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1.  Evaluation of blood-brain barrier permeability in tryptophan hydroxylase 2-knockout mice 
The blood-brain barrier (BBB) is critical to the health of the central nervous system (CNS). The possibility that 5-hydroxytryptamine (5-HT) participates in the alteration of the BBB has been previously demonstrated. Tryptophan hydroxylase 2 (TPH2) is a unique genetic enzyme isoform that catalyzes the rate-limiting step in the biosynthesis of 5-HT in the CNS; however, its role in the permeability changes of the BBB remains unclear. In the present study, TPH2-knockout mice were utilized in the assessment of BBB disruption, as measured by the Evans Blue (EB) extravasation or fluorescein isothiocyanate-albumin leakage assay in the brain. EB was not found to be retained in the brain in the TPH2-knockout mice or the wild-type controls. The results of the study demonstrate that TPH2 knockout has no effect on BBB permeability, indicating that TPH2 and the 5-HT system in the CNS are not sufficient to influence the BBB leakage.
doi:10.3892/etm.2014.1938
PMCID: PMC4186353  PMID: 25289042
blood-brain barrier; tryptophan hydroxylase 2; 5-hydroxytryptamine
2.  Association study between SNP rs150689919 in the DNA demethylation gene, TET1, and Parkinson’s disease in Chinese Han population 
BMC Neurology  2013;13:196.
Background
Recent studies suggest that epigenetic factors may play an important role in the pathogenesis of Parkinson’s disease (PD). In our previous work, we sequenced the exomes of sixteen patients from eight Chinese PD families using whole exome sequencing technology, consequently three patients from different pedigrees were found sharing the variant c.1460C > T (rs150689919) in the coding region of the Tet methyl cytosine dioxygenase 1 (TET1) gene.
Methods
In order to evaluate the possible association between sporadic PD and the single nucleotide polymorphism (SNP) rs150689919 in TET1, a case–control cohort study was conducted in 514 sporadic PD patients and 529 normal controls. Genotyping was determined by PCR and direct sequencing. Statistical significance was analyzed by the Chi-squared test.
Results
There was no statistical significance in TET1 rs150689919 genotype or allele frequencies between the PD cases and healthy controls, even after being stratified by gender and age at onset.
Conclusions
Our findings suggest that rs150689919 in TET1 may not be associated with PD in Chinese population. However, due to the limited data in this study, replication studies in larger sample and other populations are required.
doi:10.1186/1471-2377-13-196
PMCID: PMC4028872  PMID: 24325350
TET1; Parkinson’s disease; Epigenetics; Chinese
3.  SUMO-1 Modification on K166 of PolyQ-Expanded aTaxin-3 Strengthens Its Stability and Increases Its Cytotoxicity 
PLoS ONE  2013;8(1):e54214.
Post-translational modification by SUMO was proposed to modulate the pathogenesis of several neurodegenerative diseases. Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by polyQ-expanded ataxin-3. We have previously shown that ataxin-3 was a new target of SUMOylation in vitro and in vivo. Here we identified that the major SUMO-1 binding site was located on lysine 166. SUMOylation did not influence the subcellular localization, ubiquitination or aggregates formation of mutant-type ataxin-3, but partially increased its stability and the cell apoptosis. Our findings revealed the role of ataxin-3 SUMOylation in SCA3/MJD pathogenesis.
doi:10.1371/journal.pone.0054214
PMCID: PMC3561348  PMID: 23382880
4.  Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias 
Brain  2011;134(12):3490-3498.
Paroxysmal kinesigenic dyskinesias is a paroxysmal movement disorder characterized by recurrent, brief attacks of abnormal involuntary movements induced by sudden voluntary movements. Although several loci, including the pericentromeric region of chromosome 16, have been linked to paroxysmal kinesigenic dyskinesias, the causative gene has not yet been identified. Here, we identified proline-rich transmembrane protein 2 (PRRT2) as a causative gene of paroxysmal kinesigenic dyskinesias by using a combination of exome sequencing and linkage analysis. Genetic linkage mapping with 11 markers that encompassed the pericentromeric of chromosome 16 was performed in 27 members of two families with autosomal dominant paroxysmal kinesigenic dyskinesias. Then, the whole-exome sequencing was performed in three patients from these two families. By combining the defined linkage region (16p12.1–q12.1) and the results of exome sequencing, we identified an insertion mutation c.649_650InsC (p.P217fsX7) in one family and a nonsense mutation c.487C>T (p.Q163X) in another family. To confirm our findings, we sequenced the exons and flanking introns of PRRT2 in another three families with paroxysmal kinesigenic dyskinesias. The c.649_650InsC (p.P217fsX7) mutation was identified in two of these families, whereas a missense mutation, c.796C>T (R266W), was identified in another family with paroxysmal kinesigenic dyskinesias. All of these mutations completely co-segregated with the phenotype in each family. None of these mutations was identified in 500 normal unaffected individuals of matched geographical ancestry. Thus, we have identified PRRT2 as the first causative gene of paroxysmal kinesigenic dyskinesias, warranting further investigations to understand the pathogenesis of this disorder.
doi:10.1093/brain/awr289
PMCID: PMC3235563  PMID: 22120146
proline-rich transmembrane protein 2; paroxysmal kinesigenic dyskinesias; whole-exome sequencing; linkage analysis
5.  A rare Von Hippel–Lindau disease that mimics acute myelitis: case report and review of the literature 
Neurological Sciences  2010;32(2):305-307.
Von Hippel–Lindau disease (VHL) comprises a series of complicated clinical manifestations. We hereby report one unique case of VHL with a natural history that mimics acute myelitis. MRI and biopsy in this patient showed multiple solid hemangioblastomas of the central nervous system and kidney. This study further confirmed that VHL is of highly clinical, imaging, and pathological heterogeneity. Diagnosis for VHL should be based on combination of clinical, radiological, pathological, and genetic data.
doi:10.1007/s10072-010-0413-3
PMCID: PMC3056988  PMID: 20927563
Von Hippel–Lindau disease; Hemangioblastoma; Clinical manifestation; Magnetic resonance image; Histopathology
6.  1-[1-(Hydroxy­imino)eth­yl]-N-(2-methoxy­phen­yl)cyclo­propane­carboxamide 
The title compound, C13H16N2O3, adopts an E configuration with respect to the C=N bond and an intra­molecular N—H⋯N hydrogen bond results in the formation of a six-membered ring. In the crystal, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into a chain propagating along the b axis. Very weak π–π stacking inter­actions [centroid–centroid distance = 4.18 (2) Å] may further consolidate the packing, forming a two-dimensional supra­molecular network.
doi:10.1107/S1600536809022260
PMCID: PMC2969475  PMID: 21582888
7.  Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride 
Journal of Clinical Investigation  2000;106(5):681-688.
We have previously shown that in renal cortex, COX-2 expression is localized to macula densa and surrounding cortical thick ascending limb of Henle (cTALH). Dietary salt restriction increases local expression of COX-2, which mediates renin production and secretion. Given that decreased luminal chloride [Cl–] at the level of the macula densa increases renin production and secretion, we investigated the role of extracellular ion concentration on COX-2 expression. Quiescent rabbit cTALH cells were incubated in a physiological salt solution containing high or low levels of NaCl. Immunoreactive COX-2 expression increased significantly in the low NaCl solution. COX-2 expression also increased after administration of the Na+/K+/2Cl– cotransport inhibitor, bumetanide. Selective substitution of chloride led to increased COX-2 expression, whereas selective substitution of sodium had no effect. The p38 MAP kinase inhibitor PD169316 decreased low NaCl-induced COX-2 expression. Low-salt or low-chloride medium induced cultured cTALH to accumulate ≥ 3-fold higher levels of pp38, the activated (phosphorylated) form of p38; low-salt medium also increased pJNK and pERK levels. Feeding rats a low-salt diet for 14 days induced a significant increase in renal cortical pp38 expression, predominantly in the macula densa and cTALH. These results suggest that reduced extracellular chloride leads to increased COX-2 expression, which may be mediated by activation of a p38-dependent signaling pathway.
