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Biomedical subjects

M Fay

Publications and source records attributed to M Fay.

At least 91 records · Page 5Linked to original sources
PubMed1985

Lymphocyte glutathione status in relation to their Con A proliferative response.

We studied the intracellular total, oxidized and reduced glutathione levels in thymus and spleen rat lymphocytes cultured with or without Con A and 2-mercaptoethanol (2-ME). After 48 h culture, the total glutathione level decreased and the oxidized glutathione level increased in the two types of unstimulated and stimulated cells. In the presence of 2-ME, the tritiated thymidine incorporation increased in splenocytes but not in thymocytes; on the other hand, the two types of stimulated cells increased their total and oxidized glutathione content. The enhancement of the GSSG/GSH + GSSG ratio, irrespective of culture conditions, indicates a severely disturbed redox state of the cells. 2-ME acts on the glutathione synthesis of stimulated lymphocytes but is unable to maintain a normal redox state of these cells.

Animals↗
PubMed1985

High concentrations of oxygen modulate in vitro Con A responses of rat lymphoid cells. Effect of 2-mercaptoethanol.

The effects of different normobaric oxygen concentrations (40, 60 and 95%) on the survival and the proliferative response to Con A of rat lymphoid cells were studied. Spleen, thymus and peripheral blood mononuclear cells were tested. We found that oxygen concentrations modulated the proliferative response independently of cell survival. The addition of 2-mercaptoethanol (2-ME) partially prevented the toxic effects of hyperoxia but the population of thymocytes which responded to Con A stimulation appeared to be less sensitive to the protective action of 2-ME. The relationship between oxygen concentrations and the lymphoid proliferative response could be used as a model of oxidant immunodepression for evaluating pharmacological effects of antioxidant compounds.

Animals↗
PubMed1985

Immune oxidative injury induced in mice exposed to normobaric O2: effects of thiol compounds on the splenic cell sulfhydryl content and Con A proliferative response.

In vivo exposure of mice to normobaric O2 depresses the cellular immune response by a mechanism that remains unknown. In vitro oxidative injury leads to decreased sulfhydryl groups (SH) in lymphocytes. To determine whether in vivo exposure to O2 would have similar effects, we measured the SH content in spleen cells both from mice that had been exposed to normobaric O2 (O2 SC) and from controls exposed to ambient air (Air SC). The SH content of the fresh O2 SC was slightly decreased, whereas after 48 hr of culture, the SH content and the proliferative response of these cells were found to vary with the type and concentration of thiol or disulfide compounds added to the culture medium. Under standard culture conditions, i.e., RPMI 1640 medium containing 0.41 mM half-cystine, the SH content in O2 SC decreased sharply to about 10 and 20% that of Air SC in the absence or presence of Con A (2 micrograms/ml), respectively. Under these culture conditions, the proliferative response of O2 SC was 20.5% +/- 3.2 of Air SC. In cystine-free RPMI 1640 medium supplemented with various concentrations of L-cystine, L-cystine and 2-mercaptoethanol (2-ME), L-cysteine, or reduced glutathione (GSH), the proliferative response to Con A and the SH content of the O2 SC varied in parallel and were correlated (p less than 0.01). Half-cystine (0.41 mM) plus 2-ME (5 X 10(-5) M) or L-cysteine alone (4 mM) completely protected the SH content of O2 SC and induced a proliferative response 82% +/- 6 that of the controls. In cystine-free RPMI 1640 medium supplemented with GSH (4 mM), the SH content and proliferative response of O2 SC were 79 and 67.5% of Air SC, respectively. Other concentrations of these compounds were less effective. Oxygen scavengers such as SOD, catalase, mannitol, and vitamin E did not protect against the decrease of the O2 SC. The induced oxidative cellular damage might be related in part to a membrane lipid peroxidative process. These data show that in vivo exposure of mice to normobaric O2 induced lesions in splenic cells manifested under standard culture conditions by a decrease in both SH content and Con A proliferative response. The extent of these alterations could be modulated by variations of the thiol environment. Protection of the SH content correlated with protection of the proliferative response of the O2 SC.

Animals↗
PubMed1984

Effect of D-thyroxine on serum sex hormone binding globulin (SHBG), testosterone, and pituitary-thyroid function in euthyroid subjects.

