肝硬変におけるIgGの終末糖化産物量測定

BACKGROUND/AIMS:Our previous report showed that IgG levels are strongly correlated with the indocyanine green (ICG) retention rate in patients with liver cirrhosis (LC). This correlation suggests that hyperglobulinemia in LC could be explained by impairment of hepatic removal function. To estimate IgG turnover in LC, in the present paper was determined the advanced glycation end-products (AGE) on IgG as a marker of half-life.METHODOLOGY:Serum samples were obtained from patients with LC, rheumatoid arthritis (RA), and Sjögren syndrome (SjS), and from age-matched control patients. IgG was purified from serum by the protein G-based affinity method, concentrated by filtration, and used for assay of Nepsilon-(carboxymethyl) lysine (CML), a predominant AGE, by ELISA.RESULTS:CML on IgG was significantly lower in patients with LC than in control patients, whereas there was no significant difference in total serum CML levels among patients with LC, RA, and SjS, and control patients. CML levels on IgG were negatively correlated with serum IgG levels in patients with LC, RA, and Sjögren syndrome SjS.CONCLUSIONS:Based on these findings, it is suggested that IgG turnover is not likely to be prolonged but rather may be shortened in LC It may be concluded that, hyperglobulinemia is primarily caused by enhanced synthesis followed by up-regulation of catabolism of immunoglobulins.博士（医学）・乙第1301号・平成24年7月26日Hepato Gastroenterology © 200

EFFECT OF 12-O-TETRADECANOYLPHORBOL 13-ACETATE ON DNA SYNTHESIS IN PROLIFERATING RAT HEPATOCYTES IN PRIMARY CULTURE

DNA synthesis in primary culture of rat hepatocytes was initiated over 16h after the beginning of culture and reached a peak between 32h and 40h under the conditions of this study. The addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) (100 ng/ml) during the initial 24h of culture inhibited DNA synthesis, while addition between 16h or 20h and 24h stimulated DNA synthesis. Chelator-extractable and calcium-dependent protein kinase activity in the soluble fraction of hepatocytes with TPA addition during the initial 24h of culture was apparently reduced at 8, 12, 16 and 24h. It is suggested that TPA addition just prior to the initiation of DNA synthesis activates proten kinase C (PKC) and stimulates DNA synthesis, whereas TPA addition at an early stage of culture inhibits DNA synthesis, possibly because of PKC depletion

Amino acid and vitamin supplementation improved health conditions in elderly participants

The purpose of this study was to investigate the effects of supplementation with amino acids and vitamins on health conditions in unhealthy older people. One bedridden inpatient group (n = 10; mean age, 79.8 ± 8.5 y) and one outpatient group (n = 9; mean age, 72.9 ± 12.2 y) participated in this study. A mixture supplementation with amino acids containing arginine (500 mg/day), glutamine (600 mg/day), and leucine (1200 mg/day), and 11 kinds of vitamins was daily administrated for 8 weeks. In both groups, general blood biomarkers such as white blood cell count, natural killer cell activity, and C-reactive protein levels were measured. All measurements were taken before (baseline), at 4 weeks (mid-point), and after each trial (post-point). At mid-point, natural killer cell activity in the outpatient group increased significantly compared to baseline. At post-point, natural killer cell activity in the outpatient and inpatient groups increased significantly compared to baseline. The other blood biomarkers did not show any significant change throughout the trial. This pilot study suggested that a mixture of arginine, glutamine, leucine, and vitamins is useful to support innate immunity in unhealthy older people, even if their diseases, symptoms, and prescribed medicines are different

重症慢性肝疾患における高γク口ブリン血症の意義 : とくに血清グ口プリン/IgG とICG除去能との相聞に関連して

BACKGROUND/AIMS:Although hyperglobulinemia is frequently detected in severe chronic liver diseases (CLD) such as liver cirrhosis (LC), the mechanism for this is still uncertain. Hyperglobulinemia may represent a functional aspect of the liver.METHODOLOGY: The correlation between serum globulin (GLB) level and each of various liver function tests including the indocyanine green (ICG) retention rate at 15 min (ICGR15) was studied using 146 patients with liver dysfunction. The correlations among GLB, IgG and ICGR15 were also studied in other 32 patients with LC, in whom the glycosylation pattern of IgG was determined by enzyme-linked immunosorbent assay to detect terminal galactose (Gal) and neuraminic acid (NA) using biotinylated lectins.RESULTS:GLB level was predominantly correlated with ICGR15 (r = 0.449) among various liver function tests in 146 patients with liver dysfunction. In the 32 patients with LC, strong positive correlations between GLB and IgG (r = 0.875), between GLB and ICGR15 (r = 0.435), and between IgG and ICGR15 (r = 0.557) were evident. The glycosylation pattern of IgG showed that the proportions of both Gal and NA were inversely correlated with serum IgG levels (r = -0.516 and -0.390, respectively) in these patients. Significant decreases of the proportions were found in patients with IgG elevation (> 20 g/L, n = 13).CONCLUSIONS:The correlation between GLB and ICGR15 suggested that hyperglobulinemia is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity. The removal of immunoglobulins by the liver may be impaired in patients with severe liver dysfunction because the liver is a major catabolic site for immunoglobulins. The glycation pattern suggested that the proportions of asialo IgG and agalactosyl IgG were increased in the LC patients with IgG elevation possibly by deficient receptor-mediated removal in the liver. Although further investigations will be needed, hyperglobulinemia could be predictive for a certain impaired hepatic function estimated by ICG clearance in severe CLD such as LC.博士（医学）・乙第1301号・平成24年7月26日Hepato Gastroenterology © 200

