RESUMEN
Eosinophilic pleural effusion (EPE) is defined as pleural eosinophilia greater than 10%. EPE can be seen in almost all conditions that can cause pleural effusion, but some aetiologies have to be investigated due to their frequency or potential severity. The most common aetiology of EPE is the presence of air or blood in the pleural cavity. Other frequent aetiologies include bacterial pneumonia, tuberculosis, parasitic disease and certain drugs. Although often considered to be a sign of a benign condition, pleural eosinophilia may be associated with malignancies. EPE may also indicate the presence of Churg and Strauss syndrome. We report the case of a 27-year-old man, in whom the exploration of EPE led to the diagnosis of Churg and Strauss syndrome with the association of asthma, blood and alveolar eosinophilia, myopericarditis and positive antineutrophil cytoplasmic antibodies (ANCA). This case report enables us to discuss the different causes of EPE and to illustrate how it may be a manifestation of Churg and Strauss syndrome.
Asunto(s)
Síndrome de Churg-Strauss/diagnóstico , Eosinofilia/etiología , Derrame Pleural/etiología , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Anticuerpos Anticitoplasma de Neutrófilos , Asma/diagnóstico , Asma/tratamiento farmacológico , Lavado Broncoalveolar , Broncodilatadores/uso terapéutico , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/inmunología , Eosinofilia/diagnóstico , Humanos , Masculino , Derrame Pleural/diagnóstico , Derrame Pleural/diagnóstico por imagen , Radiografía Torácica , Pruebas de Función Respiratoria , Terapia Respiratoria , Tomografía Computarizada por Rayos XRESUMEN
The emergence of ABL point mutations is the most frequent cause for imatinib resistance in chronic myelogenous leukemia (CML) patients and can occur during any phase of the disease; however, their clinical impact remains controversial. In this study, we retrospectively analyzed the predictive impact of 94 BCR-ABL kinase domain mutations (18 T315I, 26 P-loop, 50 in other sites) found in 89 imatinib-resistant CML patients. At imatinib onset, 64% of patients (57/89) were in chronic phase (CP), 24% (21/89) in accelerated phase (AP) and 12% (11/89) in blastic phase (BP). T315I and P-loop mutations were preferentially discovered in accelerated phase of BP CML, and other types of mutations in CP (P=0.003). With a median follow-up of 39.2 months (6.3-67.2), since imatinib initiation, overall survival (OS) was significantly worse for P-loop (28.3 months) and for T315I (12.6 months), and not reached for other mutations (P=0.0004). For CP only, multivariate analysis demonstrated a worse OS for P-loop mutations (P=0.014), and a worse progression-free survival (PFS) for T315I mutations (P=0.014). Therefore, P-loop and T315I mutations selectively impair the outcome of imatinib-resistant CML patients, in contrast to other mutations, which may benefit from dose escalation of imatinib, able to improve or stabilize disease response.
Asunto(s)
Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Mutación Puntual , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Benzamidas , Análisis Mutacional de ADN , Relación Dosis-Respuesta a Droga , Femenino , Francia , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Infection with human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma (KS)-associated herpesvirus, is associated with all forms of KS, with primary effusion lymphoma (PEL), and with some forms of multicentric Castleman's disease (MCD), but the pathogenic role of HHV8 in these tumors and the clonal nature of KS are still unclear. The purpose of this study was to examine whether the number of terminal repeats (TRs) contained in the fused TR region of HHV8 could be used as a marker of clonality in HHV8-associated tumors. METHODS: Pulsed-field gel electrophoresis (PFGE) and multiple-probe Southern blot analysis of the HHV8 TR region were performed on high-molecular-weight DNA obtained from tumoral KS, PEL, and MCD lesions. RESULTS: These analysis showed that the fused TR region contains a large but variable number of TR units (ranging from 16 to 75) and that the viral genome is present as extrachromosomal circular DNA in these tumors in vivo, with occasional ladders of heterogeneous linear termini reflecting lytic replication. All PEL tumors and PEL-derived cell lines as well as some KS tumors contained monoclonal or oligoclonal fused TR fragments; however, the TR region appeared polyclonal in MCD tumors and in a few KS lesions. CONCLUSION: Several KS and PEL lesions are monoclonal expansions of a single infected cell, suggesting that HHV8 infection precedes tumor growth and thus supporting an etiologic role of latent HHV8 in these proliferations. Our finding that nodular KS lesions display all possible patterns of clonality supports the model according to which KS begins as a polyclonal disease with subsequent evolution to a monoclonal process.