Concentrations of serum sex hormone binding globulin (SHBG) and free testosterone (T) were examined in 10 euthyroid subjects (5 men and 5 women) before, during and after 30 days of the daily ingestion of 1 or 4 mg D-thyroxine (D-T4), the thyroxine analog that has only 1-15% of the calorigenic effect of L-thyroxine (L-T4). No changes in serum L-T4 or triiodothyronine (T3), serum cholesterol, SHBG, T, progesterone, estradiol-17 beta, or free T concentrations were observed in response to the 1 mg dose, but there was a slight elevation in the free thyroxine index (FTI) and a significant (p less than 0.02) suppression of the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH). The 4 mg dose of D-T4 induced an increase in SHBG levels in all but one man. There was a significant negative correlation between the SHBG and percent free T (p less than 0.05) although the mass of free T did not change. As a group, the women responded with a greater increase in SHBG and decrease in percent free T than the men. Serum cholesterol decreased (p less than 0.01), all serum thyroid hormone values measured by RIA were increased (p less than 0.01), and the TSH response to TRH was completely suppressed. Despite these changes, the subjects remained clinically euthyroid. Concentrations of testosterone, progesterone and estradiol-17 beta remained unchanged. Serum luteinizing hormone (LH), which was evaluated in the men only, also did not change during the daily administration of 4 mg D-T4.

Adult↗
PubMed1984

The effects of propylthiouracil, iodothyronines, and other agents on thyroid hormone metabolism in human placenta.

Human and rat placental homogenates contain inner ring deiodinase activity (PT4ase) towards T4 and T3. This activity may decrease the transfer of T4 and T3 across the placenta and influence thyroid hormone disposal in the fetal circulation. Data are now presented on human PT4ase in subcellular fractions, the Km of human PT4ase, and the effects of drugs and other compounds on human and rat PT4ase. The specific activity (nanograms of rT3 produced per min/mg protein) of each fraction of human placenta was as follows: nuclear, 0.07; mitochondrial, 0.15; lysosomal, 0.19; microsomal, 1.30; and cytosol, 0.01. The apparent Michaelis-Menton (Km) for PT4ase in human placental microsomes was 1.2 X 10(-7) M. T3, 3,3'-diiodothyronine, iopanoic acid, iodoacetic acid, diamide, and propranolol all exhibited dose-dependent inhibition of human and rat PT4ase when tested in the presence of 10 mM dithiothreitol (DTT). Propylthiouracil did not inhibit PT4ase at 10 mM DTT, but when the DTT concentration was lowered to 0.25 mM, up to 71% inhibition was noted. Many drugs, as noted in other organs with respect to outer and inner ring iodothyronine deiodinases, inhibited human PT4ase. These studies may be relevant to the practice of administering propylthiouracil, propranolol, and iopanoic acid to pregnant women.

Animals↗
PubMed1984

Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy.

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Adult↗
PubMed1984

In vivo normobaric oxygen exposure depresses spleen cell in vitro Con A response. Effects of 2-mercaptoethanol and peritoneal cells.

Normobaric O2 exposure decreased spleen cell (SC) response to T cell mitogen Con A. 3H-TdR incorporation of SC from O2 exposed mice (O2SC) compared to those of control mice (Air SC) decreased significantly after 72 and 87 h O2 exposure. The dose response kinetics to Con A were identical in O2SC or Air SC. Increasing SC number did not restore the response to Con A and the depressed hyperoxic effect was not related to suppressor cells in the spleen of O2 exposed mice. Response of O2SC to Con A was restored by the thiol compound 2-mercaptoethanol (2-ME), and the degree of restoration by 2-ME, was inversely proportional to the depressed response. Addition of intact peritoneal cells (PC) induced restoration within the same range as 2-ME. Restoration of the mitogenic response by 2-ME involved antioxidant properties and suggested that macrophages were functionally injured by O2 exposure. In cases where mitogen response was highly depressed, restoration was only partial; in these conditions in vivo O2 injury probably involved both macrophages and splenic T cells. The mechanisms of O2 toxicity have been discussed in terms of free radical generation under hyperoxic conditions.

Animals↗
PubMed1983

Preincubation of thyroxine with sulfhydryl-reducing agents does not stimulate thyroxine inner or outer ring deiodination.

