Cloning of an isoform of mouse TGF-β type II receptor gene

AbstractA variant of transforming growth factor-β type II receptor (TGF-βRII) cDNA was isolated from a mouse brain cDNA library. The predicted receptor is identical to previously reported mouse TGF-βRII except that the isoform has an insertion sequence of 25 amino acids in the predicted ligand-binding domain. By the use of reverse transcription-polymerase chain reaction (RT-PCR), transcripts for both isoforms were detected in all tissues and developing embryos examined. The isoform transiently expressed in COS cells showed a similar ligand-binding specificity to authentic TGF-βRII. These results suggest that the mouse TGF-βRII gene generates multiple isoforms, possibly by alternative splicing, as reported for activin type IIB receptor; and an isoform which has the extra sequence in the ligand-binding domain is also involved in the TGF-β signal transduction

進行下部直腸癌に対する術前化学放射線療法(CRT:chemoradiotherapy)の治療効果に関する免疫学的検討

学位の種別:課程博士University of Tokyo(東京大学

Influence of Cigarette Smoking on Estimated Glomerular Filtration Rate (eGFR) in Japanese Male Workers

The link between changes in estimated glomerular filtration rate (eGFR) and cigarette smoking was evaluated in Japanese male workers with a 5-year follow-up. We examined the data of 456 Japanese male workers, aged 22-70 years, who were taking no medications, and from this group, 286 men (43.5±8.2 years) were followed for 5-years. Habits of cigarette smoking were obtained during interviews by well-trained staff. The influence of cigarette smoking on eGFR was evaluated. In the first analysis, there was no significant difference in eGFR between subjects with and without cigarette smoking. In the second analysis, eGFR was significantly reduced after 5 years in all subjects. Changes in eGFR in subjects with cigarette smoking (－1.90±12.31ml/min/1.73m2) were significantly smaller than those in subjects without cigarette smoking (－4.97±12.05ml/min/1.73m2). At follow-up, we found that eGFR was weakly and negatively correlated with the number of cigarettes smoked (/day). The present study indicated that cigarette smoking may be an important modifiable factor for eGFR in Japanese male workers who are not taking any medications

Somatosensory Evoked Potential (SEP) in schizophrenics

The differences between schizophrenics and healthy subjects in Somatosensory Evoked Potential (SEP) were studied with 174 schizophrenics (98 male and 76 female) and 200 healthy subjects (100 male and 100 female). SEPs evoked by electric stimuli to the right median nerve were recorded through the two derivations (monopolar : C3’→A1+2; bipolar: C3’→Cz), averaging 100 responses, with 1024 msec of analysis time. Individual SEPs were subjected to the component analysis, and the following statistically significant results were obtained. 1. In male schizophrenics, the peak latencies of SEP components were significantly longer in short-latency component, P1 (bipolar), compared with healthy subjects, and shorter in middle-latency component, P2. In female schizophrenics, those were longer in middle-latency components, N2, P3, N3 (monopolar), and N1, P3, N3 (bipolar). 2. The inter-peak amplitudes in schizophrenics of both sexes were significantly larger in middle-latency components without any changes in short-latency components. 3. A few components with significant differences in latencies and inter-peak amplitudes between the subjects taking neuroleptics more than 600 mg, in chlorpromazine equivalent values, or not, as well as between medicated and unmedicated subjects, coincided with those also between the schizophrenics and healthy subjects. Theses differences in SEPs confirmed in the present study, regardless of schizophrenic subtypes, suggest the dysfunction in somatosensory information processing in schizophrenics, and SEP abnormalities may serve as possible elctrophysiological indices for cognitive dysfunction in schizophrenics

Visual Evoked Potential (VEP) in schizophrenics

The differences between schizophrenics and healthy subjects in Visual evoked potential (VEP) were studied with 174 schizophrenics (98 male and 76 female) and 200 healthy subjects (100 male and 100 female). VEPs evoked by flash stimuli were recorded through the two derivations (monopolar: O1→A1+2; bipolar: O1→Cz), averaging 100 responses, with 1024 msec of analysis time. Individual VEPs were subjected to the component analysis, and the following statistically significant results were obtained. 1. In schizophrenics, the latencies in short-latency components were significantly longer in P2 (male, monopolar), N2, P3, N3 (male, bipolar) and N3 (female, monopolar). Those in middle-latency components were significantly shorter in P4~N5 (male, monopolar) and P6 (female). 2. The inter-peak amplitudes in short-latency components were significantly smaller in P3-N3 (male, mopolar), and larger in P1-N1, N1-P2, P2-N2 (male, bipolar). Those in middle-latency components were significantly smaller in N3-P4 (male, monopolar), and larger in N4-P5 (female, bipolar). 3. A few components with significant differences in latencies and interpeak amplitudes between the subjects taking neuroleptics more than 600 mg, in chlorpromazine equivalent values, or not, as well as between medicated and unmedicated subjects, coincided with those also between the schizophrenics and healthy subjects. Theses differences in VEPs confirmed in the present study, regardless of schizophrenic subtypes, suggest the dysfunction in visual information processing in schizophrenics, and VEP abnormalities may serve as possible elctrophysiological indices for cognitive dysfunction in schizophrenics

Challenge for multifaceted data acquisition around active volcanoes using uncrewed surface vessel

