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Background: Neuroblastoma is one of the most common childhood solid tumors. Because tumor suppressor genes are often hypermethylated in cancers, DNA methylation has emerged as a target for cancer therapeutics. Nanaomycin A, an inhibitor of DNA methyltransferase 3B, which mediates de novo DNA methylation, reportedly induces death in several types of human cancer cells. Objective: To study the antitumor activity of nanaomycin A against neuroblastoma cell lines and its mechanism. Methods: The anti-tumor effect of nanaomycin A on neuroblastoma cell lines was evaluated based on cell viability, DNA methylation levels, apoptosis-related protein expression, and neuronal-associated mRNA expression. Results: Nanaomycin A decreased genomic DNA methylation levels and induced apoptosis in human neuroblastoma cells. Nanaomycin A also upregulated the expression of mRNAs for several genes related to neuronal maturation. Conclusions: Nanaomycin A is an effective therapeutic candidate for treating neuroblastoma. Our findings also suggest that the inhibition of DNA methylation is a promising anti-tumor therapy strategy for neuroblastoma.

Background Small-for-gestational-age (SGA) infants are at increased risk for transient thrombocytopenia. The aim of this study was to determine whether thrombocytopenia in human SGA infants is due to insufficient thrombopoietin (TPO) production. Methods A prospective study of 202 infants with gestational age less than 37 weeks was conducted; 30 of them were SGA infants, and 172 were non-SGA infants. Thrombocytopenia was seen in 17 of 30 SGA infants and 40 of 172 non-SGA infants. Results Platelet counts were significantly lower in the SGA group than in the non-SGA group at the time of the lowest platelet count within 72 h of birth. The platelet count and immature platelet fraction (IPF) were negatively correlated in non-SGA infants, but not in SGA infants. In addition, the platelet count and TPO were negatively correlated in non-SGA infants. IPF and TPO were significantly lower in SGA than in non-SGA infants with thrombocytopenia. Conclusion IPF increased with thrombocytopenia to promote platelet production in non-SGA infants due to increasing TPO, but not in SGA infants. This study found an association between insufficient TPO production and thrombocytopenia in SGA infants. In addition, this study is important for understanding the etiology of thrombocytopenia in SGA infants. Impact The immature platelet fraction was low, and serum thrombopoietin was not increased in small-for-gestational-age (SGA) infants with thrombocytopenia. Thrombocytopenia in SGA infants is due to insufficient thrombopoietin production. This study is important for understanding the etiology of thrombocytopenia in SGA infants.

The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.

BACKGROUND Acetaminophen is widely administered to neonates but its effect on unbound bilirubin (UB) levels remains unclear. The aim of this study was to clarify whether administration of acetaminophen is related to an elevation of UB levels. METHOD Infants with a birthweight of ˂1,500 g admitted to our neonatal intensive care unit between January 2017 and April 2020 were retrospectively reviewed. Seventy-one infants were enrolled, five of whom had received acetaminophen. Clinical data were analyzed when the highest UB value (UB peak) in each infant was recorded. Demographic data and information on treatment within the 24 h before the UB peak were also collected. UB was determined by the glucose oxidase-peroxidase (GOD-POD) method. Infants were categorized according to the presence or absence of acetaminophen administration (acetaminophen and no acetaminophen groups) within 24 h of the UB peak. The relationship between UB values and various clinical variables was then compared. RESULTS Both the peak UB value and the ratio of gastrointestinal disease were higher in the acetaminophen group than in the no acetaminophen group. Univariate analysis revealed that a total of seven variables were potentially correlated with UB peak values (P

