Is complex fault zone behaviour a reflection of rheological heterogeneity?

Fault slip speeds range from steady plate boundary creep through to earthquake slip. Geological descriptions of faults range from localized displacement on one or more discrete planes, through to distributed shearing flow in tabular zones of finite thickness, indicating a large range of possible strain rates in natural faults. We review geological observations and analyse numerical models of two-phase shear zones to discuss the degree and distribution of fault zone heterogeneity and effects on active fault slip style. There must be certain conditions that produce earthquakes, creep and slip at intermediate velocities. Because intermediate slip styles occur over large ranges in temperature, the controlling conditions must be effects of fault properties and/or other dynamic variables. We suggest that the ratio of bulk driving stress to frictional yield strength, and viscosity contrasts within the fault zone, are critical factors. While earthquake nucleation requires the frictional yield to be reached, steady viscous flow requires conditions far from the frictional yield. Intermediate slip speeds may arise when driving stress is sufficient to nucleate local frictional failure by stress amplification, or local frictional yield is lowered by fluid pressure, but such failure is spatially limited by surrounding shear zone stress heterogeneity. This article is part of a discussion meeting issue 'Understanding earthquakes using the geological record'.

Epidemiological features of a newly described serotype of Shigella boydii.

We report the clinical, microbiological, and epidemiological features of an emerging serotype, Shigella boydii 20. We interviewed patients about symptoms, and history of travel and visitors during the week before illness onset. Seventy-five per cent of the 56 patients were Hispanic. During the week before illness onset, 18 (32%) travelled abroad; 17 (94%) had visited Mexico. Eight (21%) out of 38 who had not travelled had foreign visitors. There were eight closely related patterns by PFGE with XbaI. S. boydii 20 may be related to travel to Mexico and Hispanic ethnicity. Prompt epidemiological investigation of clusters of S. boydii 20 infection may help identify specific vehicles and risk factors for infection.

Bilateral internal thoracic artery operations in the elderly.

BACKGROUND: Elderly surgical patients have higher operative morbidity and mortality than younger cohorts, particularly when the procedure is lengthy and complex. While use of bilateral internal thoracic arteries (BITA) is often associated with increased surgical risk, we nevertheless hypothesized that the use of BITA in elderly coronary artery bypass patients would not significantly increase their operative risk beyond that encountered using single internal thoracic arterial (SITA) or saphenous vein grafts (SVG). We maintained that arterial grafts remain essentially unaffected by arteriosclerosis, and that extension of a high-quality life is a desirable outcome regardless of age at operation. EXPERIMENTAL DESIGN: We studied myocardial revascularization in 673 patients over 65 years of age at the time of operation. All operations were conducted or supervised by a single surgeon during a ten-year period from January 1986 to January 1996. Preoperative and operative dates were recorded prospectively. SETTING: All patients underwent coronary artery bypass grafting. INTERVENTIONS: The study compared outcomes in patients having all veins, SITA or BITA operations. For the first analysis, 673 patients were divided into three groups: 163 patients (Group 1) had saphenous vein used for all bypasses; 338 patients had a SITA with supplemental vein grafts (Group 2); and 172 patients (Group 3) had BITAs with additional vein grafts as needed. In the second analysis, Group 3 was subdivided and grouped by the coronary arteries which received the ITA grafts, and the analysis was repeated. One hundred and sixteen patients (Group 3A) underwent traditional placement of ITA bypasses (left ITA to the LAD, right ITA to the RCA); in Group 3B, 56 patients received revascularization of branches of the left coronary artery (left ITA to the circumflex system, right ITA to the LAD). MEASURES: We communicated directly with 90.5% of the patients, their families, or their physicians. The survival status of the remainder was determined through the National Social Security Death Index Network. This allowed us to obtain follow-up longevity data for 100% of the study sample at a mean observation period of 5.03+/-3.1 years with variation between 10.8 years to 2.4 years. RESULTS: A multivariate analysis showed that placement of both ITA grafts to left-sided arteries in older patients independently improved long-term survival (p=0.031). CONCLUSIONS: The BITA procedure does not have greater operative morbidity or mortality in the elderly despite the length or complexity of the surgery. To realize improved long-term survival rates, however, both ITAs must be grafted to the left coronary artery branches.

