Biomedical subjects

S M Collins

Publications and source records attributed to S M Collins.

At least 109 records · Page 6Linked to original sources

PubMed1994

Lumen centerline detection in complex coronary angiograms.

We have developed a method for lumen centerline detection in individual coronary segments that is based on simultaneous detection of the approximate positions of the left and right coronary borders. This approach emulates that of a clinician who visually identifies the lumen centerline as the midline between the simultaneously-determined left and right borders of the vessel segment of interest. Our lumen centerline detection algorithm and two conventional centerline detection methods were compared to carefully-defined observer-identified centerlines in 89 complex coronary images. Computer-detected and observer-defined centerlines were objectively compared using five indices of centerline position and orientation. The quality of centerlines obtained with the new simultaneous border identification approach and the two conventional centerline detection methods was also subjectively assessed by an experienced cardiologist who was unaware of the analysis method. Our centerline detection method yielded accurate centerlines in the 89 complex images. Moreover, our method outperformed the two conventional methods as judged by all five objective parameters (p < 0.001 for each parameter) and by the subjective assessment of centerline quality (p < 0.001). Automated detection of lumen centerlines based on simultaneous detection of both coronary borders provides improved accuracy in complex coronary arteriograms.

Algorithms↗

PubMed1994

Mechanism underlying tumor necrosis factor-alpha suppression of norepinephrine release from rat myenteric plexus.

We studied the effect of tumor necrosis factor-alpha (TNF-alpha) on the release of [3H]norepinephrine ([3H]NE) from longitudinal muscle-myenteric plexus preparations of rat jejunum. TNF-alpha had no immediate effect on [3H]NE release. Preincubation of the tissue with TNF-alpha caused a suppression of [3H]NE release stimulated by KCl or electrical field stimulation. The action of TNF-alpha was time and concentration dependent (0.1-50 ng/ml) and was not due to endotoxin contamination. The effect of TNF-alpha was biphasic, occurring after 30 min and again after 120 min of preincubation. The early component was independent of protein synthesis but was inhibited by piroxicam or indomethacin, indicating the involvement of cyclooxygenase metabolites. The late component was dependent on protein synthesis, was blocked by an interleukin-1 receptor antagonist, and was inhibited by piroxicam or indomethacin. These results indicate that TNF-alpha suppresses NE release by two mechanisms, one of which is due to the synthesis and release of interleukin-1, each involving arachidonic acid metabolites.

Animals↗

PubMed1994

Central interleukin-1 receptors contribute to suppression of feeding after acute colitis in the rat.

Experimental colitis, induced in rats by intrarectal administration of trinitrobenzenesulfonic acid (TNB), results in a suppression of eating for 3 days. Because interleukin-1 (IL-1) is elevated within 24 h after TNB treatment, and because chronic administration of IL-1 leads to a pattern of anorexia similar to that seen after TNB, we evaluated the role of endogenous IL-1 in the anorexia observed in the TNB model. Human recombinant IL-1 receptor antagonist (rhIL-1ra) was administered chronically via osmotic minipump either peripherally or centrally after TNB treatment. Peripheral delivery of 40 micrograms/h rhIL-1ra significantly attenuated TNB-induced anorexia. However, 24 micrograms/h rhIL-1ra attenuated TNB-induced anorexia only when delivered centrally, not peripherally. These findings implicate central IL-1 receptors in the suppression of eating during acute experimental colitis but leave open a possible involvement of peripheral IL-1 receptors.

Animals↗

PubMed1993

Validation by high-frequency epicardial echocardiography of a new method of analyzing coronary angiography quantitatively in coronary artery disease.