Significant advancements have been achieved in the quality of treatment for relapsed/refractory multiple myeloma (RRMM). Currently, daratumumab (DARA) is a highly effective drug widely used for RRMM; however, the knowledge on its efficacy and safety in Japanese patients remains limited. Accordingly, we aimed to evaluate the efficacy and safety of DARA therapy for RRMM. We reviewed the medical records of patients who received DARA combination therapy and evaluated its efficacy and safety in our hospital. DARA was administered to 44 patients between October 2017 and March 2019. The median number of previous therapies was three (range 1–9). The rates of ≥ complete response and overall response were 27.3% and 61.4%, respectively. The median progression-free survival (PFS) duration was 12.3 months [95% confidence interval (CI) 5.1 to not reached (NR)] and estimated 2-year overall survival rate was 63.7% (95% CI 46.9–76.5%). In the multivariate analysis, patients with ≥ three previous lines of therapy and mass lesions showed significantly shorter PFS durations. The observed grade 3/4 adverse events (≥ 10%) included neutropenia (59.0%), thrombocytopenia (29.5%), anemia (36.4%), lymphopenia (38.6%) and febrile neutropenia (18.2%). None of the patients discontinued DARA therapy in spite of these AEs. DARA is an effective treatment option for most patients and is tolerable. However, patients with heavy treatment before DARA therapy and mass lesions are likely to show poorer outcomes. Our findings suggest the use of DARA therapy early in the course of the disease.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. The pathological mechanism of FPIES is intestinal inflammation, and cell-mediated hypersensitivity is presumed to play an important role in its development. Case Report: The first case in which significant fetal intestinal distension suggested fetal onset of FPIES is reported. A 2,334-g male was born at 34 weeks by vaginal delivery. Results: In utero, he had significant intestinal distension on ultrasonography and MRI. A few hours after the first feeding, he produced bloody stool and showed abdominal distension. In this case, FPIES was not only caused by cow’s milk protein diagnosed clinically and by an allergen-specific lymphocyte stimulation test, but also by breast milk diagnosed by oral food challenge. The clinical course and laboratory results strongly suggested not only fetal sensitization but also fetal onset. Conclusion: This report might be helpful for prompt diagnosis and treatment and, furthermore, lead to elucidation of the pathogenesis and pathophysiology of FPIES.

BACKGROUND Antenatal magnesium sulfate (MgSO4 ) has been used in mother, but the influence of MgSO4 on the fetus is unclear. The purpose of this study is to determine whether longer antenatal MgSO4 exposure correlates with adverse effects in newborns. METHODS The clinical data of 77 infants born to mothers treated with MgSO4 were collected. The infants were divided into two groups according to the serum Mg concentration, cumulative Mg dose, and duration of maternal antenatal Mg treatment. RESULTS The serum Mg level of the infants correlated with that of the mothers but not with the duration of Mg treatment or the cumulative dose of Mg. There were no significant differences in the infants' clinical variables according to either the duration of Mg treatment or the cumulative dose of Mg. By contrast, enteral feeding tolerance began at a significantly later age and the heart rate on admission was significantly lower in infants with a serum Mg level ≥ 4.0 mmol/l than in those with a serum Mg level < 4.0 mmol/l. CONCLUSIONS Modest effects on the clinical variables of infants with higher serum Mg levels were determined, whereas neither the duration of Mg treatment nor the cumulative Mg dose correlated with the clinical variables of the infants. Thus, in newborns with only moderately elevated serum Mg levels serious adverse effects are unlikely.

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test

Arterial stiffness is an important risk factor for cardiovascular disease (CVD) in patients with end-stage renal failure. However, little is known about the factors that contribute to arterial rigidity in peritoneal dialysis (PD) patients. The aim of this study was to define the pattern and determinants of the longitudinal change in arterial stiffness after PD initiation.Arterial stiffening was estimated for 46 PD patients by using brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT). The cross-sectional relationship between the arterial markers and their clinical determinants was studied. The longitudinal effects of blood pressure (BP), body fluid status, and glucose were studied over the two years after initiating PD.Multivariate analysis showed that higher baPWV was associated positively with urinary protein excretion (P < 0.001), systolic BP (P = 0.001), and hemoglobin A1c (P = 0.003). In contrast, increased cIMT correlated with smoking (P = 0.004) and hypoalbuminemia (P = 0.04), suggesting that endothelial dysfunction is implicated in the atherogenic process. Neither cIMT nor baPWV correlated significantly with other PD-related covariates of volume overload, peritoneal solute transport, kidney function, and C-reactive protein. Longitudinal observation demonstrated that BP had a greater influence on baPWV changes than hyperglycemia or fluid status.Our study indicates that 1) baPWV represent an arterial marker that integrates multifactorial interaction between modifiable variables including BP and plasma glucose; and 2) intervention aimed at controlling BP as well as nutritional conditions (glucose and albumin) may reduce CVD risk in PD patients.

Background Late‐onset circulatory collapse (LCC) is the transient development of refractory hypotension and oliguria after the early neonatal period, which may cause periventricular leukomalacia (PVL). The aim of this study was to evaluate the endogenous cortisol response to corticotrophin‐releasing hormone (CRH) and determine whether it is effective for elucidating the pathology and selecting treatment in LCC. Methods This retrospective study examined infants admitted to the neonatal intensive care unit. Included were preterm (gestational age

The bile salt export pump is expressed at the canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. 4-Phenylbutyrate (4 PB), a drug used to treat ornithine transcarbamylase deficiency, has been found to increase the hepatocanalicular expression of bile salt export pump. The beneficial effects of 4-phenylbutyrate therapy have been reported for patients with progressive familial intrahepatic cholestasis, an inherited autosomal recessive liver disease. This is the first study to show the therapeutic effect of 4 PB in a preterm infant with cholestasis and liver fibrosis. The preterm infant had severe cholestasis with jaundice and failure to thrive refractory to ursodeoxycholic acid. Histology indicated giant cell hepatitis, cholestasis, and severe fibrosis. Bile salt export pump immunostaining showed lower expression than in a control. Oral 4 PB was started at a daily dose of 200 mg/kg/day. After the start of 4 PB therapy, cholestasis improved.

