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American Family Physician Jan 2005Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders. Electrophoresis separates proteins based on their... (Review)
Review
Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders. Electrophoresis separates proteins based on their physical properties, and the subsets of these proteins are used in interpreting the results. Plasma protein levels display reasonably predictable changes in response to acute inflammation, malignancy, trauma, necrosis, infarction, burns, and chemical injury. A homogeneous spike-like peak in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy. Monoclonal gammopathies are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrom's macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis. The quantity of M protein, the results of bone marrow biopsy, and other characteristics can help differentiate multiple myeloma from the other causes of monoclonal gammopathy. In contrast, polyclonal gammopathies may be caused by any reactive or inflammatory process.
Topics: Blood Protein Disorders; Blood Protein Electrophoresis; Guidelines as Topic; Humans
PubMed: 15663032
DOI: No ID Found -
Science Advances Nov 2021Artificial enzymes have attracted wide interest in disease diagnosis and biotechnology due to high stability, easy synthesis, and cost effectiveness. Unfortunately,...
Artificial enzymes have attracted wide interest in disease diagnosis and biotechnology due to high stability, easy synthesis, and cost effectiveness. Unfortunately, their catalytic rate is limited to surface electron transfer, affecting the catalytic and biological activity. Here, we report an oligomeric nanozyme (O-NZ) with ultrafast electron transfer, achieving ultrahigh catalytic activity. O-NZ shows electron transfer of 1.8 nanoseconds in internal cores and 1.2 picoseconds between core and ligand molecule, leading to ultrahigh superoxidase dismutase–like and glutathione peroxidase–like activity (comparable with natural enzyme, Michaelis constant = 0.87 millimolars). Excitingly, O-NZ can improve the 1-month survival rate of mice with acute brain trauma from 50 to 90% and promote the recovery of long-term neurocognition. Biochemical experiments show that O-NZ can decrease harmful peroxide and superoxide via in vivo catalytic chain reaction and reduce acute neuroinflammation via nuclear factor erythroid-2 related factor 2–mediated up-regulation of heme oxygenase-1 expression.
PubMed: 34757781
DOI: 10.1126/sciadv.abk1210 -
Mediterranean Journal of Hematology and... 2018The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light... (Review)
Review
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are rarer and associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain. These patients may occasionally be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Fanconi syndrome, on the other hand, can be primary (inherited) or secondary (acquired). The only exception to this rule is the idiopathic form. Adult acquired Fanconi syndrome can be a rare complication of a monoclonal gammopathy. At diagnosis, most patients have an MGUS or smoldering multiple myeloma, with renal failure and evidence of osteomalacia. During follow-up, patients can develop an end-stage renal disease. Chemotherapy provides little benefit on renal function.
PubMed: 29326807
DOI: 10.4084/MJHID.2018.011 -
Nature Communications Jul 2023Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which...
Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.
Topics: Humans; Genes, Immunoglobulin Heavy Chain; Genes, Immunoglobulin; Alleles; Germ-Line Mutation; Immunoglobulin Heavy Chains
PubMed: 37479682
DOI: 10.1038/s41467-023-40070-x -
Diagnostic Pathology Aug 2022Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The... (Review)
Review
BACKGROUND
Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood.
CASE PRESENTATION
We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum.
CONCLUSIONS
Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia.
Topics: Heavy Chain Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis; Lymphoma; Mutation; Myeloid Differentiation Factor 88; Waldenstrom Macroglobulinemia
PubMed: 35932039
DOI: 10.1186/s13000-022-01244-1 -
Oncology (Williston Park, N.Y.) Jan 2014Heavy chain diseases are a family of rare, systemic syndromes typically associated with or representing a variant of a B-cell neoplasm. Their characteristic feature is... (Review)
Review
Heavy chain diseases are a family of rare, systemic syndromes typically associated with or representing a variant of a B-cell neoplasm. Their characteristic feature is production of a mutated immunoglobulin heavy chain incapable of either partnering with light chains in the formation of a full immunoglobulin molecule or of being degraded by the proteasome. The abnormal heavy chain is detected in urine and/or serum without an associated light chain, a pathognomonic finding. Depending on the subtype of the altered heavy chain, these conditions can be subclassified as alpha, gamma, or mu heavy chain disease. We discuss the clinical presentation; epidemiology; laboratory, radiologic, and pathologic features; and treatment options for each of the heavy chain diseases, emphasising the importance of an accurate pathologic diagnosis and correct interpretation of immunologic studies in their identification.
Topics: Heavy Chain Disease; Humans; Immunophenotyping; Prognosis
PubMed: 24683718
DOI: No ID Found -
BMC Nephrology Jun 2023Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis...
BACKGROUND
Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.
