Biomedical subjects

K E Carr

Publications and source records attributed to K E Carr.

At least 37 records · Page 2Linked to original sources

PubMed1996

Gastrointestinal uptake and translocation of microparticles in the streptozotocin-diabetic rat.

Uptake and translocation of particulates across the mucosal barrier of the gastrointestinal (GI) tract is now generally recognised but the effect of pathophysiologically induced changes on this process is less well established. This study evaluated the effect of diabetes mellitus on GI absorption of particles, comparing particle localisation and particle loading in different microanatomical sites of the primary organ (small intestine) and possible particle translocation pathways to selected secondary organs (mesenteric lymph nodes, liver, spleen) in normal and streptozotocin-induced diabetic animals. Fluorescent polystyrene latex particles (approximately 2 microns diameter) were fed orally to young adult Sprague-Dawley rats and quantitative bulk tissue and morphological techniques used to chart particle transit across the small intestine to secondary organs 0.5 h postadministration. In the normal animal, epifluorescence and confocal laser scanning microscopy provided confirmatory evidence for particle absorption within the primary organ and transport to other sites in the body. By contrast, in the diabetic animal, particle translocation and peripheral distribution were reduced with approximately 30% decrease in particle loading in the epithelial/nonepithelial tissue compartments. This could be a consequence of gastric retention and altered intestinal motility and permeability which are known to be associated with diabetes.

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PubMed1995

Uptake and translocation of microparticles in small intestine. Morphology and quantification of particle distribution.

The intestinal transit of large (micro-) particles to other sites of the body remains a controversial issue of relevance in various fields of study. In this report fluorescent polystyrene latex microparticles in the size range of 2 microns were used as models for nonspecifically absorbed nonbiodegradable particulates. They were administered to young adult rats as a single oral dose of 1.65 x 10(9) particles; Peyer's patches and surrounding normal absorptive small intestinal tissue were collected at various time points. Quantification of solubilized tissue samples and fluorescence (epi- and confocal) qualitative and quantitative microscopy showed uptake of latex microparticles in all parts of the intestine sampled, but with the proximal segment the preferential site of absorption. The maximum uptake of particles occurred 0.5 hr after dosing in all three segments of the small intestine; there were progressively smaller numbers with distance from the pylorus and with time. Translocation of small numbers of particles to the mesenteric lymph nodes was also detected at 0.5 hr. Transmucosal passage of particles occurred primarily in the villous tissues adjacent to the Peyer's patch regions. These studies give confirmatory evidence for the uptake and translocation of microparticulates across the mucosal barrier and provide new information regarding site- and time-related effects on particle uptake and the involvement of the villous epithelium in particle translocation.

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PubMed1995

A commentary on morphological and quantitative aspects of microparticle translocation across the gastrointestinal mucosa.

It is now generally accepted that particulates in the nano-range (< 1 micron) can and do cross the intestinal mucosa. However, the issue is less well resolved for particles in the micro-range (> 1 micron) and this is discussed in relation to the variety of experimental designs present in the literature. Emphasis is placed on the relative contributions of quantitative bulk tissue analysis with respect to qualitative and quantitative morphological analysis. The discussion is extended to observations on factors influencing the particle translocation process including variation in particle uptake in relation to intestinal region and time post-dose administration based on data for uptake of -2 microns latex particles by rat Peyer's patch tissue. Although a significant body of data now identifies the intestinal processus of particle translocation it is underlined that discrepancies may arise as a consequence of different analytical approaches and that this is an issue to be addressed for valid comparisons of data.

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PubMed1995

Morphological aspects of particle translocation in vivo following ingestion of the yeast Saccharomyces boulardii.

Particle translocation in vivo was studied in mice using the non-pathogenic yeast Saccharomyces boulardii (SB). Seven day old BALB/c mice were given either saline (control) or 1.5 g/Kg SB (every six hours, up to 48 hours), by intubation, and killed by decapitation 48 hours post-treatment. Light and scanning electron microscopy (SEM) examination of specimens prepared from the middle intestine revealed the presence of yeast inclusions localised in the cytoplasm of enterocytes.

