Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9

Search results for: amyloidosis

9 Renal Amyloidosis in Domestic Iranian Sheep

Authors: Keivan Jamshidi, Fateme Behbahani, Sara Omidi, Nadia Shahi, Alireza Farkhonde

Abstract:

Amyloidosis represents a heterogenous group of diseases that have in common the deposition of fibrils composed of proteins of beta-pleated sheet structure, which can be specifically identified by histochemistry using the Congo red or similar stains. Between October 2013 to April 2014 (6 months) different patterns of renal amyloidosis was diagnosed on histopathological examination of kidneys belong to 196 out of 7065 slaughtered sheep subjected to postmortem examination. Microscopic examination of renal tissue sections stained with H&E and CR staining techniques revealed 3 patterns of renal amyloid deposition; including glomerular (22.72%), medullary (68.18%), and vascular (9.09%) were recognized. Renal medullary amyloidosis (RMA) was detected as the most prevalence pattern of renal amyloidosis in domestic sheep.

Keywords: sheep, amyloidosis, kidney, slaughterhouse

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8 Gallbladder Amyloidosis Causing Gangrenous Cholecystitis: A Case Report

Authors: Christopher Leung, Guillermo Becerril-Martinez

Abstract:

Amyloidosis is a rare systemic disease where abnormal proteins invade various organs and impede their function. Occasionally, they can manifest in a solidary organ such as the heart, lung, and nervous systems; rarely do they manifest in the gallbladder. Diagnosis often requires biopsy of the affected area and histopathology shows deposition of abnormally folded globular proteins called amyloid proteins. This case presents a 69-year-old male with a 3-month history of RUQ pain, diarrhea and non-specific symptoms of tiredness, etc. On imaging, both his US and CT abdomen showed gallbladder wall thickening and pericholecystic fluid, which may represent acute cholecystitis with hypodense lesions around the gallbladder, possibly representing liver abscesses. Given his symptoms of abdominal pain and imaging findings, this gentleman eventually had a laparoscopic cholecystectomy showing a gangrenous gallbladder with a mass on the liver bed. On histopathology, it showed amorphous hyaline eosinophilic material, which Congo-stained confirmed amyloidosis. Amyloidosis explained his non-specific symptoms, he avoided further biopsy, and he was commenced immediately on Lenalidomide. Involvement of the gallbladder is extremely rare, with less than 30 cases around the world. Half of the cases are reported as primary amyloidosis. This case adds to the current literature regarding primary gallbladder amyloidosis. Importantly, this case highlights how laparoscopic cholecystectomy can help with the diagnosis of gallbladder amyloidosis.

Keywords: amyloidosis, cholecystitis, gangrenous cholecystitis, gallbladder, systemic amyloidosis

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7 Comparative Study of Propensity for Amyloidogenesis in Male and Female Mice

Authors: Keivan Jamshidi, Afshin Zahedi

Abstract:

Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the propensity for amyloidogenesis in male and female rats on spatio-temporal pattern was evaluated. For this purpose a total of 40 male and female Swiss mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatment groups [ 10 male (Group A1) and 10 female (Group B1) each], and 2 control groups [10 male (Group A2) and 10 female (Group B2) each]. At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen samples of each animal were obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. The data obtained from polarized microscopic quantitative analysis did show significant differences between groups A1 and B1. A preferential expression of reactive amyloidosis is concluded in male, indicating sex differences in amyloidosis.

Keywords: amyloidosis, amyloidogenesis, mice, gender

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6 Comparative Study of Amyloidogenic Potential of AgNO3 and Freund's Adjuvant (AF) with That of Vitamin Free Casein, on Spatio-Temporal Pattern of Experimental Amyloidosis in Mice

Authors: Alireza Javed, Keivan Jamshidi

Abstract:

Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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5 IgA/λ Plasma Cell Myeloma with λ Light Chain Amyloidosis: A Case Report

Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

Abstract:

Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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4 Molecular Basis for Amyloid Inhibition by L-Dopa: Implication towards Systemic Amyloidosis

Authors: Rizwan H. Khan, Saima Nusrat

Abstract:

Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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3 Text Mining Techniques for Prioritizing Pathogenic Mutations in Protein Families Known to Misfold or Aggregate

Authors: Khaleel Saleh Al-Rababah

Abstract:

Amyloid fibril forming regions, which are known as protein aggregates, in sequences of some protein families are associated with a number of diseases known as amyloidosis. Mutations play a role in forming fibrils by accelerating the fibril formation process. In this paper we want to extract diseases that caused by those mutations as a result of the impact of the mutations on structural and functional properties of the aggregated protein. We propose a text mining system, to automatically extract mutations, diseases and relations between mutations and diseases. We presented an algorithm based on finite state to cluster mutations found in the same sentence as a sentence could contain different mutation cause different diseases. Also, we presented a co reference algorithm that enables cross-link sentences.

Keywords: amyloid, amyloidosis, co reference, protein, text mining

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2 Anti-Fibrillation Propensity of a Flavonoid Baicalein against the Fibrils of Hen Egg White Lysozyme: Potential Therapeutics for Lysozyme Amyloidosis

Authors: Naveed Ahmad Fazili

Abstract:

More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20 fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in congo red assay and appearance of a network of long rope like fibrils in TEM analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150 μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 nm and 450 nm respectively together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.

Keywords: amyloid fibrils, baicalein, congo red, negative ellipticity, therapeutics

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1 Amyloid Deposition in Granuloma of Tuberculosis Patients: A Pilot Study

Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

Abstract:

Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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