COMPLEMENT-MEDIATED ADIPOCYTE LYSIS BY NEPHRITIC FACTOR SERA

Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage

Statistical language models within the algebra of weighted rational languages

Statistical language models are an important tool in natural language processing. They represent prior knowledge about a certain language which is usually gained from a set of samples called a corpus. In this paper, we present a novel way of creating N-gram language models using weighted finite automata. The construction of these models is formalised within the algebra underlying weighted finite automata and expressed in terms of weighted rational languages and transductions. Besides the algebra we make use of five special constant weighted transductions which rely only on the alphabet and the model parameter N. In addition, we discuss efficient implementations of these transductions in terms of virtual constructions

The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections

Background The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). Methods The retrospective evaluation (2002–2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002–2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. Results In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0–11 months (by 87.8%), 6–10 years (by 84.2%) and 11–18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0–11 months. Conclusions UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE

Purification of the food-borne carcinogens 2-amino-3-methylimidazo [4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in heated meat products by immunoaffinity chromatography

A rapid and simple scheme has been developed for the isolation and purification of two of the major mutagenic heterocyclic amines formed in heated beef products by affinity chromatography using monoclonal antibodies which recognize 2-amino-3-methylimidazo(4,5-f]quinoline (IQ). Two cell lines producing IgG antibodies were established following fusion of Sp2 or P3x.63 myeloma cells with spleen cells of immunized BALB/cby mice. The antigen was bovine gamma globulin haptenized with 2-(3-carboxypropylthio)-3-methylimidazo[4,5-f]quinoline. The antibodies were immobilized on CNBr-activated Sepharose 4B. IQ and MeIQx formed in heated beef products were partially purified by XAD-2 chromatography and then applied to the affinity columns. Purification by affinity chromatography was adequate for subsequent quantitative analysis by HPLC with UV detection. With this purification scheme as little as 1 g of beef extract or 15 g of fried beef could be assayed for IQ and MeIQx at the part per billion level. Both antibodies had similar affinity constants for IQ (9.3 × 106 and 6.7 × 106 M−1) and for MeIQx (7.1 × 105 and 2.7 × 105 M−1) and both were suitable for immunoaffinity purification of IQ from complex mixtures. MAb2 could be used as well to selectively remove MeIQx from meat products after partial purification by XAD-2. MAb1, despite having a 3-fold higher affinity than MAb2 for MeIQx, could not be used for affinity chromatography for this mutage

Marked Increase in Avidity of SARS-CoV-2 Antibodies 7-8 Months After Infection Is Not Diminished in Old Age

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays

Chlamydophila abortus Pelvic Inflammatory Disease

We report the first documented case of an extragestational infection with Chlamydophila abortus in humans. The pathogen was identified in a patient with severe pelvic inflammatory disease (PID) by sequence analysis of the ompA gene. Our findings raise the possibility that Chlamydiaceae other than Chlamydia trachomatis are involved in PID

Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa

BACKGROUND: Invasive meningococcal disease (MD), caused by Neisseria meningitidis infection, is endemic in South Africa, with a seasonal peak in winter and spring. There were 2 432 laboratory-confirmed cases between 2006 and 2010. Human deficiency of the fifth complement component (C5D) or complete absence of the sixth component (C6Q0) leads to increased risk of MD, which is often recurrent. All attacks are serious and can lead to death or severe long-term consequences. OBJECTIVE: To determine the frequency of specific disease-associated C5 and C6 gene mutations in patients presenting with MD in the Western Cape. RESULTS: In 109 patients with confirmed invasive MD investigated for local mutations known to cause C5D and C6Q0, 3 were C5D and 11 were C6Q0. In 46 black patients tested, 3 were C5D and 7 were C6Q0. In 63 coloured patients, none were C5D and 4 were C6Q0. All deficient patients were followed up and offered prophylaxis. CONCLUSION: C5D and C6Q0 are not rare genetic diseases in South Africa and affected patients are susceptible to repeated MD; 12.8% of MD patients tested were C5D or C6Q0. Blacks were at greatest risk with 21.7% being either C5D or C6Q0. We strongly recommend diagnostic testing for complement C5 and C6 deficiency in the routine work-up of all MD cases in South Africa. Prophylactic treatment should be started in susceptible individuals