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PubMed1995

A morphological and microanalytical investigation into the uptake of particulate iron across the gastrointestinal tract of rats.

The uptake and translocation of particulate iron across the gastrointestinal (GI) mucosa of young adult rats has been investigated using a range of morphological techniques and X-ray microanalysis (XRMA). In animals fed a suspension of iron powder constituted of metallic iron particles ranging in size from 6-9 microns down to 5-30 nm, light microscopic histochemistry has clearly revealed iron deposits within the tissues of the duodenum. Scanning electron microscopy of the duodenal tissue by back-scattered electron imaging has complemented the light microscopic observations and revealed a selective localization of iron in the villi with variation in levels of iron uptake by the mucosal cells. Ultrastructural and XRMA analysis of duodenum has established the presence of metallic iron nanoparticles within the brush border, lateral intercellular spaces of the mucosal cells, mitochondrial cristae and cytoplasm of both mucosal and stromal cells. The observations indicate that metallic iron particles, in the nano-size range, may be taken up by the GI mucosa and that the passage of such particles across the epithelial barrier may take place through both a paracellular as well as a transcytotic process.

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PubMed1994

Heavy ion induced changes in small intestinal parameters.

The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

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PubMed1994

Electron irradiation slows down wound repair in rat skin: a morphological investigation.

To date, there have been few morphological investigations of the effect of electron radiation on the healing of skin wounds in rats. The present morphological study examines the wound repair process in electron-irradiated rat skin by electron microscopy. Standardized, full-thickness, incisional wounds were made in the lower dorsal skin of animals which had been locally irradiated with 9.6 Gy electron radiation 7 days previously. The irradiation dose was maximal at 3 mm depth. Twenty-four rats were used in the investigation; 12 were irradiated and 12 sham-irradiated. Three rats from each experimental group were killed at 1, 3, 7 and 14-day time intervals after wounding. The morphological effect of electron irradiation on the repair of each wound was investigated by light microscopy (LM) and scanning electron microscopy (SEM). New granulation tissue visualized by SEM was quantified using computerized image analysis. The results suggest that a single, partial-body, controlled depth dose of electron irradiation delays wound repair. LM showed that there is a depression of the inflammatory cell and tissue exudate response, slowing of epithelial migration, and a decrease in fibroblast representation, together with a delay in the formation of collagen bundles. Granulation tissue formation was impaired up to 7 days post-wounding, but was restored to around control values by day 14, indicating that healing was delayed. However, as the healing of normal tissue was not prevented, this study supports a preoperative role for the use of low-dose electron irradiation therapy for the treatment of electron-sensitive superficial pathologies in surgical practice.

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PubMed1993

Structural and morphometric analysis of murine small intestine after indomethacin administration.

Indomethacin, a nonsteroidal anti-inflammatory drug, induces the formation of gastrointestinal ulceration both in experimental animals and in humans. A study of indomethacin-induced ulcers in the mouse showed that two doses of indomethacin, each administered subcutaneously at 85 mg/kg body weight, induced well-defined gastrointestinal ulcers in C57 mice, accompanied by inflammatory and vascular changes in the stomach and small intestine. Maximal damage was observed 20 h after the second dose of indomethacin. Morphometric analysis identified changes in all compartments of the small intestine. There was a marked reduction in the length of the small intestine, intestinal dilatation, a significant decrease in villous height, with the formation of subepithelial blisters or blebs within villi, and submucosal vascular dilatation. There was no change in the number of villi or of submucosal arterioles or in the total amount of muscle present in the wall of the intestine. The tissue changes identified in this study may have implications for gut function at specific periods during indomethacin treatment.

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PubMed1993

Rabbit and human non-keratinising stratified squamous oesophageal epithelium displays similar microridge structure by scanning electron microscopy.

Since the oesophageal epithelium of common laboratory animals, rats and mice, is keratinized it is unsuitable for comparison with typical non-keratinized stratified squamous human epithelium. It is thus important to find a suitable animal model for the study of human oesophageal tissue changes. This study investigated the microridge structure of immature and adult rabbit specimens, and adult human biopsies by scanning electron microscopy and morphometry. The investigation revealed a similarity between typical squamous human and adult rabbit oesophageal mucosal epithelium. While human epithelium specimens subdivided into two other groups (non-typical squamous and non-squamous); all typical squamous human biopsies were from patients who had normal endoscopy reports and no reflux symptoms. The surface cells of typical squamous human epithelium displayed complex microridge patterns (64% of cell surface) but patterns in non-typical squamous specimens were more variable (38%) (P < 0.001) and cell boundaries less obvious. Rabbit squames displayed clear microridge patterns with an elevation in the percentage of cell surface covered by microridges, with increasing age, from immature to adult specimens (P < 0.001). There was no statistically significant differences between adult rabbit, and 'typical squamous' human biopsies (range 51-65%), results which suggest potential use of a rabbit model to study changes in human oesophageal tissue.

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PubMed1992

Characterization through a data display of the different cellular responses in X-irradiated small intestine.

Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points.

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PubMed1992

Early effects on the morphology of mouse small intestine of single or combined modality treatment with hyperthermia and X-irradiation.

This study describes the effects of hyperthermia and X-irradiation on the morphological appearance of normal, at risk tissues in the ileum of the mouse. The early morphological effects 1 day after a combined modality treatment are compared with those due to either hyperthermia or X-irradiation given alone. The response was assessed qualitatively and semiquantitatively using scanning electron microscopy and a villous scoring technique. Early post-irradiation effects on topography did not differ significantly from those observed after small intestine exteriorisation without treatment. The villous scores for the combined modality treatments reflected greater damage than would be expected from the sum of villous scores for each modality treatment on its own. This suggests that the combined modality treatment had a synergistic or enhancing effect. A 4 hour time interval between the two treatments did not seem to reduce the enhancing effect. Further studies are required to investigate the effects of fractionated combined treatment.

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PubMed1992

Relationship between villous shape and mural structure in neutron irradiated small intestine.

Previous work on irradiation of mouse small intestine has assessed the changes produced by counting crypts/microcolonies, scoring villous shape or examining morphological changes in specific parts of the wall. This paper used scanning and transmission electron microscopy to study the effects of whole body irradiation with 5 Gy neutrons on the surface and internal features of the intestinal wall of CFLP mice, 1 day, 3 days and 7 days after treatment. Empirical scores from the ultrastructural findings were inserted into a Morphological Index display calculated from analytical data based on cell counts and area measurements obtained from resin histology sections. The final data display showed that the neutron irradiation produced marked structural changes in different cells and tissues by 1 day. These changes were maximal at 3 days with substantial improvement by 7 days. When this data display was compared with scores taken from scanning electron microscopy of the mucosal surface, the change in villous shape from erect fingerlike projections to lower profiles less suited to absorption was seen to correlate more with changes in the smooth muscle than with the epithelial cryptal compartment.

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PubMed1991

Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm.

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.

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PubMed1991

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.

Adult↗

PubMed1991

Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat.

Sprague-Dawley rats (3 weeks old) were fed on isoenergetic diets in which 40% of the total energy was provided as fat either in the form of butter (high saturated fat), olive oil (high monounsaturated fat) or maize oil (high polyunsaturated fat), with one group on low-fat (10% of total energy) standard diet as a control. Animals were killed after 8.4 (se 0.8) weeks by cardiac puncture. Similar pieces of jejunum and ileum were prepared for morphometric studies. Extracts of tissue from the proximal and distal segments of the whole small intestine from four animals per group were assayed using established techniques for enteroglucagon, motilin, neurotensin, somatostatin, substance P and vasoactive intestinal peptide (VIP). We found that maize oil and olive oil increased villus height: crypt depth ratio in both jejunum and ileum. Maize oil increased tissue concentrations of somatostatin (P less than 0.05) and substance P (P less than 0.005) in the proximal segment. Both maize oil and olive oil increased tissue concentrations of neurotensin and substance P (P less than 0.005) in the distal segments. These observations may explain the improvement of intestinal absorption of fluid following supplementation with polyunsaturated fat.

