Differential Scanning Calorimetric Studies on the Melting Behavior of Water in Stratum Corneum

The melting behavior of water in human stratum corneum (s. corneum) has been studied by sing differential scanning calorimetry (DSC) in the temperature range from -40° to 20°C. The DSC thermogram was analyzed in terms of the amount of about water and the melting temperature of water in s. corneum. Extraction of the s. corneum with the mixed solvent of chloroform: methanol (2:1, v/v) or 0.5% sodium dodecyl sulfate aqueous solution decreased the bound water content, whereas extraction with water did not change the bound water content. The melting temperature of water in the s. corneum was lowered as the water contents decreased. Extraction of the water-soluble components from the s. corneum increased the melting temperature of water when the water contents were constant. The results suggest that 20–30% of water in the s. corneum is bound water interacting strongly with the protein or lipids in the s. corneum, and the excess of water over the bound water content is unbound water solubilizing the water-soluble components such as amino acids and urea in the s. corneum. The thermodynamic theory for freezing-point depression is favourably applied to the melting temperature change of the unbound water, which implies that the water-soluble components are present as an aqueous solution in the s. corneum. Measurements of the melting-point depression of water in s. corneum provides us the quantitative information on the amount of water-soluble components in the s. corneum. This technique is a sensitive and useful tool to evaluate the hydration behavior of s. corneum

Novel CLCN7 mutations in IARO

Osteopetrosis is a heritable disorder of the skeleton that is characterized by increased bone density on radiographs caused by defects in osteoclast formation and function. Mutations in >10 genes are identified as causative for this clinically and genetically heterogeneous disease in humans. We report two novel missense variations in a compound heterozygous state in the CLCN7 gene, detected through targeted exome sequencing, in a 15-year-old Japanese female with intermediate autosomal recessive osteopetrosis

Deep intronic GPR143 mutation in a Japanese family with ocular albinism

Deep intronic mutations are often ignored as possible causes of human disease. Using whole-exome sequencing, we analysed genomic DNAs of a Japanese family with two male siblings affected by ocular albinism and congenital nystagmus. Although mutations or copy number alterations of coding regions were not identified in candidate genes, the novel intronic mutation c.659-131 T > G within GPR143 intron 5 was identified as hemizygous in affected siblings and as heterozygous in the unaffected mother. This mutation was predicted to create a cryptic splice donor site within intron 5 and activate a cryptic acceptor site at 41nt upstream, causing the insertion into the coding sequence of an out-of-frame 41-bp pseudoexon with a premature stop codon in the aberrant transcript, which was confirmed by minigene experiments. This result expands the mutational spectrum of GPR143 and suggests the utility of next-generation sequencing integrated with in silico and experimental analyses for improving the molecular diagnosis of this disease

Novel CUL4B mutation in Cabezas syndrome

Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome

A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements

Background: Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Case presentation: Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. Conclusions: To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single-nucleotide polymorphism probes with further analyses of the breakpoint junctions are recommended in cases suspected of having complex chromosomal abnormalities based on discrepancies between clinical and conventional cytogenetic findings

Role of hepatic STAT3 in brain-insulin action on hepatic glucose production

SummarySTAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production

Correlative study of hippocampal atrophy assessed by MRI and clinical features in temporal lobe epilepsy.

側頭葉てんかん患者39例の海馬萎縮をMRIを用いて評価し,臨床像との関連を検討した｡MRIの冠状断short SE像で海馬の幅を計測し,萎縮側海馬の村側海馬に対する比(a)を求め,海馬萎縮(+)群;a<0.8,11例,境界群;0.8≦a<0.9,13例,海馬萎縮(-)群;a≧0.9,15例の3群に分けた｡海馬萎縮(+)群で罹病期間が長い傾向があった｡また,発作間歇期脳波の焦点側は海馬委縮(+)群の11例中9例で萎縮側と一致した。しかし,発病年齢,MRI撮影時年齢,発作頻度,全般化発作の有無,抗てんかん薬総服用量,知能障害,精神症状,生下時仮死の有無については3群間で差が認められなかった｡この結果から,側頭葉てんかんにおける海馬萎縮は,生下時や全身けいれん発作時の低酸素状態によるものではなく,脳局所の反復するてんかん性発射と関連する可能性が示唆され,海馬萎縮の機序を考えるうえで興味深く思われた。We studied hippocampal atrophy in 39 patients with temporal lobe epilepsy using MRI. The ratio (a) of the width of the hippocampus on the atrophic side to that on the contralateral side was measured in coronal sections of the short SE in MRI. According to this ratio, the patients were divided into three groups : 11 with hippocampal atrophy (a<0.8), 13 with borderline atrophy (0.8≦a≦0.9), and 15 with no hippocampal atrophy (a≧0.8). In the patients of the group with hippocampal atrophy, the clinical history of epilepsy tended to be long, and the site of hippocampal atrophy was consistent with that of interictal spike foci on the electroencephalogram in 9 out of 11 patients. However, there was no difference between the three groups, with regard to age at onset, age when MRI was conducted, frequency of seizures, generalized seizures, the types and doses of antiepileptic drugs used, history of neonatal asphyxia, intelligence and epilpetic psychosis. These results suggest that hippocampal atrophy in temporal lobe epilepsy may be related to repetition of epileptic dischargges in a localized part of the brain

