Abnormal Wrist Sagittal Kinematics in Gymnasts With Dorsal Wrist Pain: A New Syndrome.

BACKGROUND: The pathology of dorsal wrist pain in gymnasts without abnormal radiographic findings remains unclear. PURPOSE/HYPOTHESIS: The purpose of this study was to identify abnormal wrist sagittal kinematics in gymnasts with dorsal wrist pain. It was hypothesized that gymnasts with dorsal wrist pain would show abnormal sagittal kinematics with reversible hypermobility of the intercarpal joint. STUDY DESIGN: Controlled laboratory study. METHODS: Participants included 19 wrists in male gymnasts with dorsal wrist pain, 18 wrist in male gymnasts without wrist pain, and 20 adult men without a history of wrist pain. Magnetic resonance imaging (T2-weighted sagittal images) findings at 0°, 30°, 60°, and 90° of wrist extension were used in kinematic analysis. The angles and translations of the radiolunate, capitolunate, and third carpometacarpal joint were measured and compared between the 3 groups. RESULTS: At 90° of wrist extension, gymnasts with dorsal wrist pain had a significantly lower radiolunate joint angle (28.70°± 6.28° vs 36.19°± 7.81°; P = .020) and a significantly higher capitolunate joint angle (57.99°± 6.15° vs 50.50°± 6.98°; P = .004) and distal translation (1.17 ± 0.50 mm vs 0.46 ± 0.62 mm; P = .002) than gymnasts without dorsal wrist pain. CONCLUSION: Gymnasts with dorsal wrist pain showed abnormal wrist sagittal kinematics. These novel findings may facilitate understanding of dorsal wrist pain, which can be recognized as a new syndrome termed "gymnast's lunate dyskinesia."

[Current status and future prospects of nursing education in Japan].

The Bachelor of Nursing program is being held at 255 universities in 2017. There are various initiatives universities to meet the needs of society, nurturing high-quality nurses, but securing the level of education is one of the tasks. The Ministry of Education, Culture, Sports, Science and Technology established a nursing education model core curriculum for solving the problem. Each university is expected that the curriculum will be built with reference to this model core curriculum for quality assurance of education.

Dietary Supplementation with Isoflavones Prevents Muscle Wasting in Tumor-Bearing Mice.

Proinflammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent TNF-α-induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary flavonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isoflavone diet (CI); and tumor-bearing mice fed the isoflavone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofiber size of gastrocnemius muscle in TN significantly decreased, compared with those in CN. Interestingly, the wet weight and myofiber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isoflavone supplementation did not affect the increased tumor mass or concentrations of proinflammatory cytokines, such as TNF-α and IL-6, in the blood. Moreover, increased expression of muscle-specific ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was significantly inhibited by the supplementation of isoflavones. In parallel with the expression of muscle-specific ubiquitin ligases, dietary isoflavones significantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isoflavones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells.

Strengths and capabilities of Chinese patients with severe ocular injuries: a qualitative study.

The purpose of this qualitative study is to illustrate health-centred nursing by assessing the capabilities of patients with acute and severe ocular injuries. This study draws upon analyzing 17 nursing encounters with four adult male patients admitted to the ophthalmological ward of a university hospital in a rural Chinese city. The analysis identified that patients demonstrated the following strengths: (i) comprehension; (ii) self-reflection and examination; (iii) cooperation; (iv) patience and self-control; (v) self-efficacy; (vi) proactive acceptance; (vii) independence and a positive attitude towards challenges; (viii) support from family members; (ix) volition; and (x) flexibility. The results of this study highlight the importance of observing patients, assessing their abilities and helping them mobilize these strengths for recovery.

Combination therapy of natural human interferon-beta and ribavirin for chronic hepatitis C patients with injection drug use.

AIM: The aim of this study was to evaluate the efficacy and safety of combination therapy using natural human interferon-ß and ribavirin (IFN-ß/RBV) for chronic hepatitis C patients who were injection drug users (IDU) and resident in the Airin district of Osaka, containing the biggest slums in Japan. METHODS: Twenty-nine IDU with chronic hepatitis C received combination therapy of IFN-ß/RBV. The psychiatrist in charge evaluated the scores of the Zung Self-rating Depression Scale (SDS), a self-rating scale based on 20 questions. Univariate logistic regression analyses were used to determine the factors that significantly contributed to complete treatment and a sustained virological response (SVR). RESULTS: Thirteen of the 29 patients achieved SVR according to the intention to treat analysis. All patients with a rapid virological response achieved SVR. No patient required a reduced dose of RBV because of a decrease in their hemoglobin level, or of IFN-ß because of a low level of white blood cells and platelet count. Two patients had psychological side-effects and stopped the therapy early in the treatment; one patient had depression and the other had anxious depression. Univariate logistic regression analyses indicated that the stage of fibrosis was the only factor that contributed to SVR, and that the SDS test and past drug abuse contributed to completion of the treatment. CONCLUSION: IFN-ß/RBV combination therapy is useful for treating IDU.

