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1.
Comput Inform Nurs ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38453422

ABSTRACT

The nursing charge system for inpatient accounting has been utilized in healthcare institutions for years. However, the level of its effectiveness in meeting the needs of nursing services, including further development, has not been systematically evaluated. A cross-sectional study based in Delone and McLean's information system success model was applied to explore the level of effective nursing charge system usage across the five dimensions of system quality, information quality, service quality, user satisfaction, and net benefits. We conducted a survey of the inpatient units of a medical center in Taiwan from June 23, 2021, to July 23, 2021. A total of 214 valid questionnaires were collected. Using a 5-point Likert scale, the dimension with the highest score was information quality (3.71), followed by service quality (3.37), user satisfaction (3.36), net benefits (3.31), and system quality (3.23). Older nurses (r = -0.176) and those with more clinical experience (r = -0.151) viewed the nursing charge system as having less information quality. The comfort level with using the computer was positively associated with system quality (r = 0.396), information quality (r = 0.378), service quality (r = 0.275), user satisfaction (r = 0.417), and net benefits (r = 0.355). The opinions of nurses are vital. User feedback and advice should be investigated regularly to achieve system optimization.

2.
Cell Death Dis ; 13(2): 123, 2022 02 08.
Article in English | MEDLINE | ID: mdl-35136023

ABSTRACT

Low testosterone level is an independent predictor of osteoporotic fracture in elderly men as well as increased fracture risk in men undergoing androgen deprivation. Androgens and androgen receptor (AR) actions are essential for bone development and homeostasis but their linkage to fracture repair remains unclear. Here we found that AR is highly expressed in the periosteum cells and is co-localized with a mesenchymal progenitor cell marker, paired-related homeobox protein 1 (Prrx1), during bone fracture repair. Mice lacking the AR gene in the periosteum expressing Prrx1-cre (AR-/Y;Prrx1::Cre) but not in the chondrocytes (AR-/Y;Col-2::Cre) exhibits reduced callus size and new bone volume. Gene expression data analysis revealed that the expression of several collagens, integrins and cell adhesion molecules were downregulated in periosteum-derived progenitor cells (PDCs) from AR-/Y;Prrx1::Cre mice. Mechanistically, androgens-AR signaling activates the AR/ARA55/FAK complex and induces the collagen-integrin α2ß1 gene expression that is required for promoting the AR-mediated PDCs migration. Using mouse cortical-defect and femoral graft transplantation models, we proved that elimination of AR in periosteum of host mice impairs fracture healing, regardless of AR existence of transplanted donor graft. While testosterone implanted scaffolds failed to complete callus bridging across the fracture gap in AR-/Y;Prrx1::Cre mice, cell-based transplantation using DPCs re-expressing AR could lead to rescue bone repair. In conclusion, targeting androgen/AR axis in the periosteum may provide a novel therapy approach to improve fracture healing.


Subject(s)
Fractures, Bone , Receptors, Androgen , Androgen Antagonists/pharmacology , Androgens/pharmacology , Animals , Fractures, Bone/therapy , Homeodomain Proteins/genetics , Humans , Male , Mice , Periosteum/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Testosterone
3.
Oncogene ; 38(41): 6723-6736, 2019 10.
Article in English | MEDLINE | ID: mdl-31399647

