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Biomedical subjects

L Bell

Publications and source records attributed to L Bell.

At least 73 records · Page 4Linked to original sources
PubMed1990

Influence of the angiotensin system on endothelial and smooth muscle cell migration.

The blood vessel wall's response to injury is an important determinant of luminal size and vessel function. The physiologic migration of endothelial cells from the edges of a wound and the pathophysiologic migration of medial smooth muscle cells into the intima are two important components of the vessel wall's response to injury. The influence of the angiotensin system on endothelial and smooth muscle cell migration have not been examined. In the present study, the influence of angiotensin system components on bovine aortic endothelial cell (BAEC) and bovine aortic smooth muscle cell (BASMC) migration after release of cultured cell monolayers from contact inhibition was determined. The angiotensin-converting enzyme (ACE) inhibitor lisinopril increased BAEC migration 41% +/- 3% (P less than 0.001), as did the specific angiotensin II antagonist sar1, ile8-angiotensin II (SAR) (41% +/- 3% (P less than 0.001). Exogenous angiotensin I and angiotensin II did not affect BAEC migration. Exogenous angiotensin II abolished the effect of lisinopril on BAEC migration. Lisinopril increased cell-associated u-plasminogen activator (u-PA) 23% +/- 3% (P less than 0.001) in migrating BAEC and angiotensin II abolished this increase. SAR increased u-PA 33% +/- 0% (P less than 0.001). In contrast, these agents had the opposite effect on smooth muscle cells. Angiotensin II increased smooth muscle cell migration 40% +/- 3% (P less than 0.001), and this effect was abolished by SAR. Angiotensin II also increased cell-associated u-PA 83% +/- 7% (P less than 0.001) in migrating BASMC. The increase in BAEC migration with inhibition of endothelial cell angiotensin II stimulation, either with lisinopril or SAR, also was associated with an increase in cell-associated u-PA. These results indicate that lisinopril interrupts an autocrine pathway in endothelial cells, in which endothelial cell-derived angiotensin I is converted to angiotensin II by ACE, and imply that angiotensin-converting enzyme inhibitors in vivo would act to reduce vessel wall injury by directly increasing the rate of endothelial cell wound closure; by increasing the antithrombotic tendency of the endothelium via enhanced u-PA; and indirectly, by decreasing production of angiotensin II and thereby the rate of smooth muscle cell migration into the intima.

Angiotensins↗
PubMed1990

Influence of the new inotropic agent DPI 201-106 on the total capacitance vasculature in dogs.

Recent investigations have demonstrated that the piperazinyl-indole DPI 201-106 (DPI) acts to increase contractility independent of increases in cAMP or inhibition of Na+, K(+)-ATPase. Since associated changes in the capacitance vasculature would also be expected to influence ventricular performance, the influence of DPI on total intravascular volume (IV) was examined. In eight anesthetized dogs undergoing prior sinoaortic baroreceptor denervation and bilateral cervical vagotomy, blood from the venae cavae was drained to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in IV could be recorded as reciprocal changes in reservoir volume. Racemic DPI at 50 micrograms/kg/min for 20 min was associated with a 65 +/- 7 ml (P less than 0.0001) decrease in total IV and a decrease in mean arterial pressure from 80 +/- 7 to 74 +/- 5 mmHg (P less than 0.0001). DPI administration was associated with a 67 +/- 9 ml (P less than 0.05) decrease in IV after beta adrenergic blockade and a 68 +/- 11 ml (P less than 0.05) decrease in IV after alpha and beta adrenergic blockade. Abdominal evisceration abolished the IV decrement due to DPI. Radionuclide imaging studies demonstrated that decreases in hepatic and splenic IV contributed to the decrease in splanchnic IV. Thus, DPI acts to decrease total IV. The IV decrement is due entirely to a decrease in splanchnic IV and is not mediated by baroreceptor stimulation or by adrenergic receptor stimulation. In the animal with an intact circulation, the total IV decrement would be expected to increase venous return and thereby act to maintain ventricular end diastolic pressure.

