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The formation of a dineutron in the ^{11}Li nucleus is found to be localized to the surface region. The experiment measured the intrinsic momentum of the struck neutron in ^{11}Li via the (p,pn) knockout reaction at 246 MeV/nucleon. The correlation angle between the two neutrons is, for the first time, measured as a function of the intrinsic neutron momentum. A comparison with reaction calculations reveals the localization of the dineutron at râ¼3.6 fm. The results also support the density dependence of dineutron formation as deduced from Hartree-Fock-Bogoliubov calculations for nuclear matter.
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Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.
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Bromocriptina/química , Bromocriptina/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Cor , Estabilidade de Medicamentos , Iluminação , Fotólise , Comprimidos/química , Comprimidos/efeitos da radiação , TemperaturaRESUMO
The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216 MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst) MeV with the width of Γ=4.7±0.8 MeV. The integrated GT strength up to E_{x}=25 MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.
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INTRODUCTION: High blood pressure is a major cardiovascular risk factor. Patients with cardiovascular risk factors are at risk of developing COVID-19. The objective of this study was to determine epidemiology of Covid-19 infected in patients with high blood pressure. PATIENTS AND METHOD: Descriptive cross-sectional study from April 2020 to June 2020 about patients hospitalized for Covid 19 by PCR diagnosis at the Hopital du Mali Bamako and having high blood pressure. Admission registry and patient charts were used to collect data. RESULTS: We collected 78 out of 484 in patients which mean hospital frequency of 16.11%. The mean age was 55.21 +/- 14.61 years. Sex ratio M / F was 1.36. Patients were followed for high blood pressure in 59% of cases. Medical history was ischemic heart disease in 2.6% and dilated cardiomyopathy in 2.6%. Main functional signs were cough in 41.02% and lost of taste in 11.53%. High blood pressure on admission was grade 2 in 37.2% and grade 3 in 3.8%. Treatments received were calcium channel blockers 41.02%, inhibitors of the reninangiotensinaldosterone system 16.66% and combinations 15.38%. Hospital mortality was 10.3%. There was no statistically significant difference in mortality between known hypertensive patients and de novo hypertensive patients. There was also no statistically significant difference in mortality by grade of hypertension. CONCLUSION: High blood pressure can be associated to Covid 19. Treatment is based on calcium channel blockers and reninangiotensinaldosterone system inhibitors. It has an impact on the prognosis of the disease with significant mortality.
INTRODUCTION: L'hypertension artérielle (HTA) est un facteur de risque cardiovasculaire majeur. Dans la littérature elle est fréquemment retrouvée chez les patients atteints de la COVID-19.L'objectif de cette étude est de décrire l'épidémiologie de cette association chez les patients hospitalisés pour Covid-19. PATIENTS ET MÉTHODE: L'Etude est transversale et descriptive ; elle a été réalisée sur la période du 1erAvril 2020 au 30 Juin 2020. Elle a concerné les patients hospitalisés pour Covid 19 avec un test PCR positif à l'hôpital du Mali de Bamako et ayant une HTA. Les registres d'admission et les dossiers des patients ont servi pour la collecte des données. RÉSULTATS: Nous avons colligé 78 sur 484 patients hospitalisés soit une fréquence de 16,11%. L'âge moyen était de 55,21 +/- 14,61 ans. Le sex ratio H/F était de 1,36.Les patients étaient suivis pour HTA dans 59% des cas. Les antécédents médicaux étaient la cardiopathie ischémique chez 2,6% et la cardiomyopathie dilatée chez 2,6%. Les principaux signes fonctionnels étaient la toux chez 41,02% et l'agueusie chez 11,53%. L'HTA à l'admission était de grade 2 dans 37,2% des cas et de grade 3 dans 3,8% des cas. Les traitements reçus étaient les inhibiteurs calciques 41,02%, les inhibiteurs du système rénine angiotensine aldostérone 16,66% et les associations 15,38%. La mortalité hospitalière était de 10,3%. Il n'y avait pas de différence statistiquement significative concernant la mortalité entre les patients connus hypertendus et les patients hypertendus de novo. Il n'y avait pas non plus de différence statistiquement significative concernant la mortalité selon le grade de l'HTA. CONCLUSION: l'HTA peut être associée au Covid 19. Le traitement est basé sur les inhibiteurs calciques et sur les inhibiteurs du système rénine angiotensine aldostérone. Elle a un impact sur le pronostic de la maladie avec une mortalité importante.
