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1.
Eur Neurol ; 83(1): 65-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32344417

RESUMO

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS: In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean: 58, median: 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS: This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32211343

RESUMO

Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.

3.
Cancer Biomark ; 26(3): 303-312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31322543

RESUMO

Glutamate dehydrogenase (GDH) is a key enzyme in glutaminolysis and can regulate allosteric functions. Immunohistochemical study found that GDH expressed in gastric cancer cell cytoplasm and membrane, and a few located in the nucleus, ranging from light yellow to tan to sepia. According to the analysis by Kaplan Meier survival curve and the Log-Rank test, the median survival of GDH high expression in patients was 51.7 months with 95% confidence intervals (CI) was 41.138-55.262. The expression level of GDH was significantly reduced after silencing GDH gene in gastric cancer cells and tissues. Further, after silencing GDH gene, gastric cancer cell migration and invasion ability were decreased significantly. Protein expression of. In addition, tumor growth was significantly reduced after silencing GDH gene. In vivo and in vitro experiments suggest that GDH can decrease gastric cancer cell migration and invasion, thus inhibiting tumor growth.

4.
J Med Microbiol ; 68(8): 1204-1210, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31184572

RESUMO

INTRODUCTION: In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection. AIM: We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM). METHODOLOGY: A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM. RESULTS: India ink staining and culture of the CSF were positive for Cryptococcus in 83.33 % (10/12) of the samples; 100 % (11/11) were positive via CrAg EIA. The mNGS results of the CSF identified DNA sequences corresponding to Cryptococcus in 75 % of samples (9/12). However, the DNA of both C. neoformans s.l. and C. gattii s.l. was detected concurrently in 33.33 % (4/12). CONCLUSION: mNGS is helpful for identifying Cryptococcus species. The application of mNGS, together with India ink staining, culture methods, and CrAg, may significantly improve the diagnostic precision in CM, thereby informing choice of appropriate antifungal treatment courses.


Assuntos
Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/microbiologia , Metagenômica , Técnicas de Diagnóstico Molecular/métodos , Adolescente , Adulto , Idoso , Coinfecção/diagnóstico , Cryptococcus gattii/isolamento & purificação , Cryptococcus neoformans/isolamento & purificação , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/normas , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Técnicas Microbiológicas , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Análise de Sequência de DNA
5.
Neurotox Res ; 35(1): 160-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30120712

RESUMO

Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.


Assuntos
Ansiedade/etiologia , Ansiedade/metabolismo , MicroRNAs/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Ansiedade/patologia , Corticosterona/metabolismo , Dendritos/metabolismo , Dendritos/patologia , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Receptores de Glutamato/metabolismo , Restrição Física , Estresse Psicológico/patologia
6.
Eur Neurol ; 80(5-6): 283-288, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30763937

RESUMO

BACKGROUND: There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. MATERIALS AND METHODS: We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. RESULTS: Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. CONCLUSIONS: NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections.


Assuntos
Viroses do Sistema Nervoso Central/diagnóstico , DNA Viral/análise , Infecções por Herpesviridae/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
7.
Mol Med Rep ; 15(2): 703-711, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28000860

RESUMO

The ß1­adrenergic receptor (AR) is the primary ß­AR subtype in the heart and is the target of metoprolol (Met), which is commonly used to treat angina and hypertension. Previous studies have revealed a positive correlation between the methylation levels of the adrenoreceptor ß1 gene (Adrb1) promoter in the myocardium with the antihypertensive activity of Met in spontaneously hypertensive rats (SHR), which affects ß1­AR expression in H9C2 cells. The aim of the present study was to investigate the effects of myocardial ß1­AR downregulation using short­hairpin RNA (shRNA) against Adrb1 on the antihypertensive activity of Met in SHR. Recombinant adeno­associated virus type 9 (rAAV9) vectors carrying Adrb1 shRNA (rAAV9­Adrb1) or a negative control sequence (rAAV9­NC) were generated and used to infect rat hearts via the pericardial cavity. The results of reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and western blotting analyses demonstrated that cardiac ß1­AR expression in the rAAV9­Adrb1 group was significantly downregulated when compared with the rAAV9­NC group (P<0.001, P<0.001 and P=0.032, respectively). In addition, a greater reduction in systolic blood pressure (SBP) was observed in the rAAV9­NC group compared with the rAAV9­Adrb1 group following Met treatment (P=0.035). Furthermore, downregulation of myocardial ß1­AR was associated with a significant decrease in SBP (P<0.001). In conclusion, these data suggest that suppression of ß1­AR expression in the myocardium reduces SBP and sensitivity to Met in SHR.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Regulação para Baixo , Metoprolol/farmacologia , Miocárdio/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Animais , Anti-Hipertensivos/uso terapêutico , Linhagem Celular , Dependovirus/genética , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células HEK293 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , Metoprolol/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Endogâmicos SHR , Receptores Adrenérgicos beta 1/química
8.
Basic Res Cardiol ; 111(4): 47, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27298141

