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Biomedical subjects

G O'Dowd

Publications and source records attributed to G O'Dowd.

13 recordsLinked to original sources
PubMed2002

Vasorelaxant properties of isolated human radial arteries: comparison with internal mammary arteries.

Radial arteries, used in revascularisation surgery, are prone to spasm. We have examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP) channel openers to cause vasodilation, and to attenuate contractions due to depolarisation and receptor activation in radial and mammary arteries used in coronary artery bypass graft surgery. Two to three millimetre rings of artery obtained from patients at surgery were studied in organ baths in vitro. Constriction to KC1 and phenylephrine was examined before and again after treatment of the rings with drug or vehicle. Calcium channel blockers were the only compounds to inhibit contractions to both KC1 and phenylephrine. Sodium nitroprusside attenuated constriction to phenylephrine but not KC1 in both vessels. K(ATP) channel openers similarly attenuated constriction to phenylephrine in radial arteries but were much less effective in mammary arteries. These studies support the continued use of calcium blockers after revascularisation with radial artery but suggest that other classes of drug may be as effective at minimising spasm due to receptor mediated constriction.

Adult↗
PubMed1999

beta-catenin expression in primary and metastatic colorectal carcinoma.

beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.

Adult↗
PubMed1999

Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein.

Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease. The normal physiological role of beta-amyloid precursor protein in the brain was evaluated in a cross-sectional analysis of mice deficient in beta-amyloid precursor protein. Compared with wild-type control mice the beta-amyloid precursor protein-null mice developed age-dependent deficits in cognitive function and also had impairments in long-term potentiation. In addition, the brains of the beta-amyloid precursor protein-null mice had marked reactive gliosis in many areas, especially in the cortex and hippocampus. A subpopulation of mice (n = 15) died prematurely (between three and 18 months of age). Analysis of another six mice from the same population that were showing weight loss and hypolocomotor activity exhibited a marked reactive gliosis as detected by immunoreactivity for glial fibrillary acidic protein and a profound loss of immunoreactivities for the presynaptic terminal vesicle marker proteins synaptophysin and synapsin and the dendritic marker microtubule-associated protein-2 in many brain areas, but most predominantly in the cortex and hippocampus. These results suggest that normal beta-amyloid precursor protein may serve an essential role in the maintenance of synaptic function during ageing. A compromise of this function of the beta-amyloid precursor protein may contribute to the progression of the memory decline and the neurodegenerative changes seen in Alzheimer's disease.

Aging↗
PubMed1998

Observations on pathology trends in 62,537 prostate biopsies obtained from urology private practices in the United States.

OBJECTIVES: To evaluate pathology trends of 62,537 first-time prostate needle-core biopsies submitted by office-based urologists, processed at a single pathology laboratory. METHODS: Prostate biopsy cases obtained over a 2-year period were assessed. Patient information included age, digital rectal examination (DRE) status, and prostate-specific antigen (PSA) serum levels. Biopsy pathology results included the number of tissue samples per case, Gleason score, presence of Gleason grades 4 or 5, percent of biopsy length with evidence of cancer, number of samples with cancer per biopsy, and determination of DNA ploidy status using microspectrophotometry. RESULTS: Adenocarcinoma, suspicious lesions, and isolated high-grade prostatic intraepithelial neoplasia (PIN) were diagnosed in 38.3%, 2.9%, and 4.1% of the biopsies, respectively. For each serum PSA and age range assessed, the positive biopsy rate and incidence of critical pathologic features increased consistently. The average percentage of biopsy length with evidence of tumor, the percentage of cases with Gleason grades 4 or 5, and the percentage of cases with an abnormal DNA ploidy all decreased significantly over the 2-year period (P <0.01). CONCLUSIONS: The number of tissue cores and anatomic sites (locations) being sampled per biopsy are increasing. The tumor size detected and percentage of cases with Gleason grades 4 and 5 are decreasing. There has been a slight increase in the number of biopsies performed on men younger than 60 years of age and a slight decrease in biopsies performed on men older than 70 years of age. The decline in meaningful pathologic features observed in biopsies over time may be clinically relevant to improved disease management.

Aged↗
PubMed1997

c-erbB2 and p53 expression are not associated with stage progression of gastric cancer in Britain or Japan.

The results of surgical treatment for gastric cancer are apparently better in Japan than in Western countries. It has been proposed that this is because of a biological difference between the tumours in Japan and in the West. We have previously reported very similar frequencies of positive immunohistochemical staining for the c-erbB2 oncogene and mutant p53 proteins in British and Japanese gastric cancers, findings which do not seem to support the 'biological difference' hypothesis. We realized that these studies did not rule out differences in the mechanism of cancer progression which might show themselves by a different association between p53 and c-erbB2 expression and stage in the two populations. We therefore re-analysed our data to look for differences in the frequency of p53 and c-erbB2 expression in the British and Japanese populations. Comparison of fixed tissue from 88 British and 89 Japanese tumours showed no significant association of c-erbB2 or p53 with stage progression in either population. Logistic regression showed no difference between the two populations in the relationship between stage and oncogene expression. These results do not support the idea of biologically different cancers in Japan and Britain. Other possible explanations for the difference in results such as the stage migration effect, better efficacy of Japanese-style surgery, or a difference in the host resistance to cancer in the two countries should be considered.

Humans↗
PubMed1995

Absence of overexpression of p53 protein by intestinal carcinoid tumours.

A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and overexpression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti-p53 protein antibody D07, overexpression was absent from a series of 22 intestinal carcinoid tumours (ten ileal, nine appendiceal, and three colorectal), nine overtly malignant, but was readily demonstrable in five of five colorectal adenocarcinomas, five of six cloacogenic carcinomas, and four of five squamous carcinomas of the anal canal used as controls. These observations are in keeping with previous similar studies of pulmonary carcinoid tumours and suggest possible differences in the pathogenesis of such neoplasms in comparison with non-endocrine differentiated tumours arising at equivalent sites.

Carcinoid Tumor↗
PubMed1995

Helicobacter pylori infection increases following cholecystectomy.

Cholecystectomy is frequently linked with duodenogastric reflux and gastritis but its effect on Helicobacter Pylori (H pylori) infection has not been examined. In a prospective study, twenty two patients with documented cholelithiasis underwent upper gastrointestinal endoscopy and biopsy and 24hr dual channel pH monitoring prior to cholecystectomy and again at 3-6 months post-operatively. The antral biopsies were histologically assessed for H pylori and gastritis and awarded an alkaline reflux score. The number of patients with H pylori infection increased from 7 (32%) preoperatively to 15 (68%) post-cholecystectomy (p < 0.05). Cholecystectomy was also associated with an increase in the incidence of gastritis from 7 to 15 (p < 0.05). The increase in H pylori infection rate occurred in association with an increase in the percentage time gastric pH > 4 in the supine position, from 9.6 (2.2) to 22.2 (4.8) percent, (p < 0.01). The median chemical gastritis score, however, did not change significantly following surgery [8(3-11) vs 7(3-11)]. Seven patients remained symptomatic following cholecystectomy all of whom were H pylori positive and had gastritis. H pylori can survive in the alkaline environment which follows cholecystectomy and may contribute to the post-cholecystectomy syndrome.

Adult↗
PubMed1994

Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett's esophagus.

BACKGROUND: This study examined the effect of the lower esophageal milieu on the healing of a mucosal defect. METHODS: With a canine model a mucosal defect was created in the lower esophagus, and acid reflux was promoted by a cardioplasty and pentagastrin injection in 10 animals. At 3 months the regenerated mucosa was excised and underwent histologic examination. Six of these animals underwent an antireflux procedure, had their acid secretion suppressed, and were followed up for a further 3 months, at which time they were killed and the entire esophagus underwent histologic examination. RESULTS: When reflux was stimulated, healing of the mucosal defect was by columnar epithelium alone in seven of 10 animals. After reflux control in six animals healing was again by columnar epithelium, but in all six cases islands of squamous epithelium occurred. Histologic examination showed both types of regenerating epithelium to be in continuity with the ducts of the esophageal glands, lined in their proximal two thirds by columnar and in their distal one third by squamous cells. CONCLUSIONS: It is suggested that the type of regenerating epithelium is determined by the depth of injury to mucosa or gland ducts. If both cell types survive, a mixed pattern of regeneration may occur, but columnar repair will usually predominate because of its more rapid turnover. If the squamous cells of the mucosa and ducts are destroyed, however, repair will be by columnar epithelium alone.

Animals↗
PubMed1988

The utility of cytodiagnostic urinalysis for monitoring renal allograft injury. A clinicopathological analysis of 87 patients and over 1,000 urine specimens.

Cytodiagnostic urinalysis was tested to determine its utility in the evaluation of allograft dysfunction in renal transplant patients. Specimens were prepared using the Papanicolaou stain on cytocentrifuge preparations of standardized quantities of urine. Differential counts of blood cells (neutrophils, lymphocytes, red cells), renal tubule cells (convoluted, collecting duct, necrotic), and casts (i.e. hemoglobin, renal tubule cell) were included in the sediment evaluation. Receiver operating characteristic curves demonstrated collecting duct cell exfoliation at 20 per 10 hpf to be a more sensitive and specific reflector of acute rejection than lymphocytes at their optimum decision point of 13 per 10 hpf. Sixty-four percent of cytodiagnostic urinalysis diagnoses preceded the clinical diagnoses. Ciclosporin nephrotoxicity was differentiated by the exfoliation of renal tubule convoluted cells in excess of collecting duct cells. The advantages of this technique over membrane-filter or phase-microscopic techniques for examining urine sediment of both transplant and nephrology patients include improved sensitivity and specificity in identification of sediment elements and reliable quantitative data for use in detecting renal disease and for monitoring therapy.

Cyclosporins↗