Search PubMed⌕ Search

Biomedical subjects

A O'Brien

Publications and source records attributed to A O'Brien.

At least 19 recordsLinked to original sources
PubMed1992

A major solid undifferentiated carcinoma pattern correlates with tumour progression in locally advanced prostatic carcinoma.

Solid undifferentiated carcinoma was the major microscopic pattern in 24 prostatic carcinomas, 12 of which were clinically recurrent. Tumour cells were uniform, with moderately hyperchromatic nuclei and indistinct cytoplasm, and were arranged in solid or focally irregular aggregates. In areas, the tumour cells were large with vesicular nuclei, nucleoli and more abundant cytoplasm. In previous specimens, solid undifferentiated carcinoma was absent or was a minor pattern. Twenty of 23 cases showed prostate specific antigen and prostatic acid phosphatase immunoreactivity, and nine of 17 cases contained scattered argyrophilic or chromogranin-immunoreactive cells. On proliferating cell nuclear antigen immunostaining of 12 specimens, the mean tumour proliferative fraction in solid undifferentiated carcinoma (range: 10.5-18%) was greater than in areas of grade 3 prostatic carcinoma (range: 3-6%). In all 22 stage C and D cases, there was a close correlation with clinical evidence of tumour progression, and the overall 2-year survival rate was only 16.7%. It is concluded that a major solid undifferentiated pattern correlates with increased biological aggressiveness and a poor prognosis in locally advanced prostatic carcinoma.

Carcinoma↗
PubMed1992

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis.

A tail-suspension (TS) rat model used to simulate microgravity was tested for its effects on the anatomy, cell structure, and function of the testis and epididymis in sexually mature male rats. Rats suspended for 7 days without inguinal canal ligation exhibited a significant (P less than or equal to 0.05) reduction in testis weight compared with controls (1.55 +/- 0.04 to 1.1 +/- 0.02 g). Except for the liver, epididymis, and adrenals of TS rats and TS rats allowed to recover for 7 days, no significant (P less than or equal to 0.05) change was observed in the weight of other body and accessory sex organs. A histological examination of the testes and epididymides of model animals revealed disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. A significant (P less than or equal to 0.05) increase in serum luteinizing hormone (53.1 +/- 6.7 to 66.2 +/- 10.1 ng/ml) and follicle-stimulating hormone (257 +/- 25 to 305 +/- 38 ng/ml) was observed in TS nonligated rats, whereas serum prolactin and testosterone levels were observed to decline from 8.3 +/- 1.3 to 5.1 +/- 0.29 and 7.1 +/- 1.3 to 3.8 +/- 0.25 ng/ml, respectively. Decreases in testis protein content and testosterone levels of the testis, interstitial fluid, and epididymis were also observed in model animals. These data demonstrate that the suspension procedure used in the National Aeronautics and Space Administration TS model results in the testis and epididymis translocating into the abdominal cavity, causing cellular degeneration and organ dysfunction.

Animals↗
PubMed1991

A critical analysis of the use of sialic acid determination in the diagnosis of malignancy.

The measurement of serum sialic acid in sera from individuals with leukemia, breast, gastrointestinal, lung and bladder cancers, brucellosis and manic depression is described. The serum sialic acid levels were also examined in mice bearing Landschutz ascites tumours. The presence of sialic acid-enriched glycopeptides in serum was shown. The results indicate that while sialic acid may be significantly elevated in sera of some tumour-bearing individuals, it is not solely tumour-derived. Its application as a tumour marker is limited and requires critical analysis.

Animals↗
PubMed1991

The basolateral amygdala-ventral striatal system and conditioned place preference: further evidence of limbic-striatal interactions underlying reward-related processes.

The effects on the expression of a conditioned place preference of bilateral, excitotoxic amino acid-induced lesions of the basolateral region of the amygdala, or the ventral striatum, or asymmetric, unilateral lesions of both structures were studied. The place preference was conditioned by exposing hungry rats to sucrose in a distinctive environment. Following acquisition, bilateral quisqualate-induced lesions of the basolateral amygdala, as well as bilateral quinolinate-induced lesions of the ventral striatum, abolished the conditioned place preference. Bilateral ventromedial, but not dorsolateral, quinolinate-induced caudate-putamen lesions attenuated the place preference. Combining a unilateral lesion of the basolateral amygdala with a contralateral lesion of the ventral striatum also disrupted the conditioned place preference. These data provide further support for the hypothesis that the basolateral amygdala and ventral striatum are important parts of a neural system subserving stimulus-reward associations.

Amygdala↗
PubMed1991

The relationship between development of lung inflammation and changes in bone marrow populations in guinea-pigs following inhaled antigen challenge.

Sensitised guinea-pigs were exposed to aerosolised antigen. The resultant cellular infiltration into the lung was assessed in lung tissue and bronchoalveolar lavage fluid 6, 24, 72 h and 7 days later. An early neutrophil infiltration peaking at 6 h was succeeded by eosinophil migration which persisted for 7 days, at which time some of the eosinophils appeared immature. The lung eosinophilia was accompanied by an initial fall in eosinophilic cells in the bone marrow, followed by an increase in this population. Treatment with dexamethasone (25 mg/kg i.p.) given daily for 7 days after antigen challenge reduced the lung eosinophilia and observed bone marrow changes.

Administration, Inhalation↗
PubMed1991

Proliferation of normal and malignant human epithelial cells post irradiation.

Fragments of human oesophageal mucosa, urothelium, squamous and adenocarcinoma of the oesophagus and carcinoma of the bladder have been plated in culture and irradiated. The cells growing from the explanted tissues have then been studied for four weeks post irradiation to assess the overall rate of growth from the irradiated explants and the fraction of proliferating cells. The results show that when using cell number as an endpoint it is possible to derive growth curves from this type of data which permit a doubling time to be obtained for the cell population surviving different doses. In an attempt to determine the proliferating fraction of the cell population, cultures were labelled at appropriate intervals with tritiated thymidine and were also stained with Ki-67 antiproliferating antigen. The results show an interesting relationship between the dose response obtained for cell labelling with tritiated thymidine and area of cellular outgrowth. Ki-67 staining when used carefully and analysed as described was a useful indicator of proliferating cells. The results provide a means of determining the post irradiation growth potential of fragments of tissue from human organs and may be important for determined overall response of the tumour bulk to proposed treatment.

Autoradiography↗
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↗
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↗