Monitoring of volcanic eruptions, the atmosphere, and the ocean, along with their scientific understanding, can be achieved through multifaceted observations that include camera images, topographic deformations, elastic waves, geology, and the chemical constituents and temperatures of air and water. However, regions of increased volcanic activity and/or shallow waters are difficult to access by crewed ship due to danger or grounding risk. To overcome these difficulties, we used an uncrewed surface vessel (USV), Bluebottle, to operate multiple observation around oceanic volcanoes in the Bonin Island arc in May 2023. Even under adverse sea conditions, the USV successfully reached a remote observation site, Nishinoshima volcano, which is about 130 km away from Chichijima Island where the USV started out from. The USV conducted five days of observations at shallower than 500 m water depth around Nishinoshima Island, the first time after violent eruptions of Nishinoshima in June 2020. The USV is equipped with various sensors and data collection technologies, including a single-beam echosounder, oceanographic and meteorological sensors, an Acoustic Doppler Current Profiler, and a time-lapse camera. These tools have provided a multi-dimensional view of the underwater landscape and marine conditions near the volcano for the first time in the world. We obtained new bathymetric data, sub-bottom images, and measurements of temperature, salinity, and pH. This study leverages advanced technologies and innovative methodologies to enhance our understanding of marine and geological phenomena

Decadal–centennial-scale solar-linked climate variations and millennial-scale internal oscillations during the Early Cretaceous

Understanding climate variability and stability under extremely warm ‘greenhouse’ conditions in the past is essential for future climate predictions. However, information on millennial-scale (and shorter) climate variability during such periods is scarce, owing to a lack of suitable high-resolution, deep-time archives. Here we present a continuous record of decadal- to orbital-scale continental climate variability from annually laminated lacustrine deposits formed during the late Early Cretaceous (123–120 Ma: late Barremian–early Aptian) in southeastern Mongolia. Inter-annual changes in lake algal productivity for a 1091-year interval reveal a pronounced solar influence on decadal- to centennial-scale climatic variations (including the ~ 11-year Schwabe cycle). Decadally-resolved Ca/Ti ratios (proxy for evaporation/precipitation changes) for a ~ 355-kyr long interval further indicate millennial-scale (~ 1000–2000-yr) extreme drought events in inner-continental areas of mid-latitude palaeo-Asia during the Cretaceous. Millennial-scale oscillations in Ca/Ti ratio show distinct amplitude modulation (AM) induced by the precession, obliquity and short eccentricity cycles. Similar millennial-scale AM by Milankovitch cycle band was also previously observed in the abrupt climatic oscillations (known as Dansgaard–Oeschger events) in the ‘intermediate glacial’ state of the late Pleistocene, and in their potential analogues in the Jurassic ‘greenhouse’. Our findings indicate that external solar activity forcing was effective on decadal–centennial timescales, whilst the millennial-scale variations were likely amplified by internal process such as changes in deep-water formation strength, even during the Cretaceous ‘greenhouse’ period

Usefulness of central venous oxygen saturation monitoring during bidirectional Glenn shunt

A PediaSat(TM) oximetry catheter (PediaSat : Edwards Lifesciences Co., Ltd., Irvine, CA, U.S.A.), which facilitates continuous measurement of central venous oxygen saturation (ScvO2), may be useful for surgery for pediatric congenital heart disease. We used PediaSat during a bidirectional Glenn shunt. The patient was a 13-month-old boy. Under a diagnosis of left single ventricle (pulmonary atresia, right ventricular hypoplasia, atrial septal defect) and residual left aortic arch/left superior vena cava, a modified right Blalock- Taussig shunt was performed. Cyanosis deteriorated, so a bidirectional Glenn shunt was scheduled. After anesthesia induction, a 4.5 Fr double-lumen (8 cm) PediaSat was inserted through the right internal jugular vein for continuous ScvO2 monitoring. Furthermore, the probe of a near-infrared, mixed blood oxygen saturation-measuring monitor was attached to the forehead for continuous monitoring of the regional brain tissue mixed blood oxygen saturation (rSO2) (INVOS(TM) 5100C, Covidien ; Boulder, CO, U.S.A.). Blockage of the right pulmonary artery and right superior vena cava decreased the oxygen saturation, ScvO2, and rSO2, but increased the central venous pressure. Although changes in ScvO2 were parallel to those in rSO2, the former showed more marked changes. A combination of ScvO2 and rSO2 for monitoring during Glenn shunt may be safer

The Effect of Enzymatically Polymerised Polyphenols on CD4 Binding and Cytokine Production in Murine Splenocytes

High-molecular weight polymerised polyphenols have been shown to exhibit anti-influenza virus, anti-HIV, and anti-cancer activities. The purpose of this study was to evaluate the immunomodulating activities of enzymatically polymerised polyphenols, and to clarify the underlying mechanisms of their effects. The cytokine-inducing activity of the enzymatically polymerised polyphenols derived from caffeic acid (CA), ferulic acid (FA), and p-coumaric acid (CoA) was investigated using murine splenocytes. Polymerised polyphenols, but not non-polymerised polyphenols, induced cytokine synthesis in murine splenocytes. Polymerised polyphenols induced several cytokines in murine splenocytes, with interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most prominent. The underlying mechanisms of the effects of the polymerised polyphenols were then studied using neutralising antibodies and fluorescent-activated cell sorting (FACS) analysis. Our results show that polymerised polyphenols increased IFN-γ and GM-CSF production in splenocytes. In addition, the anti-CD4 neutralised monoclonal antibody (mAb) inhibited polymerised polyphenol-induced IFN-γ and GM-CSF secretion. Moreover, polymerised polyphenols bound directly to a recombinant CD4 protein, and FACS analysis confirmed that interaction occurs between polymerised polyphenols and CD4 molecules expressed on the cell surface. In this study, we clearly demonstrated that enzymatic polymerisation confers immunoactivating potential to phenylpropanoic acids, and CD4 plays a key role in their cytokine-inducing activity