CASE PRESENTATION
We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.
CONCLUSIONS
This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.
Topics: Female; Humans; Aged; Congo Red; Amyloidosis; Immunoglobulins; Multiple Myeloma; Amyloid; Mass Spectrometry; Immunoglobulin Light Chains
PubMed: 37365566
DOI: 10.1186/s12882-023-03207-0 -
Methods in Molecular Biology (Clifton,... 2021Opioid use has substantially increased over recent years and remains a major driver of new HIV infections worldwide. Clinical studies indicate that opioids may... (Review)
Review
Opioid use has substantially increased over recent years and remains a major driver of new HIV infections worldwide. Clinical studies indicate that opioids may exacerbate the symptoms of HIV-associated neurocognitive disorders (HAND), but the mechanisms underlying opioid-induced cognitive decline remain obscure. We recently reported that the μ-opioid agonist morphine increased neuronal iron levels and levels of ferritin proteins that store iron, suggesting that opioids modulate neuronal iron homeostasis. Additionally, increased iron and ferritin heavy chain protein were necessary for morphine's ability to reduce the density of thin and mushroom dendritic spines in cortical neurons, which are considered critical mediators of learning and memory, respectively. As altered iron homeostasis has been reported in HAND and related neurocognitive disorders like Alzheimer's, Parkinson's, and Huntington's disease, understanding how opioids regulate neuronal iron metabolism may help identify novel drug targets in HAND with potential relevance to these other neurocognitive disorders. Here, we review the known mechanisms of opioid-mediated regulation of neuronal iron and corresponding cellular responses and discuss the implications of these findings for patients with HAND. Furthermore, we discuss a new molecular approach that can be used to understand if opioid modulation of iron affects the expression and processing of amyloid precursor protein and the contributions of this pathway to HAND.
Topics: Analgesics, Opioid; Animals; Cognitive Dysfunction; Dendritic Spines; Ferritins; HIV Infections; Humans; Iron; Morphine; Neurocognitive Disorders; Neurons; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 32975796
DOI: 10.1007/978-1-0716-0884-5_13 -
Nucleus (Austin, Tex.) 2014Polyadenylation is the RNA processing step that completes the maturation of nearly all eukaryotic mRNAs. It is a two-step nuclear process that involves an... (Review)
Review
Polyadenylation is the RNA processing step that completes the maturation of nearly all eukaryotic mRNAs. It is a two-step nuclear process that involves an endonucleolytic cleavage of the pre-mRNA at the 3'-end and the polymerization of a polyadenosine (polyA) tail, which is fundamental for mRNA stability, nuclear export and efficient translation during development. The core molecular machinery responsible for the definition of a polyA site includes several recognition, cleavage and polyadenylation factors that identify and act on a given polyA signal present in a pre-mRNA, usually an AAUAAA hexamer or similar sequence. This mechanism is tightly regulated by other cis-acting elements and trans-acting factors, and its misregulation can cause inefficient gene expression and may ultimately lead to disease. The majority of genes generate multiple mRNAs as a result of alternative polyadenylation in the 3'-untranslated region. The variable lengths of the 3' untranslated regions created by alternative polyadenylation are a recognizable target for differential regulation and clearly affect the fate of the transcript, ultimately modulating the expression of the gene. Over the past few years, several studies have highlighted the importance of polyadenylation and alternative polyadenylation in gene expression and their impact in a variety of physiological conditions, as well as in several illnesses. Abnormalities in the 3'-end processing mechanisms thus represent a common feature among many oncological, immunological, neurological and hematological disorders, but slight imbalances can lead to the natural establishment of a specific cellular state. This review addresses the key steps of polyadenylation and alternative polyadenylation in different cellular conditions and diseases focusing on the molecular effectors that ensure a faultless pre-mRNA 3' end formation.
Topics: 3' Untranslated Regions; Gene Expression Regulation, Developmental; Genetic Diseases, Inborn; Humans; Poly A; Polyadenylation; RNA Stability; RNA, Messenger
PubMed: 25484187
DOI: 10.4161/nucl.36360 -
JACC. Case Reports Oct 2019Nonbacterial thrombotic endocarditis is characterized by sterile thrombi on cardiac valves. This report describes the case of nonbacterial endocarditis without...
Nonbacterial thrombotic endocarditis is characterized by sterile thrombi on cardiac valves. This report describes the case of nonbacterial endocarditis without pathologic findings of fibrin or platelet deposition. Quadrivalvular endocarditis was found to be due to immunoglobulin M heavy chain deposition. This was a case of nonbacterial, nonthrombotic quadrivalvular endocarditis, which was termed noninfective endocarditis. ().
PubMed: 34316824
DOI: 10.1016/j.jaccas.2019.07.026