RESUMEN

INTRODUCTION: The Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) requiring a rapid diagnosis due to its poor prognosis. CASE REPORT: We report the first case of an eighty-nine-year-old woman who presented with concomitant Sezary syndrome and anasarca, revealing a nephrotic syndrome caused by a minimal change nephropathy associated with immunoglobulin A (IgA) deposits. Scarce literature described rare cases associating these two entities (nephrotic syndrome and nephropathy). However, the nephrotic syndrome was delayed from disease onset, secondary to immunosuppressive treatment of SS, or due to the weaning of SS therapy. Thus, the direct link between the glomerular lesion and the cutaneous lymphoma was difficult to establish. However, the synchronous occurrence of both SS and glomerulopathy in our patient, along with Sezary cells in both urines (urinary cytology) and biopsy, and resolution of nephropathy after treatment of SS, support the likely attributability of SS in glomerulopathy. CONCLUSION: Practitioners must acknowledge the possible occurrence of glomerular involvement in SS.

Asunto(s)

Glomerulonefritis por IGA , Nefrosis Lipoidea , Síndrome Nefrótico , Síndrome de Sézary , Neoplasias Cutáneas , Anciano de 80 o más Años , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Humanos , Inmunoglobulina A , Nefrosis Lipoidea/complicaciones , Nefrosis Lipoidea/diagnóstico , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico , Síndrome de Sézary/complicaciones , Síndrome de Sézary/diagnóstico , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico

RESUMEN

We report a case of spinal cord toxoplasmosis occurring as a primary infection in a 31-year-old immunocompetent man. Exhaustive immunologic and genetic investigations did not identify any immunodeficiency. The causative agent was a typical type 2 strain. In cases of spinal cord lesions, toxoplasmosis should be considered, even in an immunocompetent patient.

Asunto(s)

Carne/parasitología , Repeticiones de Microsatélite/genética , Toxoplasma/genética , Toxoplasmosis Cerebral/diagnóstico , Adulto , Animales , Genotipo , Humanos , Masculino , Sus scrofa/parasitología , Toxoplasma/clasificación , Toxoplasmosis Cerebral/parasitología

RESUMEN

Immune thrombocytopenic purpura (ITP) is a disease characterized by antibody-mediated platelet destruction. The T- and B-cell subsets have been extensively studied in primary ITP, but the NK cell compartment has been less thoroughly explored. We investigated the NK cell receptor repertoire and the functionality of NK cells in the peripheral blood and spleen in patients with primary ITP. An immunophenotypic analysis of peripheral blood lymphocytes from patients revealed that the numbers of CD19+ B lymphocytes, CD4+ and CD8+ T lymphocytes and CD3-CD56+ NK cells were within the normal range. No major alteration to the expression of distinct inhibitory or activating NK cell receptors was observed. The functionality of NK cells, as evaluated by their ability to degranulate in conditions of natural cytotoxicity or antibody-dependent cell cytotoxicity (ADCC), was preserved in these patients. By contrast, these stimuli induced lower levels of IFNγ production by the NK cells of ITP patients than by those of healthy controls. We then compared the splenic NK cell functions of ITP patients with those of cadaveric heart-beating donors (CHBD) as controls. The splenic NK cells of ITP patients tended to be less efficient in natural cytotoxicity conditions and more efficient in ADCC conditions than control splenic NK cells. Finally, we found that infusions of intravenous immunoglobulin led to the inhibition of NK cell activation through the modulation of the interface between target cells and NK cells.

Asunto(s)

Células Asesinas Naturales/inmunología , Púrpura Trombocitopénica Idiopática/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Células Cultivadas , Femenino , Humanos , Inmunoglobulinas Intravenosas/farmacología , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Interferón gamma/sangre , Interferón gamma/inmunología , Células K562 , Células Asesinas Naturales/efectos de los fármacos , Leucocitos Mononucleares , Masculino , Ratones , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Bazo/citología , Bazo/inmunología , Adulto Joven

RESUMEN

CONTEXT: Marseille, the second largest city in France, has a large population of homeless persons. A mental health outreach team was created in 2005 as a response to high rates of mental illness among this group. In a national political context where security is a government priority, a new central police station was created in Marseille in 2006 to address robberies, violence and illegal traffic in the downtown area of the city. While not directly related to such crimes, police also are responsible for public safety or behavioral issues related to the presence of individuals who are homeless in this area. OBJECTIVE: This report on a two-year pilot study (2009-2011) addresses collaborative work between a mental health outreach team and the police department responding to the clinical needs of persons who are homeless with serious psychiatric disorders. It also describes the homeless persons' interactions with, and perceptions of the presence of, police and mental health professionals on the streets. METHODS: Investigators adopted a mixed-methods approach. Data were collected on 40 interactions using brief standardized report for each interaction. Focus groups were conducted with police officers, outreach team members, peer workers, and service users. Minutes of partnership meetings between police officers and outreach workers also served as a source of qualitative data. RESULTS: Outreach workers initiated just over half (n=21) of the encounters (n=40) between police and outreach workers. Interactions mainly involved persons with psychosis (77%), the vast majority (80%) of which involved persons in an acute phase of psychosis. Two key themes that emerged from data analysis included the violent nature of life on the streets and the high percentage of ethnic minorities among subjects of the interactions. In addition, it was found that the practices of the outreach workers are sometimes similar to those of the police, especially when outreach workers use coercive methods. "Users" (homeless persons) described police as sometimes using less coercion than the outreach team, and noted that they were more fearful of psychiatrists than police. CONCLUSION: Formal initiatives between mental health outreach teams and police departments involve some common street practices. This study demonstrates the potential for closer working relationships between the two parties to help persons who are homeless with mental illnesses receive needed care, and to reduce inappropriate coercion including involuntary hospitalization and arrests.

Asunto(s)

Intervención en la Crisis (Psiquiatría)/métodos , Personas con Mala Vivienda/psicología , Enfermos Mentales , Grupo de Atención al Paciente/organización & administración , Adulto , Coerción , Femenino , Grupos Focales , Francia , Humanos , Masculino , Proyectos Piloto , Población Urbana

RESUMEN

To investigate whether tumour necrosis factor alpha (TNFalpha) plays a role in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinaemia (HCV-MC), we measured soluble TNFalpha and its soluble p55 (sTNFR1) and p75 (sTNFR2) receptors in the serum of patients with HCV-MC. TNFalpha, sTNFR1 and sTNFR2 were measured in the serum of 32 patients with HCV-MC, 18 patients with hepatitis C without MC (HCV) and 18 healthy volunteers, using specific immunoassays. Correlations between clinical and biological parameters and the concentrations of TNFalpha and sTNFRs were established by studying detailed clinical records of the 32 HCV-MC patients. Although higher, TNFalpha levels were not significantly different in HCV-MC patients compared with healthy or HCV controls. sTNFR1 and sTNFR2, however, were significantly higher in HCV-MC compared with controls or with HCV patients, and higher concentrations of sTNFR1 and sTNFR2 were observed in patients with severe visceral vasculitis, compared with patients with limited purpura. sTNFR1 concentrations positively correlated with fibrinogen levels but TNFalpha, sTNFR1 and sTNFR2 did not correlate with other biological parameters such as rheumatoid factor concentrations, CH50 or C4 values. These data suggest a role for TNFalpha in the pathogenesis of the immune complex-mediated vasculitis associated with HCV-MC.

Asunto(s)

Antígenos CD/inmunología , Crioglobulinemia/inmunología , Hepatitis C/inmunología , Receptores del Factor de Necrosis Tumoral/inmunología , Anciano , Anciano de 80 o más Años , Complejo Antígeno-Anticuerpo , Antígenos CD/sangre , Crioglobulinemia/sangre , Crioglobulinemia/etiología , Femenino , Hepatitis C/sangre , Hepatitis C/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Vasculitis Leucocitoclástica Cutánea/etiología , Vasculitis Leucocitoclástica Cutánea/inmunología

RESUMEN

Thrombin is a procoagulant and proinflammatory molecule in vivo. In vitro, thrombin has been shown to induce endothelial activation, notably IL-8 secretion and adhesion molecule expression. In this study, we showed that thrombin may induce a new cascade leading from acute to chronic inflammation. Thrombin was able to induce the production of both IL-6 and monocyte chemotactic protein-1 (MCP-1) by HUVEC independently of IL-1alphabeta and TNF-alpha. Addition of physiological concentrations of exogenous soluble IL-6Ralpha (sIL-6Ralpha) to thrombin-activated HUVEC was sufficient to increase the amounts of MCP-1 produced, but not those of IL-8. These effects could be blocked by anti-IL-6 or anti-sIL-6Ralpha blocking mAb, demonstrating the existence of an autocrine loop of MCP-1 secretion, involving the IL-6/IL-6Ralpha/gp130 complex on HUVEC. In addition, we identified IL-8-activated neutrophils as a potential source of sIL-6Ralpha because IL-8 induced IL-6Ralpha shedding from the neutrophil membranes and increased in parallel sIL-6Ralpha concentrations in neutrophil supernatants. Furthermore, addition of neutrophils to thrombin-activated HUVEC significantly increased MCP-1 secretion, which could be decreased by blocking IL-6. Thus, thrombin-activated endothelium may induce a cascade of events characterized by IL-8 secretion, neutrophil local infiltration, and the release of IL-6Ralpha from neutrophil membranes. sIL-6Ralpha may then complex with IL-6 and increase the amount of MCP-1 produced by thrombin-activated endothelium, favoring monocyte infiltration, and the transformation of acute into chronic inflammation.

Asunto(s)

Comunicación Autocrina/fisiología , Quimiocina CCL2/metabolismo , Quimiocinas CXC , Quimiotaxis de Leucocito/fisiología , Endotelio Vascular/efectos de los fármacos , Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Interleucina-6/metabolismo , Neutrófilos/efectos de los fármacos , Receptores de Interleucina-6/fisiología , Trombina/farmacología , Enfermedad Aguda , Animales , Coagulación Sanguínea/fisiología , Células Cultivadas , Quimiocina CXCL1 , Factores Quimiotácticos/farmacología , Enfermedad Crónica , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Sustancias de Crecimiento/farmacología , Humanos , Interleucina-1/farmacología , Interleucina-8/metabolismo , Interleucina-8/farmacología , Sustancias Macromoleculares , Ratones , Modelos Animales , Neutrófilos/metabolismo , Receptores de Interleucina-6/genética , Proteínas Recombinantes de Fusión/farmacología , Transducción de Señal/efectos de los fármacos , Solubilidad , Trombina/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Venas Umbilicales

RESUMEN

Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its substrate, ATF-2, was observed in human umbilical vein endothelial cells (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation. Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) protein production and messenger RNA steady-state levels. In addition, SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1 agonist peptide (TRAP), suggesting functional links between the thrombin G protein-coupled receptor and the p38 MAPK pathway. Furthermore, endothelial activation in the presence of SB203580 decreased the chemotactic activity of thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or TRAP-induced endothelial chemokine production, because there was no reduction in the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate that the p38 rather than p42/44 MAPK signaling pathway plays an important role in thrombin-induced endothelial proinflammatory activation and suggest that inhibition of p38 MAPK may be an interesting target for anti-inflammatory strategies in vascular diseases combining thrombosis and inflammation. (Blood. 2001;98:667-673)

Asunto(s)

Quimiocinas/biosíntesis , Quimiotaxis de Leucocito/efectos de los fármacos , Endotelio Vascular/metabolismo , Proteínas Quinasas Activadas por Mitógenos/fisiología , Transducción de Señal/efectos de los fármacos , Trombina/farmacología , Células Cultivadas , Quimiocina CCL2/biosíntesis , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Humanos , Inflamación/metabolismo , Interleucina-8/biosíntesis , Cinética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Venas Umbilicales/citología , Proteínas Quinasas p38 Activadas por Mitógenos

RESUMEN

Endothelial cells play a key role in prominent immunological and pathological processes such as leukocyte trafficking, inflammation, atheroma or cancer cell metastasis. Umbilical veins are probably the most widely used source for human endothelial cells, since they are more easily available than many other vessels, they are free from any pathological process and they are physiologically more relevant than many established cell lines. Here, we describe a standard protocol for preparation, maintenance and quality control of these cells.

Asunto(s)

Técnicas de Cultivo de Célula/métodos , Endotelio Vascular/citología , Cordón Umbilical/citología , Células Cultivadas , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Celular Vascular/biosíntesis

RESUMEN

In human cultured monocytic cells stimulated by cytokines, CD43 was demonstrated to exhibit a modification of sialylated epitopes (dys-sialylation) [Soler et al: Leukoc Biol 1997;61:609-618]. Therefore, we chose to investigate CD43 behavior on patients who present pathological status implicating monocytes after renal graft (KTR). We performed flow cytometry after immune staining using monoclonal antibodies to CD43 sialic acid-dependent (L60) and -independent (L10) epitopes. Compared to normal controls, mean fluorescence intensity was never altered on lymphocytes. Conversely, on monocytes, we found different profiles with L60: 26% of patients having normal CD43 expression, 54% displayed decreased values and 20% had a double population of monocytes, the major one being normal and the minor one with a very low staining. Decreased values were more frequent among KTR during the first 3 months following transplantation. L10 immunostaining was not altered on monocytes in patients with low values of CD43 staining by L60, confirming that the mechanism involved was a CD43 dys-sialylation. We investigated a possible role of cyclosporin (CsA) on human monocytic (THP-1) and lymphoid (Jurkat) cell lines. CsA decreases CD43 expression in monocytic and not in lymphoid cell lines and could be responsible for the specific dys-sialylation of KTR monocytes. Whatever, CD43 dys-sialylation might lead to functional abnormalities of monocytes in KTR, possibly involving the adhesion process.

Asunto(s)

Antígenos CD , Trasplante de Riñón/inmunología , Linfocitos/metabolismo , Monocitos/metabolismo , Sialoglicoproteínas/biosíntesis , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales , Células Cultivadas , Ciclosporina/farmacología , Epítopos/metabolismo , Femenino , Humanos , Inmunosupresores/farmacología , Células Jurkat , Leucosialina , Linfocitos/citología , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Monocitos/citología , Monocitos/efectos de los fármacos , Ácido N-Acetilneuramínico/metabolismo , Sialoglicoproteínas/análisis , Sialoglicoproteínas/inmunología

RESUMEN

The beneficial metabolic effects of dietary soybean lecithin on lipid metabolism are now more clearly established. The intestinal absorption of cholesterol is decreased by soybean phosphatidylcholine-enriched diet and results in a cholesterol-lowering effect. There is an enhancement of the cholesterol efflux by endothelial cells incubated with soybean phosphatidylcholines, and a stimulation of the reverse cholesterol transport by high density lipoprotein-phosphatidylcholines. As a result of all these processes, phosphatidylcholines provided by the soybean lecithin metabolism appear to be key molecules controlling the biodynamic exchanges of lipids. They regulate homeostasis of cholesterol and fatty acids by decreasing their synthesis and promoting cholesterol oxidation into bile salts. Finally, the outcome is the increase in bile secretion of these lipids and/or their metabolite forms. Such findings constitute promising goals in the field of nutritional effects of soybean lecithin in the treatment or prevention of hyperlipidemia and related atherosclerosis.

RESUMEN

We report the outcome of 12 children who underwent unrelated cord blood transplant (U-CBT) in a single institution between February 1997 and July 1998. The 1 year event-free survival was 67% (95% CI of 26%). Four children died with infectious complication as cause of death in three cases. Immune reconstitution was studied during first year post transplant by assaying total lymphocyte counts, B cells, NK cells and T cell subsets in the eight disease-free surviving patients. We observed a prompt recovery of CD19+ cell number which was greater than 500/microl at 9 months for all patients except the one with severe cGVHD. B cells constituted the predominant lymphocyte subset at 6 and 9 months post transplant with normal or elevated B cell numbers according to normal paediatric range. We noted normal serum immunoglobulin levels at 6 months post transplant for IgA and IgM and at 9 months for IgG. The CD3+ cell count and particularly the CD3+CD8+ T cell subset remained depressed until 12 months post transplant. Six months after unrelated CBT, seven out of eight patients had less than 100 CD3+CD8+ cells/microl. CD3+CD4+ cell recovery was less impaired with all children achieving an absolute count of CD3+CD4+ cells greater than 200/microl during the first year in a median of 5 months. The percentage of NK cells was elevated during the first 6 months after CBT but their absolute count remained within the normal range. Bone Marrow Transplantation (2000) 25, 53-57.

Asunto(s)

Sangre Fetal , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunidad , Adolescente , Niño , Preescolar , Trasplante de Tejido Fetal , Prueba de Histocompatibilidad , Humanos , Lactante , Trasplante Homólogo

RESUMEN

OBJECTIVE: Recent studies have shown that in vitro endothelial cells are activated by antiphospholipid antibodies and may support leukocyte adhesion. We studied levels of soluble intercellular adhesion molecule 1 (sICAM-1, sCD54), soluble vascular cell adhesion molecule 1 (sVCAM-1, sCD106), and soluble E-selectin (soluble endothelial leukocyte adhesion molecule 1 [sELAM-1, sCD62E]) in sera from patients with primary antiphospholipid syndrome (primary APS), and compared them with those from patients with systemic lupus erythematosus-associated APS (SLE-APS) or pure SLE, as well as with those from 2 control groups composed of healthy volunteers and patients with thrombosis unrelated to autoimmune diseases. METHODS: Serum samples from 24 patients with primary APS, 15 patients with SLE-APS, 22 patients with pure SLE, 48 control patients with thrombosis, and 18 healthy volunteers were examined using enzyme-linked immunosorbent assays specific for sICAM-1, sVCAM-1, and sELAM-1. RESULTS: Serum levels of sVCAM-1, but not sICAM-1 or sELAM-1, were significantly increased in all patient study groups compared with thrombosis control patients and healthy volunteers, but did not differ between the groups of patients with primary APS, SLE-APS, or pure SLE. Concentrations of sVCAM-1 were significantly higher in primary APS or SLE-APS patients with severe, recurrent thrombosis and were negatively correlated with platelet counts in primary APS patients. In patients with primary APS, sVCAM-1 levels were higher if there was thrombotic kidney involvement and correlated with creatinemia. CONCLUSION: Serum sVCAM-1 concentrations are increased in patients with primary APS, especially those with repeated thrombotic events or kidney involvement. These findings suggest that endothelial/ monocyte interaction may be important in the pathogenesis of primary APS.

Asunto(s)

Molécula 1 de Adhesión Intercelular/sangre , Lupus Eritematoso Sistémico/sangre , Trombosis/sangre , Adulto , Anciano , Encefalopatías/sangre , Encefalopatías/etiología , Creatina/sangre , Selectina E/sangre , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/etiología , Circulación Renal , Estudios Retrospectivos , Solubilidad , Trombosis/etiología , Molécula 1 de Adhesión Celular Vascular/sangre

