Transcriptional responses of host peripheral blood cells to tuberculosis infection.

Host responses following exposure to Mycobacterium tuberculosis (TB) are complex and can significantly affect clinical outcome. These responses, which are largely mediated by complex immune mechanisms involving peripheral blood cells (PBCs) such as T-lymphocytes, NK cells and monocyte-derived macrophages, have not been fully characterized. We hypothesize that different clinical outcome following TB exposure will be uniquely reflected in host gene expression profiles, and expression profiling of PBCs can be used to discriminate between different TB infectious outcomes. In this study, microarray analysis was performed on PBCs from three TB groups (BCG-vaccinated, latent TB infection, and active TB infection) and a control healthy group. Supervised learning algorithms were used to identify signature genomic responses that differentiate among group samples. Gene Set Enrichment Analysis was used to determine sets of genes that were co-regulated. Multivariate permutation analysis (p < 0.01) gave 645 genes differentially expressed among the four groups, with both distinct and common patterns of gene expression observed for each group. A 127-probeset, representing 77 known genes, capable of accurately classifying samples into their respective groups was identified. In addition, 13 insulin-sensitive genes were found to be differentially regulated in all three TB infected groups, underscoring the functional association between insulin signaling pathway and TB infection.

Early transcriptional responses of HepG2-A16 liver cells to infection by Plasmodium falciparum sporozoites.

Invasion of hepatocytes by Plasmodium sporozoites deposited by Anopheles mosquitoes, and their subsequent transformation into infective merozoites is an obligatory step in the initiation of malaria. Interactions between the sporozoites and hepatocytes lead to a distinct, complex and coordinated cellular and systemic host response. Little is known about host liver cell response to sporozoite invasion, or whether it is primarily adaptive for the parasite, for the host, or for both. Our present study used gene expression profiling of human HepG2-A16 liver cells infected with Plasmodium falciparum sporozoites to understand the host early cellular events and factors influencing parasite infectivity and sporozoite development. Our results show that as early as 30 min following wild-type, non-irradiated sporozoite exposure, the expressions of at least 742 genes was selectively altered. These genes regulate diverse biological functions, such as immune processes, cell adhesion and communications, metabolism pathways, cell cycle regulation, and signal transduction. These functions reflect cellular events consistent with initial host cell defense responses, as well as alterations in host cells to sustain sporozoites growth and survival. Irradiated sporozoites gave very similar gene expression pattern changes, but direct comparative analysis between liver gene expression profiles caused by irradiated and non-irradiated sporozoites identified 29 genes, including glypican-3, that were specifically up-regulated only in irradiated sporozoites. Elucidating the role of this subset of genes may help identify the molecular basis for the irradiated sporozoites inability to develop intrahepatically, and their usefulness as an immunogen for developing protective immunity against pre-erythrocytic stage malaria.

Time course proteomic profiling of human myocardial infarction plasma samples: an approach to new biomarker discovery.

BACKGROUND: The aim of this study was to identify novel candidate biomarker proteins differentially expressed in the plasma of patients with early stage acute myocardial infarction (AMI) using SELDI-TOF-MS as a high throughput screening technology. METHODS: Ten individuals with recent acute ischemic-type chest pain (<12 h duration) and ST-segment elevation AMI (1STEMI) and after a second AMI (2STEMI) were selected. Blood samples were drawn at six times after STEMI diagnosis. The first stage (T0) was in Emergency Unit before receiving any medication, the second was just after primary angioplasty (T2), and the next four stages occurred at 12 h intervals after T0. Individuals (n=7) with similar risk factors for cardiovascular disease and normal ergometric test were selected as a control group (CG). Plasma proteomic profiling analysis was performed using the top-down (i.e. intact proteins) SELDI-TOF-MS, after processing in a Multiple Affinity Removal Spin Cartridge System (Agilent). RESULTS: Compared with the CG, the 1STEMI group exhibited 510 differentially expressed protein peaks in the first 48 h after the AMI (p<0.05). The 2STEMI group, had ~85% fewer differently expressed protein peaks than those without previous history of AMI (76, p<0.05). Among the 16 differentially-regulated protein peaks common to both STEMI cohorts (compared with the CG at T0), 6 peaks were persistently down-regulated at more than one time-stage, and also were inversed correlated with serum protein markers (cTnI, CK and CKMB) during 48 h-period after IAM. CONCLUSIONS: Proteomic analysis by SELDI-TOF-MS technology combined with bioinformatics tools demonstrated differential expression during a 48 h time course suggests a potential role of some of these proteins as biomarkers for the very early stages of AMI, as well as for monitoring early cardiac ischemic recovery.

Time course proteomic profiling of human myocardial infarction plasma samples: An approach to new biomarker discovery

Background: The aim of this study was to identify novel candidate biomarker proteins differentially expressedin the plasma of patients with early stage acute myocardial infarction (AMI) using SELDI-TOF-MS as a highthroughput screening technology.Methods: Ten individuals with recent acute ischemic-type chest pain (b12 h duration) and ST-segmentelevation AMI (1STEMI) and after a second AMI (2STEMI) were selected. Blood samples were drawn at sixtimes after STEMI diagnosis. The first stage (T0) was in Emergency Unit before receiving any medication, thesecond was just after primary angioplasty (T2), and the next four stages occurred at 12 h intervals after T0.Individuals (n=7) with similar risk factors for cardiovascular disease and normal ergometric test were selectedas a control group (CG). Plasma proteomic profiling analysis was performed using the top-down (i.e. intactproteins) SELDI-TOF-MS, after processing in a Multiple Affinity Removal Spin Cartridge System (Agilent).Results: Compared with the CG, the 1STEMI group exhibited 510 differentially expressed protein peaks in thefirst 48 h after the AMI (pb0.05). The 2STEMI group, had ~85% fewer differently expressed protein peaks thanthose without previous history of AMI (76, pb0.05). Among the 16 differentially-regulated protein peakscommon to both STEMI cohorts (compared with the CG at T0), 6 peaks were persistently down-regulated atmore than one time-stage, and also were inversed correlated with serum protein markers (cTnI, CK and CKMB)during 48 h-period after IAM.Conclusions: Proteomic analysis by SELDI-TOF-MS technology combinedwith bioinformatics tools demonstrateddifferential expression during a 48 h timecourse suggests a potential role of someof these proteins as biomarkersfor the very early stages of AMI, as well as for monitoring early cardiac ischemic recovery.

Evolution of telemedicine in Russia: the influence of the space program on modern telemedicine programs.

Telemedicine education and application throughout Russia has its roots in Russia's space program. The concepts of telemedicine have evolved during the course of 40 years of space exploration. This paper reviews the evolution of telemedicine and the achievements of the Soviet/Russian Space Program.