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Sample records for al amyloidosis patients

  1. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  2. Short- and long-term outcomes of AL amyloidosis patients admitted into intensive care units.

    PubMed

    Guinault, Damien; Canet, Emmanuel; Huart, Antoine; Jaccard, Arnaud; Ribes, David; Lavayssiere, Laurence; Venot, Marion; Cointault, Olivier; Roussel, Murielle; Nogier, Marie-Béatrice; Pichereau, Claire; Lemiale, Virginie; Arnulf, Bertrand; Attal, Michel; Chauveau, Dominique; Azoulay, Elie; Faguer, Stanislas

    2016-09-01

    Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.

  3. Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis

    PubMed Central

    Sachchithanantham, Sajitha; Offer, Mark; Venner, Christopher; Mahmood, Shameem A.; Foard, Darren; Rannigan, Lisa; Lane, Thirusha; Gillmore, Julian D.; Lachmann, Helen J.; Hawkins, Philip N.; Wechalekar, Ashutosh D.

    2015-01-01

    Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005–2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival – 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed. PMID:26294730

  4. Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis

    PubMed Central

    Merlini, G; Lousada, I; Ando, Y; Dispenzieri, A; Gertz, M A; Grogan, M; Maurer, M S; Sanchorawala, V; Wechalekar, A; Palladini, G; Comenzo, R L

    2016-01-01

    Amyloid light-chain (LC) amyloidosis (AL amyloidosis) is a rare and fatal disease for which there are no approved therapies. In patients with AL amyloidosis, LC aggregates progressively accumulate in organs, resulting in organ failure that is particularly lethal when the heart is involved. A significant obstacle in the development of treatments for patients with AL amyloidosis, as well as for those with any disease that is rare, severe and heterogeneous, has been satisfying traditional clinical trial end points (for example, overall survival or progression-free survival). It is for this reason that many organizations, including the United States Food and Drug Administration through its Safety and Innovation Act Accelerated Approval pathway, have recognized the need for biomarkers as surrogate end points. The international AL amyloidosis expert community is in agreement that the N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) is analytically validated and clinically qualified as a biomarker for use as a surrogate end point for survival in patients with AL amyloidosis. Underlying this consensus is the demonstration that NT-proBNP is an indicator of cardiac response in all interventional studies in which it has been assessed, despite differences in patient population, treatment type and treatment schedule. Furthermore, NT-proBNP expression is directly modulated by amyloidogenic LC-elicited signal transduction pathways in cardiomyocytes. The use of NT-proBNP will greatly facilitate the development of targeted therapies for AL amyloidosis. Here, we review the data supporting the use of NT-proBNP, a biomarker that is analytically validated, clinically qualified, directly modulated by LC and universally accepted by AL amyloidosis specialists, as a surrogate end point for survival. PMID:27416985

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

    PubMed

    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

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

    PubMed

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2015-01-01

    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. PMID:26199769

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

    PubMed Central

    Golombick, Terry; Diamond, Terrence H.; Manoharan, Arumugam; Ramakrishna, Rajeev

    2015-01-01

    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. PMID:26199769

  8. 77 FR 6466 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... hemic and lymphatic systems to include AL amyloidosis. This regulatory action is necessary to add AL... lymphatic systems, 38 CFR 4.117, by creating diagnostic code 7717. The schedule previously did not contain a... amyloidosis because it was the first available diagnostic code in the Hemic and Lymphatic Systems listed...

  9. Primary Systemic Al Amyloidosis Presenting as Temporal Arteritis

    PubMed Central

    Emmungil, Hakan; Kalfa, Melike; Başarık, Burcu; Kahraman, Hasip; Tanhan, Ferhat; Yaman, Banu; Öztürk, Atiye; Erdemir, Zehra; Kandiloğlu, Gülşen; İnal, Vedat; Kabasakal, Yasemin

    2014-01-01

    Temporal arteritis is most common vasculitis in elderly and imitated by miscellaneous disorders. Temporal artery biopsy is the gold standard test in the diagnosis of giant cell arteritis (GCA). Hereby, we describe a case of a 67-year-old man who presented initially with temporal arteritis; however, a lip biopsy then revealed AL amyloidosis. In this respect, temporal artery biopsy should be performed for definitive diagnosis of GCA particularly patients with systemic symptoms and treatment resistant. PMID:24551471

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

    PubMed

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

    2013-06-01

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

  11. Amyloidosis.

    PubMed

    Pinney, Jennifer H; Hawkins, Philip N

    2012-05-01

    The term amyloid describes the deposition in the extracellular space of certain proteins in a highly characteristic, insoluble fibrillar form. Amyloidosis describes the various clinical syndromes that occur as a result of damage by amyloid deposits in tissues and organs throughout the body. The clinical significance of amyloid varies enormously, ranging from incidental asymptomatic deposits to localized disease through to rapidly fatal systemic forms that can affect multiple vital organs. Currently available therapy is focused on reducing the supply of the respective amyloid fibril precursor protein and supportive medical care, which together have greatly improved survival. Chemotherapy and anti-inflammatory treatment for the disorders that underlie AL and AA amyloidosis are guided by serial measurements of the respective circulating amyloid precursor proteins, i.e. serial serum free light chains in AL and serum amyloid A protein in AA type. Quality of life and prognosis of some forms of hereditary systemic amyloidosis can be improved by liver and other organ transplants. Various new therapies, ranging from silencing RNA, protein stabilizers to monoclonal antibodies, aimed at inhibiting fibril precursor supply, fibril formation or the persistence of amyloid deposits, are in development; some are already in clinical phase. PMID:22402917

  12. AL amyloidosis with temporal artery involvement simulates giant-cell arteritis.

    PubMed

    Audemard, Alexandra; Boutemy, Jonathan; Galateau-Salle, Françoise; Macro, Margaret; Bienvenu, Boris

    2012-03-01

    Light-chain (AL) amyloidosis may present with features suggesting vasculitis, including giant-cell arteritis (GCA). We describe a case of an 80-year-old man, who initially presented with bilateral jaw claudication, bi-temporal headache and arthralgia, however a temporal-artery biopsy then revealed AL amyloidosis. A diagnosis of AL amyloidosis complicating multiple myelome simulates GCA and polymyalgia rheumatica was established. The patient was successfully treated with melphalan and dexamethasone: the free kappa light chains decreased, the patient's jaw claudication and headache disappeared. Then we discuss similarities between GCA and AL amyloidosis and potential confusion in diagnosis. We suggest that, in patients with clinical features of GCA without any temporal-artery typical findings, specimens are stained with Congo red, which then results in a different diagnosis and treatment.

  13. Amyloidosis

    PubMed Central

    Khan, M; Falk, R

    2001-01-01

    Amyloidosis is not a single disease but a series of diseases in which there is extracellular deposition of a protein which, although it may be derived from different and unrelated sources, folds into a β pleated sheet.
There have recently been significant advances in elucidating the pathogenesis and in the treatment of this group of disorders. By identifying the source of precursor protein, treatment is aimed at eliminating or reducing the extent of deposition and is tailored for each patient.
Early diagnosis is required for the optimal effect of treatment on patient survival and quality of life. An increased awareness among physicians of the spectrum of the disease and tools to aid its diagnosis is of increasing importance.


Keywords: amyloidosis PMID:11677276

  14. Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

    PubMed

    Tsukune, Yutaka; Yahata, Yuriko; Sasaki, Makoto; Hiki, Makoto; Tsutsui, Miyuki; Hamano, Yasuharu; Itoh, Seigo; Miyazaki, Tetsuro; Dohi, Tomotaka; Maruyama, Masaki; Gotoh, Akihiko; Komatsu, Norio

    2016-08-01

    Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis. PMID:27599413

  15. Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

    PubMed

    Tsukune, Yutaka; Yahata, Yuriko; Sasaki, Makoto; Hiki, Makoto; Tsutsui, Miyuki; Hamano, Yasuharu; Itoh, Seigo; Miyazaki, Tetsuro; Dohi, Tomotaka; Maruyama, Masaki; Gotoh, Akihiko; Komatsu, Norio

    2016-08-01

    Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

  16. Recurrent Syncope and Cardiac Arrest in a Patient with Systemic Light Chain Amyloidosis Treated with Bortezomib.

    PubMed

    Jaipaul, Navin; Pi, Alexander; Zhang, Zhiwei

    2016-05-10

    About 10-15% of patients with multiple myeloma develop light chain (AL) amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation. PMID:27499835

  17. Recurrent Syncope and Cardiac Arrest in a Patient with Systemic Light Chain Amyloidosis Treated with Bortezomib

    PubMed Central

    Jaipaul, Navin; Pi, Alexander; Zhang, Zhiwei

    2016-01-01

    About 10-15% of patients with multiple myeloma develop light chain (AL) amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation. PMID:27499835

  18. 75 FR 65279 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... the schedule of ratings for the hemic and lymphatic systems to include AL amyloidosis. This regulatory... diagnostic code in the Hemic and Lymphatic Systems listed in Sec. 4.117. VA proposes to assign a 100 percent... diagnostic code 7716, to read as follows: Sec. 4.117 Schedule of ratings--hemic and lymphatic systems....

  19. [Cardiac amyloidosis].

    PubMed

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

    2008-03-15

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

  20. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study.

    PubMed

    Bochtler, Tilmann; Hegenbart, Ute; Kunz, Christina; Benner, Axel; Kimmich, Christoph; Seckinger, Anja; Hose, Dirk; Goldschmidt, Hartmut; Granzow, Martin; Dreger, Peter; Ho, Anthony D; Jauch, Anna; Schönland, Stefan O

    2016-07-28

    Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P = .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P = .05) and a trend for better overall survival (median, not reached vs 93.7 months; P = .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations.

  1. Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes.

    PubMed Central

    Dubrey, S. W.; Cha, K.; Skinner, M.; LaValley, M.; Falk, R. H.

    1997-01-01

    OBJECTIVE: To determine whether patients with myocardial amyloidosis due either to AL (primary) amyloid or familial amyloid have distinguishing echocardiographic or electrocardiographic features; and to compare the prevalence of heart failure and survival in the two types of amyloidosis in relation to echocardiographic findings. DESIGN: Blinded group comparison of randomly selected cases of cardiac amyloidosis. SETTING: International referral centre for amyloid research and treatment. PATIENTS: 36 patients with cardiac amyloid heart disease, of whom 12 had familial and 24 had primary AL amyloidosis. RESULTS: Familial and AL echocardiograms were morphologically indistinguishable, with similar left ventricular wall thickness, mean (SD) 15.4 (2.3) nu 15.8 (2.5) mm, respectively; right ventricular wall thickness was also similar between amyloid types: 9.6 (2.8) nu 9.7 (6.5) mm, respectively. Doppler indices of left and right ventricular function, left ventricular volume, and ejection fraction were also similar. Low voltage electrocardiograms (< 0.5 mV) were more common in the AL (16/24, 67%) than in the familial group (4/12, 25%), P < 0.05. The one year survival for familial and AL forms was 92% (11/12) nu 38% (6/24), respectively, with virtually all deaths due to cardiac causes. CONCLUSIONS: Although cardiac involvement is echocardiographically indistinguishable, cardiac mortality is very different between the two forms of amyloidosis. Preservation of electrocardiographic voltage in familial amyloidosis suggests that the particular biochemical characteristics of distinct types of amyloid fibril have different pathological effects on the myocardium. This distinction becomes critical in the evaluation, treatment, and management of patients who have a diagnosis within the spectrum of the protein deposition diseases. Images PMID:9290406

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

    PubMed

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

    2015-06-01

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

  3. Bilateral kidney infarction due to primary Al amyloidosis: a first case report.

    PubMed

    Mihout, Fabrice; Joseph, Laure; Brocheriou, Isabelle; Leblond, Véronique; Varnous, Shaïda; Ronco, Pierre; Plaisier, Emmanuelle

    2015-05-01

    Primary Amyloid Light-chain (AL) amyloidosis is a rare form of plasma cell dyscrasia characterized by tissue deposition of monoclonal immunoglobulin light chain. Kidney involvement is the most frequent manifestation, and patients usually present with glomerular disease.We report an exceptional case of bilateral kidney infarcts caused by AL amyloidosis. A 34-years-old man presented with progressive dyspnea, loin pain, recurrent macroscopic hematuria, and acute kidney injury. Computed tomography showed bilateral kidney infarcts.The diagnosis of AL amyloidosis was established on the kidney biopsy with the characterization of major vascular amyloid deposits that selectively stained with antilambda light chain antibody. An amyloid restrictive cardiomyopathy was also present, responsible for the life-threatening conduction disturbance, but without patent cardioembolic disease. The patient then underwent emergency heart transplantation, followed by a conventional chemotherapy with bortezomib, melphalan, and dexamethasone. More than 3 years later, the patient has subnormal renal function, a well-functioning heart transplant, and a sustained hematologic response.In addition to the very uncommon presentation, this case illustrates the tremendous progress that has occurred in the management of severe forms of AL amyloidosis.

  4. Bilateral kidney infarction due to primary Al amyloidosis: a first case report.

    PubMed

    Mihout, Fabrice; Joseph, Laure; Brocheriou, Isabelle; Leblond, Véronique; Varnous, Shaïda; Ronco, Pierre; Plaisier, Emmanuelle

    2015-05-01

    Primary Amyloid Light-chain (AL) amyloidosis is a rare form of plasma cell dyscrasia characterized by tissue deposition of monoclonal immunoglobulin light chain. Kidney involvement is the most frequent manifestation, and patients usually present with glomerular disease.We report an exceptional case of bilateral kidney infarcts caused by AL amyloidosis. A 34-years-old man presented with progressive dyspnea, loin pain, recurrent macroscopic hematuria, and acute kidney injury. Computed tomography showed bilateral kidney infarcts.The diagnosis of AL amyloidosis was established on the kidney biopsy with the characterization of major vascular amyloid deposits that selectively stained with antilambda light chain antibody. An amyloid restrictive cardiomyopathy was also present, responsible for the life-threatening conduction disturbance, but without patent cardioembolic disease. The patient then underwent emergency heart transplantation, followed by a conventional chemotherapy with bortezomib, melphalan, and dexamethasone. More than 3 years later, the patient has subnormal renal function, a well-functioning heart transplant, and a sustained hematologic response.In addition to the very uncommon presentation, this case illustrates the tremendous progress that has occurred in the management of severe forms of AL amyloidosis. PMID:25929920

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

    PubMed Central

    Gjeorgjievski, Mihajlo; Purohit, Treta; Amin, Mitual B.; Kurtin, Paul J.; Cappell, Mitchell S.

    2015-01-01

    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. PMID:26366309

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

    PubMed

    Gjeorgjievski, Mihajlo; Purohit, Treta; Amin, Mitual B; Kurtin, Paul J; Cappell, Mitchell S

    2015-01-01

    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. PMID:26366309

  7. Systemic AL amyloidosis in a Beech Marten (Martes foina).

    PubMed

    Scaglione, F E; Mignone, W; Ferrero, E; Poggi, M; Biolatti, B; Bollo, E

    2013-10-01

    A wild Beech Marten (Martes foina), was referred for necropsy to the Department of Animal Pathology of the University of Turin (Italy). At gross examination, whitish and firm masses, 10-mm in diameter, were found on the heart and in the kidney. Spleen showed lighter color and greater consistency, and the cut surface of the liver appeared scattered with whitish-yellow coalescing foci homogeneously distributed. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the heart, liver, and kidneys. Amyloid stained positively with Congo red with and without 5% potassium permanganate pretreatment and showed green birefringence observable under polarized light. A diagnosis of systemic AL amyloidosis was made. This is the first description of systemic AL amyloidosis in a wild Stone Marten.

  8. Bilateral Chronic Subdural Nontraumatic Hematoma in a Woman Affected by AL Amyloidosis

    PubMed Central

    Luongo, M.; Grassi, M.; Godano, U.

    2015-01-01

    Chronic subdural hematoma (CSDH) is a condition frequently seen in neurosurgical practice, especially among the elderly. It is often preceded by head injury, even a trivial trauma. Light chain (AL) amyloidosis is a disorder involving extracellular tissue deposition of misfolded native proteins called amyloids. The several types of amyloidosis differ by source of proteins, organ involvement, treatment, and prognosis. We describe the case of a 59-year-old woman affected by AL amyloidosis, harboring surgically treated bilateral chronic nontraumatic subdural hematoma, and we suggest a possible correlation between the clinical entities of CSDH and AL amyloidosis. PMID:26251797

  9. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  10. AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Ueno, Toshiharu; Sumida, Keiichi; Hoshino, Junichi; Suwabe, Tatsuya; Mise, Koki; Hazue, Ryo; Hayami, Noriko; Hiramatsu, Rikako; Kawada, Masahiro; Imafuku, Aya; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Kinowaki, Keiichi; Ohashi, Kenichi; Fujii, Takeshi; Nishida, Aya; Ubara, Yoshifumi

    2016-01-01

    A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. PMID:27580556

  11. Malnutrition, pharmaconutrition and other considerations in AL amyloidosis, a rare disease with masquerading symptoms and usually delayed diagnosis.

    PubMed

    Franco-López, Ángeles; Culebras, Jesús M

    2015-06-01

    Amyloid Light-chain (AL) amyloidosis is a very rare disease. Nutritional and pharmaconutrional aspects are described. Nutrition repletion of malnourished AL patients is an essential strategy for improving treatment efficacy and clinical outcomes. Early diagnosis of AL amiloidosis is difficult to establish due to the fact that signs and symptoms appearing mimic other processes that delay the final correct histological diagnosis. Untreated patients with this disease have a dismal outcome, with a median survival of 10-14 months from diagnosis. The sooner the treatment is established the better the results are. Modern chemotherapeutical agents, based primarily in cyclophosphamide, bortethomid and dexametasone, produce a rapid, deep, and durable response in the majority of patients. Autologous stem cell transplantation remains restricted to selected patients who are generally without advanced cardiac amyloidosis.

  12. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy.

    PubMed

    Falk, Rodney H; Alexander, Kevin M; Liao, Ronglih; Dorbala, Sharmila

    2016-09-20

    The amyloidoses are a group of protein-folding disorders in which ≥1 organ is infiltrated by proteinaceous deposits known as amyloid. The deposits are derived from 1 of several amyloidogenic precursor proteins, and the prognosis of the disease is determined both by the organ(s) involved and the type of amyloid. Amyloid involvement of the heart (cardiac amyloidosis) carries the worst prognosis of any involved organ, and light-chain (AL) amyloidosis is the most serious form of the disease. The last decade has seen considerable progress in understanding the amyloidoses. In this review, current and novel approaches to the diagnosis and treatment of cardiac amyloidosis are discussed, with particular reference to AL amyloidosis in the heart. PMID:27634125

  13. Spontaneous bilateral kidney rupture during autologous stem cell transplantation in a patient affected by amyloidosis

    PubMed Central

    Ferrannini, Michele; Vischini, Gisella; De Angelis, Gottardo; Giannakakis, Konstantinos; Arcese, William

    2011-01-01

    Kidney spontaneous rupture is not a recognized complication neither for amyloidosis nor of autologous stem cell transplantation (ASCT). A 46-year-old white woman, affected by nephrotic syndrome, was diagnosed as AL amyloidosis by renal biopsy. We report the singular case of a bilateral spontaneous kidney rupture during ASCT for AL with renal rescue. PMID:25984105

  14. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis.

    PubMed

    Sanchorawala, V; Wright, D G; Seldin, D C; Dember, L M; Finn, K; Falk, R H; Berk, J; Quillen, K; Skinner, M

    2001-10-01

    Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses

  15. Presumptive service connection for disease associated with exposure to certain herbicide agents: AL amyloidosis. Final rule.

    PubMed

    2009-05-01

    This document amends the Department of Veterans Affairs (VA) adjudication regulations concerning presumptive service connection for a certain disease based on the most recent National Academy of Sciences (NAS) Institute of Medicine committee report, "Veterans and Agent Orange: Update 2006" (Update 2006). This amendment is necessary to implement a decision of the Secretary of Veterans Affairs that there is a positive association between exposure to herbicides used in the Republic of Vietnam during the Vietnam era and the subsequent development of AL amyloidosis. The intended effect of this amendment is to establish presumptive service connection for AL amyloidosis based on herbicide exposure. PMID:19507326

  16. Bortezomib-based induction for transplant ineligible AL amyloidosis and feasibility of later transplantation.

    PubMed

    Cornell, R F; Zhong, X; Arce-Lara, C; Atallah, E; Blust, L; Drobyski, W R; Fenske, T S; Pasquini, M C; Rizzo, J D; Saber, W; Hari, P N

    2015-07-01

    Recent studies support the use of bortezomib-based therapies in light chain amyloidosis (AL). We performed a retrospective analysis of the safety, efficacy and long-term survival (median follow-up 3 years) after bortezomib-based treatment in 28 consecutive patients with de novo AL deemed ineligible at initial presentation. The first 14 patients received bortezomib and dexamethasone (VD), and the second 14 patients received cyclophosphamide, bortezomib and dexamethasone (CVD; CyBorD). Both regimens were well tolerated with no treatment-related mortality. The overall hematological response (HR) rate was 93% in both the groups. Median time to response was shorter in the CVD group (39 days vs 96 days in the VD group; P=0.002). Hematological and organ responses induced with bortezomib-based therapy enabled 8 (33%) of initially transplant ineligible patients to undergo autologous hematopoietic stem cell transplantation (AHCT), including 4 patients with cardiac stage III or IV. Seven of the eight patients (88%) who underwent subsequent AHCT achieved sustained HR at a median of 33 months posttransplant. These data suggest that bortezomib-based induction followed by AHCT is a viable therapeutic strategy for transplant-ineligible AL. Larger, multicenter prospective trials are necessary to confirm our findings.

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

    PubMed

    Magy-Bertrand, N

    2016-08-01

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

  18. Cardiac Amyloidosis

    MedlinePlus

    ... abbreviation AL stands for Amyloidosis formed from Light chains, and it is a disease of the bone ... proteins that make up antibodies, known as light chains. These light chains circulate in the blood and ...

  19. Renal AA Amyloidosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Díez, Ramón; Madero, Magdalena; Gamba, Gerardo; Soriano, Juan; Soto, Virgilia

    2014-01-01

    Background Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease and a major cause of cardiovascular disease (CVD) mortality. Inflammation is closely involved in the pathogenesis of T2DM, and reactive amyloidosis occurs in the presence of chronic inflammation. We hypothesized that patients with T2DM may have a higher prevalence of renal AA amyloidosis (RAAA) and that this could contribute to worse atherosclerosis and CVD. Materials and Methods We analyzed 330 autopsy kidneys from patients with a previous T2DM diagnosis. The kidney tissue was evaluated in order to determine the presence of diabetic nephropathy and RAAA, and systemic vessels were evaluated for the presence of atherosclerosis. Results RAAA was detected in 9% of our study population and was associated with an increased risk for nodular sclerosis [OR (95% CI)] [11 (2.04-59.16)], for chronic ischemic cardiomyopathy [4.59 (2.02-10.42)], for myocardial infarction [3.41 (1.52-7.64)] as well as for aortic [4.75 (1.09-20.69)], coronary [3.22 (1.47-7.04)], and intrarenal atherosclerosis [3.84 (1.46-10.09)]. Conclusions RAAA is prevalent in T2DM and is associated with worse CVD and renal disease, likely because RAAA is a marker of severe chronic inflammation. PMID:25337080

  20. Systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency.

    PubMed

    Taniyama, H; Yamamoto, S; Sako, T; Hirayama, K; Higuchi, H; Nagahata, H

    2000-01-01

    Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein-Friesian cow with systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine kappa-light chain and reacted weakly against bovine X-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin kappa-light chains of precursor protein in cattle. PMID:10643989

  1. Topical application of ankaferd hemostat in a patient with gastroduodenal amyloidosis complicated with gastrointestinal bleeding.

    PubMed

    Beyazit, Yavuz; Onder, Fatih Oguz; Torun, Serkan; Tas, Adnan; Purnak, Tugrul; Tenlik, Ilyas; Turhan, Nesrin

    2013-10-01

    Amyloidosis rarely manifests itself as gastrointestinal hemorrhage, especially in the absence of systemic involvement. Despite urgent endoscopic and/or pharmacological therapy, bleeding due to gastric amyloidosis usually recurs after a short period and has considerable morbidity and mortality rates, even in patients undergoing gastrointestinal surgery. For this reason, there is a need for a therapeutic armamentarium for such cases that is effective, easily applicable and has minimal side effects. In this respect, ankaferd blood stopper (ABS) offers a well tolerated and effective alternative approach for these patients. Herein we would like to report a 77-year-old man who had massive bleeding from a gastric ulcer complicating primary gastroduodenal amyloidosis, in whom topical ABS was successfully applied. PMID:23751610

  2. Systemic AA amyloidosis: epidemiology, diagnosis, and management

    PubMed Central

    Real de Asúa, Diego; Costa, Ramón; Galván, Jose María; Filigheddu, María Teresa; Trujillo, Davinia; Cadiñanos, Julen

    2014-01-01

    The term “amyloidosis” encompasses the heterogeneous group of diseases caused by the extracellular deposition of autologous fibrillar proteins. The global incidence of amyloidosis is estimated at five to nine cases per million patient-years. While amyloid light-chain (AL) amyloidosis is more frequent in developed countries, amyloid A (AA) amyloidosis is more common in some European regions and in developing countries. The spectrum of AA amyloidosis has changed in recent decades owing to: an increase in the median age at diagnosis; a percent increase in the frequency of primary AL amyloidosis with respect to the AA type; and a substantial change in the epidemiology of the underlying diseases. Diagnosis of amyloidosis is based on clinical organ involvement and histological evidence of amyloid deposits. Among the many tinctorial characteristics of amyloid deposits, avidity for Congo red and metachromatic birefringence under unidirectional polarized light remain the gold standard. Once the initial diagnosis has been made, the amyloid subtype must be identified and systemic organ involvement evaluated. In this sense, the 123I-labeled serum amyloid P component scintigraphy is a safe and noninvasive technique that has revolutionized the diagnosis and monitoring of treatment in systemic amyloidosis. It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. Nevertheless, novel therapeutic strategies targeting the formation of amyloid fibrils and amyloid deposition may generate new expectations for patients with AA amyloidosis. PMID:25378951

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

    PubMed Central

    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 retention in the myocardium. Myocardial biopsies revealed the presence of amyloid by Congo red staining. Further immunohistochemical analysis showed ATTR amyloidosis. DNA sequencing revealed a point mutation of the transthyretin gene leading to a single amino acid substitution. The only effective treatment in patients with manifest cardiac ATTR amyloidosis is combined heart and liver transplantation. Our patient was placed on a list for this procedure, but unfortunately she died during the standby procedure due to urosepsis. PMID:22400056

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

    PubMed

    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 retention in the myocardium. Myocardial biopsies revealed the presence of amyloid by Congo red staining. Further immunohistochemical analysis showed ATTR amyloidosis. DNA sequencing revealed a point mutation of the transthyretin gene leading to a single amino acid substitution. The only effective treatment in patients with manifest cardiac ATTR amyloidosis is combined heart and liver transplantation. Our patient was placed on a list for this procedure, but unfortunately she died during the standby procedure due to urosepsis.

  5. Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis.

    PubMed Central

    Hawkins, P N; Wootton, R; Pepys, M B

    1990-01-01

    125I-Serum amyloid P component (SAP), injected intravenously into 10 normal subjects, remained predominantly intravascular with mean (SD) T1/2 (half time) in plasma of 24.5 (5.9) h. The fractional catabolic rate of 68 (19)% of the plasma pool per day was more rapid than other reported human plasma proteins. All radioactivity was excreted in the urine by 14 d. In 16 patients with monoclonal gammopathy or chronic inflammatory diseases, but without amyloidosis, 125I-SAP metabolism was normal. However, among 45 patients with biopsy-proven systemic amyloidosis (25, amyloid A type; 20, amyloid L type), 125I-SAP was cleared from the plasma more rapidly, accumulated in the amyloid deposits, and persisted there. The T1/2 in amyloid, measured directly with 131I-SAP, was 24 d. Repeat studies after 6-18 mo were notably consistent in normals but changed significantly in amyloid patients, generally correlating with clinical signs of disease progression. Measurements of 125I-SAP turnover may thus be of value for diagnosis and monitoring of amyloidosis. Analysis of SAP metabolism in amyloidosis suggests that plasma SAP is in dynamic equilibrium with a very large amyloid pool, and in two autopsies the total mass of SAP in the amyloid deposits was 2,100 and 21,000 mg, respectively. Images PMID:2254450

  6. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis.

    PubMed

    Reece, Donna E; Hegenbart, Ute; Sanchorawala, Vaishali; Merlini, Giampaolo; Palladini, Giovanni; Bladé, Joan; Fermand, Jean-Paul; Hassoun, Hani; Heffner, Leonard; Kukreti, Vishal; Vescio, Robert A; Pei, Lixia; Enny, Christopher; Esseltine, Dixie-Lee; van de Velde, Helgi; Cakana, Andrew; Comenzo, Raymond L

    2014-10-16

    CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m(2) and twice-weekly 1.3 mg/m(2) bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ≥1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00298766. PMID:25202139

  7. Primary systemic amyloidosis as a real diagnostic challenge – case study

    PubMed Central

    Jerzykowska, Sonia; Gil, Lidia A.; Balcerzak, Andrzej; Pupek-Musialik, Danuta; Komarnicki, Mieczysław A.

    2014-01-01

    Primary amyloidosis (AL) is a rare variety of plasma cell dyscrasia, the diagnosis of which is often difficult to establish. Pathogenesis of amyloidosis involves extracellular deposition of insoluble protein fibrils in tissues, leading to insufficiency of affected organs. According to various sources, mean survival rate of patients with primary amyloidosis ranges from 12 to 24 months, making primary amyloidosis a disease with a very poor prognosis. Survival rate is significantly lowered in case of cardiac manifestation of amyloidosis (about 6 months survival in untreated patients). In recent years a considerable progress in AL treatment has been observed. Nowadays we are able not only to delay progression of amyloidosis, but also to improve the function of the affected organs. Unfortunately as first signs and symptoms of AL are usually nonspecific, the diagnosis of AL is often delayed, resulting in late introduction of optimal therapy. There are many diagnostic tests which can be used in diagnostic process of amyloidosis, i.e. electrophoresis, serum and urine immunofixation or affected organs and bone marrow biopsy. On establishing the diagnosis in a patient with suspected amyloidosis it should be remembered that particular diagnostic methods vary considerably in sensitivity. The aim of this paper is to present a case report of a 27-year-old patient with primary amyloidosis focusing on diagnostic aspect of this condition. On the basis of this case, the authors would like to emphasize the value of precise diagnostic process, with immunological techniques playing undoubtedly a crucial role. PMID:26155101

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

    PubMed

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

    2003-01-01

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

  9. Successful Treatment of Amyloid Light-chain Amyloidosis in a Charcot-Marie-Tooth Disease Patient with Lenalidomide, Cyclophosphamide, and Dexamethasone.

    PubMed

    Kikukawa, Yoshitaka; Hata, Hiroyuki; Ueda, Mitsuharu; Yamashita, Taro; Nasu, Singo; Ide, Kazuhiko; Ueno, Shikiko; Ando, Yukio; Mitsuya, Hiroaki; Okuno, Yutaka

    2016-01-01

    A 70-year-old woman with Charcot-Marie-Tooth disease (CMT) suffered from nephrotic syndrome and a renal biopsy revealed non-AA amyloid depositions that contained immunoglobulin light chain λ. Her serum λ free LC was elevated to 80.8 mg/L and she was diagnosed with primary amyloid light-chain (AL) amyloidosis. She was subsequently treated with lenalidomide, cyclophosphamide, and dexamethasone (RCD). After 14 cycles of RCD, she achieved complete remission. Her serum albumin levels gradually normalized to 3.1 g/dL. No exacerbation of neurologic symptoms related to CMT was observed. Thus, RCD may be a well-tolerated and effective regimen for treating AL amyloidosis in patients with CMT disease. PMID:27629972

  10. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    SciTech Connect

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-08-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  11. Histomorphological patterns of renal amyloidosis: a correlation between histology and chemical type of amyloidosis.

    PubMed

    Looi, L M; Cheah, P L

    1997-07-01

    A retrospective study was conducted to investigate whether there was a correlation between the histological pattern of renal amyloidosis, the chemical type of amyloid protein involved and the clinical presentation. Eighteen consecutive cases of systemic amyloidosis that had renal biopsies processed and examined histopathologically at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur were reviewed. The age range of patients was 25 to 64 yrs (mean, 46 yrs). The male:female ratio was 2.6:1. Three patients were Malay, 9 Chinese, 3 Indian, 1 Indonesian, 1 Iban, and 1 Bisaya. According to the predominant site of amyloid deposition, 14 cases showed a glomerular pattern and 4 a vascular pattern. 8 cases were designated as 2 anti-human amyloid-A (AA) amyloidosis on the basis of permanganate-sensitivity and immunoreactivity of deposits with anti-human AA protein antibody. Ten cases contained deposits that were permanganate-resistant and nonimmunoreactive for AA protein and were designated as AL in type. The histomorphologic pattern of renal amyloidosis did not provide a reliable means of differentiating AA from AL amyloidosis. The glomerular pattern tended to present with renal manifestations such as nephrotic syndrome and chronic renal failure, whereas the vascular pattern tended to present with nonrenal manifestations such as diarrhoea. These findings may have a bearing on the pathophysiology of amyloidosis and provide clues to appropriate management. PMID:9224755

  12. Anterior Orbit and Adnexal Amyloidosis

    PubMed Central

    Al Hussain, Hailah; Edward, Deepak P.

    2013-01-01

    Purpose: To describe six cases of anterior orbital and adnexal amyloidosis and to report on proteomic analysis to characterize the nature of amyloid in archived biopsies in two cases. Materials and Methods: The clinical features, radiological findings, pathology, and outcome of six patients with anterior orbit and adnexal amyloidosis were retrieved from the medical records. The biochemical nature of the amyloid was determined using liquid chromatography/mass spectroscopy archived paraffin-embedded tissue in two cases. Results: Of the six cases, three had unilateral localized anterior orbit and lacrimal gland involvement. Four of the six patients were female with an average duration of 12.8 years from the time of onset to presentation eyelid infiltration by amyloid caused ptosis in five cases. CT scan in patients with lacrimal gland involvement (n = 3) demonstrated calcified deformable anterior orbital masses and on pathological exmaintionamyloid and calcific deposits replaced the lacrimal gland acini. Ptosis repair was performed in three patients with good outcomes. One patient required repeated debulking of the mass and one patient had recurrenct disease. Proteomic analysis revealed polyclonal IgG-associated amyloid deposition in one patient and AL kappa amyloid in the second patient. Conclusion: Amyloidosis of the anterior orbit and lacrimal gland can present with a wide spectrum of findings with good outcomes after surgical excision. The nature of amyloid material can be precisely determined in archival pathology blocks using diagnostic proteomic analysis. PMID:24014979

  13. The rate and significance of type 1/type 2 serum amyloid A protein gene polymorphisms in patients with ankylosing spondylitis and amyloidosis.

    PubMed

    Yildirim Cetin, Gozde; Ganiyusufoglu, Eda; Solmaz, Dilek; Cagatay, Yonca; Yılmaz Oner, Sibel; Erer, Burak; Sagliker, Hasan Sabit; Avci, Ali Berkant; Akar, Servet; Pamuk, Omer Nuri; Kılınc, Metin; Kasifoglu, Timucin; Direskeneli, Haner; Gul, Ahmet; Sayarlioglu, Mehmet

    2015-01-01

    A relationship between the presence of amyloidosis and SAA1 genotype has been shown in recent studies of (principally) familial Mediterranean fever patients. We found that the SAA1 rs12218 polymorphism was significantly more prevalent in ankylosing spondylitis patients with amyloidosis.

  14. Beta 2-microglobulin amyloidosis presenting as esophageal perforation in a hemodialysis patient.

    PubMed

    Khan, G A; Lewis, F I; Dasgupta, M

    1997-01-01

    A 45-year-old male with hypertensive end-stage renal disease and on maintenance hemodialysis for 13 years is reported. He presented with life-threatening hematemesis, secondary to esophageal rupture. Immunohistological staining and electron microscopy examination of the esophageal perforation showed depositions of beta 2-microglobulin (beta 2-M) amyoloid. The unique aspect presented here is the localized esophageal involvement with beta 2-M amyloidosis. This is the first reported patient with esophageal perforation, due to the deposition and infiltration of the lower esophagus with beta 2-M which predisposed to its rupture. PMID:9426849

  15. Role of amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arthritis.

    PubMed

    Sanai, Toru; Nanishi, Fumio; Nagata, Masatoshi; Hirano, Tadashi; Suematsu, Eiichi; Esaki, Yukio; Miyahara, Hisaaki; Iida, Mitsuo

    2007-02-01

    The role of secondary amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arthritis (RA) was examined in 22 patients with a mean age of 60.1 years included 21 renal amyloidosis. RA duration until the start of dialysis was 19.5 +/- 7.2 years and the observation period after introduction 27.1 +/- 26.4 months. Of the 14 dead cases, four died due to sepsis, three due to gastrointestinal tract bleeding, two due to congestive heart failure, and eight cases died within 5 months after starting dialysis. When comparing the eight survivors and the nine non-survivors who died within 2 years after the start of dialysis, the former patients showed significantly higher serum albumin, and lower electrocardiogram score and cardiothoracic ratios at the time of introduction to dialysis. The careful prevention and treatment of infection, cerebrovascular and/or gastrointestinal tract complications seem to be necessary to improve the prognosis of RA patients after the initiation of renal replacement therapy.

  16. Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death

    PubMed Central

    Warsame, R; Kumar, S K; Gertz, M A; Lacy, M Q; Buadi, F K; Hayman, S R; Leung, N; Dingli, D; Lust, J A; Ketterling, R P; Lin, Y; Russell, S; Hwa, L; Kapoor, P; Go, R S; Zeldenrust, S R; Kyle, R A; Rajkumar, S V; Dispenzieri, A

    2015-01-01

    Importance of interphase fluorescent in situ hybridization (FISH) with cytoplasmic staining of immunoglobulin FISH (cIg-FISH) on bone marrow is not well understood in light chain amyloidosis (AL). This is in contrast with multiple myeloma where prognostic and treatment related decisions are dependent on cytogenetic testing. This retrospective study reviewed 401 AL patients with cIg-FISH testing performed at our institution between 2004 and 2012. Eighty-one percent of patients had an abnormal cIg-FISH. Common abnormalities involved translocations of chromosome 14q32 (52%), specifically: t(11;14) (43%), t(14;16) (3%) and t(4;14) (2%). Other common abnormalities include monosomy 13/deletion 13q (30%), trisomies 9 (20%), 15 (14%), 11 (10%) and 3 (10%). Median overall survival for this cohort of patients is 3.5 years. When plasma cell burden was greater than 10% trisomies predicted for worse survival (44 vs 19 months), and when it was ⩽10% t(11;14) predicted for worse survival (53 months vs not reached). Abnormal cIg-FISH was significantly associated with advanced cardiac involvement, and remained a prognostic factor on multivariate analysis. This large AL cohort demonstrates that abnormal FISH at diagnosis is prognostic for survival and advanced cardiac disease. Particularly, trisomies and t(11;14) affect survival when degree of plasma cell burden is considered. PMID:25933374

  17. Primary amyloidosis A. Immunohistochemical and biochemical characterization.

    PubMed Central

    Picken, M. M.; Pelton, K.; Frangione, B.; Gallo, G.

    1987-01-01

    Primary "idiopathic" amyloidosis is usually related to immunoglobulin light chain (AL) associated with immunocytic dyscrasias, while secondary "reactive" amyloidosis (AA) is related to serum amyloid A protein (SAA) and typically occurs with chronic inflammation, malignancy, or familial Mediterranean fever. In the present study, amyloid fibril protein extracted from frozen and paraffin-embedded tissue from a patient (CAR) with primary systemic amyloidosis proved to be AA protein by immunohistochemical, immunochemical, and amino terminal sequence. Extracts from both frozen and formalin-fixed paraffin-embedded kidney and spleen yielded similar monomers and dimers of the AA protein. The additional high-molecular-weight bands and a distinct 12,000-dalton fragment in the amyloid protein extracted from the formalin-fixed paraffin-embedded lung suggest that different processing of proteins, ie, by polymerization and/or degradation, may occur in different organs. Images Figure 1 Figure 2 Figure 3 PMID:3425691

  18. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  19. Does AL amyloidosis have a unique genomic profile? Gene expression profiling meta-analysis and literature overview.

    PubMed

    Kryukov, Fedor; Kryukova, Elena; Brozova, Lucie; Kufova, Zuzana; Filipova, Jana; Growkova, Katerina; Sevcikova, Tereza; Jarkovsky, Jiri; Hajek, Roman

    2016-10-15

    Immunoglobulin light chain amyloidosis (ALA) is a plasma cell dyscrasia characterized by deposition of amyloid fibrils in various organs and tissues. The current paper is devoted to clarify if ALA has a unique gene expression profile and to its pathogenetic argumentation. The meta-analysis of ALA patients vs. healthy donors, monoclonal gammopathy of undetermined significance, smoldering and multiple myeloma patients' cohorts have revealed molecular signature of ALA consists of 256 genes representing mostly ribosomal proteins and immunoglobulin regions. This signature appears pathogenetically supported and elucidates for the first time the role of ribosome dysfunction in ALA. In summary of our findings with literature overview, we hypothesize that ALA development is associated not only with changes in genes, coding amyloidogenic protein itself, but with post-transcriptional disbalance as well. Based on our data analysis in ALA, ribosome machinery is impaired and the affected link mainly involves translational initiation, elongation and co-translational protein folding. PMID:27288311

  20. Primary amyloidosis

    MedlinePlus

    ... Swelling in the arms and legs Weak hand grip Weight loss Other symptoms that may occur with ... kidney involvement may lead to organ failure and death. Body-wide ( systemic ) amyloidosis can lead to death ...

  1. [Heart failure and arterial hypertension disclosing amyloidosis].

    PubMed

    Habbal, R; Noureddine, M; Hachim, K; Zahraoui, M; Azzouzi, L; Fadouach, S; Zaid, D; Chraibi, N

    1997-01-01

    Amyloidosis results from protein infiltration of the extracellular space of organs and tissues. Several amyloidosis proteins have been identified. Protein AL, (deriving from immunoglobulin light chain), protein AA and prealbumin are the most involved in this disease. When AL amyloidosis involves the heart, the illness is often terminal. Most clinical symptoms are heart failure and arrhythmia or block conduction. This case was characterised by the unusual combination of hypertension and amyloidosis. The diagnosis suggested by the echocardiographic but was confirmed by the damaged organ's biopsy. The present case concerns a young woman, who has hypertension and a pulmonary oedema. The echocardiographic scan showed a septal hypertrophy with a shining and granite-like aspect which is compatible with heart amyloidosis. Systolic and diastolic disorder with mitral and aortic regurgitation were also revealed. The kidney and rectum biopsies confirmed amyloidosis AL of the Kappa dysglobulinemia type, without extraosseous plasmocytoma. The heart and kidney failure symptoms disappeared after treatment with diuretics and ACE inhibitors.

  2. Insulin-derived amyloidosis

    PubMed Central

    Gupta, Yashdeep; Singla, Gaurav; Singla, Rajiv

    2015-01-01

    Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms “insulin amyloidosis”. Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014. PMID:25593849

  3. Multifocal fibrosclerosis and renal amyloidosis.

    PubMed Central

    Hamilton, D. V.; Thiru, S.

    1983-01-01

    A 34-year-old female with a 14-year history of multifocal fibrosclerosis developed the nephrotic syndrome due to renal amyloidosis. Although the association between chronic inflammatory processes and amyloidosis is well known, this is the first report of amyloidosis occurring in a patient with multifocal fibrosclerosis. Other interesting features of this case are the involvement of subcutaneous adipose tissue in the inflammatory-fibrotic process and the presence of features of multifocal fibrosclerosis in the patient's twin sister. Images Fig. 1 PMID:6622334

  4. Nuclear Imaging of Amyloidosis

    PubMed Central

    Cytawa, Wojciech; Teodorczyk, Jacek; Lass, Piotr

    2014-01-01

    Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. 123I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. 99mTc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as 201Tl, 123I-mIBG, together with 111In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. 67Ga-citrate and 99mTc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with 131I or 111In. Among PET tracers, 11C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge. PMID:25071873

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

    PubMed

    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

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

    PubMed

    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.

  7. Amyloidosis and Kidney Disease

    MedlinePlus

    ... body has fewer red blood cells than normal. Dialysis-related Amyloidosis People who suffer from kidney failure ... weight loss [ Top ] What are the symptoms of dialysis-related amyloidosis? The symptoms of dialysis-related amyloidosis ...

  8. Corneal amyloidosis associated with keratoconus.

    PubMed

    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

  9. Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy.

    PubMed

    Muchtar, Eli; Buadi, Francis K; Dispenzieri, Angela; Gertz, Morie A

    2016-01-01

    Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

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

    PubMed Central

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

    2014-01-01

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

  11. [Pulmonary Amyloidosis: A Diagnostic Challenge].

    PubMed

    Alves, Ana; Alfaro, Tiago M; Madama, Daniela; Freitas, Sara; Robalo-Cordeiro, Carlos; Gamboa, Fernanda

    2015-01-01

    Amyloidosis is characterized by amyloid extracellular deposition in organs and tissues. Pulmonary involvement is a rare manifestation of the disease and it can be focal or as part of systemic amyloidosis. We report two cases. Case 1: 71 year-old female with bronchiectasis and Sjogrenâ syndrome, who complained of anorexia, weight loss and a productive cough. The diagnostic study included a surgical lung biopsy and histological examination demonstrated pulmonary amyloidosis. Case 2: 83 year-old male patient, ex-smoker, asymptomatic, whose routine chest x-ray showed a nodular opacity in the right lung field. A transthoracic biopsy revealed an amyloid lung tumor. These cases illustrate a rare disease which in Case 1 also coexisted with Sjögrenâs syndrome and bronchiectasis. The most important differential diagnosis is cancer and so a definitive diagnosis is essential, as amyloidosis is usually benign and indolent.

  12. Pseudotumoral amyloidosis of beta 2-microglobulin origin in the buttock of a patient receiving long term haemodialysis.

    PubMed Central

    Fernández-Alonso, J; Rios-Camacho, C; Valenzuela-Castaño, A; Rocha-Castilla, J L

    1993-01-01

    A 52 year old man who had been receiving haemodialysis for 13 years, with a history of renal tuberculosis, right ischial tuberculous osteomyelitis, and dialysis arthropathy, developed a soft tissue tumour in his left buttock. Histological analysis, immunohistological staining, and electron microscopic examination of the surgically removed tumour showed massive deposits of beta 2-microglobulin (beta 2-M) amyloid. This case shows the expanding clinical spectrum of this type of amyloidosis, and it is suggested that amyloid infiltration should be considered in the differential diagnosis of gluteal tumours in these patients. Images PMID:8408708

  13. Single Nodular Pulmonary Amyloidosis: Case Report

    PubMed Central

    Ko, Young Chun; Jeong, Jong Pil; Park, Chan Woo; Seo, Seok Ho; Kim, Jong Taek; Park, Dae Won; Bak, Cheol Min; Moon, Seung Ki; Jo, Shin Hyoung; Kim, Se Mi; Jung, Ah Lon

    2015-01-01

    Amyloidosis is defined as the presence of extra-cellular deposits of an insoluble fibrillar protein, amyloid. The pulmonary involvement of amyloidosis is usually classified as tracheobronchial, parenchymal nodular, or diffuse alveolar septal. A single nodular lesion can mimic various conditions, including malignancy, pulmonary tuberculosis, and fungal infection. To date, only one case of nodular pulmonary amyloidosis has been reported in Korea, a case involving multiple nodular lesions. Here, we report and discuss the case of a patient having single nodular amyloidosis. PMID:26508930

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

    PubMed

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

    1979-07-01

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

  15. Duodenal Amyloidosis Masquerading as Iron Deficiency Anemia

    PubMed Central

    Hurairah, Abu

    2016-01-01

    The present study is a unique illustration of duodenal amyloidosis initially manifesting with iron deficiency anemia. It underscores the importance of clinical suspicion of amyloidosis while performing upper gastrointestinal endoscopy with a biopsy to establish the definite diagnosis in patients with unexplained iron deficiency anemia. PMID:27625911

  16. [Optimization of the immunohistochemical diagnosis of AL amyloidosis using novel antibodies].

    PubMed

    Mikhaleva, L M; Gioeva, Z V; Reken, K

    2015-01-01

    Цель — улучшение иммуногистохимической диагностики AL-амилоидоза путем создания новых пептидных антител, направленных к вариабельному и константному регионам каппа-легких цепей. Материал и методы. В научной литературе, а также в базе данных национального центра биотехнологической информации (NCBI) провели поиск всех амилоидогенных каппа-легких цепей. На основании полученных данных составлена цепь из наиболее часто встречающихся аминокислотных остатков, из которых и были выбраны пептидные регионы для иммунизации. Четыре антитела были генерированы в результате иммунизации кроликов двумя пептидами, которые соответствовали вариабельному и константному регионам каппа-легких цепей. Результаты. Специфичность полученных антител подтверждена на серии из 222 биоптатов, полученных у 193 пациентов с AA-, AL-амилоидозом, транстиретиновым и инсулиновым амилоидозом. Все новые поликлональные пептидные антитела дали позитивную окраску в случаях с AL-каппа-амилоидозом. Заключение. Созданные нами поликлональные антитела, направленные к вариабельному и константному регионам каппа-легких

  17. Primary breast amyloidosis presenting as microcalcifications only.

    PubMed

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

    2013-01-01

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

  18. Primary Breast Amyloidosis Presenting as Microcalcifications Only

    PubMed Central

    Shim, Youngsub; Kim, Min Jung; Ryu, Han Suk

    2013-01-01

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

  19. Immunoglobulin synthesis in primary and myeloma amyloidosis.

    PubMed Central

    Preud'homme, J L; Ganeval, D; Grünfeld, J P; Striker, L; Brouet, J C

    1988-01-01

    Bone marrow cells from 14 patients with primary amyloidosis and two patients with myeloma amyloidosis were studied by immunofluorescence and biosynthesis experiments after incorporation of radioactive amino acids. Cells from four patients affected with non-myeloma secondary amyloidosis were also studied as controls. In primary amyloidosis, monoclonal plasma cell populations were demonstrated by immunofluorescence in virtually every case, even in patients without serum and urine monoclonal immunoglobulin and with a normal percentage of bone marrow plasma cells. Biosynthesis experiments showed the secretion of large amounts of free light chains, most often of the lambda type, in every primary or myeloma amyloidosis case and the presence of light chain fragments in almost all cases. Special features in certain patients were the synthesis of short gamma chains (two cases), assembly block at the HL half molecule level of a monoclonal IgA (one case) and secretion of decameric abnormally large kappa chains (one case). This is in contrast with non-myelomatous secondary amyloidosis where the distribution of bone marrow plasma cells was normal by immunofluorescence and where normal sized immunoglobulins were synthesized, without free light chain secretion and fragments. These data confirm that primary amyloidosis belongs to plasma cell dyscrasias and emphasize the role of free light chains and light chain fragments in the pathogenesis of amyloid deposition. PMID:3145161

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

    PubMed Central

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

    2016-01-01

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

  1. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    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

  2. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    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

  3. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians.

    PubMed

    Larsen, Christopher P; Ismail, Wesam; Kurtin, Paul J; Vrana, Julie A; Dasari, Surendra; Nasr, Samih H

    2016-04-01

    Large case series of renal amyloidosis subtypes have recently been published in the United States and Europe showing AL amyloidosis to be the predominant subtype in this part of the world. However, the most common subtypes of renal amyloidosis throughout the rest of the world are unknown. We present here the first large case series detailing the subtypes of renal amyloidosis among Egyptians. In this population, AA amyloidosis was the most common type of amyloidosis on renal biopsy at 48%. The newly described leukocyte chemotactic factor 2 amyloidosis (ALECT2) was the second most common type and represented nearly one-third of renal amyloid cases at 31%. AL accounted for only 20% of cases. The pathologic findings in ALECT2 cases were similar to those previously described in other case series. Thus ALECT2, which was initially thought to affect mainly Hispanics in the United States, appears to represent an important and likely underrecognized etiology of chronic kidney disease among Egyptians and probably in other ethnic groups around the world. PMID:26867784

  4. A Rare Case of Ascites due to Peritoneal Amyloidosis

    PubMed Central

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

    2016-01-01

    Patient: Male, 65 Final Diagnosis: Peritoneal amyloidosis Symptoms: Anasarca • Dyspnea • Orthopnea Medication: — Clinical Procedure: Paracentesis and peritoneal biopsy Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course 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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

  7. Amyloidosis: an unusual cause of portal hypertension.

    PubMed

    Takayasu, Vilma; Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete E; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

  8. Amyloidosis: an unusual cause of portal hypertension

    PubMed Central

    Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete e; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

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

    PubMed Central

    Kertowidjojo, Elizabeth; Zhang, Yue; Patel, Pruthvi

    2016-01-01

    Hepatic amyloidosis is a rare disease entity that results from insoluble amyloid protein deposition in the liver. The disease often presents with vague, nonspecific clinical features. Currently, there is little literature describing treatment outcomes for biopsy-proven hepatic amyloidosis and current treatment guidelines recommend that patients enroll in a clinical trial due to insufficient evidence to suggest an optimal treatment regimen. Here, we present two cases of hepatic amyloidosis at an academic medical center and describe their presentation, treatment, and outcomes. These cases highlight the poor outcomes and difficult management of hepatic amyloidosis. Further understanding and investigation of this rare disease are warranted. PMID:27774327

  10. Increased Serum Free Light Chains Precede the Presentation of Immunoglobulin Light Chain Amyloidosis

    PubMed Central

    Weiss, Brendan M.; Hebreo, Joseph; Cordaro, Daniel V.; Roschewski, Mark J.; Baker, Thomas P.; Abbott, Kevin C.; Olson, Stephen W.

