Juyeon Kim

Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinsons disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

Electronic and magnetic properties of the electron-doped superconductorSm1.85Ce0.15CuO4−δ

Temperature-dependent magnetization (M(T)) and specific heat (C_p(T)) measurements were carried out on single crystal Sm_{1.85}Ce_{0.15}CuO_{4-delta} (T_c = 16.5 K). The magnetic anisotropy in the static susceptibility, chi {equiv} M/H, is apparent not only in its magnitude but also in its temperature dependence, with chi_{perp} for H{perp}c larger than chi_{parallel} for H{parallel}c. For both field orientations, chi does not follow the Curie-Weiss behavior due to the small energy gap of the J = 7/2 multiplet above the J = 5/2 ground-state multiplet. However, with increasing temperature, chi_{parallel}(T) exhibits a broad minimum near 100 K and then a slow increase while chi_{perp}(T) shows a monotonic decrease. A sharp peak in C_p(T) at 4.7 K manifests an antiferromagnetic ordering. The electronic contribution, gamma, to C_p(T) is estimated to be gamma = 103.2 (7) mJ/moleSmK^2. The entropy associated with the magnetic ordering is much smaller than Rln2, where R is the gas constant, which is usually expected for the doublet ground state of Sm^{+3}. The unusual magnetic and electronic properties evident in M(T) and C_p(T) are probably due to a strong anisotropic interaction between conduction electrons and localized electrons at Sm^{+3} sites.

Mortality of advanced Parkinson's disease patients treated with deep brain stimulation surgery

OBJECTIVEnDespite the widespread use of deep brain stimulation (DBS) for patients with Parkinsons disease (PD), long-term outcomes remain unclear. We aimed to analyze the mortality of advanced PD patients who received DBS surgery.nnnMETHODSnWe assessed the survival rate of 158 consecutive advanced PD patients who underwent DBS surgery between April 2002 and May 2014. Kaplan-Meier survival curves were constructed using death as the endpoint. Cox proportional hazards regression models were used to assess the association of clinical risk factors with survival.nnnRESULTSnTwenty-seven (17.1%) PD patients (13 men and 14 women) died during the mean follow-up period of 5.3±3.1years. The survival rate was 97% at 3years and 85% at 5years after DBS surgery. Pneumonia (n=7) was the most common specific cause of death. Orthostatic hypotension was more frequent in deceased patients than in survivors (P=0.026). In a step-wise Cox regression analysis, male sex (hazard ratio (HR) = 2.58; 95% confidence interval (CI) = 1.19–5.60; P = 0.016), visual hallucination (HR = 9.53; 95% CI = 3.50–26.01; P < 0.001), and nursing home admission (HR = 6.76; 95% CI = 2.40–18.99; P < 0.001) predicted poor survival.nnnCONCLUSIONnThe poor survival of advanced PD patients who underwent DBS surgery was associated with male sex, orthostatic hypotension, visual hallucination, and nursing home admission.

Association of metals with the risk and clinical characteristics of Parkinson's disease

INTRODUCTIONnWhile metals have been implicated in the pathophysiology of Parkinsons disease (PD), the clinical evidence is scarce. Further, the contribution of metals for the risk or clinical presentation of PD remains to be explored.nnnMETHODSnTo investigate the associations between the level of metals in blood serum and PD risk or clinical presentation, including sex-related differences, we studied 325 PD patients and age- and sex-matched 304 controls. We collected clinical data of the PD patients, including age at onset, PD duration, levodopa-equivalent dose (LED), Hoehn and Yahr stage (H-Y stage), presence of motor fluctuation, levodopa-induced dyskinesia (LID), freezing of gait, hallucination, and Mini-Mental State Examination (MMSE) score. Iron, copper, and zinc levels in serum were assayed by inductively coupled plasma mass spectrometry. Statistical analyses were performed to determine the sex-related differences in metal levels.nnnRESULTSnAmong the three metal elements tested, serum copper levels showed significant correlations with PD risk or clinical presentation. Higher copper levels were associated with a decreased PD risk. Higher copper or lower iron levels were associated with the risk of LID in women. Serum copper levels were negatively correlated with MMSE scores in PD patients.nnnCONCLUSIONSnThis clinical study suggests significant associations between serum metal levels and PD risk or essential clinical features, demonstrating the possible roles of metals in PD pathogenesis or symptom development.

Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease

BACKGROUNDnAlpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinsons disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals.nnnMETHODSnThe study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped.nnnRESULTSnIn patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (ORu202f=u202f5.96, 95% CIu202f=u202f1.70-20.97, Pu202f=u202f0.01). In an interaction analysis, SNP rs11931074-PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (ORu202f=u202f7.33, 95% CIu202f=u202f1.58-33.88, Pu202f=u202f0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS.nnnCONCLUSIONnThis exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.

Comparison of Pallidal and Subthalamic Deep Brain Stimulation in Parkinson’s Disease: Therapeutic and Adverse Effects

Objective To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson’s disease (PD). Methods We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups. Results At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697). Conclusion The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.

P02.04: Rapid growth of perivascular epithelioid cell tumor (PEComa) in the female genital organs combined with lymphangioleiomyomatosis: a case report

(P = 0.000). The proportion of breast cancer (4.26%, 23/540 breast) in fatty type was higher than that in fibroglandular-2 type (2.06%, 59/2865 breast) and in fibroglandular-1 (0.88%, 15/1705 breast) which was significant difference (P = 0.000). There was no breast cancer in glandular type. Pathology examination: the involution of the breast was most obviously in the in fatty type which showed severe atrophy of the breast terminal duct lobular unit (TDLU), and the involution wasn’t too severe in the fibroglandular-2 and was lighter in the fibroglandular-1 which displayed the hyperplasia and the involution of the TDLU coinstantaneous, but it was the most light in the glandular which revealed hyperplasia of the TDLU. Conclusions: These results demonstrated correlation between the mammary involution and ultrasound types which show the mammary age, it was important in screening programme of breast lesion.