Range of Motion Measurements of the Hip Joint Are Useful in Screening for Acetabular Dysplasia in Healthy Young Japanese Women.

The purpose of this study is to clarify whether a hip range of motion (ROM) measurement is useful in screening for early hip osteoarthritis with acetabular dysplasia (AD). Subjects were 58 healthy Japanese women volunteers (21.1 ± 0.7 (20 - 22)). We evaluated a total of 116 hip joints in these 58 cases. Sharp angle and centeredge angle were 44.1° ± 3.1° (37.0° - 51.5°) and 30.7°± 6.2° (19.5° - 47.0°), respectively. AD was present in 47.4%, but there were no severe cases. First, we compared the ROM of the hip joints with AD (AD group) and without AD (control group) according to the Mann-Whitney U test. Extension angles and external rotation angles in the AD group were significantly smaller than in the control group (18.9°± 6.1° VS. 22.1°± 4.2°, p= 0.01636, 26.3°± 8.9° VS. 34.1°± 8.8°, p= 0.001362, respectively). Next, we evaluated the following factors associated with AD by logistic regression analysis after adjustment for age: flexion, extension and internal and external rotation angles of the hip joint. As a result, internal rotation and external rotation were extracted as related factors. The area under the ROC curve was determined to have a moderate accuracy (0.72996). Cut off values of internal rotation and external rotation angles were 50 degrees and 35 degrees, respectively. Our findings suggest that ROM measurement of the internal and external rotation angles would be useful as a screening for AD in healthy young Japanese women without symptoms.

Electrophysiological evaluation of an anticancer drug gemcitabine on cardiotoxicity revealing down-regulation and modification of the activation gating properties in the human rapid delayed rectifier potassium channel.

Gemcitabine is an antineoplastic drug commonly used in the treatment of several types of cancers including pancreatic cancer and non-small cell lung cancer. Although gemcitabine-induced cardiotoxicity is widely recognized, the exact mechanism of cardiac dysfunction causing arrhythmias remains unclear. The objective of this study was to electrophysiologically evaluate the proarrhythmic cardiotoxicity of gemcitabine focusing on the human rapid delayed rectifier potassium channel, hERG channel. In heterologous hERG expressing HEK293 cells (hERG-HEK cells), hERG channel current (IhERG) was reduced by gemcitabine when applied for 24 h but not immediately after the application. Gemcitabine modified the activation gating properties of the hERG channel toward the hyperpolarization direction, while inactivation, deactivation or reactivation gating properties were unaffected by gemcitabine. When gemcitabine was applied to hERG-HEK cells in combined with tunicamycin, an inhibitor of N-acetylglucosamine phosphotransferase, gemcitabine was unable to reduce IhERG or shift the activation properties toward the hyperpolarization direction. While a mannosidase I inhibitor kifunensine alone reduced IhERG and the reduction was even larger in combined with gemcitabine, kifunensine was without effect on IhERG when hERG-HEK cells were pretreated with gemcitabine for 24 h. In addition, gemcitabine down-regulated fluorescence intensity for hERG potassium channel protein in rat neonatal cardiomyocyte, although hERG mRNA was unchanged. Our results suggest the possible mechanism of arrhythmias caused by gemcitabine revealing a down-regulation of IhERG through the post-translational glycosylation disruption possibly at the early phase of hERG channel glycosylation in the endoplasmic reticulum that alters the electrical excitability of cells.

Nitric oxide down-regulates voltage-gated Na+ channel in cardiomyocytes possibly through S-nitrosylation-mediated signaling.

Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and-independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.

[A Case of Pneumocystin a Patient with Pneumonia That Developed during Chemotherapy for Sigmoid Cancer].

A 63-year-old man was diagnosed with advanced sigmoid cancer of pT3, pN0, sM1c, sP3, fStage Ⅳ post-operation. After CAPOX plus Bmab as the first-line chemotherapy, he underwent IRIS plus Bmab as the second-line chemotherapy. After 1 course of IRIS plus Bmab, he was admitted to the hospital for fever, dyspnea, and general fatigue. The white blood cell count was 6.2×10 3/mL, and the C-reactive protein was elevated to 12.9 mg/dL. The PaO2 of the artery blood gas analysis in room air was 46.3 mmHg, suggesting respiratory failure. He was diagnosed with PCP based on the bilateral diffused ground-glass opacities on chest CT along with an elevated serum b-D-glucan. The treatment of trimethoprim-sulfamethoxazole and steroid was then initiated. After the patient's clinical condition improved, he was discharged on day 27 post-admission.

