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Therapeutic Strategy Based on the Pathogenesis for Sjögren’s Syndrome
Get PDFPathogenesis of many autoimmune diseases has been still unclear, and establishment of the radical therapy based on the pathogenesis has been coveted by a number of patients with autoimmunity. Sjögren’s syndrome (SS) is well known to be one of systemic autoimmune diseases in the exocrine glands. Detailed cellular and molecular pathogenesis of SS also remains a mystery. In this review article, the history of SS mouse models and the significant findings were described and discussed according to the previous reports including our data. In addition, recent results focusing on T cell and macrophage were explained. Finally, a possible therapeutic strategy based on the results using immune checkpoint molecules was discussed. We have to overcome the challenge to help numerous patients suffering from various severe symptoms; even a journey of a thousand miles begins with a single step to solve a lot of problems in the intractable diseases.journal articl
Bidirectional signals generated by Siglec-7 and its crucial ligand tri-sialylated T to escape of cancer cells from immune surveillance
Get PDFSiglec-7, an inhibitory receptor expressed on natural killer (NK) cells, recognizes sialic acid-containing glycans. However, the ligand glycan structures of Siglec-7 and its carrier proteins have not been comprehensively investigated. Here, we identified four sialyltransferases that are used for the synthesis of ligand glycans of Siglec-7 and two ligand O-glycan-carrier proteins, PODXL and MUC13, using a colon cancer line. Upon binding of these ligand glycans, Siglec-7-expressing immune cells showed reduced cytotoxic activity, whereas cancer cells expressing ligand glycans underwent signal activation, leading to enhanced invasion activity. To clarify the structure of the ligand glycan, podoplanin (PDPN) identified as a Siglec-7 ligand-carrier protein, was transfected into HEK293T cells using sialyltransferase cDNAs. Mass spectrometry of the products revealed a ligand glycan, tri-sialylated T antigen. These results indicate that Siglec-7 interaction with its ligand generates bidirectional signals in NK and cancer cells, leading to the efficient escape of cancers from host immune surveillance.journal articl
2型糖尿病患者における推定塩分摂取量に関わる臨床因子の探索
Get PDF【Introduction】
Salt restriction is important for the treatment of hypertension and there is evidence that reducing salt intake to less than 6 g/day has an effective antihypertensive effect and is expected to reduce cardiovascular events and cardiovascular death. However, many diabetic patients with hypertension fail to decrease their salt intake sufficiently in clinical practice.
【Objective】
To effectively restrict salt intake in individuals with type 2 diabetes （T2D）, the aim of this study was to clarify the clinical factors that influence estimated salt intake （eSI）.
【Methods】
We continuously enrolled 268 individuals with T2D and assessed their eSI using Tanakaʼs formula through spot urine analysis at Anan Medical Center, Tokushima Japan. The relationships between eSI and the clinical factors were statistically evaluated.
【Results】
Multivariate analysis including clinical factors and medications used for the determinants of eSI showed positive associations of BMI and duration of diabetes with eSI and showed a negative association of serum uric acid and taking α-glucosidase inhibitor （α-GI） with eSI.
【Discussion】
It is possible that α-GI reduces sodium absorption from the intestine, which leads to decreased urinary sodium excretion, given the fact that α-GI inhibits sodium and glucose absorption from the intestine. In addition, since the urate transporter - 1 promotes reabsorption of uric acid and sodium in the renal tubules, reduced urinary excretion of uric acid may be associated with reduced urinary sodium excretion.
