To study the biology of the endothelium and the media of the vascular wall, full layer vascular wall model was constructed in vitro. In the experimental vascular wall model, endothelial cell (EC)s were grown on a collagen lattice containing multilayers of smooth muscle cell (SMC)s and a EC-free portion was made by a cloning ring on the culture disc. As conditioned culture media of ECs-SMCs contain biologic mediators that may promote the growth of SMCs, the availability of this vascular wall model promptly us to examine the extent to which ECs regulate the migration and proliferation of SMCs when these cells are maintained with or without covering EC lining in coculture. Morphologic characteristics of full layer vascular wall model was a whitish, non-transparent membrane. Outer boundaries and the zone of no EC were thicker than that of central portion. By light microscope imaging, luminal surface was composed of EC monolayer, and SMCs and collagen fibers were distributed between the polyethylene terephtalate (PET) membrane and EC monolayer. SMCs and collagen fibers were mainly located near the PET membrane. Venous SMCs were densely infiltrated as compared to arterial SMCs. By scanning electron microscopy, EC monolayer and dense collagen fibers in the zone of no EC were clearly shown. On the effects of platelet derived growth factor (PDGF) in the proliferation of SMCs and modeling of full layer vascular wall model, no effect on SMC in the zone of EC covering was seen however, active migration and proliferation of SMCs were noted in the zone of no EC. Wall thickness was two times greater than that of control. On the effects of EGF, it was observed that EGF markedly stimulated migration of SMCs with or without EC coverings in contrast to the control group. On the effects of FGF, results were similar to the PDGF group. Results on the effect of IGF-1 were similar to the PDGF group. As conclusions, full layer vascular wall model in this study was proved to be a good laboratory model for basic vascular research. And SMCs migration and proliferation were more active in venous SMCs compared to arterial SMCs. The collagen fibers were also richer and the wall was more thickened. EGF was most the potent SMC stimulator. PDGF, FGF, and IGF-1 were moderate SMC stimulator in the zone of no EC covering. These results strongly support why intimal hyperplasia eventually occured in autogenous venous bypass graft.
Biology ; Clone Cells ; Cloning, Organism ; Coculture Techniques ; Collagen ; Culture Media, Conditioned ; Endothelial Cells ; Endothelium ; Epidermal Growth Factor ; Hyperplasia ; Insulin-Like Growth Factor I ; Membranes ; Microscopy, Electron, Scanning ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Phenobarbital ; Platelet-Derived Growth Factor ; Polyethylene ; Transplants

Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3Rmutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis.Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective death of motor neurons in the central nervous system. The main cause of the disease remains elusive, but several mutations have been associated with the disease process. In particular, mutant superoxide dismutase 1 (SOD1) protein causes oxidative stress by activating glia cells and contributes to motor neuron degeneration. KCHO-1, a novel herbal combination compound, contains 30% ethanol and the extracts of nine herbs that have been commonly used in traditional medicine to prevent fatigue or inflammation. In this study, we investigated whether KCHO-1 administration could reduce oxidative stress in an ALS model. KCHO-1 administered to ALS model mice improved motor function and delayed disease onset. Furthermore, KCHO-1 administration reduced oxidative stress through gp91(phox) and the MAPK pathway in both classically activated microglia and the spinal cord of hSOD1(G93A) transgenic mice. The results suggest that KCHO-1 can function as an effective therapeutic agent for ALS by reducing oxidative stress.
Amyotrophic Lateral Sclerosis* ; Animals* ; Central Nervous System ; Ethanol ; Fatigue ; Inflammation ; Medicine, Traditional ; Mice ; Mice, Transgenic ; Microglia ; Models, Animal* ; Motor Neurons ; Neurodegenerative Diseases ; Neuroglia ; Oxidative Stress* ; Spinal Cord ; Superoxide Dismutase

This study investigated the spectrum of chromosomal abnormalities in 325 leukemia patients and developed optimal profiles of leukemic fusion genes for multiplex RT-PCR. We prospectively analyzed blood and bone marrow specimens of patients with acute leukemia. Twenty types of chromosomal abnormalities were detected in 42% from all patients by commercially available multiplex RT-PCR for detecting 28 fusion genes and in 35% by cytogenetic analysis including FISH analysis. The most common cytogenetic aberrations in acute myeloid leukemia patients was PML/PARA, followed by AML1/MGT8 and MLL1, and in acute lymphoid leukemia patients was BCR/ABL, followed by TEL/AML1 and MLL1 gene rearrangement. Among the negative results for multiplex RT-PCR, clinically significant t(3;3)(q21;q26.2), t(8;14)(q24;q32) and i(17)(q10) were detected by conventional cytogenetics. The spectrum and frequency of chromosomal abnormalities in our leukemia patients are differed from previous studies, and may offer optimal profiles of leukemic fusion genes for the development of new molecular detection systems.
Adaptor Proteins, Signal Transducing/genetics ; Adult ; Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 8 ; Core Binding Factor Alpha 2 Subunit/genetics ; Female ; Fusion Proteins, bcr-abl/genetics ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia/diagnosis/*genetics ; Leukemia, Myeloid, Acute/diagnosis/genetics ; Male ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein/genetics ; Oncogene Proteins, Fusion/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics ; Reverse Transcriptase Polymerase Chain Reaction

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.
Adolescent ; Anemia, Hemolytic ; Autoantibodies ; Child ; Endothelial Cells ; Humans ; Immunoglobulin G ; Plasma ; Plasma Exchange ; Purpura ; Purpura, Thrombotic Thrombocytopenic ; Steroids ; Thrombocytopenia ; Thrombotic Microangiopathies ; Thymine Nucleotides

