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Biomedical subjects

D Israël-Biet

Publications and source records attributed to D Israël-Biet.

At least 19 recordsLinked to original sources
PubMed2004

Impairment of beta chemokine and cytokine production in patients with HIV related Pneumocystis jerovici pneumonia.

BACKGROUND: Pneumocystis jerovici pneumonia (PJP) remains a frequent opportunistic infection in HIV infected patients which markedly upregulates HIV replication by mechanisms so far poorly elucidated. PJP triggers the production of proinflammatory mediators with activating effects on HIV. However, anti-inflammatory factors with inhibiting effects on HIV are normally produced in parallel. We postulated that an imbalance of mediators normally controlling HIV replication could underlie its marked increase during PJP. METHODS: The production of tumour necrosis factor alpha (TNFalpha), interleukins IL-6 and IL-10, and beta-chemokine by bronchoalveolar lavage (BAL) cells recovered from HIV infected patients with and without PJP was compared. The pulmonary viral load was determined and correlations with cytokine and chemokine production were examined. RESULTS: TNFalpha and IL-6 release was similar in patients with and without PJP but IL-10 and beta-chemokine release was markedly lower in the PJP group (IL-10: p<10(-2), RANTES, MIP-1alpha and MIP-1beta: p<0.001). The pulmonary viral load was markedly higher in patients with PJP (p<0.001) and correlated negatively with levels of MIP-1alpha, RANTES and IL-10 in BAL fluid cells (p<0.05). CONCLUSION: Pulmonary IL-10 and beta-chemokine production is markedly defective in HIV infected patients with PJP, while pulmonary TNFalpha and IL-6 levels are normal. The resulting excess of these latter factors, which are known to upregulate HIV replication, might contribute to the increase in pulmonary viral load and to the more rapid HIV disease progression observed in patients with PJP.

AIDS-Related Opportunistic Infections↗
PubMed2004

[Endothelial vasoactive factors: predictive markers of the results of the Fontan intervention?].

UNLABELLED: We retrospectively analyzed the pulmonary biopsies of a Fontan intervention in order to identify predictive markers of its result. The pulmonary biopsies of 17 patients who benefited from the Fontan intervention and 6 controls were studied. The histomorphometric measurements and endothelial expression of vasoactive factors (NO synthase, endothelin-1) and angiogenic factors (VEGF) were analyzed with immunohistochemistry at the level of intra-acini pulmonary arterioles. Eight patients presented a good surgical result (group 1). Distal arterioles presented a thin and regular wall: the NO synthase, endothelin and VEGF expression was low. Nine patients presented a failure of the Fontan operation (group 2). The distal arterioles were slightly musculated (p<0.01 vs. group 1 and group control). The endothelin-1 expression was comparable to that observed in group 1. Conversely, the NO synthase and VEGF expressions were significantly increased in that group (<0.001 vs. group 1 and group control). CONCLUSION: In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. This study could be able to define predictive factors of the evolution and refine the selection of patients candidate for a Fontan operation.

Adolescent↗
PubMed2003

[Pulmonary anti-Aspergillus defences].

The lung, constantly exposed to inhaled infectious particles, uses a very efficient immune system to insure sterility of the airways. It has to be tightly regulated for the tissues to be kept from its potentially deleterious effects. Pulmonary anti-Aspergillus defences are based upon the concurrent action of innate immunity, non specific but rapidly mobilisable, and of adaptative immunity. The former first consists in natural barriers, namely the respiratory epithelium and its antimicrobial peptides (complement, defensins, collectins). Then come the phagocytic cells (macrophages and neutrophils), but also the dendritic cells, able to stimulate adaptative responses through the presentation of antigens they have phagocytised ans processed. The Toll-like receptors are among the key ones involved in the recognition of fungal components. Chemokines have a crucial role for the recruitment, maturation and activation of neutrophils, while anti-inflammatory cytokines tightly influence T lymphocytes functional differentiation. These latter, cornerstones of the adaptative immunity, differentiate into two mutually exclusive pathways according to the type of cytokines which they produce. The Th1 one is largely protective in the context of Aspergillus, while the Th2 one is deleterious. However, a good cooperation between these 2 pathways is required for an efficient protection. Pulmonary anti-Aspergillus defences are multifactorial. Innate immunity is crucial but a capacity of the host to generate specific responses is also warranted.

Antibody Formation↗
PubMed2002

[Bilateral pleurisy and cardiac tamponade. A rare etiology: pancreatico-pleural fistula].

Pancreatico-pleural fistula is a rare complication of chronic pancreatitis. It commonly presents with small, but recurrent, pleural effusions. Pericarditis rarely occurs in this context. We report a case presenting with bilateral large pleural effusions associated with cardiac tamponade. The diagnosis was suspected on detection of high concentration of pancreatic enzyme in the pleural fluid and was confirmed by both endoscopic retrograde pancreatography and magnetic resonance pancreatography. Both examinations demonstrated a fistula and a calculus of the Wirsung duct. In addition, they identified a pancreas divisum, a congenital abnormality which can rarely lead to complications. The usual medical and endoscopic management of this condition failed and a surgical solution for the fistula was needed. This case is unique due to the dramatic presentation of this complication of pancreas divisum and to the complexity of treatment required.

Cardiac Tamponade↗
PubMed2001

Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.

BACKGROUND: Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. METHODS: Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis. RESULTS: Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months. CONCLUSIONS: Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.

Aged↗
PubMed2001

Increased endothelin-1 associated with bacterial infection in lung transplant recipients.

BACKGROUND: Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infectious processes. Episodes of infection are suspected to be involved in the development of bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS. We, therefore, set up this study to assess ET-1 expression in relation to complications of the graft in human lung transplant recipients. METHODS: ET-1 mRNA was quantified by reverse transcription-competitive polymerase chain reaction in cells from 119 samples of bronchoalveolar lavage (BAL) fluid from 17 lung transplant recipients. ET-1 and big ET-1 proteins were assessed in BAL cell culture supernatants by enzyme immunoassay. Transbronchial biopsies (n=21) were stained immunohistochemically for ET-1 receptors. RESULTS: Episodes of bacterial infection strongly correlated with increased ET-1 mRNA and protein expression. ET-1 receptors were also upregulated during these episodes, especially on endothelial and smooth muscle cells. Five of the seven patients with the highest ET-1 levels subsequently developed BOS. CONCLUSIONS: These results raise the possibility that ET-1, part of whose production is triggered by infectious postgraft complications, might play a role in the development of BOS through its potential effects on airway remodeling.

Adult↗
PubMed2000

Insulinlike growth factor-1 in lung transplants with obliterative bronchiolitis.

Bronchiolitis obliterans syndrome (BOS) is the major complication limiting survival of lung transplant recipients (Tx patients). The mechanisms underlying this fibrotic process are not known. We assessed IGF-1 and IGFBP-3 expression, critical mediators in different models of pulmonary fibrosis, in nine Tx patients. Three of them developed a BOS at 8, 14, and 17 mo postgraft, respectively. Two of the remaining six displayed a recurrent cytomegalovirus (CMV) infection, and four are in stable condition. IGF-1 mRNA expression was quantitated by RT-PCR in cells from four to six BAL per patient performed during the first 6 mo postgraft. Contrasting with a constantly low expression of IGF-1 mRNA in BAL cells from the six patients without BOS, the three patients with BOS presented marked peaks of IGF-1 on two to five occasions during the study period. These peaks, 3- to 13-fold increased compared with values from the former patients, preceded the diagnosis of BOS by 7, 13, and 17 mo, respectively. On the other hand, IGFBP-3 was highly and exclusively expressed in the three patients with BOS, the mRNA as well as the gene product as demonstrated by Western blotting. Our data strongly argue for a role of IGF-1 and IGFBP-3 in the fibrotic process underlying BOS, and for their possible value as an early marker of this complication.

Biopsy↗
PubMed2000

An uncommon etiology of isolated pleural effusion. The ovarian hyperstimulation syndrome.

We report three cases of pleural effusion in the context of ovarian stimulation for in vitro fertilization. The ovarian hyperstimulation syndrome usually causes pleural effusion and ascites. When the latter is lacking, an isolated pleural effusion in a pregnant patient can be mistaken for pulmonary embolism. Early recognition of the condition should allow for an appropriate diagnostic and therapeutic management. Except for some rare but life-threatening complications, such as major hypovolemia or respiratory distress syndrome, the spontaneous outcome is usually favorable. The pathogenesis of this condition may involve an increase of capillary permeability due to the release of vasoactive mediators.

