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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 -
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 -
JPMA. the Journal of the Pakistan... Apr 2022To assess the association of single nucleotide polymorphisms in fatty acid binding protein-2 (rs1799883) and glutathione S-transferase pi (rs1695) genes with...
A study of association between presence or absence of GSTT1 and GSTM1 and/or single nucleotide polymorphism in FABP2 and GSTP1 with incidence of diabetes type 2: A case-control study.
OBJECTIVE
To assess the association of single nucleotide polymorphisms in fatty acid binding protein-2 (rs1799883) and glutathione S-transferase pi (rs1695) genes with presence/absence of glutathione S-transferase mu and glutathione S-transferase theta genes in type 2 diabetes.
METHODS
The cross-sectional case-control study was conducted at Institute of Molecular Biology and Biotechnology during March till September 2019 and comprised type 2 diabetes patients and non-diabetic controls from two districts in southern Punjab. Polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system-polymerase chain reaction were applied to investigate glutathione S-transferase theta, mu and pi genes as well as fatty acid binding protein-2, as appropriate. The association of single nucleotide polymorphisms in all genes with the disease were studied either individually or in various combinations. Data was analysed using Minitab 18.
RESULTS
Of the 448 subjects, 248(55.4%) were patients and 200(44.6%) were controls. Overall there were 213(47.5%) males and 235(52.5) were females, and 141(31.5%) were aged 30-46 years. The presence of rs1799883 in fatty acid binding protein-2 (p=0.03) and the absence of glutathione S-transferase mu gene (p<0.001) had significant association with type 2 diabetes, while the presence of glutathione S-transferase theta and rs1695 in glutathione S-transferase pi genes were not associated with the disease. Individuals with glutathione S-transferase mu gene null and Ileu/Ileu or Ileu/Val genotype of rs1695 in glutathione S-transferase pi gene have potential to develop type 2 diabetes in their lifetime (p<0.05).
CONCLUSIONS
The presence of rs1799883 in fatty acid binding protein-2 and the absence of glutathione S-transferase mu gene were found to play significantly in the development of type 2 diabetes.
Topics: Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Acid-Binding Proteins; Female; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Incidence; Male; Polymorphism, Single Nucleotide
PubMed: 35614607
DOI: 10.47391/JPMA.1337 -
Journal of Clinical Laboratory Analysis Mar 2022Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear....
OBJECTIVE
Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.
METHODS
After the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme-linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17A at baseline of RA patients were also detected by ELISA.
RESULTS
ITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2-213.5) ng/mL) than in HCs (306.8 (IQR: 238.9-435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C-reactive protein (CRP) (r = -0.358, p < 0.001) and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) (r = -0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF-α (r = -0.337, p = 0.001), IL-6 (r = -0.221, p = 0.033), and IL-17A (r = -0.368, p < 0.001) in RA patients, but not correlated with IL-1β (r = -0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).
CONCLUSION
Circulating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.
Topics: Alpha-Globulins; Arthritis, Rheumatoid; Biomarkers; Blood Sedimentation; Humans; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 35064701
DOI: 10.1002/jcla.24231 -
Children (Basel, Switzerland) Jul 2023Bronchopulmonary dysplasia (BPD) is a devastating disease in preterm infants concurrent with neurodevelopmental disorders. Chronic hyperoxia exposure might also cause...
INTRODUCTION
Bronchopulmonary dysplasia (BPD) is a devastating disease in preterm infants concurrent with neurodevelopmental disorders. Chronic hyperoxia exposure might also cause brain injury, but the evidence was insufficient.
METHODS
Neonatal C57BL/6J mice were exposed to hyperoxia from P0 to induce a BPD disease model. Lung histopathological morphology analyses were performed at P10, P15, and P20. Cerebral myelination was assessed using MBP (myelin basic protein, a major myelin protein), NfH (neurofilament heavy chain, a biomarker of neurofilament heavy chain), and GFAP (glial fibrillary acidic protein, a marker of astrocytes) as biomarkers by western blot and immunofluorescence.
