Up-regulation of acid-sensing ion channels in the capsule of the joint in frozen shoulder.

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay. The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group. This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder.

Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin-proteasome system.

The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells. The increases in UPS activity and degradation of E6/E7 oncoproteins were associated with DHA-induced overproduction of mitochondrial reactive oxygen species (ROS). Exogenous oxidative stress and pharmacological induction of mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS production abolished UPS activation, E6/E7 viral protein destabilization, and apoptosis. These findings identify a novel role for DHA in the regulation of UPS and viral proteins, and provide evidence for the use of DHA as a mechanistically unique anticancer agent for the chemoprevention and treatment of HPV-associated tumors.

Src homology 2-containing protein tyrosine phosphatase-2 acts as a negative regulator for MUC5AC transcription via the inhibition of the ERK1/2 MAPK signalling pathway in the airway.

AIMS: Mucus hypersecretion has been frequently observed in inflammation respiratory diseases. However, the negative regulators for mucus overproduction have not been readily identified. Our work focused on identifying novel negative regulator that modulates mucus overproduction in the human respiratory system. Herein, we examined whether H2 O2 could induce MUC5AC transcription in a dose-dependent manner and activate tyrosine phosphatase (SHP)-2 in human airway epithelial cells. METHODS: We performed qRT-PCR to detect the changes in MUC5AC transcription and dot-blotting analysis to investigate MUC5AC secretion as regulated by SHP-2. RESULTS: H2 O2 induced MUC5AC transcription in a dose-dependent manner and dramatically activated SHP-2. In addition, whereas wild-type SHP-2 completely inhibited H2 O2 -induced MUC5AC transcription, siRNA-SHP-2 restored it interestingly, suggesting that SHP-2 may act as a negative regulator for mucus overproduction and hypersecretion in the human respiratory tract. Moreover, SHP-2 inhibited the ERK1/2 MAPK pathway, thus abolishing the signalling for MUC5AC transcription. CONCLUSION: We found that H2 O2 induced SHP-2 activation, which acted as a suppressor in H2 O2 signalling to regulate MUC5AC transcription in the airway.

CT findings of pulmonary non-tuberculous mycobacterial infection in non-AIDS immunocompromised patients: a case-controlled comparison with immunocompetent patients.

OBJECTIVE: To describe CT findings of non-tuberculous mycobacteria (NTM) pulmonary infection in non-AIDS immunocompromised patients (ICPs) and to compare these findings with those in immunocompetent patients. METHODS: From July 2000 to August 2007, 369 patients (mean age 58.3 years; 169 males and 200 females) with pulmonary NTM infection were retrospectively reviewed. Of these 369 patients, 24 ICPs (mean age 64.8 years; 15 males and 9 females) were identified. 16 patients had diabetes mellitus, and 6 patients had received long-term steroid therapy. One had received solid organ transplantation and one had received high-dose chemotherapy for haematological disease. 24 age- and sex-matched immunocompetent patients (mean age 64.6 years; 15 males and 9 females) were selected as the control group from the same registry. CT images were reviewed in consensus by three chest radiologists, who were blinded to immune status. Each lung lobe was evaluated in terms of extent of the lesion, bronchiectasis, parenchymal opacity and the presence of ancillary findings. results: A total of 287 lobes were evaluated in ICPs and the control group. The ICPs showed a higher prevalence of ill-defined nodules, with cavities and large opacity >2 cm with/without cavity (p=0.03, 0.04 and 0.02, respectively). Regardless of the immune status, the most common CT findings were bronchiectasis and ill-defined nodules without cavity. CONCLUSION: The most common CT findings of pulmonary NTM infection in ICPs were bronchiectasis and ill-defined nodules, similar to those in the control group. Ill-defined nodules with cavity and large opacity >2 cm with/without cavity were more frequently found in ICPs. ADVANCES IN KNOWLEDGE: In patients affected by NTM infection, large opacities and cavitation in pulmonary nodules are more frequent in ICPs than in immunocompetent patients.

c-Ets1 inhibits the interaction of NF-κB and CREB, and downregulates IL-1ß-induced MUC5AC overproduction during airway inflammation.

