Involvement of STAT3 in Bladder Smooth Muscle Hypertrophy Following Bladder Outlet Obstruction

We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness 1 week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between > or = 2.0 and < or = 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (1 Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy

Successful Management of Pregnancy Complicated by Klippel-Trenaunay Syndrome Using MR Angiography-Based Evaluation

Klippel-Trenaunay syndrome (KTS) is a rare congenital disease, and extensive cutaneous hemangiomas and abnormal venous vessels are characteristic. In our case, to manage her pregnancy with KTS, whole-body MRA was performed before delivery. A 29-year-old woman was referred at 28 weeks because of prominent vulvovaginal varicosities due to KTS. At 35 weeks, hypertrophy and multiple venous varicosities of her leg as well as massive vulvovaginal varicosities became prominent with a normal coagulation profile. Systematic MRAs revealed hemangiomas and varicosities in the right leg, the lower abdomen, and the pubic region, while no obvious AVM was detected around the bronchial tube and spine. We decided to deliver her baby by cesarean section at 37 weeks under general anesthesia, and a healthy baby was delivered. No blood transfusion was required. Prophylaxis against thrombosis was performed after the operation. She was discharged with her baby. Her vulvovaginal varicosities shrunk considerably one month later

Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury

Immunophilin ligands prevent H2O2-induced apoptotic cell death by increasing glutathione levels in neuro 2A neuroblastoma cells.

We examined the effects of FK506 and its non-immunosuppressive derivative, GPI1046, on H2O2-induced reduction of cell viability and apoptotic cell death in Neuro 2A cells. Our results suggest that the protective properties of GPI1046 against H2O2-induced reduction of cell viability are equipotent with those of FK506 and may be mediated by increased intracellular concentrations of glutathione (GSH). In addition, both FK506 and GPI1046 prevented apoptotic cell death in Neuro 2A cells, although the antiapoptotic effect of FK506 was somewhat stronger than that of GPI1046. These findings suggest that non-immunosuppressive immunophilin ligands such as GPI1046 might be potentially useful in treatment of neurodegenerative diseases without serious side effects such as immune deficiency.</p

Site-specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer: possible implication for the differential diagnosis of cancer

Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported observed in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 in only cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core-type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers

Experimental Verification of Finite Element Analysis for a Thermoplastic Orthodontic Aligner

In recent years, good outcomes have been reported using transparent and removable orthodontic appliances known as aligners. However, unpredicted tooth movement that contradicted 3-dimensional image simulations was observed in some cases. These anomalies could relate to biomechanical factors ; in particular, the characteristics of mechanical loading applied to the periodontal ligament and the tooth crown by aligners remain unclear. This study examines the biomechanical characteristics of aligners by a new method as follows : 1) development of an experimental model using artificial teeth and plastic aligners ; 2) finite element (FE) modeling and analysis using computed tomography (CT) images of the experimental model ; and, 3) comparison among observations of this actual model and standard FE analysis results. Roots of two artificial teeth were covered by silicone material at 1.0 mm intervals for each coronal proximal surface and plastic clear aligners were manufactured based on another model in which the interval was reduced to 0.0 mm to simulate bodily movement. An FE analysis model of this 1.0 mm teeth interval was reconstructed from the CT images. A virtual aligner based on the FE model was also generated with a 0.0 mm interval. Changes in space between the root surface and silicone in both the actual and FE model were compared with the aligner fitted in the initial model. Identical tendencies of movement were observed in both experimental results - the artificial teeth and computational results of FE analysis. Our method using an experimental and computational approach proved useful to examine aligner characteristics ; the use of such a biomechanical approach could further our understanding of aligner treatments

