Meteorin regulates mesendoderm development by enhancing nodal expression

During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

Genotypic Characterization of Vibrio vulnificus Clinical Isolates in Korea

AbstractObjectivesVibrio vunificus is known to cause septicemia and severe wound infections in patients with chronic liver diseases or an immuno-compromised condition. We carried out the molecular characterization of V. vulnificus isolates from human Vibrio septicemia cases based on pulsed-field gel electrophoresis (PFGE) using NotI and SfiI.Methods and ResultsPFGE was used to characterize a total of 78 strains from clinical cases after NotI or SfiI digestion. The geographical distribution of PFGE patterns for the strains from the southern part of Korea, a high-risk region for Vibrio septicemia, indicated that the isolates from southeastern Korea showed a comparatively higher degree of homology than those from southwestern Korea.ConclusionsWe report the genetic distribution of V. vulnficus isolated from Vibrio septicemia cases during 2000–2004 in Korea. This method has potential use as a subspecies-typing tool for V. vulnificus strains isolated from distant geographic regions

A Case of Pathologic Splenic Rupture as the Initial Manifestation of Acute Myeloid Leukemia M2

A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy

The effect of alpha lipoic acid in a porcine in-stent restenosis model

SummaryBackgroundThe aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.MethodsIn protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.ResultsProtocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0±1.0mm2 vs. 1.5±0.7mm2, p<0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, p<0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm2 vs. 1.0±0.4mm2, p<0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, p<0.001) were reduced in the α-LA coated stent group compared to the control stent group.Conclusionsα-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC

Interaction between the p75 neurotrophin receptor and a novel adaptor protein

The neurotrophin plays an important role in the development, differentiation and survival of the nervous system in vertebrates. It exerts its cellular effects through two different receptors, the Trk receptor tyrosine kinase neurotrophin receptor and the p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. Trk and p75 neurotrophin receptors utilize specific target proteins to transmit signals into the cell. An ankyrin-rich membrane spanning protein (ARMS) was identified as a new p75 interacting protein and serves as a novel downstream target of p75 neurotrophin receptor. We sought to delineate the interaction between p75 and ARMS by deletion constructs of p75 and green fluorescent protein (GFP)-tagged ARMS. We examined the interaction between these two proteins after overexpressing them in HEK-293 cells. Using both Western blot analysis and immunocytochemistry followed by confocal laser scanning microscopy, we found out that the intracellular domain of the p75 neurotrophin receptor was important for the interaction with ARMS. The results from this study suggest that ARMS may play an important role for mediating the signals from p75 neurotrophin receptor into the cell