RESUMEN

Thrombin, a central molecule in coagulation, is also involved in inflammation. Notably, thrombin induces endothelial neutrophil adhesion, P- and E-selectin expression, and chemokine production. We show here that thrombin induces expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) on human umbilical vein endothelial cells (HUVECs) associated with increased adhesion of monocytes. Thrombin increased mRNA steady-state levels and expression of ICAM-1 over 24 hours. Thrombin-induced VCAM-1 expression exhibited unusual kinetics, reaching maximum levels after 6 to 12 hours, but decreasing to near baseline after 24 hours. Thrombin activity on HUVECs was mediated through interaction with its specific receptor, because ICAM-1 and VCAM-1 expression were similarly induced by the 14-amino acid thrombin receptor-activating peptide. Thrombin-induced ICAM-1 and VCAM-1 expression was significantly inhibited by hirudin, but not by interleukin-1 receptor antagonist or anti-tumor necrosis factor alpha monoclonal antibody (MoAb). Thrombin-activated HUVECs significantly increased greater numbers of adhering THP-1 macrophagic cells, peripheral blood mononuclear cells, or purified monocytes than unstimulated HUVECs. This adhesion was inhibited by anti-CD18 and anti-CD49d MoAb, demonstrating that thrombin-induced ICAM-1 and VCAM-1 were functional. These results show that, in addition to selectins, thrombin directly induces a cytokine-independent expression of adhesion molecules of the Ig superfamily on HUVECs that may support firm leukocyte attachment during inflammation.

Asunto(s)

Endotelio Vascular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/fisiología , Leucocitos Mononucleares/citología , Monocitos/citología , Trombina/farmacología , Molécula 1 de Adhesión Celular Vascular/fisiología , Anticuerpos Monoclonales/farmacología , Adhesión Celular , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Hirudinas/farmacología , Humanos , Molécula 1 de Adhesión Intercelular/genética , Proteína Antagonista del Receptor de Interleucina 1 , Fragmentos de Péptidos/farmacología , ARN Mensajero/biosíntesis , Receptores de Trombina/efectos de los fármacos , Receptores de Trombina/fisiología , Sialoglicoproteínas/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Venas Umbilicales , Molécula 1 de Adhesión Celular Vascular/genética

RESUMEN

We have previously described an inverse relationship between Cdx1 and Cdx2 mRNA levels and the extent of dysplasia and severity of clinical outcome in colorectal carcinoma, suggesting that altered expression of these genes was associated with colorectal carcinogenesis or tumor progression. To investigate further their involvement in the physiopathology of colorectal cancer, HT29 colon carcinoma cells that show very low Cdx expression were transfected with Cdx1 and/or Cdx2 cDNA to elicit their overexpression. Growth rate, tumorigenicity, resistance to apoptosis, and migration potential of the corresponding cells were analyzed. Growth rate of cells overexpressing Cdx2 decreased by half, whereas overexpression of Cdx1 had no effect. However, cells overexpressing both Cdxs had a growth rate reduced to 20% of control. In cells overexpressing Cdx1 or Cdx2, tumorigenicity and resistance to apoptosis induced by serum starvation, ceramide, or staurosporine were not changed compared with control cells; yet phorbol ester-stimulated cell migration was decreased by 50%. In cells overexpressing both Cdx1 and Cdx2, tumorigenicity was decreased by 50%, resistance to apoptosis was significantly lowered, and stimulated cell migration was further decreased to 15% of control compared with cells expressing Cdx1 or Cdx2. Finally, cells overexpressing both Cdxs showed strongly decreased Bcl-2 expression, which could account for their increased sensitivity to apoptosis. These findings show that, in HT29 cells, both Cdx1 and Cdx2 genes must be expressed to reduce tumorigenic potential, to increase sensitivity to apoptosis, and to reduce cell migration, suggesting that the two genes control the normal phenotype by independent pathways. This may explain why loss of Cdx1 or Cdx2 expression is associated with tumor development and invasiveness in colorectal tumors.

Asunto(s)

Proteínas Aviares , Neoplasias del Colon/genética , Genes Homeobox , Proteínas de Homeodominio/genética , Apoptosis/efectos de los fármacos , Secuencia de Bases , Factor de Transcripción CDX2 , División Celular , Movimiento Celular/efectos de los fármacos , Ceramidas/farmacología , Neoplasias del Colon/patología , Medio de Cultivo Libre de Suero , Cartilla de ADN , Regulación hacia Abajo , Genes bcl-2 , Células HT29 , Humanos , Estaurosporina/farmacología , Acetato de Tetradecanoilforbol/farmacología , Transactivadores , Transfección

RESUMEN

Lymphocyte adhesion to endothelium, extravasation, and adhesion to hepatocytes are mediated by adhesion molecules and constitute important steps in the liver inflammation due to chronic hepatitis C (HCV-CH). We measured soluble intercellular adhesion molecule (sICAM-1, sCD54), vascular cell adhesion molecule (sVCAM-1, sCD106), E-selectin (sCD62E), as well as interleukin (IL)-1 beta, IL-8, and tumor necrosis factor-alpha (TNF-alpha) concentrations in the serum of 22 patients with HCV-CH in comparison to 20 seronegative healthy volunteers. sICAM-1, sVCAM-1, sCD62E, TNF-alpha, and IL-8 but not IL-1 beta concentrations were significantly elevated in patients. sICAM-1 and sCD62E correlated with TNF-alpha and aspartate amino transferases levels. sICAM-1 correlated with liver lobular inflammation whereas sVCAM-1, sCD62E, and IL-8 correlated with liver fibrosis. Measurement of soluble adhesion molecules may be an easy way to follow liver inflammation and fibrosis during HCV-CH.

Asunto(s)

Citocinas/sangre , Selectina E/sangre , Hepatitis C Crónica/sangre , Molécula 1 de Adhesión Intercelular/sangre , Cirrosis Hepática/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Humanos , Interleucina-1/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/análisis

RESUMEN

In addition to its role in coagulation, thrombin is involved in the inflammatory process by inducing vessel neutrophilic infiltration. Thrombin induces endothelial P-selectin expression and platelet activating factor release, which participate to induce early neutrophil adhesion and activation. We employed HUVEC and now show that thrombin induces the production of the chemokine IL-8 in a time- and dose-dependent fashion. Similarly, thrombin induced E-selectin expression on HUVEC. Both IL-8 secretion and E-selectin expression were preceded by an increase in steady state levels of the respective mRNAs. Thrombin action on HUVEC was inhibited by the specific thrombin inhibitor, hirudin. In addition, these effects of thrombin on HUVEC were mimicked by the 14-amino acid thrombin receptor agonist peptide, which triggers the native thrombin receptor in a similar fashion to thrombin itself. Although IL-1 and TNF-alpha also induce IL-8 and E-selectin, the thrombin effects in these experiments were not mediated by those cytokines, since neither IL-1 receptor antagonist nor anti-TNF-alpha Ab inhibited the effects of thrombin. Furthermore, IL-1alpha, IL-1beta, and TNF-alpha were not detected in the supernatants of thrombin-activated HUVEC. Although intracellular IL-1alpha was found in thrombin-activated HUVEC, antisense IL-1alpha had no inhibitory effect on IL-8 secretion. These results demonstrate that in addition to short term endothelial activation, thrombin also functions as a long acting proinflammatory agent by inducing endothelial synthesis of the mediators required for neutrophils activation and extravazation during inflammation.

Asunto(s)

Selectina E/biosíntesis , Endotelio Vascular/efectos de los fármacos , Interleucina-8/metabolismo , Trombina/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/inmunología , Humanos , Inflamación/inmunología , Inflamación/patología , Interleucina-1/inmunología , Factor de Necrosis Tumoral alfa/inmunología

RESUMEN

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Asunto(s)

Adipocitos/patología , Tejido Adiposo/patología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/efectos adversos , Factor de Necrosis Tumoral alfa/fisiología , Adipocitos/efectos de los fármacos , Adipocitos/fisiología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/fisiopatología , Adulto , Atrofia , Diferenciación Celular , Citocinas/biosíntesis , Femenino , Humanos , Interleucina-6/biosíntesis , Activación de Linfocitos , Linfocitos/inmunología , Valores de Referencia , Factor de Necrosis Tumoral alfa/biosíntesis