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Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events.
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A magnitude 7.2 earthquake in 1975 caused the south flank of Kilauea Volcano, Hawaii, to move seaward in response to slippage along a deep fault. Since then, a large part of the volcano's edifice has been adjusting to this perturbation. The summit of Kilauea extended at a rate of 0.26 meter per year until 1983, the south flank uplifted more than 0.5 meter, and the axes of both the volcano's rift zones extended and subsided; the summit continues to subside. These ground-surface motions have been remarkably steady and much more widespread than those caused by either recurrent inflation and deflation of the summit magma chamber or the episodic propagation of dikes into the rift zones. Kilauea's magmatic system is, therefore, probably deeper and more extensive than previously thought; the summit and both rift zones may be underlain by a thick, near vertical dike-like magma system at a depth of 3 to 9 kilometers.
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The south flank of Kilauea volcano has experienced two large [magnitude (M) 7.2 and M 6.1] earthquakes in the past two decades. Global Positioning System measurements conducted between 1990 and 1993 reveal seaward displacements of Kilauea's central south flank at rates of up to about 10 centimeters per year. In contrast, the northern side of the volcano and the distal ends of the south flank did not displace significantly. The observations can be explained by slip on a low-angle fault beneath the south flank combined with dilation deep within Kilauea's rift system, both at rates of at least 15 centimeters per year.
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OBJECTIVE: Severe congenital neutropenia (SCN), also known as Kostmann syndrome (SCN3, OMIM 610738), includes a variety of haematological disorders caused by different genetic abnormalities. Mutations in ELA2 are most often the cause in autosomal dominant or sporadic forms. Recently, mutations in HAX1 have been identified as the cause of some autosomal recessive forms of SCN, including those present in the original pedigree first reported by Kostmann. We sought to determine the relationship between HAX1 gene mutations and the clinical characteristics of Japanese cases of SCN. METHODS: The genes implicated in SCN (ELA2, HAX1, Gfi-1, WAS, and P14) were analysed in 18 Japanese patients with SCN. The clinical features of these patients were obtained from medical records. Immunoblotting of HAX1 was performed on cell extracts from peripheral blood leucocytes from patients and/or their parents. RESULTS: We found five patients with HAX1 deficiency and 11 patients with mutations in the ELA2 gene. In HAX1 deficiency, a homozygous single base pair substitution (256C>T), which causes the nonsense change R86X, was identified in three affected individuals. Two sibling patients showed a compound heterozygous mutation consisting of a single base pair substitution (256C>T) and a 59 bp deletion at nucleotides 376-434. There was no detectable phenotype in any heterozygous carrier. All patients with HAX1 deficiency had experienced developmental delay. Three patients carrying R86X also suffered from epileptic seizures. In contrast, no SCN patient with heterozygous mutations in the ELA2 gene suffered from any neurodevelopmental abnormality. CONCLUSIONS: These findings suggest that the R86X mutation in the HAX1 gene is an abnormality in Japanese SCN patients with HAX1 deficiency and may lead to neurodevelopmental abnormalities and severe myelopoietic defects.
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Deficiências do Desenvolvimento/genética , Mutação , Neutropenia/congênito , Neutropenia/genética , Proteínas/genética , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Bases , Feminino , Homozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Introduction : La maladie thromboembolique veineuse (MTEV) regroupe : la thrombose veineuse profonde(TVP) et l'embolie pulmonaire(EP).Ce travail a été initié pour identifier les particularités féminines si elles existent. Matériels et Méthode : il s'agissait d'étude rétrospective, descriptive réalisée dans le service de cardiologie du CHU de Kati sur une période allant du 01 janvier 2014 au 31 décembre 2021. Ont été inclues les patientes hospitalisées durant la dite période pour maladie thromboemboliqueveineuse. Les variables étudiées étaient les données sociales démographiques, les facteurs de risque, les paramètres cliniques et paracliniques, les aspects thérapeutiques et évolutifs. Résultats : Au total nous avons enregistré 68 cas de MTEV dont 40 (58,8%) femmes. Il s'agissait 12 (30%) cas de TVP, 25 (62,5%) d'EP et leur association dans 3 (7,5%) cas. La majorité (82,5%) des patientes était des femmes au foyer.Le post partum représentait 10% des cas. La probabilité clinique, selonle score de Wells était élevée chez 93% des TVP, intermédiaire pour les cas d'embolie pulmonaire avec 50%. L'angioscanner révélait que l'embolie pulmonaire était bilatérale dans 80% des cas. L'héparine et l'AVK ont été les plus utilisés. La mortalité était de 7,5%. Conclusion : les femmes sont plus victime des maladies thromboemboliques veineuses que les hommes. Le post partum est une situationparticulière chez la femme. Les récidives ne sont pas rares
Introduction: Venous thromboembolic disease (MTEV) includes: deep venous thrombosis (DVT) and pulmonary embolism (PE).This work was initiated to identify the female particularities if they exist.Materials and Method: This was a retrospective, descriptive study conductedin the cardiology department of the Kati university hospital over a period from January 01, 2014 to December 31, 2021.Patients hospitalized during the period for venousthromboembolic disease were included.The variables studied were demographic social data, risk factors, clinical and para-clinical parameters, therapeutic and evolutionary aspects. Results: In total we recorded 68 cases of MTEV of which 40 (58.8%) women. There were 12 (30%) cases of deep vein thrombosis, 25 (62.5%) cases of pulmonary embolism and their association in 3 (7.5%) cases.The majority (82.5%) of patients were housewives.Thepostpartum accounted for 10% of cases.The clinical probability according to the Wells score was high in 93% of deep vein thrombosis, intermediate for cases of pulmonary embolism with 50%.Angio-CT showed that pulmonary embolism was bilateral in 80% of cases. Heparin and anti-vitamin K were the most commonly used. Mortality was 7.5%. Conclusion: women are more victims of venous thromboembolic diseases than men. Postpartum is a special situation for women. Recurrences are not uncommon
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We initially conducted a multicenter, randomized trial (n=43), and subsequently a questionnaire study (n=209) of participating hospitals, to evaluate whether infused fresh frozen plasma (FFP) could prevent the occurrence of hepatic veno-occlusive disease (VOD) after stem cell transplantation (SCT). Forty-three patients were divided into two groups: 23 receiving FFP infusions and 20 not receiving it. VOD developed in three patients not receiving FFP. Plasma von Willebrand factor (VWF) antigen levels were lower at days 0, 7 and 28 after SCT in patients receiving FFP than in those not receiving it, whereas plasma ADAMTS13 activity (ADAMTS13:AC) did not differ between them. Plasma VWF multimer (VWFM) was demonstrated to be defective in the high approximately intermediate VWFM during the early post-SCT phase, but there was a significant increase in high VWFM just before VOD onset. This suggests that a relative enzyme-to-substrate (ADAMTS13/high-VWFM) imbalance is involved in the pathogenesis of VOD. To strengthen this hypothesis, the incidence of VOD was apparently lower in patients receiving FFP infusions than in those not receiving it (0/23 vs 3/20) in the randomized trial. Further, the results combined with the subsequent questionnaire study (0/36 vs 11/173) clearly showed the incidence to be statistically significant (0/59 vs 14/193, P=0.033).
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Proteínas ADAM/sangue , Hepatopatia Veno-Oclusiva/prevenção & controle , Plasma , Transplante de Células-Tronco , Fator de von Willebrand/análise , Proteína ADAMTS13 , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Plasma/enzimologiaRESUMO
The t(11;17) has been described in patients with acute myeloid leukemia (AML), and the AF17 gene was previously cloned as a fusion partner of the MLL gene in t(11;17)(q23;q21)-AML. We analyzed one patient with de novo AML and one with therapy-related AML with t(11;17)(q23;q25) and identified the AF17q25 gene on chromosome 17q25, a putative septin family gene, fused with MLL. AF17q25 encoded at least three kinds of proteins [type I (568 a.a.), type II (594 a.a.), and type III (574 a.a.)] that contained two kinds of different amino acid sequences at the COOH terminus. The MLL-AF17q25 fusion transcript consisted of type I AF17q25 transcript. The AF17q25 protein is homologous to septin family proteins, including H5, NEDD5, CDC10, and hCDCrel, which is one of the fusion partners of MLL in t(11;22)(q23;q11)-AML. These results suggest that AF17q25 and hCDCrel might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia.
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Cromossomos Humanos Par 11 , Cromossomos Humanos Par 17 , Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Adulto , Sequência de Aminoácidos , Fusão Gênica Artificial , Sequência de Bases , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , RNA Mensageiro/análiseRESUMO
The MLL gene is fused with the cAMP-responsive element binding protein-binding protein (CBP) gene in t(11;16)(q23;p13), which has been reported to be associated with therapy-related acute leukemia. We established a novel myeloid cell line, SN-1, from a patient with T-cell acute lymphoblastic leukemia with t(11;16)(q23;p13) having in-frame MLL-CBP fusion transcripts. The majority of the SN-1 cells were positive for myeloperoxidase when examined using an electron microscope and expressed CD13, CD33, CD56, and HLA-DR antigens, but not CD7, CD10, CD19, CD34, or CD41 antigens, suggesting that these cells are of myeloid origin. SN-1 cells underwent functional and morphological differentiation when treated with actinomycin D or sodium butyrate, but not with all-trans-retinoic acid (ATRA) or 1alpha,25-dihydroxyvitamin D3 (VD3). Exposure of SN-1 cells to ATRA hardly affected cell growth and differentiation, whereas the growth of HL-60 and NB4 cells treated with ATRA was effectively inhibited, and differentiation into mature granulocytes was induced. SN-1 cells were relatively insensitive to VD3 with respect to inhibiting the cell growth and inducing the ability to reduce nitroblue tetrazolium, lysozyme activity, and morphological differentiation, although the expression of CD11b was slightly induced by VD3. These results suggest that the cell line was impaired in the signal transduction systems of ATRA and VD3. This cell line should be useful for the study of the role of CBP as a transcriptional regulator in leukemia differentiation and for the functional analysis of the MLL-CBP fusion gene, which will provide new insights into leukemogenesis caused by 11q23 translocations.
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Colecalciferol/uso terapêutico , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 16 , Leucemia-Linfoma de Células T do Adulto/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Tretinoína/uso terapêutico , Sequência de Aminoácidos , Sequência de Bases , Pré-Escolar , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Histona-Lisina N-Metiltransferase , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Células Tumorais CultivadasRESUMO
PURPOSE: We sought to identify the clinical variables most critical to successful treatment of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH). PATIENTS AND METHODS: Among the factors tested were age at diagnosis (< 2 years or > or = 2 years), time from diagnosis to initiation of treatment with or without etoposide-containing regimens, timing of cyclosporin A (CSA) administration during induction therapy, and the presence or absence of etoposide. RESULTS: By Kaplan-Meier analysis, the overall survival rate for the entire cohort of 47 patients, most of whom had moderately severe to severe disease, was 78.3% +/- 6.7% (SE) at 4 years. The probability of long-term survival was significantly higher when etoposide treatment was begun less than 4 weeks from diagnosis (90.2% +/- 6.9% v 56.5% +/- 12.6% for patients receiving this agent later or not at all; P <.01, log-rank test). Multivariate analysis with the Cox proportional hazards model demonstrated the independent prognostic significance of a short interval from EBV-HLH diagnosis to etoposide administration (relative risk of death for patients lacking this feature, 14.1; 95% confidence interval, 1.16 to 166.7; P =.04). None of the competing variables analyzed had significant predictive strength in the Cox model. However, concomitant use of CSA with etoposide in a subset of patients appears to have prevented serious complications from neutropenia during the first year of treatment. CONCLUSION: We conclude that early administration of etoposide, preferably with CSA, is the treatment of choice for patients with EBV-HLH.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Histiocitose de Células não Langerhans/tratamento farmacológico , Histiocitose de Células não Langerhans/virologia , Adolescente , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Criança , Pré-Escolar , Ciclosporina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Histiocitose de Células não Langerhans/mortalidade , Humanos , Lactente , Masculino , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
WAVE isoforms, which consist of WAVE-1, WAVE-2 and WAVE-3, are members of the Wiskott-Aldrich syndrome protein (WASP) family. They are implicated in the regulation of actin-cytoskeletal reorganization downsteam of the small GTPase, Rac. Since platelet attachment to extracellular matrices leads to filopodial and lamellipodial extension, we examined the expression and subcellular localization of WAVEs in platelets. Employing primary megakaryocytic cells derived from cord blood as well as megakaryocytic cell lines, we also examined their expression during megakaryocytic differentiation. Immunoblotting and immunohistochemical analysis revealed that platelets expressed WAVE-1 and WAVE-2, whereas WAVE-3 expression was hardly to be detected. WAVE-1 expression was associated with megakaryocytic differentiation, whereas WAVE-2 and WAVE-3 expression was not changed by the differentiation. In adhered platelets both WAVE-1 and WAVE-2 were localized at the edge of the lamellipodia and at the tips of filopodia. In WASP-deficient platelets we found normal lamellipodial formation and localization of WAVE-1 and WAVE-2 at the edges of lamellipodia. Furthermore, we demonstrated that WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation. These results suggest that WAVE-1 and WAVE-2 regulate actin reorganization during platelet spreading and aggregate formation.
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Plaquetas/química , Megacariócitos/química , Proteínas dos Microfilamentos/metabolismo , Plaquetas/citologia , Diferenciação Celular , Linhagem da Célula , Citoesqueleto/metabolismo , Citosol/metabolismo , Humanos , Megacariócitos/citologia , Proteínas dos Microfilamentos/análise , Adesividade Plaquetária , Transporte Proteico , Proteínas , Pseudópodes/química , Família de Proteínas da Síndrome de Wiskott-AldrichRESUMO
We have analyzed the frequency and clinical significance of the MLL gene rearrangements in 42 cases of infant acute leukemias; including 37 cases of acute lymphoblastic leukemia (ALL) and five cases of acute myeloid leukemia (AML). MLL gene rearrangements were found in 27 of the 37 ALL cases (73 percent), and in all five AML cases. Cytogenetic studies showed 11q23 abnormalities in 24 of 27 ALL cases with MLL gene rearrangements. MLL gene rearrangements were significantly correlated with absence of CD10 expression and poor prognosis, but not with age under 6 months, hyperleukocytosis, myeloid-associated antigen expression, or CNS leukemia. The 3-year overall survival rate for ALL cases with MLL gene rearrangements was 5.3 +/- 5.2 percent, compared with 88.9 +/- 10.5 percent for cases with germline MLL (P=0.0001). Absence of CD10 expression was also associated with poor prognosis (9.9 +/- 6.6 percent vs 85.7 +/- 13.2 percent, P = 0.0003). Of the five AML cases, three have remained alive for 27 months to 67 months. These findings suggest that infant ALL with MLL gene rearrangement is strongly associated with poor prognosis. We consider that infant ALL should be treated on different chemotherapy protocols according to the presence or absence of MLL gene rearrangement.
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Aberrações Cromossômicas , Transtornos Cromossômicos , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição , Antígenos CD/análise , Southern Blotting , Medula Óssea/patologia , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 4 , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Recém-Nascido , Cariotipagem , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos , Masculino , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Translocação Genética , Dedos de ZincoRESUMO
Prognostic factors of juvenile myelomonocytic leukemia (JMML) have not been clarified because of its very low incidence and inaccuracy in the diagnosis. The purpose of this study was to evaluate children with JMML given an allogeneic hematopoietic stem cell transplantation (SCT) and the role of different variables potentially influencing outcome in a nationwide survey in Japan based on the newly proposed criteria by the International JMML Working Group. The study patients were 27 children who underwent SCT among 55 JMML patients retrospectively collected in the survey. The source of grafts was HLA-identical siblings in 12 cases, HLA-matched unrelated individuals in 10 and others in five. Total body irradiation was used in 18 cases. Event-free and overall survival (OS) at 4 years after SCT were 54.2 +/- 11.2% (s.e.) and 57.9 +/- 11.0% (s.e.), respectively. Six patients died of relapse and three of complications. Patients with abnormal karyotypes showed a significantly lower OS than those with normal karyotypes (P < 0.001). Patients below 1 year of age showed a significantly higher OS than those of 1 year of age or more (P = 0.02). Patients with grade 0-1 acute graft-versus-host disease (GVHD) or chronic GVHD had a more favorable OS than those without them, although they were not statistically significant (P > 0.05). Other variables studied were not associated with OS. A multivariate analysis of these factors yielded the abnormal karyotype as the only significant risk factor for lower OS (risk ratio: 11.0; 95% CI: 2.7-45.1).
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica/terapia , Adolescente , Medula Óssea/patologia , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Antígenos HLA-A/imunologia , Antígenos HLA-A/metabolismo , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Cariotipagem , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/mortalidade , Masculino , Metotrexato/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante HomólogoRESUMO
In recent pediatric collaborative studies of acute myeloid leukemia (AML), patients with Down's syndrome (DS) have better outcome than other patients when they were treated according to their intensive AML protocols. This may be attributed to enhanced sensitivity of DS AML cells to selected chemotherapeutic agents. We evaluated a less intensive chemotherapeutic regimen which was specifically designed for children with AML-DS. Remission induction chemotherapy consisted of daunorubicin (25 mg/m2/day for 2 days), cytosine arabinoside (100 mg/m2/day for 7 days), and etoposide (150 mg/m2/day for 3 days). Patients received one to seven courses of consolidation therapy of the same regimen. Thirty-three patients were enrolled on the study and their clinical, hematologic and immunophenotypic features were analyzed. Of the 33 patients, all were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia or myelodysplastic syndrome. All patients achieved a complete remission and estimated 8 year event-free survival rate was 80+/-7%. Three patients relapsed and two died due to cardiac toxicity and one due to septic shock. The results of our study showed that patients with AML-DS constitute a unique biologic subgroup and should be treated according to a less intensive protocol designed for AML-DS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome de Down/complicações , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pré-Escolar , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Leucemia Megacarioblástica Aguda/complicações , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Probabilidade , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype. OBJECTIVE: To examine MUNC13-4 mutations and the cytotoxic function of MUNC13-4 deficient T lymphocytes in Japanese FHL patients METHODS: Mutations of MUNC13-4 and the cytotoxicity of MUNC13-4-deficient cytotoxic T lymphocytes (CTL) were analysed in 16 Japanese families with non-FHL2 subtype. RESULTS: Five new mutations of the MUNC13-4 gene were identified in six families. The mutations were in the introns 4, 9, and 18, and exons 8 and 19. Two families had homozygous mutations, while the remaining four had compound heterozygous mutations. Cytotoxicity of MUNC13-4 deficient CTL was low compared with control CTL, but was still present. Clinically, the onset of disease tended to occur late; moreover, natural killer cell activity was not deficient in some FHL3 patients. CONCLUSIONS: MUNC13-4 mutations play a role in the development of FHL3 through a defective cytotoxic pathway.
Assuntos
Histiocitose de Células não Langerhans/genética , Mutação/genética , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Idade de Início , Análise Mutacional de DNA , Éxons/genética , Feminino , Histiocitose de Células não Langerhans/imunologia , Histiocitose de Células não Langerhans/fisiopatologia , Humanos , Lactente , Íntrons/genética , Japão , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Morphophenotypic lineage switches occur in a small percentage of those with acute leukemia, and the underlying mechanisms are not clear. In this study, we attempted to induce a lineage switch in acute myelocytic leukemia (AML) with monosomy 7, whose lineage had switched from acute T-lymphocytic leukemia (T-ALL) during chemotherapy, in severe combined immunodeficient (SCID) mice. Although the transplanted myeloid cells were engrafted in SCID mice without cytokine administration, T-ALL developed in SCID mice treated with recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. Analysis of the nucleotide sequences of the rearranged T-cell receptor gamma-chain (TCR-gamma) gene revealed that this lineage switch resulted from the selection of the T-lineage subclone in SCID mice, which had expanded at onset. In addition, we found that the T-lineage and myeloid cells belonged to the distinct subclones, which were different in TCR-gamma gene rearrangements, but were derived from a common clone with an identical N-ras gene mutation for both subclones. In in vitro cultures, only the myeloid subclone grew; the T-lineage subclone failed to grow even in the presence of recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. These results suggested that the initial diagnostic T-lymphoid subclone, whose growth was dependent on these cytokines and the hematopoietic microenvironment, emerged from a bipotential T-lymphoid/myeloid leukemic stem cell, and further genetic event(s) induced the myeloid subclone, which grew independently of these cytokines and the microenvironment.
Assuntos
Linhagem da Célula , Cromossomos Humanos Par 7 , Leucemia Mieloide/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Monossomia , Doença Aguda , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sequência de Bases , Pré-Escolar , DNA de Neoplasias , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-3/farmacologia , Cariotipagem , Leucemia Mieloide/genética , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Masculino , Camundongos , Camundongos SCID , Dados de Sequência Molecular , Transplante de Neoplasias , Proteínas Recombinantes/farmacologia , Células Tumorais CultivadasRESUMO
This study investigated the role of protein kinase C (PKC) in the pathogenesis of vasospasm after experimental subarachnoid hemorrhage (SAH). PKC activation by intracisternal injection of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TP)] induced dose-dependent, slowly developing, severe contraction of the basilar artery. A single intracisternal injection of TP (5 x 10(-9) M in the CSF) induced sustained contraction lasting over 3 days, which almost paralleled the changes of membrane-bound PKC activity in the basilar arterial wall. In a two-hemorrhage SAH model, membrane-bound PKC activity in the basilar artery increased up to day 4 and returned to the control level by day 14, whereas angiographic contraction reached a maximum on day 7 and still persisted at a moderate level on day 14. Thus, there was a discrepancy between arterial PKC activity and arterial contraction. Multiple intracisternal injections of TP produced 30-40% sustained contraction of the basilar artery lasting for more than 10 days along with sustained activation of PKC to levels compatible with that observed in the SAH model. However, TP injection caused considerably milder histological changes in the basilar artery than those noted in the SAH model. We concluded that cerebral vasospasm after SAH cannot be explained solely on the basis of activation of the PKC pathway.