RESUMO

In the past 10 years, several publications have highlighted the role of the regulator of G protein signalling (RGS) family in multiple diseases, including cardiovascular diseases. As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis. However, the role of RGS14 in cardiovascular diseases remains unclear. In the present study, we used a genetic approach to examine the role of RGS14 in pathological cardiac remodelling in vivo and in vitro. We observed that RGS14 was down-regulated in human failing hearts, murine hypertrophic hearts, and isolated hypertrophic cardiomyocytes. Moreover, the extent of aortic banding-induced cardiac hypertrophy and fibrosis was exacerbated in RGS14 knockout mice, whereas RGS14 transgenic mice exhibited a significantly alleviated response to pressure overload. Furthermore, research of the underlying mechanism revealed that the RGS14-dependent rescue of cardiac remodelling was attributed to the abrogation of mitogen-activated protein kinase (MEK)-extracellular signal-regulated protein kinase (ERK) 1/2 signalling. The results showed that constitutive activation of MEK1 nullified the cardiac protection in RGS14 transgenic mice, and inhibition of MEK-ERK1/2 by U0126 reversed RGS14 deletion-related hypertrophic aggravation. These results demonstrated that RGS14 attenuated the development of cardiac remodelling through MEK-ERK1/2 signalling. RGS14 exhibited great potential as a target for the treatment of pathological cardiac remodelling.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas RGS/metabolismo , Remodelação Ventricular/fisiologia , Animais , Western Blotting , Cardiomegalia/metabolismo , Imunofluorescência , Insuficiência Cardíaca/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
9.
J Neuroimmunol ; 295-296: 1-8, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27235341

RESUMO

Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse.


Assuntos
Síndrome de Creutzfeldt-Jakob/fisiopatologia , Poliendocrinopatias Autoimunes/diagnóstico , Idoso , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/imunologia , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Poliendocrinopatias Autoimunes/fisiopatologia , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(5): 645-8, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27222178

RESUMO

OBJECTIVE: To prepare a specific polyclonal antibody against full-length SUN5 for detecting the expression of SUN5 in human germ cells. METHODS: Bioinformatic methods were used to compare the full-length SUN5 and its variant SUN5ß, and a short peptide was designed based on the differential region to prepare SUN5 antibody. The prepared antibody was used to detect the expression of SUN5 in Ntera-2 cells and in human germ cells by Western blotting and immunofluorescence assay. RESULTS: The short peptide was correctly synthesized and SUN5 antibody was obtained and purified. Western blotting showed that the prepared antibody was capable of recognizing full-length SUN5 in Ntera-2 cells, and SUN5 expression was localized on the nuclear membrane and in the cytoplasm as shown by immunofluorescence assay. Using this antibody, we detected SUN5 expression in the spermatocytes, round spermatids and sperms in human germ cells. CONCLUSION: We successfully prepared SUN5-specific antibody. SUN5 is expressed in the spermatocytes, round spermatids and sperms in human germ cells, suggesting its important role in spermatogenesis.


Assuntos
Anticorpos/química , Proteínas/metabolismo , Espermátides/metabolismo , Espermatócitos/metabolismo , Espermatozoides/metabolismo , Western Blotting , Citoplasma/metabolismo , Imunofluorescência , Humanos , Masculino , Membrana Nuclear/metabolismo , Proteínas/imunologia , Espermatogênese
11.
Infect Dis (Lond) ; 47(10): 694-700, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26100526

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is a relatively common opportunistic infection in patients with human immunodeficiency virus (HIV) infection and can also occur in patients with no underlying disease. The aim of this study was to evaluate the clinical manifestations, laboratory findings, diagnosis and misdiagnosis, treatment, and prognosis of CM at a tertiary care hospital. METHODS: We performed a retrospective study of 55 patients at a tertiary care hospital from January 1, 1992 to December 31, 2013. All the patients had a definite diagnosis based on etiology. RESULTS: All 55 patients had a positive cerebrospinal fluid (CSF) India ink staining result. The predominant change observed on magnetic resonance imaging (MRI) was leptomeningeal liner enhancement, which is also called 'lumbriciform-enhancing.' Only 15 patients were first diagnosed with CM, indicating a misdiagnosis rate of 72.7%. At the follow-up end point, 8 patients were cured, 33 had improved, and 14 had died. The overall response rate was 74.5%. The voriconazole group had a response rate of 100%, which was significantly higher than the other two groups. CONCLUSIONS: Most CM patients in China were previously healthy without any potential risk factors. CM was easily misdiagnosed due to the lack of specificity of early clinical symptoms. Repeated CSF India ink staining should be performed to identify the pathogen. Voriconazole could be administered to the patients with CM, especially to patients who had a treatment failure with amphotericin B alone or accompanied by fluconazole.