Esophagectomy after pneumonectomy: a surgical challenge.

Esophagectomy after pneumonectomy has been reported rarely, and the surgical approach presents a challenge. We report a case of a transthoracic esophagectomy in a 54-year-old man who had undergone right pneumonectomy for non-small cell lung cancer 16 years previously.

Vascular smooth muscle mechanics in isolated perfused segments of carotid arteries.

BACKGROUND: We hypothesized that smooth muscle contraction and relaxation responses in a muscle bath (isometric tension) would be different than responses of intact vessels (isotonic tension). METHODS: Bovine carotid artery contractile responses to the catecholamine, norepinephrine, and smooth muscle relaxant, 3-isobutyl-1-methylxanthine, were examined in strips of vessels in a muscle bath and in intact whole vessels in an isolated perfused whole-vessel perfusion apparatus. RESULTS: The maximal tension in the muscle bath depended on the length of the strip. The responses of whole vessels to increasing pressure was curvilinear. The maximal decrease in vessel diameter in intact vessels in response to the catecholamine and norepinephrine occurred at low intraluminal pressures. The dose-response curve to norepinephrine was shifted to the left in intact vessels compared with strips of vessels in the muscle bath, which suggests that whole vessels were more sensitive to norepinephrine. The maximal increase in diameter to increasing intraluminal pressure occurred in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, which suggests that there was significant intrinsic tone in the vascular smooth muscle. CONCLUSIONS: These results suggest that there are differences in the contractile properties of the vascular smooth muscle that are related to the ex vivo system used to examine smooth muscle responses. Responses obtained in isolated perfused whole vessels may more closely approximate in vivo responses.

Cellular stress inhibits vascular smooth muscle relaxation.

PURPOSE: Cellular stress has been shown to induce a group of proteins called heat shock proteins (HSPs). Recent evidence suggests that a group of small HSPs may modulate vascular smooth muscle contraction (HSP27) and/or relaxation (HSP20). In this investigation, we hypothesized that cellular stress would alter contraction and/or relaxation of intact vascular smooth muscles and would lead to changes in the induction and/or phosphorylation of the small HSPs. METHODS: Bovine carotid arteries were obtained from an abattoir, and physiologic contractile responses were determined in a muscle bath. Phosphorylation state-specific antibodies were produced and characterized against HSP27. Phosphorylation events were determined with phosphorylation state-specific antibodies or whole-cell phosphorylation and two-dimensional gel electrophoresis. RESULTS: Cellular stress induced by arsenite or heat shock did not alter basal tone or the magnitude of contractions induced by serotonin or high extracellular potassium chloride. However, cellular stress led to inhibition of forskolin and sodium nitroprusside-induced vasorelaxation. This impaired vasorelaxation was associated with increases in the phosphorylation of HSP27 and decreases in forskolin-induced phosphorylation of HSP20. CONCLUSION: Cellular stress, which leads to increases in the phosphorylation of HSP27, inhibits cyclic nucleotide-dependent vascular relaxation and cyclic nucleotide-dependent increases in the phosphorylation of HSP20.

Natural infection of domestic goats with Ehrlichia chaffeensis.

Thirty-eight domestic goats from an area of Ehrlichia chaffeensis endemicity were tested for antibodies reactive to E. chaffeensis and for E. chaffeensis-specific 16S rRNA gene fragments by an indirect fluorescent antibody test and a nested PCR assay, respectively. Twenty-eight of 38 (73.7%) goats had antibodies reactive to E. chaffeensis (>/=1:128), and 6 of 38 (15.8%) goats were positive by diagnostic PCR; E. chaffeensis was isolated in cell culture from one goat. Our data indicate that goats in areas of endemicity are naturally exposed to and infected with E. chaffeensis.

