Search PubMedSearch

Biomedical subjects

J F Moreau

Publications and source records attributed to J F Moreau.

At least 19 recordsLinked to original sources

Activation of the erythropoietin receptor by the Friend spleen focus-forming virus gp55 glycoprotein induces constitutive protein tyrosine phosphorylation.

The erythropoietin receptor (EPO-R) can be activated to signal cell growth by binding either EPO or gp55, the Friend spleen focus-forming virus (SFFV) glycoprotein. EPO binding induces tyrosine kinase activity and rapid tyrosine phosphorylation of several cellular substrates. To test for gp55-induced tyrosine kinase activity, we performed immunoblots on two murine cell lines that stably express EPO-R and gp55. Stimulation of the parental cell line, Ba/F3, with murine interleukin-3 (IL-3) resulted in rapid, dose-dependent tyrosine phosphorylation of a 97-Kd substrate. Stimulation with IL-3 or EPO of the Ba/F3 cells expressing the recombinant EPO-R (Ba/F3-EPO-R) resulted in tyrosine phosphorylation of the same p97 substrate. These latter cells, when transformed to growth factor-independence by the Friend gp55 glycoprotein, exhibited constitutive tyrosine phosphorylation of the 97-Kd substrate. Other growth factor-independent Ba/F3 subclones, transformed with either the oncoprotein, v-abl, or with a constitutively activated EPO-R, also had constitutive phosphorylation of a 97-Kd substrate. In CTLL-2-EPO-R cells, a T-lymphocyte line stably transfected with the EPO-R, the 97-Kd substrate was tyrosine-phosphorylated in response to IL-2 or EPO. The 97-Kd protein was constitutively phosphorylated in CTLL-2-EPO-R-gp55 cells. In conclusion, a 97-Kd protein found in two murine cell lines is tyrosine-phosphorylated in response to multiple growth factors and viral oncoproteins, and appears to be a central phosphoprotein in signal transduction.

Animals

[Imaging of renal cancer in adults].

In its typical form renal carcinoma shows at imaging as a solid, heterogeneous and vascularized mass deforming the kidney; its CT scan appearance is usually very suggestive. Atypical forms (small or cystic carcinomas, large carcinomas with exorenal extension, haemorrhagic carcinomas) mainly raise problems of characterization; the lesional image is always suspicious at CT or combined US, CT and MRI examinations. The detection of small tumours primarily rests on CT with contrast injection, a technique which is more sensitive (94%) than all other techniques. Among non-tumoral lesions which may look like renal carcinomas, some pseudotumoral inflammatory lesions and suspicious atypical cysts often require histological examination. With the exception of angiomyolipoma with its fat content detectable at CT or MRI, there is no truly specific criterion to differentiate benign tumour from cancer. The diagnosis of renal carcinoma extension primarily rests on MRI. In a number of cases the results are so inadequate for the study of renal veins and caval vein that a complementary exploration of these veins by Doppler ultrasonography or MRI must be requested.

Adult

Fluoroscopically guided percutaneous transrenal electroincision of ureterointestinal anastomotic strictures.

A new technique for electroincision of a strictured ureterointestinal anastomosis is described that uses a sphincterotome and high frequency current. After placement of a percutaneous nephrostomy tube a 7F "wire guided" sphincterotome was placed into the stenosis. The cutting wire was then deflected while cutting current was applied intermittently. Injection of contrast medium through the papillotome probe assessed the depth of the incision. A 10 mm. angioplasty balloon was inflated at low pressure to verify that the anastomosis had been incised to a depth of 1 cm. The anastomosis was then stented for 8 weeks with an 18F stent. The operative time did not exceed 45 minutes. A total of 9 stenoses was treated in 7 patients: 4 were ileal conduit diversions and 5 were enterocystoplasties. No immediate complication was observed. In 1 case a small urinoma was surgically drained at removal of the stent. Six stenoses are patent with 2, 3, 4, 4, 10 and 13 months of followup after removal of the stent. One patient died of bladder tumor metastases during the stenting period and 1 with bilateral incision still has a stent. The technique can be performed without major complication (bleeding or digestive fistula). Long-term results remain to be assessed.

Constriction, Pathologic

Correction of severe secondary hyperparathyroidism in two dialysis patients: surgical removal versus percutaneous ethanol injection.

Two chronic hemodialysis patients had recurrent, severe secondary hyperparathyroidism. The first had no sonographically visible parathyroid gland in the neck. Computed tomography (CT) scan indicated the existence of a parathyroid mass in the upper mediastinum, which was removed surgically. The second patient had two intracervical, hyperplastic parathyroid glands visible on ultrasound examination. He volunteered for nonsurgical removal via sonographically guided percutaneous injection of ethanol. In both patients, serum total calcium concentration decreased dramatically to values near 1.5 mmol/L 24 hours after treatment. In patient 1, serum immunoreactive parathyroid hormone (iPTH) (1-84) decreased from 1,582 pg/mL before surgery to 34 pg/mL after 24 hours (normal range, 10 to 65 pg/mL). In contrast, serum iPTH (1-84) decreased only progressively in patient 2, from 1,680 pg/mL before ethanol injection to 865 pg/mL after 24 hours and to 378 pg/mL after 72 hours to reach 30 pg/mL after 14 days. Thus, patient 2 had a striking decrease of plasma calcium immediately after parathyroid gland destruction, even though circulating iPTH was still very high. The reason for such a discrepancy remains unexplained at present, and further study will be necessary to solve this issue.

Adult

HILDA/LIF urinary excretion during acute kidney rejection.

Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.

Antibodies, Monoclonal

The erythropoietin receptor transmembrane region is necessary for activation by the Friend spleen focus-forming virus gp55 glycoprotein.

The erythropoietin receptor (EPO-R), a member of the cytokine receptor superfamily, can be activated by binding either erythropoietin (EPO) or gp55, the Friend spleen focus-forming virus glycoprotein. The highly specific interaction between gp55 and EPO-R triggers cell proliferation and thereby causes the first stage of Friend virus-induced erythroleukemia. We have generated functional chimeric receptors containing regions of the EPO-R and the interleukin-3 receptor (AIC2A polypeptide), a related cytokine receptor which does not interact with gp55. All chimeric receptors were expressed at similar levels, had similar binding affinities for EPO, and conferred EPO-dependent cell growth. Only those chimeric receptors which contained the EPO-R transmembrane region were activated by gp55. These results demonstrate that the transmembrane region of the EPO-R is critical for activation by gp55. In addition, analysis of a soluble, secreted EPO-R and cysteine point mutants of the EPO-R show that the extracytoplasmic region of the EPO-R specifically interacts with gp55.

Binding Sites

Gd-DOTA-enhanced MR imaging and color Doppler US of renal allograft necrosis.

In 21 recipients of renal transplants suspected of allograft necrosis, the authors correlated the results of imaging to pathologic and histologic data in order to describe the magnetic resonance (MR) imaging and color Doppler ultrasonographic (US) characteristics of infarction. All patients underwent MR imaging performed with and without gadolinium tetraazacyclododecanetetraacetic acid (DOTA) and color Doppler US. Nonenhanced T1-weighted images showed no obvious changes, whereas nonenhanced T2-weighted images demonstrated a slight increase in signal intensity in areas of ischemic necrosis and low or heterogeneous signal intensity in areas of hemorrhagic necrosis. Gd-DOTA-enhanced MR images showed no contrast material uptake in infarcted areas. Color Doppler US characteristics of infarction included absence of Doppler signal and alteration of the cortical echogenic structure, particularly in cases of ischemic necrosis. Color Doppler US allows measurement of vascular resistance and assessment of intrarenal vasculature and the renal pedicle. Gd-DOTA-enhanced MR imaging is useful in confirming the diagnosis of infarction and provides an accurate evaluation of the extent of the infarct.

Adult

[What may be expected from endorectal echography and magnetic resonance imaging in the evaluation of local extension of cancer of the prostate?].

Thirty patients presenting with a clinical stage A or B cancer underwent TRUS and MRI with a body coil prior to radical prostatectomy. Imaging and pathology were correlated to assess the limits of TRUS and MRI in pre-operative staging of prostatic carcinoma. Results showed that TRUS and MRI had a sensitivity of 42 and 66% and a specificity of 89 and 94% respectively, for the diagnosis of macroscopic capsular effraction. Seminal vesicle invasion was diagnosed by TRUS with a sensitivity of 16% and a specificity of 81%. With MRI, the sensitivity and the specificity were 85 and 94% if only gross infiltration was considered. Sensitivity dropped to 45% if microscopic invasion was included. We conclude that: 1) postero-lateral venous plexus are more easily delineated by MRI, permitting a more accurate diagnosis of capsular penetration. 2) Seminal vesicle invasion cannot be diagnosed by TRUS as the echo-structure of the cancer and the caudal junction of the seminal vesicles and vas deferent are similar. 3) A normal caudal junction on TRUS or a normal bilateral hypersignal of the seminal vesicles on MRI are associated with seminal vesicle invasion in less than 5% of cases. 4) A normal caudal junction on TRUS eliminates false positive cases of MRI related to non tumoral hyposignals of the seminal vesicles.

Aged

[Role of MRI in the diagnosis of cancer of the kidney].

The recent technical developments in magnetic resonance imaging (MRI) and the use of paramagnetic contrast media (gadolinium compounds) have considerably improved the performances of MRI for the detection and characterization of renal tumors. MRI does not have specific merits for the diagnosis of the typical form of cancer, nor for the detection of small kidney tumors, both being mainly based on computed tomography (CT). On the other hand, it can be used for the diagnosis of atypical forms of cancers (small, hypovascular, cystic or hemorrhagic cancers) which raise problems of differential diagnosis with some pseudotumoral lesions, complex cysts and benign tumors. Its complementarity to CT for the characterization of an atypical mass results from the signal information it provides, from a better contrast resolution, and from the possibility to make sections in all planes of space. Except for angiomyolipoma, which has a fatty content, there is no really specific MR criterion as present to evidence benign renal tumors. Concerning regional extension, CT remains the primary technique of choice, as it allows studying the limits of the tumor, the renal compartment and its walls, the renal vein and the inferior vena cava, the neighboring organs and the contralateral kidney all together. Its findings allow defining the indications of MRI, which, as a complementary exploration, is often decisive to assess venous invasion.

Adenocarcinoma

Human interleukin for DA cells (HILDA) does not affect the proliferation and differentiation of hematopoietic progenitor cells in human long-term bone marrow cultures.

Human Interleukin for DA cells (HILDA), a cytokine also known as leukemia inhibitory factor (LIF), induces proliferation without concurrent differentiation of murine embryonic stem cells. Therefore, we investigated the effects of recombinant HILDA/LIF on the proliferation and differentiation of human hematopoietic progenitor cells (HPC) grown in long-term bone marrow cultures (LTBMC). Pre-established stromal cell layers were reinoculated with autologous cryopreserved mononuclear phagocyte- and T-lymphocyte-depleted bone marrow cells in the presence or absence of HILDA/LIF (200 U/ml). At weekly intervals cultures were sacrificed, and the cells in the adherent and the nonadherent cell fractions were counted. The numbers of HPC were determined by culturing these cells in semisolid medium stimulated with phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM), and LTBMC supernatants were assayed in semisolid cultures for the presence of colony-stimulating activity (CSA). The total number of cells, their differential counts, the number of HPC, and the concentrations of CSA in culture supernatants were similar for long-term cultures containing HILDA/LIF and for controls. These data suggest that HILDA/LIF may not play a role in the proliferation and differentiation of normal human (early) HPC in LTBMC. Moreover, HILDA/LIF did not stimulate the proliferation of relatively mature progenitor cells in semisolid cultures, not did it influence the colony formation induced by other colony-stimulating factors (CSF). Finally, using a [3H]thymidine suicide test we could not find an effect of HILDA/LIF on the cell-cycle status of HPC.

Bone Marrow

[Aseptic osteonecrosis of the knee induced by corticoids. MRI aspects].

Authors report the results of a series of 29 knees examined by magnetic resonance imaging in 16 patients subjected to a long-term corticosteroid therapy (6 systemic lupus erythematosus and 10 kidney transplanted people). Abnormal signals of condyles or tibial plateaus were observed in 12 patients (19 knees). Lesions, which were asymptomatic in 37% of the cases studied, mostly showed (12/24 condyles) a fatty signal area marked out by a hypointense signal strip in T1 edged with a hyperintense signal in T2. Some developed lesions were hypointense whichever the sequence. Our study confirmed the frequency of the lateral condyle involvement (60%) and the bilateral aspect of the lesions (50%) in osteonecrosis of the condyles following the corticosteroid therapy. The associated lesions of articular surfaces (3 cases) could be well assessed through magnetic resonance imaging on T2 or T2* weighted images. In two cases, the abnormal signals of the condyles suggesting a medullary edema (hypointense signal in T1 and hyperintense signal in T2) spontaneously disappeared 6 and 9 months after their discovery. Abnormal signals related to medullary infarcts (10 knees) were always associated with abnormal condyles. Most time their aspect in magnetic resonance imaging, except old calcified lesions, was characteristic: serpiginous hypointense signal isolating areas of fatty signal edged with a hyperintense signal strip in T2. In risk patients, magnetic resonance imaging allows early detecting knee necroses, precising the extent of epiphyseal and metaphyso-diaphyseal lesions and their impact on articular surfaces.

Adult

Macrophage colony-stimulating factor (CSF-1) gene expression in human T-lymphocyte clones.

Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species. This pattern of expression is typical for CSF-1 mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency. Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium. Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.

Antigens