Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization

Background  

HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells.     

Human oligodendroglial cells express low levels of C1 inhibitor and membrane cofactor protein mRNAs

Background  

Oligodendrocytes, neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing complement inhibitor proteins. Oligodendrocytes are vulnerable to complement attack, which is particularly observed in multiple sclerosis. This vulnerability may be related to a deficiency in their ability to express complement regulatory proteins.     

Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: Implications for the development of severe anemia

Background  

Severe anemia due to Plasmodium falciparum malaria is a major cause of mortality among young children in western Kenya. The factors that lead to the age-specific incidence of this anemia are unknown. Previous studies have shown an age-related expression of red cell complement regulatory proteins, which protect erythrocytes from autologous complement attack and destruction. Our primary objective was to determine whether in a malaria-endemic area red cells with low levels of complement regulatory proteins are at increased risk for complement (C3b) deposition in vivo. Secondarily, we studied the relationship between red cell complement regulatory protein levels and hemoglobin levels.     

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Background  

Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.     

Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> after spinal cord injury

Background  

The complement system has been suggested to affect injury or disease of the central nervous system (CNS) by regulating numerous physiological events and pathways. The activation of complement following traumatic CNS injury can also result in the formation and deposition of C5b-9 membrane attack complex (C5b-9/MAC), causing cell lysis or sublytic effects on vital CNS cells. Although complement proteins derived from serum/blood-brain barrier breakdown can contribute to injury or disease, infiltrating immune cells may represent an important local source of complement after injury. As the first immune cells to infiltrate the CNS within hours post-injury, polymorphonuclear leukocytes (PMNs) may affect injury through mechanisms associated with complement-mediated events. However, the expression/association of both early and terminal complement proteins by PMNs has not been fully characterized in vitro, and has not observed previously in vivo after traumatic spinal cord injury (SCI).     

Differential Deposition of C4d and MBL in Glomeruli of Patients with ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis

Objective  

Our previous study suggested involvement of alternative pathway activation of complement in ANCA-positive pauci-immune crescentic glomerulonephritis (CrGN). This study was to investigate the evidence of complement activation in renal biopsy specimens of patients with ANCA-negative pauci-immune CrGN.     

Serum complement C3 has a stronger association with insulin resistance than high sensitive C-reactive protein in non-diabetic Chinese

Objective  

To compare association of complement C3 (C3) and high sensitive C-reactive protein (hs-CRP) with insulin resistance.     

Contribution of gender and body fat distribution to inflammatory marker concentrations in apparently healthy young adults

Objective  

This cross-sectional study assessed the potential contribution of gender, body fat distribution, and their interactions to some inflammatory marker concentrations [C-reactive protein (CRP), complement factor 3 (C3), and ceruloplasmin (Cp)] in young adults.     

Learning while evaluating: the use of an electronic evaluation portfolio in a geriatric medicine clerkship

Background  

Electronic evaluation portfolios may play a role in learning and evaluation in clinical settings and may complement other traditional evaluation methods (bedside evaluations, written exams and tutor-led evaluations).     

Plaque complement activation and cognitive loss in Alzheimer's disease

Background  

Complement activation is increased in Alzheimer's disease (AD), but its significance is unclear. The objective of this study was to determine the relationship between complement activation and cognition during the development of AD.     

The effect of human complement C3 protein applied at different times in treatment of polymicrobial sepsis

Objective  

This study was designed to investigate the effect of exogenous complement C3 administration on outcomes of sepsis and identify an optimal time for this therapy.     

The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice

Background  

Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials.     

Expression of complement system components during aging and amyloid deposition in APP transgenic mice

Background  

A causal role of the complement system in Alzheimer's disease pathogenesis has been postulated based on the identification of different activated components up to the membrane attack complex at amyloid plaques in brain. However, histological studies of amyloid plaque bearing APP transgenic mice provided only evidence for an activation of the early parts of the complement cascade. To better understand the contribution of normal aging and amyloid deposition to the increase in complement activation we performed a detailed characterization of the expression of the major mouse complement components.     

Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

Background  

The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC) and its inhibitor-protein CD59.     

Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease

Background  

Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity.     

Electronic learning can facilitate student performance in undergraduate surgical education: a prospective observational study

Background  

Our institution recently introduced a novel internet accessible computer aided learning (iCAL) programme to complement existing surgical undergraduate teaching methods. On graduation of the first full cycle of undergraduate students to whom this resource was available we assessed the utility of this new teaching facility.     

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

Background

Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.

Results

We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.

Conclusions

Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.     

Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study

Background  

Inflammatory processes are increased in the Parkinson's disease (PD) brain. The long-term use of nonsteroidal anti-inflammatory drugs has been associated, in retrospective studies, with decreased risk for PD, suggesting that inflammation may contribute to development of this disorder. The objective of this study was to determine the extent of complement activation, a major inflammatory mechanism, in PD.     

Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Background  

The complement system is thought to be involved in the pathogenesis of numerous neurological diseases. We previously reported that pre-treatment of murine cortico-hippocampal neuronal cultures with the complement derived anaphylatoxin C5a, protects against glutamate mediated apoptosis. Our present study with C5a receptor knock out (C5aRKO) mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injury in vivo. In this study we explored potential upstream mechanisms involved in C5a mediated neuroprotection in vivo and in vitro.     

Genetic variants of Complement factor H gene are not associated with premature coronary heart disease: a family-based study in the Irish population

Background  

The complement factor H (CFH) gene has been recently confirmed to play an essential role in the development of age-related macular degeneration (AMD). There are conflicting reports of its role in coronary heart disease. This study was designed to investigate if, using a family-based approach, there was an association between genetic variants of the CFH gene and risk of early-onset coronary heart disease.