Quality of Life in Patients with Minimal Change Nephrotic Syndrome

Aim. The goal of the study was to investigate quality of life (QOL) in adult patients with minimal change nephrotic syndrome (MCNS) and to test the relationship of QOL with the level of self-care. Materials and Methods. We distributed two questionnaires to 30 outpatients with MCNS. The MOS 36-item Short Form Health Survey (SF-36v2) was used to examine health-related QOL in comparison with normative data from the general Japanese population and a population with two chronic diseases. SF-36v2 consists of 36 questions classified into 8 subscales. We also used the Self-Care Behavior Scale for patients with chronic kidney disease (CKD), which consists of 31 questions with 4 subscales. Results. The SF-36v2 social functioning subscale was most impaired and bodily pain was least affected in patients with MCNS. The self-care subscales of information/communication and positive behavior had positive correlations with the QOL subscales of mental health () and vitality (). The correlation between social functioning and information/communication was close to significant (). Conclusion. In MCNS, social functioning was particularly impaired. Our results suggest that better self-care can have a positive impact on QOL in patients with MCNS

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined. CASE PRESENTATION: A 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN. CONCLUSION: Combination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection

Histomorphometric analysis of minimodeling in the vertebrae in postmenopausal patients treated with anti-osteoporotic agents

AbstractMinimodeling is a type of focal bone formation that is characterized by the lack of precedent bone erosion by osteoclasts. Although this form of bone formation has been described for more than a decade, how anti-osteoporotic agents that are currently used in clinical practice affect the kinetics of minimodeling is not fully understood. We performed a bone morphometric analysis using human vertebral specimens collected from postmenopausal patients who underwent spinal surgery. Patients were divided into three groups according to osteoporosis medication; non-treated, Eldecalcitol (ELD, a vitamin D derivative that has recently been approved to treat patients with osteoporosis in Japan)-treated, and bisphosphonate-treated groups. Five to six patients were enrolled in each group. There was a trend toward enhanced minimodeling in ELD-treated patients and suppressed of it in bisphosphonate-treated patients compared with untreated patients. The differences of minimodeling activity between ELD-treated and bisphosphonate-treated patients were statistically significant. The present study suggests that ELD and bisphosphonates have opposite effects on minimodeling from one another, and show that minimodeling also takes place in vertebrae as has been described for the ilium and femoral head in humans

Crry, a complement regulatory protein, modulates renal interstitial disease induced by proteinuria11See Editorial by Quigg, p. 2315

Crry, a complement regulatory protein, modulates renal interstitial disease induced by proteinuria.BackgroundRecent studies have suggested a role for urinary complement components in mediating tubulointerstitial damage, which is known to have a good correlation with progression of chronic renal diseases. Although accumulating evidence suggests that complement regulatory proteins play an important protective role in glomeruli, their role in renal tubules remains unclear. In order to establish the role of a complement regulatory protein, Crry, in renal tubular injury, we employed a molecular biological approach to block the expression of Crry in tubules of animals with proteinuria induced with puromycin aminonucleoside nephritis (PAN).Methods and ResultsTwo different antisense oligodeoxynucleotides (ODNs) against Crry were designed and applied to cultured rat mesangial cells in vitro in order to establish their efficacy. Antisense ODN treatment resulted in decreased expression of Crry protein associated with increased sensitivity to complement attack in cell lysis assays compared with control ODN treatment or no treatment (44.7, 1.50, and 1.34%, respectively). Antisense ODNs did not affect the expression of Thy1 as a control, confirming the specificity of our ODNs. In vivo, we performed selective right renal artery perfusion to administer antisense ODNs to the kidney and showed prominent uptake of ODNs by proximal tubular cells. Reduced expression of Crry protein was demonstrated in proximal tubular cells in antisense ODNs-treated kidneys. Normal rats treated with the antisense ODNs did not show any pathological changes. However, in PAN, rats with massive proteinuria showed increased deposition of C3 and C5b-9 in tubules in antisense-treated kidneys, and histological assessment revealed more severe tubulointerstitial injury in antisense-treated animals compared with controls.ConclusionThese results establish a pathogenic role for complement in leading to tubulointerstitial injury during proteinuria and, to our knowledge for the first time, show a protective role of a complement regulatory protein, Crry, in renal interstitial disease