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Biomedical subjects

R Walsh

Publications and source records attributed to R Walsh.

At least 19 recordsLinked to original sources
PubMed2007

Local involvement of the urinary bladder in primary colorectal cancer: outcome with en bloc resection.

BACKGROUND: Colorectal cancers that adhere to the urinary bladder require en bloc partial or total cystectomy to achieve negative tumor margins. METHODS: This prospective study evaluated the outcome of combined bladder resection for carcinoma of the colon or rectum at a unit specializing in gastrointestinal cancer. RESULTS: Patients (n = 63) with colorectal tumors adherent to the bladder at operation and without distal metastases were followed. Fifty-eight patients (92%) had tumors of the sigmoid colon or upper rectum. Operative morbidity and mortality rates were 18% and 1.5%, respectively. Histological staging demonstrated bladder adherence in 46% (29/63) and invasion in 54% (34/63). Overall disease-specific survival was 54%, with a mean follow-up of 7.6 (range 5-12) years. Five-year survival for margin negative patients was 72% (26/36) and 27% (4/15) for node negative and positive tumors, respectively. The bladder was closed primarily in 48 patients and reconstructed by enterocystoplasty in five, with ten patients requiring urinary diversion. CONCLUSIONS: En bloc bladder resection for adherent or invading tumors of the colon and rectum achieves good local control, but an infiltrative extravesical margin denotes poor prognosis. The potential for cure in completely excised node negative tumors is good. Bladder reconstruction is achievable in most patients.

Adult↗
PubMed2006

Local involvement of the urinary bladder in primary colorectal cancer: outcome with en-bloc resection.

BACKGROUND: Colorectal cancers that adhere to the urinary bladder require en-bloc partial or total cystectomy to achieve negative tumor margins. METHODS: This prospective study evaluated the outcome of combined bladder resection for carcinoma of the colon or rectum at a unit specializing in gastrointestinal cancer. RESULTS: Patients (n = 63) with colorectal tumors adherent to the bladder at operation and without distal metastases were followed. Fifty-eight patients (92%) had tumors of the sigmoid colon or upper rectum. Operative morbidity and mortality rates were 18% and 1.5%, respectively. Histological staging demonstrated bladder adherence in 46% (29/63) and invasion in 54% (34/63). Overall disease-specific survival was 54% with a mean follow-up of 7.6 years (range 5-12). Five-year survival for margin-negative patients was 72% (26/36) and 27% (4/15) for node-negative and -positive tumors, respectively. The bladder was closed primarily in 48 patients and reconstructed by enterocystoplasty in 5, with 10 patients requiring urinary diversion. CONCLUSIONS: En-bloc bladder resection for adherent or invading tumors of the colon and rectum achieves good local control, but an infiltrative extravesical margin denotes poor prognosis. The potential for cure in completely excised node-negative tumors is good. Bladder reconstruction is achievable in most patients.

Adult↗
PubMed2006

Synchronized, interactive teleconferencing with digital cardiac images.

St James's Hospital is a tertiary referral center for percutaneous intervention and cardiothoracic surgery for a number of referring hospitals. This article reports on the development and implementation of a synchronized, interactive teleconferencing system for cardiac images that links St. James's Hospital with a remote site (Sligo General Hospital) and overcomes the problems of transmission of large image files. Teleconferencing was achieved by setting up lossless auto transmission of patient files overnight and conferencing the next morning with linked control signals and databases. As a suitable product was not available, a commercially new software was developed. The system links the imaging databases, monitors and synchronizes progress through imaging sequences, and links a range of image processing and control functions. All parties to the conference are ensured that they are looking at the same images as they are played or at specific aspects of an image that the other party is highlighting. The system allows patient management decisions to be made at a weekly joint teleconference with cardiothoracic surgeons and interventional cardiologists from both sites. Rapid decision making was facilitated with 70% of decisions obtained within 24 h, and 88% within 1 week of their procedure. In urgent cases, data can be transmitted within 20 min of the diagnostic procedure. The system allows increased access to angiography for patients living in rural areas, and provides a more focused referral for revascularization. Participation of the referring cardiologist has improved the quality of decision making.

Academic Medical Centers↗
PubMed2006

Mitochondrial cytopathies, phenotypic heterogeneity and a high incidence.

Mitochondrial respiratory chain disorders account for significant and varied presentations in paediatric practice. The true prevalence of these disorders in the paediatric population is still not well documented with predicted geographic variation. We report a retrospective analysis over a seven year period of cases presenting to a tertiary care centre and associated clinical features. The overall prevalence of mitochondrial disorders in our population is higher than expected (1/9,000 births), explained in part by multiple presentations in a consanguineous subgroup of the population (Irish travellers).

Humans↗
PubMed2005

The roles of proteolysis and nuclear localisation in the toxicity of the polyglutamine diseases. A review.

The polyglutamine disorders consist of a group of nine neurodegenerative diseases with overlapping phenotypes, but which affect distinct neuronal subsets, causing neuronal dysfunction and death. In the majority of these, the causative proteins share no homology to other known proteins, or to each other apart from the polyglutamine tract. The polyglutamine tracts themselves are toxic over a disease-specific threshold, and this common feature has suggested a common pathogenesis. The pathogenic mechanism(s) of this group of diseases is hotly debated, with proteolytic cleavage and nuclear accumulation both popular hypotheses. Such cleavage is thought to release toxic fragments containing an expanded polyglutamine tract, and may itself facilitate entry of cytoplasmic polyglutamine proteins to the nucleus. Numerous downstream effects including accumulation and apoptotic activation, misfolding, aggregation, and sequestration of other proteins including transcription factors and chaperones may then be initiated. It is uncertain whether all of the polyglutamine proteins undergo cleavage in vivo. Even in those in which proteolysis has been demonstrated, it remains unclear to what extent this also occurs in the wild-type proteins, or whether it is dependent on, or increased by, the expanded polyglutamine tract. Similarly, in at least one of these disorders (spinocerebellar ataxia type 6), nuclear localisation has not been demonstrated. The contradictory evidence for the production and role of proteolytic fragments and for nuclear localisation in toxicity, reviewed in this article, suggests that neither may be uniformly necessary steps in the pathogenesis of this group of diseases, and that, for all their apparent similarities, the exact pathogenic mechanisms may not be identical in each.

Animals↗
PubMed2004

Time course toxicogenomic profiles in CD-1 mice after nontoxic and nonlethal hepatotoxic paracetamol administration.

Adverse drug reactions are a major clinical problem. Drug-induced hepatotoxicity constitutes a large percentage of these reactions. A thorough understanding of the genetic events, specifically, the early "decision-making" processes underlying biological changes caused by drugs and metabolites, is required. To assist in the understanding of these events, we have employed the model hepatotoxin, paracetamol (APAP), and GeneChip technology to investigate global genetic events seen after nontoxic and toxic doses in the mouse. Mice were dosed [vehicle, nontoxic APAP (1 mmol/kg), and toxic APAP (3.5 mmol/kg)], and individual hepatic RNA samples were hybridized to separate chips to determine interanimal variation. Statistical analysis detected 175 CD-1 mouse genes that were significantly regulated (P < 4.1 x 10(-6)), and nonsignificant genes were discarded. For clarity, the significantly regulated genes were then binned into categories according to their major function-antioxidant, glutathione, metabolism, transcription, immune, and apoptosis. There was no hepatic stress observed after dosing 1 mmol/kg APAP, when measured by serum alanine aminotransferase levels. Hepatic toxicity was observed at both 4 and 24 h after a 3.5 mmol/kg dose of APAP. Time course expression profiles for selected genes have been created. These results demonstrate that most active gene expression occurs around 4 h after a toxic dose of APAP. Down-regulation of these genes is observed over 24 h, coinciding with the development of overt toxicity. These data provide a deeper understanding of the in vivo time course of physiological responses of the liver to chemical stress and provide a logical step forward for the investigation of new chemical entities demonstrated positive in chemically reactive metabolite screens. The complete data set can be viewed at http://www.ebi.ac.uk/arrayexpress/. The accession number is E-MEXP-82.

Acetaminophen↗
PubMed2003

Objective measurement of breast cancer oestrogen receptor status through digital image analysis.

AIMS: The authors have previously described quantitative, computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer. The aim of this study was to validate the aforementioned system against the commonly used methods of assessing oestrogen receptor status. METHODS: Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-alpha-oestrogen receptor monoclonal antibody (1D5) using a standard immunohistochemical protocol. Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software. A nuclear mask was obtained by digitally selecting the nuclear area. Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics. Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 randomly sampled nuclei from ten high powered fields HPF. Cut off value for positivity was taken as 10%. Cytosolic oestrogen receptor concentration was measured through enzyme immunisation. Cut off value for ER positivity was taken as 200 fmol/g (wet tissue). RESULTS: One hundred and fifty-six sections were studied of which 41 were ER negative. Median percentage positivity in the remainder was 90% (17-100) by manual assessment. The median red scale value was 108 (58-156). A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually (P<0.0001). There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration (P<0.001). CONCLUSION: Oestrogen receptor positivity can be accurately assessed through digital image analysis. This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei, which express oestrogen receptors.

Adult↗
PubMed2001

Conrotatory photochemical ring opening of alkylcyclobutenes in solution. A test of the hot ground-state mechanism.

Quantum yields for photochemical ring opening of six alkylcyclobutenes have been measured in hexane solution using 228-nm excitation, which selectively populates the lowest pi,R(3s) excited singlet states of these molecules and has been shown previously to lead to ring opening with clean conrotatory stereochemistry. The compounds studied in this work-1,2-dimethylcyclobutene (1), cis- and trans-1,2,3,4-tetramethylcyclobutene (cis- and trans-5), hexamethylcyclobutene (8), and cis- and trans-tricyclo[6.4.0.0(2,7)]dodec-1(2)-ene (cis- and trans-9)-were selected so as to span a broad range in molecular weight and as broad a range as possible in Arrhenius parameters for thermal (ground-state) ring opening. RRKM calculations have been carried out to provide estimates of the rate constants for ground-state ring opening of each of the compounds over a range of thermal energies from 20 000 to 49 000 cm(-1). These have been used to estimate upper limits for the quantum yields of ring opening via a hot ground-state mechanism, assuming a value of k(deact) = 10(11) s(-1) for the rate constant for collisional deactivation by the solvent, that internal conversion to the ground state from the lowest Rydberg state occurs with close to unit efficiency, and that ergodic behavior is followed. The calculated quantum yields are significantly lower than the experimental values in all cases but one (1). This suggests that the Rydberg-derived ring opening of alkylcyclobutenes is a true excited-state process and rules out the hot ground-state mechanism for the reaction.

Journal Article↗
PubMed2001

Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.

1. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) are enzymes that catalyze the hydrolysis of esters of choline. 2. Both AChE and BuChE have been shown to copurify with peptidases. 3. BuChE has also been shown to copurify with other proteins such as transferrin, with which it forms a stable complex. In addition, BuChE is found in association with beta-amyloid protein in Alzheimer brain tissues. 4. Since BuChE copurifies with peptidases, we hypothesized that BuChE interacts with these enzymes and that this association had an influence on their catalytic activities. One of the peptidases that copurifies with cholinesterases has specificity similar to trypsin, hence, this enzyme was used as a model to test this hypothesis. 5. Purified BuChE causes a concentration-dependent enhancement of the catalytic activity of trypsin while trypsin does not influence the catalytic activity of BuChE. 6. We suggest that, in addition to its esterase activity, BuChE may assume a regulatory role by interacting with other proteins.

Acetylcholinesterase↗
PubMed2001

SPATULA, a gene that controls development of carpel margin tissues in Arabidopsis, encodes a bHLH protein.