Visit-to-visit blood pressure variability has been shown to be an independent risk factor for cardiovascular diseases. High visit-to-visit blood pressure variability and endothelial dysfunction are observed in patients with chronic kidney disease. It is therefore assumed that high variability in visit-to-visit blood pressure measurements may be associated with endothelial dysfunction in these patients. The present study investigated the associations between visit-to-visit blood pressure variability and renal and endothelial function in patients with chronic kidney disease. We analyzed 150 consecutive patients with predialysis chronic kidney disease who visited our outpatient clinic from January 2006 to December 2010. The study examined the relationships between variability in visit-to-visit systolic blood pressure levels or mean systolic blood pressure (M SBP) and estimated glomerular filtration rate (eGFR) and flow-mediated dilation, an index of endothelial function. Variability in visit-to-visit systolic blood pressure showed a significant negative association with eGFR, independent of age, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol and uric acid, whereas M SBP did not. Similarly, variability in SBP showed a significant negative association with flow-mediated dilation, independent of age, eGFR, HbA1c, LDL cholesterol and M SBP. These data indicate that variability in visit-to-visit blood pressure measurements is associated with impaired renal and endothelial function in patients with chronic kidney disease. This finding suggests that reducing blood pressure fluctuations might have beneficial effects in patients with chronic kidney disease, although this point needs to be addressed by future studies.

Granulomatous mastitis (GM) is a rare, benign, granulomatous inflammation of the breast, of unknown etiology [1]. Differing from common mastitis, which usually affects postpartum women, GM reportedly affects pregnant women as well as postpartum women and is occasionally accompanied by erythema nodosum (EN) and arthralgia [2, 3]. We report a case of GM plus EN and oligoarthralgia in a pregnant woman.A 35-year-old 25-week pregnant woman with mastitis refractory to antibiotics developed painful indurated [...]

Arterial stiffness is an important risk factor for cardiovascular disease (CVD) in patients with end-stage renal failure. However, little is known about the factors that contribute to arterial rigidity in peritoneal dialysis (PD) patients. The aim of this study was to define the pattern and determinants of the longitudinal change in arterial stiffness after PD initiation.Arterial stiffening was estimated for 46 PD patients by using brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT). The cross-sectional relationship between the arterial markers and their clinical determinants was studied. The longitudinal effects of blood pressure (BP), body fluid status, and glucose were studied over the two years after initiating PD.Multivariate analysis showed that higher baPWV was associated positively with urinary protein excretion (P0.001), systolic BP (P = 0.001), and hemoglobin A1c (P = 0.003). In contrast, increased cIMT correlated with smoking (P = 0.004) and hypoalbuminemia (P = 0.04), suggesting that endothelial dysfunction is implicated in the atherogenic process. Neither cIMT nor baPWV correlated significantly with other PD-related covariates of volume overload, peritoneal solute transport, kidney function, and C-reactive protein. Longitudinal observation demonstrated that BP had a greater influence on baPWV changes than hyperglycemia or fluid status.Our study indicates that 1) baPWV represent an arterial marker that integrates multifactorial interaction between modifiable variables including BP and plasma glucose; and 2) intervention aimed at controlling BP as well as nutritional conditions (glucose and albumin) may reduce CVD risk in PD patients.

Background Pierre Robin sequence (PRS) refers to the association of micrognathia, glossoptosis, and airway obstruction. Cases with severe dyspnea due to upper airway obstruction immediately after birth are very rare. We here report two cases with PRS who developed severe dyspnea due to morphological abnormality immediately after birth and were rescued by fiberoptic nasotracheal intubation. Case presentation The patient in case 1 had micrognathia and cleft palate, and his tongue protruded into the nasal cavity via a cleft palate. His invaginated tongue was considered an extreme type of glossoptosis and he was diagnosed as Pierre Robin sequence. The patient in case 2 also had micrognathia and cleft palate same as case 1 and accompanied some anomalad. Her chromosome analysis confirmed a diagnosis of 1p36 deletion syndrome and she diagnosed as 1p36 deletion syndrome complicated with Pierre Robin sequence. In both cases, tongue protruded into the nasal cavity via a cleft palate occupied pharynx and nasal cavity, resulting in severe dyspnea. Only the backside of the tongue was visible by laryngoscopy and oropharyngeal intubation was impossible. Therefore, fiberoptic nasotracheal intubation was done to secure the airway for resuscitation. Conclusion We conclude that extreme type of glossoptosis in PRS concludes tongue invaginated into nasal cavity which have not reported before and that such cases require resuscitation by fiberoptic intubation immediately after birth. As such, neonatologists should obtain the skill of fiberoptic intubation.