Phosphorylation events associated with cyclic nucleotide-dependent inhibition of smooth muscle contraction.

Activation of cyclic nucleotide-dependent signaling pathways leads to relaxation of bovine carotid artery smooth muscle contractions and is associated with increased phosphorylation of the small heat shock-related protein (HSP20). Previous reports have shown that human umbilical artery smooth muscle is uniquely resistant to cyclic nucleotide-dependent relaxation, and HSP20 is not phosphorylated. In this investigation, we determined the phosphorylation events associated with cyclic nucleotide-dependent inhibition of smooth muscle contraction. In carotid artery, activation of cyclic nucleotide-dependent signaling pathways inhibited contractile responses to serotonin but did not inhibit myosin light chain phosphorylation or oxygen consumption. The inhibition of contraction was associated with increases in HSP20 phosphorylation. In umbilical artery, activation of cyclic nucleotide-dependent signaling pathways did not inhibit serotonin-induced contraction or myosin light chain phosphorylation. The lack of contractile inhibition in umbilical artery was not associated with significant increases in HSP20 phosphorylation. In conclusion, cyclic nucleotide-dependent contractile inhibition is independent of the inhibition of myosin light chain phosphorylation or oxygen consumption but does correlate with increased HSP20 phosphorylation.

Endothelial-dependent vasodilation is associated with increases in the phosphorylation of a small heat shock protein (HSP20).

PURPOSE: Increases in the phosphorylation of a small heat shock protein (HSP20) are associated with cyclic nucleotide-dependent vasorelaxation. The effect of pressure and flow on vessel diameter was studied. We hypothesized that physiologic conditions that induce vasorelaxation would lead to increases in HSP20 phosphorylation. METHODS: Flow-dependent changes in vessel diameter, at different intraluminal pressures, were measured with a laser optical micrometer in intact bovine carotid arteries. Experiments were performed in the presence and absence of norepinephrine (10(-5) mol/L). Increases in the phosphorylation of HSP20 were determined with isoelectric focusing immunoblots. RESULTS: The increase in vessel diameter was most significant at low intraluminal pressures (20 mm Hg), high flow rates (200 mL/min), and in the presence of the vasoconstrictor norepinephrine (10(-5) mol/L). The addition of methylene blue (a guanylate cyclase inhibitor) completely inhibited flow-induced vasodilation. Under conditions in which maximal flow induced vasodilation occurred, there were significant increases in the phosphorylation of HSP20. CONCLUSION: Flow-dependent vasodilation in isolated perfused segments of bovine carotid arteries was maximal when the intraluminal pressures were low and when the vessels were precontracted with norepinephrine. Flow-dependent vasodilation was inhibited by methylene blue and was associated with increases in the phosphorylation of HSP20, suggesting that the vasodilation was mediated by endothelial production of nitric oxide.

The small heat shock-related protein, HSP20, is phosphorylated on serine 16 during cyclic nucleotide-dependent relaxation.

The small heat shock-related protein 20 (HSP20) is present in four isoforms in bovine carotid artery smooth muscles. Three of the isoforms are phosphorylated and one is not. Increases in the phosphorylation of two isoforms of HSP20 (isoform 3, pI 5.9; and 8, pI 5.7) are associated with cyclic nucleotide-dependent relaxation of bovine carotid artery smooth muscles. Increases in the phosphorylation of another isoform (isoform 4, pI 6.0) are associated with phorbol ester-induced contraction of bovine carotid artery smooth muscles. In this investigation we determined that isoforms 3 and 8 are phosphorylated on Ser16 of the HSP20 molecule during activation of cAMP-dependent signaling pathways. Phosphorylation state-specific antibodies produced against a peptide containing phosphorylated Ser16 recognized isoforms 3 and 8 but not isoform 4. In human vascular tissue, only isoform 3 is present. Incubation of transiently permeabilized strips of bovine carotid artery smooth muscle with synthetic peptides in which Ser16 is phosphorylated, inhibits contractile responses to high extracellular KCl and to serotonin. These data suggest that phosphorylation of HSP20 on Ser16 modulates cAMP-dependent vasorelaxation.

