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Malnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization.We explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values.In addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log-rank p 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log-rank p 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96-0.98, p 0.001] and IC (HR: 0.94, 95% CI: 0.91-0.97, p 0.001).Preprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.

Purpose:Hypoglycemia is a common and life-threatening complication in type 1 diabetes mellitus (T1DM) patients. Current guidelines recommend glucagon for treating hypoglycemia in out-of-hospital settings; however, glucagon is reportedly underused in such patients. We conducted a doctor-oriented, questionnaire-based survey of pediatricians and physicians to determine the glucagon prescription rate and identify the reason(s) for its underuse in T1DM patients.Methods:A questionnaire was mailed to 415 pediatricians and 200 physicians employed at 66 facilities with >100 general wards throughout Hyogo, Japan. The following variables were surveyed: doctor’s specialty, glucagon prescription rate, familiarity with glucagon use guidelines, barriers to prescribing glucagon, and attitude changes after education.Results:After 16 doctors were found to have retired, 599 doctors were enrolled; 305 (187 pediatricians and 118 physicians) returned a completed questionnaire. In all, 45 pediatricians and 104 physicians were treating T1DM patients, of whom 24% and 28% reported prescribing glucagon, respectively. The guideline familiarity rate among pediatricians was lower than that among physicians. The major barrier to prescribing glucagon was the complex preparation procedure required by patients/caregivers. More than half of the doctors who did not prescribe glucagon began doing so after being educated about the guidelines.Conclusion:The glucagon prescription rate was low among both pediatricians and physicians in Japan.

Context: CHARGE association consists of congenital malformation of Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies and/or deafness. It is often caused by CHD7 gene mutation, which also one of the causative gene for Kallmann syndrome. The endocrine dysfunction in CHARGE association has been reported but not fully understood. Objective: To clarify the mode of growth and frequency of endocrine dysfunction in CHARGE association. Subjective: We investigated the characteristics of growth and puberty, and endocrine function in 23 children (15 males and 8 females, 0~20 years old) with CHARGE association. Results: The birthweight was from -2.74 to +1.14 SDS and the birth length was from -2.86 to +1.10 SDS. 5 children were born small for gestational age. The height below -2SDS in 18 children. GH secretion was evaluated in 11 children with short stature (-9 to -2.3SD) except for one with normal height (-0.3 SD in 6 years old girl); 5 children including one with normal stature were revealed to have GH deficiency. One short girl with GH deficiency previously showed normal GH response to provocation test at 1 year old but has developed to be GH deficient at 7 years old. Gonadotropin-releasing hormone loading tests were performed in 7 males and 3 females. Nine out of 10 children showed hypogonadotropic hypogonadism; one girl showed hypergonadotropic hypogonadism, whose ovaries were undetectable on ultrasound. Human chorionic gonadotrophin (HCG) tests were performed in 6 males with micropenis and/or cryptorchidism. Peak testosterone levels after HCG stimulation were from 0 to 6.99 ng/ml. 4 patients showed peak testosterone levels less than 1 ng/ml. Four boys showed combined gonadotropin deficiency and primary hypogonadism. Conclusions: Our data showed the diversity of endocrine function in children with CHARGE association. GH deficiency can be developed over time. Hypogonadotropic hypogonadism is common, while isolated/combined primary hypogonadism should be taken into consideration in children with CHARGE association.

A Japanese woman aged in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low‐set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis showed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT (short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay) syndrome. Administration of a sodium–glucose cotransporter 2 inhibitor lowered the proband's hemoglobin A1c level and allowed a reduction in her insulin dose without treatment‐related adverse events including ketoacidosis, exaggerated loss of body mass or hypoglycemia. Sodium–glucose cotransporter 2 inhibitors might thus offer an additional option for the treatment of genetic syndromes of severe insulin resistance.

Duchenne muscular dystrophy (DMD) is a fatal progressive muscle wasting disease of childhood. Titin in sarcomere is digested by calcium dependent protease. To explore muscle damage in DMD, the urinary concentrations of the N-terminal fragment of titin were determined using a newly developed enzyme linked immune sorbent assay kit. The urinary titin concentrations were normalized to creatinine (Cr). A total of 145 urine samples were obtained at a single Japanese hospital from 113 DMD patients aged 3-29years. Normalized urinary titin concentration was 965.8±1011.9 (Mean±SD) pmol/mg Cr in patients with DMD. This was nearly 700-fold higher than healthy children (1.4±0.8pmol/mg Cr). The concentration was significantly higher in DMD than in BMD patients who had significantly higher urinary titin than normal. Urinary titin in DMD patients tended to decrease with age. The median concentration of urinary titin in the youngest (aged 3-7years) and oldest (aged ≥16years) groups was 1468.3 and 411.3pmol/mg Cr, respectively, with significant difference. Urinary concentration of titin correlated significantly with serum creatine kinase concentration, the best-known biomarker of DMD. The N-terminal fragment of titin in urine has potential as a diagnostic and clinical biomarker for DMD.

Background One of the main complications in patients with muscular dystrophies is cardiac dysfunction. The literature on cardiac involvement in patients with Fukuyama congenital muscular dystrophy (FCMD) is limited. Aim To compare cardiac involvement between patients with FCMD and Duchenne muscular dystrophy (DMD). Methods We compared cardiac involvement between 30 patients with FCMD and 181 patients with DMD using echocardiography and serum biomarkers. All patients were receiving regular checkups at Kobe University Hospital. We used single regression analysis to compare echocardiographic parameters, age, and serum biomarkers. Results Almost all clinical and echocardiographic parameters were lower in patients with FCMD than DMD. The brain natriuretic peptide concentration in patients with FCMD showed no correlation with age or left ventricular ejection fraction ( r = 0.231, p = 0.22 and r = 0.058, p = 0.76, respectively). A log-rank test revealed that the risk of left ventricular systolic dysfunction was lower in patients with FCMD than DMD ( p = 0.046, hazard ratio = 0.348). Conclusion The clinical progression of cardiac dysfunction is significantly milder in patients with FCMD than DMD, while skeletal muscle involvement is significantly worse in patients with FCMD. These data suggest that the pathophysiological findings of FCMD can be explained by less severe cardiac dysfunction in FCMD than DMD.

Duchenne and Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene and are characterized by severe and mild progressive muscle wasting, respectively. Short stature has been reported as a feature of DMD in the Western hemisphere, but not yet confirmed in Orientals. Height of young BMD has not been fully characterized. Here, height of ambulant and steroid naive Japanese 179 DMD and 42 BMD patients between 4 and 10 years of age was retrospectively examined using height standard deviation score (SDS). The mean height SDS of DMD was -1.08 SD that was significantly smaller than normal (p

Background Glutaryl carnitine (C5DC) in dried blood spots is used as a biomarker for glutaric aciduria type 1 (GA-1) screening. C5DC, however, is the only screening marker for this condition, and various pathological conditions may interfere with C5DC metabolism. Recently, C5DC elevation has been reported in cases of renal insufficiency. Method Five patients who were positive for GA-1 on newborn screening with tandem mass spectrometry between September 2012 and March 2015 at Kobe University Hospital were enrolled in this study. Results GA-1 was not confirmed on urinary organic acids analysis in any of the patients. C5DC decreased immediately in four patients, but one patient, who had high C5DC for at least 4 months, was diagnosed with bilateral renal hypoplasia. Conclusion In the case of persistently elevated C5DC, renal insufficiency should be considered as a differential diagnosis.

