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Biomedical subjects

G Laflamme

Publications and source records attributed to G Laflamme.

12 recordsLinked to original sources

Eosinophil activation status and corticosteroid responsiveness in severe asthma.

BACKGROUND: Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma. METHODS: Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (DeltaFEV(1)) >/= 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (DeltaFEV(1) </= 15%, n = 9) and dependent (>/= 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. RESULTS: Calcium ionophore-induced leukotriene (LT) C(4) release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC(4) release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p </= 0.02) and decreased GM-CSF-enhanced LTC(4) release in CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily dose of oral CS (35 +/- 8 mg), blood counts of eosinophils from CS-dependent subjects were higher (p = 0.03) and GM-CSF enhancement of LTC(4) release was greater (2.8-fold) than in CS-sensitive (2. 1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM-CSF enhancement of LTC(4) release by eosinophils of CS-sensitive asthmatics (p = 0.001). CONCLUSIONS: Eosinophils from CS-dependent asthmatics have an impaired response to CS, whereas serum from CS-resistant subjects contains an inhibitor of eosinophil response to GM-CSF.

Administration, Oral↗

Common respiratory viruses in lower airways of patients with acute hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP), a lung disease with "flulike" symptoms, results from repeated exposures to well defined, nonpathogenic antigens. This study examined whether respiratory viruses are present in the lower airways, the likely site of hypersensitivity reaction, in patients with HP. The polymerase chain reaction (PCR) method was used to test for 10 common respiratory viruses in bronchoalveolar lavage (BAL) cells obtained from patients with acute HP and from unexposed healthy volunteers. Immunocytochemistry was subsequently used to localize viral proteins within BAL cells. The results of PCR showed that influenza A virus was the most frequently detected virus in the BAL cells of our study patients (six of 13) and control subjects (two of six). Influenza A proteins were detected within alveolar macrophages in nine of 13 patients and in two of six control subjects. The number of total BAL cells, but not lymphocytes, was higher in patients with documented influenza A proteins than in patients with no influenza A proteins (p = 0.017) and correlated with the proportion of influenza-A-positive alveolar macrophages (r = 0.7; p = 0.036). This report documents the presence of viruses in the lower airways of patients with acute HP. The findings may imply a potential role for influenza A in the modulation of HP during antigen exposure.

Acute Disease↗

5' untranslated sequences modulate rapid mRNA degradation mediated by 3' AU-rich element in v-/c-fos recombinants.

One major determinant of rapid mRNA decay is the presence of AU-rich sequences located in 3' untranslated regions (UTR). To assess for the contribution of upstream sequences on the activity of the 3' AU-rich destabilizing element, we have determined the decay-rates of v-/c-fos hybrid transcripts by quantitative RNA protection analysis. In a transient expression assay, v-/c-fos recombinants generated two mRNA populations via alternative splicing and removal of an optional intron entirely located in the 5' UTR. Both mRNA species were found to be relatively stable in constructs lacking the c-fos AU-rich destabilizing element. Unexpectedly, in recombinants where intrinsic AU sequences were kept intact, only the full-length mRNA population showed high instability whereas the spliced mRNA species remained relatively stable. A v-/c-fos 5' UTR fragment encoding the optional intron was inserted into alpha-globin genes harboring either the c-fos or GM-CSF destabilizing element. The splicing and degradation patterns of these heterologous transcripts paralleled that of v-/c-fos recombinants. These observations unmasked a 5' cis-acting element in v-/c-fos mRNA whose presence is required for the activity of the AU-rich destabilizing element. They demonstrate the important role of interactions between distinct sequences on the regulation of mRNA stability.

3T3 Cells↗

Study of the natural antihistamine-like substance in bile in mammals.

A natural antihistamine substance (NAS) present in bile has been investigated. It was found that the antihistamine activity was not due to proteins, lipids, pigments, or amino acids. On ion exchange chromatography and thin-layer chromatography, this activity was associated with bile acids. Many bile acids could, in varying degrees, inhibit this histamine induced guinea pig ileum contraction, desoxycholic acid being the most potent. However NAS activity could be separated from bile acids and their conjugates using a different solvent system. Furthermore, NAS showed a higher antihistamine activity than bile acids. This substance seems to be responsible for 15-20% of the activity of whole bile. The substance has not yet been identified.

Animals↗

[Natural antiallergenic factors in bile].

Two groups of substances having an antihistaminic activity were found on purifying bovine bile. It has already been found that bile acids inhibit contraction of guinea pig ileum; another principle has been isolated which is one thousand times more active than the bile acids; this (these) substance(s)--SAN (" substance antiallergique naturelle ")--seems to have more inhibitory effect on smooth muscle contraction induced by SRSA than histamine, acetylcholine, bradikinin and serotonin. SAN is also able to inhibit the Schultz-Dale reaction. These findings indicate that SAN could be a possible antiallergic agent.

Animals↗