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.     

Factors Associated with Blunt Cerebrovascular Injury in Patients with Cervical Spine Injury

Blunt cerebrovascular injury (BCVI) is known to be a potentially fatal complication of cervical spine injury (CSI). Methods for screening the appropriate population remain to be elucidated, especially in Japan. This retrospective study was conducted to predict the risk factors relevant to BCVIs. Among 92 patients with CSI transferred to our institution from April 2007 to March 2012, 40 patients (35 men, 5 women) with neurological deficits and/or significant cervical spine fracture including fracture of transversarium, facet, body, lamina, and spinous process, underwent multi-detector computed tomography angiography (MDCTA) and magnetic resonance angiography (MRA), which identified 10 patients with BCVI [2 carotid artery injuries (BCAIs) and 9 vertebral artery injuries (BVAIs); 1 patient suffered both]. Univariate analyses exploring associations between individual risk factors and BCVI and BVAI were performed using Fisher''s exact test and Chi-square test for dichotomous variables and the unpaired t-test for continuous variables. Multiple logistic regression analyses for BCVI and BVAI were carried out using stepwise methods. On univariate and multivariate analysis, hyperextension injury was significantly associated with BVAI (p = 0.01 and p = 0.02), and subluxation (dislocation of vertebral body > 5 mm) was a significant predictor of BCVI (p = 0.04 and p = 0.03) and BVAI (p = 0.01 and p = 0.01). Prompt evaluation for BCVIs is recommended in CSI patients with hyperextension injury and dislocation of the vertebral body.     

Intraluminal exfoliated cancer cells and effectiveness of bowel ligatures during sigmoidectomy for sigmoid colon cancer

Purposes

To establish the efficiency of bowel ligatures in colon cancer surgery, focusing on the extent to which exfoliated cancer cells are shed in the colonic lumen during sigmoidectomy.

Methods

Twenty consecutive patients who underwent sigmoidectomy for sigmoid colon cancer were prospectively randomized into two groups: the “ligatures group”, in which bowel ligatures were placed, 3, 5, 10 cm from the tumor proximally and distally before dissection; and the “no ligatures group”, in which the corresponding sites were ligated only immediately before taking the specimen out. Each colonic segment ligated was irrigated with saline and samples were sent for blind cytological examination.

Results

Cancer cells were found in the colonic segment where the tumor was located, in 18 of 20 samples. The frequency of free cancer cells decreased from 50 to 0 % (p < 0.04) in the distal 3–5 cm colonic segment and from 80 to 20 % (p < 0.03) in the proximal colonic segment after performing bowel ligatures. Free cancer cells were confirmed in 1 of 10 samples at both colonic segments 5–10 cm from the tumor, even after bowel ligatures.

Conclusions

Intraluminal exfoliated cancer cells could be eliminated by placing bowel ligatures during sigmoidectomy. Measures should be considered to eliminate exfoliated cancer cells during colectomy, even after placing bowel ligatures.     

Dominant β-Thalassemia with Hemoglobin Hradec Kralove: Enhanced Hemolysis in the Spleen

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.     

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.