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P Gosset

Publications and source records attributed to P Gosset.

At least 55 records · Page 3Linked to original sources
PubMed2000

Developmentally regulated expression of the murine ortholog of the potassium channel KIR4.2 (KCNJ15).

The gene KIR4.2 (K(+) inwardly rectifying channel 4.2) has been recently identified in the Down syndrome Chromosome Region 1. We have cloned the mouse ortholog of KIR4.2 and characterized its expression pattern. In situ hybridization showed a restricted and developmentally regulated pattern of expression. The expression is starting at E12.5 and expands at E14.5 in different tissues and organs, which may be affected in Down syndrome: heart, thymus, thyroid gland, and perichondrium. At E17.5, additional epithelia (kidney, bladder, stomach, lung) expressed also strongly the gene.

Animals↗
PubMed2000

Solitary fibrous tumour of the kidney.

Solitary fibrous tumours are relatively rare neoplasms initially described in the pleura. Such lesions are now reported in many extrathoracic sites. To our knowledge, only 8 cases have been reported in the kidney. All these cases were benign. We report a patient with a solitary fibrous tumour of the kidney with infiltration of the wall of the renal vein. Microscopic examination showed proliferation of spindle cells with a prominent vascular haemangiopericytoma-like pattern. Hypercellular areas were admixed with hyalinized collagenous zones. The neoplastic cells stained for vimentin and CD34. CD31 was negative. Biologically, we did not find any arguments for malignancy: the flow cytometric study showed diploid histograms, and immunostaining for p53 was negative.

Aged↗
PubMed2000

CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus. Potential implication in eosinophil recruitment.

In status asthmaticus (SA), severe bronchial inflammation is associated with acute respiratory failure. Neutrophils are the prominent cells found in bronchi from SA patients, but eosinophils are also recruited within the first 48 h after the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC chemokines have been directly implicated in the pathophysiology of allergic asthma. However, their involvement in SA had not been determined. The aim of this study was to evaluate the production of CC chemokines and of IL-5 in airways from ventilated patients with SA as compared with mild asthma (A), and to assess the role of these mediators in eosinophil recruitment. We measured levels of the chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in bronchial lavage fluid (BLF) from 10 SA patients, four patients without respiratory disease but undergoing ventilation (V) who were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1, MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxin values were not significantly different in the SA and other groups; however, their levels, as well as those of MIP-1alpha, RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic activity in BLF was increased in asthmatic subjects (A and SA groups) as compared with the other groups, and in SA patients as compared with A patients. Addition of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies significantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines and IL-5 are increased in airways of SA patients, and are potentially involved in eosinophil recruitment.

Adult↗
PubMed1999

Identification of beta-amyloid-responsive genes by RNA differential display: early induction of a DNA damage-inducible gene, gadd45.

Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of amyloid beta-peptide (A beta), presumed to play a pathogenic role. However, the precise molecular mechanisms of its neurotoxicity are not fully understood. Recent studies have suggested that it may exert its toxic effect via activation of transcription factors. We investigated A beta-responsive genes in human preneuron NT2 cells, at early stages of A beta (25-35) exposure, by RNA differential display. A beta induced the expression of (i) the growth arrest and DNA damage-inducible gene (gadd45) implicated in the DNA excision-repair process; (ii) a stress-signaling kinase gene encoding the mitogen-activated protein kinase/Erk kinase kinase-1 (MEKK1); (iii) a new growth factor-inducible immediate-early gene, CYR61, the product of which functions as an extracellular matrix signaling molecule; (iv) other immediate-early genes, such as c-jun and c-fos; (v) the gene encoding the basic fibroblast growth factor (bFGF); (vi) a gene encoding a constituent of the mitochondrial pyruvate dehydrogenase complex, the dihydrolipoamide dehydrogenase-binding protein (E3-BP); and (vii) an unidentified human gene (KIAA0099). A beta not only activates but also respresses genes: (i) the gene encoding "hinge" protein, a subunit of the mitochondrial cytochrome-c reductase and (ii) the SRp55 gene encoding a splicing factor involved in constitutive pre-mRNA splicing and alternative splice site selection. Our results underscored A beta-responsive genes that play key roles in the response (damage/recovery) of neuron cells to A beta exposure. In particular, the strong upregulation of gadd45, indicating DNA damage, was detected early in A beta cytotoxicity. This suggests that DNA strand breaks occurred rapidly in cells exposed to A beta, which may be a critical event in A beta neurotoxicity.

