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Biomedical subjects

D Hopwood

Publications and source records attributed to D Hopwood.

At least 109 records · Page 6Linked to original sources

The ultrastructural localisation of De-Nol (colloidal tripotassium dicitrato-bismuthate--TDB) in the upper gastrointestinal tract of man and rodents following oral and instrumental administration.

In the presence of hydrochloric acid, tripotassium dicitrato-bismuthate forms a particulate precipitate which is electron dense. In upper gastrointestinal tract endoscopic biopsies, following a single oral dose, precipitate was detected between superficial oesophageal epithelial cells and also lining lipid droplets within oesophageal cells. The precipitate does not appear to penetrate the thick mucus barrier in the normal stomach but reaches the epithelial cell surface in the duodenum and proximal jejunum. Small particles of bismuth complex are endocytosed by the enterocyte and enter multivesicular bodies. A similar series of events was observed in rodents and an approximate time course for adsorption and endocytosis was estimated.

Animals↗

Uptake of cationized ferritin by colonic epithelium.

Guinea-pig, rat and mouse were used in this electron microscopic study to demonstrate endocytosis in absorptive and goblet cells of the surface epithelium of the colon. Cationised ferritin was used as the electron dense tracer which attached in vivo to negatively charged membrane components. Both coated and uncoated vesicles entered the cells. The major pathway for the vesicles was to the secondary lysosomes and occurred within 10-30 min. This demonstrates a new pathway of absorption in the adult rodent colon with potential for the uptake of macromolecules. It may provide new clues to the immunology, physiology and pathology of the tissue.

Animals↗

Gallbladder epithelial acid hydrolases in human cholecystitis.

The lysosomal enzymes beta-glucuronidase and acid phosphatase were studied in 112 patients with cholecystitis. Acid phosphatase activity was generally lower in patients with cholesterol stones compared with cases with pigment stones. beta-glucuronidase activity was higher in acalculous cholecystitis than in any other group, a fact compatible with the concept that in lithiasis the enzyme is secreted into the bile and therefore may participate in nidus formation. Histochemistry at light microscopical level clearly demonstrates the lysosomal distribution of these enzymes and their presence in the macrophages infiltrating lamina propria in cholesterolosis. Electron histochemistry in 45 patients showed acid phosphatase activity in lysosomes and some in mucous droplets. Thiamine pyrophosphatase activity, a marker for the Golgi system, showed a close association with these mucous droplets. The secretion of mucus will be accompanied by a secretion of acid phosphatase, and by implication other acid hydrolases, into the bile.

Acid Phosphatase↗

Tissue culture of guinea-pig gall-bladder epithelium.

Tissue culture of gall-bladder was attempted in the following media: Dulbecco, Eagle's minimum essential medium, NCTC 135, medium 199 and Ham's F12. Growth occurred in all of them for up to 2 weeks assessed by light microscopy. No enhancement of growth was induced by collagenase trypsin insulin or hydrocortisone. Scanning electron microscopy confirmed that new cells colonised the free surface of the explant. Transmission electron microscopy showed good preservation of the original tall epithelial cells for the period of study. The new migrating cells were flatter, but retained the morphological features of the columnar cells. Secretory granules were absent after 1 day in culture but increased amounts of glycogen and lipid began to appear in the epithelium.

Animals↗

Mucosal alkaline phosphatase and bile lipids in the gallbladder in cholecystitis.

Histochemically, alkaline phosphatase was localised in epithelial brush-border and capillary endothelium of the lamina propria in 41 gallbladders studied. Three distinct patterns of the brush-border enzyme distribution were observed, namely, complete delineation, patchy localisation and a brush-border totally devoid of enzyme activity. Where no histochemical activity was found, biliary chenodeoxycholate was 50 per cent. higher than in cases of patchy distribution and twice as high as in cases with complete staining of the brush-border. Conversely, biliary cholate levels were significantly higher in completely stained cases. Biliary cholesterol was higher in the cases with no histochemical activity and this was reflected in a significantly higher lithogenic index. Significant quantities of cholesterol esters were found in bile from the focal activity group only. Total alkaline phosphatase activity assayed in gallbladders from 112 patients with cholecystitis and/or lithiasis showed that activity was significantly lower in patients with pigment stones than patients with cholecystitis and/or cholesterol stones. This activity was not related to biliary lipid composition in the 77 bile samples analysed. This evidence indicates that biliary lipid composition is associated with the histochemical distribution of alkaline phosphatase in gallbladder mucosa.

Alkaline Phosphatase↗

Potentiation of pancreatic carcinogenesis in the rat by DL-ethionine-induced pancreatitis.

We have assessed the influence of an attack of acute pancreatitis on the incidence of experimentally induced pancreatic cancer in rats. A low-protein diet plus repeated injections of DL-ethionine produced acute pancreatitis in rats. The animals were then fed either a diet of raw soya flour or a non-soya-containing diet and given repeated injections of azaserine, a weak pancreatic carcinogen. The rats that had recovered from acute pancreatitis developed pancreatic cancer, whereas those without previous pancreatitis did not. We conclude that the interaction of recovery from acute pancreatitis with a pancreatic carcinogen predisposes to pancreatic cancer in rats.

Acute Disease↗

The uptake of cationised ferritin and its subsequent redistribution by gallbladder epithelium in vivo.

Cationised ferritin was injected into the gallbladders of guinea pigs at operation and its subsequent fate studied with an electron microscope over a 24-hr period. The apical cell membrane of the epithelium was tagged and showed patching. The cationised ferritin was internalised into small vesicles, some derived from coated pits, within 5 min. Other vesicles were found at the same time near the lateral cellular membrane. Cationised ferritin was found in lysosomes and in residual bodies in large quantities and occasionally in multivesicular bodies and vesicles near the Golgi apparatus. Clumps of (cationised) ferritin appeared in the lateral intercellular space, 2 hr after exposure, increasing in number with time up to 5 hr. Similar clumps also were found between the basal cell membrane and the lamina rara interna of the basement membrane in a fairly regular pattern. By 5 hr the marker was beginning to pass through the basement membrane. The process was largely complete by 10 hr. Twenty-four hours after injection of cationised ferritin, virtually no marker was found in either the epithelium or underlying connective tissue.

Animals↗

Primary biliary cirrhosis in elderly females.

A series of 29 patients with primary biliary cirrhosis has been studied in the last seven years. An unusual feature of this group was that 38% wee over the age of 65, and 24% over the age of 70 at presentation. Detailed analysis of the seven patients presenting over the age of 70 is provided. All of these patients had symptomatic primary biliary cirrhosis rather than representing prolonged survival of the asymptomatic state. It is important that primary biliary cirrhosis be included in the differential diagnosis of liver disease presenting in the elderly.

Adult↗

Cirrhosis and primary liver cell carcinoma in Tayside: a five year study.

Despite Scotland's well-recognised alcohol problem, there is scant information of the aetiology of cirrhosis in this country. This study of 222 patients, reviewed 197 cases presenting as cirrhosis and 25 cases presenting as primary liver cell carcinoma (PLCC) in the East Tayside area of Scotland between 1975 and 1979. The survey was based on an analysis of all histologically proven cases of cirrhosis and PLCC encountered during a five-year period. There was a constant rate of presentation of cirrhosis of about 40 new patients per year, with a stable pattern of aetiology. About 55 per cent were due to alcohol, and there was no significant change in this proportion over the study. No evidence was found for an increasing female susceptibility or earlier female morbidity in alcoholic cirrhosis. Cryptogenic cirrhosis, cardiac cirrhosis and secondary biliary cirrhosis were more often diagnosed at post mortem. Ninety one per cent of patients with primary biliary cirrhosis were females, but the expected male preponderance in haemochromatosis was not present. In addition to the 25 patients presenting with PLCC, three of the cirrhotic patients developed the tumour by the end of 1979. Seventy one per cent of PLCC cases arose in already cirrhotic livers, none were HBsAg positive. Bronchopneumonia, hepatic failure, gastrointestinal bleeding and cardiac failure were the most frequent causes of death.

Adolescent↗

The cholesterol/dry weight ratio: a simple substitute for lithogenic index.

The limiting solubility of cholesterol in bile has been defined by several lithogenic indices which all require determination of phospholipids, cholesterol, and bile salt concentrations. These technically demanding assays are not widely available and restrict general application of lithogenic index studies while the indices in use do not accommodate differences in water content of bile. Consequently, a simple index that requires only measurement of biliary cholesterol concentration and bile dry weight has been assessed by comparison with a commonly used lithogenic index. This simple index correlates well with the conventional sophisticated lithogenic index and is not influenced by use of bile obtained by direct aspiration or by duodenal drainage. Similarly, division into patient groups based on various clinical parameters does not influence the correlation. This simple index will allow routine laboratories to assess bile lithogenicity.

Bile↗

Oesophageal epithelial ultrastructure after incubation with gastrointestinal fluids and their components.

Oesophageal biopsies from endoscopically normal patients were incubated in the following for up to 30 min-Ham's F10 medium:isotonic saline:0.1 N HCl:20, 2 and 0.2 mM bile acids:trypsin:pepsin:lipase; autologous gastric and duodenal juices. The biopsies were then examined by electron microscopy. No morphological change was produced by Ham's F10 or saline. HCl caused little damage. Gastric juice produced widespread severe damage, as did pepsin. Duodenal juice and the enzymes tested caused lysis and internalisation of desmosomes and peripheral cytoplasmic vacuolation. Bile acids split desmosomes and induced microvesiculation of cell membranes. Similar microvesiculation was also induced by duodenal juice. All media except hydrochloric acid eventually produced organelle damage and leaky and disrupted cells. The functional and superficial cells appeared to be able to withstand attack from these experimental media better then did prickle and basal cells. Membrane coating granules were secreted in the presence of hydrochloric acid, but not with enzymes.

Bile Acids and Salts↗

Effects of bile acids and hydrogen ion on the fine structure of oesophageal epithelium.

Oesophageal mucosal biopsies were incubated in 20, 0, and 0.2mM solutions of cholic, chenodeoxycholic, ursodeoxycholic, and deoxycholic bile acids. Both conjugated and unconjugated bile acids were studied at pH 1 and 7 singly and in combination. Observations were also made using 0.1 N hydrochloric acid and human gastric juice at pH 1-3 and 7-8. After incubation for up to 15 minutes the mucosa was examined under transmission electron microscopy. We concluded that high and moderate concentration of all the common bile acids damaged the oesophagus irrespective of the pH, that low concentrations of bile acids were damaging only at high acid levels, and that damage to the epithelium did not occur when the pH of the gastric juice had been raised.

Bile Acids and Salts↗

Interaction of azaserine and raw soya flour on the rat pancreas.

Rats have been fed for up to 2 years with either raw soya flour or control diets of heated soya flour or rat chow not containing soya flour. In addition, the rats received weekly injections of either a weak pancreatic carcinogen (azaserine) or control injection of saline. We found that rats fed a diet of raw soya flour and given weekly injections of azaserine developed benign and malignant neoplasms of the pancreas earlier in life and much more frequently than rats given raw soya flour alone, whereas azaserine alone in the dose used in this study did not produce pancreatic cancer. We conclude that raw soya flour sensitizes the pancreas to the action of azaserine.

Animals↗

Cholecystitis: a fine structural analysis.

The epithelial cells from 40 gallbladders showing chronic cholecystitis and five with cholesterolosis were examined by electron microscopy. A number of features of non-specific cytological injury were noted some of which may have been related to the disease and others to anoxia. The basement membrane showed reduplication. Intraepithelial cells were identified as lymphocytes, polymorphonuclear leukocytes, macrophages and mast cells. Lipid droplets in the epithelial cells were found in 60 per cent. of the specimens.

Basement Membrane↗

A comparative trial of liver biopsy needles.

A sheathed needle (Tru-Cut) was compared with a suction biopsy needle (Menghini) in a randomised prospective trial over 18 months to determine whether the former offered any special advantages in routine percutaneous liver biopsy. Seventy-seven consecutive biopsies were performed by a single operator. Although biopsy fragmentation was commoner with the suction needle, the length and volume of the largest core obtained was similar to results with the sheathed needle. Cytology provided useful additional information with the Menghini technique. The suction needle was repeatedly reusable and considerably cheaper than the sheathed needle, which may be used once only.

Biopsy, Needle↗