Michael Steven Hershfield

Journal Article J Allergy Clin Immunol · August 23, 2024 BACKGROUND: Deficiency of adenosine deaminase (ADA or ADA1) has broad clinical and genetic heterogeneity. Screening techniques can identify asymptomatic infants whose phenotype and prognosis are indeterminate, and who may carry ADA variants of unknown sign ... Full text Link to item Cite

Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.

Journal Article J Clin Immunol · April 27, 2024 PURPOSE: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hemato ... Full text Link to item Cite

Comparison of disease phenotypes and mechanistic insight on causal variants in patients with DADA2.

Journal Article The Journal of allergy and clinical immunology · September 2023 BackgroundDeficiency of adenosine deaminase 2 (DADA2) results in heterogeneous manifestations including systemic vasculitis and red cell aplasia. The basis of different disease phenotypes remains incompletely defined.ObjectiveWe sought to ... Full text Cite

Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience.

Journal Article J Allergy Clin Immunol Pract · June 2023 BACKGROUND: ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein. OBJ ... Full text Link to item Cite

Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement.

Journal Article JAMA Netw Open · May 1, 2023 IMPORTANCE: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more co ... Full text Link to item Cite

Case Report: Deficiency of Adenosine Deaminase 2 (DADA2) as a Cause of Brainstem Stroke in a 3-Year-Old Girl and the Importance of Early Fast-Track Genetic Diagnostics to Influence Therapy.

Journal Article Neuropediatrics · December 2022 Deficiency of adenosine deaminase 2 (DADA2) is a rare Mendelian, autoinflammatory multiorgan disease. We report the case of a 3.8-year-old female patient who was admitted with an acute brainstem stroke and was diagnosed with DADA2 by early initiation of ex ... Full text Link to item Cite

Newborn tandem mass spectroscopy screening for adenosine deaminase deficiency.

Journal Article Ann Allergy Asthma Immunol · December 2022 BACKGROUND: Newborn screening (NBS) by means of T cell receptor excision circles (TREC) is now universal in the United States, Puerto Rico, and the Navajo Nation as a strategy to identify severe combined immunodeficiency (SCID) in newborns. Owing to the ch ... Full text Link to item Cite

Correction to: Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Journal Article J Clin Immunol · October 2022 Full text Link to item Cite

Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC.

Journal Article Blood · August 18, 2022 Adenosine deaminase (ADA) deficiency causes ∼13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 patients with ADA-SCID ... Full text Link to item Cite

Common Variable Immunodeficiency in a Carrier of the ADA2 R169Q Variant: Coincidence or Causality?

Journal Article J Clin Immunol · July 2022 Full text Link to item Cite

Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.

Journal Article Adv Sci (Weinh) · April 2022 Protein therapeutics, except for antibodies, have a short plasma half-life and poor stability in circulation. Covalent coupling of polyethylene glycol (PEG) to protein drugs addresses this limitation. However, unlike previously thought, PEG is immunogenic. ... Full text Link to item Cite

Elucidating the pathogenesis of adenosine deaminase 2 deficiency: current status and unmet needs

Journal Article Expert opinion on orphan drugs · March 28, 2022 Introduction Humans have two adenosine deaminase isozymes, ADA1 and ADA2, which differ in affinity for their substrates, adenosine (Ado) and 2ʹdeoxyadenosine (dAdo), and their localization. Inherited deficiencies of ADA1 and ADA2 compromise different aspe ... Full text Open Access Cite

Elucidating the pathogenesis of adenosine deaminase 2 deficiency: current status and unmet needs

Response to: 'Total adenosine deaminase highly correlated with adenosine deaminase 2 activity in serum' by Gao et al.

Journal Article Ann Rheum Dis · February 2022 Full text Link to item Cite

Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach.

Journal Article J Allergy Clin Immunol · January 2022 BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by deleterious ADA2 variants. The frequency of these variants in the general population, and hence the expected disease prevalence, remain unknown. OBJECTIVE: We ... Full text Link to item Cite

Case Report: Consistent disease manifestations with a staggered time course in two identical twins affected by adenosine deaminase 2 deficiency.

Journal Article Front Immunol · 2022 Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including vasculitis, immunodeficiency, and hematologic manifestations, potentially progressing over time. The present st ... Full text Link to item Cite

Diagnosis of deficiency of adenosine deaminase type 2 in adulthood.

Journal Article Scand J Rheumatol · November 2021 Full text Link to item Cite

Intrinsic Defects in B Cell Development and Differentiation, T Cell Exhaustion and Altered Unconventional T Cell Generation Characterize Human Adenosine Deaminase Type 2 Deficiency.

Journal Article J Clin Immunol · November 2021 PURPOSE: Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodefic ... Full text Link to item Cite

Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency.

Conference Blood · October 2021 Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with ge ... Full text Cite

Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.

Journal Article J Clin Immunol · October 2021 PURPOSE: Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) through an accumulation of toxic metabolites within lymphocytes. Recently, ADA deficiency has been successfully treated using lentiviral-transduced autologous CD34 ... Full text Link to item Cite

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Journal Article J Clin Immunol · October 2021 PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages) ... Full text Link to item Cite

Deficiency of Adenosine Deaminase 2-a Monogenic Cause of Wunderlich Syndrome.

Journal Article J Clin Immunol · October 2021 Full text Link to item Cite

ADA2 deficiency (DADA2) associated with Evans syndrome and a severe ADA2 genotype.

Journal Article Rheumatology (Oxford) · July 1, 2021 Full text Link to item Cite

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.

Journal Article N Engl J Med · May 27, 2021 BACKGROUND: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency. METHODS: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom ... Full text Link to item Cite

Uncontrolled Epstein-Barr Virus as an Atypical Presentation of Deficiency in ADA2 (DADA2).

Journal Article J Clin Immunol · April 2021 Full text Link to item Cite

Sequence-Based Screening of Patients With Idiopathic Polyarteritis Nodosa, Granulomatosis With Polyangiitis, and Microscopic Polyangiitis for Deleterious Genetic Variants in ADA2.

Journal Article Arthritis Rheumatol · March 2021 OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of vasculitis that can resemble polyarteritis nodosa (PAN). This study was undertaken to identify potential disease-causing sequence variants in ADA2 in patients with idiopathic PAN ... Full text Link to item Cite

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.

Journal Article Arthritis Rheumatol · February 2021 OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care provider ... Full text Link to item Cite

Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience.

Journal Article Front Immunol · 2021 Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation. Objective: To describe spectrum of clinical, imm ... Full text Link to item Cite

Elucidating the pathogenesis of adenosine deaminase 2 deficiency: current status and unmet needs

Journal Article Expert Opinion on Orphan Drugs · January 1, 2021 Introduction: Humans have two adenosine deaminase isozymes, ADA1 and ADA2, which differ in affinity for their substrates, adenosine (Ado) and 2ʹdeoxyadenosine (dAdo), and their localization. Inherited deficiencies of ADA1 and ADA2 compromise different aspe ... Full text Open Access Cite

A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma.

Journal Article J Clin Immunol · August 2020 BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency accounts for about 4% of severe combined immunodeficiency diseases. PNP deficiency is a variable disease with recurrent infections and neurodevelopmental delay. Autoimmunity and malignancy can st ... Full text Link to item Cite

Deficiency of Adenosine Deaminase 2 (DADA2): Hidden Variants, Reduced Penetrance, and Unusual Inheritance.

Journal Article J Clin Immunol · August 2020 PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disorder that manifests with fever, early-onset vasculitis, strokes, and hematologic dysfunction. This study aimed to identify disease-causing variants by conventional Sanger an ... Full text Link to item Cite

Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Journal Article Ann Rheum Dis · February 2020 OBJECTIVE: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan fail ... Full text Link to item Cite

Morbidity in an adenosine deaminase-deficient patient during 27 years of enzyme replacement therapy.

Journal Article Clin Immunol · February 2020 INTRODUCTION: Adenosine deaminase (ADA) deficiency causes severe immunodeficiency that is lethal in infancy. Enzyme replacement therapy (ERT) can improve the metabolic, immune and non-immune abnormalities in patients prior to transplantation, however, its ... Full text Link to item Cite

Unreported Missense Mutation in the Dimerization Domain of ADA2 Leads to ADA2 Deficiency Associated with Severe Oral Ulcers and Neutropenia in a Female Somalian Patient-Addendum to the Genotype-Phenotype Puzzle.

Journal Article J Clin Immunol · January 2020 Full text Link to item Cite

Deficiency of adenosine deaminase 2: a case series revealing clinical manifestations, genotypes and treatment outcomes from Turkey.

Journal Article Rheumatology (Oxford) · January 1, 2020 Full text Link to item Cite

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India.

Journal Article Front Immunol · 2020 BACKGROUND: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce. OBJECTIVE: To ... Full text Link to item Cite

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

Journal Article Ann Rheum Dis · November 2019 OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-rel ... Full text Link to item Cite

Homozygous Splice ADA2 Gene Mutation Causing ADA-2 Deficiency.

Journal Article J Clin Immunol · November 2019 Full text Link to item Cite

Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers.

Journal Article Cell Chem Biol · May 16, 2019 Biopharmaceuticals have become increasingly attractive therapeutic agents and are often PEGylated to enhance their pharmacokinetics and reduce their immunogenicity. However, recent human clinical trials have demonstrated that administration of PEGylated co ... Full text Link to item Cite

Treatment Strategies for Deficiency of Adenosine Deaminase 2.

Journal Article N Engl J Med · April 18, 2019 Full text Link to item Cite

Architectural Modification of Conformal PEG-Bottlebrush Coatings Minimizes Anti-PEG Antigenicity While Preserving Stealth Properties.

Journal Article Adv Healthc Mater · April 2019 Poly(ethylene glycol) (PEG), a linear polymer known for its "stealth" properties, is commonly used to passivate the surface of biomedical implants and devices, and it is conjugated to biologic drugs to improve their pharmacokinetics. However, its antigenic ... Full text Link to item Cite

Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout.

Journal Article Arthritis Care Res (Hoboken) · March 2019 OBJECTIVE: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n = 130 ... Full text Link to item Cite

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.

Journal Article J Allergy Clin Immunol · March 2019 Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID) known as severe combined immune deficiency caused by adenosine deaminase defects (ADA-SCID). Most affected infants can receive a diagnosis while still ... Full text Link to item Cite

Human adenosine deaminase 2 deficiency: A multi-faceted inborn error of immunity.

Journal Article Immunol Rev · January 2019 Human adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (D ... Full text Link to item Cite

Childhood Hodgkin Lymphoma: Think DADA2.

Journal Article J Clin Immunol · January 2019 Full text Link to item Cite

Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia.

Journal Article Cold Spring Harb Mol Case Stud · December 2018 Diamond-Blackfan Anemia (DBA) is a rare polygenic disorder defined by congenital hypoplastic anemia with marked decrease or absence of bone marrow erythroid precursors. Identifying the specific genetic etiology is important for counseling and clinical mana ... Full text Link to item Cite

Warts and DADA2: a Mere Coincidence?

Journal Article J Clin Immunol · November 2018 Full text Link to item Cite

Renal Amyloidosis in Deficiency of Adenosine Deaminase 2: Successful Experience With Canakinumab.

Journal Article Pediatrics · November 2018 Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease that was firstly described in patients with early-onset strokes, livedo reticularis, and periodic fever resembling polyarteritis nodosa. In reported case series, researchers des ... Full text Link to item Cite

Disrupted N-linked glycosylation as a disease mechanism in deficiency of ADA2.

Journal Article J Allergy Clin Immunol · October 2018 Deficiency of adenosine deaminase 2 is characterized by vasculitis, early-onset strokes, immunodeficiency, and bone marrow failure. We describe a novel pathogenic mutation affecting a consensus N-linked glycosylation sequence and illustrate the essential r ... Full text Link to item Cite

ADA2 Deficiency Mimicking Idiopathic Multicentric Castleman Disease.

Journal Article Pediatrics · September 2018 Multicentric Castleman disease (MCD) is a rare entity that, unlike unicentric Castleman disease, involves generalized polyclonal lymphoproliferation, systemic inflammation, and multiple-organ system failure resulting from proinflammatory hypercytokinemia, ... Full text Link to item Cite

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

Journal Article J Clin Immunol · May 2018 INTRODUCTION: Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was ... Full text Link to item Cite

ADA2 deficiency: Clonal lymphoproliferation in a subset of patients.

Journal Article J Allergy Clin Immunol · April 2018 Full text Link to item Cite

A case of severe combined immunodeficiency caused by adenosine deaminase deficiency with a new mutation.

Journal Article Pediatr Neonatol · February 2018 Full text Link to item Cite

ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation.

Journal Article Front Immunol · 2018 Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (CECR1) gene, currently named ADA2. The disease has a wide clinical spectrum encompassing early-onset vasculopathy (t ... Full text Link to item Cite

Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2.

Journal Article Blood · December 14, 2017 Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1 DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, and intracr ... Full text Link to item Cite

Hematopoietic Stem Cell Transplantation in ADA2 Deficiency: Early Restoration of ADA2 Enzyme Activity and Disease Relapse upon Drop of Donor Chimerism.

Journal Article J Clin Immunol · November 2017 Full text Link to item Cite

Successful reduced intensity hematopoietic cell transplant in a patient with deficiency of adenosine deaminase 2.

Journal Article Bone Marrow Transplant · November 2017 Full text Link to item Cite

Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders.

Journal Article Curr Rheumatol Rep · October 5, 2017 PURPOSE OF REVIEW: A new autoinflammatory disease, deficiency of adenosine deaminase 2 (DADA2), caused by mutations in the CECR1 gene, was first reported in 2014. This review aims to update progress in defining, treating, and understanding this multi-facet ... Full text Link to item Cite

A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol.

Journal Article Nat Commun · September 12, 2017 Conjugation of polyethylene glycol (PEG) to therapeutic molecules can improve bioavailability and therapeutic efficacy. However, some healthy individuals have pre-existing anti-PEG antibodies and certain patients develop anti-PEG antibody during treatment ... Full text Link to item Cite

Autoimmune phenotype with type I interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation.

Journal Article Pediatr Rheumatol Online J · August 22, 2017 BACKGROUND: Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitu ... Full text Link to item Cite

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood.

Journal Article Arthritis Rheumatol · August 2017 OBJECTIVE: We aimed to test the relevance of deficiency of adenosine deaminase 2 (DADA2) in patients with antibody deficiency and describe the clinical picture of the disease in adulthood. METHODS: We screened for DADA2 in a cohort of 181 patients with ant ... Full text Link to item Cite

Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.

Journal Article J Clin Invest · May 1, 2017 BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID wh ... Full text Link to item Cite

Extending the Clinical Phenotype of Adenosine Deaminase 2 Deficiency.

Journal Article J Pediatr · October 2016 Adenosine deaminase 2 deficiency is an autoinflammatory disease, characterized by various forms of vasculitis. We describe 5 patients with adenosine deaminase 2 deficiency with various hematologic manifestations, including pure red cell aplasia, with no ev ... Full text Link to item Cite

Adenosine deaminase type 2 deficiency masquerading as GATA2 deficiency: Successful hematopoietic stem cell transplantation.

Journal Article J Allergy Clin Immunol · August 2016 Full text Link to item Cite

Novel compound heterozygous variants in CECR1 gene associated with childhood onset polyarteritis nodosa and deficiency of ADA2.

Journal Article Rheumatology (Oxford) · June 2016 Full text Link to item Cite

Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer.

Journal Article J Allergy Clin Immunol · May 2016 Full text Link to item Cite

Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency.

Journal Article J Clin Immunol · April 2016 PURPOSE: Determining the monogenic cause of antibody deficiency and immune dysregulation in a non-consanguineous family with healthy parents, two affected children, and one unaffected child. METHODS: Whole Exome Sequencing (WES) was performed in the index ... Full text Link to item Cite

Two patients with novel missense mutation in the purine nucleoside phosphorylase gene without serious or recurrent infections

Journal Article Clinical and Experimental Neuroimmunology · February 1, 2016 Purine nucleoside phosphorylase (PNP) deficiency is characterized by T-B+NK+ combined immune deficiency, presenting with neurological deterioration and recurrent infections. PNP is an essential enzyme taking a part in the purine salvage pathway, converting ... Full text Cite

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update.

Journal Article Clin Pharmacol Ther · January 2016 The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature and concluded that none of the evidence would change the ... Full text Link to item Cite

A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient.

Journal Article Pediatrics · January 2016 Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) en ... Full text Link to item Cite

A brush-polymer conjugate of exendin-4 reduces blood glucose for up to five days and eliminates poly(ethylene glycol) antigenicity.

Journal Article Nat Biomed Eng · 2016 The delivery of therapeutic peptides and proteins is often challenged by a short half-life, and thus the need for frequent injections that limit efficacy, reduce patient compliance and increase treatment cost. Here, we demonstrate that a single subcutaneou ... Full text Link to item Cite

Combined immunodeficiencies: Twenty years experience from a single center in Turkey

Journal Article Central European Journal of Immunology · January 1, 2016 Combined immunodeficiencies (CIDs) include a group of inherited monogenic disorders. CIDs are characterized by defective cellular and humoral immunities that lead to severe infections. CIDs can be classified according to immunologic phenotypes as T-B-NK- C ... Full text Cite

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.

Journal Article Orphanet J Rare Dis · December 18, 2015 Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfuncti ... Full text Link to item Cite

Effects of enzyme replacement therapy on immune function in ADA deficiency patient.

Journal Article Clin Immunol · December 2015 Full text Link to item Cite

Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.

Journal Article J Clin Immunol · October 2015 PURPOSE: We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunol ... Full text Link to item Cite

The deficiency of adenosine deaminase type 2-results of therapeutic intervention

Journal Article Pediatric Rheumatology · September 28, 2015 Full text Cite

Adenosine Deaminase-Deficient Severe Combined Immunodeficiency and Diffuse Large B-Cell Lymphoma

Journal Article Pediatric, Allergy, Immunology, and Pulmonology · June 1, 2015 Adenosine deaminase (ADA) deficiency is an inherited disorder of purine metabolism resulting in severe combined immunodeficiency (SCID). In patients who lack an HLA-identical bone marrow donor, enzyme replacement therapy with polyethylene glycol-conjugated ... Full text Cite

Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning.

Journal Article J Clin Immunol · May 2015 OBJECTIVE: We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical tria ... Full text Link to item Cite

30. Phase II Clinical Trial of Gene Therapy for Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID) Using a γ-Retroviral Vector

Conference Molecular Therapy · May 2015 Full text Cite

A successful unrelated peripheral blood stem cell transplantation with reduced intensity-conditioning regimen in a patient with late-onset purine nucleoside phosphorylase deficiency.

Journal Article Pediatr Transplant · March 2015 PNP deficiency is a rare combined immunodeficiency with autosomal recessive mode of inheritance. The immunodeficiency is progressive with normal immune functions at birth, but then, T-cell deficiency with variable B-cell functions usually presents by the a ... Full text Link to item Cite

Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency.

Journal Article J Allergy Clin Immunol · January 2015 Full text Link to item Cite

HSCT Rescues the Immunological and Vascular Phenotype of ADA2-Deficiency

Conference JOURNAL OF CLINICAL IMMUNOLOGY · October 1, 2014 Link to item Cite

ADA Deficiency - The First Described Genetic Defect Causing PID

Chapter · August 26, 2014 The serendipitous discovery of adenosine deaminase (ADA) deficiency in 1972 preceded by two decades the identification of gene defects in other forms of severe combined immune deficiency (SCID). During that interval, a great deal was accomplished: with kno ... Full text Cite

LATE-ONSET PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY WITH SPASTIC PARAPLEGIA

Conference JOURNAL OF CLINICAL IMMUNOLOGY · August 1, 2014 Link to item Cite

LATE-ONSET PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY WITH SPASTIC PARAPLEGIA

Conference JOURNAL OF CLINICAL IMMUNOLOGY · August 1, 2014 Link to item Cite

Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots.

Journal Article J Allergy Clin Immunol · July 2014 BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosin ... Full text Link to item Cite

Phase II Clinical Trial of Gene Therapy for Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID)

Conference MOLECULAR THERAPY · May 1, 2014 Link to item Cite

Impulse Oscillometry (IOS) Reveals Increased Pulmonary Impedence in Children with Adenosine Deaminase-Deficient Severe Combined Immunodeficiency (ADA-SCID)

Conference JOURNAL OF CLINICAL IMMUNOLOGY · April 1, 2014 Link to item Cite

Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients.

Journal Article Arthritis Res Ther · March 7, 2014 Featured Publication INTRODUCTION: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single do ... Full text Link to item Cite

Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients

Journal Article Arthritis Research and Therapy · March 7, 2014 Introduction: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single do ... Full text Cite

Early-onset stroke and vasculopathy associated with mutations in ADA2.

Journal Article N Engl J Med · March 6, 2014 Featured Publication BACKGROUND: We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because th ... Full text Link to item Cite

ADA Deficiency - The First Described Genetic Defect Causing PID

Chapter · 2014 Link to item Cite

Elevated IgE and atopy in patients treated for early-onset ADA-SCID.

Journal Article J Allergy Clin Immunol · December 2013 Full text Link to item Cite

A 22-YEAR REPLACEMENT THERAPY FOR AN ADENOSINE DEAMINASE (ADA) DEFICIENT PATIENT

Conference ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY · November 1, 2013 Link to item Cite

FRI0390 DUKE-3: A 15-week open-label trial of pegloticase in refractory gout including patients with solid organ transplant or prior pegloticase treatment

Conference Annals of the Rheumatic Diseases · June 2013 Full text Cite

FRI0372 Pharmacokinetics and immunogenicity of pegloticase (PL) infused every 3 weeks to treat refractory gout (RG), including in organ transplant recipients (TR)

Conference Annals of the Rheumatic Diseases · June 2013 Full text Cite

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

Journal Article J Allergy Clin Immunol · June 2013 Featured Publication BACKGROUND: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidi ... Full text Link to item Cite

KRECs BUT NOT TRECs IDENTIFY PATIENTS WITH DELAYED- ONSET ADENOSINE DEAMINASE (ADA) DEFICIENCY IN NEONATAL SCREENING

Journal Article JOURNAL OF CLINICAL IMMUNOLOGY · April 1, 2013 Link to item Cite

SEVERE COMBINED IMMUNODEFICIENCY DUE TO ADENOSINE DEAMINASE DEFICIENCY: EVIDENCE FROM THREE CASE REPORTS

Conference JOURNAL OF CLINICAL IMMUNOLOGY · April 1, 2013 Link to item Cite

Successful bone marrow transplantation with reduced intensity conditioning in a patient with delayed-onset adenosine deaminase deficiency.

Journal Article Pediatr Transplant · February 2013 In this case report, we describe successful BMT with RIC in a patient with delayed-onset ADA deficiency. A three-yr-old Japanese boy was diagnosed with delayed-onset ADA deficiency because of recurrent bronchitis, bronchiectasia, and lymphopenia. In additi ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing.

Journal Article Clin Pharmacol Ther · February 2013 Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson ... Full text Link to item Cite

Elevated IgE and atopy in patients treated for early-onset ADA-SCID

Journal Article Journal of Allergy and Clinical Immunology · January 1, 2013 Full text Cite

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

Journal Article Blood · November 1, 2012 We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated ... Full text Link to item Cite

Delayed-onset adenosine deaminase deficiency: strategies for an early diagnosis.

Journal Article J Allergy Clin Immunol · October 2012 Full text Link to item Cite

US RESULTS OF GENE THERAPY FOR ADENOSINE DEAMINASE DEFICIENCY

Conference JOURNAL OF CLINICAL IMMUNOLOGY · September 1, 2012 Link to item Cite

ADA酵素蛋白の安定性を相乗的に阻害する"WAZA-ARI"変異を認めたADA欠損症の1例

Journal Article 北海道醫學雜誌 = Acta medica Hokkaidonensia · August 1, 2012 Cite

Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis.

Journal Article Int J Hematol · June 2012 Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune-mediated demyelinating disorder that can appear after either immunizations or, more often, infections. Magnetic resonance imaging of patients shows inflammatory lesions in the brain and sp ... Full text Link to item Cite

Systemic Effects of PEG-ADA Withdrawal with or Without Chemotherapy (CHTX) and Cytotherapy (CTX) in Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID)

Conference JOURNAL OF CLINICAL IMMUNOLOGY · April 1, 2012 Link to item Cite

Gout

Chapter · 2012 Link to item Cite

Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

Journal Article Scand J Immunol · November 2011 Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagno ... Full text Link to item Cite

Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.

Journal Article Blood · September 8, 2011 Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient patients often present a ... Full text Link to item Cite

ADA-SCID with 'WAZA-ARI' mutations that synergistically abolished ADA protein stability.

Journal Article Br J Haematol · June 2011 Full text Link to item Cite

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation.

Journal Article Proc Natl Acad Sci U S A · February 1, 2011 Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjec ... Full text Link to item Cite

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo.

Journal Article Proc Natl Acad Sci U S A · August 10, 2010 Featured Publication A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associ ... Full text Link to item Cite

Late-onset adenosine deaminase deficiency presenting with Heck's disease.

Journal Article Eur J Pediatr · August 2010 Focal epithelial hyperplasia, also known as Heck's disease, is a rare but distinctive entity of viral etiology with characteristic clinical and histopathological features. It is a benign, asymptomatic disease of the oral mucosa caused by human papilloma vi ... Full text Link to item Cite

307 HIGH PREVALENCE OF PRE-EXISTING ANTIBODIES AGAINST POLYETHYLENE GLYCOL (PEG) IN HEPATITIS C (HCV) PATIENTS WHICH IS NOT ASSOCIATED WITH IMPAIRED RESPONSE TO PEG-INTERFERON

Conference Journal of Hepatology · April 2010 Full text Cite

Purine nucleoside phosphorylase deficiency with fatal course in two sisters.

Journal Article Eur J Pediatr · March 2010 Purine nucleoside phosphorylase (PNP) deficiency is a rare combined immunodeficiency disorder presenting with clinically recurrent infections, failure to thrive, various neurological disorders, malignancies, and autoimmune diseases. Here, we report two sis ... Full text Link to item Cite

A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels.

Journal Article Clin Biochem · November 2009 BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive disease in which affected children present with recurrent infection and may present with failure to thrive, neurological impairment, autoimmunity, or malignancy. The dia ... Full text Link to item Cite

How I treat ADA deficiency.

Journal Article Blood · October 22, 2009 Featured Publication Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treat ... Full text Link to item Cite

Immune Reconstitution after Gene Therapy for Adenosine Deaminase Deficient Severe Combined Immune Deficiency (ADA-SCID)

Conference MOLECULAR THERAPY · May 1, 2009 Link to item Cite

Reassessing serum urate targets in the management of refractory gout: can you go too low?

Journal Article Curr Opin Rheumatol · March 2009 Featured Publication PURPOSE OF REVIEW: Growing awareness of patients with refractory gout is prompting a reassessment of treatment strategy. This article reviews the current practice of targeting serum urate concentrations (sUA) in the mid-normal range (roughly 4-6 mg/dl) and ... Full text Link to item Cite

Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.

Journal Article Clin Immunol · February 2009 Featured Publication We report detailed genetic and immunologic studies in a patient diagnosed with adenosine deaminase (ADA) deficiency and combined immune deficiency at age 5 years. At the time of diagnosis, although all other lymphocyte subsets were depleted, circulating CD ... Full text Link to item Cite

Development of PEGylated mammalian urate oxidase as a therapy for patients with refractory gout

Chapter · 2009 Full text Cite

Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients.

Journal Article Ann Saudi Med · 2009 Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients wi ... Full text Link to item Cite

The Pattern of Joint Involvement in Patients with Treatment Failure Gout

Conference ARTHRITIS AND RHEUMATISM · December 1, 2008 Link to item Cite

An unconditioned bone marrow transplantation in a child with purine nucleoside phosphorylase deficiency and its unique complication.

Journal Article Pediatr Transplant · June 2008 Purine nucleoside phosphorylase deficiency is a rare immunodeficiency syndrome characterized by recurrent infections, neurological dysfunction, and autoimmunity. Early diagnosis and hematopoietic stem cell transplantation may reverse the dismal prognosis i ... Full text Link to item Cite

In memoriam: J. Edwin Seegmiller, M.D. (1920-2006).

Journal Article Nucleosides Nucleotides Nucleic Acids · June 2008 Full text Link to item Cite

Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.

Journal Article Blood · April 15, 2008 Mutations in the adenosine deaminase (ADA) gene are responsible for a form of severe combined immunodeficiency (SCID) caused by the lymphotoxic accumulation of ADA substrates, adenosine and 2'-deoxy-adenosine. The molecular mechanisms underlying T-cell dys ... Full text Link to item Cite

A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency.

Journal Article Eur J Haematol · October 2007 Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inac ... Full text Link to item Cite

Uricase and other novel agents for the management of patients with treatment-failure gout.

Journal Article Curr Rheumatol Rep · June 2007 Successful management of chronic gout depends on reducing body pools of urate. The benchmark of success is to maintain serum urate levels at less than 6 mg/dL using therapies such as probenecid or allopurinol. In a subset of patients with gout, these medic ... Full text Link to item Cite

Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006).

Journal Article Clin Immunol · May 2007 Adenosine deaminase (ADA) deficiency is a disorder of purine salvage that has its most devastating consequences in the immune system leading to severe combined immunodeficiency (SCID). Management options for ADA SCID include hematopoietic stem cell transpl ... Full text Link to item Cite

Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.

Journal Article Blood · April 15, 2007 Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell ... Full text Link to item Cite

Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout.

Journal Article Arthritis Rheum · March 2007 Featured Publication OBJECTIVE: To evaluate the efficacy, immunogenicity, and tolerability of intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG-uricase) for the treatment of severe gout. METHODS: Single infusions of PEG-uricase (at doses ranging from 0.5 mg t ... Full text Link to item Cite

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

Journal Article Blood · January 15, 2007 A patient with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfa ... Full text Link to item Cite

Steady ongoing hematological and immunological reconstitution achieved in ADA-deficiency patients treated by stem cell gene therapy with no myelopreparative conditioning

Conference JOURNAL OF GENE MEDICINE · December 1, 2006 Link to item Cite

Measurement of exchangeable uric acid pool size: Potential utility for evaluating the therapy of gout.

Conference ARTHRITIS AND RHEUMATISM · September 1, 2006 Link to item Cite

Author's reply [3]

Journal Article Clinical and Vaccine Immunology · March 1, 2006 Full text Cite

1088. Stem Cell Gene Therapy with No Pre-Conditioning for the ADA-Deficiency Patients Leads to Generalized Detoxification and Delayed, but Steady Hematological Reconstitution

Conference Molecular Therapy · 2006 Full text Cite

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase.

Journal Article Arthritis Res Ther · 2006 Featured Publication PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single ... Full text Link to item Cite

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase

Journal Article Arthritis Research and Therapy · December 2, 2005 PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single ... Full text Cite

Cerebral lymphoma in an adenosine deaminase-deficient patient with severe combined immunodeficiency receiving polyethylene glycol-conjugated adenosine deaminase.

Journal Article Pediatrics · December 2005 Polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) provides an alternate therapy to mismatched stem cell transplantation for patients with ADA-deficient severe combined immunodeficiency. Although replacement therapy with PEG-ADA is effective in p ... Full text Link to item Cite

Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).

Journal Article Clin Immunol · November 2005 Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-c ... Full text Link to item Cite

Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients.

Journal Article Eur J Immunol · November 2005 Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is associated with a severe combined immunodeficiency (SCID). Polyethylene glycol-modified ADA (PEG-ADA) has provided noncurative, life-saving treatment for these patients, but ful ... Full text Link to item Cite

CD28 costimulatory signal induces protein arginine methylation in T cells.

Journal Article J Exp Med · August 1, 2005 Featured Publication Protein phosphorylation initiates signal transduction that triggers lymphocyte activation. However, other posttranslational modifications may contribute to this process. Here, we show that CD28 engagement induced protein arginine methyltransferase activity ... Full text Link to item Cite

polyethylene glycol-conjugated adenosine deaminase (ADA) therapy provides temporary immune reconstitution to a child with delayed-onset ADA deficiency.

Journal Article Clin Diagn Lab Immunol · July 2005 We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with "delayed-onset" ADA deficiency and marked ... Full text Link to item Cite

New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency.

Journal Article Eur J Immunol · January 2005 There is growing interest in manipulating adenosine (Ado) signal transduction to control inflammation and autoimmunity. This concept probably originated with the discovery of severe combined immunodeficiency disease (SCID) in infants with inherited deficie ... Full text Link to item Cite

Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation.

Journal Article J Pediatr · November 2004 Purine nucleoside phosphorylase deficiency is a primary immunodeficiency syndrome characterized by the triad of recurrent infection, neurologic dysfunction, and autoimmunity. This patient presented atypically with few infections and normal T-cell function. ... Full text Link to item Cite

A Phase I study of pegylated-uricase (Puricase (R)) in subjects with gout.

Conference ARTHRITIS AND RHEUMATISM · September 1, 2004 Link to item Cite

Antibodies to polyethylene glycol (PEG) during Phase I investigation of PEG-(R)) for refractory gout

Conference ARTHRITIS AND RHEUMATISM · September 1, 2004 Link to item Cite

Severe gout is associated with impaired quality of life and functional status.

Conference ARTHRITIS AND RHEUMATISM · September 1, 2004 Link to item Cite

The danger within.

Journal Article N Engl J Med · June 24, 2004 Full text Link to item Cite

Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells.

Journal Article J Biol Chem · May 14, 2004 Adenosine deaminase (ADA) is expressed intracellularly by all cells, but in some tissues, it is also associated with the cell surface multifunctional glycoprotein CD26/dipeptidyl peptidase IV. By modulating extracellular adenosine, this "ecto-ADA" may regu ... Full text Link to item Cite

Genotype is an important determinant of phenotype in adenosine deaminase deficiency.

Journal Article Curr Opin Immunol · October 2003 Featured Publication Adenosine deaminase (ADA) deficiency is associated with a broad clinical and mutational spectrum. Defining the relationship of genotype to phenotype among patients with different degrees of immunodeficiency has been complicated because the disease is rare, ... Full text Link to item Cite

Corrective gene transfer into bone marrow CD34+cells for adenosine deaminase (ADA) deficiency: Results in four patients after one year of follow-up

Conference MOLECULAR THERAPY · May 1, 2003 Link to item Cite

Discontinuation of PEG-ADA replacement therapy in a patient with ADA-deficiency previously treated with retroviral-mediated, T cell-directed gene therapy

Conference MOLECULAR THERAPY · May 1, 2003 Link to item Cite

E. coli expression system for identifying folding mutations of human adenosine deaminase.

Journal Article Methods Mol Biol · 2003 Full text Link to item Cite

Clinical evaluation of retroviral vectors for corrective gene transfer of adenosine deaminase (ADA) deficiency.

Conference BLOOD · November 16, 2002 Link to item Cite

Severe morbidity associated with refractory gout.

Conference ARTHRITIS AND RHEUMATISM · September 1, 2002 Link to item Cite

Clinical evaluation of retroviral vectors for gene therapy of adenosine deaminase (ADA) deficiency.

Conference CLINICAL IMMUNOLOGY · June 1, 2002 Link to item Cite

Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV.

Journal Article J Biol Chem · May 31, 2002 Featured Publication Human adenosine deaminase (ADA) occurs as a 41-kDa soluble monomer in all cells. On epithelia and lymphoid cells of humans, but not mice, ADA also occurs bound to the membrane glycoprotein CD26/dipeptidyl peptidase IV. This "ecto-ADA" has been postulated t ... Full text Link to item Cite

Flow cytometry analysis of adenosine deaminase (ADA) expression: a simple and reliable tool for the assessment of ADA-deficient patients before and after gene therapy.

Journal Article Hum Gene Ther · February 10, 2002 Clinical gene therapy trials for adenosine deaminase (ADA) deficiency have shown limited success of corrective gene transfer into autologous T lymphocytes and CD34(+) cells. In these trials, the levels of gene transduction and expression in hematopoietic c ... Full text Link to item Cite

Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy.

Journal Article Blood · February 1, 2002 Featured Publication Four patients from 3 Saudi Arabian families had delayed onset of immune deficiency due to homozygosity for a novel intronic mutation, g.31701T>A, in the last splice acceptor site of the adenosine deaminase (ADA) gene. Aberrant splicing mutated the last 4 A ... Full text Link to item Cite

Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase.

Journal Article J Am Soc Nephrol · May 2001 Featured Publication Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene ... Full text Link to item Cite

T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation.

Journal Article Blood · May 1, 2001 Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occ ... Full text Link to item Cite

Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.

Journal Article J Immunol · February 1, 2001 Adenosine deaminase (ADA) deficiency causes an autosomal recessive form of severe combined immunodeficiency and also less severe phenotypes, depending to a large degree on genotype. In general, ADA activity in cells of carriers is approximately half-normal ... Full text Link to item Cite

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.

Journal Article Blood · February 1, 2001 Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but n ... Full text Link to item Cite

Purine nucleoside phosphorylase deficiency presenting with lymphopenia and hypogammaglobulinemia

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · February 1, 2001 Link to item Cite

Primary immunodeficiency mutation databases.

Journal Article Adv Genet · 2001 Primary immunodeficiencies are intrinsic defects of immune systems. Mutations in a large number of cellular functions can lead to impaired immune responses. More than 80 primary immunodeficiencies are known to date. During the last years genes for several ... Full text Link to item Cite

The binding site of human adenosine deaminase for CD26/Dipeptidyl peptidase IV: the Arg142Gln mutation impairs binding to cd26 but does not cause immune deficiency.

Journal Article J Exp Med · November 6, 2000 Featured Publication Human, but not murine, adenosine deaminase (ADA) forms a complex with the cell membrane protein CD26/dipeptidyl peptidase IV. CD26-bound ADA has been postulated to regulate extracellular adenosine levels and to modulate the costimulatory function of CD26 o ... Full text Link to item Cite

Metabolites from apoptotic thymocytes inhibit thymopoiesis in adenosine deaminase-deficient fetal thymic organ cultures.

Journal Article J Clin Invest · November 2000 Murine fetal thymic organ culture was used to investigate the mechanism by which adenosine deaminase (ADA) deficiency causes T-cell immunodeficiency. C57BL/6 fetal thymuses treated with the specific ADA inhibitor 2'-deoxycoformycin exhibited features of th ... Full text Link to item Cite

The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities.

Journal Article J Biol Chem · October 13, 2000 Adenosine deaminase (ADA) deficiency results in a combined immunodeficiency brought about by the immunotoxic properties of elevated ADA substrates. Additional non-lymphoid abnormalities are associated with ADA deficiency, however, little is known about how ... Full text Link to item Cite

Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.

Journal Article J Exp Med · June 19, 2000 We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that ... Full text Link to item Cite

Inhibition of fetal thymic caspases abrogates the consequences of adenosine deaminase deficiency.

Journal Article Adv Exp Med Biol · 2000 Full text Link to item Cite

Biochemical and immunological abnormalities in purine nucleoside phosphorylase deficient mice.

Journal Article Adv Exp Med Biol · 2000 Full text Link to item Cite

Immunodeficiency caused by adenosine deaminase deficiency

Journal Article Immunology and Allergy Clinics of North America · January 1, 2000 Adenosine deaminase (ADA) deficiency occurs in approximately 15% of patients with SCID, and also causes less severe forms of combined immunodeficiency. Immunodeficiency results from effects of the ADA substrates, adenosine and deoxyadenosine, and their met ... Full text Cite

Amendment to Clinical Research Project. Project 90-C-195. April 1, 1993. Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with autologous lymphocytes transduced with a human ADA gene.

Journal Article Hum Gene Ther · February 10, 1999 Full text Link to item Cite

Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy.

Journal Article Semin Hematol · October 1998 Featured Publication Adenosine deaminase (ADA) deficiency is the first known cause of severe combined immunodeficiency disease (SCID). Over the past 25 years, the metabolic basis for immune deficiency has largely been established. The clinical spectrum associated with ADA defi ... Link to item Cite

Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles.

Journal Article Am J Hum Genet · October 1998 Featured Publication Adenosine deaminase (ADA) deficiency causes lymphopenia and immunodeficiency due to toxic effects of its substrates. Most patients are infants with severe combined immunodeficiency disease (SCID), but others are diagnosed later in childhood (delayed onset) ... Full text Link to item Cite

A quantitative ranking system for relating genotype to phenotype in adenosine deaminase (ADA) deficiency, based on the expressed activity of 29 mutant alleles in E. coli

Journal Article Molecular Immunology · August 1998 Full text Cite

T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates.

Journal Article Nat Med · July 1998 Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four ... Full text Link to item Cite

Adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency in common variable immunodeficiency.

Journal Article Clin Diagn Lab Immunol · May 1998 The clinical presentations of adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency are widely variable and include clinical and immunologic findings compatible with common variable immunodeficiency. The screening of 44 patients wit ... Full text Link to item Cite

Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.

Journal Article Nat Struct Biol · May 1998 S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethi ... Full text Link to item Cite

Food allergy in a patient with adenosine deaminase deficiency undergoing enzyme replacement with polyethylene glycol-modified adenosine deaminase.

Journal Article J Allergy Clin Immunol · April 1998 Full text Link to item Cite

Loss of adenosine deaminase activity inhibits beta selection in murine fetal thymic organ culture

Conference FASEB Journal · March 20, 1998 Murine fetal thymic organ cultures (FTOC) treated with the ADA inhibitor 2′-deoxycoformycin (dCF) were used as a model system to investigate the mechanism by which T cell differentiation is inhibited in adenosine deaminase (ADA)-deficient humans. The metab ... Cite

Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online.

Journal Article Hum Mutat · 1998 The degree of immunodeficiency associated with deficiency of adenosine deaminase (ADA) is variable. Most patients are infants with severe combined immunodeficiency (SCID), but in about 20 percent immune dysfunction becomes manifest later in childhood ("del ... Full text Link to item Cite

Clinical expression, genetics and therapy of adenosine deaminase (ADA) deficiency.

Journal Article J Inherit Metab Dis · June 1997 Adenosine deaminase (ADA) deficiency was the first known cause of primary immunodeficiency. Over the past 25 years the basis for immune deficiency has largely been established. Now it appears that ADA deficiency may also cause hepatic toxicity, raising new ... Full text Link to item Cite

Generation of normal lymphocyte populations following transplantation of adenosine-deaminase-deficient fetal liver cells.

Journal Article Bone Marrow Transplant · June 1997 Adenosine-deaminase-deficient mice were generated to investigate the role of adenosine deaminase (ADA) in lymphocyte maturation and to test treatment options for the severe combined immunodeficiency (SCID) associated with the absence of ADA in man. Whereas ... Full text Link to item Cite

Crystallization and preliminary X-ray analysis of human placental S-adenosylhomocysteine hydrolase.

Journal Article Acta Crystallogr D Biol Crystallogr · May 1, 1997 A recombinant form of human placental S-adenosylhomocysteine (AdoHcy) hydrolase expressed in E. coli, which was inactivated by a type-I mechanism-based inhibitor, has been crystallized using the hanging-drop vapour-diffusion technique. The crystals grow as ... Full text Link to item Cite

Adenosine deaminase deficiency in adults.

Journal Article Blood · April 15, 1997 Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combi ... Link to item Cite

Biochemistry and immunology of polyethylene glycol-modified adenosine deaminase (PEG-ADA)

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 13, 1997 Link to item Cite

Biochemistry and immunology of poly(ethylene glycol)-modified adenosine deaminase (PEG-ADA)

Journal Article American Chemical Society, Polymer Preprints, Division of Polymer Chemistry · April 1, 1997 Enzyme conjugation with polyethylene glycol (PEG) is one method for solving problems in enzyme replacement therapy for metabolic diseases. An intramuscular injection of bovine adenosine deaminase (ADA) conjugated with 5 kDa mono-methoxy PEG was used to tre ... Cite

Biochemistry and Immunology of Poly(ethylene glycol)-Modified Adenosine Deaminase (PEG-ADA)

Journal Article ACS Symposium Series · January 1, 1997 Poly(ethylene glycol)-modified bovine adenosine deaminase (PEG-ADA) was the first PEGylated protein to undergo clinical trial. It has been effective in correcting the toxic biochemical effects of ADA substrates, and in treating the fatal immune deficiency ... Full text Cite

Full genetic rescue of adenosine deaminase-deficient mice through introduction of the human gene.

Journal Article Hum Mol Genet · October 1996 We have shown recently that adenosine deaminase (ADA)-deficient mice die perinatally with severe liver cell degeneration. In addition to enzyme substitution, we report the restoration of viability through introduction of the human ADA gene. The ADA gene is ... Full text Link to item Cite

Brief report: hepatic dysfunction as a complication of adenosine deaminase deficiency.

