Search PubMed⌕ Search

Biomedical subjects

M Fay

Publications and source records attributed to M Fay.

At least 73 records · Page 4Linked to original sources
PubMed1988

Enhancement of interleukin 2 production by quinolone-treated human mononuclear leukocytes.

Previous studies have shown that lectin-induced human mononuclear leukocyte (MNL) proliferation was influenced by quinoline derivative antibiotics (quinolones), depending on both the dose and the antimicrobial agent used. Since the production of interleukin-2 (IL-2) is known to be involved in the proliferation of immune cells, we investigated the effects of three quinolones: ciprofloxacin (Cip), ofloxacin (Ofl) and pefloxacin (Pef) on IL-2 production in vitro by phytohemagglutinin (PHA)-stimulated human MNL. IL-2 activity in the supernatants of PHA-stimulated MNL was found to be enhanced by quinolones in a dose- and time-dependent manner. Increased IL-2 activity was observed using Cip, Ofl or Pef at therapeutically achievable blood concentrations (5-10 micrograms/ml). Since at these concentrations the PHA-induced proliferative response of MNL was not impaired by quinolones, the increased recovered IL-2 activity was not related to a decreased absorption of IL-2 by activated MNL. At high antibiotic concentrations (25 micrograms/ml), the enhanced IL-2 activity might be related (i) to increased accumulation resulting from the decreased proliferation induced by the quinolones at these concentrations, and (ii) to a true increased IL-2 production by the cells. In fact, an increased IL-2 recovery in presence of quinolones was always observed after blocking the cell cycle by mitomycin C, and was therefore independent of DNA-synthesis. Furthermore, the expression of IL-2 receptors was not modified by Cip, Ofl or Pef. These data show that quinolones increased IL-2 synthesis by MNL and suggest the potential usefulness of these antibiotics, not only as antimicrobial agents, but also as modulators of immune responses.

Anti-Infective Agents↗
PubMed1988

Interleukin-1 production by antibiotic-treated human monocytes.

The effects of penicillin, macrolides (spiramycin and erythromycin), cephalosporins (cefaclor and cefadroxil), tetracycline (doxycycline) and quinolones (pefloxacin, ciprofloxacin and ofloxacin) on extracellular and cell-associated interleukin 1 (IL-1) activity from human adherent mononuclear leucocyte cells were investigated in vitro. When cells were treated with an antibiotic concentration of 10 mg/l, no apparent effect could be detected for penicillin, erythromycin, cephalosporins or quinolones, while a slight increase of extracellular IL-1 activity associated with a decrease of intracellular IL-1 activity was observed with spiramycin and doxycycline. When high antibiotic concentration were used, extracellular IL-1 activity was increased by macrolides and tetracycline, while both cell-associated and class II human monocyte antigen expression were decreased. A toxic effect may have been exerted by these antimicrobial agents, since cell viability was altered when they were used at high concentrations. In contrast, extracellular IL-1 activity was found to be decreased by quinolones and cephalosporins. Intracellular IL-1 activity was also decreased by cephalosporins, while quinolones did not modify either cell-associated IL-1 activity or class II human monocyte antigen expression. The effect induced by quinolones and cephalosporins occurred without modification of cell viability. IL-1 activity was shown to be affected by antibiotics over the same range of concentrations which are known to inhibit mononuclear leucocyte proliferation. Our data may help in defining the mechanism by which the mitogen-induced mononuclear proliferative response is suppressed by antimicrobial agents since this appears to involve the inhibition of IL-1 production or of its release.

Anti-Bacterial Agents↗
PubMed1988

Today's crisis in radiologic technology human resources: a call for action.

The authors, from their perspective of educational program accreditation, comment on issues related to the lack of adequate radiologic technical personnel. Economic and social factors that affect student recruitment are identified as well as suggestions for managing the problem. The authors propose an all-out effort by the profession to initiate the necessary actions to identify and achieve a long-term solution.

Career Choice↗
PubMed1988

Mechanisms by which oxidative injury inhibits the proliferative response of human lymphocytes to PHA. Effect of the thiol compound 2-mercaptoethanol.