PMCID: PMC381289  PMID: 10974021
8.  Angiotensin II attenuates renal cortical cyclooxygenase-2 expression 
Journal of Clinical Investigation  1999;103(7):953-961.
We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2) expression is localized to cTALH cells in the region of the macula densa, and that dietary salt restriction increases COX-2 expression. Administration of the angiotensin converting inhibitor, captopril, further increased COX-2 mRNA and renal cortical COX-2 immunoreactivity, with the most pronounced expression in the macula densa. Administration of an AT1 receptor antagonist, losartan, also significantly increased cortical COX-2 mRNA expression and COX-2 immunoreactivity. Mutant mice homozygous for both Agtr1a and Agtr1b null mutations (Agtr1a–/–,Agtr1b–/–) demonstrated large increases in immunoreactive COX-2 expression inthe cTALH/macula densa. To determine whether increased COX-2expression in response to ACE inhibition mediated increases in renin production, rats were treated with captopril for one week with or without the specific COX-2 inhibitor, SC58236. Plasma renin activity increased significantly in the captropril group, and this increase was significantly inhibited by simultaneous treatment with SC58236. Thus, these studies indicated that angiotensin II inhibitors augment upregulation of renal cortical COX-2 in states of volume depletion, suggesting that negative feedback by the renin-angiotensin system modulates renal cortical COX-2 expression and that COX-2 is a mediator of increased renin production in response to inhibition of angiotension II production.
PMCID: PMC408259  PMID: 10194467
9.  Emerging tobacco hazards in China: 2. Early mortality results from a prospective study 
BMJ : British Medical Journal  1998;317(7170):1423-1424.
Objective
To monitor the evolving epidemic of mortality from tobacco in China following the large increase in male cigarette use in recent decades.
Design
Prospective study of smoking and mortality starting with 224 500 interviewees who should eventually be followed for some decades.
Setting
45 nationally representative small urban or rural areas distributed across China.
Subjects
Male population aged 40 or over in 1991, of whom about 80% were interviewed about smoking, drinking, and medical history.
Main outcome measure
Cause specific mortality, initially to 1995 but later to continue, with smoker versus non-smoker risk ratios standardised for area, age, and use of alcohol.
Results
74% were smokers (73% current, only 1% former), but few of this generation would have smoked substantial numbers of cigarettes since early adult life. Overall mortality is increased among smokers (risk ratio 1.19; 95% confidence interval 1.13 to 1.25, P<0.0001). Almost all the increased mortality involved neoplastic, respiratory, or vascular disease. The overall risk ratios currently associated with smoking are less extreme in rural areas (1.26, 1.12, or 1.02 respectively for smokers who started before age 20, at 20-24, or at older ages) than in urban areas (1.73, 1.40, or 1.16 respectively).
Conclusion
This prospective study and the accompanying retrospective study show that by 1990 smoking was already causing about 12% of Chinese male mortality in middle age. This proportion is predicted to rise to about 33% by 2030. Long term continuation of the prospective study (with periodic resurveys) can monitor the evolution of this epidemic.
Key messagesIn recent years most young men in China have become persistent cigarette smokers, starting at about age 20; this will cause high mortality in middle age and old ageCurrently, however, most middle aged and older smokers (particularly in rural areas) have not persistently used substantial daily numbers of cigarettes ever since they were young adults, so their current tobacco attributed mortality is more limitedNationally representative retrospective and prospective studies now show that in about 1990 “only” about 12% of adult male deaths in middle age were caused by smokingContinuation of the present prospective study will monitor the growth of the epidemic of tobacco related deaths in China over the next few decades
PMCID: PMC28720  PMID: 9822394

Results 1-9 (9)