Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer.

Aims: Durvalumab (Durva) administration after chemoradiation therapy (CRT) in locally advanced non-small-cell lung cancer (NSCLC) is the standard of care, associated with relatively prolonged progression-free (PFS) and overall survival. However, pneumonitis occurs in 73.6% of Japanese patients.

Dermatan-4--Sulfotransferase-1 Contributes to the Undifferentiated State of Mouse Embryonic Stem Cells.

Mouse embryonic stem cells (mESCs) have the properties of self-renewal and pluripotency. Various signals and growth factors maintain their undifferentiated state and also regulate their differentiation. Glycosaminoglycans are present on the cell surface and in the cell matrix as proteoglycans.

Site-specific O-GlcNAcylation of Psme3 maintains mouse stem cell pluripotency by impairing P-body homeostasis.

Mouse embryonic stem cell (ESC) pluripotency is tightly regulated by a complex network composed of extrinsic and intrinsic factors that allow proper organismal development. O-linked β-N-acetylglucosamine (O-GlcNAc) is the sole glycosylation mark found on cytoplasmic and nuclear proteins and plays a pivotal role in regulating fundamental cellular processes; however, its function in ESC pluripotency is still largely unexplored. Here, we identify O-GlcNAcylation of proteasome activator subunit 3 (Psme3) protein as a node of the ESC pluripotency network.

A defined glycosylation regulatory network modulates total glycome dynamics during pluripotency state transition.

Embryonic stem cells (ESCs) and epiblast-like cells (EpiLCs) recapitulate in vitro the epiblast first cell lineage decision, allowing characterization of the molecular mechanisms underlying pluripotent state transition. Here, we performed a comprehensive and comparative analysis of total glycomes of mouse ESCs and EpiLCs, revealing that overall glycosylation undergoes dramatic changes from early stages of development. Remarkably, we showed for the first time the presence of a developmentally regulated network orchestrating glycosylation changes and identified polycomb repressive complex 2 (PRC2) as a key component involved in this process.

Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells.

Dermatan sulphate (DS), a glycosaminoglycan, is present in the extracellular matrix and on the cell surface. Previously, we showed that heparan sulphate plays a key role in the maintenance of the undifferentiated state in mouse embryonic stem cells (mESCs) and in the regulation of their differentiation. Chondroitin sulphate has also been to be important for pluripotency and differentiation of mESCs.

[Dispatch of Psychiatrists to Okinawa and their Activities].

As a part of the medical assistance project for Okinawa, where the land and their people were devastated by the Pacific War, the Japanese Government launched a program to dispatch medical doctors. The dispatch of psychiatrists started in 1964, and lasted for 13 years. During this period, a total of 83 doctors joined this project.

Point mutation of cytochrome P450 2A6 (a polymorphic variant CYP2A6.25) confers new substrate specificity towards flavonoids.

CYP2A6 is a major hepatic member of the cytochrome P450 family in humans. Much variation in CYP2A6 levels and activity can be attributed to genetic polymorphisms of this gene. CYP2A6*25 comprises an amino acid substitution, F118L.

Metabolism of 7-ethoxycoumarin, safrole, flavanone and hydroxyflavanone by cytochrome P450 2A6 variants.

CYP 2A6 is a human enzyme that metabolizes many xenobiotics including coumarin, indole, nicotine and carcinogenic nitrosamines. The gene for CYP2A6 is polymorphic. There are few data available to clarify the relationship between P450 genetic variants and the metabolism of materials in food.

Thermoelectric response near a quantum critical point of β-YbAlB4 and YbRh2Si2: a comparative study.

The thermoelectric coefficients have been measured down to a very low temperature for the Yb-based heavy-fermion compounds β-YbAlB4 and YbRh2Si2, often considered as model systems for the local quantum criticality case. We observe a striking difference in the behavior of the Seebeck coefficient S in the vicinity of their respective quantum critical point (QCP). Approaching the critical field, S/T is enhanced in β-YbAlB4, but drastically reduced in YbRh2Si2.

L/T-type and L/N-type calcium-channel blockers attenuate cardiac sympathetic nerve activity in patients with hypertension.

Sympathetic nerve activity is augmented by calcium-channel blocker treatment as a result of decreased blood pressure. Dihydropyridine calcium-channel blockers are divided into three different types. The purpose of the present study was to investigate whether treatment effects on hemodynamics, cardiac autonomic nerve activity and plasma norepinephrine levels differ among amlodipine (L type), efonidipine (L + T type) and cilnidipine (L + N type).

Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study.

The goal of the present study was to investigate inter-individual and age-dependent variation of global DNA methylation in human tissues. In this work, we examined 5-methyldeoxycytidine ((met)C) content by HPLC in human peripheral blood leukocytes obtained from 76 healthy individuals of ages varying from 4 to 94 years (yr), and 39 human placentas from various gestational stages. The HPLC analysis revealed a significant variation of (met)C across individuals and is consistent with the previous findings of age-dependent decrease of global methylation levels in human tissues.

Overexpression, purification, and characterization of human and bovine mitochondrial ATPase inhibitors: comparison of the properties of mammalian and yeast ATPase inhibitors.

