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1.
Sci Rep ; 11(1): 982, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441837

RESUMO

We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a-/-) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a-/- and wild-type (AT1a+/+) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a+/+ mice, such a development was not provoked in the AT1a-/- mice. Although the AT1a+/+ mice were administered hydralazine to maintain the same systolic blood pressure (SBP) levels as the AT1a-/- mice with lower SBP levels, hydralazine did not reproduce the renoprotective effects observed in the AT1a-/- mice. Acute tubular injury at 3 days postischemia was similar between the AT1a-/- mice and the AT1a+/+ mice. From our investigations using IR kidneys at 3, 14, and 28 days postischemia, the multiple molecular mechanisms may be related to prevention of severe chronic TID postischemia in the AT1a-/- mice. In conclusion, inactivation of the AT1 receptor may be useful in preventing the transition of acute kidney injury to chronic kidney disease.

2.
PLoS One ; 16(1): e0244885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33449947

RESUMO

Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.

3.
Structure ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33264604

RESUMO

Prostaglandin E receptor EP4, a class A G protein-coupled receptor (GPCR), is a common drug target in various disorders, such as acute decompensated heart failure and ulcerative colitis. Here, we report the cryoelectron microscopy (cryo-EM) structure of the EP4-heterotrimeric G protein (Gs) complex with the endogenous ligand at a global resolution of 3.3 Å. In this structure, compared with that in the inactive EP4 structure, the sixth transmembrane domain is shifted outward on the intracellular side, although the shift is smaller than that in other class A GPCRs bound to Gs. Instead, the C-terminal helix of Gs is inserted toward TM2 of EP4, and the conserved C-terminal hook structure formsthe extended state. These structural features are formed by the conserved residues in prostanoid receptors (Phe542.39 and Trp3277.51). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors.

4.
J Virol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268525

RESUMO

An RNA virus-based episomal vector (REVec) whose backbone is Borna disease virus 1 (BoDV-1) can provide long-term gene expression in transduced cells. To improve the transduction efficiency of REVec, we evaluated the role of the viral envelope glycoprotein (G) of the genus Orthobornavirus, including that of BoDV-1, in the production of infectious particles. By using G-pseudotype assay in which the lack of G in G-deficient REVec (ΔG-REVec) was compensated for expression of G, we found that excess expression of BoDV-1-G does not affect particle production itself but results in uncleaved and aberrant mature G expression in the cells, leading to the production of REVec particles with low transduction titers. We revealed that the expression of uncleaved G in the cells inhibits the incorporation of mature G and vgRNA into the particles. This feature of G was conserved among mammalian and avian orthobornaviruses; however, the cleavage efficacy of canary bornavirus 1 (CnBV-1)-G was exceptionally not impaired by its excess expression, which led to the production of the pseudotype ΔG-REVec with the highest titer. Chimeric G proteins between CnBV-1 and -2 revealed that the signal peptide of CnBV-1-G was responsible for the cleavage efficacy through the interaction with intracellular furin. We showed that CnBV-1 G leads to the development of pseudotyped REVec with high transduction efficiency and a high-titer recombinant REVec. Our study demonstrated that the restricted expression of orthobornavirus G contributes to the regulation of infectious particle production, the mechanism of which can improve the transduction efficiency of REVec.IMPORTANCE Most viruses causing persistent infection produce few infectious particles from the infected cells. Borna disease virus 1, a member of the genus Orthobornavirus, is an RNA virus that persistently infects the nucleus and has been applied to vectors for long-term gene expression. In this study, we showed that, common among orthobornaviruses, excessive G expression does not affect particle production itself but reduces the production of infectious particles with mature G and genomic RNA. This result suggested that limited G expression contributes to suppressing abnormal viral particle production. On the other hand, we found that canary bornavirus 1 has an exceptional G maturation mechanism and produces a high-titer virus. Our study will contribute to not only understanding the mechanism of infectious particle production but also improving the vector system of orthobornaviruses.

5.
J Cardiol Cases ; 22(4): 152-155, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33014193

RESUMO

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction and occurs predominantly in young women without conventional cardiovascular risk factors. Emotional or physical stress and hormone imbalance are associated with the occurrence of SCAD, but the precise mechanisms have not been sufficiently elucidated. Furthermore, there is a paucity of data regarding the underlying disease in patients with SCAD. We herein report a case involving a 48-year-old man who developed acute myocardial infarction due to SCAD in the distal segment of the left anterior descending artery and was successfully treated with conservative medical therapy. A repeat coronary angiography examination performed 2 weeks later revealed complete angiographic healing. In addition, he was treated for suspected Behçet's disease because he had a history of recurrent aphthous stomatitis, nodular erythema, and genital ulcers. After thorough assessment, he was finally diagnosed with vascular Behçet's disease based on additional evidence of bilateral deep vein thrombosis. This case report highlights a rare case of vascular Behçet's disease complicated with SCAD in a male patient. Physicians should be aware that SCAD may occur in association with systemic inflammatory disease including Behçet's disease, even in male patients. .

