oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Mannose Binding Lectin Deficiency: More than Meets the Eye
Michelle Halbrich, Moshe Ben-Shoshan and Christine McCusker
Clinical Medicine Insights: Pediatrics , 2012, DOI: 10.4137/CMPed.S9860
Abstract: This case report describes a 5-year-old boy who presented to the emergency department with clinical symptoms and chest X-ray findings suggestive of pneumonia. Further history revealed multiple other infections, and workup for immunodeficiency revealed a deficiency of mannose-binding lectin (MBL), a pattern recognition receptor involved in activation of the complement system. Innate immunodeficiency may be more common than currently appreciated, with mutations of MBL affecting up to 50% of individuals in some populations. While pneumonia is a common presentation in the Pediatric Emergency Department, clinical presentations of children with defects of innate immunity can be unpredictable. Children may initially appear well with sudden deterioration. These cases pose particular challenges to physicians, and the level of suspicion for innate defects must remain high. It is crucial to identify patients with such impairments to better manage and prevent future complications.
Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease  [cached]
Albert RK,Connett J,Curtis JL,Martinez FJ
International Journal of COPD , 2012,
Abstract: Richard K Albert,1 John Connett,2 Jeffrey L Curtis,3,4 Fernando J Martinez,3 MeiLan K Han,3 Stephen C Lazarus,5 Prescott G Woodruff51Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO, 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, 4Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, 5Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USABackground: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Methods: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Results: Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.Conclusion: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.Keywords: COPD, acute exacerbations, mannose-binding lectin
Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease
Albert RK, Connett J, Curtis JL, Martinez FJ, Han MK, Lazarus SC, Woodruff PG
International Journal of Chronic Obstructive Pulmonary Disease , 2012, DOI: http://dx.doi.org/10.2147/COPD.S33714
Abstract: nnose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease Original Research (852) Total Article Views Authors: Albert RK, Connett J, Curtis JL, Martinez FJ, Han MK, Lazarus SC, Woodruff PG Published Date November 2012 Volume 2012:7 Pages 767 - 777 DOI: http://dx.doi.org/10.2147/COPD.S33714 Received: 09 May 2012 Accepted: 09 July 2012 Published: 23 November 2012 Richard K Albert,1 John Connett,2 Jeffrey L Curtis,3,4 Fernando J Martinez,3 MeiLan K Han,3 Stephen C Lazarus,5 Prescott G Woodruff5 1Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO, 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, 4Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, 5Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USA Background: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated. Methods: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment. Results: Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined. Conclusion: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.
Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series
Bárbara Padilla-Docal, Alberto J Dorta-Contreras, Raisa Bu-Coifiu-Fanego, René H Martínez-Alderete, Olga de Paula-Almeida, Hansotto Reiber, Jens Jensenius
Journal of Medical Case Reports , 2011, DOI: 10.1186/1752-1947-5-330
Abstract: Three Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis were studied. Serum immunoglobulin A (IgA), IgM, IgG, and complements C3c and C4 levels were quantified by using an immunodiffusion technique. Immunoglobulin E in serum was quantified by nephelometry and mannose-binding lectin by time-resolved fluorometry. Mannose-binding lectin deficiency was observed in the three patients. The first patient showed a reduction in the levels of IgA and IgM and an increase in the values of IgE and C4. The second patient showed a reduction in mannose-binding lectin level with increased IgG, C4 and IgE levels, and the third patient showed a decrease in mannose-binding lectin level and increased levels of IgM and complement C3c as well as a low level of C4.To the best of our knowledge, this is the first report of mannose-binding lectin deficiency associated with Angiostrongylus cantonensis meningoencephalitis in children, and it may contribute to the understanding of the participation of this component of the lectin pathway in the development of the disease.Eosinophilic meningitis, a potentially fatal disease caused by Angiostrongylus cantonensis, a parasitic nematode, is considered an emerging infectious disease [1]. Adult A. cantonensis live in the pulmonary arteries of its definitive hosts, that is, rodents, especially rats, which pass infective first-stage larvae (L1) in their feces. The life cycle also involves mollusks harboring larval stages. In humans, larvae fail to mature, and hence humans and their excreta play no role in the transmission and direct dissemination of the parasite. Humans become infected by ingesting third-stage larvae (L3) in raw or undercooked intermediate host mollusks (for example, snails and slugs) or paratenic hosts (for example, freshwater prawns, crabs, frogs and fish) [1]. Lettuce and vegetable juice have also been identified as sources of
Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus
Irene EM Bultink, D?rte Hamann, Marc A Seelen, Margreet H Hart, Ben AC Dijkmans, Mohamed R Daha, Alexandre E Voskuyl
Arthritis Research & Therapy , 2006, DOI: 10.1186/ar2095
Abstract: Infections are an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Infectious complications occur in 25% to 45% of SLE patients in case series [1,2], and infection as cause of death has been reported in up to 50% of patients with SLE [3,4]. The increased infection rate in patients with SLE has been attributed in part to defects in the complement system, which has an important role in host defence against microorganisms [3].Genetic deficiencies of early components of the classical pathway of complement activation are strongly associated with the development of SLE [5]. In particular, deficiency of C1q is a major predisposing risk factor for SLE. C1q plays a role in the recognition and clearance of apoptotic material [6] and binds predominantly to antibodies and protein structures on bacteria and viruses, resulting in complement activation.More recently, the lectin pathway of complement activation has also been suggested to play a role in the pathogenesis of SLE [7] and in the occurrence of infections in SLE [8-10]. Mannose-binding lectin (MBL) is a serum protein with characteristics very similar to those of C1q [11]. MBL may activate complement through the lectin pathway by interacting with MBL-associated serine proteases (MASPs). Furthermore, MBL can directly opsonise pathogens and enhance the activity of phagocytes [12].Homozygosity for variant MBL alleles is probably a minor risk factor for the presence of SLE, as shown by a recent meta-analysis of all available case-control studies. In that study, a significant association between MBL codon 54 variant B and SLE was demonstrated [13]. Genetic and phenotypic deficiency in producing MBL has been associated with recurrent or serious infections, mainly in children [14] and in immune-compromised individuals [15].In three previous studies, SLE patients homozygous for MBL variant alleles were at an increased risk for serious infections compared with patients who were heteroz
Mannose-Binding Lectin Deficiency Is Associated With Smaller Infarction Size and Favorable Outcome in Ischemic Stroke Patients  [PDF]
Michael Osthoff, Mira Katan, Felix Fluri, Philipp Schuetz, Roland Bingisser, Ludwig Kappos, Andreas J. Steck, Stefan T. Engelter, Beat Mueller, Mirjam Christ-Crain, Marten Trendelenburg
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021338
Abstract: Background The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment. Methodology/Principal Findings In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation. Conclusions MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.
Mannose-Binding Lectin Deficiency Is Associated with Myocardial Infarction: The HUNT2 Study in Norway  [PDF]
Inga Thorsen Vengen, Hans O. Madsen, Peter Garred, Carl Platou, Lars Vatten, Vibeke Videm
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042113
Abstract: Objectives Mannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (MBL2) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in MBL2 and ficolin genes in relation to the risk of MI. Methods and Results Using the population-based HUNT Study in Norway, 57133 persons were followed up for a first-time MI from 1995–1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in MBL2 and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant MBL2 haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29–3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk. Conclusion In a young to middle aged and relatively healthy Caucasian population, MBL2 variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.
Genetically-Defined Deficiency of Mannose-Binding Lectin Is Associated with Protection after Experimental Stroke in Mice and Outcome in Human Stroke  [PDF]
Alvaro Cervera,Anna M. Planas,Carles Justicia,Xabier Urra,Jens C. Jensenius,Ferran Torres,Francisco Lozano,Angel Chamorro
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008433
Abstract: The complement system is a major effector of innate immunity that has been involved in stroke brain damage. Complement activation occurs through the classical, alternative and lectin pathways. The latter is initiated by mannose-binding lectin (MBL) and MBL-associated serine proteases (MASPs). Here we investigated whether the lectin pathway contributes to stroke outcome in mice and humans.
Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study  [PDF]
Michael Osthoff, Hue Mun Au Yong, Melinda M. Dean, Damon P. Eisen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076218
Abstract: Background Pathways coordinated by innate pattern recognition receptors like mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2 (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus) bloodstream infections (BSI) in animal models, but human data are limited. Here, we investigated the role of MBL deficiency and NOD2 mutations in the predisposition to and severity of S. aureus BSI. Patients and Methods A matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2 polymorphisms were analyzed. Results After adjusting for potential confounders, MBL deficiency (<0.5 μg/ml) was found less frequently in cases than controls (26 vs. 41%, OR 0.4, 95% confidence interval (CI) 0.20-0.95, p=0.04) as were low producing MBL genotypes (11 vs. 23%, OR 0.2, 95% CI 0.08-0.75, p=0.01), whereas NOD2 polymorphisms were similarly distributed. Cases with NOD2 polymorphisms had less organ dysfunction as shown by a lower SOFA score (median 2.5 vs. 4.5, p=0.02), whereas only severe MBL deficiency (<0.1 μg/ml) was associated with life-threatening S. aureus BSI (OR 5.6, 95% CI 1.25-24.85, p=0.02). Conclusions Contrary to animal model data, our study suggests MBL deficiency may confer protection against acquiring S. aureus BSI. NOD2 mutations were less frequently associated with multi-organ dysfunction. Further human studies of the innate immune response in S. aureus BSI are needed to identify suitable host targets in sepsis treatment.
Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study
Koert M Dolman, Nannette Brouwer, Florine NJ Frakking, Berit Flat?, Paul P Tak, Taco W Kuijpers, ?ystein F?rre, Anna Smerdel-Ramoya
Arthritis Research & Therapy , 2008, DOI: 10.1186/ar2386
Abstract: In a retrospective cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n = 151), clinical and laboratory disease variables were obtained by clinical examination and chart reviews. Healthy Caucasian adults (n = 194) served as control individuals. MBL2 gene mutations were determined by Taqman analysis to identify genotypes with high, medium and low expression of MBL. Functional MBL plasma concentrations were measured using enzyme-linked immunosorbent assay. Associations between clinical and laboratory variables and MBL2 genotypes were determined by Kruskal-Wallis and χ2 tests.MBL2 genotype frequencies were similar in polyarthritis and oligoarthritis patients as compared with control individuals. MBL plasma concentrations were associated with the high, medium and low MBL genotype expression groups (P < 0.01). In polyarthritis patients, the presence of low-expressing (deficient) MBL2 genotypes was associated with early age at onset of disease (P = 0.03). In oligoarthritis patients, patients with low-expressing MBL2 genotypes were more often in remission (81%) than patients in the medium (54%) and high (56%) genotype groups (P = 0.02). The remaining clinical and laboratory variables, such as arthritis severity index, presence of radiographic erosions and antinuclear antibody positivity, were not associated with MBL2 genotypes.Genetically determined MBL deficiency does not increase susceptibility to JRA, but MBL deficiency is associated with a younger age at onset of juvenile polyarthritis. On the other hand, MBL-deficient children with juvenile oligoarthritis are more often in remission. Therefore, MBL appears to play a dual role in JRA.Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a rheumatic disease of childhood, and includes a heterogeneous group of patients with differing characteristics, clinical manifestations, serological parameters and genetic background. Although the aetiology of JRA remains u
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.