Use of the Putamen/Caudate Volume Ratio for Early Differentiation between Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease

BACKGROUND AND PURPOSE: Neuropathological studies have demonstrated that multiple system atrophy (MSA) produces selective atrophy of the putamen with sparing of the caudate nucleus, while both structures are spared in idiopathic Parkinson's disease (PD). In this study we evaluated the clinical efficacy of using putaminal atrophy in brain MRI to differentiate MSA and PD. METHODS: We measured the putamen/caudate volume ratio on brain MRI in 24 patients with MSA and 21 patients with PD. Two clinicians who were blinded to the patients' diagnoses and to each other's assessments measured the volume ratio using a computer program. RESULTS: The measured volume ratios of the two investigators were highly correlated (r=0.72, p<0.0001). The volume ratio was significantly lower in MSA (1.29+/-0.28) than PD (1.91+/-0.29, p<0.0001). Setting an arbitrary cutoff ratio of 1.6 resulted in about 90% of patients with MSA falling into the group with a lower ratio, whereas more than 80% of patients with PD belonged to the other group. CONCLUSIONS: The present results demonstrate that putaminal atrophy in MSA as measured on brain MRI represents an effective tool for differentiating MSA from PD.ope

FE65 as a link between VLDLR and APP to regulate their trafficking and processing

<p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p

The effect of body mass index and fasting glucose on the relationship between blood pressure and incident diabetes mellitus: a 5-year follow-up study

There is no consensus on the relationship between high blood pressure (BP) and incident diabetes mellitus (DM). Therefore, the aim of the current study was to investigate the independent association between BP and incident DM and identify the metabolic components that influence incident DM in Korean subjects. The current study included 14 054 non-diabetic subjects (mean age of 41 years) at the start of the study who were followed for an average of 5 years. We measured the risk for incident DM according to the subjects' baseline BP. Subjects were separated into three groups as follows: normotensive (<120/80 mm Hg), pre-hypertensive (120/80 mm Hg ⩽BP <140/90 mm Hg) and hypertensive (⩾140/90 mm Hg). The overall incidence of DM was 1.8% (246 subjects), comprising 0.9% of the normotensive group, 1.9% of the pre-hypertensive group and 4.0% of the hypertensive group (P<0.01). Within the hypertensive group, subjects with high body mass index (BMI) and high fasting-glucose levels were 40 times more likely to develop DM compared with those with low BMI and low glucose levels (0.3 vs. 13.2%, P=0.001). The risk for incident DM was significantly higher in the hypertensive group compared with that in the normotensive group (OR 3.41 vs. 1.00, P<0.0001). However, the significance disappeared after making adjustments for the baseline BMI and fasting glucose levels (OR 1.18 vs. 1.00, P=0.83). We found that the significance of high BP in predicting incident DM was influenced by the baseline BMI and fasting glucose levels of the subjects

Prognostic parameters for recurrence of papillary thyroid microcarcinoma

<p>Abstract</p> <p>Background</p> <p>Papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma less than or equal to 1.0 cm in size. Independent prognostic factors for clinical recurrence of PTMC have not been clearly delineated.</p> <p>Methods</p> <p>Clinicopathological parameters predicting PTMC recurrence were determined by retrospective analysis of 307 patients.</p> <p>Results</p> <p>Of the 293 patients eligible for analysis, 14 (5%) had recurrence during a median follow-up time of 65 months. Recurrence was observed in 8 of 166 patients (0.5%) treated with total or near-total thyroidectomy; gender (P = 0.02) and presence of lateral cervical node metastases at initial surgery (P = 0.01) were associated with recurrence. Six of the 127 patients (0.5%) treated with hemi- or subtotal thyroidectomy experience recurrences, but no significant prognostic factor for recurrence was identified. Multivariate Cox-regression analysis showed that gender and cervical lymph node metastasis were significant variables</p> <p>Conclusion</p> <p>PTMC showed very diverse disease extent and could not be regarded as indolent, relatively benign disease based on the primary tumor size. The extent of surgery should be based on prognostic parameters, such as gender and lateral neck node metastasis, in patients with PTMC.</p

Quantitative and Qualitative Analysis of the Antifungal Activity of Allicin Alone and in Combination with Antifungal Drugs

The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy

Effects of Interleukin-10 Polymorphisms, Helicobacter pylori Infection, and Smoking on the Risk of Noncardia Gastric Cancer

OBJECTIVE: Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans. METHODS: We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer. RESULTS: The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction  = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI]  = 17.76 [6.17-51.06]) or the -592C (OR [95% CI]  = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction  = 0.080). CONCLUSIONS: Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer

Apolipophorin-III Mediates Antiplasmodial Epithelial Responses in Anopheles gambiae (G3) Mosquitoes

Apolipophorin-III (ApoLp-III) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. However, there is no evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects such as Drosophila and mosquitoes.We report the molecular and functional characterization of An. gambiae apolipophorin-III (AgApoLp-III). Mosquito ApoLp-IIIs have diverged extensively from those of lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is similar to that of Manduca sexta (tobacco hornworm). We found that AgApoLp-III mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain) mosquitoes in response to Plasmodium berghei infection. Furthermore, immunofluorescence stainings revealed that high levels of AgApoLp-III protein accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing increases the intensity of P. berghei infection by five fold.There are broad differences in the midgut epithelial responses to Plasmodium invasion between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III participates in midgut epithelial defense responses that limit Plasmodium infection

Circulating and PBMC Lp-PLA2 Associate Differently with Oxidative Stress and Subclinical Inflammation in Nonobese Women (Menopausal Status)

BACKGROUND: This study aimed to determine the association of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in circulation and peripheral blood mononuclear cells (PBMCs) with inflammatory and oxidative stress markers in nonobese women and according to menopausal status. Lp-PLA(2) activity, a marker for cardiovascular risk is associated with inflammation and oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Eighty postmenopausal women (53.0±4.05 yr) and 96 premenopausal women (39.7±9.25 yr) participated in this study. Lp-PLA(2) activities, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β in plasma as well as in PBMCs were measured. Plasma ox-LDL was also measured. Postmenopausal women demonstrated higher circulating levels of ox-LDL and IL-6, as well as IL-6, TNF-α, and IL-1β in PBMCs, than premenopausal women. In both groups, plasma Lp-PLA(2) activity positively correlated with Lp-PLA(2) activity in PBMCs and plasma ox-LDL. In premenopausal women, Lp-PLA(2) activities in plasma and PBMCs positively correlated with IL-6, TNF-α, and IL-1β in PBMCs. In postmenopausal women, plasma ox-LDL positively correlated with PBMC cytokine production. In subgroup analysis of postmenopausal women according to plasma ox-LDL level (median level: 48.715 U/L), a significant increase in Lp-PLA(2) activity in the plasma but not the PBMCs was found in the high ox-LDL subgroup. Plasma Lp-PLA(2) activity positively correlated with unstimulated PBMC Lp-PLA(2) activity in the low ox-LDL subgroup (r = 0.627, P<0.001), whereas in the high ox-LDL circulating Lp-PLA(2) activity positively correlated with plasma ox-LDL (r = 0.390, P = 0.014) but not with Lp-PLA(2) activity in PBMCs. CONCLUSIONS/SIGNIFICANCE: The lack of relation between circulating Lp-PLA(2) activity and Lp-PLA(2) activity in PBMCs was found in postmenopausal women with high ox-LDL. This may indicate other sources of circulating Lp-PLA(2) activity except PBMC in postmenopausal women with high ox-LDL. We also demonstrated that circulating Lp-PLA(2) and PBMC secreted Lp-PLA(2) associate differently with markers of oxidative stress and sub clinical inflammation in nonobese women, particularly according to the menopausal states