RESUMO
We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.
Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Varicela , Prednisolona/administração & dosagem , Trombocitemia Essencial/tratamento farmacológico , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/etiologia , Autoanticorpos/sangue , Varicela/sangue , Varicela/etiologia , Feminino , Seguimentos , Hemoglobinas/análise , Humanos , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Contagem de Plaquetas , Síndrome , Trombocitemia Essencial/sangue , Trombocitemia Essencial/etiologiaRESUMO
The Notch/Notch ligand system controls diverse cellular processes. The proteolytic cleavage generates transmembrane and soluble forms of Notch ligands. We examined the effect of a soluble Notch ligand, human Jagged-1, on human cord blood (CB) CD34+ cells, under serum-deprived conditions, using soluble human Jagged-1-immunoglobulin G1 chimera protein (hJagged-1). Soluble hJagged-1 inhibited myeloid colony formation but not erythroid-mix or erythroid colony formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and erythropoietin. Cytological analysis revealed that the decrease in myeloid colonies resulted mainly from the inhibition of macrophage colony formation. Furthermore, soluble hJagged-1 led to the inhibition of macrophage colony formation supported by M-CSF plus SCF and GM-CSF plus SCF. Delayed-addition experiments and the analysis of colony sizes demonstrated that soluble hJagged-l inhibited the growth of macrophage progenitors by acting in the early stage of macrophage development. The direct action of hJagged-1 was confirmed by the enhanced expression of the HES-1 (hairy enhancer of the split-1) gene. These results suggest that soluble hJagged-1 may regulate human hematopoiesis in the monocyte/macrophage lineage.
Assuntos
Células-Tronco Hematopoéticas/citologia , Macrófagos/citologia , Proteínas/farmacologia , Receptores de Superfície Celular , Fatores de Transcrição , Antígenos CD/sangue , Antígenos CD34/sangue , Proteínas de Ligação ao Cálcio , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura Livres de Soro , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Proteínas/genética , Receptor Notch1 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Serrate-JaggedRESUMO
We describe a 55-year-old Japanese woman with therapy-related myelodysplastic syndrome (t-MDS) with 2 independent clones, t(1;2)(p36;p21) and t(11;12)(pl5;ql3). She was diagnosed with acute myeloid leukemia (AML) with cytological features of the bone marrow and peripheral blood. Cytogenetic evaluation revealed a 46,XX karyotype. She received chemotherapy and achieved complete remission (CR). Despite maintenance chemotherapy, she suffered a relapse. Chromosomal analysis showed t(1;2)(p36;p21) in 2 of 20 metaphases. At second CR, this clone transiently disappeared. Nine months later, t(1;2) (p36;p21) was detected again in 3 of 20 metaphases while the patient remained in CR. Six months later, bone marrow examination disclosed trilineage dysplasia without an excess of blasts, suggesting MDS. t(1;2)(p36;p21) was observed in 16 of 20 metaphases. The clinical course and serial cytogenetic findings were diagnostic of t-MDS. The duration of t-MDS was 6 years. During this period, persistent t(1;2)(p36;p21) and transient t(11;12)(p15;q13) were found. When t-MDS evolved toAML, cytogenetic evaluation revealed 46,XX,t(1;2)(p36;p21),del(7)(q22),add(19)(p13).
Assuntos
Leucemia Mieloide/tratamento farmacológico , Síndromes Mielodisplásicas/induzido quimicamente , Doença Aguda , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 2 , Células Clonais/patologia , Análise Citogenética , Feminino , Humanos , Leucemia Mieloide/complicações , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Translocação GenéticaRESUMO
Hemostatic abnormalities in 26 patients following bone marrow transplantation (BMT) were examined. In the event-free survival group, the plasma levels of antithrombin (AT) and protein C (PC) were significantly decreased 1 and 2 weeks after BMT, and the plasma levels of thrombomodulin (TM) and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA-PAI-I complex) were significantly increased from 4 weeks to 13 weeks after BMT. Excepting AT, there was no significant difference in hemostatic parameters before BMT among the event-free survival, 6-month survival, and death within 6 months groups. On day 0 following BMT, only plasma AT levels were significantly lower in the 6-month survival group than in the death within 6 months group. From 1 to 3 weeks after BMT, plasma levels of AT or PC were significantly lower in the death within 6 months group than in the 6-month survival group. From 1 to 5 weeks after BMT, the plasma levels of TM and tissue type plasminogen activator-plasminogen activator inhibitor-I complex (tPA-PAI-I complex) were significantly higher in the 6-month survival group than in the death within 6 months group. From 1 to 13 weeks after BMT, the plasma levels of D-dimer or soluble fibrin monomer (SFM) were significantly higher in the death within 6 months group than in the 6-month survival group. There was no remarkable difference in plasma levels of thrombin-antithrombin comlex or plasmin-plasmin inhibitor complex following BMT between these groups of patients. These findings suggest that the decrease in the plasma AT or PC level reflects early occurrence of complications of prognostic significance and that the increase in vascular endothelial cell markers such as plasma levels of TM or tPA-PAI-I complex reflects occurrence of complications during the middle course of BMT. Plasma levels of D-dimer and SFM may be useful markers for predicting complications associated with poor prognosis after BMT.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Hemostasia/fisiologia , Adulto , Antitrombina III/análise , Inibidores dos Fatores de Coagulação Sanguínea/análise , Fatores de Coagulação Sanguínea/análise , Transplante de Medula Óssea/mortalidade , Intervalo Livre de Doença , Feminino , Fibrina/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Trombomodulina/análiseRESUMO
We report two cases of honeycomb gallbladder as a new category of acquired pseudo-multiseptate gallbladder associated with chronic cholecystitis with stones. The two patients were elderly women without any abdominal symptoms or abnormality of laboratory data. On the imaging examinations, a hyperechoic collection with acoustic shadowing on the inferior surface of the liver was typically observed on ultrasonography, with multiloculated gallbladder being observed on computed tomography. Macroscopic findings of the cut plane of the gallbladder showed a characteristic appearance, with thin pseudo-septations arising from the wall and bridging the lumen from side to side, with a honeycomb appearance, including small stones. Microscopic findings suggest that these septational structures could have developed over a chronic inflammatory course after acute obstruction of the cystic duct. Cholecystectomy should be the choice of treatment for honeycomb gallbladder from the viewpoint of clinical management.
Assuntos
Doenças da Vesícula Biliar/patologia , Idoso , Idoso de 80 Anos ou mais , Colecistectomia , Feminino , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/fisiopatologia , Doenças da Vesícula Biliar/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Severe deficiency of vWF-cleaving protease (vWF-CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy. STUDY DESIGN AND METHODS: The activities of vWF-CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic-uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF-CPase activity. RESULTS: Eight of nine patients with HUS had more than 40 percent of vWF-CPase activity, whereas one had 28 percent of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF-CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF-CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF-CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF-CPase inhibitor had relapsed and required an immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF-CPase activity. CONCLUSION: Assays of vWF-CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF-CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF-CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/terapia , Síndrome Hemolítico-Urêmica/terapia , Metaloendopeptidases/deficiência , Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia , Proteínas ADAM , Proteína ADAMTS13 , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Autoanticorpos/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/enzimologia , Doenças Autoimunes/etiologia , Biomarcadores , Terapia Combinada , Feminino , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/induzido quimicamente , Síndrome Hemolítico-Urêmica/enzimologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/sangue , Metaloendopeptidases/imunologia , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/enzimologia , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Falha de Tratamento , Fator de von Willebrand/metabolismoRESUMO
It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic neutrophils into macrophages in culture. When the CD15+CD14- cell population, which predominantly consists of band neutrophils, was cultured with granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha, interferon-gamma, and interleukin-4, and subsequently with macrophage colony-stimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they up-regulated nonspecific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15+CD14- cells proceeded to macrophages through the CD15-CD14- cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15+CD14- neutrophils had phagocytic function. Data obtained using 3 different techniques, including Ki-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15+CD14- neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal hematopoiesis.
Assuntos
Macrófagos/citologia , Neutrófilos/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular , Células Cultivadas , Perfilação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Substâncias de Crescimento/farmacologia , Antígenos HLA-DR/metabolismo , Hematopoese , Humanos , Interferon gama/farmacologia , Interleucina-4/farmacologia , Antígenos CD15/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Mitose , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Fagocitose , Fenótipo , Proteínas Recombinantes , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
We examined the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) on human monocytes, using a serum-free culture system. GM-CSF and IL-3 did not promote the differentiation of monocytes into macrophages but rather into cells with a phenotype compatible with that of immature dendritic cells (DCs). The addition of fetal bovine serum to serum-free cultures with GM-CSF or IL-3 restored the differentiation of monocytes into macrophages. Cells generated with GM-CSF or IL-3 elicited phagocytic activity. Cells generated in the presence of GM-CSF or IL-3, followed by the addition of tumor necrosis factor-alpha, displayed a phenotype of mature DCs, and primed and stimulated immunogenic peptide-specific T lymphocytes. Surprisingly, GM-CSF and IL-3 inhibited macrophage colony-stimulating factor (M-CSF)-dependent differentiation of monocytes into macrophages and induced differentiation into immature DCs. We asked if the inhibition of M-CSF-dependent differentiation into macrophages by GM-CSF or IL-3 was associated with the expression of M-CSF receptors (M-CSFR). GM-CSF or IL-3 down-regulated the expression of M-CSFR. These data demonstrate that GM-CSF and IL-3 primarily support the differentiation of monocytes into DCs and inhibit M-CSF-dependent differentiation into macrophages by suppressing the expression of M-CSFR, thereby promoting differentiation into DCs.