Self-heating of Hay and Grain in Dewar Flasks and the Development of Farmer's Lung Antigens

In moist hay allowed to self-heat aerobically in Dewax flasks, the pattern of temperature change with time was affected considerably by the type of hay and duration of storage, but there was a relationship between water content and maximum temperature reached, Below 29 yo water con-tent there was little heating or antigen production; in the critical range of 29-34 yo water content, different lots of hay self-heated to different tem-peratures between 33 and 55 " and varied widely in their content of farmer's lung hay antigen complex (FLH), the wetter hays usually producing the more antigen; all samples with 40 % water heated to c. 6.5 ' and produced FLH antigen, associated with the presence of Thermopolysporu polyspora. Pro-gressively less antigen, especially in the lower regions of the flasks, was produced as water content increased from 47 to 68 yo. Moist barley and oat grain also self-heated and produced FLH antigen, usually only in the middle of the grain mass, where T. polysporu was most abundant; the drier upper layers and the lower regions where excess water accumulated were free from the antigen

Unraveling the directional link between adiposity and inflammation: a bidirectional mendelian randomization approach

<b>Context</b>: Associations between adiposity and circulating inflammation markers are assumed to be causal, although the direction of the relationship has not been proven. <b>Objective</b>: The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian randomization approach. <b>Methods</b>: In the PROSPER study of 5804 elderly patients, we related C-reactive protein (CRP) single nucleotide polymorphisms (SNPs) (rs1800947 and rs1205) and adiposity SNPs (FTO and MC4R) to body mass index (BMI) as well as circulating levels of CRP and leptin. We gave each individual two allele scores ranging from zero to 4, counting each pair of alleles related to CRP levels or BMI. <b>Results</b>: With increasing CRP allele score, there was a stepwise decrease in CRP levels (P for trend < 0.0001) and a 1.98 mg/liter difference between extremes of the allele score distribution, but there was no associated change in BMI or leptin levels (P ≥ 0.89). By contrast, adiposity allele score was associated with 1) an increase in BMI (1.2 kg/m2 difference between extremes; P for trend 0.002); 2) an increase in circulating leptin (5.77 ng/ml difference between extremes; P for trend 0.0027); and 3) increased CRP levels (1.24 mg/liter difference between extremes; P for trend 0.002). <b>Conclusions</b>: Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels, with no evidence for any reverse pathway. Future studies should extend our findings to other circulating inflammatory parameters. This study illustrates the potential power of Mendelian randomization to dissect directions of causality between intercorrelated metabolic factors

A 58-Year-Old Woman with Abdominal Symptoms and Elevated C-Reactive Protein

Babak Javid and colleagues discuss the differential diagnosis, investigation, and management of a woman with abdominal symptoms and a raised C-reactive protein

Non-fibrillar components of amyloid deposits mediate the self-association and tangling of amyloid fibrils

Amyloid deposits are proteinaceous extra-cellular aggregates associated with a diverse range of disease states. These deposits are composed predominantly of amyloid fibrils, the unbranched, beta-sheet rich structures that result from the misfolding and subsequent aggregation of many proteins. In addition, amyloid deposits contain a number of non-fibrillar components that interact with amyloid fibrils and are incorporated into the deposits in their native folded state. The influence of a number of the non-fibrillar components in amyloid-related diseases is well established; however, the mechanisms underlying these effects are poorly understood. Here we describe the effect of two of the most important non-fibrillar components, serum amyloid P component and apolipoprotein E, upon the solution behavior of amyloid fibrils in an in vitro model system. Using analytical ultracentrifugation, electron microscopy, and rheological measurements, we demonstrate that these non-fibrillar components cause soluble fibrils to condense into localized fibrillar aggregates with a greatly enhanced local density of fibril entanglements. These results suggest a possible mechanism for the observed role of non-fibrillar components as mediators of amyloid deposition and deposit stability

C-reactive protein is essential for innate resistance to pneumococcal infection

Summary: No deficiency of human C-reactive protein (CRP), or even structural polymorphism of the protein, has yet been reported so its physiological role is not known. Here we show for the first time that CRP-deficient mice are remarkably susceptible to Streptococcus pneumoniae infection and are protected by reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies. Autologous mouse CRP is evidently essential for innate resistance to pneumococcal infection before antibodies are produced. Our findings are consistent with the significant association between clinical pneumococcal infection and non-coding human CRP gene polymorphisms which affect CRP expression. Deficiency or loss of function variation in CRP may therefore be lethal at the first early-life encounter with this ubiquitous virulent pathogen, explaining the invariant presence and structure of CRP in human adults

New methodology for specific inhalation challenges with occupational agents

<p>Abstract</p> <p>Background</p> <p>Inhalation challenges are used for diagnosing occupational asthma (OA). The initial methodology consisted of a "realistic" exposure without monitoring nor controlling exposure. Our aim was to design an equipment, called the GenaSIC, that allows the generation of various agents regardless of the formulation and to assess the feasibility of its use in patients investigated for OA.</p> <p>Results</p> <p>GenaSIC can generate lactose, flour, malt, isocyanates, formaldehyde and N-butyl acetate with precise and fairly stable concentrations. Using N-butyl-acetate as a control agent and real time measurement, we show that normal breathing has a negligible effect on the concentration. We exposed forty-four different subjects to a control agent and/or to a suspected occupational agent. Nineteen of the subjects were only exposed to N-butyl acetate as a control agent without experiencing any significant irritant effect (no significant changes in spirometry thereafter). Eight subjects who were exposed to both N-butyl acetate and formaldehyde did not show significant reactions. Seven subjects were exposed to dry particles (flour in six instances, malt in the other) and five showed immediate asthmatic reactions which changes in FEV1 from 20% to a maximum of 28%. Finally, ten subjects were exposed to isocyanates, four of whom showed a positive reaction, including one subject with immediate maximum changes in FEV1 of 22%.</p> <p>Conclusion</p> <p>GenaSIC offers the possibility of reliable and safe exposures to dry particles, formaldehyde and isocyanates in the investigation of OA.</p

Exercise-induced bronchoconstriction and atopy in Tunisian athletes

<p>Abstract</p> <p>Background</p> <p>This study is a cross sectional analysis, aiming to evaluate if atopy is as a risk factor for exercise induced bronchoconstriction (EIB) among Tunisian athletes.</p> <p>Methods</p> <p>Atopy was defined by a skin prick test result and EIB was defined as a decrease of at least 15% in forced expiratory volume in one second (FEV1) after 8-min running at 80–85% HRmaxTheo. The study population was composed of 326 athletes (age: 20.8 ± 2.7 yrs – mean ± SD; 138 women and 188 men) of whom 107 were elite athletes.</p> <p>Results</p> <p>Atopy was found in 26.9% (88/326) of the athletes. Post exercise spirometry revealed the presence of EIB in 9.8% of the athletes including 13% of the elite athletes. Frequency of atopy in athletes with EIB was significantly higher than in athletes without EIB [62.5% vs 23.1%, respectively].</p> <p>Conclusion</p> <p>This study showed that atopic Tunisian athletes presented a higher risk of developing exercise induced bronchoconstriction than non-atopic athletes.</p