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    7857 results match your criteria Severe Combined Immunodeficiency

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    Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer.
    Cancer Cytopathol 2018 Apr 25. Epub 2018 Apr 25.
    Sexually Transmitted Infection/Human Immunodeficiency Virus Unit, San Gallicano Dermatological Institute, IFO-IRCCS, Rome, Italy.
    Background: Anal cytology may be useful for evaluating lesions associated with human papillomavirus (HPV) in individuals at increased risk for anal cancer.

    Methods: Liquid-based cytology was used to assess anal cytological lesions among human immunodeficiency virus (HIV)-infected and HIV-uninfected men who have sex with men (MSM). The Linear Array HPV genotyping test was used for HPV detection. Read More

    Adenosine deaminase deficiency: a review.
    Orphanet J Rare Dis 2018 Apr 24;13(1):65. Epub 2018 Apr 24.
    Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
    Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, leading to adenosine deaminase-deficient severe combined immunodeficiency. Whilst most notable affects are on lymphocytes, other manifestations include skeletal abnormalities, neurodevelopmental affects and pulmonary manifestations associated with pulmonary-alveolar proteinosis. Affected patients present in early infancy, usually with persistent infection, or with pulmonary insufficiency. Read More

    Dysregulation of Epstein-Barr virus infection in hypomorphic ZAP70 mutation.
    J Infect Dis 2018 Apr 19. Epub 2018 Apr 19.
    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
    Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes.

    Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. Read More

    Utility of DNA, RNA, Protein, and Functional Approaches to Solve Cryptic Immunodeficiencies.
    J Clin Immunol 2018 Apr 18. Epub 2018 Apr 18.
    Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
    Purpose: We report a female infant identified by newborn screening for severe combined immunodeficiencies (NBS SCID) with T cell lymphopenia (TCL). The patient had persistently elevated alpha-fetoprotein (AFP) with IgA deficiency, and elevated IgM. Gene sequencing for a SCID panel was uninformative. Read More

    Droplet Digital PCR-Based Chimerism Analysis for Primary Immunodeficiency Diseases.
    J Clin Immunol 2018 Apr 18. Epub 2018 Apr 18.
    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
    Objective: In the current study, we aimed to accurately evaluate donor/recipient or male/female chimerism in samples from patients who underwent hematopoietic stem cell transplantation (HSCT).

    Methods: We designed the droplet digital polymerase chain reaction (ddPCR) for SRY and RPP30 to detect the male/female chimerism. We also developed mutation-specific ddPCR for four primary immunodeficiency diseases. Read More

    Defective immuno- and thymoproteasome assembly causes severe immunodeficiency.
    Sci Rep 2018 Apr 13;8(1):5975. Epub 2018 Apr 13.
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstr. 30, 81675, Munich, Germany.
    By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results in the single amino acid exchange G170W in multicatalytic endopeptidase complex subunit-1 (MECL-1), the β2i-subunit of the immuno- and thymoproteasome. Yeast mutagenesis and crystallographic data suggest that the severe TUB6-phenotype compared to the MECL-1 knockout mouse is caused by structural changes in the C-terminal appendage of β2i that prevent the biogenesis of immuno- and thymoproteasomes. Read More

    Impact of TGF-β family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients.
    Eur Cell Mater 2018 Apr 13;35:209-224. Epub 2018 Apr 13.
    Department of Health Sciences, University of Jaén, Jaén E-23071, Spain.mperan@ ujaen.es.
    The success of cell-based approaches for the treatment of cartilage defects requires an optimal autologous cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. The objective of this study was to compare the chondrogenic capacity of mesenchymal stem cells (MSCs) isolated from lipoaspirates (ASCs) and the infrapatellar fat pad (IFPSCs) of osteoarthritic patients and treated with transforming growth factor (TGF)-β family-related growth factors. Cells were cultured for 6 weeks in a 3D pellet culture system with the chimeric activin A/bone morphogenic protein (BMP)-2 ligand (AB235), the chimeric nodal/BMP-2 ligand (NB260) or BMP-2. Read More

    [Cannabinoid therapy in practice].
    Urologe A 2018 Apr 12. Epub 2018 Apr 12.
    Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Bonn, Bonn, Deutschland.
    Background: In recent years, the media and scientists have shown increased interest in cannabis-based drugs.

    Objectives: Background information about cannabis-based drugs and their mechanism of action as well as discussion of possible applications as supportive therapy or in palliative medicine, respectively, are presented.

    Materials And Methods: The recent literature was examined and evaluated. Read More

    Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID.
    Orphanet J Rare Dis 2018 Apr 6;13(1):49. Epub 2018 Apr 6.
    GlaxoSmithKline, Brentford, Middlesex, UK.
    Background: Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. Existing primary immunodeficiency registries are tailored to transplantation outcomes and do not capture the breadth of safety and efficacy endpoints required by the EMA for the long-term monitoring of gene therapies. Furthermore, for extended monitoring of Strimvelis, the young age of children treated, small patient numbers, and broad geographic distribution of patients all increase the risk of loss to follow-up before sufficient data have been collected. Read More

    Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system.
    Stem Cell Res Ther 2018 Apr 6;9(1):92. Epub 2018 Apr 6.
    State Key Laboratory of Experimental Hematology, Key Laboratory of Gene Therapy of Blood Diseases, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
    Background: Replacement therapy for hemophilia remains a lifelong treatment. Only gene therapy can cure hemophilia at a fundamental level. The clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) system is a versatile and convenient genome editing tool which can be applied to gene therapy for hemophilia. Read More

    Bevacizumab Promotes T-Cell-Mediated Collagen Deposition in the Mouse Model of Conjunctival Scarring.
    Invest Ophthalmol Vis Sci 2018 Mar;59(3):1682-1692
    Singapore Eye Research Institute, Singapore.
    Purpose: We determine the effects of bevacizumab on collagen production in a mouse model of conjunctival scarring.

    Methods: Experimental surgery was performed as described for the mouse model of conjunctival scarring, and bevacizumab was introduced by conjunctival injection. The capacity of bevacizumab to recognize conjunctival VEGF-A was determined by ELISA. Read More

    X-Linked Severe Combined Immunodeficiency and Hepatoblastoma: A Case Report and Review of Literature.
    J Pediatr Hematol Oncol 2018 Apr 3. Epub 2018 Apr 3.
    Pediatric Department, Paediatric Oncology Unit, Universitary Regional Málaga Hospital.
    Severe combined immunodeficiency is an inherited disease with profoundly defective T cells, B cells, and natural killer cells. X-linked severe combined immunodeficiency is the most common form. In this report, we describe a 4-month-old male infant who was admitted to our hospital with progressive breathlessness and abdominal mass. Read More

    Fatal P. jirovecii and Cytomegalovirus Infections in an Infant with Normal Trecs Count: Pitfalls of Newborn Screening for Severe Combined Immunodeficiency.
    Pediatr Infect Dis J 2018 Apr 2. Epub 2018 Apr 2.
    Paediatric Infectious Diseases, Rheumatology and Immunodeficiencies Department, Hospital Infantil Universitario Virgen del Rocio. Instituto de Biomedicina (IBiS), Seville, Spain.
    Newborn screening (NBS) for severe combined immunodeficiency (SCID) using T-cell receptor-excision circles (TRECs) allows prompt diagnosis and initiation of supportive and curative therapy thereby reducing morbidity and mortality. However, profound combined immunodeficiencies with normal numbers of non-functional T cells will go undetected. We present a patient with ORAI1 deficiency and normal TREC numbers observed after diagnosis at the age of 14 months who suffered from disseminated fatal cytomegalovirus and Pneumocystis jirovecii infection, demonstrating a potential pitfall of the current NBS program. Read More

    Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome.
    Pediatrics 2018 Apr;141(Suppl 5):S408-S411
    Department of Dermatology, Case Western Reserve University, Cleveland, Ohio.
    We describe a case of Omenn syndrome displaying exudative erythroderma and other characteristic features, including alopecia, absent B and naïve T cells, hyper immunoglobulin E levels, and eosinophilia. A pathogenic recombination-activating homozygous genetic mutation confirmed the diagnosis. She required frequent antibiotics at both treatment and prophylactic doses, which alone did not control her erythroderma, but her high risk of infection precluded the use of systemic agents such as cyclosporine, which would further suppress her already severely compromised immune system. Read More

    Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.
    Mol Ther 2018 Mar 6. Epub 2018 Mar 6.
    Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address:
    X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RG gene editing with a vector that does not contain a functional promoter or IL2RG gene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rg cDNA at the endogenous Il2rg locus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4 and CD8 T cells. Read More

