Role of protein kinase C in angiotensin II-induced constriction of renal microvessels

Role of protein kinase C in angiotensin II-induced constriction of renal microvesselsBackgroundAlthough angiotensin II (Ang II) exerts its action through multiple vasomotor mechanisms, the contribution of phosphoinositol hydrolysis products to Ang II-induced renal vasoconstriction remains undetermined.MethodsThe role of protein kinase C (PKC) in Ang II-induced afferent (AFF) and efferent (EFF) arteriolar constriction was examined using the isolated perfused hydronephrotic rat kidney.ResultsAng II (0.3 nmol/L)-induced EFF constriction was refractory to inhibition of voltage-dependent calcium channels by pranidipine (1 μmol/L, 19 ± 2% reversal) but was completely reversed by a PKC inhibitor, chelerythrine (1 μmol/L, 96 ± 2% reversal). Furthermore, direct PKC activation by phorbol myristate acetate (PMA; 1 μmol/L) caused prominent EFF constriction, and this constriction was inhibited by manganese and free calcium medium. In contrast, Ang II-induced AFF constriction was completely abolished by pranidipine (98 ± 4% reversal) and was partially inhibited by chelerythrine (55 ± 3% reversal). Although PMA elicited marked AFF constriction, this constriction was insensitive to the calcium antagonist, but was totally inhibited by manganese or free calcium medium.ConclusionsPKC plays an obligatory role in Ang II-induced EFF constriction that requires extracellular calcium entry through nonselective cation channels. In contrast, in concert with our recent findings demonstrating a complete dilation by thapsigargin, Ang II-induced AFF constriction is mainly mediated by inositol trisphosphate (IP3) and voltage-dependent calcium channel pathways, but could not be attributed to the PKC-activated calcium entry pathway (for example, nonselective cation channels). Rather, Ang II-stimulated PKC may cross-talk to the IP3/voltage-dependent calcium channel pathway and could modulate the vasoconstrictor mechanism of the AFF. Thus, the role of PKC during Ang II stimulation differs in AFF and EFF, which may constitute segmental heterogeneity in the renal microvasculature

Structural and Electronic Properties of a Triangular Lattice Magnet NaPrTe2_2 Compared with NaNdTe2_2 and NaTbTe2_2

NaPrTe2, NaNdTe2, and NaTbTe2 are found to be triangular lattice magnets with the alpha-NaFeO2 structure, where lanthanoid atoms with 4f electrons form a triangular lattice, based on the structural analysis and physical property measurements of synthesized polycrystalline samples. The alpha-NaFeO2 structure is a new polymorph of NaPrTe2, which has been reported to crystallize in the cubic LiTiO2 structure. Polytypism in NaPrTe2 was discussed based on the structural parameters determined by the Rietveld analysis. NaPrTe2 is suggested to be in the proximity of the phase boundary between the LiTiO2 and alpha-NaFeO2 types, as compared to NaNdTe2 and NaTbTe2, indicating that this compound might be interesting from the perspectives of the dimensional control of geometrically frustrated lattices. The magnetic susceptibility and heat capacity data indicated that NaPrTe2 do not show long-range magnetic order or a spin-glass transition above 2 K.Comment: 6 pages, 7 figure

