Contrast-enhanced CT rim sign may predict vestibular schwannoma adhesion and postoperative complications.

AIM: To investigate the clinical and radiological features to predict adhesion between vestibular schwannoma (VS) and brain tissue which is a critical risk factor for postoperative infarction and residual tumour. MATERIAL AND METHODS: One hundred and seven consecutive VS surgeries were analysed. After excluding cases without contrast-enhanced (CE) computed tomography (CT), Koos grades 1 and 2, and cases with incomplete clinical data, 44 patients were finally included in the study. Enhancement of the tumour capsule on the brainstem side on CE-CT was defined as the CE-CT rim sign, which was analysed along with clinical characteristics, including tumour adhesion and postoperative complications. RESULTS: Eight patients exhibited CE-CT rim signs; 17 had tumour adhesions. Four patients had postoperative infarction at the ipsilateral middle cerebellar peduncle; 18 exhibited postoperative infarction and/or residual tumour at the middle cerebellar peduncle. The CE-CT rim sign significantly correlated with tumour adhesion, postoperative infarction, and postoperative infarction and/or residual tumour in the cerebellar peduncle. Univariate regression analysis revealed that the CE-CT rim sign significantly correlated with tumour adhesion (odds ratio [OR] 6.81, 95% confidence interval [CI] 1.18-39.25, p=0.032) and postoperative infarction and/or residual tumour at the cerebellar peduncle (OR 6.00, 95% CI 1.04-34.31, p=0.044). CONCLUSION: The CE-CT rim sign was identified in 18.2% of patients with VS and significantly correlated with tumour adhesion and postoperative complications, such as postoperative infarction and residual tumour. This study highlights the importance of the preoperative CE-CT rim sign in VS, which is predictive of tumour adhesion and postoperative complications.

TRPV1, ASICs and P2X2/3 expressed in bone cells simultaneously regulate bone metabolic markers in ovariectomized mice.

OBJECTIVES: Nociceptors are expressed at peripheral terminals of neurons. Recent studies have shown that TRPV1, a nociceptor, is expressed in bone tissue and regulates bone metabolism. We have demonstrated that a TRPV1 antagonist improved pain-like behavior in ovariectomized (OVX) mice. The aim of this study was to determine whether nociceptors, including TRPV1, acid-sensing ion channel (ASIC) and P2X2/3 are expressed in bone cells, and to examine the effects of nociceptor antagonists on bone metabolism. METHODS: The expression of nociceptors in femoral bone tissue and cultured bone marrow cells in OVX and sham-operated mice were examined. The effects of nociceptor antagonists on the up-regulated expression of bone metabolic markers, Runx2, Osterix, osteocalcin and RANKL, were also examined. RESULTS: TRPV1, ASIC 2 and 3, and P2X2 and 3, were expressed in bone tissue and bone marrow cells, and the expression levels of ASIC1 and 2, and P2X2 were significantly increased in OVX mice in comparison with those in sham mice. Treatment with nociceptor antagonists significantly inhibited the expression of bone metabolic markers in OVX mice. CONCLUSION: An array of nociceptors, TRPV1, ASICs and P2X2/3, could simultaneously regulate not only increases in skeletal pain but also bone turnover in OVX mice.

Tumour necrosis factor inhibitor-associated sinusitis.

AIM: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. METHODOLOGY: A retrospective review of the medical records between 2003 and 2011 revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. RESULTS: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. CONCLUSION: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.

Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non-eosinophilic chronic rhinosinusitis (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was determined using double-immunofluorescent staining for IgE and cell-type-specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class-switch-related molecules, including IL-4, IL-5, IL-13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS: The concentrations of total IgE and number of IgE-positive cells were significantly higher in the eosinophilic polyps compared with control and non-eosinophilic polyps. IgE-positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1-positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non-eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE-related profiles between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Arthrography in thumb polydactyly with bifurcation at the interphalangeal or metacarpophalangeal joints provides practical information at surgery.

We carried out arthrography in 19 thumbs of 18 patients in whom duplication was observed at the interphalangeal (Wassel type II) or metacarpophalangeal (Wassel type IV) joints on radiographs. The average age at surgery was 12.3 months and average duration of post-surgical follow-up was 21.3 months. Based on the arthrographic findings, the types of cartilaginous connections were subdivided into five groups. In group 1, there was a cartilaginous connection at the base of duplicated phalanges. In group 2, there was a cartilaginous connection of the radial digit between the distal and proximal phalanges, or between the proximal phalanx and metacarpal. In group 3, the phalanges separated at a common joint without any cartilaginous connection. In group 4, the radial digit demonstrated fibrous attachment to the capsule without any joint formation. In group 5, each joint was completely separated without any cartilaginous connection. These arthrographic findings could not be detected on radiographs. Different surgical procedures were carried out according to the form of cartilaginous connection.

[Long-term results of aortic root replacement with a composite graft].

We analyzed the long-term results of aortic root replacement with a composite graft. Since 1992, 127 patients had undergone aortic root replacement with a composite graft. There were 92 men and 35 women with a mean age of 56.5 years. There were 69 patients with annuloaortic ectasia, 17 aortic dissections, and 41 ascending aortic dilatation due to aortic valve disease. Marfan syndrome was diagnosed in 19 patients. As surgical procedure, button technique was used in 90 patients, Cabrol technique in 11, and Piehler technique in 26. Open distal anastomosis was performed in 82 patients to avoid clamp injury of rest aorta. Early mortality was 3.1% and no major morbid events had occurred. Follow-up was completed in 95.9% of the patients and the mean follow-up period was 6.1 years. Actuarial survival at 5, 10, and 15 years was 86.2%, 83.4%, and 83.4%, respectively. Actuarial freedom from aortic valve reoperation at 10 and 15 years was 99.2% and 95.7%, respectively. The results of aortic root replacement with a composite graft were excellent. This procedure should be the 1st choice for surgical treatment of the aortic root disease.

B(0)-B(0) mixing in unquenched lattice QCD.

We present an unquenched lattice calculation for the B(0)-B(0) transition amplitude. The calculation, carried out at an inverse lattice spacing 1/a=2.22(4) GeV, incorporates two flavors of dynamical quarks described by the O(a)-improved Wilson fermion action and heavy quarks described by nonrelativistic QCD. Particular attention is paid to the uncertainty that arises from the chiral extrapolation, especially the effect of pion loops, for light quarks, which we find could be sizable for the leptonic decay constant, whereas it is small for the B parameters. We obtain f(B(d))=191(10)(+12-22) MeV, f(B(s))/f(B(d))=1.13(3)(+13-2), B(B(d))(m(b))=0.836(27)(+56-62), B(B(s))/B(B(d))=1.017(16)(+56-17), and xi=1.14(3)(+13-2), where the first error is statistical, and the second is systematic, including uncertainties due to chiral extrapolation, finite lattice spacing, heavy quark expansion, and perturbative operator matching.

Reuse of sewage sludge as raw material of Portland cement in Japan.

A potential alternative of sewage sludge reuse is the substitute of raw material for Portland cement. This paper overviews Japanese implementation of this and discusses the best selection of pretreatment for this purpose. The pretreatment includes dewatering, incineration, and lime treatment.

Valgus deformity of the ankle following harvesting of a vascularized fibular graft in children.

Progressive valgus ankle deformity is a problematic postoperative donor-site morbidity of a vascularized fibular graft in children. To prevent this complication, tibiofibular metaphyseal synostosis (the Langenskiöld procedure) has been recommended. The authors objectively evaluated the preventive and therapeutic effects of this procedure on five children who had received free vascularized fibular grafts. Their average age at the time of operation was 3 years (range: 1 to 9 years). The Langenskiöld procedure was performed primarily in four patients, and not in one patient. The anteroposterior (A-P) mortise angle and the empirical axis of the donor-site ankle were measured radiographically. With regard to the A-P mortise angle, four of five patients showed valgus with a mild lateral wedging of the distal tibial epiphysis. The patient who did not receive the operation showed the largest A-P mortise angle and mild osteoarthritic changes. The empirical axis exceeded normal range in all of the five patients. These observations indicated that valgus deformity of the ankle in children after harvesting a vascularized fibular graft is inevitable, even if the Langenskiöld procedure is performed. The procedure can delay the ankle valgus. The authors recommend close follow-up of the children who receive the Langenskiöld procedure after harvesting a vascularized fibular graft.

