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Objectives Epigenetic phenomena are changes in gene expression not involving the DNA sequence. DNA methylation is a major occurrence underlying epigenetic changes in human cells. Although aberrant DNA methylation is well documented in malignant lesions, limited information has been shown on the involvement of DNA methylation in oral lichen planus and oral lichenoid lesions (OLP). The present study aimed to investigate DNA methylation of E‐cadherin and p16 in OLP, and compare the findings with those in non‐inflamed gingiva (Non), radicular cyst (RC), and oral squamous cell carcinoma (SCC). Materials and methods Paraffin‐embedded surgical biopsy specimens were sliced, DNA was extracted, bisulfite treatment was applied, and methylation‐specific polymerase chain reaction was performed. Immunohistochemistry was performed to observe the relative expression patterns of these genes. Results E‐cadherin was hypermethylated in OLP (p

Thymic carcinoma is a rare malignant disease with no standard systemic chemotherapy. The purpose of the present study was to investigate tumor-infiltrating immune cells (TIIC) in the tumor microenvironment (TME), focusing on the impact of TIIC and program death-ligand 1 (PD-L1) expression on clinical outcomes in thymic cancer. Patients with thymic carcinoma resected between 1973 and 2017 were investigated. The tissue specimens were analyzed through immunohistochemical staining to elucidate the prognostic effects of TIIC, their ratios and PD-L1 in a preliminary cohort (n = 10). The density of TIIC as well as PD-L1 expression was evaluated in intraepithelial and tumor-stromal areas on the representative whole section of tumors. The immune factors showing significant association with disease-free survival (DFS) were evaluated in the total cohort (n = 42). TIIC in the preliminary population showed no significant difference between the two groups. However, CD8, CD20, CD204, FOXP3 and CD20/CD204 ratio demonstrated a tendency to act as predictive markers for recurrence. In the total cohort, significant differences were observed for CD8+ , CD20+ and CD204+ cells in tumor islets, and for CD8+ , CD20+ and FOXP3+ cells as well as the CD8/CD204 and CD20/CD204 ratios in the stroma, indicating their prognostic effect. The prognostic effect of the PD-L1 expression in tumor cells could not be established, possibly because of intratumoral heterogeneity. CD8, CD20 and CD204 positive TIIC in stroma were identified as possible better prognostic biomarkers, considering the heterogeneity of other biomarkers. The present study paves the way for exploring strategies of combination immunotherapy targeting B cell immunity in thymic carcinoma.

Background Several studies have previously demonstrated the survival benefit of both EGFR‐TKI treatment and chemotherapy in patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR‐TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs). Methods Between January 2010 and December 2016, consecutive patients with EGFR‐mutated NSCLC who were started on first‐line EGFR‐TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post‐progression survival (PPS) after failure of EGFR‐TKI were investigated. Results A total of 393 patients were started on first‐line EGFR‐TKI during the study period. After excluding patients maintained on EGFR‐TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR‐TKI (TKI‐Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI‐only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11–0.43, P

Background Although non-small cell lung cancers (NSCLCs) harboring EGFR mutations initially respond well to EGFR-tyrosine kinase inhibitors (TKIs), they typically progress after approximately one year. The EGFR T790M mutation is the most common resistance mechanism. NSCLCs with T790M respond well to osimertinib; however, the heterogeneity of NSCLCs may limit the efficacy. Some patients exhibit a mixed response (MR), in which some lesions shrink and others progress, but little is known of the incidence and characteristics of such a response. We sought to determine the frequency and clinical course in MR patients. Methods We retrospectively reviewed the records of patients who had received osimertinib for NSCLC with EGFR T790M. Results Between April and December 2016, 48 patients were administered osimertinib. Seven patients (15%) exhibited one of two MR types: (i) progressive lesions that did not include the re-biopsy site (5 patients), and (ii) progressive lesions that included the re-biopsy site (2 patients). The most frequent progressive sites were liver and lung metastases (4 patients). Three patients continued osimertinib following an MR, one of whom had received local therapy for liver metastasis and achieved disease control on osimertinib for an additional four months. Conclusion An MR was detected in 15% of NSCLC patients with T790M. This finding suggests that several different resistance mechanisms are active within a single patient who develops resistance to EGFR-TKIs. Osimertinib is basically effective for tumors that acquire resistance to EGFR-TKIs as a result of T790M mutation. Therefore, additional local therapy may be beneficial for patients who develop an MR to osimertinib.

