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Current Gastroenterology Reports Jan 2018The purpose of this review is to discuss current knowledge and recent findings regarding pathogenesis, outcome, and treatment for heavy chain disease (HCD) involving the... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to discuss current knowledge and recent findings regarding pathogenesis, outcome, and treatment for heavy chain disease (HCD) involving the small bowel, focusing on alpha HCD or immunoproliferative small intestinal disease (IPSID), the HCD subtype typically affecting the small bowel.
RECENT FINDINGS
A link between Campylobacter jejuni infection and IPSID has been established, but there is controversy as to the role played by this organism in disease pathogenesis. While cytogenetic abnormalities involving various immunoglobulin loci and PAX5 have been reported, these have been described in rare, single cases, limiting their ability to shed further light on disease pathogenesis. IPSID is typically regarded as a pre-lymphomatous condition with eventual progression to frank lymphoma; however, recent reports of longstanding non-progressive cases have expanded its clinical spectrum. IPSID is an uncommon disorder affecting the small intestine. This review focuses on current knowledge and novel insight regarding its pathogenesis, outcome, and treatment, with an emphasis on future directions.
Topics: Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Campylobacter Infections; Campylobacter jejuni; Humans; Immunoproliferative Small Intestinal Disease; Prognosis
PubMed: 29372346
DOI: 10.1007/s11894-018-0608-y -
Biochimica Et Biophysica Acta Apr 2015The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle... (Review)
Review
The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21 nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Topics: Animals; Contracture; Frontotemporal Dementia; Humans; Muscle Fibers, Skeletal; Muscular Dystrophies, Limb-Girdle; Mutation; Myosin Heavy Chains; Myositis, Inclusion Body; N-Acetylneuraminic Acid; Ophthalmoplegia; Osteitis Deformans; Protein Processing, Post-Translational
PubMed: 25149037
DOI: 10.1016/j.bbadis.2014.08.007 -
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 -
Frontiers in Neurology 2018There is a need for biomarkers for amyotrophic lateral sclerosis (ALS), to support the diagnosis of the disease, to predict disease progression and to track disease... (Review)
Review
There is a need for biomarkers for amyotrophic lateral sclerosis (ALS), to support the diagnosis of the disease, to predict disease progression and to track disease activity and treatment responses. Over the last decade multiple studies have investigated the potential of neurofilament levels, both in cerebrospinal fluid and blood, as biomarker for ALS. The most widely studied neurofilament subunits are neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH). Neurofilament levels are reflecting neuronal injury and therefore potentially of value in ALS and other neurological disorders. In this mini-review, we summarize and discuss the available evidence about neurofilaments as diagnostic and prognostic biomarker for human ALS.
PubMed: 30713520
DOI: 10.3389/fneur.2018.01167 -
The American Journal of Dermatopathology Dec 2020Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is...
Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Different histologic variants have been described during the past years. We present a case of atypical fibroxanthoma containing a dense inflammatory infiltrate, which in conjunction with the existence of immunoblast-like and Reed-Sternberg-like neoplastic cells could be misinterpreted as a lymphoid neoplasm. Immunohistochemical studies revealed strong positivity of tumor cells for CD10 and negativity for cytokeratins, p63, p40, S100, SOX10, ERG, actin, desmin, B and T-cell markers, BCL6, CD15, and CD30. The inflammatory infiltrate contained a mixed reactive T- and B-cell population with negative T-cell receptor and immunoglobulin heavy rearrangements. We discuss the differential diagnosis of this entity in which clinical, immunohistochemical, and molecular features are essential to avoid the diagnosis of a lymphoproliferative disease.
Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Gene Rearrangement, T-Lymphocyte; Genes, Immunoglobulin Heavy Chain; Genes, T-Cell Receptor; Humans; Immunohistochemistry; Male; Neoplasms, Fibrous Tissue; Polymerase Chain Reaction; Predictive Value of Tests; Pseudolymphoma; Skin Neoplasms
PubMed: 32769551
DOI: 10.1097/DAD.0000000000001761 -
Diabetes, Metabolic Syndrome and... 2022Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus (DM), may progress to end-stage renal disease (ESRD). Current... (Review)
Review
Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus (DM), may progress to end-stage renal disease (ESRD). Current biochemical biomarkers, such as urinary albumin excretion rate (UAER), have limitations for early screening and monitoring of DN. Recent studies have identified some metabolites as candidate biomarkers for early detection of DN. In this review, we summarize the role of dysregulated acylcarnitines (AcylCNs) in DN pathophysiology. Lower abundance of short- and medium-chain AcylCNs and higher long-chain AcylCNs often occurred in DM with normal albuminuria and microalbuminuria, compared with advanced stages of DN. The increase of long-chain AcylCNs was supposed to be an adaptive compensation in fat acids (FAs) oxidation in the early stage of DN. Conversely, the decrease of long-chain AcylCNs was due to incomplete oxidation of FAs in advanced stage of DN. Thus, AcylCNs may serve as sensitive biomarkers in predicting the risk of DN.
