Biomedical subjects

K E Carr

Publications and source records attributed to K E Carr.

At least 55 records · Page 3Linked to original sources

PubMed1990

Collared crypts in irradiated small intestine.

Crypts of Lieberkuhn are radiosensitive: the technique of crypt counting is an established method of assessing radiation induced changes in the small intestine. However, there has been little work done on the surface contours of the crypts, as they open into the intervillous cleft. The current paper describes the structure of control mouse crypt mouths as unobtrusive openings approximately 5 microns in diameter. After radiation with heavy ion particles, the crypt mouths are substantially larger (up to 10 microns in diameter) with a marked collar which is similar to that sometimes seen in coeliac disease. The shape and incidence of the collared crypts is described for specimens irradiated with neon, silicon and iron ions, with treatment with iron producing the most marked collars: it is suggested that the size and incidence of the collared crypts may be related to the LET of the beam used. It is of interest that the abnormal crypts are not produced after single doses of X-irradiation. The consideration of the structure of the collared crypts may require a redefinition of the terms crypt and villus with priority being given to the position of subepithelial vessels rather than surface shape. Finally, although the collared crypts can not be directly equated with 'tunnel' or 'channel' lesions, it is pointed out that they do represent localised damage with a specific position and shape.

Animals↗

PubMed1990

Exudate variation in the rabbit gastrointestinal tract: a scanning electron microscope study.

The mucosal exudate from the gastrointestinal tract of six adult female New Zealand rabbits was studied using scanning electron microscopy and without any attempt being made to clean the luminal surface before screening. The exudate consisted of mucus, debris and bacteria. Qualitative assessment showed that the nature and distribution of exudate varied along the length of the gastrointestinal tract from the oesophagus to the anal canal, with little variation from animal to animal. Bacterial counts for rod-shaped bacteria were carried out on areas randomly selected from the upper, middle and lower oesophagus and the oesophageal-cardiac junction. The degree of bacterial colonisation was found to decrease along the length of the oesophagus from upper to lower parts, but it was increased at the oesophageal-cardiac junction. This assessment was not undertaken in the other regions of the gastrointestinal tract as the mucosal surface areas could not be easily measured owing to their undulating nature. The study indicates the variability of the mucosal exudate, which should be recognised as part of the true interface between ingested food and the cell surface along the gastrointestinal tract.

Animals↗

PubMed1990

Early morphological changes in blood capillaries of mouse duodenal villi induced by X-irradiation.

The mouse has been used extensively as a model for radiobiological studies. In particular, the cellular compartments of the intestinal villi have been examined, in an effort to gain an understanding of the gastrointestinal disturbances which follow radiotherapy of the abdomen. The response of the blood vessels has been, however, largely neglected. This paper examines the early response of the duodenal capillaries to an X-ray dose of 10 Gy using conventional light and transmission electron microscopy. The villous capillaries were examined at 6 h, 1 day and 3 days after treatment. The results showed that the capillaries responded to X-irradiation within 6 h. exhibiting marked vasodilation similar to that observed in acute inflammation. Significantly there was no ultrastructural evidence of endothelial cell disruption or loss of junctional attachment between the cells, but the characteristic fenestrae of these vessels were less apparent than in the controls. One day after treatment the capillaries had become constricted, with many vessels totally non-patent. The cytoplasm and nuclei of the endothelial cells showed changes consistent with vascular damage, such as nuclear shape alterations and luminal cytoplasmic projections. Three days after treatment there was variation in the capillary patency, as some vessels showed signs of incipient necrosis whilst others were relatively normal in appearance. The results suggest that the early vascular response typically involves a phase of vasodilation followed by constriction within the first 24 h after treatment, a finding consistent with the radiation response of skin capillaries in what has been described as 'transient erythema'. The ultrastructural changes associated with the phasic changes in patency did not suggest large scale endothelial death, but rather alteration of the functional capacity of the vessels which may in turn affect the other cell populations in the villi.

Animals↗

PubMed1990

Radiation induced changes in the blood capillaries of rat duodenal villi: a corrosion cast, light and transmission electron microscopical study.