6.
Front Oncol ; 10: 1674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974207

RESUMO

Background: Intraoperative confocal microscopy can enable high-resolution cross-sectional imaging of intact tissues as a non-invasive real-time alternative to gold-standard histology. However, all current means of intraoperative confocal microscopy are hindered by a limited field of view (FOV), presenting a challenge for evaluating gliomas, which are highly heterogeneous. Objective: This study explored the use of image mosaicking with handheld dual-axis confocal (DAC) microscopy of fresh human glioma specimens. Methods: In this preliminary technical feasibility study, fresh human glioma specimens from 6 patients were labeled with a fast-acting topical stain (acridine orange) and imaged using a newly developed DAC microscope prototype. Results: In comparison to individual image frames with small fields of view, mosaicked images from a DAC microscope correlate better with gold-standard H&E-stained histology images, including the ability to visualize gradual transitions from areas of dense cellularity to sparse cellularity within the tumor. Conclusion: LS-DAC microscopy provides high-resolution, high-contrast images of glioma tissues that agree with corresponding H&E histology. Compared with individual image frames, mosaicked images provide more accurate representations of the overall cytoarchitecture of heterogeneous glioma tissues. Further investigation is needed to evaluate the ability of high-resolution mosaicked microscopy to improve the extent of glioma resection and patient outcomes.

7.
Case Rep Rheumatol ; 2020: 1926908, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158583

RESUMO

Systemic sclerosis (SSc) is characterized by skin sclerosis and multiple organ damages which may cause mortality and is usually accompanied with several specific autoantibodies, each of which is associated with characteristic complications. Among them, anticentriole antibody is recently reported to be highly associated with SSc-associated pulmonary arterial hypertension (SSc-PAH). In general, several vasodilators are used as therapeutic drugs for SSc-PAH, whereas immunosuppressive therapies are not. Here, we report the case of a 62-year-old female with anticentriole antibody-positive SSc-PAH treated with immunosuppressants and vasodilators. She presented with two-year exertional dyspnea and was diagnosed with PAH and SSc owing to the centriole staining pattern and other symptoms without digital sclerosis. Oral vasodilators were initially administered but were not sufficiently effective on dyspnea. Immunosuppressants such as prednisolone and cyclophosphamide were started. Both of them improved mean pulmonary arterial pressure and 6-minute walk distance, and the anticentriole antibody also disappeared. In this case, SSc-PAH with anticentriole antibody was properly diagnosed and immunosuppressants and vasodilators improved the hemodynamics of PAH with anticentriole antibody and stably maintained it and, in addition, reduced the titer of anticentriole antibody. This indicates that anticentriole antibody might represent a good responsive group to therapies among subgroups of patients with SSc-PAH.

8.
Nat Commun ; 11(1): 1334, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170079

RESUMO

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas , Éxons/genética , Vesículas Extracelulares/metabolismo , Nanopartículas/química , RNA Guia/metabolismo , Sequência de Bases , Sobrevivência Celular , Dimerização , Edição de Genes , Vetores Genéticos/metabolismo , Células HEK293 , Protease de HIV/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Ligantes , Luciferases/metabolismo , Processamento de RNA/genética , RNA Catalítico/metabolismo , Ribonucleoproteínas/metabolismo , Doadores de Tecidos , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
9.
Intern Med ; 59(1): 93-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902910

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Laparoscopia/efeitos adversos , Hemorragia Pós-Operatória/complicações , Microangiopatias Trombóticas/tratamento farmacológico , Miomectomia Uterina/efeitos adversos , Adulto , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Doenças Raras , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia
10.
J Antibiot (Tokyo) ; 72(12): 956-969, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31558775

RESUMO

Novel muraminomicin derivatives with antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) were synthesized by esterification of the hydroxy group on the diazepanone ring of muraminomicin Z1. Compound 1b (DS14450354) possessed a diheptoxybenzyl-ß-Alanyl-ß-Alanyl group and exhibited minimum inhibitory concentrations (MICs) against MRSA comparable to those against methicillin-susceptible S. aureus (MSSA). The MICs that inhibited 50 and 90% of the strains were 1 and 2 µg/mL, respectively. Compound 1a (DS60182922) possessed an aminoethylbenzoyldodecylglycyl moiety and showed bactericidal activity against MSSA Smith. The bactericidal activity of 1a against MRSA 10925 was comparatively lower, whilst 1b exhibited dose-dependent bactericidal activity against MRSA 10925. The mutation frequency of 1b was lower than that of 1a. An amino acid substitution (F226I) was observed in MraY mutants isolated from culture plates containing 1a or 1b. Subcutaneous 1a and 1b administration showed good therapeutic efficacy in murine systemic infection models with MSSA Smith and MRSA 10925, comparable to that of vancomycin, suggesting that the novel muraminomicin derivatives may be effective therapeutic agents against MRSA that warrant further investigation. A scheme for the formulation of the key ester intermediate, requiring no HPLC preparation, was also established.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Proteínas de Bactérias/genética , Avaliação Pré-Clínica de Medicamentos , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Camundongos Endogâmicos , Testes de Sensibilidade Microbiana , Taxa de Mutação , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Transferases/genética
11.
Rheumatol Int ; 39(11): 1989-1994, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31388749

RESUMO

Takayasu arteritis (TAK) is a subtype of the large-vessel vasculitis, affecting the aorta and its major branches. Although T cell-mediated autoimmunity is mainly involved in vascular inflammation, in recent years, accumulating evidence suggests the important role of B cells in the pathogenesis and effectiveness of B-cell-targeted therapy with rituximab (RTX), a chimeric anti-CD20 monoclonal antibody in refractory TAK. Herein, we report for the first time a case involving a 34-year-old man with TAK who was refractory to four different biologic agents, such as one selective T-cell co-stimulation modulator (abatacept), one anti-interleukin-6 receptor monoclonal antibody (tocilizumab), and two tumor necrosis factor-α inhibitors (infliximab and etanercept), but eventually achieved remission with RTX. He received a total of six courses of RTX, and doses of prednisolone and methotrexate were tapered without relapse. The current case provided further evidence to the potential role of RTX therapy in patients with refractory TAK, and its efficacy needs to be validated in a controlled trial.


Assuntos
Fatores Imunológicos/uso terapêutico , Rituximab/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Abatacepte/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Infliximab/uso terapêutico , Masculino , Falha de Tratamento , Resultado do Tratamento
12.
J Antibiot (Tokyo) ; 72(12): 943-955, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31413314

RESUMO

We screened for bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (MraY: EC 2.7.8.13) inhibitors with the aim of discovering novel antibiotics and observed inhibitory activity in the culture broth of an actinomycete, SANK 60501. The active compounds, muraminomicins A, B, C, D, E1, E2, F, G, H, and I exhibited strong inhibitory activity against MraY with IC50 values of 0.0105, 0.0068, 0.0104, 0.0099, 0.0115, 0.0109, 0.0089, 0.0134, 0.0186, and 0.0094 µg ml-1, respectively. Although muraminomicin F exhibited favorable antibacterial activity against drug-resistant Gram-positive bacteria, this activity was reduced with the addition of serum. To efficiently supply the core component for chemical modification studies, production was carried out in a controlled trial by adding myristic acid to the medium, and a purification method suitable for large-scale production was successfully developed.


Assuntos
Actinomycetales/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Actinomycetales/genética , Antibacterianos/biossíntese , Proteínas de Bactérias/antagonistas & inibidores , Ácidos Graxos/química , Fermentação , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Transferases/antagonistas & inibidores
13.
Front Oncol ; 9: 592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334117

RESUMO

Low-power fluorescence microscopy of 5-ALA-induced PpIX has emerged as a valuable intraoperative imaging technology for improving the resection of malignant gliomas. However, current fluorescence imaging tools are not highly sensitive nor quantitative, which limits their effectiveness for optimizing operative decisions near the surgical margins of gliomas, in particular non-enhancing low-grade gliomas. Intraoperative high-resolution optical-sectioning microscopy can potentially serve as a valuable complement to low-power fluorescence microscopy by providing reproducible quantification of tumor parameters at the infiltrative margins of diffuse gliomas. In this forward-looking perspective article, we provide a brief discussion of recent technical advancements, pilot clinical studies, and our vision of the future adoption of handheld optical-sectioning microscopy at the final stages of glioma surgeries to enhance the extent of resection. We list a number of challenges for clinical acceptance, as well as potential strategies to overcome such obstacles for the surgical implementation of these in vivo microscopy techniques.

14.
Front Physiol ; 10: 252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30914972

RESUMO

Sperm motility patterns are continuously changed after ejaculation to fertilization in the female tract. Hyperactivated motility is induced with high glucose medium in vitro or the oviduct fluids in vivo, whereas sperm maintain linear motility in the seminal plasma or the uterine fluids containing low glucose. Therefore, it is estimated that sperm motility patterns are dependent on the energy sources, and the mitochondrial oxidative phosphorylation is activated to produce ATP in low glucose condition. To elucidate these hypotheses, boar sperm was incubated in different energy conditions with the transcription and translation inhibitors in vitro. Sperm motility parameters, mitochondrial activity, ATP level, gene expression and protein synthesis were analyzed. Sperm progressive motility and straight-line velocity were significantly increased with decreasing glucose level in the incubation medium. Moreover, the mitochondrial protein turnover meaning transcription and translation from mitochondrial genome in sperm is activated during incubation. Incubation of sperm with mitochondrial translation inhibitor (D-chloramphenicol) suppressed mitochondrial protein synthesis, mitochondrial activity and ATP level in sperm and consequently reduced the linear motility speed, but not the motility. Thus, it is revealed that the mitochondrial central dogma is active in sperm, and the high-speed linear motility is induced in low glucose condition via activating the mitochondrial activity for ATP generation.

15.
PLoS One ; 14(3): e0213354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30849128

RESUMO

There is a growing impetus to increase marine protected areas coverage globally from 6% to 30% in 2030. Successfully establishing and maintaining marine protected areas require incorporating public preferences into their establishment and management. We investigate the role of alternate management regimes (top-down and bottom-up) on preferences for marine protected areas and the marginal rate of substitution between natural and man-made capital using a case study in the Asia-Pacific region of Okinawa, Japan. We implemented a choice experiment survey to infer which attributes of marine protected areas are most important for the respondents. We use our survey results to calculate respondents' willingness to support marine protected areas in Okinawa. This study contributes to the policy debate on management of marine protected areas with empirical data that characterizes the perception of Okinawan residents with respect to the role of local coastal communities (bottom-up) compared to central government based agencies (top-down) management. We extend the analysis and estimate the trade-offs to residents in Okinawa between natural capital (i.e. coral coverage and marine biodiversity attribute) and man-made capital (i.e. restrictions on coastal development). We find that the underlying management regime affects the local residents' valuation of the marine protected area with residents showing a higher willingness to support bottom-up management regimes. There is also substantial differences in the willingness to support different characteristics of marine protected areas by management type. Finally, we find that the marginal rate of substitution between natural capital and man-made capital varies by management type such that residents would need to be compensated relatively less in terms of man-made capital in the presence of a policy scenario that proposes an increase in natural capital under a bottom-up management regime.


Assuntos
Organismos Aquáticos , Conservação dos Recursos Naturais/métodos , Animais , Biodiversidade , Ecossistema , Pesqueiros/organização & administração , Humanos , Japão , Modelos Logísticos , Inquéritos e Questionários
16.
Virology ; 531: 126-140, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30875489

RESUMO

The influenza A virus genome consists of eight single-stranded negative-sense RNA segments. The noncoding regions located at the 3'- and 5'- ends of each segment are necessary for genome packaging, and the terminal coding regions are required to precisely bundle the eight segments. However, the nucleotide residues important for genome bundling are not defined. Here, we introduced premature termination codons in the hemagglutinin (HA) or matrix protein 2 (M2) gene and constructed virus libraries containing random sequences in the terminal coding regions. Using these virus libraries, we identified nucleotide residues involved in efficient virus propagation. Viral genome packaging was impaired in viruses that contained single mutations at these identified residues. Furthermore, these single mutations altered the local structure of the viral ribonucleoprotein complex. Our results show that specific nucleotide residues in the viral protein coding region are involved in forming the precise structure of the viral ribonucleoprotein complex.


Assuntos
Vírus da Influenza A/fisiologia , Ribonucleoproteínas/química , Ribonucleoproteínas/genética , Montagem de Vírus , Sequência de Bases , Linhagem Celular , Genoma Viral , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A/química , Vírus da Influenza A/genética , Fases de Leitura Aberta , Mutação Puntual , RNA Viral/genética , RNA Viral/metabolismo , Ribonucleoproteínas/metabolismo , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo
17.
Opt Lett ; 44(3): 671-674, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30702707

RESUMO

A handheld line-scanned dual-axis confocal (LS-DAC) microscope has been developed for high-speed (16 frames/s) fluorescence imaging of tissues with sub-nuclear resolution. This is the first miniature fluorescence LS-DAC system that has been fully packaged for handheld clinical use on patients. A novel micro-electro-mechanical system scanning mechanism, with synchronized tilting and pistoning, is used to achieve flat-field en face imaging. We show that this facilitates video mosaicking to generate images that sample an extended lateral field of view.


Assuntos
Sistemas Microeletromecânicos , Microscopia Confocal/instrumentação , Imagem Óptica/instrumentação , Animais , Desenho de Equipamento , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Camundongos
18.
Aging (Albany NY) ; 11(2): 707-723, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30677748

RESUMO

Reproductive organs play a pivotal role in asthma development and progression, especially in women. Endocrine environment changes associated with the menstrual cycle, pregnancy, and menopause can exacerbate the clinical features of asthma. Factors secreted by reproductive organs may be responsible for the gender difference and age-related changes in adult asthma. Here, we show that mammalian seminal fluid has anti-asthma effects exclusively in females. Exposure to murine seminal fluid markedly reduced eosinophilic airway inflammation in 2-month-old female mice upon ovalbumin inhalation. The anti-asthma effect with seminal fluid from 10-month-old males was double that with fluid from 2-month-old males, suggesting that it depended on male sexual maturation. We further found that seminal fluid from middle-aged human volunteers had beneficial effects in asthmatic female mice; these effects were associated with transcriptional repression of osteopontin and IL-17A, which are poor prognostic factors for asthma. In 2-month-old male mice, however, human seminal fluid failed to decrease asthmatic features and even enhanced osteopontin and IL-17A transcription. Our data demonstrate that age-related seminal fluid exerts opposing effects in asthmatic male and female mice. These findings may help the development of novel approaches to control the prevalence and age-related progression of asthma in women.


Assuntos
Envelhecimento/fisiologia , Asma/imunologia , Sêmen/imunologia , Adulto , Animais , Células da Medula Óssea , Líquido da Lavagem Broncoalveolar , Células Dendríticas , Feminino , Humanos , Imunoglobulina E/sangue , Interleucina-13/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Ovalbumina/toxicidade , Caracteres Sexuais
19.
Semin Thorac Cardiovasc Surg ; 31(3): 574-580, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30529159

RESUMO

This study was performed to investigate the association between the esophagectomy surgical Apgar score (eSAS) and 30-day morbidity after esophagectomy. We retrospectively identified patients who underwent esophagectomy in our facilities database from January 2011 through December 2015. We calculated the eSAS and modified eSAS, which was adjusted for the blood loss volume, according to our patients' data. After estimating the cut-off point of the eSAS using a receiver operating curve, the morbidity rates between the 2 groups were compared using Fisher's exact test. In addition, logistic regression analysis was performed to adjust the results by factors associated with morbidity. In total, 246 patients were included. Of these patients, 144 presented with major morbidity. The optimal cut-off value of the eSAS was 4 points. A total of 145 patients had an eSAS of <4 points, and 89 of them developed morbidity. A total of 101 patients had an eSAS of ≥4 points, and 55 of them developed morbidity. Fisher's exact test showed that an eSAS of <4 points was not significantly associated with morbidity after esophagectomy (P = 0.29). The association was improved after modification for the blood loss volume (P = 0.004). Multivariable analysis revealed that the modified eSAS and age were significantly associated with morbidity (odds ratio, 0.47 and 1.04, respectively). The validity of the eSAS to predict morbidity after esophagectomy could be low, and the modified blood loss volume may improve the predictive effect.


Assuntos
Perda Sanguínea Cirúrgica , Técnicas de Apoio para a Decisão , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Bases de Dados Factuais , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Case Rep Nephrol Dial ; 8(3): 246-252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574506

RESUMO

Immunoglobulin (Ig) A glomerulonephritis (GN) is a heterogeneous disease affected by various factors. Genetic and other factors "hit" DNA, causing IgA malformation and ultimately glomerular injury. We describe a rare case of crescentic IgA GN with sternoclavicular (SC) arthritis in a 75-year-old woman. Despite active IgA GN with cellular crescents, the patient achieved remission of IgA GN without glucocorticoid therapy after remission of SC arthritis was achieved. Considering the patient's clinical course, this case suggested a relationship between IgA GN and SC arthritis.

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