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Biomedical subjects

G Campbell

Publications and source records attributed to G Campbell.

At least 181 records · Page 10Linked to original sources

Flow cytometric quantification of cholesteryl ester-containing "foam" cells. I. Analysis of aortas from normolipidemic swine.

We have quantified using flow cytometry foam cells of aortas from normolipidemic swine varying in age from 6 months to 12 years. These swine were maintained throughout their lives on a low-fat, cholesterol-free diet. Intimal-medial tissues removed from the swine aortas were enzymatically dissociated to prepare Formalin-fixed cell suspensions. Foam cells were labeled by specific staining of their intracellular cholesteryl ester using the fluorescent dye filipin. This was carried out by first removing cellular unesterified cholesterol with ethanol, then enzymatically hydrolyzing cellular cholesteryl ester, and finally staining with filipin the unesterified cholesterol derived from hydrolysis of cholesteryl ester. Results of flow cytometric analysis indicated that thoracic foam cell densities of female swine became more variable and tended to increase with age. It appeared that there were two subgroups of female swine with either high or low levels of thoracic foam cells. A similar finding was not observed for abdominal foam cells in female swine nor for thoracic or abdominal foam cells in the smaller number of older male swine. Abdominal foam cell densities in younger males, however, also appeared to be comprised of low and high foam cell groups. Foam cell densities did not correlate with serum cholesterol or triglyceride levels. However, a genetic basis for some of the variability in foam cell densities among these animals was suggested by the observation that females with high thoracic foam cell densities had greater commonality among ancestors than did females with low thoracic foam cell densities.

Age Factors↗

Flow cytometric quantification of cholesteryl ester-containing "foam" cells. II. Analysis of aortas from cholesterol-fed swine.

We have examined foam cell accumulation in abdominal and thoracic aortic segments of swine with experimentally induced atherosclerosis. Young (less than 1-year-old) male swine were divided into four groups that were fed control, lard (20%), lard (20%) plus cholesterol (1%), and regression (3 months cholesterol-lard followed by 3 months control) diets for 6 months. Aortas were removed from animals and enzymatically dissociated. Foam cells were detected by specifically staining their cholesteryl ester inclusions with the fluorescent dye filipin. Flow cytometry was used to quantify the number of foam cells in each aortic cell suspension. Cholesterol-lard feeding increased serum cholesterol levels 6-fold and induced a substantial increase in both abdominal and thoracic foam cell densities. Lesion development in cholesterol-lard-fed animals, as assessed by macroscopic evaluation of aortas, correlated with foam cell accumulation as determined by flow cytometry. Accumulation of foam cells was extremely variable from animal to animal and did correlate significantly with serum cholesterol but not with serum triglyceride levels. Interestingly, although serum cholesterol levels increased 1.5-fold in swine fed the lard diet, foam cells did not increase significantly as compared to control animals. Animals placed on a control diet following 3 months of the cholesterol-lard diet showed a trend toward lower foam cell densities as compared to animals fed the cholesterol-lard diet for the entire 6 months. Flow cytometric analysis of filipin-stained aortic foam cells provides a new means to evaluate atherosclerotic lesion development.

Animals↗

Target-controlled differentiation of axon terminals and synaptic organization.

These experiments investigate the processes regulating the morphological differentiation of synaptic connections. Electron microscopy showed that the terminal boutons and synaptic complexes of retinal afferent axons in the main thalamic visual nucleus, the dorsal lateral geniculate nucleus, differ in their morphology from those of ascending afferent axons in the main thalamic somatosensory (ventrobasal) nucleus. Developing retinal ganglion cell axons in hamsters were made to project permanently to the ventrobasal nucleus, rather than to the lateral geniculate nucleus. With respect to most of the ultrastructural features examined, the terminals and synaptic complexes of mature, anterogradely labeled retino-ventrobasal axons more closely resembled those of normal somatosensory afferents to the ventrobasal nucleus than they did those of normal retinofugal axons within the lateral geniculate nucleus. These results suggest that the ultrastructural differentiation of axon terminals and synaptic complexes is regulated largely by the target environment, although some features appear to be intrinsic to the afferent axons themselves.

Animals↗

Neurotoxic effects of combined treatment of 2,5-hexanedione and triethyllead chloride.

Triethyllead chloride and 2,5-hexanedione are known neurotoxicants that apparently work through separate mechanisms. The effect of combined treatment of triethyllead chloride and 2,5-hexanedione for 6 weeks on Fischer 344 rats was investigated. Ten rats were given 0.7 mg/kg triethyllead chloride in a volume of 2 ml/kg by gavage while another group was given 0.5% 2,5-hexanedione in drinking water and vehicle by gavage (2 ml/kg). A third group was given a combination of the two treatments. A fourth group served as controls and was given vehicle by gavage. 2,5-Hexanedione produced a reversible loss of body weight, decreased grip strength, and decreased horizontal motor activity. Triethyllead chloride alone increased hot-plate latencies. Triethyllead chloride and 2,5-hexanedione treated animals recovered 4 weeks after cessation of treatment. Neither treatment alone produced fatalities. In combination (2,5-hexanedione + triethyllead chloride) decreases in body weight appeared additive and there was a 40% mortality by 6 weeks of dosing. Rats given the combined treatment had significant loss of both grip strength and increased hot-plate latencies. Neurobehavioral deficits and neuropathological changes were greater in the combined treatment with 2,5-HD and TEL than when either chemical was used alone; there was little indication of a synergistic interaction between these two types of neurotoxicants.

Administration, Oral↗

Ganzfeld electroretinographic findings in parkinsonism: untreated patients and the effect of levodopa intravenous infusion.

Two groups of patients with primary Parkinsonism were studied with the ganzfeld electroretinogram (ERG): seven patients who had never received dopamimetic agents, and six patients given an infusion of levodopa following a period of medication withdrawal. Patients in the first category had a subtle increase in the latency of their short-wavelength sensitive cone response recorded from the retina ipsilateral to their more symptomatic side. Most patients in the second category demonstrate an improvement in their ERG when the responses recorded following levodopa infusion were compared with baseline responses obtained during the period of medication withdrawal. These results suggest that one role of retinal dopamine may be maintenance of normal retinal responsiveness to flash stimuli.

Electroretinography↗

Cotransmission.

Cotransmission, defined here as the control of a single target cell by two or more substances released from one neuron in response to the same neuronal event, does occur in experimental situations. It has not been shown to occur in the normal operation of an animal, but the likelihood that it does is great. There are many examples of potential transmitters coexisting in one neuron, suggesting that cotransmission might be widespread in the peripheral nervous system. But many transmissions still seem to be mediated by a single transmitter. In such cases, coreleased substances might act on other targets or modulate the receptors for the main transmitter. But the possibility also exists that some colocalized "transmitters" have no function in transmission. It is increasingly difficult to retain a simple classification of neuronal types based on transmitter substances. However, there are indications that some combinations of colocalized substances are "preferred" and that certain combinations typify the innervation of a particular target tissue.

Animals↗

A major difference between serum and fibronectin in the divalent cation requirement for adhesion and spreading of BHK21 cells.

Adhesion and spreading of BHK21 cells on adsorbed bovine and foetal bovine serum require addition to the medium of a divalent cation. Divalent cations are effective in the order Mn2+ greater than Co2+ greater than Mg2+ greater than Ca2+, with Ca2+ ineffective below 10(-4)M. On purified fibronectin, however, no added divalent cation is required, since the requirement is largely met by adventitious Ca2+ (circa 10(-5)M) in nominally divalent cation-free saline. In such background Ca2+, adhesion and spreading on fibronectin are only slightly slower than in optimal Mg2+, and appear identical, morphologically, and in sensitivity to cytochalasin D. Cells also spread on fibronectin in response to Mg2+, when Ca2+ is buffered below 10(-6)M, showing that external Ca2+ is not needed as a source for an increase in internal Ca2+. Cells can be induced to spread on serum in low Ca2+ by substantially increasing the fibronectin concentration; this supports other evidence that at its unsupplemented concentration, fibronectin contributes little to the spreading of these cells on serum. The Ca2+ requirement for spreading on preparations of vitronectin (serum spreading factor), partially purified from bovine serum, is similar to that on whole serum. Thus the difference in divalent cation requirement between serum and fibronectin may arise because, on serum, the dominant protein responsible for induction of spreading is vitronectin rather than fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons.