Feeding behavior in cnidarians has been studied as a model experimental system in physiology and neurobiology. Although the feeding response in cnidarians, such as

Feeding behavior in cnidarians has been studied as a model experimental system in physiology and neurobiology. Although the feeding response in cnidarians, such as Hydra, is triggered by chemical signals, the underlying molecular mechanisms that ensure their precise execution are not well understood. It could be largely due to the lack of genetic analysis in cnidarian experimental systems. Cladonema pacificum is a hydrozoan jellyfish that is easy to maintain and cross for genetic analysis in the laboratory. To establish C. pacificum as a model experimental animal in cnidarians, we have been inbreeding strains of jellyfish. Here, we document our progress in developing C. pacificum inbred lines and feeding-defective strains that we isolated in the course of inbreeding. In the inbred lines, an increasing number of feeding-defective strains appeared as descending generations and finally all the F5 progeny showed a feeding-deficient phenotype presumably owing to inbreeding depression. Feeding behaviors of these strains were analyzed by video microscopy and we found that the feeding-defective strains captured prey, but could not kill them. After trapping prey, wild-type medusae contracted their tentacles tightly and then bent the tentacles to bring the prey to the mouth; however, feeding-defective medusae rarely contracted their tentacles and did not bend. These feeding-defective phenotypes are caused by lack of stinging nematocytes in their tentacle batteries. These findings furnish a clue to the regulatory aspects of feeding behavior, but also reveal the mechanisms of stinging nematocyte transport in tentacles.

With the development of IoT applications, a wide variety of healthcare systems are available. A decrease in birthrate and an aging population have led to increased importance of health care for older adults. In such environments, a monitoring system is useful, in which a targeted person can be continuously viewed through a camera, and reports regarding the person's health can be automatically transmitted through email. However, the application does not take security into account enough because most systems are connected to the Internet. The system should be protected from a wide variety of risks to keep both personal data and sensors safe. Therefore, we developed SinkNet. This program connects several sensors and constructs a private network that can automatically perform a series of actions for client devices, such as collecting logs, detecting problems through machine learning, and checking to avoid and solve problems. In addition, SinkNet manipulates multiple sensors and recognizes living habits (e.g., hand and face washing, gargling) from the sound of water flow and talks interactively to users through synthetic sounds. This paper describes SinkNet, focusing on its implementation and initial evaluation.

The procedure of 3-D finite element meshing for skewed rotor induction motors has been developed. In this method, the mesh distortion caused by the rotor-node rotation for skew modeling is reduced using the iterative node displacement and element swapping. The advantages and necessity of the proposed method are confirmed by comparing the conventional mesh-generation method and motor experiments. It is revealed that the accuracy of the calculated loss is considerably deteriorated by the distorted mesh and it is significantly improved by the proposed mesh-generation procedure.

Few long-term cohort studies have addressed changes in the ambulatory capacity of patients with Duchenne muscular dystrophy (DMD), and no reports have evaluated the factors associated with ambulatory capacity in Japanese.The longitudinal changes in 10-meter run/walk ability and associated factors were retrospectively investigated using general practice data. The factors associated with loss of this ability before the age of 10 years were explored by logistic regression analysis using parameters of genetic mutations, corticosteroid use, the manual muscle test (MMT), and the joint range of motion (ROM). Explanatory variables of MMT grade included hip flexors, knee flexors, and knee extensors; ROM included hip extension, knee extension, and ankle dorsiflexion.Among 418 patients diagnosed with DMD, 145 patients underwent the 10-meter run/walk test between March 1999 and July 2015. The median age at loss of 10-meter walking ability was 10.4 (interquartile range: 9.2-11.3) years. The 10-meter run/walk speed began to decline 3 years before the loss of 10-meter walking ability, and the median was1 m/s 1 year before the loss of 10-meter walking ability. MMT grade for knee flexors and ROM for hip and knee extension were identified as independent predictors. Based on the change over time of these three items, limitation of the hip extension ROM preceded knee flexor weakness and limitation of the knee extension ROM.This knowledge can be used in optimizing rehabilitation programs and evaluating effect of treatment for DMD patients.

The Duchenne muscular dystrophy (DMD) gene is one of the largest genes in the human genome. The gene exhibits a complex arrangement of seven alternative promoters, which drive the expression of three full length and four shorter isoforms. Dp116, the second smallest product of the DMD gene, is a Schwann cell-specific isoform encoded by a transcript corresponding to DMD exons 56–79, starting from a promoter/exon S1 within intron 55. The physiological roles of Dp116 are poorly understood, because of its extensive homology with other isoforms and its expression in specific tissues. This review summarizes studies on Dp116, focusing on clinical findings and alternative activation of the upstream translation initiation codon that is predicted to produce Dp118.

Background The DMD gene encoding dystrophin is mutated in Duchenne muscular dystrophy, a fatal progressive muscle wasting disease. DMD has also been shown to act as a tumor suppressor gene. Rhabdomyosarcoma (RMS) is a mesodermal sarcoma that shares characteristics of skeletal muscle precursors. Products of the DMD gene in RMS have not yet been fully clarified. Here, DMD products were analyzed in CRL-2061 cells established from alveolar RMS. Methods The 14-kb long DMD cDNA was PCR amplified as 20 separated fragments, as were nine short intron regions. Dystrophin was analyzed by Western blotting using an antibody against the C-terminal region of dystrophin. Results Sixteen of the 20 DMD cDNA fragments could be amplified from CRL-2061 cells as muscle cDNA. Three fragments included aberrant gene products, including one in which exon 71 was omitted and one each with retention of introns 40 and 58. In one fragment, extending from exon 70 to 79, no normally spliced product was obtained. Rather, six alternatively spliced products were identified, including a new product deleting exon 73, with the most abundant product showing deletion of exon 78. Although dystrophin expression was expected in CRL-2061 cells, western blotting of cell lysates showed no evidence of dystrophin, suggesting that translation of full-length DMD mRNA was inhibited by intron retention that generated a premature stop codon. Intron specific PCR amplification of nine short introns, showed retention of introns 40, 58, and 70, which constituted about 60, 25 and 9%, respectively, of the total PCR amplified products. The most abundant DMD transcript contained two abnormalities, intron 40 retention and exon 78 skipping. Conclusions Intron-specific PCR amplification showed that DMD transcripts contained high levels of introns 40, 58 and 70. Retention of these introns may have been responsible for the lack of dystrophin expression by CRL-2061 cells, thereby abolishing the tumor suppressor activity of dystrophin.

Incidence and neonatal risk factors for short stature in preterm children born small for gestational age (SGA) have not been fully investigated in Japan. In this prospective study, infants born ≤32 weeks’ gestational age (GA) from 2004–2015 were enrolled and followed for 3 years. Incidence of short children born SGA and short stature treated with growth hormone (GH) were investigated. Neonatal risk factors were analysed using univariate and multivariate analyses. GA cut-off value was determined using receiver operating characteristic (ROC) curve analyses. Of 604 infants born ≤32 weeks’ GA, 76 (13%) were SGA at birth. Twenty-seven infants (36%) developed short stature at age 2 and 14 infants (19%) received GH treatment at age 3. GA, birthweight, birth length, birth head circumference, and chronic lung disease at 36 weeks’ corrected GA were determined as risk factors by univariate analyses (p

Background Duchenne muscular dystrophy (DMD), the most common inherited muscular disease in childhood, is caused by dystrophin deficiency because of mutations in the DMD gene. Although DMD is characterized by fatal progressive muscle wasting, cardiomyopathy is the most important nonmuscle symptom threatening the life of patients with DMD. The relationship between cardiac involvement and dystrophin isoforms has not been analyzed. Methods and Results The results of 1109 echocardiograms obtained from 181 Japanese DMD patients with confirmed mutations in the DMD gene were retrospectively analyzed. Patients showed an age-related decline in left ventricular ejection fraction. Patients were divided by patterns of dystrophin isoform deficiency into 5 groups. The cardiac dysfunction-free survival was significantly higher in the group with mutations in the Dp116 coding region than the others, whereas no significant differences in the other 3 groups. At age 25 years, the cardiac dysfunction-free rate was 0.6 in the Dp116 group, but only 0.1 in others. PCR amplification of Dp116 transcript in human cardiac muscle indicated promoter activation. Conclusions Left ventricular ejection fraction in DMD declined stepwise with age. Cardiac dysfunction was less frequent in Dp116-deficient than other patients with DMD. Dp116 transcript was identified in human cardiac muscle for the first time. These results indicate that Dp116 is associated with cardiac involvement in DMD.

Background: The clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are unknown. We investigated the clinical characteristics and described detailed treatment of weekly intramuscular interferon β-la (IFNβ-1a) in children aged

Next-generation sequencing (NGS) discloses nucleotide changes in the genome. Mutations at splicing regulatory elements are expected to cause splicing errors, such as exon skipping, cryptic splice site activation, partial exon loss or intron retention. In dystrophinopathy patients, prediction of splicing outcomes is essential to determine the phenotype: either severe Duchenne or mild Becker muscular dystrophy, based on the reading frame rule. In a Vietnamese patient, NGS identified a c.9361+1G>A mutation in the dystrophin gene and an additional DNA variation of A>G at +117 bases in intron 64. To ascertain the consequences of these DNA changes on dystrophin splicing, minigene constructs were prepared inserting dystrophin exon 64 plus various lengths of intron 64. Exon 64 skipping was observed in the minigene construct with 160 nucleotide (nt) of intron 64 sequence with both c.9361+1A and +117G. In contrast, minigene constructs with larger flanking intronic domains resulted in cryptic splice site activation rather than exon skipping. Meanwhile, the cryptic splice site activation was induced even in +117G when intron 64 was elongated to 272 nt and longer. It was expected that cryptic splice site activation is an in vivo splicing outcome.

Enterovirus D68 (EV-D68) infection is associated with upper and lower respiratory tract symptoms such as fever, cough, and wheezing. Pediatric patients with EV-D68 infection easily develop more severe respiratory complications compared to patients infected with other species of enterovirus, and consequently, have a higher rate of hospitalization and admission to intensive care units. Therefore, the clinical picture of respiratory complications associated with EV-D68 infection needs to be elucidated. Here, we report a 4-year-old girl of EV-D68 infection that required artificial respiration management within 24 h from the onset of cold symptoms. The patient was diagnosed with interstitial pneumonia on the basis of chest imaging findings with patchy, funicular and frosted glassy shadows, increased blood markers of surfactant protein-A, surfactant protein-D and sialylated carbohydrate antigen KL-6, and increased neutrophils and lymphocytes in the bronchoalveolar lavage. Steroids showed a remarkable effect in her treatment. Further investigations are needed to confirm the efficacy of steroids for interstitial pneumonia due to EV-D68 infection. As rapid deterioration of respiratory status is observed in EV-D68 infection, the possibility of interstitial pneumonia may be considered.

Objective: To determine whether dried umbilical cords (UCs) are useful for retrospective diagnosis of intrauterine enterovirus (EV) infection.Methods: Dried UCs in two patients with neonatal EV sepsis and 10 neonates without infectious signs were enrolled. Viral RNA was extracted from their dried UCs, and nested reverse transcription polymerase chain reaction (RT-PCR) was performed.Results: Infection routes estimated by the clinical course were intrauterine infection in Case 1 and post-natal horizontal infection in Case 2. EV-RNA was detected from dried UC in Case 1, but not in Case 2 and 10 neonates.Conclusions: This report showed the potential use of dried UCs for retrospective diagnosis of intrauterine EV infection.

Background: Dystrophin Dp71 is one of the isoforms produced by the DMD gene which is mutated in patients with Duchenne muscular dystrophy (DMD). Although Dp71 is expressed ubiquitously, it has not been detected in normal skeletal muscle. This study was performed to assess the expression of Dp71 in human skeletal muscle. Methods: Human skeletal muscle RNA and tissues were obtained commercially. Mouse skeletal muscle was obtained from normal and DMDmdx mice. Dp71 mRNA and protein were determined by reverse-transcription PCR and an automated capillary Western assay system, the Simple Western, respectively. Dp71 was over-expressed or suppressed using a plasmid expressing Dp71 or antisense oligonucleotide, respectively. Results: Full-length Dp71 cDNA was PCR amplified as a single product from human skeletal muscle RNA. A ca. 70 kDa protein peak detected by the Simple Western was determined as Dp71 by over-expressing Dp71 in HEK293 cells, or suppressing Dp71 expression with antisense oligonucleotide in rhabdomyosarcoma cells. The Simple Western assay detected Dp71 in the skeletal muscles of both normal and DMD mice. In human skeletal muscle, Dp71 was also detected. The ratio of Dp71 to vinculin of human skeletal muscle samples varied widely, indicating various levels of Dp71 expression. Conclusions: Dp71 protein was detected in human skeletal muscle using a highly sensitive capillary Western blotting system.