Studies involving mutants of the gene SPATULA indicate that it promotes the growth of carpel margins and of pollen tract tissues derived from them. We show that it encodes a new member of the basic-helix-loop-helix family of transcription factors. SPATULA is expressed in marginal and pollen tract tissues throughout their development confirming its role in regulating their growth. It is also expressed in many other tissues where it may act redundantly to control growth, including the peripheral zone of the shoot apical meristem, and specific tissues within leaves, petals, stamens and roots. Expression in the stomium, funiculus and valve dehiscence zone indicates an additional role in abscission. SPATULA expression does not require the function of the other carpel development genes CRABS CLAW and AGAMOUS, although its expression is repressed in first whorl organs by the A function gene APETALA2. Further, we have shown that disruptions to gynoecial pattern formation seen in ettin mutants can largely be attributed to ectopic SPATULA action. ETTIN's role seems to be to negatively regulate SPATULA expression in abaxial regions of the developing gynoecium. SPATULA is the first basic-helix-loop-helix gene in plants known to play a role in floral organogenesis.

AGAMOUS Protein, Arabidopsis↗
PubMed2001

Laryngocele and squamous cell carcinoma of the larynx.

We present a case report of a lady with a laryngocele and a squamous cell carcinoma of the larynx. The pathogenesis of the relationship between these two entities is discussed and the literature reviewed. This association means a carcinoma must be outruled if a laryngocele is detected clinically or radiologically.

Aged↗
PubMed2001

Comparison of immunoperoxidase staining of 3 different types of CD5 antibodies in a spectrum of breast lesions.

CONTEXT: We recently described a patient with chronic lymphocytic leukemia who presented with a breast carcinoma that stained positive for CD5 using a commercially available antibody (CD5-4C7, Novocastra, Newcastle upon Tyne, UK). OBJECTIVES: To study the distribution of CD5 immunoreactivity in tissue sections of a variety of benign and malignant breast lesions using the antibody CD5-4C7 and to compare the results with those obtained with 2 other commercially available CD5 antibodies (CD5/54/F6, Dako, Ely, Cambridgeshire, UK, and CD5/54/B4, Novocastra). DESIGN: Paraffin sections of 102 breast biopsy specimens with various diagnoses were examined using the avidin-biotin immunoperoxidase complex technique. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: The staining results obtained with CD5-4C7 were different from those obtained with the other 2 antibodies. With 4C7, the normal and benign biopsy specimens showed varying numbers of positive epithelial cells and lymphocytes. Heterogeneous positive staining was also present in 47 (78%) of 60 invasive female breast carcinomas and in all 3 male breast carcinomas examined. A statistically significant correlation was found between CD5 positivity and tumor grade, with grade 3 tumors being less likely to be CD5 positive than grades 1 and 2 (P =.0035). No correlation was found between CD5 positivity and patient's age, tumor histologic type, axillary lymph node status, or progesterone receptors. On the other hand, the CD5/54/F6 and CD5/54/B4 antibodies only stained lymphocytes and occasional normal breast ducts, mostly those showing apocrine metaplasia. All other normal benign and malignant epithelial cells were negative. CONCLUSIONS: Positive staining for CD5 using the antibody 4C7 is seen in normal and benign breast tissue and 78% of invasive breast carcinomas. The positivity is more common in low-grade tumors. No significant staining was seen with the 2 other CD5 clones used in this study. The significance of the positive staining obtained with CD5-4C7 is not obvious, but this clone may be more sensitive than the others, or it may be recognizing an epitope shared by another antigen.

Antibodies↗
PubMed2000

Enhancement of DNA vaccine potency by electroporation in vivo.

The potential of electric current-mediated delivery technology to enhance DNA delivery and DNA vaccine potency was evaluated. Higher levels of reporter gene expression were observed in muscle cells of mice inoculated with luciferase or beta-galactosidase DNA followed by the application of electrical current, compared with DNA injected with no current. Similarly, substantially higher levels of immune responses (up to 20-fold) were demonstrated in mice vaccinated with HIV gag DNA and electric current. These enhanced responses were observed after one or two inoculations, and were maintained for at least 12 weeks. Therefore, the present studies demonstrate the utility of electroporation for enhancement of DNA vaccine potency in animals.

Animals↗