Disturbances of gastrointestinal function are an important limiting factor in radiotherapy of the abdominal and pelvic regions. The pathogenesis of radiation induced intestinal dysfunction is not completely understood, although the intestinal mucosa has been shown to respond to irradiation by a progressive reduction in villous size. Since blood vessels in other organs have been implicated in the initiation of post-irradiation changes, the present study examines the response of villous blood vessels to an X-ray dose of 10 Gy after 3 days. Vascular corrosion casts and light and transmission electron microscopy (TEM) were used to study the post-irradiation vascular response. In control and sham-irradiated animals, the villous plexus was fountain-like: an arteriole entered the villous base and divided apically into two terminal branches. Villous capillaries apparently derived from the terminal branches, and united to form venules. In capillary loops the vertical inter-capillary distance was greater than the horizontal inter-capillary distance. After irradiation, the vessels became tortuous and the plexus was compressed apico-basally, shown by a decrease in the vertical inter-capillary distance. The capillary luminal diameter, as measured on resin semi-thin sections, was significantly increased. TEM showed that the endothelium was irregular and there was evidence of plasma leakage. These results suggest that villous damage seen after irradiation can include changes in the villous vasculature.

Animals↗

PubMed1989

Examination of mucosal surfaces by scanning electron microscopy before and after removal of debris.

A rapid method is described whereby gastrointestinal biopsy specimen surfaces can be examined by scanning electron microscopy with overlying tract contents (debris) intact, and also re-examined after cleaning to determine the structure of the underlying mucosal surface. The conductive coating of gold is removed using mercury, a non-wetting agent. The specimen surface is suitably cleaned of debris after a brief ultrasonication in absolute ethanol which mixes with the transitional fluid (CO2) used for critical point drying.

Animals↗

PubMed1989

Internal structure of the intestinal villus: morphological and morphometric observations at different levels of the mouse villus.

The internal structure of the mouse jejunal villus was examined from apex to base in transverse serial sections. The villi were arbitrarily divided into apical (1-160 microns), middle (161-320 microns) and basal (321-480 microns) thirds. Histological and ultrastructural morphometry was performed on villous epithelium, stroma, blood vessels and lacteals at the three levels. The cross sectional area and the number of cells/section increased apico-basally in both the villous epithelium and the stroma, but the increase was greater in the latter. The enterocytes in the villous basal third were narrow and had oblong nuclei. The enterocytes gradually became wider and their nuclei attained a more round or oval shape towards the villous apex. The microvilli of these cells also increased in length from the villous base to apex. Although the number of capillaries/section was approximately the same at the three levels examined, it appeared that the apical third was relatively more vascular if the overall apico-basal increase in the villous size was taken into consideration. The villi had a single lacteal, whose cross sectional area generally increased towards the villous base. The results of this study indicate that the internal structure of the intestinal villus is not uniform along its length. Therefore, it is important that when studying normal and abnormal villi, like should be compared with like so as to ensure that the normally occurring variations in the villous morphology are not confused with those induced by disease or experimental processes.

Animals↗

PubMed1988

Radiation-induced changes in mouse duodenal papilla.

Radiation-induced changes in duodenal mucosal morphology as seen by scanning electron microscopy have been widely reported in the literature. However, no comment has previously been made on any post-irradiation alteration in the duodenal papilla. This paper describes the preliminary results of an investigation into the effects of X rays on the papilla. The duodenal papilla was difficult to find in untreated and sham irradiated mice. It was identified in only two of six mice examined and was located 5.37 and 4.43 mm from the gastroduodenal junction. Eighteen hours after irradiation with 15 Gy X rays, there was little change in position or prominence of the papilla. However, 3 days after treatment, the papilla was only 2.19-3.83 mm from the pylorus. It was also more prominent, being found in all three animals studied and having a widely dilated orifice in contrast to the closed structure seen in the unirradiated specimens. It is concluded that treatment with X rays alters the structure of the duodenal papilla. There may be implications for duodenal function in this marked change in the papilla, which controls the flow of pancreatic and biliary secretions.

Ampulla of Vater↗

PubMed1988

Topographical variation in the mucosal surface of oesophageal biopsies.

There have been comparatively few scanning electron microscopic (SEM) studies of mucosal biopsies of the human upper gastrointestinal tract. This study reviews the use of SEM in human oesophageal research and deals with the results of a SEM study of thirty two biopsies of human oesophagus, taken from eighteen patients during endoscopy for upper gastrointestinal symptoms. For each biopsy, three areas of the mucosal surface chosen at random were examined using standard magnifications. The SEM showed three mucosal patterns, which were designated typical squamous, atypical squamous and nonsquamous, each displaying common features in relation to desquamation, cell boundaries and microridges. The two squamous epithelial groups showed surface microridges. The typical group displayed clear cut cell boundaries and well developed microridges arranged in rows. The atypical squamous group showed desquamation, less well developed cell boundaries and variation in microridge patterns. Many nonsquamous specimens displayed simple columnar epithelium, similar to mucosa of gastric type. Care was taken to correlate the surface structure of the oesophagus with the endoscopic appearance. The two assessments were done independently and the material was coded throughout. The broad subdivision of the biopsies into groups using these qualitative topographical criteria gave good correspondence with the endoscopic appearance.

Biopsy↗

PubMed1988

Development of villous damage in mouse small intestine after local hyperthermia or irradiation.

Damage to mouse small intestine has been assessed in the period up to twenty-four hours after heating a portion of the gut for 20 min at 43 degrees C and also in the period up to nine days after 10 Gy/whole body X-irradiation. The surface changes and the light microscopic appearances after the two types of treatment were described. The damage was evaluated using scores produced by assessing villous collapse as seen with a scanning electron microscope (SEM). Maximum damage was seen two hours after hyperthermia and was more pronounced in antimesenteric portions of the same specimen. Maximum damage was observed three days after X-irradiation. Despite the difference in the time scale and severity of development of surface changes after the two types of treatment, the structure of the damaged and recovering villi looked similar, except for the apical extrusion of the enterocytes immediately following the heat treatment.

Animals↗

PubMed1987

Cytochemical localization of alkaline and acid phosphatase in human vanishing bone disease.

This report is the first cytochemical investigation of vanishing bone disease "Gorham's Disease" (Gorham and Stout 1955). The ultrastructural localization of non-specific alkaline phosphatase and of specific and non-specific acid phosphatase activity was studied in slices of tissue removed from a patient with this rare disorder. Sodium beta-glycerophosphate and phosphorylcholine chloride were used as substrates. Alkaline phosphatase was present around the plasma membranes of osteoblasts and associated with extracellular matrix vesicles in new woven bone. This is consistent with the proposed role for this enzyme (Robison 1923) and for matrix vesicles (Bonucci 1967) in the mineralization of bone (Bernard and Marvaso 1981). Concentrations of specific secretory acid phosphatase reaction product in the cytoplasm of degenerating osteoblasts may contribute to the imbalance between bone formation and resorption. Osteoclasts, while few in number, showed non-specific and specific acid phosphatase activity. The Golgi apparatus and heterophagic lysosomes of mononuclear phagocytes were rich in non-specific acid phosphatase. This was also present in the Golgi lamellae and lysosomes of endothelial cells. Acid phosphatase cytochemistry suggests that mononuclear phagocytes, multinuclear osteoclasts and the vascular endothelium are involved in bone resorption in this disease.

Acid Phosphatase↗

PubMed1987

Morphological criteria for comparing effects of X-rays and neon ions on mouse small intestine.

Several techniques have been used to assess changes in different parts of mouse small intestine three days after a single dose of either 16.5 Gy X-rays or 11 Gy neon beam. The doses were chosen to be approximately equivalent in terms of their effect on the number of microcolonies present. In qualitative terms, villous damage was seen after both types of radiation exposure: collared crypts, similar to those seen in biopsies taken from patients suffering from coeliac disease, were conspicuous after neon irradiation. In semi quantitative terms the doses used, although estimated from previous work to give biologically equivalent damage, produced a greater drop in microcolony numbers after X-irradiation. This makes all the more important the fact that significantly greater changes were seen after neon irradiation-a greater drop was seen in the number of villous profiles and the number of goblet cells per villus. There was also greater breakdown in the integrity of the villous basement membrane. Different responses after the two types of irradiation are therefore seen in the cryptal and villous compartment. Progress is being made towards identifying and quantitating radiation induced changes in different populations of cells or tissues in the small intestine.

