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Biomedical subjects

R P Thompson

Publications and source records attributed to R P Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mechanisms of aluminum absorption in rats.

Aluminum has become a dietary toxin in modern times but its mechanism of absorption is poorly understood. After ingestion, the systemic transfer of aluminum is small but it is greatly affected by the coingestion of certain dietary agents, such as citrate, that complex with the metal in the intestinal lumen or transiently alter the permeability of the mucosa. Here, mechanisms of aluminum absorption were studied by using freshly prepared aluminum hydroxide and aluminum citrate. Everted sacs of rat gut were used to investigate the site of absorption, effect of chemical charge on absorption of aluminum citrate, and presence of active or passive absorption with use of the metabolic inhibitor ouabain. Absorption was biphasic with a large tissue uptake that was consistent with adhesion to mucus-mucosal surface but little tissue transport, which was consistent with passive paracellular permeation. Citrate reduced the uptake-transport ratio both by competing with the mucosal uptake and by increasing mucus-mucosal permeation but not by affecting the charge of the luminal aluminum species. Despite the potential for hydroxypolymerization of aluminum at intestinal pH, the small bowel and colon absorbed aluminum passively and paracellularly but the stomach did not. The predominantly proximal absorption of aluminum observed in vivo is a reflection of the proximal absorption, and therefore removal, of dietary constituents (eg, citrate) that enhance mucosal permeation of aluminum. The colon should be investigated further as a site of significant paracellular permeability.

Aluminum↗
PubMed1997

Dissociated spatial patterning of gap junctions and cell adhesion junctions during postnatal differentiation of ventricular myocardium.

Nonuniformity in the spatial patterning of gap junctions between heart muscle cells is now recognized as an important determinant of electromechanical function in working myocardium. Breakdown of the normal geometry of electrical intercellular connectivity in diseased myocardium correlates with reentry, arrhythmia, and conduction disturbance. The developmental mechanism(s) that determines this precise spatial order in gap junction organization in normal myocardium is at present unknown. To examine this question, we have used immunoelectron and immunoconfocal microscopy to analyze the spatial distributions of gap junctional (connexin43), desmosomal (desmoplakin), and adherens junctional (N-cadherin) components during maturation of rodent and canine left ventricular myocardium. In rats, a striking divergence in the distribution of gap junctions and cell adhesion junctions emerged within the first 20 days of postnatal life. It was found that although gap junctions initially demonstrated dispersed distributions across myocyte cell membranes, desmosomes and adherens junctions showed more rapid polarization toward cell termini (ie, nascent intercalated disks) after birth. Over subsequent postnatal development (20 to 90 postnatal days), gap junctions became progressively concentrated in these cell adhesion junction-rich zones of membrane. Quantitative analyses of this process in a series of rats aged 15 embryonic and 1, 5, 10, 20, 40, 70, and 90 postnatal days indicated that significantly higher levels (P < .01) of N-cadherin and desmoplakin than of connexin43 were immunolocalized to cell termini by as early as postnatal day 5. Although all three junctions types showed increasing polarization to myocyte termini with development, variation between junctions remained significant (P < .05) at all times points between 5 and 70 postnatal days. Only at 90 postnatal days, when the animals were nearly full grown, did the proportions of gap junction, desmosome, and adherens junction at intercalated disks become statistically similar (P > .05). Examination of myocardium from 1- and 3-month-old canines revealed that related differential changes to the spatiotemporal distribution of intercellular junctions occurred during postnatal maturation of the dog heart, suggesting that the process was not rodent specific. It is concluded that this progressive change in the organization and pattern of association between gap junctions and cell adhesion junctions is likely to be an important factor in maturation of electromechanical function within the mammalian heart.

Animals↗
PubMed1997

Binding of lectins to novel migration promoters on cardiac mesenchymal cells in the chick.