Simultaneous treatment with camptothecin and valproic acid suppresses induction of Bcl-X(L) and promotes apoptosis of MCF-7 breast cancer cells.

Camptothecin derivatives have been widely used for chemotherapy in patients with various cancers, but intrinsic and acquired drug resistance is major drawback to be overcome. In the present study, we demonstrated that simultaneous treatment with camptothecin and valproic acid induced apoptosis of MCF-7 cells, whereas neither agent alone could efficiently induce apoptosis. This induction of apoptosis was associated with loss of the mitochondrial membrane potential and was caspase dependent. Further investigation showed that concurrent treatment modulated the expression of pro-apoptotic and anti-apoptotic genes. Bcl-X(L) expression was induced in MCF-7 cells treated with camptothecin alone, but not in cells treated simultaneously with camptothecin and valproic acid. Ectopic overexpression of Bcl-X(L) in MCF-7 cells completely suppressed the induction of apoptosis, even with simultaneous treatment. On the other hand, efficient induction of apoptosis was achieved by treatment with camptothecin and Bcl-X(L) inactivation (using siRNA or BH3 mimetic). The cytotoxic effect of camptothecin combined with valproic acid was more than additive for MCF-7 cells. Taken together, our results suggest that simultaneous administration of camptothecin and valproic acid might be useful for anticancer therapy.

Radial head dislocation with ulnar plastic deformation in children: an osteotomy within the middle third of the ulna.

This retrospective study includes 6 patients (average age, 8.7 years) with a dislocation of the radial head and ulnar plastic deformation. All were Monteggia fractures, Bado type I equivalents. The maximum ulnar bow was near the midulna. Five patients underwent an ulnar osteotomy, with elongation and reduction of the angulation within the middle third of the ulna, and open reduction of the radial head. One patient underwent an ulnar osteotomy with only elongation. The osteotomy sites were stabilized by a plate and screws or Kirschner wires. Mean follow-up was 3.4 years. Postoperatively, the average elbow range of motion was extension to 0 degrees, flexion to 138 degrees, forearm supination to 90 degrees, and forearm pronation to 88 degrees. Results in all patients were rated as excellent. One nonunion occurred. An osteotomy performed within the middle third of the ulna, combined with open reduction of the radial head, resulted in excellent clinical outcomes.

MLF1-interacting protein is mainly localized in nucleolus through N-terminal bipartite nuclear localization signal.

BACKGROUND: The myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1LP, also called KLIP1 and CENP-50) is reported to localize in both the nucleus and the cytoplasm. To investigate the functions of MLF1IP, its subnuclear localization was studied. MATERIALS AND METHODS: MLF1IP was tagged with green fluorescent protein (EGFP). Fibrillarin was tagged with red fluorescent protein (DsRed). EGFP-tagged MLF1IP deletion vectors were also constructed. Plasmid-constructs were transfected into human cervical adenocarcinoma HeLa cells or monkey kidney fibroblast COS-7 cells, and the localization was studied by either confocal fluorescence microscopy or fluorescence microscopy. RESULTS: Ectopically expressed MLF1IP was localized mainly in the nucleolus. In some cells, small dot-like particles of MLF1IP fluorescence were observed in the nucleoplasm. Co-staining of fibrillarin disclosed that MLF1IP was co-localized with fibrillarin in the nucleolus. Deletion mutants of MLF1IP revealed that the N-terminal bipartite nuclear localization signal (NLS) was responsible for nucleolar targeting. CONCLUSION: MLF1IP was localized mainly in the nucleolus through the N-terminal bipartite NLS and partly in the nucleoplasm featuring small dot-like particles. These findings suggest that MLF1IP may have multi-functions and its different localizations may contribute to carcinogenesis.

JAS-R, a new megakaryo-erythroid leukemic cell line that secretes erythropoietin.

BACKGROUND: The processes of leukemogenesis and differentiation of the megakaryo-erythroid lineage remain poorly understood. Leukemic cell lines derived from megakaryocytic leukemia are valuable reagents for studies on these events. MATERIALS AND METHODS: A new cell line, JAS-R, was established from a 64-year-old patient with acute megakaryocytic leukemia (AML M7). Its characteristics were studied by morphological, immunophenotypic and molecular biological analysis. RESULTS: Immunophenotyping showed that the JAS-R cells were positive for CD33, CD41 and CD61, as well as moderately to weakly positive for CD4, CD7, CD13 and glycophorin A. Chromosomal analysis revealed a composite karyotype, but no major translocation abnormalities were observed. Electron microscopy disclosed that the JAS-R cells had numerous surface blebs and some cells also had alpha-granules and demarcation membranes. The mRNAs of 4 major proteins (platelet factor 4, beta-thromboglobulin, selectin-P and thrombospondin 1) found in alpha-granules were all expressed by the JAS-R cells. In particular, expression of platelet factor 4 was high. To further characterize JAS-R cells, comparison with 4 other megakaryo-etythroid cell lines (CMK, MEG-01, K562 and KU812) was done by gene expression profiling using an oligo-DNA microarray. The results showed that JAS-R was a distinctive cell line. It was noteworthy that the JAS-R cells secreted erythropoietin and expressed erythropoietin receptor. A neutralizing antibody for erythropoietin partly inhibited the proliferation of the cells. CONCLUSION: JAS-R may be a useful cell line for investigating the differentiation and leukemogenesis of megakaryo-erythroid cells and for studying the influence of erythropoietin on these cells.

Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cells.

Irinotecan hydrochloride, a camptothecin derivative, is one of the most effective drugs for colorectal cancer, and SN-38 is its main active metabolite. Development of resistance is a major obstacle to the clinical application of this drug. We established an SN-38-resistant subline from DLD-1 human colon cancer cells by continuous exposure to SN-38 and studied the mechanisms of resistance. The resistant subline (designated as DLDSNR6) had 10- to 100-fold higher resistance to camptothecin derivatives but showed no cross-resistance to doxorubicin, mitomycin C, and etoposide. DLDSNR6 cells carried a missense mutation in one allele of the DNA topoisomerase I gene that substituted glycine for serine at amino acid residue 365 accompanied by loss of the latter part of the remaining wild-type allele. Topoisomerase I expression was equal in DLDSNR6 and DLD-1 cells, but the nuclear extract of DLDSNR6 cells showed lower topoisomerase I catalytic activity. Moreover, exposure to camptothecin caused less accumulation of topoisomerase I-DNA complexes in DLDSNR6 cells than in DLD-1 cells. These findings suggest that the mutation interfered with both the catalytic activity of topoisomerase I and the stability of the ternary complex between topoisomerase I, DNA, and SN-38. This SN-38-resistant DLDSNR6 cell line may be useful for understanding the mechanisms of topoisomerase I function and drug-enzyme interactions.

Depsipeptide-resistant KU812 cells show reversible P-glycoprotein expression, hyper-acetylated histones, and modulated gene expression profile.

Depsipeptide (FK228), a histone deacetylase inhibitor, is a promising new anticancer agent. The mechanism of resistance to this agent was studied using KU812 cells. Depsipeptide-resistant KU812 cells expressed P-glycoprotein (P-gp) and their resistance was abolished by co-treatment with verapamil. P-gp expression returned to the parental cell level when resistant cells were cultured in depsipeptide-free medium, while resistant cells cultured in the medium containing 16 nM depsipeptide still showed hyper-acetylation of histones. Moreover, resistant cells showed erythroid differentiation. Microarray analysis revealed that 28 genes showed increased expression and three genes showed decreased expression in resistant cells compared with parental cells. These 31 genes had various functions relating to signal transduction, cell cycle, apoptosis, and control of cell morphology and differentiation. Among the 28 genes that were upregulated, 15 genes also showed an increased expression in parental cells treated with 4 nM depsipeptide for 48 h, while the other 13 genes including P-gp were different. Among the three genes with decreased expression, HEP27 was most dramatically downregulated. These findings suggest that continuous exposure to depsipeptide reversibly induces P-gp, which contributes to the onset of resistance, but the altered gene expression profile of resistant cells may also play a role.

Herbert screw fixation of capitellar fractures.

From 1993 to 2003, 6 patients with displaced fractures of the humeral capitellum were treated by open reduction and internal fixation of the capitellar fragments with Herbert bone screws. By use of the criteria of Grantham et al, there were 2 type II-A fractures, 1 type II-B fracture, 1 type II-C fracture, and 2 type III-A fractures. A lateral approach was used in 4 patients and a posterior approach with olecranon osteotomy in 2. The elbows were immobilized postoperatively for 4 to 28 days (mean, 13.5 days). We evaluated the range of motion, stability, and pain using the criteria of Grantham et al. The follow-up period ranged from 2.5 to 9.3 years (mean, 5.6 years). All patients had a stable, pain-free elbow with good range of motion at follow-up. All fractures healed, and there was no evidence of avascular necrosis or degenerative change.

