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1.
Org Biomol Chem ; 17(1): 165-171, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30534678

RESUMO

The 211At-labeled compound, 4-[211At]astato-l-phenylalanine, is one of the most promising amino acid derivatives for use in targeted alpha therapy (TAT) for various cancers. Electrophilic demetallation of a stannyl precursor is the most widely used approach for labeling biomolecules with 211At. However, the low acid-resistance of the stannyl precursor necessitates the use of an N- and C-terminus-protected precursor, which results in a low overall radiochemical yield (RCY) due to the multiple synthetic steps involved. In this study, a deprotected organosilyl compound, 4-triethylsilyl-l-phenylalanine, was employed for the direct synthesis of astatinated phenylalanines. 211At was separately recovered from the irradiated 209Bi target using chloroform (CHCl3) and N-chlorosuccinimide-methanol (NCS-MeOH) solution. The RCYs of 4-[211At]astato-l-phenylalanine obtained from the triethylsilyl precursor with the use of 211At, isolated in CHCl3 and NCS-MeOH solution, were 75% and 64% respectively. In both cases, the retention time of the 4-[211At]astato-l-phenylalanine was found to be about 20 min, which showed reasonable correlation with the retention time of non-radioactive 4-halo-l-phenylalanines (4-chloro-, 4-bromo-, and 4-iodo-l-phenylalanine). The one-step reaction examined in this study involved mild reaction conditions (70 °C) and a short time (10 min) compared to the other currently reported procedures for astatination. Electrophilic desilylation was found to be very effective for the labeling of aromatic amino acids with 211At.

2.
Cancer Sci ; 108(11): 2187-2194, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28837253

RESUMO

In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin-induced and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15-activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes.


Assuntos
Araquidonato 15-Lipoxigenase/genética , Morte Celular/efeitos dos fármacos , Fibrossarcoma/genética , Neoplasias Pancreáticas/genética , Carbolinas/administração & dosagem , Linhagem Celular Tumoral , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Piperazinas/administração & dosagem , RNA Interferente Pequeno , Neoplasias Pancreáticas
3.
Microbiology (Reading) ; 163(4): 531-540, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28443813

RESUMO

Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the growth of Gram-negative bacteria by disrupting the outer membrane permeability barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae cells, suggesting the presence of a molecular ligand assisting the vacuole-targeting mobilization of the peptide in the organism. Vma1p, a cytoplasmic subunit constituent of the yeast vacuolar-type ATPase, was identified as one of the PMB-binding proteins by means of mass spectrometry. Mutant cells carrying a deletion of Vma1p but not those with deletions in two separate PMB-binding proteins were shown to be resistant to the vacuolar membrane disruptive action of PMB. Furthermore, the mutant cells were resistant to PMB lethality even when treated with PMB in combination with allicin, an allyl sulfur compound, which can selectively enhance the vacuole-targeting fungicidal activity of the peptide. In contrast, the parent cells were not made resistant to the vacuolar membrane disruptive action of PMB even if cells were pre-treated with bafilomycin A1, a specific inhibitor of the yeast vacuolar-type H+-ATPase. However, the parent cells were rendered more resistant to PMB consequent to Vma1p-GFP localization in the cytoplasm. These findings suggested a role for Vma1p in the vacuole-targeting fungicidal activity of PMB comparable to that of LPS in the outer membrane of Gram-negative bacteria.


Assuntos
Antifúngicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Polimixina B/farmacologia , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Saccharomyces cerevisiae/metabolismo , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , Proteínas da Membrana Bacteriana Externa/metabolismo , Membrana Celular/patologia , Macrolídeos/farmacologia , Ligação Proteica , Saccharomyces cerevisiae/efeitos dos fármacos , Proteínas de Saccharomyces cerevisiae/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Vacúolos/metabolismo
4.
Chemistry ; 23(36): 8615-8618, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28466481

RESUMO

Synergistic control over the SH 2 transition states of hydrogen abstraction exploiting polar and steric effects provides a promising cooperative strategy for site-selective C(sp3 )-H functionalization using decatungstate anion photocatalysis. By using this photocatalytic approach, the C-H bonds of substituted lactones and cyclic ketones were functionalized selectively. In the remarkable case of 2-isoamyl 4-tert-butyl cyclohexanone (1 t) bearing five methyl, five methylene, and three methine C-H bonds, one methine C-H bond in the isoamyl tether was selectively functionalized.

5.
Biochem J ; 473(6): 769-77, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26759376

RESUMO

Pharmacological challenges to oncogenic Ras-expressing cancer cells have shown a novel type of cell death, ferroptosis, which requires intracellular iron. In the present study, we assessed ferroptosis following treatment of human fibrosarcoma HT1080 cells with several inhibitors of lysosomal activity and found that they prevented cell death induced by the ferroptosis-inducing compounds erastin and RSL3. Fluorescent analyses with a reactive oxygen species (ROS) sensor revealed constitutive generation of ROS in lysosomes, and treatment with lysosome inhibitors decreased both lysosomal ROS and a ferroptotic cell-death-associated ROS burst. These inhibitors partially prevented intracellular iron provision by attenuating intracellular transport of transferrin or autophagic degradation of ferritin. Furthermore, analyses with a fluorescent sensor that detects oxidative changes in cell membranes revealed that formation of lipid ROS in perinuclear compartments probably represented an early event in ferroptosis. These results suggest that lysosomal activity is involved in lipid ROS-mediated ferroptotic cell death through regulation of cellular iron equilibria and ROS generation.


Assuntos
Morte Celular/fisiologia , Ferro/metabolismo , Lisossomos/fisiologia , Ácido Aspártico Proteases/antagonistas & inibidores , Linhagem Celular Tumoral , Desferroxamina/farmacologia , Humanos , Pepstatinas/farmacologia , Piperazinas/farmacologia , Espécies Reativas de Oxigênio
6.
Cancer Sci ; 107(4): 514-20, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26782353

RESUMO

Even with current promising antitumor antibodies, their antitumor effects on stroma-rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa-2; moderate, BxPC-3; and abundant, Capan-1 and Ope-xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra-abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa-2 model, moderate (1063) in the BxPC-3 model, and negative in the Capan-1 and Ope-xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8-fold (2980, 3015) in the BxPC-3 model, 2.5- or 4.8-fold (1881, 3615) in the Capan-1 model, and 3.2- or 4.2-fold (1469, 1922) in the Ope-xeno model, respectively. Cetuximab was effective in treating even stroma-rich and k-ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Hipertermia Induzida , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Receptores ErbB/metabolismo , Humanos , Camundongos , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Microbiology (Reading) ; 162(5): 848-854, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26940206

RESUMO

In this study, we demonstrated that in distilled water, a nutrient-starved condition that elicits autophagy in Saccharomyces cerevisiae, an array of autophagy-deficient mutants are resistant to the fungicidal effects of amphotericin B. In addition, we found that a dansyl-labelled derivative of the antibiotic colocalized with disintegrated vacuoles throughout the cytoplasm in the amphotericin B-sensitive parental strain suspended in distilled water. In contrast, the dansyl-labelled derivative was not internalized in the Δatg18 strain, which is deficient in the formation of autophagosomes, a key early step in autophagy. However, the derivative accumulated without significant toxicity in structurally intact vacuoles in the Δvma1 mutant, which is deficient in the degradation of autophagic bodies, the final stage in autophagy. Our data support the idea that amphotericin B can utilize autophagy-dependent trafficking into the intra-vacuolar lumen, where it interacts with the luminal leaf of the membrane to cause structurally catastrophic effects.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Farmacorresistência Fúngica/genética , Proteínas de Membrana/genética , ATPases Translocadoras de Prótons/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Autofagossomos/metabolismo , Autofagia/fisiologia , Ergosterol/metabolismo , Deleção de Genes , Saccharomyces cerevisiae/genética
8.
J Med Virol ; 87(8): 1361-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25907669

RESUMO

The single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) and mutations in the core region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. However, whether this IL-28B SNP affects responses to INF therapy for HCV genotype 3a is not known. The aim of this study is to investigate whether this IL-28B SNP (rs8099917) and specific missense mutations in the HCV core region affect the response to IFN therapy for HCV genotype 3a. Patients (n = 19; median age 44.5) infected with HCV genotype 3a who received IFN therapy were studied. Of the 19 patients, 12 (63.1%) achieved sustained virological response. Of those 12 patients, 11 had the TT genotype (11/16; 68.7%), and one had the TG genotype (1/3; 33.3%). The difference in the sustained virological response rate between IL-28B genotype groups was not significant (P = 0.5232). HCV core region was well conserved; however, polymorphisms at position 72 were identified. Of the 19 HCV samples; 15 carried a glutamic acid at position 72, and these were defined as E type; the others (4/19) were defined as non-E type. Notably, there was a significant difference in the sustained virological response rate between E type and non-E-type; 12 of the 15 patients with E-type achieved sustained virological response, but none of the four patients with non-E-type achieved sustained virological response (P = 0.009). A glutamic acid at position 72 in the core region of HCV genotype 3a was associated with a good response to IFN therapy. J. Med. Virol. 87:1361-1367, 2015. © 2015 Wiley Periodicals, Inc.


Assuntos
Variação Genética , Genótipo , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Interleucinas/genética , Proteínas do Core Viral/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
9.
J Org Chem ; 80(18): 9365-9, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26317400

RESUMO

A photocatalytic synthesis of homoallyl ketones was achieved via a one-pot procedure starting from a Norrish Type I reaction of cyclopentanones, followed by a decatungstate-catalyzed hydroacylation of electron-deficient olefins by the resulting 4-pentenals. The site-selective formyl H-abstraction in the second step can be explained by radical polar effects in the transition state.

10.
Radiol Case Rep ; 19(8): 2984-2987, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38737185

RESUMO

Epipericardial fat necrosis is a rare cause of acute pleuritic chest pain and is a benign and self-limiting condition. It is important to distinguish epipericardial fat necrosis from other diseases that cause acute chest pain, such as acute myocardial infarction, pulmonary embolism, and acute pericarditis, because conservative treatment is recommended for epipericardial fat necrosis. This report presents the case of a 25-year-old man with severe pleuritic chest pain located on the left anterior side that was associated with dyspnea. Electrocardiogram and laboratory data were normal, except for a slight elevation of C-reactive protein level. Contrast-enhanced chest computed tomography revealed a fatty ovoid lesion surrounded by a thick rim on the left side of the pericardial fat. Fat stranding was observed both inside and adjacent to the fatty ovoid lesion. A slight contrast enhancement of the thick rim and a slight linear enhancement inside the lesion were observed. Furthermore, a small amount of left pleural effusion was observed. The patient was diagnosed with epipericardial fat necrosis and treated with analgesics, and the symptoms improved 1 week after the emergency department visit. Radiologists should be familiar with epipericardial fat necrosis to prevent overlooking and misdiagnosing the condition.

11.
Turk Neurosurg ; 34(1): 160-166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282595

RESUMO

AIM: To report mechanical thrombectomy (MT) for internal carotid artery (ICA) occlusion with cross-flow through the communicating artery ("with" group), and to compare it with ICA or middle cerebral artery occlusion without cross-flow ("without" group). MATERIAL AND METHODS: This study included 10 and 57 cases of the "with" and "without" groups, respectively. Cases analyzed by rapid processing of perfusion and diffusion (RAPID) since October 2020 were included. RESULTS: Puncture-to-reperfusion time was 78.5 and 39 min (p=0.0155), the National Institutes of Health Stroke Scale score at discharge was 10.5 and 4 (p=0.0166), decline from pre to post Diffusion-Weighted Image-Alberta Stroke Program Early computed tomography (CT) Score was 0.5 and 0 (p=0.0495), and the modified Rankin Scale score at 90 days was 4 and 2 (p=0.0195) in the "with" and "without" groups, respectively. Furthermore, Tmax values of > 6 s (50 cc vs. 164 cc; p=0.0277) and Tmax > 4 s/Tmax > 6 s ratio (3.23 vs. 1.55) (p=0.0074) were significantly different between the "with" and "without" groups. CONCLUSION: The "with" group may have been affected by the longer treatment time and being at high risk of distal migration of thrombus due to poor prognosis. Although the region with a Tmax of > 6 s tends to be small in patients of the "with" group, it indicates a low-perfusion state that can lead to cerebral infarction, and MT should be performed.


Assuntos
Doenças das Artérias Carótidas , Acidente Vascular Cerebral , Trombose , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Trombectomia/métodos , Angiografia Cerebral/métodos , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/cirurgia , Estudos Retrospectivos
12.
Radiol Case Rep ; 19(3): 876-880, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38188963

RESUMO

Transcatheter arterial embolization is a useful treatment for postpancreatectomy hemorrhage, a severe complication of pancreatic surgery. N-butyl cyanoacrylate is a liquid and permanent embolic material that is widely used in transcatheter arterial embolization. However, its use can lead to the adherence of the catheter to the vessel wall and occlusion of the catheter lumen. This case report presents the case of a 63-year-old man with a postpancreatectomy posterior superior pancreaticoduodenal artery pseudoaneurysm, which ruptured and bled into a drain tube. The patient underwent transcatheter arterial embolization using N-butyl cyanoacrylate and a gelatin sponge without the incidence of adherence or occlusion of the drain tube. Gelatin sponge, which was used as a temporary embolic material, was effective in preventing the drain tube from adhering and occluding.

13.
J Neuroendovasc Ther ; 18(5): 137-141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808016

RESUMO

Objective: The double origin of the posterior inferior cerebellar artery (DOPICA) is a rare variant of PICA. Vertebral artery dissecting aneurysm (VADA) with DOPICA is an extremely rare occurrence. Herein, we report a case of VADA located between DOPICA that was successfully treated with endovascular internal trapping. Case Presentation: A 48-year-old male, found collapsed at his workplace, was admitted to our hospital for emergency medical assistance. Head CT revealed a subarachnoid hemorrhage (Fisher group 3), and cerebral angiography revealed right VADA with DOPICA. The VADA was located distal to the proximal component of the posterior inferior cerebellar artery (PCPICA) and just proximal to the hypoplastic distal component of PICA (DCPICA). Emergency endovascular internal trapping was performed using a total of 13 coils from the distal end of the VADA to just the distal of the branching point of PCPICA. VADA was not visualized, and antegrade flow through DOPICA to the basilar artery was confirmed. Head magnetic resonance angiography (MRA) showed antegrade flow via DOPICA, and the patient was discharged home on Day 46 with a modified Rankin Scale 0. Conclusion: Endovascular internal trapping for VADA with DOPICA was considered useful, especially when VADA is distal to PCPICA and proximal to DCPICA.

14.
Jpn J Radiol ; 42(5): 460-467, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38148339

RESUMO

PURPOSE: To evaluate the diagnostic performance and feasibility of a modified computed tomography (CT) scan protocol, we performed a serial assessment of the computed tomography angiography for pulmonary artery (CTA-P) and systemic artery (CTA-S) (CTA-PS) using a reduced contrast agent dose to diagnose systemic artery-to-pulmonary artery shunts (SPSs). MATERIALS AND METHODS: Twenty-five patients who underwent multiphase contrast-enhanced chest CT and conventional chest angiography were included. Three image sets (CTA-P, CTA-S, and CTA-PS) were evaluated by two board-certified radiologists. The visualization of the CT image findings associated with SPSs, such as filling defects and enhancement in the pulmonary arteries, was evaluated using a 5-point scale. RESULTS: The diagnostic performance (sensitivity, specificity, and accuracy) of CT imaging findings associated with SPSs in CTA-P and CTA-PS were as follows: CTA-P, 57.1%, 87.5%, and 62.0%; CTA-PS, 81.0%, 100.0%, and 84.0%. CT findings associated with SPSs in CTA-P were significantly sensitive to the CTA-PS protocol. There were no significant differences between the CTA-S and CTA-PS protocols. The area under the curve (AUC) of the CT imaging findings associated with SPSs in the CTA-P and CTA-PS groups was 0.835 and 0.911, respectively (P = 0.191). The AUC of the CT imaging findings associated with SPSs in CTA-S and CTA-PS were 0.891 and 0.926, respectively (P = 0.373). CONCLUSION: CTA-PS using a reduced contrast agent dose protocol could improve the overall diagnostic confidence of SPSs, owing to better visualization of CT imaging findings associated with SPSs compared to individual assessments of CTA-P or CTA-S. Therefore, CTA-PS can be used as an alternative preembolization evaluation modality to conventional angiography in patients with hemoptysis suspected of having SPSs.


Assuntos
Angiografia por Tomografia Computadorizada , Meios de Contraste , Estudos de Viabilidade , Artéria Pulmonar , Sensibilidade e Especificidade , Humanos , Meios de Contraste/administração & dosagem , Masculino , Feminino , Artéria Pulmonar/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Reprodutibilidade dos Testes
15.
Cancer Sci ; 104(8): 1127-34, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23679813

RESUMO

CD44(+) /CD24(+) /EpCAM(+) cells have been reported to be cancer stem cells in pancreatic cancer; however, the histological and clinical importance of these cells has not yet been investigated. Here we clarified the characteristics of CD44(+) /CD24(+) /EpCAM(+) cells in clinical specimens of pancreatic cancer using immunohistochemical assay. We used surgical specimens of pancreatic ductal adenocarcinoma from 101 patients. In view of tumor heterogeneity, we randomly selected 10 high-power fields per case, and triple-positive CD44(+) /CD24(+) /EpCAM(+) expression was identified using our scoring system. The distribution, histological characteristics, and prognostic importance of CD44(+) /CD24(+) /EpCAM(+) cells were then analyzed. As a result, the distribution of CD44(+) /CD24(+) /EpCAM(+) cells varied widely among the 101 cases examined, and CD44(+) /CD24(+) /EpCAM(+) expression was correlated with poor glandular differentiation and high proliferation. Survival analysis showed that CD44(+) /CD24(+) /EpCAM(+) expression was not correlated with patient outcome; however, CD44(+) /CD24(+) expression appeared to be correlated with poor prognosis. In conclusion, CD44(+) /CD24(+) /EpCAM(+) expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. In particular, the presence of double-positive CD44(+) /CD24(+) expression seemed to have clinical relevance, associating with poor prognosis.


Assuntos
Antígenos de Neoplasias/biossíntese , Antígeno CD24/biossíntese , Moléculas de Adesão Celular/biossíntese , Receptores de Hialuronatos/biossíntese , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Antígeno CD24/genética , Antígeno CD24/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular/genética , Processos de Crescimento Celular/genética , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Prognóstico , Análise de Sobrevida
16.
Microbiology (Reading) ; 159(Pt 5): 939-947, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23475946

RESUMO

Here, we sought to investigate the vacuole-targeting fungicidal activity of amphotericin B (AmB) in the parent strain and AmB-resistant mutant of Saccharomyces cerevisiae and elucidate the mechanisms involved in this process. Our data demonstrated that the vacuole-targeting fungicidal activity of AmB was markedly enhanced by N-methyl-N″-dodecylguanidine (MC12), a synthetic analogue of the alkyl side chain in niphimycin, as represented by the synergy in their antifungal activities against parent cells of S. cerevisiae. Indifference was observed only with Δerg3 cells, indicating that the replacement of ergosterol with episterol facilitated their resistance to the combined lethal actions of AmB and MC12. Dansyl-labelled amphotericin B (AmB-Ds) was concentrated into normal rounded vacuoles when parent cells were treated with AmB-Ds alone, even at a non-lethal concentration. The additional supplementation of MC12 resulted in a marked loss of cell viability and vacuole disruption, as judged by the fluorescence from AmB-Ds scattered throughout the cytoplasm. In Δerg3 cells, AmB-Ds was scarcely detected in the cytoplasm, even with the addition of MC12, reflecting its failure to normally incorporate across the plasma membrane into the vacuole. Thus, this study supported the hypothesis that ergosterol is involved in the mobilization of AmB into the vacuolar membrane so that AmB-dependent vacuole disruption can be fully enhanced by cotreatment with MC12.


Assuntos
Anfotericina B/metabolismo , Antifúngicos/metabolismo , Ergosterol/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Vacúolos/metabolismo , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Farmacorresistência Fúngica , Saccharomyces cerevisiae/genética , Vacúolos/efeitos dos fármacos
17.
Cureus ; 15(5): e39311, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37346212

RESUMO

Delayed onset of facial spasm following surgery for unilateral facial spasm after microvascular decompression (MVD) of the distal facial nerve is rare. We report a case of unilateral facial spasm caused by compression of the distal facial nerve successfully treated with MVD resulting in delayed peripheral facial nerve palsy. A 51-year-old male patient with a left facial spasm showed a gradual worsening of symptoms. Head imaging revealed that the left anterior inferior cerebellar artery (AICA) was in contact with the distal portion of the left facial nerve; hence, MVD was performed. The AICA was pressing on the distal facial nerve, so the AICA was transpositioned. Postoperatively, the facial spasm improved. On the eighth postoperative day, the patient showed left peripheral facial nerve palsy and was given conservative treatment. The patient was discharged home on the sixteenth postoperative day. One month after discharge, the facial palsy was in complete remission. Distal facial nerve compression may cause unilateral facial spasms. Although delayed facial nerve palsy may occur, the prognosis is good.

18.
Brain Behav ; 13(8): e3163, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37469274

RESUMO

OBJECTIVE: Endovascular therapy (EVT) is performed for acute ischemic stroke (AIS) with large vessel occlusion (LVO), however, the treatment strategies and clinical outcomes differ between cardiac embolism (CE) and intracranial arteriosclerosis-derived LVO (ICAS-LVO). We analyzed whether the time-to-max (Tmax) volume derived from perfusion imaging predicted clinical classification in AIS patients before EVT. METHODS: Consecutive AIS patients with anterior circulation LVO evaluated by automated imaging software were retrospectively identified. Patients were classified into a CE group and an ICAS-LVO group, and parameters were compared between groups. RESULTS: Thirty-nine patients were included and Tmax volume and Tmax > 6 s volume/Tmax > 4 s volume were significantly greater in the CE group than in the ICAS-LVO group (Tmax > 4 s volume: 261 mL vs. 149 mL, p = .01, Tmax > 6 s volume: 143 mL vs. 59 mL, p = .001, Tmax > 6 s volume/Tmax > 4 s volume: 0.59 vs. 0.40, p < .001). Multiple logistic regression analysis indicated an association between clinical classification and high Tmax > 6 s volume/Tmax > 4 s volume (p = .04). CONCLUSION: The Tmax volume derived from perfusion imaging predicts the clinical classification of AIS patients before EVT.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Estudos Retrospectivos , Trombectomia/métodos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodos , Resultado do Tratamento
19.
Cureus ; 15(3): e35911, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033540

RESUMO

Fulminant fat embolism syndrome (FES) occurring within 1 h after trauma is extremely rare. We report a case of fulminant FES that developed hyperacute nature after a traumatic injury. A 66-year-old woman was injured when she fell approximately 1.5 m down the stairs. She was rushed to our hospital. One minute after arrival, which was 49 min after the injury, her consciousness and respiratory status deteriorated. Thoracoabdominal and pelvic computed tomography revealed preexisting interstitial pneumonia, a left femoral neck fracture, and a left sacral fracture. Head magnetic resonance imaging (diffusion-weighted imaging) showed diffuse high-signal areas and susceptibility-weighted imaging showed diffuse small perivascular of perivascular hemorrhages. She was diagnosed with fulminant FES. After conservative treatment, she was transferred to a rehabilitation hospital with a Glasgow Coma Scale (GCS) of 8 and a modified Rankin Scale of 5 on Day 45. The possibility of fulminant FES should be considered a cause of early impaired consciousness after a fracture.

20.
Nagoya J Med Sci ; 85(4): 713-724, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38155627

RESUMO

In this study, we elucidate if synthetic contrast enhanced computed tomography images created from plain computed tomography images using deep neural networks could be used for screening, clinical diagnosis, and postoperative follow-up of small-diameter renal tumors. This retrospective, multicenter study included 155 patients (artificial intelligence training cohort [n = 99], validation cohort [n = 56]) who underwent surgery for small-diameter (≤40 mm) renal tumors, with the pathological diagnosis of renal cell carcinoma, during 2010-2020. We created a learned deep neural networks using pix2pix. We examined the quality of the synthetic enhanced computed tomography images created using this deep neural networks and compared them with real enhanced computed tomography images using the zero-mean normalized cross-correlation parameter. We assessed concordance rates between real and synthetic images and diagnoses according to 10 urologists by creating a receiver operating characteristic curve and calculating the area under the curve. The synthetic computed tomography images were highly concordant with the real computed tomography images, regardless of the existence or morphology of the renal tumor. Regarding the concordance rate, a greater area under the curve was obtained with synthetic computed tomography (area under the curve = 0.892) than with only computed tomography (area under the curve = 0.720; p < 0.001). In conclusions, this study is the first to use deep neural networks to create a high-quality synthetic computed tomography image that was highly concordant with a real computed tomography image. Our synthetic computed tomography images could be used for urological diagnoses and clinical screening.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Inteligência Artificial , Estudos Retrospectivos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Neoplasias Renais/diagnóstico por imagem
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