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Biomedical subjects

I C Talbot

Publications and source records attributed to I C Talbot.

At least 145 records · Page 8Linked to original sources

Brush border enzymes in coeliac disease: histochemical evaluation.

Two hundred and ninety four duodenal and jejunal mucosal biopsy specimens from patients with coeliac disease, treated and untreated, and other conditions were examined histologically and by histochemical staining for five peptidase and three disaccharidase enzymes to determine profiles of activity. Suppression of activity paralleled the histology with the following enzymes: lactase, trehalase, brush border endopeptidase, dipeptidyl peptidase II and isomaltase. Lactase, trehalase, and brush border endopeptidase were specifically suppressed in untreated coeliac disease and were diagnostically useful. Examination of a combination of enzymes is recommended.

Adolescent↗

Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients.

Multiple gastric and duodenal biopsy specimens from 102 asymptomatic patients with familial adenomatous polyposis, taken during a prospective endoscopic screening programme were examined. One hundred patients had microscopic gastroduodenal pathology, often in the absence of macroscopic lesions. Adenomas were found in 94 patients in the duodenum, in the second and third parts. Hyperplasia of villous and crypt epithelium was also seen, sometimes in the absence of adenomas: this may be a precursor of neoplastic change. In the stomach fundic gland polyps were the commonest abnormality, seen microscopically in 44 patients. Chronic antral gastritis was common in patients without fundic polyps. Gastric adenomas were present in six patients, all of whom also had duodenal adenomas. If duodenal adenomas in familial adenomatous polyposis have a similar malignant potential to those in the colorectum sequential endoscopy and biopsy are necessary to detect cancer in these patients.

Adenomatous Polyposis Coli↗

Fluorescent location of human colonic tumour cells by means of an enzyme-inhibitor complex.

We studied the enzymic status of the tumour cell surface protease, guanidinobenzoatase (GB) in frozen sections of a human colonic tumour grown in nude mice and also in human colons. Active enzyme was demonstrated by the binding of a synthetic fluorescent probe for the active centre of guanidinobenzoatase (GB). It was observed that tissue derived inhibitors of GB blocked the binding of this fluorescent probe and that enzyme inhibitor complex formation could be controlled by lowering the pH of the medium with lactic acid. The presence of an inhibitor of GB in the mouse tumour extract was taken advantage of by making two fluorescent derivatives of this inhibitor; both of which located GB on colonic tumour cells in frozen sections of human colon.

Aminacrine↗

Identification of a human ribosomal protein mRNA with increased expression in colorectal tumours.

A human ribosomal protein cDNA was selected from a normal colon cDNA library on the basis of overexpression in familial adenomatous polyposis. Nucleotide sequence analysis was used to identify this cDNA as corresponding to the human equivalent of the rat ribosomal protein L31 (HL31). We have quantified the expression of HL31 mRNA in colorectal tumours and found overexpression in 23 out of 23 cases. Our results indicate that HL31 is associated with a malfunction of normal growth regulatory mechanisms in these tumours, and suggest a role for HL31 in proliferation and neoplasia.

Adenocarcinoma↗

Anal and cervical intraepithelial neoplasia: possible parallel.

This study evaluated prospectively the use of an endoscope in examination of the anal canal for the detection of premalignant lesions. All patients underwent endoscopy and anal epithelial biopsy; the biopsy samples were examined histologically and human papillomavirus (HPV) DNA hybridisation was done. No evidence of anal intraepithelial neoplasia (AIN) was found in 20 control patients with anal fissure or fistula. Of 82 patients with anal HPV infection, 23 had evidence of AIN. The prevalence of AIN was significantly higher among homosexual than among heterosexual men (17 of 28 vs 1 of 26) with anal HPV infection. Of 28 women with anal HPV infection, 10 had cervical intraepithelial neoplasia (CIN); 5 of the 10 also had AIN, whereas no woman had AIN in the absence of CIN. The study shows that AIN occurs and can be diagnosed endoscopically in a manner similar to CIN. Further detailed prospective studies on the natural history of AIN and of groups at risk are required.

Adolescent↗

Upper gastrointestinal cancer in patients with familial adenomatous polyposis.

102 patients with familial adenomatous polyposis underwent upper gastrointestinal endoscopy as a screening test for gastroduodenal adenomas. 100 had duodenal abnormalities (dysplasia in 94, and hyperplasia in 6), usually in the second and third parts of the duodenum (91%). The periampullary area was abnormal in 87 of 97 patients who had a biopsy specimen taken from this site (dysplasia 72, hyperplasia 13, and inflammation 2). By contrast, gastric dysplasia was found in only 6 patients. Classification of duodenal polyposis on a 5-grade scale (stages 0-IV), based on polyp number, size, histology, and severity of dysplasia, showed that 11 had stage IV disease: these patients are at greatest risk of malignant change and require close surveillance. The pattern of dysplasia observed in the upper gastrointestinal tract resembled the pattern of mucosal exposure to bile.

Adenoma↗

In situ hybridization demonstration of poly-adenylated RNA sequences in formalin-fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe.