An organic salt composed of 2-naphthalenesulfonic acid and n -butylamine yielded polymorphic crystals: the block-like Form A and the plate-like Form B . The former was obtained from 1-propanol by slow cooling, while the latter was dominantly done from 1,4-dioxane, m -xylene and so on. Interestingly, the former was transformed to the latter by mechanical grinding and the reverse occurred by heat treatment at 120 °C. X-ray crystallographic studies clarified that the former has π–π interactions among naphthalene rings and hydrogen bonding network involving two oxygen atoms of sulfonate group, while the latter has CH–π interactions and the network involving three oxygen atoms. Luminescent properties were different in these crystals and continuously switched with the transformation.

In nuclear plant, as water feeding into reactor have much effect on thermal power of plant, it is important to measure accurately the flow rate of water. Flow nozzle is on of typical differential pressure type flow meters and the discharge coefficient is used to calculate the flow rate. This coefficient is given by actual experiment and theory. We studied the theoretical assumption of the discharge coefficient curve using numerical simulation and evaluated the effect of flow nozzle configuration on the coefficient numerically and experimentally. As the result, numerical simulation can predict the discharge coefficient of theoretical curve within 0.3%. And we found that the throat length and throat tapping location of flow nozzle have much effect on the coefficient.

Background: The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen’s original article was published in 1912. Methods: We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease. Results: Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35βH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas. Conclusions: Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.

Oxidized LDL has been obtained by incubation with copper ions (Cu-LDL) or various kinds of cells. LDL incubated with xanthoma tissues (x-LDL) is considered a model of in vivo oxidized LDL that has extravasated into xanthoma lesions. To investigate the mechanism of x-LDL formation, we studied the effects of various enzyme inhibitors or antioxidants on the oxidation process of LDL. Thiobarbituric acid-reactive substance (TBARS) levels, electrophoretic mobility and spectrophotometric pattern of the oxidized LDL were examined. Antioxidants suppressed TBARS formation in both x-LDL and Cu-LDL. Enzyme inhibitors inhibited TBARS levels in x-LDL, but not in Cu-LDL. All the enzyme inhibitors and antioxidants, except for the cyclooxygenase inhibitor, inhibited the anodic electrophoretic mobility of x-LDL. The anodic electrophoretic mobility of Cu-LDL was suppressed only with antioxidants. Spectrophotometry indicated that an increase in the absorbance at 240 nm was observed in Cu-LDL, but not in x-LDL. x-LDL oxidation is primarily catalyzed by phospholipase A 2 , and subsequently generated polyunsaturated free fatty acids propagate the peroxidation. Fatty acid hydroperoxides conjugated with dienes are not synthesized in x-LDL. On the other hand, non-enzymatic oxidants, such as superoxide anion and hydroxyl radicals generate Cu-LDL with diene-conjugated fatty acid hydroperoxides.

Background Activated mast cells enhance the uptake of mast cell–derived proteoglycan–low-density lipoprotein complexes by macrophages. Objective We sought to investigate mast cell contribution to the pathogenesis of xanthoma. Methods Twenty cases of xanthelasma palpebrarum and 6 cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results Xanthelasma lesions contained up to 5-fold more tryptase-stained mast cells than tuberous xanthoma lesions. Tuberous xanthoma lesions especially showed extensive staining of tryptase around mast cells and within some macrophages and foam cells. More than 99% of mast cells in xanthelasma lesions contained both tryptase and chymase. Approximately 60% of mast cells represented only tryptase in tuberous xanthoma lesions where the ratio of macrophages to tryptase-stained mast cells was extremely high (15:1) as compared with xanthelasma lesions (2:1). Limitations A change in mast cell phenotype has not been necessarily proven. Conclusion Mast cells are activated under the microenvironment in which macrophages predominate rather than mast cells, which thus reflects the clinical phenotypes of xanthoma lesions.

Summary Background The source of accumulated lipids in the foam cells of xanthoma is primarily the lipoproteins existing in the lesional dermis. Objective This study was designated to clarify the contribution of low density lipoprotein (LDL) density substances existing in xanthoma tissue to foam cell formation. Methods An LDL density fraction was obtained from homogenized rabbit experimental xanthoma tissue. Biochemical and functional characteristics of xanthoma-extracted LDL density substance were examined. The in vivo foam cell-inducing ability of xanthoma-extracted LDL density substance was examined microscopically at the intradermal injection site. Results Xanthoma-extracted LDL density substance showed more negatively charged mobility on agarose gel electrophoresis than plasma native LDL. A small amount of aggregated material remained at the origin on agarose gel electrophoresis. Xanthoma-extracted LDL density substance contained much higher level of lipid peroxides than native LDL. Mouse peritoneal macrophages internalized xanthoma-extracted LDL density substance extensively and transformed into foam cells by incubation with xanthoma-extracted LDL density substance. Intradermal injection of the xanthoma-extracted LDL density substance induced foam cell infiltration in the skin of a normolipemic rabbit. Conclusion LDL density substances prepared ex vivo from experimental xanthoma tissue contained lipid–protein complexes that have physiochemical properties of oxidized LDL. The lipid–protein complexes were incorporated into foam cells. The substances were considered to contribute to foam cell recruitment during the persistence of xanthoma lesions.

Summary Background Xanthoma is a foam cell infiltrating lesion similar to atherosclerosis. Glycosaminoglycans and proteoglycans have long been considered to play a role in atherogenesis. Objective The purpose of this study is to investigate the role of hyaluronan, the main dermal glycosaminoglycan, in xanthoma formation. Methods The complex formation of low density lipoprotein (LDL) with hyaluronan was investigated by assaying the cholesterol level of precipitates that were formed by incubating LDL, hyaluronan and cetylpyridinium chloride in the presence of Ca 2+ . The uptake of LDL by mouse peritoneal macrophages was studied by assaying the cellular cholesterol esterification activity. The responsible receptor for the LDL internalization was examined by saturating hyaluronan receptor and blocking class A macrophage scavenger receptor (CD204). Hyaluronan was injected into the dorsal skin of diet-induced hypercholesterolemic rabbits to reveal the xanthoma inducing activity of hyaluronan. Results Cetylpyridinium chloride precipitated hyaluronan, which had formed complexes with LDL. The macrophages incorporated hyaluronan–LDL complexes and oxidized LDL via CD204. Foam cell infiltration and cholesterol accumulation were induced by intradermal injections of hyaluronan in diet-induced hypercholesterolemic rabbits. Conclusion Hyaluronan, like other sulfated glycosaminoglycans, retains LDL by forming a complex. Via macrophage scavenger receptors, macrophages incorporate not only LDL–hyaluronan complexes, but also oxidized LDL, which has been oxidized during the retention time.

Most switchboards are used for a long term of about 30 years. As for the switchboard, the situation of the use and maintenance is individually and greatly different. So the life-expectancy presumption technique of the switchboards has not been established. We executed the deterioration diagnosis for the switchboards that had been used for 30 years. We paid attention to the surface deterioration of the insulation materials that is the main element that decides the life-expectancy of the switchboards. We evaluated the life-expectancy presumtion technique of aged switchboards based on MTS (Mahalanobis Taguchi system) method. This technique attracts attention in recent years. And we confirmed the presumption result was corresponding to the result of the verification with temperature controlled bath actually.

