Elevated soluble CD30 characterizes patients with hepatitis C virus-induced liver allograft cirrhosis

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) significantly accelerates progression to allograft cirrhosis. Current biochemical parameters to monitor progression of chronic HCV after OLT have yielded low specificity and sensitivity. Here we investigated the HCV-specific immunity and serum levels of soluble CD30 (sCD30), a novel marker of Th2 immunity, in patients with and without allograft cirrhosis. Patients with hepatic inflammation but no cirrhosis (HIN, n=20) revealed elevated serum interferon (IFN)-gamma and high frequency of IFN-gamma producing CD4 T(h1) cells compared to those with hepatic cirrhosis (HFC, n=20) that had high interleukin (IL)-5 and IL-5 producing CD4 T(h2) cells. Patients with HFC, but not HIN, were found to have significantly higher levels of sCD30. Therefore, we conclude that lack of optimal Th1-type CD4 T cells is associated with HCV-induced allograft cirrhosis. Further, sCD30 may represent a novel marker for surveillance of hepatic cirrhosis in transplant recipients with chronic HCV infection.     

Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection

BACKGROUND: Chronic human lung allograft rejection, represented by bronchiolitis obliterans syndrome (BOS), is the single most important factor that limits the long-term survival following lung transplantation (LT). However, the pathogenesis of BOS remains unclear. We hypothesized that the early posttransplant inflammation would promote the development of donor anti-human leukocyte antigen (HLA) alloimmunity and predispose to BOS. METHODS: Serum levels of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, IP-10, MIG, MCP-1, MIP-1alpha, MIP-1beta, RANTES, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, granulocyte-macrophage colony-stimulating factor, IL-1Ralpha, and IL-2R were serially analyzed in 31 BOS+ and matched 31 BOS- patients using quantitative multiplex bead immunoassays. Donor-specific HLA class II cellular immunity was analyzed using enzyme-linked immunospot (ELISPOT) by testing recipient peripheral blood mononuclear cells against mismatched donor HLA-DR peptides. Anti-HLA class II antibodies were monitored using flow panel reactive antibodies. RESULTS: There was early posttransplant elevation in basal serum levels of proinflammatory chemokines IP-10 and MCP-1 and Th1-cytokines IL-1beta, IL-2, IL-12, and IL-15 in BOS+ patients, compared to BOS- and normal subjects. In addition, a threefold decline in IL-10 levels was found during BOS development. BOS+ patients revealed increased development of HLA class II alloantibodies and Th1-predominant donor-specific cellular immunity with high frequency of IFN-gamma and low IL-5 producing T-cells. CONCLUSION: Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.     

AID Biology: A pathological and clinical perspective

Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.     

Eudragit S100 Coated Citrus Pectin Nanoparticles for Colon Targeting of 5-Fluorouracil

In the present study, Eudragit S100 coated Citrus Pectin Nanoparticles (E-CPNs) were prepared for the colon targeting of 5-Fluorouracil (5-FU). Citrus pectin also acts as a ligand for galectin-3 receptors that are over expressed on colorectal cancer cells. Nanoparticles (CPNs and E-CPNs) were characterized for various physical parameters such as particle size, size distribution, and shape etc. In vitro drug release studies revealed selective drug release in the colonic region in the case of E-CPNs of more than 70% after 24 h. In vitro cytoxicity assay (Sulphorhodamine B assay) was performed against HT-29 cancer cells and exhibited 1.5 fold greater cytotoxicity potential of nanoparticles compared to 5-FU solution. In vivo data clearly depicted that Eudragit S100 successfully guarded nanoparticles to reach the colonic region wherein nanoparticles were taken up and showed drug release for an extended period of time. Therefore, a multifaceted strategy is introduced here in terms of receptor mediated uptake and pH-dependent release using E-CPNs for effective chemotherapy of colorectal cancer with uncompromised safety and efficacy.     

Sagittal spinopelvic parameters in children with achondroplasia: identification of 2 distinct groups

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.     

Regulation and dysregulation of epithelial Na+ channels

Epithelial Na⁺ channels (ENaC) form a highly regulated pathway for the reabsorption of Na⁺ from urine. This regulation can take place at a number of different levels, including synthesis of channel protein, trafficking of the protein between the surface and internal membranes, proteolytic cleavage and channel gating. This article reviews the role of these different modes of regulation under physiological conditions and considers the possible contributions of dysregulation of these processes in disease states, particularly hypertension.