RESUMO
Transforming growth factor beta1 (TGFbeta1) is an important immunosuppressive cytokine. Defects in its production by lymphocytes and the failure of TGFbeta1 to regulate immunological functions have been described in SLE. Expression of TGFbeta1 and the related signaling pathway was studied in the peripheral lymphocytes of SLE patients. The total plasma TGFbeta1 level in active and inactive SLE patients compared to healthy controls was also measured. TGFbeta1 and all downstream signaling elements were expressed in normal cells. However, in more than 50% of SLE patients the isolated T cell population showed no TGFbeta1 mRNA expression and at least one member of the TGFbeta1 pathway was also missing (TGFbeta-RI, Smad2 and Smad3) in more than half of the patients. Total plasma TGFbeta1 level was increased in both active and inactive SLE groups compared to normal controls (p< 0.05). These data raise questions about the availability of TGFbeta1 signaling in lymphocytes in SLE patients, however, the elevated total plasma TGFbeta1 level suggests that the failure of TGFbeta1 effects is not the consequence of low level of this cytokine in SLE.
Assuntos
Lúpus Eritematoso Sistêmico/genética , Linfócitos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Proteína Smad2/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Adolescente , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto JovemRESUMO
Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematological disorders characterized by ineffective hematopoiesis, enhanced bone marrow apoptosis and frequent progression to acute myeloid leukemia. Several recent studies suggested that, besides the abnormal development of stem cells, microenvironmental alterations are also present in the MDS bone marrow. In this study, we have examined the relative frequencies of stem and progenitor cell subsets of MDS and normal hematopoietic cells growing on stromal cell layers established from MDS patients and from normal donors. When hematopoietic cells from MDS patients were co-cultured with normal stromal cells, the frequency of either early or late cobblestone area-forming cells (CAFC) was significantly lower compared to the corresponding normal control values in 4 out of 8 patients. In the opposite situation, when normal hematopoietic cells were incubated on MDS stromal cells, the CAFC frequencies were decreased in 5 out of 6 patients, compared to normal stromal layer-containing control cultures. Moreover, a soluble Notch ligand (Jagged-1 protein) was an inhibitor of day-35-42 CAFC when normal hematopoietic cells were cultured with normal or MDS stromal cells, but was unable to inhibit MDS stem and early progenitor cell growth (day-35-42 CAFC) on pre-established stromal layers. These findings suggest that in early hematopoietic cells isolated from MDS patients the Notch signal transduction pathway is disrupted. Furthermore, there was a marked reduction in the plasticity of mesenchymal stem cells of MDS patients compared with those of normal marrow donors, in neurogenic and adipogenic differentiation ability and hematopoiesis supporting capacity in vitro. These results are consistent with the hypothesis that when alterations are present in the myelodysplastic stroma environment along with intrinsic changes in a hematopoietic stem/progenitor cell clone, both factors might equally contribute to the abnormal hematopoiesis in MDS.
Assuntos
Células-Tronco Hematopoéticas/citologia , Células-Tronco Mesenquimais/citologia , Síndromes Mielodisplásicas/patologia , Receptores Notch/metabolismo , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/citologia , Proteínas de Ligação ao Cálcio/farmacologia , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Feminino , Hematopoese , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Proteína Jagged-1 , Masculino , Proteínas de Membrana/farmacologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismo , Proteínas Serrate-Jagged , Células Estromais/citologiaRESUMO
Although it is clear that immunologic mechanisms play a significant role in the pathophysiology of many hematologic diseases, there are relative few situations where it is possible to gain a detailed understanding of immune damage in vivo in humans. Autoimmune hemolytic anemia, immune thrombocytopenia and immune neutropenia as antibody-mediated cell-specific disorders are of particular interest in this regard. Autoimmune hemolytic anemia represents a group of disorders in which individuals produce antibodies directed toward one or more of their own erythrocyte membrane antigens. This leads to destruction of the antibody-coated erythrocytes. The pathophysiology of the decreased erythrocyte survival has been examined with increasing sophistication for many years. This paper first discusses the underlying mechanisms responsible for autoimmune hemolytic anemias then consider immune thrombocytopenia and immune neutropenia.
