脱髄性ニューロパチーにおける糖脂質-蛋白複合抗原に対する自己抗体の解析と病態解明

脱髄性ニューロパチーの病態解明を目的として、ギラン・バレー症候群の患者血清を用いて末梢神経に局在する2種類の糖脂質抗原（GM1・GD1b）と3種の傍絞輪部蛋白抗原（NF155・CNTN1・CASPR1）を混合した6種の混合抗原に対する抗体反応性について調べたが、糖脂質-蛋白複合抗原に対する特異的抗体は確認できなかった。また、自己免疫性ノドパチーが疑われる患者血清を用いてCaイオン依存性の傍絞輪部蛋白抗体について検討したがCaイオン依存性の自己抗体は検出されなかった。一方、慢性炎症性脱髄性多発根神経炎の患者血清においてGQ1b抗原に対する反応性をもつ抗体が稀ながら存在することが明らかとなった。For elucidation of pathology in immune-mediated demyelinating neuropathies, we examined antibodies to glycolipid-protein complex which are consisting of one glycolipid (GM1 or GD1b) and one protein (NF155, CNTN1, or CASPR1) using ELISA. However, such antibody reactivities to glycolipid-protein complex were not observed in Guillain-Barre syndrome. Additionally, we examined Ca2+-dependent antibodies to paranodal proteins in patients who were suspected to be autoimmune nodopathies, whereas these were not detected. On the other hand, we clarified the presence of antibody reactivities to GQ1b in a few patients with chronic inflammatory demyelinating polyradiculoneuropathy.研究分野：神経内科

Analysis of antibodies to glycolipid-protein complexes and elucidation of pathology in autoimmune-mediated demyelinating neuropathies

脱髄性ニューロパチーの病態解明を目的として、ギラン・バレー症候群の患者血清を用いて末梢神経に局在する2種類の糖脂質抗原（GM1・GD1b）と3種の傍絞輪部蛋白抗原（NF155・CNTN1・CASPR1）を混合した6種の混合抗原に対する抗体反応性について調べたが、糖脂質-蛋白複合抗原に対する特異的抗体は確認できなかった。また、自己免疫性ノドパチーが疑われる患者血清を用いてCaイオン依存性の傍絞輪部蛋白抗体について検討したがCaイオン依存性の自己抗体は検出されなかった。一方、慢性炎症性脱髄性多発根神経炎の患者血清においてGQ1b抗原に対する反応性をもつ抗体が稀ながら存在することが明らかとなった。For elucidation of pathology in immune-mediated demyelinating neuropathies, we examined antibodies to glycolipid-protein complex which are consisting of one glycolipid (GM1 or GD1b) and one protein (NF155, CNTN1, or CASPR1) using ELISA. However, such antibody reactivities to glycolipid-protein complex were not observed in Guillain-Barre syndrome. Additionally, we examined Ca2+-dependent antibodies to paranodal proteins in patients who were suspected to be autoimmune nodopathies, whereas these were not detected. On the other hand, we clarified the presence of antibody reactivities to GQ1b in a few patients with chronic inflammatory demyelinating polyradiculoneuropathy.研究分野：神経内科

Intravenous Immunoglobulin (IVIg) with Methylprednisolone Pulse Therapy for Motor Impairment of Neuralgic Amyotrophy: Clinical Observations in 10 Cases

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第914号）・内藤康介Background Neuralgic amyotrophy (NA) is a distinct peripheral nervous system disorder characterized by attacks of acute neuropathic pain and rapid multifocal weakness and atrophy unilaterally in the upper limb. The current hypothesis is that the episodes are caused by an immune-mediated response to the brachial plexus, however, therapeutic strategies for NA have not been well established. Methods and Results We retrospectively reviewed 15 case series of NA; 10 of the 15 patients received intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy (MPPT) and 9 of these10 patients showed clinical improvement of motor impairment. Conclusion Our clinical observations do not contradict the possibility that IVIg with MPPT may be one of the potential therapeutics for NA, however the efficacy remains to be established. Further confirmatory trials are needed in patients with various clinical severities and phases of NA. Further basic research and confirmatory trials should be performed to survey the efficacy of such immunomodulation therapy for NA.ArticleINTERNAL MEDICINE. 51(12):1493-1500 (2012)journal articl

Intravenous Immunoglobulin (IVIg) with Methylprednisolone Pulse Therapy for Motor Impairment of Neuralgic Amyotrophy: Clinical Observations in 10 Cases

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第914号）・内藤康介Background Neuralgic amyotrophy (NA) is a distinct peripheral nervous system disorder characterized by attacks of acute neuropathic pain and rapid multifocal weakness and atrophy unilaterally in the upper limb. The current hypothesis is that the episodes are caused by an immune-mediated response to the brachial plexus, however, therapeutic strategies for NA have not been well established. Methods and Results We retrospectively reviewed 15 case series of NA; 10 of the 15 patients received intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy (MPPT) and 9 of these10 patients showed clinical improvement of motor impairment. Conclusion Our clinical observations do not contradict the possibility that IVIg with MPPT may be one of the potential therapeutics for NA, however the efficacy remains to be established. Further confirmatory trials are needed in patients with various clinical severities and phases of NA. Further basic research and confirmatory trials should be performed to survey the efficacy of such immunomodulation therapy for NA.ArticleINTERNAL MEDICINE. 51(12):1493-1500 (2012)journal articl

The Comprehensive Complication Index in Ulcerative Colitis: A Comparison with the Clavien‒Dindo Classification

