RESUMO
We are reporting an unusual case of a 54-year-old woman with polycythemia vera (PV) who developed Ph chromosome positive chronic myelogenous leukemia (CML) 8 years after the initial diagnosis of PV, and terminating in acute lymphoblastic leukemia (ALL), 11 years after the initial diagnosis. Cytogenetic studies revealed a normal female karyotype at the time of diagnosis of PV and the presence of a Ph chromosome at the time of appearance of CML. Southern blot hybridization revealed a bcr rearrangement in both mononuclear cells and granulocytes. The diagnosis of ALL was established on the basis of morphology, positive TdT staining, and monoclonal antibody studies positive for 12, B4, and J5. This case demonstrates the transition of PV into CML, followed by a blastic transformation into acute lymphocytic leukemia. At termination of her disease there were findings compatible with bi-phenotypic leukemia. These findings would suggest that the disease arose in a primitive multipotential stem cell.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Policitemia Vera/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Proteínas Tirosina Quinases , Doença Crônica , Citogenética , Feminino , Rearranjo Gênico , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Pessoa de Meia-Idade , Policitemia Vera/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcrRESUMO
The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated spleen cell-conditioned medium (PWCM). Nonadherent cells from STLC were sampled daily for acetylcholinesterase-positive cells and megakaryocyte progenitor cells (CFU-M). CFU-M were assayed in the soft-gel colony-forming system using PWCM as a source of colony-stimulating activity. Proliferative capacity of CFU-M obtained from liquid culture was determined from megakaryocyte colony size (number of megakaryocytes per colony) following plating of cells in a secondary colony-forming assay. Megakaryocytes were grouped into four maturation classes and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cells using an eye-piece micrometer. TSF produced no CFU-M-derived colonies in the soft-gel colony-forming assay. Addition of TSF to STLC had no effect on the total number of CFU-M, megakaryocyte colony size, or total number of megakaryocytes compared to unstimulated STLC. However, on days 4-9 there was a significant increase in megakaryocyte diameter and the proportion of mature (stage III, IV) megakaryocytes obtained from TSF containing STLC compared to unstimulated STLC. In contrast, 5 days after addition of PWCM to STLC a sixfold increase in the total number of CFU-M per flask and a threefold increase in megakaryocytes was observed compared to unstimulated STLC. However, megakaryocyte colony size and megakaryocyte size were significantly reduced and a greater number of immature (stage I, II) megakaryocytes were present in STLC containing PWCM compared to unstimulated STLC. These results indicate that TSF accelerates the maturation of megakaryocytes in vitro and that a factor or factors present in spleen cell-conditioned medium, in addition to influencing megakaryocyte progenitor cell proliferation, also affect(s) megakaryocyte size.
Assuntos
Células da Medula Óssea , Fatores Estimuladores de Colônias/fisiologia , Glicoproteínas/fisiologia , Hematopoese , Megacariócitos/citologia , Proteínas/fisiologia , Trombopoetina/fisiologia , Acetilcolinesterase , Animais , Diferenciação Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura/análise , Proteínas Ligadas por GPI , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/citologia , Masculino , Megacariócitos/classificação , Megacariócitos/enzimologia , Glicoproteínas de Membrana , Mesotelina , Camundongos , Mitógenos de Phytolacca americana , Baço/citologia , Fatores de TempoRESUMO
The feasibility of in vitro interleukin 2 (IL-2) activation and expansion of mononuclear cells (MNCs) derived from adult patients with acute myelogenous leukemia (ANLL) was studied. Patients' natural killer (NK) and lymphokine-activated killer (LAK) cell activity was compared with that of normal donors in terms of: (a) cytolytic activity (four-hour 51Cr release assay) against an NK-sensitive target (K562), NK-resistant targets (Raji/Daudi), and fresh/cryopreserved autologous and allogeneic leukemic blasts; (b) proliferation and expansion in culture with 1,000 U/mL recombinant IL 2 (rIL 2); and (c) the cell surface phenotype of the cultured cells. In 21 of 24 patients with active disease (AP) MNCs derived from the peripheral blood (PBL) or bone marrow (BM) could be cultured and expanded in the presence of rIL 2. These cultures initially contained between 30% and 50% blasts, and during 2 to 4 weeks of culture destruction of blasts and enrichment of up to 60% in cells with the morphology of large granular lymphocytes (LGLs) was observed. Expansion in culture varied between two- and 100-fold. MNCs from all patients in remission (RP) could be activated by rIL 2 and expanded up to 30-fold after 1 to 3 weeks in culture. NK activity of fresh PBLs from AP was significantly lower than in normal controls, whereas NK activity of RP was within the normal range. High levels of postactivation NK and LAK activity on K562/Raji/Daudi and on fresh/cryopreserved leukemic blasts was generated in approximately 50% of cases of AP and in most RP. Cell surface phenotype studies showed that cultured cells derived from ANLL patients were significantly enriched (up to 40%) in NKH-1 (Leu 19) positive cells, with RP LAK cells also expressing a high proportion of CD16 positive cells (up to 40%). This study has shown that it is feasible to activate and significantly expand killer cells derived from active disease and remission ANLL patients during 1 to 3 weeks culture with IL 2 with good maintenance of cytolytic activity. Both initial NK activity and LAK generation was optimal in remission patients. Based on data from this study, a clinical protocol has been developed for treatment of early relapse ANLL patients with LAK cells cultured for 1 to 3 weeks and systemic IL 2.
Assuntos
Células Sanguíneas/fisiologia , Medula Óssea/fisiopatologia , Interleucina-2/farmacologia , Células Matadoras Naturais/fisiologia , Leucemia/fisiopatologia , Linfocinas/farmacologia , Doença Aguda , Medula Óssea/patologia , Estudos de Viabilidade , Humanos , Cinética , Leucemia/patologia , Leucócitos Mononucleares/fisiologia , Fenótipo , Indução de Remissão , Células Tumorais CultivadasRESUMO
The effect of pokeweed mitogen-stimulated spleen cell conditioned medium (PWCM) on the proliferation of megakaryocytes and megakaryocyte progenitor cells (CFU-M) was studied with a short-term liquid culture (STLC) system. Adherent and nonadherent cells were sampled daily for acetylcholinesterase-positive cells and CFU-M. The proliferative capacity of CFU-M was determined by culturing cells from STLC in secondary methylcellulose cultures and counting the number of megakaryocytes per colony. Positive dose-related effects were observed between the number of megakaryocytes and CFU-M in liquid culture and the concentration of PWCM in the culture. In contrast, the proliferative capacity of CFU-M was lower in cultures containing high concentrations of PWCM compared with cultures containing low concentrations of PWCM. Furthermore, mean megakaryocyte diameter was significantly smaller in cultures containing high levels of PWCM compared with cultures with low concentrations. These data suggest that at low levels of conditioned medium, megakaryocytopoiesis is characterized by production of fewer CFU-M with a higher proliferative capacity and fewer large megakaryocytes. In turn, high concentrations of PWCM promote the production of a greater number of CFU-M with reduced proliferative capacity and an increased number of small megakaryocytes.
Assuntos
Células da Medula Óssea , Ensaio de Unidades Formadoras de Colônias/métodos , Meios de Cultura/farmacologia , Hematopoese/efeitos dos fármacos , Megacariócitos/citologia , Animais , Adesão Celular , Divisão Celular , Masculino , Camundongos , Camundongos Endogâmicos , Mitógenos de Phytolacca americana/farmacologia , Baço/citologia , Fatores de TempoRESUMO
To determine how megakaryocyte progenitor cells (CFU-M) of W/Wv mice are affected by the hematopoietic stem cell abnormality, megakaryocytopoiesis was studied in the spleen and marrow of these genetically anemic W/Wv mice. CFU-M were assayed in the soft gel colony-forming system. Megakaryocyte colony size was determined by counting the number of megakaryocytes per colony, and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cell preparations with use of an eyepiece micrometer. In spite of normal blood platelet levels, megakaryocyte level was reduced in the spleen and humerus to about 60% that of +/+ littermates. Megakaryocyte diameters were increased in W/Wv mice. CFU-M in W/Wv mice were reduced to 40% the number seen in the spleen of +/+ mice and to 62% in the humerus. In cell cycle studies, significantly fewer marrow CFU-M were in DNA synthesis in W/Wv mice compared with +/+ animals, but similar numbers of cells were in cycle in the spleen for both genotypes. No difference was observed between W/Wv and +/+ CFU-M in their requirement for exogenous colony-stimulating activity or in the distribution of colony sizes. However, CFU-M-derived colonies cloned from adherent cell-depleted marrow cells were significantly smaller compared with those cultured from unfractionated marrow cells. Results for granulocytes and granulocyte-macrophage progenitor cells (CFU-GM) were similar to those obtained for the megakaryocyte series, indicating that the abnormalities are present in different cell lineages. These results suggest that the macromegakaryocytosis of W/Wv mice appears to be a compensation for the megakaryocytopenia. Cells in the progenitor cell compartment appeared not to be involved in this compensation. Furthermore, adherent cells appear to elaborate a factor regulating megakaryocyte development. These findings are compatible with two-level regulation of megakaryocyte formation and a complex mechanism of blood platelet level regulation.
Assuntos
Células da Medula Óssea , Hematopoese , Células-Tronco Hematopoéticas/citologia , Baço/citologia , Animais , Ciclo Celular , Células Cultivadas , Granulócitos/citologia , Hematócrito , Masculino , Megacariócitos/citologia , Camundongos , Contagem de PlaquetasRESUMO
Previous studies have reported that exposure of mice to hypoxic conditions results in a decrease in blood platelets. To further explore the effect of hypoxia on megakaryocytopoiesis, megakaryocytes and their progenitor cells (CFU-M) were studied in hypoxic mice. Mice were exposed to hypoxia by enclosure in cages covered with dimethyl-silicone rubber membranes for up to 10 d. At various times during the hypoxic and ex-hypoxic periods the total megakaryocytes and CFU-M were determined in the humerus and spleen. CFU-M were assayed in the soft gel colony forming assay using pokeweed mitogen-stimulated spleen cell conditioned medium (PWCM) as a source of colony stimulating activity. After 10 d of hypoxia, packed red cell volume (PRCV) increased to 148% of control levels and blood platelets decreased to 40% of controls. Total megakaryocytes and CFU-M per humerus decreased to 18% and 50% of controls respectively. 4 d into the ex-hypoxic phase, PRCV was still increased at 128% of controls while marrow megakaryocytes and CFU-M increased to normal levels. Platelet recovery was somewhat slower, returning to normal by d 6. In contrast to the findings in the marrow, total spleen megakaryocytes and CFU-M increased to about 3- and 5-fold of control levels respectively by 6 d of hypoxia. During the exhypoxic phase, CFU-M decreased to normal on d 4, followed by a rebound of 3-fold control values on d 8. Spleen megakaryocytes decreased more slowly, returning to normal by d 10. A marked granulocytosis was observed during the hypoxic phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Granulócitos/patologia , Hipóxia/patologia , Megacariócitos/patologia , Animais , Contagem de Células , Divisão Celular , Hematócrito , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos , Contagem de Plaquetas , Células-Tronco/patologiaRESUMO
The relationships between replicative DNA synthesis and retinoic acid (RA)-induced differentiation of human promyelocytic leukaemic (HL-60) cells are evaluated with the use of Aphidicolin, a specific and reversible inhibitor of DNA polymerase alpha (alpha). Addition of a sublethal concentration of Aphidicolin (0.4 microM) in culture for 3 days suppresses DNA synthesis to a similar level of the resting stage (day 8) in control cultures. DNA synthesis is reactivated to the level observed in the growing stage of control cultures once Aphidicolin is removed after 3 days in culture. The level of DNA synthesis at the early stage of RA-induction (day 3) is suppressed by only 17% when compared to control cultures. The inhibitory effect of Aphidicolin on DNA synthesis in both control cultures and RA-induced cell cultures is similar. However, no reactivation of DNA synthesis is observed after removal of Aphidicolin on day 3 from RA-induced cell cultures. Flow cytometric analysis of DNA content on day 3 reveals that cells accumulate in G1 and early S phases of the cell cycle after exposure to Aphidicolin with or without RA. Of interest is the fact that, while Aphidicolin alone did not induce cells to differentiate, neither did it interfere with RA-induced cell differentiation (the rate of RA-induced cell differentiation in the presence of Aphidicolin is similar to that of RA-treated cultures in the absence of Aphidicolin). These results suggest that the combined use of Aphidicolin and RA may inhibit leukaemic cell proliferation more effectively without causing severe cytotoxicity and without interfering with RA-induced cell differentiation.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Diterpenos/farmacologia , Tretinoína/farmacologia , Afidicolina , Linhagem Celular , Interações Medicamentosas , Citometria de Fluxo , Humanos , Cinética , Leucemia Mieloide AgudaRESUMO
Megakaryocytopoiesis and granulopoiesis of marrow cells from W/Wv mice were studied using a continuous liquid marrow culture system. Cells in the suspension phase were assayed weekly over a 16-week period for total nucleated cells, megakaryocytes, granulocytes, megakaryocytes and granulocyte-macrophage progenitor cells (CFU-Ms, CFU-GMs), and spleen colony-forming cells (CFU-Ss). Without hydrocortisone supplementation, proliferation of megakaryocytes, granulocytes, and their progenitor cells was significantly less in W/Wv cultures than in +/+ cultures. These cells became undetectable in both W/Wv and +/+ cultures at seven to 11 weeks in culture, after which only monocytes and macrophages proliferated in the cultures. Treatment of cultures with hydrocortisone improved megakaryocytopoiesis and granulopoiesis in both W/Wv and +/+ cultures. Following an initial lag phase of three to four weeks, proliferation of megakaryocytes, granulocytes, and their progenitor cells in W/Wv cultures equalled that observed in +/+ cultures and was sustained for 16 to 24 weeks. This improvement was associated with a sustained reduction in monocytes and macrophages. Despite improvements in megakaryocytopoiesis and granulopoiesis, production of macroscopic and microscopic spleen colonies by cells from W/Wv cultures remained severely reduced or absent. Studies of DNA synthesis rates of fresh marrow cells indicated that significantly fewer CFU-Ms and CFU-GMs were in cycle in W/Wv mice compared with +/+ mice. However, in hydrocortisone-treated W/Wv cultures, DNA synthesis rates of CFU-Ms and CFU-GMs increased markedly and equalled those observed for +/+ cultures. These results suggest that the improvements in megakaryocytopoiesis and granulopoiesis in hydrocortisone-treated liquid cultures is associated with a reduction in monocytes and macrophages and that progenitor cells of W/Wv mice have a proliferative defect that is correctable by hydrocortisone treatment in vitro.
Assuntos
Células da Medula Óssea , Granulócitos/citologia , Hematopoese , Megacariócitos/citologia , Animais , Divisão Celular , Ensaio de Unidades Formadoras de Colônias , Técnicas de Cultura , DNA/biossíntese , Células-Tronco Hematopoéticas/citologia , Masculino , Camundongos , Camundongos Mutantes , Baço/citologiaRESUMO
Mature blood cells have a finite life span and therefore continued production is required to maintain a constant level in tissues. Continuous replenishment is achieved by a constant feed-in from normal functioning hematopoietic stem cell compartments. The hematopoietic stem cell (HSC) system is characterized as follows: A totipotent hematopoietic stem cell (THSC) gives rise to all hematopoietic cells. Separate cells exist that are more differentiated progeny of THSC and are pluripotent for the myeloid system (PMSC: CFU-S, CFU-GEMM) and for the lymphoid system (PLSC). The PMSC gives rise to still more differentiated progenitor cells committed to erythrocytes (BFU-E, CFU-E), neutrophil-macrophages (CFU-NM) and megakaryocytes (CFU-MEG). One class of PMSC (CFU-S) is assayed in vivo. A second class of PMSC (CFU-GEMM), and most other types of progenitors (CFU-E, CFU-NM, CFU-MEG, etc.), are assayed in vitro. The mouse is the usual vehicle for the in vivo study of the CFU-S (colony-forming unit-spleen). Bone marrow cells are infused into lethally irradiated recipient mice, lodge in the spleen, and proliferate to form macroscopic colonies on the surface. There is no similar assay available in man, but the ability to clone mixed colonies (CFU-GEMM) in vitro allows one to study human pluripotent stem cells. In the presence of appropriate stimuli, CFU-GEMM form colonies in soft gel that contain granulocytes, erythroid cells, macrophages, and megakaryocytes. In addition to this class of PMSC, the differentiated progenitors that are committed to produce erythroid cells, neutrophils, megakaryocytes, or monocytes-macrophages also form colonies in vitro. A third method of determining the effect of antineoplastic agents on marrow cells is by use of the diffusion chamber (DC) culture technique. Marrow cells are inoculated into a diffusion chamber that is then implanted into the peritoneum of a mouse. After various time periods, chambers are removed and the number and differentiated cell types are determined. Modifications of the DC chamber technique include suspending marrow cells in a plasma clot or in agar within the chambers, which permits the growth of colonies within the chamber. A fourth method of assessing toxicity is by the use of the continuous long-term in vitro culture system. In this system, proliferation of marrow cells is supported by an adherent layer of marrow stromal cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Diferenciação Celular , Ensaio de Unidades Formadoras de Colônias , Macrófagos/citologia , Camundongos , Neutrófilos/citologia , Técnicas de Cultura de Órgãos , Baço/citologiaRESUMO
Thrombopoiesis and granulopoiesis following murine cytomegalovirus infection were investigated by studying changes in megakaryocytes, megakaryocyte and granulocyte-macrophage progenitor cells, and spleen colony-forming cells. The soft gel in vitro culture system was used to assay for megakaryocyte and granulocyte-macrophage progenitor cells in marrow and spleen. Murine cytomegalovirus produced a mild thrombocytopenia to 90% of control values 1 day after infection at a time when marrow megakaryocyte levels were normal, suggesting a mild direct toxic effect of the virus on platelets. A reduction of megakaryocytes, megakaryocyte and granulocyte-macrophage progenitor cells, and spleen colony-forming cells to 40% to 60% of control values occurred within 24 to 48 hours of infection in association with an additional decrease in platelets to 58% of control levels on day 4. In vitro inoculation of marrow cell cultures with murine cytomegalovirus also resulted in a reduction of megakaryocyte- and granulocyte-macrophage colony-forming cells within 24 to 48 hours, suggesting that murine cytomegalovirus-induced thrombocytopenia and granulocytopenia may be in part caused by direct infection of precursor cells. The recovery of cells in the spleen was followed by a striking seven- to 10-fold increase in spleen colony-forming cells and megakaryocyte and granulocyte-macrophage progenitor cells in the spleen. These marked increases followed significant increases in spleen cell production of colony-stimulating activities within 2 days of murine cytomegalovirus infection, suggesting that hematopoietic cell recovery is mediated by increased local production of colony-stimulating activities in the spleen.
Assuntos
Infecções por Citomegalovirus/complicações , Granuloma/etiologia , Megacariócitos/microbiologia , Animais , Ensaio de Unidades Formadoras de Colônias , Infecções por Citomegalovirus/sangue , Úmero/microbiologia , Masculino , Camundongos , Baço/microbiologia , Células-Tronco/microbiologiaRESUMO
A 60-kilodalton protein was identified in chromatin digested by micrococcal nuclease during retinoic acid-induced differentiation of human leukemia (HL-60) cells to mature-like granulocytes. The protein was not detected in a retinoic acid-resistant variant of the HL-60 cell line treated with retinoic acid, in HL-60 cells induced with dimethyl sulfoxide, or in normal human granulocytes. This protein may have an important role in the regulation of retinoic acid-induced leukemic cell differentiation.
Assuntos
Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/isolamento & purificação , Nucleossomos/metabolismo , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Centrifugação com Gradiente de Concentração , Dimetil Sulfóxido/farmacologia , Eletroforese em Gel de Poliacrilamida , Granulócitos/metabolismo , Humanos , Tretinoína/farmacologiaRESUMO
CTX is a marrow-suppressant drug that has been reported to have a "sparing effect" on blood platelets. To investigate whether CTX spares platelet precursor cells as well as platelets, blood platelets, megakaryocytes, and CFU-M were studied in mice after the injection of CTX. The soft gel in vitro culture system was utilized to assay for CFU-M in marrow and spleen. CTX produced only a mild thrombocytopenia to 88% to 95% of control values. This was followed by a modest, but significant thrombocytosis of 120% of controls on day 10. Despite the slight effect on blood platelets, striking changes were observed in megakaryocytes and CFU-M. Megakaryocytes and CFU-M were decreased to 10% to 25% of control values within 24 hr of CTX administration. This was followed by a recovery of spleen megakaryocytes and CFU-M to normal within 6 days, followed by a 24-fold increase above control values in spleen megakaryocytes and a 29-fold increase in spleen CFU-M. In contrast, recovery of megakaryocytes and CFU-M in the marrow was delayed for 2 weeks. An increase in marrow CFU-M above control values was not observed, although megakaryocytes increased to 150% of control. Granulocytes and their progenitor cells (CFU-GM) responded in a similar manner after CTX administration. These results indicate that blood platelet levels are only slightly decreased after a single injection of CTX whereas CFU-M and megakaryocytes are markedly decreased. The recovery and increased production of megakaryocytes and CFU-M in the face of a near-normal platelet level suggests that factors other than the platelet level are responsible for production of CFU-M and megakaryocytes.
Assuntos
Ciclofosfamida/farmacologia , Granulócitos/efeitos dos fármacos , Megacariócitos/efeitos dos fármacos , Animais , Plaquetas/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos , Baço/efeitos dos fármacos , Fatores de TempoRESUMO
A patient with monoclonal IgG lambda rheumatoid factor was observed over a period of four years. During this time, serum level of the monoclonal protein fluctuated around 150 mg/dL and homogeneous lambda light chains were present in the urine. The patient died of squamous-cell carcinoma of the lung and no evidence of multiple myeloma was present at the time of autopsy. However, the patient had systemic amyloidosis that affected primarily the blood vessels in most organs. Both the vascular and parenchymal amyloid deposits stained for lambda light chains by the immunoperoxidase technique. These data support the hypothesis that amyloidogenic monoclonal immunoglobulins may be autoantibodies.
Assuntos
Amiloidose/imunologia , Carcinoma de Células Escamosas/imunologia , Cadeias Leves de Imunoglobulina/imunologia , Cadeias lambda de Imunoglobulina/imunologia , Neoplasias Pulmonares/imunologia , Fator Reumatoide/imunologia , Amiloidose/complicações , Amiloidose/diagnóstico , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Vasos Coronários , Diagnóstico Diferencial , Eletroforese , Humanos , Hipercalcemia/complicações , Hipercalcemia/diagnóstico , Hipercalcemia/imunologia , Técnicas Imunoenzimáticas , Cadeias lambda de Imunoglobulina/análise , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Miocárdio/imunologia , Pâncreas/irrigação sanguínea , Pâncreas/imunologia , Fator Reumatoide/análiseRESUMO
Three patients with leukemia developed corneal toxicity while receiving high doses (3 g/m2) of systemic cytarabine. Symptoms began five to seven days after initiation of treatment with high doses of systemic cytarabine and consisted of ocular pain, tearing, foreign-body sensation, photophobia, and blurred vision. All three patients developed bilateral conjunctival hyperemia and fine corneal epithelial opacities and refractile microcysts that were more numerous in the central than in the peripheral cornea. The symptoms disappeared without treatment in approximately one week. The corneal changes we observed with high doses of systemic cytarabine resembled descriptions of corneal toxicity from topical cytarabine and were probably secondary to inhibition of DNA synthesis in the corneal epithelium.
Assuntos
Doenças da Córnea/induzido quimicamente , Citarabina/efeitos adversos , Leucemia Mieloide/complicações , Doenças da Córnea/patologia , Opacidade da Córnea/induzido quimicamente , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
In 19 patients with Felty's syndrome, marrow production of neutrophils and neutrophil distribution were studied. Despite accelerated marrow release and disappearance of mature blood neutrophils, there was little or no increase in the marrow mitotic pool or in vitro progenitor cells. Only two patients had an increase in marrow neutrophils and precursors. Antineutrophil antibody was detected in seven of nine patients studied. Neither abnormal margination of blood neutrophils nor impaired marrow release of cells was detected. Skin exudate cellularity tended to correspond to prior history of infections, asymptomatic patients having more cellular exudates. Sustained neutrophil increments were observed in six of 10 patients following splenectomy, but in no patient did neutrophil kinetics return completely to normal. Three of four patients who failed to respond to splenectomy with sustained increments in blood neutrophils had a reduced mass of marrow neutrophils and neutrophil precursors when studied prior to splenectomy. No diminution in neutropenia was observed in any of five patients treated with lithium carbonate. This study indicates that multiple factors are involved in the pathogenesis of neutropenia in Felty's syndrome. In particular, neutropenia was associated with inadequate marrow granulocytopoiesis. The severity of the impairment, as determined by the mass of marrow neutrophils and precursor cells, may be useful in predicting response to splenectomy.
Assuntos
Agranulocitose/etiologia , Síndrome de Felty/sangue , Neutropenia/etiologia , Neutrófilos/patologia , Idoso , Medula Óssea/patologia , Síndrome de Felty/cirurgia , Feminino , Seguimentos , Hematócrito , Hematopoese , Humanos , Técnicas In Vitro , Cinética , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Neutropenia/sangue , Contagem de Plaquetas , EsplenectomiaAssuntos
Antibióticos Antineoplásicos/farmacologia , Granulócitos/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Lítio/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Fatores Estimuladores de Colônias/biossíntese , Meios de Cultura , Ciclofosfamida/farmacologia , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Neutrófilos , Vimblastina/farmacologiaAssuntos
Fatores Estimuladores de Colônias/biossíntese , Granulócitos/efeitos dos fármacos , Lítio/farmacologia , Células da Medula Óssea , Adesão Celular , Ensaio de Unidades Formadoras de Colônias , Humanos , Linfócitos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Fagócitos/efeitos dos fármacosAssuntos
Bussulfano/toxicidade , Ensaio de Unidades Formadoras de Colônias , Hematopoese/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Eritropoese/efeitos dos fármacos , Eritropoese/efeitos da radiação , Feminino , Hematócrito , Ferro/metabolismo , Radioisótopos de Ferro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Quimera por RadiaçãoRESUMO
The adult mouse spleen retains granulocytic progenitor cells that are capable of proliferation and maturation. In mice given cyclophosphamide, spleen weight and cell content increased. In vitro granulocyte progenitor cells increased more than 300-fold in the spleen and remained elevated 14 days following cyclophosphamide. Proliferative and nonproliferative granulocytes were increased above controls until Days 21 and 28, respectively. In splenectomized mice, blood neutrophil recovery was delayed when compared to nonsplenectomized mice following cyclophosphamide. Although marrow cell number was similar in both groups, maximum marrow granulocyte progenitor cells were 2-fold greater in nonsplenectomized animals. These studies demonstrate that the murine spleen becomes a markedly granulopoietic organ and is a major contributor to recovery of granulocytes following cyclophosphamide. Splenic granulopoiesis should be taken into account in studies which measure toxicity of various agents in murine hematopoiesis.