    2014-01-01

    Purpose Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis. Patients and Methods We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples. Results An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001). Conclusion Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years. PMID:25024082

  11. Study on epidemiology of cutaneous amyloidosis in northern India and effectiveness of dimethylsulphoxide in cutaneous amyloidosis

    PubMed Central

    Krishna, Arvind; Nath, Bhola; Dhir, G. G.; Kumari, Ranjeeta; Budhiraja, Virendra; Singh, Kalpana

    2012-01-01

    Context: Amyloidosis, which is characterized by the extracellular deposition of a proteinaceous substance, is usually associated with considerable tissue dysfunction. However, the etiology of the disease remains uncertain and the treatment disappointing. Aim: 1. To know the epidemiology of cutaneous amyloidosis 2. To evaluate the effect of dimethylsulphoxide on cutaneous amyloidosis. Settings and Design: Data was collected from patients attending the Outpatient Department (OPD) over a period of one year. Material and Methods: Patients were screened on the basis of signs and symptoms and then confirmed histologically. A total of 62 patients who were suspected to be suffering from amyloidosis on the basis of clinical signs and symptoms and 38 patients who were further confirmed histopathologically underwent the treatment. Statistical Analysis Used: Chi-square test was used for testing the significance of proportions. Results: 63.15 percent of the patients had macular amyloidosis and the interscapular area was the most common area involved (52.63%). Pruritus, pigmentation, and papules responded excellently to dimethylsulphoxide after one month of treatment. Conclusions: Cutaneous amyloidosis is a disease found in middle-aged persons, with a female preponderance, and dimethylsulphoxide seems to be an effective therapy. PMID:23189250

  12. [Light Chain Amyloidosis: an Update for Treatment].

    PubMed

    Shen, Kai-Ni; Li, Jian

    2015-06-01

    Systemic light chain amyloidosis (AL amyloidosis) is the most common type of amyloidosis, in which deposition of misfolded monoclonal light chain secreted by underlying clonal plasma cells leads to organ dysfunction. Tissue biopsy of involved organ is needed to confirm the type of amyloid deposits, thus proper treatment could be applied. Laser microdissection followed by mass spectrometry, performed on formalin-fixed paraffin-embedded specimens, has been proven superior to traditional methods on accurate diagnosis of amyloidosis. Prognosis depends on the extent of cardiac involvement. The Mayo staging system using NT-ProBNP, cardiac troponin-T and free light chain, is the most robust method for risk stratification and treatment guidance. The introduction of autologous stem cell transplantation (auto-ASCT) resulted in long-term survival in responders, while treatment-related toxicity substantially limited the number of eligible candidates. Novel agents, especially bortezomib, thalidomide and lenalidomide hold promise to achieve comparable hematological responses with auto-ASCT, which might play significant role in treatment of recurrent or refractory AL amyloidosis. PMID:26117060

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

    PubMed

    Martin, Emily B; Williams, Angela; Heidel, Eric; Macy, Sallie; Kennel, Stephen J; Wall, Jonathan S

    2013-06-21

    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 therapeutics for the treatment of amyloid diseases.

  14. Macular Amyloidosis and Epstein-Barr Virus

    PubMed Central

    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

  15. Genetic factors in amyloidosis.

    PubMed Central

    Thomas, P K

    1975-01-01

    In the absence of biochemical distinctions, the nosography of the inherited amyloidoses must at present depend largely upon clinical subdivisions. In the broad classification adopted here, the disorders have for convenience been grouped according to the anatomical system that is predominantly affected. It is evident that the amyloid syndromes display considerable heterogeneity. However, they overlap. Thus in the Iowa type classified with the hereditary amyloid neuropathies (van Allen et al, 1969; Gimeno et al, 1974), renal involvement was frequent and was the usual cause of death. In the English (Zalin et al, 1974) and Scandinavian (Andersson, 1970) families with neuropathy as the predominant feature, cardiac involvement was a common finding. In certain of the conditions discussed, such as medullary carcinoma of the thyroid and Down's syndrome, amyloid deposition is merely an incidental aspect of the disorder. In those conditions in which generalized or localized amyloid deposition occupies a more central position in the clinical syndrome, an autosomal dominant inheritance has been established or suggested in the majority. An autosomal recessive inheritance has so far only been recognized in familial Mediterranean fever. In the family with hereditary amyloid heart diseases reported by Fredricksen et al (1962), the disorder was confined to a single sibship, raising the possibility of recessive inheritance. This could also be true in sporadic examples of primary amyloidosis. The dominantly inherited amyloidoses comprise a number of geographically widely scattered families with clinical pictures that do not show consistent differences between some families. The families that do not show consistent differences are not necessarily harbouring nutations at the same locus, or the same mutation at any particular locus. However, many of these dominantly inherited clinical syndromes are sufficiently different from each other and the clinical manifestations of each

  16. What is new in diagnosis and management of light chain amyloidosis?

    PubMed

    Palladini, Giovanni; Merlini, Giampaolo

    2016-07-14

    Light chain (AL) amyloidosis is caused by a usually small plasma cell clone producing a misfolded light chain that deposits in tissues. Survival is mostly determined by the severity of heart involvement. Recent studies are clarifying the mechanisms of cardiac damage, pointing to a toxic effect of amyloidogenic light chains and offering new potential therapeutic targets. The diagnosis requires adequate technology, available at referral centers, for amyloid typing. Late diagnosis results in approximately 30% of patients presenting with advanced, irreversible organ involvement and dying in a few months despite modern treatments. The availability of accurate biomarkers of clonal and organ disease is reshaping the approach to patients with AL amyloidosis. Screening of early organ damage based on biomarkers can help identify patients with monoclonal gammopathy of undetermined significance who are developing AL amyloidosis before they become symptomatic. Staging systems and response assessment based on biomarkers facilitate the design and conduction of clinical trials, guide the therapeutic strategy, and allow the timely identification of refractory patients to be switched to rescue therapy. Treatment should be risk-adapted. Recent studies are linking specific characteristics of the plasma cell clone to response to different types of treatment, moving toward patient-tailored therapy. In addition, novel anti-amyloid treatments are being developed that might be combined with anti-plasma cell chemotherapy. PMID:27053535

  17. Abnormal scintigraphic evolution in AA hepatic amyloidosis

    SciTech Connect

    Lomena, F.; Rosello, R.; Pons, F.; Grau, M.; Garcia, A.; Catafau, A.; Setoain, J.

    1988-03-01

    A patient with AA amyloidosis secondary to ankylosing spondylitis showed intense liver uptake of Tc-99m MDP on bone imaging. The biopsy showed hepatic amyloid deposition. A repeat bone scan with Tc-99m MDP 1 year later was negative, although the clinical signs and liver function tests of the patient had not changed. A mechanism might exist, other than the affinity of amyloid to calcium, which would explain the extraosseous uptake of pyrophosphates and diphosphonates in organs and soft tissues affected by systemic amyloidosis.

  18. [Systemic amyloidosis secondary to xanthogranulomatous pyelonephritis].

    PubMed

    Almirall, J; López, T; Sáez, A; Gratacós, J; Prats, J

    2001-01-01

    Secondary amyloidosis is a relatively common pathology in which chronic infectious diseases are common causes, especially infected bronchiectasis, osteomyelitis or chronic ulcers. The association of xanthogranulomatous pyelonephritis and systemic amyloidosis is extremely rare. To our knowledge, despite innumerable cases of xanthogranulomatous pyelonephritis reported in the literature, this association has been reported in only 8 previous cases. Patients usually complain of fever, back or flank pain and urinary tract symptoms. A long lasting evolution of the process is frequent. We report a 70 year old patient who developed amyloidosis secondary to xanthogranulomatous pyelonephritis. As well as the rarity of this association, this case is exceptional in its clinical presentation, without any urinary tract symptoms that could suggest the diagnosis.

  19. Surgical management of advanced ocular adnexal amyloidosis.

    PubMed

    Patrinely, J R; Koch, D D

    1992-06-01

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

  20. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

    PubMed Central

    Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J.; Herrey, Anna S.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Manisty, Charlotte H.; Schelbert, Eric B.; Kellman, Peter; Gillmore, Julian D.; Hawkins, Philip N.

    2015-01-01

    Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P<0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after

  1. Transthyretin Cardiac Amyloidosis in Black Americans.

    PubMed

    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.

  2. Transthyretin Cardiac Amyloidosis in Black Americans.

    PubMed

    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

  3. Unusual Combination of Tracheobronchopathia Osteochondroplastica and AA Amyloidosis

    PubMed Central

    Kırbaş, Gökhan; Dağlı, Canan Eren; Tanrıkulu, Abdullah Çetin; Yıldız, Fetin; Bükte, Yaşar; Kıyan, Esen

    2009-01-01

    Tracheobronchopathia osteochondroplastica (TO) is a rare disorder of unknown cause characterized by the presence of multiple submucosal osseous and/or cartilaginous nodules that protrude into the lumen of the trachea and large bronchi. A simultaneous diagnosis of TO and amyloidosis is rarely reported. In this report, a case initially suspected to be asthma bronchiole that could not be treated, was radiologically diagnosed as TO, and also secondary amyloidosis is presented. A 53 years, man patient reported a 3 years history of dyspnea. Pulmonary function tests (PFTs) showed an obstructive pattern. Chest X-rays revealed right middle lobe atelectasis. FOB and CT detected nodular lesions in the trachea and in the anterior and lateral walls of the main bronchi. AA amyloidosis was confirmed by endobronchial biopsy. In the abdominal fat pad biopsy, amyloidosis was not detected. Asthma bronchiole was excluded by PFTs. This case illustrates that it is possible for TO and amyloidosis to masquerade as asthma. TO and amyloidosis should be suspected in patients of older ages with asthma and especially with poorly treated asthmatic patients. Although nodular lesions in the anterior and lateral tracheobronchial walls are typical for TO, a biopsy should be obtained to exclude amyloidosis. PMID:19881980

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

    PubMed

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

    2014-01-01

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

  5. Magnetic resonance imaging in cardiac amyloidosis

    SciTech Connect

    O'Donnell, J.K.; Go, R.T.; Bott-Silverman, C.; Feiglin, D.H.; Salcedo, E.; MacIntyre, W.J.

    1984-01-01

    Primary amyloidosis (AL) involves the myocardium in 90% of cases and may present as apparent ischemia, vascular disease, or congestive heart failure. Two-dimensional echocardiography (echo) has proven useful in the diagnosis, particularly in differentiating AL from constrictive pericarditis. The findings of thickened RV and LV myocardium, normal LV cavity dimension, and a diffuse hyperrefractile ''granular sparkling'' appearance are virtually diagnostic. Magnetic resonance (MR) imaging may improve the resolution of anatomic changes seen in cardiac AL and has the potential to provide more specific information based on biochemical tissue alterations. In this preliminary study, the authors obtained both MR and echo images in six patients with AL and biopsy-proven myocardial involvement. 5/6 patients also had Tc-99 PYP myocardial studies including emission tomography (SPECT). MR studies utilized a 0.6 Tesla superconductive magnet. End diastolic gated images were obtained with TE=30msec and TR=R-R interval on the ECG. 6/6 pts. showed LV wall thickening which was concentric and included the septum. Papillary muscles were identified in all and were enlarged in 3/6. 4/6 pts. showed RV wall thickening but to a lesser degree than LV. Pericardial effusions were present in 4 cases. These findings correlated well with the results of echo although MR gave better RV free wall resolution. PYP scans were positive in 3 pts. but there was no correlation with degree of LV thickening. The authors conclude that there are no identifiable MR findings in patients with cardiac AL which encourage further attempts to characterize myocardial involvement by measurement of MR relaxation times in vivo.

  6. Amyloidosis of the renal pelvis: a harbinger of mammary carcinoma?

    PubMed

    Grigor, Thomas; Munro, Nicolas

    2015-01-01

    We describe a rare case of light chain immunoglobulin amyloid (AL) accumulation in the central and lower pole renal calyces. Our patient, a woman aged 60, presented with several episodes of gross haematuria. Radiological imaging detected a filling defect in the left renal pelvis. Rigid ureteroscopy showed a corresponding mucosal abnormality resembling transitional cell carcinoma. A definitive preoperative tissue diagnosis could not be reached. Laparoscopic-assisted left nephroureterectomy was indicated. Histopathological examination excluded malignancy, revealing congophilic deposits of submucosal amyloid. A constellation of findings confirmed localised or primary amyloidosis with an AL immunophenotype but no evidence of clonal B-cell disease in the amyloid-associated lymphoplasmacytic cell infiltrate. Investigation for systemic plasma cell dyscrasia and echocardiography and scintigraphy for visceral amyloid deposits were negative for systemic disease. At a follow-up period of 30 months, there is no recurrence. However, our patient was diagnosed with breast cancer 21 months ago. PMID:25596296

  7. ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction

    PubMed Central

    Yilmaz, Mahmut Ilker; Sonmez, Alper; Saglam, Mutlu; Qureshi, Abdul R.; Carrero, Juan Jesus; Caglar, Kayser; Eyileten, Tayfun; Cakir, Erdinc; Oguz, Yusuf; Vural, Abdulgaffar; Yenicesu, Mujdat; Lindholm, Bengt; Stenvinkel, Peter; Axelsson, Jonas

    2008-01-01

    Asymmetric dimethyl-arginine (ADMA), a residue of the proteolysis of arginine-methylated proteins, is a potent inhibitor of nitric oxide synthesis. The increased protein turnover that accompanies proteinuric secondary amyloidosis may increase circulating levels of ADMA, and this may contribute to endothelial dysfunction. We performed a cross-sectional study of 121 nondiabetic proteinuric patients with normal GFR (including 39 patients with nephrotic-range proteinuria and secondary amyloidosis) and 50 age-, sex-, and BMI–matched healthy controls. The proteinuric patients had higher levels of serum ADMA, symmetric dimethyl-arginine (SDMA), high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment index) than controls. Compared with controls, brachial artery flow-mediated dilatation (FMD), serum L-Arginine, and the L-Arginine/ADMA ratio were significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA and SDMA levels and lower L-Arginine/ADMA ratios and FMD measurements (P < 0.001 for all). Finally, even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. We propose that ADMA synthesis may be increased in chronic kidney disease, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality. PMID:18199801

  8. Nodular pulmonary amyloidosis.

    PubMed Central

    Pinto, A; Rasmussen, S L; Campbell, T M; Lester, W M

    1984-01-01

    An elderly man had a 10-year history of multiple pulmonary nodules that he had refused to have investigated. He died of a ruptured abdominal aortic aneurysm. At autopsy the nodules were shown to consist of amyloid. There was no evidence of systemic amyloidosis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 1 Fig. 2 PMID:6744167

  9. High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis.

    PubMed

    Kongtim, P; Qazilbash, M H; Shah, J J; Hamdi, A; Shah, N; Bashir, Q; Wang, M; Champlin, R; Manasanch, E E; Weber, D; Orlowski, R Z; Parmar, S

    2015-05-01

    Cardiac involvement in light-chain amyloidosis (AL) predicts poor prognosis and is associated with higher TRM and morbidity during high-dose therapy and auto-SCT (HDT-ASCT). We studied the outcomes of 30 patients with cardiac amyloidosis undergoing HDT-ASCT at our center between January 1998 and March 2012. The median age of the patients was 53 years (range, 36-74) with a median follow-up of 35 months (range, 0.4-97 months). Twenty-seven patients (90%) had more than one organ involved besides the heart with 37% with cardiac stage ⩾3. Melphalan-based conditioning regimen (140-200 mg/m(2)) was used for HDT-ASCT. One-year TRM is 10%. Three-year OS and EFS from HDT-ASCT was 83% and 56.8%, respectively. Cumulative incidence of relapse at 3 years was 38.5%. Negative factors affecting survival included age >60 years, lack of novel induction therapy and BM plasmacytosis >10%. We conclude that HDT-ASCT is well tolerated in patients with high-risk cardiac amyloidosis and can lead to improved overall outcomes.

  10. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    PubMed Central

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

    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 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. PMID:26521788

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

    SciTech Connect

    Martin, Emily B.; Williams, Angela; Heidel, Eric; Macy, Sallie; Kennel, Stephen J.; Wall, Jonathan S.

    2013-06-21

    Highlights: •Polybasic peptide p5 binds human light chain amyloid extracts. •The binding of p5 with amyloid involves both glycosaminoglycans and fibrils. •Heparinase treatment led to a correlation between p5 binding and fibril content. •p5 binding to AL amyloid requires electrostatic interactions. -- Abstract: In previously published work, we have described heparin-binding synthetic peptides that preferentially recognize amyloid deposits in a mouse model of reactive systemic (AA) amyloidosis and can be imaged by using positron and single photon emission tomographic imaging. We wanted to extend these findings to the most common form of visceral amyloidosis, namely light chain (AL); however, there are no robust experimental animal models of AL amyloidosis. To further define the binding of the lead peptide, p5, to AL amyloid, we characterized the reactivity in vitro of p5 with in situ and patient-derived AL amyloid extracts which contain both hypersulfated heparan sulfate proteoglycans as well as amyloid fibrils. Histochemical staining demonstrated that the peptide specifically localized with tissue-associated AL amyloid deposits. Although we anticipated that p5 would undergo electrostatic interactions with the amyloid-associated glycosaminoglycans expressing heparin-like side chains, no significant correlation between peptide binding and glycosaminoglycan content within amyloid extracts was observed. In contrast, following heparinase I treatment, although overall binding was reduced, a positive correlation between peptide binding and amyloid fibril content became evident. This interaction was further confirmed using synthetic light chain fibrils that contain no carbohydrates. These data suggest that p5 can bind to both the sulfated glycosaminoglycans and protein fibril components of AL amyloid. Understanding these complex electrostatic interactions will aid in the optimization of synthetic peptides for use as amyloid imaging agents and potentially as

  12. Mitral valve involvement as a predominant feature of cardiac amyloidosis

    PubMed Central

    Viswanathan, Girish; Williams, James; Slinn, Simon; Campbell, Philip

    2010-01-01

    Cardiac involvement in systemic amyloidosis carries poor prognosis with a median survival of 5 months.1 The authors report an unusual presentation of cardiac amyloidosis in the form of predominant mitral regurgitation. The patient responded very well to medical therapy with subsequent improvement of mitral valve dysfunction. The authors would like to highlight this multisystem involvement and the presence of a complex overlap of systemic features. PMID:22767536

  13. Chronic eyelid swelling as an initial manifestation of myeloma-associated amyloidosis.

    PubMed

    Chee, Elaine; Kim, Yoon-Duck; Lee, Jung Hye; Woo, Kyung In

    2013-01-01

    Orbital amyloidosis is uncommon and difficult to diagnose due to their variable clinical presentations. The authors report a case of a patient who presents with chronic eyelid swelling as an initial manifestation of myeloma-associated amyloidosis. This patient was also found to have retrobulbar infiltration with no visual impairment. The authors also describe the first documentation of the atypical necrotic appearance of amyloidosis in the involved eyelid tissues. Myeloma-associated amyloidosis can present as chronic, nonspecific periorbital swelling, hence a biopsy of the affected tissues is important in preventing a delay in the correct diagnosis.

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

    PubMed

    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

  15. Hereditary apolipoprotein AI-associated renal amyloidosis: A diagnostic challenge.

    PubMed

    Samillán-Sosa, Kelly Del Rocío; Sención-Martínez, Gloria; Lopes-Martín, Vanessa; Martínez-González, Miguel Angel; Solé, Manel; Arostegui, Jose Luis; Mesa, Jose; García-Díaz, Juan de Dios; Rodríguez-Puyol, Diego; Martínez-Miguel, Patricia

    2015-01-01

    Hereditary renal amyloidosis is an autosomal dominant condition with considerable overlap with other amyloidosis types. Differential diagnosis is complicated, but is relevant for prognosis and treatment. We describe a patient with nephrotic syndrome and progressive renal failure, who had a mother with renal amiloidosis. Renal biopsy revealed amyloid deposits in glomerular space, with absence of light chains and protein AA. We suspected amyloidosis with fibrinogen A alpha chain deposits, which is the most frequent cause of hereditary amyloidosis in Europe, with a glomerular preferential affectation. However, the genetic study showed a novel mutation in apolipoprotein AI. On reviewing the biopsy of the patient's mother similar glomerular deposits were found, but there were significant deposits in the renal medulla as well, which is typical in APO AI amyloidosis. The diagnosis was confirmed by immunohistochemistry. Apo AI amyloidosis is characterized by slowly progressive renal disease and end-stage renal disease occurs aproximately 3 to 15 years from initial diagnosis. Renal transplantation offers an acceptable graft survival and in these patients with hepatorenal involvement simultaneous liver and kidney transplantation could be considered.

  16. Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics.

    PubMed

    Nasr, Samih H; Dogan, Ahmet; Larsen, Christopher P

    2015-11-01

    Amyloidosis derived from leukocyte cell-derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell-derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell-derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis

  17. Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics.

    PubMed

    Nasr, Samih H; Dogan, Ahmet; Larsen, Christopher P

    2015-11-01

    Amyloidosis derived from leukocyte cell-derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell-derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell-derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis

  18. Amyloid Goiter Associated with Amyloidosis Secondary to Rheumatoid Arthritis

    PubMed Central

    Uzum, Gungor; Kaya, Fatih Oner; Uzum, Ayse Kubat; Kucukyilmaz, Meltem; Duzkoylu, Yigit; Leblebici, Cem; Koc, Oguz

    2013-01-01

    Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. The most common forms of systemic amyloidosis are primary amyloidosis (PA) of light chains and secondary amyloidosis (SA) caused by chronic inflammatory diseases such as rheumatoid arthritis (RA). Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is a rare occurrence. In SA, the deposition of amyloid associated (AA) protein is associated with atrophy of thyroid follicles. The clinical picture of these patients is characterized by rapid, painless thyroid gland enlargement which may be associated with dysphagia, dyspnea, or hoarseness. Thyroid function is not impaired in most cases. Although amyloid goitre secondary to systemic amyloidosis due to chronic inflammatory diseases is relatively common, specifically related to RA is much more uncommon one and it is reported less in the literature. In this report, A 52-old-year female patient with amyloid goiter associated with amyloidosis secondary to rheumatoid arthritis is presented. PMID:24368922

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

    PubMed

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

    2012-04-01

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

  20. [The effect of a water-cooled vest on heat intolerance in a patient with anhidrosis due to familial amyloidosis of Finnish type].

    PubMed

    Ohnishi, A; Sagawa, S; Ishiguchi, H; Yamamoto, T; Murai, Y

    1996-10-01

    The patient was a 70-year-old male with familial amyloidosis of Finnish type who complained of heat intolerance due to anhidrosis during outdoor activities in summer. A water-cooled TM-2 vest was tried for this patient to reduce his body heat during exercises. Following the morning activities including jogging in August his body temperature rose up to 38.0 degrees C without wearing the partly frozen vest. However, when he wore it, his temperature rose up to only 37.2 degrees C after the exercises, which was 0.8 degree C lower than when he did not wear the vest. Headache and tachycardia during and following the morning activities did not appear by wearing the vest. In the heat loading test, in which the room temperature was raised from 28.0 degrees C to 38.0 degrees C for 15 minutes and kept at 38.0 degrees C for 60 minutes with 60% humidity, the rises of his skin and esophageal temperatures with wearing the partly frozen vest for the last 60 minutes were 1.2 degrees C and 0.4 degree C lower, respectively, than his skin and esophageal temperatures without wearing it. Concomitantly, the increase of heart rate was suppressed in the same test condition. Wet vest in running water showed the similar effects. Therefore, we concluded that the use of water-cooled TM-2 vest was effective in alleviating the symptoms and signs of his heat intolerance. PMID:8997146

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

    PubMed

    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. Renal leukocyte chemotactic factor 2 (LECT2) amyloidosis in First Nations people in Northern British Columbia, Canada: a report of 4 cases.

    PubMed

    Hutton, Holly L; DeMarco, Mari L; Magil, Alex B; Taylor, Paul

    2014-11-01

    Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently identified type of amyloidosis that may represent an underdiagnosed cause of chronic kidney disease. LECT2 amyloidosis typically is reported as being renal limited and, in the United States, more prevalent in Hispanic patients. We add to the epidemiologic data of this condition by describing 4 First Nations people from Northern British Columbia, Canada, who presented with slowly progressive chronic kidney disease that was found to be due to LECT2 amyloidosis.

  3. Dystrophic amyloidosis: a local complication of tissue damage with heterogeneous distribution.

    PubMed

    Looi, L M

    1991-08-01

    Seventeen consecutive patients with dystrophic amyloidosis are reported here (eight Chinese, three Indian, three Iban, two Malay and one Caucasian). Ten were females and seven males, with ages ranging from 12 to 80 years (mean of 48 years). Five instances of dystrophic amyloidosis occurred in areas of tissue damage in the cardiovascular system, including fibrotic cardiac valves and an atheromatous plaque. Three occurred in osteoarthritic joint tissue. Of note were three occurrences in endometriotic cyst walls, four in the fibrotic walls of epidermal cysts, one in a hernial sac and one at the edge of a skin ulcer. All deposits were congophilic and exhibited green-birefringence and permanganate-resistance. Immunohistochemistry did not reveal reactivity for AA protein or immunoglobulin lambda or kappa light-chains. AP protein was detected in 35% of cases. Our results show that, besides the usual sites of osteoarthritic joints and damaged heart valves, dystrophic amyloidosis can complicate other areas of chronic tissue damage and fibrosis such as walls of cysts and ulcers. While the pathogenesis and biochemical nature remain unresolved, immunohistochemistry indicates that neither AA nor AL proteins are present in the deposits, and suggests that a different amyloid protein is involved. PMID:1757071

  4. Evolving landscape in the management of transthyretin amyloidosis

    PubMed Central

    Hawkins, Philip N.; Ando, Yukio; Dispenzeri, Angela; Gonzalez-Duarte, Alejandra; Adams, David; Suhr, Ole B.

    2015-01-01

    Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID:26611723

  5. Evolving landscape in the management of transthyretin amyloidosis.

    PubMed

    Hawkins, Philip N; Ando, Yukio; Dispenzeri, Angela; Gonzalez-Duarte, Alejandra; Adams, David; Suhr, Ole B

    2015-01-01

    Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTR(Rx), an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID:26611723

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-09-01

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

  9. [Osteoarticular amyloidosis caused by dialysis].

    PubMed

    Orzincolo, C; Bedani, P L; Scutellari, P N; Cardona, P; Farinelli, A; Vita, G

    1988-01-01

    The accumulation of amyloid in the bone and joint system has recently been recognized as a peculiar disease in patients undergoing long-term hemodialysis (5 years at least), especially in those who use cuprophan membranes. The pathology of amyloidosis is characterized by deposits of amyloid (beta 2-microglobulin mainly) in the bone, in the synovia, and in pericapsular soft tissues. The skeleton of 46 long-term hemodialysis patients (19 males and 27 females) was studied by X-ray: bone and joint abnormalities due to amyloid deposition were observed in 45% of cases. The shoulder, hip, and wrist were the most frequently involved joints. Destructive spondyloarthropathy was present in 15% of cases. The radiographic patterns of AOD are generally divided into axial and peripheral lesions. In the appendicular skeleton abnormalities include: well-defined lytic areas (geodes), pathologic fractures, marginal erosions, and periarticular soft tissue swelling. Destructive spondyloarthropathy is frequently present in the cervical spine (85% of our cases), and is characterized by narrowing of the intervertebral space, marginal erosion, and subchondral bone sclerosis of the vertebral body.

  10. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor

    PubMed Central

    Özgül, Mehmet Akif; Uzun, Oğuz; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important.

  11. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor

    PubMed Central

    Özgül, Mehmet Akif; Uzun, Oğuz; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  12. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor.

    PubMed

    Tanrıverdi, Elif; Özgül, Mehmet Akif; Uzun, Oğuz; Gül, Şule; Çörtük, Mustafa; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  13. Amyloidosis and Waldenström's macroglobulinemia.

    PubMed

    Gertz, Morie A; Merlini, Giampaolo; Treon, Steven P

    2004-01-01

    Primary systemic amyloidosis is an immunoglobulin light chain disorder that is 1/5th as common as multiple myeloma. Amyloidosis is regularly seen in the practice of a hematologist and has recently undergone major advances in terms of the ability to evaluate responses as well as new therapeutic options that were not available when this topic was covered as an education session at the American Society of Hematology meeting 5 years ago. Waldenström macroglobulinemia (WM) is rarer than amyloidosis (1500 per year WM versus 3000 per year amyloid in the US), and recent consensus panels have established the definition of the disease, the diagnostic criteria, criteria for initiation of therapy and a new classification scheme. In this session, new developments in amyloid and macroglobulinemia, from suspicion of the diagnosis to treatment, are covered. In Section I, Dr. Morie Gertz answers four specific questions: (1) When should amyloidosis be suspected? (2) How does one heighten ones index of suspicion for amyloid? (3) How is the diagnosis confirmed and the type classified as primary? (4) What is the prognosis and how is it accurately assessed? Recent findings on cardiac biomarkers, presenting features and use of the free light chain assay are reviewed. Staging for amyloid and recently proposed criteria of response and progression are covered. In Section II, Dr. Giampaolo Merlini comprehensively reviews therapy of amyloidosis from the use of standard melphalan/prednisone to the recently described standard dose therapies including dexamethasone, thalidomide/dexamethasone, melphalan/dexamethasone and IV melphalan/dexamethasone. An extensive discussion of the role of high-dose therapy with stem cell reconstitution follows and includes patient selection, predictors of immediate morbidity and mortality, and survival expectation. Finally, a therapeutic strategy is proposed. In Section III, Drs. Steven Treon and Giampaolo Merlini review the most current information on WM. The

  14. Diagnostic approach to cardiac amyloidosis: A case report.

    PubMed

    Fernandes, Andreia; Caetano, Francisca; Almeida, Inês; Paiva, Luís; Gomes, Pedro; Mota, Paula; Trigo, Joana; Botelho, Ana; Cachulo, Maria do Carmo; Alves, Joana; Francisco, Luís; Leitão Marques, António

    2016-05-01

    The authors present a case of systemic amyloidosis with cardiac involvement. We discuss the need for a high level of suspicion to establish a diagnosis, diagnostic techniques and treatment options. Our patient was a 78-year-old man with chronic renal disease and atrial fibrillation admitted with acute decompensated heart failure of unknown cause. The transthoracic echocardiogram revealed severely impaired left ventricular function with phenotypic overlap between hypertrophic and restrictive cardiomyopathy. After an extensive diagnostic workup, which included an abdominal fat pad biopsy, the final diagnosis was amyloidosis.

  15. UNUSUAL PRESENTATION OF GENERALIZED MACULAR AMYLOIDOSIS IN A YOUNG ADULT

    PubMed Central

    Kudur, Mohan H; B, Sathish Pai; H, Sripathi; Prabhu, Smitha

    2008-01-01

    Macular amyloidosis is a common problem seen dermatology out-patient department. Generalized macular amyloidosis presenting with a poikilodermatous appearance is rare. In our case, an 18-year-old male presented with generalized hypopigmented macules with a poikilodermatous appearance of 10-year duration. His developmental milestones were normal with negative family history of similar complaints. Histopathology of hyperpigmented lesions revealed hyperkeratosis and acanthosis of epidermis and hypopigmented lesion showing only hyperkeratosis. Both lesions were showing the deposition of amorphous, hazy material in the tips of papillary dermis with perivascular inflammatory infiltrate. Congo red staining of the amorphous material was positive for amyloid. PMID:19882037

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

    PubMed

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

    2003-01-01

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

  17. Distinctive Patterns of Transthyretin Amyloid in Salivary Tissue: A Clinicopathologic Study of 92 Patients With Amyloid-containing Minor Salivary Gland Biopsies.

    PubMed

    Jamet, Marie-Pierre; Gnemmi, Viviane; Hachulla, Éric; Dhaenens, Claire-Marie; Bouchindhomme, Brigitte; Delattre, Claire; Glowacki, François; Hatron, Pierre-Yves; Lacour, Arnaud; Lamblin, Nicolas; Launay, David; Leleu, Xavier; Guiochon-Mantel, Anne; Valleix, Sophie; Maurage, Claude-Alain; Copin, Marie-Christine; Buob, David

    2015-08-01

    Accurate typing of amyloidosis is still a major issue for pathologists and clinicians. Besides clinical data and immunohistochemistry, the histologic distribution of amyloid could represent a useful tool to prevent typing errors, such as the misdiagnosis of hereditary and senile amyloidosis as light chain-related amyloidosis (AL). Minor salivary gland biopsy (MSGB) is a widely performed procedure for amyloidosis diagnosis and typing. In the largest clinicopathologic series of amyloid-containing MSGB specimens to date, we investigated for the first time whether amyloidosis subtypes can be distinguished according to their pattern of salivary amyloid deposition. The histologic distribution and semiquantification of amyloid within salivary tissue were thoroughly reassessed for each case using Congo red-fluorescence. Clinical data were retrospectively collected. The cohort included 92 patients with amyloid-containing minor salivary gland biopsies. The type of amyloidosis was AL in 51 patients (55.4%), non-V30M mutant ATTR in 10 (10.9%), V30M mutant ATTR in 8 (8.7%), serum amyloid A-derived amyloidosis (AA) in 6 (6.5%), wild-type ATTR in 4 (4.3%), gelsolin in 3 (3.3%), and unclassified in 10 (10.9%). Amyloid was more abundant in AL and AA compared with ATTR amyloidosis, because of more extensive basement membranes and vascular deposits. Conversely, non-V30M mutant ATTR and wt-ATTR were strongly associated with peculiar amyloid nodules located in close contact with salivary excretory ducts, with a specificity of 91.7%. In conclusion, our study suggests for the first time that MSGB, in addition to its high sensitivity for amyloidosis diagnosis, is a simple and effective tool for the recognition of ATTR amyloidosis.

  18. Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures

    PubMed Central

    Kurian, Sunil M.; Novais, Marta; Whisenant, Thomas; Gelbart, Terri; Buxbaum, Joel N.; Kelly, Jeffery W.; Coelho, Teresa; Salomon, Daniel R.

    2016-01-01

    Background: Early diagnosis of familial transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease-modifying therapies. Endomyocardial biopsies are typically amyloid positive when cardiomyopathy is suspected, but this disease manifestation is generally diagnosed late. Early diagnosis is often difficult because patients exhibit apparent symptoms of polyneuropathy, but have a negative amyloid biopsy. Thus, there is a pressing need for an additional early diagnostic strategy for TTR-aggregation-associated polyneuropathy and cardiomyopathy. Methods and Findings: Global peripheral blood cell mRNA expression profiles from 263 tafamidis-treated and untreated V30M Familiar Amyloid Neuropathy patients, asymptomatic V30M carriers, and healthy, age- and sex-matched controls without TTR mutations were used to differentiate symptomatic from asymptomatic patients. We demonstrate that blood cell gene expression patterns reveal sex-independent, as well as male- and female-specific inflammatory signatures in symptomatic FAP patients, but not in asymptomatic carriers. These signatures differentiated symptomatic patients from asymptomatic V30M carriers with >80% accuracy. There was a global downregulation of the eIF2 pathway and its associated genes in all symptomatic FAP patients. We also demonstrated that the molecular scores based on these signatures significantly trended toward normalized values in an independent cohort of 46 FAP patients after only 3 months of tafamidis treatment. Conclusions: This study identifies novel molecular signatures that differentiate symptomatic FAP patients from asymptomatic V30M carriers as well as affected males and females. We envision using this approach, initially in parallel with amyloid biopsies, to identify individuals who are asymptomatic gene carriers that may convert to FAP patients. Upon further validation

  19. 'Dialysis related arthropathy': a survey of 95 patients receiving chronic haemodialysis with special reference to beta 2 microglobulin related amyloidosis.

    PubMed Central

    Hurst, N P; van den Berg, R; Disney, A; Alcock, M; Albertyn, L; Green, M; Pascoe, V

    1989-01-01

    Ninety five patients receiving chronic haemodialysis (CHD) were surveyed to determine the prevalence of rheumatic disease and, where possible, its aetiology. At least three distinct rheumatic syndromes were identified--a group of patients with a syndrome consisting of large and medium joint synovial swelling, restricted hips and shoulders, tenosynovitis, carpal tunnel syndrome, and bone cysts due to deposition of beta 2 microglobulin related amyloid (AM beta 2m); a second group with erosive azotaemic osteoarthropathy; and a third group with age related degenerative disease of small, large, and axial joints. The data presented suggest that in patients receiving CHD (a) the prevalence of AM beta 2m deposition and the associated syndrome increases with duration of dialysis, but in patients who have been dialysed for more than 10 years the risk of developing AM beta 2m is related to age; (b) AM beta 2m deposition in subchondral cysts, but not synovium, causes joint destruction; also, AM beta 2m may be more prone to deposition in synovium of joints already damaged by other processes; (c) in the absence of synovial iron deposition synovial AM beta 2m is not associated with an inflammatory infiltrate; (d) hyperparathyroidism and perhaps other factors such as synovial iron deposition are probably more important than AM beta 2m as causes of peripheral joint degeneration and destructive spondyloarthropathy in patients receiving CHD. Images PMID:2658876

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

    PubMed Central

    Siepen, Fabian aus dem; Bauer, Ralf; Aurich, Matthias; Buss, Sebastian J; Steen, Henning; Altland, Klaus; Katus, Hugo A; Kristen, Arnt V

    2015-01-01

    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. PMID:26673202

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

    PubMed

    Scala, Raffaele; Maccari, Uberto; Madioni, Chiara; Venezia, Duccio; La Magra, Lidia Calogera

    2015-01-01

    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.

  2. Primary Systemic Amyloidosis with Unusual Dermatological Manifestations: A Rare Case Report

    PubMed Central

    Vyas, Kapil; Morgaonkar, Manjaree; Gupta, Savera; Jain, Suresh Kumar

    2016-01-01

    Amyloidosis is a group of heterogeneous diseases characterized by pathological deposition of proteinaceous substance extracellularly in various tissues. The clinical presentation depends on the site of amyloid deposition, with predominant involvement of mesenchymal elements and cutaneous findings in 30–40% of patients in case of primary systemic amyloidosis. We present a case of idiopathic primary systemic amyloidosis presenting with an unusual finding of nodulo-ulcerative lesion over tongue along with multiple skin-colored nodules, mimicking squamous cell carcinoma of tongue with secondary cutaneous metastasis, as well as lacking the classical presentation of purpura, macroglossia, waxy papules, and plaques. PMID:27057028

  3. Growth Hormone and Cerebral Amyloidosis.

    PubMed

    Benvenga, S; Guarneri, F

    2016-08-01

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

  4. Stem Cells Deemed Safe for ALS Patients

    MedlinePlus

    ... baby step forward," said lead researcher Dr. Jonathan Glass, of Emory University, in Atlanta. "We can say this procedure is doable in ALS patients," Glass said. "Now we have to test whether it's ...

  5. Neurologic complications of primary systemic amyloidosis.

    PubMed

    Kelly, John J

    2006-01-01

    Amyloid is a botanical term that denotes a waxy, amorphous, eosinophilic material and is used to describe similar pathological findings in humans. The deposits in primary systemic amyloidosis are derived from monoclonal serum proteins in plasma cell dyscrasia, which are degraded locally in tissues and deposited in insoluble sheets that damage organs. The cause of organ damage in amyloidosis is unclear but most likely due to the direct toxic effects of amyloid. Symptoms of the disorder include neuropathy, myopathy, and cardiac or renal insufficiency; there is often multiple-organ involvement. Congestive heart failure and nephrotic syndrome are predominant causes of death. Differential difficulties exist in diagnosing the disorder, and familial amyloid polyneuropathy directly mimics the disease. Diagnostic tools include electromyography, laboratory testing for abnormalities in serum and urine, and histological investigation of appropriate tissue. The median survival of patients is 2 years. However, melphalan and prednisone treatment for at least 1 year has resulted in increased survival rates. There have also been reports of benefit from high-dose chemotherapy followed by peripheral blood stem cell transplantation. Without early therapy, however, the disease has a dismal prognosis, and peripheral neuropathy usually persists or worsens despite therapy and improvement in other organs.

  6. THE AUTOIMMUNE CONSTELLATION IN LICHEN AMYLOIDOSIS.

    PubMed

    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. THE AUTOIMMUNE CONSTELLATION IN LICHEN AMYLOIDOSIS.

    PubMed

    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.

  8. Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.

    PubMed

    Paiva, Bruno; Martinez-Lopez, Joaquin; Corchete, Luis A; Sanchez-Vega, Beatriz; Rapado, Inmaculada; Puig, Noemi; Barrio, Santiago; Sanchez, Maria-Luz; Alignani, Diego; Lasa, Marta; García de Coca, Alfonso; Pardal, Emilia; Oriol, Alberto; Garcia, Maria-Esther Gonzalez; Escalante, Fernando; González-López, Tomás J; Palomera, Luis; Alonso, José; Prosper, Felipe; Orfao, Alberto; Vidriales, Maria-Belen; Mateos, María-Victoria; Lahuerta, Juan-Jose; Gutierrez, Norma C; San Miguel, Jesús F

    2016-06-16

    Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n = 11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs. PMID:27069257

  9. Extrusion of amyloid fibrils to the extracellular space in experimental mesangial AL-amyloidosis: transmission and scanning electron microscopy studies and correlation with renal biopsy observations.

    PubMed

    Teng, Jiamin; Turbat-Herrera, Elba A; Herrera, Guillermo A

    2014-04-01

    In vitro studies have provided much information regarding the process of glomerular AL-amyloidogenesis. Research efforts have been successful in deciphering how glomerulopathic light chains interact with mesangial cells. The sequential steps involved in the genesis of amyloid fibrils include interactions with surface caveolae in mesangial cells and internalization of the monoclonal light chains through a clathrin-mediated process followed by trafficking in the mesangial cells to the mature lysosomal compartment where fibrils are formed. This manuscript focuses on how mesangial cells, once amyloid has been formed, deliver the fibrils to the extracellular matrix. The delivery of amyloid fibrils to the outside of the cells is carried out by lysosomes, which abut the mesangial cell membranes and extrude their contents into the extracellular space. This final step responsible for the fibrils to be present predominantly in the extracellular space is well demonstrated with scanning electron microscopy.

  10. Pressure-Volume Relationships in Patients With Transthyretin (ATTR) Cardiac Amyloidosis Secondary to V122I Mutations and Wild-Type Transthyretin Transthyretin Cardiac Amyloid Study (TRACS)

    PubMed Central

    Bhuiyan, Taslima; Helmke, Stephen; Patel, Ayan R.; Ruberg, Frederick L.; Packman, Jeff; Cheung, Kin; Grogan, Donna; Maurer, Mathew S.

    2016-01-01

    Background ATTR cardiac amyloidosis can result from a mutated variant of transthyretin (eg, V122I) or wild-type variant (ATTRwt). We evaluated pressure-volume (PV) indices at baseline and over time to further characterize abnormal pump function in these subjects. Methods and Results Twenty-nine subjects (18 with ATTRwt and 11 with ATTRm (V122I) had 2-dimensional echocardiograms with complete Doppler measures at baseline and every 6 months for up to 2 years. PV indices were derived from echocardiographic measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Clinical, demographic, and PV indices were compared between V122I and ATTRwt subjects and between survivors and nonsurvivors at baseline and over time. Cox proportional hazards model identified correlates for mortality. Stroke volume decline was associated with alterations in ventricular-vascular coupling and a decrease in ventricular capacitance with significant decrement in ejection fraction (56 ± 12% to 48 ± 14%, P = 0.0001) over 18 months. PVAiso was lower in V122I subjects compared with wild-type at baseline and declined over time. Twelve (41%) subjects died or underwent a cardiac transplant after a mean follow-up of 478 days (range, 31 to 807). Multivariable survival analysis demonstrated that initial ejection fraction (a measure of ventricular-vascular coupling) <50% was associated with increased mortality (hazard ratio, 6.6; 95% confidence interval, 1.1 to 40.3). Conclusions In ATTR cardiac amyloidosis secondary to a V122I mutation and wild-type transthyretin, PV analysis reveals alterations that are associated with reductions in the ability of the ventricle to perform work and, ultimately, with reduced survival in these subjects. PMID:21191093

  11. Systemic amyloidosis: unusual presentation mistaken for a recurrent scabies infection.

    PubMed

    Haley, Erin M; Nabatian, Adam S; Kopp, Sandra A; Falasca, Gerald F; Haupt, Helen M; Halpern, Analisa V

    2014-06-01

    We report the case of a 63-year-old woman with a history of undifferentiated connective-tissue disease, polyarthritis, and bilateral carpal tunnel syndrome who presented with generalized pruritus and erythematous and excoriated papules on the trunk and extremities. Empiric scabies treatment was unsuccessful. Patch testing and T-cell receptor gene rearrangement studies were unremarkable. The patient was found to have mild interstitial lung disease and hypogammaglobulinemia. Eventually a diagnosis of primary systemic amyloidosis was made after she developed frank lingual hypertrophy despite normal initial serum protein electrophoresis and negative abdominal fat pad aspiration. Diagnosis was confirmed with lingual biopsy. This case demonstrates an unusual presentation of primary systemic amyloidosis consisting of arthritis and intense debilitating pruritus without primary skin lesions for a full year prior to diagnosis of multiple myeloma. The patient responded to treatment with chemotherapy and corticosteroids.

  12. AA amyloidosis in vaccinated growing chickens.

    PubMed

    Murakami, T; Inoshima, Y; Sakamoto, E; Fukushi, H; Sakai, H; Yanai, T; Ishiguro, N

    2013-01-01

    Systemic amyloid-A (AA) amyloidosis in birds occurs most frequently in waterfowl such as Pekin ducks. In chickens, AA amyloidosis is observed as amyloid arthropathy. Outbreaks of systemic amyloidosis in flocks of layers are known to be induced by repeated inflammatory stimulation, such as those resulting from multiple vaccinations with oil-emulsified bacterins. Outbreaks of fatal AA amyloidosis were observed in growing chickens in a large scale poultry farm within 3 weeks of vaccination with multiple co-administered vaccines. This study documents the histopathological changes in tissues from these birds. Amyloid deposits were also observed at a high rate in the tissues of apparently healthy chickens. Vaccination should therefore be considered as a potential risk factor for the development of AA amyloidosis in poultry.

  13. Localized axillary milia en plaque: a rare cutaneous case presentation of systemic amyloidosis.

    PubMed

    Dickison, P; Howard, V; Wylie, B; Smith, S D

    2016-10-01

    Systemic AL amyloidosis is known to be associated with plasma cell dyscrasias, including multiple myeloma. The cutaneous manifestations of systemic AL amyloidosis are varied, but typically include waxy plaques or subcutaneous nodules. We report a woman who presented with bilateral eruptions of hyperpigmented plaques in her axillae, which were diagnosed as milia en plaque. She had a history of multiple myeloma, for which she was under the care of a haematologist. This is the first documented case, to our knowledge, of an eruption in the axillae being milia en plaque.

  14. Localized axillary milia en plaque: a rare cutaneous case presentation of systemic amyloidosis.

    PubMed

    Dickison, P; Howard, V; Wylie, B; Smith, S D

    2016-10-01

    Systemic AL amyloidosis is known to be associated with plasma cell dyscrasias, including multiple myeloma. The cutaneous manifestations of systemic AL amyloidosis are varied, but typically include waxy plaques or subcutaneous nodules. We report a woman who presented with bilateral eruptions of hyperpigmented plaques in her axillae, which were diagnosed as milia en plaque. She had a history of multiple myeloma, for which she was under the care of a haematologist. This is the first documented case, to our knowledge, of an eruption in the axillae being milia en plaque. PMID:27663153

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

    PubMed Central

    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

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

    PubMed

    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

  17. Primary Amyloidosis of Celiac/Para-Pancreatic Lymph Nodes Diagnosed by Endosonography-Guided Fine Needle Aspiration: A Case Report.

    PubMed

    Akbar, Nuralhuda; Kubbara, Aahd; Nawras, Ali

    2015-01-01

    Introduction. Primary amyloidosis is a disorder resulting from the deposition of fibrillary protein in extracellular tissue. Diagnosis of primary amyloidosis in the celiac/para-pancreatic lymph nodes via endoscopic ultrasound-guided fine needle aspiration has not been reported in the literature. In this article, we report our first observation. Our patient is a 64-year-old Caucasian man who was referred to our institution from an outlying hospital for recurrent abdominal pain. Radiological imaging revealed an enlarged abdominal lymph node that was already biopsied under computed tomography needle guidance but diagnosis was not achieved on pathological examination. At our institution, endoscopic ultrasound-guided fine needle aspiration showed enlarged para-celiac/pancreatic lymph nodes. Endosonography-guided fine needle aspiration revealed the diagnosis of primary amyloidosis. The patient tolerated the procedure well with follow-up as an outpatient. Conclusions. Lymph node involvement in amyloidosis is not uncommon. However, the involvement of the pancreatic/celiac lymph nodes by amyloidosis is obscure in this case. This case shows a rare presentation of amyloidosis diagnosed for the first time by the technique of endosonography-guided fine needle aspiration. In the future, this might serve as an establishment to standardize diagnosing abdominal lymph node amyloidosis, once suspected, by endosonography-guided fine needle aspiration. PMID:26904706

  18. Tracheobronchial amyloidosis and confocal endomicroscopy.

    PubMed

    Newton, Richard C; Kemp, Samuel V; Yang, Guang-Zhong; Darzi, Ara; Sheppard, Mary N; Shah, Pallav L

    2011-01-01

    Tracheobronchial amyloidosis is one of many causes of endobronchial stenosis and nodularity, the concrete diagnosis of which currently requires the finding of apple-green birefringence from endobronchial biopsies. Bronchoscopic probe-based confocal endomicroscopy (pCLE) is a novel optical biopsy technique which provides real-time images of the lattice structure of the bronchial basement membrane - a finding lost in malignancy. This case study outlines the imperfect, essentially palliative management of this rare disease, and shows for the first time the unusual dappled in vivo pCLE images of amyloid-affected endobronchium.

  19. Familial Amyloidosis Cutis Dyschromica in Three Siblings: Report from Indonesia

    PubMed Central

    Hermawan, Melyawati; Rihatmadja, Rahadi; Sirait, Sondang Pandjaitan

    2014-01-01

    Amyloidosis cutis dyschromica (ACD) is an extremely rare type of primary cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide; some were reported affecting several family members. Its resemblance to other common pigmentation disorders makes it rarely recognized at first sight. Our patient, the 12-year-old firstborn son of non-consanguineous parents presented with generalized mottled pigmentation starting from lower extremities. His siblings suffered from similar condition. The clue for diagnosis is the amyloid deposition in the papillary dermis. The etiology of ACD is still unknown, but genetic factors and ultraviolet radiation are implicated. It is proposed that disturbance of keratinocyte repair following ultraviolet radiation results in amyloid deposition. The treatment remains a challenge. Oral acitretin treatment, thought to repair keratinization defect, gave a slight improvement in our case. Our is the first case of ACD reported in Indonesia. PMID:25386328

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

    PubMed

    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

  1. [Communication with ALS patients: neurosurgical approach].

    PubMed

    Yoshimine, Toshiki; Yanagisawa, Takufumi; Sawada, Jin-Ichi; Hazama, Takanori; Mochizuki, Hideki; Hirata, Masayuki

    2013-01-01

    By progression of the disease, motor neurons degenerate in patients with amyotrophic lateral sclerosis (ALS) eventually lose nearly all voluntary muscles in the body. They are awake and aware but cannot move or communicate (locked-in state). Since the function of the brain is preserved, one possible measure to support their communication is to interpret their motor intention by decoding (deciphering) brain signals and present it with external devices. This technology called "brain-machine interface (BMI)" is now close to clinical use in Japan and USA.In our system, we record electrocorticogram (ECoG) obtained with subudural electrodes during their motor imagery, decode it and determine the movement they intended. So far, one patient of ALS with severe paralysis, implanted with this electrodes, successfully operated the PC communication tool only by thinking.

  2. Renal amyloidosis followed more than 5 years: report of 12 cases.

    PubMed

    Kaaroud, H; Boubaker, K; Béji, S; Abderrahim, E; Moussa, F Ben; Turki, S; Goucha, R; Hedri, H; El Younsi, F; Kheder, A; Maiz, H Ben

    2004-01-01

    Renal involvement with amyloidosis is common but causes patient survival to be poor, rarely reaching 5 years. In this study, we retrospectively reviewed clinical and biological characteristics as well as treatments and outcomes of patients with renal amyloidosis followed for more than 5 years. Between 1975 and 2003, 485 patients were diagnosed with renal amyloidosis including only 12 patients who were followed more than 5 years. The six men and six women of mean age 42.4 years (range 18 to 66 years) displayed renal signs of lower limb edema in all cases; hypertension in four cases, proteinuria on urinalysis in all cases with microscopic hematuria in five cases. Biological tests showed nephrotic syndrome in 11 patients, normal renal function in nine patients, and renal failure in three patients whose mean creatinine was 481.6 micromol/L (range 294 to 726). The amyloidosis was AA type in 11 cases and non-AA in one case. An etiologic survey revealed spondylarthropathy in one patient, pulmonary tuberculosis in two patients, chronic bronchitis in three patients, hepatic hydatic cyst in one patient, Mediterranean familial fever in two patients, Crohn's disease in one patient, Hodgkin's lymphoma in one patient, and multiple myeloma in one patient. Specific treatment was initiated with colchicine in seven patients. At a 110-month mean follow-up (range 53 to 153 months), remission of nephrotic syndrome was observed in four cases, progression to chronic renal failure in two patients, and to end-stage renal failure in five cases (range 53 to 196 months), with stabilization of renal function in seven patients. In conclusion, primary amyloid disease should be optimally suppressed in patients with renal involvement. The role of this treatment in remission of renal amyloidosis is not well established. This efficacy of the treatment has been demonstrated in some patients with improved survival.

  3. [New trends in the treatment of amyloidosis].

    PubMed

    Martínez-Valle, Fernando; Gironella-Mesa, Mercedes; Solans-Laqué, Roser

    2012-05-26

    Amyloidosis is a clinical disorder caused by extracellular deposition of proteins that are normally soluble as insoluble fibrils that damage different organs. More than 20 proteins can form amyloid deposits. All types of amyloid fibrils have a secondary structure with a β folded shape that is characteristic and makes them to adopt a green birefringence after stained with Congo red and viewed under cross-polarized light. Amyloidosis can be acquired or hereditary, systemic or localized, and are classified by the fibril precursor protein. Advances in the knowledge of the pathogenesis of amyloidosis allows the development of new diagnostic and therapeutical schemes that are currently under investigation.

  4. Glial reactions and the clearance of amyloid beta protein in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type.

    PubMed

    Maat-Schieman, Marion L C; Yamaguchi, Haruyasu; Hegeman-Kleinn, Ingrid M; Welling-Graafland, Corrie; Natté, Remco; Roos, Raymund A C; van Duinen, Sjoerd G

    2004-05-01

    Although the amyloid beta protein (Abeta) E693Q mutation enhances Abeta fibrillization in vitro and cerebral amyloid angiopathy (CAA) in vivo, brain parenchymal Abeta deposition and tau pathology in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) are limited. To evaluate whether clearance of Abeta by glial cells may play a role in this regard, this immunohistochemical study of frontal cortex of 14 HCHWA-D autopsy brains was performed using double staining with glial markers and end-specific antibodies to Abetax-42 (Abeta42) and Abetax-40 (Abeta40). Tau pathology was also assessed. Numerous microglia and/or astrocytes carrying cytoplasmic Abeta42(+)40(-) granules were scattered among non-fibrillar (Congo red-negative) Abeta deposits, i.e., clouds, fine diffuse plaques, and Abeta42(+)40(-) dense diffuse plaques. On the other hand, activated microglia and reactive astrocytes associated with fibrillar (Congo red-positive) Abeta deposition, i.e., Abeta42(+)40(+) dense diffuse plaques and CAA invading the parenchyma, were virtually devoid of Abeta granules. Tau pathology was scant and most frequently associated with CAA. These results suggest that relatively non-fibrillar parenchymal Abeta deposits may be liable to glial clearance. Abeta sequestration by glial cells may be a factor limiting the levels of neurotoxic soluble Abeta oligomers in HCHWA-D brain.

  5. Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial.

    PubMed

    Sanchorawala, Vaishali; Brauneis, Dina; Shelton, Anthony C; Lo, Stephen; Sun, Fangui; Sloan, J Mark; Quillen, Karen; Seldin, David C

    2015-08-01

    The depth of hematologic response has been shown to correlate with survival and organ responses for patients with light chain (AL) amyloidosis. We conducted a prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a twice a week schedule followed by conditioning with bortezomib and high-dose melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives were hematologic responses, tolerability, and survival. Thirty-five patients were enrolled from 2010 to 2013. Of these, 30 proceeded with SCT, whereas 5 did not because of clinical deterioration during induction (n = 3) or complications after stem cell collection (n = 2). Two patients developed features of an autologous graft-versus-host disease-like syndrome post-SCT, which responded to steroids; no other unusual complications were seen. Treatment-related mortality occurred in 8.5% (3/35). Hematologic responses were achieved by 100% of the 27 assessable patients (63% complete response, 37% very good partial response [VGPR]) who completed the planned treatment. By intention-to-treat, hematologic responses occurred in 77% of patients (49% complete response, 29% VGPR). With a median follow-up of 36 months, the median overall survival and progression-free survival were not reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic responses after HDM/SCT in patients with AL amyloidosis.

  6. Primary sjögren syndrome manifested as localized cutaneous nodular amyloidosis.

    PubMed

    Wey, Shiow-Jiuan; Chen, Yi-Ming; Lai, Po-Ju; Chen, Der-Yuan

    2011-10-01

    Localized cutaneous nodular amyloidosis (LCNA) is the rarest type of cutaneous amyloidosis. Typically presenting as waxy nodules on the lower extremities, it demonstrates localized deposition of AL-type amyloid in immunohistologic study and is often associated with focal plasma cell proliferation. Sjögren syndrome, an autoimmune lymphoproliferative disorder, is characterized by keratoconjunctivitis sicca and xerostomia with lymphocytic infiltration of exocrine glands. As shown in case reports, the association of LCNA with Sjögren syndrome is considerable. Herein, we report a 78-year-old woman with LCNA, who was further surveyed and diagnosed with Sjögren syndrome. In light of the significant relation between these 2 diseases, further examination for coexistence of Sjögren syndrome in addition to systemic amyloidosis is well warranted. Prompt identification of an underlying Sjögren syndrome in LCNA with polyclonal immunoglobulin amyloid may have important therapeutic consequences.

  7. Serum transthyretin levels in senile systemic amyloidosis: effects of age, gender and ethnicity.

    PubMed

    Buxbaum, Joel; Koziol, James; Connors, Lawreen H

    2008-12-01

    Serum transthyretin (TTR) levels are reduced in familial amyloidotic polyneuropathy (FAP). A single study of patients with senile systemic amyloidosis (SSA) in Sweden found that those individuals also had a significantly lower mean serum TTR concentration than age- and gender-matched controls. To determine if the same phenomenon prevailed in an ethnically more heterogeneous population, we compared the serum TTR levels, as determined by ELISA, in 45 documented SSA patients with congestive heart failure, 20 AL patients with congestive heart failure and population controls. Serum TTR concentrations in the controls were influenced in a statistically significant manner by age, gender and ethnicity. Although it is unlikely that such differences are clinically relevant, they must be considered when assessing the meaning of serum TTR concentrations in any clinically defined population. The serum concentrations in patients with SSA did not differ from age, gender and ethnically matched controls or from a group of AL patients with significant clinical cardiac involvement. We also compared TTR concentrations in 12 African-Americans carrying the TTR V122I allele with those in 826 African-Americans who were homozygous wild type at the TTR locus. The TTR V122I carriers had significantly lower serum TTR concentrations than appropriate controls even though the majority of such individuals had not reached the age of clinical or anatomic risk, i.e. over 60. Thus, as in carriers of other TTR mutations the serum TTR level is lower than normal, despite having a much later appearance of clinical disease. PMID:19065297

  8. Amyloidosis: Modern Cross-sectional Imaging.

    PubMed

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

    2015-01-01

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

  9. Atypical tumour-like involvement of the colon in secondary systemic amyloidosis which vanished after 1 month of observation

    PubMed Central

    Ando, Katuyoshi; Fujiya, Mikihiro; Ito, Takahiro; Sugiyama, Ryuji; Nata, Toshie; Nomura, Yoshiki; Ueno, Nobuhiro; Kashima, Shin; Ishikawa, Chisato; Inaba, Yuhiei; Moriichi, Kentaro; Okamoto, Kotaro; Ikuta, Katsuya; Mizukami, Yusuke; Tokusashi, Yoshihiko; Miyokawa, Naoyuki; Watari, Jiro; Kohgo, Yutaka

    2011-01-01

    Amyloidosis occurs as a result of the extracellular deposition of protein fibrils in organs and tissues, thus causing mild to severe pathophysiological changes. The gastrointestinal tract is a common site of amyloid deposition. While intestinal amyloidosis frequently results in polypoid lesions, ulcerations, nodules and petechial mucosal haemorrhage, tumour-like lesions are rarely developed and infrequently diagnosed before the resection because of the difficulty in differentiating them from colon cancer. The authors herein reported a case of intestinal amyloid A amyloidosis with a complication of a tumour-like lesion endoscopically resembling a malignant lesion, which was completely diminished after 1 month of observation with bowel rest. Such conservative treatment is a feasible option to cure intestinal tumour-like lesions in patients with intestinal amyloidosis when no neoplastic change is histologically detected, possibly decreasing the need for surgery of the fragile mucosa. PMID:22699464

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  11. Cell Damage in Light Chain Amyloidosis: FIBRIL INTERNALIZATION, TOXICITY AND CELL-MEDIATED SEEDING.

    PubMed

    Marin-Argany, Marta; Lin, Yi; Misra, Pinaki; Williams, Angela; Wall, Jonathan S; Howell, Kyle G; Elsbernd, Laura R; McClure, Megan; Ramirez-Alvarado, Marina

    2016-09-16

    Light chain (AL) amyloidosis is an incurable human disease characterized by the misfolding, aggregation, and systemic deposition of amyloid composed of immunoglobulin light chains (LC). This work describes our studies on potential mechanisms of AL cytotoxicity. We have studied the internalization of AL soluble proteins and amyloid fibrils into human AC16 cardiomyocytes by using real time live cell image analysis. Our results show how external amyloid aggregates rapidly surround the cells and act as a recruitment point for soluble protein, triggering the amyloid fibril elongation. Soluble protein and external aggregates are internalized into AC16 cells via macropinocytosis. AL amyloid fibrils are shown to be highly cytotoxic at low concentrations. Additionally, caspase assays revealed soluble protein induces apoptosis, demonstrating different cytotoxic mechanisms between soluble protein and amyloid aggregates. This study emphasizes the complex immunoglobulin light chain-cell interactions that result in fibril internalization, protein recruitment, and cytotoxicity that may occur in AL amyloidosis. PMID:27462073

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

    PubMed

    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

  13. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    PubMed Central

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  14. Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis

    SciTech Connect

    Falk, R.H.; Lee, V.W.; Rubinow, A.; Hood, W.B. Jr.; Cohen, A.S.

    1983-03-01

    To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (r . 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.

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

    PubMed

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

    1991-12-01

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

  16. Transthyretin Ile 122: Gene frequency and risk of cardiac amyloidosis in African Americans

    SciTech Connect

    Buxbaum, J. |; Pastore, R.; Yaghoubian, R.

    1994-09-01

    Point mutations in the protein transthyretin (TTR) cause familial amyloidosis involving mainly the heart and peripheral nerves. To determine the TTR Ile 122 gene frequency in African Americans, the allele encoding TTR Ile 122 was identified by PCR-Primer Introduced Restriction Analysis of TTR exon 4 and FokI digestion on 1659 control DNA samples from 1659 African Americans: 64 were heterozygous and one homozygous (allele frequency .02). To determine the risk to gene carriers of developing cardiac amyloidosis, immunohistochemical and genetic studies were performed on amyloid-containing samples identified among 52,370 autopsy samples examined over 32 years. In autopsy samples from patients over age 60, isolated cardiac amyloidosis was more common in African Americans (1.6%) than in White Americans (.40%), suggesting a genetic risk factor. All 29 samples from African Americans were immunohistochemically TTR-positive, and 5 were heterozygous for the TTR Ile 122 allele (17%), as compared with 5/108 heterozygotes (4.6%) among age-matched (over age 60) African American controls without amyloidosis from the same autopsy study (one-tailed P value < .03). Among the 29 amyloid-positive samples were 16 with 1+ or 2+ deposition and 13 with 3+ or 4+ deposition. All 5 TTR Ile 122 heterozygotes had 3+ or 4+ deposition. None of 15 samples from White Americans with cardiac amyloidosis was TTR Ile 122-positive. Extrapolating from the 5/29 samples from which we were able to obtain genetic data, we estimate that 9/54 samples containing cardiac amyloid were TTR Ile 122 heterozygotes. We conclude that heterozygosity for TTR Ile 122 is associated with a greater frequency (relative risk 5.8) and greater severity of cardiac amyloid deposition than in non-carriers of the TTR Ile 122 gene. Of over 40 TTR point mutations associated with amyloidosis described to date, TTR Ile 122 appears to be the most common worldwide and to have the lowest penetrance in causing disease.

  17. Spontaneous pancreatic islet amyloidosis in 40 baboons.

    PubMed

    Hubbard, G B; Steele, K E; Davis, K J; Leland, M M

    2002-04-01

    Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7-28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans.

  18. Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

    PubMed

    Montagna, Giovanni; Cazzulani, Benedetta; Obici, Laura; Uggetti, Carla; Giorgetti, Sofia; Porcari, Riccardo; Ruggiero, Rubina; Mangione, P Patrizia; Brambilla, Moreno; Lucchetti, Jacopo; Guiso, Giovanna; Gobbi, Marco; Merlini, Giampaolo; Salmona, Mario; Stoppini, Monica; Villa, Giuseppe; Bellotti, Vittorio

    2013-09-01

    Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of β2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits β2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging. PMID:23734692

  19. Molecular tweezers targeting transthyretin amyloidosis.

    PubMed

    Ferreira, Nelson; Pereira-Henriques, Alda; Attar, Aida; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Gales, Luís; Saraiva, Maria João; Almeida, Maria Rosário

    2014-04-01

    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 amyloidogenic proteins in vitro, including TTR, by interfering with hydrophobic and electrostatic interactions known to play an important role in the aggregation process. In addition, CLR01 showed therapeutic effects in animal models of Alzheimer's disease and Parkinson's disease. Here, we assessed the ability of CLR01 to modulate TTR misfolding and aggregation in cell culture and in an animal model. In cell culture assays we found that CLR01 inhibited TTR oligomerization in the conditioned medium and alleviated TTR-induced neurotoxicity by redirecting TTR aggregation into the formation of innocuous assemblies. To determine whether CLR01 was effective in vivo, we tested the compound in mice expressing TTR V30M, a model of familial amyloidotic polyneuropathy, which recapitulates the main pathological features of the human disease. Immunohistochemical and Western blot analyses showed a significant decrease in TTR burden in the gastrointestinal tract and the peripheral nervous system in mice treated with CLR01, with a concomitant reduction in aggregate-induced endoplasmic reticulum stress response, protein oxidation, and apoptosis. Taken together, our preclinical data suggest that CLR01 is a promising lead compound for development of innovative, disease-modifying therapy for TTR amyloidosis.

  20. Primary diffuse tracheo-bronchial amyloidosis

    PubMed Central

    Antunes, Maria L.; Da Luz, J. M. Vieira

    1969-01-01

    A case of diffuse tracheo-bronchial amyloidosis in a 62-year-old woman thought to have chronic bronchitis is reported. The immunological mechanism in the pathogenesis of this condition is considered and the need for bronchological investigation in chronic bronchial disorders is stressed. Images PMID:5810372

  1. Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining.

    PubMed

    Manabe, Shun; Hatano, Michiyasu; Yazaki, Masahide; Nitta, Kosaku; Nagata, Michio

    2015-12-01

    AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.

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

    PubMed

    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

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

    PubMed Central

    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.

    2016-01-01

    Abstract 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

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

    PubMed

    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.

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

    PubMed Central

    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 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. PMID:25432650

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

    PubMed Central

    Hesse, A; Altland, K; Linke, R P; Almeida, M R; 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 natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyretin). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant transthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so far were heterozygotes for a single nucleotide change in the gene for TTR that resulted in amino acid substitutions in the mature protein. A new TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. Electrocardiography was suggestive of a pseudoinfarction pattern, and echocardiography and cardiac catheterisation showed signs of hypertrophic nonobstructive cardiomyopathy with increased ventricular filling pressures and a prominent "a" wave. Amyloid of the TTR type was identified by immunohistochemistry in the endomyocardial biopsy specimen. Hybrid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from all known TTR variants so far. The patient died in an accident before investigations were complete. Electrophoretic analysis of the plasma from his first degree relatives (son, daughter, brother, and mother) identified the asymptomatic 22 year old son as an apparently heterozygous carrier of the mutant TTR protein. Comparative tryptic peptide mapping and sequencing showed that isoleucine at

  7. Localized amyloidosis masquerading as nasopharyngeal tumor: a review.

    PubMed

    Panda, Naresh K; Saravanan, Karuppiah; Purushotaman, Gilbert Pragache; Gurunathan, Ramesh Kumar; Mahesha, Vankalakunti

    2007-01-01

    Amyloidosis comprises a diverse collection of disease characterized by the presence of amorphous extracellular eosinophilic deposits of unique protein fibrils that gives apple green birefringence under polarized light after staining with Congo red. Head and neck region is the commonest site for localized form of amyloidosis. We report a case of a 43-year-old man with localized amyloidosis of nasopharynx with oropharyngeal extension and its management, along with a review of relevant literatures.

  8. [Osteo-articular amyloidosis caused by dialysis. Clinical and radiologic aspects].

    PubMed

    Baldrati, L; Brunetti, L; Rocchi, A; Bonsanto, R; Docci, D; Turci, F

    1990-10-01

    Twenty-nine patients who had received chronic hemodialysis for more than 5 years provided the material for the present study. In 12 of them (41%) there were radiological findings of dialysis related amyloidosis, mainly destructive spondyloarthropathy of the cervical spine (n = 11) and geodes of the shoulder (n = 5). When compared with negative patients, these patients were significantly older (p less than 0.001 and had been dialyzed for longer periods of time (p less than 0.01). Moreover, in such patients there was an higher incidence of carpal tunnel syndrome (p less than 0.025) and shoulder pain (p less than 0.001). Our results confirm that osteoarticular amyloidosis is a frequent long-term complication of chronic hemodialysis and underline the correlation between clinical and radiological findings.

  9. Gastrointestinal Amyloidosis Presenting with Multiple Episodes of Gastrointestinal Bleeding

    SciTech Connect

    Kim, Sang Hyeon Kang, Eun Ju; Park, Jee Won; Jo, Jung Hyun; Kim, Soo Jin; Cho, Jin Han; Kang, Myong Jin; Park, Byeong Ho

    2009-05-15

    Amyloidosis is characterized by the extracellular deposition of amyloid protein in various organs. Gastrointestinal involvement in amyloidosis is common, but a diagnosis of amyloidosis is often delayed. Severe gastrointestinal hemorrhage in amyloidosis is rare but can be fatal in some cases. We experienced a case of a 49-year-old man who presented with recurrent massive hematochezia. Although embolization was performed eight times for bleeding from different sites of the small intestine, hematochezia did not cease. We report the case, with a review of the literature.

  10. Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation.

    PubMed

    Sandberg-Gertzén, H; Ericzon, B G; Blomberg, B

    1998-11-01

    A 61-yr-old man with cholestatic jaundice soon after presentation had an emergency operation because of spontaneous rupture of the spleen. This was found to be caused by primary systemic amyloidosis. After the splenectomy, the patient deteriorated with liver failure and was successfully treated with liver transplantation. Osteopenic fractures of the thoracic columna developed after transplantation. Except for this, the patient is well 18 months after transplantation.

  11. Spontaneous resolution of multiple nodular pulmonary AA amyloidosis.

    PubMed

    Fukatsu, Hirotoshi; Miyoshi, Haruka; Ishiki, Kuniharu

    2010-01-01

    A 62-year-old man presented with a two-week history of dry cough. A chest computed tomography (CT) showed three nodular masses of soft tissue density without calcification or cavitary formation in the right lung. F-18 fluorodeoxyglucose PET/CT scan revealed high FDG uptake in two out of three pulmonary nodules. Transbronchial lung biopsy specimens consisted of amorphous eosinophilic deposits that were demonstrated to be amyloid because they were positive for Congo Red staining. After oxidation with permanganate solution, the Congo Red staining disappeared, indicating that this amyloid was amyloid A protein-derived type. There was no evidence of any systemic diseases. We diagnosed the patient as having multiple nodular pulmonary AA amyloidosis. The patient was conservatively managed without treatment, and the pulmonary nodules disappeared spontaneously three months later. PMID:21048364

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

    PubMed

    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

  13. Nodular pulmonary amyloidosis associated with asbestos exposure.

    PubMed

    Hiroshima, K; Ohwada, H; Ishibashi, M; Yamamoto, N; Tamiya, N; Yamaguchi, Y

    1996-01-01

    A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 x 18 mm in diameter 2 years ago, but it has become large, 25 x 25 mm in diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis. PMID:10846552

  14. A Familial Poikiloderma-Like Cutaneous Amyloidosis

    PubMed Central

    Unni, Mahesh; Ankad, Balachandra; Naidu, Varna; Sudakar Rao, KM

    2014-01-01

    Familial poikiloderma-like cutaneous amyloidosis(FPLCA) is a rare, generalized but genetic dyschromic skin disorder characterized by amyloid deposits in dermis due to defective DNA repair secondary to sunlight damage. Clinically, it presents with diffuse brownish pigmentation with hypo-pigmented macules and many brownish scattered lichenoid papules with normal developmental milestones. The condition is autosomal dominant with incomplete penetrance. We are here reporting a rare familial case of FPLCA with a review of the literature PMID:25484425

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed Central

    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

  18. Light chain amyloidosis of the urinary bladder. A site restricted deposition of an externally produced immunoglobulin

    PubMed Central

    Livneh, A; Shtrasburg, S; Martin, B; Baniel, J; Gal, R; Pras, M

    2001-01-01

    Aims—To identify the amyloid protein in a patient with amyloidosis localised to the urinary bladder, and to see whether subtyping of the protein by sequence analysis increases the understanding of the selection of the urinary bladder as the site of amyloid deposition. Methods—A patient with gross haematuria and a congophilic mass in his urinary bladder was evaluated further. Characterisation of the amyloid protein was performed using conventional histological and immunohistochemical methods. Determination of the N-terminal amino acid sequence of the amyloid protein was performed using protein sequencers. Results—The patient's history, physical examination, and laboratory evaluation excluded the involvement of other organs, justifying a diagnosis of amyloidosis localised to the urinary bladder. Histological and immunological studies showed that the amyloid protein deposited in the urinary bladder of the patient was probably of the amyloid light chain type. No plasma cells or lymphocytes were seen in sections of the urinary bladder and lower ureter adjacent to the amyloid deposits. Molecular analysis showed the sequence NFMLTQPHSISGSPG, which assigned the amyloid protein to either the VλI or the VλVI immunoglobulin (Ig) light chain families. Conclusions—The findings suggest that the amyloid protein in this patient originated outside the urinary bladder. The heterogeneity of the Ig proteins in known cases of amyloidosis of the lower urinary tract suggests that the amino acid residues, which determine the Vλ subtyping, have no major role in restricting the deposited protein to the urinary bladder. Key Words: primary amyloidosis • urinary bladder • λ light chain • amino acid sequence PMID:11729210

  19. Idiopathic systemic AA-amyloidosis in a skunk (Mephitis mephitis).

    PubMed

    Elhensheri, Mohamed; Linke, Reinhold P; Blankenburg, Anja; Beineke, Andreas

    2012-03-01

    This report describes a case of systemic amyloidosis in a captive striped skunk. At necropsy, bilateral alopecia, as well as reno-, hepato-, and splenomegaly were present. Congo red staining and immunohistochemistry revealed depositions of AA-amyloid in different organs. The lack of a predisposing disease is suggestive of idiopathic systemic AA-amyloidosis. PMID:22448530

  20. Idiopathic systemic AA-amyloidosis in a skunk (Mephitis mephitis).

    PubMed

    Elhensheri, Mohamed; Linke, Reinhold P; Blankenburg, Anja; Beineke, Andreas

    2012-03-01

    This report describes a case of systemic amyloidosis in a captive striped skunk. At necropsy, bilateral alopecia, as well as reno-, hepato-, and splenomegaly were present. Congo red staining and immunohistochemistry revealed depositions of AA-amyloid in different organs. The lack of a predisposing disease is suggestive of idiopathic systemic AA-amyloidosis.

  1. Gene expression profile in hereditary transthyretin amyloidosis: differences in targeted and source organs

    PubMed Central

    Olsson, Malin; Nyström, Hanna; Ericzon, Bo Göran; de Tayrac, Marie; Genin, Emmanuelle; Planté-Bordeneuve, Violaine; Suhr, Ole B

    2014-01-01

    Introduction Hereditary transthyretin amyloidosis (ATTR) is a genetic disease caused by a point mutation in the TTR gene that causes the liver to produce an unstable TTR protein. The most effective treatment has been liver transplantation in order to replace the variant TTR producing liver with one that produces only wild-type TTR. ATTR amyloidosis patients’ livers are reused for liver sick patients, i.e. the Domino procedure. However, recent findings have demonstrated that ATTR amyloidosis can develop in the recipients within 7–8 years. The aim of this study was to elucidate how the genetic profile of the liver is affected by the disease, and how amyloid deposits affect target tissue. Methods Gene expression analysis was used to unravel the genetic profiles of Swedish ATTR V30M patients and controls. Biopsies from adipose tissue and liver were examined. Results and Conclusions ATTR amyloid patients’ gene expression profile of the main source organ, the liver, differed markedly from that of the controls, whereas the target organs’ gene expression profiles were not markedly altered in the ATTR amyloid patients compared to those of the controls. An impaired ER/protein folding pathway might suggest ER overload due to mutated TTR protein. PMID:24601850

  2. Omental transplantation in a patient with mild ALS.

    PubMed

    Rafael, Hernando

    2016-01-01

    To demonstrate that amyotrophic lateral sclerosis (ALS) is not a neurodegenerative disease. The patient, a 33-year-old man began with symptoms of the bulbar form of ALS, characterized by burning pain in both feet during two months and then, he presented right crural monoparesis, fasciculations, slight dysarthria and he walked with help of orthopedic devices. A preoperative MRI scans showed atherosclerosis at the V4 segment of the left vertebral artery. On May 2012, he received an omental transplantation on the anterior, left lateral and posterior surface of the medulla oblongata. About 48 hours after surgery, the dysarthria disappeared and the voluntary movement of the right foot improved. Three days later, he walked without aid of orthopedic device. At present, four years after operation he present complete reversal of symptoms. In conclusión, this patient confirms that bulbar ALS is of ischemic origin and therefore, mild ALS can be cured. PMID:27508110

  3. Omental transplantation in a patient with mild ALS

    PubMed Central

    Rafael, Hernando

    2016-01-01

    To demonstrate that amyotrophic lateral sclerosis (ALS) is not a neurodegenerative disease. The patient, a 33-year-old man began with symptoms of the bulbar form of ALS, characterized by burning pain in both feet during two months and then, he presented right crural monoparesis, fasciculations, slight dysarthria and he walked with help of orthopedic devices. A preoperative MRI scans showed atherosclerosis at the V4 segment of the left vertebral artery. On May 2012, he received an omental transplantation on the anterior, left lateral and posterior surface of the medulla oblongata. About 48 hours after surgery, the dysarthria disappeared and the voluntary movement of the right foot improved. Three days later, he walked without aid of orthopedic device. At present, four years after operation he present complete reversal of symptoms. In conclusión, this patient confirms that bulbar ALS is of ischemic origin and therefore, mild ALS can be cured. PMID:27508110

  4. Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial.

    PubMed

    Cohen, Adam D; Zhou, Ping; Chou, Joanne; Teruya-Feldstein, Julie; Reich, Lilian; Hassoun, Hani; Levine, Beth; Filippa, Daniel A; Riedel, Elyn; Kewalramani, Tarun; Stubblefield, Michael D; Fleisher, Martin; Nimer, Stephen; Comenzo, Raymond L

    2007-10-01

    High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving < or =2 organ systems were assigned to MEL 100, 140, or 200 mg/m(2) with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients. PMID:17897298

  5. Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type

    PubMed Central

    Muchtar, Eli; Dispenzieri, Angela; Kumar, Shaji K.; Dingli, David; Lacy, Martha Q.; Buadi, Francis K.; Hayman, Suzanne R.; Kapoor, Prashant; Leung, Nelson; Chakraborty, Rajshekhar; Russell, Stephen; Lust, John A.; Lin, Yi; Go, Ronald S.; Zeldenrust, Steven; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2016-01-01

    Clinical tools to guide in the appropriate treatment selection in immunoglobulin light chain (AL) amyloidosis are not well developed. We evaluated the response and outcome for various regimens at first-line treatment (n=681) and first progression (n=240) stratified by the immunoparesis status at diagnosis. Immunoparesis was assessed by the average relative difference of the uninvolved immunoglobulins, classifying patients into a negative average relative difference (i.e. significant immunoparesis) or a positive average relative difference (no/modest immunoparesis). Treatment was categorized as autologous stem cell transplant and four non-transplant regimens (melphalan-based; bortezomib-based, immunomodulatory drug-based and dexamethasone alone). Patients with significant immunoparesis who underwent stem cell transplant had a significantly lower rate of very good partial response or better response (58%), progression-free survival (median 30 months) and overall survival (108 months), compared to those without significant immunoparesis (80%, 127 months, median not reached, respectively; P<0.001 for all comparisons). Among the non-transplant regimens, melphalan resulted in an unfavorable progression-free survival (11 vs. 27 months; P<0.001) and overall survival (30 vs. 74 months; P=0.001) in patients with significant immunoparesis compared to those without significant immunoparesis. In contrast, no significant difference in outcomes between the immunoparesis groups was seen for those treated with bortezomib or immunomodulatory drugs. At first progression, immunoparesis status did not impact response or survival of any regimen. Melphalan at first-line provided poorer outcomes for patients with significant immunoparesis, while bortezomib or immunomodulatory drugs were more likely to overcome the adverse prognosis associated with significant immunoparesis. PMID:27479823

  6. New trace element determinations in the fingernails of ALS patients

    SciTech Connect

    Van Dalsem, D.J.; Ehmann, W.D.; Robinson, L.

    1996-12-31

    Amyotrophic lateral sclerosis (ALS) afflicts 2 of every 100,000 people in the United States each year. A well-known example of ALS today is Stephen Hawking. He is a theoretical physicist, the author of A Brief History of Time, and is virtually immobilized by ALS. Diseases that cause progressive paralysis because of motor neuron degeneration in the central nervous system are termed motor neuron disorders (MND). Amyotrophic lateral sclerosis is a common form of MND. Pain-free, progressive muscular weakness is the most common clinical symptom. There is chronic weakness with atrophy of the affected muscles by the time the disease is diagnosed. Atrophy eventually results in wheelchair confinement and then only bed without the ability to speak or swallow. Death often occurs as a result of respiratory problems. Unlike other neurodegenerative diseases, in ALS the patient`s bladder and bowel control, eye movement, and mental faculties are preserved. The question today is whether or not certain trace elements are involved in the etiology or pathogenesis of ALS. A collaborative study was undertaken by the University of Kentucky and Oak Ridge National Laboratory (ORNL) using neutron activation analysis (NAA) to study trace element concentrations in ALS patients fingernails to determine if there existed statistically significant imbalances.

  7. Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin.

    PubMed

    Valleix, Sophie; Gillmore, Julian D; Bridoux, Frank; Mangione, Palma P; Dogan, Ahmet; Nedelec, Brigitte; Boimard, Mathieu; Touchard, Guy; Goujon, Jean-Michel; Lacombe, Corinne; Lozeron, Pierre; Adams, David; Lacroix, Catherine; Maisonobe, Thierry; Planté-Bordeneuve, Violaine; Vrana, Julie A; Theis, Jason D; Giorgetti, Sofia; Porcari, Riccardo; Ricagno, Stefano; Bolognesi, Martino; Stoppini, Monica; Delpech, Marc; Pepys, Mark B; Hawkins, Philip N; Bellotti, Vittorio

    2012-06-14

    We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding. PMID:22693999

  8. The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias: Etiologic Implications.

    PubMed

    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

  9. The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias: Etiologic Implications

    PubMed Central

    Hemminki, Kari; Försti, Asta; Tuuminen, Raimo; Hemminki, Otto; Goldschmidt, Hartmut; Sundquist, Kristina; Sundquist, Jan; Li, Xinjun

    2016-01-01

    Plasma cell dyscrasias, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia (WM) and light chain AL amyloidosis, are characterized by clonal expansion of plasma cells which produce a vast amount of an immunoglobulin-derived M-protein. We noted that MGUS diagnosis often coincided with diagnoses of senile cataract and glaucoma and tested the associations of MGUS, MM, WM and AL amyloidosis with subsequent eye diseases identified from the Swedish patient registers between 1997 and 2012. Standardized incidence ratios (SIRs) for senile cataract was significantly increased to 1.80 after MGUS, 1.70 after MM, 1.85 after WM and 2.31 after AL amyloidosis. The SIR for glaucoma was 1.60 after MGUS, 1.76 after WM and 2.18 after AL amyloidosis. All SIRs decreased systematically from age below 60 years to over 79 years, but most risks were also significant in age group over 79 years. The M-protein and the related increase in blood viscosity could be a novel etiologic discovery for these common eye diseases. As MGUS prevalence is around 3% at 60 years and close to 10% at age over 80 years, its contribution to the eye disease burden is expected to be remarkably high. PMID:27328652

  10. Multiple myeloma-associated skin light chain amyloidosis: A case of misdiagnosis

    PubMed Central

    XIAO, LI; LIN, FENGXIA; XIAO, RONG; HU, CHUN; DENG, MINGYANG; LI, DAIQIANG; SHE, XIAOLING; LIU, FUYOU; SUN, LIN

    2016-01-01

    The present study reports the case of a 42-year-old male with multiple myeloma (MM)-associated skin light chain amyloidosis who presented with skin purpura as the initial symptom, which was misdiagnosis as Henoch-Schönlein purpura nephritis prior to admission to the Second Xiangya Hospital (Changsha, Hunan, China). The patient presented with purpura, papules petechiae and spontaneous ecchymosis, which was located scattered around the neck, chest and limbs, accompanied by a small amount of bleeding in the conjunctival and oral mucosa, and a swollen tongue. Upon laboratory examination, the serum immunological change showed increased serum immunoglobulin G and λ light chain levels, and a urine Bence Jones protein level of >1 g/24 h. This was accompanied with an abnormal result for immunofixation electrophoresis, and positive staining with Congo red showing apple-green birefringence in skin biopsy specimens. Thus, the patient was diagnosed with MM-associated skin amyloidosis with the initial symptom of skin purpura. Following treatment with chemotherapy consisting of prednisone and bortezomib, the skin lesions markedly improved. The present study indicates that the presentation of skin purpura in systemic amyloidosis associated with MM may be an important aid in the diagnosis and direct treatment of this disease in the clinic. PMID:27284363

  11. Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Ravani, Pietro; Obici, Laura; Dallera, Nadia; Del Barba, Andrea; Negrinelli, Alessandro; Tardanico, Regina; Nardi, Matilde; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2015-06-01

    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.

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

    PubMed Central

    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 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

  13. New trace element determinations in the fingernails of ALS patients

    SciTech Connect

    Van Dalsem, D.J.; Robinson, L.; Ehmann, W.D.

    1996-02-01

    ORNL`s High Flux Isotope Reactor was used in a neutron activation analysis experiment to determine selected elemental composition of fingernails from patients afflicted with amyotrophic lateral sclerosis (AL). While no statistical difference were found in aluminium a suggestive difference was observed for copper concentrations.

  14. Communication of ALS Patients by Detecting Event-Related Potential

    NASA Astrophysics Data System (ADS)

    Kanou, Naoyuki; Sakuma, Kenji; Nakashima, Kenji

    Amyotrophic Lateral Sclerosis(ALS) patients are unable to successfully communicate their desires, although their mental capacity is the same as non-affected persons. Therefore, the authors put emphasis on Event-Related Potential(ERP) which elicits the highest outcome for the target visual and hearing stimuli. P300 is one component of ERP. It is positive potential that is elicited when the subject focuses attention on stimuli that appears infrequently. In this paper, the authors focused on P200 and N200 components, in addition to P300, for their great improvement in the rate of correct judgment in the target word-specific experiment. Hence the authors propose the algorithm that specifies target words by detecting these three components. Ten healthy subjects and ALS patient underwent the experiment in which a target word out of five words, was specified by this algorithm. The rates of correct judgment in nine of ten healthy subjects were more than 90.0%. The highest rate was 99.7%. The highest rate of ALS patient was 100.0%. Through these results, the authors found the possibility that ALS patients could communicate with surrounding persons by detecting ERP(P200, N200 and P300) as their desire.

  15. Sympathetic dysfunction of central origin in patients with ALS.

    PubMed

    Karlsborg, M; Andersen, E B; Wiinberg, N; Gredal, O; Jørgensen, L; Mehlsen, J

    2003-05-01

    Amyotrophic lateral sclerosis (ALS) is a severe, progressive disease affecting both the central and peripheral parts of the motor nervous system. Some studies have shown unequivocal indications of a more disseminated disease also affecting the autonomic nervous system. We therefore evaluated the centrally and peripherally mediated autonomic vascular reflexes by (i) the local 133-Xenon washout technique, and (ii) the head-up tilt table test. The results correlated to clinical scores. We examined nine ALS patients and 15 age-matched controls. The 133-Xenon washout test showed a significant reduction in the centrally mediated sympathetic vasoconstrictor response, but a preserved locally mediated response in the patients. In the head-up tilt table test, the patients had a significantly higher mean arterial blood pressure (MAP) compared with controls, probably due to a general increase in vascular resistance. There were no correlations between the ALS Severity Scores and blood flow changes, diastolic blood pressure or MAP. Our study supports previous results, but indicates abnormalities consistent with a solely centrally located sympathetic dysfunction in ALS, independent of the stage of the disease. PMID:12752395

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2007-01-01

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

  18. A Rare Case of Amyloidosis of the Eyelid and Conjunctiva

    PubMed Central

    Fernando, Bertie

    2016-01-01

    Amyloidosis of the eyelid is uncommon and is typically associated with systemic associations. In contrast, amyloidosis of the conjunctiva is often localised with no other associations. We present a rare case of a 92-year-old gentleman with both cutaneous lid lesions and conjunctival amyloid with no systemic involvement. Biopsy demonstrated the hallmarks of amyloid and treatment has remained conservative. He remains at the department to be monitored for secondary glaucoma. PMID:27752377

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

    SciTech Connect

    Truong, Minh Tam; Kachnic, Lisa A.; Grillone, Gregory A.; Bohrs, Harry K.; Lee, Richard; Sakai, Osamu; Berk, John L.

    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.

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

    PubMed

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

    2016-01-01

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

  1. Assessing and predicting successful tube placement outcomes in ALS patients.

    PubMed

    Beggs, Kathleen; Choi, Marcia; Travlos, Andrew

    2010-01-01

    This study reviews feeding tube placement outcomes in 69 ALS outpatients seen at an outpatient interdisciplinary ALS clinic in British Columbia, Canada. The objective was to determine at which point the risks outweigh the benefits of tube placement by reviewing outcomes against parameters of respiratory function, nutritional status and speech and swallowing deterioration. The study was a retrospective review of tube placements between January 2000 and 2005, analysing data on respiratory function (forced vital capacity and respiratory status), weight change from usual body weight (UBW) and speech/swallowing deterioration using ALS Severity Score ratings (Hillel et al., 1989) at time of tube placement. Results show a statistically significant association between nutritional status and successful tube placement outcomes (p=0.003), and none between respiratory status, speech/swallowing variables, or number of deteriorated variables in each patient. Study findings were impacted by lack of available respiratory data. The only study variable that predicted successful tube placement outcome was a body weight greater than or equal to 74% UBW at time of tube placement. In the absence of access to respiratory testing, the relatively simple assessment of weight may assist patients and caregivers in appropriate decisions around tube placement.

  2. Confocal Cornea Microscopy Detects Involvement of Corneal Nerve Fibers in a Patient with Light-Chain Amyloid Neuropathy Caused by Multiple Myeloma: A Case Report

    PubMed Central

    Sturm, Dietrich; Schmidt-Wilcke, Tobias; Greiner, Tineke; Maier, Christoph; Schargus, Marc; Tegenthoff, Martin; Vorgerd, Matthias

    2016-01-01

    Changes in the subbasal corneal plexus detected by confocal cornea microscopy (CCM) have been described for various types of neuropathy. An involvement of these nerves within light-chain (AL) amyloid neuropathy (a rare cause of polyneuropathy) has never been shown. Here, we report on a case of a patient suffering from neuropathy caused by AL amyloidosis and underlying multiple myeloma. Small-fiber damage was detected by CCM. PMID:27482195

  3. New Light Chain Amyloid Response Criteria Help Risk Stratification of Patients by Day 100 after Autologous Hematopoietic Cell Transplantation.

    PubMed

    D'Souza, Anita; Huang, Jiaxing; Hari, Parameswaran

    2016-04-01

    Hematologic response criteria in light chain (AL) amyloidosis were updated in 2012 to incorporate free light chain responses. These criteria have been validated in autologous hematopoietic cell transplantation in AL at 6 and 12 months after transplantation. Using a transplantation registry, we assessed day 100 responses in AL amyloidosis. We validate the prognostic significance of the new criteria at this time point. Further, we show that patients who do not achieve at least a very good partial response by this time point have equally worse outcomes, regardless of depth of response (partial versus no response). Thus, we conclude that the new criteria help identify the poor responders by day 100 after transplantation and that this subset of patients should be studied for early evaluation in consolidation trials.

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

    PubMed

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

    2008-05-01

    A high prevalence of systemic amyloidosis was documented in the black-footed cat (Felis nigripes) based on a retrospective review of necropsy tissues (n = 38) submitted as part of ongoing disease surveillance. Some degree of amyloid deposition was present in 33 of 38 (87%) of the examined cats, and amyloidosis was the most common cause of death (26/38, 68%). Amyloid deposition was most severe in the renal medullary interstitium (30/33, 91%) and glomeruli (21/33, 63%). Other common sites included the splenic follicular germinal centers (26/31, 84%), gastric lamina propria (9/23, 39%), and intestinal lamina propria (3/23, 13%). Amyloid in all sites stained with Congo red, and in 13 of 15 (87%) cats, deposits had strong immunoreactivity for canine AA protein by immunohistochemistry. There was no association with concurrent chronic inflammatory conditions (P = .51), suggesting that amyloidosis was not secondary to inflammation. Adrenal cortical hyperplasia, a morphologic indicator of stress that can predispose to amyloid deposition, was similarly not associated (P = .09) with amyloidosis. However, adrenals were not available from the majority of cats without amyloidosis; therefore, further analysis of this risk factor is warranted. Heritability estimation suggested that amyloidosis might be familial in this species. Additionally, tissues from a single free-ranging black-footed cat had small amounts of amyloid deposition, suggesting that there could be a predilection for amyloidosis in this species. Research to identify the protein sequence of serum amyloid A (SAA) in the black-footed cat is needed to further investigate the possibility of an amyloidogenic SAA in this species. PMID:18487501

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

    PubMed

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

    2008-05-01

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

  6. Survey on spontaneous systemic amyloidosis in aging mice.

    PubMed

    Majeed, S K

    1993-02-01

    The incidence of systemic amyloidosis in CD-1 mice (Charles River, caesarian derived) obtained from long term studies over more than a 15-year period is reported. The survey included samples of visceral organs, peripheral and central nervous tissues, bone and bone marrow. The total incidence in all mice of this survey did not show any clear evidence of a difference between males and females. Amyloidosis deposits were mainly seen in the stomach (glandular), heart, small intestines, kidney, liver, spleen, thyroid, parathyroid, adrenals, salivary glands and ovaries, but not in the brain, spinal cord, bone or bone marrow. The survey showed that amyloidosis in CD-1 mice was spontaneous, systemic and it is age-related. Amyloid deposition was extracellular and it stained positively with Congo Red and also stained positively with Oil Red O and Alcian blue. In general, amyloidosis in CD-1 mice, was higher in comparison with B6C3F (cross between C57BL/C6 NCRLB and C3H/HEN NCRLB, (bred by Charles River), CFLP strain (hysterectomy derived strain of Swiss origin) and MAGF: TIF (SPF). This survey also showed that spontaneous systemic amyloidosis in CD-1 mice, was one of the major factors contributory to death in aging CD-1 mice. PMID:8457241

  7. Cognitive impairment in ALS patients and validation of the Spanish version of the ALS-CBS test.

    PubMed

    Turon-Sans, Janina; Gascon-Bayarri, Jordi; Reñé, Ramon; Rico, Imma; Gámez, Cristina; Paipa, Andres; Povedano, Monica

    2016-01-01

    Our aim was to develop and validate the Spanish version of the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) and investigate behavioural/cognitive impairment in our ALS patients. We enrolled 50 patients with definite or probable ALS, evaluated by the Motor Neuron Disease Unit (using El Escorial criteria) and Dementia Unit, and assessed with the Spanish ALS-CBS. The patients' cognitive/behavioural status was classified according to current criteria. Patients were classified into each diagnostic category: ALS-no impairment, 36%; ALS-mild cognitive impairment, 34%; ALS-mild behavioural impairment, 6%; ALS-mild cognitive/behavioural impairment, 12%; ALS-frontotemporal dementia, 12%. Cognitive impairment was more common in bulbar (90.9%) than spinal (48.7%) forms (p < 0.012). The Spanish ALS-CBS was validated. Performance to differentiate normal vs. impaired individuals was: 1) cognition (cut-off 15; AUC, 84.7%): sensitivity 86.2%, specificity 62%, positive predictive value 75.8%, negative predictive value 76.5%; 2) behaviour (cut-off 36; AUC, 83.3%): sensitivity 93.3%, specificity 74.3%, positive predictive value 61%, negative predictive value 96.3%. Performance to differentiate between patients with and without dementia: 1) cognition (cut-off 8; AUC, 87.3%): sensitivity 83.3%, specificity 75%, positive predictive value 31.3%, negative predictive value 97.1%; 2) behaviour (cut-off 35; AUC, 80.9%): sensitivity 83.3%, specificity 69%, positive predictive value 25%, negative predictive value 96.7%. In conclusion, cognitive impairment is common in ALS patients, particularly in bulbar forms. The Spanish version of the ALS-CBS is useful for screening cognitive/behavioural impairment in this population.

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

    PubMed

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

    2015-09-30

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

  9. Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation

    PubMed Central

    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 amyloid. The horizontal sections showed that the sebaceous glands were preserved which supports the nonscarring pattern of the alopecia. PMID:26903748

  10. Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

    PubMed Central

    Hwang, Kristy S.; Avila, David; Elashoff, David; Kohannim, Omid; Teng, Edmond; Sokolow, Sophie; Jack, Clifford R.; Jagust, William J.; Shaw, Leslie; Trojanowski, John Q.; Weiner, Michael W.; Thompson, Paul M.

    2015-01-01

    Background: The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. Methods: We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1–42 (Aβ42) ≤192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. Results: The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. Conclusions: Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. Classification of evidence: This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%). PMID:25609767

  11. A marked decline in the incidence of renal replacement therapy for amyloidosis associated with inflammatory rheumatic diseases - data from nationwide registries in Finland.

    PubMed

    Immonen, Kai; Finne, Patrik; Grönhagen-Riska, Carola; Pettersson, Tom; Klaukka, Timo; Kautiainen, Hannu; Hakala, Markku

    2011-03-01

    Risk for amyloidosis in rheumatic diseases is associated with a long-lasting inflammation. To assess possible changes in the incidence of terminal uraemia due to amyloidosis associated with rheumatic diseases on a nationwide basis, we scrutinised the files of the Finnish Registry for Kidney Diseases for patients suffering from amyloidosis associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) or juvenile idiopathic arthritis (JIA) over the period 1995-2008. The registry has an estimated 97-99% coverage of all patients accepted for renal replacement therapy (RRT) in the country. Data on the consumption of antirheumatic drugs were collected from two sources: the Social Insurance Institution's Drug Reimbursement Register, and the Sales Register of the National Agency for Medicines from the above period. Altogether 264 cases were identified. Two hundred twenty-nine of them had RA, 15 AS and 20 JIA. When the total annual number of new admissions to RRT varied between 20 and 37 at the end of 1990s, it was under half of that from 2002 onwards. Over this period, the number of users of low-dose methotrexate (MTX) has increased 3.6-fold, the drug being the most frequently used disease modifying anti-rheumatic drug in Finland. The present nationwide series is the first to show that the incidence of end-stage renal disease due to amyloidosis associated with rheumatic diseases is decreasing. An obvious reason for this is intensive anti-rheumatic drug therapy.

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

    PubMed

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

    1994-01-01

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

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

    PubMed Central

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

    2016-01-01

    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

  14. Experimental murine amyloidosis: a model system for studying amyloid formation.

    PubMed Central

    Baumal, R.; Wilson, B.; Pass, E.

    1975-01-01

    Myeloma-associated and casein-induced murine amyloidosis were used as models to study the role of lymphocytes and macrophages in amyloid formation. Amyloidosis occurred rarely and in small amounts in Balb/C mice with immunoglobulin (Ig)-producing myeloma tumours but large amounts could be induced by injections of casein. Fluorescent staining of both forms of amyloid deposits by means of anti-casein- and anti-myeloma-amyloid antibodies indicated that they either crossreacted or coexisted. Nor abnormality of Ig biosynthesis was detected in amyloidosis, suggesting that abnormal degradation was responsible for production of the Ig form of amyloid. Although spleen lymphocytes of casein-injected mice with amyloidosis demonstrated diminished cellular immunologic responses, this did not indicate generalized immunologic incompetence. The non-Ig form of amyloid in casein-injected mice was shown to be produced by macrophages, and a technique was developed for increasing the yield of amyloid-containing cells. Images FIG. 1 FIG. 2 FIG. 3 FIG. 6 FIG. 7 FIG. 8 PMID:1080430

  15. Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice*

    PubMed Central

    Mori, Takashi; Koyama, Naoki; Segawa, Tatsuya; Maeda, Masahiro; Maruyama, Nobuhiro; Kinoshita, Noriaki; Hou, Huayan; Tan, Jun; Town, Terrence

    2014-01-01

    Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway. PMID:25157105

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

    PubMed

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

    2013-01-01

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

  17. C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population.

    PubMed

    Abramycheva, Natalya Y; Lysogorskaia, Elena V; Stepanova, Maria S; Zakharova, Maria N; Kovrazhkina, Elena A; Razinskaya, Olga D; Smirnov, Andrey P; Maltsev, Andrey V; Ustyugov, Alexey A; Kukharsky, Michail S; Khritankova, Inna V; Bachurin, Sergey O; Cooper-Knock, Johnathan; Buchman, Vladimir L; Illarioshkin, Sergey N; Skvortsova, Veronika I; Ninkina, Natalia

    2015-10-01

    Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central European Russian ALS patients is significantly lower than in Western European or Northern American ALS patients of Caucasian origin but higher than in Asian ALS patients.

  18. Buccal mucosa graft urethroplasty in a case of urethral amyloidosis presenting with long anterior urethral stricture

    PubMed Central

    Kurbatov, Dmitry; Stojanovic, Borko; Dubskiy, Sergey; Lepetukhin, Alex; Djordjevic, Miroslav L.