RESUMEN

INTRODUCTION: Capillary leak syndrome is a specific entity among syndromes with capillary hyperpermeability. Endothelial cell activation is related to the higt level of adhesion molecules (sICAM-1, sVCAM-&, sCD62E) possibly due to several cytokines (IL-2, TNF ...). CASE REPORT: An 84-year-old woman was hospitalized for erythroderma. Ofujui papuloerythroderma was diagnosed and edema was attributed to capillary leak. A kinetic study of several cytokines and adhesion molecules sCD62E, sVCAM-1 and sICAM-1 was done. Outcome was favorable with corticopuvatherapy. DISCUSSION: The capillary leak syndrome reported here is simlar to that described in other erythrodermas with or without lymphoma. The keratinocyte would be activated by the CD4 T lymphocyte via the gamma-interferon mediator. The T cell secretes cytokines (interleukin-1, tumor necrosis factor ...) which activates the endothelium and increases vascular permeability. The level of adhesion molecules and changes observed during the episode of edema demonstrated the endothelial activation.

Asunto(s)

Síndrome de Fuga Capilar/etiología , Dermatitis Exfoliativa/complicaciones , Anciano , Anciano de 80 o más Años , Síndrome de Fuga Capilar/fisiopatología , Moléculas de Adhesión Celular/análisis , Citocinas/análisis , Dermatitis Exfoliativa/diagnóstico , Endotelio/metabolismo , Femenino , Humanos , Inmunohistoquímica

RESUMEN

Mediterranean spotted fever due to infection by Rickettsia conorii, is characterized by a general vasculitis. This vasculitis is thought to be due to a direct injury to endothelial cells induced by R. conorii. However, production and activity of cytokines on endothelial cells is an important pathway in inflammation, and part of the underlying mechanism of vasculitis. In the present studies, human umbilical vein endothelial cells (HUVEC) infected with R. conorii actively secrete high levels of IL-8 and IL-6 (P < 0.002, and P < 0.03, respectively, compared with uninfected cells). IL-1alpha, IL-1beta, or TNFalpha were not detected in the culture supernates. Nevertheless, IL-6 and IL-8 production was due, in a large part, to a cell-associated form of IL-1 alpha expressed on R. conorii-infected HUVEC, since production of these cytokines was suppressed by 80% (P = 0.0001) and 85% (P < 0.04) by the addition of IL-1 receptor antagonist, or anti-IL-1alpha antibodies (60% inhibition, P < 0.01 and 65% inhibition, P < 0.05, respectively) and IL-1alpha was measured after lysis of R. conorii-infected HUVEC but not in uninfected cells (P < 0.01). Rickettsial lipopolysaccharide does not seem to be involved, since polymyxin B did not reduce cytokine secretion. On the contrary, infection by intracellular R. conorii appears to be necessary to induce IL-1alpha and subsequently IL-8, since formalin-fixed R. conorii did not induce cytokine production. These observations demonstrate that R. conorii-infected HUVEC secrete IL-6 and IL-8 via the induction of cell-associated IL-1alpha, providing a possible mechanism for the vasculitis observed in Mediterranean spotted fever.

Asunto(s)

Endotelio Vascular/inmunología , Interleucina-1/fisiología , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Rickettsia/inmunología , Anticuerpos/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Interleucina-1/inmunología , Interleucina-1/farmacología , Cinética , Factores de Tiempo , Venas Umbilicales

RESUMEN

Leishmania is considered an opportunistic agent during cellular immunodeficiency. The authors report the case of a patient living in the south of France presenting visceral leishmaniasis with cutaneous manifestations in the course of a severe nervous depression. This case report illustrates the possible relationships between stress and immunity.

Asunto(s)

Trastorno Depresivo/complicaciones , Leishmaniasis Cutánea/etiología , Leishmaniasis Visceral/etiología , Adulto , Trastorno Depresivo/inmunología , Femenino , Humanos , Interferón gamma/deficiencia , Leishmaniasis Cutánea/inmunología , Leishmaniasis Visceral/inmunología