A giant plexiform schwannoma of the brachial plexus: case report

We report the case of a patient who noticed muscle weakness in his left arm 5 years earlier. On examination, a biloculate mass was observed in the left supraclavicular area, and Tinel's sign caused paresthesia in his left arm. Magnetic resonance imaging showed a continuous, multinodular, plexiform tumor from the left C5 to C7 nerve root along the course of the brachial plexus to the left brachia. Tumor excision was attempted. The median and musculocutaneous nerves were extremely enlarged by the tumor, which was approximately 40 cm in length, and showed no response to electric stimulation. We resected a part of the musculocutaneous nerve for biopsy and performed latissimus dorsi muscle transposition in order to repair elbow flexion. Morphologically, the tumor consisted of typical Antoni A areas, and immunohistochemistry revealed a Schwann cell origin of the tumor cells moreover, there was no sign of axon differentiation in the tumor. Therefore, the final diagnosis of plexiform Schwannoma was confirmed

TSU-68 Ameliorates Hepatocellular Carcinoma Growth by Inhibiting Microenvironmental Platelet-derived Growth Factor Signaling

13301甲第4437号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：ANTICANCER RESEARCH 35(3) pp.1423-1432 2015. International Institute of Anticancer Research. 共著者：YASUMASA HARA, TARO YAMASHITA, NAOKI OISHI, KOUKI NIO, TAKEHIRO HAYASHI, YOSHIMOTO NOMURA, MARIKO YOSHIDA, TOMOYUKI HAYASHI, TOMOMI HASHIBA, YOSHIRO ASAHINA, MITSUMASA KONDO, HIKARI OKADA, HAJIME SUNAGOZAKA, MASAO HONDA, SHUICHI KANEK

Correlation of histopathology with magnetic resonance imaging in Kienböck disease.

PURPOSE:Diagnosis and treatment remain controversial for Kienböck disease. A few reports have correlated magnetic resonance imaging (MRI), which is essential for early diagnosis, and histopathology of Kienböck biopsy specimens, but histopathological correlations of whole lunate bones or histological slices compared with MRI images are lacking. The purpose of this study was to compare presurgical MRI scans with corresponding histological slices of Kienböck-diseased lunates.METHODS:We excised whole lunates at the time of surgery from 6 patients with Kienböck disease (stage IIIB) undergoing tendon-ball replacement or a Graner procedure. We stained paraffin-embedded, coronally sectioned specimens with hematoxylin-eosin and compared them with presurgical coronal scans using MRI with a 47-mm microscopy surface coil.RESULTS:Toward the center of the lunates, the signal intensity in the proton density-weighted images was reduced, whereas the dorsal and palmar sides of the lunates exhibited no changes in intensity. In correlation, histopathological findings revealed strongly disrupted trabeculae toward the center of the lunates and intact trabeculae in the dorsal side of the lunates. Likewise, the necrotic and vitalized bone exhibited low and high signal intensities, respectively, in the proton density-weighted images; however, in the fast-field echo images, there were no correlations with histopathological observations.CONCLUSIONS:Proton density-weighted MRIs but not fast-field echo images using a 47-mm microscopy coil reflected the extent and localization of the necrotic area in Kienböck-diseased lunates, as evidenced by comparison with histological analyses of the lunate specimens.CLINICAL RELEVANCE:Proton density-weighted MRIs accurately reflect the vascular status of the lunate and may help plan treatment on a case-by-case basis

Heparin cofactor II reduces albuminuria

Aims/Introduction: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria. Materials and Methods: Plasma HCII activity and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females). Results: The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate-regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log-transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL-FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log-transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively). Conclusions: The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria

Heparin Cofactor II and NAFLD in T2DM

Aims: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD. Methods: A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated. Results: Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p＜0.001), NFS (p＜0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012). Conclusions: Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM

Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16.Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system

The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma

Background & Aims: Recent evidence suggests that hepatocellular carcinoma can be classified into certain molecular subtypes with distinct prognoses based on the stem/maturational status of the tumor. We investigated the transcription program deregulated in hepatocellular carcinomas with stem cell features. Methods: Gene and protein expression profiles were obtained from 238 (analyzed by microarray), 144 (analyzed by immunohistochemistry), and 61 (analyzed by qRT-PCR) hepatocellular carcinoma cases. Activation/suppression of an identified transcription factor was used to evaluate its role in cell lines. The relationship of the transcription factor and prognosis was statistically examined. Results: The transcription factor SALL4, known to regulate stemness in embryonic and hematopoietic stem cells, was found to be activated in a hepatocellular carcinoma subtype with stem cell features. SALL4-positive hepatocellular carcinoma patients were associated with high values of serum alpha fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced spheroid formation and invasion capacities, key characteristics of cancer stem cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell markers, together with attenuation of the invasion capacity. The SALL4 expression status was associated with histone deacetylase activity in cell lines, and the histone deacetylase inhibitor successfully suppressed proliferation of SALL4-positive hepatocellular carcinoma cells. Conclusions: SALL4 is a valuable biomarker and therapeutic target for the diagnosis and treatment of hepatocellular carcinoma with stem cell features. © 2013 European Association for the Study of the Liver