The use of normobaric exposure to O2 as a model for in vitro oxidative injury prevented phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) from undergoing the G0 to G1 transition, but 5 x 10(-6) M 2-mercaptoethanol (2-ME) almost protected the cells from this blockade. The percentage of cells with IL-2 and transferrin-receptors was reduced by the O2 exposure and, like the cell cycle transition, was protected by 2-ME against oxidative injury. By contrast, IL-2 recovery in the supernatants of O2-exposed PHA-stimulated PBMC was enhanced. This enhancement may be due partly to the reduced IL-2 consumption caused by the decreases in IL-2 receptor expression and in proliferation. On the other hand, IL-2 recovery in the supernatants of O2-treated PBMC was always enhanced compared to the IL-2 control recovery after DNA synthesis was blocked in G1/S by mitomycin c, and the G0/G1 transition was protected by 2-ME. Furthermore, PHA-stimulated monocytes exposed to O2 produced more IL-1 than control cells. This enhanced IL-1 production was not modified by 2-ME. These results suggest that oxidative injury reduces the proliferation of PBMC by interfering with the cellular events that lead to the transition from the G0 to the G1 phase of the cell cycle. The protective effects of 2-ME suggest that thiol compounds have a critical role in the early events of the cell cycle. By contrast, exposure to O2 induced increases in the production of both IL-1 and IL-2 that may not be related to alterations in the thiol status of the cell.

Cell Cycle↗
PubMed1987

Effects of quinolones on interleukin 1 production in vitro by human monocytes.

The new quinoline derivative antibiotics (quinolones), pefloxacin and ciprofloxacin at concentrations higher than 50 micrograms/ml inhibit the PHA response of the human mononuclear leukocytes in vitro. Since monocytes have been shown to be accessory cells for the activation of lymphocytes by mitogens, we investigated the effects of pefloxacin and ciprofloxacin on extracellular interleukin 1 (IL-1) and cell-associated IL-1 from lipopolysaccharide-stimulated human monocytes. Pefloxacin and ciprofloxacin decreased the extracellular IL-1 in a dose-dependent manner, while cell-associated IL-1 was not altered. These effects were observed even after a short period of incubation (1 or 2 h). No inhibitory activity against purified IL-1 or IL-2 could be demonstrated in the dialyzed supernatants from pefloxacin- or ciprofloxacin-treated monocytes. Neither pefloxacin nor ciprofloxacin modified the biological activity of preformed IL-1. The decrease of extracellular IL-1 induced by pefloxacin and ciprofloxacin could, in part, account for the observed decrease in the proliferative response of human mononuclear leukocytes to phytohemagglutinin, as extracellular IL-1 and proliferative response were positively correlated (at various concentrations of pefloxacin and ciprofloxacin). The decrease in extracellular IL-1 was not associated with any alteration in the expression of the HLA-DR antigen on the monocytes membrane. These data suggested that pefloxacin and ciprofloxacin could antagonize IL-1 production and release by lipopolysaccharide-stimulated monocytes. These quinolones could be interesting tools to study the production, processing, transport and release from the monocytes of IL-1.

Adult↗
PubMed1987

Glutathione status of rat thymocytes and splenocytes during the early events of their ConA proliferative responses.

Glutathione plays an important role in the lymphocyte mitogenic response. We have demonstrated that 2-ME increases the ConA proliferative response of rat splenocytes and in parallel, causes an enhancement of glutathione synthesis in these cells. On the other hand, 2-ME had the same action on the glutathione level of thymocytes during the late phase of their mitogenic response, but it had no effect on the [3H]thymidine uptake of these cells. To clarify this discrepancy and the role of glutathione during the mitogenic response, we studied the glutathione status of thymus cells during the early phase of the ConA-induced proliferative response in the presence or the absence of 2-ME in parallel with that of whole spleen cells and the T cell fraction of splenocytes. During the early events of the mitogenic response, i.e., during the 24th h, we observed a normal 2 GSSG/GSH + 2 GSSG ratio in cultured cells, indicating a normal redox state, and that ConA involved an increased glutathione level in thymocytes but not in whole splenocytes and in splenic T cells. 2-ME had no effect on the glutathione level of stimulated thymocytes during the early phase of the mitogenic response. This phenomenon could be related to an absence of its effect on [3H]thymidine uptake. On the other hand, 2-ME induced an enhancement of the glutathione level and [3H]thymidine uptake in the two types of stimulated splenocytes. This study suggest that thymocytes do not have the same mechanism of glutathione synthesis induction as that which occurs in splenocytes during the ConA proliferative response. This mechanism could be related to the maturation state of the T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Comparative effects of quinolones on human mononuclear leucocyte functions.