Adult↗
PubMed1999

Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.

Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.

Adolescent↗
PubMed1998

Peaks of transforming growth factor-beta mRNA in alveolar cells of lung transplant recipients as an early marker of chronic rejection.

BACKGROUND: Chronic lung rejection (CLR) induces a fibroproliferative disorder leading to the occlusion of small airways. It has emerged as the major factor limiting the survival of lung transplant recipients. Predictive markers of CLR are lacking, and its diagnosis is generally ascertained when the fibrosis process is irreversible. METHODS: We have quantified the expression of transforming growth factor-beta (TGF-beta), a critical mediator of fibrogenesis, in alveolar cells from lung transplant recipients using a competitive reverse transcriptase polymerase chain reaction method. RESULTS: We have shown that patients with CLR presented marked peaks of TGF-beta mRNA expression, in contrast with patients without CLR. These peaks preceded the diagnosis of CLR by several months in two of three patients who died within 2 years of diagnosis. CONCLUSIONS: Our data suggest that TGF-beta expression in alveolar cells could serve as an early predictive and prognostic marker of chronic lung rejection.

Bronchoalveolar Lavage Fluid↗
PubMed1998

[HIV replication and pulmonary opportunistic infections].

The lung is a privileged target of opportunistic pathogens during HIV infection, due to the dramatic immunodeficiency which characterizes the disease. Proviral forms of the virus are frequently detected in the lung, particularly in macrophages, which constitute an important viral reservoir, and in T lymphocytes. The frequency of these proviral forms increases in the lung with the progression of the HIV disease. Some opportunistic pathogens themselves, or the mediators produced during immune responses toward these pathogens, are able to activate in vitro the HIV replication. An important increase of viral load is observed in the lung during P. carinii pneumonia and during tuberculosis. It has been shown that tuberculosis generated a microenvironment able to activate T lymphocytes present at the site of the disease and to increase their productive infection by HIV. TNF alpha and IL6, among other cytokines, could be involved in this phenomenon. The massive replication of HIV during pulmonary infections could influence the general prognosis of the disease through the increase of the systemic viral load. In this context, new therapeutic strategies might have to be defined, including not only a wider prophylaxis but also antiretroviral treatments at the time of infectious episodes.

AIDS-Related Opportunistic Infections↗
PubMed1997

Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV.

Tuberculosis (TB) contributes to the progression of HIV disease but, so far, the mechanism involved is not clear. Several cytokines accumulating in vivo at the site of mycobacterial infection up-regulate HIV expression in vitro. In this study, we assessed the role of pleural fluids recovered from seronegative patients with TB on HIV replication in acutely infected blast cells. Pleural fluids from subjects with congestive heart failure served as controls. In all cases, TB pleural fluids stimulated HIV replication in vitro. TNF-alpha, IL-6, IFN-gamma, and granulocyte/macrophage (GM)-CSF, as well as very low levels of IL-2, were detected in TB pleural fluids. An anti-IL-2 Ab preincubated with TB pleural fluids exhibited no blocking effect on HIV replication similarly to anti-IFN-gamma and anti-GM-CSF Abs. In contrast, anti-TNF-alpha and anti-IL-6 Abs decreased HIV replication by 60 and 90%, respectively. Recombinant TNF-alpha and IL-6 stimulated HIV replication, while IFN-gamma and GM-CSF had a more ambiguous role. The capacity of pleural fluids to stimulate HIV replication was specific for TB, since the capacity of control fluids was significantly lower. Finally, in contrast to PBL, which require in vitro activation for their productive infection by HIV, unstimulated tuberculous pleural lymphocytes were productively infectable by HIV. Taken together, our data suggest that the microenvironment generated by TB might increase the HIV burden in infected subjects, partly through cytokines other than IL-2, namely TNF-alpha and IL-6.

Bronchoalveolar Lavage Fluid↗
PubMed1996

[Physiopathologic mechanisms of drug-induced lung diseases in man].

