Fucosyltransferase 1 Mediates Angiogenesis in Rheumatoid Arthritis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108009/1/art38648.pd

Monocyte or white blood cell counts and β₂ microglobulin predict the durable efficacy of daratumumab with lenalidomide

BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts

Circulating KCNH2 Current-Activating Factor in Patients with Heart Failure and Ventricular Tachyarrhythmia

It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF.We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia.Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF

Primary cilia disappear in rat podocytes during glomerular development

Most tubular epithelial cell types express primary cilia, and mutations of primary-cilium-associated proteins are well known to cause several kinds of cystic renal disease. However, until now, it has been unclear whether mammalian podocytes express primary cilia in vivo. In this study, we determined whether primary cilia are present in the podocytes of rat immature and mature glomeruli by means of transmission electron microscopy of serial ultrathin sections. In immature glomeruli of fetal rats, podocytes express the primary cilia with high percentages at the S-shaped body (88 ± 5%, n = 3), capillary loop (95 ± 4%, n =  4), and maturing glomerulus (76 ± 13%, n = 5) stages. The percentage of ciliated podocytes was significantly lower at the maturing glomerulus stage than at the former two stages. In mature glomeruli of adult rats, ciliated podocytes were not found at all (0 ± 0%, n = 11). These findings indicate that the primary cilia gradually disappear in rat podocytes during glomerular development. Since glomerular filtration rate increases during development, the primary cilia on the podocytes are subjected to a stronger bending force. Thus, the disappearance of the primary cilia presumably prevents the entry of excessive calcium-ions via the cilium-associated polycystin complexes and the disturbance of intracellular signaling cascades in mature podocytes

Delaying repatriation: Japanese technicians in early postwar China

Research on the Japanese living in Manchukuo in August 1945 has generally fostered the assumption that all Japanese there wanted to return to Japan as soon as possible. Yet, some made the conscious and voluntary decision to stay, at least for the short to medium term. Among those who chose to delay repatriation were a number of technicians employed by Mantetsu’s (South Manchurian Railroad Company) Ch¯uo Shikenjo. This paper looks at the political and personal realities faced by these technicians when making their decisions as whether to stay or leave in terms of the concepts of voluntary and involuntary repatriation. It shows that the circumstances faced, and consequently the decisions made by the technicians, differed over time. It argues that there were three main reasons behind any decision to stay: pragmatism, a sense of responsibility for Japan’s activities during the war and a sense of loyalty

ドッキョウ イカ ダイガク ビョウイン コキュウキ・アレルギー ナイカ ニオケル HIVカンセン カンジャ ノ カイセキ : トクニ ニューモシスチス ハイエン ノ ガッペイ レイ ニ ツイテ

獨協医科大学病院呼吸器・アレルギー内科を受診したHIV感染者を解析し,わが国および栃木県のHIV 感染者との比較検討を行った.対象は,2002年7月より2009年6月までの間,当科に受診歴のある34名(男27名,女7名,日本人29名,外国人5名),平均年齢は44.2歳(29歳&#12316;67歳).男性の感染理由は,異性間(風俗,不特定)40.7%,同性間37.0%,女性はパートナーからの感染が57.1 %であった.64.7%がAIDS 発症によりHIV感染が判明し,HIV感染判明時の精査では79.4%がAIDSを発症しており,全症例の55.9%にニューモシスチス肺炎の合併を認めた.治療開始が推奨されているCD4陽性細胞低値(350/m l以下)は,97.1%の症例に認めた.以上の結果より,感染理由や年齢層については,全国の平均と同様な傾向を認めた.全国的には,HIV感染判明者の約7割がAIDS 発病前のキャリアの状態でHIV 感染が判明し,栃木県でも同様の傾向である.しかし,当科では大多数がAIDS 発症後およびAIDS 発症直前の低免疫状態でHIV 感染が判明しており,早期発見および早期介入が課題と考えられた.To be clear the clinical characteristics in Tochigi, we analyzedpatients with HIV infection in our department. Patientswith HIV infection between July 2002 and June 2009were 34 subjects (Man:Woman=27:7, Japanese:Foreigner=29:5), and mean age was 44.2 years old. In reasonof HIV infection for men, men who were infected by sexualintercourse with indefinite women were 40.7 % and menwho were infected by sexual intercourse with men were37.0 %. Women who were infected by their partners were57.1 %. 64.7 % of patients were recognized HIV infection byshowing AIDS. 79.4% of patients already had complicationsindicating AIDS, when they came to our hospital, and 55.9% of patients had pneumocystis jiroveci pneumonia. In 97.1% of patients, the number of CD4 positive cells were under350/m l. In conclusion, around 70 % of patients were recognizedHIV infection before they become AIDS in Japan. But,a large majority of patients in our department were withbecoming AIDS or just before AIDS. We need to developthe system of early intervention for HIV infection

