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Biomedical subjects

Dominique Henin

Publications and source records attributed to Dominique Henin.

11 recordsLinked to original sources
PubMed2006

Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice.

Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway, experience a painful type of skin photosensitivity called erythropoietic protoporphyria (EPP), which is caused by the excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial results have been reported regarding hematologic status and iron status of patients with EPP. We thoroughly explored these parameters in Fechm1Pas mutant mice of 3 different genetic backgrounds. FECH deficiency induced microcytic hypochromic anemia without ringed sideroblasts, little or no hemolysis, and no erythroid hyperplasia. Serum iron, ferritin, hepcidin mRNA, and Dcytb levels were normal. The homozygous Fechm1Pas mutant involved no tissue iron deficiency but showed a clear-cut redistribution of iron stores from peripheral tissues to the spleen, with a concomitant 2- to 3-fold increase in transferrin expression at the mRNA and the protein levels. Erythrocyte PPIX levels strongly correlated with serum transferrin levels. At all stages of differentiation in our study, transferrin receptor expression in bone marrow erythroid cells in Fech(m1Pas) was normal in mutant mice but not in patients with iron-deficiency anemia. Based on these observations, we suggest that oral iron therapy is not the therapy of choice for patients with EPP and that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen, and the bone marrow.

Anemia, Hypochromic↗
PubMed2006

Immunohistochemical expression of prion protein (PrPC) in the human forebrain during development.

The cellular prion protein (PrPC) is a ubiquitous protein whose expression in the adult brain occurs mainly in synapses. We used monoclonal antibodies to study fetal and perinatal PrPC expression in the human forebrain. Double immunofluorescence and confocal microscopy with GFAP, Iba1, MAP2, doublecortin, synaptophysin, and GAP-43 were used to localize PrPC. PrPC immunoreactivity was observed in axonal tracts and fascicles from the 11th week to the end of gestation. Synapses expressed PrPC at increasing levels throughout synaptogenesis. At midgestation, a few PrPC-labeled neurons were detected in the cortical anlage and numerous ameboid and intermediate microglial cells were PrPC-positive. In contrast, at the end of gestation, microglial PrPC expression decreased to almost nothing, whereas neuronal PrPC expression increased, most notably in ischemic areas. In adults, PrPC immunoreactivity was restricted to the synaptic neuropil of the gray matter. At all ages, choroid plexus, ependymal, and endothelial cells were labeled, whereas astrocytes were only occasionally immunoreactive. In conclusion, the early expression of PrPC in the axonal field may suggest a specific role for this molecule in axonal growth during development. Moreover, PrPC may play a role in early microglial cell development.

Adult↗
PubMed2006

Integrating anatomical pathology to the healthcare enterprise.

For medical decisions, healthcare professionals need that all required information is both correct and easily available. We address the issue of integrating anatomical pathology department to the healthcare enterprise. The pathology workflow from order to report, including specimen process and image acquisition was modeled. Corresponding integration profiles were addressed by expansion of the IHE (Integrating the Healthcare Enterprise) initiative. Implementation using respectively DICOM Structured Report (SR) and DICOM Slide-Coordinate Microscopy (SM) was tested. The two main integration profiles--pathology general workflow and pathology image workflow--rely on 13 transactions based on HL7 or DICOM standard. We propose a model of the case in anatomical pathology and of other information entities (orders, image folders and reports) and real-world objects (specimen, tissue samples, slides, etc). Cases representation in XML schemas, based on DICOM specification, allows producing DICOM image files and reports to be stored into a PACS (Picture Archiving and Communication System.

Diagnostic Imaging↗
PubMed2005

Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta: relationship between signal loss and macrophage infiltration.

OBJECTIVE: Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10-enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits. METHODS AND RESULTS: Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10-induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r=0.82; P<0.05). CONCLUSIONS: Ferumoxtran-10-enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.

Animals↗
PubMed2005

Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors.

AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.

Adult↗
PubMed2004

Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs.

Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PGE(2), and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg i.p.) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 micromol/kg i.p.). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs.

Allergens↗
PubMed2003

[Primary hepatic vipoma].

Vipoma is a rare neuroendocrine tumor most frequently localized in the pancreas. When it is extrapancreatic, it is most often neurogenic. We report a case of primary extrapancreatic vipoma that is non neurogenic localized in the right liver in a patient with severe diarrhea and hypokaliema. Computed tomography, magnetic resonance imaging, intraoperative tomography and surgical exploration did not show any other extrahepatic primary lesion. The diagnosis was performed by immunochemistry, tumorous cells were positives with anti-VIP antibody. Forty two months after right hepatectomy, the patient was asymptomatic.

Adult↗
PubMed2002

Vagal stimulation rapidly increases leptin secretion in human stomach.

BACKGROUND & AIMS: Leptin production has been reported in the rat and in human stomach. It initiates intestinal nutrient absorption. In this study, we analyzed the effect of vagal stimulation on leptin release in the human stomach. METHODS: We studied the secretion of gastric acid and leptin on stimulation with insulin (a stimulant of vagal pathways via hypoglycemia) and pentagastrin in 11 healthy men (normal endoscopy and normal histological gastric mucosa), 5 with previous highly selective vagotomy (HSV), and 6 without HSV. Fundic biopsies were performed for immunostaining of leptin. RESULTS: There was no difference between the 2 groups with respect to age, body mass index, basal leptin (4.8 +/- 1.2 ng/15 minutes) and gastric acid (0.7 +/- 0.2 mmol/15 minutes) outputs. Leptin-immunoreactivity was found in the fundic glands, and its distribution and density were similar in 2 groups. Insulin caused a rapid (15-minute) increase in leptin output in men without HSV (31 +/- 9 ng/15 minutes), but not in those with HSV (7.7 +/- 3.2 ng/15 minutes). Insulin-stimulated gastric leptin was biphasic, with a rapid increase (15 minutes after injection) followed by a second steady and sustained increase (39.9 +/- 7.6 ng/15 minutes at 120 minutes after injection). Pentagastrin increased gastric leptin output in individuals with (30 +/- 4.9 ng/15 minutes) and without (26 +/- 3.2 ng/15 minutes) HSV. Insulin and pentagastrin did not modify plasma leptin, whatever HSV status. CONCLUSIONS: Vagal stimulation of leptin release in the human stomach suggests that leptin is released during the cephalic phase of gastric secretion. Luminal leptin may be involved in vagus-mediated intestinal functions.

Adult↗
PubMed2002

Effect of anal epidermoid cancer-related viruses on the dendritic (Langerhans') cells of the human anal mucosa.

PURPOSE: The incidence of anal cancer is high in patients with anal condyloma. HIV increases this risk. We analyzed anal mucosa from normal individuals and individuals with condyloma. EXPERIMENTAL DESIGN: Normal anal mucosa from 155 consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with anal condyloma was compared with that obtained from 30 HIV-negative patients after hemorrhoid surgery (controls). Langerhans' cells (LCs), T lymphocytes, and viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus (HPV) types] in anal mucosa and HIV load and CD4 T-lymphocyte counts in the serum were characterized. RESULTS: None of the control individuals had anal squamous intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients with anal condyloma (P = 0.07). The number of LCs/mm in anal tissue was significantly higher in HIV-negative patients with condylomata (median, 30; range, 2-130) than in HIV-positive patients (median, 15; range, 0-100) or in controls (median, 17; range, 4-35). In HIV-negative individuals, the occurrence of condylomata was linked with a higher number of LCs. Significant differences were observed between HIV-positive and HIV-negative patients with anal condylomata:number of LCs/mm anal tissue, oncogenic HPV (26% versus 8%), other current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate regression analysis found HIV as the only risk factor for a decrease in the number of LCs (odds ratio, 6; 95% confidence interval, 2.28-16.1; P < 0.001) and the serum HIV load (odds ratio, 4.9; 95% confidence interval, 1.1-21.4 log/ml; P < 0.03) but not the serum CD4 T-lymphocyte rate as a predictive risk factor for having <17 LCs/mm tissue. CONCLUSION: HPV increases the number of LCs in anal mucosa in HIV-negative individuals. HIV alters anal dendritic cells, likely leading to an increase in anal cancer risk.

Adolescent↗
PubMed2002

IGF-I: from diagnostic to triple-helix gene therapy of solid tumors.

Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.

Apoptosis↗