Subclinical articular involvement in primary Sjögren's syndrome assessed by ultrasonography and its negative association with anti-centromere antibody.

Objectives: To evaluate the subclinical articular involvement in patients with primary Sjögren's syndrome (pSS) using musculoskeletal ultrasound (MSUS), and to correlate the findings with laboratory results and clinical manifestations.

Methods: Forty-eight consecutive patients with pSS were enrolled. The bilateral metacarpophalangeal, proximal interphalangeal, and interphalangeal joints were examined using MSUS, and the synovial hypertrophy and power Doppler signal were recorded for each joint using semi-quantitative scores (0 = normal, 1 = mild change compared with undamaged joint, 2 = moderate change, and 3 = severe change).

Pharmacokinetics and dosing estimation of meropenem in Japanese patients receiving continuous venovenous hemodialysis.

The pharmacokinetics of meropenem have not yet been examined in Japanese patients receiving Continuous venovenous hemodialysis (CVVHD). The aim of this clinical investigation was to determine the pharmacokinetic parameters of meropenem in critically ill patients receiving CVVHD in order to estimate dosing regimens for the patient population in Japan. The values of pharmacokinetic parameters were 17.

Practical application of color Doppler ultrasonography in patients with ejaculatory dysfunction.

We describe two cases in which dynamic analysis of ejaculation using color Doppler ultrasonography was useful in diagnosis of ejaculatory dysfunction and planning of therapy. The first patient was a 32-year-old man with a diagnosis of retrograde ejaculation. A bladder neck collagen injection was carried out, as the main cause was thought to be the bladder neck remaining open during ejaculation.

One-Pot Production of L-threo-3-Hydroxyaspartic Acid Using Asparaginase-Deficient Escherichia coli Expressing Asparagine Hydroxylase of Streptomyces coelicolor A3(2).

We developed a novel process for efficient synthesis of L-threo-3-hydroxyaspartic acid (L-THA) using microbial hydroxylase and hydrolase. A well-characterized mutant of asparagine hydroxylase (AsnO-D241N) and its homologous enzyme (SCO2693-D246N) were adaptable to the direct hydroxylation of L-aspartic acid; however, the yields were strictly low. Therefore, the highly stable and efficient wild-type asparagine hydroxylases AsnO and SCO2693 were employed to synthesize L-THA.

Single nucleotide polymorphisms of cytarabine metabolic genes influence clinical outcome in acute myeloid leukemia patients receiving high-dose cytarabine therapy.

Cytarabine arabinoside (Ara-C) is the most important agent for treating acute myeloid leukemia (AML). Here, we genotyped 11 single nucleotide polymorphisms (SNPs) of seven Ara-C metabolism-related genes in 39 AML patients who had received high-dose Ara-C as a single-agent treatment. Univariate analysis identified three SNPs that were significantly associated with shorter time-to-relapse (TTR): CTPS rs12144160 GG compared to AA/AG, DCTD rs9990999 AG/GG compared to AA, and SLC29A1 rs693955 CC compared to AA/AC.

Therapeutic outcomes of neoadjuvant and concurrent androgen-deprivation therapy and intensity-modulated radiation therapy with gold marker implantation for intermediate-risk and high-risk prostate cancer.

Objectives: To investigate the therapeutic outcomes of neoadjuvant and concurrent androgen-deprivation therapy and intensity-modulated radiation therapy with gold marker implantation for intermediate- and high-risk prostate cancer.

Methods: This was a retrospective study of 325 patients with intermediate- or high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines who underwent androgen-deprivation therapy and intensity-modulated radiation therapy (76 Gy) after gold marker implantation between 2001 and 2010.

Results: The 5-year distant metastasis-free survival rate was significantly lower for very high-risk patients than for intermediate- and high-risk patients (82.

Hydroxamate-based colorimetric assay to assess amide bond formation by adenylation domain of nonribosomal peptide synthetases.