Alzheimer Disease↗
PubMed1999

Eosinophilic airway inflammation in nasal polyposis.

BACKGROUND: Asthma and asymptomatic bronchial hyperresponsiveness (BHR) are frequent findings in patients with nasal polyposis (NP). OBJECTIVE: To elucidate mechanisms responsible for the development of BHR, we initiated a prospective study of bronchial inflammation as assessed by bronchial lavage (BL) and bronchial biopsy specimens in 35 patients with noninfectious NP. METHODS: BHR was determined with methacholine provocation testing. Differential cell count, ECP, and histamine and tryptase levels were determined in BLs. Pathologic examination of bronchial biopsy specimens was performed with May-Grünwald-Giemsa stain to assess the number of lymphocytes. Indirect immunoenzymatic methods were used to identify eosinophils and mast cells. RESULTS: Fourteen patients did not exhibit BHR (group A); 7 patients had asymptomatic BHR (group B); and 14 patients had BHR associated with asthma (group C). Patients of group C tended to have a longer duration of nasal symptoms than those of groups A and B. FEV1 (L) was significantly lower in group C than in groups A and B. The number and percentage of eosinophils were significantly higher in BLs in groups B and C than in group A (P <. 05). Patients of groups B and C had a significantly higher number of eosinophils in bronchial submucosa (14.0 +/- 1.5/mm2 and 19.0 +/- 1. 9/mm2, respectively) than patients of group A (0.1 +/- 0.1/mm2). The number of lymphocytes was also higher in groups B and C than in group A. FEV1 (percent of predicted value) and eosinophil number within bronchial mucosa correlated negatively. CONCLUSION: Our results demonstrate that patients with NP and asymptomatic BHR had an eosinophilic bronchial inflammation similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR do not feature eosinophilic lower airways inflammation. The clinical relevance of these results requires careful follow-up to determine whether eosinophilic inflammation in these patients precedes and is responsible for the development of obvious asthma.

Adult↗
PubMed1999

Production of chemokines and proinflammatory and antiinflammatory cytokines by human alveolar macrophages activated by IgE receptors.

BACKGROUND: The alveolar macrophage (AM) expresses the low affinity IgE receptor and has the ability to produce not only several proinflammatory cytokines (TNF-alpha, IL-1, IL-6) but also antiinflammatory cytokines (IL-1 receptor antagonist [IL-lra], IL-10), chemokines (IL-8, monocyte chemotactic protein-1 [MCP-1]), and macrophage inflammatory protein-1alpha (MIP-1alpha). OBJECTIVE: The aim of this study was to evaluate the capacity of the AM from patients with allergic asthma and control subjects to produce chemokines and antiinflammatory versus proinflammatory cytokines after activation by IgE receptors and to define the role of CD23 in this activation. METHODS: AMs were collected by bronchoalveolar lavage from 13 patients with allergic asthma and 14 healthy subjects. Adherent AMs were activated either by the successive addition of IgE and anti-IgE or by monoclonal mouse IgG anti-CD23 or by a control monoclonal mouse antibody. TNF, IL-1beta, IL-1ra, IL-10, IL-8, MCP-1, and MIP-1alpha levels were evaluated in supernatants of AMs incubated for 18 hours and in some cases after 4 hours of incubation. RESULTS: Activation by IgE and anti-IgE antibodies significantly increased the production of TNF, IL-1beta, IL-8, MCP-1, MIP-lalpha, and IL-10 in both control subjects and patients with asthma, whereas the increase for IL-1ra was only significant for the control subjects. Whereas F(ab) fragments of anti-CD23 antibodies inhibited IgE plus anti-IgE-induced cytokine production, activation by monoclonal IgG anti-CD23 antibodies reproduced the effect of IgE immune complexes. At 4 hours, the secretion of proinflammatory cytokines was increased by activation by IgE receptors, in contrast to antiinflammatory cytokines. In addition, analysis of the balance between proinflammatory and antiinflammatory cytokines showed that IgE-dependent activation largely favored the proinflammatory cytokines, particularly in patients with asthma. CONCLUSION: IgE-dependent activation by the FcepsilonRII receptor upregulates the synthesis of both chemokines and antiinflammatory cytokines in addition to proinflammatory cytokines. However, AMs from patients with allergic asthma may promote airway inflammation after activation by IgE receptors through its preferential effect on proinflammatory cytokines.

Animals↗
PubMed1999

Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages.

Reactive oxygen intermediates exert signalling functions and modulate gene transcription, particularly for pro-inflammatory cytokines. Since exogenous as well as endogenous thiols could be potent inhibitors of the production of cytokines, the effects of N-acetylcysteine (NAC), glutathione (GSH) and modulated GSH synthesis on the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 by human alveolar macrophages (AMs) was evaluated, as well as the potential role of intracellular GSH depletion on the effect of exogenous thiols. AMs were stimulated with lipopolysaccharide (LPS) and cytokine production was measured by evaluating messenger ribonucleic acid (mRNA) expression and protein secretion. Depletion of intracellular GSH by treatment with buthionine sulphoximine (BSO) reached 45.2% after 3 h and was nearly complete at 24 h. Whereas a 24-h preincubation of AMs with BSO significantly increased LPS-induced secretion of TNF-alpha and IL-8, a 3-h preincubation only enhanced LPS-stimulated production of IL-8 (p<0.05). Treatment with NAC and GSH did not significantly increase intracellular content of GSH even after a 48-h incubation. Addition of GSH and NAC significantly reduced the secretion of TNF-alpha (mean+/-SEM 21.2+/-5 and 44.7+/-4.4% inhibition, respectively) as well as LPS-induced IL-6 and IL-8 (p<0.05). Similarly, NAC inhibited the production of TNF-alpha, IL-6 and IL-8 in GSH-depleted AMs obtained by BSO pretreatment. In conclusion, N-acetylcysteine and glutathione inhibit the production of tumour necrosis factor-alpha, interleukin-8 and interleukin-6 by alveolar macrophages by a mechanism independent of glutathione metabolism. However, total depletion of glutathione within alveolar macrophages significantly increases tumour necrosis factor-alpha and interleukin-8 synthesis whereas it does not modulate interleukin-6 secretion.

Acetylcysteine↗
PubMed1999

Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus.

Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF-alpha, and of the active form of TGF-beta1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1beta was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1beta (79% inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies).

Adult↗
PubMed1999

Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus.

In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA, together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5 micrograms gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; in addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change in ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.

Adult↗
PubMed1999

Overexpression of alveolar macrophage gelatinase B (MMP-9) in patients with idiopathic pulmonary fibrosis: effects of steroid and immunosuppressive treatment.