Mitochondrial ATP synthase (F1F0-ATPase) is regulated by an intrinsic ATPase inhibitor protein. In this study, we overexpressed and purified human and bovine ATPase inhibitors and their properties were compared with those of a yeast inhibitor. The human and bovine inhibitors inhibited bovine ATPase in a similar way.

Increased rate of P300 latency prolongation with age in drug-naive and first episode schizophrenia.

Objective: Previous studies have found an increased rate of P300 latency prolongation with age in medicated chronic patients with schizophrenia, suggesting a pathological neurodegenerative process. In this study, we investigated whether this abnormality was identified in drug-naive and first episode patients with schizophrenia.

Methods: P300 from auditory stimuli was recorded from 20 drug naive and first episode male patients with schizophrenia and compared with 23 age and handedness matched healthy male controls.

The N200 abnormalities of auditory event-related potentials in patients with panic disorder.

Cognitive impairment in patients with panic disorder (PD) has been studied using event-related potentials (ERPs). However, previous studies obtained ERP data only at a few scalp sites, and seldom investigated N200 measurements from the difference waveforms. In the present study, auditory ERPs were recorded at 16 scalp sites during an active discrimination task of oddball paradigm.

N400 abnormalities in unmedicated patients with schizophrenia during a lexical decision task.

A lexical decision task was used to investigate semantic processing in schizophrenia. Eighteen unmedicated schizophrenics and 18 gender/age-matched controls were tested. Subjects were visually presented with pairs of words.

Abnormalities of auditory P300 cortical current density in patients with schizophrenia using high density recording.

While P300 current density analysis has been performed in schizophrenic patients, the event-related potential data have never been obtained using a high density recording, nor have their cortical images been well demonstrated. In this study, the auditory P300 elicited by an oddball paradigm was recorded using a high density recording system of 128 channels. Thirteen male patients who met DSM-IV criteria for schizophrenia were compared with 20 healthy male controls.

Sex effects on rate of change of P300 latency with age.

Objective: Recent MRI evidence suggests that neuroanatomic structures may change more rapidly with age in males compared with females. Sex differences for P300 latency were tested to determine whether similar results might appear for P300 latency, a neurophysiological measure sensitive to age and neurodegenerative processes.

Methods: Auditory event related potentials (ERPs) were recorded using an auditory 'oddball' to elicit the N200 and P300 components.

N2 and P3b components of the event-related potential in students at risk for psychosis.

The N2 and P3b components of event-related potentials (ERPs) were studied in students who were identified as being at high risk for psychosis on the basis of their scores on the Chapman Psychosis Proneness Scales (PPS). The Magical Ideation subscale (MIS), the Perceptual Aberration subscale (PABS), and the Social Anhedonia subscale (SAS) were administered to 2,022 undergraduate university students. To determine if there were any relationships between these psychometric instruments and electrophysiological measures, 40 high-risk students were compared with 40 age- and gender-matched control students using auditory ERPs obtained from three midline electrodes (Fz, Cz, Pz) in a standard oddball paradigm.

Assessment of psychosocial stressors and maladjustment among foreign students of the University of the Ryukyus.

An extensive survey of problems encountered by foreign students of the University of the Ryukyus and the resulting levels of stress was carried out in order to determine the main stressors hindering academic progress and personal adjustment. Subjectively perceived stress levels after arrival in Japan were obtained from 134 subjects through a comprehensive questionnaire for reporting specific stressors. The 30-item General Health Questionnaire (GHQ) was included to assess mental health state.

Abnormalities of auditory event-related potentials in schizophrenia prior to treatment.

Background: P300 amplitude reduction is a consistent finding in schizophrenic patients, but it is unclear if this abnormality predates neuroleptic treatment or is present at onset of illness.

Methods: Auditory event-related potentials (ERPs), during a standard oddball paradigm, were recorded from 45 neuroleptic-naive schizophrenics, 56 drug-free, previously treated schizophrenics, and 73 healthy normal controls. Forty-seven of the schizophrenic subjects had their first episode within the past year.

[Developing the portable type sleep apnea detector, and verifying the usefulness of the device].

Polysomnographic recording is indispensable in the diagnosis of sleep apnea syndrome (SAS). However, this method has a number of drawbacks, for example, subjects cannot sleep naturally like at their homes, and the methodology involved is complicated. We have now developed Portable Type Sleep Apnea Detector (PSD) that needs to equipment to provide subject's body.

Transient P300 abnormality of event-related potentials following unilateral temporal lobectomy.

Event-related potentials (ERP) were recorded during auditory oddball tasks for a patient prior to and soon after left anterior temporal lobectomy. The N100 amplitude decreased bilaterally although the latency did not change after the lobectomy. The P300 amplitude decreased in the left hemisphere at 1 and 2 weeks after surgery, then recovered to the pre-operative level at 4 weeks.

Prevalence of senile dementia in Okinawa, Japan. COSEPO Group. Study Group of Epidemiology for Psychiatry in Okinawa.

METHODS. The prevalence of dementia was investigated in Okinawa Prefecture, Japan. In all, 3524 subjects, > or = 65 years old, were sampled randomly (urban and rural populations 61.