ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

Roles of postsynaptic density-95/synapse-associated protein 90 and its interacting proteins in the organization of synapses

Synapses are central stages for neurotransmission. Neurotransmitters are released from the presynaptic membrane of one neuron, and bind to the receptors accumulated at the postsynaptic membrane, followed by the activation of the other neuron. The strength of a synapse is modified depending on the history of the previous neurotransmissions. This property is called synaptic plasticity and is implicated in learning and memory. Synapses contain not only the components essential for neurotransmission but also the signalling molecules involved in synaptic plasticity. The elucidation of the molecular structures of synapses is one of the key steps to understand the mechanism of learning and memory. Recent studies have revealed postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 as a core component in the architecture of synapses. In this review, we summarize up-to-date information about PSD-95/SAP90 and its interacting proteins, and the organization of synapses orchestrated     

Purification of α-ketoaldehyde dehydrogenase from the human liver and its possible significance in the control of glycation

Summary Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.     

Plasma cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate response to methacholine in man

Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man.     

Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice

Rheumatoid arthritis (RA), which afflicts about 1% of the world population, is a chronic systemic inflammatory disease of unknown aetiology that primarily affects the synovial membranes of multiple joints. Although CD4(+) T cells seem to be the prime mediators of RA, it remains unclear how arthritogenic CD4(+) T cells are generated and activated. Given that highly self-reactive T-cell clones are deleted during normal T-cell development in the thymus, abnormality in T-cell selection has been suspected as one cause of autoimmune disease. Here we show that a spontaneous point mutation of the gene encoding an SH2 domain of ZAP-70, a key signal transduction molecule in T cells, causes chronic autoimmune arthritis in mice that resembles human RA in many aspects. Altered signal transduction from T-cell antigen receptor through the aberrant ZAP-70 changes the thresholds of T cells to thymic selection, leading to the positive selection of otherwise negatively selected autoimmune T cells. Thymic production of arthritogenic T cells due to a genetically determined selection shift of the T-cell repertoire towards high self-reactivity might also be crucial to the development of disease in a subset of patients with RA.     

Microstructural evolution and mechanical properties of a low-carbon quenching and partitioning steel after partial and full austenitization

In this work, low-carbon steel specimens were subjected to the quenching and partitioning process after being partially or fully austenitized to investigate their microstructural evolution and mechanical properties. According to the results of scanning electron microscopy and transmission electron microscopy observations, X-ray diffraction analysis, and tensile tests, upper bainite or tempered martensite appears successively in the microstructure with increasing austenitization temperature or increasing partitioning time. In the partially austenitized specimens, the retained austenite grains are carbon-enriched twice during the heat treatment, which can significantly stabilize the phases at room temperature. Furthermore, after partial austenitization, the specimen exhibits excellent elongation, with a maximum elongation of 37.1%. By contrast, after full austenitization, the specimens exhibit good ultimate tensile strength and high yield strength. In the case of a specimen with a yield strength of 969 MPa, the maximum value of the ultimate tensile strength reaches 1222 MPa. During the partitioning process, carbon partitioning and carbon homogenization within austenite affect interface migration. In addition, the volume fraction and grain size of retained austenite observed in the final microstructure will also be affected.     

Elevation of plasma dopamine-β-hydroxylase activity during insulin-induced hypoglycemia in man

Résumé Nous avons étudié l'activité de la dopamine--hydroxylase du plasma humain. Elle a été remarquablement accure par l'administration de grandes quantités d'insuline. Les corrélations entre cette activité et celle des systèmes nerveux sympathiques sont également discutées.     

Effect of lower bainite/martensite/retained austenite triplex microstructure on the mechanical properties of a low-carbon steel with quenching and partitioning process

We present a study concerning Fe–0.176C–1.31Si–1.58Mn–0.26Al–0.3Cr (wt%) steel subjected to a quenching and partitioning (Q&P) process. The results of scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and tensile tests demonstrate that the microstructures primarily consist of lath martensite, retained austenite, lower bainite (LB), and a small amount of tempered martensite; moreover, few twin austenite grains were observed. In the microstructure, three types of retained austenite with different sizes and morphologies were observed: blocky retained austenite (~300 nm in width), film-like retained austenite (80–120 nm in width), and ultra- fine film-like retained austenite (30–40 nm in width). Because of the effect of the retained austenite/martensite/LB triplex microstructure, the specimens prepared using different quenching temperatures exhibit high ultimate tensile strength and yield strength. Furthermore, the strength effect of LB can partially counteract the decreasing strength effect of martensite. The formation of LB substantially reduces the amount of retained austenite. Analyses of the retained austenite and the amount of blocky retained austenite indicated that the carbon content is critical to the total elongation of Q&P steel.