Research on satisfaction of elderlies with dementia in health care facilities.

2つの老人保健施設に入所している痴呆老人について,観察者による彼らの満足度とその時に観察された行動の関係を明らかにすることを目的とする｡調査対象者は,2つの老人保健施設に入所中で,本人または家族より調査への了系の得られた,歩行可能な痴呆老人各14名,合計28名である｡観察者は対象者の行動を48時間観察し,どこで誰と何を行っているかとその時の満足度を調査票に記録した｡満足度は対象者の表情や態度から観察者が判断し,大変満足を⑤とし,どちらとも言えないを③,大変不満足を①とした5段階評定で示した｡その結果以下の3点が明らかとなった｡ 1)両施設で満足度の高い時間帯は,レクリエーションが含まれる"午前中の時間"であった｡ 2)満足度が高いのは,居場所では,"レクリエーションルーム･屋外"であった｡ 3)同行者は,"家族","観察者",行動は,"話をする",手伝いをするなど"自発的な行為"が多くみられた｡以上により,2つの施設で満足度ごとの時間帯,居場所,同行者と行動が似通っていたことから,客観的に痴呆老人の満足度を把握することは可能であると考える｡The purpose of this study was to clarify if there is a relationship between the satisfaction of elderlies with dementia in health care facilities by subjective views of the investigator and their actions. The subjects of this investigation were 28 fully functional elderly clients with dementia who were living in 2 health care facilities. They or their family consented to take part in our research. 14 clients were chosen from each facilities. The investigators observed the clients for 48 hours and recorded where they were, with whom they were, what they did, as well as the client's level of satisfaction. The satisfaction levels were judged from the clients' appearances or attitudes by the investigations. There were five satisfaction including from 1 : unsatisfied to 5 : great satisfaction. The following three points were observed both in two facilities in common ; (1) the high satisfaction time period was "morning" when recreation was included. (2) the client received a high level of satisfaction when they were in the "recreation-room" or "outdoors", (3) the client received a high level of satisfaction whom they stayed with "their family" or "observers", when talking to someone or helping someone positively. Analysis of these results demonstrated there was similar pattern between the time of day and place and their companion or their actions among the subjects in two facilities. It can be assumed that it is able to observe elderlies with dementia satisfaction degree objectively

Inhibition of Hsp90 Leads to Cell Cycle Arrest and Apoptosis in Human Malignant Pleural Mesothelioma

IntroductionHeat shock protein 90 (Hsp90) is an abundant molecular chaperone that mediates the maturation and stability of a variety of proteins associated with the promotion of cell growth and survival. Inhibition of Hsp90 function leads to proteasomal degradation of its mis-folded client proteins. Recently, Hsp90 has emerged as being of prime importance to the growth and survival of cancer cells and its inhibitors have already been used in phase I and II clinical trials.MethodsWe investigated how 17-allylamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is implicated in human malignant pleural mesothelioma (MM).ResultsWe found that 17-AAG led to significant G1 or G2/M cell cycle arrest, inhibition of cell proliferation, and decrease of AKT, AKT1, and survivin expression in all human malignant pleural mesothelioma cell lines examined. We also observed significant apoptosis induction in all MM cell lines treated with 17-AAG. Furthermore, 17-AAG induced apoptosis in freshly cultured primary MM cells and caused signaling changes identical to those in 17-AAG treated MM cell lines.ConclusionThese results suggest that Hsp90 is strongly associated with the growth and survival of MM and that inhibition of Hsp90 may have therapeutic potential in the treatment of MM