[The weather chart pattern inducing asthma attack: the advocacy of "fine mist" as a provocative factor].

Outbreaks of asthma attack on 345 patients were studied in relation to the atmospheric phenomena. About 76% of days in which multiple attacks took place were fit with either of the following atmospheric conditions, 1) the trough of atmospheric pressure, 2) the approach of Typhoon, 3) the cold advection, in Japan. The common feature of these different atmospheric conditions are the tendency to turn excess vapor into fine water particles (fine mist). The fine mist could stimulate irritable airway to asthma attacks ("fine mist" hypothesis). To verity this hypothesis each asthmatic attack was further studied. It fitted in 70.7% of the attacks (fitting group) and not in 29.3% of the attacks (non-fitting group). Frequency of asthmatic attacks varied in every month on fitting group, but was nearly constant on non-fitting group. The average of the daily change of vapor density was calculated monthly. And it appeared that its graphic pattern was similar to the graphic pattern of asthmatic attack frequency. Thus it is supposed that there are at least two factors that could induce asthmatic attacks, one would be fine mist, others are unknown.

Prediction of progression of spinal deformity in Duchenne muscular dystrophy: a preliminary report.

STUDY DESIGN: Discriminatory power was statistically estimated for multiple combinations of risk indicators for the progression of spinal deformity in Duchenne muscular dystrophy (DMD). OBJECTIVE: To differentiate DMD cases in which spinal deformity will rapidly and severely progress from those with lesser progression of spinal deformity. SUMMARY OF BACKGROUND DATA: Early surgical intervention using instrumentation has recently been advocated for DMD patients to prevent the progression of spinal deformity. However, early determination of cases needing surgical intervention is difficult because of variations in the severity of the clinical courses of DMD patients. METHODS: Charts and spinal radiographs of 12 DMD patients were reviewed retrospectively. Patterns of progression in spinal deformity were classified into three types according to Oda's classification. Discriminant analysis was conducted to categorize the patients into either a severe progression group (type-1 and type-2 patients) or a less severe progression group (type-3 patients and patients without spinal deformity) on the basis of four predictors: 1) vital capacity at the age of 10 years, 2) the age at which ambulation ceased, 3) curve pattern of spinal scoliosis, and 4) Cobb angles of spinal scoliosis at the age of 10 years. RESULTS: Eleven of the twelve DMD patients showed spinal deformity. Three were classified as type 1, six were classified as type 2, and two were classified as type 3. The remaining patient showed no spinal deformity. Multiple discriminant analysis correctly predicted the severity of the clinical course of 91.7% of the DMD patients. Vital capacity at age 10 was found to be the strongest predictor among the variables. CONCLUSIONS: Through multiple discriminant analysis, the clinical course of spinal deformity in DMD patients was correctly predicted in 92% of subjects. This method would be useful to determine early which DMD cases need surgical intervention for treatment of spinal deformity.

Correlation between progression of spinal deformity and pulmonary function in Duchenne muscular dystrophy.

The purpose of this study was to investigate how age at and value of the plateau of vital capacity (VC plateau) correlate with the severity of the progression of spinal deformity in patients with Duchenne muscular dystrophy (DMD). Changes in spinal deformity and pulmonary function in 36 DMD patients were examined in a retrospective longitudinal study. Patterns of progression of spinal deformity were classified into three types according to Oda's classification. Of the 32 patients who showed spinal deformity, six were classified as type 1, 19 as type 2, and seven as type 3. The correlation between the patterns of progression of spinal deformity and the VC plateau was examined using a discriminant analysis. Rapid and severe progression of spinal deformity could be expected in patients whose VC plateau was less than 1,900 mL and in those in which it occurred before age 14 years. Thus VC plateau may be an indicator of the severity of the progression of spinal deformity in DMD patients.