Aims: Symptomatic treatment is insufficient for chemotherapy- or targeted therapy-induced oral mucositis (OM) pain, and benzydamine mouthwash is not commercially available in Japan. We evaluated the analgesic effects of an in-hospital preparation of 0.25% indomethacin spray (IMS) on anticancer drug-induced OM pain. Methods: This single-arm prospective trial enrolled 20 patients (median age 62.0 years) with OM and numerical rating scale scores of >= 5 who were undergoing chemotherapy or targeted therapy in our hospital. Pain scores were recorded using a visual analog scale (VAS) before and 30 min after IMS administration. Pain relief (PR) scores were recorded at 15, 30, and 60 min after IMS administration; total PR after 60 min (TOTPAR(60)) was calculated, and the mean PR score after 3 days (PR3days) was determined. Results: The median (interquartile range) OM grade of the participants was 2.0 (2.0-2.3). The VAS score decreased significantly at 30 min after IMS administration (p = .001). The median (interquartile range) TOTPAR(60) and PR3days were 6.0 (3.8-7.3) and 2.0 (2.0-3.0), respectively. Conclusions: IMS helped improve patients' quality of life. The risk of systemic adverse effects was low because of the low dose administered. IMS effectively relieved anticancer drug-induced OM pain and may be useful for immediate self-medication.

We report a 7-year-old male patient who developed severe atrioventricular block after transcatheter closure of the atrial septal defect with an Occlutech Figulla® Flex II ASD occluder (FSO). He had a small aortic rim and the defect measuring 22.3 mm by balloon sizing. When a 24 mm FSO was deployed, he developed Wenckebach second-degree heart block; however, it recovered to sinus rhythm. Hence, the device was implanted. The rhythm deteriorated to a fixed 2:1 heart block within 7 hr. He underwent surgical retrieval of the device and closure of the defect. Intraoperative findings demonstrated the right atrium disk compressing the triangle of Koch, resulting in a small hematoma. The rhythm recovered completely by 7 days after the surgery. Care must be taken when a relatively large device is deployed in a patient with small rims as even "soft and flexible" device like the FSO can injure the endocardium.

Human noroviruses (NoVs) are a major cause of epidemic and sporadic acute gastroenteritis worldwide. Public and personal hygiene is one of the most important countermeasures to prevent the expansion of NoV infection. However, initial tests of the virucidal effectiveness of anti-NoV disinfectants and sanitizers have been performed using surrogate viruses because of the lack of a practicable cell culture system for NoV. In this study, we used NoV virus-like particles (VLPs) as a new surrogate for NoVs, and developed a method to evaluate NoV inactivation. Our method is based on morphological changes in VLPs after treatment with sodium hypochlorite. We found VLP specimens were deformed and degraded in a concentration-dependent manner. Based on these results, we classified the effects of sodium hypochlorite on VLPs according to morphological changes and number of particles in four phases. Using these criteria, we evaluated the efficacy of ethanol, carbonates, and alkali solutions against VLPs. Deformation and aggregation of VLPs were observed after treatment with the disinfectants under specific conditions. To determine the degradation mechanism, VLPs were examined by SDS-PAGE and immunoblotting after treatment with sodium hypochlorite and ethanol. The band corresponding to the major capsid protein, VP1, was not detected after treatment with sodium hypochlorite at concentrations greater than 500 ppm, but remained after treatment with ethanol. These results suggest that VLPs have excellent potential as a surrogate marker for NoVs and can be used in initial virucidal effectiveness tests to determine the mechanism of chemical agents on NoVs.

We developed a new scaffold material—oriented collagen tubes (OCT)—and evaluated the potential of OCTs combined with basic fibroblast growth factor (bFGF) to repair of a 15 mm sciatic nerve defect in rats. The treatment groups consisted of OCT with adsorbed bFGF (OCT/bFGF group), OCT in phosphate-buffered saline (PBS) (OCT/PBS group), and a no-treatment group (Defect group). Functional evaluation of nerve regeneration was performed using the CatWalk system, and histological analyses of the defect sites were also performed. In rats treated with either OCT/bFGF or OCT/PBS, the walking function parameter of max contact area returned to normal levels by 4 weeks after grafting, and the regeneration of myelinated fibers was detected after 8 weeks. However, more regenerated myelinated fibers were observed in the OCT/bFGF group compared with the OCT/PBS group at 4 weeks. In addition, the max contact area and swing speed in the OCT/bFGF group were significantly recovered compared to the OCT/PBS and Defect groups at 8 weeks. Although the combination of bFGF and OCT was superior to OCT alone for nerve regeneration and functional recovery, the present findings demonstrate that OCT alone or in combination with bFGF accelerates nerve repair in a large peripheral nerve defect in rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 8–14, 2017.

Introduction: In this study we evaluated the relationships among the behavioral changes after muscle injury, histological changes, changes in inflammatory cytokines in the injured muscle, and changes in the sensory nervous system innervating the muscle in rats. Methods: We established a model of muscle injury in rats using a dropped weight. Behavior was assessed using the CatWalk system. Subsequently, bilateral gastrocnemius muscles and dorsal root ganglia (DRGs) were resected. Muscles were stained with hematoxylin and eosin, and inflammatory cytokines in injured muscles were assayed. DRGs were immunostained for calcitonin gene–related peptide (CGRP). Results: Changes of behavior and upregulation of inflammatory cytokines in injured muscles subsided within 2 days of injury. Repaired tissue was observed 3 weeks after injury. However, upregulation of CGRP in DRG neurons continued for 2 weeks after injury. Conclusion: These findings may explain in part the pathological mechanism of persistent muscle pain. Muscle Nerve 54: 776–782, 2016

Lumbar interbody fusion has become a popular technique for treating pathological spinal conditions such as spondylolisthesis, degenerative disk disease, recurrent disk herniation, and spinal deformity 1. However, failed spinal intervertebral fusion sometimes requires salvage surgery when symptomatic 2. Posterior revision surgery sometimes causes severe perioperative complications such as a dural tear, nerve injury, and symptomatic neurologic disorders, especially in those with lumbosacral lesions 3. The current report describes a safe revision option for a case of failed posterior transforaminal lumbar interbody fusion (TLIF) at the lumbosacral level treated using the anterior approach.

The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain-related mediators, such as interleukin-6 (IL-6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL-6 and IL-6 receptor (IL-6R) expression after IVD injury as well as determine the involvement of IL-6/IL-6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL-6 and IL-6R in IVDs by enzyme-linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL-6 inhibitor by evaluating pain-related protein, calcitonin gene-related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL-6 and IL-6R. IL-6 and IL-6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL-6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL-6 and IL-6R expression levels are responsive to IVD injury and that inhibition of IL-6/IL-6R signaling may be a promising analgesic treatment for degenerative disc diseases.

This study aimed to evaluate the time course of local changes during the acute phase of gastrocnemius muscle strain, in a rat model, using an in vivo imaging system. Thirty-eight, 8-week-old Sprague-Dawley male rats were used in our study. Experimental injury of the right gastrocnemius muscle was achieved using the drop-mass method. After inducing muscle injury, a liposomally formulated indocyanine green derivative (LP-iDOPE, 7 mg/kg) was injected intraperitoneally. We evaluated the muscle injuries using in vivo imaging, histological examinations, and enzyme-linked immunosorbent assays. The fluorescence peaked approximately 18 h after the injury, and decreased thereafter. Histological examinations revealed that repair of the injured tissue occurred between 18 and 24 h after injury. Quantitative analyses for various cytokines demonstrated significant elevations of interleukin-6 and tumor necrosis factor-α at 3 and 18 h post-injury, respectively. The time course of fluorescence intensity, measured using in vivo imaging, demonstrated that the changes in cytokine levels and histopathologic characteristics were consistent. Specifically, these changes reached peaked 18 h post-injury, followed by trends toward recovery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1034–1038, 2015.