Assuntos
Antifúngicos/uso terapêutico , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Voriconazol/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/líquido cefalorraquidiano , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Carbono , China , Cryptococcus neoformans/isolamento & purificação , Erros de Diagnóstico , Quimioterapia Combinada , Feminino , Fluconazol/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Voriconazol/administração & dosagem
12.
J Neurol ; 262(6): 1440-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25860342

RESUMO

The objective of this study is to investigate the hyperintense lesions on diffusion-weighted magnetic resonance imaging (DWI) and its clinical correlation in sporadic Creutzfeldt-Jakob disease (sCJD). Patients who suffered from sCJD and followed up at the Department of Neurology at the General Hospital of the People's Liberation Army during the period of June 1, 2007 to July 1, 2014 were reviewed. The location of the hyperintense lesions on DWI, apparent diffusion coefficient (ADC) values of the hyperintense lesions were correlated with symptoms and clinical course. A total of 58 sCJD patients and ten healthy controls were included. Hyperintense lesions on DWI were observed in all the patients. The patients with basal ganglia (BG) hyperintense lesions on DWI had shorter disease duration and higher incidence of myoclonus (92 versus 44 %) than those without BG hyperintense lesions. The patients with occipital cortex hyperintense lesions on DWI had shorter disease duration between symptom onset and akinetic mutism than those without these lesions. The lower of the BG ADC value the faster presence of akinetic mutism and the shorter disease duration the patients will have. The presence of BG and occipital cortex hyperintense lesions on DWI and BG ADC values is correlated with the clinical course and clinical symptoms.


Assuntos
Gânglios da Base/patologia , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Encefalopatia Espongiforme Bovina/diagnóstico , Encefalopatia Espongiforme Bovina/fisiopatologia , Estatística como Assunto , Adulto , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Neuropsychopharmacology ; 39(12): 2777-87, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24889368

RESUMO

Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure.


Assuntos
Ansiedade/fisiopatologia , Giro Denteado/fisiopatologia , Abrigo para Animais , Fator de Crescimento Insulin-Like II/metabolismo , Morfina/toxicidade , Entorpecentes/toxicidade , Animais , Ansiedade/etiologia , Ansiedade/patologia , Ansiedade/terapia , Western Blotting , Dendritos/patologia , Dendritos/fisiologia , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/patologia , Comportamento Exploratório/fisiologia , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Imuno-Histoquímica , Fator de Crescimento Insulin-Like II/genética , Lentivirus/genética , Masculino , Exposição Materna/efeitos adversos , Aprendizagem em Labirinto/fisiologia , Exposição Paterna/efeitos adversos , Ratos Sprague-Dawley
14.
PLoS One ; 8(3): e58442, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23516482

RESUMO

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57). Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11), and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%). The sensitivity of EEG was 79.6% (43/54). For DWI and PET examinations, the sensitivities were 94% (47/50) and 94.1% (16/17), respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the diagnosis of sCJD.


Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Adulto , Fatores Etários , Idoso , Encéfalo/patologia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
15.
Zhonghua Yi Xue Za Zhi ; 93(40): 3207-10, 2013 Oct 29.
Artigo em Chinês | MEDLINE | ID: mdl-24405542

RESUMO

OBJECTIVE: To explore the correlation between serum levels of Cystatin C and metabolic syndrome. METHODS: This study was randomly conducted in 506 persons, including 191 patients with metabolic syndrome (MS), 210 with metabolic disorder (MD) and 105 persons in normal control (NC) group. According to serum levels of Cys C, the clinical data were also divided into 3 groups of lower tertile (T1, n = 165), middle tertile (T2, n = 172) and upper tertile (T3, n = 169). Body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein (HDL), creatinine (Cr), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were measured and their mutual relations evaluated. RESULTS: Statistically significant differences (all P < 0.01) existed among T1, T2 and T3 groups in the mean values of BMI, waist circumference, WHR, FPG, LDL-C, TG, Cr, eGFR, MAU, SBP, DBP and PP. As tertile levels of Cys C increased, MS morbidity rates became all remarkably augmented (P < 0.01). The MS component scores had significant statistical differences among the patients of T1, T2 and T3 groups (P < 0.01). As the MS component scores increased, the level of Cys C rose in these patients. The higher MS marks were, the higher serum concentration of Cys C was in these patients. The plasma concentration of Cys C in MS patients was closely related with WC, LDL-C, FBG and blood pressure (all P < 0.05), not related with TG levels and negatively correlated with HDL-C levels (r = -0.352, P = 0.01). WC, Cys C, LDL-C, MAU and PP were significantly associated with MS. And the value of OR between Cys C and MS was 2.943 (95% CI 1.276-3.914). CONCLUSION: Cys C is significantly associated with MS. As MS scores rise, the level of Cys C increases.


Assuntos
Cistatina C/sangue , Síndrome Metabólica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Am J Med Sci ; 345(3): 200-10, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22652821

RESUMO

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, histiocytic proliferative disorder, the infrequent occurrence of which limits in-depth studies. Consequently, many characteristics of this disease remain unknown, restricting early diagnosis and proper treatment. METHODS: In this study, the literature was reviewed and a retrospective analysis of the medical records of 13 patients with RDD conducted to investigate the demographic data, clinical data, laboratory and imaging results, treatment, and prognosis of this disease. RESULTS: Of the 13 cases in our sample, 10 (77%) were purely extranodal RDD, 2 (15%) were both nodal and extranodal, and 1 (8%) was purely nodal. The locations of the 10 purely extranodal RDD lesions included the central nervous system (n = 6, 60%), nasal cavity and paranasal sinuses (n = 3, 30%), and the cutis (n = 1, 10%). The locations of the central nervous system-related RDD lesions included the cerebral subdura (n = 2, 29%), the sellar region (n = 3, 14%), the cerebral parenchyma (n = 1, 14%) and the spinal subdura (n = 1, 14%). Ten patients (77%) had stable conditions, 3 (23%) experienced recurrence, and 2 (15%) experienced recurrence and lesion metastasis. CONCLUSIONS: RDD is rare, requiring knowledge of its clinical manifestations for a rapid and correct diagnosis. In light of the possibility of recurrence and lesion metastasis, long-term follow-up is needed. Treatment is still controversial. Future efforts should be directed at investigating the etiology and postoperative treatment for relapsing cases or those with subresected lesions.


Assuntos
Histiocitose Sinusal/metabolismo , Histiocitose Sinusal/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/metabolismo , Cavidade Nasal/patologia , Seios Paranasais/metabolismo , Seios Paranasais/patologia , Prognóstico , Estudos Retrospectivos , Medula Espinal/metabolismo , Medula Espinal/patologia
17.
J Clin Neurosci ; 19(10): 1354-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22795494

RESUMO

18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG PET/CT) scanning may be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), as it may reveal lowered cellular glucose transport and metabolism in the cortex, cerebellum and basal ganglia. The aim of the present study was to compare the findings from PET/CT, MRI and electroencephalography (EEG) for patients with sCJD, to explore whether typical sites or reliable patterns of regional metabolic change could be found and to evaluate the results of diagnostic imaging in the light of clinical symptomatology. Five patients with biopsy-confirmed sCJD and nine with probable sCJD (aged 36-68 years) were evaluated using PET/CT, diffusion-weighted (DW)-MRI and EEG. In 13 of the 14 patients (92.86%), PET/CT imaging detected extra regions with abnormalities in addition to the hyperintense areas shown with DW-MRI. Two patients with no abnormal DW-MRI findings in the basal ganglia had bilateral extrapyramidal signs accompanied by basal ganglia hypometabolism on PET. Eight patients (57.14%) had decreased FDG uptake in the thalamic nuclei on PET scans; however, DW-MRI did not identify corresponding hyperintense changes in the thalamic nuclei. In 11 patients (78.57%), DW-MRI revealed more regions with abnormalities than EEG, and 10 patients (71.43%) had DW-MRI abnormalities in the thalamic nuclei and basal ganglia that EEG was unable to detect. There was a high level of correspondence among the PET/CT, DW-MRI and EEG results, with PET revealing more abnormal regions than the other imaging modalities. In the absence of neuropathological findings, FDG-PET could improve the accuracy of sCJD diagnosis when combined with DW-MRI and EEG, particularly for differentiating sCJD from paraneoplastic syndromes. Our results suggest that PET/CT is able to detect sCJD at an earlier stage and with greater sensitivity than DW-MRI.


Assuntos
Síndrome de Creutzfeldt-Jakob , Imagem de Difusão por Ressonância Magnética/métodos , Eletroencefalografia/métodos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
DNA Cell Biol ; 30(11): 875-82, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21711156

RESUMO

SUN domain-containing proteins belong to a novel protein family. To date, several members--SUN1, SUN2, SUN3, and SPAG4--have been identified as nuclear envelope (NE) proteins. In this study, we sought to characterize and define the potential function of SPAG4L, a newly identified SUN protein. Using bioinformatic analysis, we found that SPAG4L contained a conserved SUN domain in the C-terminal. Subcellular localization analysis indicated that the expression of green fluorescent protein-labeled full-length SPAG4L was localized to the NE and the endoplasmic reticulum (ER). Deletion analysis revealed that the transmembrane region and the coiled-coil domain, but not the SUN domain, were required for localization of SPAG4L to the NE and ER. Subsequently, we confirmed that the human testes expressed endogenous SPAG4L as a 43-kDa protein. Further studies revealed that mouse Spag4L colocalized with the NE marker Lamin B1 and the ER marker PDI in isolated mouse spermatocytes. In addition, the expression of Spag4L was observed in meiosis I and II stages, suggesting that Spag4L may be involved in NE reconstitution and nuclear migration occurring during the process of spermatocyte division. Together, the findings indicate that SPAG4L, a new NE protein, may play an important role in the meiotic stage of spermatogenesis.


Assuntos
Meiose , Proteínas de Membrana/metabolismo , Membrana Nuclear/metabolismo , Espermatogênese , Sequência de Aminoácidos , Animais , Biologia Computacional , Retículo Endoplasmático/metabolismo , Regulação da Expressão Gênica , Células HeLa , Humanos , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Transporte Proteico , Homologia de Sequência de Aminoácidos , Espermatócitos/citologia , Espermatócitos/metabolismo , Transfecção
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(10): 2233-6, 2241, 2010 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20965812

RESUMO

OBJECTIVE: To evaluate the impact of surface modification on the DNA-binding ability of nano-hydroxyapatite (nHA). METHODS: Chemical co-precipitation-hydrothermal synthesis was utilized to prepare the nHA particles, and polyethylenimine (PEI) was used for surface modification of the nHA. Transmission electron microscopic (TEM) observation and zeta potential detection of the nHA were carried out before and after surface modification. The abilities of the nanoparticles, at different pH values and different concentrations, for DNA-binding and DNA protection against nuclease digestion were assessed before and after surface modification by electrophoresis. RESULTS: TEM observation showed a short rod-like morphology of PEI-modified nHA with uniform particle size and good dispersion; the nHA without the modification tended to aggregate with poor dispersion. With a positive zeta potential, the PEI-modified nHA showed an obviously enhanced ability of DNA binding at different pH values and concentrations, with strong capacity to protect the DNA against Dnase I digestion. At the concentration of 250 µg/ml and a pH value of 7.0, the nHA-PEI showed an optimal efficiency of DNA-binding and DNA protection. CONCLUSION: nHA with surface modification by PEI can serve as an effective vector for DNA binding and transfer.


Assuntos
DNA/química , Durapatita/química , Vetores Genéticos , Nanopartículas/química , Motivos de Aminoácidos , Técnicas de Transferência de Genes , Polietilenoimina/química
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(10): 962-5, 2010 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20937229

RESUMO

AIM: to construction of eukaryotic expression vector of the human SOD1 (Cu/Zn superoxide dismutase, SOD1) and expression in HeLa cells. METHODS: the open reading frame (ORF) of SOD1 was amplified from human peripheral blood by RT-PCR. TA cloning strategy was used to insert the target fragments into pUCm-T vector. The recombinant plasmid was identified and noted as pUCm-T-SOD1. Then, SOD1 was subcloned into pTracer-CMV/Bsd, a eukaryotic expression vector. The plasmid of pTracer-CMV/Bsd-SOD1 was sequenced and was introduced into HeLa cells by Lipofectamine(TM); 2000. The expression of green fluorescence protein (GFP) was observed by the fluorescence microscope. The expression of SOD1 was detected by RT-PCR and Western blot after screening by blasticidin for 4 weeks. RESULTS: the eukaryotic expression plasmid pTracer-CMV/Bsd-SOD1 was successfully constructed. The GFP was observed in transfected cells by the fluorescence microscope. The expression of SOD1 was detected in transfected cells by RT-PCR and Western blot. CONCLUSION: the recombinant eukaryotic expression vector of pTracer-CMV/Bsd-SOD1 has been constructed successfully which could express GFP and SOD1, respectively, providing a tool for further gene therapy study.


Assuntos
Vetores Genéticos/genética , Superóxido Dismutase/metabolismo , Western Blotting , Regulação Enzimológica da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Microscopia de Fluorescência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/genética
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