51 research outputs found

    Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant.

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    Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant

    Paleopathological characteristics of Neolithic early rice farmers in the lower reaches of the Yangtze river

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    Paleopathological investigations of human remains from the Neolithic Hemudu culture in the lower reaches of the Yangtze River in southern East Asia were conducted to clarify the health status of people in early rice-farming societies. Our results show that the occurrence ratios of cribra orbitalia and enamel hypoplasia did not differ significantly between early rice farmers and hunter-gatherers. By contrast, the occurrence ratios of periosteal reactions, dental caries, and antemortem tooth loss in adults were higher among the early rice farmers. Based on these findings and the results of archaeological research on the Hemudu culture, it was suggested that: 1) the Hemudu culture adopted a diversified livelihood strategy that was not overly dependent on rice as a food resource, which did not lead to an extreme decline in health status, 2) the work in the rice fields or the working environment caused stress to the workers, and 3) the rice-farming society’s dietary habits led to a decline in oral health. Our results provide new paleopathological insights into the health status of early rice farmers in East Asia. However, the sample size of early rice farmers used in this study was small, and more data are needed to verify the validity of the views presented here

    Lipid Transfer Proteinに対するモノクローナル抗体を用いたリンゴ使用量の評価系の確立

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    In order to establish evaluation system for apple content in foods, monoclonal antibodies were raisedagainst apple lipid transfer protein (LTP). A sandwich-type of enzyme-linked immunosorbent assay (ELISA)was developed by using two of the five monoclonal antibodies obtained. This ELISA showed a practicalworking range of 0.03-10 ng/mL for apple LTP and no cross-reactivity with other fruits tested except plum.LTP could be determined with this ELISA in peel selectively and in foods with apple labeling such as applejuice, vegetable juice and even in curry roux

    Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 369

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    Summary Background Drugs that inhibit the renin-angiotensin-aldosterone system benefi t patients at risk for or with existing cardiovascular disease. However, evidence for this eff ect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was eff ective in Japanese patients with cardiovascular disease

    C/EBPβ Promotes Transition from Proliferation to Hypertrophic Differentiation of Chondrocytes through Transactivation of p57Kip2

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    BACKGROUND: Although transition from proliferation to hypertrophic differentiation of chondrocytes is a crucial step for endochondral ossification in physiological skeletal growth and pathological disorders like osteoarthritis, the underlying mechanism remains an enigma. This study investigated the role of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) in chondrocytes during endochondral ossification. METHODOLOGY/PRINCIPAL FINDINGS: Mouse embryos with homozygous deficiency in C/EBPbeta (C/EBPbeta-/-) exhibited dwarfism with elongated proliferative zone and delayed chondrocyte hypertrophy in the growth plate cartilage. In the cultures of primary C/EBPbeta-/- chondrocytes, cell proliferation was enhanced while hypertrophic differentiation was suppressed. Contrarily, retroviral overexpression of C/EBPbeta in chondrocytes suppressed the proliferation and enhanced the hypertrophy, suggesting the cell cycle arrest by C/EBPbeta. In fact, a DNA cell cycle histogram revealed that the C/EBPbeta overexpression caused accumulation of cells in the G0/G1 fraction. Among cell cycle factors, microarray and real-time RT-PCR analyses have identified the cyclin-dependent kinase inhibitor p57(Kip2) as the transcriptional target of C/EBPbeta. p57(Kip2) was co-localized with C/EBPbeta in late proliferative and pre-hypertrophic chondrocytes of the mouse growth plate, which was decreased by the C/EBPbeta deficiency. Luciferase-reporter and electrophoretic mobility shift assays identified the core responsive element of C/EBPbeta in the p57(Kip2) promoter between -150 and -130 bp region containing a putative C/EBP motif. The knockdown of p57(Kip2) by the siRNA inhibited the C/EBPbeta-induced chondrocyte hypertrophy. Finally, when we created the experimental osteoarthritis model by inducing instability in the knee joints of adult mice of wild-type and C/EBPbeta+/- littermates, the C/EBPbeta insufficiency caused resistance to joint cartilage destruction. CONCLUSIONS/SIGNIFICANCE: C/EBPbeta transactivates p57(Kip2) to promote transition from proliferation to hypertrophic differentiation of chondrocytes during endochondral ossification, suggesting that the C/EBPbeta-p57(Kip2) signal would be a therapeutic target of skeletal disorders like growth retardation and osteoarthritis

    Quality Control System for Beer Developed with Monoclonal Antibodies Specific to Barley Lipid Transfer Protein

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    Non-specific lipid transfer protein (LTP) in barley grain reacted with the IgE in sera drawn from food allergy patients. A sandwich-type of enzyme-linked immunosorbent assay (ELISA) was developed with mouse monoclonal antibodies raised against LTP purified with barley flour. This ELISA showed a practical working range of 0.3–3 ng/mL and no cross-reactivity with wheat, adlay and rye. Using this ELISA, LTP was determined in several types of barley-foods, including fermented foods such as malt vinegar, barley-malt miso and beer. LTP content in beer of the same kind was approximately constant, even if manufacturing factory and production days were different. Not only as a factor of foam formation and stability but also as an allergen, controlling and monitoring of LTP in beer should be considered. Taken together, our LTP-detecting ELISA can be proposed as an appropriate system for the quality control of beer

    自己理解と他者とのつながりを育む幼小接続期での自己表現プログラムの開発について

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    Based on the Reggio Emilia approach, the purpose of this research is to develop the creativity of each child and create a foundation for them to act in their own way in a group.In this research, we focus our research on children from kindergarten to the lower grades of elementary school, especially from the 5 year old class of kindergarten to the first grade of elementary school. First, we summarize the characteristics of Reggio Emilia. Next, I summarize the practice of childcare and classes based on the Reggio Emilia approach.Based on the results, we develop, implement, and verify educational practices that can be realized in our school. Finally, we consider the ideal way of self expression to bring out the creativity of each child
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