The effects of three quinoline derivatives--pefloxacin, ciprofloxacin and ofloxacin--were investigated in mitogen-stimulated human peripheral blood mononuclear leucocytes (MNL). At concentrations of 50 mg/l or more, pefloxacin, ciprofloxacin or ofloxacin significantly inhibited MNL proliferation in response to phytohaemagglutinin. This inhibition was more marked with ciprofloxacin than pefloxacin or ofloxacin. To determine the possible mechanism(s) involved in the inhibition of MNL proliferation following exposure to pefloxacin, ciprofloxacin or ofloxacin, we assessed (1) interleukin-1 (IL-1) activity in supernatants from monocytes treated with the quinolones and (2) the effects of 2-mercaptoethanol (2-ME) a thiol compound which acts as an antioxidant agent and the effect of indomethacin (INDO) an inhibitor of prostaglandin E2 synthesis. 2-ME and INDO did not prevent the decrease in the proliferation. IL-1 activity was shown to be decreased for the same range of antibiotic concentrations as observed for the inhibition of MNL proliferation. Cellular viability of the MNL or monocytes was not modified by any of the quinolones at the concentrations tested. Taken together, these results suggest that pefloxacin, ciprofloxacin and ofloxacin act as immunomodulators. The mechanism involved with the cascade of events that leads to the lymphocyte proliferation and the clinical relevance need further investigation.

Cell Survival↗
PubMed1986

Glutathione status during the mitogenic response of rat splenocytes. Effects of oxygen concentration: FO2 21% versus FO2 7%.

Glutathione is known to be an important parameter for ConA proliferative response of murine splenocytes. We studied the glutathione status of ConA-stimulated rat splenocytes during the early and late phase of the mitogenic response under low (FO2 7%) and standard (FO2 21%) oxygen concentrations. We determined the intracellular total, oxidized and reduced glutathione levels after 6, 12, 24 and 48 h of culture with or without ConA and/or 2-ME, under FO2 7% and 21%. Our results showed that: The 2 GSSG/GSH + 2 GSSG ratio, which indicated the redox state of the cells, remained normal during the early period of culture (0-24 h), irrespective of culture conditions. After 48 h of culture, this ratio increased dramatically under FO2 21% and less under FO2 7%. The maintenance of the redox state seems to be an oxygen concentration-dependent phenomenon. ConA stimulation involved a glutathione consumption during the early stages of culture; under these conditions 2-ME increased the glutathione synthesis, which was higher under FO2 7% than under FO2 21%. On the other hand, the presence of 2-ME involved an increase of tritiated thymidine uptake in stimulated splenocytes, which was significantly higher under FO2 21% than under FO2 7%. Low oxygen tension (FO2 7%) can induce a higher increase of glutathione synthesis, whereas the respective ConA proliferative response is lower than that observed under standard O2 conditions.

Animals↗
PubMed1986

Macrolides and immunity: effects of erythromycin and spiramycin on human mononuclear cell proliferation.

Macrolides are actively concentrated by leucocytes. The dose-effect responses of spiramycin (Sp) and erythromycin (Er) on phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) stimulated human mononuclear leucocytes (MNL) were studied. Cell viability was not altered at any antibiotic concentration (1-100 mg/l). Both Sp and Er showed dose-related inhibition of the proliferative response of PHA and PWM stimulated MNL. Very marked effects were observed at high antibiotic concentrations and the effects observed at low concentrations (1-10), although small, were also significant. Similar results were observed for the mitogen PWM. A decrease in tritiated thymidine (3H-TdR) incorporation occurred only if Sp and Er were added during the first 8 h of culture. Sp and Er also induced a decrease in tritiated uridine (3H-UdR) uptake. These data suggest that Sp and Er interfered with an early event in the cell cycle. However Sp did not affect PHA binding to MNL. The clinical significance of these findings is discussed.

Cell Division↗
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↗