Aim At Hokkaido University Hospital, selective serotonin re-uptake inhibitors (SSRI) or serotonin and norepinephrine re-uptake inhibitors (SNRI) are the first-line medications for burning mouth syndrome (BMS). Occasionally, when standard SSRI/SNRI are deemed inappropriate because of certain side-effects, treatment incompatibility, age concerns, or doctor discretion, a kampo medicine called rikkosan can be used. The purpose of this study was to evaluate the effectiveness of rikkosan for BMS. Methods This retrospective study included 48 patients (four men, 44 women; mean age, 70 years) who were diagnosed with BMS in the present department between 2006 and 2014. Only patients who received rikkosan (7.5 g/day) for >4 weeks were included. Patients who were taking other medicines for BMS were excluded. Pain was assessed using a visual analog scale. Results Improvement was seen in 54% of patients (26/48). Conclusion Rikkosan is an effective alternative treatment for BMS.

Organizing pneumonia (OP) is a clinicopathological entity that occurs idiopathically or in association with several conditions such as connective tissue diseases. Multicentric reticulohistiocytosis (MRH) is a systemic disease characterized by polyarthritis and mucocutaneous lesions, but lung involvement is uncommon. We report a patient with MRH associated with OP. This case may be of interest when considering the pathophysiological mechanisms of both diseases.

It has been postulated that physical immobilization is an essential factor in developing chronic pain after trauma or surgery in an extremity. However, the mechanisms of sustained immobilization-induced chronic pain remain poorly understood. The present study, therefore, aimed to develop a rat model for chronic post-cast pain (CPCP) and to clarify the mechanism(s) underlying CPCP. To investigate the effects of cast immobilization on pain behaviours in rats, one hindlimb was immobilized for 2 weeks with a cast and remobilization was conducted for 10 weeks. Cast immobilization induced muscle atrophy and inflammatory changes in the immobilized hindlimb that began 2 h after cast removal and continued for 1 week. Spontaneous pain-related behaviours (licking and reduction in weight bearing) in the immobilized hindlimb were observed for 2 weeks, and widespread mechanical hyperalgesia in bilateral calves, hindpaws and tail all continued for 5-10 weeks after cast removal. A sciatic nerve block with lidocaine 24 h after cast removal transitorily abolished bilateral mechanical hyperalgesia in CPCP rats, suggesting that sensory inputs originating in the immobilized hindlimb contribute to the mechanism of both ipsilateral and contralateral hyperalgesia. Intraperitoneal injection of the free radical scavengers 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxy1 or N-acetylcysteine 24 h after cast removal clearly inhibited mechanical hyperalgesia in bilateral calves and hindpaws in CPCP rats. These results suggest that cast immobilization induces ischaemia/reperfusion injury in the hindlimb and consequent production of oxygen free radicals, which may be involved in the mechanism of widespread hyperalgesia in CPCP rats.

Background: Cumulative interceptive supportive therapy (CIST) is currently used as a guideline for treating peri-implant diseases. The objectives of this study were to determine the detection rate and measure the number of periodontopathic bacteria in lesions of different CIST levels and thereby characterize peri-implant disease from a bacteriological viewpoint. Methods: This study included 105 patients who had both residual natural teeth and implants with peri-implant disease. A total of 105 implants were divided into levels A, B, C and D according to the CIST classification. Bacterial samples were collected from peri-implant pockets and four periodontopathic bacteria were measured by PCR and PCR-Invader assay. Results: The number of periodontopathic bacteria increased in line with CIST level, and the detection rate was also associated with CIST level. However, no difference was found in the bacterial detection rate of P. gingivalis and T. denticola between CIST-B and CIST-C. There was a higher detection rate of all periodontopathic bacteria for CIST-D. Conclusions: The number of periodontopathic bacteria and detection rate increased as peri-implant disease advanced. However, there were no major differences in the detection rate between CIST-B and CIST-C. On the other hand, a higher detection rate of periodontopathic bacteria was seen for CIST-D.

Gemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes. Expressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis. p53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC50 > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway. Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.

The "crazy paving" appearance consists of ground-glass opacity superimposed on a network of linear opacities on thin-section computed tomography (CT) images of the lung. This finding has been described in a variety of diseases but is extremely rare in patients with non-specific interstitial pneumonia (NSIP). We describe a 45-year-old woman with biopsy-proven NSIP associated with clinically amyopathic dermatomyositis that showed a "crazy paving" appearance on thin-section CT of the lung. Clinicians should include NSIP in the differential diagnosis in patients presenting with "crazy paving" appearance on thin-section chest CT.

