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Biomedical subjects

J F Moreau

Publications and source records attributed to J F Moreau.

At least 73 records · Page 4Linked to original sources
PubMed1997

Refolding of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) from urea.

The insoluble inclusion bodies of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) was solubilized in 8 M urea on the unfolding transitions, and several factors on the aggregate formation were indirectly analyzed for the refolding of gp 190 sol DAF. Results indicate that the refolding yield can be considerably increased at lowering concentration of the unfolding protein, a little soluble protein with the slow refolding appears in the process of the aggregate formation and the concentration of the denaturant must be down to a minimum level for its refolding.

Glycerol↗
PubMed1997

Epitope-function relationships of human leukemia inhibitory factor receptors using a novel set of anti-gp190 mAB.

The binding and functional properties of a set of six mAb directed against the human gp190 [leukemia inhibitory factor (LIF) receptor] signal transducing molecule were determined. Each of the antibodies reacted with a distinct epitope on gp190 expressed either by gp190-transfected Chinese hamster ovary cells or by the LIF receptor-positive choriocarcinoma JAR cell line. Two of the antibodies (1B4 and 6E6) had binding stoichiometries that were approximately 2-fold lower than those of other mAb (10B2, 12D9 and 7G7), suggesting either that gp190 is present as a pre-associated homodimer in the cell membrane or that part of gp190 is pre-associated with another component. Two mAb (1C7 and 1B4) were found to inhibit LIF binding on the two cell types studied. On JAR cells, this inhibition was, however, restricted to the high-affinity LIF component, suggesting different modes of LIF engagement with the low- and high-affinity receptor species. mAb 1C7 and 1B4 were also found to synergize for inhibiting LIF high-affinity binding. This synergy also extended to the inhibition of LIF- or oncostatin M (OSM)-induced proliferation of a Ba/F3 cell line co-transfected with human gp130 and gp190. However, this mAb combination inhibited LIF- but not OSM-induced haptoglobin secretion by HepG2 cells, suggesting that whereas haptoglobin secretion induced by LIF involves gp130/gp190 common LIF/OSM type I receptors, that induced by OSM mainly involves type II OSM receptors.

Animals↗
PubMed1997

Ultrasound contrast agents. Examples of blood pool agents.

PURPOSE: The concept of contrast agents has been extended to ultrasonography (US) almost 30 years ago. Due to technical limitations, the development of US contrast agents (USCA) was slow until the last decade. The ideal USCA should be nontoxic, i.v. injectable, capable to cross the pulmonary capillary bed after a peripheral injection, and be stable enough to achieve enhancement for the total duration of the examination. It should provide not only Doppler but also B-mode enhancement, at a reasonable cost. The efficacy of the most advanced USCA has been reviewed. RESULTS AND CONCLUSION: Doppler examinations improved in cases of deep or small vessels, vessels with low or slow flow, or vessels studied with a bad insonation angle. USCA also enhanced detection of flow within normal and abnormal vessels, including tumor and stenotic vessels. Ischemic areas were better delineated. Specific settings and software developed by US equipment manufacturers and US sequences (such as second harmonic imaging or transient imaging) prefigured the necessary adaptation of US units to the new potentials of USCA. Second harmonic properties will improve detection of smaller vessels including neovascularization associated with tumors. Targeting possibilities will increase the efficacy of USCA, and allow specific delivery of active drugs such as anticoagulants or cytotoxic compounds. New generations of USCA appear very promising, and are becoming part of the US future.

Contrast Media↗
PubMed1997

[Abnormal endometrial reactivity to colony stimulating factor 1 and leukemia inhibitory factor dependent female infertility].

Maternal LIF is essential for embryo implantation in mice and it may also be the case in humans. We recently reported that endometrial LIF secretion from infertile women presenting repeated failures of embryonic implantation or unexplained sterility was significantly lower than the secretion of explants from fertile women. We now report on the modulation of the endometrial LIF secretion according to the obstetrical status. CSF-1 has little effect or increases LIF secretion from fertile women whereas it inhibits secretion from infertile women with repeated failures of embryonic implantation.

