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1.
Cell Prolif ; 54(8): e13082, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34152047

RESUMO

OBJECTIVES: To investigate whether human HLA-homozygous induced pluripotent stem cell (iPSC)-derived neural precursor cells (iPSC-NPCs) can provide functional benefits in Huntington's disease (HD), we transplanted them into the YAC128 transgenic HD mouse model. MATERIALS AND METHODS: CHAi001-A, an HLA-homozygous iPSC line (A*33:03-B*44:03-DRB1*13:02), was differentiated into neural precursor cells, and then, they were transplanted into 6 months-old YAC128 mice. Various behavioural and histological analyses were performed for five months after transplantation. RESULTS: Motor and cognitive functions were significantly improved in transplanted animals. Cells transplanted in the striatum showed multipotential differentiation. Five months after transplantation, the donor cells had differentiated into neurons, oligodendrocytes and astrocytes. Transplantation restored DARPP-32 expression, synaptophysin density, myelin basic protein expression in the corpus callosum and astrocyte function. CONCLUSION: Altogether, these results strongly suggest that iPSC-NPCs transplantation induces neuroprotection and functional recovery in a mouse model of HD and should be taken forward for clinical trials in HD patients.


Assuntos
Diferenciação Celular , Doença de Huntington/patologia , Células-Tronco Neurais/transplante , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Comportamento Animal , Linhagem Celular , Corpo Caloso/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Humanos , Doença de Huntington/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo
2.
J Stroke Cerebrovasc Dis ; 30(7): 105804, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33906072

RESUMO

BACKGROUND: Prolonged dysphagia is an important stroke-related complication that imposes a substantial burden on patients and families. However, simple scoring tool to predict prolonged dysphagia is not existing. MATERIALS AND METHODS: This retrospective cohort study used data from April 2010 to March 2016. Adult patients with first-ever stroke were included. The outcome was swallowing function at discharge from the subacute care hospital to the patient's home. We collected the following factors obtained at discharge from the University of Fukui Hospital: age, sex, type of stroke, comorbidities, smoking status, alcohol use, denture use, functional dependency in daily living before admission, National Institutes of Health Stroke Scale score (NIHSS) at admission, and Functional Independence Measure(FIM). Data were divided into a training set (70%) and test set (30%). Lasso and logistic regression were used for feature selection, a scoring system was then developed, and its prediction performance evaluated. RESULTS: This study enrolled 462 patients with acute stroke. Using lasso and logistic regression, three variables (functional dependency before admission, Functional Independence Measure [FIM]-cognitive and FIM-motor scores at transfer) remained statistically significant predictors of prolonged dysphagia. Risk scores were categorized as low risk (0-2), moderate risk (3-4), and high risk (5-7), with dysphagia rates of 0%-1%, 13%-29%, and 50%-100%, respectively. A newly developed score ≥3 was the optimal cutoff for identifying patients with the potential risk of prolonged dysphagia (C-statistics, 0.92 in the test set). CONCLUSION: The developed scoring system is simple and has a high performance in predicting prolonged dysphagia after acute stroke.


Assuntos
Regras de Decisão Clínica , Transtornos de Deglutição/diagnóstico , Deglutição , Alta do Paciente , Acidente Vascular Cerebral/diagnóstico , Cuidados Semi-Intensivos , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/reabilitação , Feminino , Estado Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral , Fatores de Tempo , Adulto Jovem
3.
Acute Med Surg ; 8(1): e637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717490

RESUMO

AIM: To evaluate whether vital signs can predict whether hypoglycemia can be eliminated as the cause of impaired consciousness in prehospital settings. METHODS: We extracted the data of patients who underwent blood glucose measurements by paramedics in Kobe City, Japan from April 2015 to March 2019. We used receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the validity of the vital signs in distinguishing hypoglycemia. We also calculated stratum-specific likelihood ratios to examine the threshold at which hypoglycemia becomes less likely for each vital sign. RESULTS: Of the 1,791 patients, 1,242 were eligible for analysis. Hypoglycemia was observed in 324 patients (26.1%). Significant differences in each vital sign were noted between the hypoglycemic and non-hypoglycemic groups. Body temperature was moderately accurate in differentiating between the two groups (AUC, 0.71; 95% confidence interval, 0.68-0.74). Furthermore, in patients with systolic blood pressure <100 mmHg and body temperature ≥38°C, it was unlikely that hypoglycemia caused impaired consciousness (stratum-specific likelihood ratios 0.12 and 0.15; 95% confidence intervals, 0.05-0.25 and 0.06-0.35, respectively). CONCLUSION: In the prehospital assessment of patients with impaired consciousness, high fever or hypotension was helpful in differentiating between hypoglycemia and non-hypoglycemia. In particular, body temperature ≥38°C or systolic blood pressure <100 mmHg indicated a low likelihood of hypoglycemia. A validation study is needed to confirm the findings in this study.

4.
Am J Emerg Med ; 38(12): 2658-2660, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33039219

RESUMO

INTRODUCTION: Tube thoracostomy is an important treatment for traumatic hemothorax and pneumothorax. The optimal tube diameter remains unclear. To reduce invasiveness, we use small-bore chest tubes (≤20 Fr) for all trauma patients for whom tube thoracostomy is indicated in our emergency department (ED). The aim of this study was to investigate the effectiveness and safety of small-bore tube thoracostomy for traumatic hemothorax or pneumothorax. METHOD: We conducted a retrospective observational study at a single emergency medical center. This study included adult patients (≥18 years old) who had undergone tube thoracostomy for chest trauma in the ED during the 5 years from October 2013 to September 2018. We used 20 Fr chest tubes or 8 Fr pigtail catheters. The examined outcome was tube-related complications, such as tube obstruction, retained hemothorax, and unresolved pneumothorax. RESULTS: A total of 107 tube thoracostomies were performed in 102 patients. The mean Injury Severity Score of these patients was 17.8 (±9.6), and the mean duration of the tube placement period was 3.9 days (±1.8). Eight patients developed tube-related complications (7.8%) (retained hemothorax: 4 patients (3.9%), unresolved pneumothorax: 4 patients (3.9%)). None of these cases were caused by tube obstruction. Although the drainage itself was effective, they underwent definitive invasive interventions to stop bleeding or air leak. CONCLUSION: Our study showed that the use of small-bore (≤20 Fr) chest tubes to treat traumatic hemothorax/pneumothorax achieved the purposes of tube thoracostomy. It might be possible to safely manage chest trauma with small-bore chest tubes.


Assuntos
Tubos Torácicos , Hemotórax/cirurgia , Pneumotórax/cirurgia , Traumatismos Torácicos/terapia , Toracostomia/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Embolização Terapêutica , Feminino , Fixação Interna de Fraturas , Hemotórax/etiologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Redução Aberta , Pneumotórax/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fraturas das Costelas/cirurgia , Traumatismos Torácicos/complicações , Cirurgia Torácica Vídeoassistida , Falha de Tratamento , Adulto Jovem
5.
Cell Prolif ; 53(9): e12884, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32713053

RESUMO

OBJECTIVES: Human-induced pluripotent stem cells (hiPSCs) are a promising cell source for treating ischaemic stroke. Although autologous hiPSCs provide the advantage of avoiding immune rejection, their practical limitations, such as substantial amount of time and costs to generate individual iPSC lines, have hampered their widespread application in clinical settings. In this study, we investigated the therapeutic potential of neural precursor cells derived from human HLA-homozygous induced pluripotent stem cells (hiPSC-NPCs) following intracerebral transplantation into a rodent model of middle cerebral artery occlusion (MCAo). MATERIALS AND METHODS: We differentiated a GMP-grade HLA-homozygous hiPSC line (CMC-hiPSC-004) into neural precursor cells for transplantation into rats at the subacute stage of ischaemic stroke (ie at 7 days after the induction of MCAo). To investigate functional recovery, the transplanted animals were subjected to five behavioural tests, namely the rotarod, stepping, mNSS, staircase and apomorphine-induced rotation tests, for up to 12 weeks, followed by histological analyses. RESULTS: We observed that the hiPSC-NPC transplantation produced significant behavioural improvements. At 12 weeks post-transplantation, a high proportion of transplanted cells survived and had differentiated into MAP2+ mature neurons, GABAergic neurons and DARPP32+ medium spiny neurons. The transplanted cells formed neuronal connections with striatal neurons in the host brain. In addition, hiPSC-NPC transplantation gave rise to enhanced endogenous repair processes, including decreases of post-stroke neuroinflammation and glial scar formation and an increase of proliferating endogenous neural stem cells in the subventricular zone as well as the perilesional capillary networks. CONCLUSIONS: These results strongly suggest that HLA-homozygous hiPSC-NPCs may be useful for treating ischaemic stroke patients.


Assuntos
Antígenos HLA , Células-Tronco Pluripotentes Induzidas/transplante , Infarto da Artéria Cerebral Média/terapia , Células-Tronco Neurais/transplante , Animais , Linhagem Celular , Modelos Animais de Doenças , Antígenos HLA/genética , Homozigoto , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Células-Tronco Neurais/metabolismo , Neurogênese , Ratos Sprague-Dawley , Transplante de Células-Tronco/métodos
6.
Ann Lab Med ; 38(5): 481-483, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29797820

RESUMO

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×109/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.


Assuntos
Leucemia Mielomonocítica Crônica/diagnóstico , Idoso , Feminino , Humanos , Janus Quinase 2/genética , Leucemia Mielomonocítica Crônica/classificação , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Contagem de Plaquetas , Estudos Retrospectivos , Trissomia , Organização Mundial da Saúde
7.
Cryobiology ; 78: 65-69, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28716596

RESUMO

Umbilical cord blood (CB) banks usually freeze and store CB for clinical transplantation using conventional controlled-rate freezer or the automated BioArchive system. The aim of this study is to compare the quality of CB cryopreserved with conventional and automated methods and to make clear the cause of the quality difference between the two methods. The experiment used 80 CB units: 40 were conventionally cryopreserved and the remainder were cryopreserved with a BioArchive. After thawing, the following measures of CB quality were compared: recovery rates of cell count, cell viability of total nucleated cells (TNCs), mononuclear cells (MNCs), and CD34+ cells, as well as colony-forming unit-granulocyte/macrophage (CFU-GM) content. Additionally, processing and storage records were reviewed to quantify the number of exposures of CB units at room temperature (transient warming event, TWE), which was analyzed in relation to CB quality. MNC and CD34+ cell viability were as follows: MNC, 78.2% ± 6.8% (conventional), 81.7% ± 7.2% (automated); CD34+ cell, 90.6% ± 6.9% (conventional), 94.7% ± 3.5% (automated). The absolute CFU-GM content per CB unit was 7.1 × 105 ± 5.9 × 105 with conventional cryopreservation and 12.3 × 105 ± 12.0 × 105 with automated cryopreservation. CBs cryopreserved with BioArchive showed significantly higher MNC and CD34+ cell viability, and CFU-GM content than those conventionally cryopreserved. The CB quality comparison depending on the amount of TWEs showed no significant quality difference between groups that were more exposed to TWEs and groups that were less exposed. CBs cryopreserved with BioArchive were of higher quality than conventionally cryopreserved CBs, and the cause of quality difference might be due to the difference of freezing conditions rather than the TWE effect.


Assuntos
Criopreservação/métodos , Sangue Fetal/citologia , Sangue Fetal/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Leucócitos Mononucleares/fisiologia , Antígenos CD34/metabolismo , Contagem de Células , Sobrevivência Celular , Temperatura Baixa , Ensaio de Unidades Formadoras de Colônias , Humanos
8.
Transfusion ; 55(8): 2017-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25858170

RESUMO

BACKGROUND: Successful hematopoietic stem cell transplantation using stored umbilical cord blood (CB) largely depends on cell dose and quality of CB units. The aim of this study was to assess the degree of early apoptosis, in addition to cell viability and hematopoietic potential, in umbilical CB units after storage. STUDY DESIGN AND METHODS: Sixty CB units that had been cryopreserved for up to 8 years in a single public CB bank were investigated. After the CB units were thawed, cell viability and early apoptosis of total nucleated cells (TNCs), mononuclear cells (MNCs), and CD34+ cells were determined using flow cytometric method based on 7-aminoactinomycin D (7-AAD) and annexin V staining. Next, clonogenic assays to predict graft potency were performed. RESULTS: Postthawing cell viability values determined by 7-AAD were as follows: TNCs, 78.8% ± 5.8%; MNCs, 88.4% ± 5.8%; and CD34+ cells, 94.1% ± 3.2%. Cell viability values using 7-AAD and annexin V dual staining were as follows: TNCs, 71.2% ± 11.3%; MNCs, 83.1% ± 7.0%; and CD34+ cells, 88.8% ± 6.0%. Early apoptotic cells (7-AAD-negative and annexin V-positive cells) in TNCs, MNCs, and CD34+ cells were 6.4% ± 3.5%, 5.4% ± 3.1%, and 5.3% ± 4.1%, respectively. The corrected colony-forming unit-granulocyte-macrophage content per 100 CD34+ cells was 67.5 ± 48.7. CONCLUSIONS: Postthawing cell viability determined by flow cytometric methods was in the following order: TNCs < MNCs < CD34+ cells. CD34+ cell viability was nearly identical to that of fresh CB 48 hours after collection. Necrosis or apoptosis in cryopreserved CB units did not accelerate during storage.


Assuntos
Preservação de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Criopreservação , Sangue Fetal/citologia , Antígenos CD34/sangue , Apoptose , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Dactinomicina , Citometria de Fluxo , Corantes Fluorescentes , Granulócitos/citologia , Humanos , Macrófagos/citologia , Monócitos/citologia , Fatores de Tempo
9.
J Am Geriatr Soc ; 63(3): 439-46, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25739422

RESUMO

OBJECTIVES: To study the association between total and differential white blood cell (WBC) count and incident stroke in an older Asian population. DESIGN: Prospective population-based study with 8 years of follow-up. SETTING: The Honolulu Heart Program, Oahu, Hawaii. PARTICIPANTS: Japanese-American men aged 71 to 93 who were free of stroke and had baseline WBC counts measured in 1991-93 (N=3,342). MEASUREMENTS: Participants were divided into quartiles of total and differential WBC count for analysis and were followed for incident stroke (thromboembolic and hemorrhagic (hemorrhagic)) for 8 years using data from a comprehensive hospital surveillance system. RESULTS: Age-adjusted incident stroke rates increased significantly with increasing WBC quartile (Q1, 7.68; Q2, 9.04; Q3, 9.26; Q4, 14.10 per 1,000 person-years of follow-up, P=.001). Hazard ratios (HRs) for stroke for each quartile of total and differential WBC count were obtained using Cox regression analysis, with the lowest quartile as the reference group. After full adjustment, including age; cardiovascular risk factors; fibrinogen; prevalent coronary heart disease, cancer, or chronic obstructive pulmonary disease, and nonsteroidal anti-inflammatory drug use, HRs were 1.62 (95% confidence interval (CI)=1.04-2.52, P=.03) in the highest quartile of total WBC and 2.19 (95% CI=1.41-3.39, P<.001) in the highest quartile of neutrophil counts. Significant associations were also seen for thromboembolic but not for hemorrhagic strokes. No significant associations were found between lymphocyte or monocyte counts and incident stroke or subtypes. CONCLUSION: In elderly Japanese-American men, higher total WBC and neutrophil counts were independent predictors of overall stroke, as well as thromboembolic stroke.


Assuntos
Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Asiático , Havaí , Humanos , Incidência , Contagem de Leucócitos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Tempo
10.
J Dermatol ; 41(4): 319-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24517547

RESUMO

Plate-like osteoma cutis (PLOC) is a dermatological disorder characterized by superficial ossification and rarely occurs without any underlying tissue abnormalities or pre-existing calcification. The hereditary form of PLOC is mainly due to inactivating mutation in the GNAS gene. Inactivating mutation of the GNAS gene is associated with several diseases, which commonly manifest heterotopic ossification and hormonal resistance; however, the development of malignant neoplasm has never been reported. Herein, we report a case of a patient with a novel nonsense mutation in the GNAS gene, who presented with concurrent PLOC and medulloblastoma.


Assuntos
Doenças Ósseas Metabólicas/genética , Neoplasias Cerebelares/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Meduloblastoma/genética , Neoplasias Primárias Múltiplas/genética , Ossificação Heterotópica/genética , Dermatopatias Genéticas/genética , Sequência de Bases , Doenças Ósseas Metabólicas/patologia , Cromograninas , Códon sem Sentido , DNA de Neoplasias/genética , Evolução Fatal , Homozigoto , Humanos , Lactente , Masculino , Ossificação Heterotópica/patologia , Dermatopatias Genéticas/patologia
11.
Blood Res ; 48(1): 31-4, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23589792

RESUMO

BACKGROUND: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. METHODS: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. RESULTS: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×10(9)/L and 2.7 to 124.0 (median 54.5)×10(9)/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 µg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). CONCLUSION: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.

12.
J Immunol ; 190(3): 1312-8, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23293355

RESUMO

NF-κB is one of the key transcription factors activated by receptor activator of NF-κB ligand (RANKL) during osteoclast differentiation. The 8-kDa dynein L chain (LC8) was previously identified as a novel NF-κB regulator. However, its physiological role as an NF-κB inhibitor remains elusive. In this study, we showed the inhibitory role of LC8 in RANKL-induced osteoclastogenesis and signaling pathways and its protective role in osteolytic animal models. LC8 suppressed RANKL-induced osteoclast differentiation, actin ring formation, and osteoclastic bone resorption. LC8 inhibited RANKL-induced phosphorylation and subsequent degradation of IκBα, the expression of c-Fos, and the consequent activation of NFATc1, which is a pivotal determinant of osteoclastogenesis. LC8 also inhibited RANKL-induced activation of JNK and ERK. LC8-transgenic mice exhibited a mild osteopetrotic phenotype. Moreover, LC8 inhibited inflammation-induced bone erosion and protected against ovariectomy-induced bone loss in mice. Thus, our results suggest that LC8 inhibits osteoclast differentiation by regulating NF-κB and MAPK pathways and provide the molecular basis of a new strategy for treating osteoporosis and other bone diseases.


Assuntos
Reabsorção Óssea/prevenção & controle , Dineínas do Citoplasma/fisiologia , Osteoclastos/patologia , Osteólise/prevenção & controle , Ligante RANK/antagonistas & inibidores , Transdução de Sinais/fisiologia , Actinas/análise , Animais , Diferenciação Celular , Dineínas do Citoplasma/genética , Dineínas do Citoplasma/toxicidade , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática , Regulação da Expressão Gênica/fisiologia , Genes fos , Humanos , Proteínas I-kappa B/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/biossíntese , Fatores de Transcrição NFATC/genética , Osteólise/fisiopatologia , Osteopetrose/genética , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/prevenção & controle , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Recombinantes de Fusão/fisiologia , Proteínas Recombinantes de Fusão/toxicidade
13.
Acta Haematol ; 128(3): 131-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22854283

RESUMO

More than 70 different mixed lineage leukemia (MLL) rearrangements involving 11q23 have been molecularly characterized in acute leukemia. Among these, the MLLT11 gene is highly unique as MLL fusion partner because the entire open reading frame is usually fused in-frame to the N-terminal portion of the MLL gene. By using molecular genetic methods, we identified the chromosomal fusion site within MLL exon 10 sequences which were fused to the MLLT11 intron 1 sequences. This unusual break site results in the creation of two in-frame MLL-MLLT11 fusion transcripts in this acute myeloid leukemia patient with t(1;11)(q21;q23). One fusion transcript represents a normal splice product, while the other contains intronic sequences and a cryptic splice event in order to generate an intact fusion transcript. We also reviewed all published articles which have reported t(1;11)(q21;q23) in myeloid or lymphoid neoplasm and attempted to summarize these published data. Of interest, pediatric patients displayed a significant larger portion of unique balanced translocations (n = 40), while complex karyotypes were less often identified (n = 12). Vice versa, in adult leukemia patients, complex karyotypes (n = 5) were more frequent than unique balanced translocations (n = 2).


Assuntos
Cromossomos Humanos Par 11/genética , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Sequência de Bases , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Splicing de RNA , Translocação Genética
16.
Korean J Hematol ; 47(4): 302-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23320011

RESUMO

Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patients with TRALI show improvement within 48-96 hours, our patient's condition rapidly worsened, and he did not respond to supportive treatment. TRALI is a relatively common and serious adverse transfusion reaction that requires prompt diagnosis and management.

17.
Ann Clin Lab Sci ; 41(3): 267-72, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22075511

RESUMO

SET-NUP214 rearrangements have been rarely reported in T-cell acute lymphoblastic leukemia (T-ALL), acute undifferentiated leukemia, and acute myeloid leukemia, and most documented cases have been associated with normal karyotypes in conventional cytogenetic analyses. Here, we describe a novel case of T-ALL associated with a mediastinal mass and a SET-NUP214 rearrangement, which was masked by a complex karyotype at the time of initial diagnosis. Using multiplex reverse transcriptase-polymerase chain reaction analysis, we detected a cryptic SET-NUP214 rearrangement in our patient. As only 11 cases (including the present study) of T-ALL with SET-NUP214 rearrangement have been reported, the clinical features and treatment outcomes have not been fully determined. Further studies are necessary to evaluate the incidence of SET-NUP214 rearrangement in T-ALL patients and the treatment responses as well as prognosis of these patients.


Assuntos
Chaperonas de Histonas/genética , Neoplasias do Mediastino/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Fatores de Transcrição/genética , Cariótipo Anormal , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA , Rearranjo Gênico , Chaperonas de Histonas/metabolismo , Humanos , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Fatores de Transcrição/metabolismo
18.
Korean J Lab Med ; 30(2): 117-21, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20445327

RESUMO

The translocation t(10;11)(p13;q14q21) has been found to be recurrent in acute lymphoblastic and myeloid leukemias, and results in the fusion of the clathrin assembly lymphoid myeloid leukemia (CALM) gene with the AF10 gene; these genes are present on chromosomes 11 and 10, respectively. Because the CALM-AF10 rearrangement is a rare chromosomal abnormality, it is not included in routine molecular tests for acute leukemia. Here, we describe the cases of 2 patients with the CALM-AF10 fusion gene. The first patient (case 1) was diagnosed with T-cell ALL, and the second patient (case 2) was diagnosed with AML. Both patient samples showed expression of the homeobox A gene cluster and the histone methyltransferase hDOT1L, which suggests that they mediate leukemic transformation in CALM-AF10-positive and mixed-lineage leukemia-AF10-positive leukemias. Both patients achieved complete remission after induction chemotherapy. The first patient (case 1) relapsed after double-unit cord blood transplantation; there was no evidence of relapse in the second patient (case 2) after allogenic peripheral blood stem cell transplantation. Since CALM-AF10- positive leukemias have been shown to have poor prognosis with conventional therapy, molecular tests for CALM-AF10 rearrangement would be necessary to detect minimal residual disease during follow-up.


Assuntos
Leucemia Mieloide Aguda/genética , Proteínas Monoméricas de Montagem de Clatrina/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Medula Óssea/patologia , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 11 , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Histona Metiltransferases , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Recidiva , Translocação Genética
19.
J Clin Invest ; 119(4): 813-25, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19258703

RESUMO

Regulation of the formation and function of bone-resorbing osteoclasts (OCs) is a key to understanding the pathogenesis of skeletal disorders. Gene-targeting studies have shown that the RANK signaling pathway plays a critical role in OC differentiation and function. Although pharmaceutical blockade of RANK may be a viable strategy for preventing bone destruction, RANK is implicated in multiple biological processes. Recently, a cytoplasmic motif of RANK was identified that may be specifically involved in OC differentiation. Here, we developed a cell-permeable inhibitor termed the RANK receptor inhibitor (RRI), which targets this motif. The RRI peptide blocked RANKL-induced OC formation from murine bone marrow-derived macrophages. Furthermore, RRI inhibited the resorptive function of OCs and induced OC apoptosis. Treatment with the peptide impaired downstream signaling of RANK linked to Vav3, Rac1, and Cdc42 and resulted in disruptions of the actin cytoskeleton in differentiated OCs. In addition, RRI blocked inflammation-induced bone destruction and protected against ovariectomy-induced bone loss in mice. These data may be useful in the development of selective therapeutic agents for the treatment of osteoporosis and other bone diseases.


Assuntos
Reabsorção Óssea/prevenção & controle , Osteoclastos/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/antagonistas & inibidores , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Reabsorção Óssea/patologia , Reabsorção Óssea/fisiopatologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Mutagênese Sítio-Dirigida , Oligopeptídeos/genética , Oligopeptídeos/farmacologia , Osteoclastos/citologia , Osteoclastos/fisiologia , Proteínas Proto-Oncogênicas c-vav/fisiologia , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/fisiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/fisiologia , Transdução Genética
20.
Yonsei Med J ; 44(5): 928-30, 2003 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-14584114

RESUMO

This report documents a case of myeloid erythrophagocytosis in a patient with myeloproliferative disorder. The patient had pancytopenia and his marrow was hyperplastic with erythrophagocytosis by myeloid cells of various stages, including myeloblasts. He was diagnosed to have a prefibrotic stage of chronic idiopathic myelofibrosis. The erythrophagocytosis by myeloid cells persisted even after 2 months of treatment for the primary disorder.


Assuntos
Eritrócitos/patologia , Células Mieloides/patologia , Transtornos Mieloproliferativos/patologia , Fagocitose , Humanos , Masculino , Pessoa de Meia-Idade , Pancitopenia/patologia
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