Asunto(s)
Enfermedad de Castleman/virología , Herpesvirus Humano 8/genética , Linfoma/virología , Sarcoma de Kaposi/virología , Secuencias Repetidas Terminales , Adulto , Anciano , Biopsia , Southern Blotting , Enfermedad de Castleman/patología , Células Clonales , ADN de Neoplasias/genética , ADN Viral/genética , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Linfoma/patología , Masculino , Persona de Mediana Edad , Derrame Pleural/patología , Derrame Pleural/virología , Sarcoma de Kaposi/patología , Células Tumorales CultivadasRESUMEN
The liver-type pyruvate kinase (L-PK) gene is controlled positively by insulin and carbohydrates, negatively by glucagon and fasting. Diet-inducible models of carcinogenesis were obtained using the L-PK gene promoter and regulatory sequences to control the expression of c-myc and SV40 T oncogenes in transgenic mice. L-PK/c-myc and L-PK/Tag animals fed a carbohydrate-rich diet developed hepatocarcinomas. In addition, L-PK/Tag animals developed diet-dependent, aggressive endocrine pancreatic tumors, preceded by islet hyperplasia involving the different analysed cell populations (alpha, beta and delta). Expression of the L-PK gene was demonstrated in pancreatic tumors, in rat isolated islets and in rat insulinoma-derived cells (RIN line), revealing a new tissue specificity of the L-PK gene. Our results suggest that this gene may be expressed in islet progenitor cells from which the different mature endocrine cells derive.
Asunto(s)
Carbohidratos de la Dieta/efectos adversos , Neoplasias Hepáticas Experimentales/etiología , Neoplasias Pancreáticas/etiología , Piruvato Quinasa/genética , Animales , Antígenos Transformadores de Poliomavirus/genética , Secuencia de Bases , Regulación Neoplásica de la Expresión Génica , Genes myc/genética , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Especificidad de Órganos , Regiones Promotoras GenéticasRESUMEN
Activation of the spi-1/PU.1 proto-oncogene and loss of p53 function are genetic alterations associated with the emergence of Friend malignant erythroleukemic cells. To address the role of p53 during erythroleukemogenesis, spi-1 transgenic mice (spi-1-Tg) which develop erythroleukemia were bred with p53-deficient mice. Three classes of spi-1 transgenic mice differing in their p53 functional status (p53(+/+), p53(+/-) and p53(-/-)) were generated. These mice developed a unique pattern of erythroleukemia. In wild-type p53 spi-1-Tg mice, none of the primary erythroleukemic spleen cells displayed autonomous growth in vitro and in vivo. In contrast, in p53(+/-) spi-1-Tg mice, erythroleukemic cells gave rise to growth factor-independent cell lines and generated tumors in vivo. Malignancy was associated with loss of the wild-type p53 allele. The p53(-/-) spi-1-Tg mice developed erythroleukemia with a total incidence and a reduced latency compared to the two other genotypes. Unexpectedly, 50% of p53(-/-) spi-1-Tg erythroleukemic spleens generated cell lines that were strictly dependent upon erythropoietin (Epo) for proliferation, whereas the remainder proliferated independently of cytokines. Moreover, only 70% of these spleen cells were tumorigenic. These findings indicate that p53 germ-line deletion did not confer malignancy to spi-1-transgenic proerythroblasts. Moreover Epo independence and tumorigenicity appear as separable phenotypic characteristics revealing that the spi-1-Tg proerythroblasts progress towards malignancy through multiple oncogenic events.