The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.

Adrenergic Fibers↗

A pharmacological and immunohistochemical study of the splanchnic innervation of ileal longitudinal muscle in the toad Bufo marinus.

A study was made of the innervation of the longitudinal muscle of the toad ileum with particular emphasis on the splanchnic innervation by non-adrenergic, non-cholinergic (NANC) nerves. Nerve fibres containing substance P-like immunoreactivity (SP-LI) were observed in the gut wall and in the ileal wall after degenerative section of the splanchnic nerves. Incubation overnight in a high concentration of capsaicin (3 X 10(-4) M) caused degeneration of SP-LI fibres. No evidence was obtained for enteric neurons containing SP-LI. Substance P caused a contraction of the longitudinal muscle similar to that produced by nerve stimulation. The response to nerve stimulation was decreased by about 60% by treatment with alpha-chymotrypsin. Capsaicin normally evoked a contraction of the longitudinal muscle, but did not do so after degenerative section of the splanchnic nerves. Prolonged treatments with high concentrations of capsaicin (5 X 10(-5) M) abolished the excitatory response to nerve stimulation. The results suggest that substance P is the transmitter mediating the NANC contraction. The fibres releasing the transmitter are possibly antidromically activated, sensory afferents. Both transmural stimulation and capsaicin caused a NANC inhibition of longitudinal muscle. Stimulation of perivascular nerves after splanchnic nerve section caused a NANC excitation, as did transmural stimulation even after nerve section or capsaicin treatment.

Animals↗

Randomized trial of chlorambucil for primary biliary cirrhosis.

Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials.

Adult↗

Endothelium-dependent relaxation is unaltered by hypertension, cholesterol or intimal thickening.

The effect of cellophane wrap hypertension (WRAP) and hypercholesterolemia (1% cholesterol diet, CHOL) for 4 weeks was assessed on the endothelium-dependent vasodilator response to acetylcholine in conscious rabbits after pharmacological autonomic blockade. Dose-response curves for the hindlimb vascular resistance (ear artery pressure/lower aortic blood flow; Doppler flowmeter) and acetylcholine infusion (i.v.) doses were unaltered in sensitivity (ED50) for any of the treatment groups. The range and slope of the curves were significantly altered by WRAP, CHOL or WRAP plus CHOL for acetylcholine and adenosine infusions consistent with medial hypertrophy in resistance vessels and raised serum viscosity. The effect of intimal thickening on the response to endothelium derived relaxing factor (EDRF) was tested in dog carotid artery ring segments in vitro 4 weeks after endothelium removal. The relaxation responses to acetylcholine (EDRF-dependent) and adenosine or nitroglycerin were not significantly altered by the neo-intima. Therefore the response to EDRF released by acetylcholine in resistance vessels was unaltered by hypertension, hypercholesterolemia or both together. Neo-intimal thickening in response to initial endothelium loss does not appear to alter EDRF responses in the carotid artery.

Animals↗

Esophageal perforations: the role of computerized tomography in diagnosis and management decisions.

External drainage is indicated when a neck abscess results from esophageal or hypopharyngeal perforation. Diagnosis, extent of disease, and timing of abscess drainage have traditionally challenged the surgeon in management of the perforated esophagus or hypopharynx. Diagnosis and management decisions are enhanced by use of computerized tomography (CT) as an adjunctive study. Five specific case presentations feature diagnosis and management.