We demonstrated the usefulness of a hydroxamate-based colorimetric assay for predicting amide bond formation (through an aminoacyl-AMP intermediate) by the adenylation domain of nonribosomal peptide synthetases. By using a typical adenylation domain of tyrocidine synthetase (involved in tyrocidine biosynthesis), we confirmed the correlation between the absorbance at 490 nm of the l-Trp-hydroxamate-Fe(3+) complex and the formation of l-Trp-l-Pro, where l-Pro was used instead of hydroxylamine. Furthermore, this assay was adapted to the adenylation domains of surfactin synthetase (involved in surfactin biosynthesis) and bacitracin synthetase (involved in bacitracin biosynthesis).

Sonographic measurements of low-echoic synovial area in the dorsal aspect of metatarsophalangeal joints in healthy subjects.

Introduction: Assessment of synovitis in the metatarsophalangeal (MTP) joints with ultrasound has been shown to improve the accuracy of assessment of rheumatoid arthritis (RA). However, the presence of intraarticular low-echoic synovial area (LESA) in the MTP joints in healthy subjects complicates the sonographic assessment of these joints.

Method: Healthy subjects with no arthritic symptoms in their MTP joints were recruited.

Refined regio- and stereoselective hydroxylation of L-pipecolic acid by protein engineering of L-proline cis-4-hydroxylase based on the X-ray crystal structure.

Enzymatic regio- and stereoselective hydroxylation are valuable for the production of hydroxylated chiral ingredients. Proline hydroxylases are representative members of the nonheme Fe(2+)/α-ketoglutarate-dependent dioxygenase family. These enzymes catalyze the conversion of L-proline into hydroxy-L-prolines (Hyps).

Regio- and stereoselective oxygenation of proline derivatives by using microbial 2-oxoglutarate-dependent dioxygenases.

We evaluated the substrate specificities of four proline cis-selective hydroxylases toward the efficient synthesis of proline derivatives. In an initial evaluation, 15 proline-related compounds were investigated as substrates. In addition to l-proline and l-pipecolinic acid, we found that 3,4-dehydro-l-proline, l-azetidine-2-carboxylic acid, cis-3-hydroxy-l-proline, and l-thioproline were also oxygenated.

Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein-Barr virus (EBV)-positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV-positive DLBCL is controversial.

[A case of severe systemic juvenile idiopathic arthritis introduced tocilizumab in early phase of the disease].

A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital.

Pathogenesis of systemic inflammatory diseases in childhood: "Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrin-associated periodic fever syndrome".

Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo.

Long-term outcomes and complications of trabeculectomy for secondary glaucoma in patients with familial amyloidotic polyneuropathy.

Objective: Secondary glaucoma is a serious complication in patients with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). We assessed the long-term outcomes and complications of trabeculectomy with mitomycin C (MMC) for secondary glaucoma associated with FAP.

Methods: Medical case records of Kumamoto University Hospital were retrospectively reviewed.

Discrepancy between clinical and radiological responses to tocilizumab treatment in patients with systemic-onset juvenile idiopathic arthritis.

Objective: Tocilizumab (TCZ), an antiinterleukin-6 receptor monoclonal antibody, is clinically beneficial in patients with systemic-onset juvenile idiopathic arthritis (sJIA). We investigated the clinical and radiological outcomes of TCZ therapy in patients with sJIA.

Methods: We retrospectively evaluated 2 clinical trials (NCT00144599 and NCT00144612) involving 40 patients with sJIA who received intravenous TCZ (8 mg/kg) every 2 weeks.

Targeting of EGF-displayed protein nanoparticles with anticancer drugs.

The development of protein-based carriers for drug delivery has been well studied. We previously constructed a protein-based nanoparticle consisting of genetically engineered elastin-like polypeptides (ELPs) with a fused poly-aspartic acid tail (ELPD ). The size of the self-assembled ELPD nanoparticles was regulated by charged repulsion of the poly-aspartic acid chains.

Application of a new immunohistology scoring system (IH score): analysis of TNF-α in synovium related to disease activity score in infliximab-treated patients with rheumatoid arthritis.

Objectives: This study aimed to analyze the relationship between the expression of tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) in synovium and the disease activity score (DAS) 28 (C-reactive protein, CRP) in treatment of infliximab for rheumatoid arthritis (RA).

