Decreased serum phosphate levels are a useful biomarker to predict occurrence and severity of cytokine release syndrome in chimeric antigen receptor T-cell therapy

サイトカイン放出症候群の発症と重症化を予見する新たな指標 --キメラ抗原受容体T細胞療法における血清リン値が鍵--. 京都大学プレスリリース. 2022-10-19

Effect of a Rehabilitation Program After Mesenchymal Stromal Cell Transplantation for Advanced Osteonecrosis of the Femoral Head: A 10-Year Follow-Up Study

Objective: To assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier. Design: Retrospective study. Setting: University clinical research laboratory. Participants: Patients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment. Intervention: A 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation. Main Outcome Measures: Radiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment. Results: Upon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation. Conclusions: The 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition

Clinical significance of nuclear non-phosphorylated beta-catenin in acute myeloid leukaemia and myelodysplastic syndrome

Wnt signaling activates the canonical pathway and induces the accumulation of non-phosphorylated beta-catenin (NPBC) in the nucleus. Although this pathway plays an important role in the maintenance of haematopoietic stem cells as well as in oncogenesis, the significance of nuclear NPBC remains unclear in malignant haematopoiesis. This study examined the expression of nuclear NPBC in bone marrow specimens from 54 and 44 patients with de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), respectively. On immunohistochemistry with an anti-NPBC antibody, the nuclei were positively stained in 22 and 18 of AML and MDS specimens, respectively. Staining of nuclear NPBC was associated with AML subtypes (M6 and M7), low complete remission (CR) rate, and poor prognosis. Nuclear NPBC was also associated with a high score when using the International Prognostic Scoring System (IPSS) for MDS and with −7/−7q and complex karyotypes. These findings suggest that in situ detection of nuclear NPBC by immunohistochemistry could provide new insights into the pathogenesis and prognosis of AML and MDS

Starch biosynthesis in rice endosperm requires the presence of either starch synthase I or IIIa

Starch synthase (SS) I and IIIa are the first and second largest components of total soluble SS activity, respectively, in developing japonica rice (Oryza sativa L.) endosperm. To elucidate the distinct and overlapping functions of these enzymes, double mutants were created by crossing the ss1 null mutant with the ss3a null mutant. In the F2 generation, two opaque seed types were found to have either the ss1ss1/SS3ass3a or the SS1ss1/ss3ass3a genotype. Phenotypic analyses revealed lower SS activity in the endosperm of these lines than in those of the parent mutant lines since these seeds had different copies of SSI and SSIIIa genes in a heterozygous state. The endosperm of the two types of opaque seeds contained the unique starch with modified fine structure, round-shaped starch granules, high amylose content, and specific physicochemical properties. The seed weight was ∼90% of that of the wild type. The amount of granule-bound starch synthase I (GBSSI) and the activity of ADP-glucose pyrophosphorylase (AGPase) were higher than in the wild type and parent mutant lines. The double-recessive homozygous mutant prepared from both ss1 and ss3a null mutants was considered sterile, while the mutant produced by the leaky ss1 mutant×ss3a null mutant cross was fertile. This present study strongly suggests that at least SSI or SSIIIa is required for starch biosynthesis in rice endosperm

Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling

健康・スポーツ科学科の科目と資格に対する学生ニーズ

The purpose of the research is to reconsider the curriculum in Department of Health and Sports. In this research, the consideration of each grade to subjects and qualifications was analyzed. The results were summarized as follows: 1． Students thought that the important subject studied at the university was“ Nutrition”,“ Medicine”, and “Couching”. 2． University students are aspiring becoming the teacher. College students are aspiring finding employment in the enterprise. 3． Students of any grade also think that the acquisition of the qualification is important. Especially, it thinks the acquisition of the teacher\u27s license to be very important. 4． Students had selected the qualification acquisition by“ Qualification concerning health” and“ Qualification concerning athlete”

