Basic Study of Susceptibility-Weighted Imaging at 1.5T

With the aim of sequence optimization in susceptibility-weighted imaging (SWI), 2 image acquisition parameters (slice thickness and matrix size) and 2 image processing conditions (number of slices per minimum intensity projection (MIP) and Sliding Window) were investigated using a 1.5-T magnetic resonance imaging (MRI) system. The subjects were 12 healthy volunteers and the target region for scanning was the whole brain. Informed consent was obtained from all subjects. First, susceptibility-weighted images were acquired with various slice thicknesses from 1mm to 5mm and various matrix sizes from 256x256 to 512x512, and the images were assessed in terms of the contrast-to-noise ratio (CNR) and were also visually evaluated by three radiologists. Then, the number of slices per MIP and the usefulness of the Sliding Window were investigated. In the study of the optimal slice thickness and matrix size, the results of visual evaluation suggested that a slice thickness of 3mm and a matrix size of 448x448 are optimal, while the results of evaluation based on CNR were not significant. As regards the image processing conditions, the results suggested that the number of slices per MIP should be set to a minimum value of 2 and that the use of Sliding Window is effective. The present study provides useful reference data for optimizing SWI sequences.</p

NK cells control tumor-promoting function of neutrophils in mice

Although NK cells are recognized as direct antitumor effectors, the ability of NK cells to control cancer-associated inflammation, which facilitates tumor progression, remains unknown. In this study, we demonstrate that NK cells control tumor-promoting inflammation through functional modification of neutrophils. NK cells control the tumor-promoting function of neutrophils through an IFNgamma-dependent mechanism. Tumor progression in an NK cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK cell-depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by up-regulation of VEGF-A expression, which promotes tumor growth and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth in NK cell-depleted mice was dependent on neutrophils. Furthermore, the systemic neutropenia caused by an anti-metabolite treatment showed an anti-cancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils

Factors Predicting Difficult Biliary Cannulation during Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones

Background/Aims Difficult biliary cannulation is an important risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Therefore, this study aimed to identify the factors that predict difficult cannulation for common bile duct stones (CBDS) to reduce the risk for PEP. Methods This multicenter retrospective study included 1,406 consecutive patients with native papillae who underwent ERCP for CBDS. Factors predicting difficult cannulation for CBDS were identified using univariate and multivariate analyses. Results Univariate analysis showed that six factors significantly predicted difficult cannulation: ERCP performed by non-expert endoscopists, low-volume center, absence of acute cholangitis, normal serum bilirubin, intradiverticular papilla, and type of major duodenal papilla. Multivariate analysis identified ERCP performed by non-expert endoscopists (odds ratio [OR], 2.5; p<0.001), low-volume center (OR, 1.6; p<0.001), intradiverticular papilla (OR, 1.3; p=0.007), normal serum bilirubin (OR, 1.3; p=0.038), and absence of acute cholangitis (OR, 1.3; p=0.049) as factors significantly predicting difficult cannulation for CBDS. Conclusions Initial cannulation by an experienced endoscopist, early rescue cannulation, or early takeover by an experienced endoscopist should be considered when performing ERCP for CBDS in the presence of factors predicting difficult cannulation

Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) caused by PKD1 mutations is one of the most common hereditary disorders. However, the key pathological processes underlying cyst development and exacerbation in pre-symptomatic stages remain unknown, because rodent models do not recapitulate critical disease phenotypes, including disease onset in heterozygotes. Here, using CRISPR/Cas9, we generate ADPKD models with PKD1 mutations in cynomolgus monkeys. As in humans and mice, near-complete PKD1 depletion induces severe cyst formation mainly in collecting ducts. Importantly, unlike in mice, PKD1 heterozygote monkeys exhibit cyst formation perinatally in distal tubules, possibly reflecting the initial pathology in humans. Many monkeys in these models survive after cyst formation, and cysts progress with age. Furthermore, we succeed in generating selective heterozygous mutations using allele-specific targeting. We propose that our models elucidate the onset and progression of ADPKD, which will serve as a critical basis for establishing new therapeutic strategies, including drug treatments

Generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body.

Nonhuman primates are valuable for human disease modelling, because rodents poorly recapitulate some human diseases such as Parkinson\u27s disease and Alzheimer\u27s disease amongst others. Here, we report for the first time, the generation of green fluorescent protein (GFP) transgenic cynomolgus monkeys by lentivirus infection. Our data show that the use of a human cytomegalovirus immediate-early enhancer and chicken beta actin promoter (CAG) directed the ubiquitous expression of the transgene in cynomolgus monkeys. We also found that injection into mature oocytes before fertilization achieved homogenous expression of GFP in each tissue, including the amnion, and fibroblasts, whereas injection into fertilized oocytes generated a transgenic cynomolgus monkey with mosaic GFP expression. Thus, the injection timing was important to create transgenic cynomolgus monkeys that expressed GFP homogenously in each of the various tissues. The strategy established in this work will be useful for the generation of transgenic cynomolgus monkeys for transplantation studies as well as biomedical research

腎血管腫

腎血管腫4例を報告した.良性血管性腫瘍である腎血管腫は腎動脈造影でも必ずしも異常陰影を示さず, 診断は困難である.うち2例の海綿状血管腫摘出例はCTで, 造影剤増強効果をもたないlow-densityな腫瘤影を示した.しかし, 動脈造影で診断した2例はCTでは異常陰影を認めなかった.このように腎血管腫の動脈造影とCTは血管腫自体の構成血管成分により種々の像を呈するものと考えるFour cases of renal hemangioma are presented. Renal hemangioma is difficult to detect because this benign vascular tumor never demonstrates any abnormalities on renal arteriography. Computed tomography in two resected cases of cavernous hemangioma revealed a low-density mass without any enhance effect, while the others diagnosed by the selective renal arteriography demonstrated no abnormality on computed tomography. We postulate that both angiographic and computed tomographic appearances of the renal hemangioma could depend on its vascular components. Related reports are also reviewed