Background: Urinary N-telopeptides of type I collagen (NTx) is a specific marker of bone resorption. The NTx levels of children have been reported to be higher than in adults, but such reports are limited. The aim of the present study was to measure the urine NTx of healthy children to define reference values, and study the circadian rhythm of urine NTx excretion between the first and second voided urines. Methods: Three hundred and sixty-two healthy Japanese children (209 boys and 153 girls; age range, 6–11 years) served as subjects to study age-related changes in NTx. Urine samples were collected as the first voided specimen of the day. To evaluate the circadian variation, we measured the excretion of urinary NTx of the first and second voided urine specimens in 30 healthy Japanese children (15 boys and 15 girls), 6–12 years of age. Urine NTx was measured on enzyme-linked immunosorbent assay (ELISA). Results: Urinary NTx levels were higher in children of both genders than in healthy adults. In boys, the urinary NTx levels decreased with age. In girls, the urinary NTx levels decreased with age between 6 and 9 years of age, but increased between 9 and 10 years of age. NTx of the first voided urine specimen was significantly higher than the second voided urine specimen. Moreover, a significant linear relationship between the first voided urine and the second void urine existed in both genders. Conclusions: Urinary NTx levels in children are higher than in adults. The urine NTx of the first voided urine specimen may be a good marker of bone resorption for children.

Patients suffering from neuropathic pain often complain of pain aggravation when the weather is changing. The exact mechanism for weather change-induced pain has not been clarified. We have previously demonstrated that experimentally lowering barometric pressure (LP) intensifies pain-related behaviors in rats with chronic constriction injury (CCI). In the present experiment we examined whether this pain aggravating effect of LP exposure in nerve injured rats is still present after lesioning of the inner ear. We used both CCI and spinal nerve ligation (SNL) models for this study. We injected into the middle ear sodium arsanilate solution (100mg/ml, 50microl/ear), which is known to degenerate vestibular hair cells, under anesthesia the day before surgery. Rats were exposed to LP (27hPa decrease over 8min) 7-9 days after CCI or 5-8 days after SNL surgery, and pain-related behavior (number of paw lifts induced by von Frey hair stimuli) was measured. When the inner ear lesioned SNL or CCI rats were exposed to LP, they showed no augmentation of pain-related behavior. On the other hand, the pain aggravating effect of a temperature decrease (from 24 to 17 degrees C) was maintained in both SNL and CCI rats. These results suggest that the barometric sensor/sensing system influencing nociceptive behavior during LP in rats is located in the inner ear.

We investigated whether direct hemoperfusion with a polymyxin B column (DHP-PMX) was able to decrease macrophage and monocyte activity in patients with sepsis. Nineteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome (SIRS) due to infection and a mean arterial blood pressure > or =65 mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for intravenous infusion, and DHP-PMX was performed twice within 24 h for 3 h each time. Serum neopterin was measured four times: before DHP-PMX, and 24, 48, 72 h after it had begun. The serum concentrations of neopterin were 654 +/- 234 nmol/L prior to DHP-PMX vs. 573 +/- 196 nmol/L at 24 h, 452 +/- 161 nmol/L at 48 h, and 372 +/- 139 nmol/L at 72 h, showing a significant decrease from 48 h onwards compared with before treatment. These data suggest that DHP-PMX decreases macrophage and monocyte activity.

The ubiquitously expressed Cyclin G-associated kinase (GAK) regulates clathrin-mediated membrane trafficking in the cytoplasm. However, the association of GAK with a nuclear protein Cyclin G1 that is unrelated to membrane trafficking suggests an unidentified role of GAK in the nucleus. Indeed, we report here that GAK localizes in both cytoplasm and nucleus by immunostaining, ectopic expression of GFP-GAK and pull-down assays using dissected GAK fragments. GAK forms complexes not only with cyclin G1 but also with other nuclear proteins such as p53, clathrin heavy chain (CHC) and protein phosphatase 2A (PP2A) B'alpha1. Moreover, CHC associates with GAK via a different domain depending on whether it is in the cytoplasm or nucleus. Immunostaining revealed that about 20-30% of B'alpha1, cyclin G1 and p53 complex with nuclear GAK. CHC also displayed dots in the nucleus and almost all nuclear CHC signals colocalized with GAK. These observations together suggest an important function of GAK in the nucleus.

