Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Localized pemphigus foliaceus exclusively involving the follicular infundibulum: a novel peau d'orange appearance

Localized pemphigus foliaceus (PF) clinically presents as red plaques with scale and crust due to acantholysis of the epidermis. The follicular infundibulum shows acantholysis, but usually with epidermal acantholysis or at least erosion. Localized PF exclusively involving the follicular infundibulum, which shows a peau d'orange appearance, has never been reported. We describe a patient with a red plaque and peau d'orange appearance on the cheek for 20 years. Dyskeratotic acantholysis in the follicular infundibulum was overlooked when the first biopsy specimen was obtained, and a disseminated lesion developed soon after, which led to the diagnosis. Although a peau d'orange appearance is a rare clinical manifestation of PF, PF should be considered as the differential diagnosis on the basis of this appearance, especially when the lesion persists on the face for long periods.     

Validity and reliability of a Self-Implementable method to evaluate masticatory performance: Use of color-changeable chewing gum and a color scale

PurposeThe objective of this study was to confirm the validity of a Self-Implementable method to evaluate masticatory performance using a newly developed color scale and color-changeable chewing gum.MethodsWe developed a dedicated color scale that enables anyone to easily check the color of the chewing gum instead of using specialist equipment. To examine the reliability of evaluating the masticatory performance by the subjects themselves, three groups of six subjects were recruited: a group of dentists, a group of adults and a group of elderly adults were asked to check the colors of the chewed samples using the color scale. The correlation between the use of the color scale and the use of a colorimeter to determine the color of the chewing gum was studied to confirm the validity of the color scale. To assess the reliability, intraclass correlation coefficients (ICCs) were determined.ResultsA strong correlation was found between the a* value measured by the colorimeter and the mean scores from the color scale. The ICCs for intra-examiner and inter-examiner consistency were more than 0.88 for all three groups.ConclusionsThis research confirmed the validity and reliability of colorimetric analysis of color-changeable chewing gum using a color scale as a Self-Implementable method of evaluating masticatory performance.     

Neural basis of altered earlier attention and higher order biological motion processing in schizophrenia

Schizophrenia patients have impairments of biological motion (BM) perception, which provides critical information about social cognition. Because social cognition is underpinned by attention, the impairments of BM perception in schizophrenia could be partially attributable to altered attention. To elucidate the impairments in attention and social perception in schizophrenia, we investigated the neural basis of impaired BM processing using MRI in respect to attention deficits by eye tracker. Voxel-based morphometry was performed to evaluate the relationship between BM perception and gray matter (GM) volume. The temporo-parietal junction (TPJ) and anterior superior temporal sulcus (aSTS) were related to task accuracy. However, when the effect of attention (i.e., eye movement) was controlled, the relationship in TPJ became non-significant, while aSTS showed a significant relationship with BM perception. Alteration in TPJ might be associated with inefficient attentional strategy, whereas dysfunctional aSTS might be correlated with deficit in higher order BM processing per se. Several cognitive levels as well as corresponding brain areas are possibly involved in the manifestation of social cognitive deficits in schizophrenia.     

Improved accuracy in predicting the presence of Gleason pattern 4/5 prostate cancer by three-dimensional 26-core systematic biopsy

OBJECTIVES: To evaluate whether three-dimensional 26-core (3D26) prostate biopsy improves the accuracy in predicting the presence of Gleason pattern 4/5 cancer compared with extended transrectal 12-core (TR12) or transperineal 14-core (TP14) biopsy schemes. METHODS: We studied 143 consecutive men in whom prostate cancer was diagnosed by the 3D26 biopsy and who underwent radical prostatectomy (RP) without neoadjuvant treatment. All histologic grading was reevaluated by a single pathologist according to the 2005 International Society of Urological Pathology Consensus Conference on Gleason Grading. Cancer grade was categorized into high grade (Gleason pattern 4/5 cancer present) and non-high grade (absent) in both biopsy and RP specimens. Since TR12 and TP14 biopsy schemes represent subsets of the 3D26 biopsy, we could compare these schemes directly in an identical patient cohort. RESULTS: There was a grade agreement between 3D26 biopsy and RP in 132 (92.3%) cancers. Grade concordance between biopsy and RP was significantly better in 3D26 biopsy than in TR12 (83.5%, p=0.025) biopsy. Risk of underestimation of cancer grade by 3D26 biopsy (26.5%) was significantly lower than that by TP14 (51.4%, p=0.034). Grade concordance between 3D26 biopsy and RP was not according to clinical variables including prostate volume, clinical stage, prostate-specific antigen (PSA), and PSA density. CONCLUSIONS: We demonstrated that the 3D26 biopsy can accurately predict the presence of Gleason pattern 4/5 cancer on RP specimens with a high concordance rate of 92.3%, a value significantly higher than that between extended TR12 biopsy and RP specimens.     

Evaluation of occlusal status of Japanese adults based on functional tooth units

ObjectivesAlthough extensive national oral health data on dental caries and periodontal diseases in Japan are available, few studies have assessed the occlusal status of the Japanese population, and none are based on national survey data. The presence and prosthodontic conditions of the molar region are important for masticatory function, and the functional tooth unit (FTU) approach can be used to evaluate the occlusal status. Thus, using the national oral health survey data, this study investigated the occlusal status of the Japanese population using FTU.MethodsOverall, 3,605 adults (aged ≥20 years) who participated in the 2011 Japanese national oral health survey were included. FTUs were used as indices for evaluating the occlusal status. FTUs were calculated according to sex, age group, and the number of teeth present, and their associations were further analysed.ResultsThe number of teeth present, posterior teeth, and FTUs decreased with age in both men and women. In the age group of those ≥60 years, all only natural teeth-FTU (n-FTU) and natural teeth and artificial teeth from fixed prostheses or implant-supported FTU (nif-FTU) scores were <8. The total-FTU scores of all age groups, except the 60-69 and 70-79 years age groups, were >10.ConclusionThis is the first study to use FTUs and national oral health survey data to investigate the occlusal status in the Japanese population. People aged ≥60 years who have low n-FTU or natural teeth and artificial teeth from fixed prostheses or implant-supported FTU scores or those aged 60-70 years who have the lowest total-FTU scores require careful evaluation of masticatory performance.     

Intake of arsenic from water, food composites and excretion through urine, hair from a studied population in West Bengal, India.

To evaluate the main intake source of arsenic by the villagers from arsenic-affected families in Jalangi and Domkol blocks in Mushidabad district, West Bengal-India, we determined the concentrations of arsenic in tube-well water and in food composites, mainly including vegetables and cereals collected from the surveyed families which were cultivated in that region. The daily dietary intakes of arsenic by the villagers were estimated and the excretions of arsenic through urine and hair were determined. The arsenic concentrations in hair and urine of the studied population living in mild (2.78 microg/L), moderate (30.7 microg/L) and high (118 microg/L) arsenic-affected families were 133, 1,391 and 4,713 microg/kg and 43.1, 244 and 336 microg/L, respectively. The linear regressions show good correlations between arsenic concentrations in water vs hair (r(2)=0.928, p<0.001) and water vs urine (r(2)=0.464, p<0.01). Approximately 29.4%, 58.1% and 62.1% of adult population from mild, moderate and high arsenic-affected families were suffering from arsenical skin manifestations. The mean arsenic concentrations of food composites (vegetables and cereals) in high arsenic-affected families are not significantly different from mild arsenic-affected families. The daily dietary intakes of arsenic from water and food composites of the studied population, living in high, moderate and mild arsenic-affected families were 568, 228 and 137 microg, respectively. The linear regressions show good correlations between arsenic concentrations in hair vs daily dietary intake (r(2)=0.452, p<0.001) and urine vs daily dietary intake (r(2)=0.134, p<0.001). The water for drinking contributed 6.07%, 26.7% and 58.1% of total arsenic in our study from mild, moderate and high arsenic-affected families. The result suggested that the contaminated water from high arsenic-affected families should be the main source for intake of arsenic. On contrary, the contribution of arsenic-contaminated food composites from mild and moderate arsenic-affected families might be the main source for intake of arsenic. The Food and Agriculture Organization/World Health Organization (FAO/WHO) provisional tolerable weekly intake (PTWI) values of arsenic in our study were 3.32, 5.75 and 12.9 microg/kg body weight/day from mild, moderate and high arsenic-affected families, respectively, which is higher than the recommended PTWI value of arsenic (2.1 microg/kg body weight/day).     

High-resolution computed tomography patterns and immunopathogenetic findings in drug-induced pneumonitis

We tried to determine whether high-resolution computed tomography (HRCT) patterns correlate with the immunopathogenetic findings and whether they could provide helpful information for predicting the outcomes in non-neoplastic drug-induced pneumonitis. The HRCT images were classified as most suggestive of pneumonitis, diffuse alveolar damage (DAD), non-specific interstitial pneumonia, organizing pneumonia (OP), hypersensitivity pneumonitis, and acute eosinophilic pneumonia (AEP) in 34 patients with non-neoplastic drug-induced pneumonitis. The patients were analyzed for the bronchoalveolar lavage (BAL) cell findings and for the circulating levels of interferon-inducible protein 10 (IP-10) and macrophage-derived chemokine (MDC), which were measured by an enzyme-linked immunosorbent assay. The cumulative dose of corticosteroids received by the patients and the day when they required supplemental oxygen were calculated as outcome markers. There were no differences in the circulating chemokine levels and the BAL cell profiles except for the eosinophil percentages among the HRCT patterns. Most of the cases with pulmonary eosinophilia belonged to the OP and AEP groups, and the circulating MDC levels correlated with BAL eosinophil percentages. We could not find any relationship between the BAL cell profiles or the chemokine levels and the outcome markers. In contrast, the HRCT patterns rather predicted the outcomes because larger cumulative dose of steroids and longer oxygen supply were required for the patients in the DAD and OP groups. In contrast, all patients with AEP recovered without steroid administration. The present study suggests that HRCT does not predict cellular pathophysiology but it may predict the corticosteroid use in non-neoplastic drug-induced pneumonitis.     

Aortic arch calcification evaluated on chest X-ray is a strong independent predictor of cardiovascular events in chronic hemodialysis patients

Vascular calcification is associated with cardiovascular disease in hemodialysis (HD) patients. Some reports have previously shown that simple assessment of aortic calcification using plain radiography is associated with cardiovascular (CV) events; however, these studies simply assessed whether aortic calcification was present or absent only, without considering its extent. Here, we evaluated the validity of grading aortic arch calcification (AoAC) to predict new CV events. We retrospectively reviewed chest X-rays in 212 asymptomatic HD patients who underwent measurement of pulse wave velocity (PWV) in 2006 without a past history of CV events. The extent of AoAC was divided into four grades (0–3). Among these subjects, the follow-up of CV events in 197 patients was completed. At baseline, AoAC grade was positively associated with age, dialysis vintage, PWV and parathyroid hormone levels, and negatively correlated with body weight and body mass index. Arterial stiffness, as determined by PWV, was also correlated with increasing AoAC grade. Eighty-nine CV events in total occurred during a mean follow-up period of 69 ± 45 months. With multivariate adjustment, Kaplan–Meier analysis showed that the incidence was significantly higher in patients with higher AoAC grade (grades 2 and 3) than in those with grade 0 or 1 (p = 0.013, log-rank test). Multivariate Cox proportional hazards analyses showed the predictive values of AoAC grade were significant (hazard ratio 1.512; p = 0.0351). AoAC detectable on chest X-ray is a strong independent predictor of CV events in accordance with PWV. Risk stratification by assessment of AoAC may provide important information for management of atherosclerotic disease in HD patients.