Biomedical subjects
Publications and source records attributed to I McColl.
This review examines the effect that a small chromosome deletion affecting a specific DNA sequence may have in producing a state of 'hemizygosity' for a gene or genes, and so triggering malignancy of the cells concerned. The association between such deletions and a variety of cancers will be considered and the implications for clinical practice will be outlined.
A study of 169 unilateral amputees under three Disablement Services Centres was performed. The study comprised 88 above-knee, 54 through-knee and 27 Gritti-Stokes amputations. Satisfactory rehabilitation occurred in 33 per cent of above-knee, 62 per cent of through-knee and 44 per cent of Gritti-Stokes patients (56 per cent overall). The better rehabilitation of through-knee versus above-knee amputees (P less than 0.02) was also found in a group of patients matched for comparable age and duration of amputation as well as in a group of age-matched vascular amputees. Through-knee amputees relied significantly less on wheelchairs than above-knee (P = 0.016) and Gritti-Stokes (P = 0.05) amputees. The prosthesis used for the through-knee and Gritti-Stokes amputations was considered unsightly in 50 per cent of cases (versus 31 per cent for the above-knee prosthesis). The superior rehabilitation with through-knee amputations should prompt us to improve both our technique for this amputation and the prostheses currently available. A through-knee amputation should be performed in preference to an above-knee amputation in the case where either is surgically possible, and a below-knee amputation not feasible.
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The incidence of pancreatic cancer is increased in patients who have undergone gastric surgery. An animal model is described in which pancreatic hyperplasia and adenoma formation developed within 56 weeks. The effects of a simple gastrojejunostomy were compared with those after a split gastrojejunostomy, in which the jejunum was transected and the two limbs implanted separately into the greater curvature of the glandular stomach 1 cm apart. After 56 weeks no animals in the simple gastrojejunostomy group had pancreatic hyperplasia whereas all 10 animals in the split gastrojejunostomy group had generalised pancreatic hyperplasia with macroscopic nodules. Microscopy of the nodules showed that in nine animals hyperplastic nodules had developed, and four of these also had adenomatous nodules. The remaining animal had enlarged lymph nodes. Pancreatic hyperplasia was associated with jejunal hyperplasia. Jejunal morphometry showed that the villus height was doubled and the villus height:crypt depth ratio was higher in the split gastrojejunostomy group compared with those animals with a simple gastrojejunostomy. This finding represents a new model for the investigation of pancreatic neoplastic change.
The management of caustic and peptic oesophageal strictures refractory to medical treatment and repeated dilatations continues to be a challenge. Colonic interposition with subtotal oesophagectomy is felt by many surgeons to be the best treatment. Complications in the short and long term are, however, frequent. We report a case of a colonic carcinoma originating in a colonic interposition and growing up into the oesophageal remnant.
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This study was designed to investigate the role of duodenogastric reflux in the genesis of gastric stump carcinoma in the rat. Carcinoma was not detected in any of the 11 control animals and in only one animal with a Roux diversion. In contrast seven of 12 animals with duodenogastric reflux developed carcinoma (p less than 0.01 and p less than 0.05 respectively). In order to determine which fraction of the reflux was implicated in the malignant process, animals with reflux of bile alone or pancreaticoduodenal secretions alone were studied. No carcinomas were found in 11 animals with bile reflux alone, but carcinoma was detected in 10 of 14 animals with reflux of pancreaticoduodenal secretions (p less than 0.01). The findings confirm that duodenogastric reflux is an important factor in the malignant process, and imply that the pancreaticoduodenal component, not bile is responsible.
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Incorporation of L-[U-14C]leucine and of D[U-14C]glucose into proteins of fresh human gastric mucosa in vitro was studied after incubation of homogenized tissue and of intact mucosal pieces. CsCl centrifugation was used to separate high-density mucus glycoproteins from other mucosal proteins, and the macromolecular nature of radioactive mucosal glycoprotein fractions was confirmed by SDS/polyacrylamide-gel electrophoresis and autoradiography of the polyacrylamide gels. In all experiments a substantial proportion of total incorporated radioactivity was associated with gastric-mucosal glycoprotein fractions (CsCl fraction L3), indicating their biosynthesis. Radioactivity of these fractions was shown to co-chromatograph with carbohydrates when fractionated either directly or after reduction and alkylation (1) Sephadex G-200 chromatography in the excluded fractions and (2) by DEAE-cellulose ion-exchange chromatography. On incubation of intact mucosa, the major portion of radioactivity associated with the glycoprotein fractions of both leucine- and glucose-labelled specimens was secreted into the mucosal media during the course of the experiment. It is suggested that biosynthesis of mucus in vivo by gastric mucosa may be associated with rapid secretion of the synthesized macromolecules into the lumen of the stomach and that investigations of the metabolic processes within the mucosa should consider the products of secretion of the tissue. Incorporation of L-[U-14C]leucine implies biosynthesis of the polypeptide components of the macromolecules.