Western Pacific Air-Sea Interaction Study

A01: Dynamics of Atmospheric CompositionA Study on the Production and Emission of Marine-Derived Volatile Halocarbons / Y. Yokouchi, A. Ooki, S. Hashimoto and N. Itoh : 05w-pass_001.pdfMeasurements of Gaseous Peroxides in the Oceanic Lower Atmosphere / S. Hatakeyama and T. Akatsuka : 06w-pass_027.pdfPhase Partitioning of NH3 and Gas to Particle Conversion / K. Osada : 07w-pass_033.pdfNew Particle Formation of Marine Aerosols / K. Miura, H. Furutani, Y. Iwamoto, K. Nagano, H. Kobayashi, M. Mochida, H. Mukai, S. Hashimoto, M. Takami and M. Uematsu : 08w-pass_037.pdfA Study of the Chemical Processes in Aerosols and Their Impacts on the Environment Using X-ray Absorption Fine Structure Spectroscopy / Y. Takahashi, M. Higashi, T. Furukawa, T. Miyoshi, M. Fujiwara and M. Uematsu : 09w-pass_043.pdfVariability in Mineral Dust Deposition over the North Pacific and Its Potential Impact on the Ocean Productivity / H. Fukushima : 10w-pass_051.pdfAtmosphere-Ocean Interaction through Atmospheric Aerosol Particles Observed in a Single Nanoparticle Aspect / H. Furutani, J. Jinyoung and M. Uematsu : 11w-pass_061.pdfSimultaneous Measurements of Hygroscopic Property and Cloud Condensation Nucleus Activity of Aerosol Particles of Marine Biogenic Origin / M. Mochida : 12w-pass_071.pdfEruption of Mt. Kilauea Impacted Cloud Droplet and Radiation Budget over North Pacific / I. Uno, K. Eguchi and K. Yumimoto : 13w-pass_083.pdfA02: Variability of Gas Exchanges at the Air-Sea InterfaceHigh-Resolution Measurement of Volatile Organic Compounds Dissolved in Seawater Using Equilibrator Inlet-Proton Transfer Reaction-Mass Spectrometry (EI-PTR-MS) / H. Tanimoto, S. Kameyama, Y. Omori, S. Inomata and U. Tsunogai : 14w-pass_089.pdfStudy of the Production Processes of Marine Biogenic Methane and Carbonyl Sulfide Using Stable Isotope Analysis / S. Toyoda, K. Yamada, Y. Ueno, K. Koba and O. Yoshida : 15w-pass_117.pdfLong-Term Changes of Greenhouse Gases in the Ocean and Their Feedback Effects on the Climate / Y. W. Watanabe, I. Yasuda and N. Tsurushima : 16w-pass_123.pdfTemporal and Spatial Variations in Carbonate System and Air-Sea CO2 Flux in the Kuroshio and Kuroshio Extension / H. Yoshikawa-Inoue, T. Midorikawa and T. R. Takamura : 17w-pass_151.pdfA03: Dynamics of the Marine EcosystemBioavailability and Biogeochemical Processes of Trace Metals in the Surface Ocean / S. Takeda, H. Obata, A. Okubo, M. Sato and Y. Kondo : 18w-pass_163.pdfDetailed Variations in Bioactive Elements in the Surface Ocean and Their Interaction with Microbiological Processes / H. Ogawa, K. Kogure, J. Kanda, F. Hashihama and M. Suzumura : 19w-pass_177.pdfPhotoheterotrophic Process in Surface Seawater Environments / K. Hamasaki, Y. Sato-Takabe, A. Taniguchi and Y. Tada : 20w-pass_199.pdfEcological Study of Bacterial Populations Related to Biogenic Gas Transformation in Marine Environments / K. Hamasaki, R. Kaneko, A. Mouri, Y. Tada, N. Kasamatsu-Takasawa and I. Nagao : 21w-pass_203.pdfA04: Modelling of the Interaction between the Ocean and the AtmosphereModeling for Evaluation and Prediction of Effects of Short-Term Atmospheric Disturbance on Air-Sea Material Cycling / M. Fujii and A. Tanaka : 22w-pass_211.pdfRelating Phytoplankton Pnysiology to North Pacific Biogeochemistry / S. L. Smith, M. N. Aita, M. Shigemitsu and Y. Yamanaka : 23w-pass_223.pdfCoupling of Physical and Bio-Geochemical Process and Monitoring Ocean Circulation Using Data Assimilation System / Y. Ishikawa, T. Awaji, M. Ikeda and T. Toyoda : 24w-pass_237.pdfPart of "Western Pacific Air-Sea Interaction Study

