A nationwide survey of pediatric acquired demyelinating syndromes in Japan.

OBJECTIVE: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. METHODS: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. RESULTS: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34-0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58-0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04-0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group. CONCLUSIONS: Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population.

Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS.

Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

Comparing i-Tree modeled ozone deposition with field measurements in a periurban Mediterranean forest.

Ozone flux estimates from the i-Tree model were compared with ozone flux measurements using the Eddy Covariance technique in a periurban Mediterranean forest near Rome (Castelporziano). For the first time i-Tree model outputs were compared with field measurements in relation to dry deposition estimates. Results showed generally a good agreement between predicted and measured ozone fluxes (least sum square=5.6 e(-4)) especially when cumulative values over the whole measurement campaign are considered. However at daily and hourly time-step some overestimations were observed in estimated values especially in hot dry periods. The use of different m values in the Ball-Berry formula in the different periods, produced the best fit between predicted and measured ozone fluxes. This suggests that a variable value for the coefficient m accounting for water availability may be appropriate to improve model estimates for Mediterranean and drought prone regions.

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Clinical and radiological features of rotavirus cerebellitis.

BACKGROUND AND PURPOSE: Neurological manifestations, such as benign convulsions and encephalitis/encephalopathy have been reported in patients with rotavirus gastroenteritis. However, cerebellitis has not attracted much attention. The purpose of this study was to identify and report the clinical and radiologic features of rotavirus cerebellitis. MATERIALS AND METHODS: Records of patients with rotavirus gastroenteritis exhibiting cerebellar lesions on MR imaging were collected from multiple centers in Japan. Their clinical, laboratory, and radiologic data were reviewed retrospectively. RESULTS: A diagnosis of acute cerebellitis concurrent with encephalitis was made for 11 of 13 patients identified. Two patients who were diagnosed as having injury due to hypovolemic shock were excluded from the study. All 11 patients with acute cerebellitis had disorders of consciousness with onset on days 2 to 4, followed by mutism in 10 patients. Other cerebellar symptoms included dysarthria following the mutism, hypotonia, ataxia, tremor, nystagmus, and dysmetria. MR imaging lesions in the vermis or cerebellar cortex were seen at some point (day 5 to 1 year) in 10 patients. A reversible splenial lesion (3 isolated and 3 with concurrent cerebellar lesions) was found in 6 patients scanned between days 4 and 6. Transient lesions in the cerebellar white matter/nuclei manifesting reduced diffusion were seen in 6 patients during days 5 through 7. The final MR imaging performed after 1 month showed cerebellar atrophy in 10 patients. CONCLUSIONS: The 11 patients with rotavirus cerebellitis exhibited nearly identical clinical and MR imaging features. Involvement of the cerebellar white matter/nuclei may be associated with the mutism. An isolated splenial lesion with homogeneously reduced diffusion is not always a benign sign indicative of complete clinical and radiologic recovery in patients with rotavirus gastroenteritis.

Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1.

Mammalian nuclear Dbf2-related (NDR) kinases (LATS1 and 2, NDR1 and 2) play a role in cell proliferation, apoptosis and morphological changes. These kinases are regulated by mammalian sterile 20-like kinases (MSTs) and Mps one binder (MOB) 1. Okadaic acid (OA), which activates MST2, facilitates the complex formation of MOB1, MST2 and NDR1 in HEK293FT cells. The in vitro biochemical study demonstrates the phosphorylation of MOB1 by MST2. The phosphorylated MOB1 alone is capable to partially activate NDR1 in vitro, but MST2 is also required for the full activation. The knockdown of MOB1 or MST2 abolishes the OA-induced NDR1 activation in HEK293FT cells. Among MOB1 mutants, in which each serine or threonine residue is replaced with alanine, MOB1 T74A and T181A mutants fail to activate NDR1. Thr74, but not Thr181, is phosphorylated by MST2 in vitro, although MOB1 is also phosphorylated by MST2 at other site(s). The interaction of MOB1 T74A with NDR1 is barely enhanced by OA treatment. These findings indicate that the phosphorylation of MOB1 at Thr74 by MST2 is essential to make a complex of MOB1, MST2 and NDR1, and to fully activate NDR1.