【Conclusion】
In addition to diet and exercise therapy, there is a possibility that oral administration of α-GI contributes to salt reduction in individuals with T2D.journal articl
Location of ethmoidal arteries in relation to ethmoid cells and the anterior skull base
Get PDFBackground : Ethmoidal arteries are at risk of accidental injury during endoscopic sinus surgery (ESS). Aims / Objectives : We aimed to examine the location of ethmoidal arteries in relation to ethmoid cells and the anterior skull base (ASB) in Japanese patients. Material and Methods : CT images of 100 sides of 50 patients were retrospectively reviewed. The location of anterior ethmoidal arteries (AEAs), middle ethmoidal arteries (MEAs) and posterior ethmoidal arteries (PEAs) in relation to ethmoidal cells and their distance from the ASB were evaluated. Results : AEAs and PEAs were present in all sides. 60% of AEAs and 9% of PEAs ran below the level of ASB. MEAs were present in 21 sides and ran below the ASB in 23.8% (5 / 21) of these sides. The incidence of AEAs running below the level of ASB was significantly higher in the sides with supraorbital ethmoid cells (SOECs) than in those without SOECs. Conclusion and significance : This study revealed the position and the distance from ASB of AEAs, PEAs, and MEAs in relation to ethmoid cells in Japanese patients. In cases with SOECs, surgeons should be careful not to injure the AEAs running below the level of ASB.journal articl
A case of completely resected cecum cancer with synchronous metastases to the small intestine found in acute appendicitis
Get PDFPurpose : Risk of malignant tumors increase with age ; hence, careful examination of older patients should be consdiered when identifying the causes of acute appendicitis. Here, we report a case of a patient with cecum cancer with synchronous metastases to the small intestine that was found during acute appendicitis. Case Report : A 74-year-old man presented with right lower abdominal pain. Physical examination revealed deep tenderness at McBurney’s point. Enhanced computed tomography scan showed an abscess around the enlarged appendix and a thickened cecum wall. Colonoscopy revealed a type 2 tumor in the ileocecal region, and pathological examination of the biopsied specimen revealed adenocarcinoma. Microscopic findings revealed two type 2 tumors in the small intestine, pathologically diagnosed as cecum cancer metastases. The final diagnosis was acute appendicitis caused by cecum cancer with synchronous metastases to the small intestine, pStage ⅣB pT4bN1aM1b. The patient received adjuvant chemotherapy and has currently been disease-free for 24 months. Conclusions : In prolonged appendicitis among older adults, the possibility of malignancy should be considered during preoperative examination and prior to selecting a treatment plan. Delays in the diagnosis of colorectal cancer and metastases may lead to missed opportunities for complete resection and poor prognosis.journal articl
徳島県内の入所系高齢者施設における感染対策上の課題と支援ニーズ : 横断的研究
Get PDF目的：高齢者施設における感染対策上の問題の解消に向けて，入所系高齢者施設の感染対策上の課題と支援ニーズを明らかにする．
方法：本調査は，横断的研究であり，質問紙調査を郵送法で実施した．調査期間は2022年12月から2023年１月，対象は徳島県内の入所系高齢者施設，回答者は施設管理者であった．
結果：133施設から有効回答が得られ，有効回答率は35．2％であった．COVID- 19について，職員からの発生があった施設は122施設（91.7％），利用者からの発生があった施設は75施設（56.4％），クラスター発生も48施設（36.1％）が経験していた．医療的ケア・身体介護依存度の高・低で施設を分け比較したところ，依存度の高い施設では有意にクラスターの発生が多かった（p=.017，Pearson's chi-squaretest）． BCP（Business Continuity Plan : BCP）の策定が行われていたのは78施設（58.6％）にとどまり，感染症対策に関する支援の中で最も要望の多かったのは訓練（シミュレーション）で65施設（48.9％）であった．
考察：調査の結果，入所系高齢者施設の中でも医療的ケアや身体介護依存度の高い利用者が多い介護老人保健施設や特別養護老人ホームでのクラスター発生が多いこと，BCP 策定が進んでいないこと，クラスター発生時に備えた訓練（シミュレーション）のニーズも高いことがわかった．個々の施設の実情に即した支援が必要である．Objective : To elucidate infection control challenges and support needs in residential elderly care facilities, aiming to address and resolve infection control issues in these facilities.
Methods : This was a cross-sectional study, utilizing a questionnaire survey distributed by mail. The survey was conducted from December 2022 to January 2023. The target population comprised residential elderly care facilities in Tokushima Prefecture, with facility managers serving as respondents.