Animals↗
PubMed1989

The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein.

The STE4 and STE18 genes are required for haploid yeast cell mating. Sequencing of the cloned genes revealed that the STE4 polypeptide shows extensive homology to the beta subunits of mammalian G proteins, while the STE18 polypeptide shows weak similarity to the gamma subunit of transducin. Null mutations in either gene can suppress the haploid-specific cell-cycle arrest caused by mutations in the SCG1 gene (previously shown to encode a protein with similarity to the alpha subunit of G proteins). We propose that the products of the STE4 and STE18 genes comprise the beta and gamma subunits of a G protein complex coupled to the mating pheromone receptors. The genetic data suggest pheromone-receptor binding leads to the dissociation of the alpha subunit from beta gamma (as shown for mammalian G proteins), and the free beta gamma element initiates the pheromone response.

Amino Acid Sequence↗
PubMed1989

Influence of verapamil on total and regional intravascular volume in dogs.

Verapamil's influence on intravascular volume (IV) in the total capacitance circulation was examined in anesthetized dogs after mecamylamine or baroreceptor denervation. Blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that IV changes could be measured as reciprocal changes in reservoir volume. In 10 dogs, verapamil (50 micrograms/min) caused a decrease in total IV of 74 +/- 12 ml (P less than 0.0005) at 20 min and a decrease in arterial pressure from 79 +/- 5 to 66 +/- 3 mmHg (P less than 0.0005). After evisceration in nine animals, verapamil caused an extrasplanchnic (XSPL) IV decrease of 97 +/- 19 ml (P = 0.08). In 11 animals with separate perfusion and drainage of the splanchnic and XSPL circulations, verapamil caused an XSPL IV decrease of 74 +/- 20 ml (P less than 0.002) and a splanchnic IV increase of 19 +/- 9 ml (P = 0.06). In four animals on cardiopulmonary bypass, IV decreased 154 +/- 66 ml (P less than 0.002) during verapamil administration. Thus total IV decreases due to a decrease in systemic extrasplanchnic volume. Because pressure decreased while arterial flow and venous outflow pressure were constant, a decrease in the resistance to blood return to the central circulation mediates the XSPL volume decrement.

Animals↗
PubMed1989

Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells.

Endothelial cell (EC) injury and the response of EC and smooth muscle cells (SMCs) to injury contribute to the pathophysiology in patients with vascular disease and atherosclerosis. Since platelets have been suggested to play an important role in modulating vascular injury, the present study was undertaken to examine the influence and mechanism of action of individual platelet factors on bovine aortic EC and SMC migration using an in vitro wound assay system. Serotonin decreased EC proliferation and reduced EC migration 21 +/- 1% (p less than 0.005), which was attenuated by imipramine. Transforming growth factor-beta reduced EC proliferation and decreased EC migration 52 +/- 3% (p less than 0.005). Norepinephrine increased EC proliferation but decreased EC migration 26 +/- 2% (p less than 0.005), which was abolished by phenoxybenzamine. Histamine increased EC proliferation but reduced EC migration 29 +/- 2% (p less than 0.005), which was attenuated by diphenhydramine. Platelet-derived growth factor decreased EC proliferation and decreased EC migration 40 +/- 2% (p less than 0.005). In contrast, serotonin increased SMC proliferation and increased SMC migration 31 +/- 2% (p less than 0.005), which was abolished by ketanserin. Transforming growth factor-beta increased SMC migration 35 +/- 5% (p less than 0.005). Norepinephrine increased SMC proliferation and increased SMC migration 43 +/- 4% (p less than 0.005), which was abolished by propranolol. Histamine increased SMC proliferation and increased SMC migration 38 +/- 3% (p less than 0.005), which was abolished by cimetidine. Platelet-derived growth factor increased SMC proliferation and increased SMC migration 40 +/- 3% (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Syphilis detection in cerebrovascular disease.

