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Biomedical subjects

C B Clark

Publications and source records attributed to C B Clark.

13 recordsLinked to original sources
PubMed2000

Temporal gradient in shear-induced signaling pathway: involvement of MAP kinase, c-fos, and connexin43.

The effect of a temporal gradient in shear and steady shear on the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/ERK2), c-fos, and connexin43 (Cx43) in human endothelial cells was investigated. Three laminar flow profiles (16 dyn/cm(2)), including impulse flow (shear stress abruptly applied for 3 s), ramp flow (shear stress smoothly transitioned at flow onset), and step flow (shear stress abruptly applied at flow onset) were utilized. Relative to static controls, impulse flow stimulated the phosphorylation of ERK1/ERK2 8.5- to 7.5-fold, respectively at 10 min, as well as the mRNA expression of c-fos 51-fold at 30 min, and Cx43 8-fold at 90 min. These high levels of mRNA expression were sustained for at least 4 h. In contrast, ramp flow was unable to significantly induce gene expression and even inhibited the activation of ERK1/ERK2. Step flow, which contains both a sharp temporal gradient in shear stress and a steady shear component, elicited only moderate and transient responses, indicating the distinct role of these fluid shear stimuli in endothelial signal transduction. The specific inhibitor of mitogen-activated protein kinase kinase PD-98059 inhibited impulse flow-induced c-fos and Cx43 mRNA expression. Thus these findings implicate the involvement of ERK1/ERK2, c-fos, and Cx43 in the signaling pathway induced by the temporal gradient in shear.

Cells, Cultured↗
PubMed1998

Equibiaxial strain and strain rate stimulate early activation of G proteins in cardiac fibroblasts.

Cardiac fibroblasts are responsible for the production of the extracellular matrix of the heart, with alterations of fibroblast function implicated in myocardial infarction and cardiac hypertrophy. Here the role of heterotrimeric GTP-binding proteins (G proteins) in the mechanotransduction of strain in rat cardiac fibroblasts was investigated. Cells in an equibiaxial stretch device were incubated with the photoreactive GTP analog azidoanalido [alpha-32P]GTP (AAGTP) and were subjected to various regimens of strain. Autoradiographic analysis showed a 42-kDa protein labeled for cells exposed to 12 cycles of 3% strain or 6 cycles of 6% strain over 60 s (strain rate of 1.2%/s), whereas 6 cycles of 3% strain (0.6%/s) elicited no measurable response. To further investigate the role of strain rate, a single 6% cycle over 10 or 60 s (1.2% and 0.2%/s, respectively) was applied, with the more rapid cycle stimulating AAGTP binding, whereas the lower strain rate showed no response. In cells subjected to a single 6% cycle/10 s, immunoprecipitation identified the AAGTP-labeled 42-kDa band as the G protein subunits G alpha q and G alpha i1. These results demonstrate that G protein activation represents one of the early mechanotransduction events in cardiac fibroblasts subjected to mechanical strain, with the rate at which the strain is applied modulating this response.

Animals↗
PubMed1996

Steady shear and step changes in shear stimulate endothelium via independent mechanisms--superposition of transient and sustained nitric oxide production.

We propose that fluid shear presents two distinct stimuli to endothelium-the rate of change of flow and flow itself, to which cells sense and respond via independent mechanochemical transduction pathways. We demonstrate that nitric oxide production occurs by two independent mechanisms; a G protein-dependent transient burst stimulated by rapid changes in flow, and a G protein-independent sustained production under steady or smoothly transitioned flow. The novel use of step, ramp, and impulse flow in this study to stimulate nitric oxide production allows the isolation of these individual production events. Impulse flow activates only the G protein-dependent transient burst, which ramp flow fails to stimulate yielding only the sustained response. Step flow, which contains both a rapid increase and a steady flow component, stimulates both pathways, with the response of the superposition of the transient burst and sustained production.

Cells, Cultured↗
PubMed1996

Fluid flow rapidly activates G proteins in human endothelial cells. Involvement of G proteins in mechanochemical signal transduction.

Fluid shear stimulates endothelial cells, with the external hemodynamic forces transduced across the plasma membrane to modulate intracellular events. We report the first direct evidence that identifies specific GTP binding proteins (G proteins) activated within 1 second of flow onset, representing one of the earliest mechanochemical signal transduction events reported to date in shear-stimulated endothelium. A nonhydrolyzable GTP photoreactive analogue, azidoanilido [alpha-32P]GTP (AAGTP), allowed irreversible labeling of flow-stimulated G proteins, with two protein bands (42 kD and 31 kD) identified in human umbilical vein endothelial cells (HUVECs) subjected to laminar flow (10 dyne/cm2) in a parallel-plate flow chamber. Immunoprecipitation of labeled whole-cell lysates identified the specific G-protein subunits G q zero/alpha 11 and G alpha i3/alpha 0) as being activated by flow. Endothelial cell membrane vesicles were sheared in a cone-and-plate viscometer, with the 42-kD protein band labeled by AAGTP, but the 31-kD protein absent, indicating that the 42-kD G protein is membrane associated and activated independently of intact cytoskeletal or cytosolic components. Our results describe one of the earliest flow-induced signaling events reported in HUVECs, providing insight into the primary mechanosensing and signal transduction mechanisms.

Cells, Cultured↗
PubMed1979

Cubital tunnel syndrome.

The symptoms of cubital tunnel syndrome in 118 patients were mainly those of muscular atrophy, but they also included sensory disturbances in the ring and little fingers and pain in the ulnar side of the forearm. The syndrome occurs equally in men and women, with no particular age preference in adults. Seven tests are useful in diagnosing the condition. Treatment consists of excising the band, which constricts the ulnar nerve at the elbow. Sensory recovery is usually complete, but muscular atrophy may not recover in older patients. In my series of 561 nerve decompressions, ulnar nerve decompression was carried out eight times more often at the elbow than at the wrist.

Adolescent↗
PubMed1978

Size and shape analysis of schistomsome egg-counts in Egyptian autopsy data.

We study egg-counts from a series of Egyptian autopsy cases with active schistosomiasis at death (Kamel, Cheever, Elwi, Mosimann and Danner 1977). The data are unique, and enable us to study the proportional distribution of eggs among various organs in relation to infection intensity for two species of schistosome worms. We develop a model for the distribution of eggs in three organs of the mesenteric circulation. Under a lognormal distribution assumption, several exact statistical procedures are presented and used to examine model consistency as well as isometry with respect to geometric means. Mesenteric egg counts for both Schistosoma mansoni and S. haematobium behave consistently with the model, and show little or no departure from isometry in cases without Symmers' fibrosis of the liver. We show that cases with Symmers' fibrosis have relatively more S. mansoni eggs in the small, as opposed to large, intestine. In the genito-urinary organs we show that the proportion of S. haematobium eggs in the bladder is high for low-intensity infections. This is consistent with the conclusion of Smith, Elwi, Kamel and Lichtenberg (1975), based on egg/gram data, that such infections may be initiated in the bladder. The correspondingly high proportion of eggs in the ureters with high-intensity infections indicates that increased intensity may have a disproportionately large pathologic effect on the infected individual.

Autopsy↗