上皮特異的に発現する蛋白輸送因子μ1Bによるバソラテラルシグナルの認識機構

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1538号, 学位授与年月日 : 平成14年6月30日, 学位授与大学 : 金沢大

Human Herpesvirus 6-Associated Hemophagocytic Syndrome in a Healthy Adult

Virus-associated hemophagocytic syndrome is a fulminant disorder associated with systemic viral infection and characterized pathologically by multiple-organ infiltration of hemophagocytic histiocytes into the lymphoreticular tissues. This is the first report of a previously healthy adult in whom Human herpesvirus 6 reactivation induced this syndrome with severe hemodynamic and respiratory distress

The effects of unilateral cochlear ablation on the expression of vesicular glutamate transporter 1 in the lower auditory pathway of neonatal rats

Objectives: Unilateral cochlear damage has profound effects on the central auditory pathways in the brain. Methods: We examined the effects of unilateral cochlear ablation on VGLUT1 expression in the cochlear nucleus (CN) and the superior olivary complex (SOC) in neonatal rats. Results: VGLUT1 expression in the CN subdivisions (the AVCN, the PVCN and the DCN-deep layers) and the SOC (the MnTB, the LSO and the MSO) ipsilateral to the ablated side was significantly suppressed by unilateral cochlear ablation. Interestingly, VGLUT1 expression in the PVCN and the DCN-deep layers contralateral to the ablated side was also reduced. Conclusion: Our findings indicate that unilateral cochlear ablation affects VGLUT1 expression in the central auditory pathways not only ipsilateral but also contralateral to the ablated side. © 2017 Elsevier B.V.in Press / Embargo Period 12 month

A case of chronic otitis media caused by Mycobacterium abscessus

金沢大学医薬保健研究域医学系Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a possible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation. © 2010

Roles of epithelial-mesenchymal transition in squamous cell carcinoma of the temporal bone

金沢大学医薬保健研究域医学系Objectives: The authors recently demonstrated that extensive bone erosion correlated with a worse prognosis of the squamous cell carcinoma (SCC) of the temporal bone. The present objective was to investigate the expressions and the roles of epithelial-mesenchymal transition (EMT) in SCC of the temporal bone. Study Design: Retrospective patient file review and immunohistochemical study of tissues of patients with SCC of the temporal bone. Patients: The authors examined the expressions of vimentin in 16 patients with SCC of the temporal bone by immunohistochemical analysis. Results: As expected, vimentin was expressed on SCC of the temporal bone. We regard the patient who has vimentin-positive cells as EMT-positive patient because gain of vimentin is a hallmark in the EMT reported in several types of cancer. EMT positive tumors significantly correlated with extensive bone erosion, and extensive bone erosion correlated with a worse prognosis of the SCC of the temporal bone. Conclusion: The study results suggest that EMT in tumor cells becomes an important indicator of poor prognosis in SCC of the temporal bone. Copyright © 2011 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited

Method of Quantifying Size of Retinal Hemorrhages in Eyes with Branch Retinal Vein Occlusion Using 14-Square Grid: Interrater and Intrarater Reliability

Purpose. To describe a method of quantifying the size of the retinal hemorrhages in branch retinal vein occlusion (BRVO) and to determine the interrater and intrarater reliabilities of these measurements. Methods. Thirty-five fundus photographs from 35 consecutive eyes with BRVO were studied. The fundus images were analyzed with Power-Point® software, and a grid of 14 squares was laid over the fundus image. Raters were asked to judge the percentage of each of the 14 squares that was covered by the hemorrhages, and the average of the 14 squares was taken to be the relative size of the retinal hemorrhage. Results. Interrater reliability between three raters was higher when a grid with 14 squares was used (intraclass correlation coefficient (ICC), 0.96) than that when a box with no grid was used (ICC, 0.78). Intrarater reliability, which was calculated by the retinal hemorrhage area measured on two different days, was also higher (ICC, 0.97) than that with no grid (ICC, 0.86). Interrater reliability for five fundus pictures with poor image quality was also good when a grid with 14 squares was used (ICC, 0.88). Conclusions. Although our method is subjective, excellent interrater and intrarater reliabilities indicate that this method can be adapted for clinical use

Clonal spread of β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) strains of non-typeable Haemophilus influenzae among young children attending a day care in Japan

金沢大学医薬保健研究域医学系Objective: Resistant strains of non-typeable Haemophilus influenzae (NTHi) are one of the principal causes of recurrent acute otitis media (otitis prone), rhinosinusitis, and pneumonia in young children. β-Lactamase-nonproducing ampicillin-resistant (BLNAR) strains are particularly common in Japan, and β-lactamase-producing amoxicillin-clavulanate resistant (BLPACR) strains are now emerging. We investigated the nasopharyngeal carriage status of these resistant strains among children attending a same day care center during a 10-year period. Methods: From 1999 to 2008, we obtained nasopharyngeal swab specimens from young children attending a same day care center and examined the incidence of resistant strains of NTHi. Antimicrobial resistance of NTHi was identified based on PCR analysis of mutation of the penicillin binding protein (PBP) genes. Pulsed-field gel electrophoresis (PFGE) was performed to examine the clonal relationship of each resistant strain. Results: The prevalence of resistant strains of NTHi among the children attending this day care has significantly increased during the past 10 years and most of this day care children recently have resistant strains with PBP gene mutations in their nasopharynx. Genetically BLPACR (gBLPACR) strains have rapidly increased since 2007 and PFGE analysis demonstrated that all gBLPACR were clonally identical. This is the first report of apparent clonal dissemination of gBLPACR strains of NTHi occurring in a certain environment such as day care. Conclusions: The rapidly increasing prevalence of resistant strains, in particular gBLPACR, in this day care center may predict a high incidence of these resistant bacteria from clinical isolates in the near future and potential serious medical problems worldwide. © 2010 Elsevier Ireland Ltd

Interstitial Pneumonia Developed in HTLV-I Carriers: Report of Two Cases

Two carriers of human T-cell lymphotropic virus type I (HTLV-I) with interstitial pneumonia are described. The first case, a 60-year-old man, was admitted with cough and dyspnea on exertion. Light microscopy of a lung specimen obtained by a transbronchial lung biopsy (TBLB ) showed thickening of the alveolar walls with infiltration of lymphocytes and fibrosis of the pulmonary parenchyma. Immunohistochemical analysis of the TBLB specimen showed positive staining in the lymphocytes for UCHL-1. This case was suspected as HTLV-I associated bronchiolo-alveolar disorder. The second case, a 74-year-old man, visited our hospital because of a persistent productive cough and dyspnea on exertion. Light microscopy of the TBLB showed a slight thickening of the alveolar walls and fibrosis of the pulmonary parenchyma with minimal infiltration of lymphocytes. Only 2.2% of the bronchoalveolar lavage fluid consisted of lymphocytes. The findings of the second case suggest that some factors other than T-lymphocytes may be related with the development of interstitial pneumonia in HTLV-I carriers. Interstitial pneumonia in HTLV-I carriers may be caused by as yet undiscovered mechanisms. A cohort study involving residents of an area where HTLV-I is endemic should be conducted to clarify the mechanism of pulmonary involvement in HTLV-I carriers

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations

Potential interest in circulating miR-BART17-5p as a post-treatment biomarker for prediction of recurrence in Epstein-Barr virus-related nasopharyngeal carcinoma

Objectives: Epstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers. Materials and Methods: Serums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients. Results: The sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100/100, 85/85, 60/95, and 25/100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors. Conclusion: The copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis. © 2016 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited