Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane

Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane. Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per μg IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals

Concordance index (C-index) for each scoring model in the training set.

<p>Abbreviations: CHIP score, Chiba hepatocellular carcinoma in intermediate-stage prognostic score; HAP score, hepatoma arterial-embolisation prognostic score.</p><p>Concordance index (C-index) for each scoring model in the training set.</p

A Prognostic Score for Patients with Intermediate-Stage Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

<div><p>Background</p><p>Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.</p><p>Methods</p><p>Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; <i>n</i> = 187) and two affiliated hospitals (validation cohort; <i>n</i> = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.</p><p>Results</p><p>The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; <i>p</i> < 0.0001). These results were confirmed in the external validation cohort (<i>p</i> < 0.0001).</p><p>Conclusions</p><p>The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.</p></div

Flow chart of study.

<p>Flow chart of study.</p

Univariate and multivariate survival analyses for clinical variables.

<p>Abbreviations: UNL, upper normal limit; AST, Aspartate aminotransferase; CRP, C-reactive protein; AFP, alpha-fetoprotein.</p><p>Univariate and multivariate survival analyses for clinical variables.</p

Kaplan-Meier survival curves according to the Bolondi model (A: training dataset, B: validation dataset), the HAP score (C: training dataset, D: validation dataset), and the Yamakado model (E: training dataset, F: validation dataset).

<p>Kaplan-Meier survival curves according to the Bolondi model (A: training dataset, B: validation dataset), the HAP score (C: training dataset, D: validation dataset), and the Yamakado model (E: training dataset, F: validation dataset).</p

Concordance index (C-index) for each scoring model in the validation set.

<p>Abbreviations: CHIP score, Chiba hepatocellular carcinoma in intermediate-stage prognostic score; HAP score, hepatoma arterial-embolisation prognostic score.</p><p>Concordance index (C-index) for each scoring model in the validation set.</p

Calculation of the prognostic score in patients with intermediate-stage hepatocellular carcinoma.

<p>Abbreviation: HCV, hepatitis C virus</p><p>Calculation of the prognostic score in patients with intermediate-stage hepatocellular carcinoma.</p

Patient characteristics.

<p>Abbreviations: AFP, alpha-fetoprotein.</p><p>Patient characteristics.</p