This study had two purposes. One was to assess gastric intramucosal pH (pHi) after early goal-directed therapy in patients with sepsis and septic shock. The other was to determine whether direct hemoperfusion with a polymyxin B fiber column (DHP-PMX) could improve the pHi if it remained low after early goal-directed therapy. The subjects were 32 patients who underwent early goal-directed therapy within 6 h of a diagnosis of sepsis or septic shock, and who achieved the following conditions: (i) central venous pressure of 8-12 mm Hg; (ii) mean arterial blood pressure >or=65 mm Hg; (iii) urine output >or=0.5 mL/kg/h; and (iv) mixed venous oxygen saturation >or=70%. A gastric tonometer was inserted in each patient and the pHi was measured before DHP-PMX, and at 24, 48, and 72 h after the start of treatment. The pHi was 7.22 +/- 0.04 immediately before DHP-PMX, 7.28 +/- 0.03 (P < 0.05) at 24 h, 7.32 +/- 0.03 (P < 0.01) at 48 h, and 7.34 +/- 0.02 (P < 0.01) at 72 h, showing a significant increase from 24 h onward compared with the pretreatment value. In patients with sepsis and septic shock, the pHi remained low after early goal-directed therapy; however, it was significantly improved from 24 h after the start of DHP-PMX and was normalized from 48 h onwards. These findings suggest that DHP-PMX improves pHi. Because this was a prospective uncontrolled observational study on a limited number of patients, larger multicenter clinical trials are required to more accurately assess the benefits of DHP-PMX.

Background and objectives: A variety of markers, such as serum angiotensin-converting enzyme (sACE) and CXR have been used to evaluate the disease activity and progression of sarcoidosis. There are patients who have developed cardiac involvement several years after the initial diagnosis despite stable or decreased disease activity. This study clarified the clinical characteristics of those patients. Methods: A total of 141 consecutive patients treated for sarcoidosis were studied. Heterochronic cardiac sarcoidosis was defined as the sudden onset of cardiac manifestations more than 2 years after the initial diagnosis despite stable lung disease and normal sACE levels. Results: Of the patients studied four showed heterochronic cardiac involvement. These patients were all middle-aged women (mean age, 50.5 years) with multiple organ involvement. The time period from the initial diagnosis of sarcoidosis to the onset of cardiac involvement ranged from 3 to 8 years, with a mean duration of 5.2 years. All patients showed fatal conduction abnormalities. Conclusions: Middle-aged women with multiple organ involvement of sarcoidosis are at risk of developing cardiac sarcoidosis.

Sjogren's syndrome (SS) is uncommon in men and there are few reports that describe their clinical features. In the present study, we investigated salivary gland manifestations in men with SS and compared the results with those in women patients. This study included 12 men and 117 women with SS, and the mean stimulated parotid flow rate in men (4.1 ml/5 min, n = 10) was higher than that of the women (3.1 ml/5 min, n = 101). The prevalence of SS-related sialographic findings, such as globular and punctate sialectasis, was significantly (P

Visual servoing is being widely investigated as a robot control method that is robust to unpredictable disturbances. Conventional visual servoing assumes calibration of the robot and camera, but such calibration proves very difficult in practice. Thus, we have proposed a method of stable visual servoing for a robot moving on a plane, with neither the robot nor its camera being calibrated. In this paper, we extend the previous method to 3D projective space, thus providing visual servoing for general uncalibrated robots operated in 3D space. In particular, we show that invariant properties in projective space defined by means of epipolar geometry play an important role in navigation. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 90(12): 50–58, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20361