Asunto(s)
Células Precursoras Eritroides/patología , Genes p53 , Leucemia Eritroblástica Aguda/etiología , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Proteína p53 Supresora de Tumor/fisiología , Animales , Animales Recién Nacidos , Células Sanguíneas/citología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/biosíntesis , Ciclinas/genética , Progresión de la Enfermedad , Células Precursoras Eritroides/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Mutación de Línea Germinal , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patología , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , ARN Neoplásico/biosíntesis , Bazo/citología , Bazo/metabolismo , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Neoplasias/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Enfermedades del Sistema Nervioso Central/inducido químicamente , Terapia Combinada , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Podofilotoxina/administración & dosificación , Embarazo , Trasplante AutólogoRESUMEN
The expression of blood group A antigen on marrow and blood cells from A1 and A2 subjects was investigated by the binding of Helix pomatia and Dolichos biflorus lectins using immunofluorescence. These two lectins stained BFU-E-derived colonies from A subjects in the early days of culture before the expression of glycophorin. The erythroid origin of these cells was ascertained by the coexpression of two other very early erythroid markers. In bone marrow, the ultrastructural immunogold method revealed that the entire erythroid lineage including proerythroblasts was labeled by HPA, whereas no staining was observed on granulomonocytic cells including myeloblasts. Platelets from A subjects were HPA-labeled and so were platelets from an O subject preincubated in A plasma. Megakaryocytes obtained in CFU-MK-derived colonies were weakly and heterogeneously labeled by the HPA lectin. Cultures from A1 and A2 subjects were the reflection of the genetic differences only when investigations were performed on mature erythroblasts. In contrast, the great majority of immature erythroblasts both from A2 and A1 subjects were equally labeled by both lectins; during further erythroid maturation, binding of both lectins markedly diminished only on A2 erythroblasts. When marrow erythroblasts were investigated at electron microscopic level, heterogeneity of labeling among all stages of maturation was clearly observed in A2 subjects, with staining stronger on immature than on mature erythroblasts. Therefore, the genetic differences between A1 and A2 subjects are revealed during terminal erythroid differentiation.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Eritrocitos/citología , Eritropoyesis , Diferenciación Celular , Células Cultivadas , Eritroblastos/citología , Eritrocitos/inmunología , Glicoforinas/análisis , Humanos , Lectinas , Microscopía Electrónica , Factores de TiempoRESUMEN
A link between chronic hepatitis C virus (HCV) infection and low-grade B-cell lymphomas has been suggested by epidemiological studies. Marginal zone lymphomas (MZLs) including splenic lymphomas with villous lymphocytes are among the most frequently reported subgroups in the setting of chronic HCV infection. In this study, we examined the effect of antiviral treatment in eight patients with HCV-associated MZL. We found that five out of eight patients have responded to interferon alpha and ribavirin. In some cases, hematologic responses were correlated to virologic responses. In addition, we report a case of large granular lymphocyte leukemia occurring in association with MZL and HCV, and responding to interferon and ribavirin. We suggest that there is an etiologic link between HCV and antigen-driven lymphoproliferative disorders.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/patogenicidad , Hepatitis C/tratamiento farmacológico , Linfoma de Células B/virología , Adulto , Anciano , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Interferón-alfa/uso terapéutico , Linfoma de Células B/complicaciones , Linfoma de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
A 46-yr-old man had typical Hashimoto's thyroiditis (HT) and a serum monoclonal immunoglobulin (MIgG kappa). There was no evidence of disseminated lymphoid malignancy. Because of rapid enlargement of the goiter with pressure symptoms, a total thyroidectomy was performed. The surgery was followed by the complete disappearance of the MIgG kappa paralleled by the disappearance of serum antithyroglobulin autoantibodies. Thyroid sections demonstrated HT. Direct immunofluorescence assay showed diffuse infiltration by lymphocytes and plasma cells that were mainly IgG kappa positive. Moreover, the serum MIgG kappa had antithyroglobulin activity, as demonstrated by two different methods, namely labeling of focused serum proteins with radioiodinated human thyroglobulin and immunoadsorption of the monoclonal IgG on a human thyroglobulin affinity column. These results demonstrate that a monoclonal antithyroglobulin autoantibody was produced within the thyroid in a patient with HT. As the production of a MIg is regarded as the last stage preceding the malignant transformation of normal B lymphocytes, this report strongly suggests that a B lymphoma can directly emerge from the intrathyroidal lymphocytes involved in the pathogenesis of Hashimoto's thyroiditis.
Asunto(s)
Anticuerpos Monoclonales/análisis , Autoanticuerpos/análisis , Tiroglobulina/inmunología , Tiroidectomía , Tiroiditis Autoinmune/inmunología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Non-Hodgkin's lymphoma occurs frequently in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We determined the association between the clinical and histologic features of HIV-related lymphoma. SUBJECTS AND METHODS: We reviewed the medical records of 291 patients with noncerebral HIV-related lymphoma who had been treated in multicenter trials coordinated by the Groupe d'Etude des Lymphomes de l'Adulte between 1988 and 1997. This study was performed mainly before the availability of combination antiretroviral therapy. RESULTS: The main histologic subtypes were centroblastic lymphoma in 131 patients (45%), immunoblastic lymphoma in 39 patients (13%), and Burkitt's lymphoma (including the classical form and the variant with plasmacytic differentiation) in 115 patients (40%). Burkitt's lymphoma was the most aggressive form, whereas immunoblastic lymphoma occurred in severely immunodeficient patients. Two-year survival after enrollment was 15% in immunoblastic lymphoma, 32% in Burkitt's lymphoma, and 31% in centroblastic lymphoma (P = 0.006), but multivariate analysis did not confirm the independent prognostic value of histologic subtype. Instead, five independent pretreatment factors increased the risk of mortality: age 40 years or older [relative risk (RR) = 1.5; 95% confidence interval (CI), 1.1 to 2.1; P = 0.005], elevated serum lactate dehydrogenase level (RR = 1.5; 95% CI, 1.1 to 2.1; P = 0.02), having a diagnosis of AIDS before lymphoma (RR = 1.8; 95% CI, 1.2 to 2.6; P = 0.006), CD4(+) cell count less than 100 x 10(6)/L (RR = 1.8; 95% CI, 1.3 to 2.6; P = 0.0004), and impaired performance status (RR = 2.4; 95% CI, 1.7 to 3.4; P <0.0001). CONCLUSION: Several pretreatment characteristics of HIV-related lymphoma were linked to the histologic form, but HIV disease parameters other than those of lymphoma were the main determinants of outcome, so the histologic features of the lymphoma were not associated with prognosis.
Asunto(s)
Linfoma de Burkitt/epidemiología , Linfoma Relacionado con SIDA/epidemiología , Linfoma Relacionado con SIDA/patología , Linfoma Inmunoblástico de Células Grandes/epidemiología , Linfoma de Células del Manto/epidemiología , Adulto , Anciano , Análisis de Varianza , Linfoma de Burkitt/mortalidad , Recuento de Linfocito CD4 , Femenino , Francia/epidemiología , Humanos , Linfoma Relacionado con SIDA/mortalidad , Linfoma Inmunoblástico de Células Grandes/mortalidad , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
BACKGROUND: Chimerism analysis is essential in understanding the etiology of graft failure occurring after allogeneic stem cell transplantation. The detection of marrow and/or blood host cells suggests graft rejection, relapse of the underlying disease, or a state of stable mixed chimerism. However, complete donor chimerism may be observed in some cases. Our objective was to characterize, by a sensitive process of chimerism analysis, six cases of graft failure occurring after transplant. METHODS: Six cases of secondary graft failure, in which previous analysis had shown complete donor chimerism by standard polymerase chain reaction amplification of variable number of tandem repeats, were studied. In order to detect a minority population of recipient cells, we increased the sensitivity of the process by using fluorescent polymerase chain reaction and analyzing the origin of T, B, and natural killer lymphocytes at the time of graft failure. RESULTS: The complete donor origin of mononuclear cells and lymphocytic populations was confirmed with this method in five of six patients. In the remaining patient, diagnosis of graft failure was clarified by the detection of a previously undetected mixed chimerism, compatible with graft rejection. In the other five patients, graft rejection was thereby excluded and graft failure could be related to viral infection or to graft-versus-host disease. CONCLUSION: Our sensitive process of fluorescent lineage-specific chimerism analysis may help in distinguishing between graft rejection and other mechanisms of graft failure, which is essential for deciding appropriate therapy.