PubMed: 35125878
DOI: 10.2147/DMSO.S350233 -
Cancer Biotherapy & Radiopharmaceuticals Mar 2021Targeted therapy is a fast evolving treatment strategy to reduce unwanted damage to healthy tissues, while increasing efficacy and specificity. Driven by... (Review)
Review
Targeted therapy is a fast evolving treatment strategy to reduce unwanted damage to healthy tissues, while increasing efficacy and specificity. Driven by state-of-the-art technology, this therapeutic approach is especially true of cancer. Antibodies with their remarkable specificity have revolutionized therapeutic strategies for autoimmune conditions and cancer, particularly blood-borne cancers, but have severe limitations in treating solid tumors. This is mainly due to their large molecular size, low stability, tumor-tissue penetration difficulties, and pharmacokinetic properties. The tumor microenvironment, rich in immune-suppressing molecules is also a major barrier in targeting solid tumors by antibody-based drugs. Nanobodies have recently emerged as an alternative therapeutic agent to overcome some of the drawbacks of traditional antibody treatment. Nanobodies are the VHH domains found on the heavy-chain only antibodies of camelids and are the smallest naturally available antibody fragments with excellent antigen-binding specificity and affinity, equivalent to conventional antibodies but with molecular weights as low as 15 kDa. The compact size, high stability, enhanced hydrophilicity, particularly in framework regions, excellent epitope interactions with protruding CDR3 regions, and improved tissue penetration make nanobodies the next-generation therapeutics (Nano-BioDrugs). In this review, the authors discuss the interesting properties of nanobodies and their advantages over their conventional counterparts and provide insight into how nanobodies are being utilized as agonists and antagonists, bispecific constructs, and drug and enzyme-conjugates to combat the tumor microenvironment and treat disease.
Topics: Humans; Immunotherapy; Single-Domain Antibodies; Tumor Microenvironment
PubMed: 32936001
DOI: 10.1089/cbr.2020.3941 -
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 -
Clinical Journal of the American... Dec 2016Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that... (Review)
Review
Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein-related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.
Topics: Amyloidosis; Cryoglobulinemia; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunoglobulin G; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney Diseases; Kidney Glomerulus; Paraproteinemias; Paraproteins; Thrombotic Microangiopathies
PubMed: 27526706
DOI: 10.2215/CJN.02980316 -
Basic & Clinical Pharmacology &... Nov 2023LAT1 and 4F2hc form a heterodimeric membrane protein complex, which functions as one of the best characterized amino acid transporters. Since LAT1-4F2hc is required for... (Review)
Review
LAT1 and 4F2hc form a heterodimeric membrane protein complex, which functions as one of the best characterized amino acid transporters. Since LAT1-4F2hc is required for the efficient uptake of essential amino acids and hormones, it promotes cellular growth, in part, by stimulating mTORC1 (mechanistic target of rapamycin complex 1) signalling and by repressing the integrated stress response (ISR). Gain or loss of LAT1-4F2hc function is associated with cancer, diabetes, and immunological and neurological diseases. Hence, LAT1-4F2hc represents an attractive drug target for disease treatment. Specific targeting of LAT1-4F2hc will be facilitated by the increasingly detailed understanding of its molecular architecture, which provides important concepts for its function and regulation. Here, we summarize (i) structural insights that help to explain how LAT1 and 4F2hc assemble to transport amino acids across membranes, (ii) the role of LAT1-4F2hc in key metabolic signalling pathways, and (iii) how derailing these processes could contribute to diseases.
Topics: Humans; Amino Acid Transport Systems; Amino Acids; Biological Transport; Fusion Regulatory Protein 1, Heavy Chain; Large Neutral Amino Acid-Transporter 1; Mechanistic Target of Rapamycin Complex 1
PubMed: 36460306
DOI: 10.1111/bcpt.13821