OBJECTIVE Dyslipidemia is a risk factor for not only cardiovascular diseases (CVD), but also chronic kidney disease (CKD). Ezetimibe, a cholesterol absorption inhibitor, lowers cholesterol levels by inhibiting both extrinsic and intrinsic cholesterol absorption via the gastrointestinal duct. However, very few studies have examined its efficacy and safety for patients with dyslipidemia complicated with CKD. METHODS Thirty-seven dyslipidemic patients (low density lipoprotein cholesterol (LDL-C) levels ≥120 mg/dL) complicated with CKD were given ezetimibe (10 mg/day) for twenty-four weeks. The efficacy and safety of the therapy, including the anti-atherosclerotic and renal protective effects, were then examined. RESULTS Significant decreases were observed in the levels of LDL-C (158.9 ± 26.9 mg/dL→123.0 ± 31.8 mg/dL; p

We describe three rare cases of neonatal central diabetes inspidus (CDI) caused by severe perinatal asphyxia. In these cases, hypernatremia, high plasma osmolality and hyposthenuria, with polyuria occurred after one week of age. CDI in one case might be due to the temporal dysfunction of hypothalamic-neurohypophyseal axis and the other two cases to permanent dysfunction. Although these cases are rare, early diagnosis and treatment of CDI are indispensable. Follow-up of serum sodium, serum and urine osmolality is necessary after acute phase to maintain water and electrocyte homeostasis in severe perinatal asphyxia.

A pneumopericardium is a very rare condition and is the least common form of air leak in neonates. A tension pneumopericardium is associated with very high mortality. Neonatal pneumopericardium is usually a complication of mechanical ventilation in premature infants with respiratory distress syndrome. The mechanism of this rare condition and the perforation site of the pericardium have largely been speculative. This case report documents an extremely low birth weight infant who developed fatal tension pneumopericardium, and the autopsy revealed airflow into the pericardial sac through a perforation site of the pericardium near the ostia of the right pulmonary vein. This is a valuable case in which the perforation site of the pericardium was confirmed.

Periventricular leukomalacia is recognized as the leading cause of cerebral palsy in preterm infants. To clarify the prevalence of periventricular leukomalacia and cerebral palsy in Japan, a nationwide survey was performed. The prevalence of periventricular leukomalacia in the group of surviving preterm infants of gestational ages less than 33 weeks born in 2007 was 2.7% (78/2883) on ultrasound diagnosis, and 3.3% (92/2824) on magnetic resonance imaging. The prevalence of cerebral palsy was 4.3% (125/2883) on clinical diagnosis. In our previous study, the prevalences of periventricular leukomalacia in 1990-1991, 1993-1994, 1996, and 1999 were 4.8%, 4.9%, 4.9%, and 5.3% on ultrasound, and 7.9%, 7.7%, 6.9%, and 7.3% on magnetic resonance imaging, respectively. The prevalence of periventricular leukomalacia has decreased significantly in Japan.

Hemodialysis techniques have improved remarkably in recent decades and the number of long-term survivors among patients with end-stage renal disease has increased. The mortality rate of hemodialysis patients has been reported to be low in Japan. However, the long-term survival rate of dialysis patients is still low: 23.6% for 15 years and 17.4% for 20 years, even in Japan, and background information on patients undergoing hemodialysis therapy for more than 20 years is scarce in this country. In the present study, we investigated the characteristics of 20-year survivors undergoing maintenance hemodialysis at our medical center. We compared the characteristics of hemodialysis patients who had survived for more than 20 years after the initiation of hemodialysis with those of patients who started hemodialysis at the same time and had already died. No patient among those who were still alive had diabetes mellitus while 15% of patients who had died had diabetes mellitus at the time of initiation of hemodialysis. Age, cardiothoracic ratio, and serum levels of total cholesterol and triglyceride 6 months after the initiation of hemodialysis, as well as decreases in body weight per year were significantly lower in those who had survived than in those who had died. These results suggest that long-term hemodialysis survivors are characterized by (i) initiation of hemodialysis at a young age (ii) being free of diabetes mellitus (iii) a well-controlled cardiothoracic ratio (iv) small successive change in body weight, and (v) being free of hypercholesterolemia and hypertriglyceridemia.