Animals↗

PubMed1987

A preliminary study of the role of gastrointestinal endocrine cells in the maintenance of villous structure following X-irradiation.

The mechanism of gastrointestinal villous damage following ionizing irradiation is complex. Various compartments within the gastrointestinal tract have in turn been considered important for the maintenance of normal villous structure. To date, however, evidence for a single overriding regulator of epithelial well-being is lacking. In this study, the role of the gastro-intestinal (enteroendocrine) cells is explored and comparison made between endocrine cell number and villous structure. Experiments were organised using both control and irradiated groups of mice. Two time points (1 and 3 days) and three radiation doses (6, 10 and 18Gy) were employed. A simple method for endocrine cell identification and subsequent quantification is described. Endocrine cell number was then compared with villous surface detail, as seen with a scanning electron microscope (SEM). Results indicated a decrease in the endocrine cell number at all three radiation doses. Whereas at low doses endocrine cell recovery occurred between 1 and 3 days, at medium and high doses further decline was noticed. A similar pattern was seen when considering villous surface structure. It is suggested that both scanning electron microscopy and endocrine cell number provide a more sensitive indicator of gastrointestinal radiation damage than do current crypt counting techniques. In addition, a link between endocrine cell number and villous structure is proposed.

Animals↗

PubMed1987

Microplication patterns on human buccal epithelia following radiotherapy: a scanning electron microscopic analysis.

Surface topographical detail in human buccal smears of normal and irradiated tissue have been studied with scanning electron microscopy. Cells collected by buccal smearing show patterns of microplicae and microvilli, although such detail is occasionally masked by mucus and to a lesser extent by debris and bacteria. Buccal smearing permits collection of numerous specimens with little discomfort to the patient, but requires caution in identification of superficial and deep cell layers and of upper and lower surfaces. The analysis of specimens derived in this way shows that variations in the pattern of surface microplicae reflect the radiotherapeutic regimes of the patients from which they were obtained. Straight parallel microplicae characteristic of normal control and pre-irradiated specimens were absent in specimens collected during early irradiation treatments (between 24-48 Gy), but instead were present as short discontinuous ridges and microvillous projections. At the highest levels of radiation treatment (54-60 Gy) cells exhibited small areas devoid of any surface projections in addition to a range of normal and early irradiated microplicae patterns. From these results it is suggested that the patterns of microplications and microvilli on cell surfaces can be used to obtain information on the state of the stratified squamous epithelium from which they come.

Epithelium↗

PubMed1986

Surface studies of duodenal lesions induced by thoracic irradiation.

Acute duodenal ulcers are produced in mice as a remote ("abscopal") effect of irradiation to the lower mediastinum. Such lesions have been examined with scanning electron microscopy at 5, 8 and 28 days after irradiation with 18 Gy of X-rays. All the ulcers occur within the first 1 cm long segment of the duodenum which is endowed with Brunner's glands. The single lesions vary in size, shape and position. The damaged area often includes much of the duodenal circumference and is distinguished by conical or rudimentary villi, or even by the complete absence of villi. In contrast, around the periphery of the ulcer the villi are mostly vertical. Although the floor of these lesions appears to be covered with a continuous epithelial layer, during the first 4 weeks after irradiation the severity of the focal duodenal damage seems to increase gradually with time. The lesions have been compared with specimens from unirradiated mice and also with samples taken 3 days after partial thoracic irradiation when little damage is seen. The pattern of fully developed duodenal lesions differs greatly from that seen after direct irradiation where damage has not included localised ulceration in the samples of jejunum so far examined. The lesions induced by partial thoracic irradiation may be related to radiation injury to vascular or autonomic nerve targets in the lower mediastinum. Such injury could result in malfunction of the pyloric sphincter or could alter the secretion by Brunner's glands and thus lead to duodenal ulceration.

Animals↗

PubMed1985

Changes in surface structure and concanavalin A-binding capacity of urothelium in the mouse bladder after whole-body neutron irradiation.

