Development of a radioiodinated thioflavin-T-Congo-red hybrid probe for diagnosis of systemic amyloidosis

2022 ◽  
pp. 116591
Author(s):  
Yoshie Haratake ◽  
Kohei Sano ◽  
Miki Tsuchiya ◽  
Kaori Minaki ◽  
Masayuki Munekane ◽  
...  
Keyword(s):  
Congo Red ◽  
Thioflavin T ◽  
Systemic Amyloidosis

scholarly journals A novel radioiodinated probe for diagnosis of systemic amyloidosis based on thioflavin-T and Congo-red hybrid structure

2021 ◽  
Vol 96-97 ◽  
pp. S54-S55
Author(s):  
Yoshie Haratake ◽  
Kohei Sano ◽  
Miki Tsuchiya ◽  
Kaori Minaki ◽  
Masayuki Munekane ◽  
...  
Keyword(s):  
Congo Red ◽  
Hybrid Structure ◽  
Thioflavin T ◽  
Systemic Amyloidosis

SYSTEMIC AMYLOIDOSIS IN YOUNG MICE INDUCED BY HUMAN SALIVA ADMINISTRATION

2021 ◽  
pp. 40-56
Author(s):  
Vadim A. Kozlov ◽  
Vera Yu. Aleksandrova ◽  
Yulia V. Vasilyeva ◽  
Sergey P. Sapozhnikov ◽  
Pavel B. Karyshev
Keyword(s):  
Visual Field ◽  
Congo Red ◽  
Healthy Person ◽  
Human Saliva ◽  
Systemic Amyloidosis ◽  
Chronic Tonsillitis ◽  
Relative Area ◽  
Congo Red Staining ◽  
Number Of Cells ◽  
Young Mice

The urgency of the study lies in the fact that for the first time it was proved in the experiment that intraperitoneal administration of human saliva to young mice causes the development of systemic amyloidosis, comparable to hereditary systemic amyloidosis in humans, induced by mutagenic changes in saliva lysozyme. The aim of the research: to test human saliva as an amyloidogen in a model experiment on young mice in comparison with the albumin model of amyloidosis that we developed earlier. White male mice weighing 20.0–25.0 g were divided into six groups: Intact mice (5); 30 days 1 time every other day were intraperitoneally administered to groups: 1 (5) soy cream substitute TU 9199-004-58706213-10 15 10 g/100 ml water 0.1 ml/10 g; 2 (3) saliva of a healthy person (SHP) 0.5 ml; 3 (3) SHP and Ciprofloxacin (C) 0.05 mg/10 g of weight; 4 (3) saliva of a person with chronic tonsillitis (remission, SCT); 5 (3) SCT+C. Kidney weight changed from 176.0±21 mg in intact mice (IM) to 197±43,0, 195,0±18,0, 195,0±18,0, 183,0±44,0, 153,0±25,0 mg, respectively. The number of cells per visual field of the tubular epithelium decreased by 1.3, 1.2, 1.6, 1.4, 1.4 times from the number of cells per visual field in IM 380.0±84.0 (p = 0.00), glomerular cells – by 1.4, 1.1, 1.3, 1.2, 1.2 times from the number of glomerular cells in IM 34.0±11.0 (p = 0.02), in groups 1-5, respectively. The glomerular area decreased by 2.4, 2.7, 2.3, 2.4, 3.0 times from the average glomerular area in IM (3163.7±832.7 mm2, p = 0.0000). The relative area of amyloid lesion when stained with Congo red: 18.4±8.2% (group 1), 26,7±10,6, 35,0±11,9, 45,7±13,2, 63,6±14,0% (groups 1-5). The spleen mass and length increased from 133.0±16.0 mg (IM) by 1.7, 1.7, 1.8, 2.1, 1.7 times and from 17.0±2.0 mm (IM) by 1.2, 1.2, 1.3, 1.4, 1.2 times, the number of cells per visual field decreased from 1318±205 (IM) by 1.7, 2.0, 3.3, 2.1, 2.0 times, groups 1-5, respectively (p < 0.01). The relative area of amyloid lesion in Congo red staining: 11,4±9,4%, 28,2±16,0, 27,9±20,8, 20,9±12,2, 16,5±8,3% (groups 1-5). The liver mass changed from 1.4±0.15 g (IM) to 1,57±0,26, 1,45±0,18, 1,53±0,1, 1,71±0,3, 1,36±0,4 g, the number of cells per visual field decreased from 67.0±15.0 (IM) by 1.9, 1.4, 1.8, 2.5, 1.9 times, the area of hepatocyte nuclei – from 54.0±12.3 µm (IM) by 3.1, 3.6, 4.2, 3.1, 3.3 times (groups 1-5, respectively, p < 0.01). The relative area of amyloid lesion in Congo red staining: 6,8±4,6%, 15,3±11,0, 24,5±12,8, 9,8±8,5, 12,6±2,3% (groups 1-5). Conclusions: 1) human saliva when administered intraperitoneally causes severe systemic amyloidosis in young mice with damage to the liver, kidneys and the spleen, which manifests more by cytotoxic effect than the volume of amyloid deposition; 2) human saliva contains a more active amyloidogen than albumin in combination with fillers of the soy cream substitute formulation; 2) human saliva of a person with chronic tonsillitis in remission is more amyloidogenic than the saliva of a healthy person; 3) Ciprofloxacin, administered in a therapeutic dose during the amyloid model formation, moderately increases the severity of amyloid organ damage; 4) human saliva can be used to simulate amyloidosis in an experiment on young mice; 5) the liver may contain enzymatic systems that perform the function of amyloidoclasia.

Development of99mTc-thioflavin-T derivatives for detection of systemic amyloidosis

2008 ◽  
Vol 51 (10) ◽  
pp. 357-367 ◽  
Author(s):  
K. Serdons ◽  
T. Verduyckt ◽  
J. Cleynhens ◽  
G. Bormans ◽  
A. Verbruggen
Keyword(s):  
Thioflavin T ◽  
Systemic Amyloidosis ◽  
Thioflavin T Derivatives

Primary Systemic Amyloidosis Presenting as Extensive Cutaneous Ulceration

2006 ◽  
Vol 10 (5) ◽  
pp. 253-256 ◽  
Author(s):  
Mohammed Alhaddab ◽  
Herbert Srolovitz ◽  
Nathan Rosen
Keyword(s):  
Crystal Violet ◽  
Congo Red ◽  
Systemic Amyloidosis ◽  
Unusual Presentation ◽  
Caucasian Woman ◽  
Advanced Stage ◽  
Amyloid Protein ◽  
Cutaneous Manifestations ◽  
The Right

Background: We report a case of primary systemic amyloidosis in a 78-year-old Caucasian woman presented as a nonhealing ulcer on the right thigh for 3 months. Histopathology of the skin revealed widely thickened walls of middermal and subcutaneous vessels from deposition of amorphous eosinophilic material that stained positively with Congo red and crystal violet. Objective: This case represents a very unusual presentation of primary systemic amyloidosis, one in which the cutaneous manifestations provided the first signs of a devastatingly widespread multiorgan infiltration of amyloid protein. Conclusion: This presentation of the disease may signify an advanced stage with a grave prognosis as our patient passed away 3 months after development of the cutaneous ulceration.

Binding modes of thioflavin T and Congo red to the fibril structure of amyloid-β(1–42)

2020 ◽  
Vol 56 (55) ◽  
pp. 7589-7592 ◽  
Author(s):  
Benedikt Frieg ◽  
Lothar Gremer ◽  
Henrike Heise ◽  
Dieter Willbold ◽  
Holger Gohlke
Keyword(s):  
Congo Red ◽  
Fluorescent Dyes ◽  
Binding Free Energy ◽  
Amyloid Β ◽  
Free Energy Calculations ◽  
Thioflavin T ◽  
Binding Modes ◽  
Fibril Structure ◽  
Binding Free Energy Calculations ◽  
Dynamics Simulations

Binding modes for the amyloid-β(1–42) fibril fluorescent dyes thioflavin T and Congo red were predicted by molecular dynamics simulations and binding free energy calculations.

scholarly journals AMYLOID GOITER AS THE FIRST RECOGNIZABLE MANIFESTATION OF IMMUNOGLOBULIN LIGHT CHAIN AMYLOIDOSIS

2019 ◽  
Vol 5 (5) ◽  
pp. e326-e329 ◽  
Author(s):  
John J. Orrego ◽  
Joseph A. Chorny
Keyword(s):  
Light Chain ◽  
Congo Red ◽  
Monoclonal Gammopathy ◽  
Amyloid Deposition ◽  
Systemic Amyloidosis ◽  
Cardiac Conduction ◽  
Light Chain Amyloidosis ◽  
Amyloid Goiter ◽  
Congo Red Staining ◽  
Bethesda System

Objective: Clinically apparent thyroid enlargement due to massive amounts of amyloid deposition, known as amyloid goiter, is rare. Endocrinologists should become familiar with this manifestation of systemic amyloidosis, which may be diagnosed by Congo red staining of the specimen obtained by fine-needle aspiration. Methods: We describe a 70-year-old man who presented with a slowly enlarging goiter. It was asymptomatic, predominantly left-sided, nontoxic, and multinodular with atypia of undetermined significance (Bethesda System category III) by cytology. The goiter tested negative using the ThyraMIR miRNA Gene Expression Classifier kit (eviCore Healthcare, Bluffton, SC). Results: Left thyroid lobectomy produced a 220-g specimen with nodular hyperplasia and prominent amyloid deposition confirmed by Congo red staining. Liquid chromatography tandem mass spectrometry detected a peptide profile consistent with light chain amyloid deposition of the lambda type, formerly called primary amyloidosis. In retrospect, he had been diagnosed with restrictive cardiomyopathy, cardiac conduction system disease, coronary artery disease, non-nephrotic range proteinuria, and chronic kidney disease, which had been attributed to his longstanding type 2 diabetes mellitus. Extensive workup subsequently demonstrated cardiac amyloidosis and monoclonal gammopathy of unknown significance, consistent with light chain amyloidosis. Conclusion: Amyloid goiter should be included in the differential diagnosis of enlarging goiters with Bethesda System category III cytology in patients with monoclonal gammopathy of uncertain significance, clinical manifestations of systemic amyloidosis, or known diagnosis of monoclonal cell dyscrasia.