(MUSCAT) is a high value computation tool for analyzing spacecraft–plasma interaction, whose typical example is charging–arcing issue, corresponding to spacecrafts in LEO, GEO and PEO. JAXA and Kyushu Institute of Technology (KIT) started the development as a joint project in November 2004 and the final version of MUSCAT was released in March 2007. The final version includes many important features to simulate spacecraft–plasma interaction and the features can be separated into four parts. The first part is its GUI named “Vineyard”. By using Vineyard, MUSCAT users can build a satellite model including not only its geometry but also material properties of the surface. As for the second part, MUSCAT includes many kinds of effects derived from space plasma environment as well as electrical functions of spacecraft. For the third part, MUSCAT can work on parallel workstation with multi-CPU. The last feature is that the computation result by MUSCAT was thoroughly validated by experiments in plasma chamber. The numerical result shows very good agreement with the code validation experiment. We also conducted trial computation of charging analysis on Greenhouse gases Observing Satellite (GOSAT) with MUSCAT. One purpose of the computation was prediction of charging status of GOSAT for the real satellite design in combination with the ground test. The other is performance assessment of MUSCAT. After the joint project, expansion and maintenance of MUSCAT will be carried out by “MUSCAT Space Engineering Ltd” which is a new enterprise made of the development team. In future we will try to conduct MUSCAT computation for various spacecrafts and also try to add useful function such as 3D CAD compatibility.

A new numerical software package to analyze spacecraft charging, named ldquomulti-utility spacecraft charging analysis toolrdquo (MUSCAT), has been developed. MUSCAT consists of an integrated graphical user interface tool called ldquoVineyardrdquo and the solver. Vineyard enables satellite engineers to compute spacecraft charging with little knowledge of the numerical calculations. Functions include 3-D satellite modeling, parameter input such as material and orbit environment, data transfer, and visualization of numerical results. Fundamental physical processes of charged-particle-surface interaction are included in the solver. These functions enable MUSCAT to analyze spacecraft charging at geostationary orbit, low Earth orbit, and polar Earth orbit (PEO). The numerical solver code is parallelized for high-speed computation, and the algorithm is optimized to achieve analysis of large-scale PEO satellite in the design phase. Variable time steps are also used to calculate the rapid change of the spacecraft body potential and the gradual change of the differential voltage in a single simulation with a practical number of iterations. In this paper, the functionality, algorithms, and simulation examples of MUSCAT are presented.

The multiutility spacecraft charging analysis tool (MUSCAT), a spacecraft charging analysis software, has been developed as a collaboration work between Japan Aerospace Exploration Agency and Kyushu Institute of Technology. Laboratory experiments for fundamental code validation were carried out in both facilities' plasma chambers. MUSCAT is a particle simulation code based on particle-in-cell (PIC) and particle tracking (PT) algorithms capable of calculating the floating-body potential of a spacecraft with respect to the plasma potential. Three experiments were carried out regarding spacecraft-plasma interaction phenomena important in LEO and PEO. A Langmuir probe was used to measure the current collection and potential distribution in static plasma to validate the PIC and PT schemes. The floating potential of an object in plasma with an energetic electron component was measured to validate the floating-body calculation as well as the PT scheme. Current collection and potential distribution in the wake structure were measured to validate the PIC and PT scheme in flowing plasma condition. The experimental results and the simulation results agreed very well in all the three experiments, validating the accuracy of the MUSCAT solver.

Space development has been rapidly increasing, and a strong demand should arise regarding the understanding of the spacecraft-plasma interactions, which is one of the very important issues associated with the human activities in space. To evaluate the spacecraft-plasma interactions including plasma kinetics, transient process, and electromagnetic field variation, the authors have started to develop a numerical plasma chamber called Geospace Environment Simulator (GES) by making the most use of the conventional full particle-in-cell plasma simulations. For the development of a proto model of GES, the authors have used the Earth Simulator, which is one of the fastest supercomputers in the world. GES can be regarded as a numerical chamber in which space experiments can be virtually performed and temporal and spatial evolutions of spacecraft-plasma interactions can be analyzed. In this paper, the authors have briefly introduced GES in terms of its concept, modeling, and research targets. As one of the research topics of GES, the authors have investigated the impedance variation of electric field antenna onboard scientific satellites in the photoelectron environment in space. From the preliminary simulation results, the large change of reactance of the antenna impedance below the characteristic frequency corresponding to the local plasma frequency determined by the photoelectron density could be confirmed