Journal Article N Engl J Med · May 23, 1996 Featured Publication Full text Link to item Cite

Correction of purine nucleoside phosphorylase deficiency by transplantation of allogeneic bone marrow from a sibling.

Journal Article J Pediatr · March 1996 Deficiency of the purine salvage pathway enzyme purine nucleoside phosphorylase causes a combined immunodeficiency and neurologic abnormalities and is usually fatal in childhood. We report the first successful transplantation of bone marrow from a sibling ... Full text Link to item Cite

Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA.

Journal Article Hum Mol Genet · November 1995 We report three novel adenosine deaminase (ADA) mutations with interesting implications. A Somali child with severe combined immunodeficiency disease (SCID) had reduced ADA mRNA in T cells and was homozygous for the nonsense mutation Q3X. Unexpectedly, her ... Full text Link to item Cite

Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency.

Journal Article Nat Med · October 1995 Haematopoietic stem cells in umbilical cord blood are an attractive target for gene therapy of inborn errors of metabolism. Three neonates with severe combined immunodeficiency were treated by retroviral-mediated transduction of the CD34+ cells from their ... Full text Link to item Cite

PEG-ADA replacement therapy for adenosine deaminase deficiency: an update after 8.5 years.

Journal Article Clin Immunol Immunopathol · September 1995 Polyethylene glycol-modified adenosine deaminase (PEG-ADA) has now been used for 8.5 years as enzyme replacement therapy for immunodeficiency due to ADA deficiency. PEG-ADA restores a metabolic environment necessary for recovery of immune function. In most ... Full text Link to item Cite

Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death.

Journal Article Nat Genet · July 1995 Featured Publication We report the generation and characterization of mice lacking adenosine deaminase (ADA). In humans, absence of ADA causes severe combined immunodeficiency. In contrast, ADA-deficient mice die perinatally with marked liver-cell degeneration, but lack abnorm ... Full text Link to item Cite

POSSIBLE MECHANISMS FOR THE ANTI-HIV ACTIVITY OF 3-DEAZA-ADENOSINE (DZA) ANALOGS

Conference FASEB JOURNAL · April 24, 1995 Link to item Cite

PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency.

Journal Article Hum Mutat · 1995 PEG-ADA is a long-circulating form of adenosine deaminase (ADA) that has been in use for > 8 years as replacement therapy for severe combined immunodeficiency disease due to ADA deficiency. Treatment with PEG-ADA almost completely corrects metabolic abnorm ... Full text Link to item Cite

Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site.

Journal Article Hum Mutat · 1995 Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + IG-->A) in the 5' splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency ... Full text Link to item Cite

PROLONGED DIRECT HYPERBILIRUBINEMIA AS A PRESENTATION OF ADENOSINE-DEAMINASE DEFICIENCY

Conference JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1995 Link to item Cite

SUCCESSFUL BONE-MARROW TRANSPLANTATION (BMT) FOR PURINE NUCLEOSIDE PHOSPHORYLASE (PNP) DEFICIENCY

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1995 Link to item Cite

Expression, purification, crystallization and preliminary X-ray analysis of human argininosuccinic acid lyase.

Journal Article J Mol Biol · June 3, 1994 Human argininosuccinic acid lyase (ASAL) has been expressed, purified and crystallized in several distinct crystal morphologies. At present only one form is suitable for X-ray diffraction analysis. These crystals grow as hexagonal prisms, with unit cell di ... Full text Link to item Cite

Failure to thrive, diarrhea, cough, and oral candidiasis in a three-month-old boy.

Journal Article Ann Allergy · May 1994 Link to item Cite

Correct splicing despite mutation of the invariant first nucleotide of a 5' splice site: a possible basis for disparate clinical phenotypes in siblings with adenosine deaminase deficiency.

Journal Article Am J Hum Genet · May 1994 Featured Publication Adenosine deaminase (ADA) deficiency usually causes severe combined immune deficiency in infancy. Milder phenotypes, with delayed or late onset and gradual decline in immune function, also occur and are associated with less severely impaired deoxyadenosine ... Link to item Cite

The mouse lethal nonagouti (a(x)) mutation deletes the S-adenosylhomocysteine hydrolase (Ahcy) gene.

Journal Article EMBO J · April 15, 1994 The lethal nonagouti (a(x)) mutation is a hypomorphic allele of the agouti coat color locus which, when homozygous, also leads to embryonic death around the time of implantation. To understand the molecular basis of these phenotypes, we identified and clon ... Full text Link to item Cite

ANALYSIS OF THE RELATIONSHIP OF GENOTYPE TO PHENOTYPE IN ADENOSINE-DEAMINASE (ADA) DEFICIENT PATIENTS UNDERGOING TREATMENT WITH POLYETHYLENE GLYCOL-MODIFIED ADENOSINE-DEAMINASE (PEG-ADA)

Conference CLINICAL RESEARCH · April 1, 1994 Link to item Cite

GENE-THERAPY FOR NEONATES WITH ADENOSINE-DEAMINASE (ADA) DEFICIENT SCID BY RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN ADA CDNA INTO UMBILICAL-CORD CD34+ CELLS

Conference PEDIATRIC RESEARCH · April 1, 1994 Link to item Cite

Heterogeneity of phenotype in two siblings with adenosine deaminase deficiency.

Journal Article J Allergy Clin Immunol · February 1994 Adenosine deaminase (ADA) deficiency is the cause of about one third of the autosomal recessively inherited cases of severe combined immunodeficiency. Disease severity in ADA deficiency is variable, presumably related in part to heterogeneity in the genoty ... Full text Link to item Cite

GENE-THERAPY FOR NEONATES WITH ADA-DEFICIENT SCID BY RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN ADA CDNA INTO UMBILICAL-CORD CD34+ CELLS

Conference JOURNAL OF CELLULAR BIOCHEMISTRY · January 4, 1994 Link to item Cite

New therapies for adenosine deaminase deficiency: Difficult choices, some problems with evaluation

Conference Clinical Immunology Newsletter · January 1, 1994 Full text Cite

GENE-THERAPY FOR NEONATES WITH ADA-DEFICIENT SCID BY RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN ADA CDNA INTO UMBILICAL-CORD CD34+ CELLS

Conference BLOOD · November 15, 1993 Link to item Cite

HEMATOPOIETIC ENGRAFTMENT FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANT (BMT) WITHOUT CYTOREDUCTION IN A CHILD WITH SEVERE COMBINED IMMUNE-DEFICIENCY (SCID)

Conference BLOOD · November 15, 1993 Link to item Cite

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

Journal Article J Clin Invest · November 1993 Featured Publication We examined the genetic basis for adenosine deaminase (ADA) deficiency in seven patients with late/delayed onset of immunodeficiency, an underdiagnosed and relatively unstudied condition. Deoxyadenosine-mediated metabolic abnormalities were less severe tha ... Full text Link to item Cite

A homozygous 5 base-pair deletion in exon 10 of the adenosine deaminase (ADA) gene in a child with severe combined immunodeficiency and very low levels of ADA mRNA and protein.

Journal Article Hum Mol Genet · September 1993 Full text Link to item Cite

COMPOUND HETEROZYGOSITY FOR SPLICING MUTATIONS IN ADENOSINE DEAMINASE-DEFICIENT SIBS WITH DISPARATE CLINICAL PHENOTYPES

Journal Article AMERICAN JOURNAL OF HUMAN GENETICS · September 1, 1993 Link to item Cite

T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase.

Journal Article J Clin Invest · August 1993 Featured Publication Adenosine deaminase (ADA) deficiency causes severe combined immune deficiency (SCID) by interfering with the metabolism of deoxyadenosine, which is toxic to T lymphocytes at all stages of differentiation. Enzyme replacement with polyethylene glycol-modifie ... Full text Link to item Cite

Suppression of an antibody to adenosine-deaminase (ADA) in an ADA-deficient patient receiving polyethylene glycol modified adenosine deaminase.

Journal Article Ann Allergy · June 1993 An adenosine deaminase (ADA) deficient patient with severe combined immunodeficiency (SCID) developed resistance to therapeutic injections of bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year-old girl was diagnosed as having partial ADA ... Link to item Cite

Enzyme Replacement Therapy with Polyethylene Glycol-Adenosine Deaminase in Adenosine Deaminase Deficiency: Overview and Case Reports of Three Patients, Including Two Now Receiving Gene Therapy

Journal Article Pediatric Research · April 1993 Full text Cite

Enzyme replacement therapy with polyethylene glycol-adenosine deaminase in adenosine deaminase deficiency: overview and case reports of three patients, including two now receiving gene therapy.

Journal Article Pediatr Res · January 1993 Featured Publication During the past 6 y, 29 adenosine deaminase (ADA)-deficient patients with combined immunodeficiency have been treated with polyethylene glycol (PEG)-modified bovine ADA (PEG-ADA). We have monitored plasma ADA activity, metabolic effects of treatment, and t ... Full text Link to item Cite

Enzyme replacement therapy of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase (PEG-ADA).

Journal Article Immunodeficiency · 1993 Link to item Cite

Molecular dissection of lymphocyte signal transduction pathways.

Journal Article Pediatr Res · January 1993 The earliest biochemical changes in lymphocyte activation include the accumulation of phosphotyrosine-containing proteins. This accumulation, catalyzed by specific protein tyrosine kinases, is required for subsequent cell activation. Experimental manipulat ... Full text Link to item Cite

Enzyme replacement therapy with polyethylene glycol-adenosine deaminase in adenosine deaminase deficiency: Overview and case reports of three patients, including two now receiving gene therapy

Journal Article Pediatric Research · January 1, 1993 During the past 6 y, 29 adenosine deaminase (ADA)-deficient patients with combined immunodeficiency have been treated with polyethylene glycol (PEG)-modified bovine ADA (PEG-ADA). We have monitored plasma ADA activity, metabolic effects of treatment, and t ... Full text Cite

Development of gene therapy for immunodeficiency: adenosine deaminase deficiency.

Journal Article Pediatr Res · January 1993 Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency. Clinical cure has been observed in several ADA-severe combined immunodeficiency patients after bone marrow transplantation in which only donor T cells were engrafted, sugg ... Full text Link to item Cite

ENZYME REPLACEMENT THERAPY WITH POLYETHYLENE GLYCOL-ADENOSINE DEAMINASE IN ADENOSINE-DEAMINASE DEFICIENCY - OVERVIEW AND CASE-REPORTS OF 3 PATIENTS, INCLUDING 2 NOW RECEIVING GENE-THERAPY

Conference PEDIATRIC RESEARCH · January 1, 1993 Link to item Cite

Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency.

Journal Article Blood · September 1, 1992 Adenosine deaminase (ADA) deficiency and its biochemical consequences cause severe combined immunodeficiency (SCID). Treatment strategies, designed to correct the biochemical abnormalities, include transplantation of matched bone marrow or haploidentical b ... Link to item Cite

Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy.

Journal Article Mol Biochem Parasitol · July 1992 A full-length gene encoding the S-adenosylhomocysteine hydrolase (AdoHcyase) enzyme has been isolated from a genomic library of Leishmania donovani DNA in lambda GEM-11 by cross-hybridization to the full-length human AdoHcyase cDNA. The nucleotide sequence ... Full text Link to item Cite

IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency.