Cyclosporine-induced renal artery smooth muscle contraction is associated with increases in the phosphorylation of specific contractile regulatory proteins.

Cyclosporine A (CSA) is a type 2B phosphatase inhibitor which can induce contraction of renal artery smooth muscle. In this investigation, we examined the phosphorylation events associated with CSA-induced contraction of bovine renal artery smooth muscle. Contractile responses were determined in a muscle bath and the corresponding phosphorylation events were determined with whole cell phosphorylation and two-dimensional gel electrophoresis. CSA-induced contractions were associated with increases in the phosphorylation of the 20 kDa myosin light chains (MLC20) and different isoforms of the small heat shock protein, HSP27. Cyclic nucleotide-dependent relaxation of CSA-induced contractions was associated with increases in the phosphorylation of another small heat shock protein, HSP20, and decreases in the phosphorylation of the MLC20, and some isoforms of HSP27. These data suggest that CSA-induced contraction and relaxation of vascular smooth muscle is associated with increases in the phosphorylation of specific contractile regulatory proteins.

Immersive virtual environment technology as a basic research tool in psychology.

Immersive virtual environment (IVE) technology has great promise as a tool for basic experimental research in psychology. IVE technology gives participants the experience of being surrounded by the computer-synthesized environment. We begin with a discussion of the various devices needed to implement immersive virtual environments, including object manipulation and social interaction. We review the benefits and drawbacks associated with virtual environment technology, in comparison with more conventional ways of doing basic experimental research. We then consider a variety of examples of research using IVE technology in the areas of perception, spatial cognition, and social interaction.

Thrombin activates MAPKAP2 kinase in vascular smooth muscle.

PURPOSE: Thrombin mediates hemostasis by promoting thrombus development and vasospasm, which reduces the size of the arterial injury. Thrombin stimulation of vascular smooth muscle is associated with activation of mitogen-associated protein kinase. The purpose of this investigation was to determine the subsequent cellular signaling events in thrombin-stimulated vascular smooth muscle contraction. METHODS: Contractile responses of bovine carotid artery smooth muscle were determined in a muscle bath and compared with phosphorylation events with two-dimensional gel electrophoresis. The activity of a novel kinase, mitogen-activated protein kinase-activated protein-2 kinase (MAPKAP2 kinase), was determined by immunoprecipitation and a phosphotransferase assay. A small heat shock protein, HSP27, was identified with immunoblotting. RESULTS: Thrombin induces contraction of vascular smooth muscle and is associated with increased activity of MAPKAP2 kinase and increased phosphorylation of HSP27. Multiple isoforms of HSP27 are the predominant phosphoproteins in vascular smooth muscle, and peptide mapping suggests that the isoforms of HSP27 are structurally related and phosphorylated within similar peptide sequences. CONCLUSIONS: Activation of the MAPKAP2 kinase pathway and phosphorylation of HSP27 are associated with thrombin-induced contraction of vascular smooth muscle.

Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction.