Chicken serum promotes migration of cardiac mesenchymal cells of chick embryos in vitro. In the present study, migration promotion of unknown migration promoters in chicken serum was examined by using lectins. Cardiac mesenchymal cells of the conotruncal and atrioventricular cushions were cultured on collagen type-I gel with medium including chicken serum. A concentration (100 micrograms/ml) of Concanavalin A (Con A), peanut agglutinin (PNA), pisum sativum agglutinin (PSA), soybean agglutinin (SBA) or wheat germ agglutinin (WGA) was added to the medium. Con A, PSA, and WGA inhibited migration, while PNA and SBA did not affect migration of cardiac mesenchymal cells. WGA inhibited migration in a concentration dependent manner. Preincubation of WGA with specific binding monosaccharides (alpha-D-N-acetylglucosamine and alpha-D-N-acetylneuraminic acid) clearly reduced the inhibition ability of WGA, while preincubation of Con A and PSA with alpha-D-mannose and alpha-D-glucose did not. On the other hand, Con A-binding proteins, eluted from a Con A affinity column with the buffer including alpha-D-mannose and alpha-D-glucose, promoted migration of cardiac mesenchymal cells, as did WGA-binding proteins. These proteins promoted migration in a concentration dependent manner. Western blotting showed that PSA bound the subunits of collagen type-I, but ConA and WGA did not. In migration inhibition assays by monosaccharides, only N-acetylneuraminic acid inhibited migration of cardiac mesenchymal cells. These results suggested that chicken serum contains novel migration promoters for chick cardiac mesenchymal cells. The promoters are proposed to have the terminal N-acetylglucosamine, N-acetylneuraminic acid, and glucose and/or mannose residues.

Animals↗
PubMed1996

Essential fatty acid supplementation in chronic hepatitis B.

BACKGROUND: Dietary supplementation with essential fatty acids and polyunsaturated lecithin may improve biochemical and histological parameters in liver disease. METHODS: Ten patients with serological and histological evidence of chronic hepatitis B received capsules of the polyunsaturated fatty acid-rich evening primrose oil in a dose of 4 g daily for 12 months, while a matched group received liquid paraffin capsules as a placebo. RESULTS: Compared to the placebo group, the patients receiving evening primrose oil showed no improvement in either biochemical or histological indices of liver damage, or in the rate of loss of circulating e antigen. CONCLUSIONS: Dietary, supplementation with this dose of essential fatty acids is unlikely to be of benefit in chronic hepatitis B.

Adult↗
PubMed1996

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation.

Aluminum Silicates↗
PubMed1996

Mesenteric vasculitis associated with Sézary syndrome.

A 71 year old lady with Sézary syndrome presented with chronic diarrhoea and cramping abdominal pains. A small bowel meal x ray examination showed two mid-ileal strictures. At laparotomy the small intestine was found to be sub-acutely obstructed and resection of a 15 cm ileal stricture and stricturoplasty of a second, 10 cm stricture were performed. Histological examination of the stricture revealed a mesenteric vasculitis with secondary ischaemic changes in the small bowel wall. Mesenteric vasculitis causing small bowel stricture may be associated with Sézary syndrome.

Aged↗
PubMed1996

Fetal surgical protocols in Yucatan miniature swine.

Thirty-nine Yucatan miniature swine were used in three fetal surgical experimental protocols. They involved antiarrhythmic administration, pacemaker implantation, and in-utero diagnosis of ventricular septal defect by intraoperative echocardiography. Because of problems encountered with surgical protocols in the initial stages, modifications were made to prevent fetal hypothermia and intraoperative mortality. These modifications included environmental temperature support, staple surgical techniques to reduce operative time, and development of fetal catheters designed to facilitate cannulation of small vessels. Postoperative care protocols were intensive and included antibiotics, analgesics, and supportive care designed to reduce discomfort and prevent abortion and sepsis. Thirty-seven of 39 sows survived the surgical procedures; experiments were performed on 117 fetuses. Twenty-two fetuses died either intraoperatively or postoperatively because of complications related to the experimental protocols. Modification of surgical and postsurgical protocols for these projects demonstrates the feasibility of using miniature swine as a model for fetal surgery, when their use was appropriate for anatomic and physiologic reasons.

Animals↗
PubMed1995

Confocal microscopy of thick sections from acrylamide gel embedded embryos.

The preparation of optically clear, thick sections of fragile embryonic tissues greatly aids the power of confocal scanning laser microscopy in imaging three-dimensional structures. We report here conditions for embedding, sectioning, and staining embryos in polyacrylamide gels for a variety of confocal imaging techniques. Infiltration of tissues in standard mixtures of 10-15% acrylamide monomer yields, upon polymerization, blocks that cut easily by vibratome between 50 and 1,000 microns. These conditions worked well for tissues previously stained or for staining gel sections with low molecular weight water-soluble fluorochromes (MW < 5 kD [e.g., propidium iodide, phalloidin]). For immunostaining of tissue after embedding and sectioning, the acrylamide concentration was reduced to 2-3% acrylamide to allow access of immunoglobulins to antigenic sites; such gels were supplemented with 1% agarose to facilitate sectioning and handling. Either method yielded abundant, optically clear, and easily handled sections for mounting and examination in water-miscible media.

Acrylic Resins↗
PubMed1995

Developmentally regulated neural protein EAP-300 is expressed by myocardium and cardiac neural crest during chick embryogenesis.

The spatiotemporal distribution of EAP-300 (embryonic avian polypeptide of 300 kDa) was analyzed in embryonic chick heart using immunohistochemistry and confocal microscopy. EAP-300 is a developmentally regulated protein initially characterized in neural cells from chick retina. Myocardial cells all along the early tubular heart were ubiquitously immunolabeled for EAP-300 by embryonic day 2 (E2, Stage 13)). At E5 (Stage 24), myocardial EAP-300 expression levels remained significant in both atrial and ventricular myocardium. At E6 (Stage 28), distinct populations of EAP-300 immunolabeled cells were also observed external to the heart, in septal mesenchymal tissue and neural ganglia adjacent to the outflow tract; these cell populations were confirmed as neural crest-derived by co-localization of EAP-300 and HNK-1. At E13 (Stage 39), myocardial immunolabeling for EAP-300 was no longer ubiquitous, but increasingly restricted to conduction tissues, including the atrioventricular bundle and subendocardial Purkinje cells. This restriction of immunolabeling could be demonstrated definitively at E15 (stage 41), by which stage subendocardial and periarterial Purkinje fibers were clearly immunoreactive for EAP-300 and several known markers of chick conduction tissue, including specific myosin heavy chain isoforms and connexin42, a gap junctional protein preferentially expressed by Purkinje fibers. Just prior to hatching at E21 (Stage 46), immunolabeling of conduction tissues was reduced, although still above that of non-conductile myocardium. This spatiotemporal map of cardiac EAP-300 expression indicates that it is independently and transiently expressed in early myocardium, cardiac conduction tissue, and neural crest derivatives during development.

Animals↗
PubMed1995

Analysis of copper and lead in hair using the nuclear microscope; results from normal subjects, and patients with Wilson's disease and lead poisoning.

We have recently developed a technique utilizing the nuclear microscope to analyse accurately the trace element content of hair at concentrations of ppm and to differentiate between the levels within hair and those due to surface contamination. Hair was analysed from four patients with Wilson's disease (systemic copper overload), one patient with sub-acute lead poisoning, and three control subjects, and the concentrations and distributions of lead and copper across the hair shafts were shown. However, there was no increase in the copper content of hair from patients with Wilson's disease compared with those of normal subjects, indicating that the high copper levels of many tissues in this disease are not reflected in hair. In contrast, hair samples from the patient with lead poisoning showed maximum concentrations of 14 (+/-2) micrograms g-1, compared with normal levels of less than 1 micrograms g-1. Further, the composition of the hairs along the shaft reflected the temporal changes of lead levels in the patient during lead elimination.

Adolescent↗
PubMed1995

Assessment of toxic metal exposure following the Camelford water pollution incident: evidence of acute mobilization of lead into drinking water.

Following the incident of acidic pollution of water by aluminium sulfate centred around Camelford in July 1988, we have carried out a retrospective analysis of the mobilization of toxic metals to residents of the area. An advanced nuclear technique was used to measure trace levels of elements within hair, thus, avoiding surface contamination. In contrast to controls, lead, but no other toxic metals, was consistently found within sections of hair that dated to mid-1988 from four residents; they must, therefore, have consumed this metal around the time of the incident. The source of this lead was probably local water pipe residue, and this was found on analysis to have a matrix specific to such soft-water areas that, prior to the incident, had slowly accumulated certain toxic metals such as cadmium and uranium and particularly lead. Lead is mobilized from such residues by acidic water and could, therefore, have heavily contaminated mains water after the incident. However, analyses of residents' plasma and whole blood, and of urine following a lead-chelation test, showed no evidence of either long-term increased body burdens of toxic metals or depletion of essential elements. In addition, we found no evidence of continued poor water quality in the area. In conclusion, during a short period following the pollution, some residents who consumed mains water would have been acutely exposed to lead and other toxic metals. Prediction of the scale of metal exposure to individuals was not possible owing to heterogeneity of the water distribution network, but long-term effects to residents from lead are not anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1995

The architecture of the atrioventricular conduction axis in dog compared to man: its significance to ablation of the atrioventricular nodal approaches.