Assuntos
Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/sangue , Neutropenia/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Autoanticorpos/metabolismo , Humanos , Imunidade CelularRESUMO
There is an increasing body of evidence that suggests that genes involved in cell fate decisions and pattern formation during development also play a key role in the continuous cell fate decisions made by adult tissue stem cells. Here we show that prolonged in vitro culture (14 days) of murine bone marrow lineage negative cells in medium supplemented with three early acting cytokines (stem cell factor, Flk-2/Flt-3 ligand, thrombopoietin) and with immobilized Notch ligand, Jagged-1, resulted in robust expansion of serially transplantable hematopoietic stem cells with long-term repopulating ability. We found that the absolute number of marrow cells was increased approximately 8 to 14-fold in all cultures containing recombinant growth factors. However, the frequency of high quality stem cells was markedly reduced at the same time, except in cultures containing growth factors and Jagged-1-coated Sepharose-4B beads. The absolute number of hematopoietic cells with long-term repopulating ability was increased approximately 10 to 20-fold in the presence of multivalent Notch ligand. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic stem cell fate and to a potential role for Notch ligand in increasing cell numbers in clinical stem cell transplantation.
Assuntos
Proteínas de Ligação ao Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas de Membrana/farmacologia , Fator de Células-Tronco/farmacologia , Trombopoetina/farmacologia , Animais , Contagem de Células , Células Cultivadas , Feminino , Transplante de Células-Tronco Hematopoéticas , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Receptores Notch/metabolismo , Sefarose/farmacologia , Proteínas Serrate-Jagged , TempoRESUMO
OBJECTIVES: Accumulating evidence suggests that non-T, non-B cell CD4+CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. METHODS: In this work we present the immunophenotypic and genotypic features of bone marrow (BM), peripheral blood (PB), lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, BM, PB, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation, and co-stimulatory molecules were used. RESULTS AND CONCLUSION: The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2, and granzyme-B corresponding to the preplasmacytoid dendritic cell developmental stage. The presence of CD11a/CD18, CD84, CD91, CD95, alphavbeta5, CDw197, and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells. Completing the immunophenotypes with multidrug resistance function can provide additional information for characterizing pDC leukemia.
Assuntos
Células Dendríticas/patologia , Leucemia/patologia , Plasmocitoma/patologia , Idoso , Células Sanguíneas/patologia , Antígenos CD4 , Antígeno CD56 , Linhagem da Célula , Citometria de Fluxo , Humanos , Imunofenotipagem , Linfonodos/patologia , Masculino , Pele/patologiaRESUMO
Notch signaling defines an evolutionarily ancient cell interaction mechanism. The signals transmitted through the Notch receptor, in combination with other cellular factors influence differentiation, proliferation and apoptotic events at all stages of development. Recent advances have elucidated both the biochemical mechanism regulating receptor activation and the molecular participants forming the intracellular signaling cascade. Authors present description of the main signaling components involved in the Notch pathway and how it can affect the growth and function of lymphocytes. Notch signaling is critical during lymphocyte development, and dysregulation of the pathway can give rise to leukemia. It is conceivable that appropriate manipulation of Notch signaling may become a useful tool in addressing a variety of human dysplastic condition and tissue regeneration.
Assuntos
Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Membrana/fisiologia , Transdução de Sinais , Animais , Diferenciação Celular , Divisão Celular , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Receptores NotchRESUMO
The aim of this study was to determine the complement functions, the serum levels of the complement components C3 and C4, and circulating immune complexes during autologous blood stem cell transplantation. Seventeen lymphoma patients receiving transplants between 1997 and 2001 were involved in this study. High-dose chemotherapy with or without total body irradiation was used for conditioning. The transplantation resulted in complete remission without complications in 14 patients. Early relapse developed in one case and two nonrelapsed patients suffered from serious toxic infection early posttransplant. Normal values of CH50, C3, C4, and immune complexes in sera of patients were detected on day -7, before the conditioning (day of transplantation was determined as day 0). After the conditioning, on day -2, the levels of the CH50, C3, and C4 decreased significantly ( p<0.05) in all patients compared with the starting values. The CH50, C3, and C4 levels exceeded the starting values in the noninfected patients from day +7. In two patients suffering from toxic infection, significantly elevated complement levels were documented early posttransplant. In the relapsed patient a significant decrease of the complement parameters was documented posttransplant accompanied by a significant elevation in the immune complex level. The results show alteration in the complement parameters during transplantation, but in the complication-free cases this remained within the normal ranges. However, an unusual elevation seemed to be the sign of infection, and the significant decrease seemed to indicate a relapse.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Complemento C3/metabolismo , Complemento C4/metabolismo , Doença de Hodgkin/metabolismo , Linfoma não Hodgkin/metabolismo , Transplante de Células-Tronco , Adulto , Ensaio de Atividade Hemolítica de Complemento , Feminino , Doença de Hodgkin/imunologia , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante , Transplante Autólogo , Irradiação Corporal TotalRESUMO
Stem cells reside in customized microenvironments (niches) that contribute to their unique ability to divide asymmetrically to give rise to self and to a daughter cell with distinct properties. Notch receptors and their ligands are highly conserved and have been shown to regulate cell-fate decisions in multiple developmental systems through local cell interactions. To assess whether Notch signaling may regulate hematopoiesis to maintain cells in an immature state, we examined the functional role of the recombinant, secreted form of the Notch ligand Jagged-1 during mouse hematopoietic stem cell (HSC) and progenitor cell proliferation and maturation. We found that ligand immobilization on stromal layer or on Sepharose-4B beads is required for the induction of self-renewing divisions of days 28-35 cobblestone area-forming cell. The free, soluble Jagged-1, however, has a dominant-negative effect on self-renewal in the stem-cell compartment. In contrast, free as well as immobilized Jagged-1 promotes growth factor-induced colony formation of committed hematopoietic progenitor cells. Therefore, we propose that differences in Jagged-1 presentation and developmental stage of the Notch receptor-bearing cells influence Notch ligand-binding results toward activation or inhibition of downstream signaling. Moreover, these results suggest potential clinical use of recombinant Notch ligands for expanding human HSC populations in vitro.
Assuntos
Diferenciação Celular/fisiologia , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Proteínas/metabolismo , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição , Animais , Proteínas de Ligação ao Cálcio , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Feminino , Substâncias de Crescimento/farmacologia , Hematopoese/efeitos dos fármacos , Fatores de Crescimento de Células Hematopoéticas/metabolismo , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Proteínas/genética , Proteínas/farmacologia , Receptor Notch1 , Receptores de Superfície Celular/efeitos dos fármacos , Proteínas Serrate-Jagged , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Bone marrow transplantation is a complex medical procedure in which hematopoietic stem and progenitor cells are infused into a patient following high-dose chemotherapy with or without irradiation. Because the allogeneic transplantation is associated with life-threatening physical morbidity, lengthy convalescence, and special isolation, the potential for significant psychosocial uncertainty and psychological morbidity is high in adult patients. This work provides an overview of the medical procedures used in allogeneic transplantation and a review of psychosocial and behavioral issues relevant to transplantation. The discussion is limited to psychosocial issues pertinent to transplant recipients and donors, even though transplantation raises significant psychological issues for medical staff, families and caregivers of recipients.
Assuntos
Adaptação Psicológica , Transplante de Medula Óssea/psicologia , Estresse Psicológico/etiologia , Tomada de Decisões , Humanos , Doadores Vivos , Psicologia Médica , Condicionamento Pré-Transplante/psicologia , Transplante HomólogoRESUMO
Relapse is the main cause of treatment failure following hematopoietic stem cell transplantation for blastic phase chronic myeloid leukemia. Treatment options including donor lymphocyte infusion, second transplantation, interferon- and re-induction chemotherapy are often unsuccessful. We report a patient with blastic phase chronic myeloid leukemia relapsing after allogeneic stem cell transplantation. The post-transplant leukemia was characterized with B-lymphoid markers and multiple genetic abnormalities including double Ph-chromosomes. The disease was treated with three courses of salvage chemotherapy combined with donor lymphocyte infusion and bcr-abl tyrosine kinase inhibitor. The leukemia proved to be non-responsive both to immune therapy and STI 571. The presented case demonstrates the need for combination approaches in post-transplant relapsed leukemia and discusses the possible contributing mechanisms of STI-571 resistance.
Assuntos
Crise Blástica/terapia , Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Leucócitos , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Antineoplásicos/uso terapêutico , Linfócitos B/patologia , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/uso terapêutico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Proteínas Tirosina Quinases/antagonistas & inibidores , Indução de Remissão , Terapia de Salvação , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
INTRODUCTION: Coeliac disease (gluten sensitive enteropathy) is a very frequent disease appearing in variegated clinical form. In the last decade--concerning the immunogenetic and immunopathological aspects of the disease many of new recognition came to alight. AIM: As the disease can lay hidden in its non classical manifesting form for a very long time, authors wished to study the efficacy of screening, which may be introduced for patients attending immunological outpatient care service. PATIENTS, METHODS AND RESULTS: In the frame of nation-wide patient care, out of the 200 potential patients sent for immunological check up, various form of coeliac disease was diagnosed in 20 cases. Among these cases there are two--presented for the first time--which are connected to bone marrow transplantation. Based on the immunogenetics and autoantibody serology as well as on small intestine biopsies the following conclusions were made. CONCLUSION: 1. Coeliac disease in Hungary is very frequent. Hidden disease should be considered first of all in cases of malabsorption symptoms. 2. Demonstration of autoantibodies on wide-scale palette helps to state the diagnosis based on the systematic auto-immune disease connection. 3. Study of Human Leukocyte Antigen allotype (HLA-DQA1*0501/DQBI*02) applied as marker can considerably support the suspicion of disease. 4. Histology test of the small intestine cannot be omitted.
Assuntos
Assistência Ambulatorial , Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Intestino Delgado/patologia , Programas de Rastreamento/métodos , Adolescente , Adulto , Idade de Início , Idoso , Biópsia , Doença Celíaca/genética , Feminino , Antígenos HLA-DQ/genética , Humanos , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Reaction patterns of the 7th Human Leukocyte Differentiation Antigen Workshop blind panel adhesion molecules were studied on CD3/CD4, CD3/CD8, CD3/TCR gamma delta double positive T cells from peripheral blood of patients with chronic graft versus host disease (n = 8) and healthy controls (n = 4). Reactivity of 14 adhesion antibodies was tested by three-colour immunophenotyping. The mean proportion of CD3+ T cells (69 +/- 19%). CD3/CD8++ (31 +/- 13%) and CD3/TCR gamma delta++ (4 +/- 2%) T sub-populations of patients were comparable with the healthy controls. However, the mean percentage of CD3/CD4++ T cell subset in patients (14 +/- 12%) proved to be significantly decreased in comparison with the normal control value (34 +/- 16%) presumably due to secondary immunodeficiency. The workshop antibodies proved to be reactive with three T cell subsets expressing the examined antigens. Based on the results of the adhesion molecule workshop new CD categories have been introduced: CD156b as a transmembrane protein, CD167a as an epithelial tyrosin kinase receptor, CD168 as a receptor for hyaluronan mediated motility (RHAMM) and CD171 as a co-stimulatory adhesion molecule. There were significant differences in the expression of the CD167a and CD156b antigens on the CD3/CD4++ subset between the samples of patients compared with the controls characterizing the CD4+ T lymphocyte subpopulation in chronic graft versus host disease.
Assuntos
Antígenos CD/metabolismo , Doença Enxerto-Hospedeiro/imunologia , Proteínas de Membrana , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Proteínas ADAM , Adulto , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Doença Crônica , Proteínas da Matriz Extracelular/metabolismo , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Receptores de Hialuronatos/metabolismo , Imunofenotipagem , Masculino , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/metabolismo , Transplante HomólogoRESUMO
The authors survey the clinical, immunophenotypic, cytogenetic, molecular genetic spectrum and pathogenetic mechanisms of donor cell derived acute leukemias after allogeneic bone marrow transplantation. The main aspects for detection of donor cell origin and the available therapeutic approaches are discussed through demonstration of one documented patient and data of the literature. Several hypotheses are summarized which try to explain how donor cell leukemia might arise including occult leukemia in the donor cells, transfer of oncogene from host to donor cells and the role of impaired immune surveillance. Investigation of donor cell leukemia cases might bring closer to understand the pathogenesis of leukemia serving as a model for studying the leukemiagenesis in vivo.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Leucemia/etiologia , Leucemia/terapia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapia , Doença Aguda , Transplante de Medula Óssea/métodos , Humanos , Imunofenotipagem , Incidência , Leucemia/imunologia , Leucemia/patologia , Segunda Neoplasia Primária/imunologia , Segunda Neoplasia Primária/patologia , Fatores de Risco , Transplante HomólogoRESUMO
Homogeneous immunoglobulins are frequently detected in the serum of patients undergoing allogeneic bone marrow transplantation (BMT). The aim of the present study was to further characterize the incidence of this phenomenon and its correlations with laboratory and clinical data. Serum samples were gathered from 29 patients undergoing allogeneic or syngeneic BMT for chronic myeloid leukemia (CML), and serial protein (IgG, IgA and IgM) quantification, electrophoresis and immunofixation were performed. Transient mono- or oligoclonal gammopathies were observed in 23 out of 29 patients between days 20 and 1,750 following transplantation. The presence of homogeneous immunoglobulins was not correlated with the following clinical parameters: graft-versus-host disease, bacterial sepsis, Epstein-Barr virus or cytomegalovirus infection or invasive fungal infection. Therefore, the development of mono- or oligoclonal immunoglobulins may represent a complex disorder of B cell regeneration which may be caused by an intrinsic B cell defect, or a failure in the regenerating T cell system, or both, manifesting itself in a restricted antibody diversity after allogeneic BMT.
Assuntos
Transplante de Medula Óssea/imunologia , Imunoglobulinas/sangue , Adolescente , Adulto , Anticorpos Monoclonais/sangue , Diversidade de Anticorpos , Linfócitos B/imunologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Modelos Imunológicos , Transplante Homólogo , Transplante IsogênicoRESUMO
We have investigated the influence of apo(a) genetics on the relationship between interleukin (IL)-6, and lipoprotein (a) [Lp(a)] levels in 154 patients with monoclonal gammopathy and 189 healthy subjects. No significant differences in Lp(a) levels and distribution of subjects with different sizes of apo(a) isoforms were found between patients and healthy controls. Relationship between IL-6 and Lp(a) levels was strongly dependent on the size of apo(a) isoforms. In patients with high-size apo(a) isoforms Lp(a) levels positively correlated (r=0.475, P=0.0007) to IL-6 concentrations, whereas no correlation was found in patients with low apo(a) isoforms. Our present finding may provide a plausible explanation for the contradictory findings about the acute phase protein nature of Lp(a).
Assuntos
Apolipoproteínas A/biossíntese , Apolipoproteínas A/química , Interleucina-6/biossíntese , Lipoproteína(a)/biossíntese , Paraproteinemias/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Polimorfismo Genético , Isoformas de Proteínas , Macroglobulinemia de Waldenstrom/metabolismoRESUMO
Stem cells have traditionally been characterized as either embryonic (pluripotent) or tissue-specific (multipotent). Thus, tissue-specific stem cells generate the cell types comprising a particular tissue in embryos and, in some cases, adults. A recent series of studies, however, has challenged the notion of lineage restriction in multipotent stem cells. These experiments have been interpreted as evidence that stem cells from one tissue can be induced to differentiate into cells of other organs, either in vitro or after transplantation in vivo. This paper reviews the current evidence for stem cell plasticity. Some of the potential caveats to the current work are also discussed and, finally, the potential underlying mechanisms of stem cell plasticity are examined.
Assuntos
Células-Tronco/citologia , Animais , Diferenciação Celular , Linhagem da Célula , Humanos , Células-Tronco Multipotentes/citologia , Células-Tronco Pluripotentes/citologia , Transdução de Sinais , Fatores de Transcrição/fisiologiaRESUMO
Telomerase is the enzyme responsible for synthesizing telomeric repeats at the ends of chromosomes to maintain telomere length. Recent studies have suggested that telomere shortening may serve as a surrogate marker of the progression of malignant disorders and seems to be accelerated in allogeneic bone marrow transplant recipients. In this study, the results of the telomere length of nine cord blood mononuclear cell samples are presented. Telomere length was measured by the flow-FISH method, using a peptide nucleic acid probe. The proportion of cord blood cell subsets (CD19/CD34/CD3) was also evaluated. The telomere length of the internal control 1301 cell line was estimated to be 100%. The mean telomere length of cord blood cells was 18.5 +/- 3.9%, compared with the internal control. The progenitor CD34+ cells were detected as 2.6 +/- 0.7% in the lymphoid gate measured. Linear correlation analysis did not find any connection between the cell subsets (CD3+, CD34+, CD19+) and the telomere length. The findings confirm that the telomere flow-FISH method is sufficient for estimation of the telomere length. Assessment of the current procedures of collection, manipulation, and ex vivo expansion of cord blood cells in terms of their effect on telomere shortening might be important.
Assuntos
Sangue Fetal/citologia , Hibridização in Situ Fluorescente , Telômero/ultraestrutura , Coleta de Amostras Sanguíneas , Técnicas de Cultura de Células , Humanos , MétodosRESUMO
An unusual case of hepatosplenic gamma delta T-cell lymphoma with leukemic phase in a 39-year-old woman is reported. At the first presentation she had splenomegaly and pancytopenia diagnosed as hypersplenia treated by splenectomy. Subsequently, she developed hepatomegaly and progressive neoplastic lymphocytosis. The bone marrow showed a sinusoidal infiltrate of medium-sized cells. Flowcytometric analysis of peripheral blood mononuclear cells demonstrated expression of CD3, CD7, CD16, CD56 antigens and T-cell receptor gamma delta. A monoclonal TCR gamma- and beta-chain gene rearrangement were detected by polymerase chain reaction. The patient was treated by traditional chemotherapy and alpha-interferon, unsuccessfully. Therefore, 2-chlorodeoxyadenosine was introduced resulting in a complete remission for 6 months. The reported case demonstrates the usefulness of 2-chlorodeoxyadenosine in treatment of hepatosplenic gamma delta T-cell lymphoma.
Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Adulto , Feminino , Hepatomegalia/tratamento farmacológico , Humanos , Linfoma de Células T/patologia , Recidiva , Indução de Remissão , Esplenomegalia/tratamento farmacológicoRESUMO
10 consecutive patients with HSV-associated chronic oral lesions were treated with Egiferon for ten days. There were a statistically significant increase in the Large Granule Lymphocyte (LGL) counts and the number of spontaneous E rosette forming cells by the end of the treatment period. Interferon alpha brought about a preferential expression of CD8, CD11b, CD14, CD25 and CD45RO cell surface molecules without any effect on the expression of CD2, CD3, CD4, CD20 and HLA-DR.