Asunto(s)
Linaje de la Célula/efectos de la radiación , Fluorescencia , Supervivencia de Injerto/efectos de la radiación , Trasplante de Células Madre Hematopoyéticas , Reacción en Cadena de la Polimerasa/métodos , Quimera por Trasplante , Adolescente , Adulto , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/terapia , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of inflammation cytokines such as TNF-alpha may damage the intestine. 2. Rats received a s.c. injection of indomethacin. Then, jejunum-ileum was taken up for the quantification of ulcerations, production of TNF-alpha, nitrites and PGE2 ex vivo and activity of calcium-independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of TNF-alpha. 3. Jejunum-ileum from rats having received indomethacin (10 mg kg(-1)) produced TNF-alpha ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded nitrite production and tissue activity of myeloperoxidase. 4. Similar intestinal ulcerations and upregulation of TNF-alpha were obtained with flurbiprofen (30 mg kg(-1)), chemically unrelated to indomethacin. 5. TNF-alpha production was proportional to the indomethacin dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and nitrite production, 24 h after indomethacin administration. 6. Pretreatment of rats with RO 20-1724, a type-IV phosphodiesterase inhibitor which inhibits TNF-alpha synthesis, substantially reduced jejunum-ileum ulcerations, TNF-alpha and nitrite production and tissue enzyme activities. 7. These findings provide evidence that TNF-alpha is increased in indomethacin-induced intestinal ulcerations and support suggestions that TNF-alpha is involved at an early stage of nonsteroidal anti-inflammatory drug toxicity for the small intestine.
Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Indometacina/toxicidad , Yeyuno/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , 4-(3-Butoxi-4-metoxibencil)-2-imidazolidinona/farmacología , Animales , Sistema Digestivo/patología , Yeyuno/metabolismo , Yeyuno/patología , Masculino , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas Wistar , Úlcera/inducido químicamente , Úlcera/prevención & controlRESUMEN
A diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency was made in four sibs at different ages. The first three, including a pair of twins, had retarded psychomotor development, poor social contact, and seizures. Biologically, hyperhomocysteinemia and hypomethioninemia were found associated with low folate levels in serum and red cells, especially undetectable methyltetrahydrofolate in red cells. In the fourth child, prenatal diagnosis was not conclusive because of moderate decrease of enzymatic activity in chorionic villi and trophoblast. The girl was also affected, as shown by hyperhomocysteinemia and low folate levels found several days after birth. A 677C-->T (Ala-->Val) mutation was found in a homozygous state in the four children and in the father. Additionally, a second homozygous mutation, 1081C-->T, changing an arginine to cysteine also was identified in all of the children, whereas the distantly consanguineous parents were heterozygous. This amino acid substitution affecting an arginine residue in a sequence located at the end of catalytic domain seems critical for the function of the enzyme. The difficulty of prenatal diagnosis is discussed given the variability found in enzymatic activity and in the clinical phenotypes.
Asunto(s)
Enfermedades en Gemelos/genética , Hiperhomocisteinemia/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/deficiencia , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Adolescente , Sustitución de Aminoácidos , Niño , Preescolar , Estabilidad de Enzimas , Exones/genética , Femenino , Ácido Fólico/metabolismo , Humanos , Hiperhomocisteinemia/enzimología , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Mutación , Núcleo Familiar , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Linaje , Polimorfismo Genético , Diagnóstico PrenatalRESUMEN
BACKGROUND: Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines. AIM: To examine TNFalpha production and the effect of preventive treatment with octreotide, during the early phase of TNB-colitis. METHODS: Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2x10 microg x day/rat) or dexamethasone (1x2 mg x day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFalpha immunohistochemistry, quantification of cytokine release ex vivo and tissue-inducible NO synthase (iNOS) activity. RESULTS: Maximal TNFalpha production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFalpha expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFalpha and colonic production of IL1beta and interferon gamma was increased; all these effects were reduced by octreotide treatment. CONCLUSIONS: TNFalpha was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon gamma. TNFalpha regulation by octreotide suggests that this drug might exert anti-inflammatory properties via smooth muscle cells.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Octreótido/uso terapéutico , Factor de Necrosis Tumoral alfa/biosíntesis , 4-(3-Butoxi-4-metoxibencil)-2-imidazolidinona/farmacología , Animales , Enfermedad Crónica , Colitis/metabolismo , Colitis/patología , Colon/metabolismo , Colon/patología , Dexametasona/farmacología , Inmunohistoquímica , Masculino , Octreótido/farmacología , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisisRESUMEN
We report herein the pulmonary recurrence of Hodgkin's disease coincidental with a marked decrease in the peripheral blood CD4 lymphocyte count in an HIV-seropositive patient with alveolar consolidation on chest roentgenogram. The diagnosis of lung parenchyma involvement was made by bronchoalveolar lavage cell analysis and illustrates the reliability of Reed-Sternberg cell identification in bronchoalveolar lavage for the diagnosis of pulmonary localization of Hodgkin's disease.
Asunto(s)
Líquido del Lavado Bronquioalveolar/patología , Infecciones por VIH , Enfermedad de Hodgkin/patología , Neoplasias Pulmonares/patología , Adulto , Infecciones por VIH/patología , Humanos , MasculinoRESUMEN
Morphological and functional abnormalities of the megakaryocytic series have been well described in myelodysplastic syndromes. Platelet peroxidase has always been demonstrated in abnormal megakaryocytes and early megakaryoblasts in such syndromes. We have studied a case of myelodysplastic syndrome with marked morphological abnormalities of megakaryocytes in which ultrastructural studies showed the coexistence of platelet peroxidase positive and platelet peroxidase negative megakaryocytes. This enzymatic deficiency was confirmed by the ultrastructural study of circulating platelets. This case appears to be the first report of a partial platelet peroxidase deficiency. It adds to the enzymatic abnormalities in myelodysplastic syndrome already described for the red cells and the granulocytic cells.
Asunto(s)
Plaquetas/enzimología , Megacariocitos/enzimología , Trastornos Mieloproliferativos/enzimología , Peroxidasas/deficiencia , Anciano , Plaquetas/ultraestructura , Médula Ósea/patología , Enfermedades de la Médula Ósea/patología , Histocitoquímica , Humanos , Megacariocitos/ultraestructura , Microscopía Electrónica , Mielofibrosis Primaria/enzimologíaRESUMEN
Two cases are reported of an apparently distinct type of immune disorder. Beginning with mild anaemia and widespread massive lymphadenopathy, the disease progressed to a fatal autoimmune type haemolytic anaemia. Serum investigation showed polyclonal hypergamma-globulinaemia and some autoantibodies. Repeat lymph node biopsies in each case showed hyperplasia within B lymphocyte territory (follicular hyperplasia and polyclonal plasmacytosis with IgG predominance) and atrophy of T dependent areas. Dilatation of lymph sinuses, vascular proliferation, and sclerosis were striking features. This appears to be a new entity, and reasons are given for separating this disease from other pseudotumourous lymph node disorders associated with dysimmunity.
Asunto(s)
Anemia Hemolítica Autoinmune/complicaciones , Hipergammaglobulinemia/complicaciones , Inmunoglobulina G/análisis , Enfermedades Linfáticas/complicaciones , Anciano , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/patología , Humanos , Hipergammaglobulinemia/inmunología , Hipergammaglobulinemia/patología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Enfermedades Linfáticas/inmunología , Enfermedades Linfáticas/patología , Masculino , SíndromeRESUMEN
Hyperhomocysteinemia, a risk factor for vascular disease, is related to vitamin B12, vitamin B6, and especially folate deficiency, or to genetic factors such as mutations in methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the remethylation pathway of homocysteine to methionine. Recently, a C677 --> T mutation identified in the MTHFR gene was found to be frequently associated with decreased MTHFR activity and an elevated plasma homocysteine concentration. Since hyperhomocysteinemia seems to be determined by both genetic and environmental factors, we studied the interactions between MTHFR (phenotype and genotype) and folate status, including methyltetrahydrofolate (methylTHF), the product of MTHFR, on the homocysteine concentration in 52 healthy subjects, (28 women and 24 men; mean age, 32.7 years). MTHFR activity seems to be dependent on folate status, as shown by a lower activity in folate-deficient subjects and a return to normal values after supplementation with folic acid, and also by a decreased enzymatic activity on phytohemagglutinin (PHA)-stimulated lymphocytes grown in a folic acid-deficient medium. Conversely, the C677 --> T mutation seems to influence folate metabolism. Subjects who were homozygous for this mutation (+/+) had significantly higher plasma homocysteine and lower plasma folate and total and methylfolate levels in red blood cells (RBCs) than heterozygous (+/-) and normal (-/-) subjects. The ratio of RBC methylfolate to RBC total folate was, respectively, 0.27 in +/+, 0.66 in +/-, and 0.71 in -/-. This mutation seems to have an impact on methylTHF generation. These data illustrate the interactions between nutritional and genetic factors.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/sangre , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/sangre , Adulto , Femenino , Ácido Fólico/administración & dosificación , Deficiencia de Ácido Fólico/enzimología , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genéticaRESUMEN
The HS has been associated with malignant hemopathies. We report here a case of HS related to Bacteroides fragilis during the course of acute monoblastic leukemia. Evolution was fatal despite remission of the leukemia process and response of the infection to appropriate antibiotic therapy.
Asunto(s)
Infecciones por Bacteroides/complicaciones , Bacteroides fragilis/patogenicidad , Histiocitosis de Células no Langerhans/etiología , Leucemia Monocítica Aguda/complicaciones , Amicacina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones por Bacteroides/tratamiento farmacológico , Ceftazidima/uso terapéutico , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Quimioterapia Combinada/uso terapéutico , Resultado Fatal , Femenino , Histiocitosis de Células no Langerhans/microbiología , Humanos , Leucemia Monocítica Aguda/tratamiento farmacológico , Persona de Mediana Edad , Moxalactam/uso terapéutico , Tonsilitis/complicaciones , Vancomicina/uso terapéuticoRESUMEN
We report here a case of acute polymyositis associated with a Ki-1 non-Hodgkin's lymphoma (NHL). This anaplastic large cell malignant lymphoma was a primary T-cell NHL lymphoma of the bone marrow. The malignant cells expressed the CD30 (Ki-1), CD3, and CD4 antigens, the beta chain of the interleukin 2 receptor (CD25), and the betaF1 antigen (alpha/beta T-cell receptor). Chemotherapy and high dose methylprednisolone pulse therapy were initiated. However, no clinical improvement was noticed, because the patient rapidly died of an acute respiratory distress syndrome. To our best knowledge, this represents the first case of Ki-1 lymphoma associated with Polymyositis.