Association between muscular strength and metabolic risk in Japanese women, but not in men

We examined whether cardiorespiratory fitness (maximal oxygen uptake, VO(2)max) and muscular strength (grip strength) are associated with individual and clustered metabolic risk factors independently of abdominal adiposity in Japanese men (n=110) and women (n=110) aged 20-69 years. Blood pressure, triglycerides (TG), HDL cholesterol, and fasting plasma glucose (FPG) were assessed and metabolic risk score was calculated, which is the sum of the z scores for each individual risk factor. Waist circumference was measured and the area of visceral fat was assessed by MRI. Multiple linear regression analysis revealed that VO(2)max was inversely associated with TG in men (p<0.05) and grip strength was negatively associated with FPG and metabolic risk score in women (p<0.001 and p<0.05, respectively), independently of waist circumference. Adjusting for visceral fat instead of waist circumference, similar results were obtained in women (p<0.01 and p<0.05, respectively), but the association between VO(2)max and TG in men was attenuated to nonsignificant. This cross-sectional study demonstrates that muscular strength is inversely associated with plasma glucose levels and clustered metabolic risk factors independently of abdominal adiposity in Japanese women, but not in men.     

Decrease of Peripheral and Intestinal NKG2A-Positive T Cells in Patients with Ulcerative Colitis

To investigate the role of inhibitory natural killer receptors (iNKRs) in inflammatory bowel disease (IBD), we analyzed the expression of NKG2A, one of the iNKRs, on T cells in a mouse colitis model and human IBD. During the active phase of dextran sulfate sodium (DSS)-induced mouse colitis, the frequency of NKG2A+ T cells was significantly decreased in the peripheral blood, and increased in the intestine, suggesting the mobilization of this T cell subset to the sites of inflammation. Administration of anti-NKG2A antibody increased the number of inflammatory foci in DSS-induced colitis, suggesting the involvement of NKG2A+ T cells in this colitis model. In ulcerative colitis (UC) patients, the frequency of peripheral blood NKG2A+ T cells was significantly decreased, compared with Crohn's disease (CD) patients and healthy controls, regardless of clinical conditions such as treatment modalities and disease activity. Notably, in sharp contrast to the DSS-induced mouse colitis model, the frequency of NKG2A+ cells among intestinal T cells was also decreased in UC patients. These results suggest that inadequate local infiltration of NKG2A+ T cells may be involved in the pathogenesis of UC.     

Intestinal microbiota and secretory immunoglobulin A in feces of exclusively breast-fed infants with blood-streaked stools

Episodes of blood‐streaked stools are not uncommon in exclusively breast‐fed infants under 6 months of age. Such bleeding is thought to be associated with food protein‐induced proctocolitis, however the pathomechanism remains unclear. The aim of this study was to investigate intestinal microbiota and secretory immunoglobulin A in the feces of exclusively breast‐fed infants with blood‐streaked stools. Fecal specimens from 15 full‐term infants with blood‐streaked stools and 15 breast‐fed healthy infants were studied and the results compared. All infants had been delivered vaginally and exclusively breast‐fed. The fecal microbiota were investigated by phylogenetic analysis combined with culture methods for some bacterial species, and feces were assessed for the presence of fecal secretory immunoglobulin A by enzyme‐linked immunosorbent assay. Phylogenetic cluster analysis revealed four major clusters of fecal bacteria, cluster A being found only in healthy infants. The Bacteroides fragilis group was observed more frequently in controls than in patients (P < 0.05). In the controls, the predominant species belonging to the Enterobacteriaceae group was Escherichia coli, whereas in the patients it was Klebsiella (P < 0.05). Concentrations of secretory immunoglobulin A were high in one third of the healthy controls. In conclusion, the pathomechanism of rectal bleeding in exclusively breast‐fed infants may be related to differences in the composition of their intestinal flora.     

Isolation of centromeric-tandem repetitive DNA sequences by chromatin affinity purification using a HaloTag7-fused centromere-specific histone H3 in tobacco

The centromere is a multi-functional complex comprising centromeric DNA and a number of proteins. To isolate unidentified centromeric DNA sequences, centromere-specific histone H3 variants (CENH3) and chromatin immunoprecipitation (ChIP) have been utilized in some plant species. However, anti-CENH3 antibody for ChIP must be raised in each species because of its species specificity. Production of the antibodies is time-consuming and costly, and it is not easy to produce ChIP-grade antibodies. In this study, we applied a HaloTag7-based chromatin affinity purification system to isolate centromeric DNA sequences in tobacco. This system required no specific antibody, and made it possible to apply a highly stringent wash to remove contaminated DNA. As a result, we succeeded in isolating five tandem repetitive DNA sequences in addition to the centromeric retrotransposons that were previously identified by ChIP. Three of the tandem repeats were centromere-specific sequences located on different chromosomes. These results confirm the validity of the HaloTag7-based chromatin affinity purification system as an alternative method to ChIP for isolating unknown centromeric DNA sequences. The discovery of more than two chromosome-specific centromeric DNA sequences indicates the mosaic structure of tobacco centromeres.     

Entry of human T-cell leukemia virus type 1 is augmented by heparin sulfate proteoglycans bearing short heparin-like structures

Three molecules have been identified as the main cellular factors required for binding and entry of human T-cell leukemia virus type 1 (HTLV-1): glucose transporter 1 (GLUT1), heparan sulfate (HS), and neuropilin 1 (NRP-1). However, the precise mechanism of HTLV-1 cell tropism has yet to be elucidated. Here, we examined the susceptibilities of various human cell lines to HTLV-1 by using vesicular stomatitis virus pseudotypes bearing HTLV-1 envelope proteins. We found that the cellular susceptibility to HTLV-1 infection did not correlate with the expression of GLUT1, HS, or NRP-1 alone. To investigate whether other cellular factors were responsible for HTLV-1 susceptibility, we conducted expression cloning. We identified two HS proteoglycan core proteins, syndecan 1 and syndecan 2, as molecules responsible for susceptibility to HTLV-1. We found that treatment of syndecan 1-transduced cells (expressing increased HS) with heparinase, a heparin-degradative enzyme, reduced HTLV-1 susceptibility without affecting the expression levels of HS chains. To further elucidate these results, we characterized the expression of HS chains in terms of the mass, number, and length of HS in several syndecan 1-transduced cell clones as well as human cell lines. We found a significant correlation between HTLV-1 susceptibility and the number of HS chains with short chain lengths. Our findings suggest that a combination of the number and the length of HS chains containing heparin-like regions is a critical factor which affects the cell tropism of HTLV-1.     

A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1

ABSTRACT: Patients with neurofibromatosis-1 (NF-1) sometime develops neuroendocrine tumors (NET). Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET). A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast enhanced computed tomography scan demonstrated a 30 mm tumor in the head of the pancreas. The scan showed showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with acinus-like structure. The tumor was diagnosed as NET G2 according to WHO classification (2010). The product of NF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.