Medical rehabilitation of the patients with spinal cord injury caused by aortic aneurysm and its operation.

OBJECTIVES: To determine the natural course of spinal cord injury (SCI) after aortic aneurysm surgery. SETTING: Acute care and semi-acute wards in Osaka Rosai Hospital, Japan. METHODS: From 1998 to 2003, 12 patients with thoracic SCI (eight men and four women; mean age: 69 years) were enrolled and evaluated by the American Spinal Injury Association (ASIA) impairment scale and Functional Independence Measure (FIM), and the results were analyzed. RESULTS: The level of SCI was distributed from T5 to L1. The ASIA impairment scale was A in four patients, B in four, C in three and D in one. Finally, six patients were discharged to home, and two patients died during hospitalization. Excluding the value of the deceased patients, the mean motor FIM was initially 32+/-15.6 (13-59) points and became 61+/-21.4 (29-88) points at discharge. Referencing the databases of SCI in Japan and USA revealed that the complication rates of pneumonia and aspiration were higher in our cases. The motor FIM before rehabilitation and at discharge were relatively lower than in the databases, but the gain and the rate of gain were similar to the Japanese database. CONCLUSION: SCI associated with aortic aneurysm surgery was noticed especially in the elderly patients using airways (for example, tracheostomy). The higher age and recurrent nerve palsy were associated with deconditioning state to develop aspiration pneumonia. This state impaired the general condition, and such vicious cycle led to poor prognosis and functional outcome.

Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4.

Junctional adhesion molecule 4 (JAM4) is a cell adhesion molecule that interacts with a tight junction protein, membrane-associated guanylate kinase inverted 1 (MAGI-1). Our previous studies suggest that JAM4 is implicated in the regulation of paracellular permeability and the signalings of hepatocyte growth factor. In this study, we performed yeast two-hybrid screening to search for an unidentified JAM4-binding protein and obtained one isoform of Ligand-of-Numb protein X1 (LNX1), LNXp70, that is an interactor of Numb. Ligand-of-Numb protein X1 is expressed in kidney glomeruli and intestinal epithelial cells, where JAM4 is also detected. Immunoprecipitation from kidney lysates supports the in vivo interaction of proteins. Biochemical studies reveal that JAM4 directly binds the second PDZ domain of LNX1 through its carboxyl terminus. Junctional adhesion molecule 4, LNX1 and Numb form a tripartite complex in vitro and are partially colocalized in heterologous cells. Ligand-of-Numb protein X1 facilitates endocytosis of JAM4 and is involved in transforming growth factor beta -induced redistribution of JAM4 in mammary epithelial cells. Experiments using dominant-negative constructs and RNA interference insure that Numb is necessary for the LNX1-mediated endocytosis of JAM4. All these findings indicate that LNX1 provides an endocytic scaffold for JAM4 that is implicated in the reorganization of cell junctions.

Unusual development of acute compartment syndrome caused by a suction injury: a case report.

There have been recent reports of acute compartment syndrome secondary to suction injuries of the hands of children. We report the case of a 68-year-old patient who developed an acute compartment syndrome of the forearm after his arm had been sucked into an exhaust port. He was treated by emergency fasciotomies and the wound was closed five days later with a small skin graft. His recovery was uneventful.

[Laparoscopic radical prostatectomy--initial 10 cases].

