Microvascular morphology alteration using relaxation rate change with gadolinium-based magnetic resonance imaging contrast agent in patients with Alzheimer's disease.

Background: Conventional magnetic resonance imaging (MRI) techniques cannot demonstrate microvascular alterations in mild Alzheimer's disease (AD). Thus, the diagnosis of microvascular pathology commonly relies on postmortem. The purpose of this study was to evaluate alterations of microvascular structures in patients with AD using a 3T clinical MRI system with a commercially available contrast agent. Methods: Eleven patients with AD and 11 cognitively normal (CN) controls were included in this cross-sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a Gadolinium (Gd)-based contrast agent injection were calculated from images obtained with a multi-echo turbo spin-echo sequence and multi-echo gradient-echo sequence to obtain microvascular index maps of blood volume fraction (BVf), mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), and microvessel-weighted imaging (MvWI). Two-sample t-test was used to compare those values between the two groups. Correlation analysis was performed to evaluate the relationship between those values and age. Results: BVfs at the corpus callosum and at the thalamus were significantly increased in the AD group (P=0.024 and P=0.005, respectively). BVf at the gray matter (P=0.020) and white matter area (P=0.012) were also significantly increased in the AD group compared with the CN group. MvWIs at the hippocampus and parahippocampal gyrus were significantly increased in the AD group compared with the CN group (P=0.020 and P=0.006, respectively). Voxel-based analysis showed both mVD and VSI were significantly decreased at the prefrontal lobe in the AD group. Q were not significant difference between CN and AD groups. MvWI were significantly positively correlated with age. Conclusions: Microvascular index was a useful non-invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as increasing BVf and microvessel-weighted.

Development and evaluation of a T1 standard brain template for Alzheimer disease.

BACKGROUND: Patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) have high variability in brain tissue loss, making it difficult to use a disease-specific standard brain template. The objective of this study was to develop an AD-specific three-dimensional (3D) T1 brain tissue template and to evaluate the characteristics of the populations used to form the template. METHODS: We obtained 3D T1-weighted images from 294 individuals, including 101 AD, 96 amnestic MCI, and 97 cognitively normal (CN) elderly individuals, and segmented them into different brain tissues to generate AD-specific brain tissue templates. Demographic data and clinical outcome scores were compared between the three groups. Voxel-based analyses and regions-of-interest-based analyses were performed to compare gray matter volume (GMV) and white matter volume (WMV) between the three participant groups and to evaluate the relationship of GMV and WMV loss with age, years of education, and Mini-Mental State Examination (MMSE) scores. RESULTS: We created high-resolution AD-specific tissue probability maps (TPMs). In the AD and MCI groups, losses of both GMV and WMV were found with respect to the CN group in the hippocampus (F >44.60, P<0.001). GMV was lower with increasing age in all individuals in the left (r=-0.621, P<0.001) and right (r=-0.632, P<0.001) hippocampi. In the left hippocampus, GMV was positively correlated with years of education in the CN groups (r=0.345, P<0.001) but not in the MCI (r=0.223, P=0.0293) or AD (r=-0.021, P=0.835) groups. WMV of the corpus callosum was not significantly correlated with years of education in any of the three subject groups (r=0.035 and P=0.549 for left, r=0.013 and P=0.821 for right). In all individuals, GMV of the hippocampus was significantly correlated with MMSE scores (left, r=0.710 and P<0.001; right, r=0.680 and P<0.001), while WMV of the corpus callosum showed a weak correlation (left, r=0.142 and P=0.015; right, r=0.123 and P=0.035). CONCLUSIONS: A 3D, T1 brain tissue template was created using imaging data from CN, MCI, and AD participants considering the participants' age, sex, and years of education. Our disease-specific template can help evaluate brains to promote early diagnosis of MCI individuals and aid treatment of MCI and AD individuals.

Association between endotoxin levels in dust from indoor swine housing environments and the immune responses of pigs.

Indoor animal husbandry environments are inevitably contaminated with endotoxins. Endotoxin exposure is associated with various inflammatory illnesses in animals. This cross-sectional study evaluated the relationship between the degree of endotoxin exposure and the cellular and humoral immune profiles of fattening pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes were determined. Peripheral-blood mononuclear cells were stimulated in vitro with concanavalin A for 48 h, and cytokines released into culture supernatants were measured. The barns in which the pigs lived were assessed for endotoxin levels in the total and respirable dust by using the limulus amebocyte lysate kinetic QCL method. Low and high endotoxin exposures were defined as ≤ 30 and ＞ 30 EU/m³, respectively. Compared to pigs with low endotoxin exposure (n = 19), highly exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNγ) and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis factor-alpha (TNFα) production. The IL-4, IFNγ, and TNFα levels significantly correlated with endotoxin level and/or pig age. Constant exposure of pigs to high levels of airborne endotoxins can lead to aberrant immune profiles.

Association between promoter polymorphisms of the LIFR gene and schizophrenia with persecutory delusion in a Korean population.

Schizophrenia has been associated with an imbalance in inflammatory cytokines. Leukemia inhibitory factor receptor α (LIFR) is an integral component of the glycoprotein 130-LIFR signaling complex, which participates in signal transduction by members of the interleukin (IL)-6 cytokine family. The aim of this study was to investigate whether genetic polymorphisms of the LIFR gene are associated with schizophrenia in the Korean population. We also explored possible associations between the polymorphisms and the clinical symptoms of schizophrenia. We selected three single nucleotide polymorphisms (SNPs) (rs2071237 -200C/G, rs2071236 -254C/T and rs6862038 -962A/G) on the promoter region of the LIFR gene and recruited 204 schizophrenia patients and 367 control subjects from the Korean population. All patients were evaluated according to the Operational Criteria Checklist for Psychotic Illness. SNP genotyping was performed by direct sequencing. An analysis of multiple logistic regression models (co-dominant 1, co-dominant 2, dominant, recessive and overdominant) was performed to evaluate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. No significant difference was revealed between schizophrenia patients and controls. However, a significant association was detected between the LIFR gene polymorphisms and schizophrenia patients with persecutory delusion (rs2071236, OR=2.18, 95% CI=1.20-3.94, P=0.009 in the overdominant model; rs6862038, OR=2.08, 95% CI=1.16-3.74, P=0.013 in the overdominant model). The present study suggests that the LIFR gene may be related to schizophrenia with persecutory delusion in the Korean population.

Squamous cell carcinoma of the lung in an autistic child who has never smoked.

Primary bronchogenic carcinoma of the lung is extremely rare in childhood, particularly the squamous cell type. Only 13 cases have been reported in the literature. We report a case of squamous cell carcinoma in an autistic, 16-year-old boy who presented with a productive cough. Interestingly, he was a never-smoker, but had been exposed to environmental tobacco smoking by his father for 13 years. The diagnosis was delayed by approximately 1 month due to his young age. He was diagnosed with squamous cell carcinoma of the lung by video-assisted thoracoscopic surgery, and chemotherapy was arranged. Considering his age, autism, and good performance status, a combined chemotherapeutic regimen with gemcitabine plus carboplatin was planned. After the second cycle of chemotherapy, the cough resolved and a computed tomography scan showed a partial response of the central conglomerated mass with the absence of the malignant pleural effusion.

No association between polymorphisms of WNT2 and schizophrenia in a Korean population.

BACKGROUND: Wingless-type MMTV integration site family member 2 (WNT2) has a potentially important role in neuronal development; however, there has yet to be an investigation into the association between single nucleotide polymorphisms (SNPs) of WNT2 and schizophrenia. This study aimed to determine whether certain SNPs of WNT2 were associated with schizophrenia in a Korean population. METHODS: e genotyped 7 selected SNPs in the WNT2 gene region (approximately 46 Kb) using direct sequencing in 288 patients with schizophrenia and 305 healthy controls. RESULTS: Of the SNPs examined, one SNP showed a weak association with schizophrenia (p = 0.017 in the recessive model). However, this association did not remain statistically significant after Bonferroni correction. CONCLUSION: The present study does not support a major role for WNT2 in schizophrenia. This could be due to the size of the population. Therefore, additional studies would be needed to definitively rule out the gene's minor effects.