Earthquake nucleation by transient deformations caused by the M = 7.9 Denali, Alaska, earthquake.

The permanent and dynamic (transient) stress changes inferred to trigger earthquakes are usually orders of magnitude smaller than the stresses relaxed by the earthquakes themselves, implying that triggering occurs on critically stressed faults. Triggered seismicity rate increases may therefore be most likely to occur in areas where loading rates are highest and elevated pore pressures, perhaps facilitated by high-temperature fluids, reduce frictional stresses and promote failure. Here we show that the 2002 magnitude M = 7.9 Denali, Alaska, earthquake triggered widespread seismicity rate increases throughout British Columbia and into the western United States. Dynamic triggering by seismic waves should be enhanced in directions where rupture directivity focuses radiated energy, and we verify this using seismic and new high-sample GPS recordings of the Denali mainshock. These observations are comparable in scale only to the triggering caused by the 1992 M = 7.4 Landers, California, earthquake, and demonstrate that Landers triggering did not reflect some peculiarity of the region or the earthquake. However, the rate increases triggered by the Denali earthquake occurred in areas not obviously tectonically active, implying that even in areas of low ambient stressing rates, faults may still be critically stressed and that dynamic triggering may be ubiquitous and unpredictable.

Fault zone connectivity: slip rates on faults in the san francisco bay area, california.

The slip rate of a fault segment is related to the length of the fault zone of which it is part. In turn, the slip rate of a fault zone is related to its connectivity with adjoining or contiguous fault zones. The observed variation in slip rate on fault segments in the San Francisco Bay area in California is consistent with connectivity between the Hayward, Calaveras, and San Andreas fault zones. Slip rates on the southern Hayward fault taper northward from a maximum of more than 10 millimeters per year and are sensitive to the active length of the Maacama fault.

Coastal uplift and mortality of intertidal organisms caused by the september 1985 Mexico earthquakes.

Coastal uplift associated with the great Mexican earthquake of 19 September 1985 and its principal aftershock produced widespread mortality of intertidal organisms along the coast of the states of Michoacán and Guerrero, Mexico. Measurements of the vertical extent of mortality at ten sites provided estimates of the magnitude of the vertical component of deformation along the coast. Within the affected area, uplift ranged from about 12 centimeters to about 1 meter, and no subsidence was observed. The observations are consistent with models of the tectonic deformation that results from buried slip on a shallow-dipping underthrust fault.

Strong ground motion from the michoacan, Mexico, earthquake.

The network of strong motion accelerographs in Mexico includes instruments that were installed, under an international cooperative research program, in sites selected for the high potenial of a large earthquake. The 19 September 1985 earthquake (magnitude 8.1) occurred in a seismic gap where an earthquake was expected. As a result, there is an excellent descripton of the ground motions that caused the disaster.

Validity and responsiveness of the spinal cord index of function: an instrument on activity level.

OBJECTIVES: To evaluate the validity and responsiveness of the Spinal Cord Index of Function (SIF), a new instrument on activity level, measuring the ability to perform various transfers in non-walking patients with a spinal cord lesion. SETTINGS: Spinal Injuries Unit, Sahlgrenska University Hospital, Gothenburg, Sweden. METHODS: Twenty-nine patients with a spinal cord lesion classified as grade A, B or C according to the American Spinal Injury Association/International Medical Society of paraplegia classification were included. Each patient was evaluated from the acute phase until discharge, every second week, by their physiotherapist, according to SIF and the Swedish physiotherapy clinical outcome variables (S-COVS). To determine validity, Spearman's rho correlation coefficient was calculated between the total scores of SIF and S-COVS, and the determination coefficient was calculated. Responsiveness was determined by computing effect sizes. RESULTS: Spearman's correlation between SIF and S-COVS was 0.933 and the determination coefficient was 0.87. The effect size for SIF was 9.1. CONCLUSION: The results of the study prove that SIF is a valid and sensitive instrument, which will be useful for physiotherapists in goal-planning programs and in evaluating progress during a patient's rehabilitation. SIF could also be used in research and in evaluating the patient's functional ability at follow-ups.

P2X3 knock-out mice reveal a major sensory role for urothelially released ATP.