ABSTRACT

ZNF322A is an oncogenic zinc-finger transcription factor. Our published results show that ZNF322A positively regulates transcription of alpha-adducin (ADD1) and cyclin D1 (CCND1) to promote tumorgenicity of lung cancer. However, the upstream regulatory mechanisms of ZNF322A protein function remain elusive. Here, we demonstrate that AKT could phosphorylate ZNF322A by in vitro kinase assay and cell-based mass spectrometry analysis. Overexpression of AKT promoted ZNF322A protein stability and transcriptional activity, whereas these effects were inhibited by knockdown of AKT or treating with AKT inhibitor. We studied AKT-mediated phosphorylation sites, viz. Thr-150, Ser-224, Thr-234, and Thr-262. ZNF322A phosphorylation at Thr-262 by AKT promoted ZNF322A protein stability thus increased ADD1 promoter activity. Interestingly, phosphorylation at Thr-150, Ser-224, and Thr-234 enhanced transcription activity without affecting protein stability of ZNF322A. Chromatin immunoprecipitation and DNA affinity precipitation assays showed that ZNF322A phosphorylation defective mutants Thr-150A, Ser-224A, and Thr-234A attenuated chromatin binding and DNA binding affinity to ADD1 and CCND1 promoters compared with wild-type ZNF322A. Furthermore, AKT-mediated Thr-150, Ser-224, Thr-234, and Thr-262 phosphorylation promoted lung cancer cell growth and metastasis in vitro and in vivo. Clinically, expression of phosphorylated ZNF322A (p-ZNF) correlated with actively phosphorylated AKT (p-AKT) in tumor specimens from 150 lung cancer patients. Multivariate Cox regression analysis indicated that combined p-AKT and p-ZNF expression profile was an independent factor to predict the clinical outcome in lung cancer patients. Our results reveal a new mechanism of AKT signaling in promoting ZNF322A protein stability and transcriptional activity in lung cancer cell, xenograft, and clinical models.


Subject(s)
Lung Neoplasms/metabolism , Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factors/metabolism , Transcription, Genetic , Cell Line, Tumor , Cell Proliferation , Epidermal Growth Factor/metabolism , Humans , Lung Neoplasms/pathology , Neoplasm Metastasis , Phosphorylation , Prognosis , Promoter Regions, Genetic , Protein Stability , Signal Transduction
4.
FEBS J ; 283(5): 899-911, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26744129

ABSTRACT

The virion host shutoff protein (vhs), encoded by the gene UL41, has RNase activity and is the key regulator of the early host shutoff response induced by type 1 herpes simplex virus. Despite low amino acid similarity, the vhs protein of the swine herpesvirus, pseudorabies virus (PrV), also exhibits RNase activity. However, the mechanism underlying the action of vhs remains undefined. Here, we report that the RNA degradation profile of PrV vhs is similar, but not identical, to that of type 1 herpes simplex virus vhs. Notably, the presence of a cap structure enhances both the degradation rate and the preferential targeting of the vhs protein towards the 3'-end of the encephalomyocarditis virus internal ribosome entry site (IRES). Furthermore, type 1 herpes simplex virus vhs produces a simple degradation pattern, but PrV vhs gives rise to multiple intermediates. The results of northern blotting using probes recognizing various regions of the RNA substrate found that PrV vhs also cleaves downstream of the IRES region and this vhs protein overall shows 5' to 3' RNase activity. Moreover, addition of the translation initiation factors eIF4H and eIF4B significantly increased the RNase activity of recombinant PrV vhs against capped RNA. Nonetheless, these proteins did not fully reconstitute the IRES-directed targeting pattern observed for vhs translated in a rabbit reticular lysate system. The interaction between PrV vhs and eIF4H/eIF4B implies that the translation initiation machinery within the cell is able to stimulate the nuclease activity of PrV vhs. However, this process remains inefficient in terms of the IRES-targeting pattern.


Subject(s)
Herpesvirus 1, Suid/chemistry , Internal Ribosome Entry Sites , RNA, Viral/chemistry , Ribonucleases/metabolism , Viral Proteins/metabolism , Virion/chemistry , Animals , Base Sequence , Eukaryotic Initiation Factors/metabolism , Gene Deletion , HEK293 Cells , Humans , Molecular Sequence Data , Protein Biosynthesis , Rabbits , Recombinant Proteins/chemistry , Transcription, Genetic
5.
Vet Res ; 46: 141, 2015 Dec 24.
Article in English | MEDLINE | ID: mdl-26704628