A broad overview has been compiled of the literature on the effects of radiation on urinary bladder and on selected cell surface markers that may give information on the pathobiological status of the urinary bladder urothelium. Scanning electron microscopy and immunogold labelling have been used in this study which examines the early (6h to 12 day) radiation response of the mouse urinary bladder following whole-body neutron irradiation. Experimentally, after 5 Gy neutron irradiation, changes in the urothelium include surface morphological abnormalities and enhanced concanavalin A surface binding. These changes were most obvious 1 to 5 days post-irradiation, but lessened in their extent from 5 to 12 days after treatment.

Animals↗

PubMed1985

Structural changes in mouse small intestinal villi following lower body hyperthermia.

Heating an exteriorised loop of mouse small intestine resulted in marked changes in the shape of the villi as reported earlier. However, the exteriorisation techniques resulted in non-uniformity in both temperature and effect around circumference of intestine and, in addition, the extent to which handling contributed to the observed damage was not known. The work has therefore been extended using lower-body heating in the temperature range 37.5 degrees - 43.0 degrees C. Heating in the temperature range 37.5 degrees C to 41.0 degrees C produced minimal to moderate structural changes, manifested as scattered, vertically collapsed villi amongst predominantly "normal" villi. No villi showed conical or rudimentary forms of collapse. Such villi were, however, seen after heating at 41.5 degrees C and were greatly increased in number after heating at 42.0 degrees C. The most severe damage was observed after heating at 43.0 degrees C. Although the lower body heating method gave information which was less complicated by technical considerations, the hyperthermic damage observed was qualitatively similar to that previously seen following local administration of hyperthermia to an exteriorised loop of intestine. Direct quantitative comparisons between the two methods of heating are difficult because of differences in equilibration time and temperature. However, using a comparable heating time, less damage was scored following the exteriorisation technique compared with in situ heating.

Animals↗

PubMed1985

Simulation with pharmacological agents of radiation damage to small intestinal villi.

Irradiation induces damage to intestinal villi, resulting in a progressive decline in villous height and changes in topography. Gamma and neutron radiation are reported to cause changes in the structure of smooth muscle and nerve twigs of the intestinal wall. It is possible, therefore, that villous collapse may be due partly to changes in the underlying stromal elements as a result of damage to nerve or muscle. To test this hypothesis, mice were treated with the drug reserpine which is known to affect the neural control of intestinal smooth muscle function and the small intestine was examined for topographical and histological changes. Two dose levels of reserpine were used and a group of mice were exposed to a single dose of whole body 15 Gy X-irradiation. Comparable villous collapse was observed in each group. Resin embedded semi-thin sections revealed changes in the smooth muscle cells of the muscularis externa after each treatment, suggesting a correlation between villous collapse and smooth muscle damage in response to both irradiation and drug treatment.

Animals↗

PubMed1985

Stromal damage in the mouse small intestine after Co60 gamma or D-T neutron irradiation.

Stromal constituents have been examined in mouse small intestine 3 1/2 days after irradiation with either 18-20 Gy gamma rays or 10 Gy neutrons. These doses were chosen for their equivalent effect on the number of intestinal crypts found after treatment. Despite the fact that the topography of the villi, as imaged by scanning electron microscopy, was altered by treatment, with gamma irradiated villi showing lateral or horizontal collapse while neutron irradiation produced conical villi, few changes were seen in the villous stromal compartments. There were, however, ultrastructural changes observed in the stroma of the pericryptal plate. Changes common to both radiation schedules included disorganisation of the subepithelial stroma and an increase in the number of irregular processes. Some changes after irradiation, however, were not identical in the two groups. Gamma irradiation resulted in pale, foamy cytoplasmic vesicles, the separation of smooth muscle cells and changes in the structure of the luminal aspect of arterial blood vessels while neutron irradiation produced dense cytoplasmic vesicles and electron dense bodies within the substance of peripheral nerve twigs. The fact that the variation in the topography of villi after the two types of radiation is matched by changes in the deep stroma rather than within the villi themselves indicates that the stromal pericryptal plate is of importance in the structure of the villus and the extent to which the villi have varied from the normal finger shaped structure.

Animals↗