Western Pacific Air-Sea Interaction Study

A01: Dynamics of Atmospheric CompositionA Study on the Production and Emission of Marine-Derived Volatile Halocarbons / Y. Yokouchi, A. Ooki, S. Hashimoto and N. Itoh : 05w-pass_001.pdfMeasurements of Gaseous Peroxides in the Oceanic Lower Atmosphere / S. Hatakeyama and T. Akatsuka : 06w-pass_027.pdfPhase Partitioning of NH3 and Gas to Particle Conversion / K. Osada : 07w-pass_033.pdfNew Particle Formation of Marine Aerosols / K. Miura, H. Furutani, Y. Iwamoto, K. Nagano, H. Kobayashi, M. Mochida, H. Mukai, S. Hashimoto, M. Takami and M. Uematsu : 08w-pass_037.pdfA Study of the Chemical Processes in Aerosols and Their Impacts on the Environment Using X-ray Absorption Fine Structure Spectroscopy / Y. Takahashi, M. Higashi, T. Furukawa, T. Miyoshi, M. Fujiwara and M. Uematsu : 09w-pass_043.pdfVariability in Mineral Dust Deposition over the North Pacific and Its Potential Impact on the Ocean Productivity / H. Fukushima : 10w-pass_051.pdfAtmosphere-Ocean Interaction through Atmospheric Aerosol Particles Observed in a Single Nanoparticle Aspect / H. Furutani, J. Jinyoung and M. Uematsu : 11w-pass_061.pdfSimultaneous Measurements of Hygroscopic Property and Cloud Condensation Nucleus Activity of Aerosol Particles of Marine Biogenic Origin / M. Mochida : 12w-pass_071.pdfEruption of Mt. Kilauea Impacted Cloud Droplet and Radiation Budget over North Pacific / I. Uno, K. Eguchi and K. Yumimoto : 13w-pass_083.pdfA02: Variability of Gas Exchanges at the Air-Sea InterfaceHigh-Resolution Measurement of Volatile Organic Compounds Dissolved in Seawater Using Equilibrator Inlet-Proton Transfer Reaction-Mass Spectrometry (EI-PTR-MS) / H. Tanimoto, S. Kameyama, Y. Omori, S. Inomata and U. Tsunogai : 14w-pass_089.pdfStudy of the Production Processes of Marine Biogenic Methane and Carbonyl Sulfide Using Stable Isotope Analysis / S. Toyoda, K. Yamada, Y. Ueno, K. Koba and O. Yoshida : 15w-pass_117.pdfLong-Term Changes of Greenhouse Gases in the Ocean and Their Feedback Effects on the Climate / Y. W. Watanabe, I. Yasuda and N. Tsurushima : 16w-pass_123.pdfTemporal and Spatial Variations in Carbonate System and Air-Sea CO2 Flux in the Kuroshio and Kuroshio Extension / H. Yoshikawa-Inoue, T. Midorikawa and T. R. Takamura : 17w-pass_151.pdfA03: Dynamics of the Marine EcosystemBioavailability and Biogeochemical Processes of Trace Metals in the Surface Ocean / S. Takeda, H. Obata, A. Okubo, M. Sato and Y. Kondo : 18w-pass_163.pdfDetailed Variations in Bioactive Elements in the Surface Ocean and Their Interaction with Microbiological Processes / H. Ogawa, K. Kogure, J. Kanda, F. Hashihama and M. Suzumura : 19w-pass_177.pdfPhotoheterotrophic Process in Surface Seawater Environments / K. Hamasaki, Y. Sato-Takabe, A. Taniguchi and Y. Tada : 20w-pass_199.pdfEcological Study of Bacterial Populations Related to Biogenic Gas Transformation in Marine Environments / K. Hamasaki, R. Kaneko, A. Mouri, Y. Tada, N. Kasamatsu-Takasawa and I. Nagao : 21w-pass_203.pdfA04: Modelling of the Interaction between the Ocean and the AtmosphereModeling for Evaluation and Prediction of Effects of Short-Term Atmospheric Disturbance on Air-Sea Material Cycling / M. Fujii and A. Tanaka : 22w-pass_211.pdfRelating Phytoplankton Pnysiology to North Pacific Biogeochemistry / S. L. Smith, M. N. Aita, M. Shigemitsu and Y. Yamanaka : 23w-pass_223.pdfCoupling of Physical and Bio-Geochemical Process and Monitoring Ocean Circulation Using Data Assimilation System / Y. Ishikawa, T. Awaji, M. Ikeda and T. Toyoda : 24w-pass_237.pdfPart of "Western Pacific Air-Sea Interaction Study

Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor

Understanding brain development remains a major challenge at the heart of understanding what makes us human. The neocortex, in evolutionary terms the newest part of the cerebral cortex, is the seat of higher cognitive functions. Its normal development requires the production, positioning and appropriate interconnection of very large numbers of both excitatory and inhibitory neurons. Pax6 is one of a relatively small group of transcription factors that exert high-level control of cortical development, and whose mutation or deletion from developing embryos causes major brain defects and a wide range of neurodevelopmental disorders. Pax6 is very highly conserved between primate and non-primate species, is expressed in a gradient throughout the developing cortex and is essential for normal corticogenesis. Our understanding of Pax6’s functions and the cellular processes that it regulates during mammalian cortical development has significantly advanced in the last decade, owing to the combined application of genetic and biochemical analyses. Here we review the functional importance of Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of cortical layers and highlight important differences between rodents and primates. We also review the pathological effects of PAX6 mutations in human neurodevelopmental disorders. Finally, we discuss some aspects of Pax6’s molecular actions including its own complex transcriptional regulation, the distinct molecular functions of its splice variants and some of Pax6’s known direct targets which mediate its actions during cortical development