Inactivation of C-1 inhibitor by proteases: demonstration by a monoclonal antibody of a neodeterminant on inactivated, non-complexed C-1 inhibitor.

Monoclonal antibodies were raised against kallikrein-C-1 inhibitor and factor XIIa-C-1 inhibitor complexes. One of the monoclonal antibodies (KII) appeared to react predominantly with C-1 inhibitor complexes in an ELISA. However, the apparent binding of KII to C-1 inhibitor complexes was probably due to the presence of proteolytically inactivated C-1 inhibitor in the complex mixture used for the coating:KII did not bind either kallikrein-C-1 inhibitor or factor XIIa-C-1 inhibitor complexes generated in plasma by dextran sulphate. SDS-PAGE analysis of C-1 inhibitor incubated with proteases revealed that KII-reactive C-1 inhibitor has a lower molecular weight than native C-1 inhibitor. We propose that the determinant that reacts with KII is exposed after cleavage of C-1 inhibitor in its reactive site. The monoclonal antibody KII will enable us to study the inactivation of C-1 inhibitor in human inflammatory disease.     

Calculating life-cycle assessment effect factors from potentially affected fraction-based ecotoxicological response functions

A new multisubstance potentially affected fraction (msPAF)-based method for calculating ecotoxicological effect factors for life-cycle assessment is introduced and compared to two other available methods of calculation. The new method is based on marginal increase of the msPAF of species. The method follows concentration-additive rules for pollutants with the same toxic mode of action (TMoA) and response-additive calculation rules for pollutants with independent action, and it combines a TMoA-specific factor, which is calculated differently in different methods, and a substance-specific factor, which is common to all methods. For 261 substances in 22 toxic modes of action, ecotoxicological effect factors for freshwater ecosystems have been calculated by different methods. Method-related differences appear to be rather small. Intersubstance differences in effect factors stem from differences in substance-specific toxic potencies, which span eight orders of magnitude, rather than from differences in TMoA-specific factors, which span only three orders of magnitude. Based on these insights, the choice of a calculation method seems to be a matter of personal (scientific) preference. The new hybrid msPAF method was greatly sensitive to data that usually are not known with sufficient certainty. Its use is recommended, entirely for reasons of scientific consistency, under strict conditions. When such conditions are not met or if necessary parameter values are unavailable, use of a fixed value for the TMoA-specific component is recommended.     

Macromolecular Crystal Engineering Based on Segmented Polymers: Influence of Heteroatoms on the Thermal Properties and Crystallization of m,n‐Polyurethanes Derived from Long‐Chain,Heteroatom‐Containing,Monodisperse α,ω‐Diols

Long‐chain heteroatom‐containing telechelic diols with 29–32 atoms in the backbone were synthesized by a one‐step, free‐radical telomerization of 10‐undecene‐1‐ol with commercially available α,ω‐dithiols. The oxygen and sulfur atoms caused a decrease in the melting point and enthalpy of the diols, compared to the corresponding purely aliphatic diols. The heteroatom‐containing α,ω‐diols HO? (CH₂)₁₁? S? (CH₂)₂? X? (CH₂)₂? S? (CH₂)₁₁? OH, where X = CH₂, O, or O? (CH₂)₂? O, were reacted in the melt with 1,6‐diisocyanatohexane O?C?N? (CH₂)₆? N?C?O, producing a series of polyurethanes containing an increasing amount of heteroatoms. Characterization by differential scanning calorimetry, infra‐red spectroscopy, thermogravimetric analysis, and wide angle x‐ray scattering of the m,n‐polyurethane series showed that, like the telechelic diols they were synthesized from, the heteroatoms caused a decrease in the melting point and enthalpy. However, they did not affect either the decomposition temperature or the crystal structure/packing.

Typical decomposition behavior of all the heteroatom‐containing m,6‐polyurethane.     