The present study explores the possible involvement of a purinergic mechanism in mechanosensory transduction in the bladder using P2X(3) receptor knock-out (P2X(3)-/-) and wild-type control (P2X(3)+/+) mice. Immunohistochemistry revealed abundant nerve fibers in a suburothelial plexus in the mouse bladder that are immunoreactive to anti-P2X(3). P2X(3)-positive staining was completely absent in the subepithelial plexus of the P2X(3)-/- mice, whereas staining for calcitonin gene-related peptide and vanilloid receptor 1 receptors remained. Using a novel superfused mouse bladder-pelvic nerve preparation, we detected a release of ATP proportional to the extent of bladder distension in both P2X(3)+/+ and P2X(3)-/- mice, although P2X(3)-/- bladder had an increased capacity compared with that of the P2X(3)+/+ bladder. The activity of multifiber pelvic nerve afferents increased progressively during gradual bladder distension (at a rate of 0.1 ml/min). However, the bladder afferents from P2X(3)-/- mice showed an attenuated response to bladder distension. Mouse bladder afferents of P2X(3)+/+, but not P2X(3)-/-, were rapidly activated by intravesical injections of P2X agonists (ATP or alpha,beta-methylene ATP) and subsequently showed an augmented response to bladder distension. By contrast, P2X antagonists [2',3'-O-(2,4,6-trinitrophenyl)-ATP and pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid] and capsaicin attenuated distension-induced discharges in bladder afferents. These data strongly suggest a major sensory role for urothelially released ATP acting via P2X(3) receptors on a subpopulation of pelvic afferent fibers.

Differential expression of voltage-gated Ca(2+)-currents in cultivated aortic myocytes.

The expression of different types of Ca(2+)-channels was studied using the whole-cell patch-clamp technique in cultured rat aortic smooth-muscle myocytes. Ca(2+)-currents were identified as either low- or high voltage-activated (ICa,LVA or ICa,HVA, respectively) based on their distinct voltage-dependences of activation and inactivation, decay kinetics using Ba2+ as the charge carrier and sensitivity to dihydropyridines. The heterogeneity in the functional expression of the two types of Ca(2+)-channels in the cultured myocytes delineated four distinct phenotypes; (i), cells exhibiting only LVA currents; (ii), cells exhibiting only HVA currents; (iii), cells exhibiting both LVA and HVA currents and (iv), cells exhibiting no current. The myocytes exclusively expressed HVA currents both during the first five days in primary culture and after the cells had reached confluence (> 15 days). In contrast, LVA currents were expressed transiently between 5 and 15 days, during which time the cells were proliferating and had transient loss of contractility. Thus, both LVA and HVA Ca(2+)-current types contribute to Ca(2+)-signalling in cultured rat aortic myocytes. However, the differential expression of the two Ca2+ current types associated with differences in contractile and proliferative phenotypes suggest that they serve distinct cellular functions. Our results are consistent with the idea that LVA current expression is important for cell proliferation.

Chronic hypoxia changes the ratio of endothelin to ATP release from rat aortic endothelial cells exposed to high flow.

Endothelial cells isolated from the thoracic aorta of normoxic and chronically hypoxic rats were perfused (0.5 ml min-1) and stimulated by increased flow rate (3.0 ml min-1). The release of ATP, endothelin and vasopressin was investigated. During periods of high flow rate, endothelial cells isolated from normoxic rats increased their release of ATP and endothelin. In comparison, in hypoxic rats, ATP release during the period of high flow rate was less, whereas endothelin release was greater. Vasopressin release was not increased during periods of stimulation in either group of animals. These results suggest that, under conditions of reduced arterial oxygen tension, a dynamic balance between ATP and endothelin release could regulate the response of vessels to shear stress.

Increased flow-induced ATP release from isolated vascular endothelial cells but not smooth muscle cells.

1. Freshly harvested smooth muscle cells and endothelial cells isolated from the rabbit aorta were perfused (0.5 ml min-1) and stimulated twice by an increase of flow rate (3.0 ml min-1) in order to compare their ability to release adenosine 5'-triphosphate (ATP). 2. In smooth muscle cells, the basal release of ATP (0.0265 +/- 0.0033 pmol ml-1 per 10(6) cells) was not increased during periods of increased flow (P = 0.2). 3. In endothelial cells, the concentration of ATP in the perfusate during periods of low flow (0.0335 +/- 0.0038 pmol ml-1 per 10(6) cells) was significantly increased by 14 times and 5 times during the first and second periods of increased flow, respectively. 4. The release of ATP by endothelial cells did not appear to be caused by the lysis of cells during the period of increased flow because it can be reproduced several times and because there was no difference between lactate dehydrogenase activity in perfused cells and that in non-perfused cells. 5. These results show that, of the two major cell types of the vascular wall, only endothelial cells react to shear stress by releasing ATP.