An in situ hybridization technique has been developed for assessing poly(A)+ RNA preservation in routine pathology specimens. The method detects poly-adenylated RNA sequences in tissue sections using a biotinylated polydeoxythymidine (poly d(T)) probe. The probe was prepared from single-stranded 25-30 base oligo d(T) and was biotinylated using the enzyme terminal deoxynucleotide transferase with biotin-11-dUTP and dTTP in the ratio 1:4. The hybridization protocol uses varying concentrations of proteinase K to unmask mRNA sequences and the biotin-labelled hybrids are demonstrated after hybridization under standard conditions by the application of streptavidin and biotinylated alkaline phosphatase. Alkaline phosphatase was visualized using a Fast Red naphthol-capture method and the sections were counterstained with haematoxylin. The results have confirmed that the method is specific for poly(A)+ RNA and shows that poly(A)+ RNA can be demonstrated in routine formalin-fixed sections using non-radioactive techniques with retention of morphology. It also provides a means of optimizing the hybridization conditions for specific mRNA probes and produces a staining pattern demonstrating the relative level of poly(A)+ RNA per cell which may reveal new information about cell activity and tissue function.

Base Sequence↗

Functional activity of intestinal epithelium demonstrated by mRNA in situ hybridization.

To elucidate the synthetic activity in relation to the morphology of the epithelial cells of the small and large intestine, in situ hybridization with a poly-deoxyribothymidine (poly d(T)) probe was applied to paraffin sections of formalin-fixed blocks. This effectively displays poly-adenylated RNA and, by implication, messenger RNA (mRNA). By minimizing proteinase K pretreatment, the relative concentrations of cellular mRNA were visualized. This revealed minimal mRNA in crypt columnar cells, and maximal mRNA in proliferating cells and in cells showing terminal differentiation. The latter include surface epithelial cells, endocrine cells, Paneth cells, and maturing, but not mature, goblet cells. The goblet cells showing positive hybridization can be regarded as active cells and show characteristic morphology. Such cells are particularly evident in untreated coeliac disease, remitting ulcerative colitis, and transitional mucosa. The proliferating cells showing increased hybridization include normal mitotically active crypt epithelium, regenerating epithelium in ulcerative colitis, adenomatous epithelium, and adenocarcinomatous epithelium. The similarity of hybridization between metaplastic polyp epithelium and surface colonocytes is consistent with the concept that metaplastic polyps are formed of cells showing premature terminal differentiation.

Adenocarcinoma↗

An electron microscope and immunohistochemical study of the intracellular location of Toxoplasma tissue cysts within the brains of mice with congenital toxoplasmosis.

The wall of intact Toxoplasma tissue cysts within the brains of mice with congenital toxoplasmosis was investigated. Smaller cysts were identified within the soma of neurones. With larger cysts, the contained cystozoites were shown by ultrastructural examination to be surrounded by a layer of microtubules; immunohistochemical staining revealed that this layer contained neurofilament protein. Interior to this layer was a much convoluted parasitophorus vacuole membrane; exterior was the host cell membrane. In most cases, synaptic plates were noted on the outer plasma membrane. In no instance were tissue cysts observed either within neuroglial cells or in the absence of host cells. These observations are discussed in relation to the pathogenesis of congenital toxoplasmosis in the brain.

Animals↗

Long-term survival after resection of ampullary carcinoma is associated independently with tumor grade and a new staging classification that assesses local invasiveness.

Long-term survival characteristics after resection for ampullary carcinoma are documented poorly. We have reviewed the clinical and histopathologic features of 23 long-term survivors who underwent resections between 1972 and 1984 (5-year survival rate, 52.1%). Twenty patients (87%) had intestinal type tumors and only two (9%) had papillary tumors. Associated adenomata were present in eight cases (35%) and distant ductular dysplasia was present in nine cases (39%). Long-term survival was correlated independently with tumor grade (P = 0.0031) and a new staging system that assesses local invasiveness (P = 0.0055). No correlation was found between survival and sex, tumor size, or presence of adenoma. Age was significant in univariate analysis (P = 0.0322) but not in multivariate analysis. A simple scoring system based on the grade and stage increased the predictability of survival (P = 0.0004). Application of this scoring system may allow an objective comparison of long-term survival results after resection from different series.

Adenocarcinoma↗

Host-parasite relationship in the brains of mice with congenital toxoplasmosis.

The wall of intact tissue cysts in the brains of mice with congenital toxoplasmosis was investigated using light and electron microscopy. Impregnation of the wall with reduced silver salts and protargol silver suggested that it was composed, at least in part, of components derived from the neuronal cytoskeleton. Electron microscopy extended these observations and revealed that intact cysts were separated from the extracellular compartment by a layer of neurofibrillae enclosed within the host cell membrane. It is suggested that this may be a means whereby intact Toxoplasma tissue cysts are protected from the host's immune response.

Animals↗

The histopathology and staging of carcinoma of the ampulla of Vater.

Review of 26 resected ampullary carcinomas revealed intestinal type adenocarcinoma in all but one and overtly papillary carcinoma in only one case. Co-existing adenoma of the ampulla was present in 11 cases, over half of which were low-grade carcinomas. Flat duct epithelial dysplasia was present in a further eight cases, the adenocarcinoma in only two of these being well differentiated. The estimated 5 year survival rate, overall, was 52% and, with well differentiated adenocarcinoma, 75%. We recommend a new staging system, based on extent of local and lymph node spread: I = invasion confined to wall of common bile duct; II = infiltration of duodenal or retroperitoneal tissues, excluding pancreas; III = infiltration of pancreas; IV = metastasis to nearby lymph nodes. Long-term survival correlates inversely with stage, both by univariate analysis and independently of grade, so that a simple scoring system, based on a combination of both grade and stage, is an excellent predictor of the long-term outcome, defining two groups, with 5 year survival rates of 79% and 0% (P less than 0.001).

Adenocarcinoma↗