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Biomedical subjects

J F Mornex

Publications and source records attributed to J F Mornex.

At least 19 recordsLinked to original sources
PubMed2005

Goat endothelial cells may be infected in vitro by transmigration of caprine arthritis-encephalitis virus-infected leucocytes.

The caprine arthritis-encephalitis lentivirus (CAEV) causes a lifelong persistent infection in goats, and induces infiltrations of leucocytes and tissue reorganization in target organs, with a cyclical pattern of viral expression. The mammary gland is an important site of infection, associated with mother-to-kid transmission by infected cells in colostrum and milk. The monocyte/macrophage is the principal target cell, but other cell types, including epithelial and endothelial cells and fibroblasts, are susceptible to in vitro infection with varying levels of viral replication. Such cells, perhaps at specific differentiation states, might play a role in the regulation and transfer of in vivo infection in target organs. In this paper we describe the in vitro infection of endothelial cell monolayers by the transmigration of monocytes carrying the CAEV provirus. The infected endothelial cells progress to expression of the viral p30 capsid antigen, suggesting viral proliferation. Such a process occurring in vivo during angiogenesis and leucocyte homing to the mammary gland in the final third of mammogenesis, might contribute to viral spread in this crucial target organ.

Animals↗
PubMed2005

Viral expression and leukocyte adhesion after in vitro infection of goat mammary gland cells with caprine arthritis-encephalitis virus.

A characteristic lesion in goats infected by the lentivirus CAEV is mastitis with lymphoid hyperplasia. In order to investigate the mechanism of lesion formation, cultures highly enriched in microvascular endothelial cells, mature and immature luminal epithelial cells, fibroblasts and myoepithelial cells were established from goat mammary gland biopsies. Their susceptibility to in vitro infection with two distinct types of CAEV was investigated by PCR, antigen expression and cytopathy. The capacity of infected mammary gland cells to bind uninfected caprine leukocytes was determined by flow cytometry. All cell types tested were susceptible to CAEV infection in vitro, with different levels of sensitivity according to cell phenotype. Our results suggest that the limited extent of natural infection of mammary gland cells reflects a protective local immune response, and that the myoepithelial cell could act as a reservoir cell. After infection, the mature luminal cell acquires the capacity to bind leukocytes in vitro, which could indicate a facilitation of cellular interactions. The distinct reactions of the different cell types to CAEV infection may be correlated with events leading to progressive lesion development during the natural infection.

Animals↗
PubMed2004

Apoptosis in right-ventricle biopsy is not predictive of graft survival.

Myocardial dysfunction is common in grafted hearts from brain-dead donors, but the mechanisms involved remain unclear, although apoptosis has been suggested to play an important role. In this study, we investigated the presence of apoptotic myocardial cells in donor hearts as compared to control hearts to determine whether pre-existing apoptosis can predict donor heart dysfunction. Apoptosis was studied by in situ DNA fragmentation assay and by Western Blotting for caspase-3, the pivotal executive caspase of the apoptotic pathway. We show that brain-death induced myocardial apoptosis was not predictive of myocardial dysfunction in transplanted hearts.

Adult↗
PubMed2004

[Biomarkers as prognostic factors in pulmonary arterial hypertension. Rationale and study design].

CURRENT SITUATION: Pulmonary arterial hypertension (PAH) is a serious disease. Its prognostic is based on the functional status quantified by the NYHA class and the 6-min walking test, and the hemodynamic data. The algorithms of treatment are solely based on the hemodynamic data and the functional status. The main objective is to test whether basal concentrations of isoprostanes, Big endotheline 1, ADMA, high sensitivity CRP, NT-Pro-BNP and cardiac troponin T are a 3-year prognostic factor in PAH using a combined criterion: death from any cause and pulmonary or cardiopulmonary transplantation. MATERIALS AND METHODS: This is a multicenter, prospective, prognostic, single blinded study (plasma and urinary samples being blinded). The study started in november 2003, running for 2 years, with a 3 year follow-up for each patient. The main inclusion criterion is PAH. The data analysis will use a multivariable Cox model, taking into account the functional and hemodynamic parameters. EXPECTED RESULTS: This study will determine whether any of the biomarkers tested provides additional prognostic information in PAH in addition to the functional and hemodynamic parameters.

Biomarkers↗
PubMed2003

Pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease.

Lung cancer is a leading cause of cancer with a poor prognosis. Bronchioloalveolar carcinoma (BAC) is a rare tumor that has always intrigued physicians. Since the last World Health Organization classification the pathology has been clarified; BAC per se is an adenocarcinoma with a pure bronchioloalveolar growth pattern and appears as an in situ alveolar adenocarcinoma. More usually BAC is a clinically recognizable entity presenting as multi-focal nodules evolving towards pneumonia associated with pulmonary shunting. Pathology is that of a multifocal mixed adenocarcinoma: bronchioloalveolar and papillar. Whatever the stage, survival is better than in other forms of non-small cell lung cancer (NSCLC). The true frequency of BAC is unknown, although it is a rare form of lung cancer; smoking cannot be excluded as a risk factor. It appears that p53 and ras genes are less often mutated than in other lung adenocarcinomas, suggesting that the cellular mechanisms involved are different. Ovine pulmonary adenocarcinoma (OPA) presents with the same symptoms as BAC in humans and is caused by a betaretrovirus Jaagsiekte sheep retrovirus. Very early on, clinical and histological similarities with human BAC were stressed. A recent series of OPA described, according to the third edition of the WHO classification for human lung cancer, mixed adenocarcinoma, BAC and papillary and/or acinar carcinoma. An immunohistochemical study suggested that some human pulmonary tumors (including BAC) may be associated with a Jaagsiekte sheep retrovirus-related retrovirus,but so far no molecular study has confirmed this observation. Thus, OPA is an exquisite model of carcinogenesis for human lung adenocarcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

Two novel fibrinogen variants found in patients with pulmonary embolism and their families.

BACKGROUND: The occurrence of dysfibrinogen is quite rare in comparison with other hemostatic defects, specially in cases of venous thrombosis. OBJECTIVES: Fibrinogen is known to have multiple functions, which are not evaluated by simple coagulation testing. We have used gel electrophoresis to search for new mutations. PATIENTS AND METHODS: Specimens of purified fibrinogen from 217 consecutive patients with familial or recurrent or early thrombosis and from 490 control subjects were evaluated by electrophoresis. Plasma fibrinogen levels and coagulation-dependent tests (electromechanical and optical coagulometric determinations, immunological measurement, thrombin and Reptilase(R) times) were normal. RESULTS: Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the Aalpha-chain gene caused a 5-kDa mobility shift of the Aalpha chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A-->G mutation was found on the Bbeta-chain gene leading to heterozygous Bbeta Tyr236--> stop codon. The predicted truncated Bbeta chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. CONCLUSIONS: Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant.

Adult↗
PubMed2000

Viral RNA in middle ear mucosa and exudates in patients with chronic otitis media with effusion.

OBJECTIVE: To evaluate viral and cytokine signaling correlates of the persistent inflammation associated with chronic otitis media with effusion (OME). DESIGN: Prospective study. METHOD: Reverse transcriptase-polymerase chain reaction targeting RNA viruses frequently associated with OME (respiratory syncytial virus and parainfluenza virus type 3, the proinflammatory cytokines interleukin 8 and interleukin 1beta, and RANTES [regulated upon activation, normal T cell expressed and secreted]) was performed on mucosal biopsy samples and on samples of the liquid and cellular compartments of inflammatory exudates obtained from 26 children (49 ears) with infected middle ears. Ribonucleic acid extracted from rapidly frozen samples was reverse transcribed by Moloney murine leukemia virus reverse transcriptase and amplified for 35 cycles using previously validated primers. Amplicons were evaluated by molecular size after agarose gel electrophoresis with ethidium bromide. RESULTS: Most children had evidence of the presence of an RNA virus in at least one specimen. Respiratory syncytial virus was present in 40% and parainfluenza virus type 3 in 8% of effusions. Interleukin 8 messenger RNA was present in 21% of inflammatory exudates but never in cells from the mucosal biopsy samples. CONCLUSIONS: Our data support a viral contribution to the cause of OME and suggest that the inflammatory cytokines observed derive more from cells in the inflammatory exudate than from those in the middle ear mucosa.

Biopsy↗
PubMed2000

Activation of small ruminant aortic endothelial cells after in vitro infection by caprine arthritis encephalitis virus.

