The PtdIns 3-kinase/Akt pathway regulates macrophage-mediated ADCC against B cell lymphoma.

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNgamma as the effectors.

Changes in cytokine concentrations in graft renal vein during reperfusion in patients with and without delayed graft function.

Introduction: The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for the subsequent damage that occurs during the reperfusion phase. Despite recent advances in immunosuppressive therapy, delayed graft function (DGF) remains an important problem after kidney transplantation.

Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K.

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe(-/-) mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe(-/-), Npc1(-/-) mice.

Immune reconstitution in the sigmoid colon after long-term HIV therapy.

Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for > or =4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments.

Breast cancer-associated fibroblasts confer AKT1-mediated epigenetic silencing of Cystatin M in epithelial cells.

The interplay between histone modifications and promoter hypermethylation provides a causative explanation for epigenetic gene silencing in cancer. Less is known about the upstream initiators that direct this process. Here, we report that the Cystatin M (CST6) tumor suppressor gene is concurrently down-regulated with other loci in breast epithelial cells cocultured with cancer-associated fibroblasts (CAF).

Limits on an energy dependence of the speed of light from a flare of the active galaxy PKS 2155-304.

In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented.

Ventilatory and cerebrovascular responses to hypercapnia in patients with obstructive sleep apnoea: effect of CPAP therapy.

The purpose of this study was to assess whether the cerebrovascular response to hypercapnia is blunted in OSA patients and if this could alter the ventilatory response to hypercapnia before and after CPAP therapy. We measured the cerebrovascular, cardiovascular and ventilatory responses to hypercapnia in 8 patients with OSA (apnoea-hypopnoea index=101+/-10) before and after 4-6 weeks of CPAP therapy and in 10 control subjects who did not undergo CPAP therapy. The cerebrovascular and ventilatory responses to hypercapnia were not different between OSA and controls at baseline or follow-up.

e-Science, caGrid, and Translational Biomedical Research.

Translational research projects target a wide variety of diseases, test many different kinds of biomedical hypotheses, and employ a large assortment of experimental methodologies. Diverse data, complex execution environments, and demanding security and reliability requirements make the implementation of these projects extremely challenging and require novel e-Science technologies.

HIV-specific T-cells accumulate in the liver in HCV/HIV co-infection.

Background And Aims: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses.

Methods: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry.

NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism.

Osteoporosis results from an imbalance in skeletal remodeling that favors bone resorption over bone formation. Bone matrix is degraded by osteoclasts, which differentiate from myeloid precursors in response to the cytokine RANKL. To gain insight into the transcriptional regulation of bone resorption during growth and disease, we generated a conditional knockout of the transcription factor nuclear factor of activated T cells c1 (Nfatc1).

Analysis of the IKKbeta/NF-kappaB signaling pathway during embryonic angiogenesis.

The nuclear factor-kappaB (NF-kappaB) signaling pathway regulates cellular growth, survival, differentiation and development. In this study, the functions of IkappaB kinase (IKK)beta in angiogenesis during mouse development were examined. Conditional disruption of the Ikkbeta locus in endothelial cells using the well-characterized Tie2-Cre transgene resulted in embryonic lethality between embryonic day (E) 13.

Tensor classification of N-point correlation function features for histology tissue segmentation.

In this paper, we utilize the N-point correlation functions (N-pcfs) to construct an appropriate feature space for achieving tissue segmentation in histology-stained microscopic images. The N-pcfs estimate microstructural constituent packing densities and their spatial distribution in a tissue sample. We represent the multi-phase properties estimated by the N-pcfs in a tensor structure.

Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections.

Members of the Mycobacterium avium complex (MAC) may cause chronic pulmonary infections in otherwise healthy elderly persons but rarely invade parts of the body outside of the lungs in immunocompetent hosts. We present a case of an isolated intracranial MAC infection in an apparently immunocompetent individual and review previous reports. We studied the T-cell and monocyte responses in healthy volunteers, individuals with a pulmonary MAC infection, and one individual with an isolated intracranial MAC infection.

The menstrual cycle and adolescent health.

Early reproductive characteristics, including menarcheal age, may have significant effects on later health outcomes. While early exposure to ovarian hormones may influence the risk for certain diseases, the degree to which this exposure is mediated by other factors is not well understood. Research on secular trends in age at menarche and subsequent outcomes in women's health across the lifespan can help to clarify the importance of age at menarche.

Splenic and parasplenic abscess as a late complication of laparoscopic nissen fundoplication--case report and review of the literature.

Purpose: To present a rare late complication of laparoscopic Nissen fundoplication.

Material And Methods: Splenic and parasplenic abscess which formed in 25 year old man sixty days after laparoscopic Nissen fundoplication was not adequately detected by a double ultrasound examination but by a CT-scan, ordered when general status of the patient deteriorated.

Results: Operative treatment comprised splenectomy with drainage and subsequent relaparotomy for intestinal obstruction.

Does calcium channel blocker improvement of perfusion impact the functioning of kidney graft in early period after transplantation?

The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation. A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion. The control group included 48 paired kidneys without verapamil addition.

Unraveling the genomic mosaic of a ubiquitous genus of marine cyanobacteria.

Background: The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this ecologically important group.

Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors.

The hepatic complications of chronic hepatitis C (CHC) usually occur only after progression to cirrhosis has taken place. Progression to cirrhosis, however, is extremely variable and depends on a broad set of host and viral factors that modify the rate at which fibrosis develops in a given individual. Despite their inherent limitations, studies of the natural history of CHC have identified several nonmodifiable factors associated with disease progression.

CEACAM1 dynamics during neisseria gonorrhoeae suppression of CD4+ T lymphocyte activation.

Neisseria gonorrhoeae colony opacity-associated (Opa) proteins bind to human carcinoembryonic antigen cellular adhesion molecules (CEACAM) found on host cells including T lymphocytes. Opa binding to CEACAM1 suppresses the activation of CD4(+) T cells in response to a variety of stimuli. In this study, we use primary human CD4(+) T cells isolated from peripheral blood to define the molecular events occurring subsequent to Opa-CEACAM1 binding.

The Ewing sarcoma protein (EWS) binds directly to the proximal elements of the macrophage-specific promoter of the CSF-1 receptor (csf1r) gene.

Many macrophage-specific promoters lack classical transcriptional start site elements such as TATA boxes and Sp1 sites. One example is the CSF-1 receptor (CSF-1R, CD115, c-fms), which is used as a model of the transcriptional regulation of macrophage genes. To understand the molecular basis of start site recognition in this gene, we identified cellular proteins binding specifically to the transcriptional start site (TSS) region.

Virus-specific interleukin-17-producing CD4+ T cells are detectable in early human immunodeficiency virus type 1 infection.

T(H)-17 cells have been shown to play a role in bacterial defense, acute inflammation, and autoimmunity. We examined the role of interleukin 17 (IL-17) production in human immunodeficiency virus type 1 (HIV-1) infection. Both HIV-1- and cytomegalovirus (CMV)-specific IL-17-producing CD4(+) T cells were detectable in early HIV-1 infection but were reduced to nondetectable levels in chronic and nonprogressive HIV-1 infection.

Detection assays for HIV proteins.

This updated unit describes four assays for detection of HIV proteins including: (1) a quantitative ELISA, (2) a quantitative immunoblotting assay, (3) a qualitative immunofluorescence assay, and (4) a functional assay to measure virus-associated reverse transcriptase activity as an indicator of viral production.