WorldWideScience

Sample records for amyloidosis

  1. Hereditary amyloidosis

    Science.gov (United States)

    ... of the blood cells (myeloma) Specific conditions include: Cardiac amyloidosis Cerebral amyloidosis Secondary systemic amyloidosis Treatment A liver transplant may be helpful. Talk to your health care ...

  2. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  3. Systemic amyloidosis.

    Science.gov (United States)

    Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N

    2016-06-25

    Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses. PMID:26719234

  4. AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Desport Estelle

    2012-08-01

    Full Text Available Abstract Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig light chains (LC (most commonly of lambda isotype usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and

  5. Respiratory manifestations in amyloidosis

    Institute of Scientific and Technical Information of China (English)

    XU Ling; CAI Bai-qiang; ZHONG Xu; ZHU Yuan-jue

    2005-01-01

    Background Amyloidosis is a collection of diseases in which different proteins are deposited. Amyloid deposits occur in systemic and organ-limited forms. In both systemic and localized forms of the disease, lung can be involved. The aim of this study was to explore the different respiratory manifestations of amyloidosis. Methods Chest radiology, clinical presentations, bronchoscopic/laryngoscopic findings and lung function data of 59 patients with amyloidosis involving respiratory tract collected during January 1986 to March 2005, were analysed.Results Of the 16 cases with localized respiratory tract amyloidosis, 8 had the lesions in the trachea and the bronchi, 2 in the larynx and the trachea, 5 in the larynx and/or the pharynx, and 1 in the lung parenchyma. Of 43 systemic amyloidosis with respiratory tract involvement, 3 had the lesions in bronchi, 13 in lung parenchyma, 33 in pleura, 8 in mediastina, 1 in nose and 1 in pharynx. Chest X-rays were normal in most cases of tracheobronchial amyloidosis. CT, unlike chest X-rays, showed irregular luminal narrowing, airway wall thickening with calcifications and soft tissue shadows in airway lumen. Localized lung parenchymal amyloidosis presented as multiple nodules. Multiple nodular opacities, patch shadows and reticular opacities were the main radiological findings in systemic amyloidosis with lung parenchymal involvement. In pleural amyloidosis, pleural effusions and pleural thickening were detected. Mediastinal and/or hilar adenopathy were also a form of lung involvement in systemic amyloidosis. The major bronchoscopic findings of tracheobronchial amyloidosis were narrowing of airway lumen, while nodular, 'tumour like' or 'bubble like' masses, with missing or vague cartilaginous rings, were detected in about half of the patients.Conclusions Localized respiratory tract amyloidosis mostly affects the trachea and the bronchi. Chest X-rays are not sensitive to detect these lesions. Systemic amyloidosis often involves

  6. Localized Tracheal Amyloidosis

    OpenAIRE

    Juričevski, Ivan; Vrčić, Mihovil; Vrčić, Alka; Budimir, Ivan; Križanac, Šimun; Tuđman, Zdenko; Varga, Damir

    2005-01-01

    Amyloidosis is a disorder characterized by localized or diffuse deposition of fibrillary proteins in the extracellular space, causing progressive damage to tissue structure and organ function. Any organ system of the body may be involved by amyloidosis. A case is presented of localized tracheal amyloidosis in a 62-year-old man treated for active lung tuberculosis. Among other procedures, diagnostic workup included bronchoscopy, which revealed tumor-like lesions of tracheal mucosa. Histologic ...

  7. Primary cutaneous amyloidosis

    OpenAIRE

    Shah Mona; Padhiar Bela; Karia Umesh; Shah Bela; Rawal R; Bilimoria F

    1997-01-01

    Three cases of primary cutaneous amyloidosis are reported. Family history was negative. Systemic involvement was ruled out. Histopathology was confirmed by congored stain. Patients responded to oral colchicine.

  8. Secondary systemic amyloidosis

    Science.gov (United States)

    ... systemic amyloidosis include: Endocrine failure Heart failure Kidney failure Respiratory failure When to Contact a Medical Professional Call your ... Cystic fibrosis Endocrine glands Hairy cell leukemia Heart failure - overview Hodgkin ... arthritis Sjögren syndrome Systemic lupus erythematosus Update ...

  9. Amyloidosis and Kidney Disease

    Science.gov (United States)

    ... a physical exam urinalysis blood tests a kidney biopsy Medical and Family History Taking a medical and family history may help ... of the kidneys with a medical and family history a physical exam urinalysis blood tests a kidney biopsy A health care provider diagnoses dialysis-related amyloidosis ...

  10. Myeloma associated systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Lakshmi Kumari N

    1993-01-01

    Full Text Available This is a case report of myeloma associated systemic amyloidosis in a 45 years old man. The patient presented with asymptomatic plaques and papules around the eyes, nostrils, anus, inguinal region and tongue. Purpuric lesions were noticed on and off over the lesions. When thorough investigations were undertaken they revealed multiple myeloma. Histopathology with amyloid stain positivity and bone marrow examination confirmed the diagnosis.

  11. Primary systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanasilović Srđan

    2007-01-01

    Full Text Available Background. Systemic amyloidosis is a rare disorder which usually occurs in aged persons and has a poor prognosis. Systemic amyloidosis can be primary, occasionally associated with multiple myeloma, or secondary, associated with another disease. Case report. We presented a 72-year-old male patient with periocular purpura ("racoon sign" and waxy papules, petechiae and ecchymoses on the neck and thoracic area. Purpuric macules were present also on the lips and tongue which was edematous (macroglossia. The skin lesions occurred two years earlier, the patient lost more than 15 kilograms of the body mass for less than a year. Immunoelectrophoresis of urine and serum demonstrated the presence of immunoglobulin light chains of the circulating monoclonal protein. Histopathological examination of skin lesions showed Congo red positive deposits in the derm. Cardiac evaluation revealed the signs of heart failure, and renal evaluation revealed nephrotic syndrome, with excessive protein lost. He was treated with oral melphalan and prednisolone, and died 7 days after starting the therapy due to heart failure. Conclusion. This patient considered as a rare case with systemic amyloidosis highlights the importance of histopathological and physical examination in any cases with periocular purpura, petechiae, ecchymoses and macroglossia.

  12. [Amyloidosis: Up-to-date].

    Science.gov (United States)

    Magy-Bertrand, N

    2016-08-01

    Amyloidosis is mainly a systemic disease belonging to protein-folding diseases. The past 10 years have shown significant progress in typing and the clinical management of amyloidosis, in the identification of novel prognostic markers for risk-stratification, and also in the development of new therapeutic agents. Biological molecular techniques are now able to type amyloidosis which were unidentified. Cardiac MRI and biomarkers allow a precise risk-stratification, especially in AL amyloidosis. If necessary, this prognostic evaluation may lead to rapid changes in the chemotherapy treatment. Emerging treatments rely on biotherapies, gene therapy, immunotherapy and blocking analogous agents. They give hope about an increase of survival of patients with systemic amyloidosis.

  13. Unique type of isolated cardiac valvular amyloidosis

    Directory of Open Access Journals (Sweden)

    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  14. Corneal amyloidosis associated with keratoconus.

    Science.gov (United States)

    Stern, G A; Knapp, A; Hood, C I

    1988-01-01

    Nodular, gray-white, central corneal opacities which extended from the subepithelial zone through the anterior four fifths of the stroma developed in a 50-year-old man with a longstanding history of hard contact lens wear for keratoconus. Results of histopathologic analysis of the corneal button obtained at the time of penetrating keratoplasty disclosed that the opacities were composed of amyloid. Corneal amyloidosis is rarely found in association with keratoconus. Although there were some similarities in the pattern of amyloid deposition to that seen in primary familial amyloidosis of the cornea, the authors believe that their patient is more likely to have had a secondary amyloidosis. Corneal amyloidosis should be considered in keratoconus patients with development of unusual forms of central corneal opacification. PMID:3278260

  15. Clinicopathological Study of Renal Amyloidosis

    Directory of Open Access Journals (Sweden)

    Usha, Rana Gopal Singh, Jai Parkash, Ruchi Kapoor, Sunita Rai, D.K. Sinha

    2006-01-01

    Full Text Available Study included 13 cases of renal amyloidosis.Oedema, feet and face was the commonest manifestation(100%, two patients (18.18% also presented with loose motions, ascites and pain in abdomen and onepatient had ankylosing spondylitis and cervical spondylitis. On clinical grounds only one case was diagnosedas primary amyloidosis of light chain type, who presented initially with cervical lymphadenopathy and 4years later with nephrotic syndrome. About 72.72% cases had some chronic disease in the terms oftuberculosis, ankylosing spondylitis, chronic ulcerative colitis, lepromatous leprosy, rheumatoid arthritisand one patient had carcinoma caecum. Congo red stain was positive in both, light chain deposit disease(LCDD and amyloidosis but polarizing microscope showed mixed birefringence (red, green, yellowonly in amyloidosis. In AFOG and PAS stain, amyloid appeared negative, only peripheral portion revealedblue and pink staining and central area appeared as cutout spaces. Congo red and methyl violet stains andpotassium permanganate treatment was not helpful in distinguishing AL amyloidosis from secondaryamyloidosis. Hence immunohistochemistry and myeloma profile is a must. It might be possible that inlight chain amyloidosis, treatment with methotrexate and prednisolone may improve survival.

  16. Review Article of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jittiporn PURATTANAMAL

    2010-06-01

    Full Text Available Cardiac amyloidosis is a term that means the deposit of abnormal proteins in the myocardium leading to global thickening of the heart walls. The clinical character is that of infiltrative cardiomyopathy. AL amyloidosis is the most common type that involves cardiac failure. Cardiac amyloid precedes clinical congestive heart failure, especially right-sided heart failure. Laboratory investigations have identified the amyloid fibril proteins deposited in the organ tissues. Immunofixation tests are the most sensitive that recognize the paraprotein mean light chain protein or immunoglobulin subtype deposit. Prognosis is poor if AL amyloidosis is untreated. Treatment of systemic involvement in AL amyloidosis is via chemotherapy such as melphalan and prednisolone. UK experts have reported the results of treatment in AL amyloidosis. Regardless of the use of adjunctive chemotherapy, the five-year survival after heart transplantation was generally poorer for AL (20 % at five years, but similar for non-AL amyloidosis (64 % at five years, than heart transplants in other cases. Progression of the systemic disease contributed to increased mortality. A specific treatment that increases the chances of survival is unknown.

  17. Primary conjunctival amyloidosis

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2014-01-01

    Full Text Available A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid.On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

  18. [Hereditary transthyretin amyloidosis].

    Science.gov (United States)

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied. PMID:25123367

  19. Primary Breast Amyloidosis Presenting as Microcalcifications Only

    OpenAIRE

    Shim, Youngsub; Kim, Min Jung; Ryu, Han Suk; Park, Sung Hee

    2013-01-01

    Amyloidosis is a rare disease characterized by the formation of pathological protein deposits in organs or tissues. It is typically a systemic disease which can occur in a localized form. Amyloidosis of the breast is uncommon. Common mammographic findings of breast amyloidosis are multiple nodules with or without calcifications. We report a case of primary localized breast amyloidosis presenting suspicious microcalcifications on mammography without associated masses. Mammography in a 72-year-...

  20. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen;

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...... cutaneous amyloidosis (PLCA). The method of treatment was compared to the risk of local recurrence....

  1. Primary diffuse tracheobrochial amyloidosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Oezer, Caner E-mail: mnduce@hotmail.com; Nass Duce, Meltem; Yildiz, Altan; Apaydin, F. Demir; Egilmez, Hulusi; Arpaci, Taner

    2002-10-01

    Respiratory amyloidosis is a rare disease that occurs in three forms: tracheobronchial, nodular parenchymal and diffuse parenchymal involvement. Tracheobronchial amyloidosis is characterized by focal or diffuse deposition of amyloid in the submucosa of the trachea and proximal bronchi. Herein, we report a case of diffuse tracheobronchial amyloidosis with plain radiography and thorax computed tomography findings.

  2. Localized Lymph Node Light Chain Amyloidosis

    Directory of Open Access Journals (Sweden)

    Binod Dhakal

    2015-01-01

    Full Text Available Immunoglobulin-derived light chain amyloidosis can occasionally be associated with localized disease. We present a patient with localized lymph node light chain amyloidosis without an underlying monoclonal protein or lymphoproliferative disorder and review the literature of lymph node amyloidosis discussing work-up and risk factors for systemic progression.

  3. [Purpura: primary systemic amyloidosis manifestation].

    Science.gov (United States)

    Lestre, Sara; Gonçalves, Andreia; João, Alexandre; Ferreira, Ana; Apetato, Margarida

    2009-01-01

    Primary Systemic Amyloidosis (AL) is the most frequent form of systemic amyloidosis and its morbilility is associated with immunoglobulin light chains deposition in vital organs. The mucocutaneous manifestations occur in about 30-40% of the cases and are important in diagnostic suspicion, once they appear in early stages of disease. We report a 71-years-old female patient, with disseminated purpura and cutaneous fragility with 6 months of evolution, accompanied by recent complaints of dysphagy. The first laboratory evaluation didn't show any alterations. The histological and immunohistochemical study of subcutaneous abdominal fat and skin biopsy showed lambda type amyloid protein. In the systemic work-up, we highlight a proteinúria > 1g/24h with Bence Jones proteins and the presence of monoclonal immunoglobulin light chain (lambda type) in serum immunoelectrophoresis. With the diagnosis of primary systemic amyloidosis, treatment with prednisolone and melphalan was started. PMID:19686633

  4. Amyloidosis in Retinal Neurodegenerative Diseases

    Science.gov (United States)

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  5. THE AUTOIMMUNE CONSTELLATION IN LICHEN AMYLOIDOSIS.

    Science.gov (United States)

    Andrese, Elena; Vâţă, D; Ciobanu, Delia; Stătescu, Laura; Solovăstru, Laura Gheucă

    2015-01-01

    Localized cutaneous amyloidosis is a rare disease among white people, being more common in South-Asia, China and South America. The disease is characterized by deposition of amyloid material in the papillary dermis without visceral involvement. Nevertheless, there is a growing list of immune-mediated disorders that have been linked to cutaneous amyloidosis. We present two cases of concomitant occurrence of lichen amyloidosis and autoimmune thyroiditis/atopic dermatitis in two Caucasian women. PMID:26793847

  6. Heparan Sulfate Dependent Mechanisms of Amyloidosis

    OpenAIRE

    Noborn, Fredrik

    2012-01-01

    A common theme in amyloid disorders is the deposition of disease-specific protein aggregates in tissues. Amyloid proteins bind to heparan sulfate (HS), a sulfated glycosaminoglycan, and HS has been found to promote the aggregation process. The present work relates to HS mediated mechanisms of amyloidosis, particularly transthyretin (TTR) amyloidosis, AA-amyloidosis and Alzheimer’s disease (AD). TTR is a transport protein present in the blood and cerebrospinal fluid, which under unclear circum...

  7. Bladder Perforation Secondary to Primary Systemic Amyloidosis

    Directory of Open Access Journals (Sweden)

    Christopher J. Dru

    2014-01-01

    Full Text Available Amyloidosis is a disorder of protein folding characterized by extracellular aggregation and deposition of amyloid protein fibrils. Light-chain amyloidosis, also known as primary systemic amyloidosis, is the most common form of the disease. We present a case of an 84-year-old male with a history of systemic primary amyloidosis causing genitourinary, cardiac, and autonomic dysfunction who presented with hematuria and hypotension secondary to bladder perforation. He underwent open repair of a large extraperitoneal bladder defect. He ultimately died as a result of medical complications from his disease.

  8. Cardiac Amyloidosis Presenting With Cardiogenic Shock.

    Science.gov (United States)

    Afzal, Ashwad; Brener, Sorin J; Narula, Navneet; Worku, Berhane; Gulkarov, Iosif

    2016-01-01

    Cardiac amyloidosis is an infiltrative disorder of the myocardium. It is the result of one of 4 types of amyloidosis: primary systemic (immunoglobulin light chain), secondary, familial (hereditary), or senile. Cardiac amyloidosis ultimately causes congestive heart failure due to irreversible restrictive cardiomyopathy. Because of the rapid progression of the disease, early recognition and determination of underlying etiology are important for tailored therapy. Current interventions range from conservative heart failure management to autologous stem cell and heart transplantation. We present a case of cardiac amyloidosis accompanying undiagnosed multiple myeloma to illustrate the rapid progression of the disease and the complexities of diagnosing and treating this disorder. PMID:26177555

  9. [Amyloidosis in infected Didelphis marsupialis].

    Science.gov (United States)

    Roa, Diana Milena; Sarmiento, Ladys; Rodríguez, Gerzaín

    2002-09-01

    A male opossum, Didelphis marsupialis, captured in Teruel (Huila), Colombia, was inoculated intraperitoneally with 1 x 10(6) promastigotes of Leishmania chagasi (MHOM/CO/84/CL044B). The animal died 5 weeks after inoculation. Autopsy revealed signs of visceral leishmaniasis along with amastigote parasite form in Kupffer cells and spleen macrophages. Amyloid deposits in liver and spleen were demonstrated by histological staining and electron microscopy. The rapid death was considered a consequence of a secondary, reactive amyloidosis. PMID:12404923

  10. Current perspectives on cardiac amyloidosis

    OpenAIRE

    Guan, Jian; Mishra, Shikha; Falk, Rodney H.; Liao, Ronglih

    2011-01-01

    Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either...

  11. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen;

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  12. Clinical approach of patients with systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke

    2011-01-01

    Amyloidosis is the name of diseases characterised by deposition of protein fibrils with a beta-sheet structure. This beta-sheet structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. The main three types of systemic amyloidosis are AA (related to underlying chroni

  13. Systemic transthyretin amyloidosis in a patient with bent spine syndrome.

    Science.gov (United States)

    Rezania, Kourosh; Pytel, Peter; Smit, Laurel J; Mastrianni, James; Dina, Michelle A; Highsmith, W Edward; Dogan, Ahmet

    2013-06-01

    Wild-type and mutant transthyretin (TTR) are implicated in systemic amyloidosis (ATTR). Myopathy is a rare complication of ATTR amyloidosis, however no patient with bent spine syndrome secondary to ATTR amyloidosis has been reported so far. We present the first case of bent spine syndrome in a patient with wild-type ATTR amyloidosis who also had concomitant Alzheimer's disease.

  14. Primary breast amyloidosis presenting as microcalcifications only.

    Science.gov (United States)

    Shim, Youngsub; Kim, Min Jung; Ryu, Han Suk; Park, Sung Hee

    2013-01-01

    Amyloidosis is a rare disease characterized by the formation of pathological protein deposits in organs or tissues. It is typically a systemic disease which can occur in a localized form. Amyloidosis of the breast is uncommon. Common mammographic findings of breast amyloidosis are multiple nodules with or without calcifications. We report a case of primary localized breast amyloidosis presenting suspicious microcalcifications on mammography without associated masses. Mammography in a 72-year-old woman displayed multiple, linearly distributed, irregular and rod-like calcifications in the subareolar area of the left breast. The patient underwent surgical excision under mammo-guided needle localization and the pathology was confirmed to be breast amyloidosis. PMID:24043964

  15. Pathophysiology and treatment of cardiac amyloidosis.

    Science.gov (United States)

    Gertz, Morie A; Dispenzieri, Angela; Sher, Taimur

    2015-02-01

    Amyloid cardiomyopathy should be suspected in any patient who presents with heart failure and preserved ejection fraction. In patients with echocardiographic evidence of ventricular thickening and without a clear history of hypertension, infiltrative cardiomyopathy should be considered. If imaging suggests the presence of amyloid deposits, confirmation by biopsy is required, although endomyocardial biopsy is generally not necessary. Assessment of aspirated subcutaneous fat and bone-marrow biopsy samples verifies the diagnosis in 40-80% of patients, dependent on the type of amyloidosis. Mass spectroscopy can be used to determine the protein subunit and classify the disease as immunoglobulin light-chain amyloidosis or transthyretin-related amyloidosis associated with mutant or wild-type TTR (formerly known as familial amyloid cardiomyopathy and senile cardiac amyloidosis, respectively). In this Review, we discuss the characteristics of cardiac amyloidosis, and present a structured approach to both the assessment of patients and treatment with emerging therapies and organ transplantation. PMID:25311231

  16. Extensive loculated ascites in hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Saranya Buppajarntham

    2014-01-01

    Full Text Available Context: Amyloidosis is a disease of extracellular deposition of misfolded proteinaceous subunits, which could be systemic or localized disease. Though hepatic amyloidosis was not uncommon in autopsy series, most cases of hepatic amyloidosis were asymptomatic. Ascites, jaundice, portal hypertension, and gastrointestinal bleeding from esophageal varices were reported in literature. Case report: A 42-year-old man with end-stage renal disease on hemodialysis and recent small bowel obstruction presented with chronic abdominal pain. Computed tomography of abdomen and pelvis showed extensive loculated ascites and multiple small bowel loops tethered to adhesions and hepatomegaly. Finally, hepatic venography and liver biopsy confirmed hepatic amyloidosis with portal hypertension. The patient was waiting for liver transplant for definite treatment. Conclusion: We report a rare case of hepatic amyloidosis with prior small bowel obstruction presented with extensive loculated ascites and multiple small bowel loops tethered to adhesions.

  17. Amyloidosis of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Kala, Zdenek [Department of Surgery, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail: zkala@tiscali.cz; Valek, Vlastimil [Department of Radiology, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail: v.valek@fnbrno.cz; Kysela, Petr [Department of Surgery, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail: pkysel@email.cz

    2007-07-15

    Amyloidosis is a rare disease characterized by forming pathological protein deposits - amyloid - in many organs and tissues. This decreases their functionality. The aim of this small study was to determine, whether the radiological picture of the small intestine involvement in amyloidosis is in some sense specific as sometimes described in literature giving rise to high suspicion for the disease in symptomatic patients. Material and methods: The prospective study comprising seven patients hospitalized in surgical department is presented together with a survey on the disease, its appearance in radiological imaging. All patients underwent abdominal ultrasound (ATL 5000 HDI, 7-12 MHz linear probe, no contrast enhancement, supine position), abdominal CT (Somatom Plus, Siemens, single detector, conventional abdominal CT protocol) and enteroclysis (Micropaque suspension 300 ml, application rate of 75 ml/min, dilution with HP-7000 being 1:1 and HP-7000 solution 2000 ml, application rate of 120 ml/min.). Results: The amyloid deposits in the small intestine could be visualized in five of seven patients with the disease. Enteroclysis revealed a diffuse slowed down intestinal motility with an obstruction-like picture in all of our seven patients. The intestinal secretion was normal, plicae were getting polyp-like shape in five of them forming so called 'thumb printing' picture. CT showed thickening of the intestinal wall due to deposits with poor blood supply and contrast retention in five of seven patients. Ultrasound visualized thickened, hypoechoic nodular plicae and slowed down motility in these five patients. The most striking finding was the pathological deposits in the intestinal wall were highly hypo-vascular. However, this picture is very similar to that of ischemic enteritis. All seven patients had proven amyloid deposits from bioptic specimens. Conclusion: The diagnosis of amyloidosis must be supported by bioptic examination as it has no pathognomic

  18. A Case of Familial Lichen Amyloidosis

    Directory of Open Access Journals (Sweden)

    Şeniz Ergin

    2008-12-01

    Full Text Available Familial lichen amyloidosis which is also referred to familial primary cutaneous amyloidosis is a rare clinical variant of cutaneous amyloidosis. Lichen amyloidosis is characterized by persistent, pruritic, small brown papules often located on anterior surfaces of legs which show tendency to form plaques. Amyloid deposits would be identified in papillary dermis in histopathological examination. In our clinic, a 42 year old woman with a widespread involvement describing that similar skin findings were present in her both daughters, elder brother and her nephew was evaluated with suspicion of lichen amyloidosis. In histopathological examination of the involved skin, because of determining amyloid deposits in papillary dermis the case was cited as lichen amyloidosis. Our case was searched for the accompanying diseases such as atopic dermatitis, chronic urticaria, lichen planus, multiple endocrine neoplasia and Kimura disease. The family history of our patient was consistent with autosomal dominant inheritance. Familial lichen amyloidosis has been reported as cases with autosomal dominant inheritance from Russia, Germany, United Kingdom and South America. The genetic researches over familial lichen amylodiosis are limited to the cases with multiple endocrine neoplasia. In this rarely reported cases, further genetical researches are necessary in order to determine the responsible gen locus. (Turkderm 2008; 42: 137-9

  19. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis

    NARCIS (Netherlands)

    Gillmore, Julian D.; Maurer, Mathew S.; Falk, Rodney H.; Merlini, Giampaolo; Damy, Thibaud; Dispenzieri, Angela; Wechalekar, Ashutosh D.; Berk, John L.; Quarta, Candida C.; Grogan, Martha; Lachmann, Helen J.; Bokhari, Sabahat; Castano, Adam; Dorbala, Sharmila; Johnson, Geoff B.; Glaudemans, Andor W. J. M.; Rezk, Tamer; Fontana, Marianna; Palladini, Giovanni; Milani, Paolo; Guidalotti, Pierluigi L.; Flatman, Katarina; Lane, Thirusha; Vonberg, Frederick W.; Whelan, Carol J.; Moon, James C.; Ruberg, Frederick L.; Miller, Edward J.; Hutt, David F.; Hazenberg, Bouke P.; Rapezzi, Claudio; Hawkins, Philip N.

    2016-01-01

    Background-Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histologica

  20. Alveolar septal pulmonary amyloidosis: a case report

    International Nuclear Information System (INIS)

    Primary pulmonary amyloidosis is a rare diesase, and is classified as either tracheobronchial or parenchymal; the latter is also divided into nodular and diffuse alveolar septal forms. The alveolar septal form is extremely rare and usually produces reticular and nodular opacities. We describe a case of alveolar septal pulmonary amyloidosis manifested as multiple small nodules on chest radiograph and disseminated micronodules mainly in centrilobular and subpleural location without reticular opacities, on HRCT

  1. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    OpenAIRE

    Ling-Chao Meng; He Lyu; Wei Zhang; Jing Liu; Zhao-Xia Wang; Yun Yuan

    2015-01-01

    Background: Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. ...

  2. Amyloidosis: Modern Cross-sectional Imaging.

    Science.gov (United States)

    Czeyda-Pommersheim, Ferenc; Hwang, Misun; Chen, Sue Si; Strollo, Diane; Fuhrman, Carl; Bhalla, Sanjeev

    2015-01-01

    Amyloidosis is a rare diverse condition caused by the pathologic extracellular deposition of abnormal insoluble proteins throughout the body. It may exist as a primary disease or, more commonly, may be secondary to a wide variety of pathologic processes ranging from chronic infection or inflammation to malignancy. Hereditary forms also exist. On the basis of the structure of the protein deposits, more than two dozen subtypes of amyloidosis have been described. A single organ or multiple organ systems may be affected. The radiologic manifestations of amyloidosis are varied and often nonspecific, making amyloidosis a diagnostic challenge for the radiologist. In the chest, the lungs, mediastinum, pleura, and heart may be involved. Lung involvement may manifest as diffuse reticulonodular interstitial thickening, consolidations, or solitary or multiple parenchymal nodules that may calcify, cavitate, and slowly enlarge. Pleural involvement most commonly manifests as pleural effusions. Tracheobronchial involvement may exhibit concentric airway thickening, mural and intraluminal nodules, submucosal calcification, and airway obstruction. Mediastinal and hilar lymph nodes may enlarge and frequently calcify. At cardiac magnetic resonance (MR) imaging, the left ventricular wall is typically thickened, with associated diastolic dysfunction. Delayed contrast material-enhanced cardiac MR imaging typically shows global transmural or subendocardial enhancement. The pathophysiology, classification, treatment, and prognosis of amyloidosis are reviewed, followed by case examples of the appearance of thoracic and cardiac amyloidosis on chest radiographs, computed tomographic (CT) images, and cardiac MR images. PMID:26230754

  3. Gastrointestinal amyloidosis: a case of chronic diarrhoea.

    Science.gov (United States)

    Fonnesu, C; Giovinale, M; Verrecchia, E; De Socio, G; Cerquaglia, C; Curigliano, V; Soriano, A; Obici, L; Grieco, A; Lauriola, L; Gasbarrini, G; Manna, R

    2009-03-01

    Amyloidosis is a rare disease caused by extracellular deposits of insoluble fibrillar proteins in various organs and tissues. There are different forms of amyloidosis distinguished by the type of protein fibrils, by the sites of deposition and by associated conditions. Gastrointestinal involvement is common both in primary and secondary amyloidosis, while isolated gastrointestinal amyloidosis is rare. We describe a case of AL amyloidosis with a gastrointestinal involvement and restrictive cardiomiopathy. A 64 year old woman came to our attention with a history of chronic diarrhoea and weight loss, associated with dysphagia, dry mouth, xerophtalmia, chronic gastritis and depression. Clinical diagnosis has been difficult because of aspecificity of symptoms that mimed other more common diseases, like gastro-paresis, epigastric discomfort, gastric or duodenal ulcers, perforation, malabsorption, intestinal pseudo-obstruction. There is an important risk of misunderstanding and diagnostic delay. Indeed in this patient a diagnosis of irritable colon syndrome was erroneously established two years before admission in our hospital. Therefore gastrointestinal amyloidosis should be considered among differential diagnoses of chronic diarrhoea and weight loss when other more common diseases have been excluded. PMID:19530511

  4. Incidence and clinical outcome of renal amyloidosis: A retrospective study

    Directory of Open Access Journals (Sweden)

    Emad Abdallah

    2013-01-01

    Full Text Available The kidneys are affected in almost all patients with amyloid A in secondary amyloidosis (AA amyloidosis but less frequently in immunoglobulin light chains in primary systemic amyloidosis (AL amyloidosis. In this study, we present the incidence, etiology, clinical manifestations, biochemical features and clinical course of renal amyloidosis. We conducted a retrospective study on a group of 40 cases with renal biopsy-proven amyloidosis. They constituted 2.5% of the total cases of renal biopsies performed in the Theodor Bilharz Research Institute, Cairo, Egypt, during the period from February 2003 to May 2009. The mean age (30 males, ten females was 36.51 ± 10.32 years. Thirty-two of the cases had secondary AA amyloidosis and eight cases had primary AL amyloidosis. The causes of secondary amyloidosis were as follows: 12 (30% familial Mediterranean fever (FMF, eight (20% pulmonary tuberculosis, four (10% chronic osteomyelitis, four (10% bronchiectasis, three (7% rheumatoid arthritis and one (2% rheumatic heart disease. The eight cases of primary AL amyloidosis comprised of five cases that were associated with myloma (13% and three (8% cases that were idiopathic. Among the 23 patients with AA amyloidosis, after six months of treatment with colchicine, the proteinuria improved, serum albumin level increased and edema disappeared in 13 patients. In four cases of AA amyloidosis who were clinically and biochemically normal after cholchicine therapy, a second renal biopsy disclosed decreased amyloid deposition compared with the first biopsy. In the three renal transplanted patients who had amyloidosis secondary to FMF and were treated with colchicines, AA amyloidosis did not recur in the transplanted kidney. It might be possible that in AL amyloidosis, treatment with methotrexate, melphalan and prednisolone may improve survival. The incidence of renal amyloidosis is increasing and colchicine can be used in secondary amyloidosis as it may have an effect

  5. Periocular and orbital amyloidosis - Clinical characteristics, management, and outcome

    NARCIS (Netherlands)

    I. Leibovitch; D. Selva; R.A. Goldberg; T.J. Sullivan; P. Saeed; G. Davis; J.D. McCann; A. Mcnab; J. Rootman

    2006-01-01

    Objective: To present the clinical features and management outcome in a large series of patients with periocular and orbital amyloidosis. Design: Retrospective, noncomparative, interventional case series. Patients: All patients diagnosed with periocular and orbital amyloidosis in 6 oculoplastic and

  6. Oral purpura as the first manifestation of primary systemic amyloidosis.

    Science.gov (United States)

    McCormick, Robert Stuart; Sloan, Philip; Farr, David; Carrozzo, Marco

    2016-07-01

    Oral blood blisters and purpura are rare features of primary systemic amyloidosis (amyloid light-chain (AL) amyloidosis). We report a case in which these unusual presentations led to a diagnosis of amyloidosis, which enabled effective treatment before organ failure. PMID:26708800

  7. Isolated laryngeal amyloidosis nodular: a case report

    Directory of Open Access Journals (Sweden)

    Azevedo, Andréia Aparecida de

    2010-06-01

    Full Text Available Introduction: Isolated amyloidosis of the larynx is rare, being the single most common location in head and neck. Can be divided into diffuse and nodular, and the surgical treatment priority. Objective: To describe a case of isolated nodular amyloidosis of the larynx, with review of literature. Case report: A female patient, 23 years, presented with complaints of dysphonia and cervical cake for about three months. A laryngoscopy revealed a polypoid lesion of large volume in the left vocal cord. Underwent microsurgery for the removal of the larynx, the histopathological report was consistent with amyloidosis, and underwent further simplified for clinical research locations extralaryngeal of amyloidosis, which was negative. It remains in clinical and laryngoscopic semester. Final Comments: The isolated amyloidosis of the larynx, although rare, should always be entertained by the otolaryngologist, since it is the most frequent clinical presentation of disease in head and neck, often indistinguishable in appearance to that of other benign lesions. It is indispensable for research extralaryngeal demonstrations.

  8. Macular Amyloidosis and Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Yalda Nahidi

    2016-01-01

    Full Text Available Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group. There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8% and control (23.8% groups (P=0.08. Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis.

  9. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  10. Surgical management of advanced ocular adnexal amyloidosis.

    Science.gov (United States)

    Patrinely, J R; Koch, D D

    1992-06-01

    Ocular adnexal amyloidosis is characterized by amyloid deposition within the deep connective tissue layers of the eyelids, conjunctiva, and anterior orbit. Management of advanced cases has traditionally been unsatisfactory, with either no surgery offered because of fear of hemorrhage or an en bloc resection performed of the entire involved area. We present two cases of advanced periorbital amyloidosis successfully managed by preserving the anatomic planes of the eyelids and meticulously debulking the deposits with a spooned curette. Lax eyelid tendons and aponeuroses were simultaneously repaired, and no sacrifice of eyelid tissues was necessary. One patient remained asymptomatic for 2 years after surgery before developing early reaccumulation in the lower eyelids. The other patient required additional eyelid debulking and ptosis revision 8 months after surgery, but was in stable condition at follow-up 2 years after surgery. This technique offers safe, easily repeatable, nondestructive treatment for advanced periocular amyloidosis.

  11. Transthyretin Cardiac Amyloidosis in Black Americans.

    Science.gov (United States)

    Shah, Keyur B; Mankad, Anit K; Castano, Adam; Akinboboye, Olakunle O; Duncan, Phillip B; Fergus, Icilma V; Maurer, Mathew S

    2016-06-01

    Transthyretin-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive and hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts black Americans, who when compared with whites with wild-type transthyretin amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a noninvasive method for early identification (genetic testing). Although reasons for this are unclear, this begs to consider the inadequate access to care, societal factors, or a biological basis. In an effort to improve awareness and explore unique characteristics, we review the pathophysiology, epidemiology, and therapeutic strategies for transthyretin amyloidosis and highlight diagnostic pitfalls and clinical pearls for identifying patients with amyloid heart disease. PMID:27188913

  12. Cardiac amyloidosis in a heart transplant patient - A case report and retrospective analysis of amyloidosis evolution

    OpenAIRE

    Kintsler, Svetlana; Jäkel, Jörg; Brandenburg, Vincent; Kersten, Katrin; Knuechel, Ruth; Röcken, Christoph

    2015-01-01

    Cardiac amyloidosis is a very rare cause of heart failure in heart transplant recipients but an important differential diagnosis in cases of progressive cardiac failure. We report a 72-year-old male patient with the diagnosis of senile systemic amyloidosis (SSA) in a transplanted heart 15 years after transplantation by the initial diagnosis of the dilated cardiomyopathy. Additionally performed immunohistochemical analysis with anti-transthyretin antibody of the cardiac biopsies of the last 15...

  13. Growth Hormone and Cerebral Amyloidosis.

    Science.gov (United States)

    Benvenga, S; Guarneri, F

    2016-08-01

    Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer's disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer's disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers' pituitaries, may have led to the observed co-occurring of Creutzfeldt-Jakob disease and Alzheimer's disease. PMID:27214308

  14. Is amyloid A (AA) amyloidosis always secondary?

    OpenAIRE

    Maury, C P; Törnroth, T; Wegelius, O

    1985-01-01

    The case is reported of a patient with systemic AA amyloidosis associated with non-specific mesenteric lymphadenitis and chronic sideropenia. Renal, small bowel, and rectal biopsies showed amyloid deposits containing AA protein, as defined by potassium permanganate sensitivity and by reactivity with AA antiserum. Reversal of the nephrotic syndrome occurred during steroid-azathioprine therapy.

  15. Amyloidosis of Seminal Vesicles; Incidence and Pathologic Characteristics

    Directory of Open Access Journals (Sweden)

    Asuman ARGON

    2012-01-01

    Full Text Available Objective: Amyloidosis is a rare disease with various etiologies with extracellular amyloid protein depositions. At present, at least 26 distinctive amyloid forms have been detected with different clinical importance and treatment. They have characteristic staning fetaures with Congo red. Amyloid may be detected in 2-10% of prostates that have been removed because of hyperplasia or carcinoma. Amyloidosis of seminal vesicles is accepted as senil amyloidosis and it is not accompanied by systemic amyloidosis or clinical symptoms. This condition is the most common form of localized amyloidosis. In this study we aimed to investigate incidence and histologic characteristics of amyloidosis of seminal vesicles in radical prostatectomy materials of the patients whose prostate carcinomas were treated surgically.Material and Method: Amyloid depositions in seminal vesicles of 207 radical prostatectomy materials that prostates had been removed due to localized prostate carcinoma. Amyloid depositions were confirmed with Congo red staining and polarization microscope.Results: Amyloidosis of seminal vesicles was detected in 10 (4.8% of cases. Mean age of the patients is 66.2 years. Amyloid depositions tend to be nodular and bilateral in subepithelial region of affected seminal vesicles. Amyloid depositions were not detected in blood vessels in seminal vesicles or prostate parenchyma.Conclusion: Localized amyloidosis of seminal vesicles is not an unusual finding. amyloidosis of seminal vesicles incidence in Turkish patients included in this study and histopathologic characteristics of these patients are not different from the other studies. Systemic AA amyloidosis is the most common form of amyloidosis in our country. To be aware of amyloidosis of seminal vesicles is of importance in discrimination from the other forms of amyloidosis.

  16. A case report of localized gastric amyloidosis

    Institute of Scientific and Technical Information of China (English)

    Dan Wu; Jian-Ying Lou; Jian Chen; Lun Fei; Gui-Jie Liu; Xiao-Yu Shi; Han-Ting Lin

    2003-01-01

    AIM: To elucidate the clinical and laboratory features of localized gastric amyloidosis via a rare report along with a review of related literatures.METHODS: The clinical manifestations, laboratory results and surgical treatment of a female patient with localized gastric amyloidosis in our hospital were summarized. The relevant literatures were reviewed on the etiology, clinical features, diagnosis, treatment and prognosis of this disease.RESULTS: The patient was lack of specific clinical manifestations and positive laboratory results. Prior to the treatment, she was suspected to be of malignization from gastric ulcer by both gastroscopy and endoscopic ultrasonography, which was denied by the gastric biopsy.The patient was treated with subtotal gastrectomy and clearance of perigastric lymph nodes. The postoperative pathological diagnosis determined the lesion to be the deposition of amyloid materials in the gastric mucosa,submucosa and blood vessel walls with intestinal metaplasia and atrophy of the gastric glands, in which no malignant tumor was found. Congo red staining with prior potassium permanganate incubation confirmed the AA type of amyloid in this case. Multiple biopsies from esophagus, remnant stomach, duodenum, colon and bone marrow in the followup survey showed no amyloidal deposition in these tissues and organs. Up to the present, no signs of recurrence have been found in this patient.CONCLUSION: Localized gastric amyloidosis, being rare in incidence, should be considered in the differentiation of gastric tumors, in which biopsy is the only means to confirm the diagnosis. Currently, surgical resection of pathological tissue and circumambient lymph nodes may be a preferable therapeutic strategy for the localized amyloidosis to prevent possible complications. Although with a benign prognosis,gastric amyloidosis possesses a recurrent tendency as suggested by the literatures.

  17. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis

    Directory of Open Access Journals (Sweden)

    Mari Kantanen

    2014-07-01

    Full Text Available Hereditary gelsolin amyloidosis (AGel amyloidosis is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA. To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.

  18. A Rare Case of Ascites due to Peritoneal Amyloidosis.

    Science.gov (United States)

    Stofer, Fernanda; Barretto, Maria Fernanda; Gouvea, Ana Luisa; Ribeiro, Mario; Neves, Marcio; Gismondi, Ronaldo Altenburg; Mocarzel, Luís Otavio

    2016-01-01

    BACKGROUND The clinical manifestations of amyloidosis depend on the type of insoluble protein as well as the location of amyloid deposits in tissues or organs. In the gastrointestinal tract, the small intestine is the most common site of amyloid deposits, whereas peritoneal involvement and ascites are rare. CASE REPORT We report on a case of ascites due to peritoneal amyloidosis. A 65-year-old patient was admitted to our institution due to anasarca and pulmonary congestion, mimicking heart failure. We started the patient on diuretics and vasodilators. Despite improvement in pulmonary congestion and peripheral edema, his ascites was not reduced. Echocardiogram revealed restrictive cardiomyopathy and a speckle-tracking pattern suggestive of cardiac amyloidosis. Subcutaneous and peritoneal biopsies revealed amyloidosis. CONCLUSIONS Amyloidosis is rare in the peritoneum and is usually asymptomatic. Ascites occurs in only 20% of patients with peritoneal amyloidosis. We searched PubMed using "ascites" and "amyloidosis" and identified only eight case reports of amyloidosis with ascites. Physicians should be particularly careful in heart failure and anasarca cases when ascites is disproportional or not responsive to diuretic treatment. To date, there is no specific treatment for peritoneal amyloidosis. PMID:27353538

  19. Poor Outcomes in Hepatic Amyloidosis: A Report of 2 Cases

    Science.gov (United States)

    Kertowidjojo, Elizabeth; Zhang, Yue; Patel, Pruthvi

    2016-01-01

    Hepatic amyloidosis is a rare disease entity that results from insoluble amyloid protein deposition in the liver. The disease often presents with vague, nonspecific clinical features. Currently, there is little literature describing treatment outcomes for biopsy-proven hepatic amyloidosis and current treatment guidelines recommend that patients enroll in a clinical trial due to insufficient evidence to suggest an optimal treatment regimen. Here, we present two cases of hepatic amyloidosis at an academic medical center and describe their presentation, treatment, and outcomes. These cases highlight the poor outcomes and difficult management of hepatic amyloidosis. Further understanding and investigation of this rare disease are warranted.

  20. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Institute of Scientific and Technical Information of China (English)

    Ling-Chao Meng; He Lyu; Wei Zhang; Jing Liu; Zhao-Xia Wang; Yun Yuan

    2015-01-01

    Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis,which occurs worldwide.To date,more and more mutations in the TTR gene have been reported.Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family.The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014.Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients,for light and electron microscopy examination.The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years.The main manifestations were paresthesia,proximal and/or distal weakness,autonomic dysfunction,cardiomyopathy,vitreous opacity,hearing loss,and glossohypertrophia.Nerve biopsy demonstrated severe loss ofmyelinated fibers in seven cases and amyloid deposits in three.One patient had skin amyloid deposits which were revealed from electron microscopic examination.Genetic analysis showed six kinds of mutations of TTR gene,including Val30Met,Phe33Leu,Ala36Pro,Val30Ala,Phe33Val,and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients,the screening for TTR mutations should be performed in all the adult patients,who are clinically suspected with hereditary TTR amyloidosis.

  1. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Directory of Open Access Journals (Sweden)

    Ling-Chao Meng

    2015-01-01

    Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

  2. Dysautonomias in Amyloidosis: : Need for an interdisciplinary approach

    NARCIS (Netherlands)

    Hazenberg, B. P. C.

    2013-01-01

    Systemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary

  3. The Prevalence and Management of Systemic Amyloidosis in Western Countries

    NARCIS (Netherlands)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    2016-01-01

    BACKGROUND: Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secon

  4. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    OpenAIRE

    Ozturk Ates; Kemal Kosemehmetoglu; Gunes Guner; Yusuf Bayraktar

    2015-01-01

    A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS) and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  5. Guideline of transthyretin-related hereditary amyloidosis for clinicians

    OpenAIRE

    Ando Yukio; Coelho Teresa; Berk John L; Cruz Márcia Waddington; Ericzon Bo-Göran; Ikeda Shu-ichi; Lewis W David; Obici Laura; Planté-Bordeneuve Violaine; Rapezzi Claudio; Said Gerard; Salvi Fabrizio

    2013-01-01

    Abstract Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand t...

  6. Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis

    Science.gov (United States)

    Gueutin, Victor; Langlois, Anne-Lyse; Shehwaro, Nathalie; Elharraqui, Ryme; Rouvier, Philippe; Izzedine, Hassane

    2013-01-01

    Nonhematologic malignancies are rarely reported to be associated with AA amyloidosis. Although the association between renal cell carcinoma and systemic AA amyloidosis has been established, the evidence linking pulmonary cancer to AA amyloidosis is scarce. Here, a case of biopsy-proven renal AA amyloidosis complicated with nephrotic syndrome associated with lung carcinoma is reported. PMID:24558629

  7. Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis

    OpenAIRE

    Victor Gueutin; Anne-Lyse Langlois; Nathalie Shehwaro; Ryme Elharraqui; Philippe Rouvier; Hassane Izzedine

    2013-01-01

    Nonhematologic malignancies are rarely reported to be associated with AA amyloidosis. Although the association between renal cell carcinoma and systemic AA amyloidosis has been established, the evidence linking pulmonary cancer to AA amyloidosis is scarce. Here, a case of biopsy-proven renal AA amyloidosis complicated with nephrotic syndrome associated with lung carcinoma is reported.

  8. Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor Gueutin

    2013-01-01

    Full Text Available Nonhematologic malignancies are rarely reported to be associated with AA amyloidosis. Although the association between renal cell carcinoma and systemic AA amyloidosis has been established, the evidence linking pulmonary cancer to AA amyloidosis is scarce. Here, a case of biopsy-proven renal AA amyloidosis complicated with nephrotic syndrome associated with lung carcinoma is reported.

  9. Amiloidosis endobronquial: CASE REPORT TRACHEOBRONCHIAL AMYLOIDOSIS

    Directory of Open Access Journals (Sweden)

    FELIPE UNDURRAGA M.

    2005-09-01

    Full Text Available La amiloidosis es un término genérico para un conjunto de enfermedades que comparten como hecho común el depósito extracelular de proteínas patológicas. A grandes rasgos se divide en sistémica y localizada. Ambas pueden presentar compromiso pulmonar. Actualmente, su clasificación, se basa en las proteínas precursoras del amiloide. Es una patología poco frecuente, reportándose en USA una incidencia de 5,1 a 12,8 por millón de personas. Presentamos un caso de un enfermo de 32 años de edad obeso con antecedentes de tabaquismo y Diabetes Mellitus 2, asintomático que frente a una neumonía con mala respuesta al tratamiento se plantea una patología maligna y el estudio histológico demuestra amiloidosis. El análisis del caso clínico configura el diagnostico de Amiloidosis localizada endobronquialAmyloidosis is a generic term for a group of diseases that share the common feature of extracelular deposit of pathologic proteins. Systemic and localized forms are recognized. Both can produce pulmonary involvement. The current classification is based on the nature of the precursor of the amyloid. It is an infrequent condition, in USA the incidence is 5.1 to 12.8 per million of people. We present a case of a 32 years old male, obese, light smoker with Diabetes Mellitus 2, asymptomatic, with a pneumonia and poor response to treatment. The first diagnostic approach was a malignant disease and the histological study showed Amyloidosis. The analysis of the case suggest the diagnosis of tracheobronchial amyloidosis

  10. Amiloidosis oral nodular Oral nodular amyloidosis

    Directory of Open Access Journals (Sweden)

    P. Martos Díaz

    2008-02-01

    Full Text Available Introducción. La amiloidosis constituye una entidad marcada por el depósito de amiloide en diferentes tejidos. En la cavidad oral se manifiesta habitualmente en forma de macroglosia, y más raramente, como nódulos dispuestos en la superficie. Caso clínico. Varón afecto de Mieloma Múltiple, que comienza con lesiones nodulares en labio inferior y lengua. A raíz de estas lesiones, mediante estudio histológico, es diagnosticado de Amiloidosis Sistémica. Discusión. Los nódulos amiloideos en la cavidad oral, constituyen una manifestación rara de la amiloidosis sistémica. Su aparición conlleva la necesidad de realizar un diagnostico diferencial con otras entidades y el diagnostico de certeza se obtiene mediante el análisis histológico.Introduction. Amyloidosis is a condition characterized by the deposit of amyloid in different tissues. In the oral cavity it is usually manifested as macroglossia and, more rarely, as nodules on the surface. Clinical case. A man had multiple myeloma that began with nodular lesions of the lower lip and tongue. As a result of these lesions, the patient was diagnosed of systemic amyloidosis by histological study. Discussion. Amyloid nodules in the oral cavity are a rare manifestation of systemic amyloidosis. Its appearance entails the necessity to make I diagnose differential with other organizations and I diagnose of certainty is obtained by means of the histological analysis.

  11. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  12. Diagnosis and the treatment of primary amyloidosis

    Directory of Open Access Journals (Sweden)

    Đunić Irena

    2010-01-01

    Full Text Available Backgraund. Primary amyloidosis belongs to a group of monoclonal plasma cell disorders, characterized by extracellular deposition of immunoglobulin light chain fibrils in various tissues and subsequent multiorgan dysfunction. Case report. We present a 51-year-old female with 2-years history of fatigue on exertion, oedema of face, abdomen and legs, bone pain and obstipation. After diagnostic procedures such as electrophoresis and immunoelectrophoresis of serum and urine proteins, immunohistohemical staining of bone marrow biopsy specimens and Congo red staining of rectal biopsy specimens, the patient received misdiagnosis of multiple myeloma and was referred to our hospital for further treatment. We reevaluated and complemented diagnostic procedures (ehocardiosonography and biopsy of subcutaneaus tissue with Congo red staining, and established diagnosis of primary amyloidosis. The therapy had started with intravenous (iv melphalan and dexamethasone (totally eight cycles and continued with peroral melphalan and iv dexamethasone. Stabilization of the disease was achieved after 35 months of the treatment. Conclusion. The case of this rare and often fatal disease emphasizes significance of early diagnosis and, consequently, initiation of specific therapies which are indispensable to improve the disease prognosis.

  13. AA amyloidosis associated with systemic-onset juvenile idiopathic arthritis.

    Science.gov (United States)

    Saha, Abhijeet; Chopra, Yogiraj; Theis, Jason D; Vrana, Julie A; Sethi, Sanjeev

    2013-10-01

    We report a 12-year-old boy with nephrotic syndrome due to renal AA amyloidosis. The AA amyloidosis was associated with a 3-year history of systemic-onset juvenile idiopathic arthritis. The presence of serum amyloid A protein was confirmed by laser microdissection of Congo Red-positive glomeruli and vessels followed by liquid chromatography and tandem mass spectrometry; this analysis excluded hereditary and familial amyloidosis. Aggressive management of the systemic-onset juvenile idiopathic arthritis resulted in improvement in clinical and laboratory parameters. The case represents an unusual cause of nephrotic syndrome in children. Early diagnosis of renal amyloidosis and management of systemic-onset juvenile idiopathic arthritis is paramount to preventing progression of kidney disease.

  14. Renal amyloidosis due to familial Mediterranean fever misdiagnosed

    Directory of Open Access Journals (Sweden)

    Iman Hama

    2012-01-01

    Full Text Available Familial Mediterranean fever (FMF, MIM 249100 is an autosomal recessive disease affecting mainly patients of the Mediterranean basin. It is an autoinflammatory periodic disorder characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The major complication of FMF is the development of renal AA amyloidosis. Treatment with colchicine prevents the occurrence of recurrent seizures and renal amyloidosis. The disease is caused by mutations in the MEFV gene. We report here the cases of two unrelated patients, who have been late diagnosed with FMF complicated by renal amyloidosis. We focus on the importance of early diagnosis of FMF, both to start rapidly treatment with colchicine and avoid renal amyloidosis, and to provide genetic counseling to families.

  15. Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis

    NARCIS (Netherlands)

    Gillmore, Julian D; Maurer, Mathew S; Falk, Rodney H; Merlini, Giampaolo; Damy, Thibaud; Dispenzieri, Angela; Wechalekar, Ashutosh D; Berk, John L; Quarta, Candida C; Grogan, Martha; Lachmann, Helen J; Bokhari, Sabahat; Castano, Adam; Dorbala, Sharmila; Johnson, Geoff B; Glaudemans, Andor W J M; Rezk, Tamer; Fontana, Marianna; Palladini, Giovanni; Milani, Paolo; Guidalotti, Pierluigi L; Flatman, Katarina; Lane, Thirusha; Vonberg, Frederick W; Whelan, Carol J; Moon, James C; Ruberg, Frederick L; Miller, Edward J; Hutt, David F; Hazenberg, Bouke P; Rapezzi, Claudio; Hawkins, Philip N

    2016-01-01

    BACKGROUND: -Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confir

  16. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Fac. de Medicina. Instituto do Coracao. Servico de Medicina Nuclear e Imagem Molecular

    2008-07-01

    Full text: Introduction: Amyloidosis is a rare disease, characterized by extracellular deposition of insoluble amyloid fibrils in organs and tissues. It may affect virtually any system, preferably heart, kidneys and liver. The cardiac involvement produces a spectrum of clinical features, usually with progressive dysfunction. Early diagnosis is important for institution of appropriate therapy. Case report: Male patient, 75 years old, with diagnosed congestive heart failure functional class III and Mobitz II second-degree atrial-ventricular block, was hospitalized for implantation of definitive cardiac pacemaker. Patient mentioned history of worsening effort dyspnoea over a one-month period, progressing to minimum effort, orthopnea, paroxysmal nocturnal dyspnoea and paroxysms of dry cough, and swelling of lower limbs. Echocardiography showed diffuse hypertrophy of left ventricle (LV), with systolic dysfunction due to diffuse hypokinesia and hyperrefringent aspect in the septum. It was questioned a cardiac infiltrating process. Cardiac amyloidosis was considered as a diagnostic hypothesis. The patient underwent a pyrophosphate-{sup 99m}Tc scintigraphy, which showed abnormal tracer uptake in the heart projection, with diffuse pattern on the left ventricle walls, compatible with the clinical suspicion cardiac amyloidosis, which was later confirmed by endomyocardial biopsy. Discussion: In this case report, the patient had clinical and other auxiliary examinations, such as electrocardiography and Doppler echocardiography, compatible with cardiac amyloidosis, which led to implementation with pyrophosphate-{sup 99m}Tc scintigraphy and later endomyocardial biopsy. Cardiac amyloidosis occurs in about half the cases of primary amyloidosis (AL) and is rare in secondary amyloidosis (AA). Its clinical presentation is polymorphic and it can be classified into four distinctive types: restrictive cardiomyopathy, systolic dysfunction, postural hypotension and conduction disorders

  17. Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation

    OpenAIRE

    Miteva, Mariya; Wei, Erin; Milikowski, Clara; Tosti, Antonella

    2015-01-01

    Alopecia in systemic amyloidosis is very rare and has been described as individual cases of diffuse nonscarring alopecia and a case of alopecia universalis. We report the trichoscopic findings in alopecia associated with systemic amyloidosis. The most prominent feature was a salmon colored halo (0.3-1 mm in diameter) surrounding the follicular ostia. Other features included broken hairs and black dots. The salmon colored halo correlated on pathology with the perifollicular deposition of amylo...

  18. [Secondary amyloidosis (AA-type) due to localized cutaneous vasculitis].

    Science.gov (United States)

    Esteve, V; Ribera, L; Ponz, E; Almirall, J; López, T; Martínez Ocaña, J C; Ibeas, J; Rodríguez Jornet, A; Andreu, X; García, M

    2007-01-01

    We report a case of a 49 year old man, diagnosed soon after the outcome of casual proteinuria, of AA-type amyloidosis in relation to small and medium vessel cutaneous vasculitis without systemic involvement. This combination is a rare entity and only two cases of cutaneous hypersensibility vasculitis complicated with AA-type amyloidosis had been reported. We describe the results of the use of several immunosuppressive drugs during four years follow up with temporally total remission of the disease. PMID:18045042

  19. Noninvasive Diagnosis of Cardiac Amyloidosis by MRI and Echochardiography

    Institute of Scientific and Technical Information of China (English)

    汪晶; 孔祥泉; 徐海波; 周国锋; 常丹丹; 刘定西; 张丽; 谢明星

    2010-01-01

    This study described the radiological features on echocardiography and MRI specific to cardiac amyloidosis confirmed on biopsy. Eleven cases of biopsy-proven cardiac amyloidosis were retrospectively reviewed in this study. All patients underwent biopsy, cardiac MRI and echocardiography. The main echocardiography and MRI findings were as follows: diffuse ventricular and septum wall thickening, atrial enlargement, pericardial effusion, restricted left ventricular (LV) systolic and diastolic function, characte...

  20. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    Directory of Open Access Journals (Sweden)

    Ozturk Ates

    2015-06-01

    Full Text Available A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  1. Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study

    OpenAIRE

    Arvidsson, Sandra

    2016-01-01

    Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with mar...

  2. Systemic AA amyloidosis induced by liver cell adenoma.

    OpenAIRE

    Fievet, P; Sevestre, H; Boudjelal, M; Noel, L H; Kemeny, F; D. Franco; Delamarre, J; Capron, J.P.

    1990-01-01

    Systemic AA amyloidosis is a rare complication of benign tumours. This report describes a patient with hepatocellular adenoma associated with reactive AA amyloidosis. He had a nephrotic syndrome with deteriorating renal function and an increase of serum concentrations of acute phase proteins, mainly C-reactive protein. Resection of the tumour was followed by improvement in renal function and a marked decrease of the serum concentrations of acute phase proteins.

  3. Amyloidosis in a Captive Zebra Finch (Taeniopygia guttata) Research Colony.

    Science.gov (United States)

    Shientag, Lisa J; Garlick, David S; Galati, Erin

    2016-01-01

    Five birds in a captive zebra finch research colony were diagnosed with systemic amyloidosis within a 7-mo period by means of postmortem Congo red staining and green birefringence under polarized light. The liver was the most frequently and usually the most seriously affected organ, followed by the spleen and then the kidney. All 5 birds had been clinically affected with various inflammatory, infectious, and neoplastic conditions associated with amyloid A (AA) amyloidosis in humans and animals. Immunohistochemistry using antisera against duck AA protein revealed that tissues from 2 of the 5 birds were positive for the presence of AA protein and systemic inflammation-associated amyloidosis. Although the development of AA amyloidosis has been associated with chronic inflammation, trauma, and various infectious and neoplastic diseases as well as possible genetic predispositions and stresses linked to overcrowding, the root causes for individual cases of AA amyloidosis are incompletely understood. As far as we know, this report is the first description of AA amyloidosis in captive, research zebra finches. PMID:27298248

  4. Sinonasal Globular Amyloidosis Simulating Malignancy: A Rare Presentation.

    Science.gov (United States)

    Kumar, Binay; Pant, Bhawna; Kumar, Vikrant; Negi, Meghna

    2016-09-01

    Primary localized amyloidosis in the head and neck region is a rare entity. The most commonly involved organ is larynx. Primary amyloidosis localized to the sinonasal tract is extremely rare. We report one such case along with a brief review of the associated literature. The aim of reporting this case is to emphasize the fact that sometimes nasal amyloidosis can also present with signs and symptoms of nasal and nasopharyngeal malignancy. The definitive diagnosis in such cases depends upon histopathology and further confirmed by immunohistochemistry. A 55-year old male presented with recurrent episodes of nasal bleed, bilateral nasal obstruction, and bilateral hearing loss from last 7 years. On clinical examination a mass was found in the nasal cavity on both sides reaching up to the nasopharynx. Contrast enhanced CT scan revealed that the mass was extending up to the skull base and destroying bony landmarks of the nasal cavity and paranasal sinuses. Mass was proved to be amyloidosis after histopathological examination. It showed multiple blotches of globular submucosal deposit of amyloid, on staining with Congo red. Immunohistochemistry confirmed AL amyloidosis with expression of mixed kappa and lambda light chain immunoglobulin (κ > λ). No evidence of systemic amyloidosis was found after proper work up. It was managed by conservative surgery. PMID:26780770

  5. AA amyloidosis as a complication of primary lymphedema.

    Science.gov (United States)

    Beloncle, François; Sayegh, Johnny; Eymerit-Morin, Caroline; Duveau, Agnès; Augusto, Jean-François

    2014-03-01

    Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis. Clinical presentation and age at onset are variable. AA amyloidosis is usually due to chronic inflammatory diseases, malignant tumors or less frequently chronic infectious diseases. We report here the first two cases of AA amyloidosis present with renal failure and nephrotic syndrome in patients with primary lymphedema-induced chronic leg ulcers. The first patient was a 62-year-old female who presented with chronic untreated leg ulcers for 8 years secondary to primary lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of AA amyloidosis. The second patient was a 54-year-old male who presented with hereditary lymphedema and elephantiasis since the age of 12. A salivary gland biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely reported to induce AA amyloidosis. Only five other cases have been reported in the literature, but none of them with chronic lymphedema. We believe that the relation between lymphedema, chronic leg ulcers and AA amyloidosis is underestimated. PMID:23964754

  6. Amyloidosis of the Unilateral Renal Pelvis, Ureter and Urinary Bladder: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Dong-liang Pan; Yan-qun Na

    2011-01-01

    @@ AMYLOIDOSIS of more than two urinary organs happened in one person is very rare.Here we reported a patient with amyloidosis of the left renal pelvis, ipsilateral ureter as well as urinary bladder occurring successively.

  7. Amyloidosis in black-footed cats (Felis nigripes).

    Science.gov (United States)

    Terio, K A; O'Brien, T; Lamberski, N; Famula, T R; Munson, L

    2008-05-01

    A high prevalence of systemic amyloidosis was documented in the black-footed cat (Felis nigripes) based on a retrospective review of necropsy tissues (n = 38) submitted as part of ongoing disease surveillance. Some degree of amyloid deposition was present in 33 of 38 (87%) of the examined cats, and amyloidosis was the most common cause of death (26/38, 68%). Amyloid deposition was most severe in the renal medullary interstitium (30/33, 91%) and glomeruli (21/33, 63%). Other common sites included the splenic follicular germinal centers (26/31, 84%), gastric lamina propria (9/23, 39%), and intestinal lamina propria (3/23, 13%). Amyloid in all sites stained with Congo red, and in 13 of 15 (87%) cats, deposits had strong immunoreactivity for canine AA protein by immunohistochemistry. There was no association with concurrent chronic inflammatory conditions (P = .51), suggesting that amyloidosis was not secondary to inflammation. Adrenal cortical hyperplasia, a morphologic indicator of stress that can predispose to amyloid deposition, was similarly not associated (P = .09) with amyloidosis. However, adrenals were not available from the majority of cats without amyloidosis; therefore, further analysis of this risk factor is warranted. Heritability estimation suggested that amyloidosis might be familial in this species. Additionally, tissues from a single free-ranging black-footed cat had small amounts of amyloid deposition, suggesting that there could be a predilection for amyloidosis in this species. Research to identify the protein sequence of serum amyloid A (SAA) in the black-footed cat is needed to further investigate the possibility of an amyloidogenic SAA in this species.

  8. Primary amyloidosis of the breast presenting as nonpalpable microcalcifications: case report

    Energy Technology Data Exchange (ETDEWEB)

    Patel, B. [Misericordia Community Hospital, Radiology and Diagnostic Imaging, Edmonton, Alberta (Canada); Torbiak, C. [Misericordia Community Hospital, Radiology and Diagnostic Imaging, Edmonton, Alberta (Canada); Univ. of Alberta, Dept. of Radiology, Edmonton, Alberta (Canada); Danyluk, J.M. [Univ. of Alberta, Dept. of Pathology, Edmonton, Alberta (Canada); Callahan, D. [Univ. of Alberta, Dept. of General Surgery, Edmonton, Alberta (Canada); Meadowlark Health Centre, Edmonton, Alberta (Canada)

    2003-12-01

    Primary amyloidosis of the breast is rare, and the few reported cases have typically presented as palpable masses. We report the case of a patient with nonpalpable primary amyloidosis of the breast that became apparent on mammography as a cluster of indeterminate microcalcifications. To our knowledge, there has only been 1 previous reported case of amyloidosis of the breast presenting in this fashion. (author)

  9. Utility of F-18-FDG PET(/CT) in patients with systemic and localized amyloidosis

    NARCIS (Netherlands)

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Noordzij, Walter; Dierckx, Rudi A. J. O.; Hazenberg, Bouke P. C.

    2013-01-01

    Purpose Amyloidosis is a group of diseases characterized by deposition of fibrils and this deposition may be localized or systemic. The presence of giant cells is typical of localized AL amyloidosis in contrast to systemic amyloidosis. Because of this presence of giant cells we hypothesize that F-18

  10. Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke P. C.; Bijzet, Johannes; Limburg, Pieter C.; Skinner, Martha; Hawkins, Philip N.; Butrimiene, Irena; Livneh, Avi; Lesnyak, Olga; Nasonov, Evgeney L.; Filipowicz-Sosnowska, Anna; Guel, Ahmet; Merlini, Giampaolo; Wiland, Piotr; Oezdogan, Huri; Gorevic, Peter D.; Ben Maiz, Hedi; Benson, Merrill D.; Direskeneli, Haner; Kaarela, Kalevi; Garceau, Denis; Hauck, Wendy; van Rijswijk, Martin

    2007-01-01

    Objective. Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis. Methods. Abdominal subcutaneous fat tissue of patients with AA amyloidosis

  11. Importance of Thioflavin T in Diagnosis of Renal Amyloidosis

    Directory of Open Access Journals (Sweden)

    Banu SARSIK

    2009-06-01

    Full Text Available Objective: Amyloidosis represents a group of diseases with deposition of amyloid fibrils. Clinical and histopathological features of renal amyloidosis vary according to the type of precursor protein. Histopathological diagnosis of amyloidosis relies on routine Congo red histochemistry. Thioflavin T may be an alternative method based on examination on ultraviolet light, but is believed to give inconsistent and inaccurate results.Materials and Method: The sensitivity and specivity of Thioflavin T and Congo red fluorescence that can be applied to the diagnosis of amyloid were compared in order to find how best to diagnose amyloid deposits on fluorescence microscopy.Results: Frozen tissue sections available from 120 native and transplant renal biopsy patients were stained with Tioflavin T. Prospectively, 10 cases of amyloidosis (8 with AA and 2 with nonAA were diagnosed on frozen Tioflavin T sections and identical Congo red fluorescence staining was found in all the cases. There were no false positives or negatives.Conclusion: The Tioflavin T method is simple to perform and easier to evaluate. It can therefore be utilized to track down even minute amyloid deposits, which might be missed by the Congo red fluorescence. In conclusion, Tioflavin T was demonstrated to be a sensitive and specific method for diagnosis of amyloid even in small frozen renal tissue sections. This method can, therefore, allow the easiest diagnosis of renal amyloidosis on fluorescence microscopy.

  12. CLINICAL PATHOLOGICAL FEATURE OF EARLY TONGUE AMYLOIDOSIS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the clinical pathological feature and diagnostic criteria of tongue amyloidosis (AL).Methods During 1992 to 2005, 25 patients pathologically diagnosed as tongue AL in our hospital were reviewed retrospectively, and all of them had no enlarged tongue. Haematoxylin and eosin (HE) and immunohistochemical staining were used to detect the amyloid deposition on the tongue.Results Totally 84 % (21/25) patients had symptoms of xerostomia and taste-blindness, 44 % (11/25) patients complained of activity limitation of tongue. Macroscopic observation showed mucosa pallescence, punctuate hemorrhage, red grain particles, and ulcers on the tongue. HE staining indicated amyloid depositions in basement membrane,muscle cell, vessel wall, and nerve fiber. Immunohistochemical study demonstrated kappa light-chain deposition in 64%(16/25) cases, and lambda light-chain deposition in 36 % (9/25) cases. They presented in vessel wall, nerve fiber, and muscle cells.Conclusion The biopsy is an important means for the diagnosis of early tongue AL, and the wide variety of amyloid light chain is helpful to differential diagnosis.

  13. [Laryngeal amyloidosis: a clinical case and review of literature].

    Science.gov (United States)

    Fries, S; Pasche, P; Brunel, C; Schweizer, V

    2015-09-30

    Amyloidosis consists of different forms of systemic or isolated organ lesions characterised by fibrillary protein deposits in extra-cellular tissue. The isolated involvement of the larynx is the most frequent form in the ENT sphere. We present a clinical case of a 67 year-old woman addressed for a sub-acute laryngitis resistant to conservative treatment, and finally diagnosed with laryngeal amyloidosis. We reviewed its physiopathology, the scientific literature as well as the different possibilities of management. Laryngeal amyloidosis is rare. A thorough additional work-up for the research of multifocal or systemic forms is highly recommended. The treatment aims at a minimal invasive endoscopic surgery with functional organ preservation.

  14. Amyloidosis cutis dyschromica: A rare reticulate pigmentary dermatosis

    Directory of Open Access Journals (Sweden)

    Shyam Verma

    2015-01-01

    Full Text Available We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling-Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica.

  15. Symptomatic Primary (AL Amyloidosis of the Stomach and Duodenum

    Directory of Open Access Journals (Sweden)

    Reidar Fossmark

    2013-01-01

    Full Text Available Primary (AL amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.

  16. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

    Directory of Open Access Journals (Sweden)

    Terry Golombick

    2015-01-01

    Full Text Available Multiple myeloma (MM, smoldering myeloma (SMM, and monoclonal gammopathy of undetermined significance (MGUS represent a spectrum of plasma cell dyscrasias (PCDs. Immunoglobulin light chain amyloidosis (AL falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

  17. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments.

    Science.gov (United States)

    Sekijima, Yoshiki

    2015-09-01

    Transthyretin (ATTR) amyloidosis is a life-threatening, gain-of-toxic-function disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin (TTR). TTR protein destabilised by TTR gene mutation is prone to dissociate from its native tetramer to monomer, and to then misfold and aggregate into amyloid fibrils, resulting in autosomal dominant hereditary amyloidosis, including familial amyloid polyneuropathy, familial amyloid cardiomyopathy and familial leptomeningeal amyloidosis. Analogous misfolding of wild-type TTR results in senile systemic amyloidosis, now termed wild-type ATTR amyloidosis, characterised by acquired amyloid disease in the elderly. With the availability of genetic, biochemical and immunohistochemical diagnostic tests, patients with ATTR amyloidosis have been found in many nations; however, misdiagnosis is still common and considerable time is required before correct diagnosis in many cases. The current standard first-line treatment for hereditary ATTR amyloidosis is liver transplantation, which allows suppression of the main source of variant TTR. However, large numbers of patients are not suitable transplant candidates. Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and tafamidis, were demonstrated in randomised clinical trials, and tafamidis has been approved for treatment of hereditary ATTR amyloidosis in European countries and in Japan. Moreover, antisense oligonucleotides and small interfering RNAs for suppression of variant and wild-type TTR synthesis are promising therapeutic approaches to ameliorate ATTR amyloidosis and are currently in phase III clinical trials. These newly developed therapies are expected to be effective for not only hereditary ATTR amyloidosis but also wild-type ATTR amyloidosis. PMID:25604431

  18. Intestinal Amyloidosis in Common Variable Immunodeficiency and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    T. Meira

    2015-01-01

    Full Text Available We present a case of reactive amyloidosis that developed secondary to common variable immunodeficiency and rheumatoid arthritis. A 66-year-old woman, with prior history of common variable immunodeficiency and rheumatoid arthritis, was referred to our clinic for chronic diarrhea investigation. The patient was submitted to colonoscopy with ileoscopy, which did not show relevant endoscopic alterations. However, undertaken biopsies revealed amyloid deposition. Since amyloidosis with GI involvement is a rare cause of chronic diarrhea, this pathology should be considered in etiologic investigation, especially when associated with chronic inflammatory diseases.

  19. Ischemic Hepatitis as the Presenting Manifestation of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Chelsey A. Petz MD

    2014-11-01

    Full Text Available An abrupt elevation in aminotransferases without clear etiology may be attributed to hypoxic hepatitis. Underlying cardiac dysfunction, an important clinical clue, is often overlooked as a cause of hypoxic hepatitis, and understanding the interdependence of the heart and liver is crucial in making this diagnosis. Causes of cardiac dysfunction may include any of many different diagnoses; infiltrative heart disease is a rare cause of cardiac dysfunction, with amyloidosis being the most common among this category of pathologies. More advanced imaging techniques have improved the ability to diagnose infiltrative heart disease, thus allowing quicker diagnosis of conditions such as amyloidosis.

  20. [Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

    Science.gov (United States)

    Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

    2003-01-01

    The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

  1. Determination of hepatic amyloidosis by technetium labeled pyrophosphate scan in primary and secondary amyloidosis and in multiple myeloma

    International Nuclear Information System (INIS)

    The role of technetium labelled pyrophosphate scanning in the detection of amyloid deposits in the liver and the spleen was investigated in patients with primary and secondary amyloidosis and multiple myeloma. All patients with primary or secondary amyloidosis had a positive pyrophosphate scan. Thus this non-invasive technique for the diagnosis of amyloidosis could be extremely useful since biopsies are often associated with severe and even fatal complications. Pyrophosphate scans were negative in all multiple myeloma patients without liver disease but positive in all multiple myeloma patients with liver disease; the specificity for the detection of amyloid deposits in myeloma patients with disturbed liver function tests remains to be established. (U.K.)

  2. Frictional amyloidosis in Oman - A study of ten cases

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2002-01-01

    Full Text Available Macular amyloidosis is an important cause for cutaneous pigmentation, the aetiology of which is poorly understood. Friction has recently been implicated the causation of early lesions, referred to as frictional amyloidosis. Confirmation of diagnosis by the detect on of amyloid using histochemical stains is inconsistent. Ten patients with pigmentation suggestive of macular amyloidosis were studied with detailed history, clinical examination, biopsy for histochemistry and electron microscopy. Nine out of ten patients had a history of prolonged friction with various objects such as bath sponges, brushes, towels, plant sticks and leaves. Amyloid was demonstrated by histochemical staining in only six out of ten cases. In the remaining four cases, amyloid was detected by electron microscopy. These consisted of aggregates of non-branching, extracellular, intertwining fibres measuring between 200-500 nm in length and between 20-25 nm in diameter. The study confirms the role of friction in the causation of this condition. Histochemical stains are not always successful in the detection of amyloid and electron microscopy is helpful for confirming its presence. The term frictional amyloidosis aptly describes the condition.

  3. Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanya L. Poshusta

    2013-11-01

    Full Text Available Light chain (AL amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.

  4. [Otolaryngological complaints in tongue amyloidosis: a case report].

    Science.gov (United States)

    Pons Rocher, F; Guallart Doménech, F; Mompó Romero, L; Artazkozl del Toro, J J; Serrano Badía, E; Dalmau Galofré, J; Faubel Serra, M

    1994-01-01

    We present a case of Amyloidosis of the oral cavity associated to multiple mieloma, with otolaryngological symptom. Review of structural characterization of the disease, its pathogenesis and clinical disorders when displayed in thyroid, oral cavity and upper respiratory tract. PMID:7864303

  5. Localized amyloidosis of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Gianluca Rotondano; Raffaele Salerno; Fabio Cipolletta; Maria Antonia Bianco; Antonino De Gregorio; Raffaele Miele; Antonio Prisco; Maria Lucia Garofano; Livio Cipolletta

    2007-01-01

    We report an unusual case of primary amyloidosis of the stomach in a patient complaining of dyspeptic symptoms. The diagnosis was confirmed histologically and other gastrointestinal site or systemic involvement was ruled out. Uncharacteristic dyspeptic symptoms may hide this rare metabolic disease.

  6. Dialysis-related amyloidosis: visceral involvement and protein constituents.

    Science.gov (United States)

    Campistol, J M; Argilés, A

    1996-01-01

    beta 2-M amyloidosis mainly concerns dialysis patients and typically presents with osteoarticular symptoms. In order to precise the incidence and gravity of visceral involvement, subcutaneous abdominal fat aspirates, skin and rectal biopsies, as well as echocardiograms were performed in 26 patients with severe beta 2-M amyloidosis. Visceral amyloidosis was confirmed in 58% and the numbers were even higher when including heart abnormalities suggestive of amyloidosis (81%). Clinical manifestations of visceral involvement were usually not severe and include odynophagia, gastrointestinal haemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction and subcutaneous tumours. The removal and synthesis rates of beta 2-M were assessed during dialysis. Serum 131I-beta 2-M levels decreased by 5-10% with cuprophane and by 40-45% with polysulfone and polyacrylonitrile membranes. These reduction rates were higher than those found with unlabelled beta 2-M suggesting an increased synthesis or release during dialysis. The protein constituents of amyloid deposits were studied. Two different preparative methods to extract the proteins from amyloid deposits were used. TCA precipitation showed the presence of several proteins which were not observed with PBS homogenizing and resuspending in guanidine. The protein constituents of amyloid fibrils were studied by both, two dimensional gel electrophoresis (2D-gel) as well as protein sequencing after gel filtration. Similarly, the technical approach used for protein analysis greatly influenced the results. It was observed that 2D-gel displayed the presence of proteins which were missed by the gel filtration technique. Some of the proteins contained in amyloid deposits in addition to beta 2-M, were identified as globin chains, kappa and lambda light chains of immunoglobulins, and alpha 2 macroglobulin. A putative participation of these other protein constituents on the pathogenesis of beta 2-microglobulin amyloidosis is

  7. Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

    Science.gov (United States)

    McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

    2013-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis. PMID:24351625

  8. Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

    OpenAIRE

    Hesse, A; Altland, K; Linke, R P; M.R. Almeida; Saraiva, M.J.; Steinmetz, A; Maisch, B

    1993-01-01

    Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriur...

  9. Circulating Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis

    OpenAIRE

    Tanaka, Komei; Essick, Eric E.; Doros, Gheorghe; Tanriverdi, Kahraman; Connors, Lawreen H.; Seldin, David C.; Sam, Flora

    2013-01-01

    Background Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain–related CMP (AL‐CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild‐type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix...

  10. Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction

    OpenAIRE

    Van-Khue Ton; Monica Mukherjee; Judge, Daniel P.

    2015-01-01

    Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress respon...

  11. SECONDARY AMYLOIDOSIS WITH LUNG INVOLVEMENT INA FEMALE PATIENT WITH RHEUMATOID ARTHRITIS

    OpenAIRE

    Irina Mikhailovna Marusenko; Ya A Avdeyeva; I I Polskaya

    2009-01-01

    The paper considers the problem of secondary amyloidosis that more frequently occurs in patients with various arthritides, both seropositive and seronegative. According to the data available in the literature, the most common manifestations of secondary amyloidosis are involvements of the kidney, liver, nervous system, and, less frequently, the lung. The authors describe their own observation of secondary amyloidosis in rheumatoid arthritis, which is accompanied by the involvement of the lung...

  12. Macular posterior pigmentary incontinence: its relation to macular amyloidosis and notalgia paresthetica.

    Science.gov (United States)

    Westermark, P; Ridderström, E; Vahlquist, A

    1996-07-01

    Patients with clinical features of dorsal macular amyloidosis but without subepidermal amyloid deposits were followed for 2-11 years. The clinical appearance was fairly stable during this period of time, with little tendency of healing. Only 2 of the patients developed typical macular amyloidosis during the follow-up. It is concluded that a condition strongly resembling macular amyloidosis but without amyloid is an entity, and the designation "macular posterior pigmentary incontinence" is proposed. The relationship between macular posterior pigmentary incontinence and the two conditions macular amyloidosis and notalgia paresthetica is discussed. PMID:8869690

  13. AA amyloidosis in the renal allograft: a report of two cases and review of the literature.

    Science.gov (United States)

    Rojas, Rebecca; Josephson, Michelle A; Chang, Anthony; Meehan, Shane M

    2012-04-01

    AA amyloidosis is a disorder characterized by the abnormal formation, accumulation and systemic deposition of fibrillary material that frequently involves the kidney. Recurrent AA amyloidosis in the renal allograft has been documented in patients with tuberculosis, familial Mediterranean fever, ankylosing spondylitis, chronic pyelonephritis and rheumatoid arthritis. De novo AA amyloidosis is rarely described. We report two cases of AA amyloidosis in the renal allograft. Our first case is a 47-year-old male with a history of ankylosing spondylitis who developed end-stage renal disease reportedly from tubulointerstitial nephritis from non-steroidal anti-inflammatory agent use. A biopsy was never performed. One year after transplantation, AA amyloidosis was identified in the femoral head and 8 years post-transplantation, AA amyloidosis was identified in the renal allograft. He was treated with colchicine and adalimumab and has stable renal function at 1 year-follow-up. Our second case is a 57-year-old male with a long history of intravenous drug use and hepatitis C infection who developed end-stage kidney disease due to AA amyloidosis. Our second patient's course was complicated by renal adenovirus, pulmonary aspergillosis and hepatitis C with AA amyloidosis subsequently being identified in the allograft 2.5 years post-transplantation. Renal allograft function remains stable 4-years post-transplantation. These reports describe clinical and pathologic features of two cases of AA amyloidosis presenting with proteinuria and focal involvement of the renal allograft.

  14. SECONDARY AMYLOIDOSIS WITH LUNG INVOLVEMENT INA FEMALE PATIENT WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Irina Mikhailovna Marusenko

    2009-01-01

    Full Text Available The paper considers the problem of secondary amyloidosis that more frequently occurs in patients with various arthritides, both seropositive and seronegative. According to the data available in the literature, the most common manifestations of secondary amyloidosis are involvements of the kidney, liver, nervous system, and, less frequently, the lung. The authors describe their own observation of secondary amyloidosis in rheumatoid arthritis, which is accompanied by the involvement of the lung, kidney, and intestine, resulting in fatal outcome. The lifetime diagnosis of amyloidosis was histologically verified.

  15. Infliximab in the treatment of amyloidosis secondary to Crohn's disease.

    Science.gov (United States)

    Cabezuelo, Juan B; Egea, Juan P; Ramos, Fernanda; Torrella, Emilio; Muray, Salomé; Alcázar, Concepción

    2012-05-14

    Secondary amyloidosis (AA) is a severe complication of progressed Crohn’s disease (CD) for which no effective treatment exists. We present the exceptional case of a 33 year-old male with moderate renal failure and proteinuria, who was simultaneously diagnosed with AA amyloid nephropathy and oligosymptomatic CD. He was treated with infliximab at 5mg/kg/8 weeks for 4 years, azathioprine at 1-1.5mg/kg/day (first year) and renin-angiotensin-aldosterone system blockers, with no complications. Treatment caused a decrease in proteinuria, improved renal function, and improved inflammatory parameters over time. Inspired by this case, we performed a review of the medical literature and found that infliximab could be a useful tool in the early treatment of amyloidosis secondary to CD.

  16. A rare cause of stridor: Isolated tracheal amyloidosis

    Directory of Open Access Journals (Sweden)

    Numbere K Numbere

    2014-01-01

    Full Text Available A 50-year-old man presented to clinic with a two-year history of progressive exertional dyspnea and voice hoarseness. This history suggested upper airways obstruction, which was confirmed on computed tomography imaging that revealed extensive thickening of the proximal tracheal wall causing severe luminal narrowing. Bronchoscopic debulking was then performed and the samples obtained confirmed tracheal amyloidoisis. Extensive investigation confirmed that disease was localized solely to the trachea. Ultimately, after multiple discussions, the chosen treatment modality was radiotherapy, which proceeded relatively uneventfully and achieved excellent radiological and clinical response. Although tracheal amyloidosis is rare, it is most commonly observed as part of a multisystem presentation. The present report describes the even more uncommon diagnosis of isolated tracheal amyloidosis and highlights the role of radiotherapy in its management.

  17. Guideline of transthyretin-related hereditary amyloidosis for clinicians

    Directory of Open Access Journals (Sweden)

    Ando Yukio

    2013-02-01

    Full Text Available Abstract Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis—and, specifically, familial amyloidotic polyneuropathy—so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials.

  18. Cardiovascular Magnetic Resonance and prognosis in cardiac amyloidosis

    Directory of Open Access Journals (Sweden)

    Roughton Michael

    2008-11-01

    Full Text Available Abstract Background Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study. Materials and methods The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE. Results Patients with were followed for a median of 623 days (IQ range 221, 1436, during which 17 (58% patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis. Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049 or diastolic function (Kaplan-Meier analysis P = 0.205. Conclusion In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden.

  19. Hereditary renal amyloidosis caused by a heterozygous G654A gelsolin mutation: a report of two cases

    OpenAIRE

    Yamanaka, Shuichiro; Miyazaki, Yoichi; Kasai, Kenji; Ikeda, Shu-ichi; Kiuru-Enari, Sari; Hosoya, Tatsuo

    2013-01-01

    Finnish-type familial amyloidosis (FAF) is a rare hereditary systemic amyloidosis that mainly exhibits cranial neuropathy. We describe a Japanese family with FAF manifested predominantly as renal amyloidosis. The proband was a 42-year-old woman with a 21-year history of proteinuria due to renal amyloidosis. Her mother was subsequently diagnosed with a similar disorder. After the first renal biopsy, both patients were followed up routinely for a period of 14 years. Genetic analysis of DNA samp...

  20. Primary amyloidosis presenting as an isolated mediastinal mass: diagnosis by fine needle biopsy.

    OpenAIRE

    Hiller, N.; FISHER, D.; Shmesh, O.; Gottschalk-Sabag, S.; Dollberg, M.

    1995-01-01

    Intrathoracic amyloidosis affecting the lungs or mediastinum is rare, and mediastinal lymphadenopathy in the absence of pulmonary involvement is even more rare. The case history is presented of a previously healthy man who developed nodular mediastinal amyloidosis without pulmonary involvement. Diagnosis was made by percutaneous fine needle biopsy.

  1. Laryngeal amyloidosis : Localized versus systemic disease and update on diagnosis and therapy

    NARCIS (Netherlands)

    Bartels, H.; Dikkers, FG; Van der Wal, JE; Lokhorst, HM; Hazenberg, BPC

    2004-01-01

    The clinical and pathological characteristics, possibility of systemic disease, and effect of local therapy were studied in laryngeal amyloidosis. Records of all patients with localized laryngeal amyloidosis in a single tertiary referral center were examined retrospectively at diagnosis and after lo

  2. Serum amyloid A and protein AA: molecular mechanisms of a transmissible amyloidosis.

    Science.gov (United States)

    Westermark, Gunilla T; Westermark, Per

    2009-08-20

    Systemic AA-amyloidosis is a complication of chronic inflammatory diseases and the fibril protein AA derives from the acute phase reactant serum AA. AA-amyloidosis can be induced in mice by an inflammatory challenge. The lag phase before amyloid develops can be dramatically shortened by administration of a small amount of amyloid fibrils. Systemic AA-amyloidosis is transmissible in mice and may be so in humans. Since transmission can cross species barriers it is possible that AA-amyloidosis can be induced by amyloid in food, e.g. foie gras. In mice, development of AA-amyloidosis can also be accelerated by other components with amyloid-like properties. A new possible risk factor may appear with synthetically made fibrils from short peptides, constructed for tissue repair.

  3. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    Science.gov (United States)

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality. PMID:27642740

  4. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    Science.gov (United States)

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality.

  5. Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease.

    Directory of Open Access Journals (Sweden)

    Gonçalo da Costa

    Full Text Available Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis.

  6. Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mihajlo Gjeorgjievski

    2015-01-01

    Full Text Available Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS, smoldering multiple myeloma (SMM, and multiple myeloma (MM. This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda- type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

  7. Therapeutic regional dermabrasion in papular lichen amyloidosis of shins

    Directory of Open Access Journals (Sweden)

    Savant S

    1995-01-01

    Full Text Available Therapeutic regional dermabrasion of shins is a useful surgical method for planing away the persistent pruritic lichenified hyperkeratotic eruptions of papular lichen amyloidosis. Nine patients (6 females and 3 males of 35 to 52 years age having papular lichen amyloidosis on shins, refractory to various medical lines of treatment for 5-12 years duration were subjected to regional dermabrasion. Extensor surfaces (shins of both lower extremities (18 sites in all 9 cases were treated by multiple sittings of spot dermabrasion. All 18 sites healed with superficial scarring and complete response (100% with total clearance of lesions was observed in all 18 sites. Pruritus stopped in all the 18 dermabraded sites immediately. No local recurrence has been observed in any sites over a minimum follow up peroid of 1½ years. Apart from superficial scarring occurring at all 18 sites the other side effect observed was varying degree of hypopigmentation in 10 out of the 18 sites dermabraded. Complication in the form of parchment like deep atrophic scarring with persistant hypopigmentation, erythema and at places depigmentation were obseved at 2 sites which were dermabraded deeply. Similar complications with delayed wound healing were observed at the 3rd site as sequel to secondary bacterial infection following spot dermabrasion

  8. Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

    Science.gov (United States)

    Kagawa, Miwako; Fujino, Yasuteru; Muguruma, Naoki; Murayama, Noriaki; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Kishi, Kazuhiro; Miyamoto, Hiroshi; Uehara, Hisanori; Takayama, Tetsuji

    2016-06-01

    A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years. PMID:27170299

  9. Light chain (AL amyloidosis: update on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Rosenzweig Michael

    2011-11-01

    Full Text Available Abstract Light chain (AL amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM followed by autologous hematopoietic stem cell transplantation (SCT or oral melphalan with dexamethasone (MDex. The use of novel agents (thalidomide, lenalidomide and bortezomib alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

  10. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  11. Renal uptake of /sup 67/Ga-citrate in renal amyloidosis due to Familiar Mediterranean Fever

    Energy Technology Data Exchange (ETDEWEB)

    Banzo-Marraco, J.; Abos-Olivares, M.D.; Iribar-Ibabe, M.C.; Prats-Rivera, E.; Banzo-Marraco, J.I.; Teijeiro-Vidal, J.; Nerin-Mora, E.; Nerin de la Puerta, I.

    1981-06-01

    Renal uptake of /sup 67/Ga-citrate is described in a patient with biopsy-proven amyloidosis of the kidneys, due to Familiar Mediterranean Fever. After administration 150 MBq (4mCi) /sup 67/Ga-citrate, scans were done at 48, 72, and 120 h. Intense uptake was noted in both kidneys. A renal biopsy done 5 days after the /sup 67/Ga-citrate scan revealed a pattern typical of amyloidosis. Gallium scanning can be useful in patients with fever of unknown origin. Renal amyloidosis can be considered when renal uptake of /sup 67/Ga-citrate associated with nephrotic syndrome is observed.

  12. A prospective study of nutritional status in immunoglobulin light chain amyloidosis

    DEFF Research Database (Denmark)

    Sattianayagam, Prayman T; Lane, Thirusha; Fox, Zoe;

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly......-diagnosed, treatment-naïve patients with immunoglobulin light chain amyloidosis attending the UK National Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score of 4 or over, indicating malnutrition requiring specialist nutritional intervention. Number of amyloidotic organs, elevated alkaline...... phosphatase, presence of autonomic neuropathy and advanced Mayo disease stage were independently associated with poor nutritional status (P...

  13. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  14. Isolated heart transplantation for familial transthyretin (TTR) V122I cardiac amyloidosis.

    Science.gov (United States)

    Thenappan, Thenappan; Fedson, Savitri; Rich, Jonathan; Murks, Catherine; Husain, Aliya; Pogoriler, Jennifer; Anderson, Allen S

    2014-06-01

    Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation. Abbreviations MMF mycophenolate mofetil NYHA New York Heart Association TTR transthyretin VE minute ventilation. PMID:24818650

  15. Acute liver failure due to primary amyloidosis in a nephrotic syndrome: a swiftly progressive course.

    Science.gov (United States)

    Cardoso, Brigite Aguiar; Leal, Rita; Sá, Helena; Campos, Mário

    2016-01-01

    AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis. PMID:26965175

  16. Intestinal amyloidosis:Two cases with different patterns of clinical and imaging presentation

    Institute of Scientific and Technical Information of China (English)

    Pier; Paolo; Mainenti; Sabrina; Segreto; Marcello; Manci

    2010-01-01

    The involvement of the small bowel in systemic forms of amyloidosis may be diffuse or very rarely focal.Some cases of focal amyloidomas of the duodenum and jejunum without extraintestinal manifestations have been reported.The focal amyloidomas consisted of extensive amyloid infiltration of the entire intestinal wall thickness.Radiological barium studies,ultrasound and computed tomography(CT)patterns of diffuse small bowel amyloidosis have been described:the signs are non-specific and may include small-bowel...

  17. The Evaluation of Amyloidosis Cases with Renal Involvement: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Yavuz AYAR

    2015-09-01

    Full Text Available OBJECTIVE: Amyloidosis is a chronic disease associated with proteinuria and can progress to renal failure. The diagnosis and treatment of the underlying cause is therefore important. In this study at a university hospital, the diagnosis of amyloidosis patients with renal biopsies was evaluated retrospectively. MATERIAL and METHODS: 69 (42 males, 27 females, mean age: 51.7 ± 14.8 years patients were diagnosed with amyloidosis with renal biopsy. Indications for biopsy was nephrotic syndrome in 42 patients (60.9%, nephritic syndrome in 27 (39.1% and renal dysfunction with proteinuria in 31 (44.9%. RESULTS: The most common causes of secondary amyloidosis were Familial Mediterranean Fever in 17 of the 62 patients, chronic inflammatory diseases in 17 patients and chronic infection in 13 patients. No cause was determined in 12 patients. Multiple myeloma was present in 5 patients with primary amyloidosis. At the time of diagnosis with amyloidosis, 19 patients were stage 1, 15 stage 2, 5 stage 3A, 12 stage 3B, 10 stage 4 and 8 stage 5. The baseline hemoglobin, serum albumin, creatinine, sodium, potassium, calcium, phosphorus, AST, ALT, PTH, SAA, CRP levels, average daily urinary protein excretion and baseline GFR values were not significantly different in primary and secondary amyloidosis patients. The treatment was medical in 62.3% of the patients, dialysis in 31.9% and renal transplantation in 5.8%. CONCLUSION: The reliability of renal biopsy in the diagnosis of amyloidosis is high. However, genetic studies for the diagnosis of idiopathic cases and special histological staining methods should be considered.

  18. Macroglossia due to Systemic Amyloidosis: Is There a Role for Radiotherapy?

    OpenAIRE

    Thibault, Isabelle; Vallières, Isabelle

    2011-01-01

    Background Macroglossia due to amyloid depositions can cause cosmetic problems and functional disability, and can lead to life-threatening airway obstruction. Management of macroglossia in systemic amyloidosis is controversial, and the role of surgery is unclear. Case Description We present a case of a 66-year-old woman affected by macroglossia due to light chain amyloidosis who presented with eating and breathing difficulties. Because of prior successful results of radiotherapy for localized...

  19. Focal Amyloidosis of the Orbit Presenting as a Mass: MRI and CT Features

    International Nuclear Information System (INIS)

    Focal orbital amyloidosis is a rare entity and little is known about its magnetic resonance imaging (MRI) features. In this case report, imaging features of a case of focal orbital amyloidosis presenting as a mass have been documented together with its histopathological findings. On MRI, a well-defined mass was seen as isointense with rectus muscle on T1-weighted images and heterogeneously hypointense on T2-weighted images. Punctuate calcifications were observed on the computerized tomography (CT) examination

  20. A new family with hereditary lysozyme amyloidosis with gastritis and inflammatory bowel disease as prevailing symptoms

    OpenAIRE

    Jean, Estelle; Ebbo, Mikael; Valleix, Sophie; Benarous, Lucas; Heyries, Laurent; Grados, Aurélie; Bernit, Emmanuelle; Grateau, Gilles; Papo, Thomas; Granel, Brigitte; Daniel, Laurent; Harlé, Jean-Robert; Schleinitz, Nicolas

    2014-01-01

    Background Systemic amyloidoses is a heterogeneous group of diseases either acquired or hereditary. Amyloidoses can involve the gastrointestinal tract and the nature of the precursor protein that forms the fibrils deposits should be identified to adjust the treatment and evaluate the prognosis. Lysozyme amyloidosis (ALys) is a rare, systemic non neuropathic hereditary amyloidosis with a heterogenous phenotype including gastrointestinal, renal and hepatic symptoms. Case presentation We report ...

  1. A Case of Cardiac Amyloidosis With Diuretic-Refractory Pleural Effusions Treated With Bevacizumab

    OpenAIRE

    Bae, Suk-Hyang; Hwang, Jin Yeon; Kim, Woo Jae; Yoon, Hyun-Hwa; Kim, Jung Min; Nam, Young Hee; Baek, Hee Gyung; Cho, Yong Rak; Park, Sun-Yi; Kim, Jeong Hwan; Kim, Sung-Hyun; Park, Tae-Ho; Lee, Gi-Nam; Rha, Seo-Hee; Kim, Young Dae

    2010-01-01

    Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleur...

  2. A case of dialysis-related amyloidosis of the hip and cervical spine: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gyung Kyu; Kang, Ik Won; Min, Seon Jung; Cho, Seong Whi; Kim, Seok Woo; Jang, Woo Young [Hallym University College of Medicine, Chuncheon (Korea, Republic of); Lee, Seon Joo [Inje University College of Medicine, Seoul (Korea, Republic of); Suh, Kyung Jin [Dankook University College of Medicine, Busan Paik Hospital, Busan (Korea, Republic of)

    2006-05-15

    Dialysis-related amyloidosis is a complication of long-term hemodialysis and it is characterized by the accumulation of {beta} 2-microglobulin in the osteoarticular structures. We describe here the imaging findings of a case of dialysis-related amyloidosis involving the hip and cervical spine in a 62-year-old woman who received long-term dialysis. We focus here on the CT and MR imaging findings of the cervical spine and we include a review of the relevant literatures.

  3. Hereditary transthyretin-related amyloidosis: clinical and physiopathologic profile and natural history

    OpenAIRE

    Gallelli, Ilaria

    2012-01-01

    Background. Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectrum of ATTR in a non-endemic, Caucasian area and evaluated prevalence, genetic background and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA) Methods and Results. In this Italian m...

  4. A Case Report of Cardiac Amyloidosis Initially Managed as Dilated Cardiomyopathy: Missing the obvious!

    OpenAIRE

    Yerramareddy Vijaya Chandra; Vellore Satyanarayanan Yogeeswari

    2016-01-01

    Amyloidosis is a rare disorder with uncertain incidence; however, in UK and US population, AL amyloidosis, the most frequently diagnosed type, has an annual incidence of 6 to 10 cases per million. [1] The deposition of amyloid, the extracellular proteinaceous material, in the tissues results in a group of disorders called amyloidoses. [2] The most commonly deposited amyloid material in various organ systems including heart are light chains, transthyretin and serum amyloid A. [2] One of th...

  5. Transthyretin cardiac amyloidosis: an under-diagnosed cause of heart failure

    OpenAIRE

    Molina O., Gabriela; Judge, Daniel; Campbell, Wayne; Chahal, Harjit; Mugmon, Marc

    2014-01-01

    Introduction: Cardiac amyloidosis is the most common cause of infiltrative cardiomyopathy and is associated with a poor prognosis. Transthyretin cardiac amyloidosis, particularly the type caused by the mutation that replaces the amino acid valine with the amino acid isoleucine at position 122 (Val122Ile), is most common among African- Americans above 65 years of age. Evidence suggests that this mutation is an important, though under-diagnosed, cause of heart failure in this population.Case pr...

  6. Genetic variation of the transthyretin gene in wild-type transthyretin amyloidosis (ATTRwt)

    OpenAIRE

    Sikora, Jacquelyn L.; Logue, Mark W.; Chan, Gloria G.; Spencer, Brian H.; Prokaeva, Tatiana B.; Baldwin, Clinton T.; Seldin, David C.; Connors, Lawreen H.

    2014-01-01

    Wild-type transthyretin amyloidosis (ATTRwt), typically diagnosed as congestive heart failure in elderly Caucasian men, features myocardial amyloid deposits of wild-type plasma protein transthyretin (TTR). ATTRwt is sporadic, its pathogenesis is poorly understood, and currently there are no biomarkers for diagnosis or prognosis. Genetic studies of variant-associated transthyretin amyloidosis (ATTRm) have suggested that non-coding TTR gene variants modulate disease. We hypothesized that cis-ac...

  7. Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis.

    Science.gov (United States)

    DiBartola, S P; Tarr, M J; Benson, M D

    1986-07-01

    The tissue distribution of amyloid deposits was studied in 15 related Abyssinian cats with familial amyloidosis. There was interstitial medullary amyloidosis in the kidneys of all 15 cats but only 11 had detectable glomerular involvement. The thyroid glands, stomach and colon were affected in all cats examined. Most of the cats also had amyloid deposits in the small intestine, spleen, heart, adrenals, pancreas, liver, lymph nodes and bladder. In 50 per cent or fewer of the cats examined, there was involvement of the parathyroids, lung and gonads. The central nervous system was not involved in any of the 3 cats evaluated. In 8 of the cats, no concurrent inflammatory disease could be detected. The tissue distribution of amyloid deposits resembled that found in other breeds of domestic cats with systemic amyloidosis. Despite the wide tissue distribution of amyloid deposits, clinical signs were related to renal amyloidosis. Familial amyloidosis in the Abyssinian cat may represent a valuable spontaneous animal model for the study of Familial Mediterranean Fever in man and the pathogenesis of reactive amyloidosis in general. PMID:3734172

  8. Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Faust Dominik

    2009-01-01

    Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

  9. A Case Report of Cardiac Amyloidosis Initially Managed as Dilated Cardiomyopathy: Missing the obvious!

    Directory of Open Access Journals (Sweden)

    Yerramareddy Vijaya Chandra

    2016-06-01

    Full Text Available Amyloidosis is a rare disorder with uncertain incidence; however, in UK and US population, AL amyloidosis, the most frequently diagnosed type, has an annual incidence of 6 to 10 cases per million. [1] The deposition of amyloid, the extracellular proteinaceous material, in the tissues results in a group of disorders called amyloidoses. [2] The most commonly deposited amyloid material in various organ systems including heart are light chains, transthyretin and serum amyloid A. [2] One of the challenges in diagnosing amyloidosis early is that it commonly manifests with nonspeci c symptoms of fatigue and weight loss. The diagnosis is generally considered only when symptoms are traceable to a speci c organ. [3] Cardiac amyloidosis presents initially with mild LV diastolic dysfunction, progressing to classical restrictive cardiomyopathy and nally even dilated cardiomyopathy like stage with end-stage heart failure. The disease can be mistaken in the early stages with hypertrophic cardiomyopathy and hypertensive heart disease and in the late stages with the common-garden variety of dilated cardiomyopathy. Here, we describe a case of cardiac amyloidosis, initially diagnosed and managed as dilated cardiomyopathy with inadequate response to management. Amyloidosis; 2D ECHO; Dilated Cardiomyopathy

  10. Primary localized cutaneous amyloidosis with lichen and poikiloderma-like lesions and an excellent response to systemic acitretin*

    Science.gov (United States)

    MA, Han; Su, Xiangyang; Zhu, Guoxing; Yin, Songchao; Lu, Chun; Lai, Wei

    2016-01-01

    Primary localized cutaneous amyloidosis is a skin-limited amyloidosis that does not involve internal organs. It is clinically subclassified into 3 general categories and some rare variants. However, there is considerable overlap within the classification. Though there are a variety of therapeutic measures, the treatment is often unsatisfactory, particularly when the disease is severe and extensive. We describe a rare case of primary localized cutaneous amyloidosis with lichen and poikiloderma-like lesions that showed an excellent response to systemic acitretin.

  11. Restrictive cardiomyopathy in inherited ATTR amyloidosis (TTR-Ser23Asn) in a patient of German-Italian extraction

    OpenAIRE

    Mueller, Iris I.; Gawaz, Meinrad; Linke, Reinhold P; Zuern, Christine; Steiner, Dagmar; Altland, Klaus; von Beckerath, Nicolas; Weig, Hans-Joerg

    2010-01-01

    Amyloidosis occurs when certain soluble proteins are transformed into amyloid fibrils in the extracellular space. Most common are the light-chain amyloidoses; less common is the AA-amyloidosis, which follows chronic inflammatory diseases, and the amyloidoses of transthyretin (TTR) origin. We report on a women of Italian-German origin with the mutation TTR (Ser23Asn). Whole body scintigraphy using TC99m-DPD showed end stage hereditary amyloidosis caused by ATTR with predominant tracer retentio...

  12. Incidental seminal vesicle amyioidosis observed in diagnostic prostate biopsies-are routine investigations for systemic amyloidosis warranted?

    Institute of Scientific and Technical Information of China (English)

    Zichu Yang; Alexander Laird; Ashley Monaghan; Morag Seywright; Imran Ahmad; Hing Y Leung

    2013-01-01

    Seminal vesicle (SV) amyloidosis is a well-documented histological entity,but it is observed infrequently.Its incidence is on the rise,which is probably related to the increasing use of prostate biopsies to investigate patients with elevated serum prostate-specific antigen levels.Here,we report seven cases of incidental SV amyloidosis over a 3-year period and consider their relationship to the previously suggested aetiological factors.Based on our series,we conclude that incidental localized SV amyloidosis observed in diagnostic prostate biopsies does not warrant formal investigations for systemic amyloidosis.

  13. Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report

    Directory of Open Access Journals (Sweden)

    Kamata Tsugumasa

    2012-08-01

    Full Text Available Abstract Introduction Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach. Case presentation A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis. Conclusions We report an unusual case of primary amyloidosis of the stomach

  14. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL) : A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

    NARCIS (Netherlands)

    Gertz, MA; Comenzo, R; Falk, RH; Fermand, JP; Hazenberg, BP; Hawkins, PN; Merlini, G; Moreau, P; Ronco, P; Sanchorawala, [No Value; Sezer, O; Solomon, A; Grateau, G

    2005-01-01

    We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of pati

  15. Outcome of kidney transplantation for renal amyloidosis:a single-center experience.

    Science.gov (United States)

    Celik, A; Saglam, F; Dolek, D; Sifil, A; Soylu, A; Cavdar, C; Temizkan, A; Bora, S; Gulay, H; Camsari, T

    2006-03-01

    The aim of this retrospective study was to investigate the results of kidney transplantation in patients with renal amyloidosis. We analyzed the results of renal transplantation in 13 amyloidotic transplant recipients compared with those in a control group of 13 nonamyloidotic patients. While the etiology of amyloidosis was rheumatoid arthritis in one patient, in all of the others it was secondary to familial Mediterranean fever. Acute rejection episodes developed once in six and twice in one patient. The renal function in these patients was improved by antirejection treatment. Chronic rejection did not develop in any patient. However six patients (46%) died due to various complications despite functional grafts. The others are still being followed with well-functioning grafts. Among the control group, acute and chronic rejection were diagnosed in three and two patients, respectively: one patient returned to hemodialysis after 26 months of transplantation, while the others are still alive with functional grafts. There was no death in the control group. The 5- and 10-year actuarial patient survival rates of the amyloidosis and control groups were 52.2%, 26.6%, and 100%, 100%, respectively (P = .002). However, the graft survivals of the amyloidosis versus control groups were 100%, 100%, versus 87.5%, 87.5, respectively (P = .47). In conclusion, we observed a high rate of early mortality among recipients with amyloidosis associated with infectious complications. Moreover, patient survivals were lower among amyloidotic renal recipients. PMID:16549141

  16. Pneumatosis intestinalis due to gastrointestinal amyloidosis: A case report & review of literature

    Science.gov (United States)

    Khalid, Filza; Kaiyasah, Hadiel; Binfadil, Wafa; Majid, Maiyasa; Hazim, Wessam; ElTayeb, Yousif

    2016-01-01

    Introduction Pneumatosis intestinalis (PI) is not a disease but a radiological finding with a poorly understood pathogenesis. It can be divided into primary/idiopathic (15%) or secondary (85%) Kim et al. 2007, based on the factors thought to play a role in its development. Amongst the rare causes of secondary PI is gastrointestinal (GI) amyloidosis. Presentation of the case We report a case of a 46-year-old gentleman who presented with a one month history of acute on chronic abdominal pain, associated with one episode of melena. Upon further investigation, he was found to have pneumoperitoneum. He was taken to the operating theatre, where he was noted to have features of pneumatosis intestinalis of the small bowel with no evidence of bowel perforation. Postoperatively, he underwent an upper GI endoscopy with biopsies that revealed GI amyloidosis. Discussion One of the rare causes that can lead to secondary PI is GI amyloidosis as proven in our case. Patients with symptomatic gastrointestinal amyloidosis usually present with one of four syndromes: gastrointestinal bleeding, malabsorption, protein-losing gastroenteropathy, and, less often, gastrointestinal dysmotility. Conclusion GI amyloidosis is a rare cause of secondary pneumatosis intestinalis. The presentation of the disease varies from patient to patient, therefore, the management should be tailored accordingly. PMID:27085104

  17. Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors.

    Science.gov (United States)

    Gaffney, P M; Witte, C; Clifford, D L; Imai, D M; O'Brien, T D; Trejo, M; Liberta, F; Annamalai, K; Fändrich, M; Masliah, E; Munson, L; Sigurdson, C J

    2016-05-01

    Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis. PMID:26419399

  18. Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging.

    Science.gov (United States)

    Narotsky, David L; Castano, Adam; Weinsaft, Jonathan W; Bokhari, Sabahat; Maurer, Mathew S

    2016-09-01

    Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function. The most common forms of systemic amyloidosis are light-chain and transthyretin-related (ATTR). ATTR can result from an autosomal dominant hereditary transmission of mutated genes in the transthyretin or from a wild-type form of disease (ATTRwt), previously known as senile cardiac amyloidosis. With the aging of the worldwide population, ATTRwt will emerge as the most common type of cardiac amyloidosis that clinicians encounter. Diagnosis of systemic amyloidosis is often delayed, either because of the false assumption that it is a rare disease, or because of misdiagnosis as a result of mistaking it with other conditions. Clinicians must integrate clinical clues from history, physical examination, and common diagnostic tests to raise suspicion for ATTRwt. The historical gold standard for diagnosis of cardiac amyloid is endomyocardial biopsy analysis with pathological distinction of precursor protein type, but this method often results in delayed diagnosis because of the limited availability of expertise to perform and interpret the endomyocardial biopsy specimen. Emerging noninvasive imaging modalities provide easier, accurate screening for ATTRwt. These modalities include advanced echocardiography, using strain imaging and the myocardial contraction fraction; nuclear scintigraphy, which can differentiate between ATTR and light-chain cardiac amyloid; and cardiac magnetic resonance imaging, using extracellular volume measurement, late gadolinium enhancement, and distinct T1 mapping. These novel approaches reveal insights into the prevalence, clinical course, morphological effects, and prognosis of ATTRwt. PMID:27568874

  19. A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

    Science.gov (United States)

    Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

    2016-09-01

    Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. PMID:27240838

  20. Protein/Peptide Aggregation and Amyloidosis on Biointerfaces

    Directory of Open Access Journals (Sweden)

    Qi Lu

    2016-08-01

    Full Text Available Recently, studies of protein/peptide aggregation, particularly the amyloidosis, have attracted considerable attention in discussions of the pathological mechanisms of most neurodegenerative diseases. The protein/peptide aggregation processes often occur at the membrane–cytochylema interface in vivo and behave differently from those occurring in bulk solution, which raises great interest to investigate how the interfacial properties of artificial biomaterials impact on protein aggregation. From the perspective of bionics, current progress in this field has been obtained mainly from four aspects: (1 hydrophobic–hydrophilic interfaces; (2 charged surface; (3 chiral surface; and (4 biomolecule-related interfaces. The specific physical and chemical environment provided by these interfaces is reported to strongly affect the adsorption of proteins, transition of protein conformation, and diffusion of proteins on the biointerface, all of which are ultimately related to protein assembly. Meanwhile, these compelling results of in vitro experiments can greatly promote the development of early diagnostics and therapeutics for the relevant neurodegenerative diseases. This paper presents a brief review of these appealing studies, and particular interests are placed on weak interactions (i.e., hydrogen bonding and stereoselective interactions that are also non-negligible in driving amyloid aggregation at the interfaces. Moreover, this paper also proposes the future perspectives, including the great opportunities and challenges in this field as well.

  1. Primary localized amyloidosis presenting as diffuse amorphous calcified mass in both orbits: case report

    Directory of Open Access Journals (Sweden)

    Allan Christian Pieroni Gonçalves

    2011-10-01

    Full Text Available Primary localized amyloidosis is rare in the orbit. We report the case of a 63-year-old woman that presented with bilateral proptosis and ophthalmoplegia. A computed tomography scan revealed an infiltrative amorphous and markedly calcified mass in both orbits while a magnetic resonance scan showed a heterogeneous hypointense signal on T2-weighted images. A biopsy was performed through an anterior orbitotomy. Microscopy revealed extracellular amorphous and eosinophilic hyaline material which stained pink with Congo red and displayed green birefringence on polarized microscopy, leading to a diagnosis of amyloidosis. The results of the systemic workup were completely normal. A two-year follow-up period without any treatment disclosed no worsening of the condition. While calcification of nonvascular orbital lesions has often been regarded as suggestive of malignant disease, our case is a reminder that it can also be a characteristic presenting sign of orbital amyloidosis.

  2. Outcome in patients treated with isolated liver transplantation for familial transthyretin amyloidosis to prevent cardiomyopathy

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Penninga, Luit; Villadsen, Gerda E;

    2015-01-01

    BACKGROUND: Familial transthyretin (TTR) amyloidosis is caused by different TTR mutations resulting in different clinical phenotypes of the disease. The Leu111Met mutation causes severe restrictive cardiomyopathy. Liver transplantation (LTx) is an established treatment option for patients with TT...... patients with familial TTR amyloidosis due to Leu111Met mutation. Appropriate timing of LTx is of utmost importance to avoid development of severe amyloid cardiomyopathy and the need for combined heart and liver transplantation.......BACKGROUND: Familial transthyretin (TTR) amyloidosis is caused by different TTR mutations resulting in different clinical phenotypes of the disease. The Leu111Met mutation causes severe restrictive cardiomyopathy. Liver transplantation (LTx) is an established treatment option for patients with TTR...... occurred. Two patients (33%) underwent cardiac transplantation during follow-up due to progressive cardiomyopathy. The remaining four patients experienced no echocardiographic or clinical deterioration of cardiac function following LTx. CONCLUSION: Isolated LTx appears to be a valuable treatment option for...

  3. Histochemical Differential Diagnosis and Polarization Optical Analysis of Amyloid and Amyloidosis

    Directory of Open Access Journals (Sweden)

    M. Bély

    2006-01-01

    Full Text Available Amyloidosis is characterized by extracellular deposition of protein fibrils of chemically heterogeneous composition. Early recognition and identification of amyloid deposits allows an early start of therapy, which may entail a better prognosis. Congo red staining according to Romhányi (1971 is a highly specific and sensitive method for early microscopic recognition of amyloidosis. The main and most important types of amyloidosis may be distinguished by classic histochemical methods of performate pretreatment according to Romhányi (1979, or by KMnO4 oxidation according to Wright (1977 followed by Congo red staining and viewed under polarized light. Differences in the speed of breakdown (disintegration of amyloid deposits according to Bély and Apáthy allow a more precise distinction of various types of amyloid.

  4. Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction.

    Science.gov (United States)

    Ton, Van-Khue; Mukherjee, Monica; Judge, Daniel P

    2014-01-01

    Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis. PMID:25628512

  5. MRI in cardiac sarcoidosis and amyloidosis; MRT bei kardialer Sarkoidose und Amyloidose

    Energy Technology Data Exchange (ETDEWEB)

    Bauner, K.U. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Wintersperger, B. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

    2013-01-15

    Sarcoidosis and amyloidosis are both multisystem disorders, which may involve the heart; however, isolated cardiac disease is rare. Diagnosis of cardiac sarcoidosis and amyloidosis is crucial because the patient prognosis is dependent on cardiac involvement and early treatment. Echocardiography is the first line imaging modality in the diagnostic work-up of both diseases, possibly giving hints towards the correct diagnosis. Besides myocardial biopsy and radionuclide studies cardiac magnetic resonance imaging (MRI) is routinely performed in patients suspect of having infiltrative cardiomyopathy. The T1 mapping procedure is currently being evaluated as a new technique for detection and quantification of global myocardial enhancement, as seen in cardiac amyloidosis. Sensitivities and specificities for detection of cardiac sarcoidosis and amyloidosis can be significantly improved by MRI, especially with late gadolinium enhancement (LGE) imaging. In cardiac sarcoidosis the use of LGE is outcome-related while in amyloidosis analysis of T1-mapping may be of prognostic value. If cardiac involvement in sarcoidosis or amyloidosis is suspected cardiac MRI including LGE should be performed for establishing the diagnosis. (orig.) [German] Die Sarkoidose und Amyloidose sind Multisystemerkrankungen, in deren Verlauf es zu einer kardialen Beteiligung kommen kann. Bildgebend wird als primaeres Verfahren die Echokardiographie eingesetzt. Zur weiteren Diagnostik wird neben der Biopsie und nuklearmedizinischen Verfahren v. a. die MRT herangezogen. Als neuere Technik zur Darstellung globaler diffuser Kontrastmittelanreicherungen, wie sie im Rahmen der Amyloidose vorkommen, wird z. Z. das T1-Mapping evaluiert. Durch den Einsatz der MRT, insbesondere des Late-Gadolinium-Enhancements (LGE), koennen die Sensitivitaet und Spezifitaet in der Diagnostik der kardialen Sarkoidose und Amyloidose entscheidend verbessert werden. Bei der Sarkoidose stellt das Vorhandensein eines LGE einen

  6. Primary localized amyloidosis presenting as a tarsal mass: Report of two cases

    Directory of Open Access Journals (Sweden)

    Saurabh Kamal

    2012-01-01

    Full Text Available Amyloidosis and its ophthalmic manifestations are rare. The unusual presentation can result in diagnostic delay and increase ocular morbidity. Additionally, there are various predisposing conditions and systemic involvement can affect various organs. Hence, localized disease warrants a thorough clinical evaluation and laboratory investigation. We report two cases of primary localized amyloidosis presenting as a tarsal mass and ptosis. The diagnosis was established on histopathology. There were no predisposing conditions and no systemic involvement. The disease was probably related to the local immunocyte disorder.

  7. Ultrasound-guided percutaneous renal biopsy-induced accessory renal artery bleeding in an amyloidosis patient

    Directory of Open Access Journals (Sweden)

    Zhang Qing

    2012-12-01

    Full Text Available Abstract Ultrasound-guided percutaneous renal biopsy is an important technique for diagnosis of glomerular diseases, and the biopsy-induced life-threatening bleeding rarely happens. Primary systemic amyloidosis is a rare disease which may lead to organ dysfunction including arterial stiffness. The accessory renal artery is a kind of renal vascular variation which goes into the renal parenchyma directly or via the renal hilum. Here we reported a rare case of percutaneous renal biopsy-induced accessory renal artery life-threatening bleeding in a renal amyloidosis patient, and our experience of successful rescue in this patient. Virtual Slides http://www.diagnosticpathology.diagnomx.eu/vs/1524207344817819

  8. Primary amyloidosis of the mesentery and the retroperitoneum presenting with lymphedema.

    Science.gov (United States)

    Halm, U; Berr, F; Tannapfel, A; Klöppel, R; Secknus, R; Mössner, J

    1998-11-01

    We report the case of a 57-yr-old woman presenting with moderate weight loss, abdominal distension, and lymphedema of the legs and vulva. Computed tomography of the abdomen revealed massive thickening of the rectal wall, mesentery, and retroperitoneum. Primary amyloidosis was diagnosed by immunohistochemistry from the rectum and duodenum. To our knowledge, lymphedema due to primary amyloidosis has not yet been reported. The diagnosis should be presumed in the case of retroperitoneal thickening and lymphedema and can be established by immunohistochemistry. PMID:9820426

  9. Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in Europe.

    Science.gov (United States)

    Sanz-Martín, Noelia; Samillán-Sosa, Kelly Del Rocío; De Miguel, Julio; Martínez-Miguel, Patricia

    2016-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main clinical manifestations involve the skin and the peripheral nervous system. Several types of nephropathy have been described in leprosy. One frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. In these patients, end-stage renal disease is an important contributor to morbidity and mortality. Here, we present the case of a patient with nephrotic syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a history of leprosy. The patient was correctly treated in her youth, which is the best way to avoid renal pathology, but she developed a nephrotic syndrome years later. PMID:27489069

  10. Endobronchial amyloidosis mimicking bronchial asthma: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Kang Hyun-Wook

    2016-06-01

    Full Text Available Among two tracheobronchial forms (local and diffuse and two parenchymal forms (nodular and alveolar septal that were reported in previous literature, localized endobronchial amyloidosis is an uncommon disease of unknown cause. Bronchial amyloid deposits can occur as focal nodules or multifocal infiltration of the submucosa. We report the case of a 47-year-old man who had complained of dyspnea and wheezing for 1 month and who had been treated for severe asthma at another hospital. Endobronchial amyloidosis was confirmed by histological examination of the bronchial biopsies.

  11. Liver transplantation in transthyretin amyloidosis: issues and challenges.

    Science.gov (United States)

    Carvalho, Andreia; Rocha, Ana; Lobato, Luísa

    2015-03-01

    Hereditary transthyretin amyloidosis (ATTR) is a rare worldwide autosomal dominant disease caused by the systemic deposition of an amyloidogenic variant of transthyretin (TTR), which is usually derived from a single amino acid substitution in the TTR gene. More than 100 mutations have been described, with V30M being the most prevalent. Each variant has a different involvement, although peripheral neuropathy and cardiomyopathy are the most common. Orthotopic liver transplantation (OLT) was implemented as the inaugural disease-modifying therapy because the liver produces the circulating unstable TTR. In this review, we focus on the results and long-term outcomes of OLT for ATTR after more than 2063 procedures and 23 years of experience. After successful OLT, neuropathy and organ impairment are not usually reversed, and in some cases, the disease progresses. The overall 5-year survival rate is approximately 100% for V30M patients and 59% for non-ATTR V30M patients. Cardiac-related death and septicemia are the main causes of mortality. Lower survival is related to malnutrition, a longer duration of disease, cardiomyopathy, and a later onset (particularly for males). Deposits, which are composed of a mixture of truncated and full-length TTR (type A) fibrils, have been associated with posttransplant myocardial dysfunction. A higher incidence of early hepatic artery thrombosis of the graft has also been documented for these patients. Liver-kidney/heart transplantation is an alternative for patients with advanced renal disease or heart failure. The sequential procedure, in which ATTR livers are reused in patients with liver disease, reveals that neuropathy in the recipient may appear as soon as 6 years after OLT, and ATTR deposits may appear even earlier. Long-term results of trials with amyloid protein stabilizers or disrupters, silencing RNA, and antisense oligonucleotides will highlight the value and limitations of liver transplantation. PMID:25482846

  12. Amyloidosis involving the respiratory system: 5-year′s experience of a multi-disciplinary group′s activity

    Directory of Open Access Journals (Sweden)

    Raffaele Scala

    2015-01-01

    Full Text Available Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients′ clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma. It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

  13. Long-term follow-up after surgery in localized laryngeal amyloidosis.

    Science.gov (United States)

    Hazenberg, Aldert J C; Hazenberg, Bouke P C; Dikkers, Frederik G

    2016-09-01

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence rate, revision surgery, progression to systemic amyloidosis, and changes in voice were monitored yearly. Eighteen patients were included. Seven women and eleven men had a median age 50 years (range 21-77 years) and median follow-up 6.4 years (2.4-17 years). Amyloid was located in subglottis (5), glottis (8), false vocal folds (8) and other supraglottic areas (5), in more than one laryngeal region (13) and bilaterally (12). Cold steel excision was used at the glottis; CO2 laser excision, sometimes assisted by microdebrider, at other laryngeal areas. Eleven patients needed revision surgery, ten within the first 4 years after surgical treatment. One patient needed his first revision surgery after 11 years. Five patients needed a second revision within 6 years after initial diagnosis. Two patients needed a third revision. Indications for first revision surgery were progression (8) with dysphonia (7), dyspnea (2), dysphagia (1), exclusion of malignancy (1), and aphonia (1). No patient developed systemic amyloidosis during follow-up. Although local progression of amyloid necessitates revision surgery once or twice in the first 4-6 years, progression slows down thereafter. Late progression, however, remains possible. PMID:27156084

  14. Irish (Donegal) amyloidosis is associated with the transthyretinALA60 (Appalachian) variant.

    Science.gov (United States)

    Staunton, H; Davis, M B; Guiloff, R J; Nakazato, M; Miyazato, N; Harding, A E

    1991-12-01

    A cluster of cases of late onset amyloidosis, presenting chiefly with peripheral neuropathy and cardiac failure, has been described in Donegal, north-west Ireland. Molecular genetic and protein analyses show that two new patients from the same region have a mutation in the transthyretin gene previously reported in a family with an Irish ancestor from the Appalachian region of the United States.

  15. Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

    DEFF Research Database (Denmark)

    Müller, Hanna; Renner, Marcus; Bergmann, Frank;

    2013-01-01

    Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense...

  16. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptom.

    Science.gov (United States)

    Kon, Tetsuo; Nakagawa, Naoki; Yoshikawa, Fumitsugu; Haba, Kazunao; Kitagawa, Nagako; Izumi, Michihiro; Kumazaki, Setsuo; Ishida, Satoshi; Aikawa, Ryuichi

    2016-08-01

    Immunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of insoluble fibrils composed of immunoglobulin light chains secreted by monoclonal plasma cells. Given the recent advances in the therapy of AL amyloidosis, it is important to diagnose this disease as early as possible. Herein, we describe the case of a 62-year-old man with hepatitis C virus (HCV)-related cirrhosis presenting with hematochezia. Colonoscopy showed multiple submucosal hematomas within the region ranging from the transverse colon to the sigmoid colon. Kappa immunoglobulin light-chain amyloid deposition was also detected. Bone marrow examination revealed a monoclonal abnormal plasma cell population. Thus, the patient was diagnosed with systemic immunoglobulin light-chain amyloidosis. The hematochezia was conservatively managed. However, because of liver failure caused by liver cirrhosis, the patient developed massive pleural effusion and died of respiratory failure. Postmortem examination revealed amyloid deposition in the esophagus, stomach, duodenum, ileum, descending colon, pancreas, heart, and lung. In these organs, amyloid deposition was limited to the vascular wall. We concluded that AL amyloidosis can present hematochezia arising from submucosal hematoma in the large colon before other systemic symptoms appear.

  17. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function

    International Nuclear Information System (INIS)

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  18. Digitally Reinforced Polarization of Hematoxylin-Eosin in the Diagnosis of Renal Amyloidosis

    Directory of Open Access Journals (Sweden)

    Sait ŞEN

    2012-09-01

    Full Text Available Objective: Systemic amyloidosis is a rare disorder, characterized by extracellular accumulation of Congo red positive fibrillar amyloid protein deposits that have an amorphous, eosinophilic appearance on hematoxylin-eosin stained preparations. The kidney is the most commonly affected organ by systemic amyloidosis. Congo red staining increases the positive birefringence of the weakly birefringent unstained amyloid. In this study, we investigated the potential diagnostic power of digitally reinforced birefringence of routine hematoxylin-eosin stained slides from renal biopsies.Material and Method: We reviewed 130 hematoxylin-eosin stained slides for polarization. Sixty-five new amyloidosis cases were diagnosed by renal biopsy. All renal biopsies were evaluated by light microscopy and immunofluorescence. Slides were reevaluated blindly using a microscope (Olympus BX51 that was attached polarization filters and connected to a digital camera (Olympus DP21, SAL. Deposits that showed green birefringence on hematoxylin-eosin preparations with digitalized microscopy were considered positive and the results were confirmed using Congo red.Results: Of the 65 Congo red confirmed amyloid positive biopsies, 61 showed green birefringence with hematoxylin-eosin. Of the 65 Congo-red confirmed amyloid negative biopsies, two were considered to be false positive. The sensitivity, specificity, and positive and negative predictive values were estimated as 94%, 97%, 97% and 94% respectively.Conclusion: We concluded that polarized hematoxylin-eosin sections can be used digitally as a fast and first step diagnostic method for renal amyloidosis

  19. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptom.

    Science.gov (United States)

    Kon, Tetsuo; Nakagawa, Naoki; Yoshikawa, Fumitsugu; Haba, Kazunao; Kitagawa, Nagako; Izumi, Michihiro; Kumazaki, Setsuo; Ishida, Satoshi; Aikawa, Ryuichi

    2016-08-01

    Immunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of insoluble fibrils composed of immunoglobulin light chains secreted by monoclonal plasma cells. Given the recent advances in the therapy of AL amyloidosis, it is important to diagnose this disease as early as possible. Herein, we describe the case of a 62-year-old man with hepatitis C virus (HCV)-related cirrhosis presenting with hematochezia. Colonoscopy showed multiple submucosal hematomas within the region ranging from the transverse colon to the sigmoid colon. Kappa immunoglobulin light-chain amyloid deposition was also detected. Bone marrow examination revealed a monoclonal abnormal plasma cell population. Thus, the patient was diagnosed with systemic immunoglobulin light-chain amyloidosis. The hematochezia was conservatively managed. However, because of liver failure caused by liver cirrhosis, the patient developed massive pleural effusion and died of respiratory failure. Postmortem examination revealed amyloid deposition in the esophagus, stomach, duodenum, ileum, descending colon, pancreas, heart, and lung. In these organs, amyloid deposition was limited to the vascular wall. We concluded that AL amyloidosis can present hematochezia arising from submucosal hematoma in the large colon before other systemic symptoms appear. PMID:27318996

  20. Analysis of the modifying effects of SAA1, SAA2 and TNF-alpha gene polymorphisms on development of amyloidosis in FMF patients.

    Science.gov (United States)

    Yilmaz, Engin; Balci, Banu; Kutlay, Sim; Ozen, Seza; Ertürk, Sensuvar; Oner, Ayse; Beşbaş, Nesrin; Bakkaloğlu, Ayşin

    2003-01-01

    The aim of this study was to examine whether polymorphisms at serum amyloid A (SAA) and tumor necrosis factor-alpha (TNF-alpha) genes are associated with development of amyloidosis in familial Mediterranean fever (FMF) patients. Seventy-three FMF patients with amyloidosis and 100 other FMF patients without amyloidosis of known genotypes and 100 healthy control subjects were analyzed. There was a significant difference in the frequency of alpha/alpha genotype at the SAA1 locus between FMF patients with amyloidosis and controls and FMF patients without amyloidosis. The frequencies of the alpha/alpha genotype and alpha alleles at SAA1 locus were significantly higher in the FMF patients with amyloidosis. The frequencies of the alpha allele at SAA1 locus in FMF patients with amyloidosis, without amyloidosis and controls were 85.6%, 49.5% and 42.5%, respectively. We demonstrated that alpha/alpha genotype at SAA1 gene might have modifying effects on the development of amyloidosis. Determination of genotypes at SAA1 locus can play a key role in conferring genetic susceptibility and patient's prognosis to renal amyloidosis.

  1. Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis.

    Science.gov (United States)

    Dasari, Surendra; Amin, Md Shahrier; Kurtin, Paul J; Vrana, Julie A; Theis, Jason D; Grogg, Karen L; Alexander, Mariam P; Nasr, Samih H; Fervenza, Fernando C; Leung, Nelson; Sethi, Sanjeev

    2016-09-01

    Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis. PMID:27262366

  2. Transthyretin cardiac amyloidosis: an under-diagnosed cause of heart failure

    Directory of Open Access Journals (Sweden)

    Gabriela Molina O

    2014-11-01

    Full Text Available Introduction: Cardiac amyloidosis is the most common cause of infiltrative cardiomyopathy and is associated with a poor prognosis. Transthyretin cardiac amyloidosis, particularly the type caused by the mutation that replaces the amino acid valine with the amino acid isoleucine at position 122 (Val122Ile, is most common among African- Americans above 65 years of age. Evidence suggests that this mutation is an important, though under-diagnosed, cause of heart failure in this population. Case presentation: A 74-year-old African American male with a diagnosis of non-ischemic cardiomyopathy for several years, presented with gradually worsening dyspnea on exertion and lower extremity edema. There is no known cardiac disease in his family. An echocardiogram was done showing a decrease in ejection fraction to 30% from 45% in the span of a year. An endomyocardial biopsy analysis identified transthyretin amyloid with the Val122Ile mutation, confirming the diagnosis of familial transthyretin cardiomyopathy. Discussion: Systemic amyloidosis is a group of diseases caused by the deposition of an abnormally folded, insoluble protein that can accumulate in multiple organs causing progressive and irreversible dysfunction.The mutations that most commonly induce variant transthyretin cardiac amyloidosis are Val122Ile, Val30Met and Thr60Ala. The Val122Ile mutation has been found to be present in 3–4% of the African American/Caribbean population. Conclusions: Familial amyloid cardiomyopathy is an uncommonly recognized cause of heart failure in the population, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. Patients that meet the high-risk profile criteria – male gender, age 65 years and older, heart failure symptoms, symmetric left ventricular (LV hypertrophy, and moderately depressed LV function – should likely undergo additional testing for cardiac amyloidosis.

  3. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis.

    Science.gov (United States)

    Fine, Nowell M; Arruda-Olson, Adelaide M; Dispenzieri, Angela; Zeldenrust, Steven R; Gertz, Morie A; Kyle, Robert A; Swiecicki, Paul L; Scott, Christopher G; Grogan, Martha

    2014-05-15

    Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings. PMID:24698461

  4. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

    Directory of Open Access Journals (Sweden)

    K Abigail Andrews

    % absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis.

  5. Curative effect observation of patients with primary systemic amyloidosis treated by the combination of bortezomib with dexmethasone and cyclophosphamide

    Institute of Scientific and Technical Information of China (English)

    路瑾

    2013-01-01

    Objective To analyze the efficacy and side effects of the combination regimen containing bortezomib,cyclophosphamide and dexamethasone(BCD)in the treatment of primary systemic amyloidosis(PSA).Methods

  6. {sup 18}F-FDG PET/CT in Primary AL Hepatic Amyloidosis Associated with Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Son, Youn Mi; Bak, Cheol Hee [Seoul Medical Center, Seoul (Korea, Republic of); Choi, Joon Young; Cheon, Mi Ju; Kim, Young Eun; Lee, Kyung Han; Kim, Byung Tae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-10-15

    We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased {sup 18}F-FDG uptake in the liver. Although there have been several case studies showing positive {sup 18}F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the {sup 18}F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously.

  7. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective

    OpenAIRE

    Rapezzi, Claudio; Quarta, Candida Cristina; Obici, Laura; Perfetto, Federico; Longhi, Simone; Salvi, Fabrizio; Biagini, Elena; Lorenzini, Massimiliano; Grigioni, Francesco; Leone, Ornella; Cappelli, Francesco; Palladini, Giovanni; Rimessi, Paola; Ferlini, Alessandra; Arpesella, Giorgio

    2013-01-01

    AIMS: Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA). METHODS AND RESULTS: In this Italian multicentr...

  8. A renal transplant recipient with delayed gastric emptying in amyloidosis due to familial Mediterranean fever improved with erythromycin: a case report.

    Science.gov (United States)

    Saglam, F; Celik, A; Cavdar, C; Sifil, A; Atila, K; Kaya, G C; Bora, S; Gulay, H; Camsari, T

    2008-01-01

    Patients with systemic amyloidosis often have symptoms related to impared gastrointestinal motility due to delayed gastric emptying, which results from autonomic nerve or smooth muscle infiltration with amyloid. There is no current report about gastric delaying secondary to amyloidosis due to familial Mediterranean fever. In this report, we have described a renal transplant recipient with delayed gastric emptying secondary to amyloidosis due to familial Mediterranean fever, which improved with erithromycin treatment. PMID:18261613

  9. Imaging cardiac amyloidosis: a pilot study using {sup 18}F-florbetapir positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dorbala, Sharmila [Brigham and Women' s Hospital, Harvard Medical School, Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, Cardiovascular Division and the Cardiac Amyloidosis Program, Department of Medicine, Boston, MA (United States); Brigham and Women' s Hospital, Boston, MA (United States); Vangala, Divya; Semer, James; Strader, Christopher; Bruyere, John R.; Moore, Stephen C. [Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Boston, MA (United States); Di Carli, Marcelo F. [Brigham and Women' s Hospital, Harvard Medical School, Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Boston, MA (United States); Falk, Rodney H. [Brigham and Women' s Hospital, Harvard Medical School, Cardiovascular Division and the Cardiac Amyloidosis Program, Department of Medicine, Boston, MA (United States); Brigham and Women' s Hospital, Boston, MA (United States)

    2014-09-15

    Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of {sup 18}F-florbetapir for imaging cardiac amyloidosis. We performed a pilot study of cardiac {sup 18}F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of {sup 18}F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A {sup 18}F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. Left and right ventricular myocardial uptake of {sup 18}F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min{sup -1}, IQR 0.034 - 0.051 min{sup -1}, vs. 0.023 min{sup -1}, IQR 0.015 - 0.025 min{sup -1}, P = 0.002; TBR 1.84, 1.64 - 2.50, vs. 1.26, IQR 0.91 - 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 - 5.65, vs. 1.35, IQR 1.17 - 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 - 1.64, vs. 0.18, IQR 0.15 - 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. {sup 18}F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied. (orig.)

  10.  Liver transplantation followed by autologous stem cell transplantation for acute liver failure caused by AL amyloidosis. Case report and review of the literature.

    Science.gov (United States)

    Elnegouly, Mayada; Specht, Katja; Zoller, Heinz; Matevossian, Edouard; Bassermann, Florian; Umgelter, Andreas

    2016-01-01

     Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT. PMID:27236160

  11. {sup 123}I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Noordzij, Walter; Glaudemans, Andor W.J.M.; Rheenen, Ronald W.J. van; Dierckx, Rudi A.J.O.; Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Hazenberg, Bouke P.C. [University of Groningen, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands)

    2012-10-15

    Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. {sup 123}I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and {sup 123}I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 {+-} 0.75, and the mean wash-out rate was 8.6 {+-} 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 {+-} 0.70 versus 2.8 {+-} 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 {+-} 9.9 % vs. 17 {+-} 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 {+-} 0.59 vs. 2.9 {+-} 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, {sup 123}I-MIBG scintigraphy can detect cardiac denervation in

  12. Renal and suprarenal insufficiency secondary to familial Mediterranean fever associated with amyloidosis: a case report

    Directory of Open Access Journals (Sweden)

    Sari Nagehan

    2011-08-01

    Full Text Available Abstract Introduction Familial Mediterranean fever is an autosomal recessive disease that predominantly affects people of the Mediterranean coast. One of the most frequent complications of the disease is amyloidosis. This clinical entity is known as secondary (also called AA amyloidosis. Case presentation In this report, we describe the case of a 33-year-old Turkish man with familial Mediterranean fever and chronic renal insufficiency. He was admitted to our clinic with symptoms of suprarenal insufficiency. The patient died three months later as a result of cardiac arrest. Conclusion Our aim is to make a contribution to the literature by reporting a case of combined insufficiency due to the accumulation of renal and adrenal amyloid in a patient with familial Mediterranean fever, which has very rarely been described in the literature. We hope that adrenal insufficiency, which becomes fatal if not diagnosed and treated rapidly, will come to mind as easily as chronic renal failure in clinical practice.

  13. Juvenile idiopathic arthritis complicated by amyloidosis with secondary nephrotic syndrome - effective treatment with tocilizumab.

    Science.gov (United States)

    Kwiatkowska, Małgorzata; Jednacz, Ewa; Rutkowska-Sak, Lidia

    2015-01-01

    A case report of a boy with juvenile idiopathic arthritis since the age of 2 years, generalized onset, complicated by nephrotic syndrome due to secondary type A amyloidosis is presented. In the patient the disease had an especially severe course, complicated by frequent infections, making routine treatment difficult. Amyloidosis was diagnosed in the 5(th) year of the disease based on a rectal biopsy. Since the disease onset the boy has been taking prednisolone and sequentially cyclosporine A, methotrexate, chlorambucil, etanercept, and cyclophosphamide. Clinical and laboratory remission was observed after treatment with tocilizumab. After 42 months of treatment with tocilizumab the boy's condition is good. There is no pain or joint edema, and no signs of nephrotic syndrome.

  14. Diaphragmatic Amyloidosis Causing Respiratory Failure: A Case Report and Review of Literature

    OpenAIRE

    Aleksey Novikov; Horatio Holzer; DeSimone, Robert A.; Ghaith Abu-Zeinah; Pisapia, David J.; Mark, Tomer M.; Pastore, Raymond D.

    2015-01-01

    Neuromuscular respiratory failure is a rare complication of systemic immunoglobulin light chain amyloidosis. We describe a case of a 70-year-old Caucasian man with multiple myeloma who presented with worsening dyspnea. The patient was diagnosed with and treated for congestive heart failure but continued to suffer from hypercapnic respiratory insufficiency. He had restrictive physiology on pulmonary function tests and abnormal phrenic nerve conduction studies, consistent with neuromuscular res...

  15. Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Balwani Manish R

    2015-04-01

    Full Text Available Common variable immunodeficiency (CVID usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR, hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.

  16. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    Directory of Open Access Journals (Sweden)

    Arahata M

    2016-08-01

    Full Text Available Masahisa Arahata,1 Shigeru Shimadoi,1 Satosi Yamatani,1 Shin-ichi Hayashi,2 Shigeharu Miwa,2 Hidesaku Asakura,3 Shinji Nakao4 1Department of Internal Medicine, Nanto Municipal Hospital, Nanto, 2Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Internal Medicine (III, 4Department of Cellular Transplantation Biology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Abstract: Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. Keywords: systemic amyloidosis, amyloid cardiomyopathy, fine-needle aspiration biopsy, subcutaneous fat tissue, hip

  17. Leptomeningeal transthyretin-type amyloidosis presenting as acute hydrocephalus and subarachnoid hemorrhage.

    Science.gov (United States)

    Bevers, Matthew B; McGuone, Declan; Jerath, Nivedita U; Musolino, Patricia L

    2016-07-01

    We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage. PMID:26896372

  18. A DNA test for Indiana/Swiss hereditary amyloidosis (FAP II).

    OpenAIRE

    Wallace, M. R.; Conneally, P M; Benson, M D

    1988-01-01

    Autosomal dominant amyloidosis of the Indiana/Swiss type is a late-onset disorder characterized by carpal tunnel syndrome, progressive peripheral neuropathy, vitreous deposits, and cardiomyopathy. This disorder was originally described in a large Indiana family of Swiss descent and is also known as familial amyloidotic polyneuropathy (FAP) type II. In the Indiana family, the genetic basis of the disease is a variant of plasma prealbumin (transthyretin), which has a serine-for-isoleucine subst...

  19. Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition

    OpenAIRE

    Sandra Arvidsson; Björn Pilebro; Per Westermark; Per Lindqvist; Suhr, Ole B.

    2015-01-01

    PURPOSE: Transthyretin V30M (ATTR V30M) amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril ...

  20. Two Types of Fibrils in ATTR Amyloidosis : Implications for Clinical Phenotype and Treatment Outcome

    OpenAIRE

    Ihse, Elisabet

    2011-01-01

    Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation ...

  1. Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

    OpenAIRE

    Westermark, Per; Gunilla T. Westermark; Suhr, Ole B.; Berg, Svante

    2014-01-01

    Background Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and tra...

  2. Genistein, a natural product from soy, is a potent inhibitor of transthyretin amyloidosis

    OpenAIRE

    Green, Nora S.; Foss, Ted R; Kelly, Jeffery W.

    2005-01-01

    The misfolding of transthyretin (TTR), including rate-limiting tetramer dissociation and partial monomer denaturation, is sufficient for TTR misassembly into amyloid and other abnormal quaternary structures associated with three amyloid diseases: senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Small molecules can bind to one or both of the unoccupied TTR thyroid hormone-binding sites, stabilizing the native tetramer more than the dissociative...

  3. Impact of regional left ventricular function on outcome for patients with AL amyloidosis.

    Directory of Open Access Journals (Sweden)

    Dan Liu

    Full Text Available OBJECTIVES: The aim of this study was to explore the left ventricular (LV deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL amyloidosis and LV hypertrophy. BACKGROUND: Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome. METHODS: LV longitudinal, circumferential and radial peak systolic strains (Ssys were assessed by speckle tracking imaging (STI in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA and in 30 normal controls. Patients were divided into compensated (n = 18 and decompensated (n = 26 group based on clinical assessment and followed-up for a median period of 345 days. RESULTS: Ejection fraction (EF was preserved while longitudinal Ssys (LSsys was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001. LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal, only basal (mild, basal and mid (intermediate and all segments of the septum (severe. This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%. Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival. CONCLUSIONS: Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV

  4. Bilateral optic neuropathy and intraretinal deposits after pars plana vitrectomy in amyloidosis

    Directory of Open Access Journals (Sweden)

    Rossetti Alberto

    2015-01-01

    Full Text Available Pathological examination of material from a nonextensive pars plana vitrectomy (PPV in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis.

  5. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis

    Institute of Scientific and Technical Information of China (English)

    Takehiro Kato; Atsumasa Komori; Sung-Kwan Bae; Kiyoshi Migita; Masahiro Ito; Yasuhide Motoyoshi; Seigo Abiru; Hiromi Ishibashi

    2012-01-01

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-yearold Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4+ plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4+ plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  6. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis.

    Science.gov (United States)

    Kato, Takehiro; Komori, Atsumasa; Bae, Sung-Kwan; Migita, Kiyoshi; Ito, Masahiro; Motoyoshi, Yasuhide; Abiru, Seigo; Ishibashi, Hiromi

    2012-01-14

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4(+) plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4(+) plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  7. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    Science.gov (United States)

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. PMID:27540285

  8. Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I.

    Science.gov (United States)

    Persey, M R; Booth, D R; Booth, S E; van Zyl-Smit, R; Adams, B K; Fattaar, A B; Tennent, G A; Hawkins, P N; Pepys, M B

    1998-02-01

    We report a family with autosomal-dominant hereditary systemic amyloidosis in three generations, presenting with renal involvement. Two members of the current generation received renal transplants for end-stage renal failure 16 and 18 years ago, and remain very well clinically despite massive visceral amyloidosis. Two other members of this generation, aged 32 and 47 years, have massive systemic amyloid but no clinical disability. Individuals known to be affected in previous generations died of renal failure in early adult life. Amyloid deposits in the proband, one of the transplanted individuals, were composed of apolipoprotein A-I (apoA-I), and among living family members there was complete concordance between amyloidosis and the presence of a novel 9 base pair in-frame deletion mutation in exon 4 of the apoA-I gene, causing a loss of residues Glu70Phe71Trp72. This predicts the acquisition of a single extra positive charge by mature apoA-I, and this variant was detected in the plasma of all carriers. All the previously reported amyloidogenic variants of apoA-I also carry an extra positive charge, indicating that this electrostatic change is likely to be relevant to the amyloidogenicity of apoA-I. PMID:9461086

  9. Amiloidosis secundaria en la enfermedad inflamatoria intestinal Secondary amyloidosis in Chrohn's disease

    Directory of Open Access Journals (Sweden)

    S. Seijo Ríos

    2008-12-01

    Full Text Available La amiloidosis es una entidad clínica que se produce a consecuencia del depósito a nivel extracelular de un material proteico amorfo, causando una desorganización de la arquitectura normal de múltiples órganos y tejidos y, por tanto, una alteración funcional de los mismos. La amiloidosis secundaria es una complicación infrecuente pero muy grave que aparece en el contexto de neoplasias, enfermedades infecciosas e inflamatorias de curso crónico, como es el caso de la enfermedad inflamatoria intestinal, principalmente enfermedad de Crohn, ensombreciendo el pronóstico de estos pacientes. A continuación presentamos dos casos clínicos correspondientes a dos pacientes con enfermedad de Crohn que desarrollaron amiloidosis secundaria.Amyloidosis is a clinical entity that results from the deposition of an extracellular protein material that causes disruption in the normal architecture of multiple organs and tissues, and impairs their function. Secondary amyloidosis is a rare but serious complication that may worsen the prognosis of patients with cancer, infection or chronic inflammatory disease, including inflammatory bowel disease, particularly Crohn's disease. We report two cases of Crohn's disease associated with secondary amyloidosis.

  10. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy.

    Science.gov (United States)

    Carr, A S; Pelayo-Negro, A L; Jaunmuktane, Z; Scalco, R S; Hutt, D; Evans, M R B; Heally, E; Brandner, S; Holton, J; Blake, J; Whelan, C J; Wechalekar, A D; Gillmore, J D; Hawkins, P N; Reilly, M M

    2015-06-01

    Hereditary transthyretin amyloidosis (ATTR) is a genetically and clinically heterogeneous disease manifesting with predominant peripheral and autonomic neuropathy; cardiomyopathy, or both. ATTR V122I is the most common variant associated with non-neuropathic familial amyloid cardiomyopathy. We present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment. PMID:25819286

  11. Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kenneth S. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI (United States); Holsbeeck, Marnix T. van [Wayne State School of Medicine, Department of Radiology, Henry Ford Hospital, Detroit, MI (United States); Abbud, Alexander [Wayne State School of Medicine, Department of Pathology, Henry Ford Hospital, Detroit, MI (United States)

    2010-01-15

    Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054-2058 and 2176-2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis - over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61-64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed. (orig.)

  12. Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2005-01-01

    Full Text Available We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3, which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.

  13. A rare case of reversible acquired AA-type renal amyloidosis in a chronic filariasis patient receiving antifilarial therapy.

    Science.gov (United States)

    Nayak, Hemanta Kumar; Daga, Mradul Kumar; Garg, Sandeep kumar; Sinha, Nitin kumar; Kumar, Rakshit; Mohanty, Pankaj Kumar; Pandey, Binay Kumar

    2011-08-01

    Lymphatic filariasis is a major health problem in India with a large number of patients tending to be asymptomatic. In the Southeast and South Asian regions, Wuchereria bancrofti is the most prevalent parasite, causing filariasis in 99.4% of cases. While kidney involvement is a rare event in chronic filariasis, this case is unique because AA-type renal amyloidosis occurs in chronic W. bancrofti infection. We present here a unique case of lymphatic filariasis. The patient, a 25-year-old male who was previously diagnosed with right lower limb filarial lymphedema and had undergone lymphovenous anastomosis, was admitted for evaluation of persistent nephrotic-range proteinuria. Autoimmune markers in the form of anti-nuclear antibodies, anti-double-stranded DNA and anti-neutrophil cytoplasmic antibody were negative; C3 was normal. Urine analysis revealed inactive sediment with moderate proteinuria. Both serum and urine electrophoresis were negative for paraproteins and bone marrow aspirate and biopsy were normal. Evidence of active filarial infection was established on the basis of microfilariae in the peripheral smear and a positive W. bancrofti antigen test. Kidney biopsy revealed renal amyloidosis when stained with Congo red and anti-AA immunostain. The patient's proteinuria improved on conservative management with angiotensin-converting enzyme inhibitors and a course of antifilarial drugs. His proteinuria returned to amyloidosis. Repeat demonstration of filarial antigen and microfilariae in the peripheral smear were negative on multiple occasions during the follow-up period. Although various chronic infections can lead to secondary renal amyloidosis, this is the first case reported in world literature where secondary amyloidosis developed as a complication of chronic filarial infection due to W. bancrofti. This is probably also the first case reported in world literature where renal amyloidosis has an etiological association with W. bancrofti infection and where

  14. Amyloid Deposits in the Bone Marrow of Patients with AL Amyloidosis Do Not Impact Stem Cell Mobilization or Engraftment

    OpenAIRE

    Cowan, Andrew J.; Seldin, David C.; Skinner, Martha; Quillen, Karen; Doros, Gheorghe; Tan, Josenia; O'Hara, Carl; Finn, Kathleen T.; Sanchorawala, Vaishali

    2012-01-01

    Amyloid deposits are often found in the bone marrow in patients with AL amyloidosis; we sought to determine whether this affects stem cell collection or engraftment following high dose melphalan and autologous stem cell transplantation (HDM/SCT). Data on 361 patients with AL amyloidosis who had Congo red staining of the pre-treatment bone marrow biopsy and underwent HDM/SCT from July 1994 to December 2011 were reviewed. Data were analyzed for stem cell yield, number of days of stem cell colle...

  15. Bronchial mucoepidermoid tumour in a child presenting with organomegaly due to secondary amyloidosis: case report and review of the literature

    International Nuclear Information System (INIS)

    Childhood bronchial mucoepidermoid tumours (BMET) are rare. A 12-year-old boy with hepatosplenomegaly underwent liver biopsy which diagnosed amyloidosis. Chest radiograph and CT, performed for recurrent respiratory symptoms, identified a left lower lobe tumour, which was subsequently excised. Histology showed a BMET. A literature review reveals 51 reported cases of BMET in children. Common presenting symptoms include fever, cough and recurrent pneumonia. Diagnosis is often delayed and patients with recurrent respiratory symptoms should undergo CT or bronchoscopy. The association between amyloidosis and BMET in this case is unique and has not been previously described, but may be coincidental. (orig.)

  16. Long-Term Results of Conformal Radiotherapy for Progressive Airway Amyloidosis

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy of conformal external beam radiotherapy (RT) for local control of progressive airway amyloidosis. Methods and Materials: We conducted a retrospective review of patients with biopsy-proven progressive airway amyloidosis treated with conformal RT between 2000 and 2006 at Boston Medical Center. The patients were evaluated for performance status and pulmonary function, with computed tomography and endoscopy after RT compared with the pretreatment studies. Local control was defined as the lack of progression of airway wall thickening on computed tomography imaging and stable endobronchial deposits by endoscopy. Results: A total of 10 symptomatic airway amyloidosis patients (3 laryngeal and 7 tracheobronchial) received RT to a median total dose of 20 Gy in 10 fractions within 2 weeks. At a median follow-up of 6.7 years (range, 1.5–10.3), 8 of the 10 patients had local control. The remaining 2 patients underwent repeat RT 6 and 8.4 months after initial RT, 1 for persistent bronchial obstruction and 1 for progression of subglottic amyloid disease with subsequent disease control. The Eastern Cooperative Oncology Group performance status improved at a median of 18 months after RT compared with the baseline values, from a median score of 2 to a median of 1 (p = .035). Airflow (forced expiratory volume in 1 second) measurements increased compared with the baseline values at each follow-up evaluation, reaching a 10.7% increase (p = .087) at the last testing (median duration, 64.8 months). Acute toxicity was limited to Grade 1-2 esophagitis, occurring in 40% of patients. No late toxicity was observed. Conclusions: RT prevented progressive amyloid deposition in 8 of 10 patients, resulting in a marginally increased forced expiratory volume in 1 second, and improved functional capacity, without late morbidity.

  17. Long-Term Results of Conformal Radiotherapy for Progressive Airway Amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Truong, Minh Tam, E-mail: mitruong@bu.edu [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Grillone, Gregory A. [Department of Otolaryngology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Bohrs, Harry K.; Lee, Richard [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Sakai, Osamu [Department of Radiology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Berk, John L. [Department of Medicine, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States)

    2012-06-01

    Purpose: To evaluate the efficacy of conformal external beam radiotherapy (RT) for local control of progressive airway amyloidosis. Methods and Materials: We conducted a retrospective review of patients with biopsy-proven progressive airway amyloidosis treated with conformal RT between 2000 and 2006 at Boston Medical Center. The patients were evaluated for performance status and pulmonary function, with computed tomography and endoscopy after RT compared with the pretreatment studies. Local control was defined as the lack of progression of airway wall thickening on computed tomography imaging and stable endobronchial deposits by endoscopy. Results: A total of 10 symptomatic airway amyloidosis patients (3 laryngeal and 7 tracheobronchial) received RT to a median total dose of 20 Gy in 10 fractions within 2 weeks. At a median follow-up of 6.7 years (range, 1.5-10.3), 8 of the 10 patients had local control. The remaining 2 patients underwent repeat RT 6 and 8.4 months after initial RT, 1 for persistent bronchial obstruction and 1 for progression of subglottic amyloid disease with subsequent disease control. The Eastern Cooperative Oncology Group performance status improved at a median of 18 months after RT compared with the baseline values, from a median score of 2 to a median of 1 (p = .035). Airflow (forced expiratory volume in 1 second) measurements increased compared with the baseline values at each follow-up evaluation, reaching a 10.7% increase (p = .087) at the last testing (median duration, 64.8 months). Acute toxicity was limited to Grade 1-2 esophagitis, occurring in 40% of patients. No late toxicity was observed. Conclusions: RT prevented progressive amyloid deposition in 8 of 10 patients, resulting in a marginally increased forced expiratory volume in 1 second, and improved functional capacity, without late morbidity.

  18. Association of Cerebral Amyloidosis, Blood Pressure, and Neuronal Injury with Late-Life Onset Depression

    Science.gov (United States)

    Byun, Min Soo; Choe, Young Min; Sohn, Bo Kyung; Yi, Dahyun; Han, Ji Young; Park, Jinsick; Choi, Hyo Jung; Baek, Hyewon; Lee, Jun Ho; Kim, Hyun Jung; Kim, Yu Kyeong; Yoon, Eun Jin; Sohn, Chul-Ho; Woo, Jong Inn; Lee, Dong Young

    2016-01-01

    Previous literature suggests that Alzheimer's disease (AD) process may contribute to late-life onset depression (LLOD). Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD) after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC). Comorbid mild cognitive impairment (MCI) was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLODMCI) showed increased cerebral 11C-Pittsburg compound B (PiB) retention and plasma beta-amyloid 1–40 and 1–42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI). LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP) than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM) density, cerebral amyloidosis, and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes—SBP elevation, in particular—are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals. PMID:27790137

  19. [Notalgia paresthetica, "posterior pigmented pruritic patch" and macular amyloidosis. Three stages of a disease].

    Science.gov (United States)

    Cerroni, L; Kopera, D; Soyer, H P; Kerl, H

    1993-12-01

    We report on nine cases of notalgia paresthetica, a cutaneous condition that has rarely been described in the dermatological literature and is characterized by localized pruritus, burning and hyperesthesia and/or paresthesia on the back. Histological and immunohistochemical studies have not clarified the pathogenesis of this disease. Several factors might be involved in various cases, including increased cutaneous innervation and neuropathy. The so-called posterior pigmented pruritic patch and macular amyloidosis may be considered as progressive evolutional stages of notalgia paresthetica. PMID:8113041

  20. A cytotoxic amyloid oligomer self-triggered and NIR- enhanced amyloidosis therapeutic system

    Institute of Scientific and Technical Information of China (English)

    Can Xu[1,2; Peng Shi[1,2; Meng Li[1,2; Jinsong Ren[1; xiaogang Qu[1

    2015-01-01

    We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell membrane disruption in the pathogenesis of amyloidosis. A graphene-mesoporous silica hybrid (GMS)-supported lipid bilayer (GMS-Lip) system was used as a drug carrier, Drugs were well confined inside the nanocarrier until encountering amyloid oligomers, which could pierce the lipid bilayer coat and cause drug release. To ensure release efficiency, use of a near-infrared (NIR) laser was also introduced to facilitate drug release, taking advantage of the photothermal effect of GMS and thermal sensitivity of lipid bilayers. To facilitate tracking, fluorescent dyes were co-loaded with drugs within GMS-Lip and the NIR laser was used once the oligomer-triggered release had been signaled. Because of the spatially and temporally controllable property of light, the NIR-assisted release could be easily and selectively activated locally by tracking the fluorescence signal. Our design is based on arnyloidosis pathogenesis, the cytotoxic amyloid oligomer self-triggered release via cell membrane disruption, for the controlled release of drug molecules. The results may shed light on the development of pathogenesis- inspired drug delivery systems,

  1. Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid P component in systemic amyloidosis

    International Nuclear Information System (INIS)

    Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid. Iodine-123 has ideal physical characteristics for scintigraphy but is expensive and not widely available. Here we report serial imaging and turnover studies in which we labelled SAP with iodine-131, a cheap alternative isotope which would be expected to yield poorer images but permit more prolonged turnover measurements. Imaging and plasma clearance and whole body retention (WBR) of tracer were studied for up to 7 days in ten patients with proven systemic AL amyloidosis and two patients in whom the diagnosis was suspected, after i.v. administration of about 37 MBq of 131I-SAP. Normal blood pool images were obtained in the latter two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h was 65% of the injected dose (i.d.). Among the other ten patients, amyloid deposits were identified in the spleen in eight cases, liver in five and kidneys in four; other sites that gave positive results included bone, joints and soft tissues, and the myocardium in one case. Up to 95% of the tracer localised into amyloid within 6-h, and the values for WBR became progressively more discriminating during the study period, exceeding the normal reference value (131I-SAP produced diagnostic scans in every patient in this series and, coupled with the detailed turnover information, is adequate for monitoring disease progress. (orig.)

  2. Systemic amyloidosis involving the diaphragm and acute massive hydrothorax during peritoneal dialysis.

    Science.gov (United States)

    Gagnon, R F; Thirlweil, M; Arzoumanian, A; Mehio, A

    2002-06-01

    Hydrothorax secondary to trans-diaphragmatic fluid leakage through a peritoneo-pleural communication is an occasional, potentially serious complication of peritoneal dialysis. The etiology of this condition is not clear, being thought to be due either to congenital or acquired diaphragmatic fenestrations or acquired scarcity of muscle fibers in the tendinous part of the diaphragm which are compounded by increased intra-abdominal pressure during the dwell period of peritoneal dialysis. We report a 54-year-old woman who developed irreversible acute renal failure from adjuvant chemotherapy for ovarian cancer previously resected surgically. Three days after the onset of continuous ambulatory peritoneal dialysis, she developed acute respiratory distress associated with a massive right hydrothorax secondary to a peritoneo-pleural communication demonstrated by scintigraphy. At autopsy 2 weeks later, systemic amyloidosis was surprisingly found and histologic examination of the right hemidiaphragm showed the presence of amyloid, among sparse muscle fibers. This is the first case report of a distinct pathological process, i.e. amyloidosis, involving the diaphragm associated with a peritoneo-pleural communication causing massive hydrothorax at the onset of peritoneal dialysis. PMID:12078953

  3. Nonfluent/Agrammatic PPA with In-Vivo Cortical Amyloidosis and Pick’s Disease Pathology

    Directory of Open Access Journals (Sweden)

    Francesca Caso

    2013-01-01

    Full Text Available The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA. She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom, post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer’s disease (AD (CERAD frequent/Braak Stage V was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.

  4. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

    Directory of Open Access Journals (Sweden)

    Lia Millucci

    2014-01-01

    Full Text Available Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.

  5. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis.

    Science.gov (United States)

    Coelho, Teresa; Merlini, Giampaolo; Bulawa, Christine E; Fleming, James A; Judge, Daniel P; Kelly, Jeffery W; Maurer, Mathew S; Planté-Bordeneuve, Violaine; Labaudinière, Richard; Mundayat, Rajiv; Riley, Steve; Lombardo, Ilise; Huertas, Pedro

    2016-06-01

    Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis. PMID:26894299

  6. Low serum levels of prohepcidin, but not hepcidin-25, are related to anemia in familial amyloidosis TTR V30M.

    NARCIS (Netherlands)

    Beirao, I.; Almeida, S.; Swinkels, D.W.; Costa, P.M.; Moreira, L.; Fonseca, I.; Freitas, C.; Cabrita, A.; Porto, G.

    2008-01-01

    Familial amyloidosis TTR V30M (FAP-I) usually presents as a sensorimotor and autonomic neuropathy. Anemia was first described in this disease more than 20 years ago and classified as an anemia of chronic disease. However, so far no studies have addressed the role of inflammatory proteins in this dis

  7. Imaging findings and literature review of {sup 18}F-FDG PET/CT in primary systemic AL amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Hee; Lee, Ga Yeon; Kim, Seok Jin; Kim, Ki Hyun; Jeon, Eun Seok; Lee, Kyung Han; Kim, Byung Tae; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-09-15

    Although several case reports and case series have described {sup 18}F-FDG PET/CT in amyloidosis, the value of {sup 18}F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of {sup 18}F-FDG PET/CT in patients with primary systemic AL amyloidosis. Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment {sup 18}F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on {sup 18}F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis. F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUV{sub max} = 7.0 ± 3.2, range 2.1–14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal {sup 18}F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). {sup 18}F-FDG uptake was negative for pancreas and gastric lesions. Although {sup 18}F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of {sup 18}F-FDG PET/CT in amyloidosis will be warranted.

  8. Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value

    NARCIS (Netherlands)

    Jager, PL; Hazenberg, BPC; Franssen, EJF; Limburg, PC; van Rijswijk, MH; Piers, DA

    1998-01-01

    In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP) h

  9. Transplante cardíaco em amiloidose primária Heart transplantation in primary amyloidosis

    Directory of Open Access Journals (Sweden)

    José Francisco Baumgratz

    2009-09-01

    Full Text Available A amiloidose cardíaca é doença altamente limitante da sobrevida, por morte súbita na maioria dos pacientes. Pela agressão contra outros órgãos, particularmente rins e sistema nervoso central, o transplante cardíaco tem sido opção questionável, face à escassez de órgãos. O objetivo é relatar a evolução, com sobrevivência de 7 anos, da paciente após transplante cardíaco por amiloidose, em boas condições. Um ano após o transplante cardíaco, houve indicação de transplante renal, também pela agressão da doença. Esta paciente contrasta com outros três pacientes de nosso serviço que foram a óbito, ainda na fase de avaliação. Apesar de sua natureza multisistêmica, a amiloidose cardíaca pode, em pacientes selecionados, justificar o transplante cardíaco, pela gravidade do seu potencial evolutivo após o início dos sintomasCardiac amyloidosis is a disease with a gloom life expectance after the beginning of the symptomatic phase, usually with sudden death as the final event. The aggression to other organs, although, can make heart transplantation a disputable form of treatment taking into consideration the shortage of donor organs. The aim is to report the evolution with a survival of seven years after heart transplantation and in very fair condition of a patient with amyloidosis. One year after the heart transplantation, there was indication of renal transplantation also from the aggression from the disease. This patient compares' favorable with three other patients also from our service, who died early after de diagnosis. Even considering the multi systemic nature of amyloidosis, we can accept that in peculiar patients justified the heart transplantation, taking in the consideration the very bad prognosis of the disease

  10. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience

    Science.gov (United States)

    Grogan, Martha; Gertz, Morie; McCurdy, Arleigh; Roeker, Lindsey; Kyle, Robert; Kushwaha, Sudhir; Daly, Richard; Dearani, Joseph; Rodeheffer, Richard; Frantz, Robert; Lacy, Martha; Hayman, Suzanne; McGregor, Christopher; Edwards, Brooks; Dispenzieri, Angela

    2016-01-01

    AIM: To determine the outcome of orthotopic heart transplantation (OHT) in immunoglobulin light chain (AL) amyloidosis. METHODS: The medical records of patients with AL who underwent orthotopic heart transplantation at the Mayo Clinic in Rochester Minnesota from 1992 to 2011 were reviewed. Patients met at least one of the following at: New York Heart Association class IV heart failure, ventricular thickness > 15 mm, ejection fraction < 40%. Selection guidelines for heart transplant included age < 60 years, absence of multiple myeloma and significant extra-cardiac organ involvement. Baseline characteristics including age, gender, organ involvement, and New York Heart Association functional class were recorded. Laboratory data, waiting time until heart transplant, and type of treatment of the underlying plasma cell disorder were recorded. Survival from the time of OHT was calculated using Kaplan-Meier survival curves. Survival of patients undergoing OHT for AL was compared to that of non-amyloid patients undergoing OHT during the same time period. RESULTS: Twenty-three patients (median age 53 years) with AL received OHT. There were no deaths in the immediate perioperative period. Twenty patients have died post OHT. For the entire cohort, the median overall survival was 3.5 years (95%CI: 1.2, 8.2 years). The 1-year survival post OHT was 77%, the 2-year survival 65%, and the 5-year survival 43%. The 5-year survival for non-amyloid patients undergoing OHT during the same era was 85%. Progressive amyloidosis contributed to death in twelve patients. Of those without evidence of progressive amyloidosis, the cause of death included complications of autologous hematopoietic stem cell transplantation for 3 patients, post-transplant lymphoproliferative disorder for 2 patients; and for the remaining one death was related to each of the following causes: acute rejection; cardiac vasculopathy; metastatic melanoma; myelodysplastic syndrome; and unknown. Eight patients had

  11. Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques.

    Science.gov (United States)

    Aljaroudi, Wael A; Desai, Milind Y; Tang, W H Wilson; Phelan, Dermot; Cerqueira, Manuel D; Jaber, Wael A

    2014-04-01

    Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook. PMID:24347127

  12. Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.

    Science.gov (United States)

    Saegusa, S; Shimizu, F; Nagase, M; Kasegawa, A

    1979-08-01

    We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed. PMID:157110

  13. The role of 3D and speckle tracking echocardiography in cardiac amyloidosis: a case report.

    Science.gov (United States)

    Nucci, E M; Lisi, M; Cameli, M; Baldi, L; Puccetti, L; Mondillo, S; Favilli, R; Lunghetti, S

    2014-01-01

    Cardiac amyloidosis (CA) is a disorder characterized by amyloid fibrils deposition in cardiac interstitium; it results in a restrictive cardiomyopathy with heart failure (HF) and conduction abnormalities. The "gold standard" for diagnosis of CA is myocardial biopsy but possible sampling errors and procedural risks, limit it's use. Magnetic resonance (RMN) offers more information than traditional echocardiography and allows diagnosis of CA but often it's impossible to perform. We report the case of a man with HF and symptomatic bradyarrhythmia that required an urgent pacemaker implant. Echocardiography was strongly suggestive of CA but wasn't impossible to perform an RMN to confirm this hypothesis because the patient was implanted with a definitive pacemaker. So was performed a Speckle Tracking Echocardiography (STE) and a 3D echocardiography: STE allows to differentiate CA from others hypertrophic cardiomyopathy by longitudinal strain value RMN cannot be performed.

  14. [Amyloidosis in turkeys (Meleagris gallopavo f. domestica)--a case report].

    Science.gov (United States)

    Breuer, Wolfram; Moser, Hubert; De Souza-Pilz, Magdalena; Lüschow, Dörte; Hafner-Marx, Angela; Deischl, Karin; Hafez, Hafez Mohamed

    2014-01-01

    High prevalence of leg disorders in fattening meat turkey farm was observed. Four birds as well as tracheal and joint swabs were submitted to the Bavarian Health and Food Safety Authority in Oberschleissheim and to the Institute of Poultry Diseases, Faculty of Veterinary Medicine, Free University of Berlin. At the post-mortem, all birds showed an inflammation of the hock joints (intertarsal joint). The histopatholical investigations revealed a chronic inflammation of the joint and amyloid deposits in the joints in two cases as well as in different tissues (liver, spleen and kidneys) in another two cases. Using polymerase chain reaction, Ornithobacterium rhinotracheale-DNA could be detected in the examined tracheal and joint swabs. On the other hand, Mycoplasma gallisepticum- and Mycoplasma synoviae-DNA could not be detected. A causal correlation between the detected infectious agent and amyloidosis in relation to the leg disorders were discussed.

  15. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Merz, G S; Schwenk, V;

    1999-01-01

    of an amyloidogenic mutation on the intracellular processing of its protein product. The protein, a mutant of the cysteine protease inhibitor cystatin C, is the amyloid precursor protein in Hereditary Cerebral Hemorrhage with Amyloidosis--Icelandic type (HCHWA-I). The amyloid fibers are composed of mutant cystatin C...... (L68Q) that lacks the first 10 amino acids. We have previously shown that processing of wild-type cystatin C entails formation of a transient intracellular dimer that dissociates prior to secretion, such that extracellular cystatin C is monomeric. We report here that the cystatin C mutation engenders...... several alterations in its intracellular trafficking. It forms a stable intracellular dimer that is partially retained in the endoplasmic reticulum and degraded. The bulk of mutant cystatin C that is secreted does not dissociate and is secreted as an inactive dimer. Thus, formation of the stable mutant...

  16. Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition.

    Directory of Open Access Journals (Sweden)

    Sandra Arvidsson

    Full Text Available Transthyretin V30M (ATTR V30M amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007 and posterior wall thicknesses (p = 0.010, lower median LV mass indexed to height (p = 0.008, and higher septal strain (p = 0.037, as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.

  17. Genetic variation of the transthyretin gene in wild-type transthyretin amyloidosis (ATTRwt).

    Science.gov (United States)

    Sikora, Jacquelyn L; Logue, Mark W; Chan, Gloria G; Spencer, Brian H; Prokaeva, Tatiana B; Baldwin, Clinton T; Seldin, David C; Connors, Lawreen H

    2015-01-01

    Wild-type transthyretin amyloidosis (ATTRwt), typically diagnosed as congestive heart failure in elderly Caucasian men, features myocardial amyloid deposits of wild-type plasma protein transthyretin (TTR). ATTRwt is sporadic, its pathogenesis is poorly understood, and currently there are no biomarkers for diagnosis or prognosis. Genetic studies of variant-associated transthyretin amyloidosis have suggested that non-coding TTR gene variants modulate disease. We hypothesized that cis-acting regulatory elements in the TTR gene non-coding regions may modify expression, affecting ATTRwt onset and progression. We studied an ATTRwt cohort consisting of 108 Caucasian males ranging in age from 59 to 87 years with cardiomyopathy due to wild-type TTR deposition; results were compared to 118 anonymous controls matched by age, sex, and race. Four predicted non-coding regulatory regions and all exons in the TTR gene were sequenced using the Sanger method. Eleven common variants were identified; three variants were significantly associated with ATTRwt (p < 0.05), though only one, rs72922940, remained near significance (p corrected = 0.083) after multiple testing correction. Exon analyses demonstrated the occurrence of the p.G26S (G6S) polymorphism in 7 % of ATTRwt subjects and 12 % of controls; this variant was predicted to be a protective factor (p = 0.051). Four variants were significantly associated with age at onset and survival. In this first genetic study of a large, well-characterized cohort of ATTRwt, non-coding and coding variants associated with disease, age at onset, and survival were identified. Further investigation is warranted to determine the prevalence of these variants in ATTRwt, their regulatory function, and potential role in assessing disease risk. PMID:25367359

  18. Cardiac Amyloidosis

    Science.gov (United States)

    ... LIBRARY Hello, Guest! My alerts Sign In Join Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Cover Doodle → Blip the Doodle Go Red For Women's Issue Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  19. Avian amyloidosis

    NARCIS (Netherlands)

    Landman, W.J.M.; Gruys, E.; Gielkens, A.L.J.

    1998-01-01

    Although amyloid deposits have been described for more than a century and a half, its proteinaceous and fibrillar nature was not revealed until after 1950. Biochemical characterization of amyloids has brought to light that several non-related proteins can re-organize into amyloid fibrils. In some do

  20. Depletion of Spleen Macrophages Delays AA Amyloid Development: A Study Performed in the Rapid Mouse Model of AA Amyloidosis

    OpenAIRE

    Katarzyna Lundmark; Aida Vahdat Shariatpanahi; Westermark, Gunilla T.

    2013-01-01

    AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM), marginal zone macrophages (MZM), metallophilic marginal zone macrophages (MMZM). MMZM and MZM are located in the marginal zone and express a unique collection of scavenger r...

  1. Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis

    OpenAIRE

    Ihse, Elisabet; Suhr, Ole B.; Hellman, Ulf; Westermark, Per

    2010-01-01

    Familial transthyretin (TTR) amyloidosis is caused by a mutation in the TTR gene, although wild-type (wt) TTR is also incorporated into the amyloid fibrils. Liver transplantation (LT) is the prevailing treatment of the disease and is performed in order to eliminate the mutant TTR from plasma. The outcome of the procedure is varied; especially problematic is a progressive cardiomyopathy seen in some patients, presumably caused by continued incorporation of wtTTR. What determines the discrepanc...

  2. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

    Directory of Open Access Journals (Sweden)

    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  3. Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis

    Directory of Open Access Journals (Sweden)

    Hund E

    2012-06-01

    removing the main source of mutant TTR. Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.Keywords: FAP, transthyretin, amyloidosis, treatment, therapy

  4. New insights into the clinical evaluation of hereditary transthyretin amyloidosis patients: a single center's experience

    Directory of Open Access Journals (Sweden)

    Suhr OB

    2012-08-01

    Full Text Available Ole B Suhr,1 Sandra Gustavsson,1 Victoria Heldestad,2 Rolf Hörnsten,3 Per Lindqvist,1 Erik Nordh,2 Urban Wiklund41Department of Public Health and Clinical Medicine, 2Department of Pharmacology and Clinical Neuroscience, 3Department of Surgical and Perioperative Sciences, Clinical Physiology, Heart Centre, 4Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, SwedenAbstract: Over the last decade, new medical treatment modalities have emerged based on increased insights into amyloid formation. With the increased possibilities for treatment of amyloidosis caused by transthyretin (TTR amyloid deposits comes the need for diagnostic procedures for early diagnosis and better tools to follow disease progression. This is of particular importance in clinical trials evaluating the efficacy of new treatments. Until recently, the treatment of TTR amyloidosis (ATTR was based solely on liver transplantation, a procedure that has halted disease progression in many patients. Liver transplantation has been especially effective in patients under the age of 50 years carrying the TTR V30M mutation, whereas the outcome of the procedure has been variable for others, particularly elderly male patients and those carrying a non-V30M mutation. This review concentrates on new insights derived from our center's experience with liver transplantation, how to implement this experience in evaluation of new treatment modalities for ATTR, and how to facilitate early diagnosis of neuropathy with easily available diagnostic tools. Attention has focused on manifestations of the disease that involve the heart and the peripheral nervous system; change in peripheral nerve function has been the primary endpoint in two controlled clinical trials, one finished and one ongoing. New insights into the amyloid formation process and the lessons learned from liver transplantation give the opportunity to design potentially effective treatment modalities for ATTR

  5. A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.

    Science.gov (United States)

    Saeedi, Marjan; Ebrahim-Habibi, Azadeh; Haghighi, Alireza; Zarrabi, Fariba; Amoli, Mahsa M; Robati, Reza M

    2014-01-01

    Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus. PMID:25054142

  6. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

    Science.gov (United States)

    Ferreira, Nelson; Gonçalves, Nádia P; Saraiva, Maria J; Almeida, Maria R

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

  7. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Teng Wei-Ping

    2010-11-01

    Full Text Available Abstract Background Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD, the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Results Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Conclusions Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

  8. Cutaneous lesion associated with multiple endocrine neoplasia type 2A: lichen amyloidosis or notalgia paresthetica?

    Science.gov (United States)

    Chabre, O; Labat, F; Pinel, N; Berthod, F; Tarel, V; Bachelot, I

    1992-01-01

    Three patients of a French family demonstrated an association of multiple endocrine neoplasia type 2A (MEN 2A) with a pruritic scapular skin lesion. The lesions are similar to those described as familial cutaneous lichen amyloidosis in unrelated MEN 2A and medullary thyroid carcinoma families, but histological, immunohistochemical, and ultrastructural analysis of skin biopsies from each patient in the French family did not show amyloid deposition. The topography of the lesion follows dermatomes C8-D3. The patients report not only pruritus but also paresthesia and hyperalgesia, and one showed touch hypoesthesia and pain hyperesthesia in the area of the lesion. Such an association of cutaneous and neurological features suggests notalgia paresthetica (NP), a neuropathy of the posterior dorsal rami nerves. We thus suggest that the cutaneous lesions associated with MEN 2A might be secondary to pathology in the neural crest-derived dorsal sensory nerves. The amyloid, when present, would be secondary to scratching. We propose that patients presenting with familial NP be suspect for MEN 2A. PMID:1362414

  9. A Novel Missense Mutation in Oncostatin M Receptor Beta Causing Primary Localized Cutaneous Amyloidosis

    Directory of Open Access Journals (Sweden)

    Marjan Saeedi

    2014-01-01

    Full Text Available Primary localized cutaneous amyloidosis (PLCA is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß. OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.

  10. Burden of cytogenetically abnormal plasma cells in light chain amyloidosis and their prognostic relevance.

    Science.gov (United States)

    Kim, Seon Young; Im, Kyongok; Park, Si Nae; Kim, Jung-Ah; Yoon, Sung-Soo; Lee, Dong Soon

    2016-05-01

    We performed cytoplasmic fluorescence in situ hybridization assays of light chain amyloidosis (AL). In total, 234 patients were enrolled: 28 patients with AL, 24 with monoclonal gammopathy of undetermined significance (MGUS), and 182 with multiple myeloma (MM). Chromosomal abnormalities were detected in 13 of 22 (59%) AL patients without MM. All 13 patients demonstrated IGH rearrangement, and t(11;14)/IGH-CCND1 was most frequent (32%). Chromosome gain was not observed in AL patients without MM. These findings were dissimilar to findings in MGUS patients, in whom trisomy 9 was the most frequent abnormality. Of 6 AL patients with MM, 5 (83%) patients had cytogenetic abnormalities: 1q gain (4/6, 67%), gains of chromosome 9 (3/6, 50%), IGH rearrangement and RB1 (13q) deletions (2/6 each, 33%). The percentage of clonal plasma cells among total plasma cells was variable (median, 75%; range, 16-100%) for AL patients without MM, which was lower than the results for MM patients (median 100%). The overall survival of AL patients without MM was not significantly different according to the presence of cytogenetic abnormalities (P=0.510). In summary, among Korean AL patients, IGH rearrangement was the most frequent cytogenetic abnormality and cytogenetic aberration patterns differ compared with MGUS and MM patients. PMID:27015231

  11. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

    Science.gov (United States)

    Minter, Myles R.; Zhang, Can; Leone, Vanessa; Ringus, Daina L.; Zhang, Xiaoqiong; Oyler-Castrillo, Paul; Musch, Mark W.; Liao, Fan; Ward, Joseph F.; Holtzman, David M.; Chang, Eugene B.; Tanzi, Rudolph E.; Sisodia, Sangram S.

    2016-01-01

    Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APPSWE/PS1ΔE9 mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis. PMID:27443609

  12. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer's disease.

    Science.gov (United States)

    Minter, Myles R; Zhang, Can; Leone, Vanessa; Ringus, Daina L; Zhang, Xiaoqiong; Oyler-Castrillo, Paul; Musch, Mark W; Liao, Fan; Ward, Joseph F; Holtzman, David M; Chang, Eugene B; Tanzi, Rudolph E; Sisodia, Sangram S

    2016-01-01

    Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer's disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APPSWE/PS1ΔE9 mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis. PMID:27443609

  13. Impact of incidental amyloidosis on the prognosis of patients with hypertrophic cardiomyopathy undergoing septal myectomy for left ventricular outflow tract obstruction.

    Science.gov (United States)

    Helder, Meghana R K; Schaff, Hartzell V; Nishimura, Rick A; Gersh, Bernard J; Dearani, Joseph A; Ommen, Steve R; Mereuta, Oana M; Theis, Jason D; Dogan, Ahmet; Edwards, William D

    2014-11-01

    To determine the impact of amyloid on the prognosis of patients with hypertrophic cardiomyopathy (HC), we reviewed outcomes of patients who underwent septal myectomy for HC from March 7, 1996, to October 9, 2012, with amyloid deposits identified in operative specimens. Amyloid subtypes were differentiated by mass spectrometry-based proteomics. The survival rate was compared with that of an age-matched population (2:1) without amyloid who underwent septal myectomy for HC. Sixteen patients (mean age ± SD 71 ± 8 years; 12 men) met study criteria. All 16 had intraventricular peak systolic gradients reduced intraoperatively from 105 ± 53 mm Hg to 3 ± 7 mm Hg (p Amyloid deposits in specimens ranged from minimal to mild. Nine patients had senile (transthyretin-type) amyloidosis, 4 had immunoglobulin-associated amyloidosis, 2 had apolipoprotein A4 amyloidosis type, and 1 had serum amyloid A type. There were no deaths before 30 days. Twelve patients had New York Heart Association class III or IV function preoperatively, and at last follow-up (median 3 years), class I or II. Only 1 patient received postoperative amyloidosis treatment. The postoperative survival rate at 2 and 4 years was 100% (n = 11 at risk) and 91% (n = 6 at risk), respectively, similar to that of the age-matched population with HC without amyloid who underwent myectomy (p = 0.13). Patients undergoing septal myectomy for HC who have histologic evidence of mild amyloidosis have early outcomes and midterm survival similar to those of patients with HC without amyloidosis who undergo myectomy. In conclusion, although longer follow-up is necessary, small amounts of amyloid, regardless of subtype, do not confer a poor prognosis on patients with HC who undergo septal myectomy. PMID:25217455

  14. Structural Changes in Synapses in the Hippocampus of a Transgenic Mouse Model of Alzheimer's Disease Aß amyloidosis

    DEFF Research Database (Denmark)

    Søderman, Andreas; Jensen, George Bach; West, Mark

     This project examines the extent to which synaptic morphology is altered by the gradual in vivo build up of beta amyloid (Aß) protein in a transgenic mouse model of Alzheimer's disease (AD) Aß amyloidosis. It constitutes a test of the amyloid cascade hypothesis for the development of Alzheimer's......'s Disease (AD), which, in its extended form, predicts that alterations in synapses during the early stages of the disease ultimately lead to the development of plaques, tangles and neuron death.              ...

  15. Noninvasive detection of cardiac amyloidosis using delayed enhanced MDCT: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Deux, Jean-Francois [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, CNRS EAC 4396, Centre de Recherches Chirurgicales, Henri Mondor Hospital, Creteil (France); Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Mihalache, Cristian-Ionut; Legou, Francois; Luciani, Alain; Kobeiter, Hicham; Rahmouni, Alain [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); Damy, Thibaud [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiology Department, Henri Mondor Hospital, Creteil (France); Mayer, Julie [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Rappeneau, Stephane [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Plante-Bordeneuve, Violaine [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Department of Neurophysiology of Neurology, Henri Mondor Hospital, Creteil (France)

    2015-08-15

    To evaluate myocardial enhancement of patients with cardiac amyloidosis (CA) using computed tomography (CT). Thirteen patients with CA and 11 control patients were examined with first-pass and delayed CT acquisition. A qualitative and quantitative analysis of images was performed. Myocardial attenuation, myocardial signal-to-noise ratio (SNR{sub myoc}), blood pool SNR (SNR{sub blood}), contrast-to-noise ratio between blood pool and myocardium (CNR{sub blood-myoc}) and relative attenuation index (RAI) defined as variation of myocardial attenuation between delayed and first-pass acquisitions were calculated. Two false negative cases (15 %) and three false positive cases (27 %) were detected on qualitative analysis. SNR{sub myoc} of patients with CA was significantly (p < 0.05) lower on first-pass (4.08 ± 1.9) and higher on delayed acquisition (7.10 ± 2.7) than control patients (6.1 ± 2.2 and 5.03 ± 1.8, respectively). Myocardial attenuation was higher in CA (121 ± 39 HU) than control patients (81 ± 17 HU) on delayed acquisition. CNR{sub blood-myoc} was significantly (p < 0.05) lower in CA (1.51 ± 0.7) than control patients (2.85 ± 1.2) on delayed acquisition. The RAI was significantly (p < 0.05) higher in CA (0.12 ± 0.25) than in control patients (-0.56 ± 0.21). Dual phase MDCT can detect abnormal myocardial enhancement in patients with CA. (orig.)

  16. The Value of Conventional Echocardiographic and Tissue Doppler Imaging in the Diagnosis of Cardiac Amyloidosis

    Institute of Scientific and Technical Information of China (English)

    Li ZHANG; Mingxing XIE; Xinfang WANG; Yali YANG; Junhong HUANG; Ming CHENG; Feixiang XIANG; Qing LU

    2008-01-01

    Transthoracic echocardiographic characteristics of 17 cases of cardiac amyloidosis (CA),a rare disease in China, were analyzed in order to improve the understanding of the disease. Seventeen cases of biopsy-proven CA, admitted to Wuhan Union Hospital from June 1994 to September 2008 were retrospectively reviewed. Twenty normal volunteers served as control group. Left atrial and ventricular functions and mitral inflow velocity were measured by two-dimensional, and Doppler echocardiography, and tissue Doppler imaging (TDI)-derived peak systolic wall motion velocities (Sv), peak early diastolic wall motion velocities (Ev), and peak late diastolic wall motion (Av) were measured at the septunm. Lateral, inferior and anterior comers of mitral annulus from the apical 4- and 2 chamber views. Compared with the control group, the interventricular septal thickness (IVSd), the left ventricular posterior wall (LVPWd), right ventricular transverse diameter (RVTDd) near the end of diastole and the interauricular septum thickness (IASs), left atrial anteroposterior diameter (LAADs), right atrial transverse diameter (RATDs) near the end of systole were increased significantly (all P<0.05) and left ventricular ejection fraction (LVEF) decreased (P<0.05) in the CA group.Compared with the control group, Sv, Ev at each wall and Av at almost all walls were significantly decreased in the CA group. In the CA group, Myocardial echoes of interventricular septum and free wall of left ventricle were enhanced evidently and distributed unevenly. The echoes presented as ground glass-like images, with some spotty hyper echoes. Both atria were enlarged, and LVEF decreased, with diastolic function impaired, and mild-moderate hydropericardium found in the CA group. It was concluded that echocardiography was a relatively sensitive and highly specific non-invasive method for the diagnosis of CA.

  17. In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study

    Science.gov (United States)

    Ami, Diletta; Lavatelli, Francesca; Rognoni, Paola; Palladini, Giovanni; Raimondi, Sara; Giorgetti, Sofia; Monti, Luca; Doglia, Silvia Maria; Natalello, Antonino; Merlini, Giampaolo

    2016-01-01

    Light chain (AL) amyloidosis, caused by deposition of amyloidogenic immunoglobulin light chains (LCs), is the most common systemic form in industrialized countries. Still open questions, and premises for developing targeted therapies, concern the mechanisms of amyloid formation in vivo and the bases of organ targeting and dysfunction. Investigating amyloid material in its natural environment is crucial to obtain new insights on the molecular features of fibrillar deposits at individual level. To this aim, we used Fourier transform infrared (FTIR) microspectroscopy for studying in situ unfixed tissues (heart and subcutaneous abdominal fat) from patients affected by AL amyloidosis. We compared the infrared response of affected tissues with that of ex vivo and in vitro fibrils obtained from the pathogenic LC derived from one patient, as well as with that of non amyloid-affected tissues. We demonstrated that the IR marker band of intermolecular β-sheets, typical of protein aggregates, can be detected in situ in LC amyloid-affected tissues, and that FTIR microspectroscopy allows exploring the inter- and intra-sample heterogeneity. We extended the infrared analysis to the characterization of other biomolecules embedded within the amyloid deposits, finding an IR pattern that discloses a possible role of lipids, collagen and glycosaminoglycans in amyloid deposition in vivo. PMID:27373200

  18. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  19. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile.

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A; Relini, Annalisa; Talmud, Philippa J; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D; Kalopissis, Athina D; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  20. Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis

    NARCIS (Netherlands)

    Glaudemans, Andor W. J. M.; van Rheenen, Ronald W. J.; van den Berg, Maarten P.; Noordzij, Walter; Koole, Michel; Blokzijl, Hans; Dierckx, Rudi A. J. O.; Slart, Riemer H. J. A.; Hazenberg, Bouke P. C.

    2014-01-01

    Objective: To assess the usefulness of bone scintigraphy with (99m)Technetium-hydroxymethylene diphosphonate (Tc-99m-HDP) for the detection of cardiac involvement in a group of patients with ATTR amyloidosis in different phases of disease, to relate the findings to echocardiography, ECG and cardiac

  1. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

    Directory of Open Access Journals (Sweden)

    Yijuan Sun

    2012-01-01

    Full Text Available AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

  2. CMR Imaging With Rapid Visual T1 Assessment Predicts Mortality in Patients Suspected of Cardiac Amyloidosis

    Science.gov (United States)

    White, James A.; Kim, Han W.; Shah, Dipan; Fine, Nowell; Kim, Ki-Young; Wendell, David C.; Al-Jaroudi, Wael; Parker, Michele; Patel, Manesh; Gwadry-Sridhar, Femida; Judd, Robert M.; Kim, Raymond J.

    2014-01-01

    OBJECTIVES This study tested the diagnostic and prognostic utility of a rapid, visual T1 assessment method for identification of cardiac amyloidosis (CA) in a “real-life” referral population undergoing cardiac magnetic resonance for suspected CA. BACKGROUND In patients with confirmed CA, delayed-enhancement cardiac magnetic resonance (DE-CMR) frequently shows a diffuse, global hyperenhancement (HE) pattern. However, imaging is often technically challenging, and the prognostic significance of diffuse HE is unclear. METHODS Ninety consecutive patients referred for suspected CA and 64 hypertensive patients with left ventricular hypertrophy (LVH) were prospectively enrolled and underwent a modified DE-CMR protocol. After gadolinium administration a method for rapid, visual T1 assessment was used to identify the presence of diffuse HE during the scan, allowing immediate optimization of settings for the conventional DE-CMR that followed. The primary endpoint was all-cause mortality. RESULTS Among patients with suspected CA, 66% (59 of 90) demonstrated HE, with 81% (48 of 59) of these meeting pre-specified visual T1 assessment criteria for diffuse HE. Among hypertensive LVH patients, 6% (4 of 64) had HE, with none having diffuse HE. During 29 months of follow-up (interquartile range: 12 to 44 months), there were 50 (56%) deaths in patients with suspected CA and 4 (6%) in patients with hypertensive LVH. Multivariable analysis demonstrated that the presence of diffuse HE was the most important predictor of death in the group with suspected CA (hazard ratio: 5.5, 95% confidence interval: 2.7 to 11.0; p < 0.0001) and in the population as a whole (hazard ratio: 6.0, 95% confidence interval 3.0 to 12.1; p < 0.0001). Among 25 patients with myocardial histology obtained during follow-up, the sensitivity, specificity, and accuracy of diffuse HE in the diagnosis of CA were 93%, 70%, and 84%, respectively. CONCLUSIONS Among patients suspected of CA, the presence of diffuse HE by

  3. Pulmonary hyalinizing granulomas in a patient with malignant lymphoma, with development nine years later of multiple myeloma and systemic amyloidosis.

    Science.gov (United States)

    Drasin, H; Blume, M R; Rosenbaum, E H; Klein, H Z

    1979-07-01

    In our patient, multiple bilateral nodular pulmonary densities appeared on a chest x-ray at the time of diagnosis of stage IV diffuse lymphocytic lymphoma. After localized radiation therapy, the patient received no further systemic therapy. The pulmonary nodules slowly became larger and more numerous. Nine years later the patient developed proven multiple myeloma. Pulmonary hyalinizing granulomas have not heretofore been associated with proven lymphoreticular neoplasia, although this has long been suspected. The occurrence of two B-cell tumors at different points in time associated with systemic amyloidosis is an extremely rare event. The authors discuss the possibility that these conditions represent an abnormality in a common cell of origin with differing expression over time. Coincidence, however, remains a likely explanation for the different immunopathies that occurred in our patient. PMID:582294

  4. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    OpenAIRE

    Orlando G. Povoas Barsottini; Adriano Arantes; Daniel Sigulem; José Mauro Kutner; Andreza Alice Feitosa Ribeiro; Luiz A. Moura; Nelson Hamerschlak

    2004-01-01

    Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis). We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL). She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of ne...

  5. Amiloidose manifestando-se com pseudo-hipertrofia muscular Amyloidosis presenting as muscle pseudohypertrophy

    Directory of Open Access Journals (Sweden)

    Rodrigo Bortoli

    2007-12-01

    Full Text Available Amiloidose tipo AL é uma doença rara causada pela deposição extracelular de fragmentos de cadeias leves monoclonais em órgãos e tecidos. Pode apresentar-se com uma ampla variedade de sinais e sintomas, e o acometimento cutâneo-muscular, simulando pseudo-hipertrofia muscular, é um achado muito raro. São descritos dois casos que apresentaram tal manifestação. CASO 1 - Mulher, 61 anos, há quatro meses com história de mialgia e aumento da massa muscular nas cinturas pélvica, escapular e região cervical. Não havia alterações significativas ao exame físico, exceto aparente hipertrofia muscular difusa e discreta macroglossia. CASO 2 - Homem, 51 anos, há dois anos com cansaço e espessamento cutâneo progressivo do dorso, pescoço e braços. Em outros serviços levantou suspeitas diagnósticas de esclerodermia ou de escleredema de Buschke; desde fevereiro de 2007 passou a ser acompanhado nesse serviço e referia, havia cerca de um ano, disfagia para sólidos, disartria e dificuldade para movimentar a língua. Chamava atenção em seu exame o porte físico atlético com musculatura torácica proeminente, porém referia não fazer exercícios físicos. Em ambos os casos, a biópsia cutânea foi realizada com identificação do depósito amilóide por meio da coloração de vermelho congo.AL amyloidosis is a rare disease secondary to extracellular deposition of light chains fragments in organs and tissues. It can cause a wide variety of signs and symptoms, being the muscular pseudohypertrophy form a very rare finding. CASE 1 - a 61-year-old female had a history of myalgia and increase of muscular mass on pelvic and scapular girdle and cervical region. Besides the generalized muscular hypertrophy and discrete macroglossia, the rest of physical examination was normal. CASE 2 - a 51-year-old male complained of tiredness and progressive cutaneous thickening on his thorax, neck and arms for the last two years. Initially, he was misdiagnosed

  6. Recent progress of research on therapeutics of amyloidosis%淀粉样变治疗学研究的最新进展

    Institute of Scientific and Technical Information of China (English)

    王学文

    2011-01-01

    During the past 10 to 15 years, there has been substantial progress in developing new treatments for the systemic amyloidosis.These advances have improved patiem outcomes but have also raised new questions with direct clinical implications.For example , development of leas intenaive treatments for AL amyloidosis has made less certain the role of autologous stem cell transplantation, and new quantitative assays should now allow determination of the importance of fully eliminating amyloidogenic light chain production in AL disease.Additionally, observations from a clinical tnal in AA amyloidosis have generated hypotheses about the relative contributions of amyloid precursors and mature fibrils to amyloidosis associated kidney disease.%既往10-15年中系统性淀粉样变新治疗的发展取得了实质性进展.这些进展改善了患者的转归,但亦带来新的临床问题.例如,由于淀粉样轻链( 或 )(AL)淀粉样变对自体造血干细胞移植的作用不太肯定,为此正在开发广泛途径的治疗研究和提供最佳支持治疗.现认为淀粉样前体和成熟原纤维促使淀粉样变相关的器官病变,显示完全清除AL淀粉样变患者促淀粉样(amyloidogenic)轻链生成的重要性,同时治疗前后需作淀粉样前体蛋白和器官病变标记的监测.

  7. Mieloma múltiple y arteritis de células gigantes sin amiloidosis Simultaneous multiple myeloma and giant cell arteritis without systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Bárbara C. Finn

    2006-12-01

    Full Text Available La amiloidosis sistémica primaria y el mieloma múltiple con amiloidosis primaria se han presentado con características clínicas e histopatológicas que simulan una arteritis de células gigantes. Hasta el momento la asociación se basaba en el rol antigénico del depósito de amiloide sobre las arterias, desencadenando la respuesta inmune que finaliza con una arteritis. Presentamos el primer caso en la literatura de un paciente con mieloma múltiple y arteritis de células gigantes sin amiloidosis sistémica, sugiriendo una relación patogénica entre estas dos entidades. En el caso de nuestro paciente se descartó la presencia de amiloide en la pared arterial, por lo que proponemos que el estímulo para el desarrollo de la arteritis podría ser una excesiva producción de interleuquina 6 fabricada por las células mielomatosas.Primary systemic amyloidosis with clinical and histopathologic features of giant cell arteritis has already been described. The association of multiple myeloma (with primary amyloidosis and giant cell arteritis is also known. We present the first case in the literature of a patient with multiple myeloma and giant cell arteritis without systemic amyloidosis, suggesting a pathogenic relationship between the two diseases.

  8. Depletion of spleen macrophages delays AA amyloid development: a study performed in the rapid mouse model of AA amyloidosis.

    Directory of Open Access Journals (Sweden)

    Katarzyna Lundmark

    Full Text Available AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM, marginal zone macrophages (MZM, metallophilic marginal zone macrophages (MMZM. MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.

  9. An autopsy case of acute pancreatitis with a high serum IgG4 complicated by amyloidosis and rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    Tatsuki Ichikawa; Kazuhiko Nakao; Keisuke Hamasaki; Kazuaki Ohkubo; Kan Toriyama; Katsumi Eguchi

    2005-01-01

    We report an autopsy case of acute pancreatitis with a high serum IgG4 concentration complicated by systemic amyloid A amyloidosis and rheumatoid arthritis (RA). The patient was a 42-year-old Japanese female with a 22-year history of rheumatoid arthritis. She was diagnosed with myasthenia gravis when she was 31-year old. At the onset of pancreatitis, the patient was anti-nuclear antibody-positive,and had high serum gamma globulin and IgG4 levels.Dexamethasone and conventional therapy induced clinical remission and significantly decreased the serum IgG4 and gamma globulin. However, despite the decreased disease parameters, the patient developed a bleeding pseudocyst and died of cardiac failure. In the autopsy examination, it was determined that pancreatitis was probably caused by ischemia due to vascular obstruction caused by amyloid deposition in the pancreas. Even though acute pancreatitis is a rare complication in RA patients, we speculate that an autoimmune pancreatitis-related mechanism and ischemia due to vascular obstruction by amyloid deposition might be attributable to a single source that leads to acute pancreatitis in our particular case.

  10. Amyloidosis, synucleinopathy, and prion encephalopathy in a neuropathic lysosomal storage disease: the CNS-biomarker potential of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Bartholomew J Naughton

    Full Text Available Mucopolysaccharidosis (MPS IIIB is a devastating neuropathic lysosomal storage disease with complex pathology. This study identifies molecular signatures in peripheral blood that may be relevant to MPS IIIB pathogenesis using a mouse model. Genome-wide gene expression microarrays on pooled RNAs showed dysregulation of 2,802 transcripts in blood from MPS IIIB mice, reflecting pathological complexity of MPS IIIB, encompassing virtually all previously reported and as yet unexplored disease aspects. Importantly, many of the dysregulated genes are reported to be tissue-specific. Further analyses of multiple genes linked to major pathways of neurodegeneration demonstrated a strong brain-blood correlation in amyloidosis and synucleinopathy in MPS IIIB. We also detected prion protein (Prnp deposition in the CNS and Prnp dysregulation in the blood in MPS IIIB mice, suggesting the involvement of Prnp aggregation in neuropathology. Systemic delivery of trans-BBB-neurotropic rAAV9-hNAGLU vector mediated not only efficient restoration of functional α-N-acetylglucosaminidase and clearance of lysosomal storage pathology in the central nervous system (CNS and periphery, but also the correction of impaired neurodegenerative molecular pathways in the brain and blood. Our data suggest that molecular changes in blood may reflect pathological status in the CNS and provide a useful tool for identifying potential CNS-specific biomarkers for MPS IIIB and possibly other neurological diseases.

  11. 原发性支气管肺淀粉样变9例临床分析%Primary bronchial and pulmonary amyloidosis:A clinical analysis of 9 cases

    Institute of Scientific and Technical Information of China (English)

    张丽娜; 孙军平; 张明月; 刘玉霞; 杨冰; 薛新颖; 汪建新

    2014-01-01

    目的:探讨原发性支气管肺淀粉样变的临床表现、影像学特征和治疗措施。方法回顾分析我院1994-2012年收治的9例原发性支气管肺淀粉样变患者的临床资料并结合文献进行分析。结果9例中男6例,女3例,平均年龄54岁。肺实质结节型和气管支气管淀粉样变主要表现为咳嗽、咳痰,可伴咯血或无症状。肺间质弥漫型主要表现为胸痛、痰中带血。肺实质结节型胸部CT均表现为肺部结节影,气管支气管淀粉样变表现为气管、支气管管壁增厚,可伴有钙化,肺间质弥漫性淀粉样变表现为双肺弥漫分布小结节影、斑片影。肺实质结节型通常预后较好。气管支气管型病变者常反复感染加重,需间断气管镜下介入治疗,抗炎、止咳化痰、平喘等综合治疗有一定疗效。呈肺间质弥漫型病变者预后较差。结论原发性支气管肺淀粉样变临床和影像学表现无特异性,确诊依据病理学检查,抗炎等对症治疗可以缓解症状。%Objective To study the clinical manifestations, imaging features and treatment of primary bronchial and pulmonary amyloidosis. Methods Clinical data about 9 patients with primary bronchial and pulmonary amyloidosis admitted to our hospital from 1994 to 2012 were retrospectively analyzed with its related literature reviewed. Results The average age of the 9 patients (6 males and 3 females) with primary bronchial and pulmonary amyloidosis included in this study was 54 years. The main clinical manifestations in patients with pulmonary nodular parenchymal and tracheobronchial amyloidosis were cough, expectoration and hemoptysis. The clinical manifestations in patients with diffuse pulmonary interstitial amyloidosis were chest pain and hemoptysis. Chest CT showed nodular shadows in parenchymal amyloidosis patients, thickened tracheobronchial wall or calcification in tracheobronchial amyloidosis patients, and nodular and patching

  12. Clinical analysis of nasal,pharyngeal and laryngeal amyloidosis%鼻、咽及喉部淀粉样变临床探析

    Institute of Scientific and Technical Information of China (English)

    符亚辉

    2015-01-01

    目的:探讨鼻、咽及喉部淀粉样变的临床特点。方法:收治鼻、咽及喉部淀粉样变患者83例,随机分为观察组和对照组,观察组43例给予手术治疗,对照组40例给予药物治疗。比较两组疗效。结果:观察组总有效率、死亡率、复发率均优于对照组(P<0.05)。结论:鼻、咽及喉部淀粉样变早期手术治疗是最佳的治疗方法。%Objective: To investigate the clinical features of nasal,pharyngeal and laryngeal amyloidosis.Methods:83 patients with the nose,pharynx and larynx amyloidosis were selected.They were randomly divided into the observation group and the control group.The observation group with 43 cases received the operation treatment.40 cases in the control group were given the drug treatment.The effects of two groups were compared.Results:The total efficiency,mortality and recurrence rate of the observation group were better than those of the control group(P<0.05).Conclusion:Nasal,pharyngeal and laryngeal amyloidosis early surgical treatment is the best method.

  13. The Effect of Bone Marrow Plasma Cell Burden on Survival in Patients with Light Chain Amyloidosis Undergoing High-Dose Melphalan and Autologous Stem Cell Transplantation.

    Science.gov (United States)

    Dittus, Christopher; Uwumugambi, Nsabimana; Sun, Fangui; Sloan, J Mark; Sanchorawala, Vaishali

    2016-09-01

    The prognosis in light chain (AL) amyloidosis has been linked to several variables, which are primarily related to end-organ damage. Recently, bone marrow plasma cell (BMPC) burden >10% has also been described as an adverse prognostic factor. We reviewed data pertaining to 546 patients with AL amyloidosis who underwent high-dose melphalan (HDM) and stem cell transplantation (SCT) to determine if BMPC > 10% was a negative prognostic factor. Of these patients, 445 had a BMPC burden ≤ 10% and 101 had a BMPC burden > 10%. Patients with BMPC > 30% were excluded from the study. The median overall survival (OS) was 7.86 years (95% confidence interval [CI], 6.69 to 9.83) in patients with BMPC ≤ 10% and 6.8 years (95% CI, 5.75 to 10.17) for those with BMPC >10% (hazard ratio, 1.106; 95% CI, .78 to 1.45; P = .70) after HDM/SCT. Of the 101 patients with a BMPC burden > 10%, 25 received induction therapy. The median OS was 7.78 years (95% CI, 5.4 to 13.4) for those without induction therapy and 5.75 years (95% CI, 3.94 to not available; P = .28) for those with induction therapy. Furthermore, hematologic response and relapse rates did not differ in these 2 groups after HDM/SCT. We conclude that BMPC > 10% and < 30% is not a poor prognostic factor with respect to survival in patients with AL amyloidosis treated with HDM/SCT and that induction therapy in this group does not impact OS. PMID:27296954

  14. Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis.

    Science.gov (United States)

    Lakshmanan, Anupama; Cheong, Daniel W; Accardo, Angelo; Di Fabrizio, Enzo; Riekel, Christian; Hauser, Charlotte A E

    2013-01-01

    The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer's and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-β-type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer's amyloid-β, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of α-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-β, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed β-sheet aggregates without going through the α-helical intermediate step, giving a unique fiber-diffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation. PMID:23267112

  15. Immunophenotypic analysis of abnormal plasma cell clones in bone marrow of primary systemic light chain amyloidosis patients

    Institute of Scientific and Technical Information of China (English)

    Hu Yang; Wang Mangju; Chen Yan; Chen Xue; Fang Fang; Liu Shiqin; Zhang Ying

    2014-01-01

    Background Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry (FCM) could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma (MM),and 5 Waldenstr(o)m's macroglobulinemia (WM) patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases (60.9%),in which the λ light chain restriction was found in 24 cases (77.4%).In MM,κ light chain restriction was found in 13 cases (61.9%),and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56+,68.6% were CD117+,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56+,38.1% were CD117+,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19+ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.

  16. Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.

    Directory of Open Access Journals (Sweden)

    Morwenna Y Porter

    Full Text Available The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of β(2-microglobulin (β(2m in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in the osteoarticular tissues, but the cellular basis for the destruction of these tissues in DRA is poorly understood. In this study we performed a systematic analysis of the interaction of monomeric and fibrillar β(2m with primary human cells of the types present in the synovial joints of subjects with DRA. Building upon observations that macrophages infiltrate β(2m amyloid deposits in vivo we demonstrate that monocytes, the precursors of macrophages, cannot degrade β(2m fibrils, and that both monomeric β(2m and fibrillar β(2m are cytotoxic to these cells. β(2m fibrils also impair the formation of bone resorbing osteoclasts from monocytes and reduce the viability of osteoblasts, the cell type that produces bone. As a consequence, we predict that β(2m amyloid will disrupt the remodelling of the bone, which is critical for the maintenance of this tissue. Moreover, we show that β(2m fibrils reduce the viability of chondrocytes, rationalizing the loss of cartilage in DRA. Together, our observations demonstrate that β(2m cytotoxicity has multiple cellular targets in the osteoarticular tissues and is likely to be a key factor in the bone and joint destruction characteristic of DRA.

  17. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  18. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    Directory of Open Access Journals (Sweden)

    Nina P. Hofmann

    2016-01-01

    Full Text Available Left ventricular (LV hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM, cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG, echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2, severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%, accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE by cardiac magnetic resonance (CMR. Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.

  19. Prognostic value of high-sensitivity cardiac troponin T in patients with en-domyocardial-biopsy proven cardiac amyloidosis

    Institute of Scientific and Technical Information of China (English)

    Geng QIAN; Chen WU; Yang ZHANG; Yun-Dai CHEN; Wei DONG; Yi-Hong REN

    2014-01-01

    Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age (56 ±12 years vs. 50 ±15 years, P=0.022), higher incidences of heart failure (36.92%vs. 16.22%, P=0.041), pericardial effusion (60.00%vs. 35.14%, P=0.023), greater thickness of interventricular septum (IVS) (15 ±4 mm vs. 13 ±4 mm, P=0.034), higher level of hs-cTnT (0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic pep-tide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006). At multivariate Cox regression analysis, heart failure (HR:1.78, 95%CI:1.09-2.92, P=0.021), greater wall thickness of IVS (HR:1.44, 95%CI:1.04-3.01, P=0.0375) and higher hs-cTnT level (HR:6.16, 95%CI:2.20-17.24, P=0.001) at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.

  20. Predictive value of assessing diastolic strain rate on survival in cardiac amyloidosis patients with preserved ejection fraction.

    Directory of Open Access Journals (Sweden)

    Dan Liu

    Full Text Available Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA, we hypothesized that speckle-tracking-imaging (STI derived longitudinal early diastolic strain rate (LSRdias could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%.Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients.Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years. Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views.Nineteen (46% out of 41 CA patients died during a median of 16 months (quartiles 5-35 months follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6 ± 2 vs. 8 ± 3 mm, global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p < 0.05. NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17-3.26, P = 0.010, global LSRdias (HR = 7.30, 95% CI 2.08-25.65, P = 0.002, and E/LSRdias (HR = 2.98, 95% CI 1.54-5.79, P = 0.001 remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68%, specificity 67%. Global LSRdias < 0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF.STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

  1. Amiloidose renal em cão Shar-Pei: Relato de Caso Renal amyloidosis in a Shar-Pei dog: A case report

    Directory of Open Access Journals (Sweden)

    J.L. Reis Jr.

    2001-08-01

    Full Text Available O presente relato descreve os achados clínicos e anatomopatológicos de um caso de amiloidose renal em um cão macho de nove anos da raça Shar-Pei. O animal apresentava quadro clínico de esporotricose e de insuficiência renal e exames positivos para erlichiose e leishmaniose. No dia anterior ao óbito, o cão apresentou apatia, desidratação e anúria. À necropsia foram observados inúmeros pontos milimétricos esbranquiçados localizados no córtex renal e hepatização do lobo diafragmático esquerdo. O achado histológico mais importante foi deposição de material eosinofílico, amorfo e acelular localizado nos tufos glomerulares que se corou positivamente pelo vermelho congo (amilóide. Observaram-se nefrite supurada multifocal, espessamento da cápsula de Bowman e broncopneumonia supurada crônica, com fibrose intensa. A origem da amiloidose, no presente caso, poderia ser hereditária, assemelhando-se à amiloidose familiar descrita em cães da raça Shar-Pei, ou ser devida à inflamação supurada crônica e/ou leishmaniose.The clinical and pathological findings of a case of renal amyloidosis in a nine-year-old male Shar-Pei dog were described. Clinically, there were signs of sporotrichosis and renal insufficiency, besides being positive to leishmaniasis and ehrlichiosis. On the day before death, the animal became apathetic, dehydrated and anuric. On gross examination, there were several whitish millimetric spots seen widespread in both renal cortices and consolidation of the left diaphragmatic pulmonary lobe. The most important microscopic finding was a deposition of amorphous acellular material on the glomerular tufts which stained positively by congo red stain. Other changes were multifocal suppurative nephritis, thickening of the Bowman capsule and chronic suppurative bronchopneumonia. The origin of the amyloidosis in this case could be hereditary, being similar to familiar amyloidosis described in Shar-Pei breed, or due to

  2. The ultrapathological diagnosis of systemic amyloidosis%系统性淀粉样变性的超微病理诊断

    Institute of Scientific and Technical Information of China (English)

    徐缓; 雷松

    2011-01-01

    Objective: To observe the histological and ultrastructure features of systemic amyloidosis by using light microscope ( LM) and transmission electron microscope ( TEM ). Methods: The biopsy specimens of kidney, adipose tissue of abdominal wall and rectal mucous membrane were obtained from 21 patients with systemic amyloidosis and processed by routine HE and Congo red stain for LM and thinsection for EM. Results; Under LM , the percentages of positive amyloid deposits in the biopsy specimens of kidney, adipose tissue of abdominal wall and rectal mucous membrane were 76. 2% ( 16/21 ) 、38. 1% (8/21 ) and 9. 5% (2/21 ) respectively. Under TEM, the amyloid deposits have the moderate -density, nonuniform cottony appearance. The amyloid fibrils are relatively straight, nonbranching, without granules and arranged reticulately and about 10 nm in diameter. The percentages of positive amyloid fibrils found in specimens of kidney, adipose tissue of abdominal wall and rectal mucous membrane were 90. 5% (19/21 ) 、66. 7% (14/21) and 42. 9% (9/21) respectively. Conclusion; Electron microscopic examination is an important aid in the ultrapathological diagnosis of systemic amyloidosis, especially in the early stage. The biopsy of both adipose tissue of abdominal wall and rectal mucous membrane is useful and safe in the diagnosis of systemic amyloidosis as well.%目的:应用光镜(LM)及透射电镜(TEM)观察不同部位淀粉样物质的沉积及超微结构特点,为系统性淀粉样变性提供可靠的病理诊断依据.方法:对21例临床拟诊为系统性淀粉样变性病例的肾脏,腹壁脂肪和直肠粘膜活检组织按常规进行LM及TEM标本制备及病理检查.结果:LM观察显示淀粉样物质在肾脏,腹壁脂肪和直肠粘膜沉积阳性率分别为76.2%(16/21)、38.1%(8/21)和9.5%(2/21),TEM观察显示淀粉样物质为排列不规则,中等致密,不均匀的絮状结构,直径约为1Onm的纤维丝状结构,排列杂乱呈密网状,局灶

  3. ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis[S

    OpenAIRE

    Wang王耀勇, Yaoyong,; Sawashita澤下仁子, Jinko,; Qian钱金泽, Jinze,; Zhang张蓓茹, Beiru,; Fu付笑影, Xiaoying,; Tian田耕, Geng,; Chen陈磊, Lei,; Mori森 政之, Masayuki,; Higuchi樋口京一, Keiichi,

    2011-01-01

    Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. ApoA-II has multiple physiological functions and can form senile amyloid fibrils (AApoAII) in mice. Most circulating apoA-II is present in lipoprotein A-I/A-II. To study the influence of apoA-I on apoA-II and AApoAII amyloidosis, apoA-I-deficient (C57BL/6J.Apoa1−/−) mice were used. Apoa1−/− mice showed the expected significant reduction in total cholesterol (TC), HDL cholesterol (HDL...

  4. Amiloidose e insuficiência renal crônica terminal associada à hanseníase Amyloidosis and end-stage renal disease associated with leprosy

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Júnior

    2010-08-01

    Full Text Available O envolvimento renal na hanseníase é diverso, incluindo glomerulonefrites, amiloidose e nefrite túbulo-intersticial. Um homem de 58 anos foi admitido com edema de membros inferiores e dispnéia. Na admissão, havia retenção de escórias nitrogenadas, anemia, hipercalemia e acidose metabólica, com necessidade de hemodiálise. Referia história de hanseníase virchoviana. Foi realizada biopsia renal, compatível com amiloidose. O paciente evoluiu estável, sem recuperação da função renal, permanecendo em tratamento hemodialítico. A hanseníase deve ser investigada em todo paciente com perda de função renal, sobretudo naqueles que apresentam lesões cutâneas ou outras manifestações sugestivas de hanseníase.Renal involvement in leprosy includes glomerulonephritis, amyloidosis and tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of lower limb edema and dyspnea. At admission, nitrogen retention, anemia, hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The patient had a history of lepromatous leprosy. A renal biopsy was performed that was compatible with amyloidosis. The patient had a stable outcome, but without renal function recovery and remained on regular hemodialysis. Leprosy should be investigated in every patient with renal function loss, particularly in those with cutaneous lesions or other manifestations suggestive of leprosy.

  5. The Val142Ile transthyretin cardiac amyloidosis: not only an Afro-American pathogenic variant? A single-centre Italian experience.

    Science.gov (United States)

    Cappelli, Francesco; Frusconi, Sabrina; Bergesio, Franco; Grifoni, Elisa; Fabbri, Alessia; Giuliani, Costanza; Falconi, Serena; Bonifacio, Stefania; Perfetto, Federico

    2016-02-01

    Transthyterin amyloidosis is a life-threatening disorder caused by the deposition of hepatocyte-derived transthyretin (TTR) amyloid in various tissues and organs. The most common worldwide pathogenic variant with almost exclusive cardiac involvement is Val142Ile with an allele frequency of 3.5% in U.S. African-American population, but supposed extremely rare, with only sporadic cases in Caucasian patients. Unexpectedly, in our amyloidosis referral centre, we identified five patients (15.1% of all TTRm diagnosed patients, three families, two singleton) with Val142Ile variant belonging to unrelated families of Caucasian origin. Molecular study was performed in a total of 10 individuals of which three were Italian families (three affected individuals and five unaffected individuals) and two were singleton (one Italian patient and one patient from Argentine with Spanish ancestry). Sequence analysis of TTR gene revealed the presence of the heterozygous Val142Ile in the five affected patients and in five asymptomatic individuals. All probands underwent, at diagnosis, a complete clinical, echocardiographic and biohumoral evaluation. To the best of our knowledge, we describe the larger report of Caucasian patients with Val142Ile cardiomyopathy. All patients at diagnosis showed symptoms of heart failure with increased thickness of left ventricular walls and systo-diastolic left ventricular dysfunction. They also showed increased plasma values of NT-proBNP and troponin I. Our data confirm that Caucasian patients with the Val142Ile pathogenic variant have phenotypic manifestations similar to that of African-American one. Moreover, our data clearly show that Val142Ile pathogenic variant is not only an African-American mutation but could be also an underestimated Caucasian variant. PMID:26428663

  6. Osteoarthropathy in dialysis amyloidosis

    International Nuclear Information System (INIS)

    Many long-term (>60 months) hemodialysis patients develop a severe osteoarticular disease, called 'dialysis arthropathy', which is characterized by the deposition in bone and synovia of a new type of amyloid made mainly of β2-microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1±13 years) undergoing chronic hemodialysis arthropathy by means of clinics and of radiological investigations (conventional radiography and computed tomography). Sixteen patients (51.6%) had radiographic evidence of dialysis arthropathy: geodes (shoulders, 12 cases; wrists, 11; hips, 2; knees, 2) and/or destructive arthropathies (cervical spine, 13 cases; dorsolumbar spine, 2; hands, 2; hips, 1). Within 24 months, these lesions were found to progress slowly in the majoriry of cases. In the diagnostic process, CT should be employed in the study of spine, shoulders and hips when the lesions have not been sufficiently demonstrated by conventional radiography in the presence of evident clinical signs. Patients with dialysis arthropathy had undergone dialysis for longer periods than those without it (p<0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p<0.0005) and shoulder pain (p<0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients end the value of diagnostic imaging in screening such patients for those lesions

  7. Macular amyloidosis and hypothyroidism

    Directory of Open Access Journals (Sweden)

    Chopra Adarsh

    1999-01-01

    Full Text Available A 53 year old woman presented with extensive pruritic hyperpigmented macules in interscapular area and extremities of four years duration.She was an established case of hypothyroidism on treatment for last four years.

  8. Soluble suppression of tumorigenicity 2 (sST2), but not galactin-3, adds to prognostication in patients with systemic AL amyloidosis independent of NT-proBNP and troponin T.

    Science.gov (United States)

    Dispenzieri, Angela; Gertz, Morie A; Saenger, Amy; Kumar, Shaji K; Lacy, Martha Q; Buadi, Francis K; Dingli, David; Leung, Nelson; Zeldenrust, Steven; Hayman, Suzanne R; Kapoor, Prashant; Grogan, Martha; Hwa, Lisa; Russell, Stephen J; Go, Ronald S; Rajkumar, S Vincent; Kyle, Robert A; Jaffe, Allan

    2015-06-01

    The use of soluble cardiac biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin has revolutionized prognostication for patients with AL amyloidosis. Soluble ST2 (sST2) and galectin-3 have also been reported to have prognostic value in other cardiac patient populations. We identified 502 patients with AL amyloidosis, who provided a research sample and consent to review their medical records between 1/1/2006-12/31/2010 within 90 days of their diagnosis. Samples were assayed for sST2 and galectin-3. Within this AL amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7 months). Receiver operating curve analyses were done to detect the best cut-points for sST2 and galectin-3 to predict both 1- and 5-year OS. The respective cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin-3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6 ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin-3 were prognostic, upon multivariate analysis, only sST2 was independent of troponin, NT-proBNP, serum immunoglobulin free light chain, and blood pressure. Not only did sST2 add to previously reported prognostication systems, but a novel prognostication 5-point system including sST2 was possible. The addition of sST2 - but not galectin-3 - to existing prognostication systems for patients with AL amyloidosis strengthens the ability to predict for death.

  9. Amiloidose pulmonar: relato de caso de achado radiológico da apresentação nodular em grande fumante Pulmonary amyloidosis: radiographic finding of nodular opacities in a heavy smoker

    Directory of Open Access Journals (Sweden)

    Jorge Montessi

    2007-06-01

    Full Text Available A amiloidose pulmonar é uma doença rara, caracterizada pelo depósito extracelular de proteínas fibrilares no pulmão. Amiloidose é um termo genérico para grupos heterogêneos de doenças, incluindo doença de Alzheimer e diabetes mellitus tipo II. Apresenta-se no aparelho respiratório sob as formas traqueobrônquica, nodular pulmonar e septal alveolar (parenquimatosa difusa. Relata-se o caso de uma mulher, tabagista (20 anos/maço, portadora de amiloidose nodular pulmonar, diagnosticada através de exames pré-operatórios à realização de colecistectomia videolaparoscópica.Pulmonary amyloidosis is a rare disease, characterized by extracellular deposition of fibrillary protein in the lungs. Amyloidosis is a generic term for a heterogeneous group of diseases, including Alzheimer's disease and type 2 diabetes mellitus. In the respiratory system, it appears in various forms: tracheobronchial; nodular pulmonary; and alveolar septal (diffuse parenchymal. We present the case of a woman who was a 20 pack-year smoker and had nodular pulmonary amyloidosis, as diagnosed through tests performed prior to laparoscopic cholecystectomy.

  10. Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

    Directory of Open Access Journals (Sweden)

    Tanya L Poshusta

    Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

  11. Different patterns of left ventricular rotational mechanics in cardiac amyloidosis-results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

    Science.gov (United States)

    Nemes, Attila; Földeák, Dóra; Domsik, Péter; Kalapos, Anita; Sepp, Róbert; Borbényi, Zita; Forster, Tamás

    2015-12-01

    Cardiac amyloidosis (CA) is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The aim of the present study was to examine left ventricular (LV) rotational mechanics in biopsy-proven CA by three-dimensional (3D) speckle-tracking echocardiography (STE). Ten patients (65.3±11.5 years, 6 males) with CA entered the study. The mean basal LV rotations were 0.3±3.8°, while mean apical LV rotations proved to be 7.0±3.3°. LV basal and apical rotations were in the same counterclockwise direction in 6 out of 10 CA patients demonstrating near absence of LV twist [LV rigid body rotation (RBR)]. Apico-basal difference was near 3 or less degrees in three patients with LV-RBR, and 6-10 degrees in the other three subjects with LV-RBR. One another patient showed normal rotational mechanics, while two patients had significant hyporotations and one had significant hyperrotations in normal directions. To conclude with, different patterns of LV rotational mechanics could be demonstrated in CA. LV RBR, the near absence of LV twist seems to be a frequent phenomenon in CA. PMID:26807368

  12. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis.

    Science.gov (United States)

    Sun, Weiyi; Sun, Jian; Zou, Lili; Shen, Kaini; Zhong, Dingrong; Zhou, Daobin; Sun, Wei; Li, Jian

    2015-01-01

    Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples. PMID:25984759

  13. Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons

    Science.gov (United States)

    Guardado-Mendoza, Rodolfo; Davalli, Alberto M.; Chavez, Alberto O.; Hubbard, Gene B.; Dick, Edward J.; Majluf-Cruz, Abraham; Tene-Perez, Carlos E.; Goldschmidt, Lukasz; Hart, John; Perego, Carla; Comuzzie, Anthony G.; Tejero, Maria Elizabeth; Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo; Halff, Glenn; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco

    2009-01-01

    β-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative β-cell volume, and increased relative α-cell volume and hyperglucagonemia. These results strongly support the concept that IA and β-cell apoptosis in concert with α-cell proliferation and hypertrophy are key determinants of islets of Langerhans “dysfunctional remodeling” and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R2 = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. PMID:19666551

  14. Usefulness of Combining Electrocardiographic and Echocardiographic Findings and Brain Natriuretic Peptide in Early Detection of Cardiac Amyloidosis in Subjects With Transthyretin Gene Mutation.

    Science.gov (United States)

    Di Bella, Gianluca; Minutoli, Fabio; Piaggi, Paolo; Casale, Matteo; Mazzeo, Anna; Zito, Concetta; Oreto, Giuseppe; Baldari, Sergio; Vita, Giuseppe; Pingitore, Alessandro; Khandheria, Bijoy K; Carerj, Scipione

    2015-10-01

    Early noninvasive identification of cardiac amyloidosis (CA) is of growing clinical importance. Low voltage on electrocardiogram (ECG), increased left ventricular (LV) septal thickness (ST), and global longitudinal strain (GLS) on echocardiography, and elevated brain natriuretic peptides (BNP) are used as surrogates of CA. Thirty-five patients (50 ± 14 years, 22 women) underwent electrocardiography to analyze low-voltage QRS (ECG was considered abnormal if at least one ECG alteration was present. Echocardiography was used to analyze LVST, E/E', and GLS. All participants also had BNP blood testing. (99m)Tc-3,3-diphosphono-1,2 propanodicarboxylic acid scintigraphy assumed as a reference method showed CA in 18 patients (51%, CA group) and no accumulation in 17 patients (no CA group). In descending order of accuracy, LVST >14 mm, E/E' >6.6, GLS 129 pg/ml, and an overall abnormal ECG showed good capability to distinguish patients with and without CA. All these parameters were predictors of CA in univariate analysis, whereas low-voltage QRS showed the worst performance. LVST >14 mm (p = 0.002) was the best independent predictor of CA, achieving sensitivity of 78% and accuracy of 89%. However, an LVST >14 mm (p = 0.005) plus an abnormal ECG (p = 0.03) show together a greater sensitivity, equal to 89%, in identifying CA. An integrated evaluation of ECG and echocardiography is a sensitive and low-cost technical approach to identify CA in patients with transthyretin gene mutation. PMID:26253999

  15. Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo

    Directory of Open Access Journals (Sweden)

    J.H. Williams

    2005-06-01

    Full Text Available A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

  16. TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice.

    Science.gov (United States)

    Devi, L; Ohno, M

    2015-05-05

    Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) significantly decrease early in Alzheimer's disease (AD). However, it remains unclear whether BDNF/TrkB reductions may be mechanistically involved in the pathogenesis of AD. To address this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout (TrkB(+/-)·5XFAD), and tested the effects of TrkB reduction on AD-like features in this mouse model during an incipient stage that shows only modest amyloid-β (Aβ) pathology and retains normal mnemonic function. TrkB(+/-) reduction exacerbated memory declines in 5XFAD mice at 4-5 months of age as assessed by the hippocampus-dependent spontaneous alternation Y-maze task, while the memory performance was not affected in TrkB(+/-) mice. Meanwhile, TrkB(+/-)·5XFAD mice were normal in nest building, a widely used measure for social behavior, suggesting the memory-specific aggravation of AD-associated behavioral impairments. We found no difference between TrkB(+/-)·5XFAD and 5XFAD control mice in cerebral plaque loads, Aβ concentrations including total Aβ42 and soluble oligomers and β-amyloidogenic processing of amyloid precursor protein. Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate receptor subunits as well as impaired signaling pathways downstream to TrkB such as CREB (cAMP response element-binding protein) and Akt/GSK-3β (glycogen synthase kinase-3β) were observed in TrkB(+/-)·5XFAD mice but not in 5XFAD mice. Among these signaling aberrations, only Akt/GSK-3β dysfunction occurred in TrkB(+/-) mice, while others were synergistic consequences between TrkB reduction and subthreshold levels of Aβ in TrkB(+/-)·5XFAD mice. Collectively, our results indicate that reduced TrkB does not affect β-amyloidosis but exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions in early AD.

  17. AL Amyloidosis and Agent Orange

    Science.gov (United States)

    ... Prisoners of War Employee Health Employee Health Home Employee Occupational Health Safe Patient Handling Health Promotion Violence Prevention Workers' Compensation Publications & Reports About Us About Public Health Post-Deployment Health Population Health About Population ...

  18. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    Directory of Open Access Journals (Sweden)

    Orlando G. Povoas Barsottini

    2004-09-01

    Full Text Available Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis. We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL. She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of neuropathy and current treatment of AL.A amiloidose é uma síndrome caracterizada pela deposição no meio extracelular de material protéico altamente insolúvel e que pode afetar vários órgãos. Pode ocorrer como doença generalizada e pode ser idiopática (amiloidose primária. Descrevemos o caso de mulher de 48 anos com neuropatia axonal associada a proteinúria na qual a investigação final resultou no diagnóstico de amiloidose primária (AL. Foi submetida a transplante autólogo de medula óssea sem complicações. Discutiremos aspectos relacionados ao diagnóstico da neuropatia e do tratamento atual da AL.

  19. Treatment of primary systemic amyloidosis with the combination of bortezomib and dexamethasone%硼替佐米联合地塞米松治疗原发性系统性淀粉样变性

    Institute of Scientific and Technical Information of China (English)

    翟勇平; 刘海宁; 于亚平; 周晓钢; 宋萍; 李锋; 王学文

    2010-01-01

    Objective To evaluate the efficacy and feasibility of bortezomib plus dexamethasone (BD) in patients with primary systemic (AL) amyloidosis. Methods Eleven AL amyloidosis patients, including four relapsed or progressed after previous therapies and 7 newly diagnosed were treated with BD. Ten patients had two or more organs involved. Precursor protein analysis showed that 1 was κ light chain, 9 λ light chain;5 patients with positive immunofixation including 1 IgG κ, 3 IgG λ and 1 IgA λ. BD was administered according to standard two-week schedule. Results Eight patients were evaluable, the median number of treatment cycles was 3 (range 1 -6). Median follow-up duration was 6 months. At least one affected organ response was observed in six patients and median time to organ response was 2 months. Three patients progressed and two of them died. Toxicities were mainly diarrhea, thrombocytopenia, peripheral neuropathy, fatigue and herpes zoster, and 7 evaluable patients who had toxicities were adjusted dosage and 2 of them interrupted therapy. Epilepsia, paralytic ileus, acute cardiac dysfunction, and postural hypotention were occurred in 3 inevaluble patients. Conclusion Bortezomib plus dexamethasone is effective in AL amyloidosis. Adverse events are common, and in some patients are severe.%目的 观察硼替佐米联合地塞米松治疗原发性系统性(AL)淀粉样变性患者的疗效和不良反应.方法 11例AL淀粉样变性患者中明确淀粉样物质者10例:κ型1例,λ型9例.免疫固定电泳阳性者5例:IgG κ型1例,IgGλ型3例,IgAλ型1例.累及肾脏、肝脏、心脏、肠道中2个或以上脏器者10例.11例患者中初治者7例,难治者4例.采用硼替佐米联合地塞米松方案治疗.结果 8例可评价疗效患者,中位疗程3(1~6)个.中位随访时间6个月.器官功能改善者6例,中位起效时间2个月.3例病情进展,2例死亡.常见的不良反应有腹泻、血小板减少、周围神经病

  20. Left Ventricular Myocardial Strain in Patients with Cardiac Amyloidosis Using Speckle Tracking Imaging%斑点追踪成像评价心脏淀粉样变性患者左心室心肌分层应变

    Institute of Scientific and Technical Information of China (English)

    张晶; 肖杨杰; 任卫东; 刘爽; 孙菲菲; 乔伟

    2013-01-01

    Purpose To evaluate the systolic function of left ventricular subendocardial and subepicardial myocardium using speckle tracking imaging (STI) in patients with cardiac amyloidosis. Materials and Methods Twenty patients with cardiac amyloidosis (CA group ) and thirty healthy subjects (control group) were examined using two-dimensional echocardiography. High frame rate two-dimensional images were recorded at left ventricular short-axis views during three consecutive cardiac cycles on basal, papillary muscle and apical planes. Peak systolic circumferential strain (CS) and radial strain (RS) were measured in subendocardial, subepicardial and transmural myocardium. The mean CS and RS were calculated in subendocardial and subepicardial myocardium. Results Compared with control group, IVSd, LVPWDd, LAESd, E/A and E/e of CA group were significantly increased (P0.05). In three short-axis and global views, CS of subendocardial myocardium was higher than that of subepicardial myocardium in both CA group and control group (P0.05)。CA组和对照组左心室短轴二尖瓣水平、乳头肌水平、心尖水平及左心室整体内膜下心肌收缩期CS峰值高于外膜下心肌(P<0.001)。对照组内膜下心肌收缩期RS峰值高于外膜下心肌(P<0.001),CA组内膜下心肌收缩期RS值均低于外膜下心肌(P<0.05)。与对照组比较,CA组左心室二尖瓣水平、乳头肌水平、心尖水平内膜下、外膜下及平面整体心肌收缩期CS峰值和RS峰值均减低(P<0.001),左心室整体内膜下、外膜下心肌收缩期CS峰值和RS峰值均减低(P<0.001),且内膜下心肌减低更明显。结论STI可以评价CA患者左心室圆周及径向心肌收缩功能,可作为临床早期诊断CA和评价病变程度的无创性检查方法。

  1. Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Keiichi Yamanaka

    Full Text Available The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases.

  2. 区分肾淀粉样变类型的病理染色方法比较%Evaluation of different pathological staining methods for classifying renal amyloidosis

    Institute of Scientific and Technical Information of China (English)

    周展眉; 曹维

    2013-01-01

    目的分析3种特殊染色及免疫染色方法对区分肾淀粉样变类型的准确性、灵敏度和着色强度的影响,以提高临床的诊治水平。方法选择30例肾淀粉样变患者的病理切片,采用3种酸化刚果红染色和5种抗原修复法,对轻链蛋白(κ、λ)、淀粉样蛋白A等指标进行冰冻组织及石蜡组织的免疫荧光、免疫组化染色。使用IPP图像分析系统进行半定量分析及荧光着色半定量分析,观察比较阳性部位着色的准确性、灵敏度和着色强度效果。结果酸化甲醇刚果红染色法优于酸化Bennhold's刚果红染色法、酸化Alkaland's刚果红染色法,IPP半定量分析冰冻组织的免疫荧光、免疫组化优于石蜡组织(P=0.02)。荧光半定量分析着色强度相差一个+左右;石蜡组织暴露抗原的方法中蛋白酶K消化优于抗原热修复、胰酶或胃酶消化(P=0.01)。结论酸化甲醇刚果红染色法在肾组织淀粉样变部位的阳性着色准确性、灵敏度、着色强度和重复率均优于Bennhold's刚果红染色法、酸化Alkaland's刚果红染色法。起到初步分型及辅助验证免疫荧光染色结果的作用;进行冰冻组织轻链蛋白(κ、λ)及淀粉样蛋白A免疫荧光染色,更有利于肾淀粉样变的准确分型,如果无冰冻组织也可选用蛋白酶K消化石蜡组织免疫荧光染色。%Objective To analyze the effect of special staining and immunohistochemical staining in distinguishing the types of renal amyloidosis to improve the diagnosis accuracy. Method Congo red staining with different methods, and immunohistochemical staining of Kappa, Lambda and Amyloid A with different antigen retrieval methods were used for staining frozen and paraffin-embedded renal tissue sections. Results Wright's Congo red staining produced a better contrast and a higher resolution and showed a greater stability than the other 2 methods after repeated use for staining

  3. Amilóidose cardíaca. Uma doença de muitas faces e diferentes prognósticos Cardiac amyloidosis. A disease with many faces and different prognoses

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Pereira Barretto

    1997-08-01

    Full Text Available OBJETIVO: Avaliar as formas de apresentação da amilóidose cardíaca em hospital terciário. MÉTODOS: Nos últimos 15 anos, foram identificados 8 pacientes com amilóidose, sendo 5 mulheres , com idades entre 23 e 83 (média 62 anos. Após anamnese e exame físico foram submetidos a eletrocardiograma (ECG, ecocardiograma (ECO, estudo com pirofosfato de tecnécio e biópsia endomiocárdica, cujos resultados permitiram caracterizar suas formas clínicas. RESULTADOS: Sete pacientes apresentavam dispnéia aos esforços, 6 quadro de insuficiência cardíaca congestiva (ICC, 1 síncopes. O ECG identificou bloqueio atrioventricular total (BAVT em 4 casos e área eletricamente inativa ântero-septal em outros 4. O ECO mostrou diâmetros normais em todos e fração de ejeção discretamente reduzida em 6. Hipertrofia do septo e parede posterior em todos, sendo em 7 com aspecto sugestivo de doença de depósito (aspecto granuloso. Os dados clínicos caracterizam dois grupos, um com BAVT e outro com cardiomiopatia restritiva. A evolução foi diferente com melhora clínica após o implante de marcapasso no primeiro grupo e má evolução no grupo com cardiomiopatia restritiva que evoluiu de maneira refratária, 3 falecendo em menos de 6 meses após diagnóstico. CONCLUSÃO: A presença de aumento da espessura das paredes ao ECO, discreta disfunção sistólica e aspecto de doença de depósito identificaram a quase totalidade dos casos. Cardiomiopatia restritiva e distúrbio de condução foram as formas de apresentação, sendo o prognóstico muito reservado nos pacientes com forma restritiva, evoluindo para ICC refratária.PURPOSE: To identify the principal forms of cardiac amiloydosis presentation in a terciary hospital. METHODS: Eight cases whith cardiac amyloidosis were identified. Five were woman, their ages ranged from 23 to 83 years (mean 62. After a medical history and clinical examination the patients, were submitted to complementary tests

  4. Primary (AL) amyloidosis with gastrointestinal involvement

    DEFF Research Database (Denmark)

    Madsen, Lone Galmstrup; Gimsing, Peter; Schiødt, Frank V

    2009-01-01

    ). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5...

  5. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur;

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  6. Classification of amyloidosis by laser micro-dissection and mass spectrometry based proteomic analysis%利用激光显微切割联合质谱蛋白质组学方法进行系统性淀粉样变性分型

    Institute of Scientific and Technical Information of China (English)

    沈恺妮; 孙维绎; 孙健; 孙伟; 钟定荣; 曹欣欣; 周道斌; 李剑

    2015-01-01

    目的 评估利用激光显微切割联合质谱蛋白质组学技术对系统性淀粉样变性进行分型的有效性.方法 以138例病理确诊为淀粉样变性患者的经福尔马林固定石蜡包埋标本为研究对象.利用显微切割收集刚果红染色阳性区域组织并行质谱蛋白质组学分析,以指数修正的蛋白质丰度指标(emPAI)为标准,根据丰度最高的致淀粉样变蛋白判定淀粉样变性亚型.结果 在138份组织标本中,腹壁脂肪占26%,舌体占19%,齿龈占11%,肾脏占9%,胃肠道占9%,心脏占6%,其余类型样本占20%.总共121例患者获得成功分型,包括轻链型106例(87.6%),遗传性甲状腺转运球蛋白型7例(5.8%),致淀粉样变蛋白A型、重链/重链+轻链型及纤维蛋白原α链型各2例(1.7%),载脂蛋白A-Ⅱ型及溶菌酶型各1例(0.8%).5例被排除淀粉样变性诊断,12例分型失败.总体诊断准确率为91.3%.在各种组织类型标本中,腹壁脂肪组织的分型成功率最低,仅为83.3%.结论 激光显微切割联合质谱蛋白质组学方法能有效鉴定出淀粉样变性亚型.%Objectives To establish a novel method to determine specific type of amyloidosis through laser microdissection and mass spectrometry (LMD/MS) based proteomic analysis.Methods There were 138 formalin-fixed and paraffin-embedded (FFPE) biopsy samples of patients who were diagnosed as systemic amyloidosis used in this study.For each case,a 10 μm section stained with congored and positive amyloid deposits were identified under fluorescent light,followed by micro-dissection and mass spectrometry analysis.The amyloidosis subtype was confirmed based on the most abundant amyloid protein.Results The tissue types of 138 specimens were as following:subcutaneous abdominal fat accounted for 26%,tongue for 19%,gingiva for 11%,kidney for 9%,intestine for 9%,heart for 6% and others for 20%.Specific types of amyloid were accurately detected in 121

  7. 75 FR 65279 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Science.gov (United States)

    2010-10-22

    ... INFORMATION: A final rule was published in the Federal Register at 74 FR 21258 amending 38 CFR 3.309(e) by... transplantation with high dose chemotherapy, an aggressive and risky treatment with serious side effects and a... organ systems. The usual cause of death is cardiac, hepatic, or renal failure, or infection. The...

  8. 倍氯米松软膏与维A酸乳膏治疗皮肤丘疹型淀粉样变的临床疗效比较%Efficacy comparison of clobetasol propionate ointment and vitamin A acid cream in the treatment of skin papule type amyloidosis

    Institute of Scientific and Technical Information of China (English)

    宋艳霞; 王云鹏; 高月兰

    2014-01-01

    目的 比较倍氯米松软膏与维A酸乳膏治疗皮肤丘疹型淀粉样变的临床疗效.方法 将皮肤丘疹型淀粉样变100例患者按随机数字表法分为观察组和对照组,每组各50例,对照组采用维A酸乳膏治疗,观察组上采用倍氯米松软膏治疗,治疗4周后,比较两组患者皮损面积、浸润情况、皮肤颜色、皮肤瘙痒评分,以及痊愈率和有效率.结果 (1)两组患者治疗后,症状好转,症状评分较治疗前逐渐减低,观察组于第1周、第2周、第3周、第4周评分分别为(9.35±1.88)分、(6.54 ±2.16)分、(4.08±1.32)分、(2.04±0.95)分,明显优于对照组的(10.86±2.08)分、(7.98 ±2.57)分、(6.25±1.44)分、(4.56±1.18)分,比较差异具有统计学意义(t =6.22、6.71、7.30、7.41,均P<0.05);(2)两组患者治疗4周后,观察组有效率和治愈率分别为94%和34%明显高于对照组的70%和22%,两组比较差异具有统计学意义(x2=9.040、8.391,均P<0.05).结论 倍氯米松软膏在治疗皮肤丘疹型淀粉样变方面较维A酸乳膏症状改善明显,临床效果确切,值得积极推广应用.%Objective To compare clinical efficacy of clobetasol propionate ointment and vitamin A acid cream in the treatment of skin papule type amyloidosis.Methods 100 cases of skin papule type amyloidosis were randomly divided into the observation group and control group,each had 50 patients.The control group was treated with Vitamin A acid cream while the observation group used clobetasol propionate ointment for treatment.Skin lesion area,infiltration,skin color,skin itching score as well as the cure rate and efficiency were compared after 4 weeks of treatment.Results The two groups' symptoms was improved,symptom scores was decreased gradually after treatment than before,the observation group's symptom scores at 1,2,3,4 weeks were (9.35 ± 1.88),(6.54 ±2.16),(4.08 ±1.32),(2.04 ± 0.95) points which was significant better than (10.86 ± 2.08),(7.98 ± 2

  9. Memory enhancement by Tamoxifen on amyloidosis mouse model.

    Science.gov (United States)

    Pandey, Deepika; Banerjee, Sugato; Basu, Mahua; Mishra, Nibha

    2016-03-01

    Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. Earlier studies show its neuroprotection via regulating apoptosis, microglial functions, and synaptic plasticity. TMX also showed memory enhancement in ovariectomized mice, and protection from amyloid induced damage in hippocampal cell line. These reports encouraged us to explore the role of TMX in relevance to Alzheimer's disease (AD). We report here, the effect of TMX treatment a) on memory, and b) levels of neurotransmitters (acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected with beta amyloid1-42 (Aβ1-42). Mice were treated with TMX (10mg/kg, i.p.) for 15 days. In Morris water maze test, the TMX treated mice escape latency decreased during training trials. They also spent longer time in the platform quadrant on probe trial, compared to controls. In Passive avoidance test, TMX treated mice avoided stepping on the shock chamber. This suggests that TMX protects memory from Aβ induced toxicity. In frontal cortex, ACh was moderately increased, with TMX treatment. In striatum, dopamine was significantly increased, 3,4-dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing dopamine metabolism and increasing ACh level in Aβ1-42 injected-breeding-retired-female mice. PMID:26435474

  10. [Myocardial pyrophosphate uptake in cardiac amyloidosis: report of case].

    Science.gov (United States)

    Redondo, Francisca; González, Patricio; Ramírez, Alfredo

    2002-03-01

    We report a previously healthy 73 years old woman, who was hospitalised with increasing dyspnea and signs of congestive heart failure. Echocardiography showed a normal left ventricular cavity with increased echogenicity of its walls and severe pulmonary hypertension. A lung ventilation/perfusion scintigraphy concluded that there was a low probability for pulmonary embolism. Coronary angiography was normal. A restrictive cardiomyopathy due to amyloid deposits was suspected. Myocardial pyrophosphate scintigraphy showed intense pyrophosphate uptake in the left ventricle wall. An abdominal fat tissue biopsy was positive for amyloid deposits. PMID:12043375

  11. A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin

    DEFF Research Database (Denmark)

    Caubet, Cécile; Bousset, Luc; Clemmensen, Ole;

    2010-01-01

    Heterozygous nonsense mutations in the CDSN gene encoding corneodesmosin (CDSN), an adhesive protein expressed in cornified epithelia and hair follicles, cause hypotrichosis simplex of the scalp (HSS), a nonsyndromic form of alopecia. Truncated mutants of CDSN ((mut)CDSN), which bear the N...

  12. Amyloidosis associated with dialysis. Dialyseassoziierte Amyloidosteopathie - radiologische Aspekte

    Energy Technology Data Exchange (ETDEWEB)

    Schadmand, S.; Klose, K.J. (Mainz Univ. (Germany, F.R.). Inst. fuer Klinische Strahlenkunde); Wandel, E. (Mainz Univ. (Germany, F.R.). 1. Medizinische Klinik und Poliklinik)

    1991-06-01

    Amongst the complications of dialysis, amyloid osteopathy is getting increasingly significant. It is due to deposition of {beta}2-microglobulin. To determine the incidence and time of development of this complication, the skeletal radiographs of 185 patients undergoing dialysis, some for up to ten years, were analysed retrospectively. In about 10% of patients, the presence of {beta}2-microglobulin osteopathy may be expected. The radiological features, sites of predilection and differential diagnosis of amyloid osteopathy and of other skeletal changes due to dialysis are discussed. (orig.).

  13. A Drosophila Disease-Model for Transthyretin-associated Amyloidosis

    OpenAIRE

    Pokrzywa, Malgorzata

    2008-01-01

    Amyloidoses comprise a group of gain-of-toxic function protein misfolding diseases, in which normally soluble proteins in their functional state undergo conformational changes into highly organized and generally intractable thread-like aggregates, termed amyloid fibrils. These structures accumulate predominantly in the extracellular space but growing evidence suggests that amyloids may start to form intracellularly. At least 26 different human proteins, intact or in fragmented form, are known...

  14. Assessment of general and local left ventricular systolic function by speckle tracking imaging in patients with cardiac amyloidosis%斑点追踪成像技术评价心脏淀粉样变性患者左心室整体及局部纵向收缩功能

    Institute of Scientific and Technical Information of China (English)

    张晶; 肖杨杰; 任卫东; 乔伟; 潘福治

    2015-01-01

    目的:应用二维斑点追踪成像技术(2D-STI)检测心脏淀粉样变性(CA)患者左心室长轴收缩功能的变化,探讨其临床应用价值。方法选择确诊的CA患者20例为CA组,其中男性13例,女性7例,平均年龄54.80岁。选取年龄和性别匹配的健康志愿者30例为正常对照组,其中男性18例,女性12例,平均年龄54.85岁。分别采集心尖四腔心切面、心尖两腔心切面和心尖左心室长轴切面的二维动态图像,应用2D-STI获取左心室18个心肌节段收缩期纵向峰值应变,计算左心室基底段、中间段、心尖段的平均纵向峰值应变及左心室整体纵向峰值应变。结果所有受检者左心室心尖段到基底段纵向峰值应变逐渐减低。 CA组左心室各节段收缩期纵向应变峰值均显著低于正常对照组,差异均有显著统计学意义(P<0.001)。 CA组左心室基底段、中间段、心尖段平均纵向峰值应变及左心室整体纵向峰值应变均显著低于正常对照组,差异均有显著统计学意义(P<0.001)。结论 CA患者左心室整体及局部纵向收缩功能均减低,2D-STI能够从长轴纵向应变的角度更敏感、准确评估CA患者收缩功能的变化,适合临床广泛开展。%Objective To evaluate the left ventricular long-axis systolic function in patients with cardiac amyloidosis (CA) by two-dimensional speckle tracking imaging (2D-STI), and investigate its clinical significance. Methods A total of 20 patients with CA were set as CA group, which included 13 males and 7 females with mean age of 54.80 years old. The 30 healthy volunteers were set as control group, which included 18 males and 12 females with mean age of 54.85 years old. The apical 4-chamber view, apical two-chamber view and apical long-axis view of left ventricle were obtained by two-dimensional dynamic images. The systolic longitudinal strain(LS) peaks of 18 myocardial segments in left ventricular

  15. 左室长轴收缩期峰值应变在原发性心脏淀粉样变性与肥厚型心肌病诊断中的价值%Value of assessing left ventricular longitudinal systolic peak strain in differential diagnosis of primary cardiac amyloidosis from hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    张璐; 智光; 王叶; 程流泉; 王晶; 周肖; 刘淼; 张威; 章明; 张波

    2014-01-01

    Objective To analyze the endocardial, myocardial, and epicardial longitudinal systolic strain (LSsys) in the left ventricle (LV) segments and walls in patients with cardiac involvement due to primary amyloidosis (AL-CA) and hypertrophic cardiomyopathy (HCM). Methods Twenty patients with biopsy-proven AL-CA, 20 with asymmetric HCM, and 20 age-matched healthy volunteers were analyzed for their clinical characteristics and underwent conventional echocardiography for evaluating LV wall thickness, left atrial and ventricle size, systolic and diastolic function and 2-dimensional velocity vector imaging for evaluating the endocardial, myocardial and epicardial LSsys of the LV segments and walls. AL-CA and HCM patients also underwent cardiac magnetic resonance to evaluate the late gadolinium enhancement (LGE) features. Results Compared with the control group, AL-CA and HCM groups, with similar clinical symptoms and physical signs, both showed increased LV wall thickness, left atrial diameter, E/A ratio, septal E/e' ratio and the prevalence of granular sparkling. LV segments and walls endocardial LSsys were significantly lower in AL-CA patients than in HCM patients and the control subjects. The endocardial-epicardial LSsys difference in all the left ventricle walls were significantly smaller in AL-CA group than in the control group, but this difference appeared variable in HCM group. The LGE also presented with different features in AL-CA and HCM:AL-CA group showed subendocardial LGE in almost all the LV walls, but HCM group showed patchy LGE with a regional, multifocal distribution. Conclusion AL-CA is characterized by a significantly reduced endocardial LSsys in the LV segments and an uniform decrease of the endocardial-epicardial LSsys difference in all the LV walls, but the changes in HCM appear variable, and 2-dimensional velocity vector imaging is therefore a useful modality to differentiate AL-CA from HCM.%目的:分利用速度向量成像(VVI)技术比较原

  16. ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    Science.gov (United States)

    2016-10-11

    Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

  17. Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: The proteases (secretases that cleave amyloid-beta (Abeta peptide from the amyloid precursor protein (APP have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Abeta production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. METHODS AND FINDINGS: We have generated a transgenic mouse model that genetically mimics the arrest of Abeta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Abeta production to levels found in nontransgenic mice. Suppression of transgenic Abeta synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Abeta deposits retain a considerable amyloid load, with little sign of active clearance. CONCLUSION: This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Abeta production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear.

  18. Type I primary neuropathic amyloidosis (Andrade, Portuguese: a clinical and laboratory study of 21 cases

    Directory of Open Access Journals (Sweden)

    Eduardo M. Azevedo

    1975-06-01

    Full Text Available The authors present a review of 21 cases with the diagnosis of type I amyloid neuropathy based on epidemiological data, clinical evolution and histopathological findings. They call attention to the possibility of cranial nerves involvement (hyposmia, diplopia, masseterian hypotrophy, peripheral facial paralysis, hypoacusis, dysphonia, laryngeal paralysis, dysphagia, and trapezium muscle hypotrophy, to the severeness of the digestive symptoms, to the precocity of the autonomic disorders, and to the rather high incidence (6 cases of heart involvement. The electromyography showed anterior horn involvement in 3 cases. The electrocardiography showed repolarization disorders in 11 cases, left ventricular overload in 6 cases and atrioventricular block in 5 cases. The serum proteins electrophoresis showed frequent abnormalities, but no typical curve could be obtained. The barium-contrasted X-rays of the gastrointestinal tract showed no anatomical lesions, but functional abnormalities (hypo or hypermotility were found in 14 examinations. The Schilling test showed impairment of vitamin B12 absorption in 50% of the cases. However, with the concomitant administration of intrinsic factor (3 cases there was improvement of its absorption. This proves that the gastric mucosa plays an important role in the disease malabsorption. The test with labeled-triolein showed slow absorption in 2 cases and steatorrhea in 3 (6 tests. For the confirmation of the amyloid deposits, the best histopathological procedure was nerve biopsy. In men, when the nerve biopsy was negative, testicular biopsy has shown to be a good option.

  19. Nonfluent/Agrammatic PPA with In-Vivo Cortical Amyloidosis and Pick’s Disease Pathology

    OpenAIRE

    Francesca Caso; Benno Gesierich; Maya Henry; Manu Sidhu; Amanda LaMarre; Miranda Babiak; Bruce L. Miller; Rabinovici, Gil D; Huang, Eric J.; Giuseppe Magnani; Massimo Filippi; Giancarlo Comi; Seeley, William W.; Maria Luisa Gorno-Tempini

    2013-01-01

    The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD) clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA). She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychol...

  20. Cutaneous lymphatic amyloid deposits in 'Hungarian-type' familial transthyretin amyloidosis : a case report

    NARCIS (Netherlands)

    Harkany, T.; Garzuly, F.; Csanaky, G.; Luiten, P.G.M.; Nyakas, C.; Linke, R.P.; Virágh, S.

    2002-01-01

    Multiple transthyretin (TTR) mutations have recently been identified and implicated in the development of familial systemic amyloidoses, but early diagnosis of these disorders is still largely unresolved. We investigated the presence and tissue distribution of TTR-derived amyloid in skin biopsies of

  1. Learning to classify neural activity from a mouse model of Alzheimer's disease amyloidosis versus controls.

    Science.gov (United States)

    Beker, Shlomit; Kellner, Vered; Chechik, Gal; Stern, Edward A

    2016-01-01

    The mechanisms underlying Alzheimer's disease (AD) onset and progression are not yet elucidated. The extent to which alterations in the activity of individual neurons of an AD model are significant, and the phase at which they can be captured, point to the intensity of the pathology and imply the stage at which it can be detected. Using a machine-learning algorithm, we present a successful cell-by-cell classification of intracellularly recorded neurons from the B6C3 APPswe/PS1dE9 AD model, versus wildtypes controls, at both a late stage and at an early stage, when the plaque pathology and behavioral deficits are absent or rare. These results suggest that the deficits present in neuronal networks of both old and young transgenic animals are large enough to be apparent at the level of individual neurons, and that the pathology could be detected in nearly any given sample, even before pathologic signs. PMID:27239535

  2. Nanotechnology drives a paradigm shift on protein misfolding diseases and amyloidosis

    Science.gov (United States)

    Bellotti, Vittorio; Stoppini, Monica

    2012-06-01

    In almost a century of scientific work on the mechanism of amyloid diseases much of the attention has been focused on the amyloid fibrils, which still represent the diagnostic hallmark of the disease and are easily identified in affected organs for their peculiar tinctorial properties and the fibrillar shape. However, it has been lately discovered that the seeds of the pathogenesis are deeply hidden in the structure and folding dynamics of proteins at the monomeric state which almost indistinguishable from the normal counterpart through classical biochemical approaches. In the recent years soluble oligomeric/prefibrillar species, putatively cytotoxic, were discovered and even more recently polymorphisms of shape and structure of fibrils was emerging as a property that could dictate the bioactivity of amyloid as well as the specificity of its tissue localization. Nanotechnology through the biophysical analysis of the single molecules (monomers or oligomers or fibrils) is the propulsive disciplines in the transformation of our knowledge on the molecular mechanism of this disease. It will provide, in the forthcoming years, precious analytical devices mimicking the biological microenvironment where the molecular events causing the amyloid formation will be monitored and possibly modulated in a real time frame.

  3. Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

    NARCIS (Netherlands)

    C. Jansen (Casper); P. Parchi (Piero); S. Capellari (Sabina); A.J. Vermeij (Ad); P. Corrado (Patrizia); F. Baas (Frank); R. Strammiello (Rosario); W.A. van Gool (Willem); J.C. van Swieten; A.J.M. Rozemuller (Annemieke)

    2010-01-01

    textabstractStop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrP

  4. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    OpenAIRE

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani,Satosi; Hayashi,Shin-ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Masahisa Arahata,1 Shigeru Shimadoi,1 Satosi Yamatani,1 Shin-ichi Hayashi,2 Shigeharu Miwa,2 Hidesaku Asakura,3 Shinji Nakao4 1Department of Internal Medicine, Nanto Municipal Hospital, Nanto, 2Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Internal Medicine (III), 4Department of Cellular Transplantation Biology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kana...

  5. Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis

    Science.gov (United States)

    Obici, Laura; Kuks, Jan B.; Buades, Juan; Adams, David; Suhr, Ole B.; Coelho, Teresa; Kyriakides, Theodore

    2016-01-01

    Purpose of review These recommendations highlight recent experience in genetic counselling for the severe autosomal-dominant, late-onset transthyretin familial amyloid polyneuropathy (TTR-FAP) disease, and present a structured approach towards identification and monitoring of asymptomatic carriers of the mutated gene. Recent findings The effectiveness of current treatment options is still limited in patients with TTR-FAP beyond stage I. Diagnosis in the early stages of TTR-FAP is essential to prevent or delay the progression of disease. Existing legal and cultural issues differ among countries within Europe. Experts of the European Network for TTR-FAP (ATTReuNET) concluded that genetic counselling for diagnosed individuals and at-risk family members is mostly beneficial and should be carried out with care by trained professionals. Systematic and regular monitoring of an asymptomatic carrier is necessary to detect early signs of TTR-FAP and maximize the effectiveness of treatment. This includes five areas of assessment: history/clinical examination, sensorimotor function, autonomic dysfunction, cardiac function, and renal function. At least two related symptoms and positive biopsy findings are required to confirm diagnosis of TTR-FAP. Summary Early detection of TTR-FAP is essential to improve the prognosis of TTR-FAP. ATTReuNET recommends genetic counselling and routine monitoring for asymptomatic carriers of TTR-FAP. PMID:26734953

  6. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis

    OpenAIRE

    Coelho, Teresa; Merlini, Giampaolo; Bulawa, Christine E.; Fleming, James A; Judge, Daniel P.; Kelly, Jeffery W.; Maurer, Mathew S.; Planté-Bordeneuve, Violaine; Labaudinière, Richard; Mundayat, Rajiv; Riley, Steve; Lombardo, Ilise; Huertas, Pedro

    2016-01-01

    Transthyretin (TTR) transports the retinol-binding protein–vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of ...

  7. Transthyretin Val30Met Mutation in an African American with Cardiac Amyloidosis

    OpenAIRE

    Schulze, P. Christian; Maurer, Mathew S.

    2010-01-01

    We report the case of a 53-year-old African American individual who presented with recurrent diarrhea and progressive exercise intolerance. Gastroenterologic studies demonstrated delayed intestinal transit and neurologic testing showed peripheral sensory and autonomic neuropathy. Cardiovascular assessment revealed concentric hypertrophic cardiomyopathy with increased left ventricular (LV) filling pressure and preserved LV function. Renal function was impaired in the absence of anemia. Cardiac...

  8. A Case of a Senile Systemic Amyloidosis Patient Presenting With Angina Pectoris and Dilated Cardiomyopathy

    OpenAIRE

    Kang, Gu Hyun; Ryu, Dong Ryeol; Song, Pil Sang; Song, Young Bin; Hahn, Joo-Yong; Choi, Seung-Hyuck; Gwon, Hyeon-Cheol

    2011-01-01

    A 77-year-old man visited our hospital complaining of aggravated exertional chest pain. He was diagnosed with syndrome X 7 years ago and underwent medical treatment in a regional hospital. Coronary angiography and echocardiography did not show any significant abnormalities. On the seventh in-hospital day, cardiogenic shock developed and echocardiography showed a dilated left ventricular (LV) cavity and severe LV systolic dysfunction. We thus inserted an intra-aortic balloon pump for hemodynam...

  9. Colchicine therapy in amyloidosis related with plasmacytic castleman disease presenting with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Saime Paydas

    2015-01-01

    Full Text Available Castleman disease (CD is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery.

  10. An autopsy case of macroglobulinemia complicated with syndrome of inappropriate secretion of ADH (SIADH) like hyponatremia, hypopituitarism and AL amyloidosis.

    Science.gov (United States)

    Yamada, Chika; Yoneda, Chihiro; Ogino, Jun; Fukushima, Sayaka; Kodama, Shoko; Asano, Chihiro; Masuda, Michihiko; Horie-Tajima, Kanako; Toyonaga, Aiko; Hiroshima, Kenzo; Kawamura, Shunji; Hashimoto, Naotake

    2014-01-01

    An 88-year-old male patient with macroglobulinemia was admitted to our hospital because of severe hyponatremia and unconsciousness. Laboratory findings showed decreased inhibition of antidiuretic hormone (ADH) and he was diagnosed with syndrome of inappropriate secretion of ADH (SIADH). Hyponatremia improved with only limitation of water intake and the patient was followed up on a continuing outpatient basis. However, soon after discharge from hospital, his legs started swelling with edema and hyponatremia worsened. He was re-admitted due to a fall at home. Hyponatremia was observed at re-admission. A CRH challenge test showed partial dysfunction of ACTH secretion. Corticosteroid therapy was performed, but the patient subsequently died from pneumonia. Pathological findings at autopsy revealed invasion of plasma cells and amyloid depositions in multiple organs, including the pituitary, adrenal cortex, heart, liver, kidney, lymph nodes and bone marrow. Consistent with these results, fibrosis was observed in the anterior lobe of the pituitary, suggesting that the autopsy findings were related to the clinical observations and diagnosis. This is the first reported case of macroglobulinemia complicated with multiple hormone dysfunction.

  11. Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis

    OpenAIRE

    Lakshmanan, Anupama; Cheong, Daniel W.; Accardo, Angelo; Di Fabrizio, Enzo; Riekel, Christian; Hauser, Charlotte A. E.

    2012-01-01

    The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer’s and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall p...

  12. Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jonathan S. Wall

    2015-04-01

    Full Text Available Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in the healthy tissues due to the high degree of sulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14, as novel agents for specifically targeting and imaging amyloid. Herein, we demonstrate that radiolabeled p5+14 effectively bound murine AA amyloid in vivo by using molecular imaging. Biotinylated peptide also reacted with the major forms of human amyloid in tissue sections as evidenced immunohistochemically. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients.

  13. Mechanisms underlying insulin deficiency-induced acceleration of β-amyloidosis in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Latha Devi

    Full Text Available Although evidence is accumulating that diabetes mellitus is an important risk factor for sporadic Alzheimer's disease (AD, the mechanisms by which defects in insulin signaling may lead to the acceleration of AD progression remain unclear. In this study, we applied streptozotocin (STZ to induce experimental diabetes in AD transgenic mice (5XFAD model and investigated how insulin deficiency affects the β-amyloidogenic processing of amyloid precursor protein (APP. Two and half months after 5XFAD mice were treated with STZ (90 mg/kg, i.p., once daily for two consecutive days, they showed significant reductions in brain insulin levels without changes in insulin receptor expression. Concentrations of cerebral amyloid-β peptides (Aβ40 and Aβ42 were significantly increased in STZ-treated 5XFAD mice as compared with vehicle-treated 5XFAD controls. Importantly, STZ-induced insulin deficiency upregulated levels of both β-site APP cleaving enzyme 1 (BACE1 and full-length APP in 5XFAD mouse brains, which was accompanied by dramatic elevations in the β-cleaved C-terminal fragment (C99. Interestingly, BACE1 mRNA levels were not affected, whereas phosphorylation of the translation initiation factor eIF2α, a mechanism proposed to mediate the post-transcriptional upregulation of BACE1, was significantly elevated in STZ-treated 5XFAD mice. Meanwhile, levels of GGA3, an adapter protein responsible for sorting BACE1 to lysosomal degradation, are indistinguishable between STZ- and vehicle-treated 5XFAD mice. Moreover, STZ treatments did not affect levels of Aβ-degrading enzymes such as neprilysin and insulin-degrading enzyme (IDE in 5XFAD brains. Taken together, our findings provide a mechanistic foundation for a link between diabetes and AD by demonstrating that insulin deficiency may change APP processing to favor β-amyloidogenesis via the translational upregulation of BACE1 in combination with elevations in its substrate, APP.

  14. DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?

    Directory of Open Access Journals (Sweden)

    Zareen Amtul

    Full Text Available Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA on beta-amyloid production and Alzheimer's disease (AD. However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA and low fat diet (low fat+DHA. Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to produce beta-amyloid peptides and amyloid plaques when fed a pep+DHA diet. The increase in beta-amyloid peptides was due to an elevated trend in the levels of beta-secretase amyloid precursor protein (APP cleaving enzyme (BACE, the proteolytic C-terminal fragment beta of APP and reduced levels of insulin degrading enzyme that endoproteolyse beta-amyloid. On the contrary, TgCRND8 mice on low fat+DHA diet (based on an approximately 18% reduction of fat intake ameliorate the production of abeta peptides and consequently amyloid plaques. Our work not only demonstrates that DHA when taken with peptamen may have a tendency to confer a detrimental affect on the amyloid plaque build up but also reinforces the importance of studying composite lipids or nutrients rather than single lipids or nutrients for their effects on pathways important to plaque development.

  15. New insights into the clinical evaluation of hereditary transthyretin amyloidosis patients: a single center's experience

    OpenAIRE

    Suhr OB; Gustavsson S.; Heldestad V; Hörnsten R; Lindqvist P; Nordh E; Wiklund U

    2012-01-01

    Ole B Suhr,1 Sandra Gustavsson,1 Victoria Heldestad,2 Rolf Hörnsten,3 Per Lindqvist,1 Erik Nordh,2 Urban Wiklund41Department of Public Health and Clinical Medicine, 2Department of Pharmacology and Clinical Neuroscience, 3Department of Surgical and Perioperative Sciences, Clinical Physiology, Heart Centre, 4Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, SwedenAbstract: Over the last decade, new medical treatment modalities have eme...

  16. Personalized medicine approach for optimizing the dose of tafamidis to potentially ameliorate wild-type transthyretin amyloidosis (cardiomyopathy).

    Science.gov (United States)

    Cho, Younhee; Baranczak, Aleksandra; Helmke, Stephen; Teruya, Sergio; Horn, Evelyn M; Maurer, Mathew S; Kelly, Jeffery W

    2015-01-01

    Placebo-controlled clinical trials are useful for identifying the dose of a drug candidate that produces a meaningful clinical response in a patient population. Currently, Pfizer, Inc. is enrolling a 400-person clinical trial to test the efficacy of 20 or 80 mg of tafamidis to ameliorate transthyretin (TTR)-associated cardiomyopathy using clinical endpoints. Herein, we provide guidance for how to optimize the dose of tafamidis for each WT TTR cardiomyopathy patient using its mechanism of action as the key readout, i.e. we identify the dose of tafamidis that maximally kinetically stabilizes TTR in the blood. Tetramer dissociation is rate limiting for TTR aggregation, which appears to drive the pathology of the TTR amyloidoses. Hence, we measure the TTR tetramer dissociation rate (kinetic stability) in the patient's plasma as a function of tafamidis dose to optimize the dose employed to maximize kinetic stability. Historical data tell us that a subset of patients exhibiting higher tafamidis plasma concentrations are maximally kinetically stabilized at the 20-mg tafamidis dose, whereas the patient studied herein required a 60 mg once daily dose to achieve maximum kinetic stabilization. We anticipate that establishing the dose of tafamidis that achieves maximal TTR kinetic stabilization will translate into a maximal clinical effect, but that remains to be demonstrated. PMID:26193961

  17. A new isoleucine substitution of Val-20 in transthyretin tetramers selectively impairs dimer-dimer contacts and causes systemic amyloidosis.

    OpenAIRE

    Jenne, D. E.; Denzel, K; Blätzinger, P; Winter, P.; Obermaier, B; Linke, R P; Altland, K

    1996-01-01

    The most frequent form of inherited amyloidoses is associated with mutations in the transthyretin (TTR) gene coding for 127-amino acid residues of four identical, noncovalently linked subunits that form a pair of dimers in the plasma protein complex. Amyloid fibrils containing the variant and to a lesser extent the wild-type form of the TTR molecule are deposited in various organs, including peripheral nerves and the myocardium, with polyneuropathy and cardiomyopathy as major clinical manifes...

  18. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study

    OpenAIRE

    aus dem Siepen F; Bauer R; Aurich M; Buss SJ; Steen H.; Altl; De, K.; Katus HA; Kristen AV

    2015-01-01

    Fabian aus dem Siepen,1 Ralf Bauer,1 Matthias Aurich,1 Sebastian J Buss,1 Henning Steen,1 Klaus Altland,2 Hugo A Katus,1 Arnt V Kristen1 1Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany; 2Institute of Human Genetics, Justus-Liebig-University, Giessen, Germany Background: Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epi...

  19. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study

    Directory of Open Access Journals (Sweden)

    aus dem Siepen F

    2015-12-01

    Full Text Available Fabian aus dem Siepen,1 Ralf Bauer,1 Matthias Aurich,1 Sebastian J Buss,1 Henning Steen,1 Klaus Altland,2 Hugo A Katus,1 Arnt V Kristen1 1Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany; 2Institute of Human Genetics, Justus-Liebig-University, Giessen, Germany Background: Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG, the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE. Methods: Twenty-five male patients (71 [64; 80] years with wtATTR-CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI (n=14, and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months. Results: A significant decrease of left ventricular (LV myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03 by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006 was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75, LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; P=0.1, and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3 by echocardiography remained unchanged. Conclusion: This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction. Keywords: wild-type ATTR, cardiomyopathy, polyphenol, EGCG

  20. 99mTc‐aprotinin – optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis

    Science.gov (United States)

    Gillings, Nic

    2016-01-01

    Abstract Technetium‐99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using 99mTc‐pertechnetate. The labelling was achieved within 25 min, with radiochemical purities of >98%. PMID:26923297

  1. DMSO and colchicine therapy in amyloid disease.

    OpenAIRE

    Scheinberg, M A; Pernambuco, J C; Benson, M D

    1984-01-01

    There is no specific therapy for primary amyloidosis, and acquired generalised amyloidosis can be treated only if the underlying disease is eliminated. In this study we have investigated the role of colchicine therapy in primary amyloidosis, and dimethylsulphoxide (DMSO) in leprosy associated secondary amyloidosis. No effect on creatinine clearance or 24 h proteinuria could be observed in the patients with primary amyloidosis. In the DMSO group renal function was considerably improved in 3 pa...

  2. Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

    OpenAIRE

    Heijden, R.A. van der; Sheedfar, F.; Bijzet, J; Hazenberg, B P; Koonen, D.P.; Heeringa, P.

    2015-01-01

    Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obe...

  3. Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

    NARCIS (Netherlands)

    Van Der Heijden, R.A.; Sheedfar, F.; Bijzet, J.; Hazenberg, B.P.; Koonen, D.P.; Heeringa, P.

    2015-01-01

    Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipo

  4. Sideritis spp. Extracts Enhance Memory and Learning in Alzheimer’s β-Amyloidosis Mouse Models and Aged C57Bl/6 Mice

    Science.gov (United States)

    Hofrichter, Jacqueline; Krohn, Markus; Schumacher, Toni; Lange, Cathleen; Feistel, Bjöorn; Walbroel, Bernd; Pahnke, Jens

    2016-01-01

    Nowadays, Alzheimer’s disease is the most prevalent epiphenomenon of the aging population. Although soluble amyloid-β (Aβ) species (monomers, oligomers) are recognized triggers of the disease, no therapeutic approach is able to stop it. Herbal medicines are used to treat different diseases in many regions of the world. On the Balkan Peninsula, at the eastern Mediterranean Sea, and adjacent regions, Sideritis species are used as traditional medicine to prevent age-related problems in elderly. To evaluate this traditional knowledge in controlled experiments, we tested extracts of two commonly used Sideritis species, Sideritis euboea and Sideritis scardica, with regard to their effects on cognition in APP-transgenic and aged, non-transgenic C57Bl/6 mice. Additionally, histomorphological and biochemical changes associated with Aβ deposition and treatment were assessed. We found that daily oral treatment with Sideritis spp. extracts highly enhanced cognition in aged, non-transgenic as well as in APP-transgenic mice, an effect that was even more pronounced when extracts of both species were applied in combination. The treatment strongly reduced Aβ42 load in APP-transgenic mice, accompanied by increased phagocytic activity of microglia, and increased expression of the α-secretase ADAM10. Moreover, the treatment was able to fully rescue neuronal loss of APP-transgenic mice to normal levels as seen in non-transgenic controls. Having the traditional knowledge in mind, our results imply that treatment with Sideritis spp. extracts might be a potent, well-tolerated option for treating symptoms of cognitive impairment in elderly and with regard to Alzheimer’s disease by affecting its most prominent hallmarks: Aβ pathology and cognitive decline. PMID:27258424

  5. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    NARCIS (Netherlands)

    van der Heijden, Roel A.; Bijzet, Johan; Meijers, Wouter C.; Yakala, Gopala K.; Kleemann, Robert; Nguyen, Tri Q.; de Boer, Rudolf A.; Schalkwijk, Casper G.; Hazenberg, Bouke P. C.; Tietge, Uwe J. F.; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complicat

  6. Value of determining the cerebrospinal fluid protein markers of amyloidosis and neurodegeneration in the diagnosis of vascular and neurodegenerative cognitive impairments

    Directory of Open Access Journals (Sweden)

    Vladimir Yuryevich Lobzin

    2013-01-01

    Full Text Available The article presents data on different forms of moderate cognitive impairments (MCI and the specific features of their transformation to dementia. Cerebrospinal fluid (CSF was investigated in 60 patients with the amnestic and neurodynamic types of MCI, in 15 patients with vascular dementia (VD, 50 patients with Alzheimer’s disease (AD, and 23 patients with mixed vascular and neurodegenerative dementia (MVND. The specific features of β-amyloid and τ-protein concentrations were established in the preclinical stages of dementia, which reflects the main components of the pathogenesis of neurodegeneration. In the amnestic form of MCI and AD, there was drastically decreased Aβ-42 and increased τ-protein levels in SCF. As cognitive impairments progressed, there was a rise in the concentration of τ-protein; its level correlated with the severity of dementia. In MND, the level of Aβ-42 was significantly reduced while the concentration of τ-protein was much increased; moreover, to a greater extent than in AD and VD. Cerebrovascular damage and neurodegeneration were related to each other and mutually worsened clinical and pathogenic effects.

  7. AAV2/1 CD74 Gene Transfer Reduces β-amyloidosis and Improves Learning and Memory in a Mouse Model of Alzheimer's Disease

    Science.gov (United States)

    Kiyota, Tomomi; Zhang, Gang; Morrison, Christine M; Bosch, Megan E; Weir, Robert A; Lu, Yaman; Dong, Weiguo; Gendelman, Howard E

    2015-01-01

    Modulation of the amyloid-β (Aβ) trafficking pathway heralds a new therapeutic frontier for Alzheimer's disease (AD). As CD74 binds to the amyloid-β precursor protein (APP) and can suppresses Aβ processing, we investigated whether recombinant adeno-associated virus (AAV) delivery of CD74 could reduce Aβ production and affect disease outcomes. This idea was tested in a mouse AD model. Cotransduction of AAV-tetracycline-controlled transactivator (tTA) and AAV-tet-response element (TRE)-CD74 resulted in CD74 expression, reduced Aβ production in mouse neurons containing the human APP with familial AD-linked mutations. Stereotaxic injection of AAV-TRE-GFP or CD74 into the hippocampi of an AD mouse, defined as a TgCRND8 × calmodulin-dependent protein kinase II derived promoter-tTA double-transgenic, reduced Aβ loads and pyramidal neuronal Aβ accumulation in the hippocampus. Immunofluorescent studies showed that APP colocalization with Lamp1 was increased in CD74-expressing neurons. Moreover, Morris water maze tasks demonstrated that mice treated with AAV-TRE-CD74 showed improved learning and memory compared to AAV-TRE-GFP control animals. These results support the idea that CD74-induced alteration of Aβ processing could improve AD-associated memory deficits as shown in mouse models of human disease. PMID:26227349

  8. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis

    OpenAIRE

    Weiyi Sun; Jian Sun; Lili Zou; Kaini Shen; Dingrong Zhong; Daobin Zhou; Wei Sun; Jian Li

    2015-01-01

    Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove ...

  9. Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet

    OpenAIRE

    Zhuo, Jia-Min; Praticò, Domenico

    2009-01-01

    Epidemiological and clinical studies indicate that elevated circulating level of homocysteine (Hcy) is a risk factor for developing Alzheimer's disease (AD). Dietary deficiency of folate, vitamin B6 and B12 results in a significant increase of Hcy levels, a condition also known as hyperhomocysteinemia (HHcy).

  10. Pilot study of the reducing effect on amyloidosis in vivo by three FDA pre-approved drugs via the Alzheimer's APP 5' untranslated region.

    Science.gov (United States)

    Tucker, Stephanie; Ahl, Michelle; Bush, Ashley; Westaway, David; Huang, Xudong; Rogers, Jack T

    2005-04-01

    A pilot study was conducted employing a well known mouse model for Alzheimer's disease to evaluate the anti-amyloid efficacy of three FDA pre-approved drugs. Paroxetine (SSRI and APP 5'UTR directed lead compound), N-acetyl cysteine (antioxidant), and erythromycin (macrolide antibiotic) were provided to the drinking water of TgCRND8 mice for three months. This report provides data that measured the steady-state levels of amyloid Abeta-40 and Abeta-42 Abeta as pmol Abeta per gram of mouse brain cortex in drug treated and placebo animals. The relative levels of Abeta peptide levels were reduced after exposure of mice to paroxetine (N=5), NAC (N=7), and erythromycin (N=7) relative to matched placebo counterparts. These results demonstrated proof-of concept for a strategy to further screen the APP 5'UTR target to identify novel drugs that exhibit anti-amyloid efficacy in vivo. These data also demonstrated a statistically significant anti-amyloid trend for paroxetine, NAC and erythromycin. The potential for conducting further studies with these compounds using larger cohorts of TgCRND8 mice is discussed.

  11. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs.

    Science.gov (United States)

    Castaño, Adam; Drachman, Brian M; Judge, Daniel; Maurer, Mathew S

    2015-03-01

    Transthyretin-cardiac amyloidoses (ATTR-CA) are an underdiagnosed but increasingly recognized cause of heart failure. Extracellular deposition of fibrillary proteins into tissues due to a variety of inherited transthyretin mutations in ATTRm or due to advanced age in ATTRwt eventually leads to organ failure. In the heart, amyloid deposition causes diastolic dysfunction, restrictive cardiomyopathy with progressive loss of systolic function, arrhythmias, and heart failure. While traditional treatments have consisted of conventional heart failure management and supportive care for systemic symptoms, numerous disease-modifying therapies have emerged over the past decade. From organ transplantation to transthyretin stabilizers (diflunisal, tafamidis, AG-1), TTR silencers (ALN-ATTR02, ISIS-TTR(Rx)), and degraders of amyloid fibrils (doxycycline/TUDCA), the potential for effective transthyretin amyloid therapy is greater now than ever before. In light of these multiple agents under investigation in human clinical trials, clinicians should be familiar with the systemic cardiac amyloidoses, their differing pathophysiology, natural histories, and unique treatment strategies. PMID:25408161

  12. The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis

    OpenAIRE

    Jiang, Xin; Buxbaum, Joel N.; Kelly, Jeffery W.

    2001-01-01

    The transthyretin (TTR) amyloid diseases are of keen interest, because there are >80 mutations that cause, and a few mutations that suppress, disease. The V122I variant is the most common amyloidogenic mutation worldwide, producing familial amyloidotic cardiomyopathy primarily in individuals of African descent. The substitution shifts the tetramer-folded monomer equilibrium toward monomer (lowers tetramer stability) and lowers the kinetic barrier associated with ra...

  13. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs

    OpenAIRE

    Castaño, Adam; Drachman, Brian M.; Judge, Daniel; Maurer, Mathew S.

    2015-01-01

    Transthyretin-cardiac amyloidoses (ATTR-CA) are an underdiagnosed but increasingly recognized cause of heart failure. Extracellular deposition of fibrillary proteins into tissues due to a variety of inherited transthyretin mutations in ATTRm or due to advanced age in ATTRwt eventually leads to organ failure. In the heart, amyloid deposition causes diastolic dysfunction, restrictive cardio-myopathy with progressive loss of systolic function, arrhythmias, and heart failure. While traditional tr...

  14. Familial Danish dementia: a novel form of cerebral amyloidosis associated with deposition of both amyloid-Dan and amyloid-beta

    DEFF Research Database (Denmark)

    Holton, J.L; Lashley, T.; Ghiso, J.;

    2002-01-01

    response using conventional techniques, immunohistochemistry, confocal microscopy, and immunoelectron microscopy. We showed that ADan is widely distributed in the central nervous system (CNS) in the leptomeninges, blood vessels, and parenchyma. A predominance of parenchymal pre-amyloid (non...

  15. Amyloid polyneuropathy caused by wild-type transthyretin

    OpenAIRE

    Lam, L.; Margeta, M; Layzer, R

    2015-01-01

    © 2015 Wiley Periodicals, Inc. Introduction: Amyloidosis derived from transthyretin (TTR) molecules is typically caused by mutations of the TTR gene. Methods: We describe an elderly patient with a severe length-dependent polyneuropathy that unexpectedly proved to be caused by wild-type transthyretin amyloidosis. Results: The diagnosis was made by muscle biopsy, because no amyloid deposits were found in the biopsied nerve segment. Most cases of wild-type transthyretin amyloidosis occur in elde...

  16. [Perioperative management for liver transplant in a patient with familial amyloid polyneuropathy with heart involvement].

    Science.gov (United States)

    López-Herrera Rodríguez, D; Guerrero Domínguez, R; Mellado Miras, P; Gómez Sosa, L

    2015-01-01

    Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic amyloidosis, is characterized by infiltration of the myocardium, leading to cardiomyopathy and conduction disturbances. Liver transplantation is the only curative option for patients with FAP. The case is presented of a 36-year-old patient with type i FAP with cardiac involvement, proposed for liver transplant surgery, which was successfully performed without any preoperative event of interest. PMID:24742789

  17. Clobetasol Propionate Compound Ointment in the Treatment of Lichenoid Amyloidosis%复方丙酸氯倍他索软膏治疗苔藓样皮肤淀粉样变病疗效观察

    Institute of Scientific and Technical Information of China (English)

    张丽萍; 孙鸿

    2012-01-01

      目的:观察复方丙酸氯倍他索软膏治疗苔藓样皮肤淀粉样变病的疗效和安全性.方法:选取皮损位于双侧小腿且左右侧基本对称的38例患者,左侧皮损设为治疗组,右侧皮损设为对照组,分别外用复方丙酸氯倍他索软膏、0.025%全反式维甲霜,连续用药4周.结果:4周后两组基本痊愈率分别为47.37%、18.42%,有效率分别为84.21%、34.21%,两组比较差异有统计学意义(P<0.01).治疗组无不良反应发生,对照组不良反应发生率为7.89%.结论:复方丙酸氯倍他索软膏治疗苔藓样皮肤淀粉样变病安全、有效.%  Objective:Toevaluatetheefficacyandreliabilityofclobetasolpropionatecompoundointmentforthetreatmentoflichenoidamyloidosis.Methods:38patientswithlichenoidamyloidosiswhoselesiondistributedintwoshanksymmetricallywereselectedandtreatedforfourweeks,andtheleftshank(treatmentgroup)wastreatedwithclobetasolpropionatecompoundointmenttherapy,therightone(controlgroup)with0.025%all-trans-retinoicacidcream.Results:Thecurativerateswere47.37%fortreatmentgroupand18.42%forcontrolgroup.Theefficacyrateswere84.21%and34.21%,respectively,therewerestatisticaldifferenceintreatmentgroupandcontrolgroup(P<0.01)inthecurativeratesandefficacyrates.Inthetreatmentgroupsnonesideeffectswasfoundandsideeffectswerefoundin7.89%patientsofcontrolgroup.Conclusion:Clobetasolpropionatecompoundointmentisaneffectiveandsafetyagentforthetreatmentoflichenoidamyloidosis.

  18. Type I primary neuropathic amyloidosis (Andrade, Portuguese: a clinical and laboratory study of 21 cases Neuropatia amilóide primária tipo I (Andrade, Portuguesa: estudo clínico e laboratorial de 21 casos

    Directory of Open Access Journals (Sweden)

    Eduardo M. Azevedo

    1975-06-01

    Full Text Available The authors present a review of 21 cases with the diagnosis of type I amyloid neuropathy based on epidemiological data, clinical evolution and histopathological findings. They call attention to the possibility of cranial nerves involvement (hyposmia, diplopia, masseterian hypotrophy, peripheral facial paralysis, hypoacusis, dysphonia, laryngeal paralysis, dysphagia, and trapezium muscle hypotrophy, to the severeness of the digestive symptoms, to the precocity of the autonomic disorders, and to the rather high incidence (6 cases of heart involvement. The electromyography showed anterior horn involvement in 3 cases. The electrocardiography showed repolarization disorders in 11 cases, left ventricular overload in 6 cases and atrioventricular block in 5 cases. The serum proteins electrophoresis showed frequent abnormalities, but no typical curve could be obtained. The barium-contrasted X-rays of the gastrointestinal tract showed no anatomical lesions, but functional abnormalities (hypo or hypermotility were found in 14 examinations. The Schilling test showed impairment of vitamin B12 absorption in 50% of the cases. However, with the concomitant administration of intrinsic factor (3 cases there was improvement of its absorption. This proves that the gastric mucosa plays an important role in the disease malabsorption. The test with labeled-triolein showed slow absorption in 2 cases and steatorrhea in 3 (6 tests. For the confirmation of the amyloid deposits, the best histopathological procedure was nerve biopsy. In men, when the nerve biopsy was negative, testicular biopsy has shown to be a good option.Os autores apresentam uma revisão de 21 pacientes com diagnóstico de neuropatia amilóide tipo I, firmado sobre os dados epidemiológicos, a evolução clínica e os achados histopatológicos. Chamam a atenção para a possibilidade de comprometimento de vários nervos cranianos, para a gravidade do quadro digestivo, a precocidade dos distúrbios neurovegetativos e a incidência relativamente alta de sintomatologia cardíaca. Constituem contribuição para o melhor conhecimento da afecção, os estudos sobre a síndrome digestiva feitos através de exames radiológicos e dos testes de absorção de vitamina B12 e trioleína radioativas.

  19. Amiloidose AL em um adulto jovem: remissão clínica e laboratorial com transplante autólogo de células tronco AL amyloidosis in a young adult: remission with autologous stem cell transplantation

    OpenAIRE

    Ricardo Prado Golmia; Isabel Clapis Bello; Eliane Rosseto; João Carlos Campos Guerra; Cristóvão Mangueira; Morton Aaron Scheinberg

    2010-01-01

    Transplante autólogo de células tronco é uma das formas de tratamento da amiloidose primária ou AL. Os autores relatam um paciente de 46 anos com hematomas periorbitais bilaterais, macroglossia, em quem, na investigação, se constatou a presença de paraproteínas IgG Kappa no soro. O diagnóstico de amiloidose primária ou AL foi confirmado, e o tratamento proposto com condicionamento com doses altas de Melfalan, seguido de transplante autólogo de células tronco, determinou a remissão completa da...

  20. 遗传性转甲状腺素蛋白淀粉样变性心肌病的临床特点%Clinical features of patients with cardiomyopathy due to hereditary transthyretin-related amyloidosis

    Institute of Scientific and Technical Information of China (English)

    田庄; 李剑; 吴炜; 陈未; 张抒扬; 方全

    2015-01-01

    目的 探讨遗传性转甲状腺素蛋白淀粉样变(ATTR)心肌病的临床特点.方法 本研究纳入13例通过组织活检、基因检测和超声心动图检查明确为遗传性ATTR心肌病的患者,同时纳入58例明确诊断为原发性淀粉样变(AL)心肌病患者作为对照.回顾性收集并分析以上患者的临床表现、实验室检查、心电图和超声心动图检查结果.结果 13例遗传性ATTR心肌病患者平均年龄26.0 ~62.0(47.0±11.0)岁,9例(69.2%)患者有家族史.与AL心肌病患者相比,遗传性ATTR心肌病患者病程较长17(14,27)个月,心脏受累症状不突出,主要表现为活动耐力减低;超声心动图主要表现为左心室肥厚但无扩大且收缩功能基本正常;遗传性ATTR心肌病患者更年轻[(47.0±1 1.0)岁比(57.0±10.0)岁,P<0.01];心电图低电压发生率较低(23.1%比55.2%,P<0.05);左心室间隔[17.0(16.0,19.0)mm比13.0(11.0,15.0) mm,P<0.001]及左心室后壁更厚[16.0(14.0,19.0)mm比12.0(11.0,14.0)mm,P<0.01];左心室舒张末内径较小[42.0(39.0,43.0) mm比46.0 (41.0,49.0)mm,P<0.05]而收缩功能更好[左心室射血分数62.0%(53.0%,65.0%)比54.0% (44.0%,61.0%),P<0.05].遗传性ATTR心肌患者心脏外受累主要表现为周围神经病变和慢性腹泻,肾、消化道和肝受累较少见;而AL心肌病患者则更多表现为肾、肝和胃肠道受累,周围神经病变和慢性腹泻少见.结论 遗传性ATTR心肌病患者主要表现为左心室肥厚而收缩功能基本正常,心电图无高电压表现;常合并周围神经或者自主神经病变及家族聚集特点.

  1. Whole body amyloid deposition imaging by 123I-SAP scintigraphy

    NARCIS (Netherlands)

    van Rheenen, Ronald; Glaudemans, Andor; Hazenberg, Bouke

    2011-01-01

    Amyloidosis is the name of a group of diseases characterized by extracellular deposition of amyloid fibrils. Deposition of amyloid can be localized or systemic. The 123I-SAP-scan can be used to image extent and distribution of amyloid deposition in patients with systemic AA, AL and ATTR amyloidosis.

  2. The transthyretin amyloidoses: advances in therapy.

    Science.gov (United States)

    Dubrey, Simon; Ackermann, Elizabeth; Gillmore, Julian

    2015-08-01

    There are two forms of transthyretin (TTR) amyloidosis: non-hereditary and hereditary. The non-hereditary form (ATTRwt) is caused by native or wild-type TTR and was previously referred to as senile systemic amyloidosis. The hereditary form (ATTRm) is caused by variant TTR which results from a genetic mutation of TTR. The predominant effect of ATTRwt amyloidosis is on the heart, with patients having a greater left ventricular wall thickness at presentation than the devastating form which is light chain (AL) amyloidosis. ATTRm amyloidosis is broadly split into two categories: a type that predominantly affects the nervous system (often called familial amyloid polyneuropathy (FAP)) and one with a predilection for the heart (often called familial amyloid cardiomyopathy (FAC)). Approximately half of all TTR mutations known to express a clinical phenotype cause a cardiomyopathy. Since the introduction of orthotopic liver transplantation for ATTRm amyloidosis in 1991, several additional therapies have been developed. These therapies aim to provide a reduction or elimination of TTR from the plasma (through genetic approaches), stabilisation of the TTR molecule (to prevent deposition) and dissolution of the amyloid matrix. We describe the latest developments in these approaches to management, many of which are also applicable to wild-type amyloidosis. PMID:26048914

  3. Amyloid Goiter Secondary to Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Bunyamin Aydin

    2016-01-01

    Full Text Available Diffuse amyloid goiter (AG is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn’s disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

  4. Melæna som debutsymptom ved amyloidose

    DEFF Research Database (Denmark)

    Jessen, Ester M B; Nielsen, Liv Bjerre Juul; Bønnelycke, Marie Kamper;

    2015-01-01

    Amyloidosis is a disease characterized by abnormal extracellular deposits of protein. The disease may affect the stomach, however, symptoms are rare in this case. Furthermore, the rare symptoms are diffuse and unspecific and the diagnosis relies on biopsy. We report the case of a 79-year-old fema...... presenting with melaena and no history of amyloidosis. Gastroscopy raised suspicion of a malignant process in the stomach, but biopsy revealed gastric amyloidosis. The treatment of gastric involvement is primarily symptomatic, and causal treatment is reserved for the few.......Amyloidosis is a disease characterized by abnormal extracellular deposits of protein. The disease may affect the stomach, however, symptoms are rare in this case. Furthermore, the rare symptoms are diffuse and unspecific and the diagnosis relies on biopsy. We report the case of a 79-year-old female...

  5. Salivary Gland Biopsy for Sjogren's Syndrome

    NARCIS (Netherlands)

    Delli, Konstantina; Vissink, Arjan; Spijkervet, Fred K. L.

    2014-01-01

    Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjogren's syndrome (SS), lymphoma accompanying SS, sarcoidosis, amyloidosis, and other connective tissue disorders. SS has characteristic microscopic findings involving lymphocytic infiltration surrounding the excretory ducts

  6. Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy

    DEFF Research Database (Denmark)

    Hornstrup, Louise S; Frikke-Schmidt, Ruth; Nordestgaard, Børge G;

    2013-01-01

    Transthyretin can cause amyloidosis attributable to destabilization of transthyretin tetramers in plasma. We tested the hypothesis that genetic stabilization of transthyretin associates with reduced risk of vascular disease and increased life expectancy. APPROACH AND RESULTS: We included 68 602 p...

  7. Nail abnormalities

    Science.gov (United States)

    ... nails include systemic amyloidosis , malnutrition, vitamin deficiency, and lichen planus . Skin cancers near the nail and fingertip ... the nail bed. Chemotherapy medicines can affect nail growth. Normal aging affects the growth and development of ...

  8. Amyloid Goiter Secondary to Ulcerative Colitis.

    Science.gov (United States)

    Aydin, Bunyamin; Koca, Yavuz Savas; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  9. Biopsy catheter (image)

    Science.gov (United States)

    ... are removed. The test is performed routinely after heart transplantation to detect potential rejection. It may also be performed when cardiomyopathy, myocarditis, cardiac amyloidosis, or other disorders are suspected.

  10. Complement activation in chromosome 13 dementias

    DEFF Research Database (Denmark)

    Rostagno, A.; Revesz, T.; Lashley, T.;

    2002-01-01

    Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits...

  11. Disease: H00288 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available a and erysipelas-like skin lesions. Renal amyloidosis is the most severe complication, leads to renal fail...ure. These symptoms start before 20 years of age in about 90% of cases. Immune syst

  12. General Information about Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... or certain chemicals . Tests that examine the blood, bone marrow, and urine are used to detect (find) and ... amyloidosis. Radiation therapy : Radiation therapy is given for bone lesions of the spine . Chemotherapy: Chemotherapy is given to ...

  13. Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

    Science.gov (United States)

    ... or certain chemicals . Tests that examine the blood, bone marrow, and urine are used to detect (find) and ... amyloidosis. Radiation therapy : Radiation therapy is given for bone lesions of the spine . Chemotherapy: Chemotherapy is given to ...

  14. Disease: H01217 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available les (macular amyloidosis). PLCA is relatively common in South America and Asia, and some cases have an autosomal dominant family hist...ory (familial PLCA, FPLCA). The genetic basis of FPLCA involves mutations in the OS

  15. Identification of MEFV-Independent Modifying Genetic Factors for Familial Mediterranean Fever

    OpenAIRE

    Cazeneuve, Cécile; Ajrapetyan, Hasmik; Papin, Stéphanie; Roudot-Thoraval, Françoise; Geneviève, David; Mndjoyan, Elizaveta; Papazian, Marina; Sarkisian, Ashot; Babloyan, Ara; Boissier, Brigitte; Duquesnoy, Philippe; Kouyoumdjian, Jean-Claude; Girodon-Boulandet, Emmanuelle; Grateau, Gilles; Sarkisian, Tamara

    2000-01-01

    Familial Mediterranean fever (FMF) is a recessively inherited disorder predisposing to renal amyloidosis and associated with mutations in MEFV, a gene encoding a protein of unknown function. Differences in clinical expression have been attributed to MEFV-allelic heterogeneity, with the M694V/M694V genotype associated with a high prevalence of renal amyloidosis. However, the variable risk for patients with identical MEFV mutations to develop this severe complication, prevented by lifelong admi...

  16. Amyloids here, amyloids there…What’s wrong with them?

    OpenAIRE

    Gharibyan, Anna

    2012-01-01

    Amyloid formation is inherent property of proteins which under certain circumstances can become a pathologic feature of a group of diseases called amyloidosis. There are about 30 known human amyloidosis and more than 27 identified proteins involved in these pathologies.  Besides these proteins, there are a growing number of proteins non-related to diseases shown to form amyloid-like structures in vitro, which make them excellent tools for studying amyloid formation mechanisms, physicochemical...

  17. Vergleichende Untersuchung bildgebender Verfahren zur Leberdiagnostik bei Falken unter besonderer Berücksichtigung der Amyloidose

    OpenAIRE

    Carnarius, Mandy

    2010-01-01

    Liver diseases in birds are very common but diagnosed rather lately. Especially amyloidosis is most often diagnosed post mortem in birds. The objective of this study was the comparison of different imaging techniques for the in vivo diagnosis of avian liver diseases in special consideration of amyloidosis for different species of falcons. Sixty-four falcons of one breeding stock were examined. First, each falcon underwent a general physical examination followed by special medical proce...

  18. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

  19. Púrpura. Manifestação de Amiloidose Sistémica Primária

    OpenAIRE

    Lestre, S; Gonçalves, A.; João, A; Ferreira, A; Apetato, M

    2009-01-01

    Primary Systemic Amyloidosis (AL) is the most frequent form of systemic amyloidosis and its morbilility is associated with immunoglobulin light chains deposition in vital organs. The mucocutaneous manifestations occur in about 30-40% of the cases and are important in diagnostic suspicion, once they appear in early stages of disease. We report a 71-years-old female patient, with disseminated purpura and cutaneous fragility with 6 months of evolution, accompanied by recent complaints of dysphag...

  20. Enlarging mediastinal/hilar lymphadenopathy with calcification.

    Science.gov (United States)

    Adachi, Takashi; Nakahata, Masashi; Moritani, Suzuko; Iida, Hiroatsu; Ogawa, Kenji

    2016-02-01

    A 77-year-old man was referred to our hospital due to enlarging mediastinal/hilar lymphadenopathy with calcification. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bone marrow aspiration were performed. Subsequently, monoclonal gammopathy of undetermined significance (MGUS) associated with mediastinal amyloidosis was diagnosed. We hereby report a case in which EBUS-TBNA led to a successful diagnosis of amyloidosis. PMID:26862422

  1. Functional amyloid signaling via the inflammasome, necrosome, and signalosome: New therapeutic targets in heart failure

    OpenAIRE

    Parry, Traci L.; Melehani, Jason H.; Ranek, Mark J.; Willis, Monte S.

    2015-01-01

    As the most common cause of death and disability globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma (MM) light chain disease and disease-causing m...

  2. Functional Amyloid Signaling via the Inflammasome, Necrosome, and Signalosome: New Therapeutic Targets in Heart Failure

    OpenAIRE

    Parry, Traci L.; Melehani, Jason H.; Ranek, Mark J.; Willis, Monte S.

    2015-01-01

    As the most common cause of death and disability, globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma light chain disease and disease-causing mutan...

  3. Untersuchungen zur Amyloidose bei Zoo- und Wildvögeln sowie zur Histo- und Immunhistochemischen Charakterisierung des aviären Amyloidproteins

    OpenAIRE

    Zoellner, Anne

    2010-01-01

    The aim of these studies was to obtain more detailed information on the occurrence and distribution of amyloidosis in captive and wild birds, to analyse the relationship of amyloidosis to other diseases and influential factors, and to characterize the avian amyloid protein histochemically and immunohistochemically. The studies were performed at the Institute for Zoo and Wildlife Research in Berlin. Their basis were post-mortem reports and a diversity of organ specimens embedded in para...

  4. Clobetasol Propionate Compound Ointment Plus NB-UVB Phototherapy in the Treatment of Primary Cutaneous Amyloidosis:A Clinical Observation in 30 Cases%复方丙酸氯倍他索软膏联合窄谱中波紫外线治疗原发性皮肤淀粉样变病30例临床观察

    Institute of Scientific and Technical Information of China (English)

    吴晓琦; 张荷香

    2014-01-01

    目的 探讨复方丙酸氯倍他索软膏联合窄谱中波紫外线治疗原发性皮肤淀粉样变病的临床疗效和安全性.方法 将入选的60例原发性皮肤淀粉样变病患者随机分成两组,各30例.治疗组:患处外搽复方丙酸氯倍他索软膏,再予窄谱中波紫外线局部隔日照射1次,3次/周;对照组仅予窄谱中波紫外线局部照射治疗,方法同治疗组.两组患者的疗程均为4周.结果 治疗结束后,治疗组有效率为83.33%,对照组为53.33%,差异有统计学意义(P<0.05).治疗组有1例局部皮肤出现潮红、浸渍;对照组有1例出现轻微灼痛感觉.结论 复方丙酸氯倍他索软膏联合窄谱中波紫外线治疗原发性皮肤淀粉样变病比单纯使用窄谱中波紫外线治疗的效果好.

  5. 探讨小鼠肌肉组织中老化淀粉样变纤维的传播性%Transmission of mouse senile amyloid fibrils in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    霍佳; 钱俊乔; 李陈莉; 樋口京一; 郭浅妤; 钱金泽

    2014-01-01

    ABSTRACT:Recently ,prion‐like transmission has been found in various amyloidosis .AApoAII amyloid fibrils in mouse senile amyloidosis have exhibited transmissibility .AApoAII amyloid fibrils ,which were excreted from mice and contained in fe‐ces or milk ,cause mouse senile amyloidosis .However ,transmissibility of AApoAII amyloid fibrils through other pathways has not yet been established .In this study ,we injected AApoAII amyloid fibrils into R1 .P1‐A poa2c mice to induce AApoAII sys‐temic amyloidosis .Two months later ,AApoAII amyloid fibrils ,which deposited in the skeletal muscles of amyloid‐affected mice ,were used to induce AApoAII systemic amyloidosis .Mouse senile amyloidosis which deposited in skeletal muscles could induce secondary transmission of AApoAII amyloidosis .The evidence of transmission through skeletal muscles in non‐prion systemic amyloidosis is found in our study .This pathway of transmission provides new insight into the potential for food‐borne pathogenesis and etiology of systemic amyloidosis .%目的:探讨淀粉样变纤维AApoAII在小鼠肌肉组织中的传播性。方法本研究采用R1.P1‐A poa2c小鼠进行系统性淀粉样变诱导实验,诱导实验进行2个月后,判断从骨骼肌组织中提取淀粉样变纤维的沉积程度,并进行2次传播实验。结果从骨骼肌组织中提取淀粉样变纤维可诱发小鼠系统性淀粉样变。结论与prion蛋白质具有相似的特点,小鼠老化淀粉样变纤维可通过骨骼肌传播淀粉样变,而此结果为淀粉样变疾病的预防及发生机制的解析提供了新的理论依据。

  6. Pulmonary hyalinizing granuloma. Electron microscopic and immunologic studies.

    Science.gov (United States)

    Guccion, J G; Rohatgi, P K; Saini, N

    1984-04-01

    We present a case of pulmonary hyalinizing granuloma (PHG). On light microscopy, the pulmonary nodular lesions consisted of extracellular, eosinophilic hyaline lamellae. Histochemical stains of the hyaline lamellae for amyloid were focally positive and the diagnosis of amyloidosis was seriously considered; however, on electron microscopic examination, the hyaline lamellae consisted of electrondense, compact, amorphous material quite unlike fibrillar amyloid. Although circulating immune complexes containing IgA were detected in our patient, immunoperoxidase stains did not reveal immunoglobulins in the hyaline lamellae. This case illustrates the value of electron microscopy in differentiating PHG from amyloidosis and supports the hypothesis that PHG represents an exaggerated immune response. PMID:6200274

  7. Aprotininskintigrafi ved amyloidose

    DEFF Research Database (Denmark)

    Haraldsen, Ate; Eskild-Jensen, Anni; Frøkiær, Jørgen

    2009-01-01

    Amyloidosis is a disease characterized by protein deposition (amyloid) in THE extracellular matrix leading to organ dysfunction and death. New treatment modalities have emphasized the need for accurate and early diagnosis. Aprotinin scintigraphy is a radionuclide imaging technique in which...... the localisation and extent of amyloid deposits are visualized. It is specific and sensitive in detecting cardiac amyloidosis, which is associated with a poor prognosis. In addition, aprotinin scintigraphy appears to be a useful tool for the monitoring of disease progression and treatment efficacy. Udgivelsesdato...

  8. Hereditär hjärnblödning. Demens vid cystatin C amyloidos

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur;

    1990-01-01

    Nineteen cases of hereditary cystatin C amyloidosis with cerebral haemorrhage are described. The first haemorrhage occurred between the ages of 20 and 41 years and the period of survival varied from 10 days to 23 years after the first insult. Progressive dementia was a striking clinical symptom...... in 17 of the patients and in two cases dementia was the first sign. At the last examination severe dementia and pronounced pathological EEG were established in the majority of the patients. Infiltration of amyloid substance positive for anti-cystatin C was found in the proximity of the blood vessels...... the name Hereditary Cystatin C Amyloidosis (HCCA)....

  9. transthyretin — EDRN Public Portal

    Science.gov (United States)

    Transthyretin, one of the three prealbumins including alpha-1-antitrypsin, transthyretin and orosomucoid, is a carrier protein that transports thyroid hormones in the plasma and cerebrospinal fluid, and also transports retinol (vitamin A) in the plasma. TT consists of a tetramer of identical subunits. More than 80 different mutations in this gene have been reported; most mutations are related to amyloid deposition, affecting predominantly peripheral nerve and/or the heart, and a small portion of the gene mutations is non-amyloidogenic. The diseases caused by mutations include amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis, and carpal tunnel syndrome.

  10. RAPID AUTOMATED ENZYME-IMMUNOASSAY OF SERUM AMYLOID-A

    NARCIS (Netherlands)

    WILKINS, J; GALLIMORE, [No Value; TENNENT, GA; HAWKINS, PN; LIMBURG, PC; VANRIJSWIJK, MH; MOORE, EG; PEPYS, MB

    1994-01-01

    Serum amyloid A (SAA), a sensitive acute-phase protein, is the precursor of AA fibrils in reactive amyloidosis. However, SAA is poorly immunogenic, and development and standardization of immunoassays of this protein have been difficult. We established an automated polyclonal/ monoclonal microparticl

  11. Parotid Gland Biopsy, the Alternative Way to Diagnose Sjögren Syndrome

    NARCIS (Netherlands)

    Spijkervet, Fred K L; Haacke, Erlin; Kroese, Frans G M; Bootsma, Hendrika; Vissink, Arjan

    2016-01-01

    Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjögren syndrome (SS), lymphoma in SS, and connective tissue disorders (sarcoidosis, amyloidosis). In SS characteristic histology findings are found, including lymphocytic infiltration surrounding the excretory ducts in combin

  12. Aggregation and cytotoxic properties towards cultured cerebrovascular cells of Dutch-mutated Abeta40 (DAbeta(1-40)) are modulated by sulfate moieties of heparin.

    NARCIS (Netherlands)

    Timmer, N.M.; Schirris, T.J.J.; Bruinsma, I.B.; Otte-Holler, I.; Kuppevelt, A.H.M.S.M. van; Waal, R.M.W. de; Verbeek, M.M.

    2010-01-01

    Glycosaminoglycans (GAGs), in particular as part of heparan sulfate proteoglycans, are associated with cerebral amyloid angiopathy (CAA). Similarly, GAGs are also associated with the severe CAA found in patients suffering from hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-

  13. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET

    DEFF Research Database (Denmark)

    Antoni, Gunnar; Lubberink, Mark; Estrada, Sergio;

    2013-01-01

    UNLABELLED: Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used in the eval...

  14. Inhibition of amyloid-beta-induced cell death in human brain pericytes in vitro.

    NARCIS (Netherlands)

    Rensink, A.A.M.; Verbeek, M.M.; Otte-Holler, I.; Donkelaar, H.J. ten; Waal, R.M.W. de; Kremer, H.P.H.

    2002-01-01

    Amyloid-beta protein (A beta) deposition in the cerebral vascular walls is one of the key features of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). A beta(1-40) carrying the 'Dutch' mutation (HCHWA-D A beta(1-40)) induces pronounced degeneration of cul

  15. Cardiac resynchronization therapy in a patient with amyloid cardiomyopathy.

    Science.gov (United States)

    Zizek, David; Cvijić, Marta; Zupan, Igor

    2013-06-01

    Cardiac involvement in systemic light chain amyloidosis carries poor prognosis. Amyloid deposition in the myocardium can alter regional left ventricular contraction and cause dyssynchrony. Cardiac resynchronization therapy (CRT) is an effective treatment strategy for patients with advanced heart failure and echocardiographic dyssynchrony. We report a clinical and echocardiographic response of a patient with amyloid cardiomyopathy, treated with a combination of chemotherapy and CRT.

  16. A 47-year-old man with tongue swelling.

    Science.gov (United States)

    Rodríguez-Roa, Maristely; Nazario, Sylvette; Ramos, Cristina

    2016-07-01

    Intermittent tongue angioedema can be the initial presentation of several disorders including angiotensin-converting-enzyme inhibitor induced angioedema and hereditary angioedema. Persistent angioedema on the other hand, can be associated with amyloidosis, tumors, thyroid disorders and acromegaly. We present a case of intermittent episodes of tongue swelling progressing to macroglossia. PMID:27401321

  17. Genetic alterations of the BR12 Gene: familial British and Danish dementias

    DEFF Research Database (Denmark)

    Ghiso, J.; Rostagno, A.; Tomidokoro, Y.;

    2006-01-01

    Classic arguments sustaining the importance of amyloid in the pathogenesis of dementia are usually centered on amyloid β (Aβ) and its role in neuronal loss characteristic of Alzheimer disease, the most common form of human cerebral amyloidosis. Two non-Aβ cerebral amyloidoses, familial British an...

  18. Alkaptonuria is a novel human secondary amyloidogenic disease

    Science.gov (United States)

    Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2012-01-01

    Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates. PMID:22850426

  19. Blood values of captive beira antelope (Dorcatragus megalotis) prior to and during an outbreak of fibrinous pleuropneumonia syndrome (FPPS).

    Science.gov (United States)

    Gull, Jessica M; Hebel, Christiana; Deb, Amrita; Arif, Abdi; Clauss, Marcus; Hatt, Jean-Michel; Hammer, Sven

    2014-12-01

    Currently the only captive population of beira antelope (Dorcatragus megalotis) is held at the Al Wabra Wildlife Preservation, Qatar. An outbreak of a severe respiratory disease--fibrinous pleuropneumonia syndrome, most likely caused by Mycoplasma ovipneumoniae--led to a marked population decline. Reactive systemic inflammatory (AA) amyloidosis was noted as a chronic manifestation of the disease. Blood samples had been collected for biochemistry and hematology baseline values prior to the outbreak. Population-level changes were analyzed before and during the course of the outbreak in selected blood parameters (white blood cells [WBC], blood urea nitrogen [BUN], and creatinine). The annual population WBC increased and decreased concurrently with the population size, with a significant correlation between the two measures (R = 0.92; P = 0.001). Both BUN and creatinine values were higher during the outbreak. These values peaked at the same time as mortality, which was 1 yr after the WBC peak. These changes were interpreted as the transition from an acute disease with a primary respiratory manifestation into a chronic condition where renal amyloidosis led to chronic renal failure and death. Also, elevated liver values in diseased animals were attributed to amyloidosis. Parallels to a literature report on a lung disease complex caused by M. ovipneumoniae in bighorn sheep (Ovis canadensis) were found. Trends in population-level blood values of the beira antelopes implicate amyloidosis as a significant, long-term consequence of the putative Mycoplasma infection.

  20. Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe

    DEFF Research Database (Denmark)

    Murugan, N. Arul; Olsen, Jógvan Magnus Haugaard; Kongsted, Jacob;

    2013-01-01

    Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T...

  1. Genetic microheterogeneity of human transthyretin detected by IEF

    NARCIS (Netherlands)

    Altland, Klaus; Benson, Merrill D.; Costello, Catherine E.; Ferlini, Alessandra; Hazenberg, Bouke R. C.; Hund, Ernst; Kristen, Arnt V.; Linke, Reinhold P.; Merlini, Giampaolo; Salvi, Fabrizio; Saraiva, Maria J.; Singer, Reinhard; Skinner, Martha; Winter, Pia

    2007-01-01

    Mutations of the human transthyretin (TTR) gene have attracted medical interest as a cause of amyloidosis. Recently, we have described in detail an electrophoretic procedure with PAGE followed by IEF in urea gradients for the study of the microheterogeneity of TTR monomers (Altland, K., Winter, P.,

  2. Hidradenitis supurativa in unusual sites

    Directory of Open Access Journals (Sweden)

    Gharami R

    2003-03-01

    Full Text Available A 35 year old man presented with multiple indurated plaques, studded with pus discharging sinuses and scarring on both legs for last 15 years. He was also having lichen amyloidosis on both forearms, Pus culture yielded growth of Staphylococcus aureus and tissue culture excluded deep fungal infection and mycobacterium tuberculosis bacilli.

  3. Hidradenitis supurativa in unusual sites

    Directory of Open Access Journals (Sweden)

    Gharami R

    2003-01-01

    Full Text Available A 35 year old man presented with multiple indurated plaques, studded with pus discharging sinuses and scarring on both legs for last 15 years. He was also having lichen amyloidosis on both forearms, Pus culture yielded growth of Staphylococcus aureus and tissue culture excluded deep fungal infection and mycobacterium tuberculosis bacilli.

  4. Native human serum amyloid P component is a single pentamer

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH;

    1995-01-01

    Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer...

  5. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2016-10-03

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  6. Glycosaminoglycans enhance the fibrillation propensity of the ß2-microglobulin cleavage variant--¿K58-ß2m

    DEFF Research Database (Denmark)

    Corlin, Dorthe B; Johnsen, Christina K; Nissen, Mogens H;

    2010-01-01

    Dialysis related amyloidosis (DRA) is a serious complication to long-term hemodialysis treatment which causes clinical symptoms such as carpal tunnel syndrome and destructive arthropathies. The disease is characterized by the assembly and deposition of ß2-microglobulin (ß2m) predominantly...

  7. Processing of nerve biopsies: a practical guide for neuropathologists.

    NARCIS (Netherlands)

    Weis, J.; Brandner, S.; Lammens, M.M.Y.; Sommer, C.; Vallat, J.M.

    2012-01-01

    Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that c

  8. Immunoglobulin-free light chain monomer-dimer patterns help to distinguish malignant from premalignant monoclonal gammopathies: a pilot study.

    Science.gov (United States)

    Kaplan, Batia; Golderman, Sizilia; Aizenbud, Boris; Esev, Konstantin; Kukuy, Olga; Leiba, Merav; Livneh, Avi; Ben-Zvi, Ilan

    2014-09-01

    Multiple myeloma (MM) and AL amyloidosis (AL) are two malignant forms of monoclonal gammopathies. For the purposes of prognosis and treatment, it is important to distinguish these diseases from the premalignant forms of monoclonal gammopathies, such as monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma (SMM). Routine serum/urine tests for monoclonal protein are insufficient for differential diagnosis. Thus, invasive procedures, such as tissue aspiration or biopsy, are applied. In this study, we aimed at characterization of serum-free light chain (FLC) monomer-dimer patterns to distinguish the malignant from the premalignant forms of monoclonal gammopathies. A quantitative Western blotting was applied to estimate the FLC monomer and dimer levels in AL, MM, MGUS, and SMM patients, and in control subjects (healthy individuals and patients with AA amyloidosis). AL and MM patients displayed an abnormally increased dimerization of monoclonal FLC, accompanied by higher clonality values of FLC dimers, as compared to that of monomers. These abnormalities of FLC patterns were not observed in patients with MGUS, SMM, AA amyloidosis, and healthy individuals. Analysis of FLC patterns helped to differentiate AL and MM from MGUS and SMM, a goal difficult to achieve using routine serum tests. Also, our technique might serve as a complimentary diagnostic tool in the cases with suspected AL amyloidosis, where the diagnosis of MM is excluded, while the results of amyloid typing by routine immunohistochemical techniques are inconclusive. PMID:24866208

  9. The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias: Etiologic Implications.

    Science.gov (United States)

    Hemminki, Kari; Försti, Asta; Tuuminen, Raimo; Hemminki, Otto; Goldschmidt, Hartmut; Sundquist, Kristina; Sundquist, Jan; Li, Xinjun

    2016-01-01

    Plasma cell dyscrasias, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia (WM) and light chain AL amyloidosis, are characterized by clonal expansion of plasma cells which produce a vast amount of an immunoglobulin-derived M-protein. We noted that MGUS diagnosis often coincided with diagnoses of senile cataract and glaucoma and tested the associations of MGUS, MM, WM and AL amyloidosis with subsequent eye diseases identified from the Swedish patient registers between 1997 and 2012. Standardized incidence ratios (SIRs) for senile cataract was significantly increased to 1.80 after MGUS, 1.70 after MM, 1.85 after WM and 2.31 after AL amyloidosis. The SIR for glaucoma was 1.60 after MGUS, 1.76 after WM and 2.18 after AL amyloidosis. All SIRs decreased systematically from age below 60 years to over 79 years, but most risks were also significant in age group over 79 years. The M-protein and the related increase in blood viscosity could be a novel etiologic discovery for these common eye diseases. As MGUS prevalence is around 3% at 60 years and close to 10% at age over 80 years, its contribution to the eye disease burden is expected to be remarkably high. PMID:27328652

  10. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity

    OpenAIRE

    Hammarström, Per; Jiang, Xin; Hurshman, Amy R.; Powers, Evan T.; Kelly, Jeffery W.

    2002-01-01

    Several misfolding diseases commence when a secreted folded protein encounters a partially denaturing microenvironment, enabling its self assembly into amyloid. Although amyloidosis is modulated by numerous environmental and genetic factors, single point mutations within the amyloidogenic protein can dramatically influence disease phenotype. Mutations that destabilize the native state predispose an individual to disease; however, thermodynamic stability alone does not reliably predict disease...

  11. Laryngeal

    Directory of Open Access Journals (Sweden)

    Brahim Bouaity

    2014-11-01

    Conclusion: Laryngeal amyloidosis is essentially a local clinical form whose main symptom is dysphonia. The treatment is usually based on local endoscopic procedures but may require a laryngectomy in advanced forms, associated with colchicine. The prognosis is much better than systemic forms.

  12. A CLINICO-HISTOPATHOLOGICAL STUDY OF FRICTIONAL MELANOSIS

    Directory of Open Access Journals (Sweden)

    Keerthi Jampani

    2016-06-01

    Full Text Available OBJECTIVE The aim of the present study was to analyse different clinical patterns of frictional melanosis and to evaluate whether sun exposure is a causative or contributing factor for frictional melanosis. Furthermore, histopathology with haematoxylin and eosin along with special stains for amyloid like Congo red was done. METHODS 50 patients with clinical diagnosis of frictional melanosis participated in this study. INCLUSION CRITERIA Patients of all ages and both sexes with classical clinical features suggestive of frictional melanosis are included. EXCLUSION CRITERIA Patients having pigmentation over areas where the frictional melanosis presents classically but have been using chemicals, hair dyes and other agents which can cause photocontact dermatitis have been excluded from the study. A detailed history regarding duration of illness, progression and precipitating factors along with detailed clinical examination regarding the location of the lesions and type of lesions was done and patients were subjected to skin biopsy after obtaining a written consent. RESULTS Out of 50 cases, 39 (78% were confirmed with histopathology as frictional melanosis and 11(22% as macular amyloidosis. Among patients of frictional melanosis, 56.41% had only skin lesions. In macular amyloidosis 63.63% patients had itching along with skin lesions. In Frictional melanosis the most frequently involved site was extensor aspect of arm (78.48%. The most frequently involved site in macular amyloidosis was extensor aspect of forearm (93.34%. CONCLUSION In this study a total number of 50 patients with clinical presentation of frictional melanosis were analysed with female preponderance. Amyloid deposition is seen in those skin biopsy specimens taken from area of friction with sun exposure, which suggests that sun exposure could be one of the predisposing factors for macular amyloidosis. Thus, these findings confirm that frictional melanosis is a variant of macular

  13. Amyloid myopathy: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Heli Tuomaala

    2009-08-01

    Full Text Available Amyloid myopathy (AM is a rare manifestation of primary systemic amyloidosis (AL. Like inflammatory myopathies, it presents with proximal muscle weakness and an increased creatine kinase level. We describe a case of AL with severe, rapidly progressive myopathy as the initial symptom. The clinical manifestation and muscle biopsy were suggestive of inclusion body myositis. AM was not suspected until amyloidosis was seen in the gastric mucosal biopsy. The muscle biopsy was then re-examined more specifically, and Congo red staining eventually showed vascular and interstitial amyloid accumulation, which led to a diagnosis of AM. The present case illustrates the fact that the clinical picture of AM can mimic that of inclusion body myositis.

  14. Exons 16 and 17 of the amyloid precursor protein gene in familial inclusion body myopathy.

    Science.gov (United States)

    Sivakumar, K; Cervenáková, L; Dalakas, M C; Leon-Monzon, M; Isaacson, S H; Nagle, J W; Vasconcelos, O; Goldfarb, L G

    1995-08-01

    Accumulation of beta-amyloid protein (A beta) occurs in some muscle fibers of patients with inclusion body myopathy and resembles the type of amyloid deposits seen in the affected tissues of patients with Alzheimer's disease and cerebrovascular amyloidosis. Because mutations in exons 16 and 17 of the beta-amyloid precursor protein (beta APP) gene on chromosome 21 have been identified in patients with early-onset familial Alzheimer's disease and Dutch-type cerebrovascular amyloidosis, we searched for mutations of the same region in patients with familial inclusion body myopathy. Sequencing of both alleles in 8 patients from four unrelated families did not reveal any mutations in these exons. The amyloid deposition in familial forms of inclusion body myopathy may be either due to errors in other gene loci, or it is secondary reflecting altered beta APP metabolism or myocyte degeneration and cell membrane degradation.

  15. Long-term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Penninga, Luit; Sander, Kaare;

    2013-01-01

    . All patients suffered from severe cardiomyopathy. RESULTS: Mean recipient age at transplantation was 48.3 ± 4.2 yr. Mean follow-up was 55 months. No peroperative mortality occured. Two patients died within the first year (infection, multi-organ failure) of transplantation. Cumulative survival at 4......BACKGROUND: The amyloidogenic transthyretin (ATTR) mutation Leu111Met causes a primarily cardiac amyloidosis: Familial amyloidotic cardiomyopathy (FAC). Combined heart-liver transplantation (CHLTx) is the preferred treatment for patients with heart failure due to familial amyloidosis......, but information on outcome of patients with Leu111Met mutation is limited. The aim of this study was to evaluate the long-term outcome of CHLTx in patients with FAC. METHODS AND MATERIALS: Between 1998 and 2009, CHLTx was performed in 7 FAC patients (four men). Six patients underwent simultaneous transplantation...

  16. Primary hepatic amyloidosis: A case report and review ofliterature

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    We describe a case of 42-year-old female presentingwith abdominal pain associated with loss of weightand fever for 8 mo. On evaluation she had grosshepatomegaly with raised alkaline phosphatase andraised GGT levels with normal transaminases andbilirubin. On imaging she had diffuse enlargement ofliver with heterogeneous contrast uptake in liver. Herviral marker and autoimmune markers were negative.Liver biopsy depicted massive deposition of amyloidin peri-sinusoidal spaces which revealed apple greenbirefringence on polarizing microscopy after Congo redstaining. Cardiac and renal evaluation was unremarkable.Abdominal fat pad and rectum biopsy was negativefor amyloid deposit. There was no evidence of primaryamyloidosis as bone marrow examination was normal.Serum and urine immunofixation electrophoresiswerenormal. Immunoperoxidase staining for serum amyloidassociated protein for secondary amyloidosis wasnegative from liver biopsy. We present this rare case ofprimary hepatic amyloidosis and review the literatureregarding varied presentationsof hepatic involvement inamyloidosis.

  17. Solitary pulmonary amyloidoma mimicking lung cancer on 18F-FDG PET-CT scan in systemic lupus erythematosus patient.

    Science.gov (United States)

    Barešić, M; Sreter, K B; Brčić, L; Hećimović, A; Janevski, Z; Anić, B

    2015-12-01

    Localized amyloid deposits (tumoral amyloidosis or amyloidoma) are uncommon form of amyloidosis and nodular pulmonary amyloidomas are rarely found. This incidental finding can mimic a bronchopulmonary neoplasm and may occur secondarily to an infectious, inflammatory or lymphoproliferative disease. We report a case of a 62-year-old female with long-standing systemic lupus erythematosus (SLE) with low compliance who presented with radiologically-verified solitary pulmonary nodule. Work-up included positron emission tomography-computed tomography (PET-CT) scan, which revealed hypermetabolic uptake of (18)F-fluorodeoxyglucose, and lobectomy was performed. Staining of the tissue was positive for Congo red and was green birefringent under polarized light. Immunohistochemical methods excluded lymphoproliferative disease and confirmed amyloidoma. SLE was controlled with antimalarials and glucocorticoids. Pulmonary amyloidoma should be considered in the differential diagnosis of solitary lung nodules.

  18. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

    OpenAIRE

    Boers, M.; Croonen, A M; Dijkmans, B A; Breedveld, F C; Eulderink, F.; Cats, A.; Weening, J.J.

    1987-01-01

    Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and no...

  19. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

    Science.gov (United States)

    Boers, M; Croonen, A M; Dijkmans, B A; Breedveld, F C; Eulderink, F; Cats, A; Weening, J J

    1987-09-01

    Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities. PMID:3675007

  20. Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

    OpenAIRE

    Carl Julien; François Marcouiller; Alexis Bretteville; El Khoury, Noura B.; Joanie Baillargeon; Sébastien S Hébert; Emmanuel Planel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphor...

  1. Lichen amyloidosus: A study of clinical, histopathologic and immunofluorescence findings in 30 cases

    OpenAIRE

    Salim T; Shenoi S; Balachandran C; Mehta Vandana

    2005-01-01

    BACKGROUND: Lichen amyloidosus (LA) is a primary localized cutaneous amyloidosis characterized clinically by discrete hyperkeratotic hyperpigmented papules and histologically by deposition of amyloid material in previously normal skin without any evidence of visceral involvement. AIMS AND OBJECTIVES: The aim of this work was to study the etiology, clinical features, histopathology and direct immunofluorescence findings in LA. METHODS: A prospective study of 30 patients with clinical, his...

  2. Amyloid myopathy presenting with respiratory failure.

    OpenAIRE

    Ashe, J.; Borel, C O; Hart, G.; Humphrey, R L; Derrick, D A; Kuncl, R W

    1992-01-01

    Amyloidosis is a rare cause of myopathy. Its prominent or presenting feature may be respiratory failure. Physiological measurement of transdiaphragmatic pressure and biopsy specimens of muscle show the pathological mechanism to be diaphragm weakness due to amyloid infiltration of the diaphragm rather than parenchymal lung involvement. Thus amyloid myopathy even without the typical macroglossia and muscle pseudohypertrophy should be considered as one of the neurological causes of respiratory f...

  3. A Case of Immunotactoid Glomerulopathy with Rapid Progression to End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Shikha Jain

    2009-01-01

    Full Text Available Immunotactoid glomerulopathy (IGN is a rare immunoglobulin deposition disease. It is often mistaken for cryoglobulinemia or amyloidosis due to the similarities on biopsy findings. The disease progresses to end-stage renal disease (ESRD within 7 months to 10 years. This is the first case reported of a patient with a diagnosis of IGN who developed acute kidney injury (AKI and ESRD within 1 week of initial presentation.

  4. Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens

    OpenAIRE

    Kuemmerle-Deschner, Jasmin B; Wittkowski, Helmut; Tyrrell, Pascal N; Koetter, Ina; Lohse, Peter; Ummenhofer, Katharina; Reess, Fabian; Hansmann, Sandra; Koitschev, Assen; Deuter, Christoph; Bialkowski, Anja; Foell, Dirk; Benseler, Susanne M.

    2013-01-01

    Objectives Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subclinical disease activity is commonly observed. Canakinumab, a fully human IgG1 anti-IL-1β monoclonal antibody, can abolish excess IL-1β. The study aim was to analyze the efficac...

  5. The “other” vasculitis syndromes and kidney involvement

    OpenAIRE

    Ozen, Seza

    2009-01-01

    There are a number of vasculitides that are not confined to a specific vessel size, do not have characteristic features, and/or are not secondary to another disease. Most of these vasculitides are rare in childhood. Behçet disease is representative of this group as it involves vessels of any size on both the arterial and venous side. In addition to renal vascular involvement, Behçet disease may involve the kidney through glomerulonephritis, secondary amyloidosis and, rarely, tubulointerstital...

  6. The Flavonoid Luteolin, but Not Luteolin-7-O-Glucoside, Prevents a Transthyretin Mediated Toxic Response

    OpenAIRE

    Irina Iakovleva; Afshan Begum; Malgorzata Pokrzywa; Malin Walfridsson; Elisabeth Sauer-Eriksson, A.; Anders Olofsson

    2015-01-01

    Transthyretin (TTR) is a homotetrameric plasma protein with amyloidogenic properties that has been linked to the development of familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy, and senile systemic amyloidosis. The in vivo role of TTR is associated with transport of thyroxine hormone T4 and retinol-binding protein. Loss of the tetrameric integrity of TTR is a rate-limiting step in the process of TTR amyloid formation, and ligands with the ability to bind within t...

  7. Alkaptonuria is a novel human secondary amyloidogenic disease

    OpenAIRE

    Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico

    2012-01-01

    Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human c...

  8. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria

    OpenAIRE

    Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

    2013-01-01

    Objective. Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. Methods. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had prev...

  9. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer´s mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan; Metaxas, Athanasios; Vea, Maria Ibanez;

    2016-01-01

    The aim of this study was to elucidate the molecular signature of Alzheimer ́s disease-associated amyloid pathology. We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycos...... disease states in patients with Alzheimer´s disease....

  10. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.

    OpenAIRE

    Pepys, M B; Rademacher, T W; Amatayakul-Chantler, S.; Williams, P.; Noble, G. E.; Hutchinson, W L; Hawkins, P N; Nelson, S R; Gallimore, J. R.; Herbert, J.

    1994-01-01

    Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyl...

  11. Vitamin E but not 17B-estradiol protect against vascular toxicity induced by B-amyloid wild type and the Dutch amyploid variant

    OpenAIRE

    Mu??oz L??pez, Francisco Jos??, 1964-; Opazo, Carlos; Gil G??mez, Gabriel; Tapia, Gladys; Fern??ndez, Virginia; Valverde, M A; Nibaldo C Inestrosa

    2002-01-01

    Amyloid ??-peptide (A??) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in A?? yielding A??Glu22???Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated A?? on vascular cells, as well as the putative protect...

  12. The use of biomarkers for the etiologic diagnosis of MCI in Europe

    DEFF Research Database (Denmark)

    Bocchetta, Martina; Galluzzi, Samantha; Kehoe, Patrick Gavin;

    2015-01-01

    usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aβ42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75......We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic...

  13. Kidney involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    P. Lazzarini

    2011-09-01

    Full Text Available Rheumatoid Arthritis (RA is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively, followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy. Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment, followed by minimal change glomerulopathy (3-14% and p-ANCA positive necrotizing crescentic

  14. Pulmonary Idiopathic Alveolar Ossification in a Raccoon (Procyon lotor)

    OpenAIRE

    Hamir, Amir N; Rupprecht, Charles E.

    2010-01-01

    Here we describe gross and histopathologic findings in a laboratory-confined adult male raccoon (Procyon lotor) with microscopic ossified areas in pulmonary alveoli. At the time of necropsy, gross lesions were present in the kidneys and in one thyroid gland. Noteworthy microscopic findings included multifocal foci of osseous tissue within the alveoli of the lungs, bilateral thyroid adenomas, pancreatic islet cell amyloidosis, cortical kidney infarcts, cystic adenomatous hyperplasia of urinary...

  15. Screening Panels for Monoclonal Gammopathies: Time to Change

    OpenAIRE

    Katzmann, Jerry A.

    2009-01-01

    The introduction of quantitative assays for serum free light chains (FLC) has changed the approach to screening for monoclonal gammopathies. Recent guidelines from the International Myeloma Working Group have recommended the use of serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and FLC as the screening panel unless primary amyloidosis (AL) is suspected. If screening for AL, then urine IFE should also be performed. We discuss the background for these recommendations...

  16. Disease: H01185 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01185 Cerebral amyloid angiopathy (CAA); Hereditary cerebral hemorrhage with amylo...h aging, several familial forms of CAA reported to date. Hereditary cystatin C am...M, Magoni M, Padovani A, Tagliavini F Hereditary cerebral hemorrhage with amyloidosis associated with the E6...93K mutation of APP. Arch Neurol 67:987-95 (2010) PMID:16612982 Palsdottir A, Snorradottir AO, Thorsteinsson L Hereditary

  17. Renal phospholipidosis possibly induced by ranolazine

    OpenAIRE

    Scheurle, Christoph; Dämmrich, Maximilian; Jan U. Becker; Baumgärtel, Martin W.

    2013-01-01

    A 76-year-old male Caucasian patient was treated in our hospital for acutely decompensated heart failure due to restrictive cardiomyopathy. Acute-on-chronic kidney failure developed with serum creatinine rising from 160 to 345 μmol/L (1.8–3.9 mg/dL); therefore, a kidney biopsy was performed. Besides secondary focal-segmental glomerulosclerosis and minimal amyloidosis, histological analysis showed zebra bodies in the cytoplasm of some podocytes, suggesting renal phospholipidosis (PL). Possible...

  18. Hereditary Amyloid Cardiomyopathy Caused by a Variant Apolipoprotein A1

    OpenAIRE

    Hamidi Asl, Ladan; Liepnieks, Juris J.; Hamidi Asl, Kamran; Uemichi, Tomoyuki; Moulin, Georges; Desjoyaux, Emmanuel; Loire, Robert; Delpech, Marc; Grateau, Gilles; Benson, Merrill D.

    1999-01-01

    Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac presentation and death from heart failure by the sixth or seventh decade was found to be associated with a previously unreported point mutation (thymine to cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene. The predicted substitution of proline for leucine at amino acid position 90 was confirmed by structural analysis of amyloid protein isolated from cardiac deposits of amyloid. The subunit protein ...

  19. Transthyretin ur ett strukturellt perspektiv

    OpenAIRE

    Hörnberg, Andreas

    2004-01-01

    Conformational changes in human proteins can induce several types of diseases. The nature of the conformational changes is largely unknown, but some lead to amyloid fibril formation. Amyloid fibrils accumulate in the extra-cellular space of tissues resulting in disruption of organ function. Transthyretin (TTR) is a plasma protein involved in three amyloid diseases, familial amyloidotic polyneuropathy, familial amyloidotic cardiomyopathy, and senile systemic amyloidosis. The latter disease inv...

  20. Contemporary treatment of amyloid heart disease.

    Science.gov (United States)

    Palecek, Tomas; Fikrle, Michal; Nemecek, Eduard; Bauerova, Lenka; Kuchynka, Petr; Louch, William E; Spicka, Ivan; Rysava, Romana

    2015-01-01

    The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in β-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied. PMID:25483951

  1. Studies of amyloid toxicity in Drosophila models and effects of the BRICHOS domain

    OpenAIRE

    Hermansson Wik, Erik

    2015-01-01

    Amyloid diseases involve specific protein misfolding events and formation of fibrillar deposits. The symptoms of these diseases are broad and dependent on site of accumulation, with different amyloid proteins depositing in specific tissues or systematically. One such protein is transthyretin (TTR) associated with senile systemic amyloidosis, familial amyloid polyneuropathy and familial amyloid cardiomyopathy. We show that the glycosaminoglycan heparan sulfate (HS) can be co-loc...

  2. Experimentally Derived Structural Constraints for Amyloid Fibrils of Wild-Type Transthyretin

    OpenAIRE

    Bateman, David A.; Tycko, Robert; Wickner, Reed B.

    2011-01-01

    Transthyretin (TTR) is a largely β-sheet serum protein responsible for transporting thyroxine and vitamin A. TTR is found in amyloid deposits of patients with senile systemic amyloidosis. TTR mutants lead to familial amyloidotic polyneuropathy and familial amyloid cardiomyopathy, with an earlier age of onset. Studies of amyloid fibrils of familial amyloidotic polyneuropathy mutant TTR suggest a structure similar to the native state with only a simple opening of a β-strand-loop-strand region e...

  3. A new transthyretin mutation associated with amyloid cardiomyopathy.

    OpenAIRE

    Saraiva, M.J.; Almeida, M do R; Sherman, W.; Gawinowicz, M; Costa, P.; Costa, P. P.; Goodman, D S

    1992-01-01

    In transthyretin (TTR) a new mutation (TTR-Thr45) has been identified in a patient with familial amyloidosis characterized clinically by prominent cardiomyopathy and the absence of peripheral neuropathy. Comparative peptide mapping by high-performance liquid chromatography of the patient's plasma TTR together with normal TTR showed the presence of an abnormal tryptic peptide in the patient's TTR. The sequence of this peptide (peptide 6, residues 36-48) demonstrated the presence of a threonine...

  4. 4′-Iodo-4′-Deoxydoxorubicin Disrupts the Fibrillar Structure of Transthyretin Amyloid

    OpenAIRE

    Palha, Joana Almeida; Ballinari, Dario; Amboldi, Nadia; Cardoso, Isabel; Fernandes, Rui; Bellotti, Vittorio; Merlini, Giampaolo; Saraiva, Maria João

    2000-01-01

    Transthyretin (TTR) is a tetrameric protein synthesized mainly by the liver and the choroid plexus, from where it is secreted into the plasma and the cerebrospinal fluid, respectively. Some forms of polyneuropathy, vitreopathy, and cardiomyopathy are caused by the deposition of normal and/or mutant TTR molecules in the form of amyloid fibrils. Familial amyloidotic polyneuropathy is the most common form of TTR amyloidosis related to the V30M variant. It is still unclear the process by which so...

  5. A new transthyretin variant (Ser 24) associated with familial amyloid polyneuropathy.

    OpenAIRE

    Uemichi, T; Gertz, M A; Benson, M D

    1995-01-01

    An American kindred with systemic amyloidosis presenting with carpal tunnel syndrome, peripheral neuropathy, and cardiomyopathy is reported. The transthyretin gene of a patient was analysed by direct DNA sequencing and both cytosine and thymine were present at the first base of codon 24. This new point mutation in exon 2 results in the amino acid substitution of serine for proline in the A-B loop of the transthyretin molecule. DNA testing for this mutant allele by restriction fragment length ...

  6. Potent Kinetic Stabilizers that Prevent Transthyretin-mediated Cardiomyocyte Proteotoxicity

    OpenAIRE

    Alhamadsheh, Mamoun M; Connelly, Stephen; Cho, Ahryon; Reixach, Natàlia; Powers, Evan T.; Pan, Dorothy W.; Wilson, Ian A.; Kelly, Jeffery W.; Graef, Isabella A.

    2011-01-01

    The V122I mutation that alters the stability of transthyretin (TTR) affects 3–4% of African Americans and leads to amyloidogenesis and development of cardiomyopathy. In addition, 10–15% of individuals over the age of 65 develop senile systemic amyloidosis (SSA) and cardiac TTR deposits due to wild-type TTR amyloidogenesis. As no approved therapies for TTR amyloid cardiomyopathy are available, the development of drugs that prevent amyloid-mediated cardiotoxicity is desired. To this aim, we dev...

  7. Extrahepatic production of acute phase serum amyloid A

    OpenAIRE

    Upragarin, N.; Landman, W.J.M.; Gaastra, W; Gruys, E.

    2005-01-01

    Amyloidosis is a group of diseases characterized by the extracellular deposition of protein that contains non-branching, straight fibrils on electron microscopy (amyloid fibrils) that have a high content of ß-pleated sheet conformation. Various biochemically distinct proteins can undergo transformation into amyloid fibrils. The precursor protein of amyloid protein A (AA) is the acute phase protein serum amyloid A (SAA). The concentration of SAA in plasma increa...

  8. b2-Microglobuline Plasma Level and Painful Shoulder in Haemodialysed Patients

    OpenAIRE

    Barišić, Igor; Ljutić, Dragan; Vlak, Tonko; Bekavac, Josip; Perić, Irena; Miše, Kornelija; Klančnik, Marisa; Janković, Stipan

    2010-01-01

    Painful shoulder in patients on chronic haemodialyis is most often associated with dialysis arthropathy or accumulation of deposits containing modified fibrils of b2- microglobuline especially in bones and joints due to insufficient elimination during the therapy. The aim of this study is to investigate whether there is connection between painful shoulder and plasma level of b2-microglobuline and to corroborate that with morphologic parameters found in proved amyloidosis. It has to be emphasi...

  9. SAP: structure, function, and its roles in immune-related diseases.

    Science.gov (United States)

    Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

    2015-01-01

    Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system.

  10. Amyloidogenic potential of foie gras.

    Science.gov (United States)

    Solomon, Alan; Richey, Tina; Murphy, Charles L; Weiss, Deborah T; Wall, Jonathan S; Westermark, Gunilla T; Westermark, Per

    2007-06-26

    The human cerebral and systemic amyloidoses and prion-associated spongiform encephalopathies are acquired or inherited protein folding disorders in which normally soluble proteins or peptides are converted into fibrillar aggregates. This is a nucleation-dependent process that can be initiated or accelerated by fibril seeds formed from homologous or heterologous amyloidogenic precursors that serve as an amyloid enhancing factor (AEF) and has pathogenic significance in that disease may be transmitted by oral ingestion or parenteral administration of these conformationally altered components. Except for infected brain tissue, specific dietary sources of AEF have not been identified. Here we report that commercially available duck- or goose-derived foie gras contains birefringent congophilic fibrillar material composed of serum amyloid A-related protein that acted as a potent AEF in a transgenic murine model of secondary (amyloid A protein) amyloidosis. When such mice were injected with or fed amyloid extracted from foie gras, the animals developed extensive systemic pathological deposits. These experimental data provide evidence that an amyloid-containing food product hastened the development of amyloid protein A amyloidosis in a susceptible population. On this basis, we posit that this and perhaps other forms of amyloidosis may be transmissible, akin to the infectious nature of prion-related illnesses.

  11. Semantic verbal fluency pattern, dementia rating scores and adaptive behavior correlate with plasma Aβ42 concentrations in Down syndrome young adults

    Directory of Open Access Journals (Sweden)

    Laura eDel Hoyo

    2015-11-01

    Full Text Available Down syndrome is an intellectual disability disorder in which language and, specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer’s disease, including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong Alzheimer’s disease predictor being the Semantic Verbal Fluency Task (SVFT a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP and the biological amyloidosis markers in Down syndrome. In the current study, we used the SVFT in young adults with Down syndrome to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR, the Adaptive Behavior Assessment System-Second Edition (ABAS-II, and plasma levels of Aβ peptides (Aβ40 and Aβ42, as a potent biomarker of Alzheimer's disease. In Down syndrome, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ42 concentrations, a higher DMR score and impaired communication skills (ABAS–II. The total word production and switching ability in SVFT were good indicators of plasma Aβ42 concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with Down syndrome.

  12. C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia.

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Noto

    Full Text Available Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM. MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Light Chains (FLC are present in the serum and urine of many patients with plasma cell diseases. The biological differences between monoclonal FLCs, produced under malignant or benign dyscrasias, has not yet been characterized. In the present study, we show that endothelial and heart muscle cell lines internalize kappa and lambda FLCs. After internalization, FLCs are rerouted in the extracellular space via microvesicles and exosomes that can be re-internalized in contiguous cells. Only FLCs secreted from malignant B Lymphocytes were carried in Hsp70, annexin V, and c-src positive vesicles. In both MM and AL Amyloidosis patients we observed an increase in microvesicle and exosome production. Isolated serum vesicles from MM, AL Amyloidosis and monoclonal gammopathy of undetermined significance (MGUS patients contained FLCs. Furthermore MM and AL amyloidosis vesicles were strongly positive for Hsp70, annexin V, and c-src compared to MGUS and control patients. These are the first data implying that FLCs reroute via microvesicles in the blood stream, and also suggest a potential novel mechanism of c-src activation in plasma cell dyscrasia.

  13. Effect of Lysine Modification on the Stability and Cellular Binding of Human Amyloidogenic Light Chains

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Hugh Michael [ORNL; Davern, Sandra M. [University of Tennessee Graduate School of Medicine; Murphy, Charles L. [University of Tennessee Graduate School of Medicine; Wall, Jonathan [ORNL; Deborah, Weiss T. [University of Tennessee Graduate School of Medicine; Solomon, Alan [ORNL

    2011-01-01

    AL amyloidosis is characterized by the pathologic deposition as fibrils of monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs and tissues. This phenomenon has been attributed to the presence in amyloidogenic proteins of particular amino acids that cause these molecules to become unstable, as well as post-translational modifications and, in regard to the latter, we have investigated the effect of biotinylation of lysyl residues on cell binding. We utilized an experimental system designed to test if BJPs obtained from patients with AL amyloidosis or, as a control, multiple myeloma (MM), bound human fibroblasts and renal epithelial cells. As documented by fluorescent microscopy and ELISA, the amyloidogenic BJPs, as compared with MM components, bound preferentially and this reactivity increased significantly after chemical modification of their lysyl residues with sulfo-NHS-biotin. Further, based on tryptophan fluorescence and circular dichorism data, it was apparent that their conformation was altered, which we hypothesize exposed a binding site not accessible on the native protein. The results of our studies indicate that post-translational structural modifications of pathologic light chains can enhance their capacity for cellular interaction and thus may contribute to the pathogenesis of AL amyloidosis and multiple myeloma.

  14. Importance of pharmacokinetic studies in the management of acquired factor X deficiency.

    Science.gov (United States)

    Lim, Ming Y; McCarthy, Timothy; Chen, Sheh-Li; Rollins-Raval, Marian A; Ma, Alice D

    2016-01-01

    Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.

  15. Semantic Verbal Fluency Pattern, Dementia Rating Scores and Adaptive Behavior Correlate With Plasma Aβ42 Concentrations in Down Syndrome Young Adults.

    Science.gov (United States)

    Hoyo, Laura Del; Xicota, Laura; Sánchez-Benavides, Gonzalo; Cuenca-Royo, Aida; de Sola, Susana; Langohr, Klaus; Fagundo, Ana B; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

    2015-01-01

    Down syndrome (DS) is an intellectual disability (ID) disorder in which language and specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer's disease (AD), including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong AD predictor being the semantic verbal fluency task (SVFT) a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP) and the biological amyloidosis markers in DS. In the current study, we used the SVFT in young adults with DS to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR), the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and plasma levels of Aβ peptides (Aβ40 and Aβ42), as a potent biomarker of AD. In DS, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ42 concentrations, a higher DMR score and impaired communication skills (ABAS-II). The total word production and switching ability in SVFT were good indicators of plasma Aβ42 concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with DS. PMID:26635555

  16. THE SPECTRUM OF RENALDISEASEIN IRAN A POST-MORTEM STUDY

    Directory of Open Access Journals (Sweden)

    K. ARMIN

    1974-07-01

    Full Text Available In order to study the incidence and histopathological aspects of renal disease and its role in the mortality rate in Iran, the protocols of 4463 autopsies, performed in the last 15 years at the Tehran University Hospitals were reviewed. Among 4463 autopsies there were 861 cases (20 % of various renal diseases including 282 cases (32.75 % of disease of the interstitium, 176 cases (20.44 % of renal lesions in tuberculous patients, 112 cases (13.0 I % of vascular disease, 101 cases (I L73 % of diseases of the glomeruli, 48 cases (5.57 % of rheumatic carditis, 30 cases (3.48 % of epithelial nephrosis, 78 cases (3.25 % of non tuberculous amyloidosis, 28 cases (3.25 % of congenital malformation, 20 cases (2.37 % of non tuberculous diabetes, 13 cases (L51 % of neoplastic disease, 10 cases (1.16 % os septicemia, 8 cases (0.93 % of eclampsia and 5 cases (0.58 % of myelomatous kidney. The underlying diseases in 35 cases of nephrotic syndrome were: tuberculosis, II cases (31 %; Non-tuberculous amyloidosis, 6 cases (17 ;;,; chronic glomerulonephritis, 5 cases (14 %; chronic pyelonephritis, 3 cases (10 %; and acute pyelonephritis, one case. The kidney was severely affected in systemic amyloidosis in 64 cases.

  17. NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers.

    Science.gov (United States)

    Vos, Stephanie J B; Gordon, Brian A; Su, Yi; Visser, Pieter Jelle; Holtzman, David M; Morris, John C; Fagan, Anne M; Benzinger, Tammie L S

    2016-08-01

    The National Institute of Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and positron emission tomography imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural magnetic resonance imaging) with longitudinal clinical follow-up. Participants were classified in preclinical AD stage 1 (β-amyloidosis) or preclinical AD stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based on neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury and has important implications for clinical trials using biomarkers for enrollment or as surrogate end point measures. PMID:27318129

  18. A Case of Multiple Myeloma Diagnosed by Skin Lesions

    Directory of Open Access Journals (Sweden)

    Fatma Gülru Erdoğan

    2010-10-01

    Full Text Available Multiple myeloma, being a malignant proliferation of plasma cells in the bone marrow, has clinical spectrum varying from monoclonal gammopathy with unknown significance to plasma cell leukemia. The presenting symptoms have usually been bone pain, pathologic fractures or repeating infections. In patients with multiple myeloma, amyloid depositions may be seen in the skin. This form, defined as primary systemic amyloidosis, is characterized by light-chain amyloid fibril depositions. Our case applied with multiple, asymptomatic, yellowish papules localized on the face, trunk, oral and genital mucosa, gradually increasing during the last two years. He had no complaints, except for slight weight loss. In routine tests, the patient had no pathological laboratory findings, except high C-reactive protein levels. Further research revealed histopathologic and immunohistochemical findings consistent with amyloidosis. Upon these results, immunoglobulin G levels were measured and found high, and in protein electrophoresis, IgG monoclonal gammopathy was determined. The diagnosis of multiple myeloma is made by bone marrow biopsy. This patient is presented for being an asymptomatic case diagnosed by skin findings of amyloidosis.

  19. Specific localization and imaging of amyloid deposits in vivo using /sup 123/I-labeled serum amyloid P component

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, P.N.; Myers, M.J.; Epenetos, A.A.; Caspi, D.; Pepys, M.B.

    1988-03-01

    Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of /sup 123/I-labeled serum amyloid P component (SAP). Interestingly, a much higher proportion (up to 40%) of the injected dose of heterologous human SAP localized to amyloid and was retained there than was the case with isologous mouse SAP, indicating that human SAP binds more avidly to mouse AA fibrils than does mouse SAP. Specificity of SAP localization was established by the failure of the related proteins, human C-reactive protein and Limulus C-reactive protein, to deposit significantly in amyloid and by the absence of human SAP deposition in nonamyloidotic organs. However, only partial correlations were observed between the quantity of SAP localized and two independent estimates, histology and RIA for AA of the amount of amyloid in particular organs. It is not clear which of the three methods used reflects better the extent or clinical significance of the amyloid deposits but in vivo localization of radiolabeled SAP, detectable and quantifiable by gamma camera imaging, is apparently extremely sensitive. These findings establish the use of labeled SAP as a noninvasive in vivo diagnostic probe in experimental amyloidosis, potentially capable of revealing the natural history of the condition, and suggest that it may also be applicable generally as a specific targeting agent for diagnostic and even therapeutic purposes in clinical amyloidosis.

  20. A look into amyloid formation by transthyretin: aggregation pathway and a novel kinetic model.

    Science.gov (United States)

    Faria, Tiago Q; Almeida, Zaida L; Cruz, Pedro F; Jesus, Catarina S H; Castanheira, Pedro; Brito, Rui M M

    2015-03-21

    The aggregation of proteins into insoluble amyloid fibrils is the hallmark of many, highly debilitating, human pathologies such as Alzheimer's or Parkinson's disease. Transthyretin (TTR) is a homotetrameric protein implicated in several amyloidoses like Senile Systemic Amyloidosis (SSA), Familial Amyloid Polyneuropathy (FAP), Familial Amyloid Cardiomyopathy (FAC), and the rare Central Nervous System selective Amyloidosis (CNSA). In this work, we have investigated the kinetics of TTR aggregation into amyloid fibrils produced by the addition of NaCl to acid-unfolded TTR monomers and we propose a mathematically simple kinetic mechanism to analyse the aggregation kinetics of TTR. We have conducted circular dichroism, intrinsic tryptophan fluorescence and thioflavin-T emission experiments to follow the conformational changes accompanying amyloid formation at different TTR concentrations. Kinetic traces were adjusted to a two-step model with the first step being second-order and the second being unimolecular. The molecular species present in the pathway of TTR oligomerization were characterized by size exclusion chromatography coupled to multi-angle light scattering and by transmission electron microscopy. The results show the transient accumulation of oligomers composed of 6 to 10 monomers in agreement with reports suggesting that these oligomers may be the causative agent of cell toxicity. The results obtained may prove to be useful in understanding the mode of action of different compounds in preventing fibril formation and, therefore, in designing new drugs against TTR amyloidosis. PMID:25694367

  1. [Transthyretin-related amyloidotic cardiomyopathy: looking for the etiological treatment].

    Science.gov (United States)

    Longhi, Simone; Gagliardi, Christian; Milandri, Agnese; Manuzzi, Lisa; Rapezzi, Claudio

    2014-05-01

    Transthyretin (TTR)-related amyloidosis is a disease caused by the deposition of insoluble fibrils deriving from the misfolding of TTR, a protein mainly produced by the liver. In the hereditary form of the disease (ATTRm), protein misfolding is secondary to a mutation in the TTR gene. ATTRm can manifest with different phenotypes: mainly neurological, mainly cardiac, or mixed. In the senile form of the disease (wild-type TTR or SSA), the deposition of non-mutated TTR occurs and, clinically, cardiomyopathy is predominant. Cardiac amyloidosis is still an underdiagnosed disease and clinical heterogeneity makes the diagnosis challenging. Until recently, no specific pharmacological treatment was available, liver transplantation being the only therapeutic option aimed at slowing disease progression in ATTRm and treatment was based on symptom relief. This review focuses on the emerging pharmacological treatments for TTR-related amyloidosis targeting different steps of the amyloidogenic process (blocking hepatic TTR synthesis, TTR tetramer stabilization and promotion of TTR amyloid fibril clearance). PMID:25002169

  2. Peptide p5 binds both heparinase-sensitive glycosaminoglycans and fibrils in patient-derived AL amyloid extracts

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Emily B.; Williams, Angela [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Heidel, Eric [Department of Surgery, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Macy, Sallie [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Kennel, Stephen J. [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Department of Radiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Wall, Jonathan S., E-mail: jwall@utmck.edu [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Department of Radiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States)

    2013-06-21

    Highlights: •Polybasic peptide p5 binds human light chain amyloid extracts. •The binding of p5 with amyloid involves both glycosaminoglycans and fibrils. •Heparinase treatment led to a correlation between p5 binding and fibril content. •p5 binding to AL amyloid requires electrostatic interactions. -- Abstract: In previously published work, we have described heparin-binding synthetic peptides that preferentially recognize amyloid deposits in a mouse model of reactive systemic (AA) amyloidosis and can be imaged by using positron and single photon emission tomographic imaging. We wanted to extend these findings to the most common form of visceral amyloidosis, namely light chain (AL); however, there are no robust experimental animal models of AL amyloidosis. To further define the binding of the lead peptide, p5, to AL amyloid, we characterized the reactivity in vitro of p5 with in situ and patient-derived AL amyloid extracts which contain both hypersulfated heparan sulfate proteoglycans as well as amyloid fibrils. Histochemical staining demonstrated that the peptide specifically localized with tissue-associated AL amyloid deposits. Although we anticipated that p5 would undergo electrostatic interactions with the amyloid-associated glycosaminoglycans expressing heparin-like side chains, no significant correlation between peptide binding and glycosaminoglycan content within amyloid extracts was observed. In contrast, following heparinase I treatment, although overall binding was reduced, a positive correlation between peptide binding and amyloid fibril content became evident. This interaction was further confirmed using synthetic light chain fibrils that contain no carbohydrates. These data suggest that p5 can bind to both the sulfated glycosaminoglycans and protein fibril components of AL amyloid. Understanding these complex electrostatic interactions will aid in the optimization of synthetic peptides for use as amyloid imaging agents and potentially as

  3. Serum Amyloid P Component Ameliorates Neurological Damage Caused by Expressing a Lysozyme Variant in the Central Nervous System of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Linda Helmfors

    Full Text Available Lysozyme amyloidosis is a hereditary disease in which mutations in the gene coding for lysozyme leads to misfolding and consequently accumulation of amyloid material. To improve understanding of the processes involved we expressed human wild type (WT lysozyme and the disease-associated variant F57I in the central nervous system (CNS of a Drosophila melanogaster model of lysozyme amyloidosis, with and without co-expression of serum amyloid p component (SAP. SAP is known to be a universal constituent of amyloid deposits and to associate with lysozyme fibrils. There are clear indications that SAP may play an important role in lysozyme amyloidosis, which requires further elucidation. We found that flies expressing the amyloidogenic variant F57I in the CNS have a shorter lifespan than flies expressing WT lysozyme. We also identified apoptotic cells in the brains of F57I flies demonstrating that the flies' neurological functions are impaired when F57I is expressed in the nerve cells. However, co-expression of SAP in the CNS prevented cell death and restored the F57I flies' lifespan. Thus, SAP has the apparent ability to protect nerve cells from damage caused by F57I. Furthermore, it was found that co-expression of SAP prevented accumulation of insoluble forms of lysozyme in both WT- and F57I-expressing flies. Our findings suggest that the F57I mutation affects the aggregation process of lysozyme resulting in the formation of cytotoxic species and that SAP is able to prevent cell death in the F57I flies by preventing accumulation of toxic F57I structures.

  4. Long term management of patients with cryopyrin-associated periodic syndromes (CAPS: focus on rilonacept (IL-1 Trap

    Directory of Open Access Journals (Sweden)

    Leigh D Church

    2008-10-01

    Full Text Available Leigh D Church1, Sinisa Savic2, Michael F McDermott21Department of Rheumatology, Division of Immunity, Infection and Inflammation, Institute for Biomedical Research, The University of Birmingham, Birmingham, UK; 2Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, University of Leeds, Leeds, UKAbstract: Cryopyrin-associated periodic syndromes (CAPS are a group of inherited inflammatory disorders consisting of familial cold-induced autoinflammatory syndrome (FCAS, Muckle-Wells syndrome (MWS, and neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome. These rare disorders are associated with heterozygous mutations in the NLRP3 (CIAS1 gene, which encodes the protein NALP3 or cryopyrin, and inflammation driven by excessive production of the cytokine interleukin-1β (IL-1β. Amyloidosis is a serious complication with 25% of MWS patients developing amyloidosis, with occasional fatal consequences, whilst up to 20% of CINCA/NOMID patients die from various complications, before reaching the early adulthood. In some CINCA/NOMID adult survivors amyloidosis can also occur. Prior to the discovery of the CIAS1 gene mutations and the advent of IL-1 targeted therapy, treatment was aimed at suppressing inflammation, with limited success. The selective blockade of IL-1β, with anakinra (IL-1 receptor antagonist, not only provided supportive evidence for the role of IL-1β in CAPS, but also demonstrated the efficacy of targeting IL-1β for treatment of these conditions. In February, 2008, ‘Orphan Drug’ approval from the Food and Drug Administration (FDA for rilonacept (IL-1 Trap/Arcalyst™, Regeneron Pharmaceuticals, Inc was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS.Keywords: cryopyrin

  5. The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever

    Science.gov (United States)

    Güncan, Sabri; Bilge, N. Şule Y.; Cansu, Döndü Üsküdar; Kaşifoğlu, Timuçin; Korkmaz, Cengiz

    2016-01-01

    Objective This study aimed to investigate the frequency in which familial Mediterranean fever (FMF) coexists with other diseases and determine whether Mediterranean fever (MEFV) gene mutations are involved in such coexistence. Material and Methods In total, 142 consecutive patients with FMF investigated for MEFV mutation were enrolled in this study [Female: 87; Male: 55, mean age 32±12 years (11–62)]. All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. A previous diagnosis of inflammatory disorder other than FMF was considered true if it met the relevant criteria. MEFV mutations were divided into 2 groups, namely M694V and its subgroup (homozygous or heterozygous) (Group I) and others (Group II). Compound heterozygosity for M694V mutation was included in Group II to form a homogeneous group for Group I. Group I and Group II were compared according to phenotypical features. The presence of MEFV mutation was investigated in exons 2, 3, 5, and 10 by the multiplex-PCR reverse hybridization method. Results Concomitant disorders were found in 17 of 73 patients with FMF (23%) in Group I and 5 of 56 patients (8.9%) in Group II (p=0.04). Concomitant disorders in Group I were as follows: 7 cases of amyloidosis, 2 cases of Behcet’s disease (BD), 4 cases of ankylosing spondylitis (AS), 1 case of antiphospholipid syndrome, 1 case of Henoch–Schonlein purpura (HSP), 1 case of combination of psoriatic arthritis, HSP, and membranoproliferative glomerulonephritis, and 1 case of AS and amyloidosis. In Group II, the following disorders were found: 1 case of amyloidosis, 1 case of BD, 1 case of AS, 1 case of ulcerative colitis, and 1 case of vitiligo. Conclusion The presence of M694V mutation may predispose patients with FMF to developing other inflammatory disorders. PMID:27733942

  6. Monoclonal Gammopathy of Undetermined Significance with Amyloid Deposition in the Lung and Non-Amyloid Eosinophilic Deposition in the Brain: A Case Report

    Directory of Open Access Journals (Sweden)

    Francois Abi-Fadel

    2010-01-01

    Full Text Available Background. Monoclonal gammopathy of undetermined significance (MGUS is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic, incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA, antinuclear antibody (ANA, rheumatoid factor (RF, cryoglobulin, and antiglomerular basement membrane (anti-GBM antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always

  7. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984).

    Science.gov (United States)

    DiBartola, S P; Rutgers, H C; Zack, P M; Tarr, M J

    1987-05-01

    The historic, physical, laboratory, and histologic findings for 74 cats with chronic renal disease were reviewed. Most cats were older, and no breed or sex predilection was detected. This most common clinical signs detected by owners were lethargy, anorexia, and weight loss. Dehydration and emaciation were common physical examination findings. Common laboratory findings were nonregenerative anemia, lymphopenia, azotemia, hypercholesterolemia, metabolic acidosis, hyperphosphatemia, and isosthenuria. The most common morphologic diagnosis was chronic tubulointerstitial nephritis of unknown cause. The other pathologic diagnoses were renal lymphosarcoma, renal amyloidosis, chronic pyelonephritis, chronic glomerulonephritis, polycystic renal disease, and pyogranulomatous nephritis secondary to feline infectious peritonitis. PMID:3583899

  8. Parotid Gland Biopsy, the Alternative Way to Diagnose Sjögren Syndrome.

    Science.gov (United States)

    Spijkervet, Fred K L; Haacke, Erlin; Kroese, Frans G M; Bootsma, Hendrika; Vissink, Arjan

    2016-08-01

    Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjögren syndrome (SS), lymphoma in SS, and connective tissue disorders (sarcoidosis, amyloidosis). In SS characteristic histology findings are found, including lymphocytic infiltration surrounding the excretory ducts in combination with destruction of acinar tissue. In this article the main techniques are described for taking labial and parotid salivary gland biopsies with respect to their advantages, postoperative complications, and usefulness for diagnostic procedures, monitoring disease progression, and evaluation of treatment. PMID:27431350

  9. Diffuse abnormalities of the trachea: computed tomography findings

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Dept. de Radiologia]. E-mail: edmarchiori@gmail.com; Pozes, Aline Serfaty [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Escola de Medicina. Dept. de Radiologia; Escuissato, Dante Luiz [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Radiologia; Irion, Klaus Loureiro [The Cardiothoracic Centre NHS Trust, Liverpool (United Kingdom); Araujo Neto, Cesar de [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Dept. de Radiologia; Barillo, Jorge Luiz; Zanetti, Glaucia [Faculdade de Medicina de Petropolis (FMP), RJ (Brazil). Dept. de Cirurgia Clinica; Souza, Carolina Althoff [University of Ottawa, Ottawa, ON (Canada)

    2008-01-15

    The aim of this pictorial essay was to present the main computed tomography findings seen in diffuse diseases of the trachea. The diseases studied included amyloidosis, tracheobronchopathia osteochondroplastica, tracheobronchomegaly, laryngotracheobronchial papillomatosis, lymphoma, neurofibromatosis, relapsing polychondritis, Wegener's granulomatosis, tuberculosis, paracoccidioidomycosis, and tracheobronchomalacia. The most common computed tomography finding was thickening of the walls of the trachea, with or without nodules, parietal calcifications, or involvement of the posterior wall. Although computed tomography allows the detection and characterization of diseases of the central airways, and the correlation with clinical data reduces the diagnostic possibilities, bronchoscopy with biopsy remains the most useful procedure for the diagnosis of diffuse lesions of the trachea. (author)

  10. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Wadhwa, Vibhor; Thakkar, Rashmi S.; Carrino, John A.; Chhabra, Avneesh [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Maragakis, Nicholas; Hoeke, Ahmet; Sumner, Charlotte J.; Lloyd, Thomas E. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States); Belzberg, Allan J. [Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, MD (United States)

    2012-07-15

    Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions. (orig.)

  11. Biotechnologically engineered protein binders for applications in amyloid diseases.

    Science.gov (United States)

    Haupt, Christian; Fändrich, Marcus

    2014-10-01

    The aberrant self-assembly of polypeptide chains into amyloid structures is a common phenomenon in several neurodegenerative diseases, systemic amyloidosis, and 'normal' aging. Improvements in laboratory-scale detection of these structures, their clinical diagnosis, and the treatment of disease likely depend on the advent of new molecules that recognize particular states or induce their clearance in vivo. This review will describe what biotechnology can do to generate proteinaceous amyloid-binders, explain their molecular recognition mechanisms, and summarize possibilities to functionalize further these ligands for specific applications.

  12. Microfibrillar cardiomyopathy: A rare case

    Directory of Open Access Journals (Sweden)

    Narender Kumar

    2011-01-01

    Full Text Available Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM. The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.

  13. Urinary capillariosis in six dogs from Italy

    Directory of Open Access Journals (Sweden)

    A. Mariacher

    2016-06-01

    Full Text Available Canine urinary capillariosis is caused by the nematode Pearsonema plica. P. plica infection is seldomly detected in clinical practice mainly due to diagnostic limitations. This report describes six cases of urinary capillariosis in dogs from Italy. Recurrent cystitis was observed in one dog, whereas another patient was affected by glomerular amyloidosis. In the remaining animals, the infection was considered an incidental finding. Immature eggs of the parasite were observed with urine sediment examination in 3/6 patients. Increased awareness of the potential pathogenic role of P. plica. and clinical disease presentation could help identify infected animals.

  14. Free and Cued Memory in relation to Biomarker-Defined Abnormalities in Clinically Normal Older Adults and Those at Risk for Alzheimer’s Disease

    Science.gov (United States)

    Papp, Kathryn V.; Amariglio, Rebecca E.; Mormino, Elizabeth; Hedden, Trey; Dekhytar, Maria; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.

    2015-01-01

    Objectives Furthering our understanding of the relationship between amyloidosis (Aβ), neurodegeneration (ND), and cognition is imperative for early identification and early intervention of Alzheimer’s disease (AD). However, the subtle cognitive decline differentially associated with each biomarker-defined stage of preclinical AD has yet to be fully characterized. Recent work indicates that different components of memory performance (free and cued recall) may be differentially specific to memory decline in prodromal AD. We sought to examine the relationship between free and cued recall paradigms, in addition to global composites of memory, executive functioning, and processing speed in relation to stages of preclinical AD. Methods A total of 260 clinically normal (CN) older adults (CDR=0) from the Harvard Aging Brain study were grouped according to preclinical AD stages including Stage 0 (Aβ−/ND−), Stage 1 (Aβ+/ND−), Stage 2 (Aβ+/ND+), and suspected non-Alzheimer’s associated pathology (SNAP; Aβ−/ND+). General linear models controlling for age, sex, and education were used to assess for stage-based performance differences on cognitive composites of executive functioning, processing speed, and memory in addition to free and cued delayed recall on the Selective Reminding Test (SRT) and Memory Capacity Test (MCT). Results Global memory performance differed between preclinical stages with Stage 2 performing worse compared with Stage 0. When examining free and cued paradigms by memory test, only the MCT (and not the SRT) revealed group differences. More specifically, Stage 1 was associated with decrements in free recall compared with Stage 0 while Stage 2 was associated with decrements in both free and cued recall. There was a trend for the SNAP group to perform worse on free recall compared with Stage 0. Finally, there was no association between preclinical stage and global composites of executive functioning or processing speed. Conclusions Clinically

  15. Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions.

    Science.gov (United States)

    Pfeifer, Kyle; Mian, Ali; Adebowale, Adeniran; Alomari, Ahmed; Kalra, Vivek; Krejci, Elise; Shin, Myung Soo

    2016-05-01

    Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions. PMID:26690551

  16. Association between cortical thickness and CSF biomarkers in mild cognitive impairment and Alzheimer’s disease

    DEFF Research Database (Denmark)

    Mohades, Sara; Dubois, Jonathan; Parent, Maxime;

    regional cortical thinning (CT) measured by Magnetic Resonance Imaging (MRI) and brain amyloidosis (measured by CSF Ab 1-42 concentrations), or tau hyperphosphorylation (tau 181; p-tau) in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) patients. We test the hypothesis that the association...... (CN; n¼8) were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Cortical surface reconstruction and group registration were generated using Freesurfer. A general linear model was used to conduct regressions between CSF markers and cortical thickness. Results: Correlation...

  17. Interconverting conformations of variants of the human amyloidogenic protein beta2-microglobulin quantitatively characterized by dynamic capillary electrophoresis and computer simulation

    DEFF Research Database (Denmark)

    Heegaard, Niels H H; Jørgensen, Thomas J D; Cheng, Lei;

    2006-01-01

    Capillary electrophoretic separation profiles of cleaved variants of beta2-microglobulin (beta2m) reflect the conformational equilibria existing in solutions of these proteins. The characterization of these equilibria is of interest since beta2m is responsible for amyloid formation in dialysis......-related amyloidosis and thus is able to attain alternative conformations that lead to irreversible aggregation and precipitation. In this study, we quantitate the increased conformational instability of cleaved beta2m by extracting rate constants and activation energies by simulating the experimental data using...

  18. B-Receptor Signaling in Cardiomyopathy

    Science.gov (United States)

    2015-11-16

    Carcinomas; Amyloidosis; Anal Cancer; Anemia; Cholangiocarcinoma of the Extrahepatic Bile Duct; Transitional Cell Carcinoma of Bladder; Bone Marrow Transplant Failure; Bone Cancer; Cancer of Brain and Nervous System; Breast Cancer; Carcinoma of the Large Intestine; Endocrine Cancer; Esophageal Cancer; Eye Cancer; Gall Bladder Cancer; Gastric (Stomach) Cancer; Gastrooesophageal Cancer; Gastrointestinal Stromal Tumor (GIST); Gynecologic Cancers; Head and Neck Cancers; Hepatobiliary Neoplasm; Kidney (Renal Cell) Cancer; Leukemia; Lung Cancer; Hodgkin Disease; Lymphoma, Non-Hodgkin; Mesothelioma; Multiple Myeloma; Myelodysplastic Syndromes (MDS); Neuroendocrine Tumors; Myeloproliferative Disorders; Pancreatic Cancer; Prostate Cancer; Skin Cancer; Soft Tissue Sarcoma; Testicular Cancer; Thymus Cancer; Thyroid Cancer

  19. Native human serum amyloid P component is a single pentamer

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH;

    1995-01-01

    Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer...... by rocket immunoelectrophoresis and electron microscopy. Thus, electron micrographs of purified SAP showed a predominance of decamers. However, the decamer form of SAP reversed to single pentamers when purified SAP was incorporated into SAP-depleted serum....

  20. Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)

    OpenAIRE

    Kyle, Robert A.; BUADI, FRANC IS; RAJKUMAR, S. VINC ENT

    2011-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk contin...

  1. Hepatitis B Associated Monoclonal Gammopathy That Resolved after Successful Liver Transplant

    Directory of Open Access Journals (Sweden)

    P. Sreenivasan

    2009-01-01

    Full Text Available Monoclonal gammopathy of undetermined significance (MGUS has been most commonly associated with diseases like multiple myeloma, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, HIV, and other lymphoproliferative disorders. There has been an isolated report of MGUS in patients coinfected with HIV and Hepatitis B, as the work by Amara et al. in 2006. Here, we report a case of IgA-kappa light chain gammopathy secondary to Hepatitis B infection, which resolved after liver transplantation. To our knowledge, this is the first reported case of M protein spike seen in the context of Hepatitis B infection only.

  2. State-of-the-Art Imaging and Staging of Plasma Cell Dyscrasias.

    Science.gov (United States)

    Amini, Behrang; Yellapragada, Sarvari; Shah, Shetal; Rohren, Eric; Vikram, Raghunandan

    2016-05-01

    Monoclonal gammopathy of unknown significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. Smoldering multiple myeloma, also called asymptomatic multiple myeloma, is an intermediate stage between MGUS and symptomatic multiple myeloma. As the name implies, extraosseous or extramedullary myeloma refers to the presence of myeloma deposits outside the skeletal system. Waldenström macroglobulinemia is a distinct subtype of plasma cell dyscrasia characterized by lymphoplasmacytic lymphoma in the bone marrow with an associated IgM monoclonal gammopathy. Amyloidosis is a condition characterized by extracellular deposition of fibrils composed of a variety of normal serum proteins. PMID:27153790

  3. Do clinical diagnoses correlate with pathological diagnoses in cardiac transplant patients? The importance of endomyocardial biopsy

    DEFF Research Database (Denmark)

    Luk, Adriana; Metawee, Mohammed; Ahn, Eric;

    2009-01-01

    of 296 surgically excised hearts over a 20-year period (January 1987 to July 2006) at one institution were examined. Patients were separated into groups based on year of heart transplantation. The tissue was examined to determine the underlying cardiac pathology leading to congestive heart failure...... amyloidosis. OBJECTIVE: To review the changes that have occurred over time in the etiology of heart disease in patients requiring heart transplantation, and to compare the clinical and histological diagnoses of explanted hearts from patients with progressive cardiac disease. METHODS: The pathological findings...

  4. Subjective cognitive concerns, amyloid-β, and neurodegeneration in clinically normal elderly

    Science.gov (United States)

    Mormino, Elizabeth C.; Pietras, Alison C.; Marshall, Gad A.; Vannini, Patrizia; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.

    2015-01-01

    Objective: To determine whether neuroimaging biomarkers of amyloid-β (Aβ) and neurodegeneration (ND) are associated with greater self-reported subjective cognitive concerns (SCC) in clinically normal older individuals. Methods: A total of 257 participants underwent Pittsburgh compound B PET, PET with fluorodeoxyglucose 18F, and structural MRI, as well as a battery of neuropsychological measures including several questionnaires regarding SCC. Individuals were classified into 4 biomarker groups: biomarker negative (Aβ−/ND−), amyloidosis alone (Aβ+/ND−), amyloidosis plus ND (Aβ+/ND+), and ND alone (Aβ−/ND+). Results: Both Aβ and ND were independently associated with greater SCC controlling for objective memory performance. By contrast, neither Aβ nor ND was associated with objective memory performance controlling for SCC. Further examination revealed greater SCC in individuals with Aβ or ND positivity compared to biomarker-negative individuals. In addition, greater SCC predicted Aβ positivity when controlling for ND status. Conclusions: When individuals were grouped by biomarker status, those who were positive on Aβ or ND had the highest report of SCC compared to biomarker-negative individuals. Findings were consistent when SCC was used to predict Aβ positivity. Taken together, results suggest that both Aβ and ND are associated with SCC, independent of objective memory performance. Enrichment of individuals with SCC may increase likelihood of Aβ and ND markers in potential participants for secondary prevention trials. PMID:26048028

  5. Extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum

    Institute of Scientific and Technical Information of China (English)

    Fabiana Pirani Carneiro; Maria de Nazareth Machado Sobreira; Livia Bravo Maia; Alesso Cervantes Sartorelli; Luiz Eduardo de Almeida Prado Franceschi; Mauro Brito Brandao; Bárbara Wosnjuk Calaca; Fernando Silva Lustosa; Joao Vieira Lopes

    2009-01-01

    We report a rare case of extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum. A 72-year-old Japanese man was admitted to our hospital presenting with a 3-mo history of epigastric pain, vomiting and weight loss. On computed tomography (CT) a wall thickening of the fourth part of the duodenum was observed. Multiple biopsies obtained from the lesion showed infiltration of plasma cells and lymphocytes, but they were not conclusive. The patient underwent resection of the lesion and, on histopathological examination, the lesion consisted of a dense and diffuse infiltrate of plasma cells and a few admixed lymphocytes with reactive follicles extending to the muscular propria. An extensive deposition of amyloid was also observed. Immunohistochemical stains revealed that a few plasmacytoid cells showed λ light chain staining, though most were κ light chain positive. These cells also were positive for CD138 and CD56 but negative for CD20 and CD79. The findings were consistent with extramedullary plasmocytoma associated with a massive deposit of amyloid in duodenum. A subsequent workup for multiple myeloma was completely negative. The patient showed no signs of local recurrence or dissemination of the disease after 12 mo follow-up. Because of the association of plasmocytoma and amyloidosis, the patient must be followed up because of the possible systemic involvement of the neoplasm and amyloidosis in future.

  6. Amyloidoma secondary to insulin injection: Cytologic diagnosis and pitfalls

    Directory of Open Access Journals (Sweden)

    Dianne Grunes

    2015-01-01

    Full Text Available Amyloidomas are rare tumors composed of deposits of amyloid protein not associated with systemic amyloidosis. They can present as an initial manifestation of a systemic disease process or can be a completely localized phenomenon. We present a case of amyloidoma associated with insulin injection site found incidentally in an 80-year-old male with multiple co-morbidities who presented with diverticulitis associated bleeding. A subcutaneous abdominal mass was found on physical examination. Imaging revealed a 5 cm Χ 1.6 cm homogenous subcutaneous lesion. A fine-needle aspiration (FNA and core biopsy were performed under ultrasound guidance to reveal amorphous material proven to be amyloidosis at insulin injection sites (AIns type amyloid. The patient had no treatment for this lesion and has had his care triaged to his more serious health problems. This is the first case of AIns type amyloidoma associated with insulin injection site reported in cytology literature. We highlight the cytologic findings and diagnostic pitfalls. As the incidence of diabetes is increasing, cytopathologists may encounter this lesion more often on FNA.

  7. The Effect of Glycosaminoglycans (GAGs on Amyloid Aggregation and Toxicity

    Directory of Open Access Journals (Sweden)

    Clara Iannuzzi

    2015-02-01

    Full Text Available Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis.

  8. Metabolic lung disease: imaging and histopathologic findings

    International Nuclear Information System (INIS)

    Metabolic lung disease includes pulmonary alveolar proteinosis (PAP), pulmonary amyloidosis, metastatic pulmonary calcification, dendritic pulmonary ossification, pulmonary alveolar microlithiasis, and storage diseases. In pulmonary alveolar proteinosis, CT demonstrates air-space consolidation with thickened interlobular septa, producing the so-called 'crazy paving' appearance. Pulmonary amyloidosis can appear as parenchymal nodules (nodular parenchymal form), diffuse interstitial deposit (diffuse interstitial form), or submucosal deposits in the airways (tracheobronchial form). Metastatic pulmonary calcification may appear on high-resolution CT as numerous 3- to 10-mm diameter calcified nodules or, more commonly as fluffy and poorly defined nodular opacities. In pulmonary microlithiasis, high-resolution CT demonstrates diffuse punctuate micronodules showing slight perilobular predominance resulting in apparent calcification of interlobular septa. Niemann-Pick disease appears as ground-glass attenuation in the upper lung zone and thickening of the interlobular septa in the lower lung zone. Radiologic study including high-resolution CT will be helpful for the diagnosis and follow-up of these diseases

  9. [Cutaneous lesion associated with multiple endocrine neoplasms type 2A (Sipple's syndrome). An early clinical marker].

    Science.gov (United States)

    Chabre, O; Labat-Moleur, F; Berthod, F; Tarel, V; Stoebner, P; Sobol, H; Bachelot, I

    1992-02-22

    We report the association of a cutaneous lesion with multiple endocrine neoplasia type 2A (MEN 2A) in three patients from a French family. These lesions are very similar to those previously described in an Italian and an American MEN 2A family and called cutaneous lichen amyloidosis. In all three families the patients presented with a pruritic and pigmented cutaneous lesion localized unilaterally on the upper back. However, in the French family the patients also complained of paroxysmal pain in the same area, in which we could elicit a touch hypoesthesia and pain hyperesthesia. Such an association of cutaneous and neurological features in the upper back is known as Notalgia Paresthetica (NP). NP is believed to represent a neuropathy of the posterior dorsal nerve rami. Unlike the two previously reported families, the histological, immunohistochemical and ultrastructural analysis of the skin biopsies of the French patients did not show any amyloid material. This suggests that the presence of amyloid may not be a constant feature of the cutaneous lesions associated with MEN 2A. We consider these lesions as a form of dorsal neuropathy rather than a cutaneous lichen amyloidosis. Whatever their origin, these cutaneous lesion usually precede the appearance of the neoplastic lesions of MEN 2A. They may act as an early clinical marker that must be searched for in each subject at risk for MEN 2A. In addition, all patients presenting with NP should be screened for MEN 2A. PMID:1348355

  10. MetAmyl: a METa-predictor for AMYLoid proteins.

    Directory of Open Access Journals (Sweden)

    Mathieu Emily

    Full Text Available The aggregation of proteins or peptides in amyloid fibrils is associated with a number of clinical disorders, including Alzheimer's, Huntington's and prion diseases, medullary thyroid cancer, renal and cardiac amyloidosis. Despite extensive studies, the molecular mechanisms underlying the initiation of fibril formation remain largely unknown. Several lines of evidence revealed that short amino-acid segments (hot spots, located in amyloid precursor proteins act as seeds for fibril elongation. Therefore, hot spots are potential targets for diagnostic/therapeutic applications, and a current challenge in bioinformatics is the development of methods to accurately predict hot spots from protein sequences. In this paper, we combined existing methods into a meta-predictor for hot spots prediction, called MetAmyl for METapredictor for AMYLoid proteins. MetAmyl is based on a logistic regression model that aims at weighting predictions from a set of popular algorithms, statistically selected as being the most informative and complementary predictors. We evaluated the performances of MetAmyl through a large scale comparative study based on three independent datasets and thus demonstrated its ability to differentiate between amyloidogenic and non-amyloidogenic polypeptides. Compared to 9 other methods, MetAmyl provides significant improvement in prediction on studied datasets. We further show that MetAmyl is efficient to highlight the effect of point mutations involved in human amyloidosis, so we suggest this program should be a useful complementary tool for the diagnosis of these diseases.

  11. Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation

    Directory of Open Access Journals (Sweden)

    Semerdjian Ronald J

    2003-08-01

    Full Text Available Abstract Background Familial Mediterranean fever (FMF is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis. The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression. Case Report We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN. Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome. Discussion Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa. Conclusion To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis.

  12. Amyloid goiter presented as a subacute thyroiditis-like symptom in a patient with hypersensitivity vasculitis.

    Science.gov (United States)

    Nagai, Y; Ohta, M; Yokoyama, H; Takamura, T; Kobayashi, K I

    1998-06-01

    We present a 25-year-old woman with amyloid goiter due to hypersensitivity vasculitis, who developed transient thyrotoxicosis resembling subacute thyroiditis. She received prednisolone (20 mg/ day) for three years for hypersensitivity vasculitis, and was diagnosed as having secondary amyloidosis by biopsies of the stomach, rectum and kidneys. She noticed neck swelling with severe right neck tenderness, palpitation, hyperhidrosis and weight loss. An elastic firm diffuse goiter was palpable, and the upper pole of the right lobe was extremely tender. Her serum free T4 and T3 levels were high, and the serum TSH was suppressed to subnormal. She was positive for serum C-reactive protein. Anti-thyroidal autoantibodies were all negative. Her thyrotoxicosis subsided spontaneously within one week. Serum titers of antibodies to various viruses were unchanged during the clinical course for two weeks, but she was positive for HLA B35. Examination of a needle-biopsy specimen of the thyroid gland showed extensive amyloid deposition and no evidence of subacute thyroiditis. We considered her transient thyrotoxicosis to be associated with amyloid goiter. The clinical course of this case was similar to the subacute thyroiditis-like syndrome, first described by Ikenoue et al. When patients with primary or secondary amyloidosis have symptoms and signs of subacute thyroiditis, but develop an unusual course, amyloid goiter should be considered. PMID:9790279

  13. Protein conformation and disease : pathological consequences of analogous mutations in homologous proteins.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, F. J.; Pokkuluri, P. R.; Schiffer, M.; Biosciences Division

    2000-12-19

    The antibody light chain variable domain (V{sub L}){sup 1} and myelin protein zero (MPZ) are representatives of the functionally diverse immunoglobulin superfamily. The V{sub L} is a subunit of the antigen-binding component of antibodies, while MPZ is the major membrane-linked constituent of the myelin sheaths that coat peripheral nerves. Despite limited amino acid sequence homology, the conformations of the core structures of the two proteins are largely superimposable. Amino acid variations in V{sub L} account for various conformational disease outcomes, including amyloidosis. However, the specific amino acid changes in V{sub L} that are responsible for disease have been obscured by multiple concurrent primary structure alterations. Recently, certain demyelination disorders have been linked to point mutations and single amino acid polymorphisms in MPZ. We demonstrate here that some pathogenic variations in MPZ correspond to changes suspected of determining amyloidosis in V{sub L}. This unanticipated observation suggests that studies of the biophysical origin of conformational disease in one member of a superfamily of homologous proteins may have implications throughout the superfamily. In some cases, findings may account for overt disease; in other cases, due to the natural repertoire of inherited polymorphisms, variations in a representative protein may predict subclinical impairment of homologous proteins.

  14. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

    Science.gov (United States)

    Kempf, Stefan J.; Metaxas, Athanasios; Ibáñez-Vea, María; Darvesh, Sultan; Finsen, Bente; Larsen, Martin R.

    2016-01-01

    The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology. We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation. We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. PMID:27144524

  15. Cardiac and pleuropulmonary AL amyloid imaging with technetium-99m labelled aprotinin

    Energy Technology Data Exchange (ETDEWEB)

    Aprile, C. [Dept. of Nuclear Medicine, Fondazione Clinica del Lavoro-IRCCS, Pavia (Italy); Marinone, G. [Inst. of Clinical Medicine II and Research Lab. Biotechnology, Policlinico S. Matteo-IRCCS, Pavia (Italy); Saponaro, R. [Dept. of Nuclear Medicine, Fondazione Clinica del Lavoro-IRCCS, Pavia (Italy); Bonino, C. [SORIN Biomedica, Saluggia VC (Italy); Merlini, G. [Inst. of Clinical Medicine II and Research Lab. Biotechnology, Policlinico S. Matteo-IRCCS, Pavia (Italy)

    1995-12-01

    Antiproteases are known to be present in amyloid deposits. We evaluated the possibility of using an anti-serine protease (aprotinin) labelled with technetium-99m (TcA), usually employed as a cortical renal tracer, for the imaging of amyloid deposits. Because of the known high uptake of TcA by the kidneys, we limited our analysis to extra-abdominal amyloid localizations. We report the scintigraphic findings observed in 24 patients with light chain amyloidosis (AL) and one with a hereditary form who were known or suspected to have extra-abdominal involvement. Planar scans obtained 100 min after i.v. TcA administration showed myocardial accumulation in 11 patients, pleuropulmonary accumulation in nine, pericardial accumulation in two and localization in the neck region (thyroid, salivary glands and tongue) in eight. TcA scintigraphy was negative in five patients without clinical or laboratory evidence of extra-abdominal involvement, as well as in 12 control group patients with cardiac and renal diseases. These preliminary results indicate TcA to be a low-cost, readily available radiopharmaceutical for imaging of extra-abdominal involvement in AL type amyloidosis. (orig.)

  16. The association of nephrotic syndrome and renal vein thrombosis: a clinicopathological analysis of eight pediatric patients.

    Science.gov (United States)

    Tinaztepe, K; Buyan, N; Tinaztepe, B; Akkök, N

    1989-01-01

    Cases with a pathological diagnosis of renal venous thrombosis (RVT) associated with nephrotic syndrome (NS) were studied retrospectively for clinicopathological evaluation. The material consisted of 21 RVT cases which were diagnosed in 2000 consecutive pediatric necropsies, with an overall incidence of about one percent. Eight of the 21 RVT cases were associated with nephrotic syndrome (34%), and this group formed 0.4 percent of the total necropsies in our pediatric center. The glomerulopathies of these nephrotic patients consisted of three cases of Finnish-type congenital NS (FCNS), three cases of renal amyloidosis secondary to familial Mediterranean fever, and two cases of membranoproliferative glomerulonephritis (MPGN). The presence of sepsis associated with disseminated intravascular coagulation, and the morphological age of the thrombi suggested that the RVT was secondary to sepsis in the FCNS cases. In the MPGN and secondary renal amyloidosis cases, the long duration of both the nephrotic state and the administration of diuretics along with glucocorticoid treatment and also the newly formed thrombi without infarction are strong evidences, although not definite, that the RVT developed as a complication of the glomerulopathy. Even though there were no definite clinical criteria for the diagnosis of most of the RVT cases, we would like to emphasize the importance of flank pain, the rapid deterioration of renal functions in a stable nephrotic patient, as well as the hypercoagulable state in the consideration of the development of RVT which indicate the need for appropriate radiological studies for confirmation of this condition during life.

  17. Amyloidotic muscle pseudohypertrophy: case report Pseudo-hipertrofia muscular associada com amiloidose: relato de caso

    Directory of Open Access Journals (Sweden)

    Rosana Herminia Scola

    2001-09-01

    Full Text Available The authors report one case of amyloidosis associated with muscular pseudohypertrophy in a 46-year-old woman, who developed weakness, macroglossia and muscle hypertrophy associated with primary systemic amyloidosis. Electromyography showed a myopathic pattern and bilateral carpal tunnel syndrome. The muscle biopsy presented with a type I and II fiber hypertrophy and infiltration of amyloid material in the interstitious space and artery walls. She underwent bone marrow transplantation with stabilization and subjective improvement of the clinical picture.Descreve-se um caso de pseudo-hipertrofia muscular associada a amiloidose primária em uma paciente do sexo feminino, com 46 anos, que apresentava astenia e macroglossia. O estudo eletromiográfico mostrou padrão miopático e síndrome do túnel do carpo, bilateral. A biópsia muscular revelou hipertrofia de fibras tipo I e II, com infiltração de material amilóide no interstício e parede dos vasos, principalmente arteriais. A paciente foi submetida a transplante autólogo de medula óssea, evoluindo com estabilização do quadro e um sentimento subjetivo de melhora.

  18. Aβ immunization worsens iron deposits in the choroid plexus and cerebral microbleeds

    Science.gov (United States)

    Joseph-Mathurin, Nelly; Dorieux, Olène; Trouche, Stéphanie G.; Boutajangout, Allal; Kraska, Audrey; Fontès, Pascaline; Verdier, Jean-Michel; Sigurdsson, Einar M.; Mestre-Francés, Nadine; Dhenain, Marc

    2014-01-01

    Anti-Aβ immunotherapy provides potential benefits in Alzheimer’s disease patients. Nevertheless, strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on Aβ1-42 or Aβ-derivative (K6Aβ1-30). We followed anti-Aβ40 IgG and IgM responses as well as Aβ levels in plasma. In-vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aβ1-42 immunogen. This treatment induced immune response and increased Aβ levels in plasma but also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of Aβ-immunization at prodromal stages of Alzheimer’s disease, and should be monitored in clinical trials. PMID:23796662

  19. Transient micro-elastography:A novel non-invasive approach to measure liver stiffness in mice

    Institute of Scientific and Technical Information of China (English)

    Cécile Bastard; Matteo R Bosisio; Michèle Chabert; Athina D Kalopissis; Meriem Mahrouf-Yorgov; Hélène Gilgenkrantz; Sebastian Mueller; Laurent Sandrin

    2011-01-01

    AIM:To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice. METHODS:A novel transient micro-elastography (TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model (CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement (0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88,P 150 kPa.LS significantly correlated with the amyloidosis index (0.93,P < 0.0001) and the plasma concentration of mutant hapoA-Ⅱ (0.62,P < 0.005). CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.

  20. The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies.

    Science.gov (United States)

    Mavrogeni, S; Markousis-Mavrogenis, G; Markussis, V; Kolovou, G

    2015-08-01

    The aim of this review is to discuss the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC task force, distinguished specific cardiomyopathies, caused by metabolic disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration disorders (amyloidosis, hemochromatosis and familial storage disorders), 3) nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4) diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen storage diseases can be presented with myopathy, liver, and heart failure. Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an inherited disorder of iron metabolism, leads to tissue iron overload in different organs, including the heart. Cardiac amyloidosis is the result of amyloid deposition in the heart, formed from breakdown of normal or abnormal proteins that leads to increased heart stiffness, restrictive cardiomyopathy, and heart failure. Finally, nutritional disturbances and metabolic diseases, such as Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may also lead to severe cardiac dysfunction. CMR, through its capability to reliably assess anatomy, function, inflammation, rest-stress myocardial perfusion, myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve as an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation, and long term follow-up of patients with metabolic cardiomyopathies. PMID:26197853