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Biomedical subjects

J D Harrison

Publications and source records attributed to J D Harrison.

At least 73 records · Page 4Linked to original sources

Measurements of the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium in experimental animals.

In order to set limits on environmental and occupational intakes of radionuclides, information is needed on their uptake and metabolism in man. Human data are very limited, particularly for long-lived alpha-emitting isotopes such as those of the actinides. Animal experiments are therefore an important source of data on the distribution of radionuclides in tissues, and the effects of factors such as subject age and the chemical form of elements on gastrointestinal absorption. The NRPB performs experimental programs using mainly rats and guinea pigs. In order to study the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium, a variety of analytical techniques are employed. These include ion exchange and solvent extraction leading to alpha spectrometry and liquid scintillation counting. The investigation of low specific-activity environmental or industrial materials, and the very low bioavailability of elements such as the actinides, means that very low levels of activity have to be measured. Contamination at the dissection and tissue separation stage, as well as during the radiochemistry, has to be rigorously avoided. Where very detailed information is needed on the location of radionuclides within tissues, such as in the study of alpha-emitter distribution in the intestine, autoradiography is used. The application and relevance of different measurement techniques to animal studies will be discussed and examples of the results presented.

Aging↗

Speciation of plutonium in potato and the gastrointestinal transfer of plutonium and americium from potato.

Complexation of Pu(IV) and Am(III) by naturally occurring agents such as citrate and phytate might enhance their uptake from the digestive tract. However, the extent to which they enhance the gastrointestinal uptake of actinides from foodstuffs is far from resolved, as this study shows. Investigations of the chemical forms of Pu(IV) and Am(III), by gel permeation chromatography, in simulated digests of potato tubers naturally radiolabelled with 239Pu(IV) and 241Am(III) have shown that neither citrate nor phytate appear to determine their chemical forms. Therefore, it is possible that these are not the complexing anions which determine the gastrointestinal transfer of these radioelements from potato meal. Isotachophoretic analyses of the juices pressed from tubers and solutions prepared by simulated digestion of potato tubers have demonstrated the presence of several low molecular weight anions. These anions might be complexing agents because they possess an isotachophoretic mobility similar to that of citrate; some of these anions remain unidentified. Whereas 239Pu and 241Am were used in the foregoing studies, 238Pu and 241Am were used to produce either in vitro or naturally radiolabelled potatoes for gastrointestinal transfer measurements using rats and hamsters. Gastrointestinal transfer values of 0.13 +/- 0.05% (mean +/- standard error of mean) and 0.16 +/- 0.06% were determined with rats for the uptake of 238Pu and 241Am, respectively, from naturally labelled potato meal. Higher gastrointestinal transfer values were obtained for hamsters: for 238Pu and 241Am the transfer values from naturally labelled meal were 0.25 +/- 0.08% and 0.33 +/- 0.07%, respectively. Similar values were observed for uptake from in vitro labelled potato meal. On the basis of the similarity of the values for the naturally labelled potato meal and for the 'spiked' potato meal it would appear that biological incorporation is not necessary for the binding of the actinides to the ligands which will determine gastrointestinal transfer.

Americium↗

Analytical ultrastructural investigation of microliths in salivary glands of cat.

Microliths in Araldite-embedded pieces of submandibular and sublingual glands of cat were stained in semithin sections by Methylene Blue and Azure II followed by Basic Fuchsin, and were examined in ultrathin sections by electron-microscopical X-ray microanalysis. Calcium and phosphorus were detected in substantial aggregates of crystals that were stained by Basic Fuchsin and appeared to be hydroxyapatite, but were not detected in granular material that was stained by Methylene Blue and Azure II and appeared to be organic. The polychromatic stain thus appears to be a useful indicator of calcified material. The majority of microliths in acini contained substantial aggregates of crystals, whereas the majority of those in ducts did not. This corresponds to the distribution of the glandular calcium, and suggests that microliths are variously enriched with calcium according to its local level.

Animals↗

Microliths in normal salivary glands of cat investigated by light and electron microscopy.

This investigation concerns the natural history of microlith in the salivary glands of cat. Microliths were detected in more sublingual than submandibular glands and were almost absent in the parotid. They were found intraparenchymally, intraluminally and interstitially, and ultrastructurally in phagosomes of acinar, ductal and myoepithelial cells, intermixed with the cytoplasm of degenerate acinar cells, and in intraparenchymal macrophages and a multinuclear giant cell. They appear to form in healthy acinar cells during autophagocytosis, and possibly to be discharged luminally, laterally or basally, and to form in the debris of degenerate cells intraparenchymally and intraluminally. They appear to be removed by expulsion in the saliva, scavenging macrophages, and possible eventual degradation in the parenchymal phagosomes. The greater occurrence of microliths in the sublingual gland may relate to a low level of secretory activity, and the near absence of microliths in the parotid to a low level of calcium. The feline salivary glands were found to be an outstanding model for the investigation of microlithiasis.

Animals↗

Histochemical and biochemical determination of calcium in salivary glands of cat.

Although feline salivary glands have been used in investigations on secretion and microlithiasis and both processes involved calcium, nothing is known about its distribution in these glands. Therefore we have demonstrated the presence of calcium by a histochemical technique using glyoxal bis(2-hydroxyanil) and a biochemical technique using dry ashing. The histochemical technique stained serous acinar cells weakly and rarely found mucous acinar cells strongly in the parotid gland, mucous acinar cells moderately to strongly and serous acinar cells weakly in the sublingual gland, and central and demilunar acinar cells moderately to strongly in the submandibular gland. The biochemical technique revealed less calcium in the parotid than in the submandibular and sublingual glands. Both techniques revealed a decrease of calcium in submandibular and sublingual glands following parasympathetic stimulation. The histochemical distribution of calcium, which corresponds to that of acinar secretory glycoprotein, and the loss of calcium following parasympathetic stimulation, which causes release of secretory granules, indicate the presence of calcium in secretory granules. The concentration of calcium in the different types of acinar cell corresponds to the acidity of the secretory glycoprotein and suggests that calcium is present as a cationic shield to allow the condensation of polyionic glycoprotein in secretory granules.

Animals↗

Histochemical and biochemical determination of calcium in salivary glands with particular reference to chronic submandibular sialadenitis.

Although salivary calcification is relatively common, little is known about the localization and content of the calcium of normal and diseased human salivary glands. We investigated this in chronic submandibular sialadenitis with a variable mixture of relatively normal and extremely atrophic parenchyma and in normal submandibular, parotid and palatal glands. Calcium was localized histochemically in mucous acinar cells of submandibular and palatal glands at moderate to high levels, in serous acinar cells of submandibular and parotid glands at low to moderate or occasionally high levels, in mucous ductal cells at moderate to high levels, and in extremely atrophic parenchyma at low levels or not at all. Calcium was determined biochemically at relatively high levels in the different glands in the order palatal, submandibular, sialadenitis and parotid. However, the differences were small. The results indicate that most salivary calcium is associated with secretory granules; this is the likely source of the calcium involved in salivary calcification.

Calcium↗

The effects of obstruction and secretory stimulation on microlithiasis in salivary glands of cat: light and electron microscopy.

Obstruction and increased secretory activity are considered to be important aetiological factors of salivary microlithiasis, which may itself be an aetiological factor of sialadenitis. However, there is a lack of substantial evidence for the importance of obstruction, and investigations on increased secretory activity used pathological doses of pharmacological agents. Therefore further investigation of these factors is essential. Feline parotid, submandibular and sublingual salivary glands, in which microliths occur normally as in man, were examined after ductal ligation to produce obstruction, electrical stimulation of the glandular nerves to produce increased secretory activity, or both. Microliths were detected in: 0 out of 38 untreated, 1 out of 55 ligated, 2 out of 17 stimulated and 2 out of 17 stimulated ligated submandibular glands; 6 out of 29 untreated, 7 out of 46 ligated, 3 out of 12 stimulated and 4 out of 14 stimulated ligated sublingual glands; and no parotid glands. The chi 2 test confirmed that the experimental procedures did not produce an increased occurrence of microliths. Microliths were detected in parenchymal cells, intercellularly in atrophic parenchyma, intraluminally, interstitially and in macrophages. The present investigation indicates that obstruction and increased secretory activity are not important aetiological factors of salivary microlithiasis.

Animals↗

Histochemical and biochemical determination of calcium in pleomorphic adenoma.

Although calcification seldom occurs in pleomorphic adenoma, it often occurs in salivary glands, and so we decided to investigate the possible role of calcium in this difference. A histochemical method using glyoxal bis(2-hydroxyanil) demonstrated a small amount of calcium outlining lumina and separated cells of epithelial structures and associated with cells of myxoid and chondroid regions in pleomorphic adenoma, and a conspicuous amount in the acini of the associated salivary glands. A biochemical method using dry ashing demonstrated a significantly higher level of calcium in the glands than in pleomorphic adenoma. The results indicate that the calcium is mainly associated with secretory granules, which are scarce in pleomorphic adenoma, and with proteoglycan present intercellularly and in stromal regions of pleomorphic adenoma. The calcium in secretory granules is of possible importance in calcification in lumina and epithelium, and that bound to proteoglycan is possibly released following necrosis to be of importance in stromal calcification. However, the overall low level of calcium in pleomorphic adenoma is the likely explanation for the usual lack of calcification.

Adenoma, Pleomorphic↗

The effect of sympathectomy on the occurrence of microliths in salivary glands of cat as studied by light and electron microscopy.

Parasympathectomy is followed by a greatly increased occurrence of microliths in the feline submandibular gland, which appears to be because of secretory inactivity. The sympathetic nerves are also important in secretory processes, and so feline submandibular, sublingual and parotid glands subjected to postganglionic sympathectomy for periods from 1 day to 1 yr have now been investigated. Microliths were detected in two out of 28 sympathectomized submandibular glands and four out of 27 untreated glands, and in 10 out of 22 sympathectomized sublingual glands and seven out of 19 untreated glands. There were no significant differences between the occurrence of microliths in sympathectomized and untreated glands. Microliths were not detected in any of 29 sympathectomized and 30 untreated parotid glands. The appearance of the sympathectomized glands was similar to that of the untreated glands. The failure of sympathectomy to affect the occurrence of microliths or the appearance of the glands is possibly because of parasympathetic nerve impulses, which produce continuing secretory activity, and also the spontaneous secretion of the sublingual gland. The results support the concept that secretory inactivity is an aetiological factor of microlithiasis.

Animals↗

Gastrointestinal absorption and retention of polonium in adult and newborn rats and guinea pigs.

The gastrointestinal absorption of 210Po was determined by comparing tissue retention after oral and systemic administration. The results indicate an increase in absorption in adult rats for 210Po administered in liver compared with 210Po nitrate with estimated absorption of 5 and 13%, respectively. For 210Po citrate, values of about 7% were obtained in 1-day-old neonate and adult rats while absorption in guinea pigs was estimated to be about 23% in 1-day-old neonates, 17% in 5-day-old neonates, and 9% in adults. Gut retention of ingested 210Po in neonates was high in rats but not guinea pigs. In adult animals, but not neonates, the liver accounted for a greater proportion of 210Po reaching the bloodstream after ingestion than after systemic injection. The significance of these results is discussed in relation to current assumptions made in the calculation of doses from 210Po.

Administration, Oral↗

Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia?

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.

Adolescent↗

Ultrastructural localization of microliths in salivary glands of cat.

Although microliths occur in normal human salivary glands and may be an aetiological factor of sialadenitis, little is known of their natural history. In an attempt to remedy this, we investigated a large archival collection of normal and experimental feline parotid, submandibular and sublingual salivary glands. In submandibular and sublingual glands, microliths were detected ultrastructurally in: all types of acinar secretory cells; myoepithelial cells; ductal cells; lumina; intercellular spaces; basement membrane; stroma; macrophages; multinuclear giant cells; and neutrophils. Microliths were not detected ultrastructurally in parotid glands. Microliths appear to form in acinar cells during autophagy and in stagnant secretory material in lumina. Microliths appear to be removed by secretion in the saliva, discharge from cells laterally and basally, and engulfment by macrophages. There appears to be a turnover of microliths, which possibly is upset by secretory inactivity with a resulting accumulation that leads to localized obstruction and sialadenitis.

Animals↗

Screening for gastric carcinoma in coal miners.

This study aimed to determine the prevalence of dyspeptic symptoms and premalignant gastric lesions in coal miners and sex matched population control subjects. Retired coal miners and men from the general population in north Nottinghamshire were sent a dyspepsia questionnaire to fill in, and those with upper gastrointestinal symptoms were invited for gastroscopy and biopsy. A total of 1272 men from the general population and 2099 retired coal miners aged 50-75 years took part in the study. Some 977 of 1272 (76.8%) control subjects and 1715 of 2099 (81.7%) miners replied to the questionnaire. A total of 308 of 977 (31.5%) controls and 620 of 1715 (36.2%) miners were positive for at least one symptom. There was a highly significant difference between the numbers of surface mine and underground workers who reported dyspeptic symptoms (66 of 300 (22%) v 425 of 1083 (32.2%) of p < 0.0001). Histology showed that significantly more miners than controls had acute on chronic gastritis (22 v 11%; p = 0.01) and intestinal metaplasia (23 v 8%; p = < 0.0001). Coal miners may be a suitable group for gastric premalignancy screening using an upper gastrointestinal symptom questionnaire and upper gastrointestinal endoscopy.

Age Factors↗

The biokinetics of plutonium-239 and americium-241 in the rat after subcutaneous deposition of contaminated particles from the former nuclear weapons site at Maralinga: implications for human exposure.

As an input to dose assessments, measurements have been made of the clearance of Pu and Am after subcutaneous implantation in rats for six particulate materials and one dust from the Maralinga test sites. The tissue distribution of Pu and Am were measured in groups of six animals at one month and 6 months after implantation. In addition, in vitro solubility tests were carried out on eight different particulate materials. Histological examination of the subcutaneous implantation site was undertaken after one year for selected materials. Autoradiographs of tissue sections showed that particles were surrounded by fibrotic tissue with macrophage and polymorphonuclear cell infiltration, the normal tissue response to foreign materials. The clearance data have been used to make estimates of the likely range in potential radiation doses in humans. To calculate the dose from dissolved 239Pu and 241Am, four different situations have been considered. For the dust, the results suggest that dissolution essentially ceases after the removal of Pu and Am from the surfaces of dust particles. From the values obtained, the acute release of a fraction of 10(-2) of both nuclides from a dust contaminated wound was assumed. For a number of particles the results suggested continued dissolution and the clearance of 10(-3) per year of both nuclides, continuing for a number of years, has therefore been considered. For the least soluble particles, there was no clear evidence of continued clearance and the acute release of 10(-4) has therefore been taken as a lower estimate for dose calculations.(ABSTRACT TRUNCATED AT 250 WORDS)

Americium↗

Development of indications and results during 10 years of orthotopic liver transplantation.

Liver transplantation has rapidly emerged in recent years from an uncommon experimental procedure, limited to a few centers, to become a major international effort to support patients with advancing and decompensating liver disease. The excellent results which can be achieved with optimal timing and expert clinical management are now no longer in doubt. The greatest emphasis now must be on obtaining suitable high quality donors at the right time to give the patient the best opportunity to make a full and complete recovery.

Blood Transfusion↗

Posterior truncal vagotomy and stapling of the anterior stomach wall in 30 patients with duodenal ulcer: acid inhibition, gastric emptying, and endoscopic dye spraying. Prospects for endoscopic vagotomy.

The use of a stapling instrument (TA90) to effect a transection of the anterior gastric wall with posterior truncal vagotomy but preserving innervation to the anterior wall of the antrum for duodenal ulcer is described. The operation resulted in the endoscopic healing of all the ulcers; however, recurrent ulceration was seen in 3 of 25 patients. Basal acid output was reduced from 7.84 (SEM 1.73) to 3.49 (SEM 1.15) mmol/h (t = 2.09, df = 15.7, p = 0.05), while peak acid output was reduced from 38.67 (SEM 3.11) to 19.26 (SEM 2.3) mmol/h (t = 5.01, df = 23.9, p = 0.0000). Solid and liquid gastric emptying studies were performed, and while some delay in solid emptying was seen, only one patient complained of transient gastric stasis. Endoscopic Congo red staining was performed postoperatively and a tongue of innervated mucosa along the lesser curve was seen in each case. The procedure was easily and rapidly performed, and early clinical results are good, with 25 of 30 patients having a good (Visick I) result.

Adult↗