Conversion of Normal Ly-1-Positive B-Lineage Cells into Ly-1-Positive Macrophages in Long-Term Bone Marrow Cultures

We obtained eight different cell lines in the long-term bone marrow culture system that showed a germ-line configuration of the joining (J) region segments of the Ig heavy-chain (IgH) genes. Their surface markers were CD45R+, Ly-1+, Lyb-2+, cIgM-, sIgM-, Ia-, Thy-1-, Mac-1-, and IL-2R (Tac)+. Use of very young mice and the presence of IL-5 were important for preferential promotion of the survival of B-lineage lymphocytes bearing the Ly-1 markers. When we treated two of them (J8 and J10) with 5-azacytidine for 24 h followed by co-culture with stromal cells and IL-.5, they became Ly-1+, sIgM+ B cells, and Ly-1+, Mac-1+ macrophagelike cells, respectively. After other early lymphoid lines (J1, J8, and J13) were maintained by co-culture with ST2 and IL-5 for more than a year, they showed a heterogeneous DNA rearrangement profile of the J region segment of the IgH gene, although only J13 rearranged the κ-light chain gene. Northern blot analysis revealed that these cell lines expressed Cμ-mRNA, and λ5-mRNA, consistent with normal pre-B cells. Intriguingly, J1, J8, and J13 expressed c-fms mRNA constitutively. When J13 cells were co-cultured with ST2 and GM-CSF in place of ST2 and IL-5, they acquired Mac-1 expression and retained Ly-1 expression. They were morphologically macrophages, nonspecific-esterase-positive, and showed phagocytosis of latex beads. These results support evidence for a close relationship between the myeloid and Ly-1+ B-cell pathways of differentiation, and indicate that our IL- 5-dependent clones are multipotential intermediates in differentiation from pro-B cells to B cells and macrophages

Characteristics of energetic electron precipitation associated with chorus emissions and pulsating aurora observed at Syowa Station: A case study on 17 May 2007

第3回極域科学シンポジウム/第36回極域宙空圏シンポジウム 11月26日（月）、27日（火） 国立極地研究所 2階ラウン

Epigenetic Silencing of HOPX Promotes Cancer Progression in Colorectal Cancer

AbstractHomeodomain-only protein X (HOPX)-β promoter methylation was recently shown to be frequent in human cancers and was suggested as tumor suppressor gene in esophageal and gastric cancer. The aim of this study was to investigate the mechanistic roles of HOPX-β promoter methylation and its clinical relevance in colorectal cancer (CRC). HOPX-β promoter methylation was assessed in human CRC cell lines and 294 CRC tissues. HOPX mRNA and protein levels were measured in relation to HOPX-β promoter methylation. The effects of forced HOPX expression on tumorigenesis were studied using in vitro and in vivo assays. The association between HOPX-β promoter methylation and clinical relevance of CRC patients was determined. HOPX-β promoter methylation is cancer-specific and frequently found in CRC cell lines and tissues, resulting in the down-regulation of HOPX mRNA and protein levels. In CRC cell lines, forced expression of HOPX suppressed proliferation, invasion, and anchorage-independent growth. DNA microarray analyses suggested critical downstream genes that are associated with cancer cell proliferation, invasion or angiogenesis. In a mouse xenograft model, HOPX inhibited tumorigenesis and angiogenesis. Finally, HOPX-β promoter methylation was associated with worse prognosis of stage III CRC patients (hazard ratio= 1.40, P = .035) and also with poor differentiation (P = .014). In conclusion, HOPX-β promoter methylation is a frequent and cancer-specific event in CRC progression. This epigenetic alteration may have clinical ramifications in the diagnosis and treatment of CRC patients

肺における散布性粒状病変の分布パターン : 気道散布性病変と血行散布性病変のX線病理学的研究

The distribution pattern of disseminated small lung nodules was radiologically stud- ied with special reference to the relationship between lesions and the bronchial branching system using inflated and fixed lungs of 6 cases Obtained from autopsy. The bronchogenous spread lesions, which were seen in endobronchial tuberculosis and bronchopneumonia, were located in the centriacinar portion of the secondary lobule. Their distribution patterns were regular and corresponded to the bronchial branching pattern. On the other hand, the hematogenous spread lesions, which were seen in miliary tuberculosis and pulmonary metastasis of carcinoma, had no relation to airway structures. They were randomly distributed regardless of bronchial branching. Recognition of these different distribution patterns is important for evaluating diffuse lung diseases by computed tomography

Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage

BACKGROUND: Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis. METHOD: We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose. RESULTS: The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients. CONCLUSION: These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

北海道とフィンランドのサルコイドーシス : 比較研究の結果

Two comparative Finnish-Japanese sarcoidosis studies were carried out. One study compared the frequencies of sarcoidosis in 1984 in Hokkaido and Finland. We found a significantly and approximately four times higher prevalence and incidence of sarcoidosis in Finland than in Hok kaido ; prevalence 28.2/100,000 in Finland and 7.2/100,000 in Hokkaido ; incidence ll.4/100,000 in Fin land and 2.8/100,000 in Hokkaido, The other study compared the clinical picture and prognosis of sarcoidosis in two large hospital series ; 686 patients in Sapporo and 571 patients in Mjolbolsta, Fin land. The sex ratio was the same with a slight female predominance in both hospitals. The Japanese patients were younger at the time of diagnosis (mean age 30 years in Sapporo compared with 42 years in Mjolbolsta), although 50% of the patients in both series had been detected via rou tine health screening procedures. Among the symptomatic patients the mode of presentation of the disease varied considerably with eye symptoms as the dominating in Sapporo, but with respiratory symptoms and Lofgren\u27s syndrome in Finland. Stage I disease was more frequent in Sapporo, (57% of the patients compared with 48% in Finland) whereas more Finnish patients had parenchymal lesions. Extrapulmonary manifestations of sarcoidosis were more often diagnosed in Sapporo ; main ly because of the eye lesions. The prognosis of pulmonary sarcoidosis in Finland was significantly less favourable than the prognosis of the Japanese patients

Hydrogen Isotope (H2 and D2) Sorption Study of CHA-Type Zeolites

Using either single H2 and D2 or H2-D2 mixed gases, the sorption abilities of CHA (chabazite)-type zeolites ion-exchanged with K, Na, or Ca were studied at 77, 201, and 250 K. The LTA (Linde Type A) (3A) and FAU (faujasite)-type zeolites were also examined for comparison. The pore diameters in these materials were found to decrease on the order of FAU > Ca-CHA > [K-CHA, Na-CHA, and LTA(3A)]. The quantities of D2 adsorbed on these zeolites were larger than the amounts of H2. At higher temperatures, the CHA-type zeolites having smaller pores exhibited superior D2/H2 selectivity compared with the LTA(3A) and FAU, suggesting that hydrogen isotope separation using zeolites is affected by pore size

Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning

Long-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected. We found that fiberoptic illumination to Purkinje cells expressing PhotonSABER in vivo inhibited cerebellar motor learning during adaptation of the horizontal optokinetic response and vestibulo-ocular reflex, as well as synaptic AMPA receptor decrease in the flocculus. Our results demonstrate that LTD and AMPA receptor endocytosis at specific neuronal circuits were directly responsible for motor learning in vivo