In coronary atherosclerosis, the arterial lumen size and shape can be markedly irregular, eccentric and variable. Traditional angiographic interpretation, emphasizing percent diameter stenosis, has been criticized as an inadequate descriptor of such diseased arteries. Computerized quantitative angiographic technologies, yielding a true lumen area measurement, may be superior. High-frequency epicardial echocardiography (HFEE) is a technique that allows on-line evaluation of coronary arterial wall and lumen at the time of cardiac surgery. It has been extensively validated and yields accurate measurements of normal and diseased coronary lumen areas. This study compares quantitative coronary angiography (QCA) estimates of lumen area to those obtained by HFEE to determine if the computerized angiographic method more accurately predicts residual luminal area than traditional angiographic percent diameter stenosis measurements. Although actual luminal morphology was quite variable, there was a good correlation between lumen areas determined by HFEE versus QCA: r = 0.85, n = 67, HFEE = 0.8 QCA - 0.1 (HFEE 4.0 +/- 0.30 mm2, mean +/- SEM range 0.3 to 14.0; QCA 5.1 +/- 0.40 mm2, range 0.7 to 11.8). Percent diameter stenosis determined from the angiograms did not correlate well with HFEE or QCA measurements of residual luminal area. Separation of "normal" arterial segments (defined as < 25% diameter stenosis) from "abnormal" segments (> 50% diameter stenosis) by angiography did not agree with lumen areas as defined by either HFEE or QCA. Better separation occurred when QCA-determined luminal areas were used to separate normal from abnormal arterial segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

On the specificity of altered muscle function in experimental colitis in rats.

BACKGROUND: Studies on muscle contraction in colitis yield conflicting data that may reflect differences in the manner in which colitis is induced. Therefore, we compared distal colonic longitudinal muscle contraction in four models of colitis in the rat. METHODS: Distal colitis was induced by intrarectal administration of trinitrobenzene sulfonic, acetic acid, or Trichinella spiralis larvae, or by intraperitoneal injection of mitomycin C. Colonic myeloperoxidase activity was used to monitor acute inflammation. RESULTS: Myeloperoxidase activity increased in each model of colitis. In trinitrobenzene-treated rats, contractile responses to carbachol, substance P, and KCl decreased by 64%, 76%, and 58%, respectively. In acetic acid treated rats, responses induced by carbachol, substance P, or KCl were each significantly decreased by 73%, 68%, and 55% and were similarly reduced by 42%, 77%, and 46%, respectively, in rats with T. spiralis colitis. In mitomycin-induced colitis, these respective responses also decreased significantly by 71%, 55%, and 54%. CONCLUSION: Decreased contractility of longitudinal muscle in acute colitis in rats is independent of the manner in which the colitis is induced and is mediated at a receptor-independent locus on the muscle cell.

Acetates↗

PubMed1993

Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus.

BACKGROUND: A marked suppression of acetylcholine (ACh) release from myenteric nerves in the inflamed intestine of rats infected by Trichinella spiralis has been shown. In this model, there is increased expression of interleukin 1 beta (IL-1 beta) in the myenteric plexus. Therefore, the ability of IL-1 beta to alter ACh release in longitudinal muscle-myenteric plexus (LMMP) preparations from noninfected rats was examined. METHODS: LMMP preparations were loaded with [3H]choline before stimulation by KCl or electrical field stimulation. ACh release was recorded by measuring 3H in the superfusate. Experiments were performed in the presence or absence of human recombinant IL-1 beta. RESULTS: IL-1 beta had no immediate effect on the basal or stimulated release of ACh. A marked suppression of ACh release was observed in tissues that had been preincubated with IL-1 beta for 60 minutes or more. The effect of IL-1 beta was concentration and time dependent with maximum suppression occurring with 10 ng/mL of the cytokine after a 90-minute incubation. The action of human recombinant (hr) IL-1 beta was abolished by boiling the cytokine for 20 minutes and was prevented by preincubating the cytokine with neutralizing antibody. The IL-1 beta effect was also blocked by cycloheximide and was spontaneously reversible after 60 minutes. CONCLUSION: It was concluded that IL-1 beta suppresses ACh release via the formation and release of a protein mediator that could be another cytokine, including IL-1. Based on these findings, we consider IL-1 beta a putative mediator of the changes in cholinergic nerve function observed in the inflamed rat intestine.

Acetylcholine↗

PubMed1993

Altered small intestinal smooth muscle function in Crohn's disease.