    HIV-associated neurocognitive disorder.
    Handb Clin Neurol 2018 ;152:75-97
    Departments of Neurology and HIV Medicine, St. Vincent's Hospital and Peter Duncan Neurosciences Unit, St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia. Electronic address:
    Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects roughly half the HIV-positive population. The symptoms of cognitive slowing, poor concentration, and memory problems can impact on everyday life. Its diagnosis is validated where possible by identifying deficits in two cognitive domains on neuropsychologic testing in patients either with or without symptoms. Read More

    Bacterial and Infections in the Lungs of Gene-Knockout Rabbits with Severe Combined Immunodeficiency.
    Front Immunol 2018 9;9:429. Epub 2018 Mar 9.
    Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI, United States.
    Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (-/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Read More

    Clinical considerations in the hematopoietic stem cell transplant management of primary immunodeficiencies.
    Expert Rev Clin Immunol 2018 Apr 11;14(4):297-306. Epub 2018 Apr 11.
    b Primary Immunodeficiency Group, Institute of Cellular Medicine , Newcastle University , Newcastle upon Tyne , UK.
    Introduction: Primary immunodeficiencies (PID) are genetic immune disorders causing increased predisposition to infections and autoimmunity. The only curative procedure is hematopoietic stem cell transplantation (HSCT), results from which have improved dramatically since 2000. Complications remain a serious issue, especially in HLA non-identical transplantation. Read More

    [Individualized Comprehensive Therapy for the Lung Cancer Patients 
with HIV Infection].
    Zhongguo Fei Ai Za Zhi 2018 Apr;21(4):327-332
    Department of Cerebral Surgery Public Health Clinical Center Affiliated, Shanghai 201508, China.
    Background: To observe clinical features, clinical stagings, types ofpathology, treatment options and clinical effects of patients suffer from HIV infection combined with lung cancer, and also to provide guidance for individualized comprehensive treatment of HIV combined with lung cancer.

    Methods: Through the retrospective analysis of 53 cases of HIV merger of lung cancer patients admitted in our department, 47 cases of non-small cell lung cancer (NSCLC), 6 cases of small cell lung cancer (SCLC), 24 cases accepted surgery combined chemotherapy, 22 patients with simple chemotherapy, 7 cases give up treatment; 28 cases are in stages I-III, 25 cases are in stage IV; 24 patients received combined chemotherapy in 28 patients with stages I-III, 2 cases gave up treatment, 2 cases with severe chronic obstructive pulmonary disease (COPD) could not tolerate chemotherapy plus surgery. According to the situation of patients before highly active anti-retroviral therapy (HAART) treatment, patients who received HAART before treatment were divided into observation group (n=27), patients who did not receive HAART were divided into control group (n=19). Read More

    Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia.
    J Clin Immunol 2018 Mar 21. Epub 2018 Mar 21.
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
    Purpose: Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2. Read More

    Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome.
    Front Immunol 2018 5;9:338. Epub 2018 Mar 5.
    Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    The activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes (encoding p110δ: APDS1 or PASLI-CD) and (encoding p85α: APDS2 or PASLI-R1). While the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe. Infections of the ears, sinuses, and upper and lower respiratory tracts are the earliest and most frequent manifestation of APDS, secondary to both respiratory viruses and to bacterial pathogens typical of defective B cell function. Read More

    Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites.
    Oncol Lett 2018 Apr 8;15(4):4849-4858. Epub 2018 Feb 8.
    Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Krakow, Poland.
    The three cell lines, designated as gastric cancer (GC)1401, GC1415 and GC1436 were derived from peritoneal effusions from patients with gastric adenocarcinoma. Cell lines were established in tissue culture and in immunodeficient, non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. All cell lines were cultured in Dulbecco's modified Eagle's medium supplemented with 5% fetal bovine serum. Read More

    A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing.
    J Microbiol Immunol Infect 2018 Mar 2. Epub 2018 Mar 2.
    Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:
    Background: Patients with severe combined immunodeficiency (SCID), which is caused by genetic defects in immune-related genes involved in the development or activation of the adaptive immune system, often died in infancy due to severe infections before definite molecular diagnosis could be made. Although recent improvement in early diagnosis has been achieved by newborn screening, the genetic basis of many of the patients is still unknown.

    Methods: Here we performed whole exome sequencing (WES) to investigate the underlying genetic causes of SCID in a proband identified with newborn screening. Read More

    Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India.
    Front Immunol 2018 16;9:188. Epub 2018 Feb 16.
    Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, India.
    Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4 T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Read More

    Integrity of IKK/NF-κB Shields Thymic Stroma That Suppresses Susceptibility to Autoimmunity, Fungal Infection, and Carcinogenesis.
    Bioessays 2018 Apr 9;40(4):e1700131. Epub 2018 Mar 9.
    Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, 21701, Maryland, USA.
    A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell-mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α (IKKα) is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic epithelial cells (mTECs) that facilitate the deletion of autoreactive T cells in the thymus. Read More

    Leukemia reconstitution in vivo is driven by cells in early cell cycle and low metabolic state.
    Haematologica 2018 Mar 8. Epub 2018 Mar 8.
    Ulm University Medical Center, Dpt. Pediatrics and Adolescent Medicine, Ulm, Germany
    In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations as defined by surface markers have shown equal abilities to reconstitute leukemia upon transplantation onto immunodeficient mice. Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, we have functionally characterized leukemia-initiating cells and found that cells in all cell cycle stages are able to reconstitute leukemia in vivo, with early cycling cells (G1blow population) exhibiting the highest leukemia-initiating potential. Read More

    [Clinical characteristics of human recombination activating gene 1 mutations in 8 immunodeficiency patients with diverse phenotypes].
    Zhonghua Er Ke Za Zhi 2018 Mar;56(3):186-191
    Department of Clinical Immunology, Children's Hospital of Fudan University, Shanghai 201102, China.
    To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes. Read More

    Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF.
    FEBS Open Bio 2018 Mar 4;8(3):426-434. Epub 2018 Feb 4.
    Institute of Clinical and Molecular Medicine (IKOM)Laboratory CenterNorwegian University of Science and TechnologyTrondheimNorway.
    DNA repair consists of several cellular pathways which recognize and repair damaged DNA. The classical nonhomologous DNA end-joining (NHEJ) pathway repairs double-strand breaks in DNA. It is required for maturation of both B and T lymphocytes by supporting V(D)J recombination as well as B-cell differentiation during class switch recombination (CSR). Read More

    High Rates of Positive Severe Combined Immunodeficiency Screening Among Newborns with Severe Intestinal Failure.
    JPEN J Parenter Enteral Nutr 2018 Jan 13;42(1):239-246. Epub 2017 Dec 13.
    Center for Advanced Intestinal Rehabilitation, Boston Children's Hospital, Boston, MA, USA.
    Purpose: Severe combined immunodeficiency (SCID) screening by T-cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA-CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes. Read More

    Antigen Loading (e.g., Glutamic Acid Decarboxylase 65) of Tolerogenic DCs (tolDCs) Reduces Their Capacity to Prevent Diabetes in the Non-Obese Diabetes (NOD)-Severe Combined Immunodeficiency Model of Adoptive Cotransfer of Diabetes As Well As in NOD Mice.
    Front Immunol 2018 16;9:290. Epub 2018 Feb 16.
    SOTIO a s., Prague, Czechia.
    Tolerogenic DCs (tolDCs) are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D). T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e. Read More

    Safety and Efficacy of Epigenetically Converted Human Fibroblasts Into Insulin-Secreting Cells: A Preclinical Study.
    Adv Exp Med Biol 2018 Mar 3. Epub 2018 Mar 3.
    Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, Milan, Italy.
    Type 1 Diabetes Mellitus (T1DM) is a chronic disease that leads to loss of insulin secreting β-cells, causing high levels of blood glucose. Exogenous insulin administration is not sufficient to mimic the normal function of β-cells and, consequently, diabetes mellitus often progresses and can lead to major chronic complications and morbidity. The physiological control of glucose levels can only be restored by replacing the β-cell mass. Read More

    A Novel Approach to the Treatment of Plasma Protein Deficiency: Ex Vivo-Manipulated Adipocytes for Sustained Secretion of Therapeutic Proteins.
    Chem Pharm Bull (Tokyo) 2018 ;66(3):217-224
    Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba University.
    Despite the critical need for lifelong treatment of inherited and genetic diseases, there are no developmental efforts for most such diseases due to their rarity. Recent progress in gene therapy, including the approvals of two products (Glybera and Strimvelis) that may provide patients with sustained effects, has shed light on the development of gene therapy products. Most gene therapy products are based on either adeno-associated virus-mediated in vivo gene transfer to target tissues or administration of ex vivo gene-transduced hematopoietic cells. Read More

    Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models.
    Int J Radiat Oncol Biol Phys 2018 Mar 6;100(4):1044-1056. Epub 2017 Dec 6.
    Department for Radiation Oncology, Ambulatory Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Purpose: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models.

    Methods And Materials: A total of 1 × 10 human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Read More

    Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors.
    Biochem Biophys Res Commun 2018 03 17;497(2):719-725. Epub 2018 Feb 17.
    Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Kyoto, 6068507, Japan. Electronic address:
    AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Read More

    Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle.
    Exp Cell Res 2018 Mar 16;364(2):217-223. Epub 2018 Feb 16.
    Sorbonne Université, INSERM, CNRS, Center for Research in Myology, Institute of Myology, F-75013, Paris, France.
    Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C. Read More

    First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature.
    Front Immunol 2018 2;9:113. Epub 2018 Feb 2.
    San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Pediatric Immunohematology and Bone Marrow Transplantation Unit, Scientific Institute San Raffaele (IRCCS), Milan, Italy.
    Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. Read More

    Intestinal immunity suppresses carrying capacity of rats for the model tapeworm, Hymenolepis diminuta.
    Parasitol Int 2018 Feb 12;67(4):357-361. Epub 2018 Feb 12.
    Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Japan.
    Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is recognized as a useful model for the analysis of cestode-host interactions. In this study, we analyzed factors affecting the biomass of the tapeworm through use of rat strains carrying genetic mutations, namely X-linked severe combined immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats after infection with 5 cysticercoids was much larger than control F344 rats from 3 to 8 weeks. Read More

    Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety.
    Mol Ther 2018 Mar 4;26(3):917-931. Epub 2018 Jan 4.
    San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132; Vita-Salute San Raffaele University, Milan, Italy, 20132. Electronic address:
    Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34-enriched cell fraction that contains CD34 cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Read More

    Critical intestinal cells originate from the host in enteroid-derived tissue-engineered intestine.
    J Surg Res 2018 Mar 28;223:155-164. Epub 2017 Nov 28.
    Department of General Pediatric Surgery, Nationwide Children's Hospital, Columbus, Ohio. Electronic address:
    Background: Enteroid-derived tissue-engineered intestine (TEI) contains intestinal subepithelial myofibroblasts (ISEMFs) and smooth muscle cells (SMCs). However, these cell types are not present in the donor enteroids. We sought to determine the origin of these cell types and to quantify their importance in TEI development. Read More

    The anti-osteosarcoma cell activity by a mTORC1/2 dual inhibitor RES-529.
    Biochem Biophys Res Commun 2018 03 9;497(2):499-505. Epub 2018 Feb 9.
    Department of Orthopaedics, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China. Electronic address:
    mTOR over-activation is important for human osteosarcoma (OS) tumorigenesis and progression. RES-529 is a mTORC1/2 dual inhibitor. Here, our results show that RES-529 inhibited viability, cell cycle progression and proliferation of the established (U2OS line) and primary human OS cells. Read More

    T-cell receptor excision circle levels and safety of paediatric immunization: A population-based self-controlled case series analysis.
    Hum Vaccin Immunother 2018 Feb 8:1-14. Epub 2018 Feb 8.
    b School of Epidemiology and Public Health, University of Ottawa , Ottawa , Canada.
    T-cell receptor excision circle levels are a surrogate marker of T-cell production and immune system function. We sought to determine whether non-pathological levels of infant T-cell receptor excision circles were associated with adverse events following immunization. A self-controlled case series design was applied on a sample of 231,693 children who completed newborn screening for severe combined immunodeficiency in Ontario, Canada between August 2013 and December 2015. Read More

    2'-Fluoro-6'-methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti-HBV agent, active against drug-resistant HBV mutants.
    Med Res Rev 2018 May 6;38(3):977-1002. Epub 2018 Feb 6.
    Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.
    Chronic hepatitis B (CHB) is one of the major causes of morbidity and mortality worldwide. Currently, clinically approved nucleos(t)ide analogs (NAs) are very efficient in reducing the load of hepatitis B virus (HBV) with minimum side effects. However, the long-term administration of antiviral drugs promotes HBV for potential drug resistance. Read More

    Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells.
    Int J Mol Med 2018 Apr 23;41(4):2201-2212. Epub 2018 Jan 23.
    Department of Reproductive Μedicine, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
    Intrauterine adhesions (IUA) are associated with the loss of stem cells in the endometrium. Menstrual blood‑derived stem cells (MenSCs) can be isolated from the menstrual blood and differentiated into endometrial cells. To check the transplantation feasibility of MenSCs for the treatment of severe IUA, MenSCs were isolated from menstrual blood, cultured in Dulbecco's modified Eagle's medium (DMEM), identified by immunocytochemistry and flow cytometry, differentiated into endometrial cells in vitro, and finally transplanted into the axillary subcutaneous tissue of non‑obese diabetic/severe combined immunodeficiency (NOD‑SCID) mice to create endometrial tissue. Read More

    Identification of IL2RG and CYBB mutations in two Chinese primary immunodeficiency patients by whole-exome sequencing.
    Immunol Invest 2018 Apr 1;47(3):221-228. Epub 2018 Feb 1.
    c Joy Orient Translational Medicine Research Center Co., Ltd , Beijing , China.
    Background: Primary immunodeficiency diseases are a group of genetic disorders that lead to increased propensity to a variety of infections, sometimes with fatal outcomes.

    Method: In this study, whole-exome sequencing (WES) was used to identify mutations in two patients suspected of having primary immunodeficiency. Sanger sequencing was used to confirm the results in the patients and their family. Read More

    Rare Clinical Presentation of Tuberculous Meningitis: A Case Report.
    Malays J Med Sci 2017 Oct 26;24(5):119-123. Epub 2017 Oct 26.
    Department of Medicine, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
    Introduction: Tuberculosis is the second leading cause of death under the category of infectious diseases, after the human immunodeficiency virus (HIV). Tuberculous meningitis (TBM) constitutes about 5% of all extrapulmonary disease worldwide. This report describes a case of Tuberculous meningitis with rare presentation in a 28-year-old woman, who was treated based on a collection of her social background, clinical findings and Multiplex PCR of tuberculosis. Read More

    Modeling Idiopathic Pulmonary Fibrosis in Humanized Severe Combined Immunodeficient Mice.
    Am J Pathol 2018 Apr 17;188(4):891-903. Epub 2018 Feb 17.
    Women's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:
    Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown etiopathogenesis with limited therapeutic options. IPF is characterized by an abundance of fibroblasts and loss of epithelial progenitors, which cumulates in unrelenting fibrotic lung remodeling and loss of normal oxygenation. IPF has been challenging to model in rodents; nonetheless, mouse models of lung fibrosis provide clues as to the natural progression of lung injury and remodeling, but many have not been useful in predicting efficacy of therapeutics in clinical IPF. Read More

    A comparative global phosphoproteomics analysis of obinutuzumab (GA101) versus rituximab (RTX) against RTX sensitive and resistant Burkitt lymphoma (BL) demonstrates differential phosphorylation of signaling pathway proteins after treatment.
    Oncotarget 2017 Dec 9;8(69):113895-113909. Epub 2017 Dec 9.
    Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
    We recently demonstrated that obinutuzumab (GA101), a novel glycoengineered type II CD20 Ab compared to rituximab (RTX) mediates significantly enhanced antibody-dependent cell cytotoxicity (ADCC) and increased overall survival in a Burkitt lymphoma (BL) xenograft non-obese diabetic severe combined immunodeficiency gamma (NSG) model. In this study we compared the phosphoproteomic changes by pathway analysis following obinutuzumab vs RTX against RTX-sensitive (Raji) and -resistant BL (Raji4RH). Phosphoproteomic analyses were performed by mass-spectrometry (MS)-based label-free quantitative phosphoproteomic profiling. Read More

    Norovirus causing severe gastrointestinal disease following allogeneic hematopoietic stem cell transplantation: A retrospective analysis.
    Transpl Infect Dis 2018 Apr 26;20(2):e12847. Epub 2018 Feb 26.
    Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Background: Norovirus (NV) can cause chronic and severe gastroenteritis with possible lethal outcome in immunocompromised patients. The knowledge of NV infections in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is limited. The aim of this study was to clarify the clinical importance of NV in a large cohort of HSCT recipients. Read More

    Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.
    Stem Cell Res Ther 2018 Jan 22;9(1):12. Epub 2018 Jan 22.
    Department of Biochemistry, Tokyo Dental College, Tokyo, Japan.
    Background: Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Read More

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