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Biomedical subjects

M Fay

Publications and source records attributed to M Fay.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparative production of IL-1 beta and IL-1 alpha by LPS-stimulated human monocytes: ELISAs measurement revisited.

There has always been an apparent discrepancy between the levels of IL-1 alpha and IL-1 beta mRNA and that of their corresponding proteins. Indeed, LPS-stimulated human monocytes produce about 10 times more IL-1 beta mRNA and IL-1 alpha mRNA, while the ratio of the corresponding proteins is the opposite, a difference that has been attributed to less efficient translation of IL-1 beta mRNA. Using a home-made ELISA that recognizes the 31-kDa precursor of IL-1 beta (proIL-1 beta), we found that LPS-stimulated human monocytes produced at least 20 times more IL-1 beta than IL-1 alpha, a ratio in accordance with the corresponding mRNA levels. This difference with previous reports is due to the fact that commercial ELISAs recognize, little if at all, proIL-1 beta. Furthermore, we found that cell lysis with CHAPS released significantly more IL-1 beta than did classical freeze-thawing.

Adult↗
PubMed1994

Dietary habits and the risk of stomach cancer: a comparison study of patients with and without intestinal metaplasia.

Patients with chronic atrophic gastritis intestinal metaplasia (IM) are suspected of being at increased risk for the intestinal type of gastric cancer. Diet is one of several etiologic components that may contribute to the development of the IM lesion. One hundred patients (50 with IM and 50 without IM) were evaluated to determine their dietary intake of nitrosating agents and vitamin C and their smoking habits. Patients with IM reported a higher consumption of two foods rich in nitrosating agents, bacon (.28 vs. .10, p = .02) and sausages (.16 vs. .02, p = .01), compared to patients without IM. Smoking and vitamin C intake were similar in both the IM-positive and the IM-negative groups.

Adult↗
PubMed1994

Restructuring the CNS role for a managed care environment.

The CNS role in a large northeast teaching hospital was the focus of a major organizational change process in response to a tightening fiscal environment. CNSs worked with the nurse executive team to restructure their role from expert consultant to case manager, nurse manager partner, and resource and consultant to the Department of Nursing. Development needs of the CNSs were assessed before and after role revision to evaluate the process and provide evidence of learning and change. The change and learning process evidenced in this article exemplifies the CNSs' ability to adapt and respond to the rapidly changing needs of today's managed care setting.

Hospital Restructuring↗
PubMed1993

Development needs of advance practice nurses in a managed care environment.

The authors describe an organizational change process driven by a critical cost containment effort in a teaching hospital in the northeastern United States. This process resulted in a major shift in the role of the clinical nurse specialist. Development priorities of clinical nurse specialists before and after redesign of the role are described.

Cost Control↗
PubMed1993

[Effects of antibiotics on production of cytokines by human monocytes].

Antibiotics do not act alone but in conjunction with the host defence system. In particular, it has been shown that antibiotics can modify cytokine production. The authors reported here the effects of antibiotics which penetrate inside the cells, such as quinolones and macrolides, on the capacity of blood monocytes to produce IL-I alpha, IL-1 beta, TNF alpha and IL-6 in response to endotoxin. Antibiotics can exert a differential effect on cytokine production: in fact, quinolones, in vitro, at concentrations higher than 25 micrograms/ml decreased IL-1 beta, TNF alpha and IL-6, while they do not modify IL-1 alpha. Moreover, ciprofloxacin orally administered (25 mg/kg for 7 days) transitory increased cytokine production. These results are discussed in terms of tissue concentration. Among the same family of antibiotics such as macrolides, differences on cytokine modulation were observed: spiramycin and erythromycin increased IL-6 production while roxithromycin did not exert any significant effect. All these results tend to prove that some antibiotics are immunomodulators; however interactions between antibiotics and immune responses are complex and studies with patients with infections will be necessary to a better understanding of these relationships.

4-Quinolones↗
PubMed1992

The role of nursing in clinical research trials.

The role of nurses and their scope of practice in various clinical settings have become better defined in recent years. Research for most nurses is either new or unfamiliar, despite the fact that research will in some way affect every nurse in clinical practice. The majority of analysis in the literature of nursing research has focused on the relationship between research and clinical practice. What abilities nurses possess and how they can be put into practice for the success of a clinical research trial are the subjects of this article.

Clinical Trials as Topic↗
PubMed1992

Use of fluoroquinolones for prophylaxis of murine Pneumocystis carinii pneumonia.

We compared the prophylactic activities of six fluoroquinolones against Pneumocystis carinii pneumonia in immunosuppressed rats. Pefloxacin was the only agent which was as effective as the reference drug trimethoprim-sulfamethoxazole. Clinical trials with pefloxacin in patients at risk for P. carinii pneumonia appear to be justified.

4-Quinolones↗
PubMed1991

Ligand-binding characteristics of rat serum-type mannose-binding protein (MBP-A). Homology of binding site architecture with mammalian and chicken hepatic lectins.

Sugar-binding characteristics of rat serum mannose-binding protein (MBP) were studied using the carbohydrate-recognition domain of this protein expressed from a cloned cDNA. To assess the binding affinity of various test compounds, they were added as inhibitors in a binding assay in which 125I-MBP was incubated with yeast cells and the extent of binding was estimated from the radioactivity associated with the pelleted cells. The results of such inhibition assays suggest that MBP has a small binding site which is probably of the trough-type. The 3- and 4-OH of the target sugar are indispensable, while the 6-OH is not required. These characteristics are shared by the rat hepatic lectin and chicken hepatic lectin, both of which are C-type lectins containing carbohydrate-recognition domains highly homologous to that of MBP. Apparently, the related primary structures of these lectins give rise to similar gross architecture of their binding sites, despite the fact that each exhibits different sugar binding specificities.

Animals↗
PubMed1991

Ciprofloxacin treatment in vivo increases the ex vivo capacity of lipopolysaccharide-stimulated human monocytes to produce IL-1, IL-6 and tumour necrosis factor-alpha.

Because in vitro treatment with quinolones, at pharmacological concentrations, modifies lipopolysaccharide (LPS) induced production of cytokines by monocytes, we studied the effect of orally administered ciprofloxacin (25 mg/kg) on the capacity of peripheral blood monocytes of healthy volunteers to produce tumour necrosis factor-alpha (TNF-alpha), IL-1 activity, IL-1 alpha, IL-1 beta and IL-6 ex vivo in response to endotoxin stimulation. After 7 days of ciprofloxacin, the extracellular and cellular production of TNF-alpha, the cellular production of IL-1 activity, the extracellular and cellular production of IL-1 alpha, and the cellular production of IL-6 increased significantly. Seven days after the end of the treatment, values returned to basal levels or even lower. To our knowledge, this is the first demonstration that ciprofloxacin can modulate in vivo the capacity of human monocytes to react to an inflammatory stimulus such as endotoxin.

Adult↗
PubMed1991

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin.

Antibiotics do not act alone but act in conjunction with the host defense system. In particular, it has been shown that some antibiotics can modify cytokine production. We compared the in vitro effects of three macrolides (roxithromycin, spiramycin, and erythromycin) actively concentrated by leukocytes on interleukin-1 alpha, (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha production by human monocytes stimulated with lipopolysaccharide. Our results show that the three macrolides tested have different effects on production of these cytokines. Spiramycin and, to a lesser extent, erythromycin increased total IL-6 production without affecting IL-1 alpha, IL-1 beta, or tumor necrosis factor alpha production, whereas roxithromycin had no effect. To our knowledge, this is the first time that an antibiotic has been shown to increase IL-6 production.

Adult↗
PubMed1990

Quinolone-induced differential modification of IL-1 alpha and IL-1 beta production by LPS-stimulated human monocytes.

We previously reported that ciprofloxacin (Cip), a quinoline-derivative antibiotic, decreases the biological activity of IL-1 released by LPS-stimulated monocytes after 24 hr of culture without affecting cell-associated IL-1 activity. To analyze further the effects of Cip on LPS-induced IL-1 alpha and IL-1 beta synthesis, each species was measured in the supernatants and cell lysates of monocyte cultures over a 4-day period using IL-1 alpha and IL-1 beta-specific ELISA methods. Cip had a post-transcriptional differential effect on the production of IL-1 alpha and IL-1 beta, reducing the total amount of IL-1 beta produced by LPS-stimulated monocytes, while that of IL-1 alpha was unaffected. In addition, the production of both species was delayed. These findings explain the discrepancy between the Cip-induced alteration of extracellular IL-1 activity and the preservation of cell-associated activity. Cip is, to our knowledge, the first pharmacological agent found to have a differential effect on the synthesis of IL-1 alpha and IL-1 beta. It may form the basis for new pharmacological agents capable of selectively reducing the systemic effects of IL-1 without affecting local activity.

Blotting, Northern↗
PubMed1990

Effects of quinolones on tumor necrosis factor production by human monocytes.

Previous studies have shown that in lipopolysaccharide (LPS)-stimulated human monocytes, interleukin 1 (IL-1) production is altered by quinoline derivative antibiotics (quinolones), in a way which depends both on the dose and on the agents used. Given that IL-1 and tumor necrosis factor alpha (TNF) are produced in response to LPS and have some overlapping and synergistic activities, we sought to determine if TNF production was altered under the above-mentioned conditions. We investigated the effects of three quinolones: ciprofloxacin (Cip), pefloxacin (Pef) and ofloxacin (Ofl). These quinolones were found to decrease extracellular TNF production in a dose-dependent manner at concentrations higher than 25 micrograms/ml as previously described by our laboratory with regard to IL-1 production. Moreover, the order of the extracellular decrease in TNF and IL-1 induced by each drug was similar. However, in contrast to IL-1 activity, the quinolones studied also reduced cell-associated TNF. The kinetics of TNF production suggested that the quinolones affected TNF production at a very early step, probably during TNF synthesis rather than during its secretion into the extracellular medium. Furthermore, the quinolone-induced accumulation of intracellular cAMP could explain the extracellular decrease in both IL-1 and TNF production.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Differential regulation of IL 6, IL 1 A, IL 1 beta and TNF alpha production in LPS-stimulated human monocytes: role of cyclic AMP.

Interleukin 6 (IL 6), IL 1 alpha, IL beta and tumor necrosis factor (TNF) alpha are four cytokines induced in monocytes by lipopolysaccharide (LPS); however, it is unclear whether the mechanisms which control their production are similar. In this study, we report the effects of prostaglandin E2 (PGE2), and two other cAMP-elevating agents, dibutyryl cAMP and 3-isobutyl-1-methyl-xanthine, on the in vitro LPS-induced production of IL 6, IL 1 alpha, IL 1 beta and TNF alpha by human monocytes. The production of these four cytokines was found to be selectively regulated in monocytes, by increases in intracellular cAMP levels. In effect, such agents enhanced, in a dose-dependent manner, both extracellular and cell-associated IL 6 production by LPS-stimulated monocytes. In contrast, it was confirmed, using the same samples, that these cAMP-elevating agents inhibit both extracellular and cell-associated TNF alpha production in a dose-dependent manner. IL 1 alpha and IL 1 beta production, measured by means of specific immunoreactive assays, were not significantly modified. Kinetic analysis showed that the potentiating effect of cAMP on IL 6 production, along with its inhibiting effect on TNF alpha production, could be seen as early as 1 hr after LPS stimulation. These results demonstrate that IL 6, TNF alpha, IL 1 alpha and IL 1 beta production can be differently modulated by an agent, PGE2, which is produced simultaneously by LPS-stimulated monocytes. Such differential autocrine modulation may play an important role in the regulation of the production of cytokines participating in immune and inflammatory responses.