BACKGROUND: Studies in animals indicate that inflammation causes changes in smooth muscle contractility. Because Crohn's disease is associated with altered motility, this study investigated the contractility of intestinal muscle resected from patients with or without Crohn's disease. METHODS: The isometric contraction of muscle strips from the small bowel of 36 patients with and 24 patients without Crohn's disease was examined. RESULTS: In longitudinal muscle from patients with Crohn's disease, there was a 55% increase in maximum contraction induced by carbachol but not histamine, but there was no change in the 50% effective dose (ED50) for these agonists. In contrast, in circular muscle from patients with Crohn's disease there was a sevenfold decrease in the ED50 value for carbachol but no change in maximum contraction. There was a 2.5-fold increase in the maximum response to histamine, but no change in ED50, in circular muscle from patients with Crohn's disease. However, there was no change in KCl-induced contraction between the two groups. The carbachol responses were atropine sensitive. Histamine responses were blocked by the H1 antagonist mepyramine but were not altered by a diamine oxidase inhibitor. All responses were tetrodotoxin insensitive. CONCLUSION: These results show altered receptor-mediated contraction in small intestinal muscle in patients with Crohn's disease.

Adolescent↗

PubMed1993

Interleukin 1 beta-induced increase in substance P in rat myenteric plexus.

BACKGROUND: Substance P (SP) is increased in the inflamed intestine of Trichinella spiralis-infected rats, but the underlying mechanism is unknown. Interleukin 1 beta (IL-1 beta) messenger RNA and protein is expressed in the longitudinal muscle-myenteric plexus (LM-MP) of this model. Thus, the purpose of the study was to examine the ability of human recombinant IL-1 beta (hrIL-1 beta) to increase SP in LM-MP preparations from the intestine of noninfected rats. METHODS: LM-MP preparations were incubated with hrIL-1 beta, and immunoreactive SP (IR-SP) was assessed in the tissues by radioimmunoassay or immunohistochemistry. RESULTS: hrIL-1 beta increased IR-SP in the tissue in a time- and concentration-dependent manner, being maximal after 6 hours at a concentration of 10 ng/mL. The IR-SP could be depleted by scorpion venom, and immunohistochemistry revealed increased staining for SP within nerves of the LM-MP. The action of IL-1 beta was dependent on protein synthesis, was receptor mediated, and was not due to endotoxin contamination of the cytokine preparation. CONCLUSIONS: hrIL-1 beta stimulates the synthesis of SP in myenteric nerves of rat intestine.

Animals↗

PubMed1993

Role of mast cells in peritoneal adhesion formation.

Postoperative adhesions are a major cause of bowel obstruction and infertility. Since mast cells in the intestinal wall have been shown to degranulate after bowel manipulation, we investigated a possible role for these cells in peritoneal adhesion formation. Adhesions were created in weanling rats using cecal scraping and the application of 95% ethanol. The rats were treated with saline or one of two mast cell stabilizers, disodium cromoglycate (DSCG) or nedocromil sodium (NED), intraperitoneally 30 minutes before laparotomy and at the time of abdominal closure. The adhesions were assessed blindly 1 week later using a standardized scale. When the results in rats treated with DSCG were compared with those in rats treated with saline, the DSCG rats had significant attenuation of adhesion formation at 2 mg/kg (1.05 +/- 1.0 versus 2.15 +/- 0.8) and 10 mg/kg (1.2 +/- 0.9 versus 2.71 +/- 0.5). The application of NED decreased adhesions at a dose of 100 mg/kg (1.33 +/- 1.2 versus 2.4 +/- 0.8) but not at 10 mg/kg (2.4 +/- 0.8 versus 2.4 +/- 0.8). Histologic analysis using toluidine blue staining was done to assess the effect of DSCG on mast cell degranulation in the same adhesion model. DSCG significantly decreased the number of degranulated mast cells in the bowel wall when compared with saline (7.16 +/- 0.6 mast cells/high-power field [hpf] versus 12.4 +/- 1.9 mast cells/hpf). These data suggest that mast cells play an important role in the initial stages of peritoneal adhesion formation. In the future, pharmacologic inhibition of mast cell degranulation may be a useful adjunct for the prevention of postoperative adhesions.

Animals↗

PubMed1993

Interleukin-1 beta modulation of norepinephrine release from rat myenteric nerves.

