RESUMO
We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion.
Assuntos
Bicamadas Lipídicas/química , Fenômenos Mecânicos , Elasticidade , Modelos MolecularesRESUMO
BACKGROUND: RHD alleles leading to a reduced expression of D antigen of the red blood cell (RBC) surface may be erroneously typed as D- by serology and may cause anti-D immunizations when transfused to recipients. METHODS: To determine the occurrence of such alleles among apparent D- blood donors, molecular typing was implemented as a routine test using a pool of DNA. A total of 2,450 pretyped D- samples were tested in pools of 10 for the RHD-specific polymorphism in intron 4 and exon 7. Samples in polymer chain reaction (PCR) positive pools were individually reevaluated by exon-specific PCRs, sequencing, and serologic methods. RESULTS: Among 2,450 serologically D- blood donor samples tested, 101 (4.1%) carried the RHD gene. Nonfunctional RHD (RHDψ, RHD*CE(2-9)-D, and RHD*CE(3-7)-D), different weak D alleles such as RHD*weak D type 1, RHD*weak D type 4.3, RHD*weak D type 5, RHD*weak D type 38, and RHD*DEL were identified. CONCLUSION: We employed a PCR-based assay for RHD as a routine test using pools of ten DNA blood donor samples. The integration of RHD genotyping into the routine screening program using pools of DNA samples was straightforward. As a consequence, 19 (0.8%) blood donors carrying a weak D and Del phenotypes with the potential of causing anti-D immunizations in recipients were reclassified as D+. For each population, it would be necessary to adapt the RHD genotyping strategy to the spectrum of prevalent alleles.
Assuntos
Alelos , Doadores de Sangue , DNA/genética , Testes Diagnósticos de Rotina/métodos , Tipagem Molecular/métodos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Brasil , Seguimentos , Humanos , Polimorfismo GenéticoRESUMO
The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions is not an easily determined complication of RBC transfusions. This report discusses one patient who developed RBC autoantibodies in association with an allogeneic blood transfusion and alloimmunization leading to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized as a result of severe anemia and received two units of ABO- and D-compatible RBCs. She had a history of two pregnancies 40 years before, but no history of RBC transfusion, and her antibody screen was negative. On the tenth day after transfusion her hemoglobin dropped, and alloanti-c was identified in her serum and eluate. At this time she received another two units of compatible blood according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3 g/ dL. The direct antiglobulin test was positive, an IgG autoantibody was present in the eluate, and the antibody investigation revealed the presence of anti-Jk(b) in addition to the previously identified alloanti-c. Her genotype was determined, and, based on the findings, two additional units were selected, found to be compatible, and transfused without incident. Transfusions were discontinued, and she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and the patient made an uneventful recovery. It was concluded that transfusion of incompatible RBCs induced the formation of an autoantibody in this patient, resulting in lysis of bystander RBCs. The need for additional blood transfusion was successfully avoided by treatment with IVIG, steroid therapy, and rituximab.
Assuntos
Autoanticorpos/biossíntese , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Eritrócitos/imunologia , Hemólise/imunologia , Reação Transfusional , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antígenos de Grupos Sanguíneos/genética , Incompatibilidade de Grupos Sanguíneos/complicações , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , RituximabRESUMO
The interaction of colony-stimulating factors (CSF) and retinoic acid (RA) in the proliferation and differentiation of HL-60 cells was examined. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated the proliferation of HL-60 cells in a dose-dependent manner at concentrations of 0.01-100 ng/ml; however, the proliferation due to GM-CSF was suppressed by 100 nM RA. Granulocyte colony-stimulating factor (G-CSF) slightly stimulated the proliferation of HL-60 cells at concentrations above 10 ng/ml. Neither G-CSF nor GM-CSF alone induced 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)- or N-formyl-methionyl-phenylalanine (FMLP)-stimulated nitro-blue tetrazolium (NBT) reduction at concentrations of 0.01-100 ng/ml. G-CSF induced TPA- and FMLP-stimulated NBT reduction in the presence of 100 nM RA, but GM-CSF induced only TPA-stimulated NBT reduction. RA in addition to G-CSF synergistically increased FMLP binding to HL-60 cells, accompanied by increased NBT reduction in response to FMLP. RA in addition to GM-CSF markedly increased FMLP binding to HL-60 cells more than that induced by RA alone, but the combined treatment with RA and GM-CSF did not increase FMLP-stimulated NBT reduction more than that induced by RA alone. The results suggest that G-CSF stimulates RA-induced morphological and functional differentiation of HL-60 cells, but the differentiation-enhancing effects of GM-CSF are limited, whereas the growth-stimulating effect of GM-CSF on HL-60 cells is greater than that of G-CSF.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Leucemia Promielocítica Aguda/metabolismo , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Receptores Imunológicos/biossíntese , Tretinoína/farmacologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Leucemia Promielocítica Aguda/patologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Nitroazul de Tetrazólio/metabolismo , Receptores de Formil Peptídeo , Timidina/metabolismo , Células Tumorais CultivadasRESUMO
We studied differentiation inducing effects of retinoic acid (RA), 1 alpha, 25-dihydroxyvitamin D3 (D3) and interferons (IFNs), alone and in combination, on fresh myeloid leukemic cells from 8 patients. RA not only induced the differentiation of leukemic cells in 5/8 cases, but potentiated differentiation by IFNs either in granulocytic or monocytic pathways. In particular, interferon-alpha enhanced granulocytic differentiation and interferon-gamma induced mono-macrophage differentiation of promyelocytic leukemic cells in the presence of RA. Differentiation induced by D3, alone or in combination with IFNs, was limited in all cases. RA plus IFNs might be an effective combination for differentiation therapy for some types of myeloid leukemia.
Assuntos
Interferon Tipo I/farmacologia , Interferon gama/farmacologia , Leucemia Mieloide Aguda/patologia , Tretinoína/farmacologia , Diferenciação Celular/efeitos dos fármacos , Colecalciferol/farmacologia , Esterases/análise , Humanos , Muramidase/análise , Nitroazul de Tetrazólio/metabolismo , Células Tumorais CultivadasRESUMO
We studied MLL rearrangements in five patients with myeloid hematologic malignancies with trisomy 11. Two had acute monocytic leukemia (AMoL), one had chronic myelomonocytic leukemia, one had refractory anemia, and the other had juvenile chronic myelogenous leukemia. Only one patient, a 15-year-old boy with AMoL and simple trisomy 11, showed rearrangement of MLL. He did not respond to chemotherapy, and successfully underwent bone marrow transplantation, but suffered a relapse 22 months later. Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing analyses of bone marrow cells revealed a tandem duplication of MLL, and his relapse was predictable by sequential RT-PCR studies before it was clinically evident. Of 16 acute myeloid leukemia patients with trisomy 11 and rearrangement of MLL reported, our patient was the youngest in age and the only one with AMoL.
Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Monocítica Aguda/genética , Proto-Oncogenes , Sequências Repetitivas de Ácido Nucleico/genética , Fatores de Transcrição , Trissomia , Adolescente , Idoso , Anemia Refratária/genética , Southern Blotting , Pré-Escolar , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielomonocítica Crônica/genética , Masculino , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide , Neoplasia Residual , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
A patient with acute myelomonocytic leukemia (M4 in FAB classification) refractory to various kinds of intensive chemotherapy was intravenously administered low doses (7 or 14 mg/m2) of aclacinomycin-A (ACM-A) daily. This increased mature neutrophils and monocytes and decreased leukemia cells in the peripheral blood. Pelger Huet-like nuclear anomaly, observed in the neutrophils, suggested the leukemic nature of these cells. The in vivo findings were clearly correlated with the in vitro results in which ACM-A could induce myelomonocytic differentiation of the leukemia cells. During the course of the treatment, the patient achieved and maintained good general condition for more than nine months after the initiation of the treatment. In clinical trials, nine patients, five with acute myeloid leukemia (AML) and four with myelodysplastic syndrome (MDS), were treated with low doses of ACM-A. Five patients, three AML and two MDS, responded to the treatment. The results suggest that low doses of ACM-A may induce in vivo differentiation of leukemia cells, and may be a potential therapeutic strategy in the treatment of AML or MDS that is refractory to conventional chemotherapy.
Assuntos
Aclarubicina/uso terapêutico , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Adulto , Calcitriol/farmacologia , Diferenciação Celular/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Humanos , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
The effects of glucocorticoid on the differentiation of myeloid leukemia cells were examined. Dexamethasone at 10(-6)M or 10(-7)M revealed marked effects not only on leukemic blasts' survival but also on its' differentiation in vitro. In 10 of 17 cases of myeloid leukemia, the obvious morphological and functional differentiation induction effects were observed in vitro. The direction of differentiation were differed in leukemia cell lineage and in cases. Granulocytic differentiation in M2 cells, mono-macrophage differentiation in M5 cells and either granulocytic or monocytic differentiation in M4 cells were induced. A AML (M2), it's leukemia cells were induced into granulocytic pathway by dexamethasone in vitro, was treated with prednisolone (40 mg per day).Ara-C (15 mg per day). The increase in peripheral leukocyte count and the decrease in immature cells were observed simultaneously. The peripheral leukocytes mainly consisted of intermediate forms of granulocytes and Pelger-Huët like neutrophils probably originated from leukemia cells. After that course, abnormal clone was eliminated from bone marrow. A AMoL, it's leukemia cells were induced into macrophage like cells completely by dexamethasone in vitro, was treated with prednisolone (30 mg per day) and complete remission was obtained without passing through a hematological nadir. It is indicated that anti-tumor effects of glucocorticoid on myeloid leukemia cells are closely related to it's differentiation inducing effect and glucocorticoid can be used as the drug intending for the differentiation induction therapy of acute myeloid leukemia.
Assuntos
Dexametasona/farmacologia , Leucemia Mieloide/patologia , Prednisolona/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citarabina/administração & dosagem , Feminino , Humanos , Leucemia Monocítica Aguda/tratamento farmacológico , Leucemia Monocítica Aguda/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Indução de Remissão , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
A 57-year-old male who had suffered from polycythemia vera (PV) and had been treated with pipobroman, carbazilquinon and busulfan for ten years presented with fever. CBC revealed anemia and thrombocytopenia without an increase of leukemic blasts (WBC, 7,700/microliters, RBC 294 x 10(4)/microliters, Hb 9.1 g/dl, Plt 1.5 x 10(4)/microliters). Bone marrow aspiration resulted in dry tap. Bone marrow biopsy showed hyperplastic marrow with fibrosis and no increase in leukemic blasts. Eleven days later the patient became leukemic and he died of DIC. Blast cells showed a high nucleo-cytoplasmic ratio, basophilic cytoplasm and cytoplasmic blebs. Cytochemical and immunophenotype analysis of the blast cells showed the following results; myeloperoxidase (-), chloroacetate esterase (-), Sudan black (-), acid phosphatase (+), acetate esterase (+), PAS (+), HLA-DR (+) and GPIIb/IIIa (+). Platelet peroxidase reaction on electron microscopy was positive in perinuclear spaces and endoplasmic reticulum. A diagnosis of megakaryoblastic transformation of PV was made. Although acute myelogenous leukemia has been shown to develop occasionally in the course of PV, acute megakaryoblastic leukemia with DIC following PV is a very rare condition.
Assuntos
Crise Blástica/patologia , Coagulação Intravascular Disseminada/complicações , Leucemia Megacarioblástica Aguda/patologia , Policitemia Vera/patologia , Bussulfano/administração & dosagem , Carbazilquinona/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pipobromano/administração & dosagem , Policitemia Vera/tratamento farmacológicoRESUMO
A 64-year-old male was admitted in September 1989 with complaints of fever and muscular weakness in the extremities. A peripheral blood examination on admission revealed WBC 10,300/microliters (monocytes 32%), RBC 195 x 10(4)/microliters, Hb 7.9 g/dl, Plt 12.8 x 10(4)/microliters with trilineage dysplasia. Bone marrow biopsy was normoplastic marrow with 25.7% of monocytes including immature blasts. Cytochemical analysis of the monocytes showed positive for peroxidase and dual esterase staining. Chromosomal analysis of peripheral blood revealed 46, XY, -7, +der(1) t(1;7)(p11;p11). A diagnosis of chronic myelomonocytic leukemia was made. Hemostatic studies revealed cryofibrinogenemia, marked platelet aggregation on blood smear, hyperfibrinogenemia and a marked increase in maximal amplitude of thrombelastogram. Treatment with prednisolone and VP16, resulted in a reduction of peripheral monocytes and a disappearance of cryofibrinogen, marked platelet aggregation and a decrease in muscular weakness. Nine months after diagnosis he died of DIC, pneumonia, lung abscess and sepsis.
Assuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 7 , Fibrinogênios Anormais/metabolismo , Leucemia Mielomonocítica Crônica/genética , Agregação Plaquetária , Translocação Genética , Temperatura Baixa , Humanos , Leucemia Mielomonocítica Crônica/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
UNLABELLED: The cryopreservation of hematopoietic stem cells can be used for rescuing the hematopoiesis after high dose chemotherapy. PURPOSE: The ice crystal formation during the freezing procedure is the key point that can be harmful to the cells. The cryopreservation of hematopoietic stem cells in a controlled-rate freezer could decrease the cell damage. METHODS: Twenty-three patients with a median age of 26 years (range 03-57) had bone marrow and/or peripheral blood stem cells harvested from March 1993 through October 1994, ending up to 86 freezing procedures. The patient's diagnoses are as follows: Non-Hodgkin's Lymphoma (n = 5); Acute Myelogenous Leukemia (n = 8); Acute Lymphocytic Leukemia (n = 6); Hodgkin's disease (n = 3); Multiple Myeloma (n = 1). The cells were frozen away in a controlled-rate freezer chamber at the following rate: -1 degree C/min from room temperature to -45 degrees C and then, at -10 degrees C/min down to -80 degrees C. After freezing, the cells were kept into mechanical freezers until the marrow infusion. To mobilize PBSC (peripheral blood stem cells), G-CSF (granulocyte colony stimulating factor) was given. RESULTS: A median of 3.16 x 10(8) cells/kg (range 0.86-24.22) of PBSC and 2.03 x 10(8) cells/kg (0.19-12.21) of bone marrow cells were frozen. The median time to reach granulocytes greater than 500/microL and platelets greater than 20,000/microL was 12 days (range 8-40) and 31 days (range 8-80), respectively. All patients had marrow engraftment after infusion of hematopoietic stem cells. CONCLUSION: The cryopreservation procedure using a controlled-rate freezer can store hematopoietic stem cells and potentially, cause less damage to the cells.
Assuntos
Medula Óssea , Criopreservação/métodos , Células-Tronco , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hematopoese , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
I.c.v. administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI), induces anorexigenic and anxiogenic-like actions in rodents. We have recently shown that, in goldfish, i.c.v. injection of ODN also reduces food consumption via the metabotropic endozepine receptor. However, there is little information regarding the structure of DBI and the psychophysiological roles of endozepines in fish. Therefore, in the present study, we isolated and cloned a cDNA encoding goldfish DBI. The deduced sequence exhibits high similarity with non-mammalian DBIs, and we investigated the effect of homologous ODN on psychomotor activity in goldfish. i.c.v. injection of synthetic goldfish ODN at 10 pmol/g body weight (BW) stimulated locomotor activity. Since intact goldfish placed in a tank with both black and white background areas prefers the black compartment, we developed a method for measuring the time taken for fish to move from the black to the white area. I.c.v. administration of diazepam (35 and 350 pmol/g BW) decreased, whereas i.c.v. administration of ODN (10 pmol/g BW) or the central-type benzodiazepine receptor inverse agonist FG-7142 (9 pmol/g BW) increased the time taken to move from the black to the white background area. The anxiogenic-like effect of ODN was blocked by the central-type benzodiazepine receptor antagonist flumazenil (100 pmol/g BW), but was not affected by the metabotropic endozepine receptor antagonist cyclo1-8[d-Leu(5)]octapeptide (100 pmol/g BW). These data indicate that ODN can potently affect locomotor and psychomotor activities in goldfish and that this action is mediated via the central-type benzodiazepine receptor-signaling pathway.
Assuntos
Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/fisiopatologia , Inibidor da Ligação a Diazepam/fisiologia , Carpa Dourada/fisiologia , Atividade Motora/fisiologia , Neuropeptídeos/fisiologia , Fragmentos de Peptídeos/fisiologia , Animais , Comportamento Animal/fisiologia , Inibidor da Ligação a Diazepam/genética , Inibidor da Ligação a Diazepam/isolamento & purificação , Modelos Animais de Doenças , Feminino , Masculino , Neuropeptídeos/genética , Neuropeptídeos/isolamento & purificação , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/isolamento & purificaçãoAssuntos
Antibióticos Antineoplásicos/farmacologia , Genes abl , Leucemia/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinonas/farmacologia , Benzoquinonas , Diferenciação Celular/efeitos dos fármacos , Humanos , Lactamas Macrocíclicas , Leucemia/patologia , Rifabutina/análogos & derivados , Células Tumorais Cultivadas/efeitos dos fármacosAssuntos
Linfoma/patologia , Neoplasias Bucais/patologia , Idoso , Bochecha , Humanos , Metástase Linfática , Masculino , Mucosa Bucal/patologia , Linfócitos TRESUMO
Generation of superoxide may be a key step in the cytotoxicity mediated by tumour necrosis factor (TNF); cells that cannot produce oxygen radicals might be resistant to TNF. Myeloid haemopoietic cells from patients with chronic granulomatous disease (CGD) cannot produce a large burst of oxygen radicals; therefore we examined the ability of TNF to inhibit clonal growth of myeloid haemopoietic cells from patients and carriers with several types of CGD. Mononuclear light-density cells from the peripheral blood of 13 CGD patients (11 patients with defects of gp91-phox and two with p47-phox), five gp91-phox carriers and 10 normal volunteers were cultured with the appropriate growth factor and TNF in methylcellulose. As expected, TNF (0.001-100 ng/ml) inhibited colony formation of myeloid cells of normal volunteers in a dose-dependent manner. In contrast, clonal growth of myeloid cells of CGD patients was resistant to inhibition by TNF < or = 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which are not capable of producing an oxygen burst, and the action of TGF-beta on clonal growth of myeloid cells, were similar in both the individuals with CGD and the normal volunteers. In X chromosome-linked female carriers of CGD (gp91-phox deficiency), TNF showed an intermediate cytotoxicity on clonal growth of myeloid cells, and analysis of NBT reduction demonstrated that the colonies derived from myeloid cells deficient in gp91-phox were resistant to TNF and those derived from the myeloid cells expressing gp91-phox were inhibited in their proliferation by TNF. This study shows for the first time that myeloid haemopoietic cells from patients with CGD are relatively resistant to the growth-inhibiting effects of high concentrations of TNF.
Assuntos
Medula Óssea/patologia , Granulócitos/patologia , Doença Granulomatosa Crônica/patologia , Linfotoxina-alfa/farmacologia , Monócitos/patologia , Fator de Necrose Tumoral alfa/farmacologia , Divisão Celular , Resistência a Medicamentos , Células Precursoras Eritroides/metabolismo , Células Precursoras Eritroides/patologia , Feminino , Granulócitos/metabolismo , Doença Granulomatosa Crônica/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Monócitos/metabolismo , Explosão Respiratória/efeitos dos fármacos , Superóxidos/metabolismoRESUMO
Ultraviolet light (UV)-induced DNA repair during myeloid leukemic cell differentiation was examined. Human myeloid leukemic cells could be induced to differentiate in vitro into mature cells by various chemical inducers that lost their proliferating potencies. In spite of decrease of proliferation capacity, almost all these terminally differentiated myeloid leukemic cells invariably showed UV-induced unscheduled DNA synthesis (UDS) at low energy of UV irradiation (3-5J/m2). This indicated that the terminally differentiated myeloid leukemic cells are functionally quite different from mature granulocytes in chronic myeloid leukemia (CML) or in normal peripheral blood. In HL-60 cells, UV-survival was enhanced in the process of differentiation induced by 1.25% DMSO or 0.6 mM sodium n-butyrate. The degree of enhancement of UV-survival was correlated with the increased amount of UDS. The process of myeloid leukemic cell differentiation which is completed without loss of capacity performing repair DNA synthesis was one of the characteristics of the terminally differentiated myeloid leukemic cells induced by chemical inducers in vitro and this function may support the hypothesis that DNA breaking and rejoining are involved in a mechanism of cytodifferentiation.
