Alzheimer's disease and Parkinson's disease genome-wide association study top hits and risk of Parkinson's disease in Korean population

Alzheimer's disease (AD) and Parkinson's disease (PD) have overlapping clinical and pathological features, suggesting a common pathway for these 2 neurodegenerative disorders. Here we investigated the association of both AD and PD GWAS top hits with PD susceptibility. We selected 25 single nucleotide polymorphisms (SNPs) in 9 genes (ABCA7, APOE, BST1, CLU, CR1, LRRK2, PARK16, PICALM, and SNCA) that were genotyped in 1036 PD case patients and 1208 controls. Case patients and controls were all ethnic Koreans. Logistic regression analysis was performed to calculate age- and sex-adjusted odds ratios. None of the AD-susceptibility loci (ABCA7, APOE, CLU, CR1, and PICALM) showed statistically significant association with PD susceptibility. In contrast, we replicated associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility in Koreans. Of those, the SNCA SNP rs11931074 showed the most significant association with PD susceptibility (adjusted odds ratio = 1.48; 95% confidence interval = 1.31–1.67; p = 2.20E-10). In a logistic regression analysis with SNPs coded under an additive model, there was no significant genetic interaction between the LRRK2 and the PARK16 locus gene RAB7L1 in PD risk. Our results confirm the associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility and fail to show significant associations of AD genome-wide association study (GWAS) top hits with PD susceptibility in a Korean population.     

Hypofractionated radiotherapy with Tomotherapy for patients with hepatic oligometastases: retrospective analysis of two institutions

To evaluate the efficacy and toxicity for patients with hepatic oligometastases, receiving hypofractionated radiotherapy with Tomotherapy to the liver. A total of 42 patients with 54 hepatic lesions, who had been treated from 2007 to 2011 at two institutions, were retrospectively reviewed for this study. All the patients received radical resections of the primary tumor, and had been presented with one to two hepatic lesions. The radiation dose of 40–75 Gy in 10–20 fractions (median, 50 Gy in 10 fractions) was delivered for the planning target volume. At a median follow-up time of 15 months, 1- and 2-year local control (LC) rates were 59.9 and 49.0 %, respectively. The 1- and 2-year overall survival (OS) rates were 60.0 and 44.0 %, respectively. Maximal tumor diameter of <3 cm and biologically effective dose (BED) of ≥100 Gy_α/β=10 were significantly associated with higher LC and OS. Primary colorectal cancer tended to be associated with higher LC (P = 0.075), and was significantly associated with higher OS (P = 0.037). 12 (28.6 %) of the 42 patients had grade 1–2 toxicities, and grade 3 or higher toxicity did not occur. Hypofractionated radiotherapy with Tomotherapy was safe for patients with hepatic oligometastases. The maximal tumor diameter of <3 cm and BED of ≥100 Gy_α/β=10 were significant prognostic factors for higher local control and survival, and primary colorectal cancer patients had statistically higher overall survival than the others.     

Action naming with impaired semantics: Neuropsychological evidencecontrasting naming and reading for objects and verbs

We contrast naming from pictures, and reading words, for objects and verbs (actions relating to the objects) in a patient with a large, posterior left-hemisphere lesion. We present evidence for spared picture naming for verbs relative to objects, whilst the opposite pattern of sparing occurred in reading. Objects were also spared relative to verbs in tasks requiring that written words be matched to either pictures or auditory words, in the presence of semantically related or unrelated distractors. We conclude that verb semantics were more impaired than semantic knowledge for objects, and that the better semantic knowledge for object names supported word reading. With pictures, however, action verb retrieval was maintained through a nonsemantic route from vision to action, or though preserved right-hemisphere “action semantics.”     

4–1BB signal stimulates the activation,expansion, and effector functions of γδ T cells in mice and humans

We show here that the expression of 4–1BB is rapidly induced in γδ T cells following antigenic stimulation in both mice and humans, and ligation of the newly acquired 4–1BB with an agonistic anti‐4–1BB augments cell division and cytokine production. We further demonstrate that γδ rather than αβ T cells protect mice from Listeria monocytogenes (LM) infection and 4–1BB stimulation enhances the γδ T‐cell activities in the acute phase of LM infection. IFN‐γ produced from γδ T cells was the major soluble factor regulating LM infection. Vγ1⁺ T cells were expanded in LM‐infected mice and 4–1BB signal triggered an exclusive expansion of Vγ1⁺ T cells and induced IFN‐γ in these Vγ1⁺ T cells. Similarly, 4–1BB was induced on human γδ T cells and shown to be fully functional. Combination treatment with human γδ T cells and anti‐hu4–1BB effectively protected against LM infection in human γδ T cell‐transferred NOD‐SCID mice. Taken together, these data provide evidence that the 4–1BB signal is an important regulator of γδ T cells and induces robust host defense against LM infection.     

Functional changes in regulatory T cells during an experimental infection with sparganum (plerocercofid of Spirometra mansoni)

Regulatory T (Treg) cells are important in the regulation of immune response, but the exact regulation of Treg‐cell function in vivo is still not well known. In the present study, we investigated the functional activity of CD4⁺ CD25⁺ Treg cells as well as the frequency and number of CD4⁺ CD25⁺ FoxP3⁺ Treg cells in the spleens of experimentally infected mice with a tissue‐migrating parasite, sparganum (plerocercoid of Spirometra mansoni) for 3 weeks. The results demonstrated fluctuations in the Treg‐cell function during the parasite infection, being up‐regulated at day 3, down‐regulated until day 14, and thereafter up‐regulated again at day 21. We also investigated the cytokine‐producing capability of the splenocytes to study the pattern of immune response of the mice to the parasite. The results showed decreased capabilities of interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ) and IL‐17α production, whereas IL‐4‐producing and IL‐10‐producing capabilities were increased along with the parasitic infection. Meanwhile, IL‐6‐producing capability was increased to reach a peak at week 2, and thereafter was decreased to the baseline level. As a regulatory mechanism, we found that Treg‐cell function was attenuated in the presence of the crude extracts of sparganum, but was enhanced in the presence of the excretory–secretory products, suggesting that sparganum products were involved in the triggering and regulation of immune response in the acute and chronic phases, respectively. Results show that Treg cells are central in the immune homeostasis in vivo that is maintained by host–parasite interactions during the parasitic infection.     

Sequence Conservation of the Region Targeted by the Abbott RealTime HBV Viral Load Assay in Clinical Specimens

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability.