scholarly journals Effects of sporadic transthyretin amyloidosis frequently on the gallbladder and the correlation between amyloid deposition in the gallbladder and heart

2021 ◽  
Author(s):  
Shojiro Ichimata ◽  
Yukiko Hata ◽  
Naoki Nishida
Keyword(s):  
Gastrointestinal Tract ◽  
Gall Bladder ◽  
Cardiac Involvement ◽  
Amyloid Deposition ◽  
Clinicopathological Features ◽  
Common Condition ◽  
Transthyretin Amyloidosis ◽  
Attr Amyloidosis ◽  
Hematoxylin And Eosin ◽  
Interstitial Deposition

Abstract The aim of the study is to evaluate the clinicopathological features of cholecystic ATTR deposition in patients with cardiac involvement, investigate the correlation of amyloid deposition severity in the gallbladder and the heart, and compare its prevalence in the gallbladder and other organs. Fifty patients with sporadic ATTR amyloidosis were identified. Of these, we evaluated 15 patients who underwent gallbladder sampling accurately. Among 10 patients (67%) with cholecystic deposition, six exhibited detectable deposition in the hematoxylin and eosin-stained specimens, and all of them displayed obstructive vascular deposition (VD). The severity of gall bladder VD was statistically correlated with that of cardiac VD and atrial interstitial deposition (ID). Additionally, all patients exhibiting cholecystic ID displayed severe ventricular and atrial IDs. In visceral organs excluding the heart, amyloid deposition was commonly observed in the lungs (93%), followed by the gastrointestinal tract (47%‒80%), liver (60%), and periosteal tissues (53%). The involvement of gallbladder was prevalent and comparable to that of the gastrointestinal tract. Moreover, the severity of cholecystic deposition was correlated with that of cardiac deposition. Therefore, pathologists should be aware that sporadic ATTR amyloidosis is a common condition and should not be overlooked.

scholarly journals Molecular Mechanisms of Cardiac Amyloidosis

2021 ◽  
Vol 23 (1) ◽  
pp. 25
Author(s):  
Yukihiro Saito ◽  
Kazufumi Nakamura ◽  
Hiroshi Ito
Keyword(s):  
Amyloid Precursor Protein ◽  
Cardiac Amyloidosis ◽  
Molecular Mechanisms ◽  
Cardiac Involvement ◽  
Amyloid Deposition ◽  
Precursor Protein ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Attr Amyloidosis ◽  
Cardiovascular Cells

Cardiac involvement has a profound effect on the prognosis of patients with systemic amyloidosis. Therapeutic methods for suppressing the production of causative proteins have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, and the prognosis has been improved. However, a method for removing deposited amyloid has not been established. Methods for reducing cytotoxicity caused by amyloid deposition and amyloid precursor protein to protect cardiovascular cells are also needed. In this review, we outline the molecular mechanisms and treatments of cardiac amyloidosis.

scholarly journals Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ivana Slamova ◽  
Rozita Adib ◽  
Stephan Ellmerich ◽  
Michal R. Golos ◽  
Janet A. Gilbertson ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Plasmin Activity ◽  
Transthyretin Amyloidosis ◽  
In Vivo Models ◽  
Transgenic Expression ◽  
Attr Amyloidosis ◽  
Amyloid Deposits

AbstractCardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.

Small Cell Carcinomas of the Gastrointestinal Tract: Clinicopathological Features and Treatment Approach

2007 ◽  
Vol 34 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Baruch Brenner ◽  
Laura H. Tang ◽  
Jinruh Shia ◽  
David S. Klimstra ◽  
David P. Kelsen
Keyword(s):  
Gastrointestinal Tract ◽  
Treatment Approach ◽  
Small Cell ◽  
Clinicopathological Features

scholarly journals A Descriptive Analysis of ATTR Amyloidosis in Spain from the Transthyretin Amyloidosis Outcomes Survey

2021 ◽  
Author(s):  
Juan González-Moreno ◽  
Inés Losada-López ◽  
Eugenia Cisneros-Barroso ◽  
Pablo Garcia-Pavia ◽  
José González-Costello ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Transthyretin Amyloidosis ◽  
Attr Amyloidosis

Temporal Trends of Wild-type Attr Amyloidosis in the Transthyretin Amyloidosis Outcomes Survey

2020 ◽  
Vol 26 (10) ◽  
pp. S82
Author(s):  
Jose Nativi-Nicolau ◽  
Alfonso Siu ◽  
Angela Dispenzieri ◽  
Mathew S. Maurer ◽  
Claudio Rapezzi ◽  
...  
Keyword(s):  
Temporal Trends ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Attr Amyloidosis