PURPOSE: We report the clinical results and efficacy of laparoscopic radical prostatectomy for localized prostate cancer. PATIENTS AND METHODS: Between December, 1999 and June, 2000 we performed transperitoneal laparoscopic radial prostatectomy on 10 patients with T1 or T2 organ confined prostate cancer according to the techniques as described by Guillonneau et al. Different points were as follows: 1) We placed double J catheters during surgery to prevent ureteral injury. 2) We treated dorsal vein complex using an Endo-GIA-stapler. 3) We dissected the bladder neck from the prostate using an ultrasound scalpel in the manner to preserve the bladder neck. RESULT: We could not completed laparoscopic prostatectomy on two patients because of massive bleeding from dorsal vein and consuming too much time to suture urethra-bladder anastomosis. The average operating time in all cases was 8.1 hours including 1.8 hours in laparoscopic pelvic lymphadenectomy. The average estimated blood loss in all cases was 859 ml. There were 2 surgical complications with bladder injury and port site hernia. The histological examination revealed prostate cancer; pT2pNO in 8, pT3pNO in 2. The surgical margin and lymph nodes were negative in all patients. The duration of an indwelling catheter ranged from 5 to 40 days mean 17 days. The duration to recovery of normal micturition was 6 to 90 days, mean 40 days. CONCLUSION: Long-term follow-up and extensive studies are necessary to evaluate the efficacy of this procedure. It might provide shorter duration of an indwelling catheter and earlier recovery of normal micturition as compared with the conventional open surgery.

Skeletal analysis of craniofacial deformities in brachycephaly: comparison with craniofacial deformities in plagiocephaly.

The deformities of craniofacial bones in brachycephaly (n = 2) and plagiocephaly (n = 2) were compared using three-dimensional skull replicas. In brachycephaly the bilateral deformities of the cranial base were similar to the unilateral deformities on the affected side in plagiocephaly. Shortening of the anterior-middle cranial fossas and expansion of the middle cranial fossas suggest downward and anterior displacement of both temporomandibular (TM) joints resulting in the underdevelopment of the middle-inferior facial bones, though this is less conspicuous in brachycephaly for three reasons. The most important one is that the patients have an imposing facial morphology characterised by high, protruding facial bones, as found on the affected side in plagiocephaly. Secondly, the frontal bones are flattened and positioned posteriorly in the anteroposterior direction, which also helps to mask the underdevelopment of the middle-inferior facial bones. Finally, as bony deformities are symmetrical in brachycephaly, they are not as obvious as they would be if they were unilateral.

Staged spinal cord decompression through posterior approach for thoracic myelopathy caused by ossification of posterior longitudinal ligament.

STUDY DESIGN: Prospective clinical study of the effect of staged elimination of anatomic factors inhibiting posterior shift of the thoracic spinal cord on the degree of posterior shift of the thoracic spinal cord and its significance in augmenting the safety of ossification of posterior longitudinal ligament (OPLL) manipulation in thoracic OPLL myelopathy. OBJECTIVES: To develop a comprehensive method that enables safe and sufficient decompression of the spinal cord for thoracic OPLL myelopathy. SUMMARY OF BACKGROUND DATA: Decompression of the spinal cord by direct manipulations of thoracic OPLLs, via either anterior or posterior approach, caused some iatrogenic catastrophic spinal cord injuries, and methods to prevent such injuries during surgery have not yet been developed. METHODS: Procedures of elimination of anatomic factors inhibiting posterior shift of the thoracic spinal cord were performed in stages at intervals of between 1 month and 11 years depending on patients' neurologic status. The first stage operation consisted of extensive cervicothoracic laminoplastic decompression with or without posterior longitudinal durotomy, and if the decompression were insufficient, measures for OPLL-spinal cord separation with or without OPLL manipulation were added. RESULTS: All 17 patients with thoracic OPLL myelopathy showed improvements of neurology comparable with those with successful anterior approaches after decompression. The mean follow-up period was 42 months (range 6-101 months). Neurologic improvements persisted for the entire follow-up period in all patients except one patient who developed arachnoid cyst compressing the dorsum of the once-decompressed spinal cord 30 months after surgery. CONCLUSIONS: Staged posterior decompression to eliminate anatomic factors inhibiting posterior shift of the thoracic spinal cord is the safest and the most reliable method of spinal cord decompression to treat thoracic OPLL myelopathy, so far. However, long-term results are required before the methods can be established.

Optimized 3-D CT scan protocol for longitudinal morphological estimation in craniofacial surgery.

Frequent three-dimensional computed tomography scanning may cause deterioration of the lenses of the eye, which are susceptible to x-rays. The authors performed an experimental study using a phantom head to establish an optimized three-dimensional computed tomography scan protocol for longitudinal morphological estimation in craniofacial surgery. Volume computed tomography scans were performed using a Hi-Speed Advantage SG CT scanner (GE Medical Systems, Milwaukee, WI) in the axial plane with a combination of scan parameters of varied values. The radiation doses induced by each scanning were measured using thermoluminescent dosimeter chips attached to the position of the lenses in the phantom. Two-dimensional images in the coronal plane and three-dimensional images of the osseous surface were generated from each accumulated data set. For each scan parameter, the images generated from data accumulated using different values were compared. The study showed that lens radiation dose increased with tube potential and was almost directly proportional to tube current and 1/pitch. The slice thickness did not affect lens radiation doses significantly. Images with good contrast resolution and low artifact level sufficient for estimating morphological changes were obtained using a low tube potential of 100 kVp and a tube current of 100 mA. In regard to z-axis spatial resolution, a slice thickness of less than 3 mm was required for precisely pointing out bony edges in the two-dimensional reformation images. These results led us to conclude that volume computed tomography for longitudinal examination in craniofacial surgery should be kept to a minimum frequency and performed using a low-dose technique, small slice thickness, and large pitch.

Localization of BAI-associated protein1/membrane-associated guanylate kinase-1 at adherens junctions in normal rat kidney cells: polarized targeting mediated by the carboxyl-terminal PDZ domains.

Brain-specific angiogenesis inhibitor (BAI)-associated protein (BAP)1 (also called membrane-associated guanylate kinase [MAGI]-1) is composed of six PSD-95/Dlg-A/ZO-1 (PDZ) domains, two WW domains, and one guanylate kinase (GK) domain. We previously reported that BAP1 is localized at tight junctions in Madine Darby canine kidney (MDCK) cells and intestinal epithelial cells. Here, we have determined the localization of BAP1 in normal rat kidney (NRK) cells that do not form tight junctions. BAP1 was colocalized with E-cadherin along the lateral membrane, suggesting its localization at adherens junctions. Green fluorescent protein (GFP)-BAP1 was distributed in the cytosol in separate NRK cells, and accumulated to the cell-cell contacts when NRK cells have contact with each other. The GFP-BAP1 mutant containing either the first PDZ and GK domains or the WW and second PDZ domains was localized in the cytosol and the nucleus. The GFP-BAP1 mutant containing the second to fourth PDZ domains was distributed in the cytosol. The construct containing the fifth and sixth PDZ domains was localized at the cell-cell contacts along the lateral membrane and slightly in the nucleus, whereas the construct lacking the fifth and sixth PDZ domains was localized in the cytosol and in the nucleus. BAP1 was tyrosine-phosphorylated in vivo, but the tyrosine phosphorylation of BAP1 was not correlated with its localization. These results suggest that the signal in the carboxyl-terminal PDZ domains functions dominantly in vivo to target BAP1 to the lateral membrane, although potential nuclear localization signals exist in the N-terminal region of BAP1.

The value of a new method for assessing the separate functions of the long tracts and involved segments in patients with cervical myelopathy.

In order to assess accurately lesions of the spinal cord in patients with cervical myelopathy we have developed a new method of examination, which is based on the Japanese Orthopaedic Association (JOA) scoring system. The method attempts to assess separately the functions of the long tract and any involved cord segments in respect to the period after treatment. It was used in 117 consecutive patients who were divided into 2 groups based on whether or not there was a T2-high-intensity lesion within the spinal cord, as revealed by a preoperative magnetic resonance imaging scan (MRI). The results of this method correlated well with the MRI findings. It was assumed that the degree of function of the upper limbs in patients with a T2-high-intensity lesion revealed more about a segment than about the long tract.