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Biomedical subjects

M Corcoran

Publications and source records attributed to M Corcoran.

At least 19 recordsLinked to original sources
PubMed1996

Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic.

Tumor cell invasion is now viewed as dysregulated physiologic invasion. Investigators have started to define the molecular events that are involved in this process. We find that there are many functional similarities with molecular events involved in physiologic process such as angiogenesis and wound healing. Matrix metalloproteinase activity is a common denominator in these pathologic conditions and in normal responses. Studies using endogenous metalloproteinase inhibitors suggest that targeting matrix metalloproteinase activity may prevent tumor cell dissemination. The development and pre-clinical testing of novel, low molecular weight matrix metalloproteinase inhibitors support this concept and suggest that an exciting new era of cancer therapy is on the horizon.

Endopeptidases↗
PubMed1996

Trisomy 12 and structural abnormalities of 13q14 occurring in the same clone in chronic lymphocytic leukaemia.

Trisomy 12 and deletions or translocations of 13q14 are the commonest cytogenetic abnormalities in chronic lymphocytic leukaemia but rarely co-exist in the same patient. We describe eight patients from a series of > 400 patients with CLL in whom trisomy 12 and t or del 13 occur in the same clone. Using FISH we have identified clones with trisomy 12 alone, t or del 13q14 alone and both abnormalities, in each of the patients studied. This implies that neither trisomy 12 nor t or del 13q14 is the initiating event in leukaemogenesis, but does not exclude the possibility of a submicroscopic abnormality of 13q14 occurring as an early event.

Aged↗
PubMed1995

Understanding the family perspective: an ethnographic framework for providing occupational therapy in the home.

This article presents a framework for providing occupational therapy services to family members caring for elderly persons in the home that is based on four key principles derived from ethnographic methodology: identification of an informant, use of an emic (insider) approach, engagement in self-reflection, and interpretation of information. The underlying strategy is to use these principles to derive an understanding of the personal meaning of caregiving, the way in which care is provided, and the specific aspects of caregiving that are problematic from the perspective of the family member. Services are then developed that reflect individual need as expressed by the caregiver and that fit the fundamental values and belief system of the family unit. A case example is presented to illustrate the framework in action in a home situation with family members caring for an elderly person with dementia.

Aged↗
PubMed1993

Transforming growth factor-beta mediates IL-1-dependent induction of IL-1 receptor antagonist.

Transforming growth factor-beta (TGF-beta) is a potent immunomodulatory molecule that promotes inflammation through recruitment of monocytes and induction of IL-1 and other cytokines. These proinflammatory processes may be modulated by the ability of TGF-beta to induce de novo synthesis and secretion of an IL-1 receptor antagonist (IL-1ra) that binds to and blocks IL-1 receptors. In this study, we show that the addition of TGF-beta to human peripheral blood monocytes induced the sequential transcription of the 1.8-kb mRNA for IL-1 beta and for IL-1ra. The expression of detectable mRNA and synthesis of IL-1 beta peptide routinely preceded that for IL-1ra, suggesting possible dependency of IL-1ra generation on IL-1 beta. Antibody to IL-1 blocked TGF-beta induction of IL-1ra mRNA expression demonstrating an unique IL-1-dependent induction of its own antagonist. Confirmatory evidence that IL-1 participates in the generation of IL-1ra was obtained when exogenously added IL-1 induced and, IL-1 receptor antagonist blocked, IL-1ra transcription. Thus, these data suggest that TGF-beta, after release at a site of inflammation, induces synthesis of IL-1 that participates in the initial cytokine cascade central to an inflammatory response, and then triggers the generation of its own natural inhibitor by autocrine or paracrine pathways. This TGF-beta-induced IL-1-dependent induction of IL-1ra may provide a negative feedback loop, thereby promoting the resolution of an inflammatory response.

Animals↗
PubMed1993

A reappraisal of serial isotope bone scans in prostate cancer.

Carcinoma of the prostate is the commonest malignancy of the genitourinary tract in the male and is frequently associated with metastatic bone disease. Serial isotope bone scans for screening secondary deposits are not cost-effective. We have evaluated the serum prostate markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as an alternative to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those who presented with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study period. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 micrograms/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 micrograms/l was 90.6%. During the follow-up period the sensitivity was 94.4%, the positive predictive value 100% and the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. When compared with PAP, PSA was found to be a statistically superior marker of bone metastases both at presentation and follow-up (p < 0.05). We recommend that PAP measurements are no longer necessary and should be replaced by PSA, and that serial serum PSA estimations should determine the need for future isotope bone scans in the patient with established prostate cancer.

Acid Phosphatase↗
PubMed1993

A curriculum based on systems theory.