BACKGROUND: Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. METHODS: Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. RESULTS: Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. CONCLUSIONS: Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.
Adolescent ; Carrier Proteins/*genetics ; Child ; Child, Preschool ; Cohort Studies ; Cytogenetic Analysis ; DNA Mutational Analysis ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Leukemia, Myeloid, Acute/*genetics/pathology ; Male ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Polymorphism, Single Nucleotide ; RNA Splicing ; Ribonucleoprotein, U2 Small Nuclear/*genetics ; Ribonucleoproteins/*genetics

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children younger than 4 years and is characterized by microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. HUS associated with diarrheal prodrome is usually caused by Shiga toxin-producing Escherichia coli O157:H7 or by Shigella dysenteriae, which generally has a better outcome. However, atypical cases show a tendency to relapse with a poorer prognosis. HUS has been reported to be associated with acute lymphoblastic leukemia (ALL) in children. The characteristics and the mechanisms underlying this condition are largely unknown. In this study, we describe the case of an 11-year-old boy in whom the diagnosis of ALL was preceded by the diagnosis of atypical HUS. Thus, patients with atypical HUS should be diagnosed for the possibility of developing ALL.
Acute Kidney Injury ; Anemia, Hemolytic ; Child ; Hemolytic-Uremic Syndrome ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Shiga-Toxigenic Escherichia coli ; Shigella dysenteriae ; Thrombocytopenia

No abstract available.
Humans ; Leukemia, Promyelocytic, Acute* ; Teratoma*

Though diagnosis of myelopathy can be easily made by history and neurological examination, modern technologies, such as MRI and evoked potential study (EPS), have played an important role in making the anatomical and pathological diagnosis of myelopathy. To assess the accuracy of clinical diagnosis and the role of the laboratory studies, we prospectively studied 26 patients with myelopathy, admitted to S.N.U.H. We tried to decide, by clinical history and examination, the anatomical location and the pathological diagnosis, and compared them with final diagnosis. 1. The final diagnosis could be made in 23 out of 26 patients. 2. Of 17 patients with the initial clinical diagnosis of intramedullary lesion (IML), two patients turned out to have extramedullary lesions (EML). Final diagnosis could not be made in three patients, and imaging studies and EPS didn't reveal definite local lesions. In another group of nine patients with the initial clinical diagnosis of EML, three patients had IML. 3. The clinically suspected levels of lesions were shown to be accurate within one level in 20 out of 26 patients after MRI. 4. Clinical diagnosis was accurate in 18 out of 26 patients. 5. Among the laboratory tests, MRI helped localize the lesions and make the final diagnosis. EPS was most helpful in making a diagnosis of multiple sclerosis by finding out asymptomatic second lesions. Even with thorough work-up the etiologies of myelopathy in three patients could not be elucidated. 6. Review of wrong diagnosis showed that diagnostic errors were attributed to incomplete history taking or examination, misinterpretation of clinical data, and unusual presentations or unsuspected rare diseases. Therefore, the authors conclude that the physician's clinical examinations in the diagnosis of neurologic diseases are still valuable despite the technology of the laboratory studies is developing further in present days.
Diagnosis ; Diagnostic Errors ; Evoked Potentials ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis ; Neurologic Examination* ; Prospective Studies ; Rare Diseases ; Spinal Cord Diseases

PURPOSE: Pericentric inv (9) occurs in about 0.8~2% of the normal population. The implication of inv (9) in hematological malignancies and/or in stem cell transplantation (SCT) has not been thoroughly elucidated. METHODS: To further delineate the characteristics, we describe our experiences of inv (9) in 2 patients who underwent SCTs and 1 patient with ALL. RESULTS: Case 1. An 11-year-old girl with AML M2 showed 46, XX, inv (9). After remission, her consolidation cycles were associated with slow platelet recovery. She underwent autologous BMT, however, the engraftment was rather slow, and relapsed at 7 months. 2nd remission was achieved after prolonged cytopenia. She underwent reduced intensity unrelated cord blood transplant. Her posttransplant course was uneventful with ANC & gt; 500/microL at D+18 and platelet > 50 k/microL at D+38. Karyotyping showed 46, XY. She is now well at 16 months after 2nd transplant. Case 2. A 10-year-old girl presented with severe aplastic anemia. Karyotyping was normal. She underwent matched sibling transplantation. Her post-transplant course was uneventful with rapid engraftment. Cytogenetics showed 46, XX, inv (9), which was originated from her sister. She is now well at 70 months posttransplant. Case 3. A 3-year-old boy with ALL had a karyotype of 46, XY, inv (9) (p11q12). His clinical course was uneventful. CONCLUSION: The first case showed typical course of delayed recovery after chemotherapy and delayed engraftment after autologous transplantation. inv (9) should be considered in cases of otherwise unexplainable delay in recovery after chemotherapy or delayed engraftment after SCT. Further studies involving larger number of cases should be warranted to delineate the exact role of inv (9) in pediatric leukemia and SCTs.
Anemia, Aplastic ; Autografts ; Blood Platelets ; Child ; Child, Preschool ; Chromosomes, Human, Pair 9* ; Cytogenetics ; Drug Therapy ; Female ; Fetal Blood ; Hematologic Neoplasms ; Humans ; Karyotype ; Karyotyping ; Leukemia* ; Male ; Siblings ; Stem Cell Transplantation* ; Stem Cells* ; Transplantation, Autologous