Assuntos
Reparo do DNA/efeitos da radiação , DNA de Neoplasias/efeitos da radiação , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Promielocítica Aguda/genética , Diferenciação Celular/efeitos da radiação , Humanos , Células Tumorais Cultivadas , Raios UltravioletaRESUMO
Chylomicrons are the lipoproteins that transport dietary lipids in the blood. Although neoplastic diseases are often accompanied by alterations in lipid metabolism, chylomicrons are scarcely explored in cancer, despite their importance for the body's energy supply. Moreover, no data are available regarding chylomicron metabolism in chronic lymphocytic leukemia (CLL). Chylomicron metabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver and is difficult to assess in the human body. Among the methods to evaluate this pathway, the determination of the plasma kinetics of triglyceride-rich emulsions that mimic chylomicrons is a practical and straightforward approach. A double-labeled chylomicron-resembling emulsion was injected into 10 patients with CLL and into 11 normolipidemic healthy subjects. The plasma kinetic curves of the emulsion 3H-triglyceride and 14Ccholesteryl ester were determined in plasma samples collected over 30 min. The fractional clearance rate (FCR) of triglycerides in CLL was not changed compared with controls. The FCR of cholesteryl esters was also no different from controls. These results indicate that chylomicron lipolysis and remnant removal are not affected in CLL.
Assuntos
Quilomícrons/sangue , Emulsões/metabolismo , Leucemia Linfocítica Crônica de Células B/sangue , Idoso , Idoso de 80 Anos ou mais , Radioisótopos de Carbono , Ésteres do Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Quilomícrons/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Trioleína/análise , TrítioRESUMO
We studied 116 patients (93 children and 23 adults) with acute lymphoblastic leukaemia (ALL) using fluorescence in situ hybridization (FISH) with the yeast artificial chromosome (YAC) clone, 964c10, which includes the recently described ETS-like gene, TEL, on 12p13. FISH revealed that nine of the patients had a t(12;21), which had not been previously detected. The nine patients were all children, seven boys and two girls, aged 1-10 years (median 3 years), had an early B immunophenotype, and achieved complete remission, although two of them experienced haematological relapse. In addition to the t(12;21), FISH also revealed that three of the nine had a del(12p) in the other homolog of chromosome 12 or in the der(12) chromosome itself, and that two others had 12p translocations in the other chromosome 12 homolog. Although chromosomal rearrangements associated with the t(12;21) were heterogenous and complex, fusion of the sequences from chromosomes 12 and 21 on the der(21)t(12;21) chromosomes was consistent, suggesting that the TEL-AML1 gene fusion on the der(21) chromosome may be critical in leukaemogenesis and that FISH or reverse transcriptase-polymerase chain reaction (RT-PCR) targeted to the chimaeric sequences on the der(21) will be most useful in detecting the t(12;21) or following a patient with the t(12;21), which is one of the most frequent chromosomal rearrangements in both Caucasian and Asian childhood ALL.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Lactente , Interfase , Cariotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
The mechanism of growth inhibition mediated by tumor necrosis factor (TNF) is unclear. Since recent data strongly suggested that generation of superoxide is a key step in cytotoxicity of TNF, we reasoned that cells expressing high levels of enzymes that degrade superoxide radicals would be resistant to TNF. Therefore, we examined the TNF-sensitivity of bone marrow progenitor cells of transgenic mice that expressed the gene for human copper zinc-superoxide dismutase (CuZn-SOD). The CuZn-SOD is a key enzyme in the metabolism of superoxide radicals. Heterozygous and homozygous transgenic mice had 3- and 5-fold increased levels of CuZn-SOD activity, respectively. Bone marrow cells of transgenic and nontransgenic mice were plated in soft gel culture with TNF (0.01-100 ng/ml). TNF inhibited myeloid colony formation supported by either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF from nontransgenic mice in a dose-dependent manner. In contrast, the myeloid clonal growth of homozygote transgenic mice was not inhibited by TNF at concentrations up to 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which do not produce superoxide, and the action of transforming growth factor-beta on myeloid progenitor cells, were similar in both transgenic and nontransgenic mice. These results suggest that the mechanism of TNF-mediated growth inhibition of hematopoietic cells occurs through production of superoxide.