Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies

PurposeAcute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies.MethodsWe retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam® and/or Tornado® coils.ResultsThe patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications.ConclusionSAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions

LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.Peer reviewe

Clinical Implication of Serum Adiponectin Levels in Adult Patients with Atopic Dermatitis

Atopic dermatitis (AD) is characterized by chronic, relapsing, pruritic inflammatory skin disease. Adiponectin has been reported to have anti-inflammatory effects not only on metabolic disorders but also on various inflammatory disorders. The study aimed to validate adiponectin as a potential biomarker for AD disease severity and treatment response. Seventy-five patients with AD and 28 healthy volunteers were enrolled in the study. Patient information, including Eczema Area and Severity Index (EASI) scores and pruritus numeric rating scales (NRSs), were collected. An enzyme linked immunosorbent assay (ELISA) was conducted to measure levels of serum adiponectin. Additionally, sera of patients treated with dupilumab were collected and measured at 16 and 52 weeks from baseline. Serum adiponectin levels were significantly lower in moderate and severe AD patients than in the control and mild AD patients. Serum adiponectin level was negatively correlated with the EASI score and pruritus NRS. However, no significant changes were observed according to biologic treatment for AD. Low serum adiponectin levels are associated with moderate to severe AD, suggesting a potential role for adiponectin as a biomarker for severity assessment of AD

An evaluation of the neonatal immune system using a listeria infection model

BACKGROUND: T helper 1 (Th1)/T helper 2 (Th2)-biased cytokine regulation may be another reason that neonates are much more susceptible to infectious disease than are adults. OBJECTIVES: We attempted to determine the ability of neonatal mice to direct the Th1 phenotype against Listeria monocytogenes (LM), because LM, an intracellular Gram-positive bacterium, induces profound cellular immunity by Th1 cells in vivo. METHODS: In order to determine whether neonatal mice evidence strong Th1 activity during LM infection, neonatal mice were compared with adult mice with regard to susceptibility to LM, cytotoxic T lymphocyte activity, and cytokine profiles. Neonatal gene profiles relevant to Th1 and Th2 differentiation during LM infection were also compared between neonatal and adult mice, via real-time PCR and RT-PCR. RESULTS: Neonatal mice were found to be far more susceptible to LM infection than adult mice, due to a lack in the induction of cytotoxic T cell activity, coupled with poor IFN-gamma secretion. Further, LM-infected neonatal mice evidenced much lower levels of expression of Th1-type immune components, including IL-12, IFN-gamma, Delta-4 and T-bet, as compared to those features in adult mice. These results may be due to the comparably lower expressions of mannose-bind lectins and some of toll-like receptors (TLRs) such as TLR-5, -6 and -9, necessary mediators to develop Th1 immune responses. CONCLUSIONS: Neonatal mice may not mount an adequate Th1 type immune response due to a significantly lower expression of Th1-type immune components as compared to adult mice, even when forced into a Th1-prone environment

Regulation of dendritic spines, spatial memory, and embryonic development by the TANC family of PSD-95-interacting proteins

PSD-95 (postsynaptic density-95) is thought to play important roles in the regulation of dendritic spines and excitatory synapses, but the underlying mechanisms have not been fully elucidated. TANC1 is a PSD-95-interacting synaptic protein that contains multiple domains for protein-protein interactions but whose function is not well understood. In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. Overexpression of TANC1 and TANC2 in cultured neurons increases the density of dendritic spines and excitatory synapses in a manner that requires thePDZ(PSD-95/Dlg/ZO-1)-binding C termini of TANC proteins. TANC1-deficient mice exhibit reduced spine density in the CA3 region of the hippocampus, but not in the CA1 or dentate gyrus regions, and show impaired spatial memory. TANC2 deficiency, however, causes embryonic lethality. These results suggest that TANC1 is important for dendritic spine maintenance and spatial memory, and implicate TANC2 in embryonic development.This work was supported by the Korea Science Foundation grant (to S.Y.C.; 313-2007-2-C00630), the Basic Science Research Program (to Y.C.B.; R13-2008-009-01001-0), and the National Creative Research Initiative Program (to E.K.) from the Korean Ministry of Education, Science, and Technology

Regulation of Dendritic Spines, Spatial Memory, and Embryonic Development by the TANC Family of PSD-95-Interacting Proteins

PSD-95 (postsynaptic density-95) is thought to play important roles in the regulation of dendritic spines and excitatory synapses, but the underlying mechanisms have not been fully elucidated. TANC1 is a PSD-95-interacting synaptic protein that contains multiple domains for protein-protein interactions but whose function is not well understood. In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. Overexpression of TANC1 and TANC2 in cultured neurons increases the density of dendritic spines and excitatory synapses in a manner that requires the PDZ (PSD-95/Dlg/ZO-1)-binding C termini of TANC proteins. TANC1-deficient mice exhibit reduced spine density in the CA3 region of the hippocampus, but not in the CA1 or dentate gyrus regions, and show impaired spatial memory. TANC2 deficiency, however, causes embryonic lethality. These results suggest that TANC1 is important for dendritic spine maintenance and spatial memory, and implicate TANC2 in embryonic development.This work was supported by the Korea Science Foundation grant (to S.Y.C.; 313-2007-2-C00630), the Basic Science Research Program (to Y.C.B.; R13-2008-009-01001-0), and the National Creative Research Initiative Program (to E.K.) from the Korean Ministry of Education, Science, and Technology. A part of this work was technically supported by the core facility service of the 21C Frontier Brain Research Center (M103KV010023-07K2201-02510).