SUMMARY Since the 1970s, deep low-frequency earthquakes (DLF) with depths ranging 20–40 km have been observed just beneath the Japan Island Arc. Almost all of these earthquakes are recognized up to now have had magnitudes less than 2.5, so that we have little information concerning DLF. Employing the theory of KM2O-Langevin equations, we develop a new method to represent the characteristics of the coda parts of DLF, and propose a new concept of ‘average dissipation spectrum’. The new averaging algorithm for the KM2O-Langevin matrix function was applied in the analysis of DLF (M: 1.0), which occurred in Akita prefecture on 2001 July 11, and we succeeded in separating the characteristics of the source vibration system and the source excitation process into the averaged dissipation term and the fluctuation term, respectively. The gaps between the arrival times of the fluctuation term's peaks at three stations near the epicentre are slightly different than the gaps between the S-wave arrival times. Assuming a homogenous crust structure with an S-wave velocity of 4.3 km s−1 and assuming the depth of the second source to be the same as that of the hypocentre, the second source lies about 1.5 km, N 56°E of the hypocentre. We estimate the common characteristics of this DLF successfully by using the ‘average dissipation spectrum’, which is made up of typical frequencies, θk, attenuation factors, Qk and amplitude factors, Ak. The common elements of (θk∼ 1.5, Qk∼−0.3) and (θk∼ 3.25, Qk∼−0.45) among all stations indicate the characteristics of the source dynamics of the Akita DLF. The major parts of the coda waves of DLF satisfy the stationary property, and the causality values for the linear and odd-degree non-linear transformations are relatively higher than those for the even-degree non-linear transformations. These characteristics are quite different from the characteristics of tectonic earthquakes. This quantitative property is common among all DLF.

Aggregation of disease proteins is believed to be a central event in the pathology of polyglutamine diseases, whereas the relationship between aggregation and neuronal death remains controversial. We investigated this question by expressing mutant huntingtin (htt) with a defective adenovirus in different types of neurons prepared from rat cerebral cortex, striatum or cerebellum. The distribution pattern of inclusions is not identical among different types of primary neurons. On day 2 after infection, cytoplasmic inclusions are dominant in cortical and striatal neurons, whereas at day 4 the ratio of nuclear inclusions overtakes that of cytoplasmic inclusions. Meanwhile, nuclear inclusions are always predominantly present in cerebellar neurons. The percentage of inclusion-positive cells is highest in cerebellar neurons, whereas mutant htt induces cell death most remarkably in cortical neurons. As our system uses htt exon 1 protein and thus aggregation occurs independently from cleavage of the full-length htt, our observations indicate that the aggregation process is distinct among different neurons. Most of the neurons containing intracellular (either nuclear or cytoplasmic) aggregates are viable. Our findings suggest that the process of mutant htt aggregation rather than the resulting inclusion body is critical for neuronal cell death.

In Caenorhabditis elegans embryogenesis, phosphorylation events are critical to chromosomal changes. To investigate the dephosphorylation of chromosome behavior, we cloned and characterized the cDNA that encodes C. elegans protein phosphatase type 1 (CeGLC-7 beta), which is composed of 333 amino acids. CeGLC-7 beta possesses a highly conserved amino acid sequence with mammalian and Drosophila protein phosphatase 1. Here, we report on the contribution of CeGLC-7 beta to the dephosphorylation of histone H3 at anaphase. At the embryonic stage, CeGLC-7 beta is associated with the nuclear membrane and chromosomes. The deletion of the Ceglc-7 beta gene and a microinjection of double-stranded RNA produce a disorganized embryogenesis. The Ceglc-7 beta gene mutation causes an abnormal accumulation of phosphorylated histone H3 and delays the mitotic process after anaphase. We propose that CeGLC-7 beta is involved in chromosome dynamics including histone H3 dephosphorylation.

A body of experimental evidence indicates that transcription and/or mRNA processing factors interacting with the polyglutamine disease gene products play crucial roles in the pathology. PQBP-1 is one of these factors and it has been shown to interact with the spinocerebellar ataxia type-1 (SCA1) disease gene product, ataxin-1. Our previous data suggested that relatively high expression of PQBP-1 in the cerebellum might explain the selective neuronal degeneration of SCA1. To further test whether PQBP-1 expression level regulates neuronal death, we generated transgenic mice of human PQBP-1 driven by a regulatory element for ubiquitous gene expression. The mice showed a late-onset and gradually progressive motor neuron disease-like phenotype, which might be related to neurogenic muscular atrophy observed in SCA1 patients. Ataxia could not be discriminated from predominant progressive weakness. Pathological examinations of the transgenic mice revealed loss of Purkinje and granular cells in the cerebellum as well as that of spinal motor neurons, corresponding to the pathology of human SCA1. These findings show that excessive action of PQBP-1 causes neuronal dysfunction and support PQBP-1 being involved in the pathology of SCA1.