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Human gastric mucosa was removed at gastrectomy for duodenal ulcers. Intact mucosal layer and homogenized mucosal scrapings were incubated in vitro with L-[U-14C]leucine and with D-[U-14C]glucose and incorporation of radioactive label into IgA was investigated. 14C of both the precursors was incorporated into tissue IgA when intact gastric mucosa was incubated indicating synthesis of IgA by the tissue in vitro. IgA isolated from the media which bathed the luminal sides of the mucosae during incubation was also radioactive implying secretion of the newly-synthesized immunoglobulin into the media. When mucosal scrapings were incubated as homogenized suspensions, radioactivity of IgA was below the level of sensitivity of our methods. For analysis, IgA was separated from the bulk of radioactive mucosal proteins of the samples by isopycnic CsCl gradient centrifugation followed by gel filtration on Sephacryl S-200 or Sephadex G200 and then Sepharose 4B. The IgA-enriched Sepharose 4B fractions were subjected (1) to immunoprecipitation in agar gels by double diffusion against specific anti alpha-chain serum and (2) to SDS-polyacrylamide gel electrophoresis after reduction. Radioactivity of precipitated IgA, and of the protein band which corresponds to the alpha-chain of IgA on SDS-PAGE gels, was demonstrated autoradiographically. It is suggested that in vivo the mucosa is involved in local synthesis of the constituent IgA of gastric mucus.
A 70-year-old woman developed dark reddish blue pigmentation in scarred areas of discoid lupus erythematosus after taking clofazimine intermittently over a period of 10 years. Although light microscopy of routinely processed tissue failed to define the cause of the pigment, fluorescent microscopy showed vivid red deposits concentrated around larger vessels within the dermis. These deposits were shown to correspond to birefringent red clofazimine crystals on fresh frozen sections. Although the hyperpigmentation may clinically resemble melanin, biopsy specimens from our patient revealed a loss of melanin pigment in lesional skin, suggesting a primary role for clofazimine in producing the color changes observed.
Peripheral aneurysms of the leg are rare, and nearly always involve the popliteal artery. We describe the unusual presentation of a swollen leg caused by a large false aneurysm of a branch of the posterior tibial artery. This developed in the absence of either a history of trauma, local infection or infective endocarditis.
The aim of this work was to investigate the involvement of lipids as possible components of the gastric mucosal barrier by studying the synthesis and secretion of lipids by the epithelial cell lining of gastric mucosa and the effect of salicylate on these processes. O-Acetylsalicylic acid reversibly reduced in vitro incorporation of [U-14C]acetate and of DL-[2-14C]mevalonic acid into lipids by isolated epithelial cells and by intact mucosa of guinea pig stomach, indicating reversible inhibition of lipid synthesis by the tissue in the presence of the drug. Inhibition of incorporation of both precursors into total lipids, into their fatty acid components, and into cholesterol is demonstrated.
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Incorporation of L-[U-14C]leucine into proteins is taken to indicate the synthesis of proteins by guinea pig gastric mucosa. Ethanol reduced the synthesis of proteins in vitro by homogenized mucosa, by isolated gastric epithelial cell preparations and by intact tissue. Intact stomach wall incubated without ethanol in phosphate buffered saline showed progressively increasing incorporation of the precursor into tissue proteins and into proteins which were secreted into the mucosal incubation media. On isopycnic CsCl gradient fractionation radioactive tissue proteins were found at the top of the gradient (fraction L1, sp.gr.1.11-1.20) while radioactive secreted proteins sedimented to the bottom of the gradient as the carbohydrate rich high density gastric mucosal glycoprotein fraction L3 (sp.gr.1.29-1.33). Ethanol significantly but reversibly reduced the incorporation of radioactive leucine by intact mucosa into both the tissue proteins and the secreted proteins. Uptake of the precursor into the intracellular acid soluble pool was not impaired by ethanol and no significant differences were detected in the specific activities of free intracellular leucine between the ethanol treated samples and the corresponding controls. It is suggested that the ulcerogenic nature of ethanol may be associated with inhibition of the synthesis of proteins within mucosal epithelium leading to reduction in the output of mucosal secretory glycoproteins with subsequent impairment of the cytoprotective properties of the dynamic mucous barrier.
An attempt was made at correcting the specific lysosomal enzyme deficiencies in 7 children with Hunter's or Hurler's diseases by transplantation of fetal fibroblasts. In spite of pretreating the young patients with stored blood, following a procedure employed successfully to avoid rejection of kidneys from incompatible donors, the use of serum-free media for culturing the cells before being harvested and incubation of the cells with chorionic gonadotrophin, the transplantation of fetal fibroblasts was not associated with biochemical or clinical changes. None of the seven patients showed immune reactions against the transplanted cells, HLA antigens, or the missing enzymes.