Characteristics of nuclear architectural abnormalities of myotubes differentiated from LmnaH222P/H222P skeletal muscle cells.

The presence of nuclear architectural abnormalities is a hallmark of the nuclear envelopathies, which are a group of diseases caused by mutations in genes encoding nuclear envelope proteins. Mutations in the lamin A/C gene cause several diseases, named laminopathies, including muscular dystrophies, progeria syndromes, and lipodystrophy. A mouse model carrying with the LmnaH222P/H222P mutation (H222P) was shown to develop severe cardiomyopathy but only mild skeletal myopathy, although abnormal nuclei were observed in their striated muscle. In this report, we analyzed the abnormal-shaped nuclei in myoblasts and myotubes isolated from skeletal muscle of H222P mice, and evaluated the expression of nuclear envelope proteins in these abnormal myonuclei. Primary skeletal muscle cells from H222P mice proliferated and efficiently differentiated into myotubes in vitro, similarly to those from wild-type mice. During cell proliferation, few abnormal-shaped nuclei were detected; however, numerous markedly abnormal myonuclei were observed in myotubes from H222P mice on days 5 and 7 of differentiation. Time-lapse observation demonstrated that myonuclei with a normal shape maintained their normal shape, whereas abnormal-shaped myonuclei remained abnormal for at least 48 h during differentiation. Among the abnormal-shaped myonuclei, 65% had a bleb with a string structure, and 35% were severely deformed. The area and nuclear contents of the nuclear blebs were relatively stable, whereas the myocytes with nuclear blebs were actively fused within primary myotubes. Although myonuclei were markedly deformed, the deposition of DNA damage marker (γH2AX) or apoptotic marker staining was rarely observed. Localizations of lamin A/C and emerin were maintained within the blebs, strings, and severely deformed regions of myonuclei; however, lamin B1, nesprin-1, and a nuclear pore complex protein were absent in these abnormal regions. These results demonstrate that nuclear membranes from H222P skeletal muscle cells do not rupture and are resistant to DNA damage, despite these marked morphological changes.

Emerin deficiency does not exacerbate cardiomyopathy in a murine model of Emery-Dreifuss muscular dystrophy caused by an LMNA gene mutation.

Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in genes encoding nuclear envelope proteins, is clinically characterized by muscular dystrophy, early joint contracture, and life-threatening cardiac abnormalities. To elucidate the pathophysiological mechanisms underlying striated muscle involvement in EDMD, we previously established a murine model with mutations in Emd and Lmna (Emd-/-/LmnaH222P/H222P; EH), and reported exacerbated skeletal muscle phenotypes and no notable cardiac phenotypes at 12 weeks of age. We predicted that lack of emerin in LmnaH222P/H222P mice causes an earlier onset and more pronounced cardiac dysfunction at later stages. In this study, cardiac abnormalities of EDMD mice were compared at 18 and 30 weeks of age. Contrary to our expectations, physiological and histological analyses indicated that emerin deficiency causes no prominent differences of cardiac involvement in LmnaH222P/H222P mice. These results suggest that emerin does not contribute to cardiomyopathy progression in LmnaH222P/H222P mice.

Preoperative factors affecting the two-year postoperative patient-reported outcome in single-level lumbar grade I degenerative spondylolisthesis.

Background: The choice of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial. The purpose of this study was to identify the preoperative factors affecting the 2-year postoperative patient-reported outcome in Meyerding grade I degenerative spondylolisthesis. Methods: Seventy-two consecutive patients who had minimally invasive decompression alone (D group; 28) or with fusion (DF group; 44) were enrolled. The parameters investigated were the Japanese Orthopaedic Association back pain evaluation questionnaire as patient-reported assessment, and L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment for radiological evaluation. Data collected prospectively at 2 years postoperatively were examined by statistical analysis. Results: Sixty-two cases (D group; 25, DF group; 37) were finally evaluated. In multiple logistic regression analysis, preoperative L4S and LASD were extracted as significant preoperative factors affecting the 2-year postoperative outcome. Patients with preoperative L4S of 6 mm or more have a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio=0.188, p=.043). Patients with a preoperative LASD of 30 mm or more have a higher rate of improvement in lumbar dysfunction due to low back pain (risk ratio=11.48, p=.021). The results of multiple logistic analysis by operative method showed that there was a higher rate of improvement in lumbar spine dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more in DF group (risk ratio=172.028, p=.01). Conclusions: Preoperative L4S and LASD were extracted as significant preoperative factors affecting patient-reported outcomes at 2 years postoperatively. Multiple logistic analyses by the operative method suggested that DF may be advantageous in improving lumbar dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more.

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia.

Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7-21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

A Case of Concomitant Lip Injury and Facial Pressure Ulcer in Lumbar Intradural Tumor Surgery With Repeated Transcranial Electrical Stimulations.

Transcranial motor evoked potential (MEP) is a common method in spinal surgery but requires strong electrical stimulation. Frequent transcranial stimulations can cause bite injury. In addition, a facial pressure ulcer is a problem in spinal surgery requiring prone positioning. We present a case of bite injury and facial pressure ulcer in prolonged lumbar tumor surgery with repeated transcranial stimulations. A 74-year-old woman developed left lower limb and low back pain. MRI revealed an intradural extramedullary tumor at L1. We performed tumor resection surgery. A silicon bite block was used, and the patient's head was placed on a sponge headrest. The tumor was a schwannoma originating from the nerve root that innervated the left anal sphincter. Intracapsular resection was performed while referring to the frequent transcranial MEP monitoring. The left lower limb and low back pain improved after surgery; however, lip injury and facial skin ulcer occurred. The face showed marked swelling and was painful, so oral intake was difficult for a week. Wound healing was obtained three months postoperatively, but hypoesthesia remained. When using MEP in prolonged spine surgery with a headrest, it is necessary to pay attention to both bite injury and facial pressure ulcer. Intraoperative assessment of the face, number of transcranial stimulations, types of a bite block, and headrest may be important.

First Case of Pyogenic Spondylodiscitis Caused by Gemella sanguinis.

A 78-year-old man presented with back pain. Magnetic resonance imaging revealed marrow edema within the L4 and L5 vertebral bodies and a spinal epidural abscess in the spinal canal. The patient was considered to have pyogenic spondylodiscitis at the L4/L5 level. The Gram-positive cocci isolated from blood cultures were subsequently identified as Gemella sanguinis using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Symptom improvement was achieved and the infection was eradicated with conservative treatment (treatment with ceftriaxone [CTRX] and minocycline [MINO]). We report the first case of G. sanguinis-associated pyogenic spondylodiscitis. MALDI-TOF MS was useful in identifying this uncommon bacterium.

Gestational Intermittent Hypoxia Induces Mitochondrial Impairment in the Geniohyoid Muscle of Offspring Rats.

Introduction Gestational intermittent hypoxia (IH), a hallmark of obstructive sleep apnea during gestation, alters respiratory neural control and diaphragm muscle contractile function in the offspring. The geniohyoid (GH) muscle is innervated by the respiratory-related hypoglossal nerve and plays a role in tongue traction and suckling, motor behaviors that then give way to chewing. Here, we aimed to investigate the effects of gestational exposure to IH on the muscle development and metabolism of GH and masseter muscles in male offspring rats. Materials and methods Pregnant Sprague-Dawley rats were exposed to IH (3-min periods of 4-21% O2) for eight hours/day during gestational days 7-20. The GH and masseter muscles from 35-day-old male offspring (n = 6 in each group) were analyzed.  Results Gestational IH induction reduced type IIA fiber size in the GH muscle of the offspring but not in the masseter muscle. Western blot analysis showed that gestational IH-induced significant downregulation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1-alpha (PGC1α) protein in the GH muscle but not in the masseter muscle. Moreover, optic atrophy 1 and mitofusin-2 proteins were decreased and mitochondrial fission 1 protein levels were increased in the GH muscle of the offspring exposed to gestational IH. Mitochondrial adenosine triphosphate (ATP) synthase subunit alpha and transcriptional factor A (TFAM) were decreased in the GH muscle post-gestational IH. Conclusion These findings suggest that gestational IH-induced impaired mitochondrial metabolism and alteration of oxidative myofibers of the GH muscle in the pre-adolescent offspring, but not the masseter muscle, owing to the susceptibility of GH muscular mitochondria to gestational IH.