ABSTRACT

Pseudorabies virus (PrV) belongs to the α-herpesvirinae of which human simplex virus (HSV) is the prototype virus. One of the hallmarks of HSV infection is shutoff of protein synthesis that is mediated by various viral proteins including vhs (virion host shutoff), which is encoded by the UL41 gene. However, the function of PrV vhs is poorly understood. Due to the low sequence similarity (39.3%) between the HSV and PrV UL41 proteins, vhs might not share the same biochemistry characteristics. The purpose of this study was to characterize the nuclease activity of the PrV vhs protein with respect to substrate specificity, its requirements in terms of cofactors, and the protein regions, as well as key amino acids, which contribute to vhs activity. Our results indicated that, similar to HSV vhs, PrV vhs is able to degrade ssRNA and mRNA. However, PrV vhs also targeted rRNA for degradation, which is novel compared to the HSV-1 vhs. Activity assays indicated that Mg(2+) alone enhances RNA degradation mediated by PrV vhs, while K(+) and ATP are not sufficient to induce activity. Finally, we demonstrated that each of the four highly conserved functional boxes of PrV vhs contributes to RNA degradation and that, in particular, residues 152, 169, 171, 172, 173 343, 345, 352 and 356, which are conserved among α-herpesviruses, are key amino acids needed for PrV vhs ribonuclease activity.


Subject(s)
Herpesvirus 1, Suid/genetics , Pseudorabies/genetics , RNA, Messenger/genetics , RNA, Ribosomal/genetics , RNA, Small Interfering/genetics , Viral Proteins/genetics , Animals , HEK293 Cells , Herpesvirus 1, Suid/metabolism , Humans , RNA, Messenger/metabolism , RNA, Ribosomal/metabolism , RNA, Small Interfering/metabolism , Viral Proteins/metabolism
6.
J Occup Rehabil ; 25(4): 717-24, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25894722

ABSTRACT

PURPOSE: Carpal tunnel syndrome (CTS) is one of the most common hand problems and a major cause of work disability. The purpose of this study was to use confirmatory factor analysis (CFA) to assess the factor structure of the Boston Carpal Tunnel Questionnaire (BCTQ) in patients with CTS. METHODS: One hundred and twenty-three patients with CTS were recruited from two hospitals. Each patient completed the functional status scale and the symptom severity scale of the BCTQ. CFA was used to assess the model fit between the data and pre-established theoretical measurement models. RESULTS: CFA showed that all three-factor models were better than the original two-factor model. Among the three-factor models, the simplified model, with 11 items assessing daytime pain, nocturnal numbness/tingling, and hand function was the best, for the model fit the data better than did the other models. Specifically, the Comparative Indices were larger than 0.95 (Tucker-Lewis Index and Comparative Fit Index values), and the Absolute Fit Indices and information-theoretic measures were the smallest. Moreover, all factor loadings were significant and high in magnitude (ranging from 0.66 to 0.99), the composite reliabilities exceeded 0.60 (ranging from 0.78 to 0.94), and the average variance extracted exceeded 0.50 (ranging from 0.61 to 0.89). CONCLUSION: The simplified model showed the highest reliability and validity, and the factor structure was the simplest/clearest one. The simplified model is recommended for clinical use due to its convenience and precision for assessing the problems of patients with CTS.


Subject(s)
Carpal Tunnel Syndrome/complications , Models, Statistical , Surveys and Questionnaires , Symptom Assessment/methods , Adult , Aged , Aged, 80 and over , Carpal Tunnel Syndrome/physiopathology , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Severity of Illness Index
7.
J Virol ; 89(9): 4966-79, 2015 May.
Article in English | MEDLINE | ID: mdl-25694596

