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Biomedical subjects

A O'Brien

Publications and source records attributed to A O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1990

The effect of radiation in combination with carcinogens on the growth of normal urothelium in explant culture.

Radiation is known to be carcinogenic to humans but attempts to demonstrate the process using human tissue culture models have met with little success. In the present study explants were established from urothelium and exposed to radiation and a range of chemical carcinogens, suspected promotor or metabolic agents. The resulting outgrowth was monitored for growth rate, proliferating epithelial fraction and development and differentiation of endothelial cells in culture. The results indicate that enhanced growth of epithelial cells can be seen when cultures are irradiated in the presence of various nitrosamines, benzo(a)pyrene or aniline. Radiation alone reduced the overall growth area measured but several proliferative foci developed on the resulting outgrowth. Their ultrastructural appearance reveals that they carry severe mitochondrial damage and exposure of treated cultures to metabolic inhibitors confirms that their respiration is defective. Endothelial cells proliferated over the surface of the epithelial monolayer and both the number and the degree of differentiation of the endothelial cells increased with increasing dose up to 10 Gy. While the cultures are not immortalised by the treatment, it appears that the epithelial cells have an extended lifespan (division capacity) and that a subpopulation has undergone a number of premalignant changes. Changes in endothelial cell proliferation also occur.

Cell Division↗
PubMed1990

The pharmacology of N-methyl LTC4; a metabolically stable LTC4-mimetic.

N-methyl LTC4 (NMLTC4) a synthetic analogue of LTC4, has been shown not to be a substrate for gamma-glutamyl transpeptidase. NMLTC4 produced contractions of the guinea pig ileum and trachea with pD2 values of 7.7 +/- 0.12 (n = 6) and 8.1 +/- 0.1 (n = 6) respectively, compared with values of 9.0 +/- 0.1 (n = 5) and 8.0 +/- 0.2 (n = 6) for LTC4. The concentration-response curve to LTC4 and NMLTC4 on ileum was displaced to the right by FPL55712. The corresponding pA2 values were 6.3 +/- 0.3 (n = 10) for LTC4 and 5.7 +/- 0.2 (n = 6) for NMLTC4. In the presence of acivicin, a gamma-glutamyl transpeptidase inhibitor, the LTC4 concentration-response curve on trachea was displaced to the left, but the NMLTC4 curve was unaffected. The comparative potencies in the presence of acivicin on trachea indicate that LTC4 is approximately 6 times more potent than NMLTC4 whereas on ileum, in the presence of FPL55712 LTC4 is approximately 14 times more potent. In-vivo NMLTC4 is a weak bronchoconstrictor substance being 20-30 less potent than LTC4. However, unlike the in-vitro studies the bronchospasm was significantly reduced by pretreatment with LTD4 antagonists. NMLTC4 administered intravenously produced a pronounced hypertensive effect which appeared to be due to peripheral vasoconstriction.

Animals↗
PubMed1990

A genetic map of mouse chromosome 1 near the Lsh-Ity-Bcg disease resistance locus.

Isozyme and restriction fragment length polymorphism (RFLP) analyses of backcross progeny, recombinant inbred strains, and congenic strains of mice positioned eight genetic markers with respect to the Lsh-Ity-Bcg disease resistance locus. Allelic isoforms of Idh-1 and Pep-3 and RFLPs detected by Southern hybridization for Myl-1, Cryg, Vil, Achrg, bcl-2, and Ren-1,2, between BALB/cAnPt and DBA/2NPt mice, were utilized to examine the cosegregation of these markers with the Lsh-Ity-Bcg resistance phenotype in 103 backcross progeny. An additional 47 backcross progeny from a cross between C57BL/10ScSn and B10.L-Lshr/s mice were examined for the cosegregation of Myl-1 and Vil RFLPs with Lsh phenotypic differences. Similarly, BXD recombinant inbred strains were typed for RFLPs upon hybridization with Vil and Achrg. Recombination frequencies generated in the different test systems were statistically similar, and villin (Vil) was identified as the molecular marker closest (1.7 +/- 0.8 cM) to the Lsh-Ity-Bcg locus. Two other DNA sequences, nebulin (Neb) and an anonymous DNA fragment (D2S3), which map to a region of human chromosome 2q that is homologous to proximal mouse chromosome 1, were not closely linked to the Lsh-Ity-Bcg locus. This multipoint linkage analysis of chromosome 1 surrounding the Lsh-Ity-Bcg locus provides a basis for the eventual isolation of the disease gene.

Animals↗
PubMed1990

The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.

Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.

Carboplatin↗
PubMed1990

Fibreoptic bronchoscopy in the management of lone pleural effusion: a negative study.

In a retrospective review of 3,000 consecutive fibreoptic bronchoscopies, fifty were performed for investigation of lone pleural effusion. While 7 patients had bronchogenic carcinoma, in only one case was it visible endoscopically. In the absence of radiological or clinical features suggesting an endobronchial lesion, fibreoptic bronchoscopy is unlikely to aid in the diagnosis of lone pleural effusion.

Bronchoscopy↗
PubMed1989

The pharmacological evaluation of LY 170680, a novel leukotriene D4 and E4 antagonist in the guinea-pig.

1. This paper describes the evaluation of LY170680 (5-less than 3-[2(R) (carboxyethylthio)-(S)-hydroxypentadeca 3(E)5(Z)-dienyl]phenyl greater than 1H tetrazole, as an antagonist of the cysteinyl leukotrienes C4, D4, E4, in a variety of in vitro and in vivo models. 2. In vitro, LY170680 was a potent, selective, and competitive antagonist of LTD4, and LTE4. It produced a concentration-dependent rightward displacement of the concentration-response curves elicited by either LTD4 or LTE4 on both the guinea-pig ileal and tracheal preparation. The pA2 values for LY170680 were estimated to be 8.1 +/- 0.2 (n = 8) and 8.1 +/- 0.1 (n = 6) on trachea, and 8.7 +/- 0.1 (n = 12) and 9.0 +/- 0.3 (n = 6) on ileum for both LTD4 and LTE4 respectively. The slopes of the Schild plots in these studies were all close to unity. 3. LY170680 was shown to be a modest antagonist of the LTC4-induced responses on guinea-pig ileum (pA2 7.0 +/- 0.2 n = 5), but had no discernable effects against contractions induced by histamine, prostaglandin E2 (PGE2), PGF2 alpha or acetylcholine. The compound also reduced the LTC4-induced responses on trachea, but in a non competitive manner. 4. Intravenous LY170680 reduced in a dose-dependent manner (ED50 3.8 mg kg-1, 60 min pretreatment) the fall in compliance in the anaesthetized guinea-pig, and the rise in total pulmonary resistance (TPR) (ED50 2.0 mg kg-1, 30 min pretreatment) in the artificially ventilated guinea-pig, produced by intraveous LTD4. 5. LY170680 (5mgkg-1, i.v.) was also effective in reducing the increase in TPR to intravenous antigen in sensitized animals pretreated with mepyramine, indomethacin and propranolol. 6. The compound was only moderately effective (ED5o 40mgkg-1 p.o.) in preventing the rise in TPR induced by intravenous LTD4, when given orally. 7. Inhaled LY170680 was particularly effective in preventing the increase in TPR produced by an exposure to aerosolised LTD4. An estimated 1-2 pg of LY170680 delivered to the airways by nebuliser 1 hour beforehand, produced a 6 fold lateral displacement to the right of the dose-response curve to LTD4. 8. Studies in conscious animals indicated that inhaled LY170680 produced a dose-dependent reduction in the increased volume of gas, trapped in the lung following exposure to aerosolised LTD4. Duration studies also indicated that an estimated inhaled dose of 10 g LY170680 significantly reduced the LTD4-induced' increase in trapped lung gas volume for at least 4 h. Inhaled LY170680 also reduced LTC4-induced increase in gas trapping in a manner similar to LTD4. However, histamine-induced gas trapping was unaffected.

Administration, Inhalation↗
PubMed1989

Seclusion.

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Adolescent↗
PubMed1988

Transcriptional activation of the glutathione S-transferase pi gene in human ureteric and bladder carcinomas.

Using a cDNA clone derived from the rat Glutathione S-Transferase P (GST-P) gene, we have investigated homologous transcripts in a range of normal and malignant human tissues. A major transcript, of 0.75 Kb, representing human GST-pi mRNA, was present in total RNA purified from peripheral white blood cells, bladder, ureteric and prostate tissues. In total RNA derived from histopathologically benign/normal tissues, peripheral leucocytes and from hyperplastic and malignant prostates, levels of the mature transcript varied by less than 1.5-fold (n = 70). In contrast, levels of transcript were significantly elevated (up to 16-fold) in total RNA derived from bladder and ureteric carcinomas, with the highest levels of elevation approaching those previously found only for the GST-P gene in experimentally induced rodent hepatocellular carcinomas. A wide range of stage and grade of tumour has been investigated (pT1 to pT4; G1 to G3, respectively), suggesting that the transcriptional activation of the GST-pi gene is a characteristic common to many bladder/ureteric carcinomas in man.

Carcinoma↗
PubMed1987

Evaluation of the effectiveness of a community-based prenatal health education program.

This study demonstrated the importance of outlining evaluation criteria for newly implemented programs. An educational program should have measurable program objectives with which the goals of the program can be evaluated. Along with a clearly defined set of program objectives, new educational programs should be implemented with the appropriate record keeping systems to facilitate information retrieval. With a measurable set of objectives and accurate data collection, ongoing evaluation of programs would enable developers to identify the programs' strengths and weaknesses as a basis for revisions to best meet the needs of the population served.

