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CEN Case Reports Nov 2014We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man...
We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man having a long history of uncontrolled diabetes mellitus with retinopathy. He showed heavy proteinuria and renal insufficiency, and did not have paraproteins. Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light chain, IgG and C1q along glomerular basement membrane (GBM). At first, we interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic nodular glomerulosclerosis. Later, we recognized one of a few case reports of monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and reconsidered the first diagnosis. The added electron microscopy (EM) showed obvious electron-dense materials in GBM, while tubular basement membrane deposits were not identified. A concurrence of LHCDD and diabetic nodular glomerulosclerosis may be suggested in this case. Like this case, IF staining in MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM. Reports of MIDD in diabetic patients are extremely rare, possibly due to being often overlooked. This case emphasizes that overall pathological examination including IF and EM is important for the accurate differentiation of nodular glomerulosclerosis, even in diabetic patients.
PubMed: 28509191
DOI: 10.1007/s13730-014-0110-9 -
International Journal of Nanomedicine 2013The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive... (Review)
Review
The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging. Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities. This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes.
Topics: Animals; Camelus; Drug Delivery Systems; Immunoglobulin Heavy Chains; Molecular Imaging; Nanomedicine; Single-Domain Antibodies
PubMed: 24204148
DOI: 10.2147/IJN.S39428 -
Journal of Clinical Pathology.... 1975
Review
Topics: Heavy Chain Disease; Humans; Immunoglobulin alpha-Chains
PubMed: 830057
DOI: 10.1136/jcp.s1-6.1.72 -
Internal Medicine (Tokyo, Japan) Sep 2005
Topics: Antineoplastic Agents; Heavy Chain Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Paraproteinemias; Prognosis; Transplantation, Autologous
PubMed: 16258202
DOI: 10.2169/internalmedicine.44.915 -
Blood Mar 2019
Topics: Aged; Autoimmune Diseases; B-Lymphocytes; Fatal Outcome; Female; Heavy Chain Disease; Humans; Immunoglobulin gamma-Chains
PubMed: 30898778
DOI: 10.1182/blood-2018-11-887133 -
Journal of Cachexia, Sarcopenia and... Dec 2022Fibro-adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at...
BACKGROUND
Fibro-adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at normal conditions. However, it is not clear how FAPs may interact with MPCs in aged muscles. Senolytics have been demonstrated to selectively eliminate senescent cells and generate therapeutic benefits on ageing and multiple age-related disease models.
METHODS
By studying the muscles and primary cells of age matched WT mice and Zmpste24 (Z24 ) mice, an accelerated ageing model for Hutchinson-Gilford progeria syndrome (HGPS), we examined the interaction between FAPs and MPCs in progeria-aged muscle, and the potential effect of senolytic drug fisetin in removing senescent FAPs and improving the function of MPCs.
RESULTS
We observed that, compared with muscles of WT mice, muscles of Z24 mice contained a significantly increased number of FAPs (2.4-fold; n > =6, P < 0.05) and decreased number of MPCs (2.8-fold; n > =6, P < 0.05). FAPs isolated from Z24 muscle contained about 44% SA-β-gal+ senescent cells, in contrast to about 3.5% senescent cells in FAPs isolated from WT muscle (n > =6, P < 0.001). The co-culture of Z24 FAPs with WT MPCs resulted in impaired proliferation and myogenesis potential of WT MPCs, with the number of BrdU positive proliferative cells being reduced for 3.3 times (n > =6, P < 0.001) and the number of myosin heavy chain (MHC)-positive myotubes being reduced for 4.5 times (n > =6, P < 0.001). The treatment of the in vitro co-culture system of Z24 FAPs and WT MPCs with the senolytic drug fisetin led to increased apoptosis of Z24 FAPs (14.5-fold; n > =6, P < 0.001) and rescued the impaired function of MPCs by increasing the number of MHC-positive myotubes for 3.1 times (n > =6, P < 0.001). Treatment of Z24 mice with fisetin in vivo was effective in reducing the number of senescent FAPs (2.2-fold, n > =6, P < 0.05) and restoring the number of muscle stem cells (2.6-fold, n > =6, P < 0.05), leading to improved muscle pathology in Z24 mice.
CONCLUSIONS
These results indicate that the application of senolytics in the progeria-aged muscles can be an efficient strategy to remove senescent cells, including senescent FAPs, which results in improved function of muscle progenitor/stem cells. The senescent FAPs can be a potential novel target for therapeutic treatment of progeria ageing related muscle diseases.
Topics: Mice; Animals; Progeria; Senotherapeutics; Adipogenesis; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal
PubMed: 36218080
DOI: 10.1002/jcsm.13101 -
Journal of Cellular and Molecular... Jan 2022This study aims to determine the serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) in...
This study aims to determine the serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) in amyotrophic lateral sclerosis (ALS) patients, and to explore their feasibility as valid biomarkers for quantifying disease progression and predicting individual prognosis. 52 patients with ALS and 30 controls with noninflammatory neurological diseases were included. NFL and pNFH levels in serum and CSF were measured by enzyme-linked immunosorbent assay. Our findings showed that serum and CSF levels of NFL and pNFH in ALS patients were significantly increased. These values were negatively correlated with disease duration (except CSF NFL with disease duration) and ALSFRS-r score, and positively correlated with disease progression rate (DPR) and upper motor neuron (UMN) score, but did not correlate with bilateral median and ulnar nerve compound muscle action potential (cMAP) amplitudes (except a weak correlation between CSF NFL and cMAP amplitudes). The optimal cut-off values with high sensitivity and specificity were obtained in ROC curve analysis to discriminate ALS from controls. Kaplan-Meier survival curves illustrated that survival was significantly shorter for patients with higher neurofilament levels at diagnosis. The Cox proportional hazards regressions confirmed that NFL and pNFH were significant predictors of survival. Overall, NFL and pNFH in serum and CSF can be used as reliable biomarkers in ALS.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Intermediate Filaments; Motor Neurons
PubMed: 34866307
DOI: 10.1111/jcmm.17100 -
Clinical Kidney Journal Apr 2015Light and heavy chain deposition disease (LHCDD) is a rare complication of monoclonal gammopathy. In all documented cases, LHCDD is the association of deposits of a...
Light and heavy chain deposition disease (LHCDD) is a rare complication of monoclonal gammopathy. In all documented cases, LHCDD is the association of deposits of a monoclonal light chain with a normal heavy chain, especially in the kidneys. We describe here a 78-year-old woman whose renal biopsy showed nodular glomerulosclerosis, initially diagnosed as diabetic nephropathy. Detailed kidney biopsy immunofluorescence study corrected the diagnosis to γ1-κ-LHCDD. Advanced immunoblot analysis showed deletion of CH1 in the both blood and kidney heavy chain. We report here, to our knowledge, the first case of γ1 LHCDD associated with a deletion of CH1.
PubMed: 25815184
DOI: 10.1093/ckj/sfv002 -
PloS One 2016To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS.
OBJECTIVE
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
METHODS
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
RESULTS
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
CONCLUSION
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Neurofilament Proteins
PubMed: 27732645
DOI: 10.1371/journal.pone.0164625 -
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