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Biomedical subjects

M Colley

Publications and source records attributed to M Colley.

9 recordsLinked to original sources

The parent's perspective.

"A wonderful son of whom I am very proud": the mother of a 14 year old boy with attention deficit/hyperactivity disorder describes her experiences.

Adolescent↗

Mechanism of action of pulsed high electric field (PHEF) on the membranes of food-poisoning bacteria is an 'all-or-nothing' effect.

Salmonella typhimurium (CRA 1005) was more sensitive than Listeria monocytogenes (NCTC 11994) to pulsed high electric field (PHEF) treatment in distilled water (10, 15 and 20 kV/cm), 10 mM tris-maleate buffer pH 7.4 (15 kV/cm) and model beef broth (0.75% w/v: 15 kV/cm). Sublethal injury could not be detected using a selective medium plating technique, indicating that bacterial inactivation by PHEF may be an 'all-or-nothing' event. PHEF-induced membrane permeabilization resulted in increased UV-leakage and a decreased ability of L. monocytogenes to maintain a pH gradient.

Cell Membrane↗

In situ distribution of the beta-subunit of platelet-derived growth factor receptor in nonneoplastic tissue and in soft tissue tumors.

The distribution of the beta-subunit of platelet-derived growth factor receptor (PDGFR-beta) was assessed by a sensitive immunoalkaline phosphatase technique using the monoclonal antibody PR7212. Frozen tissue sections of several nonneoplastic human tissues were stained along with 42 soft tissue sarcomas, 16 benign soft tissue proliferations, and 7 epithelial tumors. In all nonneoplastic tissue, there was intense labeling of cell processes of perivascular fibroblasts or pericytes in and about the walls of muscular blood vessels and of fibroblast cell processes around some glandular and ductal epithelia. No PDGFR-beta was found in the endothelial cells of muscular arteries and veins, but cells of uncertain identity within some capillaries were immunoreactive and the possibility that endothelial cells of some small capillaries express PDGFR-beta could not be excluded. In kidney there was strong labeling of glomerular mesangial cells and interstitial fibroblasts. Some histological types of soft tissue sarcomas were uniformly and strongly labeled with anti-PDGFR-beta, but other types were infrequently labeled or unreactive. The order of decreasing frequency and strength of labeling of the various types of benign and malignant soft tissue proliferations was as follows: benign fibromatosis and neurofibroma greater than malignant fibrous histiocytoma greater than liposarcoma greater than leiomyosarcoma greater than rhabdomyosarcoma. No tumor cell labeling was detected in epithelioid, synovial or clear cell sarcomas, leiomyomas, or carcinomas, but there was usually strong labeling of fibroblast and/or pericyte cell processes within tumor, especially around blood vessels. We conclude that PDGFR-beta is strongly expressed by vascular and stromal tissues of most tumors and normal organs and by tumor cells of several types of soft tissue tumors and proliferations, most notably those of fibroblastic origin.

Blood Vessels↗

In situ distribution of oncogene products and growth factor receptors in breast carcinoma: c-erbB-2 oncoprotein, EGFr, and PDGFr-beta-subunit.

An increasing body of evidence suggests that breast tumour growth is mediated by oncogene products and growth factors which are or which act through cell surface receptors. The aims of the present study were to determine how three of these receptors, c-erbB-2 protein, epidermal growth factor receptor (EGFr) and the beta-subunit of platelet-derived growth factor receptor (PDGFr-beta-subunit), can effectively be demonstrated by immunohistochemical methods in breast tumors, how these receptors are distributed at the cellular level and how their expression correlates with well-established prognostic indicators including hormone receptors and proliferative index. We examined frozen tissue sections of 50 invasive human breast carcinomas, including 45 ductal, four lobular, and one mucinous tumours, by immunocytochemical methods to determine the in situ distributions of c-erbB-2, EGFr, and PDGFr-beta-subunit. We compared staining for c-erbB-2 protein in frozen sections with that in paraffin sections of the same 50 tumours. The immunohistochemical labelling results were compared with tissue hormone receptor content and growth fraction determined by Ki-67 labelling. Strong labelling of tumour cells in frozen sections was detected in 22% of cases, all of the ductal type, stained with rabbit antiserum to c-erbB-2. Labelling for c-erbB-2 protein was generally weaker in paraffin sections than in frozen sections and in six of 11 positive cases, specific staining could be detected only in frozen sections. In immunostains with monoclonal antibody to EGFr, rare cells within tumour were labelled in 60% of the carcinomas. Using a monoclonal antibody to the beta-subunit of PDGFr, consistent labelling of fibrillary cellular processes in the walls of blood vessels and in fibrous stroma around tumour cell nests was detected, but there was no labelling of tumour cells themselves. C-erbB-2 oncoprotein positive tumours were found to be more often oestrogen receptor negative (P less than 0.005) or oestrogen and progesterone receptor negative (P less than 0.01) than c-erbB-2 negative tumours. No significant correlation was observed between c-erbB-2 expression and Ki-67 growth fraction.

Adenocarcinoma, Mucinous↗

Assessment of hormone receptors in breast carcinoma by immunocytochemistry and image analysis. I. Progesterone receptors.

Frozen sections of 30 breast carcinomas were stained for progesterone receptors (PRs) using a rat monoclonal primary antibody and an alkaline phosphatase-antialkaline phosphatase technique. The micro-TICAS image analysis system was used for evaluation of the staining, with the results obtained by image analysis compared with the results of biochemical assays for PR. Strong positive/negative concordance (90%) was observed between the immunohistochemical and biochemical assays. However, the numerical values of the positive cases in the two assays did not correlate well, possibly because the biochemical assay does not take tumor cellularity into account. Three PR distribution patterns, designated A, B and C, were identified by image analysis among the breast tumors. In the type A pattern, tumor cell nuclei were diffusely and uniformly labeled. In type B, both clearly negative as well as distinctly positive cells were present. In type C tumors, a broad range of labeling reactions (from negative to intensely positive) was observed. These results imply (1) that the PR content of human breast carcinoma may be accurately and objectively assessed by the image analysis of immunohistochemically stained frozen sections, (2) that image analysis may provide a more accurate estimate of the cellular content of PR than do biochemical assays and (3) that PR distribution patterns obtained through image analysis permit the consistent appraisal of intratumoral heterogeneity of PR expression, which is potentially of prognostic importance.

Breast Neoplasms↗

Assessment of hormone receptors in breast carcinoma by immunocytochemistry and image analysis. II. Estrogen receptors.

Frozen sections of 30 invasive breast carcinomas were stained for estrogen receptors (ERs) and the tumor cell proliferative rate by an immunoalkaline phosphatase technique. The stained sections were evaluated for ER by the microTICAS image analysis system. Seventeen tumors were ER positive and 13 were ER negative by image analysis. There was 93% concordance between the ER results obtained by image analysis and those obtained by biochemical methods. One case that was ER negative by image analysis was weakly positive by biochemical assay; a second case was ER positive by image analysis but ER negative by biochemical assay. Twelve of the 17 ER-positive tumors were diffusely positive while 5 displayed considerable intratumoral heterogeneity, with tumor cells exhibiting a broad range of intensity of receptor expression. In most cases, the image analysis ER status coincided with the progesterone receptor (PR) status, but in a large minority of cases (41%) the ER status and the PR status differed. Tumors with a high growth fraction (greater than 30%), as measured by Ki-67 immunostaining, were uniformly ER negative. The results of this investigation suggest that immunohistochemical staining of frozen sections for ER aided by automated image analysis (1) reliably detects the receptor in breast carcinoma, (2) allows for the assessment of heterogeneity within tumors and (3) may be used as part of a panel of antibodies to markers of potential prognostic importance in a single small tissue sample.

Breast Neoplasms↗

Synthesis and pharmacological evaluation of some 6-substituted 7-methyl-1,4-dioxa-7-azaspiro[4.5]decanes as potential dopamine agonists.

Three 7-methyl-1,4-dioxa-7-azaspiro[4.5]decanes that contained either the benzyl, 3-indolylmethyl, or 4-indolylmethyl group at the 6-position were synthesized via alkylation of the pyrrolidine enamine of the key intermediate, ethyl 3-oxopiperidine-1-carboxylate. The spirodecane derivatives were evaluated for in vivo central and peripheral dopamine agonist activity. None of the compounds displayed central nervous system activity; however, the 4-indolymethyl analogue exhibited potent dopamine agonist activity in the cat cardioaccelerator nerve assay and possesses an ID50 of 0.095 mumol/kg compared to apomorphine, which possesses an ID50 of 0.0348 mumol/kg in the same assay.

Alkylation↗

Reproduction of end-location and distance of movement in early and later blinded subjects.

This study examined the ability of early and later blinded subjects to reproduce the end location and distance of preselected arm movements of two different amplitudes (approximately 30 degrees and approximately 60 degrees). Both groups were found to reproduce end location with greater accuracy and less variability than distance. The early blinded subjects were less accurate however, and more variable in their reproductions of both movement cues than the later blinded subjects. The complications of these findings for the role of visual representation in memory for movement are discussed.

Journal Article↗

Attentional bias and visual field asymmetry.

In mixed list tachistoscopic presentation of abstract words and random shapes, the probability of word and shape stimuli was varied to generate attentional bias and selective activation of the left or right hemispheres. While a right visual field advantage in accuracy was observed for words, and an effect of stimulus probability was observed across both visual fields in reaction time, no interactions were found between attentional bias and visual field asymmetry. The results can therefore be explained without reference to the attentional model and did not provide evidence of hemispheric activation or priming.

Adult↗