The relationship between treatment efficacy and the pharmacokinetics (PK) and pharmacodynamics (PD) of anticancer drugs is poorly defined. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) is an alkylating agent used in the treatment of brain and other forms of cancer. It is postulated that BCNU kills cells by forming DNA interstrand cross-links. The present study was undertaken to characterize the PK and PD of BCNU in mouse L1210 cells. L1210 cells were exposed to BCNU (0-160 microM) and analyzed for intracellular BCNU concentrations, DNA interstrand cross-links, cell cycle phase, and cytotoxicity. The half-life of BCNU in cells was approximately 40 min. The maximum reduction of mitochondrial enzyme activity (maximum cell death) achieved within 24 hr after exposure to BCNU was concentration-dependent and could be described by a Hill equation. At lower concentrations, the area under the DNA interstrand cross-link-time curve linearly correlated with the maximum cell death and the area under the BCNU concentration-time curve. BCNU induced cell accumulation in the G(2)/M phase of the cell cycle, which continued even after apparent completion of cross-link repair. Loss of membrane permeability was minimal (approximately 2%) during the first 24 hr. Thereafter, cells died exponentially over the next 9 days, primarily by necrosis. In conclusion, while cytotoxicity was concentration-dependent, an indirect relationship was found among the time-course of BCNU concentrations, DNA interstrand cross-links, and cell death. Because of the disparity between the time-scale of PK and PD, focusing only on the early events may provide limited information about the process of anticancer drug-induced cell death.

Small ubiquitin-like modifiers (SUMOs) are proteins homologous to ubiquitin that possibly regulate intranuclear protein localization, nuclear transport, and ubiquitination. We examined patients of DRPLA, SCA1, MJD, and Huntington's disease and found that neurons in affected regions of the brain react strongly to SUMO-1, a family member of SUMOs. Western blot with a transgenic mouse expressing mutant ataxin-1 showed the increase of SUMOylated proteins in the cerebellar cortex, which we named ESCA1 and ESCA2. These results indicated activation of SUMO-1 system in polyglutamine diseases and predicted its involvement in the pathology.

O efeito de vídeos de desenhos com publicidade de alimentos saudáveis e não saudáveis versus vídeos neutros sobre as escolhas alimentares foi avaliado em 24 crianças de escola pública. Os vídeos foram apresentados em cinco sessões, sendo cada grupo exposto a uma sequência específica de publicidade. Após a exposição, a criança escolhia figuras de alimentos para as refeições do dia. Análises intra e entre sujeitos, por meio da Ancova de medidas repetidas, demonstraram que, com a mudança de vídeo, as crianças alteraram em até 13% a escolha de alimentos saudáveis ou não. O aumento da exibição de publicidade de alimentos saudáveis e a diminuição da publicidade de alimentos não saudáveis pode contribuir para a alimentação e peso saudáveis. __________________________________________________________________________________________ ABSTRACT The effect of cartoon videos with advertisements of healthy and unhealthy food versus neutral videos on food choices was assessed in 24 children from a public school. The videos were presented in 5 sessions. Each group was exposed to a specific sequence of advertisement. After the exposure of the videos, the child chose food figures for daily meals. Within and between subject analyses, performed by repeated measures ANCOVA, showed that with change of videos, the children altered by up to 13% their choices of healthy or unhealthy food. The increase of healthy food advertising and the decrease of unhealthy food advertising may contribute for healthy food and weight.

Introduction: Cytomegalovirus is the most common cause of intrauterine infection in developed countries. Between 10% and 15% of infants infected with congenital cytomegalovirus exhibits the clinically apparent or symptomatic form of the disease. Exchange transfusion is an established therapy for hyperbilirubinemia and severe anemia. However, to the best of our knowledge, the viral load of cytomegalovirus before and after exchange transfusion has not been previously reported. Case report: A Japanese female was delivered at 36 weeks of gestation to a 29-year-old gravida 3 para 3 by emergency Cesarean section because of non-reassuring fetal status. Hepatomegaly, splenomegaly, generalized petechiae, leptocephaly, and jaundice were noted at birth. On admission, her total bilirubin was 14.2 mg/dL, cytomegalovirus immunoglobulin M was positive (4.63 mg/dL), and her head ultrasound and computed tomography showed left intraventricular calcification and bilateral ventriculomegaly. Toxoplasma, rubella, and herpes simplex virus serologies were negative. The exchange transfusion was performed for the treatment of early onset hyperbilirubinemia, not for the treatment of congenital cytomegalovirus infection. The cytomegalovirus viral load before and after exchange transfusion was investigated by real-time polymerase chain reaction, and the plasma viral load of cytomegalovirus was not significantly decreased from before (8.7×105/mL) to after (4.3×105/mL) exchange transfusion. Conclusion: Exchange transfusion did not reduce the viral load of cytomegalovirus in severe congenital cytomegalovirus infection.