Journal Article J Clin Invest · May 1992 Polyethylene glycol (PEG)-modified bovine adenosine deaminase (ADA) is used for replacement therapy of severe combined immunodeficiency disease due to inherited ADA deficiency. We monitored IgG anti-ADA antibody in 17 patients treated by intramuscular inje ... Full text Link to item Cite

[Treatment of adenosine deaminase deficiency with adenosine deaminase combined with polyethylene glycol].

Journal Article Arch Fr Pediatr · April 1992 Adenosine deaminase (ADA) deficiency is one the causes of severe combined immunodeficiency syndrome. Treatment was, until now, based on bone marrow transplantation. HLA identical bone marrow transplantation yields excellent results while those of HLA haplo ... Link to item Cite

Design, anti-hiv activity, cellular pharmacology and conformation of BCH-189 [(±)3TC], a novel nucleoside analogue

Conference · January 1, 1992 Reverse transcriptase is an attractive target and nucleoside analogues probably still represent today one of the most promising classes of compounds for the treatment of HIV infection. Chemists at IAF BioChem have devised a novel chemical strategy leading ... Full text Cite

Recurrent infection, chronic diarrhea, and failure to thrive in a seven-month-old infant.

Journal Article Ann Allergy · October 1991 Link to item Cite

Pharmacologic purging of malignant T cells from human bone marrow using 9-beta-D-arabinofuranosylguanine.

Journal Article Transplantation · October 1991 Arabinosylguanine (araG) is a nucleoside analog that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate, resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymph ... Full text Link to item Cite

Use of site-directed mutagenesis to enhance the epitope-shielding effect of covalent modification of proteins with polyethylene glycol.

Journal Article Proc Natl Acad Sci U S A · August 15, 1991 Featured Publication Modification by covalent attachment of polyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of proteins, but the utility of this approach for any protein is restricted by the number and distribution of PEG attachment sit ... Full text Link to item Cite

ANTIBODY-RESPONSES TO BACTERIOPHAGE PHI-X174 IN PATIENTS WITH ADENOSINE-DEAMINASE DEFICIENCY

Conference CLINICAL RESEARCH · February 1, 1991 Link to item Cite

[Polyethylene glycol-adenosine deaminase: a new adenosine deaminase deficiency therapy. Value of deoxyadenosine triphosphate determination for therapeutic monitoring].

Journal Article Therapie · 1991 The effect of polyethylene glycol-adenosine deaminase (PEG-ADA) therapy on biochemical, immunological and clinical abnormalities in an ADA-deficit child with severe combined immunodeficiency has been studied. Following PEG-ADA therapy, total lymphocytes, l ... Link to item Cite

Effect of polyethylene glycol-modified adenosine deaminase (PEG-ADA) therapy in two ADA-deficient children: measurement of erythrocyte deoxyadenosine triphosphate as a useful tool.

Journal Article Adv Exp Med Biol · 1991 Full text Link to item Cite

Polyethylene glycol-adenosine deaminase: A new adenosine deaminase deficiency therapy. Interest of deoxyadenosine triphosphate determination for therapeutic monitoring

Journal Article Therapie · January 1, 1991 The effect of polyethylene glycol-adenosine deaminase (PEG-ADA) therapy on biochemical, immunological and clinical abnormalities in an ADA-deficit child with severe combined immunodeficiency has been studied. Following PEG-ADA therapy, total lymphocytes, l ... Cite

Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency.

Journal Article J Clin Invest · August 1990 T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphoc ... Full text Link to item Cite

Comparison of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy in an adenosine deaminase-deficient child: measurement of erythrocyte deoxyadenosine triphosphate as a useful tool.

Journal Article Pediatr Res · August 1990 The effect of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy on biochemical abnormalities, clinical status, and immunologic function in an adenosine deaminase-deficient child was investigated. After red cell transfusions, ... Full text Link to item Cite

SELF LIMITED THROMBOCYTOPENIA IN A PATIENT TREATED WITH POLYETHYLENE-GLYCOL (PEG) MODIFIED ADENOSINE-DEAMINASE (ADA)

Conference PEDIATRIC RESEARCH · April 1, 1990 Link to item Cite

IMMUNE-RESPONSE TO POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)

Conference CLINICAL RESEARCH · April 1, 1990 Link to item Cite

COMBINED USE OF SITE DIRECTED MUTAGENESIS AND POLYETHYLENE-GLYCOL (PEG) MODIFICATION TO DEVELOP ENZYME THERAPY FOR METABOLIC DISORDERS

Conference PEDIATRIC RESEARCH · April 1, 1990 Link to item Cite

SUPPRESSION OF AN INHIBITORY ANTIBODY TO BOVINE ADENOSINE-DEAMINASE (ADA) AND IMPROVED CELLULAR-IMMUNITY FOLLOWING INTRAVENOUS IMMUNOGLOBULIN AND PREDNISONE IN A SCID-ADA DEFICIENT CHILD RECEIVING POLYETHYLENE-GLYCOL-ADA (PEG-ADA)

Conference PEDIATRIC RESEARCH · April 1, 1990 Link to item Cite

IMMUNE-RESPONSE TO POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)

Conference PEDIATRIC RESEARCH · April 1, 1990 Link to item Cite

COMBINED USE OF SITE DIRECTED MUTAGENESIS AND POLYETHYLENE-GLYCOL (PEG) MODIFICATION TO DEVELOP ENZYME THERAPY FOR METABOLIC DISORDERS

Conference CLINICAL RESEARCH · April 1, 1990 Link to item Cite

Metabolism, Toxicity, and Anti‐HIV Activity of 2′‐Deoxy‐3′‐Thia‐Cytidine (BCH‐189) in T and B Cell Lines

Journal Article Annals of the New York Academy of Sciences · January 1, 1990 Full text Cite

METABOLISM, TOXICITY, AND ANTI-HIV ACTIVITY OF 2'-DEOXY-3'-THIA-CYTIDINE (BCH-189) IN T-CELL AND B-CELL LINES

Conference AIDS : ANTI-HIV AGENTS, THERAPIES, AND VACCINES · 1990 Cite

ADA deficiency treatment.

Journal Article Science · December 15, 1989 In the report "X-ray diffraction to 302 giga-pascals: High-pressure crystal structure of cesium iodide" by H. K. Mao et al. (3 Nov., p. 649), reference 10, to a paper by R. Reichlin et al. [Phys. Rev. Lett. 56, 2858 (1986)], was incorrectly numbered (9) in ... Link to item Cite

Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma.

Journal Article Proc Natl Acad Sci U S A · July 1989 Featured Publication We analyzed a t(1;14)(p32;q11) chromosomal translocation in a human lymphohemopoietic stem cell line derived from a patient with acute T-lymphoblastic leukemia. The chromosomal joining on the 1p+ chromosome occurred at the T-cell receptor delta diversity ( ... Full text Link to item Cite

Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase.

Journal Article Ann Hum Genet · May 1989 Featured Publication Two cDNA clones for human S-adenosylhomocysteine hydrolase isolated from a placental cDNA library were sequenced. Each contained a sequence of 1299 nucleotides encoding a 432 amino-acid protein of MW 47,660. Clone 16-1 contained 47 nucleotides 5' of the co ... Full text Link to item Cite

MOSAICISM IN PATIENTS WITH ADENOSINE-DEAMINASE (ADA) DEFICIENCY AND SEVERE COMBINED IMMUNE-DEFICIENCY DISEASE (SCID)

Conference CLINICAL RESEARCH · April 1, 1989 Link to item Cite

Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.

Journal Article Proc Natl Acad Sci U S A · March 1989 We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initia ... Full text Link to item Cite

A radiochemical-high-performance liquid chromatographic assay for urate oxidase in human plasma.

Journal Article Anal Biochem · February 1, 1989 Featured Publication Polyethylene glycol-modified urate oxidase (PEG-uricase) holds promise as a hypouricemic agent for treating gout and as an adjunct to cytolytic therapy of hematologic malignancies. Spectrophotometric assays of urate oxidase are not sensitive enough for pha ... Full text Link to item Cite

CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells.

Journal Article Blood · February 1989 Featured Publication Following our initial observation of in vivo conversion of CD7+, CD4-, CD8- acute lymphoblastic leukemia (ALL) cells from lymphoid to myeloid lineages (Proc Natl Acad Sci (USA) 81:253, 1984) we have studied eight additional cases of ALL with this leukemic ... Link to item Cite

Basis for resistance to 3-deazaaristeromycin, an inhibitor of S-adenosylhomocysteine hydrolase, in human B-lymphoblasts.

Journal Article J Biol Chem · January 15, 1989 Featured Publication Clones resistant to 3-deazaaristeromycin, a potent inhibitor of S-adenosylhomocysteine hydrolase, were selected from a nucleoside kinase-deficient derivative of the WIL-2 human B-lymphoblastoid cell line. The resistant clones took up 3-deazaaristeromycin a ... Link to item Cite

Phosphate modified analogues of 5'O-phosphorylated 2', 3'-dldeoxynucleosides: Synthesis and Anti-HIV activity

Journal Article Nucleosides and Nucleotides · January 1, 1989 Phosphonate analogues of 5'-0-phosphoryl-2'3'-dideoxyribofuranosyl adenine, cytosine, hypoxanthine and thymine were synthesized. The hypoxanthine and thymine analogues were inactive against HIV induced cytopathy in the CEM-4 T-cell lines. The 2'3'-ddC and ... Full text Cite

Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase

Journal Article Annals of Human Genetics · 1989 Two cDNA clones for human S-adenocylhomocysteine hydrolase isolated from a placental cDNA library were sequenced. Each contained a sequence of 1299 nucleotide encoding a 432 amino-acid protein of MW 47660. Clone 16-1 contained 47 nucleotides 5' of the codi ... Cite

CHARACTERIZATION OF THE MOLECULAR DEFECT IN PATIENTS WITH PURINE NUCLEOSIDE PHOSPHORYLASE (PNP) DEFICIENCY

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1989 Link to item Cite

Treatment of cutaneous T cell lymphoma with 2'-deoxycoformycin (pentostatin).

Journal Article J Am Acad Dermatol · October 1988 2'-Deoxycoformycin, a potent inhibitor of adenosine deaminase, was administered to three patients with cutaneous T cell lymphoma refractory to multiple treatment modalities. Patient 1, who received 5 mg/m2/day for 3 days at 35- to 71-day intervals, has ach ... Full text Link to item Cite

Adenosine deaminase deficiency with late onset of recurrent infections: response to treatment with polyethylene glycol-modified adenosine deaminase.

Journal Article J Pediatr · August 1988 We report a 5-year-old girl with adenosine deaminase (ADA) deficiency who was asymptomatic during the first years of life. At 3 years of age, she developed chronic and recurrent sinopulmonary infections, and at 4 1/2 years of age she had one major infectio ... Full text Link to item Cite

Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines.

Journal Article J Exp Med · August 1, 1988 Derivatives of the CEM T and WIL-2 B cell lines showed striking diversity in their responses to the HTLV-IIIB strain of the human immunodeficiency virus (HIV). Several stable phenotypic patterns could be defined, based on whether cells were permissive (P+, ... Full text Link to item Cite

Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma.

Journal Article Ann Intern Med · July 15, 1988 Featured Publication Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modifie ... Full text Link to item Cite

54 ADENOSINE DEAMINASE (ADA) EXPRESSED AT HIGH LEVEL IN T LYMPHOCYTES OF A PATIENT WITH ADA DEFICIENCY AND SEVERE COMBINED IMMUNE DEFICIENCY DISEASE (SCID)

Conference Pediatric Research · July 1988 Full text Cite

DEVELOPMENT OF POLYETHYLENE GLYCOL-MODIFIED PURINE NUCLEOSIDE PHOSPHORYLASE - AN APPROACH TO THE TREATMENT OF PURINE NUCLEOSIDE PHOSPHORYLASE-DEFICIENCY

Conference CLINICAL RESEARCH · April 1, 1988 Link to item Cite

Detection of HIV-1 neutralizing antibodies by a simple, rapid, colorimetric assay.

Journal Article AIDS Res Hum Retroviruses · February 1988 A rapid, simple, reproducible and semi-quantitative assay to measure neutralizing antibodies has been developed. It employs a unique cell line which is exquisitively sensitive to infection with all HIV isolates tested. The assay is amenable to microtiter f ... Full text Link to item Cite

277 The use of bovine polyethylene glycol-modified adenosine deaminase (PEG-ADA) in correcting the immunodeficiency in a child with severe combined immunodeficiency-adenosine deaminase deficiency (SCID-ADA[ − ])

Conference Journal of Allergy and Clinical Immunology · January 1988 Full text Cite

276 Antigen-specific humoral and cellular immune responses during treatment of adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) with polyethylene glycol-modified bovine adenosine deaminase (PEG-ADA)

Conference Journal of Allergy and Clinical Immunology · January 1988 Full text Cite

Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients.

Journal Article J Clin Immunol · September 1987 The courses of six patients with adenosine deaminase (ADA) and two with purine nucleoside phosphorylase (PNP) deficiencies were evaluated before and after therapy. The heterogeneity of immunologic and clinical parameters was striking in each enzyme deficie ... Full text Link to item Cite

Identification of a deletion in the adenosine deaminase gene in a child with severe combined immunodeficiency.

Journal Article J Immunol · May 15, 1987 A patient with adenosine deaminase-deficient severe combined immunodeficiency is described whose defect is secondary to deletion of a portion of the ADA structural gene. In Southern analyses, DNA from this patient does not hybridize to a genomic probe that ... Link to item Cite

TREATMENT OF ADENOSINE-DEAMINASE DEFICIENCY WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE (PEG-ADA)

Conference CLINICAL RESEARCH · April 1, 1987 Link to item Cite

Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

Journal Article N Engl J Med · March 5, 1987 Featured Publication We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscul ... Full text Link to item Cite

TREATMENT OF ADENOSINE DEAMINASE-DEFICIENT SEVERE COMBINED IMMUNE-DEFICIENCY (ADA-SCID) WITH POLYETHYLENE GLYCOL-MODIFIED BOVINE ADENOSINE-DEAMINASE (PEG-ADA)

Conference JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1987 Link to item Cite

Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation.

Journal Article Proc Natl Acad Sci U S A · November 1986 The use of probes to genes (IG and TCRB) encoding immunoglobulins (IG) and the beta chain of the T-cell antigen receptor (TCRB), respectively, have become a sensitive means to assess clonality and lineage in lymphoid malignancies. It has become apparent th ... Full text Link to item Cite

Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors.

Journal Article J Biol Chem · September 5, 1986 The intraerythrocytic human malaria parasite, Plasmodium falciparum, requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. Adenosine has been implicated as a major source for intraerythrocytic hypoxanthine production via deami ... Link to item Cite

EXPRESSION OF HUMAN MALARIA PARASITE PURINE NUCLEOSIDE PHOSPHORYLASE IN HOST ENZYME-DEFICIENT ERYTHROCYTE CULTURE - ENZYME CHARACTERIZATION AND IDENTIFICATION OF NOVEL INHIBITORS

Journal Article JOURNAL OF BIOLOGICAL CHEMISTRY · September 5, 1986 Link to item Cite

Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation.

Journal Article J Immunol · April 1, 1986 Recent advances in the prevention of graft-vs-host disease (GVHD) have allowed the use of haploidentical bone marrow cells for correction of lethal genetic defects of the immune system. Sequential analyses of blood lymphocyte phenotypes and functions were ... Link to item Cite

A HIERARCHY OF T-CELL GENE REARRANGEMENTS IS PRESENT IN LEUKEMIAS OF THE T-CELL SERIES

Conference CLINICAL RESEARCH · April 1, 1986 Link to item Cite

A HIERARCHY OF T-CELL GENE REARRANGEMENTS IS PRESENT IN LEUKEMIAS OF THE T-CELL SERIES

Conference PEDIATRIC RESEARCH · April 1, 1986 Link to item Cite

IMMUNODEFICIENCY WITH PURINE SALVAGE PATHWAY ENZYME DEFICIENCIES - EVALUATION OF THERAPIES

Conference JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1986 Link to item Cite

Covalent labelling of ligand binding sites of human placental S-adenosylhomocysteine hydrolase with 8-azido derivatives of adenosine and cyclic AMP.

Journal Article Biochem J · December 15, 1985 S-Adenosylhomocysteine hydrolase (AdoHcyase) has previously been identified as a cytoplasmic adenosine and cyclic AMP binding protein. In order to examine the relationship between the adenosine and cyclic AMP binding sites on this enzyme we have explored t ... Full text Link to item Cite

Establishment of the DU.528 human lymphohemopoietic stem cell line.

Journal Article J Exp Med · November 1, 1985 Featured Publication We have established the DU.528 cell line from the pretreatment leukemia cells of a patient who underwent a T lymphoblastic-to-promyelocytic phenotype conversion during treatment with the adenosine deaminase inhibitor, deoxycoformycin. The cell line and clo ... Full text Link to item Cite

S-Adenosylhomocysteine hydrolase from human placenta. Affinity purification and characterization.

Journal Article Biochem J · August 15, 1985 S-Adenosylhomocysteine hydrolase (EC 3.3.1.1) was purified to homogeneity from human placenta by using S-adenosylhomocysteine-agarose affinity chromatography. The enzyme is a tetramer with a native Mr of 189 000 and subunit Mr of 47 000-48 000; there were ... Full text Link to item Cite

HEMOLYTIC ANEMIA AND LOW RED CELL ATP/dATP RATIO IN GENETIC ADENOSINE DEAMINASE DEFICIENCY: 86

Conference Pediatric Research · July 1985 Full text Cite

A LYMPHOHEMATOPOIETIC STEM CELL MODEL FOR ADENOSINEDEAMINASE (ADA) DEFICIENCY: 105

Conference Pediatric Research · July 1985 Full text Cite

Determinants of deoxyadenosine toxicity in hybrids between human T- and B- lymphoblasts as a model for the development of drug resistance in T-cell acute lymphoblastic leukemia.

Journal Article Cancer Res · April 1985 Cultured human T-lymphoblastoid cell lines are more sensitive than B-cell lines to 2'-deoxyadenosine in the presence of 2'-deoxycoformycin, a potent inhibitor of adenosine deaminase. This difference is related to the greater efficiency with which T-lymphob ... Link to item Cite

Abnormalities in S-adenosylhomocysteine hydrolysis, ATP catabolism, and lymphoid differentiation in adenosine deaminase deficiency.

Journal Article Ann N Y Acad Sci · 1985 Full text Link to item Cite

Altered regulation of S-adenosylmethionine dependent methylation in adenosine deaminase deficiency.

Journal Article Prog Clin Biol Res · 1985 Link to item Cite

Biochemical consequences of adenosine deaminase inhibition in vivo. Differential effects in acute and chronic T cell leukemia.

Journal Article Ann N Y Acad Sci · 1985 Full text Link to item Cite

Regional localization of the human genes for S-adenosylhomocysteine hydrolase (cen----q131) and adenosine deaminase (q131----qter) on chromosome 20.

Journal Article Hum Genet · 1984 The gene loci for S-adenosylhomocysteine hydrolase ( AHCY ) and adenosine deaminase (ADA), two enzymes with related metabolic functions, have both been assigned to human chromosome 20. We have used rodent-human somatic hybrids containing translocations inv ... Full text Link to item Cite

Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin.

Journal Article Proc Natl Acad Sci U S A · January 1984 Featured Publication Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2'-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpec ... Full text Link to item Cite

Effects of treatment with 2'-deoxycoformycin and vidarabine on S-adenosylhomocysteine metabolism

Journal Article Cancer Treatment Symposia · January 1, 1984 Cite

THE ESTABLISHMENT OF A LYMPHOHEMOPOIETIC STEM-CELL LINE, A NEW MODEL FOR THE STUDY OF CELLULAR-DIFFERENTIATION

Conference PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH · January 1, 1984 Link to item Cite

ESTABLISHMENT OF A LYMPHOHEMOPOIETIC STEM-CELL LINE, A NEW MODEL FOR STUDY OF CELLULAR-DIFFERENTIATION

Conference CLINICAL RESEARCH · January 1, 1984 Link to item Cite

S-adenosylhomocysteine catabolism and basis for acquired resistance during treatment of T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin alone and in combination with 9-beta-D-arabinofuranosyladenine.

Journal Article Cancer Res · July 1983 Featured Publication A patient with refractory T-cell acute lymphoblastic leukemia was treated with eight courses of the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), over a 5-month period. After developing resistance to dCF, he responded to treatment with the combi ... Link to item Cite

SOMATIC-CELL GENETIC-ANALYSIS OF DEOXYADENOSINE TOXICITY IN HUMAN-LYMPHOCYTES

Conference CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY · January 1, 1983 Link to item Cite

Effects of mutational loss of adenosine kinase and deoxycytidine kinase on deoxyATP accumulation and deoxyadenosine toxicity in cultured CEM human T-lymphoblastoid cells.

Journal Article J Biol Chem · June 10, 1982 Featured Publication Link to item Cite

The human genes for S-adenosylhomocysteine hydrolase and adenosine deaminase are syntenic on chromosome 20.

Journal Article Science · May 14, 1982 Featured Publication Human-Chinese hamster cell hybrids and a monoclonal antibody to human S-adenosylhomocysteine hydrolase were used to identify chromosome 20 as the location of the human gene for this enzyme. The gene for adenosine deaminase had previously been mapped to thi ... Full text Link to item Cite

Mechanism of deoxyadenosine-induced catabolism of adenine ribonucleotides in adenosine deaminase-inhibited human T lymphoblastoid cells.

Journal Article Proc Natl Acad Sci U S A · April 1982 Featured Publication Loss of ATP accompanying accumulation of dATP has recently been reported to occur in the erythrocytes and lymphoblasts of patients with T lymphocytic leukemia during treatment with deoxycoformycin, an inhibitor of adenosine deaminase (adenosine aminohydrol ... Full text Link to item Cite

Mechanism of T-lymphoblast ATP depletion during treatment with deoxycoformycin

Journal Article Journal of Clinical Chemistry and Clinical Biochemistry · January 1, 1982 Cite

SYNTENY OF THE GENES FOR S-ADENOSYLHOMOCYSTEINE HYDROLASE AND ADENOSINE-DEAMINASE - EVOLUTIONARY IMPLICATIONS

Conference JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY · January 1, 1982 Link to item Cite

Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients.

Journal Article J Clin Invest · March 1981 We have examined the basis for the recently reported, but unexplained deficiency of S-adenosylhomocysteine hydrolase (AdoHcyase) in the erythrocytes of patients with genetic deficiencies of purine nucleoside phosphorylase and hypoxanthine-guanine phosphori ... Full text Link to item Cite

A biochemical genetic study of the role of specific nucleoside kinases in deoxyadenosine phosphorylation by cultured human cells.