Diagnosis and Classification of Amyloidosis in Abdominal Subcutaneous Fat Aspiration Specimens Using Mass Spectrometry Based Proteomics

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2710-2710 ◽  
Author(s):  
Julie A. Vrana ◽  
Steven R. Zeldenrust ◽  
Jason D. Theis ◽  
Jeffrey D. Gamez ◽  
Paul J. Kurtin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Congo Red ◽  
Subcutaneous Fat ◽  
Negative Control Group ◽  
Great Accuracy ◽  
Negative Control ◽  
Systemic Amyloidosis ◽  
Control Group ◽  
Diagnosis And Classification

Abstract Abdominal subcutaneous fat aspiration is one of the most practical, sensitive and specific methods for the diagnosis of systemic amyloidosis. One limitation of this method, compared to more invasive tissue biopsy based approaches, remains the technical difficulties in further classification of the amyloidosis as commonly used methods, such as immunohistochemistry, are not readily applicable to fat aspiration specimens. To overcome these difficulties we developed a method using nano-flow liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) that could identify amyloid subtypes in freshly obtained Congo Red positive fat aspirate specimens with great accuracy. Abdominal subcutaneous fat aspirate specimens were obtained from 73 patients with clinical suspicion for systemic amyloidosis. One half of the specimen was stained with Congo red and used for diagnosis of amyloidosis and the other half was processed and enzyme digested for LC-MS/MS analysis. The resulting LC-MS/MS data was correlated to theoretical fragmentation patterns of tryptic peptide sequences from the Swissprot database using Scaffold (Mascot, Sequest, and X!Tandem search algorithms). Peptide identifications were accepted if they could be established at greater than 90.0% probability and protein identifications were accepted if they could be established at greater than 90.0% probability and contain at least 2 identified spectra. The identified proteins were subsequently examined for the presence or absence of amyloid related peptides. Of the 73 cases studied, 41 were positive for Congo red consistent with systemic amyloidosis. In Congo red positive cases, LC-MS/MS peptide profiles consistent with AL-lambda (28/31), AL-kappa (6/7), and ATTR (2/3) were observed. Only one case in the Congo red negative control group (31/32) gave a kappa light chain profile which was attributed to a high level of kappa in the serum (285 mg/dL). Of the 35 out of 41 cases of systemic amyloidosis successfully classified by LC-MS/MS, additional clinical and pathology data validating the amyloid type was available. In each of these cases the MS/MS results accurately predicted the amyloid type. In conclusion, LC-MS/MS proteomic analysis of abdominal subcutaneous fat aspiration specimens involved by amyloidosis provides a highly specific (97% specificity) and sensitive (&gt;85% sensitivity) method for diagnosis and classification of amyloidosis. The method is rapid and readily applicable in a clinical setting and will greatly improve the clinical management of amyloidosis patients.

scholarly journals Candida albicans Als Adhesins Have Conserved Amyloid-Forming Sequences

2007 ◽  
Vol 7 (5) ◽  
pp. 776-782 ◽  
Author(s):  
Henry N. Otoo ◽  
Kyeng Gea Lee ◽  
Weigang Qiu ◽  
Peter N. Lipke
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Secondary Structure ◽  
Congo Red ◽  
Host Tissue ◽  
Thioflavin T ◽  
Amyloid Fibers ◽  
Conserved Sequence ◽  
Structure Changes ◽  
Cellular Aggregation

ABSTRACT The cell wall-bound Als adhesins of Candida albicans mediate both yeast-to-host tissue adherence and yeast aggregation. This aggregation is amyloid-like, with self-propagating secondary-structure changes, amyloid-characteristic dye binding, and induced birefringence (J. M. Rauceo, N. K. Gaur, K. G. Lee, J. E. Edwards, S. A. Klotz, and P. N. Lipke, Infect. Immun. 72:4948-4955, 2004). Therefore, we determined whether Als proteins could form amyloid fibers with properties like those in cellular aggregation. The β-aggregation predictor TANGO identified a heptapeptide sequence present in a highly conserved sequence with amyloid-forming potential in Als1p, Als3p, and Als5p. A tridecapeptide containing this sequence formed fibers that bound Congo red and thioflavin T and had characteristic amyloid morphology. Als5p20-431 and Als5p20-664, large fragments of Als5p containing the amyloid sequence, also formed amyloid-like fibers and bound Congo red under native conditions. Ka /Ks analysis showed that the amyloid-forming sequences are highly conserved in Als proteins and evolve more slowly than other regions of the proteins. Therefore, amyloid-forming ability itself is conserved in these proteins.

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