RESULTS
Mice exposed to hyperoxia exhibited reduced and enlarged alveoli in lungs. During hyperoxia exposure, MBP declined at P10, but then increased to a comparable level to the air group at P15 and P20. Meanwhile, GFAP elevated significantly at P10, and the elevation sustained to P15 and P20.
CONCLUSION
Neonatal hyperoxia exposure caused an arrest of lung development, as well as an obstacle of myelination process in white matter of the immature brain, with a decline of MBP in the generation period of myelin and persistent astrogliosis.
PubMed: 37628321
DOI: 10.3390/children10081321 -
Acta Pharmaceutica Sinica. B Jun 2020Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead... (Review)
Review
Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.
PubMed: 32837872
DOI: 10.1016/j.apsb.2020.06.007 -
European Journal of Ophthalmology May 2024To report a case of progressive ischemic retinopathy and optic neuropathy in a patient with heavy chain deposition disease (HCDD), a rare form of monoclonal...
PURPOSE
To report a case of progressive ischemic retinopathy and optic neuropathy in a patient with heavy chain deposition disease (HCDD), a rare form of monoclonal immunoglobulin deposition disease (MIDD).
OBSERVATIONS
Our case describes a 74-year-old woman diagnosed with IgG1 lambda HCDD. After treatment with daratumumab and intravenous IVIG therapy, the patient developed worsening ischemic retinopathy and optic neuropathy, neovascular glaucoma, and bilateral sequential vitreous hemorrhages, necessitating surgical intervention. We present multimodal imaging from the onset of ischemic retinopathy to end-stage maculopathy illustrated by optical coherence tomography (OCT) angiography. Despite discontinuing treatment with daratumumab and providing maximal ocular interventions to control the complications of neovascular disease, the patient's condition progressed, resulting in profound vision loss.
CONCLUSIONS AND IMPORTANCE
Our case illustrates the potential for HCDD to cause end-organ disease, including ischemic retinopathy and optic neuropathy, possibly worsened by the patient's underlying cardiovascular risk factor status and medications. Daratumumab, a humanized IgG1 kappa monoclonal antibody that binds to CD38 used to treat specific blood cancers, has been reported to cause disturbances in retinal blood flow, including retinal artery and vein occlusions. It remains to be determined whether careful patient selection or dose adjustments and timing of HCDD treatments could protect vision by reducing the risk of these rare yet severe ocular complications.
PubMed: 38815990
DOI: 10.1177/11206721241257553 -
Journal of Nephrology Aug 2021The development of renal disease in patients with monoclonal gammopathy of renal significance (MGRS) depends on the pathogenicity of the secreted monoclonal protein (M...
BACKGROUND
The development of renal disease in patients with monoclonal gammopathy of renal significance (MGRS) depends on the pathogenicity of the secreted monoclonal protein (M protein). However, the correlation between the types of M proteins and clinical and renal pathological features is still unclear.
METHODS
A total of 148 patients with detectable serum M protein and biopsy-proven MGRS were recruited. The patients were categorized according to the heavy and light chain types of M protein in the serum.
RESULTS
Among 148 patients, the most common M protein was IgGλ, followed by IgAλ and IgGκ. According to the type of heavy chain, patients with IgM-MGRS were more likely to have renal dysfunction, anemia and hypocomplementemia than patients with IgG-MGRS and IgA-MGRS. The λ light chain was predominant in patients with IgG-MGRS and IgA-MGRS, whereas the κ light chain was predominant in patients with IgM-MGRS. The most common renal lesion was amyloidosis in patients with IgG-MGRS and IgA-MGRS, while it was cryoglobulinemic glomerulonephritis in patients with IgM-MGRS. According to the type of light chain, patients with κ light chain were more likely to be male and to have renal dysfunction, anemia and hypocomplementemia than those with λ light chain. The types of heavy chain and light chain of M protein were not associated with patient or renal survival.
CONCLUSION
The clinicopathological features were distinct in patients with different types of M protein. Integration of the types of M protein and renal pathologic findings may shed light on individual management of patients with MGRS.
Topics: Biopsy; Female; Glomerulonephritis; Humans; Kidney; Kidney Diseases; Male; Paraproteinemias
PubMed: 32725498
DOI: 10.1007/s40620-020-00817-x -
Scandinavian Journal of Clinical and... Dec 2023Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current...
Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current research intended to discover the clinical value of serum ITIH4 quantification for AS management. Serum ITIH4 among 80 AS patients before current treatment initiation (baseline) at weeks (W) 4, 8 and 12 after treatment was detected by ELISA. Serum ITIH4 from 20 disease controls (DCs) and 20 healthy controls (HCs) was detected. ITIH4 expression was lower in AS patients than in DCs ( = 0.002) and HCs ( < 0.001). Among AS patients, ITIH4 was negatively associated with C-reactive protein (CRP) ( = -0.311, = 0.005), bath AS disease activity index (BASDAI) ( = -0.223, = 0.047), total pack pain ( = -0.273, = 0.014) and AS disease activity score (ASDAS) (CRP) ( = -0.265, = 0.018). Meanwhile, ITIH4 was negatively related to tumor necrosis factor (TNF)-α ( = -0.364, = 0.001), interleukin (IL)-1β ( = -0.251, = 0.025), IL-6 ( = -0.292, = 0.009) and IL-17A ( = -0.254, = 0.023). After treatment, the assessment of the spondylitis arthritis international society 40 response rate was 28.7% at W4, 46.3% at W8 and 55.0% at W12; ITIH4 showed an increasing trend from baseline to W12 ( < 0.001). Furthermore, ITIH4 at W8 ( = 0.020) and W12 ( = 0.035), but not at baseline or W4 (both > 0.05), was enhanced in response patients vs. nonresponse patients. Additionally, ITIH4 at W12 was increased in AS patients receiving TNF inhibitors vs. those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) ( = 0.024). Serum ITIH4 increases after treatment, and its augmentation is correlated with lower disease activity, decreased inflammation and enhanced treatment response in AS patients.
Topics: Humans; Anti-Inflammatory Agents; C-Reactive Protein; Inflammation; Spondylitis, Ankylosing; Sulfonamides; Treatment Outcome; Trypsin Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 38156824
DOI: 10.1080/00365513.2023.2250986 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2020Heavy chain disorders are rare B-cell disorders and include heavy chain disease, heavy chain deposition disease, and heavy chain amyloidosis. These disorders share the... (Review)
Review
Heavy chain disorders are rare B-cell disorders and include heavy chain disease, heavy chain deposition disease, and heavy chain amyloidosis. These disorders share the pathognomonic finding of a truncated immunoglobulin heavy chain without an associated light chain in the serum or urine in the case of heavy chain disease or in the tissues in the case of heavy chain deposition disease and heavy chain amyloidosis but are clinically distinct entities. The clinical recognition and systematic approaches to these disorders are challenging because of the rarity of the diseases, lack of consensus on treatment approaches, and minimal data with novel therapy. Herein we present a review of the literature and 5 consecutive cases at a single institution of gamma heavy chain disease and heavy chain deposition disease treated with novel agents including regimens of CRd (cyclophosphamide, lenalidomide, and dexamethasone), CyBorD (cyclophosphamide, bortezomib, and dexamethasone), R-CVP (rituximab, cyclophosphamide, vincristine, and dexamethasone), BR (bendamustine and rituximab), V-EPOCH (bortezomib, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), and autologous hematopoietic stem cell transplantation.
Topics: Female; Heavy Chain Disease; Humans; Male; Middle Aged
PubMed: 32245744
DOI: 10.1016/j.clml.2020.02.020