) was 12 mg/day/patient, CAI (clinical activity index) 9.2 in both groups. Group I patients were given up to 11 GMA sessions over 10 weeks with Adacolumn; in group II, the mean dose of PSL was increased to 30 mg/day/patient., Results: At week 12, 83% of group I and 65% of group II patients were in remission, CAI in group I was 1.7 (p < 0.001) and in group II, 2.5 (p < 0.001). Further, during the 12 weeks of treatment, the cumulative amount of PSL received per patient was 1,157 mg in group I and 1,938 mg in group II (p = 0.001)., Conclusions: GMA appeared to be an effective adjunct to standard drug therapy of moderately severe UC by promoting remission and sparing steroids.

Madin-Darby canine kidney (MDCK) cells have been used in research on crystal adhesion to epithelial cells. Recently, matrix proteins were identified, and studies of the genes and proteins expressed in renal epithelial cells have become active. The present study confirms the usefulness of the NRK-52E cell line, derived from the rat, in the study of attachment with calcium oxalate crystals. The calcium oxalate crystal suspension was distributed on top of the cells. After incubation, the monolayers were rinsed to remove non-associated crystals. After fixation, the association of crystals and NRK-52E cells was visualized using scanning electron microscopy. Calcium oxalate crystals were attached to the surface of NRK-52E cells. Under high magnification, many of the microvilli of the cells had elongated towards the crystals, and microvilli projections appeared to catch the crystals. The NRK-52E cell line is useful in the study of attachment between crystals and urinary epithelial cells in the kidney, especially for the regulation and analysis of genes and proteins., (Copyright 2001 S. Karger AG, Basel)

Purpose: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999., Patients and Methods: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy., Results and Conclusions: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer., (Copyright 2001 S. Karger AG, Basel)

Solitary fibrous tumors (SFT) are well recognized in the pleura, but their rare occurrence at other sites has become appreciated only in recent years. We experienced a 68-year-old male patient who presented with frequency of urination and difficulty in voiding. Computed tomographic scan revealed a solid and cystic mass which measured 12 x 10 cm in the prevesical space. This tumor showed typical histopathologic features of SFT, and was immunostained positive for vimentin, CD34 and CD99. This is an extremely rare case of SFT arising from the parietal peritoneum found in the prevesical space., (Copyright 2000 S. Karger AG, Basel)

Objectives: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH)., Patients and Methods: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories., Results: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score., Conclusions: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.

A 1-year-old boy was referred to us because of abnormal external genitalia; that is, his penis was kinked toward the perineal region. We diagnosed hypospadias. Chromosomal examination was performed on a sample of peripheral blood, the karyotype was 46,X+mar. Detailed karyotypic analysis revealed that the short arm of the marker chromosome originated on the ninth chromosome, but we could not determine whether the long arm was part of the Y chromosome, even with the use of quinacrine mustard. The sex-determining region of the Y was detected using the polymerase chain reaction method, which suggested that the long arm of the marker chromosome was delivered from the short arm of the Y chromosome.

Glomerular selectivity is still conserved in chronic renal failure (CRF), although it is poor when compared with non-CRF. In addition, clearances per unit nephron of 15 plasma proteins (Cprot./Ccr X 100) are markedly elevated in CRF. This reflects an effect of osmotic diuresis on tubular reabsorption of proteins, which may partially account for the tubular dysfunction shown by the augmented excretion of the low molecular proteins, such as lysozyme and insulin. Besides this, there exists certainly tubular damage, since tubuloglomerular protein ratio (Clysozyme/Ctransferrin) rises with the progress of glomerular injury.