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Biomedical subjects

T E O'Brien

Publications and source records attributed to T E O'Brien.

At least 19 recordsLinked to original sources
PubMed2001

Microglia play a role in mediating the effects of cytokines on the structure and function of the rat pineal gland.

The role of the pineal gland in regulating immune function has been extensively investigated. However, there is little information about possible feedback mechanisms of immunological factors on pineal gland neuroendocrine functions. Therefore, experiments were designed to test the effects of cytokines (interferon-gamma, IFN-gamma, interleukin-1 beta, IL-1 beta; tumor necrosis factor-alpha, TNF-alpha; transforming growth factor-beta 1, TGF-beta 1) on pinealocytes and the role of pineal microglia in mediating these cytokine effects in the pineal gland of the rat. Our studies showed that IFN-gamma enhanced 5-hydroxytryptamine (5-HT) content (measured by high-performance liquid chromatography, HPLC) and increased pinealocyte process length in pineal cultures. IL-1 beta treatment decreased 5-HT content in both cell and organ culture, but exhibited no effect on pinealocyte process length. 5-HT content and process length were decreased by TNF-alpha treatment. IFN-gamma and IL-1 beta exhibited no significant effect in the absence of microglia in cell cultures. In contrast, TNF-alpha caused a further decline in 5-HT content even in the absence of microglia in the cultures. The effects of TNF-alpha were probably due to toxic effects, since an increased number of pyknotic nuclei were observed in treated cultured explants. TGF-beta 1 treatment caused aggregation of pinealocytes in cultures and suppressed process length and 5-HT content. In conclusion, cytokine effects on pinealocytes may be mediated by microglia (IFN-gamma and IL-1 beta) or act directly on pinealocytes (TNF-alpha). The presence of IL-1 beta and TGF-beta 1 protein in the pineal gland and the suppressive effect of TGF-beta 1 on pinealocytes in cultures further suggest that endogenous cytokines play regulatory roles in response to peripheral homeostatic changes.

Animals↗
PubMed2001

Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis.

Offspring of women with pregestational diabetes mellitus are at increased risk for congenital malformations, largely attributable to poor periconceptional glycaemic control. We assessed the effect of preconception care in reducing congenital malformations, in a meta-analysis of published studies of preconception care in women with diabetes mellitus. Articles were retrieved from Medline (1970 to June 2000) and Embase (1980 to June 2000), and data abstracted by two independent reviewers. The rates and relative risks (RR) for major and minor congenital malformations were pooled from all eligible studies using a random effects model, as were early first-trimester glycosylated haemoglobin values. In 14 cohort studies, major congenital malformations were assessed among 1192 offspring of mothers who had received preconception care, and 1459 offspring of women who had not. The pooled rate of major anomalies was lower among preconception care recipients (2.1%) than non-recipients (6.5%) (RR 0.36, 95%CI 0.22-0.59). In nine studies, the risk for major and minor anomalies was also lower among women who received preconception care (RR 0.32, 95%CI 0.17-0.59), as were the early first-trimester mean glycosylated haemoglobin values (pooled mean difference: 2.3%, 95%CI 2.1-2.4). Women who received preconception care were, on average, 1.8 years older than non-recipients, and fewer smoked (19.6% vs. 30.2%). Only one study described the routine use of periconception folic acid. Out-patient preconception care probably reduces the risk of major congenital anomalies among the offspring of women with pregestational diabetes mellitus. Because many women with diabetes neither plan their pregnancy nor achieve adequate glycaemic control before conception, strategies are needed to improve access to these programs, and to maximize those interventions associated with improved pregnancy outcome, such as smoking cessation and folic acid use.

Adult↗
PubMed1999

Immunofluorescence method for quantifying the trabecular meshwork glucocorticoid response (TIGR) protein in trabecular meshwork and Schlemm's canal cells.

PURPOSE: Decreased flow of aqueous humor through the trabecular meshwork (TM) and into Schlemm's canal (SC) is believed to be a predominant factor in the development of the elevated intraocular pressure found in primary open-angle and steroid glaucoma. Recent biochemical and genetic evidence has suggested that alterations in the expression of the TM glucocorticoid response (TIGR) protein within the chamber angle may play a role in the development of these glaucomas. To understand the process of TIGR induction in outflow pathway cells we developed an assay for TIGR expression that could distinguish both individual cell responses and also provide a semi-quantitative comparison between cell cultures. The present study demonstrates this approach, using digital image capture of immunofluorescently stained human TM and SC cells after treatment with dexamethasone (Dex). METHODS: Confluent cultures of human TM and SC cells were treated with 1 M Dex or vehicle control for 10 days. The cells were then fixed, permeabilized, and stained using polyclonal antibodies produced against recombinant TIGR. Digital images of fluorescently stained cells, using the same exposure time within an experiment, were evaluated by tabulating the staining intensity of all cells on each image. Between 10 and 40 cells were evaluated per image, 8-10 frames/ sample, 2-3 samples per treatment. Each cell was ranked as either 0 (background), 1+ (minor), 2+ (moderate) or 3+ (very bright staining). RESULTS: TM cells showed a significant basal level of TIGR staining. About 20% of control cells showed appreciable levels of TIGR staining, with intensity levels evenly distributed between 1, 2 and 3+. Dex treatment increased the number of TM cells expressing TIGR to 60-80%, with the majority of cells showing 2+ to 3+ staining throughout the cytoplasm. SC cells showed no basal TIGR staining, but Dex-treated cells exhibited TIGR staining in 6-15% of cells. SC cell TIGR staining varied between 1+ to 2+ in intensity, and showed a distribution different from TM cells. Staining in SC cells was localized to a ribbon-like compartment adjacent to the nucleus. Such perinuclear localization was rarely seen in TM cells. CONCLUSIONS: The low standard errors of the mean TIGR responses within each experiment, and the reproducibility between experiments for each cell type, suggests good reliability for this method. At the same time, the consistent, marked contrast between TM and SC cells in their response to glucocorticoids demonstrates that the assay can distinguish significant differences between cell types. The data support the view that Dex has a cell type specific effect on TIGR induction. The different extent, pattern and localization of TIGR staining between cell types suggests that TIGR expression in SC cells could play a functional role in the outflow pathway, but one that may be distinct from that played in TM cells.

Adult↗
PubMed1986

Sarcoidosis of the breast.

Sarcoid granulomata were found incidentally in the mammary lobules adjacent to an excised fibroadenoma in a case of sarcoidosis of the breast. The diagnosis of sarcoidosis was established by the radiological finding of bilateral hilar lymphadenopathy, raised concentrations of serum angiotensin converting enzyme and lysozyme, and, finally, by a positive Kveim test.

Adenofibroma↗
PubMed1979

The effect of aspirin on the fibrinolytic activity of gastric juice.

Fibrinolytic activity in the gastric juice of normal subjects has been studied by a double-blind cross-over technique comparing the effect of placebo and pentagastrin against aspirin and pentagastrin. Aspirin effectively produced a gastritis and pure fibrinolytic activity was detected in the gastric juice, but the number of samples showing pure fibrinolytic activity did not differ between the two groups. In both the placebo and the aspirin groups the presence of a protease active at neutral pH and capable of dissolving fibrin is confirmed. Aspirin is unlikely to cause gastric bleeding by increasing local fibrinolytic activity within the stomach. The model, so constructed, is not sensitive enough to be of value in investigating further the role of gastric fibrinolytic activity in gastric haemorrhage.

Adult↗
PubMed1979

Fibrinolytic activity in gastric venous blood. A comparison between normal and diseased stomachs.

The fibrinolytic activity of blood draining from the stomachs of patients with gastroduodenal disease has been compared with the fibrinolytic activity of blood in the systemic venous circulation and with the blood draining from normal stomachs. Gastric venous blood from normal and diseased stomachs contains greater amounts of plasminogen activator than simultaneously sampled systemic venous blood. However, gastric venous fibrinolytic activity does not differ between the normal and diseased stomachs and thus indicates that increased gastric venous fibrinolysis is not just a characteristic of the diseased stomach. The studies suggest that stress may cause activation of the fibrinolytic system in gastric venous blood with the release of small amounts of free plasmin. It is postulated that local fibrinolysis may play a part in potentiating gastric hemorrhage.

Blood Cell Count↗
PubMed1979

The effect of intermittent compression of the calf on the fibrinolytic responses in the blood during a surgical operation.

The fibrinolytic responses in the blood during surgical operation have been studied in two groups of patients during intraoperative intermittent compression of the calf. Fibrinolytic activity did not differ significantly between the groups. The postoperative fibrinolytic shutdown was not prevented by intermittent compression of the calf. It is concluded that, whatever the mechanism by which venous thrombosis is prevented by intermittent compression of the calf, it is not by further stimulation of systemic fibrinolysis.

Dextrans↗
PubMed1977

Comparison of bovine lung and porcine intestinal heparin for arterial thrombosis in man.

The clinical effectiveness of bovine lung heparin and porcine intestinal heparin for reducing arterial thrombosis was compared in a study of 64 surgical patients (mean age, 63.8 years). Immediately prior to operation, the radial artery was cannulated. The catheters were flushed continuously at a flow rate of 3 ml/hr with 0.9% sodium chloride solution without heparin or with two units per milliliter of either beef lung or pork intestinal mucosa heparin. After 24 hours, arteriography was performed, and vessel diameter and the amount of thrombus present were recorded. The addition of heparin to the flush solution significantly reduced the accumulation of thrombotic material on the surface of intra-arterial cannulae, thus lowering the incidence of clinically detectable arterial occlusion. No significant difference was found in the anticoagulant effectiveness of beef lung-derived heparin as compared with heparin obtained from pork intestinal mucosa.

Animals↗