We examined the ability of human recombinant interleukin-1 beta (hrIL-1 beta) to alter the release of [3H]norepinephrine ([3H]NE) by KCl or electrical field stimulation in longitudinal muscle-myenteric plexus of rat intestine. The cytokine had no immediate effect on either the basal or evoked release of [3H]NE. However, hrIL-1 beta caused a biphasic time-dependent suppression of evoked [3H]NE release that was delayed in onset. IL-1 beta also stimulated the cycloheximide-sensitive uptake of [35S] methionine uptake by the tissue. The initial suppression of [3H]NE release was observed after 30 min and could not be inhibited by cycloheximide. A delayed peak was observed after 120 min and was inhibited by cycloheximide. The effect of IL-1 beta was maximal at 10 ng/ml and could be prevented by a neutralizing anti-IL-1 beta antibody or by preincubating the tissue with an IL-1-receptor antagonist. These results indicate that IL-1 beta suppresses [3H]NE release from rat myenteric plexus by two mechanisms, one of which is independent of protein synthesis and the other of which is mediated by endogenous IL-1.

Animals↗

PubMed1993

Downregulation of neutral endopeptidase (EC 3.4.24.11) in the inflamed rat intestine.

Intestinal inflammation induced by the nematode Trichinella spiralis is accompanied by increased intestinal concentrations of substance P, a mediator of inflammation and a stimulant of smooth muscle contraction, and by intestinal hypermotility. The expression of neutral endopeptidase (NEP), a cell surface enzyme that degrades substance P in the extracellular fluid, was examined in the inflamed intestine. NEP enzymatic activity, measured by a fluorometric assay, was reduced by 84-fold in jejunal mucosa-circular muscle and by 12-fold in jejunal longitudinal muscle-myenteric plexus within 6 days after infection with T. spiralis. The downregulation was unaffected by treatment with betamethasone and was still observed in athymic animals. NEP protein levels, examined by Western blotting, confirmed the loss of NEP from inflamed tissue. The specific activity for degradation of substance P was reduced by sixfold in jejunal mucosa-circular muscle and by twofold in jejunal longitudinal muscle-myenteric plexus of rats infected with T. spiralis compared with uninfected controls. Thus the downregulation of NEP resulted in reduced substance P degradation, which may contribute to functional abnormalities of the inflamed intestine.

Analysis of Variance↗

PubMed1993

Altered expression of sodium pump isoforms in the inflamed intestine of Trichinella spiralis-infected rats.

We used polymerase chain reaction (PCR) and Northern analysis to examine the effect of Trichinella spiralis infection on mRNA expression of sodium pump isoforms in rat intestine. 28S RNA was coamplified as an internal standard, and the abundance of the isoformic mRNA was expressed relative to 28S RNA. As assessed by PCR and Northern analysis, the alpha 1- and beta 1-subunits were expressed in the jejunum and ileum of noninfected control rats. However, in the jejunum the levels were suppressed after 24 h of infection. The suppression became maximal by day 6 and was reversed to normal by day 23 postinfection (PI). In contrast, no suppression was observed in the noninflamed ileum of infected rats. Further analysis revealed that alpha 1-mRNA was suppressed in jejunal mucosa by 89% and in longitudinal muscle-myenteric plexus by 62% but was not suppressed in circular muscle. Western blot analysis revealed a 61% decrease in the alpha 1-subunit protein in the mucosa and a 62% decrease in longitudinal muscle, whereas there was no change in the alpha 1-protein in circular muscle on day 6 PI. In contrast, marked (89%) suppression of beta 1-mRNA was observed only in the mucosa; there was no change in either circular or longitudinal muscle on day 6 PI. These results indicate that T. spiralis infection in the rat is accompanied by a significant decrease in the alpha 1-subunit of the sodium pump in longitudinal muscle. This reduction could result from altered regulation involving pretranslational changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

On the suppression of food intake in experimental models of colitis in the rat.