Relief of Low Back Pain After Posterior Decompression for Lumbar Spinal Stenosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to confirm that decompression for lumbar spinal stenosis (LSS) relieves low back pain (LBP) as adequately as it relieves leg pain and to identify predictors for inadequate LBP relief. SUMMARY OF BACKGROUND DATA: Although decompression for LSS is generally thought to yield worse results for LBP than for leg pain, some studies have reported similar improvements in pain scores between LBP and leg pain. To treat LBP or take measures to prevent inadequate LBP relief, reliable predictors for LBP relief should be identified. METHODS: We retrospectively reviewed 175 patients who underwent posterior element-preserving decompression and evaluated the relief of LBP and leg pain using numeric rating scales (NRSs). Associations between demographic, clinical, or imaging parameters and LBP relief at 1 and 4 years were analyzed by stepwise linear regression analyses. The imaging parameters included Modic change type 1, disc degeneration, foraminal stenosis, vertebral slipping (within Grade 1), scoliosis (<15°) and lordosis. RESULTS: The mean improvements in LBP and leg pain NRS scores from baseline were 5.22 and 4.70 points (P = 0.064, paired t test) at 1 year and 5.12 and 4.62 points (P = 0.068) at 4 years, respectively. Poor LBP scores at 4 years were significantly associated with long-lasting LBP (beta = 0.31, P < 0.0001) and moderate or severe arm symptoms with cervical spinal cord compression or intramedullary hyperintense signal on T2-weighted MRI (beta = 0.22, P = 0.0014). The imaging parameters of the lumbar spine failed to show clear associations with poor LBP scores at 4 years, although Modic change type 1 showed a significant association with poor LBP scores at 1 year (beta = 0.28, P < 0.0001). CONCLUSION: Posterior decompression relieves LBP as well as leg pain. Long-lasting LBP and concurrent symptomatic cervical myelopathy are important predictors for inadequate LBP relief. There were no reliable imaging parameters predictive of inadequate LBP relief.Level of Evidence: 4.

Deficiency of emerin contributes differently to the pathogenesis of skeletal and cardiac muscles in LmnaH222P/H222P mutant mice.

Laminopathies are tissue-selective diseases that affect differently in organ systems. Mutations in nuclear envelopes, emerin (Emd) and lamin A/C (Lmna) genes, cause clinically indistinguishable myopathy called Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy. Several murine models for EDMD have been generated; however, emerin-null (Emd) mice do not show obvious skeletal and cardiac muscle phenotypes, and Lmna H222P/H222P mutant (H222P) mice show only a mild phenotype in skeletal muscle when they already have severe cardiomyopathy. Thus, the underlying molecular mechanism of muscle involvement due to nuclear abnormalities is still unclarified. We generated double mutant (Emd-/-/LmnaH222P/H222P; EH) mice to characterize dystrophic changes and to elucidate interactions between emerin and lamin A/C in skeletal and cardiac muscles. As H222P mice, EH mice grow normally and have breeding productivity. EH mice showed severer muscle involvement compared with that of H222P mice which was an independent of cardiac abnormality at 12 weeks of age. Nuclear abnormalities, reduced muscle fiber size and increased fibrosis were prominent in EH mice. Roles of emerin and lamin A/C in satellite cells function and regeneration of muscle fiber were also evaluated by cardiotoxin-induced muscle injury. Delayed increases in myog and myh3 expression were seen in both H222P and EH mice; however, the expression levels of those genes were similar with control and regenerated muscle fiber size was not different at day 7 after injury. These results indicate that EH mouse is a suitable model for studying skeletal muscle involvement, independent of cardiac function, in laminopathies and an interaction between emerin and lamin A/C in different tissues.

Renal involvement in the pathogenesis of mineral and bone disorder in dystrophin-deficient mdx mouse.

Duchenne muscular dystrophy is a severe muscular disorder, often complicated with osteoporosis, and impaired renal function has recently been featured. We aimed to clarify the involvement of renal function in the pathogenesis of mineral and bone disorder in mdx mice, a murine model of the disease. We clearly revealed renal dysfunction in adult mdx mice, in which dehydration and hypercalcemia were contributed. We also examined the effects of dietary phosphorus (P) overload on phosphate metabolism. Serum phosphate and parathyroid hormone (PTH) levels were significantly increased in mdx mice by dietary P in a dose-dependent manner; however, bone alkaline phosphatase levels were significantly lower in mdx mice. Additionally, bone mineral density in mdx mice were even worsened by increased dietary P in a dose-dependent manner. These results suggested that the uncoupling of bone formation and resorption was enhanced by skeletal resistance to PTH due to renal failure in mdx mice.

Japanese orthopaedic association cervical myelopathy evaluation questionnaire (JOACMEQ): Part 5. Determination of responsiveness.

BACKGROUND: In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire. METHODS: A total of 137 patients with cervical myelopathy were included in the study. Each patient was interviewed twice using the JOACMEQ before and after treatment. At the second interview, the patients self-rated their condition in five domains for "worse," "somewhat worse," "no change," "somewhat better," or "better," and these scores were defined as the external assessment rating. The difference of the points in five domains between the first and the second interview was calculated against each external assessment. Based on the results, substantial clinical benefit (SCB) thresholds for the JOACMEQ were determined. RESULTS: The statistically significant median values of the acquired points were 17.5 for CF, 16.0 and 21.0 for UF, 27.0 and 20.5 for LF, 13.0 for BF, and 29.0 for QOL. After consideration of the results, the committee decided that an acquired point ≥20 could be interpreted as representing an SCB threshold for the JOACMEQ. CONCLUSION: We have concluded that a treatment can be judged to be effective for a patient if 1) The patient give all answers for the questions necessary to calculate the functional score of a domain and an increase of ≥20 points is obtained for that score, or 2) The functional score after treatment is > 90 points even if the answer for the unanswered questions was supposed to be the worst possible choice.

An intraspinal extradural lipoma with spinal epidural lipomatosis: A case report and a review of literature.

BACKGROUND: Intraspinal extradural lipomas are very rare and should be differentiated from spinal epidural lipomatosis (SEL) and/or angiolipomas. CASE DESCRIPTION: A 76-year-old male presented with left lower extremity radiculopathy. The magnetic resonance imaging (MRI) revealed hyperplasia of epidural fat at the L2-3 and L3-4 levels accompanied by a lipomatous L4-5 mass. Following resection of this mass and hyperplastic epidural fat, the histological examination was consistent with an intraspinal extradural lipoma and SEL. CONCLUSION: This case indicates that asymmetrical compression of the dural sac may be attributed to an intraspinal extradural lipoma vs. just SEL and/or an angiolipoma.

Intradural Disk Herniation Mimicking a Spinal Tumor: Radiologic Imaging, Pathogenesis, and Operative Management.

Intradural disk herniation (IDH) is a rare condition, occurring more often at the L4-5 level. We examined a case of an IDH at the L1-2 level mimicking an intradural spinal tumor. A 71-year-old woman with a long history of backache and pain radiating down the left leg was admitted to our hospital with the worsening of these symptoms. Magnetic resonance imaging and computed tomographic myelography demonstrated an intradural mass at the L1-2 level. Given the radiologic findings and the location of the mass, the preoperative differential diagnosis centered on intradural spinal tumors. Dural incision was performed using a surgical microscope to resect the mass. Contrary to our expectation, the diagnosis made during the surgery was IDH. Despite advances in imaging techniques, IDH could not be definitively diagnosed preoperatively. The pathogenesis of IDH remains unclear. In our patient, the ventral dural defect was smooth and round, and the dural tissue around the defect was thickened. These intraoperative findings suggested that the patient's IDH resulted not from an acute new event but from a chronic process. We recommend dural incision using a surgical microscope for treating IDH because it provides a clear visual field.

Expansive Suspension Laminoplasty Using a Spinous Process-Splitting Approach for Lumbar Spinal Stenosis: Surgical Technique and Outcomes Over 8 Years of Follow-up.

INTRODUCTION: To maximize the benefits of posterior decompression for severe multilevel lumbar spinal stenosis, we refined the expansive laminoplasty technique using a spinous process-splitting approach. This study tests the hypothesis that the surgical benefit of adequate decompression with posterior element preservation is maintained in the long term, over 8 years of follow-up. METHODS: Fifty-eight patients were followed up yearly for 8 years. Eight patients having nonlumbar spine surgery or Parkinson disease were excluded. The noninferiority of the 8-year versus peak-year outcomes was tested, with margins of 5 points for the Oswestry disability index and 1 point for the numeric rating scales (NRSs). RESULTS: In the 50 patients available for follow-up, the peak values of the mean improvements from baseline within the first 7 years were 35.8, 5.7, 5.9, and 2.8 points for the Oswestry disability index, low back pain NRS, leg pain NRS, and leg numbness NRS, respectively. The 95% lower confidence limits for the differences between the mean improvements from baseline at 8 years and the peak year were within the noninferiority margins for each scale. CONCLUSION: Our technique was associated with substantial improvement from baseline for each scale. The initial improvements in function and symptoms were maintained for 8 years.

Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice.

BACKGROUND: Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice. METHODS: Male dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age. RESULTS: Treatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and activator of transcription 3 in the skeletal muscle. Pathologically, a significant increase in the area of embryonic myosin heavy chain-positive myofibers and muscle diameter, and reduced fibrosis in the quadriceps muscle were observed. These results demonstrated the therapeutic effects of IL-6R blockade on promoting muscle regeneration. Consistently, serum creatine kinase levels were decreased. Despite these improvements observed in the limb muscles, degeneration of the diaphragm and cardiac muscles was not ameliorated by the treatment of mice with the MR16-1 antibody. CONCLUSION: As no adverse effects of treatment with the MR16-1 antibody were observed, our results indicate that the anti-IL-6R antibody is a potential therapy for muscular dystrophy particularly for promoting skeletal muscle regeneration.

Verification of the sensitivity of functional scores for treatment results - Substantial clinical benefit thresholds for the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).

BACKGROUND: Validity and reliability of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) had already been verified as the patients' self-rating assessment of low back pain and lumbar spinal disease and, the present study demonstrated the responsiveness of this measure. METHODS: 192 subjects who were determined by medical instructors of the Japanese Society for Spine Surgery and Related Research were analyzed. They had completed a series of treatment and both surveys before and after the treatment. Authors investigated rates of concordance between assessment by physicians and subjective assessment by patients. The mean, standard deviation, minimum, 25th percentile, median, 75th percentile and maximum values for pre-treatment, post-treatment, and acquired points were calculated, and then, we also investigated the trend between subjective assessment by patients and mean acquired points for each JOABPEQ domain and substantial clinical benefit thresholds for the JOABPEQ. RESULTS: Symptom changes as assessed by physicians did not coincide with those by patients, and acquired points in each JOABPEQ domain were significantly increased with improved self-rating by patients. In addition, patients who rated symptom changes as "slightly improved" showed a mean acquired points of ≥20, and those reporting "improved" showed a 25th percentile points of the acquired points of ≥20 approximately. CONCLUSION: A significant correlation was noted between the self-rating of patients and acquired points JOABPEQ, suggesting that ≥20 acquired points can be interpreted as substantial clinical benefit thresholds for the JOABPEQ.

Validity of the Japanese Orthopaedic Association scoring system based on patient-reported improvement after posterior lumbar interbody fusion.

BACKGROUND CONTEXT: The Japanese Orthopaedic Association (JOA) scoring system is a physician-based outcome that has been used to evaluate treatment effectiveness after lumbar surgery. However, patient-centered evaluation becomes increasingly important. There is no study that has examined the relationship between the JOA scoring system and patients' self-reported improvement. PURPOSE: The purpose of the present study was to validate the JOA scoring system for assessment of patient-reported improvement after lumbar surgery. STUDY DESIGN: This is a retrospective review of prospectively collected data. PATIENT SAMPLE: The patient sample included 273 mail-in responders of the 466 consecutive patients who underwent posterior lumbar interbody fusion for spondylolisthesis between 1996 and 2008 in a single hospital. OUTCOME MEASURES: The outcome measures were the JOA scoring system and patients' self-reported improvement. METHODS: Two hundred seventy three patients were divided into five anchoring groups based on self-reported improvement from "Much better" to "Much worse." Outcomes (ie, recovery rate, amount of change from preoperative condition, and postoperative score) based on the JOA scoring system were compared among groups. Using the patient's self-reported improvement scale as an anchor, the association among each of the outcomes was examined. The cutoff point and the area under the curve (AUC) that differentiated "Improved" from "Neither improved nor worse" was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: The recovery rate and postoperative score were significantly different in 9 of 10 pairs of anchoring groups. The amount of change was significantly different in six pairs. Spearman correlation coefficient for the 5-point scale anchors of patients' self-reported improvement was 0.20 (p=.001) for the baseline score, 0.31 (p<.001) for the amount of change, 0.55 (p<.001) for the recovery rate, and 0.56 (p<.001) for the postoperative score. According to ROC analysis, the best cutoff points and AUCs were 13 points and 0.69, respectively, for the amount of change, 67% and 0.73, respectively, for recovery rate, and 23 points and 0.72, respectively, for postoperative score. CONCLUSIONS: The JOA scoring system is a valid method for assessment of patients' self-reported improvement. Patients' self-reported improvement is more likely to be associated with the final condition, such as postoperative score or recovery rate, rather than the change from the preoperative condition.

Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade.

Skeletal muscle stem cells named muscle satellite cells are normally quiescent but are activated in response to various stimuli, such as injury and overload. Activated satellite cells enter the cell cycle and proliferate to produce a large number of myogenic progenitor cells, and these cells then differentiate and fuse to form myofibers. Zinc is one of the essential elements in the human body, and has multiple roles, including cell growth and DNA synthesis. However, the role of zinc in myogenic cells is not well understood, and is the focus of this study. We first examined the effects of zinc on differentiation of murine C2C12 myoblasts and found that zinc promoted proliferation, with an increased number of cells incorporating EdU, but inhibited differentiation with reduced myogenin expression and myotube formation. Furthermore, we used the C2C12 reserve cell model of myogenic quiescence to investigate the role of zinc on activation of myogenic cells. The number of reserve cells incorporating BrdU was increased by zinc in a dose dependent manner, with the number dramatically further increased using a combination of zinc and insulin. Akt and extracellular signal-regulated kinase (ERK) are downstream of insulin signaling, and both were phosphorylated after zinc treatment. The zinc/insulin combination-induced activation involved the phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc promotes activation and proliferation of myogenic cells, and this activation requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade.

Motor conduction measurement in myelopathy hand.

We studied the relationship between intramedullary high signal intensity (IMHSI) on T2-weighted magnetic resonance images and motor conduction in the spinal cords of cervical spondylotic myelopathy (CSM) patients. There was no significant difference between the biceps or triceps central motor conduction times (CMCTs) of the patients who did and did not exhibit IMHSI, whereas the abductor pollicis brevis CMCT was significantly longer in the patients who exhibited IMHSI (p<0.05) than in those who did not. The CMCT of the abductor pollicis brevis is sensitive to the degree of damage in the cervical spinal cord. Hand dysfunction is a characteristic of CSM regardless of the cervical level affected by the condition. The motor fibers innervating the intrinsic muscles of the hand in the long tract of the cervical spinal cord are more sensitive than other motor fibers. For this reason, we consider that myelopathy hand is a characteristic impairment of CSM. Transcranial magnetic stimulation of the hand motor cortex is useful for the evaluation of cervical myelopathy.

Dietary phosphorus overload aggravates the phenotype of the dystrophin-deficient mdx mouse.

Duchenne muscular dystrophy is a lethal X-linked disease with no effective treatment. Progressive muscle degeneration, increased macrophage infiltration, and ectopic calcification are characteristic features of the mdx mouse, a murine model of Duchenne muscular dystrophy. Because dietary phosphorus/phosphate consumption is increasing and adverse effects of phosphate overloading have been reported in several disease conditions, we examined the effects of dietary phosphorus intake in mdx mice phenotypes. On weaning, control and mdx mice were fed diets containing 0.7, 1.0, or 2.0 g phosphorus per 100 g until they were 90 days old. Dystrophic phenotypes were evaluated in cryosections of quadriceps and tibialis anterior muscles, and maximal forces and voluntary activity were measured. Ectopic calcification was analyzed by electron microscopy to determine the cells initially responsible for calcium deposition in skeletal muscle. Dietary phosphorus overload dramatically exacerbated the dystrophic phenotypes of mdx mice by increasing inflammation associated with infiltration of M1 macrophages. In contrast, minimal muscle necrosis and inflammation were observed in exercised mdx mice fed a low-phosphorus diet, suggesting potential beneficial therapeutic effects of lowering dietary phosphorus intake on disease progression. To our knowledge, this is the first report showing that dietary phosphorus intake directly affects muscle pathological characteristics of mdx mice. Dietary phosphorus overloading promoted dystrophic disease progression in mdx mice, whereas restricting dietary phosphorus intake improved muscle pathological characteristics and function.