La maladie de Castleman est une maladie ganglionnaire rare dont le nom correspond en fait à plusieurs maladies différentes. L’histologie la plus fréquente est la forme hyalino-vasculaire localisée. ...Elle atteint alors typiquement les adultes jeunes et siège dans un tiers des cas dans le médiastin. La maladie est en général asymptomatique, mais peut être accompagnée d’un pemphigus paranéoplasique. Le traitement repose sur la chirurgie d’exérèse après confirmation histologique. La présence d’un pemphigus en particulier au niveau bronchique confère toute la gravité à la maladie et justifie de traitements immunomodulateurs pré- et postopératoires.
Castleman disease is a rare lymph nodes disease whose name covers different clinical presentations. The most frequent histology is the hyaline vascular localized form. In this case, Castleman disease occurs in young adults, and is localized to the mediastinum in one third of the cases. The disease is often asymptomatic, but paraneoplasic pemphigus has been described. The management of this form of Castleman disease is based on complete surgical resection. Perioperative immunomodulating treatments may be discussed in case of paraneoplasic pemphigus, mostly when affecting the bronchial tree.
The present authors report the case of an adult with chronic granulomatous disease who developed an unusual lung fibrosis associated with severe pulmonary hypertension. Histological analysis of a ...lung biopsy showed a diffuse infiltration with pigmented macrophages without granulomas, which particularly involved the pulmonary arterial and venular walls. Clinical and histological findings were suggestive of pulmonary veno-occlusive disease. Such a clinical association has not been previously described in the literature and might be due to the persistent expression of gp91phox at a very low level. In conclusion, the present case report illustrates a novel manifestation of chronic granulomatous disease.
In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early ...antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.
We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.
A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval CI, 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.
In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).
Asthma and chronic obstructive pulmonary disease are characterized by inappropriate constriction of the airway smooth muscle. In this context, the physiological response of the human airways to ...selective relaxant agonists like PGE2 is highly relevant. The aim of this study was thus to characterize the PGE2 receptor subtypes (EP2 or EP4) involved in the relaxation of human bronchial preparations.
Human bronchial preparations cut as rings were mounted in organ baths for isometric recording of tension and a pharmacological study was performed using selective EP2 or EP4 ligands.
In the presence of a thromboxane TP receptor antagonist and indomethacin, PGE2 induced the relaxation of human bronchi (Emax = 86 ± 04% of papaverine response; pEC50 value = 7.06 ± 0.13; n = 6). This bronchodilation was significantly blocked by a selective EP4 receptor antagonist (GW627368X, 1 and 10 μmol/L) with a pKB value of 6.38 ± 0.19 (n = 5). In addition, the selective EP4 receptor agonists (ONO-AE1-329; L-902688), but not the selective EP2 receptor agonist (ONO-AE1-259), induced potent relaxation of bronchial preparations pre-contracted with histamine or anti-IgE.
PGE2 and EP4 agonists induced potent relaxations of human bronchial preparations via EP4 receptor. These observations suggest that EP4 receptor agonists could constitute therapeutic agents to treat the increased airway resistance in asthma.
Capillary electrophoresis (CE) was used as a method to determine the acidity constants of eight aromatase inhibitors. This method was validated by comparison of results obtained with a traditional ...method, UV spectroscopy, and additionally with computational calculations. We confirmed here, with our series of compounds, that capillary electrophoresis is an attractive method for pKa measurements which is based on migration time or mobilities of the ionic species over a range of pH values. The precision of pKa measurements of N-imidazole derivatives is useful to observe pKa shifts induced by chemical modifications introduced on adjacent aromatic rings such as heterocycle (benzoxa- or benzothiazolinone) or substituted benzyle. The knowledge of these pKa values is a great interest to predict migration of solutes and qualitative interactions with ionized cyclodextrines as chiral selectors in further enantioseparative CE studies.
To transfer genes into airway epithelial cells, we have generated auxotrophic
dap Escherichia coli BM2710 mutant that expresses the invasin of
Yersinia pseudotuberculosis and the listeriolysin of
...Listeria monocytogenes.
E. coli BM2710 harboring a plasmid carrying the
gfp gene was incubated with immortalized normal or cystic fibrosis (CF) airway epithelial cells or with primary bronchial epithelial cells grown as an explant-outgrowth cell culture model. Approximately 2% of immortalized cells expressed GFP. Few primary cells were transfected that were always poorly differentiated and located at the edge of the outgrowth. This was consistent with the expression of β1-integrins only on these cells and with the required interaction for cell entry of
E. coli expressing the invasin with β1-integrins. The subsequent intracellular trafficking of
E. coli BM2710 studied by confocal and electronic microscopy showed that the
E. coli-containing phagosomes rapidly matured into phagolysosomes. This is the first demonstration that recombinant bacteria are able to transfer genes into primary airway epithelial cells, provided that they are able to invade the cells.
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