Biomedical subjects

K E Carr

Publications and source records attributed to K E Carr.

At least 19 recordsLinked to original sources

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Adult↗

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↗