To determine the importance of syphilis testing in cerebrovascular disease, we prospectively assessed 218 consecutive patients with either transient ischemic attack or completed stroke. The results from this study group were compared with those from a control group of 150 neurological patients without cerebrovascular disease. Of 275 patients from both groups specifically tested by the fluorescent treponemal antibody-absorption test, 34% of the study group were seropositive compared with 18% of the controls (chi 2 = 7.7, p less than 0.01). Fifty-four percent of the patients with a positive fluorescent treponemal antibody-absorption test underwent a cerebrospinal fluid examination; meningovascular syphilis was detected in one (0.4%) of these. This patient was a homosexual male with antibodies to the human immunodeficiency virus; a second patient, with possible meningovascular syphilis, also had antibodies to this virus. Despite the relatively high rate of syphilis seropositivity noted in our study group, syphilis was not found to be a common cause of cerebrovascular disease; therefore, routine screening is seen to be of low diagnostic yield. Attention to patients who are at higher risk for syphilitic infection, patients with clinical features suggestive of meningovascular syphilis, and the proper choice of serologic studies can help make the assessment of syphilis seropositivity more clinically appropriate and cost effective.

Cerebrospinal Fluid↗
PubMed1989

The interactions of vascular cells with solid phase (matrix) and soluble factors.

The vessel wall is composed of heterogeneous cell populations residing in a variety of vascular beds. Each cell type has different functions and morphologies but all of them have a role in the repair process following vascular injury. Responses to injury vary depending upon the type and extent of the injury and the vascular bed affected. The sheet migration and proliferation exhibited by large vessel endothelial cells is in striking contrast to the migration through soft tissues and tube formation exhibited by microvascular endothelial cells in response to injury. Vascular smooth muscle cells respond to injury by migrating into the intima, proliferating and synthesizing matrix, causing intimal thickening. The response to injury by vascular cells appears to be modulated, in part, by the composition and organization of the surrounding matrix and the various platelet factors and cytokines found at sites of injury. Furthermore, evidence has been accrued in culture, suggesting that solid phase (matrix) and soluble factors modulate each other's effects on local vascular cell populations following injury.

Animals↗
PubMed1989

Endothelial cell behavior after denudation injury is modulated by transforming growth factor-beta1 and fibronectin.

Endothelial denudation injury after endarterectomy, autologous and synthetic grafting and balloon angioplasty leads to exposure of thrombogenic vessel wall material and may elicit an atherogenic response in the media of the affected vessels in which complete reendothelialization may not occur. While the role(s) of extracellular matrix composition and organization in this process are only incompletely understood, it is widely accepted that endothelial cells respond to matrix components in specific, complex fashions. In this report we demonstrate that large vessel endothelial cell migration is affected by the surrounding matrix and the soluble factor, transforming growth factor-beta1, which may mediate its effects, in part, by modulating endothelial cell matrix synthesis. Specifically, large vessel endothelial cell migration is decreased on a fibronectin substratum and in the presence of transforming growth factor-beta1, which increases fibronectin mRNA and protein accumulation in culture. Inhibition of sheet migration is also elicited by the addition of soluble fibronectin to the cultures. These in vitro findings are consistent with our in vivo findings of increased staining of fibronectin luminally and in the intima in the chronically deendothelialized region of a balloon catheter denuded carotid artery. Thus, reendothelialization after iatrogenic and natural injury appears to be a complex process which can be modulated by the underlying matrix and soluble factors, which may themselves modulate the matrix synthesis of local vascular cells.

Animals↗
PubMed1989

Timing of ovulation for artificial insemination.

Two studies involving eighty women having treatment with artificial insemination by donor (AID) have demonstrated that the use of a urinary semi-quantitative assay for luteinising hormone (LH) gives pregnancy rates comparable to those obtained using plasma LH for the timing of insemination. The advantage of self test assay is evident in a scattered region such as Grampian.

Adult↗
PubMed1988

The presence and significance of intraepithelial mesenchymal cells in human foetal colon.

