Predictors of Primary Breast Abscesses and Recurrence

Background  

We investigated the patients and microbiological risk factors that predispose to the development of primary breast abscesses and subsequent recurrence.     

Viscoelastic characterization of high concentration antibody formulations using quartz crystal microbalance with dissipation monitoring

With increasing protein concentrations, therapeutic protein formulations are increasingly demonstrating significant deviations from ideal dilute solution behavior due to protein–protein interactions. These interactions lead to unique biophysical challenges in the administration of biopharmaceuticals including high apparent viscosity and viscoelasticity as well as challenges in maintaining the physical stability of proteins in solution. Here, we describe a straightforward analytical method to calculate the complex modulus and viscosity of high concentration protein solutions from measurements made using quartz crystal microbalance with dissipation monitoring (QCM-D). Further, this methodology was used to investigate the dependence of the storage and loss moduli (G′ and G″, respectively) of a humanized monoclonal antibody solution on solution pH. Unlike recent reports, the effect of protein deposition onto the surface of the quartz sensor crystal was measured and explicitly accounted for during analysis when determining the solution's complex modulus. It was found that the ratio G″/G′ was significantly greater than unity for all solutions investigated, but demonstrated a distinct maximum at pH 5.5 indicating that the solution exhibited the greatest liquid-like behavior at this pH. In addition, measurements were made at higher frequencies, which were found to be more sensitive to the changes in pH than those made at lower frequencies. It was also found that the viscoelastic ratio was relatively insensitive to the frequency of measurement at lower pH, but showed greater dependence on frequency as pH increased. The characterization of the rheological properties of high concentration antibody solutions provides insight into protein–protein interactions, and the methodology presented here demonstrates a straightforward way to determine the viscoelastic properties using ultrasonic rheology without the drawbacks of numerical fitting. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3108–3116, 2009     

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.