OBJECTIVES: To evaluate the discriminatory power of the Pneumonia Severity Index (PSI) in elderly patients with community-acquired pneumonia (CAP) and to improve its performance. DESIGN: Retrospective review of 193 patients from 1999 to 2001 to derive prognostic rules. The rules were prospectively validated in 144 patients from 2002 to 2003. SETTING: Iwata City Hospital, a 400-bed general hospital. PARTICIPANTS: Patients aged 80 and older who had CAP and were admitted to the hospital. MEASUREMENTS: Predictors of 30-day mortality were identified using logistic regression analysis, and several rules were constructed by combining the PSI and the independent predictors. Classification and regression tree analysis was also used for constructing rules. Sensitivity and specificity were calculated. RESULTS: The original PSI, which defines PSI Class IV and V as a high-risk group, did not perform well in discriminating survivors from nonsurvivors (sensitivity 100%, specificity 15%), whereas a modified PSI, which defines only PSI Class V as a high-risk group, performed better (sensitivity 86%, specificity 63%). Three predictors for mortality were identified independent from the modified PSI: performance status (PS) Grade 3 or higher, anorexia, and partial pressure of carbon dioxide of 50 mmHg or greater. By combining the modified PSI and PS, the performance could be further improved (sensitivity 79%, specificity 80%). CONCLUSION: The modified PSI could identify low-risk patients more accurately than the original PSI. In addition, by combining the modified PSI with PS, higher performance was obtained. Such information would aid physicians in clinical decision-making without overestimating the risk for elderly patients with CAP.

Visual servoing has been widely studied as a robust method for controlling a robot that can deal with unpredictable disturbances. However, existing visual servoing methods require that the robot and camera be calibrated in advance. Although the current authors have previously proposed an uncalibrated visual servoing method that does not require the camera and robot to be calibrated, the starting position of the robot had a large influence on the control process in that method. This paper presents an uncalibrated visual servoing method that can control a robot in the same way from any starting position by determining control values without uncertainty in the magnitude. In particular, it is demonstrated that a robot can be accurately guided to a target position by using projective reconstruction, which has been studied extensively in recent years in the field of computer vision, by introducing the concept of the projection of control values. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(10): 47–56, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20314

Delayed onset muscle soreness (DOMS) is quite common, but the mechanism for this phenomenon is still not understood; even the existence of muscle tenderness (mechanical hyperalgesia) has not been demonstrated in experimental models. We developed an animal model of DOMS by inducing eccentric contraction (lengthening contraction, ECC) to the extensor digitorum longus muscle (EDL), and investigated the existence of mechanical hyperalgesia in the EDL by means of behavioural pain tests (Randall-Selitto test and von Frey hair test, applied to/through the skin on the EDL muscle) and c-Fos expression in the spinal dorsal horn. We found that the mechanical withdrawal threshold measured with the Randall-Selitto apparatus decreased significantly between 1 and 3 days after ECC, while that measured by von Frey hairs did not. The group that underwent stretching of the muscle only (SHAM group) showed no change in mechanical pain threshold in either test. These results demonstrated that the pain threshold of deep tissues (possibly of the muscle) decreased after ECC. c-Fos immunoreactivity in the dorsal horn (examined 2 days after ECC/SHAM exercise) was not changed by either ECC or compression (1568 mN) to the EDL muscle by itself, but it was significantly increased by applying compression to the EDL muscle 2 days after ECC. This increase was observed in the superficial dorsal horn of the L4 segment of the ipsilateral side, and was clearly suppressed by morphine treatment (10 mg kg(-1), i.p.). These results demonstrated the existence of mechanical hyperalgesia in the muscle subjected to ECC. This model could be used for future study of the neural mechanism of muscle soreness.

悪性症候群は,抗精神病薬や抗パーキンソン病薬の開始,変更,中断により発症するとされている。今回,われわれは抗精神病薬増量が原因と考えられる悪性症候群の1例を経験したので報告する。患者は54歳,女性。3年前から精神科通院歴があり,抗精神病薬の投与を受けていた。薬剤増量の約1週間後に,40℃を超える発熱,意識障害にて発症。全身冷却及びdantroleneの投与を行ったが,全身状態の悪化に従い,人工呼吸管理,血液透析等の集中治療を行った。Max CPKは42,550U/lであった。第10病日に人工呼吸管理から離脱し,第28病日には血液透析からも離脱した。第57病日,全身状態及び意識レベルが安定したため,当院精神科へ転科となった。悪性症候群は,精神科領域のみならず,救急医療の分野でも忘れてはならない重篤な疾患である。精神疾患治療の有無,治療薬歴,現症及び血液検査所見等より本疾患を疑った場合,血液透析等を含めた治療及び厳重な全身管理を早期より開始することが必要と考える。