During an investigation of the morphogenesis of the human foetal colon, breaks in the basal lamina underlying the surface epithelium were frequently observed at 10 1/2-11 weeks. These occurred at those sites where the mesenchyme was sweeping up into the epithelium prior to the transformation of the epithelium from stratified to a single layer. At the same time numbers of mesenchymal cells appeared among the epithelial cells and some were observed actually in the process of passing through the gaps in the basal lamina. Close contact was apparent between some mesenchymal cells and basal epithelial cells through extended breaks in the basal lamina. Many of the mesenchymal cells within the epithelium contained numbers of apoptotic bodies. This suggests that one of the functions of the intra-epithelial mesenchymal cells is to remove the debris resulting from cell death which occurs in association with the re-arrangement of cells during development of the colon.

Basement Membrane↗
PubMed1988

Fetal growth and fetal lung phospholipid content in rats fed safflower oil, menhaden oil, or hydrogenated coconut oil.

The objective was to determine if dietary fish oil decreased the degree of fatty acid saturation in rat lung phosphatidylcholine (PC). A diet containing 12% of its energy as fat was fed for 3 wk to growing male Sprague-Dawley rats (trial I) or to pregnant rats for days 8-21 of gestation (trial II). The dietary fat treatments in trial I were safflower oil (SO), menhaden oil (MO), or hydrogenated coconut oil (HCO) and in trial II were SO, MO, HCO, or SO-MO (75%:25%). Polyunsaturated fatty acids reduced (p less than 0.05) hepatic fatty acid synthetase (MO greater than SO) in growing rats but the dietary lipids had no effect on lung palmitate content. Maternal consumption of MO vs SO reduced (p less than 0.05) fetal body weight and lung weight but not lung:body wt ratio. Dietary MO and SO-MO increased (p less than 0.05) disaturated PC content of fetal lungs. The fetal lung data indicate that maternal ingestion of fish oil improve fetal lung maturation.

Animals↗
PubMed1988

Muscarinic regulation of pulmonary intravascular volume in isolated canine lungs.

The influence of acetylcholine on pulmonary intravascular volume has not been clearly identified. In 14 anesthetized dogs, the pulmonary circulation was separately perfused in situ at a constant rate and drained to an extracorporeal reservoir, so that changes in total pulmonary intravascular volume could be recorded as reciprocal changes in reservoir volume. In eight animals, acetylcholine at 100 micrograms/min for 20 min was associated with increases in pulmonary intravascular volume (PIV) and pulmonary arterial pressure of 41 +/- 5 (SE) ml (P less than 0.001) and 2.0 +/- 0.0 mmHg (P less than 0.001; 11 infusions), respectively. These responses were abolished after atropine (6 infusions). In six animals, pulmonary venous pressure was also measured, so that total pulmonary (TPR), pulmonary arterial (PAR), and pulmonary venous (PVR) resistances could be calculated. TPR and PVR increased from 21 +/- 2 to 24 +/- 3 (P less than 0.001) and from 7 +/- 1 to 11 +/- 1 mmHg.min.l-1 (P less than 0.001), respectively, while PAR did not change significantly (6 infusions). In three of the six animals, these changes were abolished by atropine (6 infusions). In the other three animals, PIV increased 56 +/- 11 ml (P less than 0.001) before and 47 +/- 6 ml (P less than 0.001) after indomethacin. The acetylcholine-associated increases in TPR and PVR were also not significantly attenuated after indomethacin. Hence, muscarinic receptor stimulation with acetylcholine is associated with an increase in pulmonary intravascular volume, which is mediated by an increase in resistance to pulmonary venous outflow. These changes are not due to release of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

The dissatisfied medical patient: predictors of intent to change doctors.

A favorable patient-doctor relationship is critical for the maintenance of a stable and productive practice. Most adults are likely to have had experiences in physician's offices that have caused upset or dissatisfaction. Many of these experiences will have resulted in changing doctors. The likelihood of changing doctors is more often related to the physician's behavior than to his or her actual competence or efficacy.

Consumer Behavior↗
PubMed1987

Trisomy 1 in an eight cell human pre-embryo.