Alveolar macrophages (AM) express gelatinase B, a member of the matrix metalloproteinase family involved in the degradation and remodeling of extracellular matrix components. We evaluated the expression of gelatinase B in the course of idiopathic pulmonary fibrosis (IPF) by studying alveolar macrophages in culture AM and bronchoalveolar lavage fluid from 12 untreated patients with IPF, 11 patients with IPF under treatment with steroid and immunosuppressive agents, and 10 control subjects. By using zymography and quantitative image analysis, latent gelatinase B, as well an 88-kD active form, were investigated in culture medium (24 h) of AMs and were found to be significantly increased (P < 0.01) in untreated patients exhibiting severe IPF when compared with control subjects (4.1 +/- 1.7 versus 0.3 +/- 0.2 10(5) arbitrary units [AU]/10(4) AM for the 92-kD form). Concomitant studies of gelatinase B levels associated with cultured AM extracts or freshly harvested AM showed similar results, both at the mRNA and protein levels, respectively. Immunocytochemical studies on freshly harvested AM demonstrated that the enzyme was located mainly at the cell, suggesting some involvement of gelatinase B in AM migration. In contrast, gelatinase B activity secreted by AM tended to be normal in patients with IPF under steroid and immunosuppressive treatment. Simultaneously, level of the gelatinase B activity in epithelial lining fluid was increased in untreated IPF patients, whereas it was normal in treated patients. These results suggest that AM of patients with IPF are primed for gelatinase B expression and that steroid and immunosuppressive treatment induces negative modulation of the gelatinase B overexpression. We conclude that gelatinase B may play a role in lung remodeling in IPF.

Base Sequence↗
PubMed1999

[112 cases of sporadic and genetically determined pheochromocytoma: a comparative pathologic study].

The aim of this study was to compare 64 genetically determined pheochromocytomas (PH) (49 MEN IIa, 3 MEN IIb, 6 Von Recklinghausen diseases, 1 von Hippel-Lindau disease, 5 familial pheochromocytomas) and 48 sporadic PH. Genetically determined PH were more often observed among men and more frequently bilateral and multicentric than sporadic PH. Sporadic tumors had more often adrenal capsular invasion, necrosis and pseudocysts. Genetically determined PH were more differentiated with an insular pattern, hyaline globules and a higher percentage of polyhedric cells. Sporadic tumors were less differentiated with more frequently a diffuse pattern and small cells. Adrenal medullar hyperplasia was significantly associated with genetically determined PH. Adrenal cortical hyperplasia was not associated with a particular type of PH. The PS100 and chromogranin immunodetection was equivalent in both groups.

Adrenal Cortex↗
PubMed1998

Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3.

The gene-rich telomeric region of 21q harbors several loci relevant to human diseases including autoimmune polyglandular disease type I, nonsyndromic deafness, Knobloch syndrome, holoprosencephaly, and bipolar affective disorder. A contig of genomic clones in this region would facilitate the isolation of these genes. However, distal 21q22.3 has yet been poorly mapped, presumably due to the presence of sequences that are underrepresented in yeast artificial chromosome (YAC) libraries. We generated a framework of YACs and used these clones as starting points for the isolation of a combination of bacterial artificial chromosome clones, P1-derived artificial chromosome clones, and cosmid clones by chromosome walking procedures. These studies resulted in the construction of a high-resolution contig map spanning the 2.5-Mb region from PFKL to the telomere, approximately 2 Mb of which are covered by ready-to-sequence contigs. Within this map we determined the location and relative distance of 21 markers. These include 9 established genetic markers, the order of which is cen-PFKL-D21S154-D21S170-D21S171-D21S1903- D21S1897- D21S112-D21S1446-D21S1575-tel. Moreover, we established the precise map position of 13 genes and 4 ESTs including the recently isolated genes C21ORF2, SMT3H1, RNA editing deaminase 1 (ADARB1), folate transporter (SLC19A1), COL18A1, lanosterol synthase (LSS-PEN), pericentrin (PCNT), and arginine methyltransferase (HRMT1L1). This integrated map provides a useful resource for the mapping and isolation of disease genes and for the construction of a complete transcription map of distal 21q as well as for large-scale sequencing efforts.

Chromosome Mapping↗
PubMed1998

Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome.

The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and mental retardation. Cosmid contigs covering 80% of the region were constructed and EcoRI maps produced. These cosmids were used for exon trapping and cDNA selection from three cDNA libraries (fetal brain, fetal liver, and adult skeletal muscle). Isolated exons and cDNAs were mapped on the EcoRI map, organized into contigs, sequenced, and used as probes for Northern blot analysis of RNA from fetal and adult tissues. We identified 27 genuine or highly probable transcriptional units evenly distributed along the CBR-ERG region. Eight of the transcriptional units are known genes.