Adult↗
PubMed1996

Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop.

We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL-10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia-inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL-10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG-6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.

Antigens, CD↗
PubMed1996

Human HLA-specific T-cell clones with stable expression of a suicide gene: a possible tool to drive and control a graft-versus-host- graft-versus-leukemia reaction?

Allogeneic bone marrow transplantation is still limited by the morbidity and mortality caused by graft-versus-host disease (GVHD), resulting from host recognition by donor T lymphocytes. It is possible to drastically reduce the T-cell content of the graft. However, transplanted T cells can also have a beneficial effect by graft enhancement and the graft-versus-leukemia effect. How can we keep the beneficial GVL effect while protecting the patient from possible GVHD? A recent report proposed the ex vivo transfer of the herpes simplex thymidine kinase (HSv-tk) gene into donor T cells before their infusion with hematopoietic stem cells. This procedure is expected to allow selective donor T-cell depletion with ganciclovir should GVHD occur, but it has two major drawbacks: reinjection of a fraction of untransfected T cells cannot be avoided and heterogeneity of the transfected population results in increased risks such as HSv-tk gene instability or dysfunction of some of the transfected T cell. Alternative approaches must be considered. We demonstrate here the feasibility of generating HSv-tk transfected HLA-specific CD4+ cytotoxic T-cell clonal populations, in which 100% of the cells have the HSv-tk gene inserted at a single site within their genome. These clones retained their specificity, their function, and their sensitivity to ganciclovir treatment. Our approach is not limited to bone marrow transplantation. Indeed, this procedure represents a useful alternative to retroviral gene transduction and is applicable to every circumstance where clinical use of gene modified T-cell clones is to be considered.

Antiviral Agents↗
PubMed1996

Human cytomegalovirus increases constitutive production of interleukin-6 and leukemia inhibitory factor by bone marrow stromal cells.

Human cytomegalovirus (CMV) infection is often associated with myelosuppression and acute inflammatory reaction in immunocompromised patients. We have previously documented that CMV exposure of bone marrow (BM) stromal cells reduces the capacity of these cells to support hematopoiesis because of a decreased production of colony-stimulating factors. This study examines the potential role of CMV on constitutive and lipopolysaccharide (LPS)-stimulated production of cytokines involved in inflammatory reaction, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) by BM stromal cells. The release of IL-6 was already detectable 2 hours post CMV-infection (2.5-fold increase in production) and the cumulative production of IL-6 after 5 days of infection was 23 +/- 1.2 ng/mL (ninefold increase in production). CMV was also able to induce a time-dependent production of LIF that was maximal 8 hours after CMV infection (2.5-fold increase in production). Concomitantly, there was no detectable release of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) by CMV-infected stromal cells. The similar IL-6 and LIF production in the presence of polymyxin B ruled out the possibility that this increase could be caused by contamination of the viral stock by endotoxin. In addition, ultraviolet-inactivated virus behaved similarly to live virus and caused the release of IL-6 and LIF. However, heat-inactivated CMV was unable to induce IL-6 and LIF secretion by BM stromal cells. The production of IL-6 and LIF was also evaluated after stimulation by LPS. After 5 days of CMV exposure, the LPS-stimulated production of IL-6 and LIF was significantly lower than uninfected controls. This LPS-induced release of cytokine production was found to be dependent of viral replication. The experiments have shown that CMV is a potent inducer of IL-6 and LIF with differential effect on constitutive and LPS-stimulated cytokine production by stromal cells; we suggest that CMV induction of IL-6 and LIF during the first hours of infection could play a role in CMV-induced inflammatory reaction. Moreover, our results show that human CMV can disturb the balanced cytokine network involved in the regulation of hematopoiesis.

Bone Marrow Cells↗
PubMed1996

High levels of leukaemia inhibitory factor in ARDS.

Although elevated concentrations of a few cytokines have been shown to be present in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with the acute (adult) respiratory distress syndrome (ARDS), the pathogenesis of ARDS is largely unknown. Leukaemia inhibitory factor (LIF), a growth factor recently recognised as a polyfunctional cytokine integrated in cytokine networks was measured in unconcentrated BALF of patients from different patient groups. LIF was measured in BALF by means of a specific and sensitive ELISA (detection limit 10 pg/ml) in BALF (lavage of 3 x 50 ml in the right middle lobe). LIF was not detected in the BALF of 13 healthy control patients and in only one (34 pg/ml) out of 25 patients at risk for ARDS (after cardiopulmonary bypass surgery) who underwent BAL 4 h after the end of the extracorporeal circulation. High and detectable levels were found in the unconcentrated BALF of 10 out of 12 patients with full-blown ARDS (212 +/- 116, mean +/- SEM, range 10-985 pg/ml). There was a good correlation between the level of LIF in the BALF and a number of markers of inflammation such as neutrophils/ml, albumin and protein levels. The biological role of LIF in these BALFs is not readily explained by its currently known actions and it is unknown whether LIF contributes to or is a response to local tissue damage. Our results indicate that this cytokine is part of the inflammatory cytokine cascade in ARDS.

Adult↗
PubMed1996

Percutaneous transrenal electro-incision of ureterointestinal anastomotic strictures: long-term results and comparison of fluoroscopic and endoscopic guidance.

PURPOSE: We determined the long-term outcome of a new technique for incising ureterointestinal anastomotic strictures using a transrenal percutaneously inserted papillotome. Procedures using fluoroscopic and endoscopic guidance were compared. MATERIALS AND METHODS: Of 33 stenoses incised in 30 patients 15 were in ileal conduit diversions and 15 were in enterocystoplasties. The papillotome was inserted percutaneously over a guide wire into the stenosis, and then deflected and gently withdrawn under fluoroscopic (11 cases) or endoscopic (22) guidance using a flexible pediatric gastroscope or a lateral duodenoscope inserted retrograde into the ileal loop or neobladder. Air filling provided an excellent view of the stenotic area. Operative time did not exceed 45 minutes. The only major complication was damage to a right internal iliac artery. RESULTS: Followup data were available for 31 stenoses, with 27 followed for longer than 12 months after stent removal. Of the stenoses 22 are completely patent (actuarial long-term patency rate 71%), 3 showed partial improvement and 6 recurred requiring further treatment. CONCLUSIONS: Combined endoscopic and fluoroscopic guidance is preferable to fluoroscopy alone. The technique is simple if the endoscope is inserted retrograde. Long-term results are satisfactory and we believe that incision should be the initial approach to strictures of uro-digestive anastomoses.

Anastomosis, Surgical↗
PubMed1996

Local staging of prostate cancer by endorectal MRI using fast spin-echo sequences: prospective correlation with pathological findings after radical prostatectomy.

OBJECTIVE: To evaluate the accuracy of endorectal magnetic resonance imaging (MRI) with fast spin-echo sequences in the local staging of clinically localized prostate cancer. PATIENTS AND METHODS: Seventy-one patients with a clinical T1 (18 patients) or T2 tumour (53 patients) underwent endorectal MRI 2-12 weeks before radical prostatectomy. Extraprostatic tumour was diagnosed if MRI showed signs of capsular penetration and/or invasion of the seminal vesicle and/or distal urethra or bladder neck. If the pathological examination showed a single positive margin with no periprostatic tissue, the tumour was classified as indeterminate and not as a T3 tumour. RESULTS: Of the 25 cases of capsular penetration. MRI correctly identified 10 (sensitivity 42%, specificity 100%). Of the 14 cases with seminal vesicle invasion, MRI correctly identified six (sensitivity 43%, specificity 100%), but showed other signs of extraprostatic tumour spread in seven of the eight unidentified cases. Overall, MRI identified 16 of the 30 patients (53%) with occult extraprostatic spread of tumour; there was only one false-positive result. The sensitivity, specificity and accuracy of MRI were 53, 96 and 74%, respectively. CONCLUSION: Endorectal MRI can reduce the rate of preoperative understaging from 42% to 22% and it can be used for a given individual because it can detect extraprostatic invasion with 96% specificity, ensuring that very few, if any, patients will be deprived of curative surgery.