Small ruminants infected by the lentiviruses caprine arthritis-encephalitis virus (CAEV), originally isolated from a goat, or maedi-visna virus, originally from sheep, typically develop an organising lymphoid infiltration of affected tissues. This could reflect modulation of the migration pattern of lymphocytes in infected animals. Possible active contribution by vascular endothelial cells was investigated using an in vitro model. Low-passage cultured ovine aortic endothelium proved susceptible to productive infection by CAEV without significant cytotoxicity. Infected endothelial cells maintained expression of endothelial markers, increased MHC class I antigen expression and initiated expression of the adhesion molecule VCAM -1 and, at a late stage, MHC class II antigens. Infected endothelial cells showed a two-fold increase in binding capacity for sheep peripheral blood leucocytes over uninfected controls. Such events could contribute to the tissue distribution of lymphoid cells and local immune responses in lentiviral infections of small ruminants.

Animals↗
PubMed2000

Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients.

OBJECTIVE: To determine the type of lesions observed in young patients infected with human immunodeficiency virus-1 (HIV-1). DESIGN: Examination of coronary networks in corpses of 13 men and two women who had died aged 23-32 years after having been infected with HIV-1 virus, having been seropositive for 2-5 years. Causes of death were infectious complications (five cases), infection with cytomegalovirus leading to gastro-intestinal haemorrhaging (one case), infection with cytomegalovirus and Kaposi's sarcoma (one case), overdoses of drugs (five cases) and sudden death (three cases). METHODS: The pathological analysis was carried out on the proximal and distal coronary networks. In order to characterize the lesions better, the cells and the cytokines involved were characterized by immunohistochemistry. RESULTS: In all 15 cases we observed thickening of intima in the proximal network at least as great as that of the media, caused by a proliferation of secreting cells, phenotypically identified as smooth muscle cells, with exaggerated production of elastic fibres and in association with an increase in the expression of tumor necrosis factor-alpha and interleukin-1 alpha. In nine cases, atherosclerosis had developed from and on the surface of this proliferation and in four cases arteriosclerosis had an unusual appearance, in the form of mamillated vegetations with endoluminal protrusions. A similar proliferation was found in the distal network in four cases, but with a significantly smaller proportion of elastic fibres. CONCLUSIONS: The lesions we examined in these young HIV-1-infected patients presented particular features and were intermediate between the lesions observed during common coronary atherosclerosis and atherosclerosis associated with chronic rejection of cardiac transplants.

Adult↗
PubMed2000

Lack of functional receptors is the only barrier that prevents caprine arthritis-encephalitis virus from infecting human cells.

Barriers to replication of viruses in potential host cells may occur at several levels. Lack of suitable and functional receptors on the host cell surface, thereby precluding entry of the virus, is a frequent reason for noninfectivity, as long as no alternative way of entry (e.g., pinocytosis, antibody-dependent adsorption) can be exploited by the virus. Other barriers can intervene at later stages of the virus life cycle, with restrictions on transcription of the viral genome, incorrect translation and posttranslational processing of viral proteins, inefficient viral assembly, and release or efficient early induction of apoptosis in the infected cell. The data we present here demonstrate that replication of caprine arthritis-encephalitis virus (CAEV) is restricted in a variety of human cell lines and primary tissue cultures. This barrier was efficiently overcome by transfection of a novel infectious complete-proviral CAEV construct into the same cells. The successful infection of human cells with a vesicular stomatitis virus (VSV) G-pseudotyped Env-defective CAEV confirmed that viral entry is the major obstacle to CAEV infection of human cells. The fully efficient productive infection obtained with the VSV-G-protein-pseudotyped infectious CAEV strengthened the evidence that lack of viral entry is the only practical barrier to CAEV replication in human cells. The virus thus produced retained its original host cell specificity and acquired no propensity to propagate further in human cultures.

Animals↗
PubMed2000

[Endogenous porcine retroviruses and xenotransplantation].

Vertebrate DNA contains numerous genomes closely related to retroviruses, i.e. endogenous retroviruses. While most of the retroviruses are pathogenous, endogenous retroviruses have rarely been shown as such. Endogenous retroviruses, as most of the retroviruses, are able to cross 'species barriers'. Porcine endogenous retroviruses were described in 1974. They are expressed in tissues and cells involved in transplantation, endothelial cells, for instance. They are capable of interspecific transmission, expressed in vitro in human cells; no evidence of in vivo interspecific transmission has been reported so far. As far as xenotransplantation is concerned, porcine endogenous retroviruses represent a risk of adaptation to humans of a new form of retrovirus. Such a risk mandates a close monitoring of recipients and their partners. This risk has already been taken with the use of tissues and stable blood-derived products from animals harboring in their genomes endogenous retroviruses.