Chromosome Mapping↗
PubMed1998

Modulation of cell adhesion molecules on human endothelial cells by eosinophil-derived mediators.

Mechanisms that allow a selective eosinophil emigration in different eosinophilic lung diseases remain poorly understood. In this study, we tested the hypothesis that eosinophils might participate in their own recruitment, particularly through adhesion molecule expression on human endothelial cells (EC). Blood eosinophils from donors with blood eosinophilia were purified and maintained in culture medium for 1 and 18 h. The expression of ICAM-1, E-selectin, and VCAM-1 on human umbilical vein endothelial cells (HUVEC) was evaluated by ELISA and flow cytometry analysis after addition of eosinophil supernatants. Eosinophil supernatants collected after 1 h induced a weak increase of CAM expression on HUVEC. In contrast, supernatants from eosinophils cultured for 18 h considerably amplified ICAM-1, E-selectin, and VCAM-1 expression on the surface of EC. These levels of CAM expression (in optical density determined by ELISA) were about two- or threefold more important than those obtained with eosinophil supernatants collected after a 1-h culture. The characterization of the implicated molecules showed that anti-IL-1beta antibodies significantly inhibited ICAM-1, E-selectin, and VCAM-1 expression, whereas anti-TNF-alpha antibodies only induced a moderate inhibition. Our data support the hypothesis that eosinophils, through the release of at least IL-1beta and TNF-alpha, might participate in the amplification of the inflammatory reaction by activating the vascular endothelium.

Cell Membrane↗
PubMed1998

Increased interleukin-6 production during the acute phase of the syndrome of episodic angioedema and hypereosinophilia.

BACKGROUND: The Gleich syndrome is rare and associates recurrent angioedema, urticaria, fever, weight gain and blood hypereosinophilia, underlying systemic and local inflammation. The pathogenesis of those symptoms remains unclear. OBJECTIVE: We wanted to address the possible implication of Interleukin-6 (IL-6) in the development of those clinical features, and to identify the cells involved in its production. METHODS: A 26-year-old man suffering of this disease was referred in hospital. During an acute attack with weight gain, fever and a diffuse oedema, a marked increase in eosinophils count (42700/mm3 was observed. Serum ECP was elevated at 47 microg/L (normal less than 16). Corticosteroid therapy administrated on the 7th day was followed by a rapid remission. Blood samples were collected (before, during the attack and under corticosteroid therapy) for measurements of serum IL-6 (ELISA, Immunotech, Marseille, France) and plasma histamine (RIA, Immunotech, Marseille, France). Blood monocytes and eosinophils were isolated and a skin biopsy was performed during the attack. RESULTS: The plasma histamine level was within normal range. The level of IL-6 in sera peaked to 74 pg/mL, concomitant with the peak of eosinophilia at the acute phase phase of the attack. Under corticosteroids, we observed a drop in the IL-6 serum level to 29 pg/mL, concomitant with the clinical remission. During the attack, an increase in IL-6 production was observed in 24 h blood monocyte supernatants (11.10(3) pg/mL compared with 2.4+/-0.8.10(3) pg/mL for BM from controls) as well as in skin endothelial cells but not in the blood and skin eosinophils. In vitro, when endothelial cells were incubated in eosinophils supernatants of the patient, liberation of IL-6 was observed (3.3 10(3) pg/mL compared with controls: 2.1 10(3) pg/mL) CONCLUSION: Serum IL-6 elevation may be related to an increased production by blood monocytes and endothelial cells, possibly stimulated by eosinophil mediator during the acute phase of the disease, and might participate in the inflammatory reaction of this syndrome.

Acute-Phase Reaction↗
PubMed1998

Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock.

Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysaccharide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFalpha levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFalpha levels, independently from the anticoagulant actions of these inhibitors.

Animals↗
PubMed1998

Bronchial neutrophilia in patients with noninfectious status asthmaticus.

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.

Adult↗