Chicago↗
PubMed1987

Malignant tumours in the neonate.

One hundred and two cases of neonatal cancers, representing 2% of all paediatric malignancies, were seen during a 60 year period at The Hospital for Sick Children, Toronto, Canada. The neonatal cancers included neuroblastoma (47%), retinoblastoma (17%), soft tissue sarcoma (12%), central nervous system tumours (9%), leukaemia (8%), and a few cases of Wilms' tumour, liver tumour, and miscellaneous tumours. The overall mortality from disease was 41%. Patients with retinoblastoma, Wilms' tumour, and neuroblastoma had the best prognosis. Forty three patients (42%) survived their neonatal cancers; all were treated with surgery or radiochemotherapy, or both, but none suffered long term major handicaps as a result of treatment. There was one instance of second malignancy of the thyroid gland induced by radiation. We conclude that although neonatal cancers are difficult management problems, many patients can be cured. Physicians should discuss with parents the possible risks associated with treatment before treatment is begun.

Female↗
PubMed1987

Campylobacter pyloridis-associated primary gastritis in children.

Campylobacter pyloridis are spiral-shaped Gram-negative bacteria that have recently been associated with gastritis and peptic ulcer diseases in adults. The organisms have been identified in biopsy specimens of the gastric antrum by staining sections with silver stain. To determine the frequency of colonization of the antral mucosa with C pyloridis in association with gastritis in childhood, we retrospectively reviewed 53 cases in patients (mean age 11.9 years) in whom upper endoscopy with antral biopsy was performed for the evaluation of symptoms referable to the upper gastrointestinal tract. A silver impregnation method was used to detect the presence of C pyloridis. Nineteen of 53 antral biopsy specimens showed evidence of mucosal inflammation. Ten of these 19 patients had no apparent predisposing etiology for gastritis, and six of these ten had C pyloridis identified on antral biopsies. Nine of the 19 patients had secondary causes of gastric inflammation (two gastroduodenal Crohn disease, two eosinophilic gastroenteritis, four drug related, and one dys-gamma-globulinemia and lymphonodular hyperplasia). In contrast, none of these nine patients had C pyloridis demonstrated on antral biopsies. Silver stain for C pyloridis was negative in all 34 of the 53 children who had normal antral histologic findings. C pyloridis was not demonstrated by silver stain on any of the duodenal sections, although eight of the 19 children with gastritis and nine of the 34 children with normal antral histologic findings had histologic evidence of duodenal inflammation. We conclude that C pyloridis is associated with primary antral gastritis but not with secondary gastritis in the pediatric population.

Adolescent↗
PubMed1986

Microbial examination of kidney lithotripter tub water and epidural anesthesia catheters.

Kidney lithotripsy patients frequently receive epidural anesthesia via indwelling epidural catheters. In our hospital, patients are immersed in a tub of warm, continuously-flowing tap water. The epidural catheter-entry site is covered by a transparent occlusive dressing. To determine the risk of microbial colonization of the epidural catheter during lithotripsy, we performed quantitative cultures of tub water and semiquantitative cultures of catheters in 63 lithotripsy procedures. Most of the tub water organisms were typical tap water and skin flora isolates. Total colony counts were generally low with no significant progression during the course of serial procedures. Forty-two epidural catheters were cultured; 34 (81%) were sterile, 8 (19%) were colonized with small numbers of flavobacteria or coagulase-negative staphylococci. Only four catheters had organisms present on catheter segments covered by the transparent occlusive dressing (in each case there was a single colony forming unit per semiquantitative plate) and these organisms were probable contaminants. We conclude that with our current lithotripsy procedures, the risk for the development of epidural catheter-associated infection seems to be low.

Anesthesia, Epidural↗
PubMed1986

Progress of bleomycin-induced lung fibrosis in rabbits.

Progression of lung fibrosis induced in rabbits by intratracheal bleomycin (BLM, 10 mg/kg) was monitored by biochemical and morphological measurements. These indicated that the evolution of fibrosis in the rabbit was slower than in other experimental animals. Histology revealed cellular and fibrocellular lesions 4 weeks after BLM. At 8 weeks these lesions still predominated, indicating continuing active disease accompanied by a progression to fibrosis. The gradual progression of the response was reflected in alterations in lung composition. Changes in lung content of collagen, protein and DNA were evident at 8 weeks after BLM, at which time concentration (micrograms/mg dry weight) of collagen and protein were also elevated (P less than 0.05). Plasma angiotensin converting enzyme (ACE), a marker of endothelial injury, decreased 1 week after BLM (P less than 0.01) and then returned to normal, indicating that endothelial injury does not parallel the fibrotic response. In summary, the continuing active inflammation and slow progress of fibrosis induced by i.t. BLM in the rabbit suggests that this model has advantages over others for the serial study of the cellular and biochemical evolution of lung fibrosis.

Animals↗