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Insulin stimulates translocation of glucose transporter 4 (GLUT4) from the perinuclear location to the plasma membrane. In the unstimulated state, intracellular vesicles containing GLUT4 are sequestered into specialized storage vesicles that have come to be known as the insulin-responsive compartment (IRC). The IRC is a functional compartment in the perinuclear region that is a target of the insulin signaling cascade, although its precise nature is unclear. Here, we report a novel molecular mechanism facilitating formation of the IRC.We determined synaptosomal-associated protein of 29 kDa (SNAP29) by mass spectrometry to be an EH domain-containing protein 1 (EHD1)-binding protein. Then, its expression was confirmed by western blotting. Subcellular localization of SNAP29 was determined by immunofluorescent microscopy. Interactions between SNAP29 and syntaxins were determined by immunoprecipitation. We measured glucose uptake and GLUT4 translocation in 3T3-L1 adipocyte expressing SNAP29 or silencing SNAP29.We found SNAP29 to be localized in the perinuclear region and to show partial co-localization with GLUT4 under basal conditions. We also found that SNAP29 binds to syntaxin6, a Qc-SNARE, in adipocytes. In SNAP29-expressing cells, vesicles containing GLUT4 were observed to aggregate around the perinuclear region. In contrast, when SNAP29 was silenced, perinuclear GLUT4 vesicles were dispersed throughout the cytosol. Insulin-stimulated glucose uptake was inhibited in both SNAP29-expressing and SNAP29-silenced cells.These data suggest that SNAP29 sequesters and anchors GLUT4-containing vesicles in the perinuclear region, and might have a role in the biogenesis of the perinuclear IRC.

Recent innovations and cost reductions in photogrammetry-based 3D modeling have enabled museum visitors to create 3D models based on photographs exhibited in galleries without breaking museum policies. While several museums make 3D museum data available on sharing platforms, museum visitors publish unofficial 3D data belonging to museum exhibits using a photogrammetry-based approach. This study shows that photogrammetry-based 3D models can be generated without breaking conventional photo policies (i.e., no use of flash and tripods), and that museum visitors can create commercial products based on these models. 3D models can enhance the value of science and promote broader and deeper interests in the natural sciences. However, the rights of owners of museum pieces are ambiguous with regard to the dissemination of unofficial data, and this also makes information attributable to the original specimen unclear, which can potentially lead to revenue loss. We propose a set of best practices for museum photo policies, which covers the data use of visitor-generated 3D models of displayed objects.

Vertebrates evolved tooth replacement over 400 million years ago. Over 200 million years later, the combination of vertical tooth replacement with thecodont implantation (teeth in bone sockets) has been considered a key morphological innovation in mammal evolution. We discovered that an extinct fish taxon, Serrasalmimus secans, that shows this same innovation in a lineage (Serrasalmimidae) that survived the end Cretaceous mass extinction. Carnassial teeth are known in both mammals and pycnodont fish, but these teeth do not share the same tissues nor developmental processes. Therefore, a serrasalmimid pycnodont fish independently acquired mammal-like tooth replacement and implantation, thus showing that fishes and mammals evolved convergent carnassial dental morphologies at about the same time, around 60 Ma, in separate ecosystems.

Aims/introduction Double C2 domain protein b (DOC2b), one of the synaptotagmins, has been shown to translocate to the plasma membrane, and to initiate membrane‐fusion processes of vesicles containing glucose transporter 4 proteins on insulin stimulation. However, the mechanism by which DOC2b is regulated remains unclear. Herein, we identified the upstream regulatory factors of DOC2b in insulin signal transduction. We also examined the role of DOC2b on systemic homeostasis using DOC2b knockout (KO) mice. Materials and Methods We first identified DOC2b binding proteins by immunoprecipitation and mutagenesis experiments. Then, DOC2b KO mice were generated by disrupting the first exon of the DOC2b gene. In addition to the histological examination, glucose metabolism was assessed by measuring parameters on glucose/insulin tolerance tests. Insulin‐stimulated glucose uptake was also measured using isolated soleus muscle and epididymal adipose tissue. Results We identified an isoform of atypical protein kinase C (protein kinase C iota) that can bind to DOC2b and phosphorylates one of the serine residues of DOC2b (S34). This phosphorylation is essential for DOC2b translocation. DOC2b KO mice showed insulin resistance and impaired oral glucose tolerance on insulin and glucose tolerance tests, respectively. Insulin‐stimulated glucose uptake was impaired in isolated soleus muscle and epididymal adipose tissues from DOC2b KO mice. Conclusions We propose a novel insulin signaling mechanism by which protein kinase C iota phosphorylates DOC2b, leading to glucose transporter 4 vesicle translocation, fusion and facilitation of glucose uptake in response to insulin. The present results also showed DOC2b to play important roles in systemic glucose homeostasis.

A woman in her fifties showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noted to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically, revealing the presence of the SFTS virus (SFTSV) antigen. The sick cat showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. The patient had no history of tick bites, and did not have skin lesions suggestive of these. She had not undertaken any outdoor activities. It is highly possible that the patient was infected with SFTSV through the sick cat&rsquo, s bite. If a patient gets sick in an SFTS-endemic region after being bitten by a cat, SFTS should be considered in the differential diagnosis.

A woman in her 50s showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noticed to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically for SFTSV antigen, which revealed the presence of SFTSV antigen. The sick cat also showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. It is highly possible that the patient was infected with SFTSV through the sick cat’s bite. If a patient gets sick in an SFTS-endemic region after a cat bite, SFTS should be considered in the differential diagnosis.

Desmostylus and Paleoparadoxia are extinct marine mammals belonging to the order Desmostylia that existed in the period between the late Oligocene and middle Miocene. All occurrences of their fossils are limited to marine strata along the coasts of the North Pacific Ocean. Although these two genera have similar body form, their paleoecologies including habitat preferences are thought to be different because their cranial structures are distinctive as well as they have been known separately in different localities. We estimated the depositional depths of their fossil occurrences on the basis of the associated mollusks and benthic foraminiferal assemblages from 45 desmostylian localities. Only data on complete or partial skeletal specimens were considered in order to exclude cases of reworking and pre-burial drift of carcasses that would confound our inference. Our results indicate that the depositional environment of Desmostylus specimens was restricted to the inner sublittoral zone shallower than 30 m in depth whereas that of Paleoparadoxia specimens ranged from the inner sublittoral (0–50 m) to upper bathyal zone (between 150 and 400 and 500 m). This finding indicates that Desmostylus lived in nearshore water while Paleoparadoxia foraged in a relatively deep, offshore water. The depositional segregation of these two genera most likely reflects their different habitat preferences.

Here, we report a new ‘discovery’ of a desmostylian fossil in the geological collection at a national university in Japan. This fossil was unearthed over 60 years ago and donated to the university. Owing to the original hand-written note kept with the fossil in combination with interview investigation, we were able to reach two equally possible fossil sites in the town of Tsuchiyu Onsen, Fukushima. Through the interviews, we learned that the fossil was discovered during construction of a debris flow barrier and that it was recognized as a ‘dinosaur’ bone among the locals and displayed in the Village Hall before/until the town experienced a fire disaster in 1954. As scientific findings, the fossil was identified to be a right femur ofPaleoparadoxia(Desmostylia), which shows well-preserved muscle scars on the surface. The age was estimated to be 15.9 Ma or younger in zircon-dating. This study shows an excellent case that historical and scientific significances could be extracted from long-forgotten uncatalogued specimens as long as the original information is retained with the specimens.

A new specimen of Paleoparadoxia found from a marine lower Miocene deposit in the Chikubetsu area, Hokkaido, Japan, is described. The material consists of a distal part of the scapula, proximal end of the humerus from the right side, as well as a fragmentary rib, preserved in a float of calcareous fine sandstone. The specimen is referred to the order Desmostylia and subsequently to the genus Paleoparadoxia sp. The well preserved shoulder girdle of this specimen provides the first detailed morphology of this anatomical region in Paleoparadoxia. We compared the specimen with a wide range of desmostylid samples to reveal new diagnostic characters for the genus, such as the greater tubercle extending toward the proximal side above the head and the distinct lesser tubercle located on the medial side, projected medially. The lower Miocene Sankebetsu Formation outcrops in the area where the float was found, and the lithology and associated fossil fauna of the float indicate that it was derived from ther...

