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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. 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

  3. 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

  4. Cardiac amyloidosis

    International Nuclear Information System (INIS)

    Amyloidosis is an infiltrative systemic disease that may involve the heart. it has a genetic etiology and is an important cause of restrictive cardiomyopathy. It may involve all heart structures but has a great affinity for myocardial tissue. Diastolic dysfunction is the most early and frequent manifestation, although due to myocardial infiltration, it may progress to systolic dysfunction, resulting in a rigid heart syndrome. There is also an involvement of the conducting system. The condition may be suspected in any patient with cardiomegalia of unexplained cause. Among the diagnostic tools, the voltage/mass relation may be kept in mind. endomyocardial biopsy is useful although it is not always positive through histological verification. The treatment consists of supportive measures and selected cases may benefit with hepatic transplantation

  5. 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 ...

  6. 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.

  7. 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 ...

  8. Genetics Home Reference: transthyretin amyloidosis

    Science.gov (United States)

    ... and weakness in the hands and fingers. The leptomeningeal form of transthyretin amyloidosis primarily affects the central ... neuropathic form may also occur. When people with leptomeningeal transthyretin amyloidosis have associated eye problems, they are ...

  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. [Cardiac amyloidosis. General review].

    Science.gov (United States)

    Laraki, R

    1994-04-01

    Cardiac amyloidosis, most often of AL type, is a non-exceptional disease as it represents 5 to 10% of non-ischemic cardiomyopathies. It realizes typically a restrictive cardiomyopathy. Nevertheless the wide diversity of possible presentation makes it a "big shammer" which must be evoked in front of every unexplained cardiopathy after the age of forty. If some associated manifestations can rapidly suggest the diagnosis, as a peripheric neuropathy especially a carpal tunnel syndrome or palpebral ecchymosis, cardiac involvement can also evolve in an apparently isolated way. The most suggestive paraclinic elements for the diagnosis are, in one hand, the increased myocardial echogenicity with a "granular sparkling" appearance seen throughout all walls of the left ventricle and, in the other hand, the association of a thickened left ventricle and a low voltage (electrocardiogram could also show pseudo-infarct Q waves). In front of such aspects, the proof of amyloidosis is brought by an extra-cardiac biopsy or by scintigraphy with labelled serum amyloid P component, so that the indications of endomyocardial biopsy are very limited today. The identification of the amyloid nature of a cardiopathy has an direct therapeutic implication: it contra-indicates the use of digitalis, calcium channel blockers and beta-blockers. The treatment of AL amyloidosis (chemotherapy with alkylant agents) remains very unsatisfactory especially in the cardiac involvement which is the most frequent cause of death (in AL amyloidosis). Last, cardiac amyloidosis is a bad indication for transplantation which results are burden by rapid progression of deposits especially in the gastro-intestinal tract and the nervous system. PMID:8059146

  11. Amyloidosis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Braconi, Daniela; Bernardini, Giulia; Lupetti, Pietro; Rovensky, Josef; Ranganath, Lakshminaryan; Santucci, Annalisa

    2015-09-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces an HGA-melanin ochronotic pigment, of hitherto unknown composition. Besides the accumulation of HGA, the potential role and presence of unidentified proteins has been hypothesized as additional causal factors involved in ochronotic pigment deposition. Evidence has been provided on the presence of serum amyloid A (SAA) in several AKU tissues, which allowed classifying AKU as a novel secondary amyloidosis. In this paper, we will briefly review all direct and indirect lines of evidence related to the presence of amyloidosis in AKU. We also report the first data on abnormal SAA serum levels in a cohort of AKU patients. PMID:25868666

  12. 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.

  13. 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.

  14. Unique type of isolated cardiac valvular amyloidosis

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    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.

  15. 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

  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. 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.

  18. 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.

  19. [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

  20. Localized Lymph Node Light Chain Amyloidosis

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    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.

  1. [Treatment of amyloidosis with dimethyl sulfoxide (DMSO)].

    Science.gov (United States)

    Morassi, P; Massa, F; Mesesnel, E; Magris, D; D'Agnolo, B

    1989-01-01

    In this study we have investigated the role of oral dimethylsulfoxide (DMSO) therapy in 2 patients with primary amyloidosis (AL) and in 2 patients with secondary amyloidosis (AA) to long-standing rheumatoid arthritis. DMSO treatment produced no beneficial effects in the patients with idiopathic amyloidosis. Instead the patients with secondary amyloidosis experienced a subjective improvement, a decrease of inflammatory activity of the rheumatoid arthritis and an unequivocal improvement of renal function following 3-6 months of DMSO therapy. No serious side effects of DMSO were observed except for unpleasant breath odour. We conclude that a treatment with oral DMSO may prolong life of patients with secondary amyloidosis. PMID:2915815

  2. [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

  3. 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

  4. Laboratory assessment of transthyretin amyloidosis.

    Science.gov (United States)

    Benson, Merrill D; Yazaki, Masahide; Magy, Nadine

    2002-12-01

    Mutations in transthyretin (TTR) are the most common cause of autosomal dominant systemic amyloidosis. To date, more than 80 TTR mutations have been associated with amyloidosis in humans. A high prevalence of some mutations like Val122Ile which is identified in 3% of African Americans indicates the necessity of thorough investigation of patients suspected of having, or to be at risk of developing, TTR amyloidosis. Laboratory tests available for evaluation of TTR amyloidosis include both DNA and protein assays. In the case of a known mutation DNA analysis is realized by restriction fragment length polymorphism (RFLP), polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA), single strand confirmation polymorpism (SSCP) or nucleotide sequencing. SSCP, PCR-non-isotopic RNAse cleavage assay (NIRCA) or nucleotide sequencing are used to identify an unknown mutation. At the protein level, two techniques are used, isoelectric focusing and mass spectrometry, in both cases (known or unknown mutation). The identification of a previously unknown mutation requires a combination of clinical, pathological and molecular studies. PMID:12553428

  5. 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...

  6. 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

  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. Pattern of renal amyloidosis in Indian patients.

    OpenAIRE

    Chugh, K S; Datta, B. N.; Singhal, P. C.; Jain, S.K.; Sakhuja, V.; Dash, S. C.

    1981-01-01

    Two hundred and thirty-three patients with renal amyloidosis were studied in an attempt to identify the incidence and pattern of the disease in northern India. The incidence of amyloidosis was 1.01% of 6431 post-mortems and 8.4% of 1980 renal biopsies from patients who presented with clinical evidence of glomerular disease. Two hundred and three patients (87.1%) had secondary amyloidosis, 22 (9.4%) had primary amyloid and 8 patients (3.5%) had amyloidosis associated with multiple myeloma. Tub...

  9. 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

  10. [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

  11. 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...

  12. 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...

  13. 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

  14. 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

  15. 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

  16. Symptomatic cardiac amyloidosis in an American family

    International Nuclear Information System (INIS)

    This report describes an American family with a high incidence of symptomatic cardiac amyloidosis among four siblings, and explores the role of echocardiography and technetium pyrophosphate myocardial scintigraphy in the detection of this infiltrative cardiomyopathy within the involved family

  17. 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

  18. 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

  19. Primary Amyloidosis Presenting as Small Bowel Encapsulation

    OpenAIRE

    Jones, Jennifer; van Rosendaal, Guido; Cleary, Cynthia; Urbanski, Stefan; Woodman, Richard C.

    2004-01-01

    Amyloidosis is a pathological process which encompasses a spectrum of diseases that result from extracellular deposition of pathological fibrillar proteins. Clinical presentations vary depending on the organs involved. There is no documented case of amyloidosis presenting as small bowel encapsulation. A previously healthy 62-year-old man developed a small bowel obstruction in 1997. At surgery, a peculiar membrane encasing his entire small bowel was discovered. This appeared to have no vascula...

  20. 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. ...

  1. 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

  2. MRI in cardiac sarcoidosis and amyloidosis

    International Nuclear Information System (INIS)

    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.)

  3. 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

  4. Macular Amyloidosis and Epstein-Barr Virus.

    Science.gov (United States)

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Meshkat, Zahra; Nazeri, Narges

    2016-01-01

    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. PMID:26981113

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Recent advances in the diagnosis and management of cardiac amyloidosis.

    Science.gov (United States)

    Sher, Taimur; Gertz, Morie A

    2014-01-01

    The heart is commonly involved in various forms of amyloidosis and cardiomyopathy is a major cause of morbidity and mortality in these patients. Diagnosis of cardiac amyloidosis is often delayed due to nonspecific presenting symptoms and failure to recognize early signs of amyloid heart disease on routine cardiac imaging. Treatment of cardiac amyloidosis depends upon the type of amyloid protein. Systemic chemotherapy with or without stem cell transplantation is used to treat immunoglobulin-related amyloidosis and liver transplantation is used for familial transthyretin amyloidosis in select patients. Clinical trials with siRNA for the treatment of transthyretin amyloid cardiomyopathies and amyloid protein stabilizers are ongoing. Prognosis depends on the type of amyloid protein with poorer outcomes noted in immunoglobulin light-chain amyloidosis. Supportive care forms the cornerstone of management and advancements in cardiac imaging and proteomics are expected to positively impact our ability to diagnose, prognosticate and treat cardiac amyloidosis. PMID:24344669

  10. 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...

  11. Laryngeal amyloidosis with laryngocele: MRI and CT

    Energy Technology Data Exchange (ETDEWEB)

    Arslan, A.; Ceylan, N.; Cetin, A.; Demirci, A. [Kocaeli Ueniversitesi, Tip Fakueltesi, Radyoloji Anabilim Dali, Izmit (Turkey)

    1998-06-01

    A case of laryngeal amyloidosis associated with a laryngocele is reported. Preoperative CT showed diffuse thickening of the epiglottis, aryepiglottic folds and false vocal cords with well-defined calcific foci. MRI revealed contrast enhancement and increased signal intensity on T2-weighted images. (orig.) With 2 figs., 10 refs.

  12. 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.

  13. 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.

  14. [Progress in the diagnosis and treatment of cardiac amyloidosis].

    Science.gov (United States)

    Jurczyszyn, Artur; Engel, Anna; Rajzer, Marek; Czepiel, Jacek; Mazurs, Grzegorz

    2014-01-01

    The heart is an organ often occupied by various forms of amyloidosis; cardiomyopathies are the leading cause of mortality in patients with amyloidosis. Cardiac amyloidosis is often diagnosed late because of nonspecific symptoms and missed early signs in the imaging routine. A method for treating cardiac amyloidosis depends on the type of amyloid protein. In the treatment of amyloidosis associated with immunoglobulins systemic chemotherapy is used without transplant or stem cell transplantation and in the treatment of familial transthyretin amyloidosis liver transplantation is used. There are still clinical studies on the use of siRNA for the treatment of cardiomyopathy associated with transthy retin amyloidosis, and on the use of amyloid protein stabilizers. The prognosis depends on the type of amyloid protein; worse results observed in the case of light chain amyloidosis. Care support is the cornerstone of treatment; it is expected that advances in cardiac imaging and proteomics positive impact on our ability to diagnosis, prognosis and treatment outcomes of amyloidosis of the heart. PMID:25344976

  15. 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

  16. Poikiloderma-like cutaneous amyloidosis - a rare presentation of primary localized cutaneous amyloidosis.

    Science.gov (United States)

    Heng, Jun Khee; Ho, Sue Ann; Tan, Kong Bing

    2016-01-01

    Poikiloderma-like cutaneous amyloidosis (PCA) is a rare variant of primary cutaneous amyloidosis. It was first described in 1929 and there are two clinical forms of PCA, the ordinary type and PCA syndrome. The characteristics of PCA include poikiloderma-like skin changes, lichenoid papules, blister formation, and cutaneous amyloid deposits on histological examination. These skin lesions usually occur at the extremities, consistent with the few cases that have been reported. We present a case of a 62-year-old man who presented with the features of poikiloderma-like cutaneous amyloidosis. Diagnosis of this unique condition is a challenge and a skin biopsy is necessary in such instances. A discussion of the differential diagnosis of this condition is also included. PMID:26990468

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Two cases of moderate proteinuria and hematuria with unexpected diagnosis of renal amyloidosis

    Directory of Open Access Journals (Sweden)

    Elena Zakharova

    2015-04-01

    Full Text Available The diagnosis of renal amyloidosis is sometimes elusive. In this manuscript, we present and discuss two cases, presenting with proteinuria, subsequently diagnosed with rare variants of renal amyloidosis: AH amyloidosis in patient with lymphoplasmacytic lymphoma, and AA amyloidosis in patient with hyperimmunoglobulinemia D syndrome.

  3. 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...

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

    OpenAIRE

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

    2012-01-01

    Purpose 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 ...

  6. 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

  7. 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....... Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in...

  8. CARDIAC AMYLOIDOSIS IN A PATIENT WITH MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Parathan

    2015-10-01

    Full Text Available Cardiac amyloidosis is a rare disorder, which is characterised by the extra cellular deposition of amyloid, a protein polysaccharide complex in the heart. This infiltrative cardiomyopathy presents with restrictive heart failure. We report a 58 year old male who pr esented with macroglossia, proteinuria and heart failure. His detailed evaluation revealed multiple myeloma with concurrent Primary (AL amyloidosis. This case report is to highlight the occurrence of cardiac amyloidosis and multiple myeloma which are two separate plasma cell dyscrasias which have presented together.

  9. 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.

  10. New insights into systemic amyloidosis: primary amyloidosis associated with tubercular lymphadenitis

    Directory of Open Access Journals (Sweden)

    Shivraj Meena, Nirmal Ghati, Rita Sood, Naval Kishore Vikram

    2014-11-01

    Full Text Available Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine department of all India institute of medical sciences , New Delhi with on & off erythematous rashes over both eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1 month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon eyes, hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib and Dexamethasone based weekly chemotherapy.

  11. 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

  12. 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.

  13. 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

  14. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    International Nuclear Information System (INIS)

    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-99mTc 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-99mTc 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. Cardiac

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation.

    Science.gov (United States)

    Misumi, Yohei; Narita, Yasuko; Oshima, Toshinori; Ueda, Mitsuharu; Yamashita, Taro; Tasaki, Masayoshi; Obayashi, Konen; Isono, Kaori; Inomata, Yukihiro; Ando, Yukio

    2016-05-01

    Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan-Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow-up for early amyloidosis detection and new treatments, including TTR stabilizers and gene-silencing therapies, are required. Liver Transplantation 22 656-664 2016 AASLD. PMID:26600212

  20. 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...

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Experimental induction and oral transmission of avian AA amyloidosis in vaccinated white hens.

    Science.gov (United States)

    Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Yanai, Tokuma; Goryo, Masanobu; Ishiguro, Naotaka

    2013-06-01

    Avian AA amyloidosis is commonly observed in adult birds afflicted with bacterial infections or chronic inflammatory disorders. Experimental AA amyloidosis in birds can be induced by repeated inflammatory stimulation, such as injection with casein or vaccination with oil-emulsified bacterins. However, the transmission of amyloidosis among avian species has not been studied well to date. In the present study, we confirm the potential induction of avian AA amyloidosis by inoculation of Salmonella enteritidis (SE) vaccine or Mycoplasma gallisepticum vaccine. To determine the transmission of chicken AA amyloidosis among white hens, we induced experimental AA amyloidosis in vaccinated chickens by intravenous or oral administration of chicken AA fibrils. Amyloid deposits were observed in chickens injected with SE and inoculated with chicken AA fibrils intravenously (21/26: 81%) and orally (8/12: 67%). These results suggest that chicken AA amyloidosis can be induced by vaccinations, and may be transmitted among like species by oral administration. PMID:23548152

  10. 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.

  11. 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.)

  12. Primary hepatic amyloidosis: A case report and review of literature.

    Science.gov (United States)

    Sonthalia, Nikhil; Jain, Samit; Pawar, Sunil; Zanwar, Vinay; Surude, Ravindra; Rathi, Praveen M

    2016-02-28

    We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT levels with normal transaminases and bilirubin. On imaging she had diffuse enlargement of liver with heterogeneous contrast uptake in liver. Her viral marker and autoimmune markers were negative. Liver biopsy depicted massive deposition of amyloid in peri-sinusoidal spaces which revealed apple green birefringence on polarizing microscopy after Congo red staining. Cardiac and renal evaluation was unremarkable. Abdominal fat pad and rectum biopsy was negative for amyloid deposit. There was no evidence of primary amyloidosis as bone marrow examination was normal. Serum and urine immunofixation electrophoresis were normal. Immunoperoxidase staining for serum amyloid associated protein for secondary amyloidosis was negative from liver biopsy. We present this rare case of primary hepatic amyloidosis and review the literature regarding varied presentations of hepatic involvement in amyloidosis. PMID:26962400

  13. Clinical features and MRI characteristics in patients with cardiac amyloidosis

    International Nuclear Information System (INIS)

    Objective: To observe the clinical features and cardiac magnetic resonance (CMR) imaging characteristics in patients with cardiac amyloidosis. Methods: A total of 5 patients (4 males and 1 female) with the diagnosis of cardiac amyloidosis (3 were proven by heart transplantation, 2 by endomyocardial biopsy) were evaluated by electrocardiogram, echocardiogram, chest X-ray and CMR with delayed Gadolinium enhancement. Results: Echocardiograms were abnormal in all five patients; chest X- ray showed pulmonary hemorrhage (3), cardiomegaly (5), pleural effusion (3); echocardiogram showed atrial enlargement, left ventricular wall thickening, limited ventricular wall motion, etc. CMR exhibited increased thickness of the left ventricular wall, mild to moderate depression of systolic function (mean ejection fraction: 32.5%±15.0%) and bilateral atrial enlargement with restriction of diastolic ventricular filling. In all patients, there were widespread enhancement of the thickened myocardium on delayed post- contrast studies. In 4 patients, global subendocardial delayed gadolinium enhancement was found, in papillary muscles, and interventricular septa with 'zebra-like' sign in 3 patients. Left ventricular transmural delayed gadolinium enhancement was found in 1 patient. Conclusions: CMR shows a characteristic pattern of global subendocardial delayed gadolinium enhancement in cardiac amyloidosis. The findings may be valuable in the diagnosis of cardiac amyloidosis. (authors)

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

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    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.

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

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    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.

  16. Cancer-testis antigen expression and immunogenicity in AL amyloidosis

    International Nuclear Information System (INIS)

    Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted

  17. 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

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Amyloidosis and crohn's disease Amiloidosis y enfermedad de Crohn

    Directory of Open Access Journals (Sweden)

    Antonio Guardiola-Arévalo

    2011-05-01

    Full Text Available Secondary amyloidosis is a rare but serious complication of inflammatory bowel disease that may influence the prognosis even more than the underlying disease. Due to a better knowledge of the association of secondary amyloidosis to inflammatory bowel disease, early diagnosis of this complication is becoming more frequent, but its treatment continues to pose a challenge. We report 4 cases of patients with Crohn's disease and amyloidosis diagnosed in the inflammatory bowel disease Units of Toledo and Ciudad Real, which represent 0.68% of the patients with Crohn's disease of our health areas. There have been not cases of amyloidosis in patients with ulcerative colitis. In our 4 patients the secondary amyloidosis was clearly related to Crohn's disease, which was often of fistulising type. The predominant clinical picture of amyloidosis was nephrotic syndrome. The patients responded to medical and surgical treatment of Crohn's disease and colchicine, which improved renal function in all cases except in one who required kidney transplantation.La amiloidosis sistémica adquirida es una complicación rara pero grave de la enfermedad inflamatoria intestinal crónica, pudiendo condicionar el pronóstico más que la propia enfermedad de base. Debido al mejor conocimiento de la asociación de amiloidosis secundaria a enfermedad inflamatoria intestinal, el diagnóstico temprano se hace cada vez con mayor frecuencia, pero su tratamiento continúa siendo un reto. Describimos 4 casos clínicos de pacientes con enfermedad de Crohn (EC y amiloidosis diagnosticados en las Unidades de EIIC de Toledo y Ciudad Real, lo que representa el 0,68% de los caso de EC de nuestras áreas sanitarias. No se ha descrito ningún caso de amiloidosis en pacientes con colitis ulcerosa. En los 4 pacientes la AA estaba claramente relacionada con la EC, y predominaron las formas estenosantes-perforantes. El cuadro clínico de presentación de la amiloidosis en la mayoría de los casos

  3. 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

  4. 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.

  5. MRI and echocardiography in the diagnosis of cardiac amyloidosis

    International Nuclear Information System (INIS)

    Objective: To assess the values of MRI and echocardiography for the diagnosis of cardiac amyloidosis (CA). Methods: Eleven cases with CA proved pathologically performed MRI and echocardiography, the findings were analyzed retrospectively. Results: The characteristic features of cardiac amyloidosis on MRI and echocardiography were: diffuse slight myocardial thickening of the left ventricular wall and interventricular septum (11 cases), slight myocardial thickening of the interatrial septum (5 cases), increased left ventricular mass (7 cases), enlarged left atrium (7 cases), impaired ventricular systolic and diastolic function (10 cases), pleural and pericardial effusions (11 and 9 cases). Echocardiography showed that myocardium was hyperechoic and presented as ground glass with some spotty hyperechoes in 6 cases. MRI revealed a distinct diffuse delayed enhancement of subendocardial and entire myocardium in 8 cases. Conclusion: Doppler echocardiography is the first-choice imaging technique and cardiac magnetic resonance imaging can provide more information for the diagnosis of CA. (authors)

  6. Guideline of transthyretin-related hereditary amyloidosis for clinicians

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    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.

  7. Ischemic Hepatitis as the Presenting Manifestation of Cardiac Amyloidosis

    OpenAIRE

    Petz, Chelsey A.; Todoran, Thomas; Rockey, Don C.

    2014-01-01

    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 a...

  8. Case Report: Isolated Cardiac Amyloidosis: An Enigma Unravelled

    OpenAIRE

    Khalid, Umair; Awar, Omar; Verstovsek, Gordana; Cheong, Benjamin; Yellapragada, Sarvari Venkata; Jneid, Hani; DESWAL, ANITA; Virani, Salim S.

    2015-01-01

    Amyloidosis is a rare, multisystem disease characterized by deposition of fibrils in extracellular tissue involving kidney, liver, heart, autonomic nervous system, and several other organs. This report discusses a 75-year-old male who presented with worsening dyspnea on exertion, orthopnea, and lower-extremity edema. On physical exam, he had elevated jugular venous pressure and lowerextremity edema. Electrocardiogram depicted low voltage in limb leads and a prolonged PR interval. Echocardiogr...

  9. A Feline Model of Experimentally Induced Islet Amyloidosis

    OpenAIRE

    Hoenig, Margarethe; Hall, Gregory; Ferguson, Duncan; Jordan, Katherine; Henson, Michael; Johnson, Kenneth; O’Brien, Timothy

    2000-01-01

    The study of the pathogenesis of islet amyloidosis and its relationship to the development and progression of type 2 diabetes mellitus has been hampered by the lack of an experimentally inducible animal model. The domestic cat, by virtue of the fact that it is one of the few species that spontaneously develop a form of diabetes mellitus that closely resembles human type 2 diabetes, including the formation of amyloid deposits derived from islet amyloid polypeptide (IAPP), was considered to be ...

  10. 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...

  11. Spontaneous rupture of the spleen secondary to amyloidosis

    International Nuclear Information System (INIS)

    Spontaneous splenic rupture (SSR) is a rare condition. It may be an idiopathic event or may occur secondary to a pathological condition of the spleen. Systemic amyloidosis is characterized by the extracellular deposition of amyloid proteins in one or more organs. The spleen can be affected in 41% of patients. Amyloidosis and consequently, splenic rupture may occur as a complication of amyloid infiltration. We present the case of a 61-year-old male with abdominal pain and hypotension. There were peritoneal signs during physical examination and falling hematocrit was reported in the laboratory tests. The patient was suspected of having an aortic dissection. Thoraco-abdominal computed tomography (CT) angiogram was negative and ultrasonography revealed splenic rupture and free fluid in the abdominal cavity. The patient underwent laparotomy when found hemoperitoneum as a consequence of splenic rupture. The subsequent histopathological report of the spleen revealed amyloidosis. Thus, in patients with abdominal pain and hypotension, we should suspect the possibility of a spontaneous splenic rupture, even without trauma or infection history. (author)

  12. 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.

  13. Primary Amyloidosis Involving Mediastinal and Cervical Lymph Nodes: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Mun, Sugn Hee; Jung, Kyung Jae [Dept. of Radiology, Catholioc University of Daegu School of Medicine, Daegu (Korea, Republic of)

    2011-08-15

    Amyloidosis is a rare disease characterized by the accumulation of an insoluble protein called 'amyloid' in various soft tissues and organs. Primary localized amyloidosis involving the mediastinal and cervical lymph nodes is extremely rare. A 68-year-old man was hospitalized a few days ago for recent cerebral infarction and was diagnosed with primary localized amyloidosis manifesting as mediastinal and cervical lymphadenopathy with calcification. In this review, we report a case of primary localized amyloidosis involving the mediastinal and cervical lymph nodes along with its computed tomography findings. Amyloidosis should be considered as part of the differential diagnosis when the lymph nodes show low central attenuation and various types of calcification.

  14. 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.

  15. A Case of Tracheobronchial Amyloidosis Treated with Endobronchial Therapy

    Directory of Open Access Journals (Sweden)

    Emine Kamiloğlu

    2013-03-01

    Full Text Available Primary isolated tracheobronchial amyloidosis is an uncommon disease. It manifests in symptoms such as progressive dyspnea, cough, and haemoptysis. Airway obstruction can cause atelectasis and recurrent bronchopulmonary infections. A 47-year old man was admitted with the complaint of dyspnea upon exertion of 15 years duration. It is learned that he had a productive cough in winter, and received treatment for bronchial asthma, but had no recovery. Hemoptysis added to his complaints for 10 days, and he had a smoking history of 30 packet/year. Upon physical examination, he had prolonged expirium, and other system signs were normal. Laboratory findings; WBC: 7.100, Hb: 14, Hct: 42.6%, Plt: 479.000, ESR: 80 mm/sec, biochemical parameters were within the normal range. The posteroanterior radiogram of the chest revealed bilateral hilar fullness, and double contour on the right diaphragm. Results of pulmonary function tests were as follows; FEV1/FVC: 44%, FEV1: 47%, FVC: 84%. A computed tomography scan of the chest showed clear emphysemal areas in lung parenchyma, and diffuse thickening on the wall of the trachea, bilateral main bronchii, and segmental bronchii. Fiberoptic bronchoscopy revealed multiple endobronchial lesions on the walls of trachea, and subsegmental bronchii, and mucosal infiltration. A biopsy from these lesions revealed pink-purple amyloid accumulation on mucosal connective tissue, mucosal gland wall, and mucosal vascules after painting with crystal violet and Kongo red. The patient was diagnosed as tracheobronchial amyloidosis, and argon plasma coagulation applied under general anesthesia first to the left main bronchus, and then the right main bronchus and trachea during 2 sessions. After coagulation, mechanical resection was applied. Cryotherapy was applied to the remaining tissue. After treatment, his symptoms were significantly improved. Although spontaneous resolution has been reported in the tracheobronchial amyloidosis, most

  16. Different morphologic aspects and clinical features in massive hepatic amyloidosis.

    Science.gov (United States)

    Melato, M; Manconi, R; Magris, D; Morassi, P; Benussi, D G; Tiribelli, C

    1984-01-01

    4 cases of massive hepatic amyloidosis are reported with special reference to their clinical profiles and histologic features. On the basis of these data, two different clinical and histologic courses of the disease can be distinguished. 2 patients showed marked hepatomegaly without cholestasis, whereas in the other 2 the clinical picture was characterized by much less pronounced hepatomegaly, but by severe and progressive intrahepatic cholestasis. The time course of the disease seems to be different in the two forms, the cholestatic form being more rapidly fatal than the other. PMID:6745505

  17. 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.

  18. Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

    Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

  19. (99m)Tc-HMDP scintigraphy rectifies wrong diagnosis of AL amyloidosis.

    Science.gov (United States)

    Galat, Arnault; Van Der Gucht, Axel; Colombat, Magali; Attias, David; Itti, Emmanuel; Meignan, Michel; Lebras, Fabien; Molinier-Frenkel, Valérie; Benhaiem, Nicole; Guellich, Aziz; Rosso, Jean; Damy, Thibaud

    2015-08-01

    A 71-year-old African man without history of cardiac disease was referred to our center for dyspnea. Transthoracic echocardiogram and cardiac MRI were suggestive of cardiac amyloidosis (CA). The diagnosis of the light-chain cardiac amyloidosis (AL-CA) was made after a first endomyocardial biopsy. Accordingly chemotherapy was started. Systematic 99mTc-HMDP scintigraphy showed moderate cardiac uptake (visual score of 2), unusual for AL-CA, and permitted to rectify the diagnosis. Hereditary transthyretin cardiac amyloidosis was confirmed by a second endomyocardial biopsy with a positive Congo-red and anti-transthyretin antibody stainings, mass spectrometry and genetic analysis (Val122Ile mutation). PMID:26002815

  20. 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.

  1. 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.

  2. Undiagnosed light chain systemic amyloidosis: does it matter to anesthesiologists? -a case report-.

    Science.gov (United States)

    Kim, Gwan Ho; Lee, Woo Kyung; Na, Se Hee; Lee, Jong Seok

    2013-11-01

    Light chain systemic amyloidosis is rare but may accompany laryngeal or pulmonary involvement, which may increase the risk in airway management. We present a case of a patient planned for resection of cervical epidural mass. The patient had face and neck ecchymoses and purpuras with an unknown cause. Mask ventilation and intubation were successful, but the operation was cancelled to evaluate bleeding from facial skin lesions. A diagnosis of light chain systemic amyloidosis prompted evaluation of involvement of other organs and treatment. This case shows the importance of preoperative evaluation and careful airway management in patients with systemic amyloidosis. PMID:24363850

  3. Proteomics and mass spectrometry in the diagnosis of renal amyloidosis.

    Science.gov (United States)

    Picken, Maria M

    2015-12-01

    The amyloidoses are a 'group' of disorders, all of which are associated with deposits that display similar staining and ultrastructural features and are toxic to tissues. Many proteins-currently 31 protein types and many more variants-have been shown to undergo such transformations. Among the various currently known amyloidoses, there are marked differences with regard to their pathogenesis and incidence, while the associated clinical picture is frequently overlapping. However, the therapies that are currently available are amyloid-type specific. The diagnosis of amyloidosis thus involves two steps: (i) a generic diagnosis, followed by (ii) an amyloid type-specific diagnosis or 'amyloid typing'. Immunofluorescence in frozen sections or immunohistochemistry (IHC) in paraffin sections has traditionally been used in the typing of amyloid. However, IHC of amyloid differs significantly from IHC in other areas of surgical pathology; both caution and experience are necessary for its interpretation. The rationale for the application of proteomic methods to amyloid typing lies in the relative abundance of amyloid proteins in tissue where, frequently, it is the 'dominant' protein. Proteomic techniques include the following steps: sample preparation, protein extraction and digestion into peptide fragments, followed by their subsequent separation and measurement by mass spectrometry (MS) and protein identification by informatics. The advantages as well as the limitations of both methods-immunohistochemistry and MS-based proteomics-are discussed. The current recommendations for the application of proteomics in renal amyloidosis are summarized. PMID:26613021

  4. 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

  5. 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.

  6. Extensive laryngeal amyloidosis presenting with stridor: Review of literature and case presentation

    Directory of Open Access Journals (Sweden)

    Hani M. Almuslim

    2014-03-01

    Conclusion: Localized laryngeal amyloidosis, although rare, must be considered among the differentials of benign laryngeal tumors. Complete clinical examination and laboratory investigations to exclude systemic involvement are of paramount value since treatment and prognosis differs markedly.

  7. 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-diagno...... phosphatase, presence of autonomic neuropathy and advanced Mayo disease stage were independently associated with poor nutritional status (P......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...

  8. 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.

  9. 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

  10. 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

  11. Direct Tissue Evaluation via Immunofluorescence: in the Diagnosis of Hereditary Transthyretin Cardiac Amyloidosis

    OpenAIRE

    Fradley, Michael G.; Thakuria, Joseph V.; Collins, A. Bernard; Moore, Stephanie A.; Stone, James R.

    2012-01-01

    Multiple precursor proteins have been shown to cause cardiac amyloidosis. The most common forms are due either to immunoglobulin light chains or to transthyretin proteins (either wild-type or mutant forms). Correct subclassification of the amyloid is paramount because treatment differs in accordance with the type of amyloidosis. Indirect diagnostic methods, including serologic analysis, can lead to misdiagnosis. Definitive diagnosis often requires analysis of amyloid in the tissue. We present...

  12. 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.

  13. 123I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    International Nuclear Information System (INIS)

    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. 123I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and 123I-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 123I-MIBG scintigraphy can detect cardiac denervation in ATTR patients before signs of amyloidosis are evident on echocardiography. (orig.)

  14. 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...

  15. 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 ...

  16. 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

  17. 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...

  18. Transthyretin Ile 122 and cardiac amyloidosis in African-Americans. 2 case reports.

    OpenAIRE

    Jacobson, D R; Ittmann, M.; Buxbaum, J. N.; Wieczorek, R; Gorevic, P D

    1997-01-01

    Two cases of cardiac amyloidosis resulting from deposition of the Ile 122 variant of transthyretin in African-Americans are presented. These cases illustrate several typical features of this disorder, including electrocardiographic abnormalities and digoxin toxicity. Transthyretin Ile 122 is a common amyloidogenic variant in African-Americans (present as a heterozygous variant in 4% of this population); therefore, the diagnosis of transthyretin Ile 122 cardiac amyloidosis should be considered...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases

    OpenAIRE

    Hemminki, Kari; Li, Xinjun; Försti, Asta; Sundquist, Jan; Sundquist, Kristina

    2013-01-01

    Background: Amyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease that is treated by liver transplantation. The non-neuropathic form includes familial autoinflammatory d...