Mucin hypersecretion is frequently observed in many inflammatory diseases of the human respiratory tract. As mucin hypersecretion refers to uncontrolled mucin expression and secretion during inflammation, studies examining the negative control mechanisms of mucin hypersecretion are vital in developing novel therapeutic medications. We hypothesized that the c-Ets1 induced by interleukin (IL)-1ß would decrease MUC5AC overproduction by inhibiting the interaction of NF-κB with cAMP response element-binding protein (CREB) in vivo. Stimulation with IL-1ß caused the direct binding of NF-κB and CREB to the MUC5AC promoter, thus increasing MUC5AC gene expression. However, IL-1ß-induced MUC5AC messenger RNA levels were surprizingly downregulated by c-Ets1 (located -938 to -930). Interestingly, c-Ets1 also suppressed IL-1ß-induced MUC5AC gene expression in vitro and in vivo by disrupting the interaction of NF-κB with CREB on the MUC5AC promoter. In addition, c-Ets1 also inhibited significant morphologic changes and inflammatory cell infiltration after IL-1ß exposure in mouse lungs infected with either wild-type or shRNA-c-Ets1. Moreover, reactive oxygen species produced by NOX4 increased c-Ets1 gene expression and MUC5AC gene expression in alveolar macrophages from bronchoalveolar lavage fluid. These results suggest a molecular paradigm for the establishment of a novel mechanism underlying the negative regulation of mucin overproduction, thus enhancing our understanding of airway inflammation.

Conservative treatment of pediatric trigger thumb: follow-up for over 4 years.

We analyzed the outcomes of our conservative treatment for pediatric trigger thumb. Since March 2004, we have used conservative treatment for all patients with pediatric trigger thumb. We prospectively analyzed 30 patients in whom 35 thumbs were affected (10 right, 15 left, 5 bilateral). The mean age at diagnosis was 28 (11-50) months. The treatment consisted of passive exercises performed by the children's mothers, 10-20 times daily. How reliably this was performed is unproven. Trigger thumb severity was graded as 0A (extension beyond 0°), 0B (extension to 0°), 1 (active extension with triggering), 2 (passive extension with triggering), and 3 (cannot extend either actively or passively i.e. locked). At diagnosis, six of the 35 thumbs (17%) were grade 1, 25 (71%) were grade 2, and four (11%) were grade 3. After a mean follow-up period of 63 (range, 49-73) months, 28 thumbs (80%) were grade 0A or 0B, 5 (14%) were grade 1 and 2 (6%) were grade 2. The bilateral cases and the patients who initially had grade 3 severity had significantly more unfavorable results than the other patients. This study suggests that conservative treatment for pediatric trigger thumb is a successful method, although cases that present with bilateral involvement or locking (grade 3) should be considered for early surgical release.

The gene expression profile of matrix metalloproteinases and their inhibitors in children with Henoch-Schönlein purpura.

BACKGROUND: Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis. OBJECTIVES: To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP. METHODS: Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction. RESULTS: MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs. CONCLUSIONS: This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.

Displaced fracture of the femoral neck in children: open versus closed reduction.

We have investigated whether early anatomical open reduction and internal fixation (ORIF) reduces the incidence of complications of fracture of the femoral neck in children, including avascular necrosis, compared with closed reduction and internal fixation (CRIF). We retrospectively reviewed 27 such fractures (15 type-II and 12 type-III displaced fractures) in children younger than 16 years of age seen in our hospital between February 1989 and March 2007. We divided the patients into three groups according to the quality of the reduction (anatomical, acceptable, and unacceptable) and the clinical results into two groups (satisfactory and unsatisfactory). Of the 15 fractures treated by ORIF, 14 (93.3%) had anatomical reduction and reduction was acceptable in one. Of the 12 treated by CRIF, three (25.0%) had anatomical reduction, eight had acceptable reduction (66.7%), and one (8.3%) unacceptable reduction. Of the 15 fractures treated by ORIF, 14 (93.3%) had a good result and one a fair result. Of the 12 treated by CRIF, seven (58.3%) had a good result, two (16.7%) a fair result and three (25.0%) a poor result. There were seven complications in five patients. ORIF gives better reduction with fewer complications, including avascular necrosis, than does CRIF in fractures of the femoral neck in children.

Radiological findings and clinical features of thoracic immunoglobulin G4-positive plasma cell granuloma: two cases.

Plasma cell granulomas, inflammatory pseudotumours and myofibroblastomas are synonymous with characteristic plasma cell infiltration in various body organs including the pancreas, liver, retroperitoneum and mediastinal structures causing idiopathic fibrosclerosis. Recently, a new concept has arisen regarding the relationship between immunoglobulin (Ig)G4-positive cell infiltration and idiopathic systemic fibrosclerosis. We report two cases showing IgG4-positive cell infiltration in the lung presenting as lung nodules with or without extrapulmonary manifestations.

The measurement of 129I for the cement and the paraffin solidified low and intermediate level wastes (LILWs), spent resin or evaporated bottom from the pressurized water reactor (PWR) nuclear power plants.

In this paper a relatively simple and low cost analysis procedure to apply to a routine analysis of (129)I in low and intermediate level radioactive wastes (LILWs), cement and paraffin solidified evaporated bottom and spent resin, which are produced from nuclear power plants (NPPs), pressurized water reactors (PWR), is presented. The (129)I is separated from other nuclides in LILWs using an anion exchange adsorption and solvent extraction by controlling the oxidation and reduction state and is then precipitated as silver iodide for counting the beta activity with a low background gas proportional counter (GPC). The counting efficiency of GPC was varied from 4% to 8% and it was reversely proportional to the weight of AgI by a self absorption of the beta activity. Compared to a higher pH, the chemical recovery of iodide as AgI was lowered at pH 4. It was found that the chemical recovery of iodide for the cement powder showed a lower trend by increasing the cement powder weight, but it was not affected for the paraffin sample. In this experiment, the overall chemical recovery yield of the cement and paraffin solidified LILW samples and the average weight of them were 67+/-3% and 5.43+/-0.53 g, 70+/-7% and 10.40+/-1.60 g, respectively. And the minimum detectable activity (MDA) of (129)I for the cement and paraffin solidified LILW samples was calculated as 0.070 and 0.036 Bq/g, respectively. Among the analyzed cement solidified LILW samples, (129)I activity concentration of four samples was slightly higher than the MDA and their ranges were 0.076-0.114 Bq/g. Also of the analyzed paraffin solidified LILW samples, five samples contained a little higher (129)I activity concentration than the MDA and their ranges were 0.036-0.107 Bq/g.

Radiological and clinical findings of pulmonary aspergillosis following solid organ transplant.

AIM: To evaluate the radiological and clinical findings in patients with pulmonary aspergillosis after solid organ transplantation. MATERIALS AND METHODS: This study included 13 consecutive patients (five liver, four kidney, and four heart transplant; 10 male and three female; median age 54 years; range 13-63 years) with histologically confirmed pulmonary aspergillosis after solid organ transplantation at a tertiary referral hospital. Chest radiographs and computed tomography (CT) examinations performed for diagnosis were available in all patients. Radiological findings, such as lesion characteristics, location, and associated findings, were assessed retrospectively by two radiologists. The changes in radiological findings and clinical response after treatment were also assessed. Clinical findings, such as time of onset, initial symptoms, clinical course, and laboratory findings, were reviewed. RESULTS: The most common radiographic and CT findings were pulmonary nodules or masses (n=12). The number of nodules or masses was less than 10 in eight patients. Associated findings were surrounding ground-glass opacity (n=4), central low density (n=8), central air cavity (n=5), and air bronchogram (n=3). Follow-up radiographs and/or CT after treatment showed improvement in eight patients, persistence in two, and deterioration in three. The onset time of pulmonary aspergillosis was a median of 32 days (range 15-165 days). The most common symptom at diagnosis was fever (n=6). Ten of 13 patients did not have leucopaenia. There were two aspergillosis-associated deaths during the follow-up period. CONCLUSION: The most common radiological finding of pulmonary aspergillosis after solid organ transplantation is multiple nodules or masses, which commonly appear within 1 month following transplantation.

Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma.

In the course of searching for BACE1 (beta-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of Smilax Rhizoma (the dried rhizomes of Smilax china L.) showed potent inhibitory activity. The active compounds were identified as a trans/cis-resveratrol mixture, oxyresveratrol, veraphenol, and cis-scirpusin A. They were shown to non-competitively inhibit BACE1 with the Ki values of 5.4 x 10(-6), 5.4 x 10(-6), 3.4 x 10(-6), and 5.4 x 10(-6)M and IC(50) values of 1.5 x 10(-5), 7.6 x 10(-6), 4.2 x 10(-6), and 1.0 x 10(-5)M, respectively. The active compounds were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

Regeneration of the proximal tibial epiphysis after infantile osteomyelitis: report of three cases with an eight- to 22-year follow-up.

We reviewed three infants with destructive osteomyelitis involving the proximal tibial epiphysis at a follow-up of eight to 22 years. All cases showed early radiographic destructive changes in the medial or lateral aspects of the epiphysis and metaphysis. Despite the ominous early appearance of the epiphysis, all cases showed spontaneous re-ossification of the epiphysis with restoration of the tibial condyle and preservation of joint congruity. The patients, however, developed a valgus or varus deformity which was treated satisfactorily with one to three proximal tibial osteotomies. The potential for regeneration of the epiphysis following infantile osteomyelitis of the proximal tibia suggests these cases should be treated expectantly with regard to joint congruity.

Case report: pericardial rupture and cardiac herniation after blunt trauma: a case diagnosed using cardiac MRI.

Pericardial rupture following blunt chest trauma is rare, and is not usually diagnosed pre-operatively. If pericardial rupture is not recognized and treated promptly, it may be fatal owing to cardiac herniation. We report a case of traumatic herniation of the heart for which a CT scan and MRI made a major contribution to the diagnosis.