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Biomedical subjects

D Dumont

Publications and source records attributed to D Dumont.

At least 19 recordsLinked to original sources

Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia.

We have recently isolated the erythroleukemic cell line, HB60-5, that proliferates in the presence of erythropoietin (Epo) and stem cell factor (SCF), but undergoes terminal differentiation in the presence of Epo alone. Ectopic expression of the ets related transcription factor Fli-1 in these cells resulted in the establishment of the Epo-dependent cell line HB60-ED that proliferates in the presence of Epo. In this study, we utilized these two cell lines to examine the signal transduction pathways that are activated in response to Epo and SCF stimulation. We demonstrate that Epo, but not SCF, phosphorylates STAT-5 in both HB60-5 and HB60-ED cells. Interestingly, SCF activates the Shc/ras pathway in HB60-5 cells while Epo does not. However, both Epo and SCF are capable of activating the Shc/ras pathway in HB60ED cells. Furthermore, enforced expression of gp55 in HB60-5 cells by means of infection with the Spleen Focus Forming virus-P (SFFV-P), confers Epo independent growth, which is associated with the up-regulation of Fli-1. Activation of the Shc/ras pathway is readily detected in gp55 expressing cells in response to both Epo and SCF, and is associated with a block in STAT-5B tyrosine phosphorylation. These results suggest that STAT-5 activation, in the absence of Shc/ras activation, plays a role in erythroid differentiation. Moreover, Fli-1 is capable of switching Epo-induced differentiation to Epo-induced proliferation, suggesting that this ets factor regulated genes whose products modulate the Epo-Epo-R signal transduction pathway.

Adaptor Proteins, Signal Transducing↗

Carpal tunnel syndrome caused by Mycobacterium szulgai.

We describe 2 cases of infection due to Mycobacterium szulgai revealed by a carpal tunnel syndrome (CTS) that was the only clinical manifestation. Both patients regularly cleaned their fish tank with bare hands. The diagnosis was made by isolation of M. szulgai from synovium. The cause of the CTS was a synovitis. Previous synovectomies were ineffective. Improvement was observed with antibiotic treatment. The only way to diagnose this unusual infection is to perform histology of synovium and to isolate the mycobacteria from synovium culture.

Aged↗

Lymphatic endothelial tumors induced by intraperitoneal injection of incomplete Freund's adjuvant.

Endothelial cells form the inner lining of blood and lymphatic vessels. In mice, only tumors of the blood vessel endothelium (haemangiomas) have been thus far reported. Here we describe a highly reproducible method for the induction of benign tumors of the lymphatic endothelial cells (lymphangiomas) in mice by intraperitoneal injection of incomplete Freund's adjuvant. Morphological and histopathological studies of the lesions revealed the presence of cells at various levels of vascular development. The lymphangiomas developed in the peritoneal cavity and expressed the endothelial markers CD31/PECAM (platelet endothelial cell adhesion molecule), CD54/ICAM-1 (InterCellular Adhesion Molecule-1), and CD102/ICAM-2, as well as the vascular endothelial growth factor (VEGF) receptor Flk-1, the endothelial cell specific receptors Tie-1 and Tie-2 and the lymphatic endothelial cell specific Flt4 receptor as shown by in situ hybridization. The Flk-1 and Flt4 receptors were also identified in immunoblots of the tumors and in cells cultured from them. When induced in beta-galactosidase knock-in Flt4(+/-) mice, the tumor endothelia could be stained blue in a number of tumor cells although the staining was of lower intensity than in normal lymphatic vessels. The tumor-derived cells could be propagated in vitro and they spontaneously differentiated, forming vessel-like structures. Murine lymphangiomas thus represent a highly reproducible and convenient source of lymphatic endothelial cells.

Animals↗

Detection of depression in elderly hospitalized patients in emergency wards in France using the CES-D and the mini-GDS: preliminary experiences.

OBJECTIVE: The purpose of this study was to evaluate the mini-GDS and the CES-D as instruments to detect depression in elderly hospitalized patients in emergency wards in France. METHODS: The CES-D was used on two cohorts of 60 non-cognitively impaired patients aged 70 or more. The mini-GDS was also used on the second of the two cohorts administered by a medical intern. These ratings were compared with a diagnosis of depressive disorder by ICD-10 criteria. RESULTS: The study population had a high (58%) prevalence of depression and a low level of active psychiatric referral. Mini-GDS and CES-D scores were well correlated (0.72, p < 0.001); the mini-GDS, with a cutoff score of 1, gave optimum sensitivity (88%) and specificity (63%). CONCLUSION: The use of the mini-GDS may aid the detection of depression in patients in emergency wards.

Aged↗

Interactive multimedia and risk communication.

As our understanding of risk factors and their interaction with individual susceptibility to disease improves, general messages designed to communicate risk seem increasingly ineffective and often misleading. Risk messages communicated through the mass media cannot convey an individual's personal susceptibility to preventable diseases or the seriousness of these diseases. The advent of new media technologies allows us to better reach the public with programs tailored to the needs and interests of individual users. Although similar in outward appearance to mass media, programs delivered through the Internet, CD-ROM, and computer kiosks offer the potential for vastly improved efficacy in communicating risk. This paper outlines the potential uses of interactive multimedia within the traditional goals of risk communication. A significant research endeavor, coupled with stronger avenues for dissemination, is recommended to achieve the potential of new media in a timely manner.

CD-ROM↗

Abducens palsy after an intrathecal glucocorticoid injection. Evidence for a role of intracranial hypotension.

We report a case of abducens palsy eight days after an intrathecal glucocorticoid injection followed by post-lumbar puncture syndrome. T1-weighted magnetic resonance imaging scans showed marked diffuse postgadolinium enhancement of the supra- and infratentorial meninges consistent with intracranial hypotension syndrome. The palsy resolved almost completely and a repeat magnetic resonance imaging scan done after four months was normal. The mechanism of the meningeal thickening and contrast enhancement is discussed.

Abducens Nerve Injury↗

Prevention of cytokine accumulation in platelets obtained with the COBE spectra apheresis system.

BACKGROUND AND OBJECTIVES: Febrile nonhemolytic transfusion reactions frequently accompany platelet transfusions and may be due to accumulation of cytokines mediating inflammation during storage of platelet concentrates (PCs). We wished to determine whether PCs collected using the COBE(R) SpectraTM Apheresis System (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine accumulation during storage. MATERIALS AND METHODS: Cytokine accumulation - interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) - and release of platelet alpha-granule - P-selectin, transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor (vWf) - or dense granule (serotonin) markers were investigated during a 7-day storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor platelets prepared from whole blood (WB). RESULTS: Leukocyte counts were reduced 99.95% comparing LR PCs (5.7 x 10(5)/l) and WB PCs (1.09 x 10(9)/l). Little or no accumulation of leukocyte-derived cytokines was observed in LR PCs during storage in contrast to WB PCs. A reduction in the release of platelet alpha-granule proteins, such as P-selectin, TGF-beta1 and PDGF-AB, was observed on day 0 for LR PCs compared to WB PCs with little or no difference observed from day 3 to 7. Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0-7. CONCLUSION: Leukocyte levels in PCs collected with the COBE Spectra Apheresis System are sufficiently low to limit cytokine production during 7 days of storage.

Blood Preservation↗

[Articular and tendon manifestations indicating the stage of rheumatoid polyarthritis].

Synovial inflammation and the destruction which results from recurrent and chronic inflammation lead to arthritis and tenosynovitis. Clinical manifestations are bilateral and symmetrical, affecting virtually all joints. The hands and the feet are the main targets. Cervical involvement should be routinely investigated. X-rays demonstrate the erosion and deformation caused by rheumatoid arthritis. Altogether, the manifestations of the disease constitute a distinct and painful handicap. Treatment should be undertaken as early as possible in the course of rheumatoid arthritis in an attempt to avoid evolution toward irreversible destruction.

Adult↗

In vitro cytotoxic effects of 4,4'-bipyridyl on normal human keratinocytes.

Recent epidemiological studies have brought to light a possible link between premalignant or neoplastic skin lesions (Bowen disease, squamous carcinoma) and occupational exposure to 4,4'-bipyridyl (4,4'B), a precursor in the synthesis of paraquat herbicide. The present study used a serum-free cell culture of normal human keratinocytes (NHK) and two skin-equivalent models to test the effects of exposure to different concentrations of 4,4'B. Cytotoxicity of 4,4'B on NHK was measured by neutral red release assay. Superoxide dismutase (SOD) activity and cell cycle were analyzed in exposed and nonexposed NHK cultures. Histological and immunohistological tests enabled evaluation of differentiation and proliferation effects in reconstructed-skin models. Results showed that significant cytotoxicity occurred after 5 to 11 days' exposure to 4,4'B concentrations of 10(-6)-10(-3) mol/L (IC50 between 10(-3) and 10(-4) mol/L 4,4'B after 11 days). Parallel modifications of SOD activity were recorded. Histological and immunohistological analysis revealed dose-related 4,4'B effects in reconstructed skin models. This involved abnormal terminal differentiation, connected with filaggrin expression, observed in skin models exposed to 10(-7) and 10(-6) mol/L 4,4'B. However, no modification of cell cycle or dysplasia was detected as a result of exposure to 4,4'B. Thus, 4,4'B appears to be cytotoxic for NHK, but as an isolated contaminant, and is unable to induce keratinocyte dysplasia in vitro. These preliminary results do not exclude a cocarcinogenic action of 4,4'B (with UVB for example).

Cell Cycle↗

Endothelial-specific gene expression directed by the tie gene promoter in vivo.

The tie gene encodes a receptor tyrosine kinase that is expressed in the endothelium of blood vessels, particularly during embryonic development and angiogenesis in adults. We have cloned and characterized the mouse tie gene and isolated the human and mouse tie promoters. The promoter activities of human and mouse tie were analyzed using luciferase reporter gene constructs in transfected cell lines and beta-galactosidase constructs in transgenic mice. In transfection assays of cultured cells, both human and mouse promoter DNA fragments showed activity that was not restricted to endothelial cells. In contrast, in transgenic mice both promoters directed expression of the reporter gene to endothelial cells undergoing vasculogenesis and angiogenesis. In adult mice, tie promoter activity in lung and many vessels of the kidney was as high as in the vessels of the corresponding embryonic tissues, whereas in the heart, brain and liver, tie promoter activity was downregulated and restricted to coronaries, cusps, capillaries, and arteries. Our results show that the endothelial cell-type specificity of the tie promoter in vivo can be transferred to heterologous genes by using relatively short promoter fragments. The tie promoter, thus, has useful properties for potential gene therapy.

Animals↗

Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.

Adenocarcinoma↗

[Clinical pitfalls in the diagnosis of microcrystalline arthritis].

Diagnosis of microcrystalline arthritis often is based on joint punctures, performed whenever possible. The clinical features of the crises may suggest diagnosis, but is not decisive. The course before or during treatment is not indicative and cannot fully exclude infection when the patient is seen during a crisis; arthritis with one or several microcrystals is possible, as in forms associated with joint infection. For well-oriented management, good knowledge of such diagnostic difficulties is necessary.

Arthritis↗

Single-dose pharmacokinetics of amineptine and of its main metabolite in healthy young adults.

The pharmacokinetics of the tricyclic antidepressant amineptine (Survector) and its main metabolite were studied in 12 young healthy adults (6 men, 6 women; mean age 35.8 yr). Plasma samples were taken over 24 h following a single oral dose of 100 mg amineptine chloryhdrate. Plasma levels of both compounds were determined by means of high performance liquid chromatography. Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 h and 1.5 h, respectively, after product administration. The mean apparent volume of distribution was large: 2.4 l.kg-1. Elimination was rapid; the mean half-lives of the 2 compounds were short: 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 l.h-1). When the results were adjusted for body weight and surface area, no significant difference in pharmacokinetic parameters was found between men and women. Given its pharmacokinetic characteristics there is no risk of amineptine accumulation and thus it is a particularly easy drug to manage. A standard dosage of amineptine was defined for use in healthy young adults.

Adult↗

[Total hip arthroplasty using the Hardinge approach. Clinical results in 63 cases].

The recently described Hardinge approach is currently widely used for implanting total hip prostheses. It is characterized by a dissociation of the fibers of the mid-gluteal, of which the anterior fibers remain continuous with the vastus lateralis. To assess the functional impact, a series of 63 prostheses implanted with the Hardinge approach was compared with an identical series performed with the posterior approach. Results show a lower frequency of dislocation with the Hardinge approach, but also a 33 p. cent residual functional deficiency of the mid-gluteal at one year, compared with 17 p. cent with the posterior approach. A modification of the technique is proposed to limit this phenomenon.

Adult↗