Introduction: The comprehensive complication index (CCI), which weights all postoperative complications according to severity and integrates them into a single formula, has been reported as a new evaluation system. We aimed to compare the CCI with the Clavien‒Dindo Classification (CDC) to patients with ulcerative colitis (UC). Methods: Patients who underwent initial surgery for UC from April 2012 to March 2020 were included. The patients were classified into a length of stay (LOS) >30 days group or an LOS ≤30 days group. We performed a multivariate analysis of risk factors for LOS >30 days in the model with the factors identified in the univariate analysis plus the CCI (the CCI model) and plus CDC (the CDC model). An ROC curve was used to test the difference in the area under the curve (AUC) between the CCI model and the CDC model. Results: The median LOS was 21 days (IQR: 16-29 days), and the rate of LOS >30 days was 119/588 (20.2%). In the CCI model, age at the time of surgery (OR=1.24, 95% CI 1.07-1.45, p=0.01), ASA score ≥3 (OR=1.94, 95% CI 1.00-3.76, p=0.04), and CCI (OR=1.07, 95% CI 1.05-1.09; p30 days. The AUC value of the CCI model (0.86) was significantly better in relation to LOS > 30 days than that of the CDC model (0.82) (p =0.02). Conclusion: The CCI was a better measure of LOS than was the CDC and was found to be a useful indicator in UC

The Impacts of Laparoscopic Restorative Proctocolectomy for Ulcerative Colitis: Systematic Review and Meta-Analysis

Introduction: Laparoscopic surgery (LAP) is now recognized as the standard procedure for colorectal surgery. However, the standard surgery for ulcerative colitis (UC) is total proctocolectomy with ileal pouch anal anastomosis (IPAA), which may be an overly complex procedure to complete laparoscopically. We conducted this systematic review and meta-analysis to evaluate the efficacy as well as the advantages and disadvantages of LAP-IPAA in patients with UC stratified by the outcome of interest. Method: We performed a systematic literature review by searching the PubMed/MEDLINE, the Cochrane Library, and the Japan Centra Reuvo Medicina databases from inception until January 2023. Meta-analyses were performed for surgical outcomes, including morbidity and surgical course, to evaluate the efficacy of LAP-IPAA. Results: A total of 707 participants, including 341 LAP and 366 open surgery (OPEN) patients in 9 observational studies and one randomized controlled study, were included. From the results of the meta-analyses, the odds ratio (OR) of total complications in LAP was 1.12 (95% CI: 0.58–2.17, p = 0.74). The OR of mortality for LAP was 0.38 (95% CI: 0.08–1.92, p = 0.24). Although the duration of surgery was extended in LAP (mean difference (MD) 118.74 min (95% CI: 91.67–145.81), p < 0.01) and hospital stay were not shortened, the duration until oral intake after surgery was shortened in LAP (MD −2.10 days (95% CI: −3.52–0.68), p = 0.004). Conclusions: During IPAA for UC, a similar morbidity rate was seen for LAP and OPEN. Although LAP necessitates extended surgery, there may be certain advantages to this procedure, including easy visibility during the surgical procedure or a shortened time to oral intake after surgery

Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis

Abstract Purpose The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. Methods Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. Results The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2–590) in the cancer/dysplasia group and 48 (1–580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7–99.6) kg: 49.9 (20.3–85.2) kg), body mass index (21.0 (13.9–32.5) kg/m2: 18.3 (11.4–34.1)kg/m2), serum albumin level (4.3 (2.7–5.0)g/dl: 3.4 (1.4–5.2)g/dl) and prognostic nutrition index (49.2 (33.2–61.2): 40.9 (17.4–61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01). Conclusion UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status

Anti-Glycolipid Antibody Examination in Five EAE Models and Theiler’s Virus Model of Multiple Sclerosis: Detection of Anti-GM1, GM3, GM4, and Sulfatide Antibodies in Relapsing-Remitting EAE

Anti-glycolipid antibodies have been reported to play pathogenic roles in peripheral inflammatory neuropathies, such as Guillain–Barré syndrome. On the other hand, the role in multiple sclerosis (MS), inflammatory demyelinating disease in the central nervous system (CNS), is largely unknown, although the presence of anti-glycolipid antibodies was reported to differ among MS patients with relapsing-remitting (RR), primary progressive (PP), and secondary progressive (SP) disease courses. We investigated whether the induction of anti-glycolipid antibodies could differ among experimental MS models with distinct clinical courses, depending on induction methods. Using three mouse strains, SJL/J, C57BL/6, and A.SW mice, we induced five distinct experimental autoimmune encephalomyelitis (EAE) models with myelin oligodendrocyte glycoprotein (MOG)35–55, MOG92–106, or myelin proteolipid protein (PLP)139–151, with or without an additional adjuvant curdlan injection. We also induced a viral model of MS, using Theiler’s murine encephalomyelitis virus (TMEV). Each MS model had an RR, SP, PP, hyperacute, or chronic clinical course. Using the sera from the MS models, we quantified antibodies against 11 glycolipids: GM1, GM2, GM3, GM4, GD3, galactocerebroside, GD1a, GD1b, GT1b, GQ1b, and sulfatide. Among the MS models, we detected significant increases in four anti-glycolipid antibodies, GM1, GM3, GM4, and sulfatide, in PLP139–151-induced EAE with an RR disease course. We also tested cellular immune responses to the glycolipids and found CD1d-independent lymphoproliferative responses only to sulfatide with decreased interleukin (IL)-10 production. Although these results implied that anti-glycolipid antibodies might play a role in remissions or relapses in RR-EAE, their functional roles need to be determined by mechanistic experiments, such as injections of monoclonal anti-glycolipid antibodies