In the primary temporal cortex (Te1) of newborn rats, we detected transient expression of alpha-type estrogen receptor (ER alpha). Since they have a pyramidal-like shape, they are considered neurons. By immunohistochemistry we found that they were absolutely devoid of glial fibrillary acidic protein but some of them contained calretinin, a calcium binding protein. It is already known that neurons in layer V of the Te1 extend their projections to the contralateral side of the Te1, the ipsilateral inferior colliculus, or the ipsilateral medial geniculate nucleus. Thus, we applied a retrograde track tracer into those regions of newborn rats and examined the possible colocalization of ER alpha signals and the tracer in the same cells. So far no clear colocalization of both signals has been detected in cells in the Te1. Thus, the cells expressing ER alpha transiently are not projecting to the assumed regions, at least at the newborn age examined in the present experiment. The possibility exists that (1) they are not projection neurons but local interneurons, (2) even though they are projection neurons, they did not have any synaptic contacts with their target region(s), (3) they may die after they are attached to the target neurons. Further analyses are needed to clarify the biological roles of ER alpha expressed transiently in these neurons. On the other hand, no ER beta cells were detected in the same region of the brain under the same condition. Thus, this finding was limited to the ER alpha.

Plant samples derived from ethno-directed and random collections were screened to determine their effect on pre-contracted rat aortic tissue. Of the 31 ethno-directed species, four were found to be potent relaxants of vascular smooth muscle. The vasoactive species were Chamguava gentlei, Alseis yucatanensis, Licaria peckii and Nectandra salicifolia. None of the 32 randomly collected samples produced a relaxation response. These data support the hypothesis that ethno-directed collection is a more efficient means of drug discovery than random plant screens.

A 73-year-old male undergoing peritoneal dialysis (PD) for end-stage renal disease due to diabetic nephropathy was diagnosed with aortic stenosis and was admitted to our hospital in September, 2009. The patient underwent replacement of the ascending aorta with an artificial blood vessel plus aortic valve replacement without any notable complications. PD was restarted 3 days after the surgery and large amounts of light red fluid from the drain placed in the pericardium were observed just after resumption of PD solution. The patient was diagnosed with peritoneopericardial communication. PD was discontinued and hemodialysis was performed only with intermittent lavage of the peritoneal cavity. The amount of drainage was spontaneously decreased, and on the 17th day after surgery, PD was resumed. The patient is undergoing PD without recurrence of peritoneopericardial communication, 59 months after the onset of symptoms. Peritoneopericardial communication in a patient with PD developing after open-heart surgery is rare because such a case has been documented in only one case report. However, since massive pericardial effusion may cause severe cardiac problems, we consider that the communication between the peritoneal cavity and the pericardium needs to be checked for in patients with PD after cardiac surgery.

Neonatal alloimmune thrombocytopenia (NAIT) is a rare but clinically important etiology of intracranial hemorrhage. There have been no reported cases of intracranial hemorrhage caused by anti-group A or anti-group B antibodies. A Japanese boy weighing 1550 g was born at 37 weeks. He suffered from refractory thrombocytopenia and developed severe intracranial hemorrhage on his second day. Despite repeated platelet, red-cell and fresh-frozen-plasma transfusions, he died at day 10 of life. Serological studies and genotyping of the patient and his parents were performed. There were no incompatible genotypes of platelet antigens between the patient and the mother. Serological studies revealed that the mother had extremely high-titer anti-group A immunoglobulin G(2) (4096-fold) that reacted strongly with the father's platelets. The reaction against the father's platelets disappeared when her serum was adsorbed with group A red blood cells. Maternal anti-group A antibody was associated with NAIT and severe bilateral intracranial hemorrhage.

The isolation and characterization is reported of a cDNA for delta 1-pyrroline-5-carboxylate (P5C) synthetase (cAtP5CS), an enzyme involved in the biosynthesis of proline, from a cDNA library prepared from a dehydrated rosette plant of Arabidopsis thaliana. Southern blot analysis suggested that only one copy of the corresponding gene (AtP5CS) is present in A. thaliana. The deduced amino acid sequence of the P5CS protein (AtP5CS) from A. thaliana exhibited 74% homology to that of the P5CS from Vigna aconitifolia. Northern blot analysis revealed that the gene for P5CS was induced by dehydration, high salt and treatment with ABA, while it was not induced by heat or cold treatment. Moreover, the simultaneous accumulation of proline was observed as a result of the former treatments in A. thaliana. A cDNA for P5C reductase (cAtP5CR) was also isolated from A. thaliana and Northern blot analysis was performed. The AtP5CR gene was not induced to a significant extent by dehydration or high-salt stress. These observations suggest that the AtP5CS gene plays a principal role in the biosynthesis of proline in A. thaliana under osmotic stress.