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A 68-year-old Japanese man developed a fever, headache, hiccups, and altered consciousness. Brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion in the right temporal lobe and multiple high-intensity white matter lesions. A brain biopsy showed pathological findings consistent with acute disseminated encephalomyelitis (ADEM), suggesting a diagnosis of acute hemorrhagic leukoencephalitis (AHLE), an aggressive ADEM variant. The patient also developed myodesopsia and was diagnosed with retinal vasculitis, likely due to a hyperimmune state caused by AHLE. Corticosteroids enabled full recovery. Although AHLE is uncommon in elderly individuals, clinicians should be aware of its occurrence in this patient subgroup and recognize potential retinal manifestations associated with AHLE.
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OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.
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Enfermedades de los Pequeños Vasos Cerebrales , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Anticoagulantes , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Fibrinolíticos/efectos adversos , Hemorragia , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , MasculinoRESUMEN
Objective: Recent studies evaluating plaque protrusion at carotid artery stenting (CAS) using optical coherence tomography showed not a few cases of plaque protrusion when using double-layer micromesh stents. We report a case of symptomatic internal carotid artery (ICA) stenosis with at-risk unstable plaques in which CAS was successfully performed using a stent-in-stent technique by the combined use of a closed-cell stent and a dual-layer micromesh stent. Case Presentation: An 87-year-old Japanese man with dysarthria and right hemiparesis was diagnosed with atheromatous cerebral embolism caused by severe left ICA stenosis on MRI and DSA. MRI with T1-weighted black blood methods showed high intensities in the plaques of the left ICA, suggesting unstable plaque characteristics with intraplaque hemorrhage components. On day 20, CAS was performed. After the pre-stent dilation under proximal and distal protection, a Carotid WALLSTENT was placed to cover the stenotic lesion. Then, a CASPER Rx was placed from the proximal left ICA to the common carotid artery to cover the Carotid WALLSTENT. Although visible plaque debris was recognized in the aspirated blood, the debris became invisible after aspiration of 1300 mL. Postoperative angiography showed enough dilation of the left ICA, with no plaque protrusion or acute stent thrombosis. The patient had an uneventful postoperative course and was discharged without any neurological sequelae. Conclusion: The present case suggests that the combined stent-in-stent technique using a closed-cell stent and a micromesh stent can be considered as one of the treatment strategies for preventing plaque protrusion and procedural ischemic complications in patients with high-risk carotid plaques.
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INTRODUCTION: The management of intracranial artery dissection (IAD) has not been established, partly because the long-term course of the disease is not well-known. We retrospectively investigated the long-term course of IAD without subarachnoid hemorrhage (SAH) as an initial clinical presentation. METHODS: Of 147 consecutive spontaneous first-ever IAD patients hospitalized between March 2011 and July 2018, 44 with SAH were excluded, and the remaining 103 were investigated. We divided the patients into two groups: Recurrence group as those with recurrent intracranial dissection >1 month after the initial dissection, and Non-recurrence group as those without them. Clinical characteristics were compared between those two groups. RESULTS: The mean follow-up period was 33 months from the initial event. Recurrent dissection occurred in 4 patients (3.9%) >7 months after the initial dissection, none of whom were on antithrombotic treatments at recurrence. Three had ischemic stroke and the other had local symptoms [range: 8 to 44 months]. Nine (8.7%) had an ischemic stroke within 1 month of the initial event. There was no recurrent dissection between 1 and 7 months after the initial event. There was no significant difference in baseline characteristics between Recurrence and Non-recurrence groups. CONCLUSIONS: Four out of the 103 (3.9%) IAD patients had recurrent IAD >7 months after the initial event. IAD patients should be followed up for more than a half year after the initial event, with consideration given to the recurrence of IAD. Further research is needed on recurrence prevention measures to IAD patients.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Estudios Retrospectivos , Arterias , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/terapia , Hemorragia Subaracnoidea/complicaciones , Accidente Cerebrovascular/etiologíaRESUMEN
OBJECTIVE: Artificial intelligence (AI)-based cytopathology studies conducted using deep learning have enabled cell detection and classification. Liquid-based cytology (LBC) has facilitated the standardisation of specimen preparation; however, cytomorphology varies according to the LBC processing technique used. In this study, we elucidated the relationship between two LBC techniques and cell detection and classification using a deep learning model. METHODS: Cytological specimens were prepared using the ThinPrep and SurePath methods. The accuracy of cell detection and cell classification was examined using the one- and five-cell models, which were trained with one and five cell types, respectively. RESULTS: When the same LBC processing techniques were used for the training and detection preparations, the cell detection and classification rates were high. The model trained on ThinPrep preparations was more accurate than that trained on SurePath. When the preparation types used for training and detection were different, the accuracy of cell detection and classification was significantly reduced (P < 0.01). The model trained on both ThinPrep and SurePath preparations exhibited slightly reduced cell detection and classification rates but was highly accurate. CONCLUSIONS: For the two LBC processing techniques, cytomorphology varied according to cell type; this difference affects the accuracy of cell detection and classification by deep learning. Therefore, for highly accurate cell detection and classification using AI, the same processing technique must be used for both training and detection. Our assessment also suggests that a deep learning model should be constructed using specimens prepared via a variety of processing techniques to construct a globally applicable AI model.
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Inteligencia Artificial , Aprendizaje Profundo , Humanos , Técnicas Citológicas/métodos , Citodiagnóstico/métodosRESUMEN
OBJECTIVE: Clinical characteristics of endovascular treatment (EVT) for acute ischemic stroke (AIS) secondary to atherosclerosis are not fully delineated. An optimal treatment strategy with considerations of stroke etiology has not yet been established. Here-in, we performed retrospective analysis of EVT for atherosclerotic AIS. METHODS: Data from patients with AIS who underwent EVT between 2017 and 2022 were analyzed. Clinical characteristics, procedural data, and outcomes were assessed. Further analysis was conducted to elucidate the factors associated with clinical outcomes. And data of patients with poor clinical outcomes (mRS, 5 or 6) were evaluated further to determine the primary cause. RESULTS: Among 194 patients who received EVT, 40 (20.6%) were diagnosed with AIS with an atherosclerotic etiology. The rates of successful reperfusion (TICI 2b or 3) and good clinical outcomes (mRS, 0-2) were 95.0% and 45.0%, respectively. No procedure-related complications were noted. Older age (p = 0.007), more severe baseline NIHSS score (p = 0.004), lesion in the posterior circulation (p = 0.025), and recanalization failure (p = 0.027) were more frequently observed in patients with poor clinical outcomes. Brainstem infarction and postprocedural intracerebral hemorrhage were the main reasons for poor clinical outcomes. CONCLUSION: The EVT for atherosclerotic AIS were effective and safe. Older age, more severe NIHSS score, lesions in the posterior circulation, and recanalization failure were the factors associated with poor clinical outcomes. It is important to recognize that these factors may aggravate the clinical response to this promising therapy, even in patient successful recanalization was attained.
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Aterosclerosis , Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Aterosclerosis/complicaciones , Trombectomía/efectos adversos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Isquemia Encefálica/cirugíaRESUMEN
BACKGROUND AND PURPOSE: Spontaneous intracranial artery dissection (IAD) can be definitively diagnosed by detecting intramural hematoma (IMH) on arterial wall imaging. However, evidence of a time-dependent natural history for the development of radiological findings is lacking. Therefore, this study aimed to determine when imaging detects IAD. METHODS: We obtained data from our cohort databases between March 2011 and August 2018 on consecutive patients who had definite, probable, or possible IAD based on the multidisciplinary expert consensus criteria. We assessed IMH on initial and follow-up high-resolution three-dimensional T1-weighted imaging (HR-3D-T1WI). We retrospectively investigated the association between IMH detection and days from symptom onset to initial HR-3D-T1WI and compared the IMH detection rate with other definitive diagnostic arterial dissection findings. RESULTS: We analyzed 106 patients (mean age = 51 ± 13 years, 31 women) with at least initial HR-3D-T1WI data. The final diagnoses were definite, probable, and possible IAD in 83, 18, and 5 patients, respectively. IMHs were observed in 63 patients (59%, 95% confidence interval [CI] = 49%-69%). Overall IMH detection rate was 55% (95% CI = 45%-64%), 20% (95% CI = 3%-60%), 40% (95% CI = 21%-64%), and 50% (95% CI = 37%-63%) on the initial HR-3D-T1WI and Days 3, 7, and 13, respectively. Among 68 patients evaluated with digital subtraction angiography and HR-3D-T1WI, IMH was confirmed more frequently than other definitive diagnostic arterial dissection findings. CONCLUSIONS: The overall IMH detection rate on HR-3D-T1WI was >50% and peaked in 1-2 weeks. IMH was a frequently detectable finding for the diagnosis of IAD compared to other radiological findings.
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Disección Aórtica , Arterias , Humanos , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Hematoma/diagnóstico por imagen , Imagenología Tridimensional , Angiografía por Resonancia Magnética/métodosRESUMEN
Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0-4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m2), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11-2.39) at category G4 (eGFR 15-<30 mL/min per 1.73 m2) and 2.05 (95% CI, 1.33-3.16) at G5 (eGFR <15 mL/min per 1.73 m2). Corresponding odds ratios relative to urinary albumin-to-creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12-1.49) for category A2 (ACR 30-<300 mg/g) and 1.37 (95% CI, 1.05-1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased. Conclusions Both reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.
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Enfermedades de los Pequeños Vasos Cerebrales , Enfermedades Renales , Accidente Cerebrovascular , Anciano , Albuminuria/complicaciones , Albuminuria/epidemiología , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Femenino , Fibrinolíticos/efectos adversos , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/complicaciones , Imagen por Resonancia Magnética , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
INTRODUCTION: Liquid-based cytology (LBC) is increasingly used for nongynecologic applications. However, the cytological preparation of LBC specimens is influenced by the processing technique and the preservative used. In this study, the influence of the processing techniques and preservatives on cell morphology was examined mathematically and statistically. METHODS: Cytological specimens were prepared using the ThinPrep (TP), SurePath (SP), and AutoSmear methods, with 5 different preservative solutions. The cytoplasmic and nuclear areas of Papanicolaou-stained specimens were measured for all samples. RESULTS: The cytoplasmic and nuclear areas were smaller in cells prepared using the 2 LBC methods, compared to that prepared using the AutoSmear method, irrespective of the preservative used. The cytoplasmic and nuclear areas of cells prepared using the SP method were smaller than those of cells prepared using the TP method, irrespective of the preservative used. There were fewer differences among the cytoplasmic areas of cells prepared with different preservative solutions using the TP method; however, the cytoplasmic areas of cells prepared using the SP method changed with the preservative solution used. CONCLUSIONS: The most significant difference affecting the cytoplasmic and nuclear areas was the processing technique. The TP method increased the cytoplasmic and nuclear areas, while the methanol-based PreservCyt solution enabled the highest enlargement of the cell. LBC is a superior preparation technique for standardization of the specimens. Our results offer a better understanding of methods suitable for specimen preparation for developing precision AI-based diagnosis in cytology.
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Citodiagnóstico , Citodiagnóstico/métodos , Técnicas Citológicas , Fijadores , HumanosRESUMEN
W present a rare case of cerebral venous sinus thrombosis after the BNT162b2 mRNA COVID-19 vaccine. A 61-year-old Japanese man developed a headache 10 days after the first dose of the vaccine. Magnetic resonance venography and contrast-enhanced brain MRI showed thrombosis in the superior sagittal sinus and the right transverse sinus. Anticoagulation with intravenous unfractionated heparin followed by oral warfarin was started. His headache improved, and brain MRI on day 22 showed resolution of thrombus. He was maintained on anticoagulation with warfarin and discharged without any neurological sequelae. This case is presented in the context of the relevant literature.
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Perivascular spaces, also known as Virchow-Robin spaces, are usually considered as a normal, asymptomatic finding. However, this finding can occasionally demonstrate an atypical appearance and can be symptomatic. We report herein a rare case of cognitive impairment associated with extremely enlarged perivascular spaces. A 68-year-old Japanese woman visited our hospital with a 1-year history of progressive memory impairment. In addition to temporal disorientation and short-term memory impairment, neuropsychological testing showed frontal lobe-related symptoms such as slowed thinking processes, reduced verbal fluency, attention deficit, and reduced working memory. Magnetic resonance imaging of the brain showed widespread enlarged perivascular spaces almost symmetrically in the subcortical white matter of bilateral hemispheres, prominently in bilateral insulas, and frontal opercula. On 99mTc-ethyl cysteinate dimer single photon emission computed tomography, hypoperfusion was apparent in bilateral insulas and frontal opercula where enlarged periventricular spaces were prominent, whereas cerebral perfusion was preserved in areas where enlargement of perivascular spaces was mild or absent. Because symptoms were consistent with the distribution of the enlarged perivascular spaces and hypoperfusion in the brain, cognitive impairment due to enlarged perivascular spaces was diagnosed. Clinicians should note enlarged perivascular spaces as a potential cause of neurological deficits including cognitive impairment.
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Dermatomyositis is a rare immune-related adverse event caused by immune checkpoint inhibitors. We herein report a 75-year-old Japanese man with small-cell lung carcinoma who developed dermatomyositis after the administration of atezolizumab. He developed rashes on day 13 and myalgia and motor weakness on day 30 of the first administration of atezolizumab. Anti-transcriptional intermediary factor 1-gamma antibody was positive, and serum interleukin-6 levels were prominently elevated in the acute phase. Symptoms were improved by corticosteroid therapy. This is the first report of dermatomyositis associated with atezolizumab. Clinicians should be aware of the possibility of dermatomyositis after the administration of immune checkpoint inhibitors.
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Carcinoma , Dermatomiositis , Neoplasias Pulmonares , Anciano , Anticuerpos Monoclonales Humanizados , Dermatomiositis/inducido químicamente , Dermatomiositis/diagnóstico , Humanos , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , MasculinoRESUMEN
Accumulation of amyloid ß peptides (Aß) is thought to be one of the causal factors of Alzheimer's disease (AD). The aspartyl protease ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting protease for Aß production, and therefore, BACE1 inhibition is a promising therapeutic approach for the treatment of AD. Starting with a dihydro-1,3-thiazine-based lead, Compound J, we discovered atabecestat 1 (JNJ-54861911) as a centrally efficacious BACE1 inhibitor that was advanced into the EARLY Phase 2b/3 clinical trial for the treatment of preclinical AD patients. Compound 1 demonstrated robust and dose-dependent Aß reduction and showed sufficient safety margins in preclinical models. The potential of reactive metabolite formation was evaluated in a covalent binding study to assess its irreversible binding to human hepatocytes. Unfortunately, the EARLY trial was discontinued due to significant elevation of liver enzymes, and subsequent analysis of the clinical outcomes showed dose-related cognitive worsening.
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Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Inhibidores de Proteasas/uso terapéutico , Piridinas/uso terapéutico , Tiazinas/uso terapéutico , Péptidos beta-Amiloides/metabolismo , Animales , Perros , Canal de Potasio ERG1/antagonistas & inhibidores , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Masculino , Ratones , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/farmacocinética , Piridinas/síntesis química , Piridinas/farmacocinética , Ratas Sprague-Dawley , Tiazinas/síntesis química , Tiazinas/farmacocinéticaRESUMEN
Spinal cord infarction (SCI) is rare, difficult to diagnose, and often fails to be detected by diffusion-weighted imaging (DWI) of spinal cord magnetic resonance imaging (MRI). Because the clinical features of SCI can vary widely, diagnosis during the acute phase of SCI is often challenging for clinicians. Although SCI shares similar etiologies with cerebral infarction, the characteristics of SCI without vessel dissection remain largely unknown. We present two older patients with mild neurological symptoms who each presented with a small, unilateral, upper cervical cord lesion, which was detected by thin-section, coronal DWI of brain MRI. Both unilateral small lesions were localized in the right lateral funiculus, and each patient showed good prognosis. The anatomical findings suggested that the pial collateral network surrounding the cervical cord contributed to lesion formation. Small and localized lesions have been associated with mild neurological symptoms and better short-term prognosis. The present report indicated that the use of thin-section coronal DWI when performing brain MRI may be helpful for the diagnosis of small, unilateral, upper cervical cord infarctions.
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BACKGROUND AND AIMS: Polymerase chain reaction-based techniques require expensive equipment for fluorescence detection of the products. However, the measurement of inorganic pyrophosphate (PPi) released during DNA synthesis can be used to quantify target genes without such equipment. Here, we devised a high-sensitivity enzymatic assay for detection of PPi. MATERIALS AND METHODS: In our assay method, PPi was converted to hypoxanthine by hypoxanthine phosphoribosyl transferase. Xanthine dehydrogenase converted the hypoxanthine to uric acid and yielded two molecules of NADH, which in turn reduced Fe3+ to Fe2+ (mediated by 1-methoxy-5-ethylphenazinium ethylsulfate). 2-Nitroso-5-(N-propyl-N-sulfopropylamino) phenol chelated the Fe2+, which resulted in an intensely colored product that could be measured using a biochemical automated analyzer. RESULTS: The assay was able to detect PPi within 10 min. It was linear between 0 and 10 µmol/L PPi, and intra-run and inter-run coefficients of variation were 1%-2%. Other validation tests with a biochemical automated analyzer were satisfactory. The assay could potentially be used to directly quantify samples after isothermal nucleic acid sequence-based amplification of a target gene. CONCLUSION: The method developed here for detection of PPi can be used to measure nucleic acid biomarkers in biological samples in clinical practice using a high-throughput biochemical automated analyzer.
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Difosfatos , Replicación de Secuencia Autosostenida , Humanos , Técnicas de Amplificación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91-106 were generated in the absence of endogenous PrPC, designated Tg(PrP∆91-106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrP∆91-106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPSc∆91-106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPSc∆91-106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrPSc∆91-104 after incubation with BSE-PrPSc-prions but not with RML- and 22L-PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91-104 into PrPSc∆91-104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91-106 or 91-104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.
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Encefalopatía Espongiforme Bovina/genética , Proteínas PrPC/genética , Proteínas PrPSc/genética , Deficiencias en la Proteostasis/genética , Scrapie/genética , Eliminación de Secuencia , Animales , Baculoviridae/genética , Baculoviridae/metabolismo , Secuencia de Bases , Encéfalo/metabolismo , Encéfalo/patología , Bovinos , Clonación Molecular , Susceptibilidad a Enfermedades , Encefalopatía Espongiforme Bovina/metabolismo , Encefalopatía Espongiforme Bovina/patología , Expresión Génica , Inyecciones Intraventriculares , Ratones , Ratones Transgénicos , Proteínas PrPC/química , Proteínas PrPC/metabolismo , Proteínas PrPSc/administración & dosificación , Proteínas PrPSc/química , Proteínas PrPSc/metabolismo , Deficiencias en la Proteostasis/metabolismo , Deficiencias en la Proteostasis/patología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Scrapie/metabolismo , Scrapie/patología , Especificidad de la EspecieRESUMEN
Although transition-metal-catalysed hydroboration reactions of alkenes have been extensively studied, only three examples using Ni complexes have been reported so far. In this study, we have examined hydroboration reactions of alkenes using Ni/phosphine complexes. The commercially available and bottleable complex NiCl2(dppe) (dppe = 1,2-bis(diphenylphosphino)ethane) serves as a catalyst for the highly Markovnikov-selective hydroboration of styrene derivatives that affords the desired Markovnikov products in high yield.
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MicroRNAs (miRNAs) exert critical roles in the majority of biological and pathological processes. Recent studies have associated miR-150 with a number of different cancer types. However, little is known about miR-150 targets in cervical cancer. In the present study, the HeLa human cervical cancer cell line was transfected with hsa-miR-150-5p mimics, hsa-miR-150-5p inhibitors or miRNA controls. miR-150 was predicted to bind the 3'untranslated region (3'UTR) of the CDKN1B gene, which encodes the cyclin-dependent kinase inhibitor 1B (p27Kip1). The direct binding between miR-150 and the 3'UTR of CDKN1B was confirmed using dual-luciferase reporter assays. The effects of miR-150 on CDKN1B mRNA expression, p27Kip1 protein expression, cell cycle and cell proliferation were determined using reverse-transcription quantitative PCR, western blot analysis, flow cytometry and WST-8 assays, respectively. miR-150 was demonstrated to directly target the 3'UTR of CDKN1B in transfected HeLa cells. The expression of CDKN1B mRNA and p27Kip1 protein was reduced by miR-150 mimics, and increased by miR-150 inhibitors. Moreover, the overexpression of miR-150 promoted cell cycle progression from the G0/G1 to the S phase and led to a significant increase in HeLa cell proliferation. The results of the present study indicated that miR-150 promotes HeLa cell cycle progression and proliferation via the suppression of p27Kip1 expression.
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Primary sclerosing cholangitis (PSC) is associated with significant risk for hepatobiliary cancers. Primary hepatic adenosquamous carcinoma (ASC), a rare subtype of cholangiocarcinoma, is composed of both adenocarcinoma and squamous cell carcinoma components. We herein report the case of a patient with PSC who was diagnosed with ASC of the liver during cancer surveillance. A 74-year-old male patient was diagnosed with PSC based on blood chemistry and magnetic resonance cholangiopancreatography findings, and regular surveillance for hepatobiliary cancers was initiated. Four years later, the level of carbohydrate antigen 19-9 rapidly increased, and abdominal imaging studies revealed a cystic mass, 40 mm in diameter, containing a solid component in the right liver lobe. Right lobectomy was performed with a pre-operative diagnosis of cholangiocarcinoma; however, the definitive diagnosis was ASC based on the presence of adenocarcinoma and squamous cell carcinoma components in the resected tumor. The patient did not receive post-operative chemotherapy, but was alive for more than 4 years without recurrence at last follow-up. The present case illustrates that regular surveillance and curative resection might achieve long-term survival in hepatic ASC, which has a poor prognosis.