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The one-pot de novo synthesis of pentasubstituted pyridines was realized following the process of Au(I)-autotandem catalysis and subsequent aromatization. The process involves aza-enyne metathesis with aryl propiolates to yield 1-azabutadienes and their addition/6π-electrocyclization sequence with the other propiolate units. The resultant 1,4-dihydropyridines were aromatized to furnish the pyridines in the presence of atmospheric oxygen. The aryl propiolates were regioselectively incorporated into the ring system to afford 2-arylpyridines as the sole product.
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We herein report a fatal case of invasive mucinous adenocarcinoma (IMA) with acute respiratory distress syndrome (ARDS) diagnosed based on autopsy findings. A 76-year-old man presented with severe respiratory discomfort on admission. Computed tomography (CT) revealed a peripheral distribution of consolidation. Although his respiratory status improved after steroid therapy, re-exacerbation occurred, and the patient died on day 131. A bronchoscopic lung biopsy had shown organizing pneumonia, but a post-mortem examination surprisingly revealed IMA with organizing pneumonia. IMA presenting with ARDS as the first symptom is extremely rare.
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Adenocarcinoma Mucinoso , Síndrome de Dificultad Respiratoria , Masculino , Humanos , Anciano , Autopsia , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/etiología , Adenocarcinoma Mucinoso/complicaciones , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologíaRESUMEN
Pyometra is a rare disease in which pus accumulates in the uterus and is typically caused by stenosis of the cervix. Only a few case reports have indicated that diverticular disease causes pyometra. We herein report an 83-year-old woman presented to our hospital with a fever, loss of appetite, general fatigue and back pain. After some inspections, she was diagnosed with pyometra and lumbar pyogenic spondylitis secondary to diverticulitis of the sigmoid colon. We performed transvaginal drainage and continued antibiotic administration for about three months. The pyometra and pyogenic spondylitis successfully resolved, and she did not experience any recurrence.
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Diverticulitis , Piómetra , Espondilitis , Femenino , Humanos , Anciano de 80 o más Años , Colon Sigmoide/diagnóstico por imagen , Piómetra/complicaciones , Diverticulitis/complicaciones , Diverticulitis/diagnóstico , Espondilitis/diagnóstico , Espondilitis/diagnóstico por imagen , DrenajeRESUMEN
Interest in the marine cyanobacteria natural products aplysiatoxin (ATX) and oscillatoxin (OTX) has been renewed recently due to the discovery of many new analogues, some exhibiting intriguing biological activities. We sought to develop a collective synthesis of these natural products, hypothesizing that ATX could serve as a common biosynthetic precursor. Herein, we reveal that the core structure of ATX has unique multiple reactivities giving access to the distinct ring structures of five of the analogues, depending upon the specific conditions used. Based on these findings, syntheses of the O-Me derivative of five analogues neo-deBr-ATX-B, OTX-H, OTX-D, neo-deBr-ATX-H, and OTX-I were achieved from the main fragment of ATX as a common intermediate in a few steps. These synthetic studies also led us to revise the relative configuration in the elucidated structures of neo-deBr-ATX-B and OTX-H, and obtain unnatural 8- and 12-membered lactones from the same intermediate.
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Productos Biológicos , Cianobacterias , Lactonas/químicaRESUMEN
A 61-year-old woman was admitted to our hospital with productive cough and fever. Computed tomography images revealed ground glass opacities in both lung fields, and a space-occupying lesion in the gallbladder. Transbronchial lung biopsy revealed a poorly differentiated adenocarcinoma with invasion of the lymph ducts; accordingly, a diagnosis of lymphangitis carcinomatosa was made. We could not administer chemotherapy due to poor performance status, and the patient died of respiratory failure 30 days after admission. Owing to pathological autopsy findings of poorly differentiated adenocarcinoma in the gallbladder, we diagnosed this as a rare case of gallbladder cancer presenting with lymphangitis carcinomatosa.
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OBJECTIVES: This study aimed to develop reliable biomarkers that improve the ability of bile cytology to diagnose cholangiocarcinoma vs benign biliary lesions. METHODS: Many studies indicate that microRNAs (miRNAs) are potential candidates for the early diagnosis of cancer. We analyzed the expression of five tumor-associated miRNAs (miR-31-5p, miR-122-5p, miR-378d, miR-182-5p, and miR-92a-3p) in cytology samples using quantitative reverse transcription polymerase chain reaction. We collected 52 surgically resected tissue samples, 84 cytologic specimens from smears (53 cases of cancer and 31 cases of noncancer), and 40 residual sediments after smearing for routine cytology at Hiroshima University Hospital. RESULTS: The expression of miR-31-5p, miR-378d, and miR-122-5p was significantly higher in cancer tissues than those in normal tissues, while miR-182-5p expression was lower. The expression of miR-31-5p, miR-378d, miR-182-5p, and miR-92a-3p was significantly higher in detached cell samples from smears of cholangiocarcinoma cases than in those from noncancer cases. CONCLUSIONS: These results suggest that the analysis of miRNAs in bile cytologic specimens is a promising auxiliary tool for distinguishing cholangiocarcinoma from benign biliary lesions.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , MicroARNs , Bilis/metabolismo , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/metabolismo , Biomarcadores de Tumor/genética , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Perfilación de la Expresión Génica/métodos , Humanos , MicroARNs/genéticaRESUMEN
Oscillatoxins (OTXs) and aplysiatoxins are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities. Although OTX-D and 30-methyl-OTX-D have been reported to show antileukemic activity against L1210 cell line, we found that their cytotoxicity in vitro against this cell line is relatively weak (IC50: 29-52 µm). In contrast, OTX-F demonstrated cell line-selective antiproliferative activity against DMS-114 lung cancer cells, which implies that OTXs target as yet unknown target molecules as part of this unique activity.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Toxinas Bacterianas/síntesis química , Toxinas Bacterianas/farmacología , Antineoplásicos/química , Toxinas Bacterianas/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Técnicas de Química Sintética , HumanosRESUMEN
OBJECTIVES: Bronchoscopy is frequently performed for patients suspected of having lung cancer; however, we sometimes fail to make a definitive diagnosis, resulting in additional invasive testing. Many studies indicate that microRNAs (miRs) are abnormally expressed in cancers. We examined the diagnostic value of 4 miRs (miR-21, miR-31, miR-182, and miR-183) extracted from liquid-based cytology (LBC) samples and validated whether they were diagnostically useful. METHODS: We collected 18 surgically resected tissue samples and 136 LBC specimens obtained during bronchoscopic examination at Hiroshima University Hospital. We extracted RNA from these samples and compared the expression of 4 miRs by reverse transcription-quantitative polymerase chain reaction. RESULTS: We confirmed that expression of the 4 miRs was significantly higher in cancer tissues than in tumor-adjacent normal tissues. We examined the expression of these miRs in 125 (cancer cases, 83; noncancer cases, 42) of 136 cytologic samples. Expression of all 4 miRs was significantly higher in patients with lung cancer than in those without lung cancer. Among samples judged as benign or indeterminate, levels of these miRs were also significantly higher in patients with lung cancer than in those without lung cancer. CONCLUSIONS: The analysis of miR expression in LBC samples might be helpful for primary lung cancer diagnosis.
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Biomarcadores de Tumor/genética , Neoplasias Pulmonares/diagnóstico , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Broncoscopía , Biología Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In this contribution, we propose a new synthetic approach to tetrodotoxin (TTX), one of the most famous marine toxins that, after first preparing a functionalized linear substrate, forms a cyclohexane core from the substrate utilizing our mercuric triflate (Hg(OTf)2)-catalyzed cycloisomerization reaction. The concept was applied to the synthesis of 11-nor-6,7,8-trideoxyTTX and 11-nor-4,9-anhydro-6,7,8-trideoxyTTX, which are unnatural TTX analogues, demonstrating the validity of our new approach.
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Physalins are a structurally complex family of 13,14-secosteroids isolated from the genus Physalis. We disclose a two-step construction of the CDE ring moiety of the physalins from a steroidal compound bearing 14-OH, 18-COOMe, and 17, 20-α-epoxide based on our biosynthetic proposal. C13-C14 bond cleavage by an alkoxy radical at C-14 and spontaneous epoxide ring opening gave a compound having a cyclononene and γ-lactone. Diastereoselective dihydroxylation of the resulting alkene with OsO4 provided the CDE ring moiety of physalin.
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Physalis/química , Secoesteroides/química , Esteroides/química , Biomimética , Estructura Molecular , Physalis/metabolismo , Secoesteroides/síntesis química , Esteroides/síntesis químicaRESUMEN
O-Methyloscillatoxin D and its analogues were concisely synthesized by a bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves the construction of a novel spiro-ether moiety.
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Compuestos de Espiro/química , Estructura Molecular , EstereoisomerismoRESUMEN
Hot tub lung is a lung disease caused by Mycobacterium avium complex. We report the first case of familial hot tub lung appearing simultaneously in a husband and wife. Our case supports the consideration that hot tub lung is a hypersensitivity pneumonitis rather than an infectious lung disease. It also suggests that the state of hot tub lung changes seasonally depending on temperature variations, in a manner similar to summer-type hypersensitivity pneumonitis. This case demonstrates similarities between hot tub lung and summer-type hypersensitivity pneumonitis in regards to familial occurrence and seasonal changes in the disease state.
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A host framework for inclusion of various guest molecules was investigated by preparation of inclusion crystals of 1,8-bis(4-aminophenyl)anthracene (1,8-BAPA) with organic solvents. X-ray crystallographic analysis revealed construction of the same inclusion space incorporating 1,8-BAPA and eight guest molecules including both non-polar (benzene) and polar guests (N,N-dimethylformamide, DMF). Fluorescence efficiencies varied depending on guest molecule polarity; DMF inclusion crystals exhibited the highest fluorescence intensity (ΦF=0.40), four times as high as that of a benzene inclusion crystal (ΦF=0.10). According to systematic investigations of inclusion phenomena, strong hostguest interactions and filling of the inclusion space led to a high fluorescence intensity. Temperature-dependent fluorescence spectral measurements revealed these factors effectively immobilised the host framework. Although hydrogen bonding commonly decreases fluorescence intensity, the present study demonstrated that such strong interactions provide excellent conditions for fluorescence enhancement. Thus, this remarkable behaviour has potential application toward sensing of highly polar molecules, such as biogenic compounds.
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Organic-inorganic hybrid salts based on 1,5-bisaminophenylanthracene were able to overcome aggregation-induced quenching and emit multiple colours of luminescence according to the counter acid employed. Moreover, the emission colour could be reversibly and dynamically changed on absorption and desorption of guest molecules.