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Biomedical subjects

C M Elliott

Publications and source records attributed to C M Elliott.

15 recordsLinked to original sources
PubMed1998

Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1.

In Swiss 3T3 fibroblasts, the Rac1-specific guanine nucleotide exchange factor Tiam1 is phosphorylated by several different agonists. We show here that PDGF induces threonine phosphorylation of Tiam1 in a time- and dose-dependent manner. Tiam1 phosphorylation was significantly reduced by the selective protein kinase C inhibitor Ro-31-8220 and by KN93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II. The Ca2+ chelator BAPTA/AM totally abrogated Tiam1 phosphorylation, indicating that Ca2+ is essential for this phosphorylation. Moreover, PDGF-stimulated Tiam1 phosphorylation was markedly reduced by 72 +/- 10% in PLC-gamma1 deficient mouse fibroblasts, compared to wild-type cells, indicating that phosphoinositide phospholipase C is involved.

3T3 Cells↗
PubMed1997

Lysophosphatidic acid induces threonine phosphorylation of Tiam1 in Swiss 3T3 fibroblasts via activation of protein kinase C.

The Rho family of GTPases plays an important role in the control of cell shape, adhesion, movement, and growth. Several guanine nucleotide exchange factors have been identified that activate Rho family GTPases by promoting the binding of GTP to these proteins. However, little is known concerning the regulation of these GDP/GTP exchange factors. In this study, we demonstrate that lysophosphatidic acid (LPA) induces a rapid, sustainable phosphorylation of the Rac1-specific nucleotide exchange factor Tiam1 in Swiss 3T3 fibroblasts. LPA stimulated Tiam1 phosphorylation in a dose-dependent manner, and the protein was phosphorylated on threonine, but not tyrosine or serine. Tiam1 phosphorylation was also induced by platelet-derived growth factor, endothelin-1, bombesin, and bradykinin but not by epidermal growth factor. Significantly, pretreatment of Swiss 3T3 fibroblasts with 1 microM phorbol 12-myristate 13-acetate for 24 h, or with the selective protein kinase C inhibitor Ro-31-8220, reduced LPA-stimulated phosphorylation of Tiam1 by approximately 75%. Moreover, acute stimulation with 100 nM phorbol 12-myristate 13-acetate was sufficient to induce Tiam1 phosphorylation in vivo, and protein kinase C could phosphorylate purified Tiam1 on threonine residues in vitro. These data indicate that agonist-induced phosphorylation of Tiam1 is a general mechanism and suggest that it is likely to be important in its regulation. Protein kinase C appears to play a key role in phosphorylation of Tiam1.

3T3 Cells↗
PubMed1996

Differential translocation of rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor.

The small GTPases of the Rho family play a key role in a number of signaling pathways activated by lysophosphatidic acid (LPA). However, little is known concerning the mechanism of regulation of these proteins. In this study we demonstrate that in Swiss 3T3 fibroblasts, LPA induces a sustained, time-dependent relocalization of RhoA to the Triton X-100-soluble low speed membrane fraction, which can be reversed by removal of LPA from the medium. Translocation was only observed with micromolar concentrations of LPA and was inhibited by pretreating the cells with pertussis toxin but not with tyrosine kinase inhibitors. LPA also induced translocation of CDC42Hs to the membranes but had no effect on the distribution of Rac1, RhoB, or Rho-GDI. Translocation of RhoA was also induced by endothelin-1. Conversely, platelet-derived growth factor did not cause the translocation of RhoA to any membrane fraction but stimulated relocalization of Rac1 to the high speed membrane fraction. Significantly, incubation of cell lysates with guanosine 5'-O-(thiotriphosphate) was sufficient to translocate RhoA, Rac1, and CDC42Hs from the cytosol to the membranes, whereas incubation with GDP had the opposite effect. These data suggest that the translocation of the Rho family proteins to the membrane fraction is controlled by their activation state and that agonists show selectivity in inducing the activation/translocation of these proteins.

3T3 Cells↗
PubMed1996

Enhanced phospholipase D activity and altered morphology in RhoA-overexpressing RAT1 fibroblasts.

Small GTP-binding proteins of the Rho family are implicated in the regulation of phospholipase D (PLD). However, few studies have addressed their role in agonist-stimulated PLD activity in vivo. Stable lines of Rat1 fibroblasts overexpressing RhoA were shown to have altered morphology. Moreover, they demonstrated increased PLD activity when stimulated with lysophosphatidic acid, platelet-derived growth factor, and phorbol ester, compared with vector-transfected cells. However, phosphoinositide phospholipase C activity was unaltered by overexpression of RhoA. These data indicate a critical downstream role for RhoA in agonist-stimulated PLD activity in intact cells.

Animals↗
PubMed1996

Evidence for Rho-mediated agonist stimulation of phospholipase D in rat1 fibroblasts. Effects of Clostridium botulinum C3 exoenzyme.

Small GTP-binding proteins of the Rho family are implicated in the in vitro regulation of phosphatidylcholine hydrolysis by phospholipase D (PLD). However, their role in agonist-stimulated PLD activity in whole cells is not clear. The ribosyltransferase C3 from Clostridium botulinum modifies Rho proteins and inhibits their function. When introduced into rat1 fibroblasts by scrape-loading, C3 inhibited PLD activity stimulated by lysophosphatidic acid (LPA), endothelin-1, or phorbol ester. Neither the time course nor agonist dose response for LPA-stimulated PLD activity was altered in C3-treated cells. In contrast to the effects of C3 on PLD activity, agonist-stimulated phosphatidylinositol-phospholipase C activity was not altered in C3-treated cells. Surprisingly, C3 treatment led to a decrease in the amount of RhoA protein, indicating that the loss of PLD activity in response to agonist was partly due to the loss of Rho proteins. As described previously, C3 treatment led to the inhibition of LPA-stimulated actin filament formation. However, disruption of actin filaments with cytochalasin D caused only a minor inhibition of LPA-stimulated PLD activity. Interestingly, stimulation of cells with LPA caused a rapid enrichment of RhoA in the particulate fraction of cell lysates. These data support an in vivo role for RhoA in agonist-stimulated PLD activity that is separate from its role in actin fiber formation.

ADP Ribose Transferases↗
PubMed1996

Redox dependent interactions of the metal sites in carbon monoxide-bound cytochrome c oxidase monitored by infrared and UV/visible spectroelectrochemical methods.

Spectroelectrochemical titration studies involving the binding of the infrared-active probe ligand carbon monoxide (CO) to the heme alpha 3/CuB site of bovine heart cytochrome c oxidase (CcO) have been reexamined. The spectroelectrochemical cell employed was constructed to monitor both the infrared (IR) and visible/Soret spectra of the CcO-CO complex as a function of the overall oxidation state of the enzyme. A number of commonly used electron transfer mediators were employed to shuttle electrons between the redox active sites within the enzyme and the electrode surface. The well-documented shift in the CO infrared stretch band maximum from 1963.3 cm-1 (CcO fully reduced) to 1965.5 cm-1 (CcO partially oxidized) was carefully titrated electrochemically. Deconvolution of the asymmetric CO stretches indicates the existence of two different states of CO vibrators within the enzyme, presumably due to two conformers which are present in a ratio of approximately 5:1. Upon incrementally stepping the potential from the fully reduced state to the partially oxidized state, we found it possible to follow the decrease in the intensity of the original pair of these conformers and the concomitant increase of a resultant pair while maintaining this 5:1 ratio between the conformers. By plotting the change in the deconvoluted CO peak intensities vs the redox potential, as well as the absorbance changes in the visible/Soret spectra vs the redox potential, we found not only that both fit an n = 1 electron process but also that the spectral changes tracked each other identically with experimental error. Furthermore, analysis of the second derivative of the Soret spectra allowed for the qualitative monitoring of the oxidation state of the Fe alpha site which again tracked identically to that of the CO shift in the IR region. These results would seem to confirm earlier suggestions that perturbing the oxidation state of Fe alpha causes a conformational change in the enzyme which affects the binding site for CO, namely heme alpha 3. As a consequence of the CO IR stretching frequencies changing by only 2 cm-1 during this redox titration, with no accompanying changes in half band width, we suggest that it is impossible that this small but significant change seen in the CO stretching frequencies could be due to an oxidation state change in CuB, given the known sensitivity of the CO stretching frequency to perturbations and the close proximity of Cu(B) to the CO binding site at heme alpha 3 (4.5 A). Therefore, it would appear that Cu(B) must remain reduced as long as CO is bound to the heme alpha 3 site. This is consistent with earlier proposals that Fe alpha 3 and Cu(B) are acting together as a two-electron donor to dioxygen.

Animals↗
PubMed1994

Mobile cardiac catheterization registry: report of the first 1,001 patients.

The purpose of this study was to evaluate prospectively the efficacy and safety of mobile cardiac catheterization. Mobile cardiac catheterization was introduced into clinical practice in 1989, but there has been no systematic study of its performance and safety. A registry was established in 1989 to monitor outcomes with mobile cardiac catheterization and is reported here. Patients were screened for eligibility for mobile cardiac catheterization using the joint AHA/ACC criteria for outpatient angiography. Eligible patients underwent mobile catheterization at eight hospitals within 120 miles of the base tertiary center. Helicopter evacuation services were available at each mobile site. The indications, findings, dispositions, and complications of mobile cardiac catheterization were recorded by means of a checklist, telephone follow-up and chart review. A total of 1,001 consecutive patients were entered into the registry in the first 20 months of operation, including 436 females and 565 males aged 22 to 84 years. Angina (Canadian Classes II-IV) was the most frequent primary indication for catheterization (46.4%), followed by atypical chest pain (36.9%), or a positive exercise stress test (25.6%). Infrequent indications for catheterization included a history of myocardial infarction (5.6%), congestive heart failure (7.1%), arrhythmias (4.1%), and valvular heart disease (0.7%). Catheterization was accomplished in 99.9% of patients. Angiographically normal studies were observed in 22.8%, and mild (< or = 50%) coronary artery disease in 13.6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Mobile cardiac catheterization: comparison with outpatient and inpatient catheterization at tertiary facilities.

The study group included 1,553 consecutive patients from areas serviced by our mobile catheterization laboratories: 719 procedures were performed in the mobile unit at their local hospitals, 277 were performed at a tertiary hospital with less than a 24 hr hospital stay, and 557 were performed at a tertiary hospital as inpatients. The indications for mobile catheterization were predominantly atypical chest pain, angina pectoris, or positive treadmill stress test, whereas patients with less than 24 hr hospitalization at the tertiary center had their catheterization performed for additional reasons. The majority of the inpatient indications were for recent myocardial infarction or unstable angina. Using the American College of Cardiology/American Heart Association (ACC/AHA) criteria for outpatient catheterization, the mobile catheterizations were performed safely with a complication rate of only 0.7% compared to a complication rate of 3.1% for inpatients demonstrating that a low risk group of patients can be prospectively identified and catheterized safely in the mobile setting. An extremely high risk group of patients with ongoing unstable angina and recent myocardial infarction was also identified which should undergo catheterization only at a tertiary center.

Adult↗
PubMed1990

Structure of bis(imidazole)(5,10,15,20-tetraphenylporphinato)iron(III) bis(cis-1,2-dicyanoethylenedithiolato)cuprate(III) Tetrakis(tetrahydrofuran) solvate.

[Fe(C44H28N4)(C3H4N2)2][Cu(C4N2S2)2].-4C4H8O, Mr = 1437.1, triclinic, P1-, a = 10.012 (4), b = 11.604 (6), c = 15.802 (7) A, alpha = 71.42 (4), beta = 87.12 (3), gamma = 78.45 (4) degrees, V = 1704 (1) A3, Z = 1, Dx = 1.40 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 6.9 cm-1, F(000) = 747, T = 143 K, R = 0.063 for 4935 unique observed reflections. Fe is six-coordinate, Fe--N(porphinato) (av.) = 1.99 (2), Fe--N(imidazole) = 1.981 (3) A; Cu--S (av.) = 2.172 (8) A.

Metalloporphyrins↗
PubMed1981

Simultaneous revascularization for complex brachiocephalic and coronary artery disease.

We have recently encountered two patients with significant coronary artery disease in addition to complex and extensive brachiocephalic occlusive disease. Both were operated upon successfully with simultaneous repair of both anatomic areas. These cases form the basis of this article. Fourteen additional patients with combined coronary and conventional carotid disease have been operated upon successfully with a simultaneous approach to both lesions. We conclude, until convincing prospective data are available possibly indicating otherwise, that a simultaneous approach to these combined lesions is indicated.

Arteriosclerosis↗
PubMed1977

Synthesis and characterization of "face-to-face" porphyrins.

The syntheses of four binary porphyrins, two of which are constrained to a "face-to-face" conformation, and their Co2+ and Cu2+ derivatives are described. Electron spin resonance indicates that the intermetallic separation in the binuclear "face-to-face" porphyrins is about 6.5-6.8 A. Electronic spectra and proton magnetic resonance spectra support the postulated "face-to-face" conformations. A hypothesis that related compounds may serve as multielectron redox catalysts for O2 and N2 is presented.

Cobalt↗
PubMed1976

Idiopathic hypertrophic subaortic stenosis associated with cutaneous neurofibromatosis: report of a case.

Although idiopathic hypertrophic subaortic stenosis has been studied extensively, its etiology has remained elusive. Recent reports of its association with neuroectodermal syndrome suggest that at least some cases may be the manifestation of a heritable defect of neuroectoderm. Consistent with this hypothesis, we report a case of idiopathic hypertrophic subaortic stenosis associated with neurofibromatosis.

Aortic Stenosis, Subvalvular↗