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1.
J Med Invest ; 71(1.2): 62-65, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38735726

RESUMO

BACKGROUND: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking. AIMS/OBJECTIVES: This study aimed to investigate the long-term prognosis of PNN. MATERIALS AND METHODS: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of >5 years and <5 years. RESULTS: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of >5 years and <5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period. CONCLUSIONS AND SIGNIFICANCE: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for >5 years. J. Med. Invest. 71 : 62-65, February, 2024.


Assuntos
Rinite Alérgica Perene , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Rinite Alérgica Perene/cirurgia , Denervação/métodos , Adulto Jovem , Inquéritos e Questionários , Satisfação do Paciente , Nariz/cirurgia , Nariz/inervação
3.
Biotechnol Biofuels Bioprod ; 17(1): 13, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281982

RESUMO

BACKGROUND: Isopropanol (IPA) is a commodity chemical used as a solvent or raw material for polymeric products, such as plastics. Currently, IPA production depends largely on high-CO2-emission petrochemical methods that are not sustainable. Therefore, alternative low-CO2 emission methods are required. IPA bioproduction using biomass or waste gas is a promising method. RESULTS: Moorella thermoacetica, a thermophilic acetogenic microorganism, was genetically engineered to produce IPA. A metabolic pathway related to acetone reduction was selected, and acetone conversion to IPA was achieved via the heterologous expression of secondary alcohol dehydrogenase (sadh) in the thermophilic bacterium. sadh-expressing strains were combined with acetone-producing strains, to obtain an IPA-producing strain. The strain produced IPA as a major product using hexose and pentose sugars as substrates (81% mol-IPA/mol-sugar). Furthermore, IPA was produced from CO, whereas acetate was an abundant byproduct. Fermentation using syngas containing both CO and H2 resulted in higher IPA production at the specific rate of 0.03 h-1. The supply of reducing power for acetone conversion from the gaseous substrates was examined by supplementing acetone to the culture, and the continuous and rapid conversion of acetone to IPA showed a sufficient supply of NADPH for Sadh. CONCLUSIONS: The successful engineering of M. thermoacetica resulted in high IPA production from sugars. M. thermoacetica metabolism showed a high capacity for acetone conversion to IPA in the gaseous substrates, indicating acetone production as the bottleneck in IPA production for further improving the strain. This study provides a platform for IPA production via the metabolic engineering of thermophilic acetogens.

4.
J Matern Fetal Neonatal Med ; 36(2): 2226789, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787637

RESUMO

OBJECTIVES: Although adenomyosis is reportedly associated with adverse pregnancy outcomes, clinical factors related to the high risk of obstetric complications are unclear. This study aimed to elucidate the characteristics of adenomyosis lesions associated with the increased incidence of obstetric complications based on imaging findings. METHODS: This was a retrospective, observational cohort study conducted in a tertiary perinatal care center. Eighty-eight singleton pregnant women with adenomyosis were included in the study. Based on magnetic resonance imaging or ultrasonography before and/or during pregnancy, patients were classified according to three types of image characteristics: the extent of adenomyosis lesion (focal type or diffuse type), location of the lesion (extrinsic type, intrinsic type, or indeterminate type), the positional relationship between the lesion and the placenta (placenta distant from adenomyosis or placenta over adenomyosis), and the incidence of obstetric complications were examined. RESULTS: Patients with diffuse type adenomyosis are significantly more likely to have spontaneous second-trimester miscarriage (diffuse type vs. focal type: 16.7 vs. 0%, p < .01), preterm premature rupture of membranes (19.4 vs. 1.9%, p < .01), and preeclampsia (25.0 vs. 7.7%, p = .02), as compared to those with focal type adenomyosis. In a comparison of the three location types, the incidence of placental malposition was higher in patients with the extrinsic type adenomyosis (extrinsic type vs. intrinsic type vs. indeterminate type: 20.0 vs. 6.7 vs. 2.3%, p = .03). Comparisons between the types of the placenta over or distant from adenomyosis lesion displayed no significant differences in the frequencies of obstetric complications. CONCLUSIONS: We demonstrated that the frequency of obstetric complications related to adenomyosis varies depending on the extent and location of the lesion; patients with diffuse type adenomyosis have an increased risk of spontaneous second-trimester miscarriage, preterm premature rupture of membranes, and preeclampsia, while patients with extrinsic type adenomyosis have an increased risk of placental malposition. Imaging evaluation of adenomyosis prior to conception or early in pregnancy may be useful for the obstetrical risk assessment among patients with adenomyosis.


