Biomedical subjects

M Fay

Publications and source records attributed to M Fay.

At least 19 recordsLinked to original sources

PubMed1997

Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial Na+ channel along rat respiratory tract.

Na+ reabsorption from the epithelial surface of the respiratory tract plays a fundamental role in respiratory physiology. As in the epithelia of the renal collecting tubule and distal colon, Na+ enters across the luminal surface of respiratory epithelial cells via a recently cloned amiloride-sensitive multisubunit (alpha, beta, gamma) epithelial Na+ channel. We have examined the cellular expression at the mRNA level of the alpha-, beta-, and gamma-subunits of rat epithelial Na+ channel (rENaC) in the rat lung and upper airway epithelial cells using in situ hybridization. A large prevalence of alpha- and gamma-rENaC subunit expression (over beta) was found in tracheal epithelium, in a subpopulation of alveolar cells, presumably type II pneumocytes, and in nasal and tracheal gland acini. In contrast, equivalent levels of expression of all three subunits were detected in bronchiolar epithelium and in rat nasal gland ducts. This diversity of expression may reflect cell-specific functions of the amiloride-sensitive Na+ channel along the respiratory tract.

Animals↗

PubMed1997

A longitudinal study of the attitudes of the dental profession towards competition and advertising.

In 1985, members of the dental profession and of four other professional groups in New Zealand were surveyed to establish their attitudes towards the developing commercialisation of their professions, particularly towards advertising. This survey was repeated in 1988, and repeated again in 1994. The results of the three surveys are presented in this paper. Over the survey period there has been a steady, if undramatic, movement of attitudes to a position that is more favourable towards the concept of an openly competitive profession. The use of informative advertising by dental practices had gained widespread acceptance by 1994, but there was still considerable opposition to persuasive advertising. However, there are still areas of professional practice, notably matters concerned with fees, where there is widespread opposition to competition and advertising.

Advertising↗

PubMed1996

An intronic polymorphic repeat sequence modulates interleukin-1 alpha gene regulation.

Recently, we characterized a polymorphism within IL-1 alpha intron 6 as a variable number of a 46 bp tandem repeat (ranging from 5 to 18 repeats). We now analyse whether this polymorphism could play a role in IL-1 alpha gene regulation. We have found that reporter gene expression driven by the IL-1 alpha promoter or a heterologous promoter was decreased by increasing numbers of the repeat sequence corresponding to the most frequent alleles seen in the human population. Furthermore, we showed that the transcription factor Sp1 can bind to the 46 bp sequence. Finally, we were unable to show a statistically-significant relation between in vitro IL-1 alpha production and the number of repeats although there was a clear trend towards an inverse relation. Taken together, these results are consistent with a negative regulatory role for IL-1 alpha intron 6 repeat sequence on IL-1 alpha basal gene transcription.

Adult↗

PubMed1996

Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1.

L-arginine-dependent reactive nitrogen intermediates have been identified as macrophage cytotoxic effector molecules against intracellular pathogens. To determine its role, ex vivo production of NO by peritoneal macrophages of C3H/HeN mice and Dunkin-Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pneumophila serogroup 1 strain was compared with bacterial clearance from the lungs. While the virulent strain was cleared from mice lungs, the guinea pigs died within 96 h. In vivo infection with both strains resulted in the production of NO by mouse peritoneal macrophages ex vivo. In contrast, guinea pig macrophages did not produce detectable NO. In addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent strain, irrespective of stimulation with lipopolysaccharide (LP) and/or interferon-gamma (ifn-gamma). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by host macrophages.

Animals↗

PubMed1996

Diagnostic and treatment guidelines for Helicobacter pylori.

Helicobacter pylori (H. pylori) has been implicated as the causative agent for most gastric and duodenal ulcers. Many patients who present to their primary care provider with dyspeptic symptoms have heard of this "stomach bacteria" and ask if they should be tested and treated for the infection. Prior to diagnosing the presence of the organism, it is essential to determine whether it is likely to be responsible for patients' symptoms. Most patients with ulcer-like symptoms do not have peptic ulcer disease. Moreover, the background prevalence of H. pylori may be high, depending on the age, race, and socioeconomic status of the patient population. Thus, antibiotic treatment to eradicate H. pylori may not provide symptom relief. H. pylori can currently be diagnosed by serology or by a number of techniques involving endoscopic biopsy. In the near future, urea breath testing will likely become the noninvasive method of choice for diagnosing and monitoring the success of treatment for H. pylori in the primary care setting. This article discusses the current issues related to diagnosis and treatment of H. pylori as they relate to the primary care provider and offers insight as to when specialty referrals should be considered.

Decision Making↗

PubMed1995

Vasopressin gene related products are markers of human breast cancer.

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.

Antibodies, Monoclonal↗

PubMed1995

Protective effect of LPS and poly A:U against immune oxidative injury: role of thiols released by activated macrophages.

Oxidative injury of immune cells has been observed both at inflammatory sites and in pathologic situations, such as human immunodeficiency virus infection. We used an ex vivo model of immune oxidative injury to test the antioxidant effect of two immunomodulating agents administered to C57B1/6 mice. Lipopolysaccharide (LPS) and the synthetic polyribonucleotide poly A:U preserved the ConA-induced proliferative response of spleen T cells against oxidative injury ex vivo. The glutathione and thiol contents of fresh spleen T cells from LPS- and poly A:U-treated mice were significantly higher than control values. In addition, spleen T cells from LPS- and poly A:U-treated mice were protected against the oxidative injury-induced decrease in glutathione content after 48 h of ConA stimulation. Because LPS and poly A:U both activate macrophages, we sought an antioxidant effect of macrophage-released compounds. Neither rhIL-1 alpha nor rhTNF alpha protected against oxidative injury in vitro. In contrast, LPS and poly A:U induced macrophages to release acid-soluble thiols, which have been reported to participate in the regulation of glutathione levels in lymphocytes and could therefore protect against immune oxidative injury.

Animals↗

PubMed1995

Absence of correlation between IL-1 alpha intron 6 polymorphism and rheumatoid arthritis.

Several studies have implicated interleukin 1 alpha (IL-1 alpha) in the pathogenesis of rheumatoid arthritis (RA). We analysed IL-1 alpha intron 6 polymorphism in relation to RA (50 patients with RA and 50 healthy controls). The study of a healthy control population confirmed the existence of the different alleles with a frequency similar to that in the Caucasian populations of northern England. Allele and genotype distributions did not differ significantly between the normal and RA populations, although the allele corresponding to 8 repeats was over-represented in the RA population (8 and 14% in the healthy and RA populations respectively). This suggests that IL-1 alpha intron 6 polymorphism could be part of a complex process involving other unidentified genetic factors in the pathogenesis of RA.

Alleles↗

PubMed1994

Otogenic meningoencephalitis induced by Streptococcus pneumoniae in gerbils.

OBJECTIVE: Study and development of a gerbil model of pneumococcal meningoencephalitis secondary to acute middle ear (ME) otitis. Preliminary data raised the hypothesis of a direct bacterial dissemination from the ME focus to the central nervous system. This infection pattern was examined. DESIGN: Animals were inoculated bilaterally by transbulla challenge with a serotype 3 strain of Streptococcus pneumoniae at various inoculum sizes. The incidence and course of meningeal complications were studied in relation to the course of ME otitis. RESULTS: After inoculation of 40 bacteria per ear, lethal meningeal complications occurred in 14 (29%) of 48 cases. A 76% rate (25 of 33 animals) of early meningeal involvement was observed after inoculation of 10(4) bacteria per ear. Actual involvement of brain was confirmed histologically for both infection schemes. Bacterial counts 20 to 22 hours after infection with the higher inoculum showed various phases of the extension of the ME infection to brain tissue, cerebrospinal fluid, and bloodstream. Bacterial counts in ME and brain tissue were strongly correlated (P < .001). Nine of the 25 animals with infection of the central nervous system had positive brain tissue cultures without bacteremia. CONCLUSION: Gradations in inflammatory aspects of the meninges and cerebral parenchyma, together with bacteriologic findings, indicate a primary invasion of meningeal spaces that can result in lethal encephalitis and septicemia. This model might be useful for preclinical therapeutic assays on pneumococcal meningeal complications, including infections due to strains with abnormal susceptibility to antibiotics.

Animals↗

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↗