Sulfhydryl reagents stimulate enzymatic conversion of T4 to T3 and rT3. A recent study suggested that such reagents stimulated T4 5'-deiodination by a direct interaction with T4. We therefore tested the ability of dithiothreitol (DTT) and other sulfhydryl reagents to enhance the susceptibility of T4 and rT3 to 5'-deiodination by liver homogenates and of T4 to 5-deiodination by placental homogenates. Preincubation of T4 with DTT in concentrations ranging from 0.5-80 mM did not result in increased T3 production from T4 in rat liver homogenates, nor was T3 production increased by preincubation of T4 with reduced glutathione or mercaptoethanol. Preincubation of rT3 with DTT also did not result in increased rT3 degradation by liver homogenates. T4 5-deiodination to rT3 by rat and human placental homogenates was not consistently increased by preincubation of T4 with DTT in concentrations ranging from 2.25-450 mM. These results do not support the hypothesis that sulfhydryl stimulation of T4 deiodination occurs as a result of sulfhydryl-T4 interaction.

Animals↗
PubMed1982

Surgical therapy for Prinzmetal's variant angina.

Fifty-two patients underwent coronary artery bypass grafting between 1973 and 1979 for variant angina, defined as pain, usually at rest, associated with S-T segment elevation. Only patients with fixed occlusive coronary artery disease, defined as greater than 70% narrowing in diameter, were included. When fixed coronary artery stenosis is present, variant angina--whether presenting as stable, unstable, or postinfarction angina, and regardless of the number of vessels diseased--is effectively treated by myocardial revascularization. Preoperative intraaortic balloon pumping is a useful therapeutic adjunct in the unstable subset refractory to medical therapy. The results of revascularization in patients with Prinzmetal's variant angina and fixed coronary disease were no different from those in patients with classic angina pectoris of comparable clinical categories.

Adult↗
PubMed1978

[Effect of a histamine aerosol in 20 subjects with histamine hyperreactivity. Application to a study of the protective properties of pipoxizine].

The authors made a study of the antihistaminic properties of Pipoxizine in 20 subjects with proven histaminic hyperreactivity. The design of the trial consisted in comparing the changes of VC, FEC1, expiratory airway resistance and V50 produced by a histamine aerosol given before and after administration of Pipoxizine. Pipoxizine was given by mouth to 10 patients and intravenously to the other 10 of the group. The statistical analysis of the results demonstrated an antagonist effect of Pipoxizine on the histamine induced bronchoconstriction. The data of this trial are confirmative of the results of other experimenters. It seems therefore reasonable to take into consideration the use of Pipoxizine in the preventive treatment of the paroxystic attacks of the asthmatic disease.

Aerosols↗
PubMed1977

Changes of P50 in hypoxaemia, hypercapnia and polycythaemia: multivariate analysis.

Multivariate analysis of P50 changes in hypoxia, hypercapnia and polycythaemia was performed in an heterogeneous group of forty three patients: hypoxic subjects with or without hypercapnia, with or without polycythaemia and polycythaemic subjects without hypoxia. A statistical analysis was undertaken using comparison of the means, study of the correlations, principal component analysis, multiple regression and correspondence analysis. In the patients studied, P50 changes were not wholly explained by those of 2-3 DPG and pH; PaCO2, per se, did not play an important part. Haemoglobin concentration and P50 value would represent an adaptative mechanism to hypoxia: when hypoxia is moderate (80 greater than PaO2 greater than or equal to 65 torr) and isolated, oxygen haemoglobin affinity decreases (P50 increases); when hypoxia is severe (PaO2 less than 65 torr) and combined with hypercapnia and disturbed acid-base equilibrium, P50 comes back to normal range but haemoglobin increases, restoring thus, the normal blood oxygen content.

Adult↗
PubMed1975

[Measurement of the oxygen affinity of hemoglobin. Application to patients with angina pectoris with normal coronography. Study of 10 cases].

A study of 2-3 D.P.C. (diphosphoglycerate) and of P50 (PO2 of half-saturation of blood at pH 7.40, PCO2 40 torr and temperature 37 degrees C) was carried out in ten subjects: eight women and two men suffering from angina pectoris with no evidence of obstruction on their coronary arteriograms. The study was made with the subjects at rest, in the absence of any acute coronary episode. The results show that these patients have a normal affinity of haemoglobin for oxygen: the 2-3 D.P.G. was 13.05 +/- 2.2 muM.g-1 Hb; P50 was 26.7 +/- 1.3 torr; Hill's "n" was 2.65 +/- 0.29. Deviation to the right of the oxyhaemoglobin curve may be seen, after effort or during a provoked attack, but this movement to the right seems to be the result rather than the cause of the myocardial ischaemia.

Adult↗