Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis

Journal of Gastroenterology - T helper (Th) and regulatory T (Treg) cell-related cytokines are implicated in inflammatory bowel diseases, including ulcerative colitis (UC). While these cytokines...     

Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes

The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24h of incubation, the AQP4 expression level increased maximally with 35mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain.     

BRCA2 protects mammalian cells from heat shock

Purpose: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway. Here, we investigate the role of BRCA2 in repairing DNA damage induced by heat shock.

Materials and methods: Chinese hamster lung fibroblast cell lines and human tongue squamous cell carcinoma SAS cells were used. RAD51 foci formation assay was used as an HR indicator. Heat sensitivity was analysed with colony forming assays. Phosphorylated histone H2AX (γH2AX) intensity, which correlates with the number of DSBs, was analysed with flow cytometry.

Results: RAD51 foci appeared with heat shock, and the number of cells with RAD51 foci was maximal at about 4?h after heat shock. Heat-induced RAD51 foci co-localised with γH2AX foci. BRCA2-deficient cells were sensitive to heat when compared to their parental wild-type cells. Heat-induced γH2AX was higher in BRCA2-deficient cells compared to parental cells. In SAS cells, cells transfected with BRCA2-siRNA were more sensitive to heat than cells transfected with negative control siRNA. Apoptotic bodies increased in number more rapidly in BRCA2-siRNA transfected cells than in cells transfected with negative control siRNA when cells were observed at 48?h after a heat treatment. In addition, cells deficient in BRCA2 were incapable of activating heat-induced G₂/M arrest.

Conclusion: BRCA2 has a protecting role against heat-induced cell death. BRCA2 might be a potential molecular target for hyperthermic cancer therapy.     

Dependence of Baroreceptor-Mediated Sympathetic Outflow on Biventricular Assist Device Driving Frequency

Abstract: To investigate the drive condition of the artificial heart from a neurophysiological point of view, the dynamic transduction characteristics of the baroreflex system were analyzed by means of sympathetic neurograms. Two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses (BVBs) in adult mongrel dogs to compare the natural heart circulation and prosthetic circulation. After BVB pumping was initiated, the natural heart was electrically fibrillated. Renal sympathetic nerve activity (RSNA) was recorded to analyze sympathetic outflow. Coherence function between the arterial pressure and RSNA was calculated to evaluate the linearity of the baroreflex system. The largest peak coherency was observed when BVB was driven at the frequency of natural heart beat prior to electrical fibrillation, which suggests that the baroreflex system shows the largest linearity at this frequency. These results suggest the possibility that the natural heart heat frequency is the setting frequency at which the baroreflex system transfers the hemodynamic rhythm to the sympathetic outflow.     

Degeneration at the insertion weakens the tensile strength of the supraspinatus tendon: A comparative mechanical and histologic study of the bone-tendon complex

The purpose of this investigation was to determine the relationship between the degree of degeneration at the supraspinatus insertion, the tensile strength, and the site of failure of this tendon. Thirty-three fresh cadaveric shoulders (average age: 62 years; range: 39-83 years) were examined. A tensile load to failure was applied at a constant crosshead speed of 25.4 mm/min to a 10 mm wide strip of the supraspinatus tendon that remained attached to the bone. Preexisting degenerative changes at the insertion were assessed and scored histologically and compared with the ultimate tensile stress. Twenty tendons failed at the insertion (the insertion group), and 11 failed in the midsubstance (the midsubstanee group). The histologic score of degeneration for the insertion group was significantly higher than that for the midsubstance group (p = 0.0026). There was a negative correlation between the ultimate tensile stress at the insertion and the degeneration score for the insertion group (r = ?0.60; p = 0.013). Histologic observations revealed that disruptions of tendon fibers were located mostly in the articular half of the tendon and that they enlarged during mechanical testing in 90% of the specimens of the insertion group. It seems that degenerative changes at the supraspinatus insertion reduce the tensile strength of the tendon and constitute a primary pathogenetic factor of rotator cuff tear.     

New prognostic factors associated with long-term survival in node-negative breast cancer patients

Background  This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Patients and Methods  Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). Results  Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. Conclusion  PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.     

The effects of air-abrasion on dentin, enamel, and metal bonding

PURPOSE: To determine the most effective emission pressure for producing effective bond strengths of an adhesive resin to enamel, dentin and metal. METHODS: Test specimens were prepared from bovine teeth for enamel and dentin samples and from alloy disks cast in an Ag-Pd-Cu-Au alloy. All specimen substrates were ground flat and finished with 600-grit SiC paper. The prepared specimens were randomly divided into groups of eight including a control (no abrasion) or air-abraded with 50 microm Al2O3 delivered at three emission pressures of 60, 45 and 30 psi, respectively. Following conditioning, 4-META/MMA-TBB resin was bonded to the specimen surfaces. Specimens were stored in 37 degrees C water for 24 hours, then thermocycled 20,000 times (4 degrees C-60 degrees C), and shear bond tested. Data were analyzed by ANOVA for statistical significance. RESULTS: Enamel specimens showed no statistically significant difference from the control (no air abrasion). Dentin specimens displayed a significant difference from control at 60 and 45 psi, but no significant difference from the control at 30 psi. Alloy specimens showed significantly higher bond strengths from the control at all emission pressures (P< 0.05).