Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor transgenic mice injected with human GM-CSF

Using a clonal assay of bone marrow (BM) cells from transgenic mice (Tg-mice) expressing the human granulocyte-macrophage colony-stimulating factor receptor (hGM-CSFR), we found in earlier studies that hGM-CSF alone supported the development not only of granulocyte-macrophage colonies, but also of erythrocytes, megakaryocytes, mast cells, blast cells, and mixed hematopoietic colonies. In this report, we evaluated the in vivo effects of hGM-CSF on hematopoietic and lymphopoietic responses in the hGM-CSFR Tg-mice. Administration of this factor to Tg-mice resulted in dose-dependent increases in numbers of reticulocytes and white blood cells (WBCs) in the peripheral blood. Morphological analysis of WBCs showed that the numbers of all types of the cell, including neutrophils, eosinophils, monocytes, and lymphocytes increased; the most remarkable being in lymphocytes that contained a number of large granular lymphocytes (LGLs) in addition to mature T and B cells. However, total cellularity of the BM of the Tg-mice decreased in a dose-dependent manner when hGM-CSF was injected. In sharp contrast to the BM, spleens of the Tg-mice were grossly enlarged. Although all types of blood cells and hematopoietic progenitors increased in the spleen, erythroid cells and their progenitors showed the most significant increase. Increased numbers of megakaryocytes and LGLs were also observed in spleen and liver of the treated Tg-mice. Flow cytometric analysis showed that LGLs expanded in Tg-mice expressed Mac-1+ CD3- NK1.1+. The thymus of Tg-mice treated with hGM-CSF exhibited a dose-dependent shrinkage and a remarkable decrease in CD4+ CD8+ cells. Thus, hGM-CSF stimulated not only myelopoiesis but also erythropoiesis and megakaryopoiesis of hGM-CSFR Tg-mice in vivo, in accordance with our reported in vitro findings. In addition, hGM-CSF affected the development of lymphoid cells, including natural killer cells of these Tg-mice.     

Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD⁺, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD⁺ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD⁺ production through the NAD⁺ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD⁺ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD⁺ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD⁺ biosynthesis pathways in mammals, the NAD⁺ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD⁺, have been developed so far. In this review, we will focus on the importance of NAD⁺ and the possible application of an activator of NAMPT to promote successive aging.     

Simulation of characteristics of a SiO2/c-axis-oriented LiNbO3/diamond surface acoustic wave

High-frequency surface acoustic wave (SAW) devices based on diamond that have been realized to date utilize c-axis-oriented ZnO as the piezoelectric thin film. This material, with SiO2 overlay, shows excellent characteristics of a high phase velocity of over 10,000 m/s and a zero temperature coefficient, and it has been successfully applied to high-frequency SAW filters and resonators. To expand on materials used on diamond, the theoretical calculation has been carried out for LiNbO3/diamond, and a high electromechanical coupling coefficient up to 9.0% is expected. In this work, the characteristics of SiO2/LiNbO3/diamond were studied by computer simulation, emphasizing a zero temperature coefficient with a high coupling coefficient. Calculations are carried out for the phase velocity, the electromechanical coupling coefficient, and the temperature coefficient of the Rayleigh wave and its higher mode Sezawa wave. As a result, SiO2/IDT/LiNbO3/diamond is found to offer a zero temperature coefficient with a very high coupling coefficient up to 10.1% in conjunction with a high phase velocity of 12,100 m/s.     

Drivability improvement on deep-submicron MOSFETs by elevation ofsource/drain regions

Deep submicron MOSFETs with elevated source/drain (S/D) structures, where S/D extension regions were partially elevated besides deep S/D regions, were fabricated by use of Si selective epitaxial growth technique. As fairly compared with a well-developed conventional MOSFET, we clarify an advantage of the elevated S/D structures, i.e., improvement upon driving performance with keeping excellent short-channel characteristics, which is enhanced for decrease in gate sidewall spacer width. The experimental results are explained in terms of the reduction in S/D parasitic resistance by addition of the Si epitaxial layer where the impurity profile is suitable     

Analysis of inhibitory effects of scutellariae radix and baicalein on prostaglandin E2 production in rat C6 glioma cells

