The genetics of white matter lesions

White matter lesions (WMLs), commonly seen as hyperintensities on T2-weighted MRI scans of healthy elderly individuals, are considered to be related to small vessel disease in the brain, and are often associated with subtle cognitive and functional impairments. WMLs also show a strong correlation with a wide range of neurodegenerative and neuropsychiatric disorders. Although a number of vascular risk factors for WMLs have been identified, genetic factors are also important with twin and family studies reporting high heritability. Mutations in several genes have been described that lead to monogenic disorders manifesting WMLs, such as Fabry disease and CADASIL. Because most individuals with WMLs do not have Mendelian disorders, most of the focus has been on single nucleotide polymorphisms as genetic risk markers for WMLs, either directly or through their interactions with other genes or medical risk factors. Candidate genes examined to date include those involved in cholesterol regulation and atherosclerosis, hypertension, neuronal repair, homocysteine levels, and oxidative stress pathways. In addition, although there have been a few genome-wide linkage studies, only one genome-wide association study has been performed. The majority of the genetic findings need independent replication, and studies need to be extended to other candidate genes. Collaborative efforts to examine genome-wide associations in large samples of both sexes of a broad age range using longitudinal studies are necessary. The identification of individuals genetically at risk of developing white matter lesions will have important implications for recognizing the etiology of WMLs and thereby developing clinical intervention strategies for their prevention.     

Source localization in magnetoencephalography to identify epileptogenic foci

Rationale

Magnetoencephalography (MEG) is useful to localize epileptic foci in epilepsy as MEG has higher spatio-temporal resolution than conventional diagnostic imaging studies; positron emission computed tomography, single photon emission computed tomography and magnetic resonance imaging (MRI).

Methods

We use 204-channel helmet-shaped MEG with a sampling rate of 600 Hz. A single dipole method calculates equivalent current dipoles to localize epileptic sources. The equivalent current dipoles are superimposed onto MRI as magnetic source imaging (MSI). Ictal MEG data are analyzed using time-frequency analysis. The power spectrum density is calculated using short-time Fourier transform and superimposed onto MRI results.

Results

Clustered equivalent current dipoles represent epileptogenic zones in patients with localization-related epilepsy. The surgical plan is reliably developed from source localizations of dipoles and power spectrum of interictal spike discharges, and ictal frequency.

Conclusion

MEG is indispensable in diagnosis and surgical resection for epilepsy to accurately localize the epileptogenic zone.     

A simplified method for stent placement in the distal duodenum: Enteroscopy overtube

The treatment of choice for patients with unresectable neoplastic obstruction of the small intestine is the placement of expandable metal stents.However,endoscopic delivery from the distal duodenum can be more diff icult.This case,shows the usefulness and technical advantages of the overtube and single balloon enteroscopy in the treatment of neoplastic stenosis affecting the small intestine.     

Polymorphisms in programmed death-1 gene are not associated with chronic HBV infection in Chinese patients

AIM:To investigate the association between the programmed death-1(PD-1) polymorphisms and genetic susceptibility of chronic hepatitis B virus(HBV) infection in Chinese patients.METHODS:Two single nucleotide polymorphisms(SNPs),PD-1.1 G > A and PD-1.2 G > A,were genotyped in 539 patients with chronic HBV infection and 353 other family members(HbsAg-) from 256 nuclear families using polymerase chain reactiorestriction fragment length polymorphisms assay.The associations between PD-1 polymorphisms and genetic susceptibilityof chronic HBV infection were analyzed usng the familybased association analysis method.RESULTS:No association or linkage was detected among 539 patients.Univariate(single-marker) familybased association tests demonstrated that PD-1 genotypes,alleles and transmitted haplotypes are not associated with chronic HBV infection(all with P value more than 0.05).Transmission/disequilibrium test and sibship disequilibrium test analysis showed no excess of the alleles from heterozygous parents to affected offspring(P = 0.688880,P = 1.000000 respectively).CONCLUSION:The data demonstrated that PD-1.1 and PD-1.2 polymorphisms are not associated with chronic HBV infection in Chinese patients.     

Association study of polymorphisms between DISC1 and schizophrenia in a Korean population

To further clarify schizophrenia (SCZ), disrupted in schizophrenia 1 (DISC1) is a promising candidate gene expressed predominantly within the hippocampus. Several lines of evidence suggest that DISC1 may be involved in susceptibility to SCZ. In this study, we investigated whether genetic polymorphisms in the coding region of DISC1 were associated with several SCZ clinical phenotypes in a Korean population. To examine any association between DISC1 and SCZ, we genotyped three clinical single nucleotide polymorphisms (SNPs) (rs3738401, R264Q; rs3738402, L465L; rs821616, S704C) in the coding region of the DISC1 gene using the Illumina Sentrix Array Matrix chip and direct sequencing in 303 patients with SCZ and 300 healthy controls. Our case-control analysis showed that none of these SNPs was associated with SCZ. In further endophenotype stratification, however, we found a significant association between rs821616 and the poor concentration subgroup of SCZ, determined using the Operational Criteria Checklist (codominant model, p=0.015). Our results suggest that DISC1 may be a susceptibility gene for poor concentration among Korean patients with SCZ.     

Single nucleotide polymorphism C/T(-13910), located upstream of the lactase gene, associated with adult-type hypolactasia: validation for clinical practice

ObjectivesTo validate C/T_-13910 polymorphism associated with primary hypolactasia for clinical practice.Design and methodsLactose breath test and PCR-RFLP for the C/T_-13910 polymorphism were performed.ResultsTwenty-seven of 28 patients with genotype CC had positive breath tests; all twenty-two patients with genotypes CT or TT had negative breath tests. Agreement of tests was high (p < 0.0001; Kappa Index 0.96).ConclusionC/T_-13910 polymorphism detection may be a new tool for primary hypolactasia diagnosis.     

Electrophysiological demonstration of both alpha 2-agonist and antagonist properties of RX 781094

The effects of RX 781094, a new and potent alpha 2-adrenoceptor antagonist, on locus coeruleus (LC) unit activity were examined. Low doses of RX 781094 produced suppression of spontaneous LC unit activity which could be reversed with yohimbine. The increase in LC firing produced by WB 4101 could also be reversed with a low dose of RX 781094. Thus, at low doses, RX 781094 has clonidine-like alpha 2-agonist activity. At higher doses, RX 781094 reversed the effects of clonidine and markedly shifted the dose of clonidine required to suppress LC unit activity. These data suggest that at high doses RX 781094 has alpha 2-antagonist properties. It is concluded that RX 781094 may be a partial agonist at alpha 2-adrenoceptors in the CNS.     

The CO single breath transfer factor of the lung

The CO single breath method for determining the transfer factor of the lung,T, and its component factors,Dm andVc, never gained wide application. The lack of generally accepted normal values has contributed to this. In this paper, based on the results of measurements in 28 normal subjects, it is shown that generally acceptable normal values can be obtained by: 1. determiningT at lung volumes above 80% TLC, and 2. expressingT, Dm andVc per unit of alveolar gas volume during breath-holding:T _v ,Dm _v andVc _v .     

Detection and Processing of Individual Components in the VEP

This paper describes a new technique for use in the field of evoked potentials research. The technique makes use of the latency corrected average method for identification of the components of the single evoked potential. Examples are presented in which this technique is utilized to separate homogeneous subsets of potentials within a set of tests.