Controlled elimination of intracellular H(2)O(2): regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification

The predominant enzymes responsible for elimination of hydrogen peroxide (H(2)O(2)) in cells are peroxiredoxins (Prxs), catalase, and glutathione peroxidases (GPxs). Evidence suggests that catalytic activities of certain isoforms of these H(2)O(2)-eliminating enzymes are extensively regulated via posttranslational modification. Prx I and Prx II become inactivated when phosphorylated on Thr(90) by cyclin B-dependent kinase Cdc2. In addition, the active-site cysteine of Prx I-IV undergoes a reversible sulfinylation (oxidation to cysteine sulfinic acid) in cells. Desulfinylation (reduction to cysteine) is achieved by a novel enzyme named sulfiredoxin. c-Abl and Arg nonreceptor protein tyrosine kinases associate with catalase in cells treated with H(2)O(2) by mechanisms involving the SH3 domains of the kinases and the Pro(293)PheAsnPro motif of catalase and activate catalase by phosphorylating it on Tyr(231) and Tyr(386). Similarily, GPx1 is activated by c-Abl- and Arg-mediated phosphorylation. The tyrosine phosphorylation is critical for ubiquitination-dependent degradation of catalase.     

Analysis of photon beam exit dose using photon point kernels

The Monte Carlo method is used to analyse the dose fall-off at the exit surface of a megavoltage photon beam. The convolution/superposition method of dose calculation using Monte-Carlo-generated homogeneous photon kernels is shown to be in error for exit dose calculation. Instead, photon kernels that incorporate modelling of the exit surface were generated, also using Monte Carlo, to analyse the problem, and the calculated dose fall-off using these kernels agrees well with measured data. In addition, the physics underlying the characteristics of the dose fall-off is analysed based on complete Monte Carlo modelling. Practical improvements to the convolution/superposition method are suggested.     

Thermal behavior,morphology and the determination of the polymer-polymer interaction parameter of polycarbonate-poly(butylene terephthalate) blends

Blends of bisphenol-A polycarbonate (PC, poly(oxycarbonyloxy-1,4-phenylene-2-isopropylidene-1,4-phenylene)) and poly(butylene terephthalate) (PBT, poly(oxytetramethyleneoxy-terephthaloyl)) have been investigated by differential scanning calorimetry and scanning electron microscopy. Blends were prepared by screw extrusion and solution casting with mass fractions of PC in the blends varying from 0,90 to 0,10. From the measured glass transition temperature (T_g) and apparent mass fractions of PC and PBT dissolved in each phase, it appears that the PBT dissolves more in the PC-rich phase than does the PC in the PBT-rich phase. Also, compatibility is greater in the case of extruded blends than in the case of solutioncast blends. The values of the Flory-Huggins polymer-polymer interaction parameter (χ₁₂) were determined and found to range from 0,042 to 0,033 for extruded blends at 250°C and from 0,054 to 0,039 for solution casting at 25°C. The χ₁₂ decreases with increase of PBT content throughout the investigated composition range. From the T_g's, the microscopy study and the extrudate swell ratios, it is concluded that compatibility is achieved in the blends having mass fractions 0,90, 0,20 and 0,10 of PC, but that these blends are not microscopically homogeneous.     

Restrictive dermopathy: a report of three cases.

We report three infants with a rare syndrome of restrictive dermopathy, in which rigidity of the skin at birth is associated with characteristic facial anomalies, generalised arthrogryposis, bony abnormalities, and lung hypoplasia. The skin has a distinctive pathology with compaction of the dermal collagen and fibrosis of the subcutaneous tissue. The inheritance is likely to be autosomal recessive and the condition appears to be fatal in the early neonatal period.     

Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers

Bcl-2 and p53 gene products have been both linked to cell death by apoptosis. In the present study, we examined the relationship of Bcl-2 and p53 protein expression, p53 mutation and apoptosis in normal human ovaries and different types of human ovarian epithelial tumors by immunohistochemical localization, in situ terminal transferase-mediated dUTP nick end labeling and polymerase chain reaction-single strand conformation polymorphism. It was found that Bcl-2 expressed strongly in the surface epithelium of normal ovaries and benign and borderline ovarian tumors but weakly in the malignant tumors. On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium. A significant inverse correlation between Bcl-2 and p53 expression was found in the malignant ovarian tumors examined. p53 gene mutation at exons 5-11 was however not a pre-requisite for p53 expression in both borderline and malignant tumors. Apoptotic activities, as reflected by apoptotic indices, were low in normal ovarian surface epithelium and benign tumors but were increased in borderline and malignant tumors, with the highest average apoptotic index found in grade III malignant tumors. Statistical analyses showed a positive correlation between apoptosis and p53 expression, but similar correlation was not found between apoptosis and Bcl-2 expression. Our results also indicate that although expression of Bcl-2 is important during ovarian carcinogenesis, the Bcl-2 protein may have other roles to play apart from being a modulator of apoptosis in human ovarian epithelial cancers.     

Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study of 5 cases.

Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic appearances and clinical patterns. Recently, it has been suggested that almost all of the histologic features described under the name of polymorphic reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can be included in those generally described for malignant lymphomas of peripheral T cell origin(PTCL). There have been few studies of pathogenesis or tissue damage mechanism in PR patients. The need for a precise mechanism for tissue damage has important therapeutic implications. Using immunohistochemical methods with polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically and pathologically typical PR demonstrating a high expression of IL-6. According to classification, 2 cases of grade 1 PR showed the highest expressions, and 2 cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This strongly implies that some cases of PR have a different mechanism of tissue damage from frank PTCL, despite the one disease spectrum. Further studies on more cases may help clarify the pathogenesis.     

Effect of biphenyl dimethyl dicarboxylate on the humoral immunosuppression by ethanol

The present study was undertaken to investigate the effect of biphenyl dimethyl dicarboxylate (PMC) on the humoral immunosuppression by ethanol (EtOH) in ICR mice. PMC at a dose of 6 mg/kg was orally administered to mice daily for 28 consecutive days, and the control mice were given vehicle. Mice treated with EtOH were given freely with 20% EtOH instead of water. The results of this study are summarized as follows; a gain of body weight and the relative weights of spleen and liver were significantly increased by combination of PMC and EtOH, as compared with those in mice treated with EtOH alone. Splenic plaque forming cells (PFC) and hemagglutination (HA) titers to sheep red blood cells (SRBC), and the secondary IgG antibody response to bovine serum albumin (BSA) were decreased by the treatment of EtOH alone, then restored to normal level by PMC treatment. The elevations of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by EtOH were reduced to normal level by the combination of PMC and EtOH. In addition, lower serum albumin and A/G ratio were also increased to normal level. These findings indicate that PMC has a protective effect against EtOH-induced humoral immunosuppression.     

Improvement of Accuracy in a High-Capacity, Six Degree-of-freedom Load Cell: Application to Robotic Testing of Musculoskeletal Joints

This study investigated a previously unaccounted for source of error in a high-capacity, six degree-of-freedom load cell used in multi-degree-of-freedom robotic testing of musculoskeletal joints, an application requiring a load cell with high accuracy in addition to high load capacity. A method of calibration is presented for reducing the error caused by changes in universal force-moment sensor (UFS) orientation within a gravitational field. Uncorrected, this error can exceed a magnitude of 1% of the full-scale load capacity—the manufacturer-stated accuracy of the UFS. Implementation of the calibration protocol reduced this error by approximately 75% for a variety of loading conditions. This improvement in load cell accuracy (while maintaining full load capacity) should improve both the measurement and control of specimen kinetics by robotic/UFS and other biomechanical testing systems. © 1999 Biomedical Engineering Society. PAC99: 8719Rr, 8780Vt, 0620Fn, 0620Dk, 8719Ff     

Hypertrophic obstructive cardiomyopathy with infundibular stenosis treated by alcohol ablation therapy

This report describes an uncommon case of hypertrophic obstructive cardiomyopathy (HOCM) accompanying infundibular stenosis of the right ventricle treated by alcohol ablation therapy, in a 28-yr-old male patient presenting with dyspnea on exertion. HOCM with infundibular stenosis was detected by echocardiogram and cardiac catheterization and patient has dynamic obstructions of both ventricular outflow tracts. We performed alcohol ablation therapy to improve clinical symptoms and to relieve dynamic obstructions of both ventricular outflow tracts. This is the first case in which HOCM with infundibular stenosis of the right ventricle was treated by alcohol ablation therapy.     

Gemella bacteraemia characterised by 16S ribosomal RNA gene sequencing

AIMS: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species. METHODS: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing. RESULTS: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence. CONCLUSIONS: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates.