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4.
Leukemia ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32203145

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) patients have an extremely poor prognosis, partly due to their immunosuppressive state. The majority of ATLL patients have leukemic cells with phenotype similar to Tregs, prompting suggestions that ATLL cells themselves have immunosuppressive functions. In this study, we detected CD39 expression on ATLL cells, particularly frequent on aggressive subtypes. CD39 and CD73 convert extracellular adenosine triphosphate (ATP) into adenosine, a key player in Tregs' immunosuppression. In vitro culture, both CD39+ ATLL cells and normal Tregs converted rapidly extracellular ATP to AMP, which was disturbed by CD39 inhibitors, and was negated in the CD39 knockout MJ cell line. The proliferation of cocultured CD4+/CD8+ normal T cells was suppressed by CD39+ MJ cells, but not by CD39 knockout MJ cells. Supplemented ATP was exhausted by an EG7-OVA T-cell line with stable CD39 induction, but not by mock. When these cell lines were subcutaneously transplanted into murine flanks, Poly(I:C) peritoneal administration reduced tumor size to 1/3 in mock-transplanted tumors, but not in CD39 induced tumors. Overall, we found that ATLL cells express CD39 at a high rate, and our results suggest that this helps ATLL cells escape antitumor immunity through the extracellular ATPDase-Adenosine cascade. These findings will guide future clinical strategies for ATLL treatment.

5.
Int J Hematol ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32200528

RESUMO

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases.

6.
Respir Investig ; 58(3): 204-211, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113934

RESUMO

BACKGROUND: Drug-induced pneumonitis is a disease encountered by pulmonologists in the clinical setting. The diagnosis generally considers the patient's clinical course and the results of peripheral blood tests, radiological examinations, and often bronchoscopic examinations. However, few studies have reported the association between radiological patterns such as ground-glass opacity (GGO) or consolidation, and bronchoalveolar lavage fluid (BALF) cell fractions. This study aimed to clarify this association. METHODS: Patients with a Naranjo's score of probable or definite were enrolled, and all 30 patients were categorized under probable. Data such as patient background, blood examination results, radiological findings, and BALF cell fractions were retrospectively collected. The association between BALF cell fractions and other factors such as chest computed tomography (CT) findings was evaluated. RESULTS: The most common radiological finding in patients with lymphocyte-dominant BALF was GGO, with only one patient exhibiting consolidation. However, patients with eosinophil-dominant BALF were more likely to have consolidation; only three cases showed crazy paving and one showed GGO. In addition, patients with a GGO-dominant pattern on CT had an increased lymphocyte fraction of 41.0%; those with a consolidation-dominant pattern showed a relatively high eosinophil fraction of 5.2%; and those with a crazy paving pattern showed elevated eosinophil and neutrophil fractions of 19.1% and 9.9%, respectively. CONCLUSIONS: In this study, a remarkable difference in radiological findings was observed among different BALF patterns.

7.
Biol Blood Marrow Transplant ; 26(5): 1028-1033, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32018061

RESUMO

Intestinal flora plays an essential role in regulating immune responses. Changes in the gut flora are associated with poor prognosis after allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to investigate the impact of diverse intestinal flora on survival after allogeneic HSCT. Using next-generation sequencing of the bacterial 16S ribosomal RNA (rRNA) gene, we found that the intestinal microbiota of patients undergoing allogeneic HSCT differed significantly from that of healthy controls. Furthermore, dysbiosis persisted for at least 1 year after transplantation. Interestingly, increased abundance of the genus Enterococcus detected by 16S rRNA sequencing as early as 1 month after transplantation was correlated with poor survival (overall survival at 2 years post-HSCT, 83.9% for patients with <1% relative abundance of Enterococcus and 47.6% for those with ≥1% relative abundance of Enterococcus), which was undetectable by conventional standard stool culture. These findings suggest that detection of Enterococcus by 16S rRNA analysis reflects compromised intestinal flora and may be a promising prognostic indicator.

9.
PLoS One ; 15(1): e0227636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917802

RESUMO

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.


Assuntos
Moléculas de Adesão Celular/sangue , Interferon gama/sangue , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pneumonia Bacteriana/sangue , Tuberculose Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico
10.
Intern Med ; 59(2): 247-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31941871

RESUMO

Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited. During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT). Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%). Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting. All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients.


Assuntos
Infecções por Vírus Respiratório Sincicial/diagnóstico por imagem , Infecções Respiratórias/diagnóstico por imagem , Idoso , Surtos de Doenças , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Sons Respiratórios , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
11.
Br J Haematol ; 188(3): 438-449, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31566729

RESUMO

The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.

12.
Korean J Intern Med ; 35(1): 249, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30099863
14.
Respir Investig ; 58(1): 1-3, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791907
15.
Respir Investig ; 58(1): 36-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791908

RESUMO

BACKGROUND: We evaluated immune reconstitution inflammatory syndrome (IRIS) in the lung in non-human immunodeficiency virus (HIV) patients. METHODS: We reviewed articles related to IRIS occurrence in the lung in non-HIV patients using a PubMed search. The keywords used for the search were "immune reconstitution syndrome" and "non-HIV." Only patients with lung involvement were included. Those with suggested IRIS caused by white blood cell recovery were excluded. RESULTS: There were 37 cases of IRIS in the lung in non-HIV patients. Complicating infections included tuberculosis (n = 17), histoplasmosis (n = 9), aspergillosis (n = 5), cryptococcosis (n = 4), and Pneumocystis pneumonia (n = 2). We also evaluated the underlying diseases, IRIS pathogenesis, management, and prognosis. IRIS was most commonly encountered in patients treated with anti-tumor necrosis factor (TNF) antibody who developed disseminated or extrapulmonary tuberculosis, leading to treatment discontinuation. CONCLUSIONS: The diagnosis and management of IRIS in the lung in non-HIV patients should be investigated further, especially in the era of anti-TNF treatment.

17.
Oncol Lett ; 18(3): 2777-2788, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452756

RESUMO

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

18.
Intern Med ; 58(22): 3349, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31327826
19.
Emerg Microbes Infect ; 8(1): 1043-1053, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31287781

RESUMO

The prevalence of nontuberculous mycobacteria (NTM) pulmonary diseases has been increasing worldwide. NTM consist of approximately 200 species and distinguishing between them at the subspecies level is critical to treatment. In this study, we sequenced 63 NTM genomes, 27 of which were newly determined, by hybrid assembly using sequencers from Illumina and Oxford Nanopore Technologies (ONT). This analysis expanded the available genomic data to 175 NTM species and redefined their subgenus classification. We also developed a novel multi-locus sequence typing (MLST) database based on 184 genes from 7547 assemblies and an identification software, mlstverse, which can also be used for detecting other bacteria given a suitable MLST database. This method showed the highest sensitivity and specificity amongst conventional methods and demonstrated the capacity for rapid detection of NTM, 10 min of sequencing of the ONT MinION being sufficient. Application of this methodology could improve disease epidemiology and increase the cure rates of NTM diseases.


Assuntos
Genoma Bacteriano , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Genômica , Humanos , Tipagem de Sequências Multilocus , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , Filogenia
20.
Respir Med Case Rep ; 28: 100889, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31304084

RESUMO

A 70-year-old Japanese man with stage IV EGFR-mutated lung adenocarcinoma complained of right mild back pain. The patient had been heavily treated with several cytotoxic or molecular targeted agents for 10 years and received a palliative radiation therapy of 2nd sacral vertebra 5 years ago. Computed tomography showed the abnormal lesion in right iliopsoas muscle. A pathological examination confirmed undifferentiated pleomorphic sarcoma, consistent with the diagnosis of radiation-induced sarcoma (RIS). Since RIS is a rare late-onset complication of radiation therapy, to our knowledge, this is the first report of RIS that was associated with advanced lung cancer and detected after palliative radiation therapy. The careful long-term follow-up is thus necessary even after palliative radiation therapy and we have to be aware of the existence of RIS.

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