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1.
AJNR Am J Neuroradiol ; 37(12): 2328-2333, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27516241

RESUMO

BACKGROUND AND PURPOSE: DWI with conventional single-shot EPI of the pituitary gland is hampered by strong susceptibility artifacts. Our purpose was to evaluate the feasibility of intravoxel incoherent motion assessment by using DWI based on TSE of the normal anterior pituitary lobe. MATERIALS AND METHODS: The intravoxel incoherent motion parameters, including the true diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*), were obtained with TSE-DWI in 5 brain regions (the pons, the WM and GM of the vermis, and the genu and splenium of the corpus callosum) in 8 healthy volunteers, and their agreement with those obtained with EPI-DWI was evaluated by using the intraclass correlation coefficient. The 3 intravoxel incoherent motion parameters in the anterior pituitary lobe were compared with those in the brain regions by using the Dunnett test. RESULTS: The agreement between TSE-DWI and EPI-DWI was moderate (intraclass correlation coefficient = 0.571) for D, substantial (0.699) for f', but fair (0.405) for D*. D in the anterior pituitary lobe was significantly higher than in the 5 brain regions (P < .001). The f in the anterior pituitary lobe was significantly higher than in the 5 brain regions (P < .001), except for the vermian GM. The pituitary D* was not significantly different from that in the 5 brain regions. CONCLUSIONS: Our results demonstrated the feasibility of intravoxel incoherent motion assessment of the normal anterior pituitary lobe by using TSE-DWI. High D and f values in the anterior pituitary lobe were thought to reflect its microstructural and perfusion characteristics.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Hipófise/diagnóstico por imagem , Adulto , Artefatos , Feminino , Humanos , Masculino , Movimento (Física)
2.
Bone Marrow Transplant ; 46(6): 820-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20818443

RESUMO

We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans retinoic acid-based induction therapy. After two courses of consolidation chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five patients had a high WBC count of more than 10 × 10(9)/L (high risk), while 15 patients had a count of less than 10 × 10(9)/L (low risk) at initial presentation. In addition, six patients, who were considered as low-risk patients at presentation, had a relapse after three cycles of consolidation and 2 years of maintenance therapy, but gained the molecular remission after re-induction and consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were still in CR at a median of 133 months (73-193 months), and six patients who underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187 months) without maintenance therapy. PML/RARα chimeric mRNA was undetectable in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases studied, our retrospective observations suggest that auto-PBSCT may be an effective treatment option to continue durable CR in the treatment of high-risk APL. We review previous reports and discuss the role of autotransplantation in the treatment of APL patients in CR.


Assuntos
Leucemia Promielocítica Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
3.
Ann Oncol ; 21(4): 833-841, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19889619

RESUMO

BACKGROUND: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has indicated an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. MATERIALS AND METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 were studied retrospectively in 671 patients treated with cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) or cyclophosphamide, vincristine, doxorubicin and prednisolone plus rituximab (R-CHOP). The median follow-up periods were 43.2 months in the CHOP group (n = 425) and 24.0 months in the R-CHOP group (n = 246). RESULTS: High Skp2 or low p27 expression correlated significantly with poor overall survival (OS) and progression-free survival (P < 0.001) in both treatment groups. The prognostic value of Skp2 or p27 expression was independent of the parameters included in the International Prognostic Index by multivariate analysis. Patients with high Skp2 expression in combination with low p27 expression showed the worst survival. CONCLUSIONS: Addition of rituximab to the CHOP regimen did not provide a beneficial outcome to patients with diffuse large B-cell lymphoma with high Skp2 expression and low p27 expression. Skp2 and p27 may be useful prognostic markers in the rituximab era.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Quinases Associadas a Fase S/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/metabolismo , Ciclofosfamida , Doxorrubicina , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona , Prognóstico , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Vincristina , Adulto Jovem
4.
Phys Med ; 24(4): 204-11, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18396083

RESUMO

PURPOSE: To clarify the effects of respiratory condition on dose calculation for stereotactic radiotherapy of small lung tumors. METHODS AND MATERIALS: Computed tomography (CT) data were obtained for nine tumors (diameter, 2.1-3.6cm; mean, 2.7cm) during the stable state, deep expiration, and deep inspiration breath-hold states. Rotational Irradiation with 3 non-coplanar arcs (Rotational Irradiation) and static irradiation with 18 non-coplanar ports (Static Irradiation) using 6-MV photons were evaluated using Fast Fourier Transform (FFT) convolution and Multigrid (MG) superposition algorithms. Dose-volume histograms (DVHs), mean path-length (PL) and mean effective path-length (EPL) were calculated. RESULTS: Although the PL was larger for the inspiration state than for the stable state and the expiration state, the EPL was 0.4-0.5cm smaller in the inspiration state than in the expiration state (p=0.01 for Rotational Irradiation; p=0.03 for Static Irradiation). The isocenter dose obtained by the FFT convolution algorithm was 7-12% higher than that obtained with the MG superposition algorithm. A leftward shift of the DVH obtained by MG superposition was noted for the inspiration state compared with the expiration state. CONCLUSIONS: The choice of the proper algorithm is important to accounting for changes in respiration state. Differences in isocenter dose were not large among the respiratory states analyzed. EPL was a little shorter for inspiration than for expiration, although there were larger and reverse trends in path length. A leftward shift of the DVH obtained for the inspiration state when MG superposition was used.


Assuntos
Algoritmos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Modelos Biológicos , Radiocirurgia/métodos , Radioterapia Assistida por Computador/métodos , Mecânica Respiratória , Idoso , Simulação por Computador , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Movimento (Física) , Dosagem Radioterapêutica , Eficiência Biológica Relativa
5.
Radiat Prot Dosimetry ; 116(1-4 Pt 2): 190-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16604625

RESUMO

The dose calculation system IMAGINE is being developed keeping in mind remotely supporting external radiation therapy using photon beams. The system is expected to provide an accurate picture of the dose distribution in a patient body, using a Monte Carlo calculation that employs precise models of the patient body and irradiation head. The dose calculation will be performed utilising super-parallel computing at the dose calculation centre, which is equipped with the ITBL computer, and the calculated results will be transferred through a network. The system is intended to support the quality assurance of current, widely carried out radiotherapy and, further, to promote the prevalence of advanced radiotherapy. Prototypes of the modules constituting the system have already been constructed and used to obtain basic data that are necessary in order to decide on the concrete design of the system. The final system will be completed in 2007.


Assuntos
Modelos Biológicos , Terapia com Prótons , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Software , Telemedicina/métodos , Carga Corporal (Radioterapia) , Redes de Comunicação de Computadores , Simulação por Computador , Japão , Método de Monte Carlo , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Design de Software
6.
Intern Med ; 40(9): 862-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11579945

RESUMO

OBJECTIVE: Recent reports have revealed that corticosteroid (PSL) therapy has a long-term beneficial effect for stabilization of renal function in progressive IgA nephropathy. PATIENTS AND METHODS: We analyzed serum creatinine (Cr), daily proteinuria and the results of other routine laboratory examinations during a short-term course of PSL therapy in 28 cases of progressive IgA nephropathy. The cases were divided into two groups according to changes in renal function during the PSL treatment period: group I (15 cases), improved renal function; group II (13 cases), no significant change in renal function. RESULTS: In group I, serum Cr and proteinuria were significantly decreased, with maximum effects observed at 3 months of PSL therapy, and remained low during the period of treatment. In contrast, group II showed no significant changes in serum Cr levels during the period of therapy, although proteinuria was transiently decreased after 3 months of therapy. Histologically, cellular/fibrocellular (C/F) crescents and/or segmental glomerular necrosis (SGN) occurred with a significantly higher incidence in group I (87%) than in group II (46%) (p < 0.05). CONCLUSIONS: These results suggested that the early response to PSL in reducing serum Cr and proteinuria by 3 months of treatment may be clinically useful to predict the prognosis of IgA nephropathy and that C/F crescents and/ or SGN may be histologically indicative of the beneficial effects of PSL therapy in IgA nephropathy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Creatinina/sangue , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/metabolismo , Prednisona/uso terapêutico , Proteinúria/metabolismo , Adulto , Feminino , Glomerulonefrite por IGA/patologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
7.
J Clin Invest ; 108(7): 1071-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11581308

RESUMO

Cells with a verapamil-sensitive ability to efflux Hoechst 33342 (termed side population [SP] cells) have been identified in adult marrow from several species including humans and in several tissues from adult mice. In mice, the SP phenotype appears to be a common feature of stem cells, but human SP cells have been less well characterized. We show here, for the first time to our knowledge, that SP cells are present in the second-trimester human fetal liver. They include all of the transplantable human hematopoietic stem cell activity detectable in NOD/SCID mice and also certain other, more differentiated hematopoietic cell types. Notably, the stem cell activity was confined to the CD34(+)CD38(-) SP(+) population, and isolation of these cells gave an approximately tenfold enrichment of transplantable stem cells. This subset was not, however, coenriched in hematopoietic progenitors detectable by either short- or long-term in vitro assays, indicating most of these to be distinct from transplantable stem cells. These findings suggest that the SP phenotype is an important and distinguishing property of human hematopoietic stem cells and that early in ontogeny they express CD34.


Assuntos
Antígenos CD34 , Antígenos CD , Células-Tronco Hematopoéticas/imunologia , Fígado/citologia , Fígado/embriologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Animais , Antígenos de Diferenciação , Biomarcadores , Separação Celular , Células Cultivadas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/classificação , Hepatócitos/classificação , Hepatócitos/citologia , Hepatócitos/imunologia , Humanos , Imunofenotipagem , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , NAD+ Nucleosidase
8.
Arch Orthop Trauma Surg ; 121(9): 501-4, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11599750

RESUMO

To investigate the demographic details and patterns of injuries related to horse handling, we reviewed 637 horse-related injuries in 581 stable- or stud-workers in a representative area of thoroughbred stabling in Japan. We found that (1) injuries occurred most frequently in a group of a relatively young workers, with a seasonal variation; (2) the principal mechanism of injury was kicks, which accounted for 39.2% of all injuries, including 11 serious and one lethal visceral injuries; (3) the upper half of the body was more frequently involved than the lower half; and (4) the peripheral bones (hand and foot) and the ribs accounted for more than half of 148 fractures. These findings are distinct from those in horse-riding injuries reported in the literature and emphasize the importance in developing preventive strategies specifically for workers in horse stables.


Assuntos
Acidentes de Trabalho , Fraturas Ósseas/etiologia , Ferimentos e Lesões/epidemiologia , Acidentes de Trabalho/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Traumatismos Cranianos Fechados/etiologia , Cavalos , Humanos , Incidência , Escala de Gravidade do Ferimento , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Lesões do Pescoço/etiologia , Estudos Retrospectivos , Estações do Ano
10.
Intern Med ; 40(11): 1085-92, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11757761

RESUMO

OBJECTIVE: The mechanism of neutrophil adhesion to the endothelium during the earliest stages of acute inflammation, especially before the induction of adhesion molecules on endothelial cells, remains unknown. We studied the possible involvement of platelets in this process. METHODS: Neutrophils were added to human umbilical vein-derived endothelial cells (HUVEC) with or without adherent platelets in the presence or absence of adhesion-blocking monoclonal antibodies (mAbs). Adhesion of neutrophils to HUVEC at dynamic flow conditions was assessed using a flow chamber. RESULTS: 1) Thrombin-activated platelets adhered to resting-HUVEC at dynamic flow conditions through platelet glycoprotein IIb/IIIa and RGD proteins. 2) Neutrophils tethered to P-selectin induced on thrombin-activated platelets, which were immobilized on HUVEC. 3) Activated neutrophils adhered, via LFA-1, to ICAM-1 on HUVEC. 4) Activated platelets induced interleukin (IL)-8 secretion by HUVEC. CONCLUSIONS: Immobilized platelets on the vessel wall with induced P-selectin on the surface biochemically and functionally promote the adhesion of neutrophils to endothelial cells.


Assuntos
Reação de Fase Aguda/sangue , Plaquetas/metabolismo , Moléculas de Adesão Celular/metabolismo , Endotélio Vascular/patologia , Ativação Plaquetária , Adesão Celular , Fibrinogênio/metabolismo , Fibronectinas/metabolismo , Citometria de Fluxo , Humanos , Interleucina-8/metabolismo , Neutrófilos/metabolismo , Inibidores da Agregação Plaquetária/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Veias Umbilicais
11.
Int J Hematol ; 74(4): 447-50, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11794702

RESUMO

A 60-year-old Japanese woman who presented with right nasal congestion and high fever was admitted to our hospital in March 1999. She was diagnosed with nasal NK/T-cell lymphoma clinical stage IVB. Because her NK/T-cell lymphoma was highly aggressive and chemo-resistant, she underwent autologous peripheral blood stem cell transplantation (PBSCT). The patient received a pretransplantation conditioning regimen of ranimustine, etoposide, carboplatin, and cyclophosphamide. On July 29, 1999, 1.0 x 10(6)/kg CD34+ cells were infused. The patient achieved first complete remission. In January 2000, NK/T-cell lymphoma relapsed in the skin and fever developed. CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone) was administered, resulting in partial regression of the skin lesions, but fever persisted. L-asparaginase (L-Asp) at a dose of 6,000 U/m2 per day was administered for 7 days, resulting in the complete disappearance of the skin lesions and resolution of the fever. The patient has been in second complete remission for more than 18 months since the completion of L-Asp treatment (as of July 2001). The effect of L-Asp in this patient was dramatic. Several cases have been reported describing the effectiveness of L-Asp in patients with nasal lymphoma and cutaneous T-cell lymphoma. A front-line chemotherapy regimen containing L-Asp for NK/T-cell lymphoma may warrant further evaluation.


Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Linfoma de Células T/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Células Matadoras Naturais/patologia , Linfoma de Células T/terapia , Pessoa de Meia-Idade , Neoplasias Nasais/terapia , Recidiva , Indução de Remissão , Transplante Autólogo
12.
Br J Haematol ; 111(1): 363-70, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11091226

RESUMO

Precursor cells that migrate into the thymus are still multipotent. Therefore, thymic epithelial cells (TECs) may provide microenvironments not only for T-cell development, but also for maintenance of multipotent precursor cells until they undergo T-cell commitment. In the present study, we performed long-term cultures of CD34+ bone-marrow (BM) cells on TEC lines that were derived from cortical epithelial cells of post-natal thymus, to investigate whether human TECs could maintain long-term nonlymphoid haematopoiesis. Haematopoietic cells maintained in direct contact with established TEC lines were able to generate clonogenic progeny to both myeloid and erythroid cells for periods in excess of 5 weeks. Their abilities to support colony-forming units of granulocytes-macrophages (CFU-GM) and burst-forming units of erythroids (BFU-E) were almost equal to those of BM stromal cells. We observed similar results by using cloned TEC lines derived by limiting dilution, as well as those by using parental TEC lines. Colony-forming activities were maintained even when haematopoietic progenitor cells were physically separated from TEC lines and cultured on microporous membrane. These observations indicate that haematopoiesis maintained in TEC-contact long-term cultures may depend on soluble factors produced by TEC lines. Our results suggest that thymic cortical epithelial cells have the ability to support not only the differentiation of haematopoietic cells, but also long-term survival of clonogenic myeloid/erythroid progenitor cells.


Assuntos
Células Epiteliais/citologia , Células Precursoras Eritroides/citologia , Linfócitos T/citologia , Timo/citologia , Antígenos CD34 , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Sobrevivência Celular , Células Clonais , Técnicas de Cocultura , Citocinas/imunologia , Células Precursoras Eritroides/imunologia , Humanos , Imuno-Histoquímica/métodos , Fatores de Tempo
14.
Biomed Pharmacother ; 54 Suppl 1: 60s-65s, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10914993

RESUMO

Secondary hyperparathyroidism (2 HPT) is a representative disease of dialysis osteopathy, with the lesion that makes fibrous osteitis and the parathyroid hyperplasia by the hyper secretion of parathyroid hormone (PTH). This research examines the usefulness of selective percutaneous ethanol injection therapy (PEIT) of parathyroid glands in order to treat and control for 2 HPT. PEIT was performed in 46 patients resistant to calcitriol pulse therapy and all glands larger than 5 mm in diameter were destroyed by ethanol guided by power Doppler flow mapping. Serum intact-PTH (iPTH) levels fell from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at three weeks and were maintained at 289.9 +/- 222.4 pg/mL at one year after PEIT. Total alkaline phosphatase activity fell from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at one year after PEIT. In 19 patients, i-PTH levels fell into relative hypoparathyroidism (iPTH < 160 pg/mL) at three weeks after PEIT: however, they recovered at one year after PEIT (191.1 +/- 29.6 pg/mL). In total, parathyroid function was maintained at optimal range (160 < iPTH < 360 pg/mL) in 80.4% of patients at one year after PEIT with appropriate medical therapy. As for the complications, recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT appears to be able to control appropriate parathyroid function and to be the method of choice to treat 2 HPT prior to parathyroidectomy.


Assuntos
Etanol , Falência Renal Crônica/complicações , Glândulas Paratireoides/fisiologia , Glândulas Paratireoides/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Prognóstico , Diálise Renal , Ultrassonografia Doppler em Cores
15.
Jpn J Antibiot ; 53(3): 135-56, 2000 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-10834146

RESUMO

Chronic hepatitis B and C virus infections have been characterized by the pathophysiological features with a high incidence of progression to cirrhosis and development of hepatocellular carcinoma. The viral persistence produced by escape mutations from virus-specific cytotoxic T lymphocytes (CTL) response may lead to upregulation of delayed-type hypersensitivity immune response, which causes hepatic tissue damage through non specific macrophage activation and CTL response and promotes pathogenesis of hepatic fibrosis. In a preliminary clinical study, a novel metalloendopeptidase-F (MEP-F) has been shown to be effective in the treatment of patients with either chronic hepatitis B or C infection. Oral administration of MEP-F resulted in a significant reduction of the serum levels of HBs antigen and HCV RNA and improvement in the liver function abnormalities. However, the mechanism of action of MEP-F is not yet well understood. There are accumulating evidences showing an important role of alpha 2-macroglobulin-proteinase complexes in regulatory mechanisms of immune response and repairing within impaired and inflammatory tissues. In this article, reviewing the pharmacological and biological properties of alpha 2-macroglobulin-proteinase complexes, the mechanism of anti-viral effect of MEP-F is examined based on the clinical findings. It is indicated that alpha 2-macroglobulin-MEP-F complexes may induce macrophage/Kuppfer cell activation and proliferation through binding their receptors on the cells and activating signaling cascades, which enhance both anti-viral specific and nonspecific immune responses. alpha 2-Macroglobulin-MEP-F complexes may also augment cellular immunity and hepatic regeneration by neutralizing the immunosuppressive and fibrogenic activities of transforming growth factor-beta.


Assuntos
Hepatite B Crônica/terapia , Hepatite C Crônica/terapia , Metaloendopeptidases/uso terapêutico , Animais , Citocinas/metabolismo , Citocinas/fisiologia , Hepatite B Crônica/imunologia , Hepatite C Crônica/imunologia , Humanos , Fígado/metabolismo , Fígado/fisiologia , Regeneração Hepática , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Macrófagos/imunologia , Metaloendopeptidases/metabolismo , Metaloendopeptidases/farmacologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/fisiologia , Linfócitos T Citotóxicos/imunologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , alfa-Macroglobulinas/metabolismo , alfa-Macroglobulinas/fisiologia
16.
Leukemia ; 14(6): 1112-21, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10865977

RESUMO

Neoplastic CD34+ cells from chronic myeloid leukemia (CML) patients proliferate in vitro in the absence of serum or defined growth factors due to an autocrine mechanism involving IL-3 and G-CSF (Jiang et al. Proc Natl Acad Sci USA 1999; 96: 12804). Detailed examination of the various cell types produced in such cultures has now demonstrated the rapid, factor-independent, generation of clonogenic progenitors for all lineages (granulocyte-macrophage, megakaryocyte and erythroid) with the additional appearance within 10 days of large numbers of mature granulocytes, macrophages, and megakaryocytes, as well as occasional erythroid cells. Inclusion of flt3-ligand, Steel factor, IL-3, IL-6, and G-CSF +/- erythropoietin (EPO) in the cultures enhanced only slightly the output of mature cells (except for the erythroid population which was much larger when EPO was added). Analogous subpopulations of normal CD34+ cells produced similar numbers and types of cells but, as expected, only when growth factors were added. Thus primitive CD34+ CML cells proliferating autonomously in vitro recapitulate the full spectrum of differentiation responses of normal CD34+ cells stimulated by IL-3 and G-CSF. These findings point to a role of autocrine IL-3 and G-CSF in the similar multi-lineage expansion of differentiating CD34+ CML cells that occurs in vivo.


Assuntos
Antígenos CD34/imunologia , Diferenciação Celular , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Células-Tronco/imunologia , Linhagem da Célula , Meios de Cultura , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia
17.
Am J Gastroenterol ; 95(2): 381-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10685739

RESUMO

OBJECTIVE: Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD. METHODS: Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment. RESULTS: Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p<0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall. CONCLUSIONS: EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.


Assuntos
Endossonografia , Inibidores Enzimáticos/uso terapêutico , Esôfago/efeitos dos fármacos , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/análogos & derivados , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Esofagite Péptica/diagnóstico por imagem , Esofagite Péptica/tratamento farmacológico , Esôfago/diagnóstico por imagem , Famotidina/uso terapêutico , Feminino , Refluxo Gastroesofágico/diagnóstico por imagem , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Mucosa/diagnóstico por imagem , Mucosa/efeitos dos fármacos , Músculo Liso/diagnóstico por imagem , Músculo Liso/efeitos dos fármacos , Omeprazol/uso terapêutico
20.
Blood ; 94(6): 1926-32, 1999 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10477721

RESUMO

Recently, several reports of lineage-negative (lin(-)) CD34(-) cells with in vivo hematopoietic activity have focused interest on the properties and growth factor response characteristics of these cells. We have now identified a combination of 5 growth factors that are necessary and sufficient to stimulate a marked mitogenic and differentiation response by a subset of human lin(-)CD34(-)CD38(-) cells present in normal adult human marrow and granulocyte colony-stimulating factor (G-CSF)-mobilized blood. Less than 0.1% of the cells in highly purified (including doubly sorted) lin(-)CD34(-)CD38(-) cells from these 2 sources formed colonies directly in semisolid medium or generated such cells after 6 weeks in long-term culture. Nevertheless, approximately 1% of the same lin(-)CD34(-)CD38(-) cells were able to proliferate rapidly in serum-free liquid suspension cultures containing human flt-3 ligand, Steel factor, thrombopoietin, interleukin-3 (IL-3), and hyper-IL-6 to produce a net 28- +/- 8-fold increase in total cells within 10 days. Of the cells present in these 10-day cultures, 5% +/- 2% were CD34(+) and 2.5% +/- 0.9% were erythroid, granulopoietic, megakaryocytopoietic, or multilineage colony-forming cells (CFC) (13 +/- 7 CFC per lin(-)CD34(-)CD38(-) pre-CFC). In contrast to lin(-)CD34(+)CD38(-) cells, this response of lin(-)CD34(-)CD38(-) cells required exposure to all of the 5 growth factors used. Up to 1.7 x 10(5) lin(-)CD34(-) adult marrow cells failed to engraft sublethally irradiated NOD/SCID-beta(2)M(-/-) mice. These studies demonstrate unique properties of a rare subset of lin(-)CD34(-)CD38(-) cells present in both adult human marrow and mobilized blood samples that allow their rapid proliferation and differentiation in vitro within an overall period of 3 to 4 weeks. The rapidity of this response challenges current concepts about the normal duration and coordinated control of these processes in adults.


Assuntos
Antígenos CD/análise , Células da Medula Óssea/citologia , Substâncias de Crescimento/farmacologia , Células-Tronco Hematopoéticas/citologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Adulto , Animais , Antígenos CD34/análise , Antígenos de Diferenciação/análise , Biomarcadores , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Glicoproteínas de Membrana , Camundongos , NAD+ Nucleosidase/análise
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