UNLABELLED: AV Node in Dog and Man. INTRODUCTION: Advances in treating patients with dual atrioventricular nodal pathways have called for a better understanding of the morphology of the approaches to the atrioventricular node. In this respect, it has recently been suggested that, in dog, anatomically discrete muscle bundles originating from the sinus node represent the substrate of the dual pathways recognized electrophysiologically in patients with atrioventricular nodal reentrant tachycardia. This concept is at odds with most anatomic studies of the human specialized atrioventricular junctional area. In this study, therefore, we studied histologically the junctional area in dog hearts, comparing them with our own findings in human heart and the descriptions of the earliest investigators. METHODS AND RESULTS: Five dog and six human hearts were prepared for histology and sectioned serially in different planes. Reconstructions were then made from each of three dog and two human hearts sectioned in orthogonal planes. Gross differences in the anatomy of the atrioventricular junctional area and in the structure of the conduction system were obvious between dog and human hearts. The penetrating portion of the conduction axis was longer in the dog, being much more extensively embedded in the central fibrous body. The atrioventricular node, in both dog and man, was composed of a zone of transitional cells overlying a compact region. The zone of transitional cells in the dog was more extensive posteriorly than anteriorly. No bundles insulated anatomically by fibrous tissue were found either in the internodal atrial myocardium or in the approaches to the atrioventricular node. Our findings in both dog and man are comparable with the initial descriptions of the atrioventricular junctional area. CONCLUSION: Although the disposition of the conduction system in dog and man is basically similar, there are important differences which relate to the gross anatomy. The anatomic substrate for functional duality of the inputs to the atrioventricular node remains unclear, since our study confirms that the concept of insulated atrionodal tract has no morphologic basis.

Animals↗
PubMed1995

Recurrent gastrointestinal bleeding associated with chronic pancreatitis.

A 52 year old man with chronic pancreatitis presented with recurrent upper gastrointestinal bleeding. Gastroscopy was normal, but visceral angiography suggested that there were gastric varices. Despite treatment with propranolol he had further episodes of bleeding and so underwent splenectomy to decompress the gastric varices. When the spleen was removed, however, an inflammatory mass in the head of the pancreas adherent to the posterior gastric wall was noted. Within it the splenic artery was visible and communicated with the gastric lumen through a small opening in the gastric wall. The artery was ligated and the patient has since had no further bleeding. Thus, chronic pancreatitis should be considered as a cause of recurrent upper gastro-intestinal bleeding, especially when gastroscopy is normal.

Chronic Disease↗
PubMed1995

Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system.

The rhythmic contraction of the vertebrate heart is dependent on organized propagation of electrical excitation through the cardiac conduction system. Because both muscle- and neuron-specific genes are co-expressed in cells forming myocardial conduction tissues, two origins, myogenic and neural, have been suggested for this specialized tissue. Using replication-defective retroviruses, encoding recombinant beta-galactosidase (beta-gal), we have analyzed cell lineage for Purkinje fibers (i.e., the peripheral elements of the conduction system) in the chick heart. Functioning myocyte progenitors were virally tagged at embryonic day 3 of incubation (E3). Clonal beta-gal+ populations of cells, derived from myocytes infected at E3 were examined at 14 (E14) and 18 (E18) days of embryonic incubation. Here, we report that a subset of clonally related myocytes differentiates into conductile Purkinje fibers, invariably in close spatial association with forming coronary arterial blood vessels. These beta-gal+ myogenic clones, containing both working myocytes and Purkinje fibers, did not incorporate cells contributing to tissues of the central conduction system (e.g. atrioventricular ring and bundles). In quantitative analyses, we found that whereas the number of beta-gal+ myocyte nuclei per clone more than doubled between E14 and E18, the number of beta-gal+ Purkinje fiber nuclei remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Omeprazole and dry mouth.

BACKGROUND: Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy. METHODS: We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes. RESULTS: Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus. CONCLUSION: Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous.

Aged↗