Results : Valid responses were obtained from 133 facilities, yielding a valid response rate of 35.3%. COVID-19 cases were reported in 122 facilities（91.7%） among staff, 75 facilities（56.4%） among patients, and 48 facilities（36.1%） experienced clusters. Comparing facilities based on their level of dependence on medical care and nursing care, significantly more clusters occurred in facilities with higher levels of dependence（p=.017, Pearson's chi-square test）. Business Continuity Plans（BCP） were in place in 78 facilities（58.6%）, and the most frequently requested support for infection control was trainin（simulation） reported by 65 facilities（48.9%）.
Discussion : The results indicated many clusters occurred in geriatric health care facilities and special nursing homes for the elderly, where a significant number of patients are dependent on medical and physical care. Furthermore, the establishment of BCP was found to be lacking. The study also highlighted a high demand for training（simulation） to prepare for cluster occurrences. Support tailored to the specific conditions of individual facilities is necessary to effectively address these challenges.journal articl
Acute accumulation of PIM2 and NRF2 and recovery of β5 subunit activity mitigate multiple myeloma cell susceptibility to proteasome inhibitors
Get PDFResistance to proteasome inhibitors (PIs) has emerged as an important clinical issue. We investigated the mechanisms underlying multiple myeloma (MM) cell resistance to PIs. To mimic their pharmacokinetic/pharmacodynamic (PK/PD) profiles, MM cells were treated with bortezomib and carfilzomib for 1 hour at concentrations up to 400 and 1,000nM, respectively. Susceptibility to these PIs markedly varied among MM cell lines. Pulsatile treatments with PIs suppressed translation, as demonstrated by incorporation of puromycin at 24 hours in PI-susceptible MM.1S cells, but not PI-resistant KMS-11 cells. Inhibition of β5 subunit activity decreased at 24 hours in KMS-11 cells, even with the irreversible PI carfilzomib, but not under suppression of protein synthesis with cycloheximide. Furthermore, the proteasome-degradable pro-survival factors PIM2 and NRF2 acutely accumulated in MM cells subjected to pulsatile PI treatments. Accumulated NRF2 was trans-localized into the nucleus to induce the expression of its target gene, HMOX1, in MM cells. PIM and Akt inhibition restored the anti-MM effects of PIs, even against PI-resistant KMS-11 cells. Collectively, these results suggest that increased synthesis of β5 proteasome subunit and acute accumulation of PIM2 and NRF2 reduce the anti-MM effects of PIs.doctoral thesi
Navigating Well-being and Academic Success : Insights From University Dormitory Life
Get PDFUniversity dormitories provide a supportive environment, yet students encounter challenges impacting academic performance and well-being. In 2024, a web survey targeted 288 undergraduates residing in campus dorms in Vietnam. Assessing participants' characteristics, physical attributes, lifestyle patterns, and mental health status (DASS-21) revealed key insights. The findings unveiled an average of 2.9 roommates (SD = 1.41), with an average sleep duration of 6.9 hours (SD = 1.43) and a bedtime around 11:58 PM (SD = 1.29). Handheld device usage averaged 6.4 hours (SD = 3.47), and self-study hours averaged 2.9 (SD = 2.06). Self-prepared meals and out-campus breakfast were prevalent. The majority abstained from alcohol (62.4%) and tobacco (96.2%). GPA correlated with age, a smaller number of roommates, and self-study hours, with older students and those engaging in more independent study exhibiting higher GPAs. Additionally, students majoring in medicine and those in higher grades tended to have higher GPAs. Blood type was correlated with depression levels. Understanding dormitory challenges, including social dynamics and adjustment issues, is crucial for effective student support. These findings provide valuable insights into lifestyle, academic behaviors, and mental health, informing potential interventions aimed at enhancing student well-being and academic success.journal articl
Pulmonary Arterial Hypertension in Neurofibromatosis Type 1 : A Case with a Novel NF1 Gene Mutation
Get PDFNeurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.journal articl