Comparison of Hepatitis B Virus DNA, RNA, and Core Related Antigen as Predictors of Lamivudine Resistance in Patients with Chronic Hepatitis B

The clinical usefulness of hepatitis B virus (HBV)DNA, RNA, and core related antigen (HBcrAg)assays for predicting the appearance of HBV DNA breakthrough was evaluated and compared in patients with chronic hepatitis B undergoing lamivudine therapy.Methods :Thirty six patients with chronic hepatitis B who received lamivudine therapy for more than 1 year were enrolled. HBV RNA was measured simultaneously with HBV DNA (HBV RNA/DNA) using a real-time detection polymerase chain reaction assay with a preceding step of reverse-transcription. HBV DNA was measured by an HBV AMPLICOR monitor kit. HBcrAg was measured using a chemiluminescence enzyme immunoassay. Results : Sixteen patients (44%) developed HBV DNA breakthrough during the median observation period of 48.4 months (range 7.4-87.8 months). Afterwards, HBV DNA breakthrough was prospected using the three parameters taken 6 months after starting lamivudine therapy. The cut-offlevels for predictions were determined by receiver operating characteristic curves, and were 2.6 log copies/ml for HBV DNA, 3.8 log U/ml for HBV RNA/DNA, and 4.0 log U/ml for HBcrAg.Sensitivity,specificity,and accuracy for predicting HBV DNA breakthrough were 25%, 100%,and 67% respectively for HBV DNA.Similarly,they were 50%,90%,and 72% for HBV RNA/DNA, and 100%, 40%, and 67% for HBcrAg. Conclusion : Our findings confirm that HBV DNA is useful for identifying patients who are at high risk for HBV breakthrough.HBcrAg is useful for isolating those who are at low risk, and HBV RNA/DNA showed predictive characteristics similar to HBV DNA with higher sensitivity and the highest accuracyArticle信州医学雑誌, 58(4):153-162 (2010)departmental bulletin pape

Feasibility study of a novel wireless localization technique using radiofrequency identification markers for small and deeply located lung lesions

Objectives: To evaluate the safety and efficacy of a novel wireless localization technique that uses radiofrequency identification markers for small and deep lung lesions. Methods: Preliminary use of the device was retrospectively evaluated in 2 Japanese centers. Under general anesthesia, a marker was placed as close as possible to the tumor via computed tomography-guided bronchoscopy in a hybrid operation theater. Surgeons located the marker without lung palpation using a detection probe the tone of which changed to indicate the marker-probe distance. Efficacy was defined as functional marker placement (bronchoscopy time and marker position) and deep margin distance. Results: Twelve markers were placed for 11 lesions (mean size, 6.8 ± 2.7 mm) located at a mean depth from the pleura of 11.4 ± 8.4 mm (range = 0-26.0 mm). Of 12 markers, 7 markers (58.3%) were placed within 10 mm from the lesion in 25.5 ± 14.4 minutes. For the 11 wedge resections, markers were placed at a mean distance of 6.7 mm (range, 0-13.0 mm) from the lesion and a mean distance of 14.4 mm (range, 3.0-42.0 mm) from the pleura. All markers were recovered without complications, and all tumors were resected with negative margins. For 5 lesions >10 mm deep to the pleura (mean depth, 18.9 ± 5.5 mm; range, 11.0-26.0 mm), the median depth of the surgical margin was 11.6 ± 2.1 mm (range, 9.0-14.0 mm). Conclusions: Radiofrequency identification marking was safe and precisely localized small lung lesions, including their depth

Expert consensus on hospitalization for assessment: a survey in Japan for a new forensic mental health system

<p>Abstract</p> <p>Background</p> <p>In Japan, hospitalization for the assessment of mentally disordered offenders under the Act on Medical Care and Treatment for the Persons Who Had Caused Serious Cases under the Condition of Insanity (the Medical Treatment and Supervision Act, or the MTS Act) has yet to be standardized.</p> <p>Methods</p> <p>We conducted a written survey that included a questionnaire regarding hospitalization for assessment; the questionnaire consisted of 335 options with 9 grades of validity for 60 clinical situations. The survey was mailed to 50 Japanese forensic mental health experts, and 42 responses were received.</p> <p>Results</p> <p>An expert consensus was established for 299 of the options. Regarding subjects requiring hospitalization for assessment, no consensus was reached on the indications for electroconvulsive therapy (ECT) or for confronting the offenders regarding their offensive behaviors.</p> <p>Conclusions</p> <p>The consensus regarding hospitalization for assessment and its associated problems were clarified. The consensus should be widely publicized among practitioners to ensure better management during the hospitalization of mentally disordered offenders for assessment.</p

Serum chemokine levels are associated with the outcome of pegylated interferon and ribavirin therapy in patients with chronic hepatitis C

Aim: Serum chemokine levels and amino acid substitutions in the interferon-sensitivity determining region (ISDR) and core region have been associated with treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)-infected patients. The present study was conducted to clarify the association between serum chemokines and treatment outcome in patients with chronic HCV-1 infection in a Japanese cohort. Methods: A total of six serum chemokines were quantified before, during and after pegylated interferon and ribavirin treatment in 79 genotype 1 chronic HCV patients using a multiple bead array system. Viral ISDR and core region variants were determined by direct sequencing. Results: The baseline serum levels of eotaxin, IP-10 and RANTES were significantly higher in chronic HCV patients than in controls. High levels of eotaxin and macrophage inflammatory protein (MIP)-1 beta before therapy and more than two mutations in the ISDR were associated with a sustained virological response, and patients with more than two mutations in the ISDR also had significantly higher MIP-1 beta levels. Receiver-operator curve analysis showed a 77% sensitivity and 73% specificity for predicting an SVR using MIP-1 beta values. Conclusion: Serum MIP-1 beta levels may predict the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR.ArticleHEPATOLOGY RESEARCH. 41(6):587-593 (2011)journal articl

Serum interleukin (IL)-10 and IL-12 levels and IL28B gene polymorphisms: pretreatment prediction of treatment failure in chronic hepatitis C

Background: Both IL28B gene polymorphisms and serum levels of interleukin (IL)-10, IL-12p40 and IL-18 have been reported to affect the outcome of natural and pegylated interferon and ribavirin-treated HCV infection. Methods: To clarify their association and predictive value in treatment outcome of genotype 1 HCV-infected patients, we measured pretreatment serum IL-10, IL-12p40 and IL-18 levels using multiplex assays and determined IL28B gene polymorphisms (rs 8099917) in 52 cases with chronic hepatitis C. Results: High baseline levels of IL-10 (P<0.001) and low levels of IL-12p40 (P<0.001) were significantly associated with a non-virological response (NVR) in our cohort. The IL28B polymorphism was tested and TT, TG or GG genotypes were found in 60%, 38% and 2% of patients, respectively, with corresponding NVR rates of 10%, 60% and 100% (P<0.001). Serum cytokine levels were significantly correlated with IL28B gene polymorphisms. When serum IL-10 levels were stratified at 5.0 pg/ml, NVR rates were 50% versus 0% (P=0.004) for the IT genotype and 87% versus 0% (P=0.001) for the TG or GG genotypes. Similarly, low IL-12p40 levels were associated with an NVR in patients with TG or GG genotypes (P=0.006). In multivariate analysis, high IL-10, low IL-12p40 and IL28B TG or GG genotypes were independently associated with an NVR. Conclusions: Serum IL-10 and IL-12p40 levels in combination with IL28B genotype, especially G-allele carriage, are strong predictive markers of an NVR to HCV treatment with pegylated interferon and ribavirin.ArticleANTIVIRAL THERAPY. 16(7):1073-1080 (2011)journal articl

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture

ヒトのiPS細胞から腱の細胞を作製する --アキレス腱断裂のラットに移植し、機能回復を確認--. 京都大学プレスリリース. 2021-08-31.Repairing tendon injuries with stem cells. 京都大学プレスリリース. 2021-08-31.Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury

Association of Serum Cytokine Levels With Treatment Response to Pegylated Interferon and Ribavirin Therapy in Genotype 1 Chronic Hepatitis C Patients

Methods. We quantified a total of 8 serum cytokines before, during, and after treatment in 79 genotype 1 chronic HCV patients. Viral ISDR and core region variants were determined by direct sequencing. Results. High levels of interleukin (IL)-12 and IL-18 and more than 2 mutations in the ISDR were associated with a sustained virological response (SVR). Conversely, high baseline IL-10 levels and glutamine at amino acid 70 of the HCV core protein (Gln70) were significantly associated with a nonresponse to treatment, and patients with Gln70 had significantly higher IL-10 levels. In multivariate analysis, low IL-10, high IL-12, and high IL-18 levels were independently associated with an SVR. These 3 cytokine levels were decreased from baseline levels 4 weeks into treatment and remained low in patients with an SVR. Conclusion. Serum IL-10, IL-12, and IL-18 levels are predictive of the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR and core region.ArticleJOURNAL OF INFECTIOUS DISEASES. 203(8):1087-1095 (2011)journal articl

Early detection of interstitial pneumonia by monitoring KL-6 in a chronic hepatitis C patient undergoing pegylated interferon and ribavirin therapy

A 58-year-old woman with chronic hepatitis C developed interstitial pneumonia (IP) while undergoing pegylated interferon (PEG IFN)-alpha-2a and ribavirin (RBV) therapy. Serum levels of sialylated carbohydrate antigen KL-6 (KL-6), a known marker of disease activity in fibrosing lung disorders, had been regularly measured once a month for early detection of IP, and had begun rising noticeably from 12 weeks to 540 U/mL at 33 weeks of treatment. On examination, remarkable fine crackles were detected by dorsal auscultation and bilateral ground-glass opacities and reticular shadows were depicted by computed tomography. The patient successfully recovered from her early-stage pneumonia by immediate discontinuation of therapy, which indicates that regular monitoring of serum KL-6 may be effective for avoidance of IP progression induced by PEG IFN and RBV therapy.ArticleHEPATOLOGY RESEARCH. 41(9):904-909 (2011)journal articl

Association analysis of toll-like receptor 4 polymorphisms in Japanese primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often result in liver failure. Toll-like receptor (TLR) 4 recognizes lipopolysaccharides of Gram-negative bacteria. Infectious agents have been suspected to play a crucial role in PBC pathogenesis since TLR4 expression was found in bile duct epithelial cells and periportal hepatocytes in liver tissues of PBC. To assess the potential contribution of TLR4 SNPs to the development of this disease, we genotyped five SNPs in TLR4 in 261 PBC patients and 359 controls using a TaqMan assay. No significant positive associations with either PBC susceptibility or progression were uncovered. These results indicate that TLR4 polymorphisms do not play a prominent role in the development of PBC in Japanese patients. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.ArticleHUMAN IMMUNOLOGY. 74(2):219-222 (2013)journal articl

Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

IL28B single nucleotide polymorphisms (SNPs) are associated with spontaneous and treatment-induced elimination of hepatitis C virus (HCV). To assess whether the IL28B rs8099917 SNP also affects the progression of chronic HCV infection, we genotyped 511 Japanese HCV patients, including 69 with hepatocellular carcinoma (HCC). The T/T genotype of rs8099917 was not associated with the development of HCC (p = 0.623), although stepwise logistic regression analysis showed that liver cirrhosis, age greater than 68 years, and serum albumin <4.2 mg/dl were associated with HCC onset. It appears that the IL28B SNP does not directly influence hepatocarcinogenesis in chronic HCV infection.ArticleHUMAN IMMUNOLOGY. 73(3):298-300 (2012)journal articl