Reactive arthritis induced by active extra-articular tuberculosis

RATIONALE: Rare cases of reactive arthritis induced by active extra-articular tuberculosis (Poncet disease) have been reported. Complete response to antitubercular treatment and evidence of active extra-articular tuberculosis are the most important clinical features of Poncet disease. We report the case of successfully treated a patient with reactive arthritis induced by active extra-articular tuberculosis with a TNF inhibitor after sufficient antitubercular treatment. PATIENT CONCERNS: A 56-year-old Japanese man was admitted to our department with polyarthralgia, low back pain, and high fever. The results of rheumatoid factor, anti-citrullinated protein antibody, human leukocyte antigen B27, and the assays for the detection of infections (with an exception of T-SPOT.TB) were all negative. Fluoro-deoxy-D-glucose-positron emission tomography with CT (PET/CT) showed moderate uptake in the right cervical, right supraclavicular, mediastinal, and abdominal lymph nodes. As magnetic resonance imaging and power Doppler ultrasonography showed peripheral inflammation (tendinitis, tenosynovitis, ligamentitis, and enthesitis in the limbs). DIAGNOSIS: A diagnosis of tuberculous lymphadenitis was eventually established on the basis of lymph node biopsy results. There was no evidence of a bacterial infection including acid-fast bacteria in his joints, and the symptoms of polyarthralgia and low back pain were improved but not completely resolved with NSAID therapy; in addition, a diagnosis of reactive arthritis induced by active extraarticular tuberculosis was made. INTERVENTIONS: The patient experienced persistent peripheral inflammation despite antitubercular treatment for more than nine months and was then successfully treated with a tumor necrosis factor inhibitor (adalimumab 40 mg every 2 weeks). OUTCOMES: Finally, the patient responded to the treatment and has been in remission for over 4 months as of this writing. LESSONS: In patients who present with symptoms associated with spondyloarthritis, it is important to distinguish between classic reactive arthritis and reactive arthritis induced by extra-articular tuberculosis infection. Introduction of biological agents should be carefully considered in settings where reactive arthritis induced by active extra-articular tuberculosis shows progression to chronicity despite sufficient antitubercular treatment

Rheumatoid arthritis-like active synovitis with T-cell activation in a case of idiopathic multicentric Castleman disease

RATIONALE: Idiopathic multicentric Castleman disease (iMCD) is a systemic disease with multiple regions of lymphadenopathy and systemic symptoms and associated with rheumatoid arthritis (RA) and collagen diseases. However, few reported have described the coexistence of iMCD and RA and the mechanisms by which iMCD induces arthritis remain elusive. We experienced a rare case of iMCD, wherein the patient exhibited symptoms of polyarthritis with high-grade fever. PATIENT CONCERNS: A 34-year-old woman was admitted to our hospital for further evaluation of a high fever with polyarthritis. The levels of both rheumatoid factor and anticitrullinated protein antibody were negative.F-fluorodeoxyglucose/positron emission tomography-computed tomography showed lymphadenopathy with increased fluoro-2-deoxy-D-glucose uptake. Magnetic resonance imaging and musculoskeletal ultrasonography revealed active synovitis in the hands which was consistent with RA. DIAGNOSES:We diagnosed iMCD based on human herpesvirus 8 negativity, HIV negativity, systemic lymphadenopathy, and pathologic findings of the lymph nodes. The patient did not satisfy the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. Cytokine assay showed elevated serum levels of interleukin-17and CXCL10, comparable to those in patients with RA. INTERVENTIONS: We administered 15?mg/d of predonisolone. OUTCOMES:After this treatment, the patient\u27s symptoms showed improvement. As of this writing, we tapered the prednisolone to 7.5?mg/d,and the patient\u27s remission has been maintained for >4 months. LESSONS: The present case suggests that RA-like active synovitis may coexist in iMCD, resulting from aberrant T-cell activation and histologic examination using lymph node biopsy may help enable early diagnosis of iMCD

読書会

写真あり第1回読書会 : 中村好花(英語英米文学科)第2回読書会 : 小根山桃子(日本語日本文学科