Abscess↗

The relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia.

The aim of this study was to document the relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia. Isolated canine hearts perfused by a support dog were subjected to 2 hours of cardioplegia at 20 degrees C. Three hearts were reperfused at each of the following pressures: 20, 40, 60, 80, 100, and 150 mm Hg. The reperfusion period lasted 30 minutes, with the pressure being raised gradually from zero to the test level over the first 2 minutes, then being held constant until the end of the period. The results showed that the normal dog heart after 2 hours of hypothermic cardioplegia is tolerant to a wide range of coronary pressures during reperfusion. Hearts reperfused at pressures between 40 and 100 mm Hg had similar values for coronary blood flow, coronary sinus oxygen saturation, myocardial oxygen consumption, lactate flux, contractility, and myocardial adenosine triphosphate content. If coronary reperfusion pressure was 20 mm Hg, [corrected] myocardial rewarming was delayed, myocardial oxygen consumption was decreased, and myocardial ischemia was manifested by marked lactate efflux, high myocardial lactate concentration, and depletion of adenosine triphosphate. If pressure was 150 mm Hg, coronary flow was excessive. To place these results in the context of coronary artery disease, we measured reperfusion pressure in coronary arteries distal to a stenosis in 10 patients studied at the time of coronary bypass grafting. In 13 arteries with major stenoses, distal mean coronary pressure averaged 31 mm Hg while the simultaneously measured mean aortic or radial artery pressure averaged 66 mm Hg. Thus the average gradient across the stenoses was 35 mm Hg (range 15 to 60 mm Hg). We concluded that in normal hearts without ischemic damage, reperfusion can be conducted satisfactorily at mean coronary pressures from 40 to 100 mm Hg. In setting the tolerable limits for reperfusion pressure in patients with severe coronary artery disease, one should make allowance for pressure gradients of up to 60 mm Hg between the aorta and the distal coronary artery.

Adenosine Triphosphate↗

Independent co-release of acetylcholine and somatostatin from cardiac vagal neurones in toad.

Vagal postganglionic neurones in toad (Bufo marinus) cause cardio-inhibition by releasing both acetylcholine and somatostatin. In isolated, electrically paced, toad atria, intracardiac neurones were stimulated by short bursts of high-voltage pulses applied during the atrial refractory period. Treatment with hemicholinium-3 (5 X 10(-4) M) for 5 h eliminated most of the acetylcholine-mediated cardio-inhibition but did not inhibit somatostatin-mediated transmission. It is concluded that somatostatin release does not depend on the simultaneous release of acetylcholine.

Acetylcholine↗

The joint neurotoxic action of inhaled methyl butyl ketone vapor and dermally applied O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens: potentiating effect.