Desmostylia is a clade of marine mammals belonging to either Tethytheria or Perissodactyla. Rich fossil records of Desmostylia were found in the Oligocene to Miocene strata of the Northern Pacific Rim, especially in the northwestern region, which includes the Japanese archipelago. Fossils in many shapes and forms, including whole or partial skeletons, skulls, teeth, and fragmentary bones have been discovered from this region. Despite the prevalent availability of fossil records, detailed taxonomic identification based on fragmentary postcranial materials has been difficult owing to to our limited knowledge of the postcranial diagnostic features of many desmostylian taxa. In this study, I propose the utilization of diagnostic characters found in the humerus to identify desmostylian genus. These characters can be used to identify isolated desmostylian humeri at the genus level, contributing to a better understanding of the stratigraphic and geographic distributions of each genus.

A 69-year-old man complained of knee pain, subsequent polyarthralgia, and pains of the muscles of the pelvic girdle and thighs. At the same time, erythema of the face and hands appeared. Biopsy of the skin and muscle revealed non-caseating granuloma of epithelioid cells. The level of serum angiotensin-converting enzyme was normal, but that of lysozyme was elevated. Chest X-ray and CT did not show bilateral hilar lymphadenopathy (BHL) but revealed infiltrative ground glass appearance-like shadows of both lungs, and a Ga scintigram disclosed accumulation in the right hilar region, but not in the muscles. These complaints were quickly ameliorated by the administration of prednisolone. The present patient represented a rare case of acute musculoskeletal system involvement in sarcoidosis not typical of Löfgren's syndrome.

WHO分類により骨髄異形成症候群／骨髄増殖性疾患myelodysplastic/myeloproliferative diseases (MDS) / (MPD) に分類されるPhiladelphia (Ph) 染色体陰性の非定型慢性骨髄性白血病atypical CML (aCML) 2例と慢性骨髄単球性白血病chronic myelomonocytic leukemia (CMML) 1例を経験した．aCMLの2症例は白血球増加，各成熟段階の顆粒球系細胞の増加，顆粒球の異形成を認めたが染色体異常は認めなかった．CA (cytosine arabinoside, aclacinomycin) 療法，interferon (IFN) -α,hydroxyurea (HU) にて治療を行うも不応性であり脳出血を起こし死亡した．CMMLの症例は当初は骨髄線維化を伴うMDSとして発症したが後に著明な単球増加を伴うCMMLへと病型移行した．CA療法，VP-16を投与するも効果なく肺真菌感染症にて死亡した．形態学のみでこれらの疾患の診断を行うのは完全ではない．将来的には分子生物学的異常が解明され，それに基づく診断と特異的治療法の開発が望まれる．

68歳，女性．２ヵ月前より両大腿筋肉痛，筋力低下，両肩・両膝関節痛が出現し，立ち上がり，歩行が困難になった．同時期より眼瞼下垂，上下肢の易疲労性を認めた．抗核抗体は陽性，抗アセチルコリンレセプター抗体は著明に高値，抗Jo-1抗体は陰性であった．エドロフォニウムテストにより眼瞼下垂は改善したが，上下肢の筋力は改善しなかった．一方CKは上昇し大腿筋生検では筋線維の不揃いの変性，著明なリンパ球や好中球などの炎症細胞浸潤が認められ，筋電図は低電位であり反復刺激ではwaningがみられた．これらの所見から重症筋無力症と，多発筋炎の同時期の合併と考えられた．プレドニゾロンの投与により徐々に大腿の筋力は回復し歩行可能になったが四肢の易疲労性，眼瞼下垂は残り，後に塩化アンベノニウムを併用することで，これらの症状は改善した．

A 48-year-old man had a 30-year history of hemolytic anemia of undetermined cause. Spherocytes were not observed, osmotic fragility was normal, and red cell enzyme activities were normal. His brother and daughter also had hemolytic anemia. The brother had previously undergone splenectomy, and the anemia had been ameliorated. In the proband and daughter, no abnormal hemoglobin was apparent in the results of isoelectric focusing and DEAE anion-exchange high-performance liquid chromatography analyses. On evaluation with the isopropanol test, unstable hemoglobin was not observed in the proband but was detected in the daughter. There was also a decreased ratio of 3 globin/3 globin chain production. Analysis of the 32 gene demonstrated the presence of a mutation (alpha43 [CE1] Phe --Leu), hemoglobin Hirosaki.

心筋梗塞によって発生する心室中隔穿孔は死に直結する重篤な合併症である.今回,80歳男性の本症患者の結腸癌によるイレウスの手術の麻酔を経験した.麻酔導入はフェンタニール,サイアミラールで行ない,硬膜外麻酔と酸素,笑気,セボフルレンの吸入で麻酔を維持した.本症の麻酔管理では肺動脈圧を上昇させないことが要点と考えられたので,硬膜外麻酔を主体として自発呼吸下で行なうことにしたが,自発呼吸が出現せず調節呼吸となった.しかし,硬膜外注入で肺動脈圧は低下し,硬膜外麻酔は有用と考えられた.また,心臓壁の運動の観察に腹部臓器用ではあったが,超音波ファイバースコープは有用なモニタであった.手術は無事終了し16日後に退院した.

Isolated extramedullary (EM) relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare. Predisposing factors include CD56 expression and the chromosomal abnormality t(8;21). We describe an AML patient showing the chromosomal abnormality t(8;21) and CD56 expression who experienced a unique EM relapse after allo-HSCT. Approximately 10 months after allo-HSCT, he experienced relapse involving the femur and lumbar vertebrae and, subsequently, an EM relapse of the stomach. Although we administered only local radiotherapy and not systemic chemotherapy, he showed no bone marrow relapse on long-term follow-up after achieving complete hematological remission. These findings suggest that the graft-versus-leukemia effect may preferentially maintain marrow remission rather than prevent EM relapse. In addition, our findings show that extended survival is possible after EM relapse following allo-HSCT in patients with marrow hematopoiesis of donor origin, and that augmentation of the graft-versus-leukemia effect may be useful.

Plasma and red blood cells cyanide concentrations during hypotension induced by sodium nitroprusside and a nitroprusside-trimetaphan mixture were studied in 29 male rabbits under halothane anesthesia. They were randomly divided into three groups; Nitroprusside (group N; n = 10), A nitroprusside-trimetaphan mixture (group M; n = 10), Controls (group C; n = 9). No changes were noted in plasma and red blood cells cyanide concentrations in group C throughout the experiment. During and after induced hypotension, in group N, plasma cyanide concentration was significantly higher than the control value. The maximum increase occurred 60min after induction of hypotension and the highest concentration of plasma cyanide was six times the control value. In contrast, in group M, plasma cyanide concentration was unchanged from the control value. However, during and after induced hypotension, red blood cells cyanide concentrations of group N and group M were significantly higher compared with the control values. Red blood cells concentrations of cyanide increased for 30 and 60 min during induced hypotension in group N (27.11 +/- 3.9 micrograms.ml-1, P less than 0.001, 46, 73 +/- 4.7 micrograms.ml-1, P less than 0.001, respectively) and in group M (0.31 +/- 0.05 micrograms.ml-1, P less than 0.05, 0.29 +/- 0.03 micrograms.ml-1, P less than 0.05, respectively). In conclusion, the data suggest that a nitroprusside-trimetaphan mixture is a safe method for hypotensive anesthesia.

