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1.
J Am Heart Assoc ; 11(6): e024749, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35253443

RESUMO

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.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Nefropatias , Acidente Vascular Cerebral , Idoso , Albuminúria/complicações , Albuminúria/epidemiologia , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Feminino , Fibrinolíticos/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Nefropatias/complicações , Imageamento por Ressonância Magnética , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
2.
Acta Cytol ; 66(1): 55-60, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34644702

RESUMO

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.


Assuntos
Citodiagnóstico , Citodiagnóstico/métodos , Técnicas Citológicas , Fixadores , Humanos
3.
Radiol Case Rep ; 16(9): 2640-2645, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34345324

RESUMO

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.

4.
Intern Med ; 60(18): 3025-3029, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33776010

RESUMO

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.


Assuntos
Carcinoma , Dermatomiosite , Neoplasias Pulmonares , Idoso , Anticorpos Monoclonais Humanizados , Dermatomiosite/induzido quimicamente , Dermatomiosite/diagnóstico , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Masculino
5.
Oncol Lett ; 20(5): 210, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963616

RESUMO

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.

6.
Clin J Gastroenterol ; 13(6): 1273-1279, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32785892

RESUMO

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.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Adenoescamoso , Colangiocarcinoma , Colangite Esclerosante , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Adenoescamoso/complicações , Carcinoma Adenoescamoso/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/diagnóstico por imagem , Humanos , Fígado , Masculino , Recidiva Local de Neoplasia
7.
J Med Case Rep ; 14(1): 88, 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32620173

RESUMO

BACKGROUND: In recent years, immune checkpoint inhibitors have been widely used as a crucial therapy in malignant tumors. Immune checkpoint inhibitors can cause various autoimmune side effects called immune-related adverse events because they generate an exaggerated inflammatory response. Encephalitis associated with atezolizumab has rarely been reported as an immune-related adverse event. A case of encephalitis caused by treatment with atezolizumab is presented. CASE PRESENTATION: A 56-year-old Japanese man with lung cancer previously treated with surgery and chemotherapy was admitted with high fever, consciousness disorder, and motor aphasia. His first atezolizumab treatment was 17 days earlier. Admission brain magnetic resonance imaging with gadolinium enhancement showed no abnormalities. Cerebrospinal fluid showed cell count 20/l, protein 166 mg/dl, glucose 73 mg/dl, and interleukin 6 82.9 pg/ml (normal< 8.7 pg/ml). Atezolizumab-induced encephalitis was diagnosed. His symptoms improved the day after steroid pulse therapy was started. Following steroid pulse therapy, oral prednisolone 30 mg was started and tapered. The cerebrospinal fluid findings normalized on day 14. He was discharged on day 16 without neurological sequelae. CONCLUSION: In this case of encephalitis associated with atezolizumab, prompt steroid pulse therapy led to a successful response, and the outcome was good. The cerebrospinal fluid level of interleukin 6 reflected the severity of the encephalitis well. Clinicians should be aware of the possibility of encephalitis after initiation of immune checkpoint inhibitors.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Encefalite/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Encefalite/líquido cefalorraquidiano , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Interleucina-6/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade
8.
Org Lett ; 22(10): 4033-4037, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32365297

RESUMO

A nickel pincer complex bearing a ß-aminoketonato-based O,N,P-tridentate ligand (1a) has been employed for the highly Markovnikov-selective hydroboration of vinylarenes using bis(pinacolato)diboron. This reaction proceeds smoothly under mild reaction conditions and affords the corresponding Markovnikov products in good to high yield.

10.
Molecules ; 24(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234296

RESUMO

A cross-coupling reaction of allylic aryl ethers with arylmagnesium reagents was investigated using ß-aminoketonato- and ß-diketiminato-based pincer-type nickel(II) complexes as catalysts. An ß-aminoketonato nickel(II) complex bearing a diphenylphosphino group as a third donor effectively catalyzed the reaction to afford the target cross-coupled products, allylbenzene derivatives, in high yield. The regioselective reaction of a variety of substituted cinnamyl ethers proceeded to give the corresponding linear products. In contrast, α- and γ-alkyl substituted allylic ethers afforded a mixture of the linear and branched products. These results indicated that the coupling reaction proceeded via a π-allyl nickel intermediate.


Assuntos
Catálise , Éteres/química , Magnésio/química , Indicadores e Reagentes/química , Estrutura Molecular , Níquel/química , Estereoisomerismo
11.
J Stroke Cerebrovasc Dis ; 28(6): 1691-1702, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30898444

RESUMO

BACKGROUND: Data on the clinical and radiological characteristics of intracranial artery dissection (IAD) have remained limited. Our purpose was to reveal the clinical and radiological characteristics of IAD according to diagnostic criteria for IAD as recently reported by a group of international experts. METHODS: Patients were retrospectively enrolled using a prospective single-center stroke registry between 2011 and 2016. Baseline characteristics and radiological findings including conventional magnetic resonance imaging (MRI) sequences, magnetic resonance angiography (MRA), high-resolution 3-dimensional T1-weighted imaging (HR-3D-T1WI), and digital subtraction angiography were reviewed. We performed statistical comparisons to determine which findings from which modalities are useful. RESULTS: We identified 118 patients with suspected artery dissection, with 64 patients (median age, 51 [interquartile range, 45-56) years; 16 women) finally meeting the criteria for definite (n = 47), probable (n = 15), or possible (n = 2) idiopathic IAD. Ischemic stroke alone was found in 31 patients (48%) on admission. There were 36 patients (56%) suffering from hypertension and 39 (61%) with smoking history. The vertebral artery alone was the most affected in 42 patients (66%). Intramural hematoma (IMH) was more frequently detected on HR-3D-T1WI than on conventional MRI/MRA (odds ratio, 4.72; 95% confidence interval, 1.71-13.00). In 54 patients (84%), the modified Rankin Scale score after 3 months was 0-1. CONCLUSIONS: Male dominance and age at IAD onset were similar to previous studies, and more than half had hypertension and smoking history. We confirmed that HR-3D-T1WI is useful for detecting IMH in the diagnostic criteria.


Assuntos
Angiografia Digital , Dissecção Aórtica/diagnóstico por imagem , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia por Ressonância Magnética , Idade de Início , Dissecção Aórtica/etiologia , Avaliação da Deficiência , Feminino , Humanos , Hipertensão/complicações , Aneurisma Intracraniano/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos
12.
Dalton Trans ; 47(24): 8003-8012, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29869657

RESUMO

In this work, three different types of acetylacetonato-based pincer-type nickel(ii) complexes (2) were prepared. Complex 2a possessed the tridentate ONN ligand, which was constructed by the condensation reaction of acetylacetone with N,N-diethylethylenediamine. Complex 2b contained the PPh2 donor group in contrast to the NEt2 group in 2a, i.e., an ONP ligand framework. Complex 2c was composed of the NNN ligand, which was prepared by the reaction of 4-((2,4,6-trimethylphenyl)amino)pent-3-en-2-one with N,N-diethylethylenediamine. In addition to X-ray diffraction analysis, these complexes were characterized spectroscopically. Their catalytic activity for a cross-coupling reaction of aryl halides with aryl Grignard reagents was also evaluated. Among these complexes, 2b acted as an effective catalyst for the cross-coupling reaction using aryl chlorides as electrophiles. The electronic properties of these Ni(ii) complexes were investigated by cyclic voltammetry and density functional theory calculations.

13.
Dig Dis ; 35(6): 574-582, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29040990

RESUMO

BACKGROUND: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. METHODS: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. RESULTS: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. CONCLUSIONS: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Gadolínio DTPA/química , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Meios de Contraste/química , Feminino , Hepatectomia , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco
14.
Dig Dis ; 34(6): 679-686, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27750237

RESUMO

OBJECTIVE: We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). METHODS: Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. RESULTS: Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. CONCLUSIONS: The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Hepatocelular/patologia , Feminino , Compostos Férricos , Humanos , Ferro , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Óxidos , Cuidados Pré-Operatórios , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Intern Med ; 55(14): 1911-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27432102

RESUMO

A 58-year-old woman with a 1-month history of right hand clumsiness and speaking difficulty was admitted to our hospital. A neurological examination revealed sensory aphasia and right hemiparesis. Her laboratory tests showed elevated serum levels of IgG and IgG4, pancytopenia, and liver dysfunction. The results of the imaging studies of her abdomen were compatible with sclerosing cholangitis. Brain MRI showed extensive signal abnormalities in the left hemisphere on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, extending from left internal capsule to the cerebral peduncle with an irregularly enhancing lesion in the left parietal lobe. A brain biopsy revealed lymphocyte and plasma cell infiltration and reactive gliosis. Most of the plasma cells were IgG positive; however, IgG4-positive plasma cells were sparsely observed. After the initiation of betamethasone treatment, her symptoms and the brain MRI abnormalities showed significant improvement. The brain biopsy results did not meet the current criteria of IgG4-related disease. This is the first reported case of a tumefactive lesion of the brain parenchyma with serum IgG4 elevation, which was responsive to steroid treatment. The accumulation of a greater number of reports on the pathological investigation of cases of possible IgG4-related disease may help to elucidate the exact role of IgG4 in IgG4-related disorders.


Assuntos
Encefalopatias/complicações , Granuloma de Células Plasmáticas/complicações , Hipergamaglobulinemia/complicações , Imunoglobulina G/sangue , Biópsia , Encefalopatias/diagnóstico , Colangite Esclerosante/diagnóstico por imagem , Feminino , Granuloma de Células Plasmáticas/diagnóstico , Humanos , Hepatopatias/complicações , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
16.
Sci Rep ; 5: 16802, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26582591

RESUMO

(18)F-fluoromisonidazole (FMISO) has been widely used as a hypoxia imaging probe for diagnostic positron emission tomography (PET). FMISO is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of its nitro group. However, its detailed accumulation mechanism remains unknown. Therefore, we investigated the chemical forms of FMISO and their distributions in tumours using imaging mass spectrometry (IMS), which visualises spatial distribution of chemical compositions based on molecular masses in tissue sections. Our radiochemical analysis revealed that most of the radioactivity in tumours existed as low-molecular-weight compounds with unknown chemical formulas, unlike observations made with conventional views, suggesting that the radioactivity distribution primarily reflected that of these unknown substances. The IMS analysis indicated that FMISO and its reductive metabolites were nonspecifically distributed in the tumour in patterns not corresponding to the radioactivity distribution. Our IMS search found an unknown low-molecular-weight metabolite whose distribution pattern corresponded to that of both the radioactivity and the hypoxia marker pimonidazole. This metabolite was identified as the glutathione conjugate of amino-FMISO. We showed that the glutathione conjugate of amino-FMISO is involved in FMISO accumulation in hypoxic tumour tissues, in addition to the conventional mechanism of FMISO covalent binding to macromolecules.


Assuntos
Diagnóstico por Imagem/métodos , Hipóxia/diagnóstico por imagem , Espectrometria de Massas/métodos , Metaboloma , Misonidazol/análogos & derivados , Sondas Moleculares/metabolismo , Animais , Masculino , Metabolômica , Camundongos Endogâmicos BALB C , Camundongos Nus , Misonidazol/metabolismo , Peso Molecular , Neoplasias/diagnóstico por imagem , Cintilografia , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Distribuição Tecidual
17.
J Pharm Sci ; 104(3): 955-961, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28756848

RESUMO

In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8±4.0% and 64.4%, fexofenadine: 6.5±0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies.

18.
J Pharm Sci ; 104(3): 955-61, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25452230

RESUMO

In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8 ± 4.0% and 64.4%, fexofenadine: 6.5 ± 0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies.


Assuntos
Antipirina/farmacocinética , Coleta de Amostras Sanguíneas/métodos , Monitoramento de Medicamentos/métodos , Ibuprofeno/farmacocinética , Pravastatina/farmacocinética , Cauda/irrigação sanguínea , Terfenadina/análogos & derivados , Administração Intravenosa , Administração Oral , Animais , Antipirina/administração & dosagem , Antipirina/sangue , Disponibilidade Biológica , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Interações Medicamentosas , Ibuprofeno/administração & dosagem , Ibuprofeno/sangue , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/metabolismo , Pravastatina/administração & dosagem , Pravastatina/sangue , Reprodutibilidade dos Testes , Rifampina/administração & dosagem , Terfenadina/administração & dosagem , Terfenadina/sangue , Terfenadina/farmacocinética , Triazóis/administração & dosagem , Veias
19.
J Am Chem Soc ; 135(22): 8141-4, 2013 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23692548

RESUMO

Mechanistic proposals for nickel-catalyzed coupling reactions often invoke five-coordinate alkyl- or aryl-bound Ni(II) and/or high-valent nickel(III) species, but because of their reactive nature, they have been difficult to study and fingerprint. In this work, we invoked the stabilizing properties of fluoroalkyl ligands to access such nickel species bearing ligands that are commonplace in organic coupling reactions. We show that five-coordinate Ni(II) complexes containing nickel-carbon bonds can readily be prepared given the appropriate precursor, and we also present evidence for the formation of Ni(III) species upon chemical and electrochemical oxidation of the five-coordinate complexes.

20.
J Neurol Sci ; 325(1-2): 156-9, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23235139

RESUMO

A 69-year-old man with rapidly evolving vertigo and ataxia was admitted to our hospital. He was presented with a dysarthric speech and chaotic eye movements, identified as opsoclonus. Neurological examination revealed limb and truncal ataxias and an inability to stand unless fully assisted. A chest CT scan revealed a mass at the anterior mediastinum, which suggested paraneoplastic neurological syndrome (PNS). However, an extensive search for anti-neuronal antibodies linked to cerebellar ataxia failed to find any autoantibodies, including cell surface autoantibodies. Subsequently, a total surgical removal of the thymic tumor was performed, leading to marked improvements in his signs and symptoms. The pathological findings by conventional and immunohistochemical examinations confirmed a squamous cell carcinoma of the thymus. Three months after onset his signs and symptoms improved and he was able to walk without support. In contrast to thymomas, PNS is extremely rare in patients with thymic carcinoma. Previous reports have shown that neurological symptoms, similar to opsoclonus or cerebellar ataxia, deteriorated in cases of thymic carcinoma that could not be controlled. The present report indicates that early diagnosis and total removal of the rare neoplasm may increase the possibility of neurological recovery.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Ataxia Cerebelar/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Neoplasias do Timo/diagnóstico , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/cirurgia , Ataxia Cerebelar/etiologia , Humanos , Masculino , Transtornos da Motilidade Ocular/etiologia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia
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