南部黒瀬川帯寒谷層と坂州不整合

The Sakashu Unconformity, a representative unconformity between Late Permian accretionary comprex and Late Triassic shallow-marine sediments in the South Kurosegawa Terrane, has investigated in stratigraphy, sedimentary facies, allochthonous and autochthonous faunas with the view point of post-accretional environmental changes. The accretion mélange of the Hisone Group, basement of the unconformity, yields Late Permian radiolarians. The lower member of the Upper Triassic Sabudani Formation is associated with two types of debris flows. One contains blocks of pelagic chert, carbonates, and greestones. The other is composed of mylonitized granitic breccias and fragments. The latter probably derived from the Mitaki Granites (400+ Ma) of the Kurosegawa Tectonic Zone that form the substratum of the Silurian limestone. The basal middle member of the Sabudani Formation contains huge blocks of weathered limestone/chert that yields late Early Permian conodont fauna (M. bisseli - S. whitei Zone). The hummocky cross-stratification in the middle member of the Sabudani Formation indicates a lower off-shore facies. Existence of the Permian conodont-bearing huge eroded limestone/chert blocks, and early Late Permian radiolarians in chert pebbles of the hummocky cross-stratified lag sediments suggests probable derivation of the conglomerates from the blocks in the Permian accretionary complexes. The Triassic mollusk fauna of the middle and upper members of the Sabudani Formation is correlative with the Carnian (-Norian) Kochigatani bivalve-fauna in the clastic facies of the Kurosegawa Terrane (Outer Zone of SW Japan) as well as with the Mine and Nabae groups, Primorye, Zabaikal and NE Siberia. From a paleobiogeographic point of view, the bivalve-fauna of the clastic sand- and marlstone Kochigatani facies is regarded to differ from that of the carbonate Tethyan facies in the South Chichibu Jurassic Accretionary Terrane

A case of hepatocellular carcinoma with skin injury of the upper abdominal wall after transcatheter arterial chemoembolization: a case report

Introduction Transcatheter arterial chemoembolization has been widely used to treat advanced hepatocellular carcinoma that cannot be treated by local ablation therapies or surgical resection. The effectiveness of transcatheter arterial chemoembolization in prolonging survival has been well established, and approximately one third of newly discovered hepatocellular carcinoma patients were repeatedly treated by transcatheter arterial chemoembolization in Japan. Various kinds of complications have been reported, and many of which are general complications such as hepatic coma, jaundice, fever-up, ascites, and bile duct injury. The hepatic falciform artery is found frequently during postmortem anatomic dissection and the incidence of hepatic falciform artery is reported to be over 60%. Hepatic falciform artery is known to be the responsible artery for supraumbilical skin rash development after arterial chemo infusion therapy; however, skin complications after transcatheter arterial chemoembolization are rare. Case presentation A 70-year-old female with chronic hepatitis C infection was diagnosed as having hepatocellular carcinoma (S4, 20 mm in diameter). Transcatheter arterial chemoembolization was performed via the left hepatic artery, which was a feeding artery of the hepatocellular carcinoma. Two days after that, supraumbilical skin rash with local tenderness and redness appeared. Retrospective analysis revealed that occlusion of the hepatic falciform artery branching from the left hepatic artery with micromaterials caused the skin lesion. Conclusion We should keep in mind that anticancer drugs or embolic materials can flow into the HFA and may cause abdominal wall injury after transcatheter arterial chemoembolization

上皮成長因子受容体を標的とした結腸直腸腫瘍の分子イメージング : 動物モデルにおける腫瘍の検出と治療評価

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope

Cancer genome profiling for GI cancers

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine’s current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n = 30), colorectal (n = 25), biliary tract (n = 15), gastric (n = 11), and hepatocellular carcinoma (n = 8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n = 1), colorectal (n = 3), and small bowel cancers (n = 1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n = 40) and the inability to participate in clinical trials (n = 10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs

Effects of audio and visual distraction on patients’ vital signs and tolerance during esophagogastroduodenoscopy : a randomized controlled trial

Background: Esophagogastroduodenoscopy (EGD) provides an indispensable and unambiguous inspection allowing the discovery upper gastrointestinal lesions. However, many patients are anxious about undergoing EGD. Few studies have investigated the influence on patients’ vital signs and tolerance during EGD using subjective and objective assessments. This study was a prospective randomized controlled study that investigated the influence of audio and visual distraction on EGD. Methods: We randomly divided 289 subjects who underwent EGD into 4 groups (control group, audio group, visual group, combination group) and examined their vital signs, heart rate variability (HRV), psychological items, and acceptance of distraction. Results: Pulse rate (PR) at post-distraction and post-EGD in the 3 distraction groups were significantly lower than those of control group (p< 0.001 and p < 0.01, respectively). Blood pressure (BP) during and post-EGD was significantly higher than that at pre-EGD in control group (p < 0.05), but no significant elevation of BP was observed during the latter half of EGD and post-EGD in the 3 distraction groups. BP at post-distraction improved significantly compared to pre-distraction in the 3 distraction groups (p < 0.05). There was a significant difference in the low-frequency (LF) power/ high-frequency (HF) power at post-distraction and post-EGD among the 4 groups (p< 0.001 and p < 0.001, respectively). The LF power/HF power at post-distraction and post-EGD in the 3 distraction groups was significantly lower than that in control group (p < 0.05). Several items of profile of mood states (POMS) and the impression of EGD at post-distraction improved significantly compared to those at pre-distraction among the 3 distraction groups (p < 0.05). Visual analog scale (VAS) of willingness for the next use of distraction in the 3 distraction groups was excellent because VAS was more than 70. Conclusions: Distractions effectively improved psychological factors, vital signs and some of HRV at pre and post-EGD. Distractions may suppress BP elevation during the latter half of EGD and lead to stability of HRV on EGD

Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)-γ remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation