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Biomedical subjects

C D Lewis

Publications and source records attributed to C D Lewis.

At least 19 recordsLinked to original sources
PubMed2001

Modulation of smooth muscle proliferation in rat carotid artery by platelet-derived mediators and fibroblast growth factor-2.

Endothelial denuding injury to the rat carotid artery stimulates smooth muscle cell proliferation in the tunica media. Fibroblast growth factor-2 (FGF2) is responsible for a significant portion of this proliferation but other factors may contribute, particularly those released from adherent platelets. We therefore tested the effects of a range of platelet-derived factors. After filament injury, which minimises FGF2 release, the proliferation rate in thrombocytopaenic rats was decreased by 74% (P < 0.02). After balloon injury, antibody neutralisation of platelet-derived growth factor (PDGF) caused a 27% decrease in proliferation (P < 0.05), while inhibition of histamine H(1) receptors caused a 53% increase (P < 0.05). When filament injury was performed 1 h after FGF2 injection, the proliferation rate increased from 2.3+/-0.7 to 32.8+/-2.7% (P < 0.001), while filament injury alone caused a proliferation rate of only 18.3+/-2.9% (P < 0.01 versus filament plus FGF2). These data suggest that platelet-derived factors interact with FGF2 that is adsorbed to the vessel wall in the control of smooth muscle cell proliferation, and that the net effect of platelets is to stimulate smooth muscle cell proliferation. PDGF, but no other platelet agonist tested, contributes to that stimulation.

Animals↗
PubMed2001

Peripheral arterial disease of the lower extremity.

Peripheral arterial disease is becoming more prevalent due to the increasing age of the population. To better evaluate and care for patients with this disease, it is essential to understand its pathophysiology and etiology. Understanding the sequelae of events and treatments associated with peripheral arterial disease will help the nurse to provide a comprehensive, outcome-focused plan of care and education plan. Nurses are in a unique position to reduce the risks associated with lower extremity arterial disease.

Age Factors↗
PubMed2001

Long-term correlations in the spike trains of medullary sympathetic neurons.

Fano factor analysis was used to characterize the spike trains of single medullary neurons with sympathetic nerve-related activity in cats that were decerebrate or anesthetized with Dial-urethan or urethan. For this purpose, values (Fano factor) of the variance of the number of extracellularly recorded spikes divided by the mean number of spikes were calculated for window sizes of systematically varied length. For window sizes < or =10 ms, the Fano factor was close to one, as expected for a Bernoulli process with a low probability of success. The Fano factor dipped below one as the window size approached the shortest interspike interval (ISI) and reached its nadir at window sizes near the modal ISI. The extent of the dip reflected the shape (skewness) of the ISI histogram with the dip being smallest for the most asymmetric distributions. Most importantly, for a wide range of window sizes exceeding the modal ISI, the Fano factor curve took the form of a power law function. This was the case independent of the component (cardiac related, 10 Hz, or 2--6 Hz) of inferior cardiac sympathetic nerve discharge to which unit activity was correlated or the medullary region (lateral tegmental field, raphe, caudal and rostral ventrolateral medulla) in which the neuron was located. The power law relationship in the Fano factor curves was eliminated by randomly shuffling the ISIs even though the distribution of the intervals was unchanged. Thus the power law relationship arose from long-term correlations among ISIs that were disrupted by shuffling the data. The presence of long-term correlations across different time scales reflects the property of statistical self-similarity that is characteristic of fractal processes. In most cases, we found that mean ISI and variance for individual spike trains increased as a function of the number of intervals counted. This can be attributed to the clustering of long and short ISIs, which also is an inherent property of fractal time series. We conclude that the spike trains of brain stem sympathetic neurons have fractal properties.

Action Potentials↗
PubMed2000

Coupling of arterial pulse and 10-Hz rhythm in sympathetic nerve discharge.

We used time series analysis to characterize the relationships among the arterial pulse (AP) and the cardiac-related and 10-Hz rhythms in sympathetic nerve discharge (SND) of urethane-anesthetized cats. We found that 10-Hz activity was more tightly coupled to the AP than to the cardiac-related rhythm. These data support the view that the dynamic coupling of AP and the 10-Hz rhythm in SND involves a direct influence of baroreceptor activity on the 10-Hz oscillator.

Animals↗
PubMed2000

Modes of baroreceptor-sympathetic coordination.

We tested the hypothesis that the cardiac-related rhythm in sympathetic nerve discharge (SND) results from the forcing of a central oscillator to the frequency of the heart beat by pulse-synchronous baroreceptor afferent nerve activity. For this purpose, time series analysis was used to examine the phase relations between the brachial arterial pulse (AP) and cardiac-related activity recorded from the postganglionic inferior cardiac sympathetic nerve (CN) in urethan-anesthetized cats. Specifically, we made cycle-by-cycle measurements of peak systolic blood pressure, heart period, CN burst amplitude, and the phase angle (and corresponding interval) between peak systole and the next peak of CN activity. As the steady-state level of systolic blood pressure was raised by increasing the rate of a constant intravenous infusion of phenylephrine, we observed transitions from no phase-locking of CN activity to the AP to either phase-locking of variable strength or phase walk through part of the cardiac-cycle on the time scale of respiration. Phase walk is defined as a progressive and systematic change in the phase lag of cardiac-related CN activity relative to peak systole. Raising blood pressure strengthened phase-locking and either increased or decreased the mean interval between peak systole and the next peak of CN activity even when the change in heart period was small. CN burst amplitude and the interval between peak systole and the next peak of CN activity were inversely related, but the strength of the relationship varied considerably with experimental conditions. The relationship was strongest during phase walk. Step-wise increases in blood pressure induced by abdominal aortic obstruction led to an abrupt increase in the phase lag of CN activity relative to peak systole even when heart rate was not changed. We refer to such changes as sharp phase transitions that are a general property of dynamical nonlinear systems. The results support the view that the cardiac-related rhythm in SND is a forced nonlinear oscillation rather than the consequence of periodic inhibition of randomly generated activity.

Animals↗
PubMed2000

Partial spectral analysis of cardiac-related sympathetic nerve discharge.

We have studied the relationship between pulse synchronous baroreceptor input (represented by the arterial pulse, AP) and the cardiac-related rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized cats by using partial autospectral and partial coherence analysis. Partial autospectral analysis was used to mathematically remove the portion of SND that can be directly attributed to the AP, while partial coherence analysis was used to removed the portion of the relationship between the discharges of sympathetic nerve pairs that can be attributed to linear AP-SND relationships that are common to the nerves. The ordinary autospectrum of SND (AS(SND)) and coherence functions relating the discharges of nerve pairs (Coh(SND-SND)) contained a peak at the frequency of the heart beat. When the predominant mode of coordination between AP and SND was a phase walk, partialization of the autospectra of SND with AP (AS(SND/AP)) left considerable power in the cardiac-related band. In contrast, when the predominant mode of coordination between AP and SND was phase-locking, there was virtually no cardiac-related activity remaining in AS(SND/AP). Partialization of Coh(SND-SND) with AP reduced the peak coherence within the cardiac-related band in both modes of coordination but to a much greater extent during phase-locking. After baroreceptor denervation, Coh(SND-SND) at the cardiac frequency remained significant, although a clear peak above background coherence was no longer apparent. These results are consistent with a model in which the central circuits controlling different sympathetic nerves share baroreceptor inputs and in addition are physically interconnected. The baroreceptor-sympathetic relationship contains both linear and nonlinear components, the former reflected by phase-locking and the latter by phase walk. The residual power in AS(SND/AP) during phase walk can be attributed to the nonlinear relationship, and the residual peak in partialized nerve-to-nerve coherence (Coh(SND-SND/AP)) arises largely from nonlinearities that are common to the two nerves. During both phase walk and phase-locking, in addition to common nonlinear AP-SND relationships, coupling of the central circuits generating the nerve activities may contribute to Coh(SND-SND/AP) because significant Coh(SND-SND) was still observed following baroreceptor denervation.

Animals↗
PubMed1997

Involvement of functional antagonism in the effects of adenosine antagonists and L-NAME in the rat isolated heart.

1. Adenosine and its analogues induced an increase in flow rate when infused into the rat isolated perfused heart. The agonist potency order obtained was 2-(rho-(2-carboxyethyl)phenethyl-amino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) > or = 5'-N-ethylcarboxamidoadenosine (NECA) > N6-cyclopentyladenosine = adenosine, although the maximal response obtained for CGS 21680 was only 70% of that achieved by NECA. NG-Nitro-L-arginine methyl ester (L-NAME), the nonselective adenosine antagonist 8-rho-(sulfophenyl)theophylline (8-SPT) and the A2a selective antagonist N-[2-(dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- diprophyl-1H-purin-8-yl)benzene sulfonamide (PD 115, 119) reduced responses to the adenosine agonists, but some of this reduction was shown to be due to a nonspecific decrease in flow rate as well as a specific inhibitory action. 2. When this functional antagonism is taken into account, the results suggest that the increase in flow rate induced by the adenosine agonists was mediated by A2 receptors, with the increase in flow rate induced by CGS 21680 mediated by A2a receptors, whereas that induced by NECA was mediated by A2b receptors. 3. L-NAME did not appear to have any effect on the increase in flow rate induced by the adenosine agonists, suggesting that these responses were probably endothelium independent and do not involve the nitric oxide pathway.

Adenosine↗
PubMed1994

Characterization of adenosine receptors in the rat isolated aorta.

1. Adenosine and its analogues relaxed the isolated rat aorta by an endothelium-dependent mechanism with an order of potency of 5'-N-ethylcarboxamidoadenosine (NECA) > 2-(p-(2-carboxy-ethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosi ne (CGS 21680) > adenosine = N6-(2-(4-amino-phenyl)ethyl)adenosine (APNEA) = N6-cyclopentyladenosine (CPA) > 5'-methylthioadenosine (MTA), although the maximal response achieved by CGS 21680 was less than that achieved by NECA. 2. Both 8-sulphophenyltheophylline (8-SPT) and MTA antagonized responses to the adenosine analogues, but there were some anomolous features of this antagonism and NECA was inhibited more powerfully than the other agonists. This suggests that as well as A2a receptors mediating relaxation, the rat aorta may relax to adenosine analogues by other mechanisms.

Adenosine↗
PubMed1990

Properties of BGP1, a poly(dG)-binding protein from chicken erythrocytes.

The chicken beta A-globin gene contains in the neighborhood of its 5' promoter a (dG)-homopolymer sequence 16 base pairs long. The 66 kD protein BGP1 (beta globin protein 1), isolated from chicken erythrocytes, has been shown to bind specifically to this sequence. We describe further purification of BGP1, measure its affinity for the beta A-globin promoter binding site, and analyze its binding properties. The minimal binding sequence is seven dG residues; methylation interference studies show that each of these residues contacts BGP1. Binding competition experiments employing (dG).(dC) oligomers of varying lengths also consistent with (dG)7 as a minimum recognition sequence. All of the data can be explained by a model in which BGP1 binds to any contiguous set of seven (dG) residues, so that the effective constant for binding to (dG)n is proportional to n minus 6. This behavior may be typical of proteins that bind specifically to repeated sequences.

Animals↗
PubMed1988

An erythrocyte-specific protein that binds to the poly(dG) region of the chicken beta-globin gene promoter.

The promoter region of the chicken adult beta-globin gene contains a sequence of 16 deoxyguanosine residues located at a nucleosome boundary in tissues where the gene is inactive. In definitive erythrocytes that express the beta-globin gene, the nucleosome is displaced, the G-string and adjacent sequences are occupied by sequence-specific DNA-binding proteins, and a nuclease hypersensitive domain is generated in this region. To gain insight into the role of the G-string in this series of events, we have examined the proteins that bind to it. Using the gel mobility shift assay and a monoclonal antibody that blocks specific binding to the G-string, we have identified a specific protein, BGP1, that is found only in chicken erythroid cells and appears at the same time, or shortly before, the changes in chromatin structure. The antibody interacts strongly with BGP1 and cross-reacts weakly with Sp1. Although both BGP1 and Sp1 require Zn2+ for their DNA-binding activity, these proteins differ in their binding-site specificities, chromatographic properties, and molecular weights. In contrast to Sp1, which is found in a wide variety of cell types, BGP1 is restricted to erythrocytes and is most abundant in definitive erythrocytes. Thus, its presence corresponds to the tissue- and stage-specific occupancy of the G-string in vivo.

Animals↗
PubMed1985

Interaction of specific nuclear factors with the nuclease-hypersensitive region of the chicken adult beta-globin gene: nature of the binding domain.

We have studied the properties of a factor or factors that bind selectively to the 5' flanking region of the chicken adult beta-globin (beta A-globin) gene. We previously showed that these components, when bound with histones on plasmids containing the region, confer on the complex a pattern of hypersensitivity to nuclease digestion similar to that in the nucleus. We have now measured the abundance of the factor(s) in partially purified preparations, and the affinity constants for binding to specific and nonspecific DNA sequences. Footprinting studies of the specific complex with DNAase I and II reveal two discrete protected regions within the hypersensitive domain. When these regions are physically separated, they interact with the factor(s) independently, suggesting that each region binds one or more distinct components. The footprint patterns of our complexes in vitro agree with the patterns observed in intact chicken erythrocyte nuclei. These complexes thus are on the transcriptionally active beta A-globin gene in vivo.

Animals↗
PubMed1984

Interphase nuclear matrix and metaphase scaffolding structures.

The protein compositions of purified metaphase chromosomes, nuclei and their residual scaffold and matrix structures, are reported. The protein pattern of nuclei on sodium dodecyl sulphate/polyacrylamide gels is considerably more complex and rich in non-histone proteins than that of chromosomes. Nuclei contain about three to four times more non-histone proteins relative to their histones than chromosomes. Besides the protein components of the peripheral lamina, several protein bands are specific or at least highly enriched in nuclei. Conversely, two proteins X0 (33 X 10(3) Mr) and X1 (37 X 10(3) Mr) are highly enriched in the pattern of metaphase chromosomes. We have compared morphologically the previously defined nuclear matrices type I and II. The type I nuclear matrix is composed of the known lamina proteins, which form the peripheral lamina structure, and a complex series of proteins that form the internal network of the matrix as observed by electron microscopy. This internal network is stabilized similarly to the metaphase scaffolding by metalloprotein interaction. Both the scaffolding and the internal network of the matrix dissociate if thiols or certain metal chelators are used in the extraction buffer. Under these conditions the resulting nuclear structure, called matrix type II, appears empty in the electron microscope, with the exception of some residual nucleolar material. This latter material can be extracted from the internal network by exhaustive treatment of the nuclei with RNase before extraction with high salt. Immunoblotting and activity studies show RNA polymerase II to be tightly bound to the type I, but not to the type II matrix, or to the scaffolding structure. No polymerase II enzyme was detected in isolated metaphase chromosomes. Another nuclear enzyme, poly(ADP-ribose) polymerase is not bound to either of the residual nuclear matrices or to the scaffolding structures. The association of RNA polymerase with the internal network of the nuclear matrix is consistent with the idea that transcription occurs in close association with this structure.

Cell Nucleus↗
PubMed1982

Higher order metaphase chromosome structure: evidence for metalloprotein interactions.

One level of DNA organization in metaphase chromosomes is brought about by a scaffolding structure that is stabilized by metalloprotein interactions. Fast-sedimenting, histone-depleted structures (4000-7000 S), derived from metaphase chromosomes by extraction of the histones, are dissociated by metal chelators or by thiol reagents. The chromosomal (scaffolding) proteins responsible for constraining the DNA in this fast-sedimenting form are solubilized under the same conditions. Chromosomes isolated in a metal-depleted form, which generate slow-sedimenting, histone-depleted structures, can be specifically and reversibly stabilized by Cu2+, but not by Mn2+, Co2+, Zn2+ or Hg2+. Metal-depleted chromosomes can also be stabilized by Ca2+ (at 37 degrees C), but this effect is less specific than that of Cu2+. The scaffolding protein pattern that is reproducibly generated following treatment with Cu2+ is composed primarily of two high molecular weight proteins--Sc1 and Sc2 (170,000 and 135,000 daltons). The identification of this simple protein pattern has depended upon the development of new chromosome isolation methods that are highly effective in eliminating cytoskeletal contamination.

Calcium↗
PubMed1978

The relative effects of lesser curvature vagotomy and esophageal vagotomy on the acid secretory effect of proximal gastric vagotomy.

Proximal gastric vagotomy is an operation consisting of division of all vagal fibers to the acid-secreting portion of the stomach. These fibers are usually divided along the lesser curvature of the stomach; however, because of a high rate of duodenal ulcer recurrence in some series, it has become apparent that it is important to divide the vagal fibers to the stomach leaving the main vagal trunks along the distal 5 cm of esophagus in order to achieve both adequate control of acid secretion and also a lower duodenal ulcer recurrence rate. The data presented in this study of ten mongrel dogs suggest that, in the dog, division of the vagal fibers along the lesser curvature is more important in reducing acid secretion than is esophageal vagotomy; but the data also emphasize the contribution of the vagal fibers along the distal esophagus since a marked reduction in 2 DG-stimulated acid secretion can only be achieved by dividing the vagal fibers around the distal esophagus as well as those along the lesser curvature.

Animals↗