Inhibitory mechanism of the water extract of Scutellariae Radix on prostaglandin E2 (PGE2) release was examined in C6 rat glioma cells. Scutellariae Radix reduced a Ca2+ ionophore A23187-induced PGE2 release by inhibition of arachidonic acid (AA) liberation. Sho-saiko-to and San'o-shashin-to, which contain Scutellariae Radix, also inhibited PGE2 release. A23187 caused phosphorylation of mitrogen-activated protein kinase (MAPK), resulting in activation of cytosolic phospholipase A2 (cPLA2). Scutellariae Radix and baicalein inhibited the phosphorylation of MAPK. Baicalein, but not baicalin, inhibited A23187-induced PGE2 release. These results suggest that baicalein in Scutellariae Radix reduces AA liberation through the inhibition of the MAPK-cPLA2 pathway.     

Junction capacitance reduction due to self-aligned pocketimplantation in elevated source/drain NMOSFETs

A new advantage of an elevated source/drain (S/D) configuration to improve MOSFET characteristics is presented. By adopting pocket implantation into an elevated S/D structure which was formed by Si selective epitaxial growth and gate sidewall removal, we demonstrate that the parasitic junction capacitance as well as the junction leakage was significantly reduced for an NMOSFET while maintaining its good short channel characteristics. These successful results are attributed to the modification of the boron impurity profile in the deep S/D regions. The capacitance reduction rate, furthermore, was more remarkable as the pocket dose was further increased. This means that the present self-aligned pocket implantation is very promising for future MOSFETs with a very short gate length, where high pocket dosage will be required to suppress the short channel effect     

Intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in interleukin-3-hyporesponsive mice

Mineralization in the pulp is a common finding in permanent as well as primary teeth and is associated with caries, aging, traumatic injuries and systemic conditions. This article describes an unusual pattern of pulpal calcification. A tube-like calcified structure formed in the dental pulp of primary incisors following mild traumatic injuries. It was studied by clinical, radiographic and histologic evaluation and by scanning electron microscopy. The tube-like structure was found to extend along the entire length of the pulp canal. Generally it was separated from the root dentin by normal pulp tissue, but was connected to the dentin in some sites. It had the histologic appearance of osteodentin with cell inclusions in a ring-like formation that was incomplete in places. The scanning electron microscope study showed rough inner and outer surfaces of a tube-like structure with openings that seemed to be dentinal tubules.     

Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells

Leptin, the product of obese gene, was originally identified as a factor regulating body-weight homeostasis and energy balance. The present study has shown that leptin acts on murine hematopoiesis in vitro. In the culture of bone marrow cells (BMC) of normal mice, leptin induced only granulocyte-macrophage (GM) colony formation in a dose-dependent manner, and no other types of colonies were detected even in the presence of erythropoietin (Epo). Leptin also induced GM colony formation from BMC of db/db mutant mice whose leptin receptors were incomplete, but the responsiveness was significantly reduced. The effect of leptin on GM colony formation from BMC of normal mice was also observed in serum-free culture, and comparable with that of GM-colony-stimulating factor (CSF ). Although leptin alone supported few colonies from BMC of 5-fluorouracil (5-FU)-treated mice in serum-free culture, remarkable synergism between leptin and stem cell factor (SCF ) was obtained in the colony formation. The addition of leptin to SCF enhanced the SCF-dependent GM colony formation and induced the generation of a number of multilineage colonies in the presence of Epo. When lineage (Lin)-Sca-1(+) cells sorted from BMC of 5-FU-treated mice were incubated in serum-free culture, leptin synergized with SCF in the formation of blast cell colonies, which efficiently produced secondary colonies including a large proportion of multilineage colonies in the replating experiment. In serum-free cultures of clone-sorted Lin-c-Kit+Sca-1(+) and Lin-c-Kit+Sca-1(-) cells, although synergism of leptin and SCF was observed in the colony formation from both cells, leptin alone induced the colony formation from Lin-c-Kit+Sca-1(-), but not Lin-c-Kit+Sca-1(+) cells. These results have shown that leptin stimulates the proliferation of murine myelocytic progenitor cells and synergizes with SCF in the proliferation of primitive hematopoietic progenitors in vitro.