Cu-doped p-type CdS (CdS:Cu) and non-doped n-type CdS films were fabricated by the vacuum deposition process. Photoluminescence (PL) spectra of CdS:Cu and CdS films were measured between 8.7 K and room temperature. Free excitonic emission (FX), neutral acceptor-bound excitonic emission (I1), and donor–acceptor pair emission (DAP) were observed from CdS:Cu films. These results suggest that crystallinity of CdS films was improved by Cu doping and that Cu atoms in CdS behave as acceptors and form shallow levels (about 80 meV above the valence band edge) in CdS. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The recognition of motions is very important for understanding dynamic actions and extracting events from video sequences. In this paper, we propose invariants on object motions, which can be extracted from image sequences, and are invariant even if the motions are viewed from arbitrary viewpoints. We call them space-time invariants since they are defined under space-time projections. We show that these invariants are very useful for extracting specific motions from video sequences. The proposed space-time invariants are implemented and tested on real image sequences. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(12): 38–46, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10147

DO11.10 transgenic mice, expressing an ovalbumin (OVA)-specific alphabeta T-cell receptor (TCR), have been used as a model of various immune diseases associated with T lymphocytes. Some studies of immunoresponse in lung have involved adoptive transfer of DO11.10 mice. As of yet, however, there have been no studies of the adoptive transfer model in the upper airway. The purpose of this study was to establish an animal model to clarify the recruitment mechanism and the roles of Th2 cells in allergic rhinitis. In accordance with the adoptive transfer system, we generated Th0, Th1 and Th2 cells from DO11.10 mice and transferred them into wild type BALB/c mice. Following nasal OVA challenge to DO11.10 mice or to the BALB/c mice into which antigen-specific Th2 cells had been transferred, the number of local antigen-specific TCR-positive cells accompanying the local eosinophilia had significantly increased. However, nasal OVA challenge to BALB/c mice into which antigen-specific Th0 or Th1 cells were transferred failed to increase the number of local OVA-specific TCR positive cells. These observations suggest that an antigen-specific homing mechanism of Th2 cells may exist in nasal mucosa. Analysis of this model will assist in the development of new therapeutic strategy, which targets Th2 cells in allergic rhinitis.

Granulomatosis with polyangiitis (GPA) frequently involves the upper respiratory tracts, but involvement of the epiglottis is extremely rare. This report describes a patient initially presenting with dysphagia and increasing stridor due to epiglottitis. Bronchoscopy showed swelling of the epiglottis with partly whitish nodular lesions, with biopsy specimens showing neutrophil infiltration and necrosis. Chest computed tomography showed multiple nodular consolidations in the bilateral lung parenchyma, and histological findings were consistent with vasculitis. The patient was diagnosed with GPA and responded well to treatment with prednisolone and cyclophosphamide. Although an uncommon manifestation, GPA should be included in the differential diagnosis of epiglottitis, especially in patients with lung parenchymal lesions suggestive of GPA.

Background and Aims: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. Methods: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. Results: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P < 0.005, P < 0.02, P < 0.01, respectively). Conclusions: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.

We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4(+) and CD8(+) T cells and NK (asialoGM1(+) ) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4(+) and CD8(+) T, as well as asialoGM1(+) cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM(+) and IgA(+) B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8(+) cells were significantly increased by treatment with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-gamma presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-gamma and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.

We describe three cases of lymphoma of bronchus-associated lymphoid tissue (BALT). All three patients had long histories of right middle lobe and/or lingula infiltrates on chest radiographs that were compatible with chronic respiratory tract infection. On histological and immunological examination of lung biopsy specimens in the three cases, a lymphoepithelial lesion was identifiable. Phenotyping of the infiltrating lymphocytes showed predominantly B cells, but the lymphocytes were negative for CD10. In two of the cases, rearrangement of the immunoglobulin heavy chain genes was positive, while rearrangements of the bcl-2 and T cell receptor genes were negative. Each patient had a long history of a productive cough, ranging from 5 to 7 years. Thus, the differential diagnosis of BALToma must be considered when serial chest radiographs show progression over years in the right middle lobe and/or lingula. Furthermore, because BALToma arises from BALT itself and hyperplasia of BALT is dependent on prolonged antigenic stimulation, the onset of these BALTomas may have been related to chronic respiratory tract infections.