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1.
Cytotherapy ; 24(9): 954-961, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534419

RESUMO

BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Adulto , Ciclofosfamida/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neoplasia Residual/etiologia , Neoplasia Residual/terapia , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Irradiação Corporal Total
2.
Hematol Oncol ; 40(5): 1041-1055, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35790020

RESUMO

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Irradiação Corporal Total , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos
3.
Proc Natl Acad Sci U S A ; 116(8): 3024-3029, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30642969

RESUMO

Polyneoptera represents one of the major lineages of winged insects, comprising around 40,000 extant species in 10 traditional orders, including grasshoppers, roaches, and stoneflies. Many important aspects of polyneopteran evolution, such as their phylogenetic relationships, changes in their external appearance, their habitat preferences, and social behavior, are unresolved and are a major enigma in entomology. These ambiguities also have direct consequences for our understanding of the evolution of winged insects in general; for example, with respect to the ancestral habitats of adults and juveniles. We addressed these issues with a large-scale phylogenomic analysis and used the reconstructed phylogenetic relationships to trace the evolution of 112 characters associated with the external appearance and the lifestyle of winged insects. Our inferences suggest that the last common ancestors of Polyneoptera and of the winged insects were terrestrial throughout their lives, implying that wings did not evolve in an aquatic environment. The appearance of the first polyneopteran insect was mainly characterized by ancestral traits such as long segmented abdominal appendages and biting mouthparts held below the head capsule. This ancestor lived in association with the ground, which led to various specializations including hardened forewings and unique tarsal attachment structures. However, within Polyneoptera, several groups switched separately to a life on plants. In contrast to a previous hypothesis, we found that social behavior was not part of the polyneopteran ground plan. In other traits, such as the biting mouthparts, Polyneoptera shows a high degree of evolutionary conservatism unique among the major lineages of winged insects.


Assuntos
Evolução Biológica , Insetos/fisiologia , Neópteros/fisiologia , Asas de Animais/fisiologia , Animais , Insetos/genética , Neópteros/genética , Filogenia
4.
Clin Exp Rheumatol ; 38 Suppl 127(5): 80-85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331270

RESUMO

OBJECTIVES: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS). METHODS: DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora. RESULTS: Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group. CONCLUSIONS: The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.


Assuntos
Síndrome de Behçet , Estomatite Aftosa , Bactérias/genética , Síndrome de Behçet/diagnóstico , Humanos , RNA Ribossômico 16S/genética , Saliva
5.
Proc Biol Sci ; 286(1895): 20182076, 2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30963947

RESUMO

Phylogenetic relationships among subgroups of cockroaches and termites are still matters of debate. Their divergence times and major phenotypic transitions during evolution are also not yet settled. We addressed these points by combining the first nuclear phylogenomic study of termites and cockroaches with a thorough approach to divergence time analysis, identification of endosymbionts, and reconstruction of ancestral morphological traits and behaviour. Analyses of the phylogenetic relationships within Blattodea robustly confirm previously uncertain hypotheses such as the sister-group relationship between Blaberoidea and remaining Blattodea, and Lamproblatta being the closest relative to the social and wood-feeding Cryptocercus and termites. Consequently, we propose new names for various clades in Blattodea: Cryptocercus + termites = Tutricablattae; Lamproblattidae + Tutricablattae = Kittrickea; and Blattoidea + Corydioidea = Solumblattodea. Our inferred divergence times contradict previous studies by showing that most subgroups of Blattodea evolved in the Cretaceous, reducing the gap between molecular estimates of divergence times and the fossil record. On a phenotypic level, the blattodean ground-plan is for egg packages to be laid directly in a hole while other forms of oviposition, including ovovivipary and vivipary, arose later. Finally, other changes in egg care strategy may have allowed for the adaptation of nest building and other novelties.


Assuntos
Baratas/classificação , Isópteros/classificação , Filogenia , Animais , Evolução Biológica , Baratas/genética , Isópteros/genética
6.
Cell Microbiol ; 19(3)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27601185

RESUMO

Streptococcus sanguinis is frequently isolated from the blood of patients with infective endocarditis and contributes to the pathology of this disease through induction of interleukin (IL)-1ß responsible for the development of the disease. However, the mechanism of IL-1ß induction remains unknown. In this study, S. sanguinis activated a murine dendritic cell (DC) to induce IL-1ß and this activity was attenuated by silencing the mRNAs of nucleotide-binding domain-like receptor containing protein 3 (NLRP3) and caspase-1. S. sanguinis induced IL-1ß production in murine bone marrow-derived macrophage, but this activity was significantly reduced in bone marrow-derived macrophages from NLRP3-, apoptosis-associated speck-like protein containing a caspase-recruitment domain-, and caspase-1-deficient mice. DC phagocytosed S. sanguinis cells, followed by the release of adenosine triphosphate (ATP). The ATP-degradating enzyme attenuated the release of ATP and IL-1ß. The inhibitors for ATP receptor reduced IL-1ß release in DC. These results strongly suggest that S. sanguinis has the activity to induce IL-1ß through the NLRP3 inflammasome in macrophage and DC and interaction of purinergic receptors with ATP released is involved in expression of the activity.


Assuntos
Células Dendríticas/imunologia , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Streptococcus sanguis/imunologia , Animais , Caspase 1/metabolismo , Camundongos
7.
Rinsho Ketsueki ; 59(7): 858-864, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30078794

RESUMO

Optimal salvage chemotherapy has not been established for patients with acute myeloid leukemia (AML) who fail to attain complete remission (CR) after one course of induction chemotherapy. This retrospective study aimed to assess the efficacy and safety of an MEC (mitoxantrone, 6 mg/m2, 1-3 days; etoposide, 80 mg/m2, 1-6 days; cytarabine, 1 g/m2, 1-6 days) regimen in patients with AML who failed to attain CR after one course of induction chemotherapy. Twenty-four patients were included in this study (median age, 58 years; range, 28-79 years). After one course of MEC, 11 patients (45.8%) attained CR. Febrile neutropenia was observed in all patients, and acute infection was observed in 7 patients (29.2%). However, no therapy-related death occurred. All patients eligible for transplantation and who attained CR after MEC salvage chemotherapy underwent allogeneic hematopoietic stem cell transplantation. The MEC regimen exhibited a good response rate with tolerable adverse events. Therefore, the MEC regimen can be safely used as a salvage treatment for patients with AML who failed to attain CR after one course of induction chemotherapy.


Assuntos
Etoposídeo/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Mitoxantrona/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
8.
Genes Cells ; 19(10): 743-54, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25205350

RESUMO

RING finger protein 4 (RNF4) represents a subclass of ubiquitin ligases that target proteins modified by the small ubiquitin-like modifier (SUMO) for ubiquitin-mediated degradation. We disrupted the RNF4 gene in chicken DT40 cells and found that the resulting RNF4(-/-) cells gradually lost proliferation capability. Strikingly, this compromised proliferation was associated with an unprecedented cellular effect: the gradual decrease in the number of intact chromosomes. In the 6 weeks after gene targeting, there was a 25% reduction in the DNA content of the RNF4(-/-) cells. Regarding trisomic chromosome 2, 60% of the RNF4(-/-) cells lost one homologue, suggesting that DNA loss was mediated by whole chromosome loss. To determine the cause of this chromosome loss, we examined cell-cycle checkpoint pathways. RNF4(-/-) cells showed a partial defect in the spindle assembly checkpoint, premature dissociation of sister chromatids, and a marked increase in the number of lagging chromosomes at anaphase. Thus, combined defects in SAC and sister chromatid cohesion may result in increased lagging chromosomes, leading to chromosome loss without accompanying chromosome gain in RNF4(-/-) cells. We therefore propose that RNF4 plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity.


Assuntos
Aberrações Cromossômicas , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Anáfase , Animais , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/genética , Galinhas , Segregação de Cromossomos , Dano ao DNA , Replicação do DNA , Pontos de Checagem da Fase M do Ciclo Celular , Mutação , Ubiquitina-Proteína Ligases/genética
9.
Mol Oral Microbiol ; 38(1): 41-47, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36333926

RESUMO

The Porphyromonas gingivalis Mfa1 fimbria is composed of the Mfa1 to Mfa5 proteins, encoded by the mfa1 to mfa5 genes, respectively, which are tandemly arranged on chromosomes. A recent study discovered that many P. gingivalis strains possess two mfa5 genes (called herein mfa5-1 and mfa5-2), which are also in tandem. This study examined the transcriptional unit and activity of mfa-cluster genes in strains with one (the ATCC 33277 and TDC60 strains) and two (the HG66 and A7436 strains) mfa5 genes. Complementary DNA was prepared from the total RNA extracted from the bacterial cells in the logarithmic growth phase using a random primer. PCR analysis for the intergenic regions from mfa1 to mfa5 or mfa5-2 showed that mfa1 to mfa5 or mfa5-2 formed a polycistronic gene cluster. Quantitative real-time PCR showed that the mfa1 transcription was 5-10 times higher than that of mfa2 in all the strains. However, mfa2 to mfa5 mostly showed a comparable expression. Both mfa5 genes were comparably transcribed in HG66 and A7436 strains. The transcriptional levels were almost consistent with the respective protein expression levels. In silico analysis identified a transcriptional terminator structure in the intergenic region between mfa1 and mfa2 that was probably responsible for the decreased transcription rate of mfa2 and the downstream genes.


Assuntos
Proteínas de Fímbrias , Porphyromonas gingivalis , Porphyromonas gingivalis/genética , Proteínas de Fímbrias/química , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Aderência Bacteriana , Fímbrias Bacterianas/química , Fímbrias Bacterianas/metabolismo , Família Multigênica , Proteínas de Bactérias/genética
10.
Transplant Cell Ther ; 29(6): 347.e1-347.e11, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36889508

RESUMO

Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematologic malignancies. CBT tolerates HLA mismatches between donors and recipients, but the HLA mismatches that generate graft-versus-tumor (GVT) effects remain unknown. Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT. A total of 492 patients with hematologic malignancies who underwent single-unit, T cell-replete CBT were included in this multicenter retrospective study. HLA epitope mismatches (EMs) were quantified using HLA matchmaker software from donor and recipient HLA-A, -B, -C, and -DRB1 allele data. Patients were dichotomized by median EM value and divided into 2 groups: patients who underwent transplantation in complete/partial remission (standard stage: 62.4%) and others (advanced stage: 37.6%). The median number of EMs in the graft-versus-host direction (GVH-EM) was 3 (range, 0 to 16) at HLA class I and 1 (range, 0 to 7) at HLA-DRB1. Higher HLA class I GVH-EM was associated with increased nonrelapse mortality (NRM) in the advanced stage group (adjusted hazard ratio [HR], 2.12; P = .021), with no significant advantage for relapse in either stage. In contrast, higher HLA-DRB1 GVH-EM was associated with better disease-free survival in the standard stage group (adjusted HR, .63; P = .020), which was attributed to lower relapse risk (adjusted HR, .46; P = .014). These associations also were observed even within HLA-DRB1 allele-mismatched transplantations in the standard stage group, indicating that EM might have an impact on relapse risk independent of allele mismatch. High HLA-DRB1 GVH-EM did not increase NRM in either stage. High HLA-DRB1 GVH-EM may lead to potent GVT effects and a favorable prognosis following CBT, especially in patients who underwent transplantation at the standard stage. This approach may facilitate appropriate unit selection and improve the overall prognosis of patients with hematologic malignancies who undergo CBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Humanos , Cadeias HLA-DRB1/genética , Epitopos/genética , Estudos Retrospectivos , Teste de Histocompatibilidade , Recidiva Local de Neoplasia/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia
11.
PLoS One ; 17(6): e0270198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35749516

RESUMO

Trepoenema denticola, a spirochetal bacterium, is associated with periodontal diseases. The type strain of the bacterium, ATCC 35405, is commonly used in a basic research. Here, we report that our stock strain derived from ATCC 35405 had a mutation on the chromosome and expressed differential characteristics from the original strain. Genome sequencing analysis revealed the lack of a phage-derived region, and over 200 mutations in the mutant strain. The mutant grew to a higher density in broth culture as compared with the origin. In addition, the mutant formed a colony on the surface of the agar medium, whereas the origin could not. On contrary, the mutant showed decreased motility and adhesion to gingival epithelial cells. There were no differences in the bacterial cell length and a chymotrypsin-like protease activity between the two strains. RNA and genome sequencing analysis could not identify the genes that introduced the phenotypic differences between the strains. This mutant is potentially useful for examining the genetic background responsible for the physiological and pathogenic characteristics of T. denticola.