THE EFFECTS OF ANTIBIOTICS ON THE SYNTHESIS OF VITAMIN B12 IN THE CHICK

1954 ◽  
Vol 32 (6) ◽  
pp. 628-635 ◽  
Author(s):  
K. J. Jenkins ◽  
J. M. Bell ◽  
J. B. O'Neil ◽  
J. W. T. Spinks
Keyword(s):  
Gastrointestinal Tract ◽  
Gall Bladder ◽  
Vitamin B12 ◽  
Marked Effect ◽  
Vitamin B ◽  
The Poor

The effects of aureomycin, terramycin, penicillin, and streptomycin on the synthesis of vitamin B12 in the gastrointestinal tract of the chick fed a vitamin B12-free diet have been studied by means of radiocobalt. Cobalt had no effect by itself but in the presence of an antibiotic resulted in a definite increase in weight. Chicks receiving antibiotics excreted more cobalt and less vitamin B12 than those without supplementation. Synthesis of vitamin B12 in the gastrointestinal tract occurs as early as the proventriculus. Both the rate and the site of synthesis are influenced by the antibiotic fed. A higher concentration of cobalt is found in the tissues of chicks not receiving antibiotics. Antibiotics appear to have no marked effect on vitamin B12 concentration in the tissues except in the blood and gall bladder. The relatively large amount of vitamin B12 in the blood of chicks not supplemented with antibiotics suggests the poor utilization of this vitamin or the synthesis of a physiologically ineffective form.

The Tenosynovitis of Fingers Associated with Transthyretin Amyloidosis

2020 ◽  
Vol 25 (03) ◽  
pp. 340-344
Author(s):  
Yukinori Hara ◽  
Yasuhito Tajiri ◽  
Kenichi Kawano ◽  
Shinya Hoshikawa ◽  
Yusuke Kita
Keyword(s):  
Early Stage ◽  
Patient Characteristics ◽  
Tendon Sheath ◽  
Clinical Findings ◽  
Amyloid Deposition ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Flexor Tendon Sheath ◽  
Tunnel Syndrome ◽  
The Mean

Background: Amyloidosis treatment has advanced rapidly along with the discovery of drugs to prevent amyloid deposition. Therefore, it is vital to detect amyloidosis at an early stage. Wild-type transthyretin, which can cause carpal tunnel syndrome, may also cause finger tenosynovitis. However, the correlation between wild-type transthyretin amyloid and finger tenosynovitis is unclear. Here, we investigated pathological and clinical findings for 20 patients with finger tenosynovitis who underwent operation at our hospital to determine the frequency of transthyretin amyloid deposition in idiopathic finger tenosynovitis. Methods: To check for the presence of amyloid deposition, all specimens (tendon synovium tissue or flexor tendon sheath) resected during the operation were stained by the direct fast scarlet method. Amyloid-positive specimens were evaluated by immunohistochemical staining using an anti-transthyretin antibody. Patient characteristics were evaluated with respect to amyloid presence. Results: Thirteen (65%) of 20 finger tenosynovitis cases had amyloid deposition. Nine (69.2%) of the 13 amyloid-positive cases exhibited extensive transthyretin staining and were considered to have transthyretin amyloid. Amyloid deposition was more frequent in men. The mean number of fingers with tenosynovitis was significantly higher in amyloid-positive cases (3.8 fingers) than in amyloid-negative cases (2.0 fingers). Conclusions: Men with multiple finger tenosynovitis tended to have transthyretin amyloid deposition. Our results support that multiple finger tenosynovitis may serve as an initial indication of evaluation for transthyretin amyloidosis.

Cardiac involvement in a large cohort of patients with Val30Met transthyretin amyloidosis from Majorca focus

Amyloid ◽  
2019 ◽  
Vol 26 (sup1) ◽  
pp. 15-16
Author(s):  
Tomas Ripoll-Vera ◽  
Jorge Alvarez ◽  
Juan Buades ◽  
Eugenia Cisneros ◽  
Yolanda Gomez ◽  
...  
Keyword(s):  
Cardiac Involvement ◽  
Large Cohort ◽  
Transthyretin Amyloidosis

scholarly journals Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis

2019 ◽  
Vol 20 (6) ◽  
pp. 1287 ◽  
Author(s):  
Nelson Ferreira ◽  
Maria Saraiva ◽  
Maria Almeida
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Current Work ◽  
Amino Acid Substitutions ◽  
Therapeutic Approaches ◽  
Transthyretin Amyloidosis ◽  
Chemical Chaperones ◽  
Attr Amyloidosis

Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.

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