Blockade by glibenclamide of the flow-evoked endothelial release of ATP that contributes to vasodilatation in the pulmonary vascular bed of the rat.

1. The effect of step augmentation of flow rate on the level of adenosine -5'-triphosphate (ATP) measured in the Krebs perfusate was investigated, and the effect of glibenclamide on the release of ATP was tested in the rat pulmonary vascular bed. 2. For flow rates between 10.38 +/- 1.18 and 28.88 +/- 2.08 ml min-1 (n = 8) 1 microM suramin, a P2-purinoceptor antagonist, significantly (P < 0.05) increased vascular resistance under conditions of step augmentation of flow rate. This suggests that endogenous ATP released during increases in flow rate dilates pulmonary vessels. 3. In response to a step augmentation in flow rate from 9.13 +/- 0.97 to 18.3 +/- 1.69 ml min-1 (n = 4) ATP levels were up to 23 fold higher (P < 0.05) for 15 s, and gradually dropped to a level of about half the initial rise. Once the ATP levels had stabilized, another step augmentation of flow rate to 27.00 +/- 3.49 ml min-1 was able to evoke a corresponding increase of ATP release. The ability of the vascular bed to respond with increased ATP release after the initial ATP responses had tapered, demonstrates that the drop in ATP levels after the initial rise is not due to depletion of ATP. Furthermore, the maximal ATP response directly precedes the vasodilatation observed following each jump in perfusion pressure produced with each step increase in flow rate. 4. In response to two 3 fold step augmentations of flow rate (8.41-27.29 ml min-1) spaced 30 min apart there were two increases in the level of ATP which were not significantly different from each other.However, perfusion with 1 microM glibenclamide between the first and the second step augmentation of flow rate (8.08-24.67 ml min-1) significantly (P<0.05; n = 6) blocked the increase in ATP release. This suggests that the release of intracellular ATP is mediated by glibenclamide-sensitive K+ channels.5. A concentration of 1 microM glibenclamide perfused for 30 min was without effect on vascular pressure at constant flow. However, under conditions where flow was augmented in a stepwise manner (between 11.50 and 36.45 ml min-1) perfusing with 1 microM glibenclamide increased vascular resistance (P <0.10).6. It is concluded that flow-induced ATP release is mediated by a glibenclamide-sensitive K+ channel,and that the release of ATP from endothelial cells probably functions to vasodilate the pulmonary vascular bed of the rat.

Effect of shear stress on the release of soluble ecto-enzymes ATPase and 5'-nucleotidase along with endogenous ATP from vascular endothelial cells.

Stimulation of endothelial cells from human umbilical vein by shear stress induced release of endogenous ATP which was accompanied by an extracellular increase in the activity of enzymes degrading both ATP (ATPases) and AMP (5'-nucleotidases). The activity of soluble ATPase was progressively increased from 1.62+/-0.27 to 12.7+/-1.0 pmoles ml(-1) h(-1) after 60 min of stimulation by shear stress. The rate of [(3)H]-ATP hydrolysis in the medium was inhibited by the purinergic agents suramin, Reactive blue 2 and pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid, and remained insensitive to the classic inhibitors of ion-pumping and intracellular ATPases. Shear stress also increased the activity of 5'-nucleotidase in the medium from 2.0+/-0.5 to 27.2+/-2.8 pmoles ml(-1) h(-1). When shear stress was applied after removal of ecto-5'-nucleotidase by phosphatidylinositol-specific phospholipase C, the release of 5'-nucleotidase was drastically reduced. These results show that soluble ATPase and 5'-nucleotidase which are released during shear stress are not released from an intracellular compartment together with ATP but have an extracellular origin.

Colocalization of endothelin, vasopressin and serotonin in cultured endothelial cells of rabbit aorta.

The localization and colocalization of endothelin-1, arginine-vasopressin and serotonin in the endothelial cells of rabbit aorta in primary culture were investigated by preembedding and postembedding immunocytochemistry. These three substances were localized in the same population of cells, where they appeared in high proportions (greater than 60%). These findings indicate: 1) that the cell population is heterogeneous, and 2) that these substances are colocalized in some of the cultured endothelial cells. Double labeling in single cells has demonstrated the simultaneous presence of 1) endothelin and vasopressin, 2) vasopressin and serotonin, and 3) endothelin and serotonin. The immunolabeling dominated in the cytoplasmic matrix.

Cytokines suppress the shear stress-stimulated release of vasoactive peptides from human endothelial cells.