Assuntos
Bacteriófagos , Treponema denticola , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Bacteriófagos/genética , Acúmulo de Mutações , Treponema/genética , Treponema denticola/genética
12.
Blood Adv ; 6(15): 4558-4569, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35737870

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising treatment for adult acute lymphoblastic leukemia (ALL), an intractable hematological malignancy. The trends in allo-HCT outcomes over the past 30 years were examined to verify the efficacy of evolving treatment methods and to identify further challenges. We analyzed data from a registry database that included 8467 adult ALL patients who underwent their first allo-HCT between 1990 and 2019. The period was divided into three 10-year intervals for analysis. Five-year overall survival improved from 48.2% to 70.2% in the first complete remission (CR1), from 25.6% to 44.1% in subsequent CR, and from 10.0% to 22.7% in non-CR. Nonrelapse mortality improved over the 3 decades in each disease stage. However, the relapse rate only improved in CR1 every decade (26.3% to 15.9% in CR1, 33.4% to 32.8% in subsequent CR, and 53.6% to 54.8% in non-CR). Although there were continual improvements in adjusted survival for Philadelphia chromosome (Ph)-positive patients, the improvement was inadequate for Ph- patients with t(4;11), t(8;14), t(14;18), or hypodiploidy. Allo-HCT outcomes for adults with ALL have improved over the past 30 years. Improved outcomes in the future will require more effective prevention of relapse in patients with ALL not in CR1 and in those with high-risk chromosomal abnormalities.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Cromossomo Filadélfia , Recidiva , Transplante Homólogo
13.
Microbiol Resour Announc ; 10(19)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986084

RESUMO

We report the draft genome sequence (143 contigs, with a total length of 2,424,805 bp and an N 50 value of 36,066 bp) of a bacterium isolated from an aggressive periodontal lesion in a patient. We assigned strain HSUH001 to Neisseria mucosa through a multilocus sequence analysis.

14.
J Microbiol Immunol Infect ; 54(6): 1159-1166, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32611503

RESUMO

BACKGROUND: Betel quid chewing is known as a crucial risk factor for oral diseases such as periodontal diseases, oral cancer, and precancerous lesions in Southeast Asian countries. Although abnormal oral bacterial flora may be linked to betel quid related-oral diseases such as oral cancer, precancerous lesions, and periodontal diseases, little information is available on alterations of their oral flora thus far. To identify these alterations, we analyzed the oral flora in betel quid chewers (BQC) and non-chewers (NC) in Sri Lanka. METHODS: Samples obtained from buccal swabs of BQC and NC were analyzed with a next generation sequencer. Data were processed and analyzed using the QIIME software package. Mann-Whitney U test and Permutational multivariate analysis of variance were used for statistical analyses. P values < 0.05 were considered to be statistically significant. RESULTS: In BQC, the proportion of periodontal pathogens including Actinomyces, Tannerella, and Prevotella was higher than that in NC (P < 0.05), while the proportion of cariogenic pathogens including Streptococcus, Lautropia, and Actinobacillus was lower than that in NC (P < 0.05). A statistically significant difference in Shannon index and PD Whole tree was observed between BQC and NC (P < 0.05). PCoA analysis detected different clusters in BQC and NC (P < 0.05). CONCLUSION: The results suggested that betel quid chewing significantly altered oral flora. Adequate oral health care may help prevent BQC from developing bacterial pathogen-related oral diseases.


Assuntos
Areca/efeitos adversos , Boca/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Análise por Conglomerados , DNA Bacteriano/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Doenças Periodontais/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sri Lanka
15.
Sci Rep ; 10(1): 21418, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293600

RESUMO

Since the introduction of leukemia-type induction therapies for T-cell lymphoblastic lymphoma (T-LBL), improvements in the long-term outcomes of T-LBL have been reported. However, indications for and the appropriate timing of hematopoietic stem cell transplantation (HSCT) have not yet been established. Therefore, we performed a multicenter retrospective cohort study of patients with T-LBL treated using leukemia-type initial therapies to compare the outcomes after HSCT at different disease stages. We enrolled 21 patients with T-LBL from a total of 11 centers, and all patients received hyper-CVAD as a leukemia-type initial regimen. HSCT was performed during the CR1/PR1 (standard disease) stage in 11 patients, while it was completed at a later or non-remission (advanced disease) stage in 10 patients. Following HSCT, the overall survival rate was significantly greater in standard disease than in advanced-disease patients (79.5% vs. 30.0% at 5 years; hazard ratio (HR) 5.97; p = 0.03), with trend to the lower incidence of relapse in the former group (27.3% vs. 60.0% at 5 years; HR 2.29; p = 0.19). A prognostic difference was not detected between cases treated with allogeneic and autologous HSCTs. Our study suggests that frontline HSCT may be a feasible treatment option for T-LBL, even in the era of leukemia-type initial therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Indução/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
16.
Clin Lymphoma Myeloma Leuk ; 19(7): e337-e342, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31053551

RESUMO

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (R/R-PTCL-NOS) usually have short survival with conventional salvage chemotherapies. Prediction of poor survival in patients who undergo conventional salvage chemotherapies might help identify candidates for novel therapies that have been recently available for R/R-PTCL-NOS. However, no prognostic marker other than the second-line International Prognostic Index (sIPI) has been reported. We aimed to investigate the prognostic value of serum soluble interleukin-2 receptor (sIL-2R) level in patients with R/R-PTCL-NOS. PATIENTS AND METHODS: We retrospectively analyzed 37 patients with R/R-PTCL-NOS who underwent salvage chemotherapy. Serum sIL-2R level was measured within a week before salvage chemotherapy initiation. We determined the cutoff level of serum sIL-2R as 4.03 times the upper limit of normal by using receiver operating characteristic curve analysis. RESULTS: The 3-year overall survival (3yOS) was 5.2% and 37.5% in high sIL-2R and low sIL-2R groups, respectively (P = .005). In multivariate analysis, high sIL-2R level was independently associated with lower 3yOS (hazard ratio, 2.30; 95% confidence interval, 1.04-5.11; P = .040). In subgroup analysis, high sIL-2R level did not affect 3yOS in patients with high-risk sIPI (NA [not available] vs. 7.1%; P = .354), but was significantly associated with poor 3yOS in patients with low-risk sIPI (NA vs. 60.0%; P = .037). CONCLUSION: Serum sIL-2R is a useful prognostic marker for patients with R/R-PTCL-NOS. In particular, high sIL-2R level can identify groups of patients with low-risk sIPI who have poor prognosis. Our results suggest that novel therapeutic approaches might be necessary for patients with high-risk sIPI and/or high sIL-2R level.


Assuntos
Linfoma de Células T Periférico/sangue , Linfoma de Células T Periférico/mortalidade , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Adulto Jovem
17.
Arthropod Struct Dev ; 47(1): 64-73, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29109050

RESUMO

The egg structure and outline of the embryonic development of Metallyticus splendidus of one of the basal Mantodea representatives, Metallyticidae, were described in the present study. The results obtained were compared with those from the previous studies, to reconstruct and discuss the groundplan of Mantodea and Dictyoptera. In M. splendidus, the egg is spheroidal, it has a convex ventral side at the center in which numerous micropyles are grouped, and it possesses a conspicuous hatching line in its anterior half. These are the groundplan features of mantodean eggs and the "grouped micropyles in the ventral side of the egg" are regarded as an apomorphic groundplan feature of Dictyoptera. A small circular embryo is formed by a simple concentration of blastoderm cells, which then undergoes embryogenesis of the typical short germ band type. Blastokinesis is of the "non-reversion type" and the embryo keeps its original superficial position and original orientation throughout embryonic development. During the middle stages of development, the embryo undergoes rotation around the egg's anteroposterior axis. These features are a part of the groundplan of Mantodea. It is uncertain whether sharing of the "non-reversion type" of blastokinesis by Mantodea and blaberoidean Blattodea can be regarded as homology or homoplasy.


Assuntos
Embrião não Mamífero/embriologia , Desenvolvimento Embrionário , Mantódeos/embriologia , Mantódeos/ultraestrutura , Animais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Óvulo/ultraestrutura
18.
Org Lett ; 9(8): 1573-6, 2007 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-17358075

RESUMO

[reaction: see text] Ethyl 1-thio-2,3,4,6-tetrakis-O-triisopropylsilyl-beta-d-glucopyranoside, ethyl 6-O-benzyl-1-thio-2,3,4-tris-O-triisopropylsilyl-beta-d-glucopyranoside, and ethyl 6-O-pivaloyl-1-thio-2,3,4-tris-O-triisopropylsilyl-beta-d-glucopyranoside induced highly beta-selective O-glucosidations. Among them, the 6-O-pivaloylated substrate provided the best selectivity up to alpha/beta = 3:97 with cyclohexylmethanol, and the substrate was used for glucosidations with secondary and tertiary alcohols in a highly beta-selective manner. The selectivity would be caused by the twist-boat conformation of the pyranose; this is the first beta-selective O-glucosidation based on conformational control of the pyranose ring.


Assuntos
Glicosídeos/química , Cicloexanos/química , Etilenos/química , Conformação Molecular , Compostos de Sulfidrila/química
19.
J Morphol ; 278(11): 1469-1489, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28707769

RESUMO

As the first step in the comparative embryological study of Blattodea, with the aim of reconstructing the groundplan and phylogeny of Dictyoptera and Polyneoptera, the embryonic development of a corydiid was examined and described in detail using Eucorydia yasumatsui. Ten to fifteen micropyles are localized on the ventral side of the egg, and aggregated symbiont bacterial "mycetomes" are found in the egg. The embryo is formed by the fusion of paired blastodermal regions, with higher cellular density on the ventral side of the egg. This type of embryo formation, regarded as one of the embryological autapomorphies of Polyneoptera, was first demonstrated for "Blattaria" in the present study. The embryo undergoes embryogenesis of the short germ band type, and elongates to its full length on the ventral side of the egg. The embryo undergoes katatrepsis and dorsal closure, and then finally, it acquires its definitive form, keeping its original position on the ventral side of the egg, with its anteroposterior axis never reversed throughout development. The information obtained was compared with that of previous studies on other insects. "Micropyles grouped on the ventral side of the egg" is thought to be a part of the groundplan of Dictyoptera, and "possession of bacteria in the form of mycetomes" to be an apomorphic groundplan of Blattodea. Corydiid embryos were revealed to perform blastokinesis of the "non-reversion type (N)", as reported in blaberoid cockroaches other than Corydiidae ("Ectobiidae," Blaberidae, etc.) and in Mantodea; the embryos of blattoid cockroaches (Blattidae and Cryptocercidae) and Isoptera undergo blastokinesis of the "reversion type (R)," in which the anteroposterior axis of the embryo is reversed during blastokinesis. Dictyopteran blastokinesis types can be summarized as "Mantodea (N) + Blattodea [= Blaberoidea (N) + Blattoidea (R) + Isoptera (R)]".


Assuntos
Baratas/anatomia & histologia , Baratas/embriologia , Desenvolvimento Embrionário , Animais , Baratas/ultraestrutura , Larva/anatomia & histologia , Larva/ultraestrutura , Óvulo/fisiologia , Óvulo/ultraestrutura , Filogenia , Fatores de Tempo
20.
J Microbiol Immunol Infect ; 50(3): 270-276, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26066542

RESUMO

BACKGROUND: Contaminated dental unit waterlines (DUWLs) are a known source of specific health care-acquired infections because of the difficulty in keeping them clean during routine dental practice. Recently, an electrolysis apparatus that uses only the chlorine normally present in municipal water, the Poseidon-S system, was developed as a novel additive-free disinfectant system to control microbial contamination in DUWLs. METHODS: The microbiological quality of water samples collected from DUWLs was assessed before and after installation of the Poseidon-S system in terms of the total viable counts (TVCs) of microorganisms. The microbicidal effects of the electrolyzed water against oral organisms and its cytotoxicity against human oral-derived cell lines were also examined. RESULTS: Water samples from the DUWLs initially had average microbial TVCs of 103-106 colony-forming units (CFU)/mL. After installation of the Poseidon-S system, the number of microorganisms in the water samples decreased to less than 1 × 102 CFU/mL. The electrolyzed water also exhibited remarkable microbicidal effects on the microorganisms present in the DUWLs as well as microorganisms commonly isolated from human oral cavities, but showed low cytotoxicity towards human oral-derived cells. CONCLUSION: This study demonstrated that routine use of the Poseidon-S system can effectively maintain low microbial levels in DUWLs.


Assuntos
Bactérias/isolamento & purificação , Descontaminação/métodos , Consultórios Odontológicos , Desinfetantes/farmacologia , Desinfecção/métodos , Microbiologia da Água , Abastecimento de Água , Linhagem Celular/efeitos dos fármacos , Linhagem Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Contagem de Colônia Microbiana , Desinfetantes/toxicidade , Humanos
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