Dynamical quark effects on light quark masses

Light quark masses are calculated in lattice QCD with two degenerate flavors of dynamical quarks. The calculations are made with improved actions with lattice spacing a = 0.22-0.11 fm. In the continuum limit we find m(M&Smacr;)(ud)(2 GeV) = 3.44(+0.14)(-0.22) MeV using the pi and rho meson masses as physical input, and m(M&Smacr;)(s)(2 GeV) = 88(+4)(-6) MeV or 90(+5)(-11) MeV with the K or straight phi meson mass as additional input. The quoted errors represent statistical and systematic combined, the latter including those from continuum and chiral extrapolations, and from renormalization factors. Compared to quenched results, two flavors of dynamical quarks reduce quark masses by about 25%.

Quenched light hadron spectrum

We present results of a large-scale simulation for the flavor nonsinglet light hadron spectrum in quenched lattice QCD with the Wilson quark action. Hadron masses are calculated at four values of lattice spacing in the range a approximately 0.1-0.05 fm on lattices with a physical extent of 3 fm at five quark masses corresponding to m(pi)/m(rho) approximately 0.75-0.4. The calculated spectrum in the continuum limit shows a systematic deviation from experiment, though the magnitude of deviation is contained within 11%. Results for decay constants and light quark masses are also reported.

Trace 5-methylaminomethyl-2-selenouridine in bovine tRNA and the selenouridine synthase activity in bovine liver.

We measured the amount of Se in bovine liver tRNA. tRNA was chromatographed on a BD-cellulose column and Se-rich tRNA was eluted from the column in front of a main tRNA peak. There was 0.3 mmol Se/mol of tRNA and this level is about one tenth that of Escherichia coli tRNA. This suggests the presence of an enzyme that modifies tRNA with Se in bovine liver. We isolated the activity of this enzyme (selenouridine synthase) by chromatography of bovine liver extracts on a DEAE-cellulose column. ATP and selenophosphate synthetase, as well as selenouridine synthase and tRNA, were necessary for the reaction. 75Se was used to label the reaction products, which were analyzed by TLC after digestion with ribonuclease T2. The position of the 75Se-nucleotide on a TLC plate was identical to that of the Se-nucleotide, 5-methylaminomethyl-2-seleno-Up, prepared from 75Se-tRNA in E. coli.

Recombinant light chain of human monoclonal antibody HB4C5 as a potentially useful lung cancer-targeting vehicle.

Recombinant lambda light chain of lung cancer-reacting human monoclonal antibody HB4C5 was expressed in Escherichia coli. Expression in bacteria ensured the generation of homogeneous light chain species devoid of activity-hampering N-linked glycosylation usually found in the light chain CDR-1 of HB4C5. Molecular engineering was also employed to eliminate the C-terminal two amino acid residues, i.e., Cys and Ser, to prevent the formation of lambda light chain dimers which are less reactive than the monomeric form. The lambda light chain was overexpressed in E. coli as inclusion bodies, which were solubilized, refolded, and treated with Aeromonas proteolytica aminopeptidase to remove the N-terminal Met with subsequent natural cyclization of the penultimate Gln residue to pyroglutamate, the same N-terminal end as that of naturally occurring lambda light chain in HB4C5. Monomeric recombinant lambda light chains, both before and after removal of the N-terminal Met residue, were 40 times more immunoreactive than the parent HB4C5. The immunostaining of lung cancer tissue sections with the recombinant lambda light chain indicated cancer-specific reactions to all specimens of adenocarcinoma, squamous cell carcinoma and large cell carcinoma histologies, but did not react with small cell carcinoma. Tumor radioimmunoimaging experiments in LC6 (lung squamous cell carcinoma line)--xenografted nude mice by the i.p. injection of 125I-labeled recombinant lambda light chain and 125I-labeled human lambda light chain control gave tumor-specific and recombinant lambda light chain-dependent images on day 5 postinjection, and images were also detectable on day 3. Biodistribution studies with 125I-labeled recombinant lambda light chain demonstrated that the lambda light chain could penetrate better into the tumor sites, both at the necrotic and solid parts of the xenograft, as compared to our previous results with 125I-labeled HB4C5 which could localize to the necrotic part only. These results suggest that the recombinant lambda light chain is potentially useful as a lung cancer-targeting vehicle, for such as radioimmunoimaging and radioimmunotherapy, with least possible adverse immunogenic effects.

Selenophosphate as a substrate for mammalian selenocysteine synthase, its stability and toxicity.

The mechanism of selenocysteine synthesis on tRNASec in mammals was previously studied by means of HSe- as a Se donor to synthesize selenocysteine. It has been recently established that HSe- in E. coli is activated by ATP to become selenophosphate (SeP). In this study, we provide evidence that [75Se]selenocysteine is produced by bovine selenocysteine synthase from Ser-tRNASec and [75Se]Sep, synthesized from elemental 75Se and Tris(trimethylsilyl)phosphite. We also studied the stability of SeP by NMR measurement. SeP was stable during storage under nitrogen at -80 degrees C for 3 months in 0.2 M Hepes buffer at pH 6.8. However, SeP decomposed at 0 degree C in air (half life 32 hrs) or at 22 degrees C under nitrogen (half life 30 hrs) at pH 6.8. The half lives of SeP at -19 degrees C in air and at 0 degree C under nitrogen at pH 6.8 were 740 and 840 hrs, respectively. At pH 4 under nitrogen at 22 degrees C, the half life was 240 hrs. The half life was only 9.2 hrs at pH 9 under nitrogen at 0 degree C. Thus, SeP was proved to be stable at low temperature, under acidic and anaerobic conditions, but labile under neutral and alkaline conditions. The LD50 of SeP administered i.p. to mice was 37.5 mg/kg body weight.

The dual identities of mammalian tRNA(Sec) for SerRS and selenocysteine synthase.

Se is an essential trace element and is found as a selenocysteine in the active site of Se-enzymes, such as glutathione peroxidase. tRNASec is first aminoacylated with serine by Ser RS and further is converted to selenocysteyl-tRNA by selenocysteine synthase. Mammalian selenocysteine tRNA has dual identities with Ser RS and selenocysteine synthase. Key identity elements for selenocysteine synthase are the long 9 bp AA- and long 6 bp D-stems. Major serine tRNA was converted to a mutant with a 9 bp AA-stem and 6 bp D-stem, instead of a 7 bp AA-stem and 3 bp D-stem. This mutant was active for selenylation as well as serylation. The relative kinetic parameter (Vmax/Km) of the mutant was 0.052 of the value (1.00) of wild-type Sec tRNA. This low value suggests that there is an unknown fine base specific for selenocysteine synthase. For serylation, mutant having 12 bp and wild type tRNASec having 13 bp of the total length of AA- + T-stems were active but the mutants having 11 or 14 bp were inactive. This shows that SerRS measures the distance between the discrimination base and long extra arm for recognition of tRNASer.

Long-term rail stance training in healthy young adult women.

Daily rail stance training was performed for no longer than 3 months on 12 healthy Japanese women volunteers with eyes open and closed. Rail width conditions were varied, during which time rail stance was repeated 30 times every day until volunteers could stand for 60 s in at least half the trials. Prolongation of stance time and retention of training effects were investigated. The rate of progress depended on the difficulty of the stance and was determined by rail width and visual conditions. However, marked differences were seen among subjects even under the same training conditions. The faster the progress, the better preserved was the training effect during the post-training period. There was no obvious difference in the learning curve between narrow rails with eyes open and wide rails with eyes closed. We concluded that the retention of the training effect parallels the rate of progress, and this is determined by the difficulty of action relative to the inherent ability of the subjects.