Journal Article J Biol Chem · January 25, 1981 Link to item Cite

Effects of deoxyadenosine (dAdo) and adenine arabinoside (AraA) during deoxycoformycin (dCF) therapy

Journal Article Proceedings of the American Association for Cancer Research · January 1, 1981 Cite

2'-deoxycoformycin (dCE) therapy in T cell acute lymphoblastic leukemia (T-all)

Conference Clinical Research · January 1, 1981 Cite

EFFECTS OF 2'-DEOXYCOFORMYCIN ON HOMOCYSTEINE METABOLISM IN ACUTE LYMPHOBLASTIC-LEUKEMIA

Conference CLINICAL RESEARCH · January 1, 1981 Link to item Cite

Elucidation of aberrant purine metabolism: application to hypoxanthine-guanine phosphoribosylstransferase- and adenosine kinase-deficient mutants, and IMP dehydrogenase- and adenosine deaminase-inhibited human lymphoblasts.

Journal Article Biochim Biophys Acta · October 17, 1980 We propose that the ratio of [14C]formate-labelled purine nucleosides and bases (both intra and extracellular) to nucleic acid purines provides, in exponentially growing cultures, a sensitive index for comparative studies of purine metabolism. This ratio w ... Full text Link to item Cite

Resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, S-adenosylhomocysteine hydrolase inactivation, and dATP accumulation.

Journal Article Proc Natl Acad Sci U S A · July 1980 Featured Publication Accumulation of dATP derived from 2'-deoxyadenosine (dAdo), causing inhibition of ribonucleotide reductase and depletion of the other deoxynucleotide substrates required for DNA synthesis, has been suggested as the cause of the lymphopenia and immune defec ... Full text Link to item Cite

S-Adenosylhomocysteine metabolism in adenosine deaminase deficient cells.

Journal Article Adv Exp Med Biol · 1980 Full text Link to item Cite

Perturbations in S-adenosylhomocysteine and S-adenosylmethionine metabolism: effects on transmethylation.

Journal Article Adv Enzyme Regul · 1980 Full text Link to item Cite

ROLE OF ADENOSINE KINASE IN MEDIATING OR MODIFYING THE TOXICITY OF 2'-DEOXYADENOSINE

Conference CLINICAL RESEARCH · January 1, 1980 Link to item Cite

S-adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin.

Journal Article Proc Natl Acad Sci U S A · May 1979 Featured Publication The human lymphoblast line WI-L2 is subject to growth inhibition by a combination of the adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4.) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and adenosine. Although adenosine-induced pyrimi ... Full text Link to item Cite

In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients.

Journal Article J Clin Invest · April 1979 Featured Publication The cytotoxic nucleoside 2'-deoxyadenosine is excreted in excessive amounts by individuals with genetic deficiency of adenosine deaminase, and may be in part responsible for the severe combined immune dysfunction from which they suffer. Earlier studies fro ... Full text Link to item Cite

Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine.

Journal Article J Biol Chem · January 10, 1979 Featured Publication Adenosylhomocysteine hydrolase from human lymphoblasts binds 2'-deoxy[3H]adenosine tightly. Binding is associated with time-dependent, saturable, irreversible inactivation of catalytic activity which occurs with first order kinetics, suggesting "suicide" i ... Link to item Cite

SECONDARY DEFICIENCY OF S-ADENOSYLHOMOCYSTEINE HYDROLASE IN ADENOSINE-DEAMINASE DEFICIENCY

Conference CLINICAL RESEARCH · January 1, 1979 Link to item Cite

ACTIVE-SITE DIRECTED INACTIVATION OF S-ADENOSYLHOMOCYSTEINE HYDROLASE - POSSIBLE BASIS FOR ANTI-VIRAL EFFECTS OF ADENINE-ARABINOSIDE

Conference CLINICAL RESEARCH · January 1, 1979 Link to item Cite

S-adenosylhomocysteine hydrolase is an adenosine-binding protein: a target for adenosine toxicity.

Journal Article Science · November 17, 1978 Featured Publication When adenosine deaminase activity is inhibited, low concentrations of adenosine are toxic to human lymphoblast mutants that are unable to convert adenosine to intracellular nucleotides. In order to identify the mediator of this cytotoxicity, we searched fo ... Full text Link to item Cite

Cytotoxic and metabolic effects of adenosine and adenine on human lymphoblasts.

Journal Article Cancer Res · August 1978 The metabolic and growth inhibitory effects of adenosine toward the human lymphoblast line WI-L2 were potentiated by the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and coformycin. EHNA, 5 micron, or coformycin, 3.5 micron, ... Link to item Cite

Purine reutilization and synthesis de novo in long-term human lymphocyte cell lines deficient in adenine phosphoribosyltransferase activity.

Journal Article Somatic Cell Genet · May 1978 Clonal lines, with either partial or total deficiency of adenine phosphoribosyltransferase (APRT) were derived from the WI-L2 long-term human lymphocyte line by selection for resistance to the adenine analogs 8-azaadenine or 2,6-diaminopurine. Resistance t ... Full text Link to item Cite

Purine reutilization and synthesis de novo in APRT deficient long-term lymphocyte lines.

Journal Article Monogr Hum Genet · 1978 Full text Link to item Cite

Inhibition of methylation by S-adenosylhomocysteine (SAH): a basis for adenosine toxicity and immune dysfunction in adenosine deaminase deficiency

Conference Clinical Research · January 1, 1978 Cite

SUICIDE INACTIVATION OF S-ADENOSYLHOMOCYSTEINE HYDROLASE BY 2'-DEOXYADENOSINE - NOVEL MECHANISM FOR IMMUNE DYSFUNCTION IN ADENOSINE-DEAMINASE DEFICIENCY

Conference CLINICAL RESEARCH · January 1, 1978 Link to item Cite

MECHANISM FOR ADENOSINE (ADO) CYTOTOXICITY IN ADENOSINE-DEAMINASE (ADA) DEFICIENCY

Conference CLINICAL RESEARCH · January 1, 1978 Link to item Cite

HUMAN CYTOPLASMIC ADENOSINE BINDING-PROTEIN - IDENTIFICATION AS S-ADENOSYLHOMOCYSTEINASE

Conference FEDERATION PROCEEDINGS · January 1, 1978 Link to item Cite

INHIBITION OF DNA AND RNA METHYLATION BY S-ADENOSYLHOMOCYSTEINE - POSSIBLE BASIS FOR IMMUNE DYSFUNCTION IN ADENOSINE-DEAMINASE DEFICIENCY

Conference FEDERATION PROCEEDINGS · January 1, 1978 Link to item Cite

Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes.

Journal Article Science · September 23, 1977 Featured Publication Mutants deficient in adenosine kinase or adenine phosphoribosyltransferase activities were selected from the WI-L2 line of human lymphoblasts. The adenosine kinase-deficient mutant was still as sensitive as its parent to growth inhibition caused by adenosi ... Full text Link to item Cite

Regulation of de novo purine synthesis in human lymphoblasts. Similar rates of de novo synthesis during growth by normal cells and mutants deficient in hypoxanthine-guanine phosphoribosyltransferase activity.

Journal Article J Biol Chem · September 10, 1977 Featured Publication Link to item Cite

Purine synthesis and excretion in mutants of the WI-L2 human lymphoblastoid line deficient in adenosine kinase (AK) and adenine phosphoribosyltransferase (APRT).

Conference Adv Exp Med Biol · 1977 Full text Link to item Cite

Purine toxicity in human lymphoblasts.

Journal Article Adv Exp Med Biol · 1977 Full text Link to item Cite

Coordinate regulation of the proximal and distal steps of the pathway of purine synthesis de nono in WI-L2 human lymphoblasts.

Journal Article Adv Exp Med Biol · 1977 Full text Link to item Cite

TOXICITY OF ADENINE AND ADENOSINE TO HUMAN LYMPHOBLASTS DOES NOT REQUIRE THEIR CONVERSION TO NUCLEOTIDES

Conference CLINICAL RESEARCH · January 1, 1977 Link to item Cite

ADENINE PHOSPHORIBOSYLTRANSFERASE (APRT) DEFICIENCY - CLINICAL AND LABORATORY STUDIES IN A NEW KINDRED

Conference CLINICAL RESEARCH · January 1, 1977 Link to item Cite

EFFECT OF APRT DEFICIENCY ON PURINE SYNTHESIS AND REUTILIZATION IN LONG-TERM LYMPHOCYTE LINES

Conference HUMAN HEREDITY · January 1, 1977 Link to item Cite

RELATIONSHIP BETWEEN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE (HPRT) DEFICIENCY, PRPP CONCENTRATION, AND DENOVO PURINE SYNTHESIS

Conference CLINICAL RESEARCH · January 1, 1977 Link to item Cite

Regulation of de novo purine biosynthesis in human lymphoblasts. Coordinate control of proximal (rate-determining) steps and the inosinic acid branch point.

Journal Article J Biol Chem · December 10, 1976 Featured Publication Purine nucleotide synthesis de novo has been studied in a permanent tissue culture line of human splenic lymphoblasts with particular attention to coordination of control of the proximal (rate-determining) steps with the distal branch point of the pathway. ... Link to item Cite

Gout and the regulation of purine biosynthesis.

Journal Article Horiz Biochem Biophys · 1976 Overproduction of purine nucleotides de novo is the cause of hyperuricemia in a substantial portion of the gouty population. Specific enzyme abnormalities--deficiency of hypoxanthine-guanine phosphoribosyltransferase (an enzyme of the purine "salvage" path ... Link to item Cite

Purine toxicity in human lymphoblasts

Journal Article Journal of Clinical Chemistry and Clinical Biochemistry · January 1, 1976 Cite

REGULATION OF PURINE SYNTHESIS DENOVO IN HUMAN LYMPHOBLASTS

Conference FEDERATION PROCEEDINGS · January 1, 1976 Link to item Cite

In vitro characterization of a mutator T4 DNA polymerase

Journal Article Genetics · December 1, 1973 Cite

In vitro characterization of a mutator T4 DNA polymerase.

Journal Article Genetics · April 1973 Featured Publication Link to item Cite

On the role of deoxyribonucleic acid polymerase in determining mutation rates. Characterization of the defect in the T4 deoxyribonucleic acid polymerase caused by the ts L88 mutation.

Journal Article J Biol Chem · February 25, 1973 Featured Publication Link to item Cite

Hydrolysis of template and newly synthesized deoxyribonucleic acid by the 3' to 5' exonuclease activity of the T4 deoxyribonucleic acid polymerase.

Journal Article J Biol Chem · June 10, 1972 Featured Publication Link to item Cite

Nuclease activity in a fragment of bacteriophage T4 deoxyribonucleic acid polymerase induced by the amber mutant am B22.

Journal Article J Biol Chem · September 10, 1971 Link to item Cite

Placental transport of free palmitic and linoleic acids in the guinea pig.

Journal Article J Lipid Res · July 1968 Featured Publication Radioisotopic tracers were used to measure the unidirectional transfer rates of free fatty acids across the placenta of fed and fasted pregnant guinea pigs. Free (14)C-labeled palmitic and linoleic acids (in serum) were injected simultaneously into a jugul ... Link to item Cite