A 56-year-old man complained of fever, anemia, thrombocytopenia and lymph node swelling. Biopsy of the lymph node demonstrated angioimmunoblastic T cell lymphoma (AITL) with the loss of normal architecture, proliferation of neoplastic T cells, small vessels mixed with eosinophils and plasma cells. Aspiration of bone marrow was dry tap, and biopsy demonstrated myelofibrosis with increased proliferation of reticulin fiber. Markedly elevated plasma levels of transforming growth factor beta1 (TGF-beta1) and soluble interleukin-2 receptor (sIL-2R) were observed, and that of platelet growth factor (PDGF) AB was slightly elevated. After chemotherapy, remission of lymphoma was achieved. The aspiration of bone marrow became possible, and the level of TGF-beta1 and PDGF AB showed normalization; thus, myelofibrosis was reversible.

The patient, a 20-year-old male, was found to have a slightly prolonged prothrombin time (PT). No episodes of bleeding were noted. The measurement of coagulation factors revealed that the level of factor X (FX) activity was solely deficient, 51% (normal range: 70–130% ), and that of FX antigen was 100%. Analysis of the entire FX gene revealed the novel missense mutation of GTG to ATG, resulting in the substitution of the 196th amino acid valine → methionine. The mother and younger brother had a normal PT time and expressed no episode of bleeding. The mother exhibited a normal level of FX activity and antigen; however the younger brother showed a slight decrease in both the parameters. This mutation was not observed in the mother and younger brother. Polymorphism is not observed at this point in healthy persons. The present novel FX mutation was named FX Hofu.

The patient had been diagnosed with hereditary protein C deficiency. She recently developed acute myeloblastic leukemia (AML). Chemotherapy for AML by cytosine arabinoside, aclarubicin followed by granulocyte colony-stimulating factor (CAG) was started. Disseminated intravascular coagulation (DIC) was observed, however thromboembolic complication was not observed during the hospital course. Hematological remission was not obtained, and the patient died of pseudomembranous pancolitis. Whether the development of these rare disorders of hereditary protein C and AML are coincidental, or involve a causal relationship remains unknown.

A 72-year-old female developed pancytopenia 4 years after breast cancer surgery. She had received regional radiation postoperatively, and tamoxifen for 4 years. Bone marrow examination demonstrated immature myeloblasts and dysplastic cells. Myelodysplastic syndrome (MDS) of refractory anemia with excess blasts (RAEB) was diagnosed, and the patient died of cerebral hemorrhage 4 months after the diagnosis of RAEB. Radiation and the administration of tamoxifen were suspected to have played a role in the development of secondary MDS.

A 51-year-old man developed anemia, and was diagnosed with pure red cell aplasia through the absence of erythroid progenitors. Initially, he was treated with cyclosporine and prednisolone for 6 months but they were ineffective. Large granular lymphocyte (LGL) leukemia with the T-cell gamma delta phenotype evolved after 6 months showing CD2+, CD3+, CD8- and CD56- with the T-cell receptor beta gene rearrangement, clonalities of gamma and delta genes and complex chromosome abnormality simultaneously with hemophagocytic syndrome (HPS). Epstein-Barr virus (EBV) genomic DNA was detected in the bone marrow cells. Administration of bolus methylprednisolone was ineffective, and the patient died one month later. In the present patient, it seemed that lymphoproliferative disease of large granular lymphocytes (LDGL) manifested initially as PRCA, gammadelta LGL leukemia evolved, and finally fatal HPS become complicated, presumably caused by the EBV reactivation in the immunodeficiency state with the administration of immunosuppressants.

Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg(-1) of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg(-1)) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg(-1) CGRP but remained unchanged at the 40 μg·kg(-1) infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg(-1). In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg(-1) produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia.

A new fringe-scanning microscope based on a coherence probe microscope is described for measuring both the surface profile and the local material of a heterogeneous sample in nanometer depth resolution. The basic configuration is a white-light double-beam interferometer with either a Michelson or Mirau objective lens. The sample stage is moved down during the measurement and an interference image is collected at every stage-height. The surface profile is reconstructed in the computer by tracing the darkest point of the white- light interferogram for each pixel. The surface material is identified pixel by pixel by calculating the amplitude and the phase reflectivity of the spectrum by Fourier transforming a local interferogram or taking a cross-correlation of it with reference ones. Experimental examples of surface profile reconstruction, including a sample with film on it, are shown. An experimental result of local material identification is also presented.