The neurotoxic action of inhaled technical grade methyl butyl ketone and dermally applied (O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN) was studied. Three groups of five hens each were treated 5 days/week for 90 days with a dermal dose of 1.0 mg/kg of EPN (85%) on the unprotected back of the neck. These groups were exposed simultaneously to 10, 50, or 100 ppm of technical methyl butyl ketone (MBK; methyl n-butyl ketone:methyl isobutyl ketone, 7:3) in inhalation chambers. A fourth group was treated only with the dose of EPN and a fifth group with only 100 ppm MBK. The control consisted of a group of five hens treated with a dose of 0.1 ml acetone. Treatment was followed by a 30-day observation period. Simultaneous exposure to EPN and MBK greatly enhanced the neurotoxicity produced when compared to the neurotoxicity produced by either chemical when applied alone. Continued exposure to EPN and MBK resulted in earlier onset and more severe signs of neurotoxicity than exposure to either individual compound. The severity and characteristics of histopathologic lesions in hens given the same daily dermal dose of EPN in combination with inhaled MBK depended on the MBK concentration. Histopathologic changes were more severe and prevalent in the 100 ppm MBK:1 mg/kg EPN group than in the others. In this group, Wallerian-type degeneration was seen along with paranodal axonal swellings. The morphology and distribution of these lesions were characteristic of those induced by MBK. In the 50 ppm MBK:1 mg/kg EPN group axonal swelling was evident but not clearly identifiable as paranodal. Hens treated with 10 ppm MBK:1 mg/kg EPN had minimal lesions with low incidence of axonal swellings. These were not as large as those seen in MBK neurotoxicity, but instead resembled the histopathologic lesions caused by EPN. The results indicate that the combined treatment gave a value for neurotoxicity coefficient which was two times the additive neurotoxic effect of each treatment alone. Pretreatment with three daily ip doses of 5 mmol/kg technical grade MBK or methyl n-butyl ketone (MnBK), equally increased chicken hepatic microsomal cytochrome P-450 content. Also, hepatic microsomes from MBK-treated hens metabolized [14C]EPN in vitro to [14C]EPN oxon to a much greater extent than those from control hens. These results suggest that MBK potentiates the neurotoxic effect of EPN, at least in part, by increasing the metabolic activation of EPN to the more neurotoxic metabolite EPN oxon.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Topical↗

Axon terminals of the projection from the superior colliculus to the olivary pretectal nucleus in the rat.

The terminals of axons projecting to the olivary pretectal nucleus have been identified by electron microscopy following injections of horseradish peroxidase into the superior colliculus of adult albino rats. The labelled terminals were equated with RD-terminals described in previous studies of this nucleus. They were 0.3-1.3 micron in diameter and contained round synaptic vesicles. Most also contained small dark mitochondria. They established Gray type 1 synaptic contacts with the dendrites of presumptive projection cells. Most terminated within non-glomerular neuropil, chiefly in the peripheral 'shell' of the nucleus; a few terminated in regions of glomerular neuropil.

Animals↗

Synaptic organization of the dorsal lateral geniculate nucleus in the adult hamster. An electron microscope study using degeneration and horseradish peroxidase tracing techniques.

The synaptic organization of the alpha sector of the dorsal lateral geniculate nucleus has been examined by electron microscopy in normal adult hamsters and in adult hamsters subjected to unilateral eye enucleation or intravitreal injection of horseradish peroxidase. Two types of neuropil are apparent. Islands of complex neuropil partially enclosed by astrocyte processes (synaptic glomeruli) are surrounded by a sea of simpler non-glomerular neuropil. The latter is dominated by small axon terminals with spherical synaptic vesicles and Gray type 1 axodendritic contacts (SR-boutons) and also contains axon terminals with flattened synaptic vesicles (F-boutons). The glomerular neuropil contains exclusively postsynaptic dendrites and dendritic protrusions of presumptive projection cells; pre- and postsynaptic pleomorphic-vesicle-containing P-boutons (interpreted as appendages of the dendrites of interneurons); large axon terminals containing spherical synaptic vesicles and large pale mitochondria (R-boutons) which were experimentally identified as retinal terminals and which are presynaptic to both projection cell dendrites and P-boutons at Gray type 1 contacts; F-boutons (minority component). F-boutons and P-boutons are presynaptic to both projection cell dendrites and P-boutons and P-boutons are the intermediate elements of various serial synapses including triplet (triadic) synapses. Medium-large terminals with spherical synaptic vesicles and dark mitochondria (RLD-boutons) which were commonly invaginated by dendritic spines of projection cells in small glomerulus-like formations were also identified. The origin of RLD-boutons is unknown but SR-boutons probably derive chiefly from ipsilateral visual cortex and possibly also from superior colliculus, and non-glomerular F-boutons probably originate in the ipsilateral thalamic reticular nucleus. No differences in synaptic organization were found between the part of the nucleus which receives uncrossed retinal input and the part which receives crossed input, nor were differences seen in the size, fine structure or relationships between the terminals of identified crossed and uncrossed retinal axons.

Animals↗