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1.
Ann Oncol ; 27(5): 887-95, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26884589

RESUMO

BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Transtornos Plaquetários/epidemiologia , Plaquetas/patologia , Neoplasias Hematológicas/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Trombocitopenia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Herdados da Coagulação Sanguínea/genética , Transtornos Herdados da Coagulação Sanguínea/patologia , Transtornos Plaquetários/genética , Transtornos Plaquetários/patologia , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Feminino , Predisposição Genética para Doença , Genótipo , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Lactente , Japão/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Trombocitopenia/genética , Trombocitopenia/patologia
2.
Transpl Infect Dis ; 12(5): 421-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20626711

RESUMO

Varicella zoster virus (VZV) disease is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). We carried out a trial of 1-year low-dose valacyclovir (VCV) prophylaxis against VZV disease to evaluate its efficacy and safety. Patients received oral acyclovir (ACV) 1000mg/day until day 35 after HSCT. Oral VCV 500mg/day, 3 times a week, was started on day 36 and continued until 1 year after HSCT. The development of VZV disease was monitored until 2 years after HSCT. A total of 40 patients with a median age of 43 years were enrolled. VCV was well tolerated in all but 1 patient who discontinued it on day 224 because of thrombocytopenia of unknown cause. Seven patients developed VZV disease at a median of 479 days (range 145-651) after HSCT, with a cumulative incidence of 18.5%. Two patients developed breakthrough disease during VCV prophylaxis. The other 5 patients developed VZV disease after the discontinuation of VCV, and 3 of these had developed extensive chronic graft-versus-host disease. Visceral involvement and serious complications were completely eliminated. All patients responded to the therapeutic dose of VCV or ACV. One-year low-dose VCV can be safely and effectively administered for the prevention of VZV disease after allogeneic HSCT.


Assuntos
Aciclovir/análogos & derivados , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/prevenção & controle , Valina/análogos & derivados , Aciclovir/uso terapêutico , Adolescente , Adulto , Feminino , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Valaciclovir , Valina/uso terapêutico
3.
Clin Exp Dermatol ; 34(8): e748-50, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19663840

RESUMO

Piloleiomyoma is a benign tumour originating in the smooth muscles of the arrector pili muscle in the skin. The lesions are often sensitive to touch, cold and emotional disturbance. We present a patient with multiple piloleiomyoma (MPL) of the submentum who underwent reconstructive surgery using a submental perforator flap. The result was excellent and there were no postoperative complications. MPL of the submental region is relatively rare; to our knowledge, ours is the first report of MPL treated successfully with a submental perforator flap.


Assuntos
Cervicoplastia/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Leiomioma/cirurgia , Neoplasias Cutâneas/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Humanos , Leiomioma/patologia , Masculino , Pescoço , Prognóstico , Neoplasias Cutâneas/patologia , Resultado do Tratamento
4.
Cancer Res ; 44(12 Pt 1): 5661-5, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6498826

RESUMO

Administration of mouse interferon (IFN; 0.5 to 1 X 10(7) reference units/mg protein) inhibited the growth of Meth A and Meth 1 fibrosarcomas, but to a lesser extent, if at all, the growth of Colon 26 adenocarcinoma in BALB/c mice. The in vitro IFN sensitivity of these three tumors was not consistent with the in vivo therapeutic response in mice bearing these tumors under the present experimental conditions; Colon 26, the most sensitive of the three tumors in the in vitro antiproliferation test, did not respond or responded most poorly to IFN therapy; furthermore, Meth A and Meth 1 tumors responded similarly well to IFN therapy, although there was about a 100-fold difference in their in vitro IFN sensitivity. These results as well as the kinetic analysis of IFN concentrations of the serum of Meth A- or Colon 26-bearing mice did not indicate that the antiproliferative activity of IFN was solely responsible for its in vivo therapeutic effect. In contrast, abrogation of T-cell immunity by alpha mouse thymocyte globulin completely nullified the IFN-dependent therapeutic effect in Meth A-bearing mice. Furthermore, the IFN-dependent therapeutic response in Meth A tumors was much weaker in T-cell-defective BALB/c (nu/nu) mice than that in immunologically competent BALB/c (+/+) mice and was marginal, if present at all, confirming that T-cell immunity was involved in the IFN-dependent therapeutic effect and suggesting that the antiproliferative activity of IFN may only be responsible to a small extent for the therapeutic effect.


Assuntos
Neoplasias do Colo/terapia , Fibrossarcoma/terapia , Imunidade Inata , Interferon Tipo I/uso terapêutico , Animais , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Fibrossarcoma/imunologia , Fibrossarcoma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Especificidade da Espécie
5.
Bone Marrow Transplant ; 51(5): 645-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26808566

RESUMO

Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto-PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD.


Assuntos
Leucemia Mieloide Aguda/terapia , Transplante Autólogo/normas , Transplante Homólogo/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transplante de Medula Óssea , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Pontuação de Propensão , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Leukemia ; 30(3): 545-54, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26488113

RESUMO

We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Análise Citogenética , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Feminino , Expressão Gênica , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
7.
Biochim Biophys Acta ; 1222(3): 411-4, 1994 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-8038210

RESUMO

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is a 90 kDa protein consisting of two non-covalently associated subunits. In addition to the previously identified 1.8 kilobase (kb) PD-ECGF/TP mRNA, the human epidermoid carcinoma cell line A431 was found to express 3.0 kb and 3.2 kb transcripts. cDNA cloning of the larger transcripts revealed that they contain long 5' leader sequences of 1.5 kb and 1.7 kb, respectively, and the same open reading frame encoding PD-ECGF/TP as that of the 1.8 kb transcript. Comparison with the published PD-ECGF/TP genomic sequence shows that the long 5' leader sequence contain 7 of 8 copies of Sp-1 binding sites present in the transcription promoter region of the 1.8 kb transcript.


Assuntos
Timidina Fosforilase/genética , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , DNA Complementar/análise , Dados de Sequência Molecular , Células Tumorais Cultivadas
8.
Exp Hematol ; 25(1): 26-33, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8989903

RESUMO

The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.


Assuntos
Citocinas/farmacologia , Transtornos Mieloproliferativos/metabolismo , Neutrófilos/metabolismo , Receptores de Superfície Celular/metabolismo , Explosão Respiratória , Transdução de Sinais , Superóxidos/metabolismo , Concanavalina A/farmacologia , Humanos , Interleucina-8/farmacologia , Transtornos Mieloproliferativos/patologia , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/patologia , Receptores de Superfície Celular/agonistas
9.
Bone Marrow Transplant ; 50(5): 727-33, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25730191

RESUMO

This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (<1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P=0.65; bacterial infection, 44 vs 41%, P=0.68; and fungal infection, 6 vs 8%, P=0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P=0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.


Assuntos
Infecções Bacterianas , Ferritinas/sangue , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Micoses , Período Pré-Operatório , Adulto , Idoso , Aloenxertos , Infecções Bacterianas/sangue , Infecções Bacterianas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Micoses/mortalidade , Estudos Prospectivos , Taxa de Sobrevida
10.
FEBS Lett ; 313(2): 129-32, 1992 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-1426279

RESUMO

Platelet-derived endothelial cell growth factor (PD-ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD-ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD-ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [125I]PD-ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half-lives of 17 min and 7 h, respectively. PD-ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half-life in the circulation, together with the specificity for endothelial cells, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine.


Assuntos
Timidina Fosforilase/farmacocinética , Animais , Injeções Intravenosas , Masculino , Ratos , Ratos Endogâmicos WKY , Timidina Fosforilase/administração & dosagem , Distribuição Tecidual
11.
Thromb Haemost ; 82(1): 24-9, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10456449

RESUMO

Thrombopoietin (TPO) isolated from thrombocytopenic plasma of various animal species has previously been shown to comprise only truncated forms of the molecule, presumably generated by proteolysis. Native TPO has now been partially purified from normal human plasma by immunoaffinity chromatography and was confirmed to be biologically active. Gel filtration in the presence of SDS revealed that TPO eluted in two peaks: a major peak corresponding to the elution position of fully glycosylated recombinant human TPO (rhTPO) consisting of 332 amino acid residues, and a minor peak corresponding to a smaller molecular size. Immunoblot analysis also revealed that most plasma-derived TPO migrated at the same position as fully glycosylated rhTPO, corresponding to a molecular size of approximately 80 to 100 kDa. Furthermore, the size distribution of circulating TPO in patients with various haematologic disorders did not differ markedly from that of plasma-derived TPO from healthy individuals. These results indicate that the truncation of circulating TPO is not related to disease pathophysiology, and that the predominant form of TPO in blood is a biologically active approximately 80- to 100-kDa species. The size distribution of TPO extracted from normal platelets was similar to that of TPO in plasma; the proportion of truncated TPO was decreased by prior incubation of platelets with hirudin. indicating that the endogenous truncated TPO, at least in platelet extract, was generated by thrombin-mediated cleavage.


Assuntos
Doenças Hematológicas/sangue , Trombopoetina/análise , Humanos , Trombopoetina/química
12.
J Dermatol Sci ; 16(3): 173-81, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9651814

RESUMO

We hypothesized that if nicotine was used in a form that was not adulterated with other hazardous substances found in tobacco, it would increase cutaneous blood flow (CBF) resulting in an increase in skin temperature. The effects of nicotine on CBF was investigated in 80 healthy volunteers and 6 patients with peripheral circulation disturbances. Each subject was required to chew nicotine gum (containing 2 mg nicotine) for 15 min and the CBF was then measured with laser blood flowmetry. Skin temperature of 35 volunteers was measured with thermography before and after chewing the gum for 15 min. A control study was performed using ordinary gum without nicotine. Increased CBF (> or = + 1 ml/min/100 g) was observed in 55 of 86 subjects (64%, 33.7-38.6 ml/min/100 g, P < 0.01). An elevation in skin temperature (> + 0.1 degree C) was also observed with nicotine gum in 26 of 35 healthy subjects (74%, + 0.62 +/- 0.96 degree C, P < 0.001). The increase in CBF was greater in subjects in which the initial CBF was lower than in others (P < 0.01). Nicotine gum was found to increase CBF (55/86) and elevate skin temperature (26/35). The smaller the initial CBF value, the greater was the increase in CBF. Nicotine or nicotine derivatives might prove to be useful agents for the treatment of peripheral circulation disturbances.


Assuntos
Nicotina/farmacologia , Temperatura Cutânea/efeitos dos fármacos , Pele/irrigação sanguínea , Adulto , Idoso , Circulação Sanguínea/fisiologia , Sistema Cardiovascular/efeitos dos fármacos , Goma de Mascar , Doenças do Tecido Conjuntivo/fisiopatologia , Feminino , Humanos , Lasers , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Valores de Referência , Fluxo Sanguíneo Regional/efeitos dos fármacos , Reologia/métodos , Dermatopatias/fisiopatologia
13.
Int J Hematol ; 68(1): 87-94, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9713172

RESUMO

We report on an 83-year-old male with chronic neutrophilic leukemia (CNL) associated initially with IgM monoclonal gammopathy and later with B cell chronic lymphocytic leukemia (CLL), in which the clone differed from that of the preceding monoclonal gammopathy. At initial presentation, the patient had hepatosplenomegaly, leukocytosis (29100 x 10(6)/l) with an increase of mature neutrophils (83%), 20q- chromosomal abnormality, an increased leukocyte alkaline phosphatase score, elevated serum levels of vitamin B12 and uric acid, a low serum level of granulocyte colony-stimulating factor, and high serum IgM (1015 mg/dl: lambda type M protein). Thereafter, lymphocytosis developed gradually. Three years after the initial presentation, the patient had no serum M protein, but showed evidence of leukocytosis (36600 x 10(6)/l) with 20q- chromosomal abnormality and an increase of mature neutrophils (51%) and small lymphocytes (43.5%), CD5+/19+/20+/HLA-DR+ and surface membrane IgM+/D+/kappa+. Gene rearrangements of the immunoglobulin heavy and kappa light chains were also present. To our knowledge, this is the first reported case of CNL associated with CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Neutrofílica Crônica/genética , Masculino
14.
Int J Hematol ; 64(3-4): 213-9, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8923783

RESUMO

Granulocyte colony-stimulating factor (G-CSF) enhances the differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA) in vitro. Accordingly, we initiated a pilot study on G-CSF in APL patients who developed neutropenia and severe infection during remission induction therapy with ATRA. Seven out of nine treated patients displayed a marked increase in granulocyte counts without leukemic regrowth, and two displayed a dramatic decrease in leukemic blasts. However, leukemic regrowth occurred in two patients under treatment for post-ATRA relapse. Our findings suggest that administration of G-CSF combined with ATRA can improve the hematological state in APL patients not previously receiving ATRA therapy.


Assuntos
Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão
15.
Int J Hematol ; 63(1): 19-23, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8713573

RESUMO

All-trans-retinoic acid (ATRA) was administered at 45 mg/m2 to 4 Japanese patients with acute promyelocytic leukemia (APL). A pharmacokinetic study revealed that the mean peak plasma concentration was 208 ng/ml and was reached at 150 min after ingestion. The mean area under the concentration x time curve (AUC) was 498 ng.h/ml. Two patients showed a good hematological response to ATRA, and they had higher peak plasma concentrations of ATRA and larger AUCs. In one patient, dose escalation of ATRA (90 mg/m2) increased the plasma concentration markedly. In another patient, the plasma concentration decreased markedly in the fasting state. A larger pharmacokinetic study is necessary to examine the influence of food on the absorption of this agent and an optimum administration schedule of ATRA in Japanese APL cases.


Assuntos
Leucemia Promielocítica Aguda/sangue , Tretinoína/farmacocinética , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Japão , Masculino , Tretinoína/administração & dosagem
16.
Leuk Lymphoma ; 34(5-6): 625-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10492090

RESUMO

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B/sangue , Linfoma Difuso de Grandes Células B/sangue , Glicoproteínas de Membrana/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Valor Preditivo dos Testes , Recidiva
17.
Naunyn Schmiedebergs Arch Pharmacol ; 305(2): 123-6, 1978 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-153477

RESUMO

An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progessively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic beta-cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin.


Assuntos
Hipertensão/induzido quimicamente , Estreptozocina/farmacologia , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catarata/induzido quimicamente , Doença Crônica , Glicosúria/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , Ratos
18.
Intern Med ; 36(9): 640-2, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9313109

RESUMO

We report a 64-year-old male with granulocytopenia and dermatitis due to cyanamide treatment. We administered cyanamide for alcoholism. After about one month he suffered from scaly erythema over his whole body and granulocytopenia (granulocyte; 140/microliter) with maturation arrest in bone marrow. After cessation of cyanamide and the start of granulocyte colony-stimulating factor administration, the skin eruption ameliorated gradually, and the peripheral blood granulocyte counts increased. Cyanamide showed positive results in the drug lymphocyte stimulation test (198%) and the patch test led to the diagnosis of granulocytopenia and dermatitis induced by cyanamide. After restarting glibenclamide and diazepam administration, his granulocytopenia did not reoccur. To our knowledge, this is the first report of a case with granulocytopenia induced by cyanamide.


Assuntos
Agranulocitose/induzido quimicamente , Cianamida/efeitos adversos , Dermatite/etiologia , Agranulocitose/diagnóstico , Agranulocitose/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Antieméticos/uso terapêutico , Dermatite/diagnóstico , Dermatite/tratamento farmacológico , Diazepam/uso terapêutico , Glibureto/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Testes do Emplastro
19.
Intern Med ; 35(4): 327-30, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8739792

RESUMO

Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Leucemia Mieloide Aguda/genética , Sequência de Aminoácidos , Sequência de Bases , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/patologia , Clonagem Molecular , DNA de Neoplasias/genética , Eosinofilia/genética , Eosinofilia/patologia , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase
20.
Intern Med ; 34(12): 1186-9, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8929647

RESUMO

A 67-year-old man presented with acute myelogenous leukemia (M2). Peripheral blood examination revealed a leukocyte count of 1,700/mu l with 1% myeloblasts, and bone marrow aspiration showed 42.6% myeloblasts with Auer bodies. Culture of his marrow cells at diagnosis showed that granulocyte colony-stimulating factor (G-CSF) promoted cell proliferation, while all-trans retinoic acid (ATRA) inhibited the proliferative effect of G-CSF and induced differentiation. Combination therapy with G-CSF, ATRA, and low-dose cytotoxic drugs achieved complete remission without severe marrow suppression.


Assuntos
Antineoplásicos/uso terapêutico , Arabinonucleotídeos/uso terapêutico , Ciclofosfamida/uso terapêutico , Monofosfato de Citidina/análogos & derivados , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Idoso , Medula Óssea/efeitos dos fármacos , Monofosfato de Citidina/uso terapêutico , Quimioterapia Combinada , Humanos , Leucemia Mieloide Aguda/patologia , Masculino
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