Endothelial cells from human umbilical vein perfused at 0.5 ml/min released vasopressin, endothelin, and substance P. Upon perfusion of the cells at 3.0 ml/min, the release of endothelin and vasopressin was significantly increased whereas the release of substance P was significantly decreased. Endothelial cells precultured for 24 h with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) released more endothelin and less substance P at low flow and there was no further increase in release at high flow rate. These results suggest that cytokines suppress the normal responses of endothelial cells to increased fluid shear stress.

Effect of changes in rate of vascular perfusion on release of substances into the effluent from the brain of the rabbit.

The cerebral vasculature of five anaesthetised rabbits was perfused with a perfluorocarbon emulsion via the internal carotid arteries, and the effluent from the jugular veins analysed for ATP, substance P (SP), endothelin (ET) and arginine vasopressin (AVP). Viability of the preparation was monitored periodically by the electrocorticogram, oxygen uptake, carbon dioxide release and perfusion pressure. The basal rate of infusion of 7.8 +/- 1.26 ml.min-1 resulted in an infusion pressure of 114.0 +/- 22.1 mmHg and when increased first to 10.5 +/- 1.53 ml.min-1 and then to 15.0 +/- 1.87 ml.min-1, rose to 163.0 +/- 33.1 mmHg and to 170.0 +/- 33.2 mmHg, respectively. Between each 3-min period of increased flow the rate was returned to the basal rate for 6 min. Of the four vasoactive substances, ET was released at the largest rate during the initial period of basal flow, 65.3 +/- 10.7 pmol.min-1. This increased further when the infusion rate rose to 10.5 ml.min-1, but was significant only when the infusion rate was increased to 15.0 ml.min-1. ATP was released at 41.5 +/- 11.5 pmol.min-1 during the initial period of basal flow. Its release significantly increased with flow and peaked at 15.0 ml.min-1. SP was released at a rate of 13.3 +/- 8.2 pmol.min-1 during the initial period of basal flow. Its rate of release was increased significantly the second time the flow was increased to 10.5 ml.min-1 and increased even further when the flow was increased to 15.0 ml.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of uptake, release and action of UTP at sympathetic perivascular nerve terminals in rabbit ear artery.

A possible role of uridine 5'-triphosphate (UTP) and uridine at sympathetic nerve terminals was studied in the rabbit ear artery after incubation of isolated vessels with [3H]uridine or [3H]noradrenaline. It was found that [3H]uridine was taken up by rabbit ear artery. This uptake was largely suppressed after the removal of endothelium and was inhibited by ethidium bromide and dipyridamole. Chemical denervation of the vessels with 6-hydroxydopamine did not reduce the uptake. Following pre-incubation of the isolated vessels with [3H]uridine, there was a release of radioactivity from the superfused rabbit ear artery. UTP, UDP, UMP and uridine were detected by thin layer chromatography both in the superfusate and inside the vessels. Transmural electric stimulation (30 V, 5 Hz) induced a contraction of the vessels but did not increase the release of uridine nucleotides into the superfusate. [3H]Noradrenaline was released during electric stimulation and the addition of UTP (100 microM) had no effects on this release. To conclude, this study shows that in contrast to endothelial cells, the sympathetic nerve terminals of the rabbit ear artery do not take up uridine and do not release uridine-derived nucleotides. UTP at 100 microM is also unable to modulate the evoked release of noradrenaline. These results mainly confine the role of UTP in endothelium-derived vasodilatation via P2Y2 and/or P2Y4 receptors.

Free radical involvement in endothelium-dependent responses of the rat thoracic aorta in moderate hypoxic conditions.

This study investigates the effects of agents which act on the production or efficacy of free radicals on the hypoxic responses of rat aorta rings. Under moderate hypoxic conditions, the resting tension of the rings was not changed but in rings precontracted with 5-hydroxytryptamine, there was a relaxation followed by a contraction. Removal of the endothelium with saponin suppressed relaxation to acetylcholine and abolished the contractions produced by hypoxia. In rings with a functional endothelium, hypoxic vasoconstriction was strongly inhibited by mannitol and exifone, but was not reduced by N(G)-nitro-L-arginine methyl ester, superoxide dismutase + catalase, or deferoxamine. Hypoxic vasodilatation was only partially inhibited by mannitol. To conclude, hypoxic constriction of the rat thoracic aorta is largely endothelium-dependent and involves free radicals whereas hypoxic dilatation is partially endothelium-dependent and partially involves free radicals. There is also indirect evidence for lack of direct involvement of nitric oxide/endothelium-derived relaxing factor (NO*/EDRF), hydroxyl radical (OH*) and superoxide anion in the hypoxic constriction and relaxation of the rat aorta.

