Springer Science and Business Media LLCActa Medica Okayama1478-63622712025Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis19ENTakahikoSugiharaDepartment of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoMasayoshiHarigaiDivision of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of MedicineHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHajimeYoshifujiDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityYasuhiroMaejimaDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Institute of Science TokyoJunIshizakiDepartment of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of MedicineYoshikoWatanabeDepartment of General Medicine, Kawasaki Medical SchoolHiroakiDobashiDivision of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa UniversityYoshinoriKomagataDepartment of Nephrology and Rheumatology, Kyorin University School of MedicineNaotoTamuraDepartment of Internal Medicine and Rheumatology, Juntendo University School of MedicineYoshikazuNakaokaDepartment of Vascular Physiology, National Cerebral and Cardiovascular Center Research InstituteJapan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS)Objective To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria.<br>
Methods Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability).<br>
Results Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976–0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894–0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530–0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700–0.813) or age (C-statistic: 0.913, 95%CI: 0.874–0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement.<br>
Conclusion The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK.No potential conflict of interest relevant to this article was reported.Hindawi LtdActa Medica Okayama2314-613320212021Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage18ENYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHaruhitoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSeveral studies have reported the efficacy and safety of polyphenols in human health; however, the verification of their efficacy remains insufficient. The aim of this study was to examine whether fisetin, one of flavonoids prevalently present in fruits and vegetables, could suppress lipopolysaccharide- (LPS-) induced inflammatory responses in macrophages. LPS increased proinflammatory mRNA abundance (MCP 1, IL-1 beta, and iNOS) but were suppressed by fisetin. The increment of nitric oxide by LPS, an oxidative stress factor, was attenuated by fisetin. In addition, LPS-enhanced phosphorylation of mitogen-activated protein kinase (ERK and JNK) was reduced. Finally, fisetin attenuated the expression or activity of uPA, uPAR, MMP-2, and MMP-9, which are known as associated factors of macrophage recruitment or infiltration. In conclusion, fisetin is a promising therapeutic agent for macrophage-related inflammation diseases, like sepsis and atherosclerosis.No potential conflict of interest relevant to this article was reported.Portland PressActa Medica Okayama0143-5221134202020Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice27712787ENYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTomoyukiMukaiDepartment of Rheumatology, Kawasaki Medical SchoolFumiakiKojimaDepartment of Pharmacology, Kitasato University School of Allied Health SciencesMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYukiKakioDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceNozomuOtakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYoshitakaMoritaDepartment of Rheumatology, Kawasaki Medical SchoolJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceThe aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813222020地域医療連携108109ENHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24680249592020Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells15761580ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiTakahashiDepartment of Nephrology, Faculty of Medical Science, University of FukuiMasayukiIwanoDepartment of Nephrology, Faculty of Medical Science, University of FukuiJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.PUBLIC LIBRARY SCIENCEActa Medica Okayama1932-6203882013Calpain-2 Compensation Promotes Angiotensin II-Induced Ascending and Abdominal Aortic Aneurysms in Calpain-1 Deficient Micee72214ENVenkateswaranSubramanianJessica J.MoorleghenAnjuBalakrishnanDeborah A.HowattAthar H.ChishtiHaruhito A.UchidaBackground and Objective
Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, we examined the relative contribution of calpain isoforms in AngII-induced ascending and abdominal AA development.
Methodology/Results
To investigate the relative contribution of calpain-1 and -2 in development of AngII-induced AAs, male LDLr −/− mice that were either calpain-1 +/+ or −/− were fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency showed no discernible effects on AngII-induced ascending and abdominal AAs. Interestingly, AngII infusion induced increased expression of calpain-2 protein, thus compensating for total calpain activity in aortas of calpain-1 deficient mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII-infusion significantly attenuated AngII-induced ascending and abdominal AA formation in both calpain-1 +/+ and −/− mice as compared to vehicle administered mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial hypertrophy and macrophage accumulation. Western blot and immunostaining analyses revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation of filamin A, an actin binding cytoskeletal protein in aorta.
Conclusion
Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-6203822013A Decreased Level of Serum Soluble Klotho Is an Independent Biomarker Associated with Arterial Stiffness in Patients with Chronic Kidney DiseaseENMasashiKitagawaHitoshiSugiyamaHiroshiMorinagaTatsuyukiInoueKeiichiTakiueAyuOgawaToshioYamanariYokoKikumotoHaruhito AdamUchidaShinjiKitamuraYoheiMaeshimaKazufumiNakamuraHiroshiItoHirofumiMakinoBackground: Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD).
Methods: We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification.
Results: The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV >= 1400 cm/sec, atherosclerosis defined as maximum IMT >= 1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075).
Conclusions: Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する16ENSatoshiMiyamotoKenichiShikataKyokoMiyasakaShinichiOkadaMotofumiSasakiRyoKoderaDaishoHirotaNobuoKajitaniTetsuharuTakatsukaHitomiKataoka UsuiShingoNishishitaChikageHoriguchi SatoAkihiroFunakoshiHisakazuNishimoriHaruhito AdamUchidaDaisukeOgawaHirofumiMakinoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2006Practical Efficacy of Telmisartan for Decreasing Morning Home Blood Pressure and Pulse Wave Velocity in Patients with Mild-to-Moderate HypertensionENHaruhitoUchidaNo potential conflict of interest relevant to this article was reported.