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Contrast-enhanced magnetic resonance (MR) imaging with a new liver-specific contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA; EOB·Primovist®) was studied in 14 normal beagles and 9 dogs with focal liver lesions. Gd-EOB-DTPA accumulates in normally functioning hepatocytes 20 min after injection. As with Gd-DTPA, it is also possible to perform a dynamic multiphasic examination of the liver with Gd-EOB-DTPA, including an arterial phase and a portal venous phase. First, a reliable protocol was developed and the appropriate timings for the dynamic study and the parenchymal phase in normal dogs using Gd-EOB-DTPA were determined. Second, the patterns of these images were evaluated in patient dogs with hepatic masses. The optimal time of arterial imaging was from 15 s after injection, and the optimal time for portal venous imaging was from 40 s after injection. Meanwhile, the optimal time to observe changes during the hepatobiliary phase was from 20 min after injection. In patient dogs, 11 lesions were diagnosed as malignant tumors; all were hypointense to the surrounding normal liver parenchyma during the hepatobiliary phase. Even with a low-field MR imaging unit, the sequences afforded images adequate to visualize the liver parenchyma and to detect tumors within an appropriate scan time. Contrast-enhanced MR imaging with Gd-EOB-DTPA provides good demarcation on low-field MR imaging for diagnosing canine focal liver lesions. [ABSTRACT FROM AUTHOR]

NK cell activity is regulated by the integration of positive and negative signals. One important source of these signals for human NK cells is the killer Ig-like receptor (KIR) family, which includes both members that transduce positive and those that generate negative signals. KIR3DL1 inhibits NK cell activity upon engagement by its ligand HLA-Bw4. The highly homologous KIR3DS1 is an activating receptor, which is implicated in the outcome of a variety of pathological situations. However, unlike KIR3DL1, direct binding of KIR3DS1+ cells to HLA has not been demonstrated. We analyzed four key amino acid differences bet- ween KIR3DL1*01502 and KIR3DS1*013 to determine their role in KIR binding to HLA. Single substitutions of these residues dramatically reduced binding by KIR3DL1. In the reciprocal experiment, we found that the rare KIR3DS1 allotype KIR3DS1*014 binds HLA-Bw4 even though it differs from KIR3DS1*013 at only one of these positions (position 138). This reactivity was unexpectedly dependent on residues at other variable positions, as HLA-Bw4 binding was lost in receptors with KIR3DL1-like residues at both positions 199 and 138. These data provide the first evidence, to our knowledge, for the direct binding of KIR3DS1+ cells to HLA-Bw4 and highlight the key role for position 138 in determining ligand specificity of KIR3DS1. They also reveal that KIR3DS1 reactivity and specificity is dictated by complex interactions between the residues in this region, suggesting a unique functional evolution of KIR3DS1 within the activating KIR family. [ABSTRACT FROM AUTHOR]

Research into cancer cells that harbor gene mutations relating to anticancer drug-resistance at the single-cell level has focused on the diagnosis of, or treatment for, cancer. Several methods have been reported for detecting gene-mutated cells within a large number of non-mutated cells; however, target single nucleotide-mutated cells within a large number of cell samples, such as cancer tissue, are still difficult to analyze. In this study, a new system is developed to detect and isolate single-cancer cells expressing the T790M-mutated epidermal growth factor receptor (EGFR) mRNA from multiple non-mutated cancer cells by combining single-cell microarray chips and peptide nucleic acid (PNA)-DNA probes. The single-cell microarray chip is made of polystyrene with 62,410 microchambers (31-40 µm diameter). The T790M-mutated lung cancer cell line, NCI-H1975, and non-mutated lung cancer cell line, A549, were successfully separated into single cells in each microchambers on the chip. Only NCI-H1975 cell was stained on the chip with a fluorescein isothiocyanate (FITC)-conjugated PNA probe for specifically detecting T790M mutation. Of the NCI-H1975 cells that spiked into A549 cells, 0–20% were quantitatively analyzed within 1 h, depending on the spike concentration. Therefore, our system could be useful in analyzing cancer tissue that contains a few anticancer drug-resistant cells. [ABSTRACT FROM AUTHOR]

Muscle strength declines with age. However, factors that contribute to such declines are not well documented and have not been extensively studied in elderly populations of Asian origin. Correlations of grip strength with a broad range of factors associated with declines in muscle strength were examined in 202 community-living elderly Japanese women. After adjustment for age, grip strength was positively correlated with body weight, height, serum albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C) and serum iron and inversely with serum copper, and log high-sensitivity C-reactive protein (hsCRP). Multiple linear regression analysis with grip strength as a dependent variable showed that 47.0% of variability of grip strength could be accounted for by height, age and haemoglobin in order of increasing R2. In conclusion, low haemoglobin may contribute to low muscle strength independently of age, anthropometric, nutritional, and inflammatory markers in the elderly, and may represent an important confounder of the association between grip strength and functional decline in community- living Japanese elderly women. [ABSTRACT FROM AUTHOR]

Aims: Elevated pulse pressure (PP) has been reported to be a risk factor for type 2 diabetes in elderly patients with hypertension., Methods: Cross-sectional relationships of PP with known risk factors for type 2 diabetes and inflammatory markers were examined in 150 elderly community-dwelling women, 79 women (52.7%) of whom had hypertension., Results: Systolic blood pressure (standardized β, 0.775), log tumor necrosis factor-α (TNF-α, standardized β, 0.110), age (standardized β, 0.140), and neutrophil count (standardized β, 0.114) emerged as determinants of PP independent of high-sensitivity C-reactive protein, interleukin-6, monocyte count, plasminogen activator inhibitor-1, homeostasis model assessment of insulin resistance, HDL-cholesterol, and adiponectin (R(2) = 0.772)., Conclusions: The present studies have demonstrated an independent association of higher PP with higher TNF-α, a marker of insulin resistance, and neutrophil count in community-living elderly women and suggest that insulin resistance and chronic low-grade inflammation may in part be responsible for the association between high PP and incident type 2 diabetes found in elderly patients with hypertension.