Aged↗
PubMed1996

Increases in CD3+CD4-CD8- T lymphocytes in AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection.

Human immunodeficiency virus type 1 (HIV-1)-infected persons frequently have increased numbers of T cells bearing the gamma delta T cell receptor for antigen (gamma delta TCR). HIV-1-seropositive patients with < 100 CD4+ cells/mm3 were selected and divided into 9 AIDS-defining illness groups. The percentages of CD4+, CD8+, or double-negative CD4-CD8- (DN) T cells (most of the latter expressing the gamma delta TCR) for 8 symptomatic groups were compared with those for a reference group of asymptomatic HIV-1-infected patients. DN T cells were increased only in patients with disseminated Mycobacterium avium-intracellulare complex (MAC) infection, toxoplasmosis, or Kaposi's sarcoma. Multivariate logistic regression analysis revealed that the percentage of DN T cells was a better predictor of MAC infection than was the percentage of CD4+T cells. The increased percentage of DN T cells might have important implications for the understanding of gamma delta T cell physiology and for the early diagnosis and management of MAC infections in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Ultrasound-guided biopsies for breast nodules: value of automatic biopsy needle].

Within 18 month, 83 solid breast nodules were biopsied with a long throw biopsy gun with 18 gauge needle (Monopty, Bard Urological, Covington) and a 13 Mhz real time AU 530 (Easote Biomedica, Italy) for the ultrasound guidance. The biopsy procedure was well tolerated with no serious complications, and with no insufficient material. US guided biopsy detected 9 cancers, 47 specific benign lesions (39 fibroadenomas, 1 lipofibroadenoma, 4 sclerosing adenoses, 1 fibromatosis, 1 cyst, 1 lymphadenopathy) and 27 non specific benign fibrocystic dystrophy. In 14 out of the 15 nodules surgically removed, the histological diagnoses were identical. In the one remaining case a fibroadenomas was assessed. In the 36 other cases no evolution occurred. US guided core biopsy with automatic device is probably a very useful approach of uncertain pathological diagnoses in mastology.

Adolescent↗
PubMed1996

[Pseudotumor form of focal acute pyelonephritis].

Two cases of focal acute pyelonephritis presenting with an unusual pseudo-tumoral appearance on CT are reported. The lesions exhibited a focal intra-parenchymal homogeneous round-shape mass without any other parenchymal or perirenal fat CT abnormalities. The final diagnosis of focal acute pyelonephritis was confirmed on following CT scans which demonstrated the total disappearance of the lesions in both cases. This particular appearance of acute focal pyelonephritis which mimicked a renal tumor should be clearly individualized in the terminology based on CT findings.

Acute Disease↗
PubMed1996

[Expression of LIF as autocrinal growth factor in human medulloblastomas].

In this study, in vivo and in vitro expression of LIF and its signal transducer genes, LIFR and gp130 in medulloblastoma cells and its role(s) in the cell proliferation were investigated by different approaches. The results revealed that 12 out of 13 cases examined were found to express LIF and more than 90% of the samples to express LIFR and gp130. Functional evaluation of LIF using Med-3 cells showed that the cell growth and DNA synthesis could be efficiently inhibited (P < 0.001) by neutralization of LIF bioactivity. Our data thus demonstrated the importance of LIF as autocrtinal growth factor in the proliferation of medulloblastoma cells and also implicated a potential new therapeutic approach for a better treatment of the tumors through blockage of LIF gene expression and/or ligand interaction.

Antigens, CD↗
PubMed1996

[Management and transmission of medical images. Main standards and norms].

Use of digital images is growing in medical imaging. To be efficient, up-to-date concepts such as distributed informatics and client/server architecture must be used. Interoperability and networks adapted to the data involved in medical imaging are prerequisites to the implementation of such concepts. This necessitates official and de facto standards. Users of medical imaging should be aware of these standards and insist on the implementation of such standards on imaging equipment. This paper presents a survey of the main standards suitable for medical image management and transmission. Particular attention is focused on DICOM which is becoming the worldwide recognized standard in the field of medical imaging.

Diagnostic Imaging↗
PubMed1995

In vitro biosynthesis of leukemia inhibitory factor/human interleukin for DA cells by human endothelial cells: differential regulation by interleukin-1 alpha and glucocorticoids.

Endothelial cell (EC) may represent a major source of cytokines in the bone marrow. In this study we have examined the production and the regulation of the production of leukemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) by EC. Human umbilical vein endothelial cells (HUVEC) were chosen as a working model as they are a well known source of cytokines. These cells secrete LIF/HILDA (90 pg/mL/10(6) cells/48 h) in basal conditions. This secretion is profoundly altered by interleukin-1 alpha (IL-1 alpha). Secretion of LIF/HILDA is increased threefold on stimulation with IL-1 alpha at a concentration of 100 IU/mL. The secreted protein is bioactive as demonstrated by its proliferative effects on DA1a cells. Modulation of the production of LIF/HILDA by glucocorticoids (GC) was also examined. In striking contrast to what was observed for IL-1 alpha, the synthetic GC dexamethasone (DXM) at a concentration of 10(-6) mol/L consistently inhibited the basal secretion of LIF/HILDA by an average of threefold and suppressed the IL-1 alpha-induced increase of the secretion of this cytokine by HUVEC. In an effort to extend results obtained with HUVEC to the bone marrow endothelium, we have also examined the production of LIF/HILDA by human bone marrow endothelial cells (HBMEC). Our study shows that HBMEC are quantitatively a very important source of this cytokine (above 7.25 ng/mL/10(6) cells/48 h) suggesting that they are a major source of LIF/HILDA in the bone marrow. Again, IL-1 alpha proved to be a very potent stimulus for the secretion of LIF/HILDA and synthetic GC such as DXM when used at a concentration of 10(-6) mol/L inhibited by an average of threefold the basal secretion of LIF/HILDA and had suppressive effect on the IL-1 alpha-induced increase of this secretion. The downregulation of LIF/HILDA production in the bone marrow by GC may be important to understand the effects of GC on hematopoiesis.

Bone Marrow↗
PubMed1995

Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11.

Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on lymphohematopoietic cells. It belongs to a family of pleiotropic and redundant cytokines that use the gp 130 transducing subunit in their high affinity receptors. By amplifying human cDNA libraries with oligonucleotide primers corresponding to the conserved WSXWS motif found in the hematopoietic cytokine receptor family, a novel cytokine receptor cDNA was identified that, based on high (82%) sequence homology with the recently cloned murine IL-11 receptor, appears to encode the human IL-11 receptor. This receptor is a 422-amino acid protein containing a signal peptide followed by extracellular, transmembrane, and cytoplasmic domains. The extracellular region has a two-domain structure homologous to those of the IL-6 and ciliary neurotrophic factor (CNTF) receptors: an immunoglobulin-like domain and a cytokine receptor-like domain. In addition, an isoform of the human IL-11 receptor that lacks the cytoplasmic domain was also identified. In agreement with the pleiotropic effects of IL-11 on different hematopoietic lineages and bone cells, IL-11 receptor transcripts were found to be expressed by the myelogenous leukemia cell line K562, the megakaryocytic leukemia cell line Mo7E, the erythroleukemia cell line TF1, and the osteosarcoma cell lines MG-63 and Saos-2.

Amino Acid Sequence↗