Animals↗
PubMed1999

Goat milk epithelial cells are highly permissive to CAEV infection in vitro.

The main route of small ruminant lentivirus dissemination is the ingestion of infected cells present in colostrum and milk from infected animals. However, whether only macrophages or other cell subtypes are involved in this transmission is unknown. We derived epithelial cell cultures, 100% cytokeratin positive, from milk of naturally infected and noninfected goats. One such culture, derived from a naturally infected goat, constitutively produced a high titer of virus in the absence of any cytopathic effect. The other cultures, negative for natural lentivirus infection, were tested for their susceptibility to infection with the CAEV-CO strain and a French field isolate CAEV-3112. We showed that milk epithelial cells are easily infected by either virus and produce viruses at titers as high as those obtained in permissive goat synovial membrane cells. The CAEV-CO strain replicated in milk epithelial cells in absence of any cytopathic effect, whereas the CAEV-3112 field isolate induced both cell fusion and cell lysis. Our results suggest that CAEV-infected milk epithelial cells of small ruminants may play an important role in virus transmission and pathogenesis.

Animals↗
PubMed1999

Parvovirus B19 infection in thoracic organ transplant recipients.

BACKGROUND: Clinical manifestations of parvovirus B19 infection in immunocompromised patients are mostly reported as acute or chronic hematologic disorders. More recently, respiratory or renal involvement has been described. OBJECTIVE: We started in 1994 a prospective study of parvovirus B19 infection in a group of lung (LTP) and heart-lung (HLTP) transplanted patients, including occasionally heart transplanted (HTP) patients. STUDY DESIGN: 62 patients (49 LTP, 11 HLTP, 2 HTP) were included in a serological survey and DNA detection by PCR was performed on each serum sample of the first 29 patients; later we performed it only when serology could suggest an acute episode, or when parvovirus infection could be suspected on clinical or biological observations. A total of 1655 sera were examined by serological tests and DNA detection was done in 500 samples. Specific IgM, seroconversion, significant increase of specific IgG levels, and/or parvovirus B19 DNA detection, were considered as markers of viral infection. RESULTS: We observed the presence of both markers of infection in 24 patients (39%), with an individual combination of positive antibody and PCR results. Acute or chronic anaemia, neutropenia were associated to these laboratory findings in 19 patients, but in five cases, an asymptomatic clinical infection suggested viral persistence. CONCLUSIONS: We report parvovirus associated acute or chronic anaemia and pancytopenia in a group of LTP, HLTP and HTP patients, as well as asymptomatic cases of infection. In the hypothesis of a parvoviral persistent or latent infection, current diagnosis methods may be unreliable to identify any other clinical manifestations.

Adolescent↗
PubMed1999

Conserved sequence motifs involving the tat reading frame of Brazilian caprine lentiviruses indicate affiliations to both caprine arthritis-encephalitis virus and visna-maedi virus.

The sequence variation in small ruminant lentiviruses from Brazilian herds of milking goats was sampled in a representative region of the pol gene and in a region including the entire tat open reading frame. Clones were amplified from cDNA derived from virus produced in vitro using primers targetting conserved sequences of the pol gene. Iterative sequencing of clones indicated that animals from two herds in the Minas Gerais area were infected by a caprine arthritis-encephalitis virus (CAEV)-like virus and that individual animals carried variant virus populations. Sequences derived from an infected goat from a herd in Pernambuco showed no nucleic acid variation and were distant from the CAEV-type sequence but marginally closer to ovine visna-maedi virus (VMV) sequences. Sequences amplified from a region including the tat gene, amplified with a common upstream primer within the vif coding region and different downstream primers because of the local divergence between CAEV- and VMV-type sequences, confirmed the affiliation of the Minas Gerais sequences to CAEV and indicated that the Pernambuco isolate was indeed related to VMV, which had not previously been reported to cause natural caprine infection. The overlap between the vif and tat open reading frames clearly distinguished between CAEV-like small ruminant lentiviruses, which shared eight common nucleotides, and the VMV group, where the overlap was reduced to a single base; the final adenine of the vif terminator (TAA) is the initial adenine of the presumptive tat initiator codon. This may be useful for epizoological tracing of the origin of outbreaks.

Amino Acid Sequence↗