ABSTRACT

UNLABELLED: Orf virus (ORFV) OV20.0L is an ortholog of vaccinia virus (VACV) gene E3L. The function of VACV E3 protein as a virulence factor is well studied, but OV20.0 has received less attention. Here we show that like VACV E3L, OV20.0L encodes two proteins, a full-length protein and a shorter form (sh20). The shorter sh20 is an N-terminally truncated OV20.0 isoform generated when a downstream AUG codon is used for initiating translation. These isoforms differed in cellular localization, with full-length OV20.0 and sh20 found throughout the cell and predominantly in the cytoplasm, respectively. Nonetheless, both OV20.0 isoforms were able to bind double-stranded RNA (dsRNA)-activated protein kinase (PKR) and dsRNA. Moreover, both isoforms strongly inhibited PKR activation as shown by decreased phosphorylation of the translation initiation factor eIF2α subunit and protection of Sindbis virus infection against the activity of interferon (IFN). In spite of this apparent conservation of function in vitro, a recombinant ORFV that was able to express only the sh20 isoform was attenuated in a mouse model. IMPORTANCE: The OV20.0 protein of orf virus (ORFV) has two isoforms and contributes to virulence, but the roles of the two forms are not known. This study shows that the shorter isoform (sh20) arises due to use of a downstream initiation codon and is amino-terminally truncated. The sh20 form also differs in expression kinetics and cellular localization from full-length OV20.0. Similar to the full-length isoform, sh20 is able to bind dsRNA and PKR, inactivate PKR, and thus act as an antagonist of the interferon response in vitro. In vivo, however, wild-type OV20.0 could not be replaced with sh20 alone without a loss of virulence, suggesting that the functions of the isoforms are not simply redundant.


Subject(s)
DNA/metabolism , Orf virus/physiology , Protein Isoforms/metabolism , Viral Proteins/metabolism , eIF-2 Kinase/antagonists & inhibitors , eIF-2 Kinase/metabolism , Amino Acid Sequence , Animals , Cell Line , Disease Models, Animal , Ecthyma, Contagious/pathology , Ecthyma, Contagious/virology , Eukaryotic Initiation Factor-2/metabolism , Humans , Mice, Inbred BALB C , Molecular Sequence Data , Phosphorylation , Protein Binding , Protein Processing, Post-Translational , RNA-Binding Proteins/genetics , Sequence Homology, Amino Acid , Viral Proteins/genetics
8.
J Occup Rehabil ; 24(1): 139-45, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23546645

ABSTRACT

PURPOSE: Carpal tunnel syndrome (CTS) is a common diagnosis occurring in the workplace when people experience hand or wrist symptoms and difficulty performing activities. This study aimed to investigate the psychometric properties of the Chinese version of the Boston Carpal Tunnel Questionnaire (BCTQ) used to evaluate patients with CTS. METHODS: A convenience sample of patients with CTS was recruited from two hospitals. The Symptom Severity Scale (SSS) and Functional Status Scale (FSS) of the BCTQ were used to assess symptoms and functional status. Test-retest reliability within 1 week was evaluated (n = 51). Construct validity was assessed by examining the relationship between the BCTQ and other well known measures (n = 99). Responsiveness of the scale was examined pre- and post-operatively for patients undergoing carpal tunnel surgery (n = 23). RESULTS: High reliability was demonstrated through intraclass correlation coefficients of 0.81 and 0.83 for SSS and FSS, respectively. The minimal detectable change was 0.86 and 0.75 for SSS and FSS, respectively. Convergent validity was supported by high correlation of both scales with Disability of the Arm, Shoulder and Hand (|rho| = 0.63, 0.75 for SSS and FSS), and moderate to high correlation with the subscales of the Short-Form 36 for SSS(|rho| = 0.72 for Body Pain) and FSS (|rho| = 0.48 for Physical Function). Responsiveness was confirmed by moderate to high standardized response means for SSS (1.03) and FSS (0.62). CONCLUSION: The Chinese BCTQ is a reliable, valid and responsive disease-specific measure for assessment of symptoms and functional status in patients with CTS.


Subject(s)
Carpal Tunnel Syndrome/diagnosis , Disability Evaluation , Psychometrics/instrumentation , Sickness Impact Profile , Surveys and Questionnaires/standards , Adult , Aged , Aged, 80 and over , Carpal Tunnel Syndrome/physiopathology , China , Female , Hand/physiopathology , Humans , Male , Middle Aged , Pain Measurement , Psychometrics/statistics & numerical data , Reproducibility of Results , Severity of Illness Index
9.
Zhonghua Yi Xue Za Zhi ; 93(25): 1962-4, 2013 Jul 02.
Article in Chinese | MEDLINE | ID: mdl-24169244

ABSTRACT

OBJECTIVE: To analyze the results of detection on respiratory virus of influenza-like illness ( ILI ) in Beijing from June 2010 to February 2012 and understand the virus spectrum of adult influenza-like fever. METHODS: A total of 502 swabs were collected and 279 throat swabs tested for 12 respiratory viruses with multiplex reverse transcription-polymerase chain reaction (RT-PCR). And 413 swabs were tested for pH1N1 by virus isolation influenza viruses. And the data were statistically analyzed. RESULTS: One or two viruses were detected in 26.9% (75/279) of the samples. Influenza A virus (FLU-A) accounted for 85.3% of positive samples and 22.9% (64/279) of ILI tested. The positive rate of other viruses was less than 3.0 %. The positive rates among the following subtypes were: 2.7% (11/413) for pH1N1, 2.4% (10/413) for H3 and 6.5% (27/413) for FLU-B. FLU-A was the predominant virus during the 2010-2011 influenza season and the positive rate peaked in January 2011 in Beijing and north China. FLU-B was the primary virus during the 2011-2012 influenza season and the positive rate peaked in January and February 2012. There was a significant reduction in the incidence of ILI in 2010 and 2011 when compared with 2009. During the 2009-2012 influenza seasons, the incidence peaked in December 2009, January 2011 and January and February 2012 in Beijing. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks. Influenza virus was the predominant virus of adult influenza-like fever cases after the pandemic period of influenza A (H1N1) 2009 and the positive rate peaked in January and February during the 2009-2012 influenza seasons.


Subject(s)
Fever/virology , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/virology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Humans , Middle Aged , Young Adult
10.
Zhonghua Yi Xue Za Zhi ; 93(26): 2043-7, 2013 Jul 09.
Article in Chinese | MEDLINE | ID: mdl-24169282

ABSTRACT

OBJECTIVE: To explore the etiologic characteristics of adult patients with community-acquired pneumonia (CAP) in Beijing. METHODS: A multicenter cohort of 510 adult CAP patients were enrolled from Beijing during the period of November 2010 to May 2012. Multiplex polymerase chain reaction (PCR), real-time fluorescence quantitative PCR and legionella urinary antigen were used to detect common respiratory viruses, Mycoplasma pneumoniae and legionella respectively. Bacteria were detected by sputum culture, blood culture and Streptococcus pneumoniae urinary antigen. Statistical analyses were performed for the etiologic characteristics and seasonal distribution of detected pathogens. RESULTS: Pathogens were detected in 240/500 (47.1%) study patients. The mixed infection of different pathogens was present in 42 cases (8.2%), viruses in 164 (32.2%), Mycoplasma pneumoniae in 91 (17.8%), bacteria in 26 (5.1%) and Legionella in 3 (0.6%). Among 164 patients infected with viruses, 194 viral strains were detected. Influenza virus represented the greatest proportion with 105 (54.1%) in viral infections. Between November 2010 to October 2011, Influenza A infections increased gradually in November 2010, peaked in February 2011 and declined by March 2011 in China. Mycoplasma pneumoniae was predominant in winter and spring. CONCLUSIONS: There is a high detection rate of virus and Mycoplasma pneumoniae in adult CAP patients in Beijing. And more consideration should be given to influenza virus and Mycoplasma pneumoniae infections in winter and early spring.


Subject(s)
Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Female , Humans , Male , Middle Aged , Mycoplasma pneumoniae/isolation & purification , Orthomyxoviridae/isolation & purification , Pneumonia/microbiology , Pneumonia/virology , Young Adult
11.
BMC Infect Dis ; 13: 309, 2013 Jul 09.
Article in English | MEDLINE | ID: mdl-23834931

ABSTRACT

BACKGROUND: Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. METHODS: A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. RESULTS: Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). CONCLUSIONS: Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.


Subject(s)
Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Adolescent , Adult , Analysis of Variance , Bacteria/classification , Bacteria/isolation & purification , China/epidemiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Female , Humans , Male , Middle Aged , Models, Statistical , Outpatients , Pneumonia/diagnosis , Pneumonia/microbiology , Pneumonia/virology , ROC Curve , Viruses/classification , Viruses/isolation & purification
13.
Clin Cardiol ; 33(6): E81-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20552613

ABSTRACT

BACKGROUND: Thrombotic, rather than hemorrhagic, events represent a major complication of hypertension. This study aims to explore the mechanism of the hypercoagulative state in hypertension and to assess its clinical significance. HYPOTHESIS: The hypercoagulative state and even the prothrombotic state exists in patients with hypertension. This may be attributed to an impairment of the endothelium. METHODS: A total of 81 patients suffering from essential hypertension were classified into 3 groups (grade 1: n = 27; grade 2: n = 36; grade 3: n = 18) and an additional 28 nonhypertensive patients were used as the control group. This study determined the changes of platelet activation marker P-selectin (CD62P), plasma fibrinogen, plasminogen activitor inhibitor-1 (PAI-1), and endothelium function. RESULTS: The percentage of CD62P+ platelets and the concentration of plasma fibrinogen and PAI-1 in the hypertension group was significantly higher than those in the control group. These increments coincided with the elevation of blood pressure. A significant difference was found between any of the 2 hypertension subgroups in the percentages of CD62P+ platelets (P < 0.001) and the concentration of PAI-I (P < 0.05). No difference was noted between the hypertension grade 1 and 2 groups in the concentration of plasma fibrinogen (P = 0.079); however, a significant difference was found between any of the other 2 subgroups (P < 0.001). Flow-mediated dilation (FMD) in the hypertension group was significantly lower than that in the control group. CONCLUSIONS: The hypercoagulative state exists in patients with hypertension and this state was more obvious with the elevation of blood pressure and coincided with an impairment in the degree of endothelium-dependent vasodilation.


Subject(s)
Blood Coagulation , Hypertension/complications , Thrombophilia/etiology , Thrombosis/etiology , Aged , Biomarkers/blood , Blood Pressure , Case-Control Studies , Chi-Square Distribution , China , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Fibrinogen/metabolism , Humans , Hypertension/blood , Hypertension/physiopathology , Male , Middle Aged , P-Selectin/blood , Plasminogen Activator Inhibitor 1/blood , Platelet Activation , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/physiopathology , Thrombosis/blood , Thrombosis/physiopathology , Vasodilation
14.
J Neurol ; 256(2): 249-55, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19242647

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan. METHODS: Mutational analysis of NOTCH3 exons 2 to 23 by direct nucleotide sequencing was performed in patients with clinically suspected CADASIL. MRI findings were retrospectively evaluated and scored using a modified Schelten's scale. RESULTS: Nine different point mutations of NOTCH3 were identified in 21 unrelated patients. Intriguingly, 47.6 % were in exon 11, and 19 % in each of exon 4 and 18. R544C was very common and present in all patients with a mutation in exon 11. Many patients with NOTCH3 R544C share the same haplotype linked to the mutation using markers D19S929 and D19S411, which flank the NOTCH3. The sensitivity of T2-weighted MRI detecting anterior temporal abnormality was only 42.9 %. Furthermore, the neuroimaging evidence of intracerebral hemorrhage (ICH) was present in 23.8 % of the 21 patients. CONCLUSIONS: A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.


Subject(s)
Brain/pathology , CADASIL/genetics , CADASIL/pathology , Genetic Predisposition to Disease/genetics , Mutation/genetics , Receptors, Notch/genetics , Adult , Aged , Asian People/ethnology , Asian People/genetics , Brain/metabolism , Brain/physiopathology , CADASIL/ethnology , DNA Mutational Analysis , Female , Founder Effect , Gene Frequency/genetics , Genetic Markers/genetics , Genetic Testing , Genotype , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Receptor, Notch3 , Taiwan
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