The coagulation and complement pathways simultaneously promote homeostasis in response to injury but cause tissue damage when unregulated. Mechanisms by which they cooperate are poorly understood. To delineate their interactions, we studied the effects of thrombin and C5 convertase on C5 in purified and plasma-based systems, measuring release of the anaphylatoxin C5a, and generation of C5b, the initial component of the lytic membrane attack complex. Thrombin cleaved C5 poorly at R751, yielding minimal C5a and C5b. However, thrombin efficiently cleaved C5 at a newly identified, highly conserved R947 site, generating previously undescribed intermediates C5(T) and C5b(T). Tissue factor-induced clotting of plasma led to proteolysis of C5 at a thrombin-sensitive site corresponding to R947 and not R751. Combined treatment of C5 with thrombin and C5 convertase yielded C5a and C5b(T), the latter forming a C5b(T)-9 membrane attack complex with significantly more lytic activity than with C5b-9. Our findings provide a new paradigm for complement activation, in which thrombin and C5 convertase are invariant partners, enhancing the terminal pathway via the generation of newly uncovered C5 intermediates. Delineating the molecular links between coagulation and complement will provide new therapeutic targets for diseases associated with excess fibrin deposition and complement activation. 相似文献
Purpose: Although the air-conduction pathway is the principal mode of sound transmission to the inner ear, this may not be true for the fetus in utero. The fetus detects and responds to sounds in the maternal environment. Exogenous sounds can reach the fetal inner ear through the ear canal and middle ear system, bone conduction, or both. This study was designed to compare the effectiveness of these two routes of sound transmission by recording cochlear microphonic potentials from the fetus in utero in response to airborne sounds.Materials and Methods: Cochlear microphonics (CMs) recorded from one round window (RW) of fetal sheep in utero were obtained in three conditions: (1) head uncovered; (2) head covered with a neoprene hood; and (3) head covered with a neoprene hood fashioned with a hole that permitted the pinna and ear canal to be exposed. Tone bursts (0.5, 1.0, and 2.0 kHz) were delivered through a loudspeaker at high intensities (100 to 135 dB sound pressure level) to the flank of the ewe. CMs were detected with indwelling electrodes, amplified, and averaged. CM input-output functions were obtained from the fetus in each of the three conditions described above.Results: CMs recorded with the head uncovered were more sensitive than were the CMs recorded with the hood in place. There was no difference in sensitivity between the condition during which the head was completely covered and the condition in which the pinna and ear canal canal are exposed.Conclusion: The principal mode of sound transmission into the fetal inner ear is through bone conduction. 相似文献
This study was undertaken to determine why U.S. Marine Hospital #17, Port Townsend, Washington, closed at the peak of its utilization. A social history approach was taken, examining the hospital's developmental changes in the context of its role in the larger society. Both firsthand and interpretive sources were reviewed, and numerous photographs and drawings confirmed the hospital was an active participant in the economy. Regarding the hospital's transitions over time as a life cycle was a useful organizing framework. Inpatient census patterns as a measure of the hospital's growth and development informed and enlightened this study. It became clear the Marine Hospital responded to and influenced events in the Port Townsend seaport whose importance diminished when other port cities at the base of the Puget Sound began and sustained rapid growth. 相似文献
Summary: The inner structure of polyurethane latex particles has been studied in situ using small‐angle X‐ray scattering (SAXS). From contrast variation SAXS measurements evidence could be given that the dispersed particles are semi‐crystalline. The semi‐crystalline structure gives a strong contribution to the measured intensities in an intermediate range of scattering vectors. This contribution, which is independent of the adjusted contrast, could be separated and the long period of the lamellar structure could thus be determined quantitatively to 11 nm. In addition, it was found that the particles exhibit a core‐shell structure which arises from electron‐rich acid groups that are preferentially located at the particle surface.
Transmission electron microscopy (TEM) picture of the PUR particles. 相似文献
The waltzing guinea pig displays severe inner ear dysfunction that involves both an auditory and a vestibular manifestation. The aim of this study was to characterize a pathological tail-like extension of the vestibular hair cells, the cytocaud. Our data suggest that nearly all type I hair cells in the waltzing guinea pig have cytocauds, which appear as membrane-bound tails containing mitochondria and cytoplasm that proceed in a basal direction toward the basement membrane. The extensions either attach to the basement membrane or penetrate it, and further proceed into the extracellular matrix. A core made of a thick and long (30 microm) actin-rich structure supports the slender long process. The actin core has cross-links that are periodically placed along the length of the cytocaud. Our data suggest that the cytocauds in vestibular hair cells of the waltzing guinea pig are highly organized structures associated with a failure to detach from the basement membrane. 相似文献
BACKGROUND: After exposure, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is excreted via the faeces, breast milk and epidermal lipids. OBJECTIVES: To determine to what extent TCDD is eliminated via the skin and to evaluate whethe cutaneous elimination can be accelerated by the application of petrolatum. METHODS: In two patients severely intoxicated with TCDD, material obtained from the skin surface and, in one patient, cerumen and the content of epithelial cysts, was analysed for TCDD. RESULTS: The TCDD concentration in the initial blood sample taken was 144 000 pg g(-1) blood fa in patient 1, and 26 000 pg g(-1) blood fat in patient 2. Six months later, when the skin tests were performed, the blood TCDD levels had decreased to 80 900 and 16 100 pg g(-1) blood fat, respectively. In the two samples of pooled cyst contents from patient 1, TCDD levels of 34 400 an 18 600 pg g(-1) fat were found. A cerumen sample contained TCDD at 20 500 pg g(-1) fat. In the material collected from the skin surface we observed a linear increase of the amount of TCD measured per test field with time, indicating a continuous elimination of TCDD via the skin. Th daily amount of TCDD eliminated via the skin was 1.51 pg cm(-2) in patient 1 and 0.57 pg cm(-2) in patient 2. Application of petrolatum led to a twofold increase in the amount of TCDD measured in patient 1, but had no significant effect in patient 2. CONCLUSIONS: In our patients, elimination of TCDD via the skin, most probably through desquamating scales, represented 1-2% of the overall daily TCDD elimination rate, with regard to the body surface and when calculated on the basis of the half-life of TCDD at the time of the skin test. If a more typical overall elimination half-life of 7 years is used as the basis for the calculatio the skin would account for 9% (patient 1) and 15% (patient 2) of the overall elimination. Although we observed an increase in TCDD in material derived from the skin surface of up to 100% after application of petrolatum in patient 1, such an approach appears not to be a feasible means to increase elimination. Owing to the small amount of TCDD measured in skin-surface material, as well as in the cyst contents and cerumen obtained from one patient, contamination of the environment and other persons appears highly unlikely. 相似文献