Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

Liver‐infiltrating CD56 positive T lymphocytes in hepatitis C virus infection

Abstract: Aim: Hepatitis C virus (HCV) is a major cause of post‐transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus‐specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV‐infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56⁺ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH‐C). Material and Methods: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH‐C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver‐infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. Results: The CD56⁺ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly γδ‐TCR. There was a correlation between the ratio of CH‐C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. Conclusion: The correlation between CD56⁺ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver‐infiltrating CD56⁺ T lymphocytes play an important pathologic role in hepatocellular injury in CH‐C.     

Influence of oral appliances on craniocervical posture in obstructive sleep apnea–hypopnea syndrome patients

PurposeThe existence of a relationship between head posture and mandibular function has been discussed by several authors. However, the relationship between head posture and the cervical spine in patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) who are using oral appliances (OAs) remains unknown. The aim of this study was to evaluate the changes in the cervical spine associated with the use of OAs in patients with OSAHS.MethodsFifteen patients (4 females and 11 males; mean age, 48 years) diagnosed with OSAHS were randomly selected. An OA was fabricated individually for each patient. Two lateral cephalometric radiographs were taken while the patient was sitting awake in an upright position. The first radiograph was taken in the intercuspal position and the second was taken while the subject was wearing the OA. Analyses based on the sella–nasion (SN) line were performed in the lateral cephalogram. Comparison of craniocervical angles in patients with and without the OA was performed using Wilcoxon's signed-rank test.ResultsCephalometric analysis showed that the craniocervical angles (CVT-C2V and SN-C4) with OA were higher than those without OA (P < 0.05). It seems that the OA caused a significant flexion of the cranium on the upper cervical spine. A significant increase in the craniocervical angle occurred in the fourth cervical segment.ConclusionThe changes in forward flexion of the upper cervical spine found in this study imply that changes in the craniocervical relationship should be evaluated periodically after an OA has been inserted.     

HLA‐C*12:02 is a susceptibility factor in late‐onset type of psoriasis in Japanese

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA‐C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA‐Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA‐Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA‐C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex‐ and age‐matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early‐onset type of psoriasis with HLA‐C*06:02 allele in Japanese. In addition, we detected the association between the late‐onset type of psoriasis and the HLA‐C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.     

Tenascin-C levels in the vitreous of patients with proliferative vitreoretinopathy

PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2-127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.     

Toward identification of susceptibility genes for sporadic Parkinson's disease

To identify susceptibility genes for Parkinson's disease (PD) and to establish tailor-made medicine for PD, we studied 20 single nucleotide polymorphisms (SNPs) in 18 candidate genes for association with PD. We found that homozygosity for the V66M polymorphism of the BDNF gene occurs more frequently in PD patients than in unaffected controls and confirmed an association with the S18Y polymorphism of the UCHL1 gene. We further started microsatellite marker-based genome-wide association studies by using the pooled DNA method. We have finished checking approximately 6800 markers and found some significant associations (p=3.9 x 10(-6)) on chromosome 1 where other studies showed a linkage. Genes in linkage disequilibrium with these markers may be associated with pathogenesis of PD.     

Immunogenetic mechanism of Beh?et's disease

In order to investigate the immunogenetic mechanism of Beh?et's disease, frequencies of HLA antigens were studied in patients. The subjects consisted of 66 patients and 99 normal controls. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR, -DQ antigens. HLA-DP antigens were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant increase of HLA-B15 was observed in the patients. In contrast, no significant difference was observed in HLA-Bw52 which possesses only two different amino acids from HLA-B15. On the contrary, frequencies of HLA-A11, HLA-Aw33, HLA-B35, HLA-B44 and HLA-DQw1 were significantly lower in the patients than in the controls. No significant difference was observed in HLA-DP antigens. These results suggest that Beh?et's disease involves both disease susceptibility factors and disease resistance factors and that such genetic factors are mapped within or very close to the HLA-B gene in the class I gene region. Additionally class II HLA-DQ antigen is associated with disease resistance factors.