[A Case of Nephrotic Syndrome Due to SOX plus Bmab Therapy for Liver Metastasis of Rectal Cancer].

A 66-year-old man was postoperatively diagnosed with pT4a, pN2, cM1a(H2), cP0, fStage Ⅳ, RAS wild type rectal cancer. He underwent SOX plus Bmab chemotherapy 4 weeks later. After 9 courses of SOX plus Bmab, he was admitted to the hospital for leg edema and proteinuria(4+). Because of severe proteinuria(14.7 g/day)and low protein(Alb 2.0 g/dL, TP 4.9 g/dL), he was diagnosed with nephrotic syndrome. His general condition improved on stopping chemotherapy and administration of conservative treatment, and he was discharged on day 20 after admission. The proteinuria improved 3 months later. He had been undergoing SOX chemotherapy for 4 months.

Ganglion cyst in the supraspinous fossa: arthroscopically undetectable cases.

Studies have demonstrated favorable outcomes of arthroscopic decompression for ganglion cyst in the supraspinous fossa; however, little attention has been paid to the difficulty in detecting these cysts during arthroscopy. In this report, we present 2 cases in which ganglion cysts in the supraspinous fossa were undetectable during arthroscopy. The ganglion cysts were not identified in these cases during surgery despite arthroscopic decompression being performed through the area in which the cyst was expected until the suprascapular nerve was entirely exposed. After surgery, magnetic resonance imaging (MRI) confirmed the disappearance of the ganglion cyst and external rotation strength was fully improved, without shoulder pain. We emphasize here that surgeons should be aware of this difficulty when performing arthroscopic decompression of ganglion cysts in the supraspinous fossa.

A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA), a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm) at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1) the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins) than the membranes of cells in S/G2/M-phase; 2) the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3) S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

Psoriasis vulgaris caused by ceramic inserts used in total hip replacement.

BACKGROUND: Ceramics are inorganic nonmetallic materials and are used as bioinert components in joint replacement surgeries. Ceramics are known to be low allergenic. We experienced a ceramic-induced psoriasis. OBJECTIVE: We report a first case of possible ceramic-induced psoriasis caused by a ceramic insert. METHODS: A 55-year-old female received an implanted ceramic-on-ceramic total hip replacement for osteoarthritis of the right hip joint. Following surgery, she developed psoriatic lesions, which continued for 10 years. We suspected that psoriasis was caused by a ceramic insert and removed it surgically. RESULTS: When the ceramic insert was replaced with a polyethylene-on-metal hip joint, the psoriatic lesions completely disappeared. CONCLUSION: The pathogenesis of psoriasis is still an enigma, although deregulation of nuclear factor κB signaling and resulting abnormal cytokine secretion are speculated to be involved. Ceramics may affect these signaling events and cause the onset of psoriasis.

A case of rheumatoid arthritis improved from Steinbrocker classification class IV to class II after multi-joint surgery.

We report the case of a patient with rheumatoid arthritis (RA) who showed a reduction in disease severity (from class IV to class II) after multi-joint surgery. The patient was a 61-year-old man with a history of RA, type-2 diabetes, chronic obstructive pulmonary disease, and nephrotic syndrome. He had been undergoing treatment for RA for the past 10 years, but his condition could not be appropriately controlled. In addition to generalized edema, marked destruction of the left elbow joint and knees was observed, and he was unable to move in bed (Steinbrocker classification: stage IV, class IV). In March 2009, he developed suppurative arthritis of the left elbow (methicillin-sensitive Staphylococcus aureus [MSSA] infection) and was referred to our institution, where the infection subsided after cleaning of the wound and administration of antibiotics. In March 2010, he underwent artificial joint replacement arthroplasty of the left elbow, followed by replacement arthroplasty of the right knee in July that year and of the left knee in November. As of December 2011, the patient showed no signs of inflammatory reactions and was able to walk using crutches (Steinbrocker classification: stage IV, class II). Recent advancements in pharmacotherapy have made it possible to control the advancement of joint destruction in RA. However, in this patient, because of the advanced stage of joint destruction, surgical methods were required to aid the patient in recovering his ability to walk.

Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone.

UNLABELLED: The impact of AGEs on human MSCs was studied. AGEs inhibited the proliferation of MSCs, induced apoptosis, and prevented cognate differentiation into adipose tissue, cartilage, and bone, suggesting a deleterious effect of AGEs in the pathogenesis of musculoskeletal disorders in aged and diabetic patients. INTRODUCTION: Advanced glycation end-products (AGEs) are accumulated on long-lived proteins of various tissues in advanced age and diabetes mellitus and have been implicated in chronic complication, including musculoskeletal disorders. Human mesenchymal stem cells (MSCs) potentially differentiate into mature musculoskeletal tissues during tissue repair, but the pathogenetic role of AGEs on MSCs is unclear. MATERIALS AND METHODS: AGEs were prepared by incubating BSA with glucose, glyceraldehydes, or glycolaldehyde (designated as AGE-1, AGE-2, or AGE-3, respectively). Proliferation, apoptosis, and reactive oxygen species (ROS) generation were assayed in AGE-treated cells. The expression of the receptor for AGE (RAGE) was examined by immunohistochemistry and Western blotting. Involvement of RAGE-mediated signaling was examined using a neutralizing antiserum against RAGE. Differentiation into adipose tissue, cartilage, and bone were morphologically and biochemically monitored with specific markers for each. RESULTS: AGE-2 and AGE-3, but not control nonglycated BSA and AGE-1, reduced the viable cell number and 5-bromo-2'deoxyuridine (BrdU) incorporation with increased intracellular ROS generation and the percentage of apoptotic cells. MSCs expressed RAGE and its induction was stimulated by AGE-2 and AGE-3. These AGEs inhibited adipogenic differentiation (assayed by oil red O staining, lipoprotein lipase production, and intracellular triglyceride content) and chondrogenic differentiation (assayed by safranin O staining and type II collagen production). On osteogenic differentiation, AGE-2 and AGE-3 increased alkaline phosphatase activity and intracellular calcium content; however, von Kossa staining revealed the loss of mineralization and mature bone nodule formation. The antiserum against RAGE partially prevented AGE-induced cellular events. CONCLUSION: AGE-2 and AGE-3 may lead to the in vivo loss of MSC mass and the delay of tissue repair by inhibiting the maturation of MSC-derived cells. The AGE-RAGE interaction may be involved in the deleterious effect of AGEs on MSCs.

Overexpression of p21Waf1 induces apoptosis in immortalized human vascular smooth muscle cells.

To understand the role of the cell cycle regulatory protein in the control of smooth muscle cell (SMC) proliferation, we tested the overexpression of p21Waf1, a cyclin-dependent kinase inhibitor, in human normal (MS9) and immortalized SMCs (ISS10) transfected with ori-minus simian virus 40 DNA, using an adenovirus-mediated system. In MS9, overexpression of p21Waf1 resulted in the inhibition of cell cycle progression at the G1/S boundary without apoptosis. On the other hand, in ISS10, overexpression of p21Waf1 induced marked apoptosis. In these cells, immunohistochemistry revealed that overexpressed p21Waf1 was localized in the nucleus. No differential expression pattern of either p53 or SV40T was observed in p21Waf1- and control gene (beta-galactosidase)-infected cells. Old-passaged ISS10 cells eventually showed growth arrest and a senescent-like phenotype. Immunohistochemistry revealed that p21Waf1 was localized in the cytoplasm of the early-passaged cells, but was found in the nucleus of the old-passaged cells. Our data suggested that nuclear accumulation of p21Waf1 plays a role in the cell death of immortalized SMC, which carries dysfunction of the cell cycle regulatory proteins such as p53. This culture model may be useful for studying the process of SMC proliferation, cell death, senescence, and cell cycle regulation.