Regulation of substance P mRNA expression in human dermal microvascular endothelial cells.

Vascular endothelial cells have been identified as a source of substance P (SP) which may act in an autocrine/paracrine fashion to bring about nitric oxide (NO)-dependent vasodilatation and mitogen-induced cell division or immunologic and inflammatory responses. Whilst SP is localised in and released from endothelial cells, an endothelial mRNA expression of SP has not previously been shown. In the present study, mRNA expression of SP in human dermal microvascular endothelial cells is demonstrated using in situ hybridisation techniques with enhancement procedures. Incubation of microvascular endothelial cells with nerve growth factor (NGF) under conditions of increased shear stress increases the mRNA expression and release of SP Endothelin (ET) release is also enhanced. These changes are pertinent to circulatory, events that may occur in Raynaud's phenomenon in systemic sclerosis.

Nitric oxide synthase (NOS) in the human umbilical cord vessels. An immunohistochemical study.

Localization of nitric oxide synthase (NOS) in endothelial cells of umbilical cord vessels and in cultured human umbilical vein endothelial cells was investigated by light and electron-microscopical (immunogold) immunohistochemistry. We observed localization of NOS-immunoreactivity in the majority (97%) of the endothelial cells of the umbilical vein and in a subpopulation (6.7%) of endothelial cells of the umbilical arteries. NOS was observed as well in the amniotic epithelium and in the cells of Wharton's jelly. Immunogold labelling in human umbilical vein endothelial cells dominated in the cellular matrix and was not associated with cellular organelles. Since human umbilical vessels are unique in lacking innervation, the functional significance of endothelium derived relaxing factor EDRF/NO in the local control of vascular flow is discussed.

Effects of abdominal binding on breathing patterns during breathing exercises in persons with tetraplegia.

STUDY DESIGN: Cross-sectional, experimental. OBJECTIVES: To investigate and compare static lung volumes and breathing patterns in persons with a cervical spinal cord lesion during breathing at rest, ordinary deep breathing, positive expiratory pressure (PEP) and inspiratory resistance-positive expiratory pressure (IR-PEP) with and without an abdominal binder (AB). SETTING: The outpatient clinic at the Spinal Unit at Sahlgrenska University Hospital, Goteborg, Sweden. METHOD: The study group consisted of 20 persons with complete cervical cord lesion at C5-C8 level. Breathing patterns and static lung volumes with and without an AB were measured using a body plethysmograph. RESULTS: : With an AB, static lung volumes decreased, vital capacity increased, breathing patterns changed only marginally and functional residual capacity remained unchanged during PEP and IR-PEP. CONCLUSION: Evidence supporting the general use of an AB to prevent respiratory complications by means of respiratory training is questionable. However, the interindividual variation in our results indicates that we cannot rule out that some patients may benefit from the treatment.

Synergistic effect of acute hypoxia on flow-induced release of ATP from cultured endothelial cells.

Human umbilical vein endothelial cells (HUVECs) in primary cultures were perfused under normoxic or hypoxic conditions. These cells were stimulated twice for 3 min by increased flow (from 0.5 to 3.0 ml/min). Under hypoxic conditions the basal release of ATP was the same as under normoxic conditions, but during increased flow the release was greater (0.58 +/- 0.07 > 0.32 +/- 0.04 pmoles/ml/10(6) cells (+78%), for the first period of stimulation; 0.39 +/- 0.05 > 0.22 +/- 0.03 pmoles/ml/10(6) cells (+79%) for the second period). Further experiments with sequential increments in flow rate showed that under both normoxic and hypoxic conditions, a positive correlation existed between ATP release and the rate of flow but there was always more ATP released under hypoxic conditions regardless of the flow rate. HUVECs in secondary culture (second passage) were similarly stimulated. No differences were observed between normoxic and hypoxic conditions. In both cases, the quantity of ATP released during high flow (0.050 +/- 0.004 pmoles/ml/10(6) cells) was significantly smaller than the quantity of ATP released during low flow (0.09 +/- 0.01 pmoles/ml/10(6) cells). To conclude, since hypoxia alone did not affect ATP release, there appears to be a synergistic relationship between increased shear stress and hypoxia in the stimulation of ATP release from HUVECs. Moreover, the release of ATP under these conditions seems to be a property of highly differentiated endothelial cells.