This paper describes an entry-level curriculum based on systems theory that was designed to promote integrated thinking and a shared image of practice among all of the members of an educational community that included students, faculty, and clinicians. Initiated in 1983, the program integrates occupational therapy theory, critical thinking, and knowledge about person-environmental transactions with traditional medical, biological, psychological, and sociological course work to create a unique educational experience. The curriculum model is based on a spiral learning process that encourages integrated thinking. Furthermore, all concepts are systematically tied to the occupation core, the central theme of the program. Fieldwork is used to reinforce ideas presented in the classroom and features discrete learning experiences where students demonstrate their integration of knowledge and skills. In an evaluation of the program, responses from 78 clinician, 51 alumni, and 132 student questionnaires; feedback from 132 fieldwork supervisors; and longitudinal data from 33 alumni confirmed that graduates are critical thinkers who appreciate the diverse needs of clients while demonstrating an appreciation for the curative effect of meaningful, goal-directed activities.

Curriculum↗
PubMed1991

Urinary cytology in the detection of bladder carcinoma.

We have analysed the accuracy of cytological examination of voided urine in a population of 265 patients presenting with suspected bladder lesions. Bladder carcinoma was confirmed by tissue histopathology in 51 patients. Of these, 42 were identified correctly by urinary cytology examination. Overall 34 patients were labelled as frankly malignant on cytology, of whom 2 were negative on final histology. 13 patients had been designated as suspicious however with 3 benign on final histological diagnosis. These data give a sensitivity for diagnosis of bladder cancer by urinary cytology of 82%, a specificity of 97%, a positive predictive value of 94%, and a negative predictive value of 96%.

Adolescent↗
PubMed1991

Automated image-based cytometry with fluorescence-stained specimens.

The combination of digitized microscopy, algorithms for object recognition and fluorescent labeling is a promising approach for reliable, quick, automated and cost-effective screening of clinical specimens. We describe two conceptually different algorithms for detecting objects in fluorescence microscopic images. One, which is partially automated, compares a mask that represents a typical object with every position in the image; the other, which is fully automated, calculates threshold intensities to segment the image into regions of objects and background. Applications of the algorithms in conjunction with a prototype image-based cytometer are demonstrated for determining the DNA ploidy distribution of cultured human endometrial cells and determining the DNA ploidy distribution and the fraction of cells expressing the E6 antigen of human papilloma virus serotypes 16 and 18 in a PAP smear. The encouraging results from this study suggest that automated image-based cytometry utilizing fluorescent stains will be a valuable asset for clinical screening.

Algorithms↗
PubMed1990

Effect of dipyridamole on transport and phosphorylation of thymidine and 3'-azido-3'-deoxythymidine in human monocyte/macrophages.

Dipyridamole (DPM), a commonly used coronary vasodilator and antithrombotic drug, was shown recently to potentiate the antiviral effect of 3'-azido-3'-deoxythymidine (AZT) in HIV-1 infected human monocyte-derived macrophages (M/M) in vitro. We report in the present study that in uninfected M/M, DPM markedly inhibited cellular uptake of [3H]thymidine (dThd) and its incorporation into the nucleotide pools, particularly the dThd-triphosphate pool. In contrast, DPM did not affect cellular uptake and phosphorylation of [3H]AZT. Since dThd counteracts the phosphorylation and antiviral action of AZT, these findings support the hypothesis that the potentiation of the anti-HIV effect of AZT is due, at least in part, to differential inhibition of nucleoside salvage.

Biological Transport↗
PubMed1990

Conditioned taste aversion and motion sickness in cats and squirrel monkeys.

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

Animals↗
PubMed1990

Urethral valves--treatment, results and urodynamic assessment.

Posterior urethral valves is an uncommon condition, but it poses many diagnostic and therapeutic problems. Long term follow up of these patients revealed that the majority of these boys have long term problems. In depth assessment of 10 boys with this problem revealed that their upper urinary tracts remained stable whereas urodynamic studies showed gross micturition abnormalities. Most methods of assessing the urinary tracts in these boys are invasive (eg. Intravenous urography, micturating cystography) and may indeed show no change in upper tract radiology despite marked abnormalities of micturition detected by urodynamics and which may require further investigation and treatment. We therefore recommend regular urodynamic assessment of these boys as it is accurate and initially non-invasive. Those boys with a detectable abnormality can progress to further studies.

Child↗
PubMed1987

Indications for investigation of post-micturition dribble in young adults.

The endoscopic and urodynamic findings in eight male patients in whom post-micturition urinary dribble (PMD) was either the sole or predominant urinary symptom have been reviewed. In three patients whose only symptom was PMD, both endoscopic and videocystometric examinations were normal. In the remaining five patients with additional urinary symptoms, a functional or anatomical abnormality of the lower urinary tract was found in every patient. We conclude that in the assessment of patients with PMD, endoscopic and/or urodynamic investigation is of value only in those patients with multiple urinary symptoms.

Adolescent↗
PubMed1984

Computer programs for handling nucleic acid sequences.

Programs have been developed that will accurately display restriction enzyme maps, open translational reading frames and the results of specific searches on a high resolution graphics terminal (Retrographics VT640). Many of our earlier programs have been upgraded to allow online access to GENBANK, the NIH data bank of DNA sequences and also to deal with sequences of any length. Progress has also been made in the automation of the DNA assembly programs.

Amino Acid Sequence↗