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Biomedical subjects

E O'Connor

Publications and source records attributed to E O'Connor.

At least 37 records · Page 2Linked to original sources

TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype.

TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.

Animals↗

Improved GC/MS analysis of opiates with use of oxime-TMS derivatives.

An improved gas chromatographic/mass spectrometric (GC/MS) assay is described for the quantitation of codeine and morphine as trimethylsyl (TMS) derivatives. The TMS derivatization of ketone-containing opiates results in the formation of multiple derivatives. Some of these products have retention times close to those of codeine-TMS and morphine-TMS. When the keto-opiates are present in samples assayed for codeine and morphine in urine, they can interfere with the quantitation of these commonly targeted opiates. The assay was improved with the addition of a pre-BSTFA derivatization step, whereby hydroxylamine was used to convert the keto-opiates into the corresponding oxime derivative. These derivatives were then reacted with BSTFA to form the TMS ethers and TMS oxime derivatives. The oxime step enabled production of single derivatives for hydrocodone and hydromorphone. In addition, the retention times for the oxime-TMS derivatives were increased so that they no longer elute near the targeted drugs of codeine and morphine. The addition of the oxime step does not affect the sylation of codeine and morphine, and the accuracy and precision of this assay were unaffected.

Codeine↗

Effects of cardiopulmonary bypass on systemic vascular resistance.

During cardiopulmonary bypass (CPB), complex neuroendocrine responses occur and result in haemodynamic changes. Systemic vascular resistance (SVR) before, during, and after CPB was documented in patients undergoing coronary artery bypass surgery. Whilst the overall effect was an increased SVR, transient profound decreases in SVR at the commencement of CPB, during the rewarming phase, and immediately on weaning off CPB were demonstrated.

Adult↗

Biosynthesis and maintenance of GSH in primary astrocyte cultures: role of L-cystine and ascorbate.

We have studied the optimal conditions to maintain the astrocyte GSH levels under normal and oxidative stress conditions. The rate of GSH synthesis from L-methionine was statistically lower than from L-cystine or N-acetyl-cysteine in astrocytes treated with diethyl-maleate, which is a substrate of GSH S-transferases. This is in accordance with the fact that cystathionase activity was not detectable. The transport of L-cystine mediated by the Na(+)-independent system Xc- is the limiting step in GSH synthesis in astrocytes. Incubation with tert-butyl hydroperoxide (t-booH) reduced GSH concentration in astrocytes. This reduction was ameliorated in part by the addition of ascorbate or dehydroascorbate. When L-cystine and ascorbate were added together to the t-booH-treated astrocytes, the GSH concentration was indistinguishable from controls. Electron micrographs of astrocytes treated with t-booH showed an increased number of vacuoles and mitochondrial swelling. This was prevented by ascorbate and dehydroascorbate. The physiological implications of the availability of GSH precursors and ascorbate in the maintenance of GSH in astrocytes are discussed.

Amino Acids↗

Effects of hepatocyte growth factor on the growth and metabolism of human hepatocytes in primary culture.

The effect of recombinant human hepatocyte growth factor (h-rHGF), a potent mitogen for hepatocytes, was investigated in primary cultures of human hepatocytes. Here, we describe a series of experiments to investigate the kinetics of its mitogenic action, as well as its metabolic effects on cultured human hepatocytes. The h-rHGF is a potent signal for initiating DNA synthesis in human hepatocytes, with maximal stimulatory effects at 10 ng/mL (0.1 pmol/L). The kinetics of DNA synthesis showed a lag of about 48 to 72 hours, followed by a maximum at 96 hours. At least 48 hours of continuous exposure to h-rHGF are required to initiate DNA synthesis in quiescent human hepatocytes. Cell cycle analysis by flow cytometry showed that most of quiescent 2c cells have left G0/G1 and entered the cell cycle (S and G2/M phases) by 96 hours of continuous exposure to h-rHGF. When compared with other growth factors, h-rHGF was a much more potent mitogen. The effects of 10 ng/mL (0.1 pmol/L) h-rHGF on DNA synthesis were only achieved by 1.5 pmol/L epidermal growth factor (EGF), 0.1 mumol/L insulin, or 1 mumol/L glucagon. It is noteworthy that the effect of h-rHGF was potentiated by glucagon but not by insulin or EGF. The stimulatory effect of HGF on DNA synthesis was gradually inhibited by h-rHGF transforming growth factor beta (TGF-beta) in the range 1 to 10 ng/ml. The HGF also influenced the expression of other hepatic genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

Patients' attitudes toward hallucinations.

OBJECTIVE: This study examined patients' attitudes toward their hallucinations by assessing their beliefs about the purposes served by hallucinations and the adverse effects of hallucinations. It also investigated whether these attitudes were related to characteristics of the hallucinations or of the patients, whether the attitudes changed after treatment, and whether attitudes before treatment predicted the presence or absence of hallucinations after treatment. METHOD: Fifty hallucinating psychiatric inpatients were given semistructured interviews shortly after admission to the hospital and again shortly before discharge. The interviews elicited detailed descriptions of 12 phenomenologic characteristics of hallucinations and 11 attitude variables. RESULTS: The majority of subjects reported some positive effects of hallucinations. The presence of olfactory hallucinations and the ability to predict hallucinations were significantly related to valuing hallucinations. Attitudes usually did not change with treatment; when they did change they usually became more positive. Subjects who valued hallucinations more before treatment were significantly more likely to be hallucinating after treatment. CONCLUSIONS: The findings are consistent with the idea that psychological factors contribute to the expression of hallucinations. Assessing adaptive functions of hallucinations may predict whether hallucinations will respond to treatment and identify fruitful areas for psychosocial intervention.

Adolescent↗

Swelling of astrocytes causes membrane potential depolarization.

Rat brain astrocytes growing in primary monolayer cultures were swollen by exposing them to media of decreasing osmolality caused by removal of NaCl, and the effects of this treatment on their membrane potentials were measured by intracellular recording. Depolarizations were seen that were proportional to the degree of swelling, reaching a maximum of around 60 mV when 80-100 mM NaCl was removed from the reaction media, which had an original total osmolality of 290 mosmolal. These effects were completely reversible, since restoring the cells to iso-osmotic medium after a 2-min exposure caused an immediate repolarization back to the original membrane potentials, and depolarizations were not seen when isotonicity was maintained by replacing NaCl with sucrose. Partial repolarization was seen during an extended period (30 min) of exposure to hypo-osmotic medium, mirroring a regulatory volume decrease we have previously described in these cells under identical conditions. In ion-replacement studies depolarizations were seen when the solution was made hypo-osmotic with the large cation N-methyl-D-glucamine totally replacing Na+ in the medium. Removal of Cl- from the medium also had no effect on the initial swelling-induced depolarization. These results show that even moderate swelling of astrocytes in primary culture results in marked depolarization of their membrane potentials; possible mechanisms for this effect and the potentially profound implications for the swelling of astrocytes seen in situ under pathological conditions are discussed.

Animals↗

Analysis by flow cytometry of rat hepatocytes from different acinar zones.

Many functional, morphological and biochemical differences among hepatocytes from different acinar zones have been described. Therefore, it will facilitate studies on liver metabolism rapid, non-destructive procedures to isolate hepatocytes from these zones. Flow cytometry is a new powerful tool which, however, has not been used thus far to accomplish the separation of hepatocytes from different acinar zones. We describe here various cytometric parameters which characterize hepatocyte populations, separated by isopycnic centrifugation in Percoll gradients. The intraacinar origin of the different hepatocytes was assessed by enzymatic and morphological measurements.

Alanine Transaminase↗

A two-channel radiotelemetry system for clinical fetal monitoring.

A radiotelemetry system for monitoring fetal heart rate and uterine contractions during labor has been developed and evaluated. The two-channel transmitter utilizes a miniature intrauterine pressure sensor which frequency modulates a subcarrier. The fetal electrocardiogram picked up by a scalp electrode is summed with the subcarrier and this direct frequency modulates the RF carrier. The transmitter has been constructed in a miniature package using conventional electronic components. A receiver system which obtains the original signals and feeds them to a conventional fetal monitor has been developed for use with this transmitter. Clinical evaluation has shown the telemetry system to provide efficacious signals.

Electrocardiography↗

Fetal breathing movements in high risk pregnancy.

In 12 normal and 50 high risk pregnancies fetal breathing and fetal trunk movements were measured by real time ultrasound after the mothers had been given oral glucose. Fetal breathing was significantly reduced in the two fetuses which subsequently died and in five of six fetuses developing fetal distress in labour. Two patterns of breathing were noted in 23 fetuses with cessation of Intrauterine growth: either reduced fetal breathing or almost continuous breathing. Fetal trunk movements were more variable than breathing movements and a reduction in trunk movements had less predictive value.

Female↗