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Biomedical subjects

D Hopwood

Publications and source records attributed to D Hopwood.

At least 91 records · Page 5Linked to original sources

Liver biopsies from patients with psoriasis related to photochemotherapy (PUVA): findings before and after 1 year of therapy in twelve patients. A blind study and review of literature on hepatotoxicity of PUVA.

In each of twelve patients with psoriasis, a liver biopsy was taken before and after 1 year of photochemotherapy (psoralen and long-wave ultraviolet light; PUVA). The mean dose of psoralen was 3,204 mg (range, 1360-5300) at the time of the latter liver biopsy, whereas the mean number of treatments was seventy-nine (range, 34-126 treatments). Analysis by the sign test showed no statistically significant differences in any of the light microscopic variables comparing pre- and posttherapy liver biopsies. No changes were found that appeared to be specific for PUVA therapy. Psoralen, in the doses given as part of PUVA therapy for 1 year in a limited number of patients, seems to have little hepatotoxicity. The literature on the possible hepatotoxicity after treatment with psoralen followed by ultraviolet A irradiation is reviewed. Patients receiving PUVA therapy should have only limited alcohol intake. From this reading, psoralens as part of PUVA therapy appear to have little or no hepatotoxicity.

Biopsy↗

Collagenous colitis associated with small intestinal villous atrophy.

Two patients diagnosed as having small intestinal hyperplastic villous atrophy and being treated with a gluten free diet were investigated because of persistent watery diarrhoea. Both were found to have collagenous colitis. Previous reports of this condition have emphasised the presence of normal small intestinal mucosal architecture and the association of collagenous colitis with intestinal villous atrophy has not previously been reported. Both cases responded to oral steroid therapy, but not to other previously recommended treatment regimens.

Atrophy↗

Macrophages and mast cells in chronic cholecystitis and "normal" gall bladders.

An attempt was made to quantify mast cells using toluidine blue and macrophages, with alpha-1-antitrypsin as a marker, from adjacent sections in the mucosa of two groups of gall bladders showing either minimal inflammatory change or established chronic cholecystitis. The results were expressed as cells/mm2 of mucosa. Alpha-1-antitrypsin showed both macrophages and mast cells, and therefore an estimate of macrophage numbers was obtained by subtraction. Mast cells comprised more than 60% of the alpha-1-antitrypsin positive cells. There were significantly (p greater than 0.001) more mast cells and macrophages in minimal inflammatory gall bladder mucosa than in established chronic cholecystitis.

Cell Count↗

Previously unreported abnormalities of dermal basement membranes and collagen fibrils in a patient with X-linked spondyloepiphyseal dysplasia tarda.

Electron microscopic findings of the skin biopsy of a boy with spondyloepiphyseal dysplasia tarda showed several novel features. The basement membrane of the epidermis showed focal irregular thickening and reduplication. The collagen fibres showed foci of fibrous long spacing collagen and marked variation in fibre diameter. Taken together these abnormalities have not been reported in any other condition.

Adolescent↗

Muscle fibre typing in the human pharyngeal constrictors and oesophagus: the effect of ageing.

Myosin-ATPase fibre typing revealed type 1 predominance (81%) in the human oesophagus and type 2 predominance in the pharyngeal constrictor (33% type 1) indicative of widely different functions. Fibre diameters were around 30 microns, significantly smaller than skeletal muscle. No significant change in mean fibre diameter or percentage of fibre type was seen with ageing, but atrophy and compensatory hypertrophy led to an increased variability in fibre diameters with age. No sex differences were observed, probably reflecting a similar usage of these muscles and contrasting with skeletal muscle.

Adolescent↗

Proteinase-like peptidase activities in malignant and non-malignant gastric tissue.

Activities of several proteinase-like peptidases have been determined in homogenates of malignant tissue, non-malignant tissue adjacent to the tumour (A-NM) and non-malignant tissue distant to the tumour (D-NM) from 17 patients undergoing surgery for histologically confirmed gastric malignancies. In homogenates of malignant tissues the activities of collagenase, cathepsin B, cathepsin (B+L), cathepsin H and cathepsin D were significantly higher than in D-NM tissues. By contrast, the levels of plasminogen activator were significantly lower in malignant tissues than in the D-NM tissues. Furthermore, the activities of collagenase-like and the cysteine-proteinase-like peptidases in the A-NM tissues were lower than in malignant tissues but higher than in the D-NM tissues. Separation of full-thickness non-malignant tissues into mucosal and seromuscular layers revealed significantly higher activities in the former. The elevated levels of these proteinase-like peptidases in homogenates of gastric cancer tissue suggests an important role for these enzymes in tumour invasion.

Aged↗

Lipid in the human gallbladder mucosa. A histochemical study by light and electron microscopy.

The distribution of lipids in the epithelium of 70 gallbladders removed for cholecystitis was investigated histochemically. Lipid was demonstrated in 68 gallbladders--cholesterol and its esters, triglycerides, free fatty acids and phospholipids. Neutral lipid was found at the bases of epithelial cells in 90 per cent and at the apex in 10 per cent of the gallbladders. Phospholipid was shown at the apex of epithelial cells in 64 per cent of the gallbladders. Electron microscopy in 12 specimens revealed cholesterol in and between the epithelial cells and in the underlying connective tissue.

Adolescent↗

The characterization and energetic potential of brown adipose tissue in man.

In adult man, brown fat can be detected in perinephric fat depots by visual inspection, electron microscopy and nucleotide binding to the tissue-specific uncoupling protein. The 32 kDa uncoupling protein is functionally active, showing a nucleotide-sensitive conductance to protons and an uncoupling response to fatty acids. The amount of uncoupling protein in human mitochondria is equivalent to that in a partially cold-adapted guinea pig, indicating some potential for thermogenesis. Respiratory capacity measurements indicate that the total perinephric fat in adult man can only account for one-fivehundredth of the whole-body response to infused noradrenaline. Thus, although brown fat has been found to be quantitatively important in animal studies, considerable caution must be exercised in extrapolating its significance to adult man.

Adipose Tissue, Brown↗

Cholesteryl esters in human gallbladder bile and mucosa.

Cholesteryl esters, identified by thin-layer and gas-liquid chromatography followed by mass spectroscopy in a few cases, were found in all human bile samples analysed. The amount varied extensively both in absolute concentration and when expressed as a percentage of the total cholesterol present. In about 30% of samples, the percentage of ester exceeded 4% of total cholesterol but there was no clear association with the presence of cholesterol gallstones or pigment stones, nor was there any association with the lithogenicity of bile.

Bile↗

Human gallbladder epithelium: non-specific esterases in cholecystitis.

Esterases active at neutral and acid pH have been demonstrated in human gallbladder epithelium. Reaction to a wide variety of inhibitors and activators suggests that they probably represent the same enzyme with two active sites while a close correlation with acid phosphatase, a known lysosomal enzyme, suggests a lysosomal localization. Esterase activity in the gallbladder mucosa in significantly decreased in chronic cholecystitis. Polyacrylamide gel electrophoresis suggests that cholesterol stones may be associated with a specific type of isoenzyme pattern. Esterase positive cells are present in the inflammatory infiltrate in the lamina propria of the gallbladder in most cases of chronic cholecystitis. Naphthol AS-D chloracetate esterase staining indicates that mast cells form a large part of the infiltrate. Bile acids modulate the enzyme activity in vitro. Although the exact substrate specificity is not known, several possibilities are discussed, implicating esterases in the pathogenesis of chronic cholecystitis.

Acid Phosphatase↗

The uptake of lead by small intestine, colon and gallbladder of the guinea pig in vivo.

The binding and uptake of lead by the jejunal, colonic and gallbladder epithelium of guinea pig has been investigated by electron microscopy. Binding occurred rapidly, the most marked by the microvilli was by the jejunum, followed by colon and gallbladder. The tracer was subsequently internalised in small membrane bound vesicles and smooth endoplasmic reticulum. By 30 min, it appeared in multivesicular bodies at all three sites.

Animals↗

Microwave fixation: its potential for routine techniques, histochemistry, immunocytochemistry and electron microscopy.

Human tissues, both biopsy and postmortem, and tissues from rodents were fixed by microwaves at various temperatures and compared against formaldehyde-fixed material. Conventional stains, including trichromes, worked well. Red cells were lysed, but white cells were fixed, thus permitting diagnoses of various inflammatory states. Malignant cells were equally well-preserved by the two methods. Histochemical investigations of mucosubstances, lipids and various hydrolases showed no significant difference between the two techniques. Some neurological stains, however, were not as good following microwave treatment. Immunocytochemical localization of IgA, IgM and IgG showed no significant difference after microwave fixation compared to that in tissues fixed with formaldehyde. Microwave fixation did not lead to a greater tissue shrinkage than that obtained with formaldehyde fixation. Both were significantly less than that following treatment with phosphate-buffered saline alone. Electron microscopy gave results which were interpretable, but with damage resembling early postmortem change. Microwave fixation is complete in approximately 1-2 min. The mechanism of fixation appears to be due to denaturation associated with disulphide bond formation and a decrease in solubility of proteins.

Animals↗

The uptake of cationized ferritin by guinea-pig gall bladder in vitro.

Tissue pieces of guinea-pig gall bladder were grown in vitro for up to ten days. Over this period at different intervals, specimens were exposed to cationized ferritin in culture medium for 1 h and then grown in ferritin free medium for up to 24 h. Other specimens were grown in culture medium containing cationized ferritin for up to 24 h. Both treatments produced a similar morphological sequence. Electron microscopy at all intervals studied showed the cationized ferritin was first bound by the apical cell membrane, clumped and internalized in large 400 nm vesicles. It was then carried to lysosomes in the region of the Golgi apparatus. Within 1 h, the marker was exocytosed in clumps into the lateral intercellular space, accumulating against the basement membrane in a roughly regular approximately 60 nm array. This pathway of cationized ferritin through the gall bladder epithelium is the same as that followed in vivo although the time taken was shorter in vitro.

Animals↗

The uptake of horseradish peroxidase and its subsequent redistribution by guinea pig gallbladder in vivo.

Horseradish peroxidase (HRP) was injected into the emptied gallbladder of guinea pigs at laparotomy. The fate of the HRP was observed by light and electron microscopy over the following 2 hr. Within 5 min. HRP appeared in pits and apical vesicles either as a rim of increased electron density or more evenly distributed throughout the pit or vesicle. The pits and vesicles were more frequently seen at the edge of the cell apex. From 15 min. HRP was identified in the basolateral cell space in increasing quantities with spill over through the basement membrane into the lamina propria: by 30 min. and 2 hr, little further change was observed. The quantity of nonspecific electron density in epithelial cell multivesicular bodies and residual bodies made the assessment of intracellular handling of the HRP impossible. Dilution of the HRP in the lamina propria made the identification of the eventual fate of the HRP difficult to determine.

Animals↗