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Journal of Clinical Pathology.... 1975
Review
Topics: Amino Acid Sequence; Heavy Chain Disease; Humans; Immunoglobulin gamma-Chains; Immunoglobulin mu-Chains; Multiple Myeloma; Myeloma Proteins
PubMed: 830056
DOI: 10.1136/jcp.s1-6.1.65 -
Texas Heart Institute Journal 1994Hypertrophic cardiomyopathy is a heterogeneous disease with autosomal dominant Mendelian inheritance. In 1989, the 1st locus for hypertrophic cardiomyopathy was mapped... (Review)
Review
Hypertrophic cardiomyopathy is a heterogeneous disease with autosomal dominant Mendelian inheritance. In 1989, the 1st locus for hypertrophic cardiomyopathy was mapped to cardiac myosin genes located on chromosome 14q1. Soon, several mutations that cosegregated with inheritance of the disease were identified in the beta-myosin heavy chain gene, or MHY7. More than 30 missense mutations and 1 deletion mutation in the beta-myosin heavy chain gene have since been described. Recently, expression of both the mutant beta-myosin heavy chain mRNA and the mutant protein has been shown in the cardiac and skeletal muscles of individuals with hypertrophic cardiomyopathy. Characterization of the clinical features of beta-myosin heavy chain mutations has shown that certain mutations, such as Arg403Gln and Arg719Trp mutations, are associated with high rate of sudden cardiac death. In addition to the beta-myosin heavy chain gene, 3 new loci for hypertrophic cardiomyopathy have recently been described, but the candidate genes have not yet been identified. Dilated cardiomyopathy can be inherited as an autosomal dominant, autosomal recessive, and X-linked disease. The familial form of dilated cardiomyopathy comprises approximately 20% of the cases of idiopathic cardiomyopathy. Echocardiographic abnormalities such as left ventricular enlargement are present in 10% of asymptomatic relatives. No gene for familial dilated cardiomyopathy has been identified, but linkage studies using polymorphic, short-tandem repeat markers are ongoing. Dilated cardiomyopathy is a common manifestation of Duchenne/Becker muscular dystrophy. Heart failure is a common cause of death in the affected individuals. The gene responsible for this disease is the dystrophin gene located on X chromosome. There have been reports in these patients of several dystrophin-gene deletion mutations, which result in a decrease in the expression of the dystrophin protein in the cardiac and skeletal tissues. X-linked cardiomyopathy, in which the disease is restricted to the heart, has also been linked to the dystrophin gene. Myotonic dystrophy is an autosomal dominant disease that commonly involves the myocardium and the conduction tissue, resulting in conduction defects and heart failure. Sudden cardiac death is the most common cause of mortality in patients with myotonic dystrophy. Recently, the myotonin protein kinase gene located on chromosome 19 was identified as the gene responsible for this disease. Expansion of the number of trinucleotide repeats in the myotonin protein kinase gene results in myotonic dystrophy. Mutations in mitochondrial DNA have been associated with hypertrophic and dilated cardiomyopathy. The inheritance of mitochondrial cardiomyopathy is maternal and the disease is associated with certain systemic disorders.
Topics: Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Dystrophin; Humans; Muscular Dystrophies; Mutation; Myosins; X Chromosome
PubMed: 8180512
DOI: No ID Found -
Blood Mar 2005Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and... (Review)
Review
Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.
Topics: Adolescent; Adult; Africa; Campylobacter Infections; Campylobacter jejuni; Child; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 9; Female; Humans; Immunoglobulin Light Chains; Immunoglobulin Variable Region; Immunoglobulin alpha-Chains; Immunoproliferative Small Intestinal Disease; Intestine, Small; Lymph Nodes; Lymphoma, B-Cell, Marginal Zone; Male; Mesentery; Middle East; PAX5 Transcription Factor; Plasma Cells; Sequence Deletion; Translocation, Genetic
PubMed: 15542584
DOI: 10.1182/blood-2004-07-2755 -
American Family Physician Apr 1999Multiple myeloma is the malignant proliferation of plasma cells involving more than 10 percent of the bone marrow. The multiple myeloma cell produces monoclonal... (Review)
Review
Multiple myeloma is the malignant proliferation of plasma cells involving more than 10 percent of the bone marrow. The multiple myeloma cell produces monoclonal immunoglobulins that may be identified on serum or urine protein electrophoresis. Bone pain related to multiple lytic lesions is the most common clinical presentation. However, up to 30 percent of patients are diagnosed incidentally while being evaluated for unrelated problems, and one third of patients are diagnosed after a pathologic fracture, commonly of the axial skeleton. Multiple myeloma must be differentiated from other causes of monoclonal gammopathy, including monoclonal gammopathy of undetermined significance, heavy chain disease, plasmacytoma and Waldenstrom macroglobulinemia. Chemotherapy with melphalan-prednisone is the standard treatment for multiple myeloma. Other treatment modalities include polychemotherapy and bone marrow transplantation. Only 50 to 60 percent of patients respond to therapy. The aggregate median survival for all stages of multiple myeloma is three years.
Topics: Diagnosis, Differential; Humans; Multiple Myeloma; Patient Education as Topic; Prognosis; Severity of Illness Index; Teaching Materials
PubMed: 10208707
DOI: No ID Found -
The Journal of International Medical... Mar 2022Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes.... (Review)
Review
Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test identified no abnormalities. Our findings provide strong evidence for a correlation between PCDs and HCDD, which could help understand the genetic background underlying abnormal heavy chains and assess disease prognosis. Further, concordant with previous findings, bortezomib-based chemotherapy had a good therapeutic effect in our patient. We summarize the experience of diagnosing and treating a case of HCDD, and combine this with a literature review to further explore the correlation between PCDs and HCDD, which has important clinical value.
Topics: Antineoplastic Agents; Bortezomib; Genes, Immunoglobulin Heavy Chain; Heavy Chain Disease; Humans; Leukemia, Plasma Cell
PubMed: 35301906
DOI: 10.1177/03000605221086428 -
Diagnostic Pathology Oct 2022
PubMed: 36266677
DOI: 10.1186/s13000-022-01265-w -
Archivum Immunologiae Et Therapiae... 2006Basement membrane antigens are frequent targets of autoantibody attack in systemic and organ-restricted autoimmunity. These specialized and highly organized matrices are... (Review)
Review
Basement membrane antigens are frequent targets of autoantibody attack in systemic and organ-restricted autoimmunity. These specialized and highly organized matrices are composed of multiple components with restricted tissue distributions and limited epitope exposure. To dissect mechanisms controlling humoral autoimmunity to nephritogenic basement membrane antigens, we developed autoantibody transgenic models. In mice bearing the LamH Ig transgene encoding B cell receptors specific for laminin, autoreactive B cells are readily generated but actively regulated in vivo. In this model, anti-laminin B cells are immunologically censored by mechanisms that include central deletion, kappa light-chain editing, and anergy. Tolerance is maintained when the transgene is established in MRL and BXSB genetic backgrounds with inherited autoimmune susceptibility, and despite provocation with potent environmental stimulants. Collectively, these studies indicate that the pathogenic anti-laminin reactivity characteristic of systemic lupus is tightly regulated. A novel anti-collagen transgenic model is used to assess the tolerogenesis of a structurally distinct pathogenic basement membrane epitope and to determine if reactivity to putative cryptic epitopes targeted in organ-restricted disease is regulated. These studies should provide insight into the molecular mechanisms controlling basement membrane autoreactivity and ultimately facilitate the development of novel strategies to inactivate autoreactive cells and treat autoimmune disease.
Topics: Animals; Anti-Glomerular Basement Membrane Disease; Autoantigens; Autoimmunity; B-Lymphocytes; Basement Membrane; Collagen Type IV; Humans; Immunoglobulin Heavy Chains; Laminin; Mice; Mice, Transgenic; Self Tolerance
PubMed: 16830221
DOI: 10.1007/s00005-006-0027-x -
The Journal of Clinical Investigation Apr 2023The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad...
The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.
Topics: Animals; Cricetinae; SARS-CoV-2; COVID-19; Antibodies; Epitopes; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 36862518
DOI: 10.1172/JCI166844 -
Methods in Molecular Biology (Clifton,... 2023Skeletal muscle is composed of long multinucleated cells, termed myofibers, that are formed through the activation and differentiation of resident muscle stem cells,...
Skeletal muscle is composed of long multinucleated cells, termed myofibers, that are formed through the activation and differentiation of resident muscle stem cells, called satellite cells. In healthy individuals, skeletal muscle enables voluntary locomotion while also playing a role in energy metabolism and thermoregulation. As skeletal muscle is integral to everyday processes, perturbations to skeletal muscle function can have devastating consequences. Here we describe an integral tool in biomedical research of skeletal muscle regeneration and disease, the immunofluorescence staining of myogenic cells. We highlight useful techniques for immunostaining myogenic cells, and we list validated antibodies for the staining of muscle proteins across different species and multiple developmental time points. This includes methods for unmasking antigens following formaldehyde fixation (using myosin heavy chain staining as an example) and practices for preserving endogenous fluorescent proteins by cardiac perfusion fixation.
Topics: Cell Differentiation; Fluorescent Antibody Technique; Formaldehyde; Humans; Muscle Development; Muscle Proteins; Muscle, Skeletal; Myosin Heavy Chains; Satellite Cells, Skeletal Muscle; Staining and Labeling
PubMed: 36152246
DOI: 10.1007/978-1-0716-2675-7_9 -
Clinical Kidney Journal Oct 2012Heavy-chain deposition disease (HCDD) is the least common of the monoclonal immunoglobulin deposition diseases with only 24 reported cases in English literature,...
Heavy-chain deposition disease (HCDD) is the least common of the monoclonal immunoglobulin deposition diseases with only 24 reported cases in English literature, including the present case. The rarity of this disease merits its documentation. We present a case of HCDD from our archival material, who presented with rapidly progressive renal failure and nephrotic syndrome and was found to have nodular glomerulosclerosis on renal biopsy which on immunofluorescence and electron microscopy confirmed HCDD of immunoglobulin G1 type without any light-chain deposition. We also present an in-depth literature review on HCDD.
PubMed: 26019812
DOI: 10.1093/ckj/sfs062