Mast cells are the major effector cells for immediate hypersensitivity and chronic allergic reactions. These cells accumulate in mucosal tissues of allergic reactions, where immunoglobulin E (IgE) is produced locally. Here we provide evidence that, in addition to antigen that can attract IgE-bound mast cells, the type of IgE molecules that efficiently activate mast cells can promote the migration of mast cells in the absence of antigen. IgE- and IgE+Ag-mediated migration involves an autocrine/paracrine secretion of soluble factors including adenosine, leukotriene B4, and several chemokines. Their secretion depends on 2 tyrosine kinases, Lyn and Syk, and they are agonists of G-protein-coupled receptors and signal through phosphatidylinositol 3-kinase γ, leading to mast cell migration. In mouse experiments, naive mast cells are attracted to IgE, and IgE-sensitized mast cells are attracted to antigen. Therefore, IgE and antigen are implicated in mast cell accumulation at allergic tissue sites with local high IgE levels. (Blood. 2005;105:3222-3229)

In order to conduct a detailed investigation of the piston effect, the peculiar heat transportation phenomenon in critical fluids, an ultra-sensitive high-speed density measurement system was developed using a very thin heater, a sensitive interferometer and a large-capacity high-speed data acquisition system. As the first step of the investigation, an experiment was conducted to measure the velocity of sound in CO2 near its critical point. Short heat pulses suppressing the disturbance of natural convection were applied to a small cell filled with almost-critical CO2 fluid and were detected by the measurement system. Because the pulses propagated through the cell at the velocity of sound and were reflected several times between the cell walls, the velocity could be precisely determined by measuring the time intervals between successive reflections. The resulting velocity profile versus temperature showed good agreement with theoretical prediction and numerical simulations. This result validated the density measurement system, and it is considered that the measurement system will be a very effective tool for further studies on critical phenomena with the aid of numerical simulation.

53歳，女性。下顎では色素沈着を残し，下腿では色素沈着を残さない固定薬疹が繰り返し出現した。パッチテスト(皮疹部および無疹部)およびスクラッチパッチテスト(無疹部)は陰性。ミノサイクリン5mg投与による内服誘発テストでは，下顎と下腿に皮疹が再燃し，前額にも紅斑が新生した。病理組織像では下腿に比べ下顎の真皮にメラノファージが著明に多く認められた。免疫組織化学では，トリプターゼ陽性肥満細胞が下腿と比較して下顎の特に真皮乳頭層において有意に多く認められた。肥満細胞由来のケミカルメディエーターやサイトカインが，メラノサイトのメラニン合成やメラニンのケラチノサイトへの輸送を促進することも色素沈着を増強させる因子であると考えた。

The purpose of this study is to apply vector finite element method to magnetohydrodynamics. Vector finite element method is one of the popular methods in the field of electromagnetism. Two types interpolation functions are defined. One is facet element and another is edge element. In applying vector finite element method to the Inductions equations solenoidal condition is satisfied automatically without iterative corrections. But classical finite element method like B method by Oki et al. needs to solve Poisson equations to satisfy the solenoidal condition. In the present study Induction equations are numerically analyzed with vector finite element method. Flow field and temperature field are analyzed using GSMAC finite element method. We call this analysis technique GSMAC-VFEM (generalized simplified marker and cell vector finite element method). Three-dimensional natural convection in a cavity under a constant magnetic field is analyzed to determine the accuracy and the efficiency of the method. Computational results are compared with B method to verify this numerical scheme. Since the numerical results obtained here agreed well with other numerical results, the new numerical method for solving Induction equations using vector finite element method was verified. Calculation time of new numerical scheme was faster than the other numerical method. The reason is that using vector finite element method for solving Induction equations solenoidal condition for magnetic flux density satisfies automatically.

Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

地震時の地盤液状化に伴う側方流動が埋設配管に与える影響を把握するために, 遠心模型振動実験およびFEMシェル解析手法による数値シミュレーションを実施した. 遠心重力場30gでの模型実験はケーソン護岸とその背後地盤によって構成され, 加振時の背後地盤液状化と護岸変位により側方流動を発生させた. 配管構造物は外径600mm, 肉厚15mmの高圧ガス導管を対象とし, 90度曲部を含む構造とした. 実験の結果, 模型管に塑性変形が生じるまでの変位が生じ, 地盤変位と管変位の関係や管の変形形状などが把握できた. さらに, 数値シミュレーションでは, 実験による模型管の変形を良好に再現でき, 手法の妥当性が確認された.