Assuntos
Aborto Espontâneo , Adenomiose , Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Aborto Espontâneo/epidemiologia , Adenomiose/complicações , Adenomiose/diagnóstico por imagem , Adenomiose/epidemiologia , Estudos de Coortes , Incidência , Placenta , Nascimento Prematuro/epidemiologia
5.
Case Rep Obstet Gynecol ; 2023: 7352947, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37766910

RESUMO

Hyperreactio luteinalis (HL) is a rare condition that presents as bilateral ovarian enlargement during pregnancy. Typically, it is thought to be caused by increased production of human chorionic gonadotropin (hCG) associated with gestational trophoblastic diseases or multiple pregnancies. The prognosis is relatively good, with many cases resulting in term birth. However, some obstetric complications, such as preeclampsia (PE) and preterm births, have been reported. We present a serious case of HL with subsequent PE that resulted in preterm delivery at 31 weeks of gestation. The soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high at the onset of PE at 24 weeks of gestation, followed by a modest decline, which then increased in proportion to the exacerbation of symptoms. Since HL cases have also been reported to be associated with PE, repeated measurement of the sFlt-1/PlGF ratio proved useful for better pregnancy management.

6.
J Biosci Bioeng ; 136(1): 13-19, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37100649

RESUMO

Acetogens grow autotrophically and use hydrogen (H2) as the energy source to fix carbon dioxide (CO2). This feature can be applied to gas fermentation, contributing to a circular economy. A challenge is the gain of cellular energy from H2 oxidation, which is substantially low, especially when acetate formation coupled with ATP production is diverted to other chemicals in engineered strains. Indeed, an engineered strain of the thermophilic acetogen Moorella thermoacetica that produces acetone lost autotrophic growth on H2 and CO2. We aimed to recover autotrophic growth and enhance acetone production, in which ATP production was assumed to be a limiting factor, by supplementing with electron acceptors. Among the four selected electron acceptors, thiosulfate and dimethyl sulfoxide (DMSO) enhanced both bacterial growth and acetone titers. DMSO was the most effective and was further analyzed. We showed that DMSO supplementation enhanced intracellular ATP levels, leading to increased acetone production. Although DMSO is an organic compound, it functions as an electron acceptor, not a carbon source. Thus, supplying electron acceptors is a potential strategy to complement the low ATP production caused by metabolic engineering and to improve chemical production from H2 and CO2.


Assuntos
Dióxido de Carbono , Moorella , Dióxido de Carbono/metabolismo , Acetona/metabolismo , Elétrons , Dimetil Sulfóxido/metabolismo , Hidrogênio/metabolismo , Moorella/genética , Moorella/metabolismo , Oxidantes/metabolismo , Trifosfato de Adenosina/metabolismo
7.
Radiol Case Rep ; 18(5): 1933-1938, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36970233

RESUMO

A case of an asymptomatic 19-year-old woman with Kimura disease presenting with a nodule in the right parotid gland is presented. She had a medical history of atopic dermatitis and noticed a mass on her right-side neck. Cervical lymphadenopathy was clinically diagnosed. The initial management plan was to observe the lesion, which had enlarged from 1 cm to 2 cm in diameter 6 months later. An excisional biopsy was performed, and the pathology confirmed an eosinophil-containing inflammatory parotid gland lesion with many squamous nests and cysts, mimicking a parotid gland tumor. High serum immunoglobulin E levels, peripheral blood eosinophilia, and pathological and genetic diagnoses confirmed Kimura disease. The lesion tested negative for human polyomavirus 6. No recurrence was observed 15 months after the biopsy. The prognosis of Kimura disease without human polyomavirus 6 infection may be favorable; however, further validation of this hypothesis is required as only 5 or 6 cases of Kimura disease have been evaluated for this viral infection. Proliferative squamous metaplasia occurring in parotid gland lesions of Kimura disease is rare and may complicate the diagnostic imaging and pathological diagnosis.

8.
Regul Toxicol Pharmacol ; 133: 105201, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35691450

RESUMO

The benchmark dose (BMD) approach is updated to create an international harmonizing process following rapid theoretical sophistication. We calculated the lower limit of BMD confidence interval (BMDL) for carcinogenicity based on 193 tumorigenicity bioassay data published in 50 pesticide risk assessment reports by the Food Safety Commission of Japan (FSCJ) to validate the appropriateness and necessity for the refinement of the FSCJ-established BMD guidance. Three well-known BMD software, PROAST, BMDS, and BBMD were used to compare their BMDLs with no-observed-adverse-effect levels (NOAELs) for carcinogenicity. Recently implemented methodologies such as model averaging or Bayesian inference were also used. Our results indicate that the BMD approach provides a point of departure similar to the NOAEL approach if the data used exhibit a clear dose-response relationship. In some cases, particularly in software with a frequentist approach, the calculation failed to provide BMDL or provided considerably lower BMDLs than NOAELs. However, most of the datasets that resulted in failed calculations or extremely low BMDLs exhibited unclear dose-response relationships, i.e., non-monotonous and sporadic responses. The expert review on the shape of the dose-response plot would help better apply the BMD approach. Furthermore, we observed that Bayesian approaches provided fewer failed or extreme BMD calculations than the frequentist approaches.


Assuntos
Benchmarking , Praguicidas , Teorema de Bayes , Benchmarking/métodos , Intervalos de Confiança , Relação Dose-Resposta a Droga , Japão , Nível de Efeito Adverso não Observado , Praguicidas/toxicidade , Medição de Risco/métodos , Software
9.
Shokuhin Eiseigaku Zasshi ; 63(1): 34-42, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35264520

RESUMO

Assessment of carcinogenicity is important for human health at dietary risk assessment of pesticide residues. This article indicated important points on interpretation of carcinogenicity in toxicological evaluation of pesticide residues based on principles of risk analysis in foods by CODEX to be a guide for risk assessors. This guidance was referred from the guidance on carcinogenicity evaluation by international and/or national organizations, and the interpretations of Food Safety Commissions of Japan (FSCJ) published in their risk assessment reports. We focused on carcinogenicity obtained from routine carcinogenicity bioassays in rodents. The guidance includes the purpose and usefulness of the bioassay studies, consideration points to be carcinogenicity and influencing factors to carcinogenicity in the test to judge carcinogenic hazard at hazard identification. Considering on human relevance as carcinogenic hazard also was proposed using practical case examples. Next, a carcinogenic hazard is evaluated on dose-response relationship to judge points of departure on carcinogenicity. At the end of this article, we challenged our recommendation on future assessment of carcinogenicity to progress from hazard to risk.


Assuntos
Testes de Carcinogenicidade , Carcinógenos , Resíduos de Praguicidas/toxicidade , Roedores , Animais , Bioensaio , Carcinógenos/toxicidade , Medição de Risco
10.
Auris Nasus Larynx ; 49(4): 697-702, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34996617

RESUMO

OBJECTIVES: This study aimed to examine whether serum SCCA levels can be used as clinical markers for monitoring recurrence of sinonasal inverted papilloma (IP) during the follow-up period after surgery. We measured long-term changes in serum levels of SCCA after surgery in patients with IP and examined whether postoperative SCCA levels were associated with IP recurrence. METHODS: Twenty-five consecutive patients (13 with primary IPs and 12 with recurrent IPs after their previous surgery) were included in this study. All patients underwent endoscopic or external surgery. Postoperative serum SCCA levels were measured 3 months after surgery and every 3 - 12months during the follow-up. The optimal cut-off values of postoperative SCCA levels to predict subsequent recurrence of IP were evaluated using ROC analysis. RESULTS: Preoperative serum levels of SCCA were higher than the upper limit of normal range in most patients with both primary and recurrent IP, and significantly decreased after surgery. Thus, the presence of IP was closely associated with elevated serum SCCA levels. Moreover, postoperative elevation of SCCA levels was closely associated with subsequent recurrence of IP. Postoperative SCCA levels in 5 patients with recurrence were significantly higher than those in 20 patients without recurrence. The optimum cut-off value of SCCA levels to predict subsequent recurrence of IP 3 months after surgery was 1.85 ng/ml, with a sensitivity of 100.0 % and a specificity of 90.0 %. CONCLUSIONS: These findings suggest that SCCA can be a tumor marker of IP. It is also suggested that postoperative elevation of SCCA levels is a clinical marker for monitoring the recurrence of IP during the follow-up period. A SCCA cut-off value of 1.85 ng/ml postoperatively may predict the subsequent recurrence of IP with high sensitivity and specificity.


Assuntos
Neoplasias Nasais , Papiloma Invertido , Neoplasias dos Seios Paranasais , Antígenos de Neoplasias , Humanos , Neoplasias Nasais/patologia , Papiloma Invertido/patologia , Neoplasias dos Seios Paranasais/cirurgia , Serpinas
11.
J Biosci Bioeng ; 132(6): 569-574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34518108

RESUMO

Gas fermentation is a promising biological process for the conversion of CO2 or syngas into valuable chemicals. Homoacetogens are microorganisms growing autotrophically using CO2 and H2 or CO and metabolizing them to form acetate coupled with energy conservation. The challenge in the metabolic engineering of the homoacetogens is divergence of the acetate formation, whose intermediate is acetyl-CoA, to a targeted chemical with sufficient production of adenosine triphosphate (ATP). In this study, we report that an engineered strain of the thermophilic homoacetogen Moorella thermoacetica, in which a pool of acetyl-CoA is diverted to ethanol without ATP production, can maintain autotrophic growth on syngas. We estimated the ATP production in the engineered strains under different gaseous compositions by considering redox-balanced metabolism for ethanol and acetate formation. The culture test showed that the combination of retaining a level of acetate production and supplying the energy-rich CO allowed maintenance of the autotrophic growth during ethanol production. In contrast, autotrophy was collapsed by complete elimination of the acetate pathway or supplementation of H2-CO2. We showed that the intracellular level of ATP was significantly lowered on H2-CO2 in consistent with the incompetence. In the meantime, the complete disruption of the acetate pathway resulted in the redox imbalance to produce ethanol from CO, albeit a small loss in the ATP production. Thus, preservation of a fraction of acetate formation is required to maintain sufficient ATP and balanced redox in CO-containing gases for ethanol production.


Assuntos
Etanol , Moorella , Acetatos , Processos Autotróficos , Moorella/genética
12.
J Reprod Immunol ; 143: 103241, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33157500

RESUMO

Secretory leukocyte protease inhibitor (SLPI) and progranulin (PGRN) are secretory proteins with an anti-inflammatory property. Their involvement in cervical remodeling in pregnant uterus is not yet elucidated. Thus, this study aimed to explore the significance of SLPI and PGRN in the maintenance of pregnancy by investigating the factors associated with their expression levels at the cervix. Concentrations of SLPI and PGRN proteins were measured in cervical mucus samples collected from asymptomatic pregnant women at 24-26 weeks of gestation (n = 166). The concentrations of those molecules were analyzed with clinical parameters related to risk for preterm delivery (PD). In pregnant mice, we evaluated the effect of lipopolysaccharide-induced inflammation and progesterone effect modulation on cervical mRNA expression of SLPI and PGRN. The cervical PGRN level was significantly lower in women with short cervix (<35 mm) and with a history of threatened PD. In women with short cervix, cervical SLPI concentrations were positively correlated with inflammatory cytokines, interleukin-6 (R2 = 0.75) and interleukin-8 (R2 = 0.71). In pregnant mice, cervical mRNA expressions of PGRN and SLPI were increased in response to progesterone supplementation and were suppressed by a progesterone antagonist, mifepristone. Lipopolysaccharide-induced inflammation caused remarkable upregulation in cervical SLPI mRNA level but not in PGRN. Progesterone and local inflammation are the factors controlling expression levels of PGRN and SLPI at the cervix. The observed relationship of PGRN and SLPI levels in the cervical mucus with PD-related clinical parameters supports that those anti-inflammatory molecules possibly play a significant role in appropriate regulation of cervical remodeling.


Assuntos
Colo do Útero/patologia , Nascimento Prematuro/imunologia , Progranulinas/metabolismo , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Adulto , Animais , Muco do Colo Uterino/imunologia , Muco do Colo Uterino/metabolismo , Colo do Útero/imunologia , Modelos Animais de Doenças , Feminino , Antagonistas de Hormônios/administração & dosagem , Humanos , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Idade Materna , Camundongos , Mifepristona/administração & dosagem , Modelos Animais , Gravidez , Segundo Trimestre da Gravidez/imunologia , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/patologia , Progesterona/administração & dosagem , Progesterona/antagonistas & inibidores , Progesterona/metabolismo , Progranulinas/análise , Inibidor Secretado de Peptidases Leucocitárias/análise , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
13.
Anal Chim Acta ; 1119: 35-40, 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32439052

RESUMO

Exosomes are expected to be biomarkers of cancer since they contain information about the cells that excrete them. In this study we developed a method to count the exosomes secreted from cancer cells in a culture medium without the need for isolation and/or preconcentration. This detection system consists of a square capillary on which a laser beam is focused in a sheet shape via the use of two cylindrical lenses. A fluorescently labeled anti-CD63 antibody is used to mark the exosomes that are then flowed into the square capillary. In this study, individual exosomes were observed on a trajectory when passing through the laser beam sheet and were counted for 10 min at a constant flow velocity. The total analysis time was less than 1.5 h including the steps required to remove large particles and allow reaction with the antibody. The results for two samples prepared with and without the isolation of exosomes showed a loss of exosomes in the isolation step. We also determined the number of the exosomes secreted by the cells to a culture medium during cultivation. As expected, the total number of exosomes in a culture medium increased with an increase in the cultivation time, and the number of exosomes released every 12 h either remained constant or showed no more than a slight increase for as long as 72 h. It was unclear whether the number exosomes was dependent on the cell population at confluences of 10-60%.


Assuntos
Biomarcadores Tumorais/análise , Meios de Cultura/química , Exossomos/química , Neoplasias/diagnóstico , Imagem Óptica , Células HeLa , Humanos , Células Tumorais Cultivadas
14.
Appl Biochem Biotechnol ; 190(4): 1360-1370, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31773396

RESUMO

Talaromyces cellulolyticus is a promising strain for industrial cellulase production. In this study, the thaB gene, which is a homologue of the hap2/B gene in other filamentous fungi, was isolated and characterized. When grown in the presence of cellulose, culture supernatants of a thaB-disrupted strain (YDTha) exhibited decreased cellulase and xylanase enzymatic activities compared to the control strain. Furthermore, YDTha exhibited lower expression of the genes encoding cellulases and xylanases compared to the control strain. When cellobiose and lactose (soluble carbon sources) were used as carbon sources, the expression of the genes encoding cellulases and xylanases was decreased in both the YDTha and the control strains, though the expression levels in YDTha remained lower than those in the control strain. These results suggested that thaB has a positive role in cellulase and xylanase production in T. cellulolyticus.


Assuntos
Celulase/química , Endo-1,4-beta-Xilanases/química , Lactose/química , Talaromyces/enzimologia , Fatores de Transcrição/genética , Trifosfato de Adenosina/química , Carbono/química , Celobiose/química , Celulose , Proteínas Fúngicas/química , Regulação Fúngica da Expressão Gênica , Microbiologia Industrial/métodos , Plasmídeos/metabolismo , Fatores de Transcrição/química
15.
J Pharmacol Sci ; 138(1): 54-62, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30301597

RESUMO

Narrowband-ultraviolet B (NB-UVB) phototherapy is used for the treatment of atopic dermatitis. Previously, we reported that irradiation with 200 mJ/cm2 of 310 nm NB-UVB suppressed phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) gene expression without induction of apoptosis in HeLa cells. However, the effect of NB-UVB irradiation on nasal symptoms is still unclear. Here, we show that low dose irradiation with 310 nm NB-UVB alleviates nasal symptoms in toluene 2,4-diisocyanate (TDI)-sensitized allergy model rats. Irradiation with 310 nm NB-UVB suppressed PMA-induced H1R mRNA up-regulation in HeLa cells dose-dependently at doses of 75-200 mJ/cm2 and reversibly at a dose of 150 mJ/cm2 without induction of apoptosis. While, at doses of more than 200 mJ/cm2, irradiation with 310 nm NB-UVB induced apoptosis. Western blot analysis showed that the suppressive effect of NB-UVB irradiation on H1R gene expression was through the inhibition of ERK phosphorylation. In TDI-sensitized rat, intranasal irradiation with 310 nm NB-UVB at an estimated dose of 100 mJ/cm2 once a day for three days suppressed TDI-induced sneezes and up-regulation of H1R mRNA in nasal mucosa without induction of apoptosis. These findings suggest that repeated intranasal irradiation with low dose of NB-UVB could be clinically used as phototherapy of AR.


Assuntos
Apoptose/efeitos da radiação , Expressão Gênica/efeitos da radiação , Mucosa Nasal/patologia , Mucosa Nasal/efeitos da radiação , RNA Mensageiro/metabolismo , Receptores Histamínicos H1/genética , Receptores Histamínicos H1/metabolismo , Raios Ultravioleta , Regulação para Cima/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Células HeLa , Humanos , Masculino , Fototerapia , Ratos , Rinite Alérgica/terapia
16.
Exp Clin Transplant ; 16(1): 116-118, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29409439

RESUMO

OBJECTIVES: Substantial numbers of patients after hematopoietic stem cell transplant need critical care. In Japan, however, data regarding the availability of an intensive care unit and intensivists at hospitals performing hematopoietic stem cell transplant are lacking. We aimed to investigate this issue using data from the 2014 Hematopoietic Cell Transplantation in Japan Annual Report of Nationwide Survey. MATERIALS AND METHODS: We examined whether hospitals have intensive care unit facilities and whether these hospitals are authorized by the Japanese Society of Intensive Care Medicine to provide intensivist training. The number of hematopoietic cell transplantations at each hospital was collected from the Transplant Registry Unified Management Program by the Japanese Data Center for Hematopoietic Cell Transplantation. RESULTS: Among 236 hospitals that perform hematopoietic stem cell transplants, 106 hospitals did not have intensive care units certified by the Japanese Society of Intensive Care Medicine. In patients who receive hematopoietic stem cell transplants with the highest mortality rate, 947 allogeneic transplants were performed at hospitals without this certification and 73 were performed at hospitals without intensive care units. CONCLUSIONS: We found that a considerable number of hematopoietic stem cell transplants are performed at hospitals with insufficient availability of critical care facilities or physicians.


Assuntos
Acessibilidade aos Serviços de Saúde/tendências , Transplante de Células-Tronco Hematopoéticas/tendências , Hospitais/tendências , Unidades de Terapia Intensiva/tendências , Certificação/tendências , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde/normas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/normas , Hospitais/normas , Humanos , Unidades de Terapia Intensiva/normas , Japão , Segurança do Paciente , Sistema de Registros , Medição de Risco , Resultado do Tratamento
17.
Sci Rep ; 7(1): 12455, 2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28963486

RESUMO

Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1α and HIF2α expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1α expression decreased and HIF2α expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2α knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1α silencing had no significant effect on PlGF secretion. In summary, HIF2α, rather than HIF1α, is most affected by reduced oxygen level during syncytialization and increases in HIF2α trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , Fator de Crescimento Placentário/genética , Pré-Eclâmpsia/genética , Trofoblastos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Estudos de Casos e Controles , Diferenciação Celular , Linhagem Celular Tumoral , Cesárea , Feminino , Regulação da Expressão Gênica , Humanos , Hipóxia/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Fisiológica/genética , Oxigênio/farmacologia , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Trofoblastos/efeitos dos fármacos , Trofoblastos/patologia
18.
Pediatr Pulmonol ; 52(10): E64-E66, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28493298

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder with an unknown etiology that commonly involves the gastrointestinal tract, and bronchopulmonary manifestations only occur in 0.4% of cases. There have not been any reports about pulmonary involvement in pediatric CD patients. We experienced a 14-year-old boy with Crohn's disease diagnosed with organizing pneumonia by chest CT-guided biopsy examination. His pneumonia was intractable despite the administration of multiple antibiotics, and steroid therapy was very effective. In pediatric patients with CD whose lung disease does not respond to antibiotics, OP should be considered as a possible diagnosis.


Assuntos
Doença de Crohn/complicações , Pneumonia/complicações , Adolescente , Humanos , Masculino , Pneumonia/diagnóstico por imagem , Tomografia Computadorizada por Raios X
19.
Oncotarget ; 8(67): 111535-111550, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29340073

RESUMO

YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1 expression and induced apoptosis in MM cells. Triple-color flow cytometric analysis revealed that YM155 potently induced cell death of MM cells in G0 phase. Quiescent primary MM cells were also sensitive to YM155. We established bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with parental cells. Interestingly, survivin expression was markedly elevated in U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1) MM cells and bortezomib-resistant cells. These unique features of YM155 may be beneficial for the development of new therapeutic strategies to eliminate quiescent MM cells and overcome bortezomib resistance.

20.
Plast Reconstr Surg Glob Open ; 4(5): e725, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27579249

RESUMO

OBJECTIVE: To ask experts in the field to evaluate a surgeon's experience with a retroseptal transconjunctival approach for the repair of the orbital floor damaged by blowout fracture that the surgeon encountered in 12 East-Asian patients. METHODS: Patients were identified from a database, and a retrospective case note review was conducted. A total of 12 conjunctival procedures were conducted for the repair of blowout fracture with no other complicating fractures. All operative procedures were done by transconjunctival approach alone without lateral canthotomy or any other additional approach. RESULTS: The repair of the orbital floor was successful in all the cases. Three patients had bone grafting to the orbital floor after reduction. The mean of overall surgical time was 48.8 minutes (range, 22-85 minutes) for orbit exposure by transconjunctival approach plus reduction and bone grafting when applicable. There were 6 urgent surgeries associated with missing or entrapment of the inferior rectus muscle, and its repair took an average of 32.0 minutes (range, 22-41 minutes). Postoperative diplopia recovered at an average of 12.4 weeks (range, 0-60 weeks); in urgent cases, it took an average of 5.3 weeks (range, 0-14 weeks) before recovery. CONCLUSIONS: A retroseptal transconjunctival approach in repairing the orbital floor is a simple, easily manageable, and effective procedure, leaving no conspicuous facial scars. It has proved to be an optimal choice in blowout fracture cases, especially when there was urgency to decompress the ischemic inferior rectus muscle in as short a surgery time as possible.

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