BACKGROUND: Cyclosporine immunosuppression for organ transplantation is associated with hypertension and nephrotoxicity. Because the effects of cyclosporine as an immunosuppressant are mediated by the effect of cyclosporine as a phosphatase inhibitor, and phosphatase inhibitors are potent vascular smooth muscle contractile agents, we hypothesized that cyclosporine might induce contraction of the renal artery vascular smooth muscle directly. METHODS: Strips of bovine renal, carotid, superior mesenteric, or coronary arteries were obtained fresh from an abattoir. The strips were equilibrated in a muscle bath, and the contractile responses to cyclosporine and FK506 were determined. RESULTS: Cyclosporine (50 to 5000 micrograms/ml), but not FK506, induced rapidly developing, sustained contractions of renal and coronary artery smooth muscle. The magnitude of the cyclosporine-induced contractions of carotid and superior mesenteric artery smooth muscles was significantly less. The magnitude of renal artery smooth muscle contractions induced by cyclosporine was enhanced in the presence of an intact endothelium. CONCLUSIONS: Although these effects occurred in vitro to relatively high doses of cyclosporine, these data suggest that cyclosporine may selectively induce renal artery smooth muscle contraction through activation of the Ca(2+)-dependent phosphatase (calcineurin) in the smooth muscle, and these contractions may be enhanced by the release of endothelial-derived contracting factors.

Thrombin-induced vasospasm: cellular signaling mechanisms.

BACKGROUND: In the setting of arterial injury, thrombin contributes to the hemostatic process by activating the coagulation cascade and platelets. We hypothesized that thrombin also contributes to hemostasis by inducing vasospasm. The purpose of this investigation was to characterize the cellular signaling mechanisms that modulate thrombin-induced vascular smooth muscle contractions. METHODS: Contractile responses of intact bovine carotid artery smooth muscles were determined in a muscle bath. Contractile responses were correlated with phosphorylation events as determined with whole cell phosphorylation and two-dimensional gel electrophoresis and with immunoblotting of glycerol-urea or two-dimensional gels. RESULTS: Thrombin (1 to 1000 units/ml) induced sustained vascular smooth muscle contractions of similar magnitude as the potent contractile agonist, endothelin. Thrombin-induced contractions were associated with increases in the phosphorylation of the myosin light chains (MLC20) and in the tyrosine phosphorylation of mitogen-activated protein kinase. CONCLUSIONS: These data suggest that thrombin is a potent physiologic contractile agonist that may modulate some forms of vasospasm. Thrombin-induced contractions are associated with the activation of two cellular signaling pathways, the myosin light chain kinase and the mitogen-activated protein kinase pathways.

Heat shock protein expression in umbilical artery smooth muscle.

Postpartum vasospasm in the umbilical arteries may be due to impaired vasorelaxation secondary to alterations in the expression of heat shock proteins. The contractile responses of pre- and full-term bovine umbilical artery smooth muscles were determined in a muscle bath. Heat shock protein expression was determined in bovine and human arterial tissues using western blotting with specific antisera. Full-term bovine and human umbilical artery smooth muscle was refractory to relaxation induced by the nitric oxide donor, sodium nitroprusside. This impaired vasorelaxation was associated with the expression of the inducible form of the heat shock protein, HSP70i, and increases in the expression of the small heat shock protein, HSP27. Small heat shock proteins have been implicated in modulating contraction and relaxation responses in vascular smooth muscles. Thus, alterations in heat shock protein expression may play a role in umbilical artery vasospasm.

Improved survival with multiple left-sided bilateral internal thoracic artery grafts.

BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.

Suitability and durability of multiple internal thoracic artery coronary artery bypasses.

OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value.

Visually perceived location is an invariant in the control of action.

We provide experimental evidence that perceived location is an invariant in the control of action, by showing that different actions are directed toward a single visually specified location in space (corresponding to the putative perceived location) and that this single location, although specified by a fixed physical target, varies with the availability of information about the distance of that target. Observers in two conditions varying in the availability of egocentric distance cues viewed targets at 1.5, 3.1, or 6.0 m and then attempted to walk to the target with eyes closed using one of three paths; the path was not specified until after vision was occluded. The observers stopped at about the same location regardless of the path taken, providing evidence that action was being controlled by some invariant, ostensibly visually perceived location. That it was indeed perceived location was indicated by the manipulation of information about target distance--the trajectories in the full-cues condition converged near the physical target locations, whereas those in the reduced-cues condition converged at locations consistent with the usual perceptual errors found when distance cues are impoverished.