Biomedical subjects
Publications and source records attributed to D Hopwood.
Rats were fed raw and heated soya flour for up to 2 years. The rats fed raw soya flour all developed pancreatic hypertrophy and hyperplastic and adenomatous nodules. Four of 26 rats fed raw soya flour continuously and 1 of 5 rats fed raw soya flour for 2 days each week developed pancreatic cancer. Preheating the soya flour seemed to protect against the pancreatic hyperplastic and neoplastic changes.
In a prospective survey jejunal biopsy samples from 11 patients with multiple sclerosis on normal diets were compared with those from controls matched for age and sex. Quantitative histology, morphometry, and electron microscopy showed no difference between the two groups. Since there was no evidence that gluten sensitivity plays a role in the aetiology of multiple sclerosis, the wide adoption of gluten exclusion by patients seems unjustified.
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A further case of a spindle cell sarcoma of the pulmonary trunk is reported, with extension to the pulmonary valve and lungs. Some spindle cells contained glycogen and their cell walls acid mucosubstances. Electron microscopy showed two types of cell. The more common were polyhedral with poorly arranged fibrils in the cytoplasm and an abundant fuzzy coat. About 5 per cent of the cells contained neurosecretory granules.
Intraperitoneal di(2-hydroxypropyl)-Nitrosamine (DHPN) caused a high incidence of oesophageal squamous carcinoma in male Wistar rats, particularly in rats killed 11 or more months after the start of injections. No control rats (injected intraperitoneally with saline) developed an oesophageal neoplasms. Histopathologically, the tumours were moderately well differentiated. Histochemical studies showed minor increases in mucin staining and mast cell population and a marked increase in bacteria in tumour-bearing oesophaguses. Electron microscopy showed the tumours to be similar to, but to differ in some respects from squamous carcinomas at other sites in humans. The possible implications of this work for human disease are twofold. It could provide a model for further study of aspects of oesophageal carcinoma and it serves to remind us that all potential oesophageal carcinogens need not act during swallowing.
At the ultrastructural level the inflamed oesophageal epithelium shows a variety of lesions. These include mitochondrial damage, intracellular oedema, membrane whorls and dilation of the endoplasmic reticulum and the appearance of keratohyaline and parakeratosis granules. The basement membrane shows changes ranging from thickening to areas of loss of continuity. There is an increase in the anchoring fibrils. The spaces between the cells are enlarged and contain varying amounts of debris rich in neutral mucosubstances. There are less membrane-coated granules in the inflamed epithelium than in the normal. The intra-epithelial intrusive cells demonstrated were lymphocytes and neutrophil polymorphs.
The distribution of cations and anions in normal human oesophageal epithelium has been investigated with the pyroantimonate and silver-osmium tetroxide techniques. There is a discontinuous distribution of both ions in the intercellular space. The ions are associated with various organelles, as has already been described in the literature. Specifically, in the oesophageal epithelium, there are a few deposits of pyroantimonate and occasional silver in the membrane coating granules, but here is no apparent relationship of either ion with the tonofilaments or glycogen particles. The superficial cells are leaky and contain fewer ions than the deeper functional layer cells.
Oesophageal epithelial cells from biopsies from normal patients showed the presence of randomly distributed anionic groups, mostly sialic acid on the cell membrane in fixed material shown by cationized ferritin. When biopsies were pulse labelled, patching occurred in all three cell layers. Patching was energy dependent and did not occur at 4 degrees C. Pulse labelled material incubated on an unlabelled medium showed progressive loss of cationized ferritin from the cell membrane. This was mostly into the medium, although some was internalized in membrane profiles. A second pulse of cationized ferritin produced further patching suggesting regeneration of cell membrane. Superficial cells were leaky, but their organelles were not.
Oesophageal biopsies were obtained from 74 patinets undergoing upper gastrointestinal fibreoptic endoscopy. Thirteen patients with histological evidence of inflammation had a raised alkaline phosphatase activity (2.7 +/- 1.6 nmol/mg protein/min) compared with 49 normal controls (1.2 +/- 0.68 nmol/mg protein/min: P less than 0.001). The acid phosphatase level was lower (8.4+/- 4.0 vs. 5.8 +/- 2.2 nmol/mg protein/min: P less than 0.05) and the glucuronidase activity raised (0.44 +/- 0.17 vs 0.81 +/- 0.32 nmol/mg protein/min: P less than 0.001) and their ratio declined (24.0 +/- 1.9 nmol/mg protein/min: P less than 0.001) in patients with oesophagitis. This may be due to differential secretion of membrane coating granules, a form of lysosome found isophagitis--was assessed by point counting. The volume density rose from 10.9 +/- 4.25% in normal biopsies to 46.4+/-12.5% (P less than 0.001) in oesophagitis. These results show a consistent pattern that possibly indicates an intermediate stage between the clinically, histologically, and biochemically normal oesophagus and one that is inflamed on endoscopy.
Di(2-hydroxypropyl)nitrosamine was administered to rats fed raw or heated (control) soya flour diets. The group fed raw soya flour developed hyperplastic and adenomatous pancreatic nodules and pancreatic adenocarcinomata. We conclude that a diet of raw soya flour augments the carcinogenicity of pancreatic carcinogens in the rat.
We have examined normal and inflamed oesophageal biopsies for the distribution of alpha-D-mannosyl and alpha-D-glucosyl residues using the concanavalin A--horse radish peroxidase--Diamino-benzidine (DAB) technique at the light and electron microscope level. Receptors were found on the epithelial surface and in the nuclear membrane and endoplasmic reticulum. A similar distribution was found with the intrusive lymphocytes and polymorphonuclear leucocytes in the inflamed state. Some of the increased intercellular debris from inflamed biopsies contained concanavalin A receptors.
Oesophageal biopsies were studied with the electron microscope. Three layers were identified, as in the light microscopy of the oesophageal epithelium: basal, prickle and funtional cell layers. A continuous basement membrane separated the lamina propria from the basal cells. The basal cell membrane carried hemidesmosomes, desmosomes and microvillous processes. Their cytoplasm contained the usual organelles plus free ribosomes and tonofirbrils. Prickle cells contained glycogen rosettes and many tonofilaments, and their cell membrane many microvillous and demosomal processes, in places elaborated into desmosome fields. In both these layers there was a wide intercellular space containing some particulate and membranous debris. The flattened cells of the functional layer had fewer desmosomes and microvilli but abundant glycogen and tonofilaments, and a narrow intercellular space. Membrane coating granules first reaching a maximum in the functional cell layer appeared in the upper prickle cell layer and few persisted into the surface cells. The apical cell membrane of the most superficial cells was thickened and had few small microvillous processes, which were covered with a filamentous "fuzzy" coat. No keratohyaline granules were present. Papillae of lamina propria contained capillaries, some with a fenestrated endothelium.
The appearances of this intercellular junctions in normal and in inflamed oesophageal epithelium are described. Typical hemidesmosomes occur along the abluminat aspect of the basal cells. Desmosomes are most frequent in the prickle cell layer, where desmosome fields may occur, and in the lower functional cell layer. Their fate in the upper layers is not known. Gap junctions are few in the basal cell layer and rare in the most superficial layers. They are maximal in the prickle cell layer. Tight junctions only occur in inflamed tissue between the most superficial cells usually as part of a lateral intercellular junctional complex that also contains belt desmosomes. They may represent attempts by a non-keratinised epithelium to increase its defences against toxic luminal contents.
Acid phosphatase activity in human normal oesophageal epithelium was studied with light and electron microscopic techniques. The maximum activity was found to be in the prickle and lower functional layers. Electron microscopic examination revealed activity to be localized in GERL, lysosomes and membrane coating granules. These last structures probably secreted their content into the intercellular space in the central part of the functional layer. Thick sections (0.5 micron) with tilting showed GERL to consist of anastomosing tubules.
Normal human oesophageal epithelium was investigated with the periodic-acid-silver methenamine technique and its variations to demonstrate neutral mucosubstances at the ultrastruct level. The results were compared with the acid phosphotungstic acid method. Neutral mucosubstances were shown in the cell coat and membrane coating granules by both techniques. The silver methods also demonstrated glycogen, the Golgi apparatus and dense bodies. The periodic acid-silver methenamine technique outlined positive material in the intercellular space of the prickle cell layer, but the other silver methods did not.
Oesophageal biopsies were obtained from patients with normal oesophagi during fibre-optic endoscopy for upper gastro-intestinal symptoms. They were studied with the prolonged osmication technique. The forming face of the Golgi apparatus was demonstrated in the basal and lower prickle cells. These cells also showed osmium deposition in their mitochondria, endoplasmic reticulum, perinuclear cisternae and lysosomes. The capillary endothelial cells also showed osmium deposition in their Golgi apparatus and endoplasmic reticulum.
The cell coat in human oesophageal biopsies was studied with Alcian Blue, Ruthenium Red, Safranin O, colloidal iron and the ferrocyanide--osmium tetroxide techniques. Alcianophilic material was found on the cell surface of the basal, prickle cell and functional layers, being most abundant on the superficial cells where it appeared as a continuous coat. In the deeper layers, it tended to have a particulate distribution. Some membrane-coating granules were alcianophilic. Ruthenium Red had a particulate distribution over all cell surfaces. Intercellular debris was also stained. Safranin O produced no staining. Colloidal iron stained the cell coat in a particulate manner. The ferrocyanide--osmium technique showed a uniform filamentous cell coat. The oesophageal epithelial cell coats are, in part, acid mucosubstances which, on the surface cells, may have a protective function.
The histochemistry of lipids and mucosubstances in normal human oesophageal epithelium were studied in biopsies obtained from 24 patients undergoing investigations of the upper gastro-intestinal tract. Neutral fat droplets, 1-2 mum in diameter, were present in all layers, the greatest number being in the functional layer cells. No unsaturated lipids or fatty acids were demonstrable. Much glycogen was present in the cytoplasm of the prickle and functional cell layers as demonstrated by PAS (and diastase digestion) techniques. The intercellular space of the most superficial of the functional cell layer contained neutral and sialic acid-rich acid mucopolysaccharides. These may be important in protecting the epithelium against physical and chemical trauma.