エチオピア高原の農牧複合民における近年の家畜頭数の減少とその原因 : ティグライ州東部ゾーンキルテ-アウラエロ郡の南部の事例から

The purpose of this research was to study in the Tigray highland of Ethiopia 1) to understand the change in the land utilization, the grazing patterns, and the change in the number of livestock, in light of the recent natural and social environmental changes, 2) to analyze the decrease in the number of livestock and its contributing factors, and 3) to discuss that the decrease in the number of domestic animals has a negative influence to the nutrition intake of local farmers. The field research while staying with a total of eight households and the survey questionnaire on a total of 14 households were conducted in September 2016 and July 2017, and the study on the farmer\u27s nutrition was also performed in March 2015 in the study area. From the imperial era through the socialist era, most of the land was still made up of grasslands and forests, which were available for grazing and logging. Each household raised from 10 to 30 cattle, making them rich financially and nutritionally. With the increase in population in the democratic era, however, there was a shortage of farmlands, and the grasslands and forests rapidly shrunk as more and more those communal lands was developed into farmlands. The grasslands and forests that had been used for grazing year-round shrunk even more when the government expanded the areas of seasonally-closed grazing land, prohibited grazing lands and protected forest lands. Furthermore, there was a shortage of herd boys who are in charge of grazing once schooling began in the villages. As a result, the number of livestock raised by a household began to dwindle. Since the farmers were only able to raise a few cattle, they could no longer obtain milk throughout the year, which led to a decreased consumption of milk products. The milk product\u27s contribution to their nutrition has become limited. The decrease in the amount of feed resources and the shortage of herd boys limited the number of livestock that could be raised by each household, and will mostly likely continue to be a major contributing factor in limiting the subsistence of the farmers in Tigray.本研究では，エチオピア国ティグライ州高地を対象とし，1）近年の自然・社会環境の変化を鑑みながら，土地利用の変化，放牧パターン，家畜頭数の変化を把握し，2）家畜頭数の減少とその要因について分析するとともに，3）家畜頭数の減少が栄養摂取に負の影響を与えていることを明らかにすることを目的とした．帝政時代から社会主義時代を通じて，大部分の土地はいまだ家畜放牧や薪伐採が自由な自然草地・森林地であった．世帯毎にウシを十数頭から三十頭ほどを飼養し，農牧複合民は資金的にも栄養摂取的にも豊かであった．人口の増加により農耕地の不足が発生し，民主主義時代になって自然草地・森林地での農耕地開拓が進行することになり，自然草地・森林地が急速に縮小していった．また，放牧禁止・森林保護地，季節禁牧地の拡大により，一年を通じて放牧できる自然草地・森林地は更に縮小していった．そして，村落における学校教育が開始され，放牧を担当する牧童が不足するようになっていった．これらの結果から，世帯当たりの飼養家畜頭数は減少していった．家畜を数頭しか飼養できなくなったため，一年を通じて搾乳できず，乳製品を頻繁に摂取できなくなり，乳製品の栄養摂取への貢献度は限定的になっているのが現状となっている．利用可能な飼料資源量の減少と牧童の減少は，世帯当たりの家畜飼養頭数を少ないままに抑制し，今後ともティグライ州の農牧複合民の生業に対して大きな制限要因となり続けていくことであろう

A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression

SummarySignaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-κB and β-catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias

A portable dermatoscope for easy, rapid examination of periungual nailfold capillary changes in patients with systemic sclerosis.

Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenic role. The presence of nailfold capillary abnormalities is useful in diagnosing SSc. Capillaroscopy, however, usually requires special equipment and may be time consuming. Dermatoscope has been presented as a new diagnostic tool for quick and efficient examination of nailfold capillaries for circumstances when standard microscope equipment is not available. To assess the practical utility of dermatoscope for assessment of capillary morphology in patients with SSc, 83 Japanese patients with SSc (68 women, 15 men) and 68 healthy controls were examined in the study. Twenty-one patients (16 women, 5 men) had diffuse cutaneous SSc and 62 (52 women, 10 men) had limited cutaneous SSc. Enlarged capillaries and hemorrhages were evaluated in all 10 fingers with either naked eyes or DermLite((R)) DL100 dermatoscope. Enlarged capillaries and hemorrhages were significantly more frequently detected with dermatoscope than without it. These findings were observed most frequently in the fourth finger. The presence of two or more enlarged capillaries in one or more fingers showed 83.1% sensitivity and 100% specificity for SSc. Among patients with SSc with anti-topoisomerase I antibody, the disease duration correlated negatively with the dermatoscopic number of enlarged capillaries and hemorrhages. Dermatoscope allows the easy and rapid identification of capillary nailfold morphological changes in SSc and should be routinely used for diagnosing SSc.The original publication is available at www.springerlink.co

Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor

To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872–11877) was composed of the interleukin 5 receptor α chain+ (IL-5Rα+) and IL-5Rα− fractions, and the former was the hEoP. The IL-5Rα+CD34+CD38+IL-3Rα+CD45RA− hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Rα− hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an “IL-5Rα–negative” criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS