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Biomedical subjects

R O'Leary

Publications and source records attributed to R O'Leary.

At least 19 recordsLinked to original sources

Tumour-induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction.

Gastrointestinal carcinomas frequently disseminate within the abdominal cavity to form secondary peritoneal metastases. Invasion of the peritoneal mesothelium is fundamental to this process, yet the underlying invasive mechanisms remain unclear. Preliminary in vitro work suggested that tumour cells can induce mesothelial apoptosis, representing a novel mechanism of peritoneal invasion. We examined the role of tumour cell-induced mesothelial apoptosis and explored the role of the death ligand/receptor system, Fas Ligand/Fas, as mediators of the apoptotic process. Cultured human mesothelial cells were used to establish in vitro co-culture models with the SW480 colonic cancer cell line. Tumour-induced mesothelial apoptosis was confirmed by phase-contrast microscopy and apoptotic detection assays. Human mesothelial cells and SW480 tumour cells constitutively expressed Fas and Fas Ligand mRNA and protein as determined by RT-PCR and confocal fluorescent microscopy. Stimulation of human mesothelial cells with anti-Fas monoclonal antibody or crosslinked soluble Fas Ligand-induced apoptosis, confirming the functional status of the Fas receptor. Pretreatment of SW480 cells with a blocking recombinant anti-Fas Ligand monoclonal antibody significantly reduced mesothelial apoptosis, indicating that tumour-induced mesothelial apoptosis may, in part, be mediated via a Fas-dependent mechanism. This represents a novel mechanism of mesothelial invasion and offers several new targets for therapeutic intervention.

Apoptosis↗

Agreement between preoperative core needle biopsy and postoperative invasive breast cancer histopathology is not dependent on the amount of clinical material obtained.

AIMS: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. METHODS: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. RESULTS: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade--nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)--agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. CONCLUSION: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.

Biopsy, Needle↗

Pathological scarring: strategic interventions.

Aberrant cutaneous scar formation is a substantial cause of postoperative morbidity. There is at present no clear consensus on the best way to prevent or treat such scarring, although recently there has been considerable progress in developing an understanding of the mechanisms of tissue repair and scarring. We carried out a literature review using Medline to establish the current understanding of the key events occurring during tissue repair and to identify potential causes of scarring. We now review the key events during tissue repair and the pathogenesis of fibroproliferative disease. Tissue repair is achieved through a multistranded, elegantly coordinated process within which the balance between synthesis and breakdown of matrix is upset during fibrotic disease. Scars form because the signals directing tissue repair are not correctly terminated, and while the initiation and propagation of repair is well understood the signals that direct its cessation have yet to be elucidated.

Cicatrix↗

Modernization and religious intermarriage in the Republic of Ireland.

There are strong theoretical reasons for hypothesizing that those sections of the population who are most exposed to modernization processes are more likely to marry outside their own religious group. We examine this for Catholic-Protestant intermarriage in the Republic of Ireland. We use a multivariate analysis on survey data to test the hypotheses that urban dwellers, persons of non-farming parents, persons with higher levels of education and the young are more likely to be religiously intermarried. While the odds of being in an intermarriage are greater for urban dwellers, this is in large part due to their being non-farmers. The farming effect is not necessarily related to religiosity. The odds of being in an intermarriage do not increase significantly for persons with third level education and this can be explained in terms of the marriage market for minority groups. It is shown that the historical context and the minority position of religious group should be taken into account in explanations which relate modernization to the pattern of religious intermarriage.

Humans↗

Curative radiotherapy for anterior commissure laryngeal carcinoma.

There is continuing controversy surrounding the most effective treatment of glottic carcinoma involving the anterior commissure (AC). Surgery has been the preferred method of treatment, since studies previously indicated early tumor invasion of the thyroid cartilage at the AC, thereby assuming less curability by radiotherapy (RT). Subsequent laryngeal anatomic studies and refinement of RT techniques have brought into question the ineffectiveness of curative irradiation. A retrospective review of 174 patients with early-stage glottic carcinoma treated with standard fractionation curative RT revealed 34 patients with T1 and T2 lesions involving the AC. Allowing for a follow-up of at least 3 years, we observed only a 12% (4 of 34 patients) local recurrence rate after RT alone, with excellent voice quality and no major complications related to the irradiation. The 4 local recurrences were controlled by total laryngectomy, although 2 patients developed distant metastatic disease. Radiotherapy represents an effective method of treating T1 squamous cell carcinoma of the glottis with AC involvement. The small number of T2 glottic carcinomas in this study prevents a meaningful conclusion concerning treatment of these lesions.

Aged↗

A three-dimensional in-vitro model for the study of peritoneal tumour metastasis.

Peritoneal metastasis is a frequent complication of gastrointestinal malignancy. We have developed a three-dimensional model of the human peritoneum that simulates the metastatic process in vitro. Peritoneal fibroblasts were incorporated into collagen lattices, allowed to contract, then overlaid with mesothelial cells. Scanning and transmission electron microscopy showed the model to have similar physical properties to human peritoneum. Mesothelial expression of the beta1 integrin family, the basement membrane proteins fibronectin, laminin, collagen types III and IV, and the cell adhesion molecules ICAM-1, VCAM-1 and PECAM were assessed and showed similar results to in vivo tissue. Gastrointestinal tumour cells seeded onto the model exhibited mesothelial adhesion, cell spreading and vesicle formation, and invasion of the mesothelial monolayer on scanning electron microscopy. Two distinct patterns of tumour cell growth were observed using light microscopy: a superficial spreading layer, and discrete invasive deposits. Invasion was accompanied by disruption of the mesothelial monolayer, degradation and re-orientation of the matrix, and rudimentary tumour cell differentiation. We believe the use of this in vitro peritoneal model will facilitate the study of the molecular mechanisms involved in the metastatic process.

Humans↗

Psychosocial factors, dental plaque levels and smoking in periodontitis patients.

Psychological disturbances may lead patients to neglect oral hygiene. This study investigated whether a number of psychosocial factors (depression, state and trait anxiety, total and average perceived stress, and loneliness) could predict dental plaque levels in patients with adult onset rapidly progressive periodontitis (RPP) and routine chronic adult periodontitis (RCAP), before periodontal treatment. It was also examined whether RPP and RCAP patients differed on plaque and smoking. Plaque was scored in a sample of 6 teeth in each of 80 subjects, 40 with RPP, 40 with RCAP, before psychosocial questionnaire completion. Multiple regression was performed between plaque as the dependent and psychosocial factors, gender, education, form of periodontitis and smoking as independent variables. Only gender contributed significantly to prediction of plaque, t=-2.70, p=0.01, partial regression coefficient -0.37, 95% CI: -0.64 to -0.10, indicating that plaque was on average 0.37 lower for females than males, after adjusting for the other predictor variables. It was confirmed that RPP and RCAP patients did not differ significantly on plaque, univariate t-test(69.99)= 0.65, p=0.13. However, RPP patients smoked significantly more than RCAP patients t(69.72)=2.36, p=0.02. There was also a marginally significant correlation between depression and smoking, r=0.16, p=0.07. One possible reason advanced for the lack of an association between psychosocial factors and plaque, and the absence of a difference in plaque between RPP and RCAP patients is the fact that the patients involved in the present study were seen as secondary referrals. The gender difference in plaque levels and the greater incidence of smoking in RPP patients may be of significance in planning interventions with patients with periodontitis.

Adult↗

The bactericidal effects of dental ultrasound on Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. An in vitro investigation.

This study investigated the possible bactericidal acoustic effects of the dental ultrasonic scaler. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis suspensions, were subjected to the vibrations of a Cavitron P1 insert for 2.5 and 5.0 min in an acoustically-simulated pocket model and the survivors enumerated. The extent of any cavitation occurring within the pocket model to which the statistically significant bactericidal activity observed might be attributed, was determined by 'sonoluminescence', which was then investigated by photomultiplication techniques. However, these failed to detect any sonoluminescence within the pocket space and, moreover, the necessary deflection of the water coolant away from the insert tip, to avoid flooding of the experimental pocket, proved to result in temperatures of 47.6 degrees C and 52.3 degrees C at the respective time intervals, and thereby constituted an alternative possible bactericidal mechanism. Examination of the effects of such temperature changes on the target bacteria then revealed statistically significant differences in the viable counts of both microorganisms after 5.0-min periods, and as such were comparable to those previously detected in relation to the pocket model. Whilst it must be presumed that the bacteriolytic effect observed in the main investigation was due to the incidental temperature changes, in the absence of acoustic cavitation the influence of any associated acoustic microstreaming cannot be discounted. Further investigations to assess the bactericidal potential of acoustic phenomena using a modified experimental to exclude any hyperthermic effects are therefore necessary.

Acoustics↗

Detection of HIV in bone allografts prepared from AIDS autopsy tissue.

Processed bone from an AIDS patient was tested for the presence of the human immunodeficiency virus type 1 (HIV-1). The preliminary procedures used to process bone allografts included removal of adventitious material and two cycles of freeze thawing. Although infectious virus was readily observed in plasma and bone marrow cells taken at autopsy, no infectious virus was detected in processed bone fragments. However, by using the polymerase chain reaction procedure, the presence of proviral HIV DNA could be demonstrated in processed bone allografts from this donor. Whereas the best safeguard against transmission of HIV by allografts is rigorous criteria for the exclusion of seropositive individuals as donors, proper procedures for processing bone allografts can further reduce the possibility of HIV transmission by bone allografts in cases where tissue from an infected donor is collected and processed.

Acquired Immunodeficiency Syndrome↗

Differential effects of bismuth and salicylate salts on the antibiotic susceptibility of Pseudomonas aeruginosa.

The influence of salicylate or bismuth salts on antibiotic action against Pseudomonas aeruginosa was assessed in broth cultures. Sodium salicylate (2.5 mM) had no significant effect on the activity of any antibiotic tested. In contrast, bismuth compounds (0.5 mM) produced a significant change in the inhibitory activity of several antibiotics against all strains. Bismuth salts reduced imipenem activity by up to 20-fold, enhanced gentamicin or amikacin activity three to five-fold, and enhanced cefpirome or cefepime activity by as much as 10-fold against antibiotic-sensitive and resistant strains. Bismuth salts had little effect on cefoperazone, ceftazidime, or mezlocillin activity. Combining bismuth salts with aminoglycosides or fourth-generation cephalosporin antibiotics may help to combat the growing problem of resistant Pseudomonas aeruginosa.

Anti-Bacterial Agents↗