  4. 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

  5. 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.

  6. 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

  7. 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...

  8. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis

    OpenAIRE

    IBI, Kanata; MURAKAMI, Tomoaki; GODA, Wael Mohamed; Kobayashi, Naoki; ISHIGURO, Naotaka; Yanai, Tokuma

    2015-01-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid...

  9. [Hereditary gelsolin amyloidosis--40 years of Meretoja disease].

    Science.gov (United States)

    Kiuru-Enari, Sari; Haltia, Matti

    2010-01-01

    Hereditary gelsolin amyloidosis is an autosomally dominantly inherited systemic disease, first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1 000, and the disease has subsequently been found in many other countries as well. It's typical initial manifestation is lattice corneal dystrophy, detected at biomicroscopic examination of the eye by the age of 25 to 30 years, followed by slowly progressing cranial neuropathy with bilateral facial palsy, polyneuropathy and generalized cutis laxa. Meretoja's disease is caused by mutations of the gelsolin gene, leading to the production and aberrant processing of variant gelsolin and deposition of its fragments in various tissues in the form of amyloid fibrils. PMID:20597346

  10. Systemic AL amyloidosis with unusual cutaneous presentation unmasked by carotenoderma

    Czech Academy of Sciences Publication Activity Database

    Hůlková, H.; Vlášková, H.; Elleder, M.; Svojanovský, J.; Ševela, K.; Krusová, D.; Hanuš, J.; Souček, M.; Vězda, P.; Márová, I.; Feit, J.; Zambo, I.; Kovačevicova, M.; Kostrouchová, V.; Kostrouch, Z.; Novák, Petr

    2014-01-01

    Roč. 21, č. 5 (2014), s. 57-61. ISSN 1350-6129 R&D Projects: GA MŠk ED1.1.00/02.0109; GA MŠk(CZ) MSM0021620806; GA MŠk(CZ) EE2.3.20.0055; GA MŠk LO1211; GA MŠk EE2.3.30.0003 Grant ostatní: Masaryk University, Brno(CZ) MUNI/A/1012/2009; GA MŠk(CZ) Prvouk-P27/LF1/1; Karlova Universita(CZ) UNCE 20422; Universita Karlova(CZ) UNCE 204011; Universita Karlova(CZ) PRVOUK-P24/LF1/3 Institutional support: RVO:61388971 Keywords : alzheimer * gene * amyloidosis Subject RIV: EC - Immunology Impact factor: 2.010, year: 2014

  11. 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.

  12. The pathogenesis of amyloidosis in periodic disease: Some aspects

    Directory of Open Access Journals (Sweden)

    Z. T. Djndoyan

    2014-07-01

    Full Text Available Sufficient information indicating the implication of dysfunction of interleukins (IL-6 and IL-1 in particular in the pathogenesis of amyloidosis in a number of autoinflammatory, rheumatic, and autoimmune diseases, including those in periodic disease (PD, has been recently accumulated. Its genetic defect – pirin mutation – gives rise to an alternative innate immune response (phagocytic cell activation to secrete IL-1 by macrophages and to activate T-helper cells. This causes imbalance in the synthesis of proinflammatory (IL-6, IL-8, and TNF-α and anti-inflammatory (IL-4, IL-10, and IL-1 receptor antagonist cytokines. Moreover, the uncontrolled macrophage (monocyte secretion of a great deal of IL-6 that together with IL-1 is a mediator of the synthesis of the serum amyloid fibril protein precursor SAA by hepatocytes, neutrophils, and fibroblasts plays one of the key roles in the pathogenesis of PD through amyloidosis. With this, IL-6 stimulates the inflammatory process, by enhancing the release of lysosomal enzymes, reactive oxygen species, and eicosanoids (prostaglandins, leukotrienes, thromboxane from the polymorphic nuclear leukocytes, macrophages, endotheliocytes, and fibroblasts and by augmenting the chemotaxis of macrophages and neutrophils, and the degranulation of the latter, i.e. through its action on the effector cells of inflammation, and prepares the tissue basis for amyloid deposits in this fashion. Thus, the analysis of literary and own materials gives grounds to suggest that pirin mutation is a trigger of the synthesis of IL-1 and IL-6 in PD and their hypersecretion is an initial link of the synthesis of SAA.

  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. 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

  16. Review of eprodisate for the treatment of renal disease in AA amyloidosis

    Directory of Open Access Journals (Sweden)

    Javaid MM

    2012-02-01

    Full Text Available Adam Rumjon1, Thomas Coats1, Muhammad M Javaid21Department of Nephrology, King's College Hospital NHS Foundation Trust, London, 2Department of Nephrology, Dartford and Gravesham NHS Trust, Darent Valley Hospital, Dartford, UKAbstract: Secondary (AA amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA, an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not eprodisate has a place in treating renal amyloid disease.Keywords: AA amyloidosis, eprodisate, pathogenesis

  17. 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

  18. 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

  19. 18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Tawada A

    2014-06-01

    Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

  20. 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

  1. Nanolayers for early diagnostics of proteins involved in degenerative amyloidosis

    Directory of Open Access Journals (Sweden)

    Martina M.R.

    2013-08-01

    Full Text Available FK-506 binding protein (FKBP12 is a protein of the family of immunophilins, involved in many neurodegenerative diseases such as Alzheimer’s syndrome where FKBP12 is known to be over-expressed in early stages of the disease. We designed and built Langmuir-Blodgett nanostructures incorporating ligands with high affinity for FKBP12: Tacrolimus (FK506 and Rifaximin as candidate nanosensors to detect low FKBP12 concentration in the initial phase of the amyloidosis. The binding process of the different ligands has been studied by means of photophysical measurements investigating the fluorescence quenching of the tryptophan residue in the binding pocket of FKBP12 by addition of the ligand in solution. Immobilization of the ligands was achieved adopting biomimetic strategy: phospholipid Langmuir-Blodgett films are proposed as nanoscaffolds for ligand inclusion. Several phospholipid nanoarchitectures differing in lipid composition, fluidity, number of layers and method of production (incubation versus co-spreading were screened. The results have shown that both FK506 and Rifaximin ligands penetrate the lipid matrix either as monomers or as aggregates depending on their initial concentration. More importantly, the experiments demonstrated that the ligands in the LB scaffolds efficiently quench FKBP12 fluorescence in solution as a consequence of ligand binding to the protein.

  2. Coexistent asymptomatic myeloma and hereditary cardiac amyloidosis: an unusual case of heart failure.

    Science.gov (United States)

    Lee, Lydia; Aziz, Michael; Wechalekar, Ashutosh; Rabin, Neil

    2011-11-01

    A 76-year-old Afro-Caribbean man presenting with heart failure was diagnosed with isolated cardiac amyloid. He had evidence of myeloma on bone marrow biopsy suggesting AL amyloid, the commonest type of systemic amyloidosis, as the underlying cause. He had no other myeloma-related organ damage. However, endocardial biopsy revealed amyloid fibrils composed of transthyretin and genetic typing established heterozygozity for the valine to isoleucine mutation at position 122 (Val122Ile). The diagnosis was therefore hereditary systemic amyloidosis as a result of a genetic transthyretin variant (ATTR) causing cardiac amyloidosis and coexistent asymptomatic myeloma. This requires symptomatic treatment of heart failure only. This article discusses a rare cause of heart failure and uses this case to illustrate that histological confirmation of the amyloid-causing protein is essential. Mistaken assumption of AL amyloid could have resulted in inappropriate cytotoxic therapy targeting the plasma cell clone. PMID:22083004

  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. 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...

  6. 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.

  7. Renal AA-amyloidosis in intravenous drug users – a role for HIV-infection?

    Directory of Open Access Journals (Sweden)

    Jung Oliver

    2012-11-01

    Full Text Available Abstract Background Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU. Recent reports have postulated a changing pattern of underlying nephropathy over the last decades. Methods Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany. Results Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036 and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069. Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1–2 years. Conclusions AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.

  8. 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

  9. 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.

  10. Inclusion body myositis, muscle blood vessel and cardiac amyloidosis, and transthyretin Val122Ile allele.

    Science.gov (United States)

    Askanas, V; Engel, W K; Alvarez, R B; Frangione, B; Ghiso, J; Vidal, R

    2000-04-01

    Typical of sporadic inclusion body myositis muscle biopsies are vacuolated muscle fibers containing intracellular amyloid deposits and accumulations of "Alzheimer-characteristic" proteins. There is no muscle blood vessel or cardiac amyloidosis. We report on a 70-year-old African-American man homozygous for the transthyretin Val122Ile allele who has both sporadic inclusion body myositis and cardiac amyloidosis. His unique pathological features included transthyretin immunoreactivity in prominent muscle blood vessel amyloid and congophilic amyloid deposits within vacuolated muscle fibers. PMID:10762172

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis.

    Science.gov (United States)

    Butler, James S; Chan, Amy; Costelha, Susete; Fishman, Shannon; Willoughby, Jennifer L S; Borland, Todd D; Milstein, Stuart; Foster, Donald J; Gonçalves, Paula; Chen, Qingmin; Qin, June; Bettencourt, Brian R; Sah, Dinah W; Alvarez, Rene; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Fitzgerald, Kevin; Meyers, Rachel E; Nochur, Saraswathy V; Saraiva, Maria J; Zimmermann, Tracy S

    2016-06-01

    ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis. PMID:27033334

  17. 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

  18. 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 compo...

  19. 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

  20. Bilateral post-arterial puncture pseudoaneurysm in a patient with amyloidosis

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    Paula Sabrina Araújo Milhomem

    2015-03-01

    Full Text Available Amyloidosis consists of deposition of insoluble fibrillar proteins in tissues and, causing dysfunction. In association with other factors, the condition can contribute to emergence of complications, such as pseudoaneurysms at arterial puncture sites. Pseudoaneurysms are becoming an ever-more common complication, which underscores the importance of identifying risk factors, so that their incidence can be minimized.

  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. Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

    Science.gov (United States)

    Larsen, Christopher P; Beggs, Marjorie L; Wilson, Jon D; Lathrop, Sarah L

    2016-06-01

    Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population. PMID:26912093

  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. 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

  8. 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...

  9. Occlusive dressing therapy using dimethyl sulfoxide in a patient presenting with primary localized amyloidosis of the urinary bladder: a case report

    OpenAIRE

    Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

    2013-01-01

    Introduction Amyloidosis is characterized by extracellular deposition of abnormal insoluble fibrils, which cause structural and functional disorders. Amyloidosis is classified into primary and secondary disease. We report a case of localized amyloidosis of the urinary bladder. In the English literature, this is the first case effectively treated with occlusive dressing therapy using dimethyl sulfoxide. Case presentation A 58-year-old Japanese woman was introduced to our department with asympt...

  10. 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

  11. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography

    International Nuclear Information System (INIS)

    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 18F-florbetapir for imaging cardiac amyloidosis. We performed a pilot study of cardiac 18F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of 18F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A 18F-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 18F-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-1, IQR 0.034 - 0.051 min-1, vs. 0.023 min-1, IQR 0.015 - 0.025 min-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. 18F-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.)

  12.  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

  13. {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

  14. Heart transplantation for homozygous familial transthyretin (TTR) V122I cardiac amyloidosis.

    Science.gov (United States)

    Hamour, I M; Lachmann, H J; Goodman, H J B; Petrou, M; Burke, M M; Hawkins, P N; Banner, N R

    2008-05-01

    Heart failure is the usual cause of death in patients with amyloid cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is associated with the Val122Ile variant of transthyretin (TTR), which is carried by 3-4% of the African American population. Here, we report the outcome of the first cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man presented with biventricular failure. Other than previous bilateral carpel tunnel syndrome, he had been well and had no evidence of extracardiac amyloidosis. An endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene indicated homozygosity for V122I. He underwent cardiac transplantation and 3 years later, remains well with no evidence of allograft or systemic amyloid deposition. PMID:18318779

  15. Bullous variant of familial biphasic lichen amyloidosis: A unique combination of three rare presentations

    Directory of Open Access Journals (Sweden)

    Vijayalaxmi Veerabasappa Suranagi

    2015-01-01

    Full Text Available A 55-year-old man presented with multiple, itchy papules and macules on the trunk and extremities. Histopathologic examination of biopsy specimens taken from three different lesions showed a subepidermal blister with amyloid deposits in the dermal papillae. No systemic disease or involvement of other organs was detected. The clinical and histological findings were compatible with a bullous variant of lichen amyloidosis (LA. Primary cutaneous localized amyloidosis usually presents with papular, macular or nodular lesions. Bullous lesions associated with LA are very rare. Furthermore, patient had seven other members in the family with similar lesions, which is also a rare occurrence. We report a case with a rare combination of biphasic, bullous variant of familial LA.

  16. 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.

  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. Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis.

    Science.gov (United States)

    Ihse, Elisabet; Rapezzi, Claudio; Merlini, Giampaolo; Benson, Merrill D; Ando, Yukio; Suhr, Ole B; Ikeda, Shu-Ichi; Lavatelli, Francesca; Obici, Laura; Quarta, Candida C; Leone, Ornella; Jono, Hirofumi; Ueda, Mitsuharu; Lorenzini, Massimiliano; Liepnieks, Juris; Ohshima, Toshinori; Tasaki, Masayoshi; Yamashita, Taro; Westermark, Per

    2013-09-01

    Abstract The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one consisting of mainly intact ATTR (type B). The fibril types are correlated to phenotypic differences. Patients with ATTR fragments have a late onset and develop cardiomyopathy, while patients without fragments have an early onset and less myocardial involvement. The present study aimed to determine whether this correlation between fibril type and phenotype is valid for familial ATTR amyloidosis in general. Cardiac or adipose tissues from 63 patients carrying 29 different TTR non-V30M mutations as well as 13 Japanese ATTRV30M patients were examined. Fibril type was determined by western blotting and compared to the patients' age of onset and degree of cardiomyopathy. All ATTR non-V30M patients had a fibril composition with ATTR fragments, except two ATTRY114C patients. No clear conclusions could be drawn about a phenotype to fibril type correlation among ATTR non-V30M patients. In contrast, Japanese ATTRV30M patients showed a similar correlation as previously described for Swedish ATTRV30M patients. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis, and suggests that fibrils composed of only full-length ATTR is an exception found only in a subset of patients. PMID:23713495

  19. 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...

  20. Radiation Emitted From Mobile Phone Induces Amyloidosis Features in Some Tissues of Infant Mice

    OpenAIRE

    N Hanafi*, F. Eid** and A. El-Dahshan

    2012-01-01

    : Investigating the effects of mobile phone–emitted radiation (MPR) on inducing histopathological changes associated with amyloidosis feature in liver, kidney and brain of infant mice. Methods: Twenty one infant mice (aged 1 day) were assigned to 3 groups, the 1st group served as control, the 2nd group exposed to mobile phone radiation ( MPR) daily for one month (¾ h /day) and the 3rd group remained for one month after stopping radiation exposure. Results: There were different degrees of dama...

  1. 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...

  2. 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 ...

  3. 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 ...

  4. 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...

  5. 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...

  6. 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.

  7. Etanercept In the treatment of AA-amyloidosis in juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    H Mihels

    2004-08-01

    Full Text Available Objective. To study effect of etanercept, an antagonist of serum A amyloid production in the AA amyloidosis treatment in juvenile idiopathic arthritis (JIA. Material and methods. Etanercept was administered to all pts with AA amyloidosis admitted to Garmisch-Paterkirchen pediatric rheumatological clinic beginning with 2000. C-reactive protein (CRP, degree of proteinuria and serum creatinin were used as preliminary outcome measures. Results. 11 pts with seronegative JIA (6 boys and 5 girls were included in the study. Mean follow up duration was l,9±l.01 years. 8 children had systemic, 2 - olygoarticular and one - polyarticular disease onset. Before the study all pts had CRP level elevation (1,03-8,29 mg/dl, mean 4,53 mg/dl. 8 from 11 had marked proteinuria (364-7400 mg/24 hours, mean 1186 mg/24 hours. 2 from 11 had serum creatinin elevation. During etanercept treatment CRP level normalized in 2 and significantly decreased in 4 pts. Proteinuria decreased in 4 from 8 pts. Significant change of creatinin level was not achieved. One girl who did not have improvement during etanercept treatment showed CRP normalization and decrease of proteinuria when the drug was changed to infliximab. Conclusion. Treatment with etanercept provided improvement in almost 2/3 from 11 pts with JIA and AA amyloidosis. Etanercept may be the drug of choice in pts with normal creatinine level in the absence of proteinuria. When it fails another tumor necrosis factor antagonist such as infliximab should be used. It is necessary to extend volume and duration of the study to get more reliable data on etanercept efficacy in JIA pts with AA amyloidosis.

  8. Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation.

    Science.gov (United States)

    Liepnieks, Juris J; Benson, Merrill D

    2007-12-01

    It has been hypothesized that transthyretin (TTR) amyloidosis may progress after orthotopic liver transplantation (OLT) as a result of continued amyloid fibril synthesis and deposition from normal TTR. To test this hypothesis amyloid fibrils were isolated from cardiac tissues of three patients who died 1(1/2) to 5(1/2) years after OLT: two with Val30Met and one with Thr60Ala TTR. The ratio of variant to normal TTR in each case was determined and compared with the ratio of variant to normal in cardiac tissues from seven patients who died with TTR amyloidosis but who had not had liver transplantation. Tissues from patients with TTR amyloidosis without OLT included three with Val30Met, two with Thr60Ala, one with deltaVal122, and one with Val122Ile. All tissues from patients without OLT had greater amounts of variant TTR than normal TTR except for the Val122Ile in which the ratio was 50:50. The overall median variant to normal ratio was 60:40 with a range of 50-70% variant. In contrast, the mean percentage of variant TTR in the three tissues from patients after OLT was 25% (range 20-35). These data are consistent with the continued deposition of normal TTR in cardiac tissue after liver transplantation. PMID:17968687

  9. 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.

  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. 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

  12. 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.

  13. Imaging findings and literature review of 18F-FDG PET/CT in primary systemic AL amyloidosis

    International Nuclear Information System (INIS)

    Although several case reports and case series have described 18F-FDG PET/CT in amyloidosis, the value of 18F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of 18F-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 18F-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 18F-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; SUVmax = 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 18F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). 18F-FDG uptake was negative for pancreas and gastric lesions. Although 18F-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 18F-FDG PET/CT in amyloidosis will be warranted

  14. A patient with AL amyloidosis with negative free light chain results.

    Science.gov (United States)

    Milani, Paolo; Valentini, Veronica; Ferraro, Giovanni; Basset, Marco; Russo, Francesca; Foli, Andrea; Palladini, Giovanni; Merlini, Giampaolo

    2016-06-01

    The detection and quantification of amyloidogenic monoclonal light chains are necessary for the diagnosis and evaluation of response to treatment in AL amyloidosis. However, the amyloid clone is often small and difficult to detect. We report the case of a 68-year-old man who was referred to our Center in April 2013 after syncope and the identification of left ventricular hypertrophy at echocardiography, suspected for amyloidosis. A commercial agarose gel electrophoresis immunofixation (IFE) did not reveal monoclonal components in serum and urine. The κ serum free light chain (FLC) concentration was 21.5 mg/L, λ 33 mg/L (κ/λ ratio 0.65), NT-proBNP 9074 ng/L (u.r.l. <332 ng/L) and an echocardiogram confirmed characteristic features of amyloidosis. The abdominal fat aspiration was positive and the amyloid typing by immune-electron microscopy revealed λ light chains deposits. A high-resolution (hr) IFE of serum and urine showed a faint monoclonal λ component in the urine. A bone marrow biopsy showed 8% plasma cells (BMPC) and a kappa/lambda light-chain restriction with λ light chain on immunofluorescence. The diagnosis of AL (λ) amyloidosis with cardiac involvement was made. In May 2013, patient was started on cyclophosphamide, bortezomib and dexamethasone. After six cycles, serum and urine hr-IFE were negative, the bone marrow biopsy showed 3% BMPC without light chain restriction by immunofluorescence, and a decrease of NT-proBNP was observed (5802 ng/L).Thus, treatment was discontinued. In this patient the amyloid clone could be detected only by in house hr-IFE of urine and bone marrow examination. The detection of the small dangerous amyloidogenic clone should be pursued with a combination of high-sensitivity techniques, including assessment of BMPC clonality. Studies of novel tools, such as mass spectrometry on serum and next-generation flow cytometry analysis of the bone marrow, for detecting plasma cell clones in AL amyloidosis and other monoclonal light

  15. 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.)

  16. 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

  17. 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...

  18. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, S.; Kader, E. [Univ. of Cape Town, Dept. of Paediatric Radiology, Rondebusch, Cape Town (South Africa)

    2001-05-01

    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.)

  20. A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing.

    Science.gov (United States)

    Connors, L H; Ericsson, T; Skare, J; Jones, L A; Lewis, W D; Skinner, M

    1998-09-30

    Variant forms of the plasma protein transthyretin (TTR) are associated with the most frequently occurring type of familial systemic amyloidosis. Organ system involvement in transthyretin type amyloidosis (ATTR) is often similar to that which occurs in light chain amyloid disease (AL). The proper diagnosis of ATTR is important since treatment (liver transplantation) differs from that in AL (chemotherapy). We present a two-step test to screen sera for variant TTRs using non-denaturing gel electrophoresis performed in 7.5% acrylamide (PAGE) followed by isoelectric focusing (IEF) between pH 4.0 and 7.0 in 2.5 M urea. Serum samples from 110 patients with amyloidosis and their relatives were tested using this IEF technique and compared to genetic mutation results. Sera from patients with ATTR who underwent liver transplantation were also examined prior to and following surgery. IEF analysis showed the presence of both wild-type and variant TTR in 74 of the 110 serum samples tested. Genomic DNA from peripheral blood was used to identify TTR gene mutations in 77 of the 110 patients. Fifteen variants including Val122Ile, preponderant in the African-American population, could be demonstrated by IEF. The sensitivity of IEF was 96% (74/77) and the specificity was 100% (33/33). The predictive values for a positive or negative result were 100% (74/74) and 92% (33/36), respectively. There were no false-positive results and 4% (3/77) false-negative results. In sera from patients with ATTR who underwent liver transplantation, variant TTR was detected by IEF before, but not after, surgery. A simple, accurate, sensitive method is presented as a useful screening test for variant transthyretins associated with ATTR. PMID:9748569

  1. 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.

  2. 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.

  3. The accessible cerebral vascular proteome in a mouse model of cerebral β-amyloidosis.

    Science.gov (United States)

    Roesli, Christoph; Fugmann, Tim; Borgia, Beatrice; Schliemann, Christoph; Neri, Dario; Jucker, Mathias

    2011-04-01

    Assessing protein changes in the cerebral vasculature of brain disorders may increase our understanding of disease pathogenesis and facilitate diagnostic and therapeutic intervention. By combining perfusion of mice with a charged reactive biotin derivative and subsequent quantification of the biotinylated proteins, the proteome accessible from the vasculature in an APPPS1 transgenic mouse model of cerebral β-amyloidosis was identified and compared to that in non-transgenic control mice. Our results provide proof-of-concept of this technology for the identification of new targets for antibody-based therapy or pharmacodelivery, and for neuroimaging in neurodegenerative diseases. PMID:21262399

  4. [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

  5. 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

    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...

  6. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis.

    Science.gov (United States)

    Ibi, Kanata; Murakami, Tomoaki; Goda, Wael Mohamed; Kobayashi, Naoki; Ishiguro, Naotaka; Yanai, Tokuma

    2015-10-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent. PMID:25985816

  7. Frequencies and geographic distributions of genetic mutations in transthyretin- and non-transthyretin-related familial amyloidosis.

    Science.gov (United States)

    Zhen, D B; Swiecicki, P L; Zeldenrust, S R; Dispenzieri, A; Mauermann, M L; Gertz, M A

    2015-10-01

    Inherited forms of amyloidosis are rare; of these, transthyretin-related (ATTR) is the most common, but non-ATTR has been described as well. We studied a large case series of ATTR and a small series of non-ATTR to better determine the mutation frequencies and geographic distributions of these inherited forms of amyloidosis in the United States. We performed a retrospective cross-sectional study of 284 ATTR and non-ATTR patients seen at Mayo Clinic in Rochester, Minnesota, from 1 January 1970 through 29 January 2013. Mutations were identified by DNA sequencing, restriction fragment length polymorphism, or mass spectroscopy. The genetic testing method was unknown for several patients, but a small proportion were identified by family history or by classical clinical presentation associated with a specific mutation. The most common ATTR mutations were Thr60Ala (24%), Val30Met (15%), Val122Ile (10%), and Ser77Tyr (5%). Non-ATTR mutations included gelsolin (n = 3), apolipoprotein A-I (n = 6), apolipoprotein A-II (n = 1), fibrinogen A-α (n = 9), and lysozyme (n = 1). Although rare, ATTR and, to a lesser extent, non-ATTR are prevalent in the United States and should be considered for patients presenting in the appropriate clinical context. PMID:25211232

  8. 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.

  9. 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.)

  10. 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

  11. 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

  12. 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,

  13. 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.

  14. 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.

  15. 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

  16. Prevalence of isolated atrial amyloidosis in young patients affected by congestive heart failure.

    Science.gov (United States)

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Tanganelli, Piero; Santucci, Annalisa

    2012-01-01

    Atrial natriuretic peptide (ANP), whose amyloid is responsible of isolated atrial amyloidosis (IAA), is known to play an important role in the pathophysiology of congestive heart failure (CHF). We provide here the microscopic examination of atrial biopsies from 36 young (mean 40 years) CHF patients distinguished in idiopathic dilated cardiomyopathy (DC) affected and hypertrophic Cardiomyopathy (HC) affected, endorsing the presumptive association of early CHF with IAA. We utilized a multiple method, using Congo red (CR) staining, CR fluorescence (CRF), and immunohistochemistry to assess the presence of IAA in CHF. Immunostaining showed a moderate deposition of IAA in the atrium surrounding working myocardium with small intracellular deposits. Our findings suggest a monitoring of young CHF cases for the development of IAA. Our study also demonstrated how the concurrent use of immunohistochemistry, CR, and CRF may greatly enhance the detection of low-grade amyloid deposits. PMID:22536133

  17. Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog.

    Science.gov (United States)

    Besancon, M Faulkner; Stacy, Brian A; Kyles, Andrew E; Moore, Peter F; Vernau, William; Smarick, Sean D; Rasor, Liberty A

    2004-04-15

    A 7-year-old castrated male Miniature Schnauzer was examined because of labored breathing and episodes of respiratory distress that progressed to collapse. On cervical radiographs, a focal soft tissue mass in the caudal cervical portion of the trachea was observed, and during tracheoscopy, a 1 x 1 cm, pedunculated, multinodular, pink, intraluminal mass extending from the dorsal tracheal membrane and obstructing approximately 80% of the tracheal lumen was seen. Tracheal resection and anastomosis was performed to remove the mass, and the dog recovered without complications. On histologic examination, the mass consisted of a large accumulation of homogeneous, faintly fibrillar eosinophilic material admixed with a predominantly plasma cell infiltrate; examination of sections stained with thioflavin T and Congo red stain confirmed that the eosinophilic material was amyloid. A diagnosis of nodular, immunocyte-derived (AL) amyloidosis was made. Seventeen months after surgery, the dog had a relapse of respiratory distress because of an extramedullary plasmacytoma involving the trachea. PMID:15112779

  18. 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

  19. Prognostic impact of T2-weighted CMR imaging for cardiac amyloidosis

    International Nuclear Information System (INIS)

    Using cardiac magnetic resonance imaging (MRI) we tested the diagnostic value of various markers for amyloid infiltration. We performed MRI at 1.5 T in 36 consecutive patients with cardiac amyloidosis and 48 healthy volunteers. The protocol included cine imaging, T2-weighted spin echo, T1-weighted spin echo before and early after contrast and late gadolinium enhancement. We compared the frequency of abnormalities and their relation to mortality. Median follow-up was 31 months. Twenty-three patients died. Mean left ventricular (LV) mass was 205 ± 70 g. LV ejection fraction (EF) was 55 ± 12%. T2 ratio was 1.5 ± 0.4. 33/36 patients had pericardial and 22/36 had pleural effusions. All but two had heterogeneous late enhancement. Surviving patients did not differ from those who had died with regard to gender, LV mass or volume. Surviving patients had a significantly higher LVEF (60.4 ± 9.9% vs. 51.6 ± 11.5%; p = 0.03). The deceased patients had a lower T2 ratio than those who survived (1.38 ± 0.42 vs. 1.76 ± 0.17; p = 0.005). Low T2 was associated with shorter survival (Chi-squared 11.3; p < 0.001). Cox regression analysis confirmed T2 ratio < 1.5 as the only independent predictors for survival. Cardiac amyloidosis is associated with hypointense signal on T2-weighted images. A lower T2 ratio was independently associated with shortened survival. (orig.)

  20. Prognostic impact of T2-weighted CMR imaging for cardiac amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Wassmuth, Ralf; Schulz-Menger, Jeanette [HELIOS Klinikum Berlin Buch, Charite Campus Buch, Berlin (Germany); Abdel-Aty, Hassan [HELIOS Klinikum Berlin Buch, Charite Campus Buch, Berlin (Germany); Cardio Imaging Center Berlin, Berlin (Germany); Bohl, Steffen [HELIOS Klinikum Berlin Buch, Charite Campus Buch, Berlin (Germany); Unfallkrankenhaus Berlin, Berlin (Germany)

    2011-08-15

    Using cardiac magnetic resonance imaging (MRI) we tested the diagnostic value of various markers for amyloid infiltration. We performed MRI at 1.5 T in 36 consecutive patients with cardiac amyloidosis and 48 healthy volunteers. The protocol included cine imaging, T2-weighted spin echo, T1-weighted spin echo before and early after contrast and late gadolinium enhancement. We compared the frequency of abnormalities and their relation to mortality. Median follow-up was 31 months. Twenty-three patients died. Mean left ventricular (LV) mass was 205 {+-} 70 g. LV ejection fraction (EF) was 55 {+-} 12%. T2 ratio was 1.5 {+-} 0.4. 33/36 patients had pericardial and 22/36 had pleural effusions. All but two had heterogeneous late enhancement. Surviving patients did not differ from those who had died with regard to gender, LV mass or volume. Surviving patients had a significantly higher LVEF (60.4 {+-} 9.9% vs. 51.6 {+-} 11.5%; p = 0.03). The deceased patients had a lower T2 ratio than those who survived (1.38 {+-} 0.42 vs. 1.76 {+-} 0.17; p = 0.005). Low T2 was associated with shorter survival (Chi-squared 11.3; p < 0.001). Cox regression analysis confirmed T2 ratio < 1.5 as the only independent predictors for survival. Cardiac amyloidosis is associated with hypointense signal on T2-weighted images. A lower T2 ratio was independently associated with shortened survival. (orig.)

  1. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis.

    Science.gov (United States)

    Sipe, Jean D; Benson, Merrill D; Buxbaum, Joel N; Ikeda, Shu-ichi; Merlini, Giampaolo; Saraiva, Maria J M; Westermark, Per

    2012-12-01

    The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIIIth International Symposium, May 6-10, 2012, Groningen, The Netherlands, to formulate recommendations on amyloid fibril protein nomenclature and to consider newly identified candidate amyloid fibril proteins for inclusion in the ISA Amyloid Fibril Protein Nomenclature List. The need to promote utilization of consistent and up to date terminology for both fibril chemistry and clinical classification of the resultant disease syndrome was emphasized. Amyloid fibril nomenclature is based on the chemical identity of the amyloid fibril forming protein; clinical classification of the amyloidosis should be as well. Although the importance of fibril chemistry to the disease process has been recognized for more than 40 years, to this day the literature contains clinical and histochemical designations that were used when the chemical diversity of amyloid diseases was poorly understood. Thus, the continued use of disease classifications such as familial amyloid neuropathy and familial amyloid cardiomyopathy generates confusion. An amyloid fibril protein is defined as follows: the protein must occur in body tissue deposits and exhibit both affinity for Congo red and green birefringence when Congo red stained deposits are viewed by polarization microscopy. Furthermore, the chemical identity of the protein must have been unambiguously characterized by protein sequence analysis when so is practically possible. Thus, in nearly all cases, it is insufficient to demonstrate mutation in the gene of a candidate amyloid protein; the protein itself must be identified as an amyloid fibril protein. Current ISA Amyloid Fibril Protein Nomenclature Lists of 30 human and 10 animal fibril proteins are provided together with a list of inclusion bodies that, although intracellular, exhibit some or all of the properties of the mainly extracellular amyloid fibrils. PMID:23113696

  2. 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.

  3. 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

  4. Response to anti-TNF-α treatment for secondary renal amyloidosis in a patient with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    A. Gallo

    2011-09-01

    Full Text Available Renal amyloidosis is a complication of ankylosing spondylitis. A possible pathogenetic role is due to TNF-α, with a direct action on glomerular receptors TNFR2 and renal injury, secondary to deposition of amyloid fibrils. The most frequent clinical manifestation is proteinuria or nephrotic syndrome. Etanercept, a soluble receptor of TNF-α, binds this circulant cytokine with a progressive improvement of renal function and reduction of deposits of amyloid. Transient leukopenia, observed during ankylosing spondylitis, should not be considered a controindication to the use of Etanercept, but it requires a constant monitoring. The benefit observed in our patient can represent an indication to the use of Etanercept for the management of amyloidosis.

  5. 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 ...

  6. 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...

  7. Amyloid A amyloidosis in non-infected and avian leukosis virus-C persistently infected inbred ducks

    Czech Academy of Sciences Publication Activity Database

    Stepanets, Volodymyr; Vernerová, Z.; Vilhelmová, Milena; Geryk, Josef; Hejnar, Jiří; Svoboda, Jan

    2001-01-01

    Roč. 30, č. 1 (2001), s. 33-42. ISSN 0307-9457 R&D Projects: GA ČR GA301/94/0713; GA ČR GA524/01/0866 Institutional research plan: CEZ:AV0Z5052915 Keywords : amyloidosis * amyloid A * persistent retroviral infection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.655, year: 2001

  8. Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta)

    OpenAIRE

    Liu, David X.; Gilbert, Margaret H; Wang, Xiaolei; Didier, Peter J.; Veazey, Ronald S.

    2012-01-01

    Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) pro...

  9. 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...

  10. The first Caucasian patient with p.Val122Ile mutated-transthyretin cardiac amyloidosis treated with isolated heart transplantation.

    Science.gov (United States)

    Ammirati, Enrico; Marziliano, Nicola; Vittori, Claudia; Pedrotti, Patrizia; Bramerio, Manuela A; Motta, Valentina; Orsini, Francesco; Veronese, Silvio; Merlini, Piera A; Martinelli, Luigi; Frigerio, Maria

    2012-06-01

    Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p.Val122Ile mutated TTR-related cardiac amyloidosis treated with heart transplantation due to this gene mutation frequent in Afro-Americans with a prevalent isolated heart involvement. The choice of isolated heart transplantation instead of combined heart and liver transplantations was based on (1) severe and progressive cardiac disease, (2) evidence of a gene mutation generally associated with isolated cardiac disease and (3) absence of relevant extra-cardiac involvement (with the possible exception of mild peripheral neuropathy). In any case, the very short post-transplant observation period of 10 months does not allow any conclusions on the long-term course of the presented strategy. Finally, it is the first European Caucasian family with the p.Val122Ile TTR mutation that has been described. Till now, very few Caucasian cases of p.Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p.Val122Ile. PMID:22449240

  11. Systemic Amyloidosis and Testicular Interstitial Tumor in a Zebra Finch (Taeniopygia guttata: a Case Report in Iran

    Directory of Open Access Journals (Sweden)

    Mehrnoush Moeini Jazani

    2011-09-01

    Full Text Available Abstract Systemic amyloidosis and testicular interstitial tumor are rare conditions in birds and this is the first report in Iran. A male zebra finch was presented because of white diarrhea, anorexia, loss of weight and lethargy. At necropsy, the small intestine was edematous and congested. The spleen appeared pale. The liver was large, firm and brown. One testis was cystic and neoplastic and the remaining testis was atrophic. Histologically, amyloid materials were seen predominantly in the liver and spleen. Hyaline substances were deposited in the Disse space and in the media of blood vessels of the liver. In spleen, marked deposits thickened the basement membranes of blood vessels and extended into the surrounding parenchyma. In addition, there were lesser degrees of amyloidosis in other organs such as small intestine. Amyloid stained positively with Congo red. In testis, there was encapsulated unilateral interstitial cell tumor, with multiple foci of necrosis and hemorrhage. The neoplastic cells were round to polyhedral, with small round hyperchromatic nuclei and finely vacuolated cytoplasm. Signs of feminization were observed. The cause of amyloidosis in this study was not conclusively identified.

  12. 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.

  13. Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization.

    Science.gov (United States)

    Green, Nora S; Palaninathan, Satheesh K; Sacchettini, James C; Kelly, Jeffery W

    2003-11-01

    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 senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Monovalent small molecules that bind to one or both of the unoccupied thyroid hormone binding sites at the TTR quaternary structure interface stabilize the native state, raising the kinetic barrier for tetramer dissociation sufficiently that the rate of dissociation, and therefore amyloidosis, becomes slow. Bivalent amyloid inhibitors that bind to both binding sites simultaneously are reported herein. The candidate bivalent inhibitors are generally unable to bind to the native TTR tetramer and typically do not engage in monovalent binding owing to a strong inhibitor orientation preference. However, the TTR quaternary structure can assemble around several of the bivalent inhibitors if the inhibitor intercepts the protein before assembly occurs. Some of the wild-type TTR.bivalent inhibitor complexes prepared in this fashion retain a tetrameric structure when subjected to substantial denaturation stresses (8 M urea, 120 h). The best bivalent inhibitor reduced acid-mediated TTR (3.6 microM) amyloid fibril formation to 6% of that exhibited by TTR in the absence of inhibitor, a significant improvement over the approximately 30% observed for the best monovalent inhibitors (3.6 microM, 72 h). The apparent dissociation rate of the best bivalent inhibitor is effectively zero, consistent with the idea that TTR tetramer dissociation and inhibitor dissociation are linked-as a result of the inhibitor-templating tetramer assembly. X-ray cocrystal structures of two of the complexes demonstrate that the bivalent inhibitors simultaneously occupy both sites in TTR, consistent with the 1:1 binding stoichiometry derived from HPLC analysis. The purpose of this study was

  14. 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

  15. 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

  16. 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

  17. 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.

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

    Science.gov (United States)

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

    2005-10-11

    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 transition state, thereby raising the kinetic barrier for tetramer dissociation. Herein we demonstrate that genistein, the major isoflavone natural product in soy, works in this fashion and is an excellent inhibitor of transthyretin tetramer dissociation and amyloidogenesis, reducing acid-mediated fibril formation to familial amyloid cardiomyopathy mutations in TTR: V30M and V122I, respectively. Genistein additionally inhibits tetramer dissociation under physiological conditions thought to lead to slow amyloidogenesis in humans. Furthermore, this natural product exhibits highly selective binding to TTR in plasma over all of the other plasma proteins. Isothermal titration calorimetry shows that genistein binds to TTR with negative cooperativity (K(d1) = 40 nM, K(d2) = 1.4 microM). The benefits of using a nutraceutical such as genistein to treat orphan diseases such as the TTR amyloidoses include known oral bioavailability and safety data. It is conceivable that some patients could benefit from simply increasing their intake of soy products or supplements. PMID:16195386

  19. Primary tracheobronchial amyloidosis associated with tracheobronchomegaly evaluated by novel four-dimensional functional CT.

    Science.gov (United States)

    Uddin, A K M Nizam; Mansfield, Darren R; Farmer, Michael W; Lau, Kenneth K

    2015-12-01

    Amyloid is a heterogeneous family of extracellular proteinaceous deposits characterized by apple-green birefringence on polarized light microscopy. There are rare case reports of these extracellular deposits accumulating in the upper and central airways. Progressive infiltration may impair glottic and airway function with some cases requiring intervention to improve flow. Bronchoscopy and lung function testing provide dynamic information to monitor for disease progression; however, the recent development of 320 multislice computed tomography (320 CT) enables dynamic, four-dimensional (4-D) evaluation of laryngeal and tracheal structure and function and presents as a noninvasive, low-radiation dose surveillance tool. We reviewed a 43-year-old man with primary amyloidosis of the larynx and central airways who presented with an 18-year history of progressive dysphonia without breathlessness and preserved lung function. 4-D CT demonstrated marked thickening of supraglottic folds and trachea with marked tracheal dilatation. Despite gross structural abnormalities, dynamic function assessed throughout inspiration and expiration was normal, demonstrating neither rigidity nor dynamic collapse. This combination of structural and functional assessment of the proximal airway by 4-D CT is a novel application to surveillance for laryngeal and tracheal amyloid. PMID:26740884

  20. 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

  1. 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

  2. Magnetic resonance imaging of dialysis-related amyloidosis of the shoulder and hip

    International Nuclear Information System (INIS)

    Objective. The purpose of this study was to evaluate the usefulness of MRI in identifying abnormalities of the periarticular structures in patients with symptoms of dialysis-related amyloid arthropathy. Design and patients. MR images of shoulders and hips in 5 dialysis patients with symptoms of amyloid arthropathy were compared to images of shoulders and hips in 4 asymptomatic dialysis patients, shoulders in 9 nondialysis patients, and hips in 12 nondialysis patients. These were evaluated for the presence of focal periarticular osseous lesions, tendinous and capsular thickening, and periarticular fluid. Results. Increased thickness of the supraspinatus tendon was found in both symptomatic and asymptomatic patients. Capsular thickening at the hip was present in all symptomatic patients, and in 3 of 8 asymptomatic hips. Joint and bursal fluid was common in the symptomatic group, and was present in some asymptomatic individuals. Osseous lesions were detected in the absence of plain film findings, and demonstrated variable signal intensity. Conclusions. MRI is useful in detecting signs of dialysis-related amyloidosis. Findings of a milder degree in asymptomatic dialysis patients suggests that MRI may also be valuable in the early diagnosis of this syndrome. (orig.)

  3. Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis

    International Nuclear Information System (INIS)

    Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. Methods: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48 months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. Results: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca2+ transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Conclusion: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart

  4. 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. PMID:27197872

  5. 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.

  6. Hereditary and Sporadic Forms of Aβ-Cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

    Directory of Open Access Journals (Sweden)

    Samir Kumar-Singh

    2009-04-01

    Full Text Available Cerebral amyloid angiopathy (CAA refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-β (Aβ-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD and Down’s syndrome. Moreover, Aβ-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Aβ domain of the amyloid precursor protein (APP such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Aβ variants or an unaltered Aβ42/Aβ40 ratio favor vascular Aβ deposition over parenchymal plaques, but higher than critical levels of Aβ40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.

  7. 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

  8. 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

  9. 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

  10. 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.              ...

  11. Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy

    Directory of Open Access Journals (Sweden)

    Halloush Ruba

    2009-01-01

    Full Text Available Introduction: Systemic amyloidosis (SA has a broad nonspecific clinical presentation. Its diagnosis depends on identifying amyloid in tissues. Abdominal fat pad fine needle aspiration (FPFNA has been suggested as a sensitive and specific test for diagnosing SA. Materials and Methods: Thirty-nine FPFNA from 38 patients (16 women and 20 men, age range 40-88 years during a 15-year period were reviewed. Smears and cell blocks were stained with Congo red (CR. A panel of antibodies (serum amyloid protein, serum amyloid A, albumin, transthyretin, kappa light chain and lambda light chain was used on six cell blocks from five patients. The FNA findings were correlated with clinical and histological follow-up. Results: FPFNAs were positive, confirmed by CR in 5/39 (13%, suspicious in 1/39 (3%, negative in 28/39 (72%, and insufficient for diagnosis in 5/39 (13% of cases. In all the positive cases, SA was confirmed within 2-16 weeks. Among the 28 negative cases, SA was diagnosed in 21, the rest were lost to follow-up. Among the insufficient cases, SA was diagnosed in four and one was lost to follow-up. Specificity was 100%, whereas sensitivity was 19%. SA typing using cell block sections was successful in three, un-interpretable in one, and negative in two cases. Conclusion: FPFNA for SA is not as good as previously reported. This may be due to different practice setting, level of experience, diagnostic technique, or absence of abdominal soft tissue involvement. A negative result of FPFNA does not exclude SA. Immune phenotyping of amyloid is possible on cell block.

  12. 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.)

  13. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    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.

  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

    -fibrillary) lesions was found. A[beta] was also present in a proportion of both vascular and parenchymal lesions. There was severe neurofibrillary pathology, and tau immunoblotting revealed a triplet electrophoretic migration pattern comparable with PHF-tau. FDD is a novel form of CNS amyloidosis with extensive...

  15. 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.

  16. [The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].

    Science.gov (United States)

    Rekhtina, I G; Zakharova, E V; Stoliarevich, E S; Sinitsina, M N; Denisova, E N

    2015-01-01

    Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis. PMID:26281203

  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. Successful treatment with humanized anti-interleukin-6 receptor antibody (tocilizumab) in a case of AA amyloidosis complicated by familial Mediterranean fever.

    Science.gov (United States)

    Hamanoue, Satoshi; Suwabe, Tatsuya; Hoshino, Junichi; Sumida, Keiichi; Mise, Koki; Hayami, Noriko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Yazaki, Masahide; Ikeda, Shuichi; Ubara, Yoshifumi

    2016-07-01

    Familial Mediterranean fever (FMF) is a well-known cause of secondary AA amyloidosis. Colchicine is generally considered to be the most effective treatment for FMF and FMF-associated amyloidosis, but the management of patients who are refractory to colchicine remains controversial. We encountered a 51-year-old Japanese man with suspected FMF, who had periodic fever with abdominal pain, polyarthritis, and nephropathy (serum creatinine of 1.9 mg/dL and 24-h protein excretion of 3.8 g). FMF was diagnosed by mutation analysis of the Mediterranean fever (MEFV) gene, which revealed that the patient was compound heterozygous for the marenostrin/pyrin variant E148Q/M694I. AA amyloidosis was diagnosed by renal and gastric biopsy. Colchicine was administered, but his arthritis persisted, and serum creatinine increased to 2.4 mg/dL. Therefore, a humanized anti-interleukin-6 receptor antibody (tocilizumab) was administered at a dose of 8 mg/kg on a monthly basis. Both arthritis and abdominal pain subsided rapidly, and C-reactive protein (CRP) decreased from 2.5 to 0.0 mg/dL. After 2 years, his serum creatinine was decreased to 1.5 mg/dL and proteinuria was improved to 0.3 g daily. In addition, repeat gastric biopsy showed a marked decrease of AA amyloidosis. This case suggests that tocilizumab could be a new therapeutic option for patients with FMF-associated AA amyloidosis if colchicine is not effective. PMID:25619282

  1. 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...

  2. Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis.

    Science.gov (United States)

    Sečník, Peter; Honsová, Eva; Jabor, Antonín; Lavríková, Petra; Franeková, Janka

    2016-06-01

    The objective of this study was to demonstrate the necessity of using different methods for amyloidogenic light chain detection. Serum and urine agarose gel electrophoresis and immunofixation, as well as serum free light chain (FLC) immunoassay measurements, were evaluated in a patient with verified multiple myeloma and consequent AL amyloidosis confirmed by Congo red staining and immunofluorescence techniques. Conventional chemistry tests [serum and urine electrophoresis (SPE and UPE); serum and urine immunofixation (SIFE and UIFE)] were inconclusive. Only quantitative FLC immunoassay (serum free light chain immunoanalysis, SFLC) provided correct diagnostic information. A combination of gel-based SIFE and UIFE with more novel quantitative FLC immunoassays appears necessary when searching for monoclonal immunoglobulin light chain-related diseases. PMID:26760309

  3. Prognostic implication of late gadolinium enhancement on cardiac MRI in light chain (AL) amyloidosis on long term follow up

    International Nuclear Information System (INIS)

    Light chain amyloidosis (AL) is a rare plasma cell dyscrasia associated with poor survival especially in the setting of heart failure. Late gadolinium enhancement (LGE) on cardiac MRI was recently found to correlate with myocardial amyloid deposition but the prognostic role is not established. The aim is to determine the prognostic significance of LGE in AL by comparing long term survival of AL patients with and without LGE. Twenty nine consecutive patients (14 females; 62 ± 11 years) with biopsy-proven AL undergoing cardiac MRI with gadolinium as part of AL workup were included. Survival was prospectively followed 29 months (median) following MRI and compared between those with and without LGE by Kaplan-Meier and log-rank analyses. LGE was positive in 23 subjects (79%) and negative in 6 (21%). Left ventricular ejection fraction was 66 ± 17% in LGE-positive and 69 ± 12% in LGE-negative patients (p = 0.8). Overall 1-year mortality was 36%. On follow-up, 14/23 LGE-positive and none of LGE-negative patients died (log rank p = 0.0061). Presenting New York Heart Association heart failure class was also associated with poor survival (p = 0.0059). Survival between two LGE groups stratified by heart failure class still showed a significant difference by a stratified log-rank test (p = 0.04). Late gadolinium enhancement is common and is associated with poor long-term survival in light chain amyloidosis, even after adjustment for heart failure class presentation. The prognostic significance of late gadolinium enhancement in this disease may be useful in patient risk-stratification

  4. Thorough investigation of a canine autoinflammatory disease (AID confirms one main risk locus and suggests a modifier locus for amyloidosis.

    Directory of Open Access Journals (Sweden)

    Mia Olsson

    Full Text Available Autoinflammatory disease (AID manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10(-8 from each analysis showed that one haplotypic pair (H13-11 was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05 renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6. These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts.

  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. The role of fibronectin in the development of experimental amyloidosis. Evidence of immunohistochemical codistribution and binding property with serum amyloid protein A.

    OpenAIRE

    Kawahara, E; Shiroo, M; Nakanishi, I.; Migita, S.

    1989-01-01

    Azocasein-induced amyloid A (AA) amyloidosis in CBA/K1Jms mice was investigated to elucidate a preference of serum amyloid A (SAA) deposition in the spleen. By indirect immunofluorescence using anti-SAA/AA antibodies the initial deposition of SAA/AA was recognized in the marginal zone of spleen at 20 days after azocasein injection. Indirect immunofluorescence using anti-fibronectin antibodies also showed meshwork positivity in the corresponding area more intensely than that in controls. Immun...

  7. Carpal tunnel syndrome in hemodialysis patients as a dialysis-related amyloidosis manifestation – incidence, risk factors and results of surgical treatment

    OpenAIRE

    Kopeć, Jerzy; Gądek, Artur; Drożdż, Maciej; Miśkowiec, Krzysztof; Dutka, Julian; Sydor, Antoni; Chowaniec, Eve; Sułowicz, Władysław

    2011-01-01

    Summary Background Carpal tunnel syndrome (CTS) is the most common complication of dialysis-related amyloidosis (DRA) developing in patients on long-term dialysis therapy. The aim of this study was to evaluate the incidence of CTS and identify factors influencing the development of CTS in patients on maintenance hemodialysis, as well as results of its surgical treatment. Material/Methods The study included 386 patients, among whom CTS was diagnosed in 40 patients (10.4%) on the basis of signs...

  8. T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

    Science.gov (United States)

    Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M

    2016-05-01

    Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. PMID:26872418

  9. 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.

  10. 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.

  11. Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis.

    Science.gov (United States)

    Olsson, Mia; Tintle, Linda; Kierczak, Marcin; Perloski, Michele; Tonomura, Noriko; Lundquist, Andrew; Murén, Eva; Fels, Max; Tengvall, Katarina; Pielberg, Gerli; Dufaure de Citres, Caroline; Dorso, Laetitia; Abadie, Jérôme; Hanson, Jeanette; Thomas, Anne; Leegwater, Peter; Hedhammar, Åke; Lindblad-Toh, Kerstin; Meadows, Jennifer R S

    2013-01-01

    Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (pELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts. PMID:24130694

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

    OpenAIRE

    Ghiso, J.; Jensson, O; Frangione, B

    1986-01-01

    A gamma-trace variant protein is the major constituent of the amyloid fibrils in patients from Iceland with hereditary cerebral hemorrhage with amyloidosis. The protein consists of 110 residues and is similar to human urinary gamma-trace basic protein (or cystatin C) beginning at its 11th amino-terminal residue. It has an amino acid substitution (glutamine for leucine) at position 58 (position 68 in gamma-trace numbering), which is near the proposed active site of related proteins--namely, cy...

  17. Disruption of corticocortical connections ameliorates amyloid burden in terminal fields in a transgenic model of Abeta amyloidosis.

    Science.gov (United States)

    Sheng, Jin G; Price, Donald L; Koliatsos, Vassilis E

    2002-11-15

    We demonstrated previously that amyloid precursor protein (APP) is anterogradely transported from the entorhinal cortex (ERC) to the dentate gyrus via axons of the perforant pathway. In the terminal fields of these inputs, APP undergoes proteolysis to generate C-terminal fragments containing the entire amyloid beta peptide (Abeta) domain. The present study was designed to test the hypothesis that APP derived from ERC neurons is the source of the Abeta peptide deposited in the hippocampal dentate gyrus in Alzheimer's disease (AD) and in transgenic mice with Abeta amyloidosis. We used mice harboring two familial AD-linked genes (human APP Swedish and presenilin1-DeltaE9), in which levels of Abeta (especially Abeta(42)) are elevated, leading to the formation of amyloid plaques, and lesioned the ERC to interrupt the transport of APP from ERC to hippocampus. Our results show that, on the side of ERC lesion, numbers of APP-immunoreactive dystrophic neurites and Abeta burden were significantly reduced by approximately 40 and 45%, respectively, in the dentate gyrus compared with the contralateral side. Reductions in APP and Abeta were more substantial in the molecular layer of the dentate, i.e., a region that contains the ERC terminals, and were associated with a parallel decrease in total APP and Abeta measured by Western blot and ProteinChip immunoassays. Silver and thioflavine staining confirmed the reduction of amyloid plaques on the side of deafferentation. These results are consistent with the hypothesis that ERC may be the primary source of amyloidogenic Abeta in the dentate gyrus, and they suggest an important role of corticocortical and corticolimbic forward connections in determining patterns of amyloid deposition in AD. PMID:12427835

  18. 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

  19. Usefulness of magnetic resonance imaging of the wrist for the early diagnosis of dialysis-related amyloidosis

    International Nuclear Information System (INIS)

    Dialysis-related amyloidosis (DRA) is a major complication of long-term hemodialysis patients. The onset of arthropathy is frequently preceded by carpal tunnel syndrome, but the early non-invasive diagnosis of DRA remains unclear. β2-microglobulin amyloid deposits in joint synovia and soft tissue precede radiological abnormalities. Magnetic resonance imaging (MRI) may play a more important role in the early diagnosis of DRA, because it allows direct visualization of synovitis and deposition of abnormal soft tissue. The purpose of this study was to evaluate the usefulness of MRI of the wrist for the early diagnosis of DRA. The study included 72 patients (male 37, female 35) undergoing hemodialysis from initiation to 20 years. The patients were examined by MR images of synovitis, deposition of abnormal soft tissue and cystic bone lesions at the wrists. Normal MR images of synovia and soft tissue were defined in 6 control subjects (2 normal 4 non-dialysis patients). Synovitis of the carpal bones was found in 23% of the patients at the start of hemodialysis. Deposition of abnormal soft tissue in the carpal canal and cystic bone lesions were detected after 1 and 2 years of hemodialysis, respectively. All findings were increased significantly with an increasing duration of dialysis. Synovitis was present in 90% of the patients with deposition of abnormal soft tissue, and in 80% of the patients with cystic bone lesions. β2-microglobulin value was significantly higher in patients with synovitis, deposition of abnormal soft tissue and cystic bone lesions than in patients without these findings. Our experience suggests that synovitis examined by MRI of the wrists is useful for the early diagnosis of DRA. Thereby, intensive follow-up and management of DRA are required in patients with synovitis at the start of hemodialysis. (author)

  20. 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.

  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. 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...

  3. 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.

  4. 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

  5. Tafamidis for transthyretin amyloidosis.

    Science.gov (United States)

    de Lartigue, J

    2012-05-01

    Tafamidis meglumine (Vyndaqel®, Pfizer) is a novel, first-in-class drug for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare neurodegenerative disorder characterized by progressive sensory, motor and autonomic impairment that is ultimately fatal. Pathogenic mutations in the transthyretin (TTR) protein lead to destabilization of its tetrameric structure and subsequent formation of amyloid aggregates. Tafamidis is a small-molecule inhibitor that binds selectively to TTR in human plasma and kinetically stabilizes the tetrameric structure of both wild-type TTR and a number of different mutants. Clinical trials indicate that tafamidis slows disease progression in patients with TTR-FAP and reduces the burden of disease, demonstrating improvement in small and large nerve fiber function, modified body mass index and lower extremity neurological examination. Tafamidis has been granted marketing authorization by the European Commission for the treatment of TTR-FAP and the U.S. Food and Drug Administration is currently reviewing this drug for the same indication. PMID:22645721

  6. 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.

  7. Amyloidosis and Kidney Disease

    Science.gov (United States)

    ... that make amyloid proteins. These medications may cause hair loss and serious side effects, such as nausea, vomiting, and fatigue. Stem cell transplant. A stem cell transplant is a procedure that ...

  8. Amyloidosis associated with dialysis

    International Nuclear Information System (INIS)

    Amongst the complications of dialysis, amyloid osteopathy is getting increasingly significant. It is due to deposition of β2-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 β2-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.)

  9. 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

  10. 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.

  11. 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

  12. Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis.

    Science.gov (United States)

    Azevedo, E P; Ledo, J H; Barbosa, G; Sobrinho, M; Diniz, L; Fonseca, A C C; Gomes, F; Romão, L; Lima, F R S; Palhano, F L; Ferreira, S T; Foguel, D

    2013-01-01

    Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage. PMID:24008733

  13. 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.

  14. 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

  15. Cardiac Findings and Events Observed in an Open-Label Clinical Trial of Tafamidis in Patients with non-Val30Met and non-Val122Ile Hereditary Transthyretin Amyloidosis

    OpenAIRE

    Damy, Thibaud; Judge, Daniel P; Kristen, Arnt V.; Berthet, Karine; Li, Huihua; Aarts, Janske

    2015-01-01

    A phase 2, open-label study in 21 patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis showed that tafamidis (20 mg daily for 12 months) stabilized these transthyretin variants. We assessed cardiac amyloid infiltration and cardiac abnormalities in this same study population. At baseline, median age was 64.3 years, 11 patients were in NYHA class II, 13 had conduction abnormalities, 14 N-terminal pro-hormone brain natriuretic peptide concentrations >300 pg/ml, and 1...

  16. 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

  17. Carpal tunnel syndrome in hemodialysis patients as a dialysis-related amyloidosis manifestation – incidence, risk factors and results of surgical treatment

    Science.gov (United States)

    Kopeć, Jerzy; Gądek, Artur; Drożdż, Maciej; Miśkowiec, Krzysztof; Dutka, Julian; Sydor, Antoni; Chowaniec, Eve; Sułowicz, Władysław

    2011-01-01

    Summary Background Carpal tunnel syndrome (CTS) is the most common complication of dialysis-related amyloidosis (DRA) developing in patients on long-term dialysis therapy. The aim of this study was to evaluate the incidence of CTS and identify factors influencing the development of CTS in patients on maintenance hemodialysis, as well as results of its surgical treatment. Material/Methods The study included 386 patients, among whom CTS was diagnosed in 40 patients (10.4%) on the basis of signs and physical symptoms, as well as by nerve conduction. The group of patients with CTS and the group of patients without CTS were compared according to age (mean 54.50 vs. 56.48 years) and duration of dialysis treatment. Initial analysis of CTS incidence by sex, presence of anti-HCV antibodies, and location of arterio-venous fistula (AV fistula) was undertaken. Results Duration of dialysis treatment was the statistically significant risk factor for the development of CTS (16.05 vs. 4.51 years; p<0.0001). Among patients treated for a long period on hemodialysis (20–30 years), 100% required surgical release procedures, while 66.66% of those treated for 15–19 years, 42.1% of those treated for 10–14 years, and 1.6% of those treated for less than 10 years. CTS was diagnosed more often in anti-HCV-positive patients as compared with anti-HCV-negative patients (47.5 vs. 6.9%; p<0.0001). No significant differences were found when comparing CTS incidence by sex or between the development of CTS requiring surgical release intervention and location of the AV fistula. Conclusions Surgical release procedure of the carpal tunnel gave good treatment results in patients with CTS. PMID:21873947

  18. 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.

  19. Quantification of the thermodynamically linked quaternary and tertiary structural stabilities of transthyretin and its disease-associated variants: the relationship between stability and amyloidosis.

    Science.gov (United States)

    Hurshman Babbes, Amy R; Powers, Evan T; Kelly, Jeffery W

    2008-07-01

    structure. The A25T mutant, associated with central nervous system amyloidosis, is highly aggregation-prone and exhibits drastically reduced quaternary and tertiary structural stabilities. The observed differences in stability among the disease-associated TTR variants highlight the complexity and heterogeneity of TTR amyloid disease, an observation that has important implications for the treatment of these maladies. PMID:18537267

  20. 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 ...

  1. Molecular Tweezers Targeting Transthyretin Amyloidosis

    OpenAIRE

    Ferreira, N; Pereira-Henriques, A; Attar, A.; Klärner, FG; Schrader, T; Bitan, G.; L. Gales; Saraiva, MJ; Almeida, de, J.R.

    2014-01-01

    Transthyretin (TTR) amyloidoses comprise a wide spectrum of acquired and hereditary diseases triggered by extracellular deposition of toxic TTR aggregates in various organs. Despite recent advances regarding the elucidation of the molecular mechanisms underlying TTR misfolding and pathogenic self-assembly, there is still no effective therapy for treatment of these fatal disorders. Recently, the “molecular tweezers”, CLR01, has been reported to inhibit self-assembly and toxicity of different a...

  2. 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.

  3. Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis.

    Science.gov (United States)

    Damy, Thibaud; Judge, Daniel P; Kristen, Arnt V; Berthet, Karine; Li, Huihua; Aarts, Janske

    2015-03-01

    A phase 2, open-label study in 21 patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis showed that tafamidis (20 mg daily for 12 months) stabilized these transthyretin variants. We assessed cardiac amyloid infiltration and cardiac abnormalities in this same study population. At baseline, median age was 64.3 years, 11 patients were in NYHA class II, 13 had conduction abnormalities, 14 N-terminal pro-hormone brain natriuretic peptide concentrations >300 pg/ml, and 17 interventricular septal thickness >12 mm. Mean (SD) left ventricular ejection fraction was 60.3% (9.96). Patients with normal heart rate variability increased from 4/19 at baseline to 8/19 at month 12 (p < 0.05). Cardiac biomarkers remained stable. Although four patients had increases in interventricular septal thickness ≥ 2 mm, the remainder had stable septal wall thickness. There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns. PMID:25743445

  4. 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.

  5. 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

  6. Transthyretin amyloidosis: a tale of weak interactions.

    Science.gov (United States)

    Saraiva, M J

    2001-06-01

    Over 70 transthyretin (TTR) mutations have been associated with hereditary amyloidoses, which are all autosomal dominant disorders with adult age of onset. TTR is the main constituent of amyloid that deposits preferentially in peripheral nerve giving rise to familial amyloid polyneuropathy (FAP), or in the heart leading to familial amyloid cardiomyopathy. Since the beginning of this decade the central question of these types of amyloidoses has been why TTR is an amyloidogenic protein with clinically heterogeneous pathogenic consequences. As a result of amino acid substitutions, conformational changes occur in the molecule, leading to weaker subunit interactions of the tetrameric structure as revealed by X-ray studies of some amyloidogenic mutants. Modified soluble tetramers exposing cryptic epitopes seem to circulate in FAP patients as evidenced by antibody probes recognizing specifically TTR amyloid fibrils, but what triggers dissociation into monomeric and oligomeric intermediates of amyloid fibrils is largely unknown. Avoiding tetramer dissociation and disrupting amyloid fibrils are possible avenues of therapeutic intervention based on current molecular knowledge of TTR amyloidogenesis and fibril structure. PMID:11412857

  7. 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....

  8. Drug Discovery Targeted to Transthyretin Related Amyloidosis

    OpenAIRE

    Blasi Pérez, Daniel

    2013-01-01

    [eng] Several drug discovery approaches has been performed to find new compounds able to interact with high affinity with the hormone binding site of the homotetrameric protein transthyretin (TTR), and stabilize this tetramer, becoming drug candidates to treat several rare amyloid diseases associated with TTR. With this aim, several computational workflows and chemico-biological databases have been developed, and in collaboration with two experimental research laboratories of our TTR Con...

  9. Nasopharyngeal and laryngeal amyloidosis: a case report

    OpenAIRE

    Yurttaş, Veysel; Bozdemir, Kazım; Tarlak, Behçet; Yazgan, Aylin

    2014-01-01

    A 49-year-old woman admitted to our clinic due to a progressive hoarse voice for 4 years, foreign body sensation in the back of her throat, otalgia, hoarseness and mouth breathing. Nasolaryngoscopy demonstrated a right nasopharyngeal mass extending to oropharynx. Indirect laryngoscopy revealed a granulomatous lesion originating from right band ventricle and extending on the right vocal fold. The granulomatous lesion did not alter correct laryngeal mobility. There was no history of difficulty ...

  10. 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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    -terminal adhesive Gly/Ser-rich domain (GS domain) of the protein, abnormally accumulate as amorphous deposits at the periphery of hair follicles and in the papillary dermis of the patient skin. Here, we present evidence that the (mut)CDSN deposits display an affinity for amyloidophilic dyes, namely Congo red and......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...... thioflavin T. We also detected the serum amyloid protein component in the dermis of HSS patients. We demonstrated that recombinant forms of (mut)CDSN and of the GS domain assemble in vitrointo ring-shaped oligomeric structures and fibrils. The amyloid-like nature of the fibrils was demonstrated by dye...

  12. 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

  13. Tracheobronchomegaly associated with laryngo-tracheal amyloidosis: First case report.

    Science.gov (United States)

    Adachi, Kazuo; Umezaki, Toshiro; Komune, Shizuo

    2016-08-01

    Tracheobronchomegaly (TBM) is a rare enlargement of the tracheal cartilage, also known as Mounier-Kuhn syndrome (MKS). Here, we describe an unusual case of acquired TBM in an adult, caused by amyloid regeneration and associated tracheal weakening, rather than by MKS. CT scan and fiberscopic examination of a 55-year-old woman suffering from severe dyspnea revealed TBM and subglottic stenosis, which was caused by deposition of amyloid tissue. We performed a tracheostomy and vaporized the subglottic stenosis with a CO2 laser, after which we installed a silicone T-tube. After the first operation, re-stenosis occurred, and the procedure was repeated; stenosis was subsequently cured and the dyspnea disappeared, after which the tracheostomy could be closed. This is the first report of adult TBM associated with amyloid deposition in the subglottis and trachea. This diagnosis is very difficult, as amyloid deposition in the trachea can have various clinical presentations. PMID:26791590

  14. [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

  15. 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...

  16. 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.).

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

    Science.gov (United States)

    2016-02-12

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

  18. Modern approaches to the treatment of amyloidosis: the critical importance of early detection in surgical pathology.

    Science.gov (United States)

    Picken, Maria M

    2013-11-01

    The amyloidoses comprise a group of disorders of diverse etiology, in which different proteins undergo abnormal folding, leading to their deposition in tissues and concomitant tissue toxicity. This process ultimately leads to tissue destruction, with organ failure and progressive disease. Recent progress in the treatment of the systemic amyloidoses has dramatically changed the outlook for affected patients and their families. From a relatively rare and esoteric disorder that was typically diagnosed only at autopsy, or was invariably fatal if diagnosed during life, it has now become a disease for which, with modern therapies, durable responses and long-term survival can be achieved. The clinical symptoms are largely nonspecific, and therefore misdiagnosis, or late diagnosis, have been major detriments in achieving better treatment outcomes. Despite advances in laboratory medicine, amyloidoses are still diagnosed on the basis of the pathologic detection of deposits in tissues. Thus, effective primary screening for these diseases requires the active engagement of the pathology community at large, while specialized laboratories and treatment centers can offer secondary consultation and assistance with further steps. This review provides an update on pathogenesis, the clinical and pathologic features, and treatments of various amyloidoses, as well as the current terminology, classification, and practical considerations that are relevant to the diagnosis. PMID:24113313

  19. 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.

  20. 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

  1. Primary tracheobronchial amyloidosis associated with tracheobronchomegaly evaluated by novel four‐dimensional functional CT

    OpenAIRE

    Uddin, A.K.M. Nizam; Mansfield, Darren R.; Farmer, Michael W.; Lau, Kenneth K.

    2015-01-01

    Abstract Amyloid is a heterogeneous family of extracellular proteinaceous deposits characterized by apple‐green birefringence on polarized light microscopy. There are rare case reports of these extracellular deposits accumulating in the upper and central airways. Progressive infiltration may impair glottic and airway function with some cases requiring intervention to improve flow. Bronchoscopy and lung function testing provide dynamic information to monitor for disease progression; however, t...

  2. 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 ...

  3. 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...

  4. 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...

  5. 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.

  6. 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...

  7. 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.

  8. 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...

  9. Kinetics of selective deposition of Apo SAA2 during development of amyloidosis in mice

    International Nuclear Information System (INIS)

    The major murine serum amyloid proteins (apoSAA1, apoSAA2) have been identified, of which only one (apoSAA2) shares amino acid sequence identity with tissue protein AA. To examine the mechanism of this apparent isotypespecific amyloid protein deposition, we have studied apoSAA metabolism at the levels of gene expression and plasma content during amyloidogenesis. In CBA mice, daily intraperitoneal casein administration resulted in a linear increase in splenic amyloid content, beginning within 10 days and reaching approximately 30% of the organ volume at 20 days. Hepatic apoSAA mRNA content, estimated by in vitro translation, was highest at day 1 (3% of total mRNA) and declined thereafter (to 1%, day 20). The relative content of apoSAA2 mRNA compared with that of apoSAA1 was unchanged throughout amyloid induction. Simultaneously, a 2-3 fold drop in total serum apoSAA levels was observed with, by contrast, a 10-fold reduction in the serum ratio of apoSAA2/apoSAA1. These results are consistent with the hypothesis that murine tissue protein AA accumulates by selective deposition of apoSAA2 from the serum

  10. 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...

  11. 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.

  12. Thorough Investigation of a Canine Autoinflammatory Disease (AID) Confirms One Main Risk Locus and Suggests a Modifier Locus for Amyloidosis

    OpenAIRE

    Olsson, Mia; Tintle, Linda; Kierczak, Marcin; Perloski, Michele; Tonomura, Noriko; Lundquist, Andrew; Murén, Eva; Fels, Max; Tengvall, Katarina; Pielberg, Gerli; Dufaure De Citres, Caroline; Dorso, Laetitia; Abadie, Jérôme; Hanson, Jeanette; Thomas, Anne

    2013-01-01

    Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amylo...

  13. 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...

  14. 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

  15. 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...

  16. 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...

  17. 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

  18. Amyloid A amyloidosis in non-infected and avian leukosis virus-C persistently infected inbred ducks

    Czech Academy of Sciences Publication Activity Database

    Stepanets, Volodymyr; Vernerová, Z.; Vilhelmová, Milena; Geryk, Josef; Hejnar, Jiří; Svoboda, Jan

    2001-01-01

    Roč. 30, č. 1 (2001), s. 33-42. ISSN 0307-9457 R&D Projects: GA ČR GA301/94/0713; GA ČR GA524/01/0866 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.655, year: 2001

  19. 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...

  20. 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...

  1. 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

  2. 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.

  3. Amiloidose na cavidade bucal: aspectos clínicos, histopatológicos e ultra-estruturais Amyloidosis in the oral cavity: clinical, histopathological and ultrastructural features

    OpenAIRE

    Paulo Rogério de Faria; Luiz Fernando Carvalho de Menezes; Paulo Hilário Nascimento Saldiva; Ricardo Della Coletta; Pablo Agustin Vargas

    2003-01-01

    Amiloidose refere-se à deposição extracelular e progressiva de proteínas fibrilares patogênicas com características microscópicas e ultra-estruturais similares. A amiloidose pode ser sistêmica ou localizada. Descrevemos três pacientes que desenvolveram amiloidose intra-oral, sendo que dois casos manifestaram amiloidose localizada e o outro caso apresentou amiloidose sistêmica com acometimento de língua. Nos três casos, o exame histopatológico evidenciou depósitos de amilóide, os quais foram c...

  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. 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 ...

  6. 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

  7. 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...

  8. 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...

  9. 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

  10. 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).

  11. Increased efflux of amyloid-β peptides through the blood-brain barrier by muscarinic acetylcholine receptor inhibition reduces pathological phenotypes in mouse models of brain amyloidosis.

    Science.gov (United States)

    Paganetti, Paolo; Antoniello, Katia; Devraj, Kavi; Toni, Nicolas; Kieran, Dairin; Madani, Rime; Pihlgren, Maria; Adolfsson, Oskar; Froestl, Wolfgang; Schrattenholz, André; Liebner, Stefan; Havas, Daniel; Windisch, Manfred; Cirrito, John R; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    The formation and accumulation of toxic amyloid-β peptides (Aβ) in the brain may drive the pathogenesis of Alzheimer's disease. Accordingly, disease-modifying therapies for Alzheimer's disease and related disorders could result from treatments regulating Aβ homeostasis. Examples are the inhibition of production, misfolding, and accumulation of Aβ or the enhancement of its clearance. Here we show that oral treatment with ACI-91 (Pirenzepine) dose-dependently reduced brain Aβ burden in AβPPPS1, hAβPPSL, and AβPP/PS1 transgenic mice. A possible mechanism of action of ACI-91 may occur through selective inhibition of muscarinic acetylcholine receptors (AChR) on endothelial cells of brain microvessels and enhanced Aβ peptide clearance across the blood-brain barrier. One month treatment with ACI-91 increased the clearance of intrathecally-injected Aβ in plaque-bearing mice. ACI-91 also accelerated the clearance of brain-injected Aβ in blood and peripheral tissues by favoring its urinal excretion. A single oral dose of ACI-91 reduced the half-life of interstitial Aβ peptide in pre-plaque mhAβPP/PS1d mice. By extending our studies to an in vitro model, we showed that muscarinic AChR inhibition by ACI-91 and Darifenacin augmented the capacity of differentiated endothelial monolayers for active transport of Aβ peptide. Finally, ACI-91 was found to consistently affect, in vitro and in vivo, the expression of endothelial cell genes involved in Aβ transport across the Blood Brain Brain (BBB). Thus increased Aβ clearance through the BBB may contribute to reduced Aβ burden and associated phenotypes. Inhibition of muscarinic AChR restricted to the periphery may present a therapeutic advantage as it avoids adverse central cholinergic effects. PMID:24072071

  12. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease

    OpenAIRE

    Priyamvada, P. S.; Morkhandikar, S.; Srinivas, B.H.; Parameswaran, S.

    2015-01-01

    Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig hea...

  13. 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...

  14. [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

  15. 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...

  16. 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.

  17. 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.

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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...

  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. Complete Remission of Nephrotic Syndrome Without Resolution of Amyloid Deposit After Anti-Tumor Necrosis Factor α Therapy in a Patient With Ankylosing Spondylitis.

    Science.gov (United States)

    Lee, Yu Ho; Kim, Eun Young; Jeong, Da Wun; Kim, Yang-Gyun; Lee, Sang-Ho; Song, Ran; Yang, Hyung In; Lim, Sung Jig; Moon, Ju-Young; Lee, Sang-Hoon

    2016-03-01

    In secondary amyloid A amyloidosis resulting from rheumatologic diseases, tumor necrosis factor α blockers have been reported to be effective in the treatment of both arthritis and amyloidosis. However, there have been few reports concerning the alterations of renal tissue histology before and after long-term tumor necrosis factor α blockers therapy in secondary renal amyloidosis. We report the histological change after tumor necrosis factor α blocker therapy in patient with amyloid A amyloidosis and nephrotic syndrome secondary to underlying ankylosing spondylitis. The patient achieved complete remission of nephrotic syndrome after 17 months of etanercept treatment. We performed the second kidney biopsy after 40 months, and there was little change in the degree of amyloid deposition in the mesangial area and capillary loops compared with the first biopsy. The interstitial inflammation and foot process effacement, however, were fully recovered. PMID:26906302

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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

  16. Pathogenesis of and therapeutic strategies to ameliorate the transthyretin amyloidoses.

    Science.gov (United States)

    Sekijima, Yoshiki; Kelly, Jeffery W; Ikeda, Shu-ichi

    2008-01-01

    Transthyretin (TTR) is a homotetrameric serum and cerebrospinal fluid protein that transports both thyroxine (T(4)) and the retinol-retinol binding protein complex (holoRBP). Rate-limiting tetramer dissociation and rapid monomer misfolding and misassembly of variant TTR results in familial amyloid polyneuropathy (FAP), familial amyloid cardiomyopathy (FAC), or familial central nervous system amyloidosis. Analogous misfolding of wild-type TTR results in senile systemic amyloidosis (SSA) characterized by sporadic amyloidosis in elderly populations. With the availability of genetic and immunohistochemical diagnostic tests, patients with TTR amyloidosis have been found in many nations worldwide. Recent studies indicate that TTR amyloidosis is not a rare endemic disease as previously thought. The only effective treatment for the familial TTR amyloidoses is liver transplantation; however, this strategy has a number of limitations, including a shortage of donors, a requirement for surgery for both the recipient and living donor, and the high cost. Furthermore, a large number of patients are not good transplant candidates. Recent studies focused on the TTR gene and protein have provided insight into the pathogenesis of TTR amyloidosis and suggested new strategies for therapeutic intervention. TTR tetramer (native state) kinetic stabilization by small molecule binding, immune therapy, and gene therapy with small interfering RNAs, antisense oligonucleotides, and single-stranded oligonucleotides are promising strategies based on our understanding of the pathogenesis of TTR amyloidosis. Among these, native state kinetic stabilization by diflunisal and Fx-1006A, a novel therapeutic strategy against protein misfolding diseases, are currently in Phase II/III clinical trials. PMID:19075702

  17. 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。

  18. 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.

  19. The 8 and 5 kDa Fragments of Plasma Gelsolin Form Amyloid Fibrils by a Nucleated Polymerization Mechanism, while the 68 kDa Fragment is Not Amyloidogenic†

    OpenAIRE

    Solomon, James P.; Isaac T. Yonemoto; Murray, Amber N; Price, Joshua L.; Powers, Evan T.; Balch, William E.; Kelly, Jeffery W.

    2009-01-01

    Familial amyloidosis of Finnish type (FAF), or gelsolin amyloidosis, is a systemic amyloid disease caused by a mutation (D187N/Y) in domain 2 of human plasma gelsolin, resulting in domain 2 misfolding within the secretory pathway. Upon passage through the Golgi, furin endoproteolysis within domain 2 occurs as a consequence of the abnormal conformations that enable furin to bind and cleave, resulting in the secretion of a 68-kDa C-terminal plasma gelsolin fragment (amino acids173–755, C68). Th...

  20. Uncovering the Mechanism of Aggregation of Human Transthyretin*

    OpenAIRE

    Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.; Sawaya, Michael R.; Cascio, Duilio; Ruchala, Piotr; Whitelegge, Julian; Jiang, Lin; Riek, Roland; Eisenberg, David S.

    2015-01-01

    Background: Transthyretin (TTR) aggregation is associated with systemic amyloidosis. Results: Residue replacements on the F and H strands hinder TTR aggregation. Conclusion: The F and H strands are aggregation-driving segments of TTR. The binding of designed peptides inhibits protein aggregation. Significance: We point the way to new therapeutic approaches against TTR aggregation by using peptides to block amyloid segments.

  1. Musculoskeletal amyloid disease: MRI features

    International Nuclear Information System (INIS)

    A case of arthropathy and soft tissue masses due to amyloid deposition in a patient with myeloma is reported. The radiologic and magnetic resonance findings of musculoskeletal amyloidosis are described. The amyloid masses show heterogeneous signal intensity, with a signal lower than muscle and intermingled areas of marked hyperintensity on T 2-weighted images. (authors). 7 refs., 2 figs

  2. Musculoskeletal amyloid disease: MRI features

    Energy Technology Data Exchange (ETDEWEB)

    Del Castillo, M.; Guerra, J.L. [Hospital Arquitecto Marcide, Ferrol (Spain); Comesana, L.; Martin, R. [Hospital Arquitecto Marcide, Ferrol (Spain)]|[Hospital Juan Canalejo, La Coruna (Spain); Rodriguez, E.; Soler, R. [Hospital Juan Canalejo, La Coruna (Spain)

    1995-12-31

    A case of arthropathy and soft tissue masses due to amyloid deposition in a patient with myeloma is reported. The radiologic and magnetic resonance findings of musculoskeletal amyloidosis are described. The amyloid masses show heterogeneous signal intensity, with a signal lower than muscle and intermingled areas of marked hyperintensity on T 2-weighted images. (authors). 7 refs., 2 figs.

  3. 75 FR 32540 - Health Effects Not Associated With Exposure to Certain Herbicide Agents

    Science.gov (United States)

    2010-06-08

    ... connection for AL amyloidosis. See 74 FR 21258 (May 7, 2009). NAS, in Update 2006, categorized certain health...). See 75 FR 14391 (Mar. 25, 2010). The discussion in this notice does not in any way affect those... Federal Register of March 25, 2010 (75 FR 14391) to establish such presumptions. We emphasize that...

  4. 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...

  5. Hereditär hjärnblödning. Demens vid cystatin C amyloidos

    DEFF Research Database (Denmark)

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

    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...

  6. 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-

  7. 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...

  8. 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

    2012-11-01

    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

  9. 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...

  10. 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

  11. 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

  12. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2016-01-28

    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

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  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. 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

  19. 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;

    Background: The dynamic biomarker hypothesis predicts that fluid biomarker abnormalities precede brain morphological changes observed in AD by many years. However, the link between early CSF abnormalities and late structural changes remains under debate. Here we investigated the association between...... 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...... between cortical thinning, amyloidosis or tau hyperphosphorylation depends on cortical regions and clinical stages of AD. Methods: T1-weighed MRIs and associated CSF markers from individuals with mild cognitive impairment (MCI; 16), Alzheimer Disease (AD; n¼7) and age-matched cognitively normal subjects...

  20. 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. PMID:26085598

  1. Irreversible Kidney Damage due to Multicentric Castleman’s Disease

    Directory of Open Access Journals (Sweden)

    Mårten Segelmark

    2008-01-01

    Full Text Available Castleman’s Disease (CD is a rare lymphoproliferative disorder accompanied by marked systemic inflammatory response. Morphological diagnosis of CD requires biopsy of the whole of the involved lymph node tissue. Three histologic variants have already been described in CD morphology (hyaline vascular, plasma-cell, and mixed. In this study, we report a case of a multicentric Castleman’s disease of the plasma cell variant type with negative Herpes Virus 8. The clinical presentation of this patient was of systemic amyloidosis as a result of both a delayed diagnosis and medical management. Previously described cases of CD with secondary amyloidosis have been of the localized type. Regardless, long-standing clinical remission of CD by cytotoxic drugs and anti-CD20 antibody therapy was achieved, but the nephrotic syndrome remained irreversible.

  2. 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.

  3. 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.

  4. 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

    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....... 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...

  5. Utility of gallium imaging of the kidneys in diagnosing primary amyloid nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gertz, M.A.; Brown, M.L.; Hauser, M.F.; Kyle, R.A. (Mayo Clinic, Rochester, MN (USA))

    1990-03-01

    We undertook a study to determine the value of gallium imaging of the kidneys in patients who had primary amyloidosis that was manifest clinically by nephrotic syndrome. We studied 28 patients with gallium-67 (67Ga) citrate scans performed 48 hr after injection. Intense (3+ to 4+) uptake was noted in both kidneys in 25 of 28 patients. Renal amyloidosis should be considered in the differential diagnosis when diffuse bilateral renal uptake of (67Ga)citrate is seen in the setting of nephrotic syndrome. Gallium uptake did not differentiate amyloid nephrotic syndrome from other causes of nephrotic syndrome. Renal gallium uptake showed a weak correlation with 24-hr urine protein excretion (p = 0.06).

  6. 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...

  7. 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...

  8. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report

    OpenAIRE

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-01-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic s...

  9. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report

    OpenAIRE

    Arash Babaei-Ghazani; Bina Eftekharsadat

    2016-01-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic s...

  10. DBA/2J Genetic Background Exacerbates Spontaneous Lethal Seizures but Lessens Amyloid Deposition in a Mouse Model of Alzheimer’s Disease

    OpenAIRE

    Jackson, Harriet M.; Onos, Kristen D.; Pepper, Keating W.; Graham, Leah C; Akeson, Ellen C.; Byers, Candice; Reinholdt, Laura G; Frankel, Wayne N.; Howell, Gareth R.

    2015-01-01

    Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but sig...

  11. 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...

  12. Diagnostic imaging in the study of popliteal masses in dialysis patients

    International Nuclear Information System (INIS)

    A new type of amyloidosis, secondary to the massive deposition of β2-microglobulin, has been identified which is peculiar to long-term (≤5 years) hemodialysis. Popliteal masses have recently been described as a possible manifestation of this type of amyloidosis. We report the results of a clinical-radiologic study of the popliteal region in 28 patients (14 males, 14 females; age 52.9±12.6 years) undergoing chronic hemodialysis for 60-212 months (mean 127±40). We aime at determining the role of diagnostic imaging (conventional radiography, ultrasonography, Computer Thomography) in this pathologic condition. Clinics detected popliteal masses in 4 patients (bilateral in 1). US allowed 2 more cases to be detected and demonstrated the cistic nature of the lesion. Ultimately, popliteal masses could be demonstrated in 6 (bilateral in 5) of 28 patients (incidence 21.4%). In the 3 patients who were investigated by CT, cysts were seen to communicate with the joint cavity (Baker's cysts). In 1 case, immunocytochemical analysis showed diffuse β2-microglobulin positive amyloid deposition within the synovial wall of the surgically removed cyst. All the 6 patiens experienced some of the mayor features of dialysis-related amyloidosis: carpal tunnel syndrome (6 cases), destructive arthropathy (5 cases), carpal and shoulder bone radiolucencies (5 and 4 cases, respectively). These findings, while documenting the high prevalence of popliteal cysts among long-term hemodialysis patients and the strong correlation with dialysis-related amyloidosis, stress the importance of diagnostic imaging in the detection and follow-up of such lesions

  13. Transthyretin Val122Ile, accumulated Abeta, and inclusion-body myositis aspects in cultured muscle.

    Science.gov (United States)

    Askanas, Valerie; Engel, W King; McFerrin, Janis; Vattemi, Gaetano

    2003-07-22

    Cultured muscle fibers (CMF) from a patient with inclusion-body myositis (IBM) and cardiac amyloidosis associated with the transthyretin (TTR) Val122Ile mutation contained aspects of the IBM phenotype: vacuolation, congophilic inclusions, and clusters of immunocolocalizing amyloid beta-peptide (Abeta) and TTR accumulations. These abnormalities are never present in normal human CMF. These perturbations were greatly increased after Abeta precursor protein gene transfer. The TTR mutation may be a genetic predisposition factor for the patient's IBM. PMID:12874414

  14. Fatal Toxoplasma gondii Dissemination in a Heart Transplant Recipient: Description of a Case

    OpenAIRE

    S. Mastrobuoni; Dell'Aquila, A. M.; Herreros, J.

    2012-01-01

    A 45-year-old heart transplant recipient presented with fever, anorexia, asthenia, and lethargy. She had received heart transplantation only 5 weeks earlier for primary systemic amyloidosis with severe cardiac involvement. Serum sodium was low, and tacrolimus through level was high. Blood cultures and serology tests for infection were negative, and atypical pneumonia was suspected. Despite broad antibiotic, antiviral, and antifungal treatment, the patient clinical condition rapidly deteriorat...

  15. Diagnostic Neglect Regarding Ureter Ligation After Hysterectomy

    OpenAIRE

    BİLGE, Yaşar

    2007-01-01

    Complications following cesarean and hysterectomy operations can occur, one of which is ureter ligation. Aims: Urological injuries that occur during hysterectomy are rare but important causes of morbidity. It was aimed to investigate in this case report whether there was any evidence to support malpractice in Court. Case Report: The patient was a woman in her 343 week of pregnancy with familial Mediterranean fever (FMF) and nephrotic syndrome with renal amyloidosis. Preterm operational di...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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...

  2. 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...

  3. Modifications of the 7-Hydroxyl Group of the Transthyretin Ligand Luteolin Provide Mechanistic Insights into Its Binding Properties and High Plasma Specificity

    OpenAIRE

    Nilsson, Lina; Larsson, Andreas; Begum, Afshan; Iakovleva, Irina; Carlsson, Marcus; Brännström, Kristoffer; Sauer-Eriksson, A. Elisabeth; Olofsson, Anders

    2016-01-01

    Amyloid formation of the plasma protein transthyretin (TTR) has been linked to familial amyloid polyneuropathy and senile systemic amyloidosis. Binding of ligands within its natural hormone binding site can stabilize the tetrameric structure and impair amyloid formation. We have recently shown that the flavonoid luteolin stabilizes TTR in human plasma with a very high selectivity. Luteolin, however, is inactivated in vivo via glucuronidation for which the preferred site is the hydroxy group a...

  4. 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.

  5. 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...

  6. 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 ...

  7. 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...

  8. The Flavonoid Luteolin, but Not Luteolin-7-O-Glucoside, Prevents a Transthyretin Mediated Toxic Response

    OpenAIRE

    Irina Iakovleva; Afshan Begum; Malgorzata Pokrzywa; Malin Walfridsson; A Elisabeth Sauer-Eriksson; 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...

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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 ...

  15. 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...

  16. 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...

  17. 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...

  18. Molecular Basis for the Cu2+ Binding-Induced Destabilization of β2-Microglobulin Revealed by Molecular Dynamics Simulation

    OpenAIRE

    Deng, Nan-Jie; Yan, Lisa; Singh, Deepak; Cieplak, Piotr

    2006-01-01

    According to experimental data, binding of the Cu2+ ions destabilizes the native state of β2-microglobulin (β2m). The partial unfolding of the protein was generally considered an early step toward fibril formation in dialysis-related amyloidosis. Recent NMR studies have suggested that the destabilization of the protein might be achieved through increased flexibility upon Cu2+ binding. However, the molecular mechanism of destabilization due to Cu2+, its role in amyloid formation, and the relat...

  19. 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...

  20. Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI

    OpenAIRE

    Klohs, Jan; Deistung, Andreas; Ielacqua, Giovanna D.; Seuwen, Aline; Kindler, Diana; Schweser, Ferdinand; Vaas, Markus; Kipar, Anja; Reichenbach, Jürgen R; Rudin, Markus

    2015-01-01

    Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of [Formula: see text] and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.4 T after injection of USP...

  1. Aβ immunization worsens iron deposits in the choroid plexus and cerebral microbleeds

    OpenAIRE

    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

    2013-01-01

    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 (K6A...

  2. Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits

    OpenAIRE

    Tamayev, Robert; Matsuda, Shuji; Fà, Mauro; Arancio, Ottavio; D’Adamio, Luciano

    2010-01-01

    According to the prevailing “amyloid cascade hypothesis,” genetic dementias such as Alzheimer’s disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mec...

  3. 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...

  4. 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

  5. Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation

    OpenAIRE

    Yoshimura, Yuichi; Lin, Yuxi; Yagi, Hisashi; Lee, Young-Ho; Kitayama, Hiroki; Sakurai, Kazumasa; So, Masatomo; OGI, Hirotsugu; Naiki, Hironobu; Goto, Yuji

    2012-01-01

    Amyloid fibrils and amorphous aggregates are two types of aberrant aggregates associated with protein misfolding diseases. Although they differ in morphology, the two forms are often treated indiscriminately. β2-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, forms amyloid fibrils or amorphous aggregates depending on the NaCl concentration at pH 2.5. We compared the kinetics of their formation, which was monitored by measuring thioflavin T fluorescence, light scat...

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  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. 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

  13. [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

  14. Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study.

    Science.gov (United States)

    Hoane, Jessica S; Johnson, Crystal L; Morrison, James P; Elmore, Susan A

    2016-07-01

    Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. PMID:27000376

  15. 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.

  16. Peptide p5 binds both heparinase-sensitive glycosaminoglycans and fibrils in patient-derived AL amyloid extracts

    International Nuclear Information System (INIS)

    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

  17. 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

  18. 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

  19. The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice

    OpenAIRE

    Vidal, Ruben; Sammeta, Neeraja; Garringer, Holly J.; Sambamurti, Kumar; Miravalle, Leticia; Lamb, Bruce T.; Ghetti, Bernardino

    2012-01-01

    Genetically engineered mice have been generated to model cerebral β-amyloidosis, one of the hallmarks of Alzheimer disease (AD) pathology, based on the overexpression of a mutated cDNA of the amyloid-β precursor protein (AβPP) or by knock-in of the murine Aβpp gene alone or with presenilin1 mutations. Here we describe the generation and initial characterization of a new mouse line based on the presence of 2 copies of the human genomic region encoding the wild-type AβPP and the L166P presenili...

  20. 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

  1. Notalgia Paraesthetica

    Directory of Open Access Journals (Sweden)

    Malakar Subrata

    1998-01-01

    Full Text Available Two cases of notalgia paraesthetica (NP are presented. Both the patients were female and above 30 years of age. Clinically the lesions closely simulated macular amyloidosis over interscapular region. However, history of associated pruritus, tingling, fornication and altered sensation over the patch pointed towards the diagnosis of NP, Histopathological examinations in both the cases revealed intraepidermal necrotic keratinocytes with desquamation remnants of necrotic keratinocytes in the stratum corneum. Congo red and crystal violet stains were negative for presence of amyloidal in thedermis. In both the patients, symptomatic improvement was observed after 3 weeks’ application of topical capsaicin.

  2. Severe heart disease in an unusual case of familial amyloid polyneuropathy type I.

    Science.gov (United States)

    Oliveira Santos, Miguel; Brito, Dulce

    2013-09-01

    Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (TTR) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications. Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs. PMID:23993291

  3. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy.

    Science.gov (United States)

    Quarta, Candida Cristina; Obici, Laura; Guidalotti, Pier Luigi; Pieroni, Maurizio; Longhi, Simone; Perlini, Stefano; Verga, Laura; Merlini, Giampaolo; Rapezzi, Claudio

    2013-03-01

    Amyloidotic cardiomyopathy is still a widely underdiagnosed condition that usually requires endomyocardial biopsy (EMB) for a definite diagnosis. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has proven highly sensitive for detecting amyloidotic cardiomyopathy due to transthyretin-related amyloid deposition. Herein we report the first description of the (99mTc-DPD scintigraphy profile in a patient with suspected amyloidotic cardiomyopathy and a final EMB- and genetically-proven diagnosis of familial apolipoprotein AI amyloidosis due to Leu174Ser variant. PMID:23231421

  4. 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 (THT), which has been used extensively to stain such fibrils. We study the fibril-environment-induced structural and spectral changes of THT at each binding site and compare the results to the fibril-free situation in aqueous solution. All binding sites are found to show a similar effect with respect...

  5. 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.

  6. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    International Nuclear Information System (INIS)

    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.)

  7. Conformational intermediate of the amyloidogenic protein beta 2-microglobulin at neutral pH

    DEFF Research Database (Denmark)

    Heegaard, N H; Sen, J W; Kaarsholm, N C; Nissen, Mogens Holst

    2001-01-01

    Aggregation and fibrillation of beta(2)-microglobulin are hallmarks of dialysis-related amyloidosis. We characterize perturbations of the native conformation of beta(2)-microglobulin that may precede fibril formation. For a beta(2)-microglobulin variant cleaved at lysine 58, we show using capillary...... organic solvent present. Circular dichroism showed a loss of beta-structures and gain of alpha-helices. Reversal to the native conformation occurred when removing the organics. Affinity capillary electrophoresis experiments showed increased specific interactions of the nonnative beta(2)-microglobulin...

  8. 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.)

  9. 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

  10. 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.

  11. 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...

  12. 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.

  13. 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

  14. Intraosseous ganglion in the first metacarpal bone

    International Nuclear Information System (INIS)

    Intraosseous ganglia occur most frequently in the long bones of the lower limbs, particularly in the medial malleolus of the tibia. They usually appear as radiographically well circumscribed juxta-articular cystic lesions, containing myxoid fibrous tissue histologically. Intraosseous ganglia in the hand are very rare. Most reported cases have involved the carpal bones, in particular the lunate and scaphoid. To our knowledge, the present case is the third report of an intraosseous ganglion appearing in the first metacarpal bone; it arose in a patient who had been on dialysis for 25 years, mimicking amyloidosis of bone. (orig.)

  15. Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid.

    Science.gov (United States)

    Sjölander, Daniel; Röcken, Christoph; Westermark, Per; Westermark, Gunilla T; Nilsson, K Peter R; Hammarström, Per

    2016-06-01

    Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. The only functional structure stained with h-FTAA showing the amyloidotypic fluorescence spectrum was Paneth cell granules in intestine. Screening of 114 amyloid containing tissues derived from 107 verified (Congo red birefringence and/or immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence (107/107, 100% sensitivity). The majority of Congo red negative control cases (27 of 32, 85% specificity) were negative with h-FTAA. Small Congo red negative aggregates in kidney, liver, pancreas and duodenum were found by h-FTAA fluorescence in five control patients aged 72-83 years suffering from diverse diseases. The clinical significance of these false-positive lesions is currently not known. Because h-FTAA fluorescence is one magnitude brighter than Congo red and as the staining is performed four magnitudes lower than the concentration of dye, we believe that these inclusions are beyond detection by Congo red. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. Use of h-FTAA can be exploited as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. Our results also implicate the potential of

  16. 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...... 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....

  17. CLINICOPATHOLOGIC CORRELATES OF FASCIOLIASIS IN TWO EASTERN GREY KANGAROOS (MACROPUS GIGANTEUS).

    Science.gov (United States)

    Portas, Timothy J; Taylor, David

    2015-12-01

    Infection with the introduced trematode Fasciola hepatica was associated with anemia, mild to moderate azotemia, hypoalbuminemia, and elevated liver enzymes and creatine kinase values in two free-ranging eastern grey kangaroos (Macropus giganteus). Both kangaroos were euthanized because of the severity of clinical signs associated with infection. Histopathologic changes included severe cholangiohepatitis, biliary hyperplasia, and fibrosis. Hepatic, splenic, and intestinal amyloidosis was present in one kangaroo and hepatic abscessation in the other; neither histologic change has been reported in macropodids with fascioliasis previously. PMID:26667560

  18. 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

  19. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET

    DEFF Research Database (Denmark)

    Antoni, Gunnar; Lubberink, Mark; Estrada, Sergio; Axelsson, Jan; Carlson, Kristina; Lindsjö, Lars; Kero, Tanja; Roland Långström, Bengt; Granstam, Sven-Olof; Rosengren, Sara; Vedin, Ola; Wassberg, Cecilia; Wikström, Gerhard; Westermark, Per; Sörensen, Jens

    2013-01-01

    -and healthy volunteers (n = 5) were investigated with PET/CT using (11)C-PIB to study cardiac amyloid deposits and with (11)C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. RESULTS: Myocardial (11)C-PIB uptake was visually evident in all...... patients 15-25 min after injection and was not seen in any volunteer. A significant difference in (11)C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with (11...

  20. 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.