Methods: Synovial tissues were obtained from 16 infliximab-treated patients and assessed for TNF-α and IL-6 with a new immunohistology (IH) scoring system. The validation of IH score was performed and applied for the analysis of correlation between synovial TNF-α or IL-6 and DAS28 (CRP) in addition to Rooney score.

Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma.

Purpose/objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM).

Methods And Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured.

Epidemiological study on tibial plateau fractures at a level I trauma center.

Objectives: To review the epidemiological aspects of fractures of the tibial plateau in a level one hospital.

Methods: We retrospectively analyzed 239 tibial plateau fractures treated surgically. We took into account age, gender, trauma mechanism, classification of the injuries, associated injuries and affected side.

Identification and characterization of 2-oxoglutarate-dependent dioxygenases catalyzing selective cis-hydroxylation of proline and pipecolinic acid from actinomycetes.

Microbial hydroxylases were screened for the capacity to effect direct hydroxylation of proline and pipecolinic acid, based on genomic information. Of the eight candidates screened, 2-oxoglutarate-dependent hydroxylase from Streptosporangium roseum NBRC 3776(T) and aspartyl/asparaginyl β-hydroxylase from Catenulispora acidiphila NBRC 102108(T) showed both proline and pipecolinic acid hydroxylation activities. In the case of l-proline hydroxylation, both enzymes catalyzed the simultaneous formation of cis-3-hydroxy-l-proline and cis-4-hydroxy-l-proline, and cis-4-hydroxy-l-proline was preferentially produced.

Enhanced synthesis of 5-hydroxy-l-tryptophan through tetrahydropterin regeneration.

5-Hydroxy-l-tryptophan (5-HTP) is a naturally occurring aromatic amino acid present in the seeds of the African plant Griffonia simplicifolia. Although 5-HTP has therapeutic effects in various symptoms, efficient method of producing 5-HTP has not been established. In this study, we developed a novel cofactor regeneration process to achieve enhanced synthesis of 5-HTP by using modified l-phenylalanine 4-hydroxylase of Chromobacterium violaceum.

Quantification of pelvic soft tissue artifact in multiple static positions.

Soft tissue artifact (STA) has been identified as the most critical source of error in clinical gait analysis. Multiple calibration is a technique to reduce the impact of STA on kinematic data, which involves several static calibrations through the range of motion of the joint of interest. This study investigated how skin markers at the pelvis were displaced in relation to anatomical body landmarks in multiple static calibration positions.

The impact of remifentanil on incidence and severity of postoperative nausea and vomiting in a university hospital-based ambulatory surgery center: a retrospective observation study.

Background: Ambulatory surgery, including short-stay surgery, has become a common choice in clinical practice. For the success of ambulatory surgery, perioperative care with safe and effective anesthesia and postoperative analgesia, which can reduce the occurrence of postoperative nausea and vomiting (PONV), is essential. The effect of remifentanil on the occurrence and severity of PONV has not been thoroughly examined, particularly, in an ambulatory surgery setting.

Analysis of gender differences in genetic risk: association of TNFAIP3 polymorphism with male childhood-onset systemic lupus erythematosus in the Japanese population.

Background: Systemic lupus erythematosus (SLE) is a systemic multisystem autoimmune disorder influenced by genetic background and environmental factors. Our aim here was to replicate findings of associations between 7 of the implicated single nucleotide polymorphisms (SNPs) in IRF5, BLK, STAT4, TNFAIP3, SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the Japanese population. In particular, we focused on gender differences in allelic frequencies.

[Arthroscopic synovectomy for rheumatoid arthritis].

Even though the paradigm shift was occurred in treatments for rheumatoid arthritis (RA), some patients are not well controlled with several treatments. Because arthroscopic techniques advanced remarkably, effectiveness of arthroscopic synovectomy is reconsidered, especially for residual synovitis in biologics unresponders. A combined therapy with biologics and arthroscopic synovectomy leads to improvement of composite measures such as DAS28.