Concurrent Criterion-Related Validity of Physical Examination Tests for Hip Labral Lesions: A Systematic Review

Hip injuries are prevalent, especially within the athletic population. Of the hip injuries in this population, some 18–55% are lesions to the labrum of the hip. Clinical diagnosis of hip labral lesions is difficult because data on prevalence are varied. In addition, data on the prevalence of internal and external risk factors are absent as are data on the correlation of these risk factors with labral lesions, making it difficult to gauge the diagnostic utility. The mechanism of injury is often unknown or not specific to labral lesions. Internal risk factors may remain hidden to physical therapists because in most jurisdictions, ordering imaging tests is not within their scope of practice. Anterior inguinal pain seems highly sensitive for the diagnosis of patients with labral lesions but can hardly be considered specific; data on other pain-related and mechanical symptoms clearly have little diagnostic utility, making these data collected during the patient history almost irrelevant to diagnosis. By way of a comprehensive literature review and narrative and systematic analysis of the methodological quality of the retrieved diagnostic utility studies, this paper aimed to determine a diagnostic physical examination test or test cluster based on current best evidence for the diagnosis of hip labral lesions. Current best evidence indicates that a negative finding for the flexion-adduction-internal rotation test, the flexion-internal rotation test, the impingement provocation test, the flexion-adduction-axial compression test, the Fitzgerald test, or a combination of these tests provides the clinician with the greatest evidence-based confidence that a hip labral lesion is absent. Currently, research has produced no tests with sufficient specificity to help confidently rule in a diagnosis of hip labral lesion. Suggestions for future research are provided.     

The impact of an additional ecotoxicity test on ecological quality standards

The present study aims to support decisions on whether or not to perform an extra toxicity test in order to improve environmental quality standards (EQSs). The impact of an additional ecotoxicity test was analyzed by predicting new ecotoxicity values with three different estimation methods and adding them to existing species sensitivity distributions (SSDs) on which the EQSs are based. The results show that EQSs are likely to increase due to increasing sample size, but the change also depends on the number of toxicity values available, the estimation method used and the representativeness of the species tested. The management consequences are illustrated in a case study on contaminated freshwater sediment in the Netherlands. It is shown that a slight increase of the EQS can result in a large reduction of sediment remediation costs without impairing regulatory protection levels. The paper identifies indicators that can be used to evaluate the potential impact of an extra ecotoxicity test.     

Detection of activation of the contact system of coagulation in vitro and in vivo: quantitation of activated Hageman factor-C-1-inhibitor and kallikrein-C-1-inhibitor complexes by specific radioimmunoassays

Radioimmunoassays (RIAs) for the detection of C-1-inhibitor (C-1-Inh) complexed to either kallikrein or activated Hageman factor (factor XIIa) are described. Kallikrein-C-1-Inh or factor XIIa-C-1-Inh complexes were bound to Sepharose to which monospecific antibodies against (pre)kallikrein or factor XII, respectively, were coupled. Bound complexes were subsequently detected by an incubation with affinity purified 125I-labeled antibodies against C-1-Inh. These RIAs were used to detect activation of the contact system of coagulation in vitro and in vivo. Addition of dextran sulfate (DXS) (20 micrograms/ml) to fresh plasma resulted at 37 degrees C in the rapid generation of amidolytic kallikrein activity, which was maximal after 1 to 2 min of incubation and subsequently decreased within a few minutes. The generation of kallikrein activity coincided with the appearance of both kallikrein-C-1-Inh and factor XIIa-C-1-Inh complexes. However, in contrast to kallikrein activity, both types of complexes remained detectable in the incubation mixtures during the incubation period. Experiments with purified kallikrein. C-1-Inh and partly purified beta-factor XIIa, and activation experiments in plasmas deficient in either factor XII or prekallikrein, demonstrated the specificity of both RIAs. The minimal amount of DXS that resulted in the generation of measurable amounts of both types of complexes in plasma was 2-3 micrograms per ml. Similar experiments with kaolin showed that with limiting amounts of activator (1-2 mg/ml), only kallikrein-C-1-Inh complexes were detected in plasma. When larger amounts of kaolin were added to plasma, factor XIIa-C-1-Inh complexes were additionally detected in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)