The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22.

We analysed a complex translocation involving chromosomes 7, 11, 19 and 22 in infant acute monocytic leukemia, and identified that the MLL gene on 11q23 was fused to the unconventional myosin type 1F, MYO1F, gene on 19p13.2-13.3. MYO1F consists of at least 28 exons and was predicted to encode a 1098-amino-acid with an N-terminal head domain containing both ATP-binding and actin-binding sequences, a neck domain with a single IQ motif, and a tail with TH1, TH2 and SH3 domains. Northern blot analysis of RNAs prepared from multiple tissues showed that the expression of approximately 4-kb transcripts appeared constant in most tissues examined. However, MYO1F was expressed in only three of 22 leukemic cell lines. The MLL-MYO1F fusion protein contains almost the entire MYO1F, however, C-terminal MYO1F has neither the transactivation domain nor the dimerization domain found in various MLL fusion partners. Further analysis of this novel type of MLL fusion protein would provide new insights into leukemogenesis. MYO1F is the fourth partner gene of MLL on 19p13. At the cytogenetic level, it may be difficult to distinguish MLL-ENL, MLL-ELL, MLL-EEN and MLL-MYO1F fusions created by t(11;19)(q23;p13), and it is likely that cases of t(11;19) lacking a known fusion gene may result in this gene fusion.

Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells.

Bcr-Abl tyrosine kinase inhibitor induces apoptosis and erythroid differentiation of K562 cells. During this erythroid differentiation, c-Myc and cyclin D1 transcripts are transiently downregulated. Accordingly, we studied the effect of cyclin D1 overexpression on erythroid differentiation. After treatment with 250 nM STI571, 90% of K562 and 25% of K562/D1 cells underwent erythroid differentiation. The basal expression of glycophorin A in K562/D1 cells was markedly diminished compared with that by parental cells. STI571 treatment failed to induce glycophorin A expression in K562/D1 cells. During STI571 treatment, ERK activity was downregulated in parental cells, while it was constantly activated in K562/D1 cells. These results suggest that ectopic expression of cyclin D1 causes the resistance of K562 cells to erythroid differentiation by modulating ERK regulation.

Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).

The NUP98 gene is involved in several chromosomal abnormalities associated with acute leukemia. The recurrent t(11;20)(p15;q11) chromosomal translocation results in generation of the NUP98/TOP1 chimeric gene. This abnormality has been observed primarily in therapy-related leukemias, and TOP1/NUP98 transcripts have not been demonstrated. We describe a case of de novo acute myeloid leukemia with t(11;20)(p15;q11), with no known history of exposure to chemicals. The translocation occurred in intron 13 of NUP98 and intron 7 of TOP1, as in the three previously reported cases. The breakpoint in NUP98 was exactly the same as that found in a previously reported case. In addition, a reciprocal TOP1/NUP98 transcript was detected for the first time in our patient.

DNA topoisomerase II inhibitor, etoposide, induces p21WAF1/CIP1 through down-regulation of c-Myc in K562 cells.

BACKGROUND: Anticancer agents modulate gene expression and these changes are essential for tumor cell killing. To investigate the mechanism by which etoposide acts as an anticancer agent, the relationship between p21WAF1/CIP1 (p21) and c-Myc was studied. MATERIALS AND METHODS: K562 cells with and without ectopic c-Myc expression were studied. Apoptosis was detected using propidium iodide and Hoechst 33342 double staining. The c-Myc and p21 levels were studied by RT-PCR and immunoblot. The p21 promoter (from -205 to +67) was investigated by the luciferase reporter gene assay. RESULTS: Ectopic c-Myc-expressing K562 (K562/c-Myc) cells showed more extensive apoptosis than K562 cells after continuous exposure to 200 microM etoposide for 24 hours. During this treatment, p21 expression was not observed in K562/c-Myc cells, and the expression of c-Myc and p21 was mutually exclusive. Etoposide activated the p21 promoter in a concentration-dependent manner, and etoposide-induced luciferase activity was suppressed by co-transfection of c-Myc. CONCLUSION: p21 promoter activity was repressed by c-Myc in proliferating K562 cells, and detoposide-induced down-regulation of c-Myc released this suppression, resulting in the induction of p21.