1-Methyl-3-isobutylxanthine↗
PubMed1990

[Effect of quinolones on TNF-alpha production by human monocytes].

Previous studies have shown that in lipopolysaccharide (LPS)--stimulated human monocytes, interleukin-1 (IL-1) production is altered by quinoline derivative antibiotics (quinolones), in a way which depends both on the dose and on the agents used. Given that IL-1 and tumor necrosis factor alpha (TNF) are produced in response to LPS and have some overlapping and synergistic activities, we sought to determine if TNF production was altered under the above-mentioned conditions. We investigated the effects of three quinolones: ciprofloxacin (Cip), pefloxacin (Pef) and ofloxacin (Ofl). These quinolones were found to decrease extracellular TNF production in a dose-dependent manner at concentrations higher than 25 micrograms/ml as previously described by our laboratory with regard to IL-1 production. Moreover, the order of the extracellular decrease in TNF and IL-1 induced by each drug was similar. However, in contrast to IL-1 activity, the quinolones studied also reduced cell-associated TNF. The kinetics of TNF production suggested that the quinolones affected TNF production at a very early step, probably during TNF synthesis rather than during its secretion into the extracellular medium. Furthermore, the quinolone-induced accumulation of intracellular cAMP could explain the extracellular decrease in both IL-1 and TNF production.

Ciprofloxacin↗
PubMed1989

Oxidative injury amplifies interleukin-1-like activity produced by human monocytes.

Exposure of human monocytes to 95% normobaric oxygen (O2) was used as an in vitro oxidative injury model to study the effects of the O2-derived species produced by phagocytes at inflammatory sites on monocyte IL-1 production. Exposure to O2 enhanced production by monocytes of IL-1-like activity whether the adherent cells were cultured in the presence of opsonized zymosan, LPS or medium alone. This O2-induced increase in production of IL-1 activity was inhibited by cycloheximide and thus resulted from de novo protein synthesis. Furthermore, the increase was prevented by the addition of the protein kinase inhibitor N-2-methylaminoethyl-5-isoquinoline sulfonamide dihydrochloride (H8). Following exposure to O2, Ca2+/phospholipid-independent protein kinase activity increased in comparison to air-exposed monocytes, whereas the dependent form decreased. Since the Ca2+/phospholipid-independent form is known to derive from the dependent form (protein kinase C) by proteolysis in the presence of a thiol proteinase, our results suggest that oxidative injury stimulates thiol proteinase activity and enhances production of IL-1 activity by human monocytes partly by interfering with protein kinase C metabolism. Among the consequences of the generation of O2-derived species by phagocytes in inflammatory sites, the augmentation of the production of IL-1-like activity could amplify the inflammatory response.

Adult↗
PubMed1988

In vitro O2-induced depression of T and B lymphocyte activation is reversed by diethyldithiocarbamate (DDC) treatment.

In this study, we tried to establish a relationship between the immunopotentiating effects and the antioxidant activity of the immunostimulating compound, diethyldithiocarbamate (DDC). We studied the effects of DDC treatment on enriched T and B murine spleen lymphocytes in an in vivo-ex vivo model of O2-induced immune depression. Female C57B1/6 mice were injected subcutaneously with a single dose of DDC (125 mg.kg-1). Eight days after DDC injection, we evaluated, in vitro, the concanavalin A response of the T cell fraction and the LPS response of the B cell fraction, under standard (air--5% CO2) and hyperoxic (60% O2--5% CO2) culture conditions. The results show that after a lag period, DDC is able to enhance the mitogenic response of T and B murine lymphocytes under standard culture conditions to restore the ConA response and to partially restore the LPS response under hyperoxic conditions. The results of this study suggest that the immunostimulatory effects of DDC could be related to the antioxidant activity of this compound on the lymphoid cellular metabolism. This activity apparently affects both T and B lymphocytes.

Animals↗