We measured daily food intake and body weight in rats before and after the induction of colitis by intrarectal administration of either 2,4,6-trinitrobenzenesulfonic acid in ethyl alcohol (TNBE) or 4% acetic acid (AA). Administration of TNBE or AA induced inflammation in the distal colon, which was reflected by a significant increase in myeloperoxidase (MPO) activity in the colon. On days 1, 2, and 3 after induction of colitis by TNBE, food intake fell by 80, 70, and 50%, respectively, compared with pretreatment values; food intake returned to normal by day 4. Body weight fell within 24 h after induction of colitis and remained 10% less than control for at least 5 days. Colitis induced by AA produced a similar pattern and degree of decreased food intake and weight loss. Treatment with the 5'-lipoxygenase inhibitor MK-886 significantly reduced concentrations of leukotriene B4 in the colon of TNBE-treated rats but did not affect food intake. In contrast, the cyclooxygenase inhibitor indomethacin decreased prostaglandin E2 concentrations in the colon but also attenuated the suppression of feeding by 52 and 64% on the first 2 days after induction of colitis by TNBE. These results identify a specific prostaglandin-mediated suppression of feeding in the rat with acute colitis induced by TNBE and illustrate the utility of this model for studying mechanisms underlying anorexia associated with inflammation of the gastrointestinal tract.

Acetates↗

PubMed1993

Characterization of suppression of food intake following acute colon inflammation in the rat.

Experimental colitis was induced in rats by intrarectal infusion of trinitrobenzenesulfonic acid and ethanol. Colitis was accompanied by a large suppression of food intake of 3 days duration. The reduction of food intake was effected through a reduction of meal size, with no change in meal frequency. Those same rats demonstrating approximately 70%-80% suppression of daily food intake showed no reduction of sham feeding. These data indicate that malaise alone is inadequate to explain the suppression of food intake associated with acute colitis. Rather, the data suggest that the suppression of eating results from an exaggerated postprandial satiety signal elaborated during the period of acute inflammation, an interpretation consistent with the demonstration of a slowed rate of gastric emptying in association with the colitis.

Analysis of Variance↗

PubMed1992

Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography.

The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.1 +/- 0.2 (mean +/- SEM) with a large range (1.3 to 7.5). Portions of the wall were normal in 16 of 31 lesions; the percent normal circumference ranged from 9% to 85%. Maximal/minimal lumen diameter ratio was 1.5 +/- 0.1 (range 1.1 to 2.9). The shape of the residual coronary lumen was noncircular in 16 lesions: oval in 13 and complex in 3. The residual coronary lumen was eccentrically placed within six arteries. These data emphasize the variability of residual lumen and wall geometry in atherosclerosis.

Coronary Artery Bypass↗

PubMed1992

Increased levels of substance P in the myenteric plexus of Trichinella-infected rats.

Changes in immunoreactive substance P concentrations were investigated in longitudinal muscle-myenteric plexus preparations from the inflamed jejunum of Trichinella spiralis-infected rats. The substance P concentration increased within 2 days of infection and increased fivefold by day 6; in contrast, there was no significant increase in substance P in the noninflamed ileum. In vitro exposure of preparations from infected rats to scorpion venom reduced substance P levels by 88%. In addition, no increase in substance P was observed in rats that had been treated with capsaicin as neonates or as adults before infection. Treatment of infected rats with betamethasone attenuated the inflammatory response to the infection and prevented the increase in substance P. Furthermore, no significant increase in substance P concentration was seen in congenitally athymic rats infected with T. spiralis. This study is consistent with the hypothesis that inflammation increases substance P in myenteric nerves by a process that involves T lymphocytes.

Animals↗

PubMed1992

Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release.

The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system.

Animals↗

PubMed1992

Inflammation causes hyperplasia and hypertrophy in smooth muscle of rat small intestine.

Inflammation of the rat jejunum with Trichinella spiralis causes altered smooth muscle contractility by day 6 postinfection (PI). We investigated the association of structural change in the smooth muscle layers with inflammation. By day 6 PI, smooth muscle area in cross sections of jejunum increased (P less than 0.05) in longitudinal (LM) and circular (CM) muscle layers. Nuclei counting in cross sections showed that cell number increased two- to threefold in CM and LM, and this increase was not reversed on day 23 PI. Estimation of cell size showed significant hypertrophy by day 6 PI in both muscle layers. [3H]thymidine autoradiography showed that the labeling index (LI) of jejunal LM and CM increased sharply on day 4 PI and peaked on day 6 PI (10- to 15-fold increase). The noninflamed ileum showed a smaller trophic response, with no significant change in area or nuclei number, the LI was increased only on day 6 PI in the ileal CM and was unchanged in LM. Thus extensive hyperplasia and hypertrophy of smooth muscle cells are associated with intestinal inflammation.

Animals↗