Macrophage inflammatory protein-2 (MIP-2)/CXCR2 blockade attenuates acute graft-versus-host disease while preserving graft-versus-leukemia activity.

Allogenic bone marrow transplantation (BMT), an important treatment for hematological malignancies, is often complicated by graft-versus-host disease (GVHD). Suppression of GVHD is associated with the unwanted diminishment of the graft-versus-leukemia (GVL) response. The aim of this study was to maintain the benefits of GVL during GVHD suppression through isolated blockade of T-cell migration factors. To this end, we developed a murine model of B-cell leukemia, which was treated with BMT to induce GVHD. Within this model, functional blockade of MIP-2/CXCR2 was analyzed by observing proteomic, histologic and clinical variables of GVHD manifestation. Luminex assay of collected tissue identified several cytokines [granulocyte colony-stimulating factor (G-CSF), keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), and interleukin-23 (IL-23)] that were upregulated during GHVD, but reduced by neutralizing the MIP-2/CXCR2 axis. In addition, donor T-cell blockade of CXCR2 combined with recipient administration of anti-MIP-2 caused a significant decrease in GVHD while preserving the GVL response. We propose that blocking the MIP-2/CXCR2 axis represents a novel strategy to separate the toxicity of GVHD from the beneficial effects of GVL after allogenic BMT.

Metabonomic understanding of probiotic effects in humans with irritable bowel syndrome.

GOALS: This study was undertaken to evaluate the effects of probiotics on adult patients with irritable bowel syndrome (IBS) through clinical parameters and H nuclear magnetic resonance (NMR)-based metabonomics. BACKGROUND: As systematic effect of probiotics on inflammatory bowel disease through metabonomics approach has been extensively studied to date, metabonomic characterization of the probiotics effect on IBS is also needed for better understanding the effect with respect to host metabolic mechanism. STUDY: Seventy-four IBS patients meeting Rome criteria were randomized to receive probiotics and placebo through a parallel-group, double-blind, randomized, placebo-controlled clinical study. Probiotic fermented milk and placebo were administered 3 times daily for 8 weeks. Improvements of IBS were assessed according to Rome III questionnaires and H NMR metabolic profiling of serum and fecal samples from all participants was used to characterize a significant change in serum and fecal metabolome before and after probiotics. RESULTS: Fecal counts of the Lactobacilli, but not Bifidobacteria species, which included in the probiotic milk, were increased significantly in feces of IBS patients receiving treatment (P=0.014). NMR data set coupled with multivariate statistical analysis identified intrinsically elevated serum levels of glucose (P=0.0265) and tyrosine (P=0.0016) in IBS patients. These levels normalized to those of healthy individuals in the probiotic administration group, but not the placebo group. CONCLUSIONS: This metabonomic study suggests that in a subset of IBS patients there exists a potential dysregulation in energy homeostasis (serum glucose) and liver function (serum tyrosine) that may be improved through probiotics supplementation. Moreover, global metabolic profiling highlights the potential of metabonomic approach for assessing bowel diseases or symptoms with respect to host metabolic perturbation.

Developing a portable gait cycle detection system using an inertial sensor and evaluating the accuracy of the gait cycle detection.

Although researches had analyzed gait using small sensors, they analyzed only normal gaits. Thus, a research that can overcome the spatial limitations of the existing motion analyses and diagnose abnormal gaits for medical treatment is needed. Accordingly, this research developed the portable gait detection system that can detect gait using a gyroscope, and evaluated the accuracy of the system. The results showed an average recognition error rate of 1.7% for the normal and abnormal gaits, and confirmed that the gait cycle was detected with a high degree of accuracy. Using these characteristics, we could distinguish or diagnose, and treat, an abnormal gait.