An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages

Cytosolic pathogen- and damage-associated molecular patterns are sensed by pattern recognition receptors, including members of the nucleotide-binding domain and leucine-rich repeat-containing gene family (NLR), which cause inflammasome assembly and caspase-1 activation to promote maturation and release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and induction of pyroptosis. However, the contribution of most of the NLRs to innate immunity, host defense, and inflammasome activation and their specific agonists are still unknown. Here we describe identification and characterization of an NLRP7 inflammasome in human macrophages, which is induced in response to microbial acylated lipopeptides. Activation of NLRP7 promoted ASC-dependent caspase-1 activation, IL-1β and IL-18 maturation, and restriction of intracellular bacterial replication, but not caspase-1-independent secretion of the proinflammatory cytokines IL-6 and tumor necrosis factor-α. Our study therefore increases our currently limited understanding of NLR activation, inflammasome assembly, and maturation of IL-1β and IL-18 in human macrophages.     

Elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in korean population

The study was designed to investigate the effect of serum glucose, insulin and insulin resistance on the risk of prostate cancer (CaP) and on the clinicopathological characteristics in Korean men. Subjects were retrospectively recruited from 166 CaP patients underwent radical prostatectomy and 166 age-matched benign prostatic hyperplasia (BPH) patients. The serum was taken on the morning of the day of operation and insulin resistance was assessed by homeostasis model assessment insulin resistance index (HOMA-IR). Men in highest tertile of insulin was associated with 55% reduced odds of CaP than those with the lowest tertile (OR = 0.45, 95% CI = 0.23-0.89, P = 0.022). The patients in highest tertile of insulin had a more than 5.6 fold risk of locally advanced stage than those in the lowest tertile (OR = 5.62, 95% CI = 1.88-16.83, P = 0.002). Moreover, the patients in the highest tertile HOMA-IR group was associated with an increased risk of locally advanced stage than the lowest tertile group (OR = 3.10, 95% CI = 1.07-8.99, P = 0.037). These results suggest that elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean patients.     

超声处理在含骨或沙砾体病理标本脱钙中的应用

病理制片是确诊含有骨化组织及沙砾体组织疾病的主要技术手段之一。常规方法脱钙需4～10h,超声处理可使脱钙时间大大缩短,只需25～60min。我们以对脑膜瘤组织进行脱钙为例,对应用超声处理进行脱钙方法概述如下。[第一段]     

Corrosion behavior and cytotoxicity of Mg-35Zn-3Ca alloy for surface modified biodegradable implant material

This study was conducted to investigate the biocompatibility of Mg-Zn-Ca ternary alloy as a biodegradable material. The casting alloy underwent anodization in an alkaline electrolyte at current density 300 mA/cm(2) and frequency 50 Hz to obtain porous oxide layer. Plasma anodization film using pulse was shown to form irregular porous oxide film. As a result of corrosion test, the corrosion current was shown to decrease and the corrosion voltage was shown to increase in the anodized group, which showed the improvement of corrosion resistance after surface treatment. Sodium silicate (0.1 M) was directly oxidized due to high charges caused by spark and then formed SiO(2), and the compounds produced inside the film were shown MgO, Mg(2) SiO(4), and SiO(2.) In the histological examination in rats, all samples of the untreated group were shown to be absorbed 3 weeks later into the body. After the magnesium alloy was implanted, blood vessel expansion and tissue change were shown in the adjacent tissues. However, the changed tissues were shown to return to normal muscle tissues 4 weeks later when the alloy was completely absorbed. These results suggest that anodized Mg-35Zn-3Ca alloy has good biocompatibility in vivo and controls the absorption rate of biomaterials.     

Genetic analysis of HAV strains isolated from patients with acute hepatitis in Korea, 2005-2006

Hepatitis A virus (HAV) is a causative agent of acute viral hepatitis, which represents a significant public health problem. HAV is usually transmitted by oral-fecal route and prevalent not only in developing countries but also in developed countries worldwide. To characterize the HAV wild type strains circulating in Korea, the VP3/VP1 and VP1/P2A junction regions were detected by RT-PCR from HAV IgM positives during 2005 and 2006. Among 160 HAV IgM positive sera, 30% (n = 48) were positive for HAV RNA. Additionally, the VP3/VP1 junction regions were detected all six stools, which collected from outbreak in Gyeonggi province. Phylogenetic analysis of the sequences obtained from 54 distinct HAV isolates revealed that most of the strains (n = 45) belonged to genotype IA and the others including nine strains belonged to genotype IIIA. Interestingly, a Q --> S amino acid change was dominantly observed at position 810 of the VP1/P2A junction region in 14 isolates. The molecular epidemiology of HAV infection in Korea has changed with the co-circulation of at least two genotypes and 810Q --> S amino acid substitutions were found to be prevalent. These results strongly suggest that various HAV strains, including genotype IIIA, might be imported from high-endemic countries into Korea.     

NEFL Pro22Arg mutation in Charcot-Marie-Tooth disease type 1

Charcot-Marie-Tooth disease (CMT) is classified into demyelinating neuropathy (CMT1) and axonal neuropathy (CMT2). Mutations in the neurofilament light chain polypeptide (NEFL) gene are present in CMT2E and CMT1F neuropathies. Two types of Pro22 mutations have been previously reported: Pro22Ser in CMT2E with giant axons, and Pro22Thr in CMT1F. In this study, we identified another Pro22 mutation, Pro22Arg, in a Korean CMT1 family. An investigation to identify the clinical and pathological characteristics of the Pro22Arg revealed that it is associated with demyelinating neuropathy features in CMT1F. Histopathological findings showed onion bulb formations but no giant axons. It appears that the Pro22 mutations may influence not only the Thr-Pro phosphorylation site by proline-directed protein kinases but also other structural alteration of the NEFL protein in a different way. J.S. Shin and K.W. Chung contributed equally to this work.     

Lattice-like collagen fiber meshwork in the iris stroma of the cat: a possible mechanism to generate the tension directed towards the iris root which is required for pupillary dilatation in the sympathectomized eye

NaOH digestion technique for collagen fiber dissection and scanning electron microscopy demonstrated a lattice-like meshwork in the anterior surface of the iris stroma of the cat. The mesh threads were made of collagen fibril bundles. In the constricted pupil, the meshes were square to rhomboid with the diagonals in the direction of the radius or circumference of the iris. In the dilated pupil, however, the meshes were strongly flattened rhomboid or ellipse with a longer diagnoal or axis in the circumferential direction. At the mesh corners facing the pupillary margin or the iris root, the collagen fibril bundles were strongly bent in the iris of the constricted pupil, while they were almost straight or slightly wavy in the iris of the dilated pupil. Accumulation of elasticity tension generated by this small distortion of the iris-mesh threads in the constricted pupil was considered to generate a tension directed towards the iris root, which is required for pupillary dilatation in the sympathectomized eye. On the posterior surface of the iris stroma, numerous thin pleats tightly woven with collagen fibrils traversed straightway through the radial length of the ciliary zone of the iris in both constricted and dilated pupils. The structural changes of these pleats in miosis and mydriasis were very small compared with the meshwork of the anterior aspect of the iris. Therefore, they were considered to work mainly as an iris skeleton.     

KIT amplification and gene mutations in acral/mucosal melanoma in Korea

Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720A>G) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population.