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PubMed1991

Radioprotectant effects of atropine on small intestinal villous shape.

Previous work has shown that irradiation produces changes in small intestinal villous shape, which can be quantified using a villous scoring system applied to scanning electron micrographs. It has already been shown that reserpine, which, like irradiation, increases gastrointestinal motility, produces a similar type of villous collapse, thereby supporting the theory that this form of injury may not be due entirely to changes in the cryptal epithelial compartment, as has been assumed previously. Atropine, chosen for its ability to decrease gut motility, produces a different form of villous shape change. The aim of the current work was to investigate the ability of atropine to decrease the villous damage caused by irradiation and thereby improve the likely absorptive capacity of the small intestine. The current experiments used crypt counting, qualitative light microscopy and villous scoring techniques. Groups of unirradiated mice examined included baseline controls and those treated with atropine, sham irradiation and a combination of these two schedules. Two irradiated groups were studied, one with and one without atropine treatment. The results show that atropine given with irradiation reduces the extent of the damage to villous shape, implying that the total effect on the neuromuscular tissues is less destructive after the combined treatment. It is also of interest that atropine appears to have an additional radioprotectant effect on the radiation induced crypt depletion, implying that neuromuscular behaviour may influence this compartment, hitherto considered as dependent on epithelial proliferative capacity.

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PubMed1991

Mucosal changes in mouse duodenum after gamma-irradiation or reserpine treatment.

Although the bulk of the literature implies that most of the radiation-induced effects on small intestine are related to epithelial damage, previous work has indicated that there are structural changes in the neuromuscular component of the wall. The short timescale of changes in villous shape produced by hyperthermia but similar to those seen after radiation, also supports the claim that there is a neuromuscular contribution involved. A preliminary report showed that the radiation-induced changes in the small intestine could be simulated by the administration of reserpine, a drug chosen for its effects on the neuromuscular component of the mucosal wall. A system of villous scoring indicated that the overall effects of the two regimes were approximately equivalent in terms of the changes produced in the shape of the villi. The current paper describes the results of experiments to compare the two regimes over the time scale 1 h to 3 days. The time points were chosen to include likely maximum damage caused by reserpine (18 h after treatment) and radiation (3 days after treatment). Mice were irradiated with 15 Gy gamma-rays from a 60Co source or treated with reserpine (1 mg/kg and 16 mg/kg). Scanning electron microscopy showed some changes in the duodenal mucosal topography of some control groups which may be related to the stress of treatment and are in keeping with previous findings. However, the changes seen in treated groups were greater than those found in the corresponding control samples. The overall villous changes were plotted using a grid score method, which showed that both radiation and reserpine treatment altered the villous morphology in a similar way. Light microscopy and transmission electron microscopy showed that smooth muscle damage was associated with the villous collapse. The work indicates that the intestinal wall can be damaged by many agents and that greater understanding of radiation-induced damage can be gained by comparing it with that produced in other ways.

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PubMed1990

An investigation of vanishing bone disease.

Vanishing bone disease is a rare condition producing local deformity and instability. Fibrovascular tissue replaces bone completely but the mechanism of bone destruction and resorption is unknown and there is controversy regarding the presence or absence of osteoclasts in the disease. Radiography, clinical chemistry, light microscopy, transmission electron microscopy (TEM) and cytochemistry were used to investigate the condition of a young woman presenting early in the disease process. We detected atypical ultrastructure in osteoblasts and endothelial cells. The rare osteoclasts, numerous mononuclear phagocytes and vascular endothelium found in the condition reacted positively for the enzyme acid phosphatase. Aggressive local excision of diseased tissue and insertion of a free vascularized bone graft at an advanced stage of the disease, accompanied by subsequent radiotherapy for residual disease only were successful in rehabilitating the affected forearm and hand.

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