パーキンソン病における運動遂行下での中脳皮質辺縁ドパミン神経系に及ぼす視床下核脳深部刺激療法の効果：PETによる研究

浜松医科大学学位論文　医博論第506号（平成25年4月19日

Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique

Tissue localization of a subcomponent of the first component of complement (CLq) was examined in one postmortem case of HBs antigen (HBs Ag) positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.</p

Scoring for Hoffa’s fat pad synovitis

AIM To investigate the reliability of the established and new scoring methods for Hoffa’s fat pad synovitis using magnetic resonance imaging (MRI). METHODS A total of 139 knees of 115 patients who underwent MRI of the knee with and without gadolinium contrast were enrolled in this study. Proton density (PD)-weighted, PD-weighted fat-suppressed (PD-FS), and postcontrast T1-weighted fat-suppressed (T1CE) images were used for evaluation. Using contrast and non-contrast images, our grading method for synovitis was performed to measure synovial thickness and signal intensity changes of the fat pad [Synovial membrane (SM) score], which was compared with the established methods, including MRI Osteoarthritis Knee Score (MOAKS), parapatellar synovitis score, Whole-Organ Magnetic Resonance Imaging Score (WORMS), and suprapatellar effusion diameter. Intraclass correlation coefficients (ICC) for intra and interobserver reproducibility and Spearman correlation coefficients (r) were calculated for the parapatellar synovitis score and each scoring method. RESULTS All of the scores presented substantial to almost perfect intrareliability. Among three readers, effusion diameter had substantial to almost perfect interreliability (ICC = 0.68-0.81) and WORMS had substantial interreliability (ICC = 0.61-0.70). For two out of three readers, there was substantial interreliability for the thickness score in T1CE (ICC = 0.55-0.69), SM scores in T1CE (ICC = 0.56-0.78) and PD-FS (ICC = 0.51-0.79), and parapatellar synovitis score in T1CE (ICC = 0.53-0.72). The parapatellar synovitis score was significantly correlated with the thickness score in T1CE (r = 0.70) and the SM score in T1CE (r = 0.81) and PD-FS (r = 0.65). CONCLUSION The newly proposed quantitative thickness score on T1CE and the semi-quantitative SM score on T1CE and PD-FS can be useful for Hoffa’s fat pad synovitis

Medical Treatment of Echinococcus multilocularis and New Horizons for Drug Discovery: Characterization of Mitochondrial Complex II as a Potential Drug Target

As an efficient drug for alveolar echinococcosis (AE) is still not available, new chemotherapy targets are necessary. The mitochondrial respiratory chain may be a good drug candidate because parasite respiratory chains are quite different from those of mammalian hosts. For example, Ascaris suum possesses an NADH‐fumarate reductase system (fumarate respiration) that is highly adapted to anaerobic environments such as the small intestine. It is composed of mitochondrial complex I (NADH‐ubiquinone reductase), complex II (succinate‐ubiquinone reductase), and rhodoquinone. We previously demonstrated that fumarate respiration is also essential in E. multilocularis. Quinazoline, a complex I inhibitor, inhibited growth of E. multilocularis larvae in vitro. These results indicate that fumarate respiration could be a target for E. multilocularis therapy. In the current chapter, we focused on complex II, which is another component of this system, because quinazoline exhibited strong toxicity to mammalian mitochondria. We evaluated the molecular and biochemical characterization of E. multilocularis complex II as a potential drug target. In addition, we found that ascofuranone, a trypanosome cyanide‐insensitive alternative oxidase inhibitor, inhibited E. multilocularis complex II at the nanomolar order. Our findings demonstrate the potential development of targeted therapy against Echinococcus complex II

Age, Symptomatic Metastatic Disease, and Malignant Pleural Effusion as Predictors of Poor Prognosis in Patients with Differentiated Thyroid Carcinoma Treated with Lenvatinib.

Background: Lenvatinib is one of the few therapeutic options available for radioiodine-refractory thyroid cancer. However, the factors that determine the therapeutic outcomes remain unknown.Methods: Patients with thyroid carcinoma treated with lenvatinib who had been dead or who had survived for longer than a halfyearwere retrospectively compared. We evaluated the clinical parameters when lenvatinib was started, and also studied the tumor volume reduction ratio, the duration until re-growth of the largest metastatic lesion, the thyroglobulin (Tg) reduction rate,and the duration until re-elevation of Tg after lenvatinib between survivors and dead patients.Results: We identified 16 patients, with an average age of 73.1±7.6 yrs and a male-to-female ratio of 5 to 11, who had advanced differentiated thyroid cancer that was treated with lenvatinib. Nine patients had died after 8.9±6.1 months, whereas 7 survived for 13.0±2.0 months after starting lenvatinib. The patients who died were older than the survivors (76.7±6.5 vs. 68.6±6.6 yrs, p=0.03).Malignant pleural effusion (p=0.017) and symptomatic metastatic disease (SMD) (p=0.039) were associated with death in a Kaplan-Meier survival analysis. Age (p=0.012, HR 1.150, CI 1.030-1.320) and SMD (p=0.014, HR 8.069, CI 1.503-61.34) wereassociated with poor outcome in a multivariate Cox proportional hazard model. The duration until the re-elevation of Tg waslonger in survivors than in patients who died (6.43±4.55 vs. 2.17±1.39 months, p=0.025).Conclusions: We identified multiple factors, including SMD, that were related to poor outcomes after lenvatinib treatment. This study suggests that lenvatinib might be started before patients develop SMD

T1rho and T2 relaxation times of the normal adult knee meniscus at 3T : analysis of zonal differences

Background: Prior studies describe histological and immunohistochemical differences in collagen and proteoglycan content in different meniscal zones. The aim of this study is to evaluate horizontal and vertical zonal differentiation of T1rho and T2 relaxation times of the entire meniscus from volunteers without symptom and imaging abnormality. Methods: Twenty volunteers age between 19 and 38 who have no knee-related clinical symptoms, and no history of prior knee surgeries were enrolled in this study. Two T1rho mapping (b-FFE T1rho and SPGR T1rho) and T2 mapping images were acquired with a 3.0-T MR scanner. Each meniscus was divided manually into superficial and deep zones for horizontal zonal analysis. The anterior and posterior horns of each meniscus were divided manually into white, red-white and red zones for vertical zonal analysis. Zonal differences of average relaxation times among each zone, and both inter- and intra-observer reproducibility were statistically analyzed. Results: In horizontal zonal analysis, T1rho relaxation times of the superficial zone tended to be higher than those of the deep zone, and this difference was statistically significant in the medial meniscal segments (84.3 ms vs 76.0 ms on b-FFE, p 0.74) or good (0.60–0.74) in all meniscal segments on both horizontal and vertical zonal analysis, except for inter-class correlation coefficients of the lateral meniscus on SPGR. Compared with SPGR T1rho images, b-FFE T1rho images demonstrated more significant zonal differentiation with higher inter- and intra-observer reproducibility. Conclusions: There are zonal differences in T1rho and T2 relaxation times of the normal meniscus

T1rho and T2 relaxation times of the normal adult knee meniscus at 3T : analysis of zonal differences

Background: Prior studies describe histological and immunohistochemical differences in collagen and proteoglycan content in different meniscal zones. The aim of this study is to evaluate horizontal and vertical zonal differentiation of T1rho and T2 relaxation times of the entire meniscus from volunteers without symptom and imaging abnormality. Methods: Twenty volunteers age between 19 and 38 who have no knee-related clinical symptoms, and no history of prior knee surgeries were enrolled in this study. Two T1rho mapping (b-FFE T1rho and SPGR T1rho) and T2 mapping images were acquired with a 3.0-T MR scanner. Each meniscus was divided manually into superficial and deep zones for horizontal zonal analysis. The anterior and posterior horns of each meniscus were divided manually into white, red-white and red zones for vertical zonal analysis. Zonal differences of average relaxation times among each zone, and both inter- and intra-observer reproducibility were statistically analyzed. Results: In horizontal zonal analysis, T1rho relaxation times of the superficial zone tended to be higher than those of the deep zone, and this difference was statistically significant in the medial meniscal segments (84.3 ms vs 76.0 ms on b-FFE, p 0.74) or good (0.60–0.74) in all meniscal segments on both horizontal and vertical zonal analysis, except for inter-class correlation coefficients of the lateral meniscus on SPGR. Compared with SPGR T1rho images, b-FFE T1rho images demonstrated more significant zonal differentiation with higher inter- and intra-observer reproducibility. Conclusions: There are zonal differences in T1rho and T2 relaxation times of the normal meniscus