Iatrogenic lung disease in man is generated by very different and often complex pathology. This explains the great clinical diversity of these disorders which may manifest as eosinophilic pneumonia, intra-alveolar haemorrhage, bronchiolitis obliterans and diffuse interstitial pneumonia even with pulmonary fibrosis. The causes are also very varied such as direct cellular toxicity, cellular oedema, an alteration of the alveolar capillary membrane, the activation of inflammatory and/or immune cells, which are responsible for the production of soluble mediators whose effects are sometimes harmful to the pulmonary parenchyma. Rather than reporting on the different clinical types of iatrogenic lung disease and indicating for each one the hypothetical or known physiopathogenic mechanism, we have chosen to examine certain fundamental lesional mechanisms and to indicate the principal nosological groups which they cover. We have centered this review on the physiopathogenic models which are the most coherent and most fully elaborated based on observations made on man or on experimental animal models. Among those we have reported here is a case of bleomycin toxicity, with its direct toxic mechanism on the epithelial or endothelial cellular targets, amiodarone lung disease and with its associated alveolar oedema, inflammatory reactions and immunological reactions whose specificity is poorly understood; also there are some alveolitides whose specificity has been demonstrated, such as those to minocycline and to BCG and finally a complex model which is both inflammatory and disturbed immunology in radiation pneumonia.

Adjuvants, Immunologic↗
PubMed1995

Site-directed bronchoalveolar lavage and transbronchial biopsy in HIV-infected patients with pneumonia.

We have assessed the diagnostic value of site-directed bronchoalveolar lavage (BAL) and combined transbronchial biopsy (TBB) in 29 HIV-infected patients with localized pneumonia, in whom a previous BAL was nondiagnostic and in whom improvement did not occur with empiric antibiotic therapy. All patients but three had a CD4 cell count < 100/microliters. A definite diagnosis could be reached in 26 of 29 (90%) individuals, including 24 pathogens. Neither the radiologic pattern nor the type of Pneumocystis carinii (PC) prophylaxis could predict the positivity of either one of these two diagnostic procedures. Site-directed BAL alone allowed a diagnosis in infection in eight (28%) cases. TBB alone led to diagnosis in eight (28%) cases, including three PC and two toxoplasma gondii, undiagnosed by the site-directed BAL. Both techniques were positive and in agreement in 10 (34%) cases. The majority of the diagnosis led to a specific treatment. Therefore, the patients' survival was positively altered by the procedure. In conclusion, the performance of site-directed BAL and combined TBB markedly optimizes the diagnostic yield of each of these procedures performed separately in HIV-infected patients with localized pneumonia.

Adult↗
PubMed1994

Perforin and granzyme B expression is associated with severe acute rejection. Evidence for in situ localization in alveolar lymphocytes of lung-transplanted patients.

To evaluate rejection episodes in lung-transplanted patients, we analyzed 31 bronchoalveolar lavage specimens for lymphocyte levels and lymphocyte expression of two intracytoplasmic activation markers, perforin, the pore-forming lytic protein, and granzyme B, a member of the serine esterase family. Using anti-human granzyme B and perforin mAbs, we show that their expression in alveolar lymphocytes is correlated with the severity of rejection as assessed by histological parameters and the patients' clinical status. The presence of these molecules may provide a prognostic parameter that will facilitate the patients' monitoring, particularly in cases with minimal acute lung rejection susceptible to rapid progression to severe rejection.

Biopsy↗
PubMed1994

Chlorambucil-associated pneumonitis.

A patient developed an interstitial pneumonitis while receiving chlorambucil for a chronic lymphocytic leukemia (cumulative dose, 8,340 mg). Withdrawal of drug treatment was followed by rapid improvement in the clinical condition. Bronchoalveolar lavage showed a T-lymphocytic alveolitis, whereas blood lymphocytes were predominantly of the B phenotype. The T-lymphocytic alveolitis persisted 6 weeks after drug therapy cessation with a predominant CD8+ phenotype, as observed in some hypersensitivity pneumonitis induced by drugs.

Alveolitis, Extrinsic Allergic↗
PubMed1994

A highly unusual combination of pulmonary pathogens in an HIV infected patient.

We report on a case with an unusual combination of pulmonary pathogens including Pneumocystis carinii, Rhodococcus equi and Toxoplasma gondii in an HIV infected patient. The multiple microbiological procedures required to ascertain the etiological diagnoses of pneumonitis in HIV-seropositive subjects are discussed.

AIDS-Related Opportunistic Infections↗