The high incidence of chromosome abnormalities in clinically recognised pregnancies is well documented, but experience of these problems at the time of conception is extremely limited. Using donated oocytes from women seeking surgical sterilisation, we have established reliable cytogenetic techniques for chromosome analysis of human pre-embryos. These have resulted in the first report of trisomy 1. The pre-embryo showed no other obvious abnormality in relation to follicular characteristics, embryo morphology, and cleavage kinetics. The usefulness of such data in explaining the high incidence of occult human pregnancy loss and the current poor success following embryo replacement is emphasised.

Chromosome Banding↗
PubMed1987

Current practices and improved recommendations for treating hereditary fructose intolerance.

A study of treatment practices of pediatric centers managing hereditary fructose intolerance and a review of recent literature on this subject were undertaken in an attempt to establish the degree of dietary liberalization allowable with age and the acceptability of foods containing trace amounts of fructose. The information was needed to plan optimal therapy and thus avoid the consequences of the disorder, namely intestinal dysfunction, metabolic imbalance, and hepatic and renal damage. Fifty responses to 113 letters to centers in Canada and the United States, as well as data from The Hospital for Sick Children, Toronto, Ontario, identified only 29 affected children and provided information on their care, including food lists and literature references. Major principles of treatment were similar, but the approach to allowing and quantifying dietary fructose differed. In response to the apparent need for standardization of treatment, the authors formulated improved recommendations for the control of dietary fructose (less than 1.5 gm/day). Only a few foods of vegetable origin are allowed, including a limited selection of vegetables and cereal products from grain endosperm. Repeated dietary counseling is advocated with regard to allowed foods, sweeteners, and medications to ensure long-term dietary compliance.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1986

The role of the splanchnic circulation in the regulation of total intravascular volume during alpha adrenergic receptor stimulation.

Previous studies have not defined the contribution of the splanchnic circulation to the total intravascular volume change associated with selective alpha adrenergic receptor stimulation. Since the splanchnic circulation is responsible for the total volume changes associated with other types of selective autonomic receptor stimulation, the present study was undertaken to examine the influence of alpha adrenergic receptor stimulation on splanchnic intravascular volume, the hemodynamic mechanism responsible for the splanchnic volume change, and the contribution of the splanchnic volume change to the change in total volume. In 35 anesthetized dogs, blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be measured as reciprocal changes in reservoir volume. Phenylephrine infusion (100 micrograms/min) for 20 min in 28 dogs was associated with a decrease in total volume of 64 +/- 17 (SEM) ml (P less than 0.0001). The response was abolished by either alpha adrenergic blockade or evisceration but was not attenuated by beta adrenergic blockade, sinoaortic baroreceptor denervation, ganglionic blockade, or splenectomy. In 5 animals with separate splanchnic perfusion and drainage, total and splanchnic volumes decreased 59 +/- 8 ml (P less than 0.0001) and 317 +/- 20 ml (P less than 0.0001), respectively, while transhepatic vascular resistance increased 17 +/- 4 cm H2O X min/l (P less than 0.0001). These responses were abolished after alpha adrenergic blockade. Thus, splanchnic volume decreases with alpha adrenergic receptor stimulation, despite an increase in hepatic resistance to splanchnic venous outflow. The splanchnic volume decrement is entirely responsible for the total volume decrement.

Adrenergic alpha-Antagonists↗
PubMed1985

An ultrastructural study of meconium corpuscles in human foetal colon.

In human foetal colon meconium corpuscles were observed in the colonic epithelium during the stage of secondary lumina development and enlargement. Transmission electron microscopy of these specimens revealed inclusion bodies in the superficial and deeper layers of the epithelium. Many of the membrane-bounded inclusion bodies contained well-preserved organelles and some inclusions contained nuclear fragments. There was evidence of nuclear fragmentation with condensed chromatin arranged in crescentic caps. The ultrastructural observations are typical of apoptosis, a mode of cell death first described in 1972 by Kerr and colleagues. Thus, meconium corpuscles are apoptotic bodies found as a result of the deletion of healthy normal cells during the reshaping and development of organs.

Colon↗