    2015-01-01

    Urethral amyloidosis is a rare condition, but clinically relevant because it can mimic urothelial carcinoma. We report a case of localized urethral amyloidosis presenting with a long anterior urethral stricture. We used extensive grafts of buccal mucosa for standard augmentation urethroplasty, with a successful outcome at the 2-year follow-up. PMID:26600896

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

    PubMed

    Westermark, Gunilla T; Westermark, Per

    2009-08-20

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

  20. Behçet's disease associated with amyloidosis in Turkey and in the world.

    PubMed Central

    Dilşen, N; Koniçe, M; Aral, O; Erbengi, T; Uysal, V; Koçak, N; Ozdogan, E

    1988-01-01

    The association of amyloidosis with Behçet's disease has infrequently been reported in published works. Twenty four such cases have been observed in the world, of which 12 are from Turkey, including eight of ours. In all our eight cases renal biopsy showed amyloidosis of type AA. Behçet's disease of male preponderance, long duration, complete type, multiple organ involvement, and positive skin pathergy test were the main characteristics of all 24 cases of Behçet's disease with amyloidosis. We conclude that amyloidosis associated with Behçet's disease is a secondary AA amyloidosis occurring as an intrinsic manifestation of Behçet's disease. Images PMID:3281606

  1. [18F]-NaF PET/CT imaging in cardiac amyloidosis.

    PubMed

    Van Der Gucht, Axel; Galat, Arnault; Rosso, Jean; Guellich, Aziz; Garot, Jérôme; Bodez, Diane; Plante-Bordeneuve, Violaine; Hittinger, Luc; Dubois-Randé, Jean-Luc; Evangelista, Eva; Sasanelli, Myriam; Chalaye, Julia; Meignan, Michel; Itti, Emmanuel; Damy, Thibaud

    2016-08-01

    Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.

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

    PubMed Central

    Ribeiro, Raquel; Gilberto, Samuel; Gomes, Ricardo A.; Ferreira, António; Mateus, Élia; Barroso, Eduardo; Coelho, Ana V.; Freire, Ana Ponces; Cordeiro, Carlos

    2015-01-01

    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. PMID:26147092

  3. Palliative care and circumstances of dying in German ALS patients using non-invasive ventilation.

    PubMed

    Kühnlein, Peter; Kübler, Andrea; Raubold, Sabine; Worrell, Marcia; Kurt, Anja; Gdynia, Hans-Jürgen; Sperfeld, Anne-Dorte; Ludolph, Albert Christian

    2008-04-01

    Non-invasive ventilation (NIV) is known to improve quality of life and to prolong survival in amyotrophic lateral sclerosis (ALS) patients. However, little is known about the circumstances of dying in ventilated ALS patients. In the light of the debate on legalizing euthanasia it is important to provide empirical data about the process of dying in these patients. In a structured interview, 29 family caregivers of deceased ALS patients were asked about their own and the patient's attitude toward physician-assisted suicide (PAS) and euthanasia, circumstances of dying, and the use of palliative medication. Quantitative and qualitative content analysis was performed on the data. Non-recurring suicidal thoughts were reported by five patients. Three patients and seven relatives had thought about PAS. Seventeen caregivers described the patients' death as "peaceful", while choking was reported in six bulbar patients. In final stages of dying, the general practitioner (GP) was involved in the treatment of 10 patients, with palliative medication including sedatives and opiates being administered in eight cases. In conclusion, in contrast to the Netherlands, where 20% of terminal ALS patients die from PAS or euthanasia, only a small minority of our patients seems to have thought about PAS. The legal situation in Germany (where euthanasia is illegal), a bias due to the selection of NIV patients as well as a high percentage of religious patients and those with good levels of social support from family and friends, might account for this. Most of our patients died peacefully at home from carbon dioxide narcosis, but choking was described in some bulbar patients. Thus, palliative care, especially the use of opiates, anxiolytics and sedatives should be optimized, and the involvement of GP should be strongly encouraged, especially in bulbar patients. PMID:18428001

  4. Mitochondrial respiratory chain function in skeletal muscle of ALS patients.

    PubMed

    Echaniz-Laguna, Andoni; Zoll, Joffrey; Ribera, Florence; Tranchant, Christine; Warter, Jean-Marie; Lonsdorfer, Jean; Lampert, Eliane

    2002-11-01

    Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic. PMID:12402260

  5. [An atypical case of cardiac amyloidosis].

    PubMed

    Giannoni, Alberto; Aquaro, Donato Giovanni; Masi, Lorenzo; Benedetti, Edoardo; Cecconi, Nadia; Passino, Claudio; Emdin, Michele

    2009-05-01

    The described report deals with the case of a patient with diagnosis of ischemic-hypertensive cardiomyiopathy based on the history of angina and inducible myocardial ischemia with normal coronary arteries. However, after cardiac magnetic resonance, the typical amyloidotic pattern is found and the final diagnosis of multiple myeloma is made at osteomedullary biopsy.

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

    PubMed Central

    Picken, Maria M.

    2015-01-01

    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

  7. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations.

    PubMed

    Rowczenio, Dorota M; Noor, Islam; Gillmore, Julian D; Lachmann, Helen J; Whelan, Carol; Hawkins, Philip N; Obici, Laura; Westermark, Per; Grateau, Gilles; Wechalekar, Ashutosh D

    2014-09-01

    Hereditary systemic amyloidosis comprises a group of rare monogenic diseases inherited in an autosomal dominant fashion. It is associated with mutations in genes encoding eight different proteins, including transthyretin, apolipoprotein AI, apolipoprotein AII, lysozyme, fibrinogen A α-chain, cystatin C, gelsolin and beta-2-microglobulin. With support from the EU FP6 EURAMY project we have designed an online registry of genes and mutations in hereditary amyloidosis including their associated clinical phenotypes, with a view to having a single free online portal for the collection and distribution of this information. Users can search the registry by either mutation, phenotype or authors who have published or submitted mutations. It provides a submission form for reporting newly identified mutations. We also wanted to introduce nomenclature which complies with recommendations set out by Human Genome Variation Society and HUGO Gene Nomenclature Committee for description of new and known genetic variants. We hope this registry would be a useful and convenient tool for the medical and scientific community. PMID:25044787

  8. Cardiac Amyloidosis: Typical Imaging Findings and Diffuse Myocardial Damage Demonstrated by Delayed Contrast-Enhanced MRI

    SciTech Connect

    Sueyoshi, Eijun Sakamoto, Ichiro; Okimoto, Tomoaki; Hayashi, Kuniaki; Tanaka, Kyouei; Toda, Genji

    2006-08-15

    Amyloidosis is a rare systemic disease. However, involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis. We report the sonographic, scintigraphic, and MRI features of a pathologically proven case of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall of both left and right ventricles. This enhancement suggested expansion of the extracellular space of the myocardium caused by diffuse myocardial necrosis secondary to deposition of amyloid.

  9. [Review of evidence of thalidomide and lenalidomide in different hematological diseases: chronic lymphocytic leukemia, primary amyloidosis, myelofibrosis and syndrome myelodysplastic].

    PubMed

    Jiménez Lozano, I; Juárez Jiménez, J C

    2013-01-01

    Lenalidomide is an immunomodulatory drug approved by the AEMPS and the EMA, in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Moreover, it has recently been approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. It has also shown to be active in other hematologic and no hematologic diseases. Growing evidence of its use entails a challenge when situating the drug in a cost-effective way to treat these diseases. On this article we review the available evidence on the use of lenalidomide in the second line treatment of patients with chronic lymphocytic leukemia, primary amyloidosis and primary myelofibrosis, and in the first line treatment of patients with myelodysplastic syndrome, and also the evidence of other immunomodulators. Different clinical practice guidelines and scientific evidence portals consider lenalidomide a valid alternative in the first-line treatment of patients with myelodysplastic syndromes, specially those with the deletion of 5q, and in second line for patients with chronic lymphocytic leukemia. However, the available evidence of lenalidomide in the treatment of patients with primary amyloidosis and primary myelofibrosis is limited, ant thus is not considered as the first choice treatment. In any case, the treatment of choice should consider the safety profile in each patient, the previous treatments that has received and the own therapeutic protocols of each center.

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

    PubMed

    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

  11. Depression and wish to die in a multicenter cohort of ALS patients.

    PubMed

    Rabkin, Judith G; Goetz, Raymond; Factor-Litvak, Pam; Hupf, Jonathan; McElhiney, Martin; Singleton, Jessica; Mitsumoto, Hiroshi

    2015-06-01

    Our objective was to determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multisite study of patients with ALS. Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329) had minor depression, and 5% (16/329) had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R (p = 0.004) and gross motor function (p < 0.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p < 0.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. In conclusion, depressive disorders are not necessarily to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such.

  12. Depression and Wish to Die in a Multi-Center Cohort of ALS Patients

    PubMed Central

    Rabkin, Judith G.; Goetz, Raymond; Factor-Litvak, Pam; Hupf, Jonathan; McElhiney, Martin; Singleton, Jessica; Mitsumoto, Hiroshi

    2015-01-01

    Objective To determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multi-site study of patients with ALS. Methods Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Results Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329)had minor depression, and 5% (16/329)had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R ( p = .004) and gross motor function (p<.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p<.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. Conclusions Depressive disorders are not only to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such. PMID:25482273

  13. Mixed systemic amyloidosis in a patient receiving long term haemodialysis.

    PubMed Central

    Fernandez-Alonso, J; Rios-Camacho, C; Valenzuela-Castaño, A; Hernanz-Mediano, W

    1994-01-01

    A 64 year old woman had been receiving haemodialysis for 11 years. She had a history of chronic renal failure, caused by probable chronic pyelonephritis, and dialysis arthropathy. She died of acute pulmonary oedema and haemorrhage. At necropsy, histological, immunohistochemical, and ultrastructural studies showed widespread visceral deposits of beta 2-microglobulin (beta 2-M) and AA amyloid. Images PMID:8063944

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

    PubMed

    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

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

    PubMed Central

    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

  16. Nomenclature of amyloid and amyloidosis. WHO-IUIS Nomenclature Sub-Committee.

    PubMed Central

    1993-01-01

    This classification of amyloid and amyloidosis is based on the amyloid fibril proteins, followed by a designation of the fibril protein precursor. Additional information includes the protein type or variant (where applicable) and the clinical diagnosis. PMID:8440029

  17. Tocilizumab attenuates inflammation in ALS patients through inhibition of IL6 receptor signaling

    PubMed Central

    Mizwicki, Mathew T; Fiala, Milan; Magpantay, Larry; Aziz, Najib; Sayre, James; Liu, Guanghao; Siani, Avi; Chan, Derrick; Martinez-Maza, Otoniel; Chattopadhyay, Madhuri; Cava, Antonio La

    2012-01-01

    Patients with amyotrophic lateral sclerosis (ALS) have evidence of chronic inflammation demonstrated by infiltration of the gray matter by inflammatory macrophages, IL17A-positive T cells, and mast cells. Increased serum levels of IL6 and IL17A have been detected in sporadic ALS (sALS) patients when compared to healthy controls. Herein we investigate, in peripheral blood mononuclear cells (PBMCs), the baseline transcription of genes associated with inflammation in sALS and control subjects and the impact of the IL6 receptor (IL6R) antibody (tocilizumab) on the transcription and/or secretion of inflammation factors (e.g. cytokines) stimulated by the apo-G37R superoxide dismutase (SOD1) mutant. At baseline, PBMCs of four sALS patients (Group 1) showed significantly increased expression of TLR2 and CD14; ALOX5, PTGS2 and MMP1; IL1α, IL1β, IL6, IL36G, IL8 and TNF; CCL3, CCL20, CXCL2, CXCL3 and CXCL5. In four other sALS patients (Group 2), most of the genes just mentioned were expressed at near control levels and a significant decrease in the expression of PPARG, PPARA, RARG, HDAC4 and KAT2B; IL6R, IL6ST and ADAM17; TNFRSF11A; MGAT2 and MGAT3; PLCG1; CXCL3 were detected. Apo-G37R SOD1 up regulated the transcription of cytokines (e.g. IL1α/β, IL6, IL8, IL36G), chemokines (e.g. CCL20; CXCL3, CXCL5), and enzymes (e.g. PTGS2 and MMP1). In vitro, tocilizumab down regulated the transcription of many inflammatory cytokines, chemokines, enzymes, and receptors, which were up regulated by pathogenic forms of SOD1. Tocilizumab also reduced the secretion of the pro-inflammatory cytokines IL1β, IL6, TNFα, GM-CSF, IFNγ, and IL17A by Group 1 PBMCs. Finally, sALS patients had significantly higher concentrations of IL6, sIL6R and C-reactive protein in the cerebrospinal fluid when compared to AD patients. This pilot study demonstrates that in vitro tocilizumab suppresses many factors that drive inflammation in sALS patients, with possible increased efficacy in Group 1 ALS patients

  18. Evidence for the experimental transmission of cerebral beta-amyloidosis to primates.

    PubMed Central

    Baker, H. F.; Ridley, R. M.; Duchen, L. W.; Crow, T. J.; Bruton, C. J.

    1993-01-01

    The brains of three marmosets (Callithrix jacchus) injected intracerebrally 6-7 years earlier with brain tissue from a patient with early onset Alzheimer's disease were found to contain moderate numbers of amyloid plaques with associated argyrophilic dystrophic neurites and cerebral amyloid angiopathy but no neurofibrillary tangles. The plaques and vascular amyloid stained positively with antibodies to beta (A4)-protein. The brains of three age-matched control marmosets from the same colony did not show these neuropathological features. The brain of one of two marmosets injected with brain tissue from a patient with prion disease with concomitant beta-amyloid plaques and cerebral amyloid angiopathy also showed beta-amyloid plaques and angiopathy but no spongiform encephalopathy. An occasional plaque was found in the brains of two of four marmosets injected with brain tissue from three elderly patients with age-related pathology, two of whom had an additional diagnosis of possible prion disease. Neither plaques nor cerebral amyloid angiopathy were found in six other marmosets who were older than the injected animals, in 12 further marmosets who were slightly younger but who had been injected several years previously with brain tissue which did not contain beta-amyloid, or in 10 younger marmosets who had been subjected to various neurosurgical procedures. These results suggest that cerebral beta-amyloidosis may be induced by the introduction of exogenous amyloid beta-protein. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8217779

  19. The UCSF screening exam effectively screens cognitive and behavioral impairment in patients with ALS.

    PubMed

    Murphy, Jennifer; Ahmed, Fizaa; Lomen-Hoerth, Catherine

    2015-03-01

    The University of California San Francisco (UCSF) Screening Battery provides clinicians with a uniquely tailored tool to measure ALS patients' cognitive and behavioral changes, adjusting for dysarthria and hand weakness. The battery consists of the ALS-CBS ( 1 ), Written Fluency Test ( 2 ), and a new revision of the Frontal Behavior Inventory (FBI-ALS) ( 3 ). The validity of each component was tested by comparing results with a gold standard neuropsychological exam (GNE). Consensus criteria-based GNE diagnoses ( 4 ) were assigned (n = 24) and concurrent validity was tested for each screening exam component. Results showed that each of the four cognitive and behavioral screening test components were significantly associated with diagnoses confirmed by GNE. GNE diagnoses were significantly associated with FBI-ALS negative score, written S-words score, and ALS-CBS cognitive score. The total FBI-ALS score and C-words tests were less predictive of GNE-diagnosed impairment. In conclusion, the UCSF Cognitive Screening Battery demonstrates good external validity compared with GNE in this modest sample, encouraging its use in larger investigations. These data suggest that this battery may provide an effective screen to identify ALS patients who will then benefit from a full examination to confirm their diagnosis. PMID:25301548

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

    PubMed

    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

  1. Very long term studies of the seeding of beta-amyloidosis in primates.

    PubMed

    Ridley, R M; Baker, H F; Windle, C P; Cummings, R M

    2006-09-01

    Cerebral beta-amyloidosis was found in 16/18 marmosets aged <10 yrs and 8/9 marmosets aged >10 yrs, injected intracerebrally with human or marmoset brain homogenate containing beta-amyloid 1-8 years previously. It was found in only 2/12 marmosets aged <10 yrs and 1/15 marmosets aged >10 yrs, injected with synthetic Abeta-peptides, CSF, or brain tissue which did not contain beta-amyloid. Cerebral beta-amyloidosis was found in 0/11 uninjected marmosets aged <10 yrs and in 5/29 uninjected marmosets aged >10 yrs. The beta-amyloidosis comprised small and large vessel angiopathy and some plaques throughout cortex and was qualitatively similar in injected marmosets and, when present, in uninjected marmosets. Of those injected marmosets which were positive, the amount of beta-amyloidosis was unrelated to age or incubation times but the 3 injected marmosets without beta-amyloidosis had incubation times of <3.5 years. We conclude that beta-amyloid, or associated factors, can initiate or accelerate the process of cerebral amyloidosis in primates.

  2. UNC13A influences survival in Italian ALS patients: a population-based study

    PubMed Central

    Chiò, Adriano; Mora, Gabriele; Restagno, Gabriella; Brunetti, Maura; Ossola, Irene; Barberis, Marco; Ferrucci, Luigi; Canosa, Antonio; Manera, Umberto; Moglia, Cristina; Fuda, Giuseppe; Traynor, Bryan J.; Calvo, Andrea

    2012-01-01

    The common variant rs12608932, located within an intron of UNC13A gene on chromosome 19p13.3, has been suggested to influence susceptibility to ALS, as well as survival, in patients of north European descent. To examine this possibility further, we evaluated the association of rs12608932 with susceptibility and survival in a population-based cohort of 500 Italian ALS patients and 1,457 Italian control samples. Although rs12608932 was not associated to ALS susceptibility in our series (p=0.124), it was significantly associated with survival under the recessive model (median survival for AA/AC genotypes = 3.5 years [IQR 2.2–6.4]; CC = 2.5 years [IQR 1.6–4.2]; p=0.017). Furthermore, rs12608932 genotype remained an independent prognostic factor in Cox multivariable analysis adjusting for other factors known to influence survival (p=0.023). Overall, minor allele carrier status of rs12608932 was strongly associated with an ~1-year reduction of survival in ALS patients, making it a significant determinant of phenotype variation. The identification of UNC13A as a modifier of prognosis among sporadic ALS patients potentially provides a new therapeutic target aimed at slowing disease progression. PMID:22921269

  3. Testicular amyloidosis in hamsters experimentally infected with Leishmania donovani.

    PubMed Central

    Gonzalez, J. L.; Gallego, E.; Castaño, M.; Rueda, A.

    1983-01-01

    Thirty hamsters were inoculated intraperitoneally with Leishmania donovani. Testes were examined grossly and histologically by light and electron microscopy. Progressive testicular atrophy developed. Spermatogenic cells of the seminiferous tubules showed vacuolar degeneration and decreased in number leading to a total azoospermia in the final weeks of the pathological process. Lymphoplasmocytic infiltrates with macrophages containing leishmanias appeared in the intertubular space. Amyloid deposits in the intertubular space and tubular basement membrane were identified by optical and ultrastructural methods. It has been suggested that testicular amyloidosis may have a pathogenic mechanism related to a dysfunction of plasma cells and stimulation of the reticuloendothial system, due to the antigenic character of the parasite. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6639870

  4. Mechanisms of Islet Amyloidosis Toxicity in Type 2 Diabetes

    PubMed Central

    Abedini, Andisheh; Schmidt, Ann Marie

    2014-01-01

    Amyloid formation by the neuropancreatic hormone, islet amyloid polypeptide (IAPP or amylin), one of the most amyloidogenic sequences known, leads to islet amyloidosis in type 2 diabetes and to islet transplant failure. Under normal conditions, IAPP plays a role in the maintenance of energy homeostasis by regulating several metabolic parameters, such as satiety, blood glucose levels, adiposity and body weight. The mechanisms of IAPP amyloid formation, the nature of IAPP toxic species and the cellular pathways that lead to pancreatic β-cell toxicity are not well characterized. Several mechanisms of toxicity, including receptor and non-receptor-mediated events, have been proposed. Analogs of IAPP have been approved for the treatment of diabetes and are under investigation for the treatment of obesity. PMID:23337872

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

    PubMed Central

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

    2016-01-01

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

  6. Clinical Experiments of Communication by ALS Patient Utilizing Detecting Event-Related Potential

    NASA Astrophysics Data System (ADS)

    Kanou, Naoyuki; Sakuma, Kenji; Nakashima, Kenji

    Amyotrophic Lateral Sclerosis(ALS) patients are unable to successfully communicate their desires, although their mentality is normal, and so, the necessity of Communication Aids(CA) for ALS patients is realized. Therefore, the authors are focused on Event-Related Potential(ERP) which is elicited primarily for the target by visual and auditory stimuli. P200, N200 and P300 are components of ERP. These are potentials that are elicited when the subject focuses attention on stimuli that appears infrequently. ALS patient participated in two experiments. In the first experiment, a target word out of five words on a computer display was specified. The five words were linked to an each electric appliance, allowing the ALS patient to switch on a target appliance by ERP. In the second experiment, a target word in a 5×5 matrix was specified by measure of ERP. The rows and columns of the matrix were reversed randomly. The word on a crossing point of rows and columns including the target word, was specified as the target word. The rate of correct judgment in the first and second experiments were 100% in N200 and 96% in P200. For practical use of this system, it is very important to determine suitable communication algorithms for each patient by performing these experiments evaluating the results.

  7. Case report of a computer-assisted psychotherapy of a patient with ALS.

    PubMed

    García Pérez, Ana Isabel; Dapueto, Juan J

    2014-01-01

    This case describes a psychotherapy intervention in a patient in advanced stages of ALS. The inability for verbal communication at these stages necessitated the inclusion of a computational system to favor augmentative and alternative communication (AAC) to provide psychological care. The association of this device and software with ongoing psychotherapy acted in a synergistic manner. AAC devices made it possible to maintain patient-therapist communication and provided material support for psychotherapy despite severe speech limitations. This bimodal protocol of intervention resulted in better symptom control, improved communication with the team and family, reduction of psychological distress, promotion of autonomy, dignity, and self-esteem. The novelty of this communication is to report how the regular psychological care could be adapted to the patient circumstances using a computer device. Clinical trials will be required to evaluate the effectiveness of this mode of psychotherapy for the general population of ALS patients. PMID:25492716

  8. Tracheostomy with invasive ventilation for ALS patients: neurologists' roles in the US and Japan.

    PubMed

    Rabkin, Judith; Ogino, Mieko; Goetz, Raymond; McElhiney, Martin; Marziliano, Allison; Imai, Takashi; Atsuta, Naoki; Morita, Mitsuya; Tateishi, Takahisa; Matsumura, Tsuyoshi; Mitsumoto, Hiroshi

    2013-03-01

    Our objective was to determine whether substantial differences in rates of TIV utilization in the U.S. and Japan are associated with the role of the treating neurologist. Questionnaires in English and Japanese were sent to neurologists who treated ALS patients in both countries. Questions included queries about rates of TIV use in their practices, level of encouragement of TIV use, the role of the neurologist in TIV decision making, management of patient/family requests to discontinue TIV once initiated, and personal choices if neurologists themselves had ALS. Results showed that 84% of American neurologists reported fewer than 10% of their patients had TIV, compared to 32% of Japanese. Americans less often encouraged TIV use (79% of American and 36% of Japanese seldom or never suggested or encouraged TIV). Finally, neurologists were asked whether they would choose TIV for themselves in the hypothetical scenario where they had ALS: over 70% of both groups declined TIV for themselves. In conclusion, consistent with past findings, Japanese neurologists were more likely to recommend TIV and more of their patients received TIV. Both groups believed their recommendations influence patient decisions. While Americans seldom recommended TIV to patients and most would not choose TIV for themselves, Japanese neurologists' recommendations and personal choices diverged.

  9. AB 4. Lung function and disability in patients with ALS at the time of respiratory assessment

    PubMed Central

    Siopi, Dimitra; Perantoni, Eleni; Michailidis, Vasilis; Alexiadis, Alexandros; Mourouzidou, Vasiliki; Tsara, Venetia

    2012-01-01

    Background Amyotrophic Lateral Sclerosis (ALS) affects the respiratory function of patients throughout the disease progress. Prompt diagnosis of pulmonary involvement is important in order to decide the ventilator support of the patients. Patients and methods We studied 54 ALS patients, who visit our chest department because of respiratory symptoms, by spirometry, arterial blood gases and respiratory muscle strength assessment (MIP, MEP). Time from diagnosis, ALSFS and demographic characteristics of all subjects were recorded. Results The time elapsed between onset of symptoms and diagnosis of ALS was 12.2±16 months and the time between diagnosis and the first assessment of respiratory function was 13.9±11 month. Twenty four patients presented with medullary symptoms. Pulmonary examination took place after 13.3±18.8 months from the diagnosis and after 10±7.3 months in patients with peripheral symptoms. Statistical significant correlation was observed between ALSFS and the time elapsed until the respiratory system examination (r=–0.483, P<0.05). Respiratory function measurements were: FVC 53.8±23%, FEV1 53.6±24%, PaO2 71.6±13.5 mmHg, PaCO2 43.4±9.2 mmHg, MIP 28.4±21 cmH2O, MEP 39.1±22.1 cmH2O. Seven patients had been hospitalized in ICU because of acute respiratory failure. They had statistical significant higher PaCO2 (P<0.05) than the other patients. Twenty nine patients accepted to use non invasive ventilation (NIV). Statistical significant difference was noted in ALSFS (P<0.05) in FVC (P<0.05), PaCO2 (P<0.001) PaO2 (P<0.01) between them and the rest of the group. Conclusions The baseline examination of pulmonary function in ALS patients was overdue, even in patients with medullary symptoms. Physical and respiratory functions were both reduced. Physicians related to ALS disease should be vigilant aiming at the prompt management of the respiratory consequences during the disease progress.

  10. Hypnosis-based psychodynamic treatment in ALS: a longitudinal study on patients and their caregivers

    PubMed Central

    Kleinbub, Johann R.; Palmieri, Arianna; Broggio, Alice; Pagnini, Francesco; Benelli, Enrico; Sambin, Marco; Sorarù, Gianni

    2015-01-01

    Background: Evidence of psychological treatment efficacy is strongly needed in ALS, particularly regarding long-term effects. Methods: Fifteen patients participated in a hypnosis treatment and self-hypnosis training protocol after an in-depth psychological and neurological evaluation. Patients' primary caregivers and 15 one-by-one matched control patients were considered in the study. Measurements of anxiety, depression and quality of life (QoL) were collected at the baseline, post-treatment, and after 3 and 6 months from the intervention. Bayesian linear mixed-models were used to evaluate the impact of treatment and defense style on patients' anxiety, depression, QoL, and functional impairment (ALSFRS-r), as well as on caregivers' anxiety and depression. Results: The statistical analyses revealed an improvement in psychological variables' scores immediately after the treatment. Amelioration in patients' and caregivers' anxiety as well as caregivers' depression, were found to persist at 3 and 6 months follow-ups. The observed massive use of primitive defense mechanisms was found to have a reliable and constant buffer effect on psychopathological symptoms in both patients and caregivers. Notably, treated patients decline in ALSFRS-r score was observed to be slower than that of control group's patients. Discussion: Our brief psychodynamic hypnosis-based treatment showed efficacy both at psychological and physical levels in patients with ALS, and was indirectly associated to long-lasting benefits in caregivers. The implications of peculiar psychodynamic factors and mind-body techniques are discussed. Future directions should be oriented toward a convergence of our results and further psychological interventions, in order to delineate clinical best practices for ALS. PMID:26136710

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

    PubMed

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

    2014-01-01

    Cardiac amyloidosis (CA) is a disorder characterized by amyloid fibrils deposition in cardiac interstitium; it results in a restrictive cardiomyopathy with heart failure (HF) and conduction abnormalities. The "gold standard" for diagnosis of CA is myocardial biopsy but possible sampling errors and procedural risks, limit it's use. Magnetic resonance (RMN) offers more information than traditional echocardiography and allows diagnosis of CA but often it's impossible to perform. We report the case of a man with HF and symptomatic bradyarrhythmia that required an urgent pacemaker implant. Echocardiography was strongly suggestive of CA but wasn't impossible to perform an RMN to confirm this hypothesis because the patient was implanted with a definitive pacemaker. So was performed a Speckle Tracking Echocardiography (STE) and a 3D echocardiography: STE allows to differentiate CA from others hypertrophic cardiomyopathy by longitudinal strain value < 12% and 3D echocardiography shows regional left ventricular dyssynchrony with a characteristic temporal pattern of dispersion of regional volume systolic change. On the basis of these results, finally was performed an endomyocardial biopsy that confirmed the diagnosis of CA. This case underlines the importance of news, noninvasive techniques such as eco 3D and STE for early diagnosis of CA, especially when RMN cannot be performed.

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

    PubMed

    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

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

    PubMed

    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

  14. Agraphia in intellectually normal Japanese patients with ALS: omission of kana letters.

    PubMed

    Satoh, Masayuki; Takeda, Katsuhiko; Kuzuhara, Shigeki

    2009-09-01

    To investigate the occurrence of a writing defect, omission of kana letters (OKL), in intellectually normal Japanese patients with amyotrophic lateral sclerosis (ALS), and define the neuroimaging profile of OKL. Sixteen Japanese adults (10 men and 6 women), similar in age (mean 62.9 +/- 9.9 years) and level of education (mean 12.6 +/- 2.13 years), with early-stage, classical ALS (mean duration 15.9 +/- 5.45 months) were investigated, including tests of motor function and ALS progression; intellectual function including writing ability; and neuroimaging, with follow-up of 1 year. Main outcome measures were as follows: Raven's Colored Progressive Matrices (RCPM: intellect and psychomotor speed); one-minute verbal fluency measurement; paired associate word-learning test (PAWLT); Western Aphasia Battery (WAB); moraic segmentation test; magnetic resonance imaging (MRI); and (123)I-isopropyl amphetamine ((123)I-IMP) or (99m)Tc-ethylcysteinate dimmer (ECD) single photon emission tomography (SPECT). Three patients (18.8%) showed OKL (WAB), with disturbance in moraic segmentation. One patient showed decreased blood flow to the bilateral frontal lobes by (123)I-IMP-SPECT. Patients with OKL did not differ significantly from those without in the RCPM (intellect), RCPM (time), verbal fluency, or PAWLT (p = 0.10, 0.84, 0.63, 0.55). Although motor dysfunction and weakness progressed during follow-up, none developed symptoms of dementia. The OKL may develop as a relatively early cognitive symptom in intellectually normal Japanese patients with classical ALS. The neuroimaging profile of OKL remains uncertain.

  15. Working memory in ALS patients: preserved performance but marked changes in underlying neuronal networks.

    PubMed

    Zaehle, Tino; Becke, Andreas; Naue, Nicole; Machts, Judith; Abdulla, Susanne; Petri, Susanne; Kollewe, Katja; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Müller, Notger G

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which affects the motor system but also other frontal brain regions. In this study we investigated changes in functional neuronal networks including posterior brain regions that are not directly affected by the neurodegenerative process. To this end, we analyzed the contralateral delay activity (CDA), an ERP component considered an online marker of memory storage in posterior cortex, while 23 ALS patients and their controls performed a delayed-matching-to-sample working memory (WM) task. The task required encoding of stimuli in the cued hemifield whilst ignoring stimuli in the other hemifield. Despite their unimpaired behavioral performance patients displayed several changes in the neuronal markers of the memory processes. Their CDA amplitude was smaller; it showed less load-dependent modulation and lacked the reduction observed when controls performed the same task three months later. The smaller CDA in the patients could be attributed to more ipsilateral cortical activity which may indicate that ALS patients unnecessarily processed the irrelevant stimuli as well. The latter is presumably related to deterioration of the frontal cortex in the patient group which was indicated by slight deficits in tests of their executive functions that increased over time. The frontal pathology presumably affected their top-down control of memory storage in remote regions in the posterior brain. In sum, the present results demonstrate functional changes in neuronal networks, i.e. neuroplasticity, in ALS that go well beyond the known structural changes. They also show that at least in WM tasks, in which strategic top-down control demands are relatively low, the frontal deficit can be compensated for by intact low level processes in posterior brain regions.

  16. Patient with amyloidoma of the ulnar nerve and salivary glands.

    PubMed

    Salameh, Johnny; Baran, Johanna L; Tick Chong, Peter Siao

    2009-12-01

    Amyloidomas of the peripheral nervous system have been reported rarely. We describe a patient with a history of localized amyloidosis of the salivary glands who presented a few years later with paresthesias of her left medial arm, forearm, and fifth digit. A mass affecting the left ulnar nerve was confirmed by MRI studies. It was excised and proven on pathological examination to be an amyloidoma. The benign course of this patient's illness is consistent with localized amyloidosis affecting two different organs.

  17. Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis.

    PubMed

    Paris, Daniel; Patel, Nikunj; DelleDonne, Anthony; Quadros, Amita; Smeed, Robert; Mullan, Michael

    2004-08-01

    Abeta peptides are naturally occurring peptides, which are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). In AD cases, levels of soluble and insoluble Abeta peptides increase in the brain as well as in the cerebrovasculature, a phenomenon that does not occur in extra-cranial vessels. There are frequently anomalies in the cerebrovasculature in AD, and despite increases in several pro-angiogenic factors in AD brain, evidence for increased vascularity is lacking; in fact there is evidence to the contrary. It has also been recently shown that Abeta peptides may have profound anti-angiogenic effects in vitro and in vivo. We therefore investigated whether there is evidence for altered angiogenesis in the vasculature in a transgenic mouse model of Abeta amyloidosis (Tg APPsw line 2576). In vitro, the formation of capillary-like structures on a reconstituted extracellular matrix by endothelial cells isolated from Tg APPsw is impaired. Ex vivo, the sprouting of new capillaries from arterial explants (over expressing Abeta) isolated from 9-month-old Tg APPsw is reduced compared to arterial explants isolated from control littermates. In addition, Tg APPsw mice show a reduction in vascular density in the cortex and hippocampus compared to control littermates. Altogether, our data suggest that the over expression of APPsw in the vasculature may oppose angiogenesis.

  18. Initial test of a T9-like P300-based speller by an ALS patient

    NASA Astrophysics Data System (ADS)

    Ron-Angevin, R.; Varona-Moya, S.; da Silva-Sauer, L.

    2015-08-01

    Objective. Visual P300-based brain-computer interface spellers offer a useful communication channel for locked-in patients, who are completely dependent in their daily lives. One of the research goals for these systems is to achieve greater communication rates by means of modifying some features of their interfaces, e.g., reducing the matrix size. However, such modifications may not work well with disabled end-users, such as patients of amyotrophic lateral sclerosis (ALS), due to a supposed reduction of their cognitive resources. The purpose of the present study was to provide a proof of concept that ALS patients could efficiently use a P300-based speller with a 4 × 3 symbol matrix based on the T9 interface developed for mobile phones. Approach. We conducted an experiment with a sample of 11 able-bodied participants and one locked-in patient with ALS. All participants tested our T9-like visual P300-based speller and also two different 7 × 6 matrix spellers based on Farwell and Donchin’s classic proposal—one of them included a word predictor system like the T9-like speller did. Main results. The performance analyses indicated that the locked-in patient benefited from using a reduced matrix size as much as healthy users did, spelling words almost 1.6 times faster and equally accurately when using the T9-like speller than when using the alternative spellers. Significance. Due to counting on only one locked-in patient, the current work constitutes a feasibility study. The actual usability of systems such as the one proposed in this paper should be determined by means of studies with a greater number of end-users in real-life conditions.

  19. Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients

    PubMed Central

    Keskin, Isil; Forsgren, Elin; Lange, Dale J.; Weber, Markus; Birve, Anna; Synofzik, Matthis; Gilthorpe, Jonathan D.; Andersen, Peter M.; Marklund, Stefan L.

    2016-01-01

    Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS. PMID:26919046

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

    PubMed

    Gonçalves, Allan Christian Pieroni; Moritz, Rodrigo Bernal da Costa; Monteiro, Mário Luiz Ribeiro

    2011-01-01

    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.

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

    PubMed Central

    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

  2. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

    PubMed Central

    Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.

    2015-01-01

    Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925

  3. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients.

    PubMed

    Jackson, Carlayne E; Gronseth, Gary; Rosenfeld, Jeffrey; Barohn, Richard J; Dubinsky, Richard; Simpson, C Blake; McVey, April; Kittrell, Pamela P; King, Ruth; Herbelin, Laura

    2009-02-01

    Twenty ALS patients with sialorrhea refractory to medical therapy were enrolled in this double-blind, randomized study to receive either 2,500 U of botulinum toxin type B (BTxb) or placebo into the bilateral parotid and submandibular glands using electromyographic guidance. Patients who received BTxb reported a global impression of improvement of 82% at 2 weeks compared to 38% of those who received placebo (P < 0.05). This significant effect was sustained at 4 weeks. At 12 weeks, 50% of patients who received BTxb continued to report improvement compared to 14% of those who received placebo. There were no significant adverse events, including dysphagia, in the BTxb group, and there was no significant increase in the rate of decline of vital capacity.

  4. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis.

    PubMed Central

    Soutar, A K; Hawkins, P N; Vigushin, D M; Tennent, G A; Booth, S E; Hutton, T; Nguyen, O; Totty, N F; Feest, T G; Hsuan, J J

    1992-01-01

    A mutation in the gene for apolipoprotein AI (apoAI) was identified in an English family with autosomal dominant non-neuropathic systemic amyloidosis. The plasma of all affected individuals contained a variant apoAI with one additional charge, as well as normal apoAI. The propositus was heterozygous; the coding region of his apoAI gene contained both the normal sequence and a single-base substitution changing the codon for residue 60 of the mature protein from CTG (leucine) to CGG (arginine). Allele-specific oligonucleotide hybridization showed that the other affected individuals were also heterozygotes and that there was concordance of the mutant allele with the presence of variant plasma apoAI. Amyloid fibrils isolated from the spleen of the propositus consisted of proteins that ran as a doublet with an apparent mass of approximately 10 kDa in SDS/PAGE and a trace band at 28 kDa. Electrospray mass spectrometry of the purified 10-kDa material revealed components with mass corresponding to the N-terminal 88, 92, 93, and 94 residues of apoAI each with substitution of arginine for leucine. These observations were confirmed by direct protein sequencing and laser desorption time-of-flight mass analysis. No material with the normal apoAI sequence was detected. The trace band at 28 kDa yielded the N-terminal sequence of mature apoAI, indicating that intact or minimally degraded apoAI was also present in the fibril preparation. Discovery of this mutation and the detailed characterization of the apoAI fragments that form the amyloid fibrils open additional avenues for investigation of amyloidogenesis. Images PMID:1502149

  5. Clasmatodendrosis and β-amyloidosis in aging hippocampus.

    PubMed

    Mercatelli, Raffaella; Lana, Daniele; Bucciantini, Monica; Giovannini, Maria Grazia; Cerbai, Francesca; Quercioli, Franco; Zecchi-Orlandini, Sandra; Delfino, Giovanni; Wenk, Gary L; Nosi, Daniele

    2016-04-01

    Alterations of the tightly interwoven neuron/astrocyte interactions are frequent traits of aging, but also favor neurodegenerative diseases, such as Alzheimer disease (AD). These alterations reflect impairments of the innate responses to inflammation-related processes, such as β-amyloid (Aβ) burdening. Multidisciplinary studies, spanning from the tissue to the molecular level, are needed to assess how neuron/astrocyte interactions are influenced by aging. Our study addressed this requirement by joining fluorescence-lifetime imaging microscopy/phasor multiphoton analysis with confocal microscopy, implemented with a novel method to separate spectrally overlapped immunofluorescence and Aβ autofluorescence. By comparing data from young control rats, chronically inflamed rats, and old rats, we identified age-specific alterations of neuron/astrocyte interactions in the hippocampus. We found a correlation between Aβ aggregation (+300 and +800% of aggregated Aβ peptide in chronically inflamed and oldvs.control rats, respectively) and fragmentation (clasmatodendrosis) of astrocyte projections (APJs) (+250 and +1300% of APJ fragments in chronically inflamed and oldvs.control rats, respectively). Clasmatodendrosis, in aged rats, associates with impairment of astrocyte-mediated Aβ clearance (-45% of Aβ deposits on APJs, and +33% of Aβ deposits on neurons in oldvs.chronically inflamed rats). Furthermore, APJ fragments colocalize with Aβ deposits and are involved in novel Aβ-mediated adhesions between neurons. These data define the effects of Aβ deposition on astrocyte/neuron interactions as a key topic in AD biology.-Mercatelli, R., Lana, D., Bucciantini, M., Giovannini, M. G., Cerbai, F., Quercioli, F., Zecchi-Orlandini, S., Delfino, G., Wenk, G. L., Nos, D. Clasmatodendrosis and β-amyloidosis in aging hippocampus. PMID:26722005

  6. Comparison of two percutaneous radiological gastrostomy tubes in the nutritional management of ALS patients.

    PubMed

    Rio, Alan; Ampong, Mary Ann; Turner, Martin R; Shaw, Ashley S; Al-Chalabi, Ammar; Shaw, Chris E; Leigh, P Nigel; Sidhu, Paul S

    2005-09-01

    Patient care and minimizing complications post gastrostomy have to date received little attention in ALS patients. We compare the complications associated with pigtail and mushroom type percutaneous radiological gastrostomy tubes in this patient group. Patients requiring PRG received either Wills-Oglesby or the skin level Entristar. Retrospective review of the clinical notes was performed capturing demographic data, peristomal infection, tube displacement, tube failure, nutritional status, site of disease onset, and survival. Thirty-five patients (Group 1) had the Wills-Oglesby tube of which 14 (40%) tubes required replacement. The Entristar tube was inserted in 29 patients (Group 2) where 8 (28%) required replacement (NS). The incidence of infection was significantly lower with the Entristar tube, (p<0.001). The mean time to tube removal in Group 2 was 223 days (SD 147; range 71-494 days) due to 'buried bumper syndrome'. We conclude that the Entristar skin level gastrostomy tube is associated with a reduction in peristomal infection, tube failure and blockage compared with the Wills-Oglesby tube.

  7. Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis

    PubMed Central

    Martin, Emily B.; Williams, Angela; Richey, Tina; Stuckey, Alan; Heidel, R. Eric; Kennel, Stephen J.; Wall, Jonathan S.

    2016-01-01

    Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US. PMID:26936002

  8. Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis.

    PubMed

    Martin, Emily B; Williams, Angela; Richey, Tina; Stuckey, Alan; Heidel, R Eric; Kennel, Stephen J; Wall, Jonathan S

    2016-03-03

    Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US.

  9. D18G transthyretin is monomeric, aggregation prone, and not detectable in plasma and cerebrospinal fluid: a prescription for central nervous system amyloidosis?

    PubMed

    Hammarström, Per; Sekijima, Yoshiki; White, Joleen T; Wiseman, R Luke; Lim, Amareth; Costello, Catherine E; Altland, Klaus; Garzuly, Ferenc; Budka, Herbert; Kelly, Jeffery W

    2003-06-10

    Over 70 transthyretin (TTR) mutations facilitate amyloidosis in tissues other than the central nervous system (CNS). In contrast, the D18G TTR mutation in individuals of Hungarian descent leads to CNS amyloidosis. D18G forms inclusion bodies in Escherichia coli, unlike the other disease-associated TTR variants overexpressed to date. Denaturation and reconstitution of D18G from inclusion bodies afford a folded monomer that is destabilized by 3.1 kcal/mol relative to an engineered monomeric version of WT TTR. Since TTR tetramer dissociation is typically rate limiting for amyloid formation, the monomeric nature of D18G renders its amyloid formation rate 1000-fold faster than WT. It is perplexing that D18G does not lead to severe early onset systemic amyloidosis, given that it is the most destabilized TTR variant characterized to date, more so than variants exhibiting onset in the second decade. Instead, CNS impairment is observed in the fifth decade as the sole pathological manifestation; however, benign systemic deposition is also observed. Analysis of heterozygote D18G patient's serum and cerebrospinal fluid (CSF) detects only WT TTR, indicating that D18G is either rapidly degraded postsecretion or degraded within the cell prior to secretion, consistent with its inability to form hybrid tetramers with WT TTR. The nondetectable levels of D18G TTR in human plasma explain the absence of an early onset systemic disease. CNS disease may result owing to the sensitivity of the CNS to lower levels of D18G aggregate. Alternatively, or in addition, we speculate that a fraction of D18G made by the choroid plexus can be transiently tetramerized by the locally high thyroxine (T(4)) concentration, chaperoning it out into the CSF where it undergoes dissociation and amyloidogenesis due to the low T(4) CSF concentration. Selected small molecule tetramer stabilizers can transform D18G from a monomeric aggregation-prone state to a nonamyloidogenic tetramer, which may prove to be a

  10. Intestinal pseudo-obstruction due to amyloidosis of the colon in association with an intestinal plasmacytoma.

    PubMed Central

    Nicholl, D.; Jones, T.

    1991-01-01

    A case of large bowel pseudo-obstruction due to colonic amyloidosis associated with an intestinal plasmacytoma is described. The association of an intestinal plasmacytoma with massive local amyloid deposition has not to our knowledge been previously reported. Images Figure 1 Figure 2 PMID:1800969

  11. Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes

    PubMed Central

    Gaffney, Patricia M.; Imai, Denise M.; Clifford, Deana L.; Ghassemian, Majid; Sasik, Roman; Chang, Aaron N.; O’Brien, Timothy D.; Coppinger, Judith; Trejo, Margarita; Masliah, Eliezer; Munson, Linda; Sigurdson, Christina

    2014-01-01

    Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins. PMID:25429466

  12. Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients

    PubMed Central

    Mitne-Neto, Miguel; Machado-Costa, Marcela; Marchetto, Maria C.N.; Bengtson, Mario H.; Joazeiro, Claudio A.; Tsuda, Hiroshi; Bellen, Hugo J.; Silva, Helga C.A.; Oliveira, Acary S.B.; Lazar, Monize; Muotri, Alysson R.; Zatz, Mayana

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is an incurable neuromuscular disease that leads to a profound loss of life quality and premature death. Around 10% of the cases are inherited and ALS8 is an autosomal dominant form of familial ALS caused by mutations in the vamp-associated protein B/C (VAPB) gene. The VAPB protein is involved in many cellular processes and it likely contributes to the pathogenesis of other forms of ALS besides ALS8. A number of successful drug tests in ALS animal models could not be translated to humans underscoring the need for novel approaches. The induced pluripotent stem cells (iPSC) technology brings new hope, since it can be used to model and investigate diseases in vitro. Here we present an additional tool to study ALS based on ALS8-iPSC. Fibroblasts from ALS8 patients and their non-carrier siblings were successfully reprogrammed to a pluripotent state and differentiated into motor neurons. We show for the first time that VAPB protein levels are reduced in ALS8-derived motor neurons but, in contrast to over-expression systems, cytoplasmic aggregates could not be identified. Our results suggest that optimal levels of VAPB may play a central role in the pathogenesis of ALS8, in agreement with the observed reduction of VAPB in sporadic ALS. PMID:21685205

  13. K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis.

    PubMed

    Mustata, Mirela; Capone, Ricardo; Jang, Hyunbum; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh; Nussinov, Ruth

    2009-10-21

    Beta(2)-microglobulin (beta(2)m) amyloid deposits are linked to dialysis-related amyloidosis (DRA) in hemodialysis patients. The mechanism by which beta(2)m causes DRA is not understood. It is also unclear whether only the full-length beta(2)m induces pathophysiology or if proteolytic fragments are sufficient for inducing this effect. Ser20-Lys41 (K3) is a digestion fragment of full-length beta(2)m. Solid state NMR (ssNMR) combined with X-ray diffraction and atomic force microscopy (AFM) revealed the characteristic oligomeric amyloid conformation of the U-turn beta-strand-turn-beta-strand motif stacked in parallel and stabilized by intermolecular interactions also shown by Abeta(9-40)/Abeta(17-42) and the CA150 WW domain. Here we use the K3 U-turn atomic coordinates and molecular dynamic (MD) simulations to model K3 channels in the membrane. Consistent with previous AFM imaging of other amyloids that show channel-like structures in the membrane, in the simulations K3 also forms ion channels with 3-6 loosely attached mobile subunits. We carry out AFM, single channel electrical recording, and fluorescence imaging experiments. AFM images display 3D ion channel topography with shapes, morphologies, and dimensions consistent with the theoretical model. Electrical conductance measurements indicate multiple single channel conductances, suggesting that various K3 oligomer sizes can constitute the channel structure. Fluorescence measurements in kidney cells show channel-mediated cell calcium uptake. These results suggest that the beta(2)m-induced DRA can be mediated by ion channels formed by its K3 fragment. Because the beta-strand-turn-beta-strand motif appears to be a universal amyloid feature, its ability to form ion channels further suggests that the motif may play a generic role in toxicity.

  14. The effects of lung volume recruitment on coughing and pulmonary function in patients with ALS.

    PubMed

    Cleary, Stuart; Misiaszek, John E; Kalra, Sanjay; Wheeler, Sonya; Johnston, Wendy

    2013-03-01

    Our objective was to study the intensity and duration of the effects of lung volume recruitment, a manual breath stacking technique, on pulmonary function and coughing in individuals with amyotrophic lateral sclerosis (ALS). Twenty-nine individuals with ALS participated in this study. A cross-over research design was used to compare effects of lung volume recruitment to a control condition. Treatment outcome measures included forced vital capacity (FVC), sniff nasal pressure (SnP) and peak cough flow (PCF). Results demonstrated that LVR had a significantly positive effect on FVC for up to 15 min following treatment but did not have a facilitative effect on SnP at any time-point. LVR had a significantly positive effect on PCF during unassisted coughing at both 15 min and 30 min following treatment, and there was no significant decrease in flow rates from baseline to 30 min later. In conclusion, lung volume recruitment may be an effective treatment for improving coughing and pulmonary function in individuals with ALS. Future research should be focused on determining patient characteristics that contribute to response to treatment, as well as randomized controlled trials of the technique.

  15. Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis

    SciTech Connect

    Wizenberg, T.A.; Muz, J.; Sohn, Y.H.; Samlowski, W.; Weissler, A.M.

    1982-04-01

    Ten consecutive patients with tissue-proven amyloidosis, seven of whom presented with congestive heart failure, were found to exhibit intense diffuse uptake of technetium-99m-pyrophosphate (Tc-99m-PYP) on cardiac radionuclide imaging. The patients exhibited echocardiographic and systolic time interval abnormalities suggesting combined restrictive and congestive cardiomyopathic changes. On M-mode echocardiograms, there was symmetrically increased thickness of the interventricular septum and left ventricular (LV) posterior wall in diastole (10 of 10), decreased fractional shortening of the LV minor axis diameter in systole (eight of nine), and decreased percent thickening of the LV minor axis diameter in systole (eight of nine) and LV posterior wall (10 of 10) in systole. Three patients demonstrated enlarged LV end-diastolic diameter. All 10 patients had abnormal PEP/LVET and eight had shortened LVETI. When combined with noninvasive tests of LV performance, positive myocardial pyrophosphate (PYP) scanning provides a new and useful adjunct in the diagnosis of amyloid heart disease.

  16. 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

    PubMed Central

    Hofmann, Nina P.; Giusca, Sorin; Klingel, Karin; Nunninger, Peter; Korosoglou, Grigorios

    2016-01-01

    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. PMID:27247807

  17. [Inconsistency between voltage of the electrocardiogram and the left ventricular wall thickness. diagnostic key in cardiac amyloidosis].

    PubMed

    Contreras, A; Beacon, E; Brenna, Eduardo J; Parisi, Gustavo R; Chamale, Roberto A; Gilardi, F; Bürguesser, M V; Salomone, O

    2013-01-01

    Restrictive cardiomyopathy is the least common form of cardiomyopathy, and the disease that most often cause it, is the system amyloidosis. We present a 62-year-old with a history of heart failure, which in its assessment highlights the discrepancy between the low voltage ventricular complexes in the electrocardiogram and the severity of left ventricular wall thickness on echocardiography. This discrepancy was the source of suspicion and subsequent confirmation of systemic amyloidosis with cardiac involvement.

  18. Increasing fatal AA amyloidosis in hunting falcons and how to identify the risk: a report from the United Arab Emirates.

    PubMed

    Hampel, Mirjam Ricarda; Kinne, Joerg; Wernery, Ulrich; Pospischil, Andreas; Kellermann, Josef; Linke, Reinhold Paul

    2009-01-01

    In hunting falcons, a fatal syndrome of wasting, weight loss, green mutes and, finally, sudden death of emaciated birds has been observed in the United Arab Emirates (UAE). Histological examination using Congo red has revealed amyloid in most organs, in particular in the liver, spleen, kidney, and adrenal glands. Moreover, a retrospective study revealed amyloidosis in 100 cases among a total of 623 necropsied falcons between August 1995 and March 2004 in Dubai/UAE (16%; varying from 8 to 30% in different raptor bird species). The amyloid was immunohistochemically classified as amyloid A (AA), which was confirmed by Western blot analysis and N-terminal amino acid sequence analysis, suggesting it to be secondary to a chronic inflammatory process. Retrospective analysis has indicated a significantly increased prevalence of bumble foot and visceral gout among falcons with amyloidosis. In addition, a significant increase of amyloidosis from 5.6% of necropsied falcons with amyloidosis in 1995 to 40.0% in 2004 has been noticed. Finally, a semi-quantitative serum test for falcon serum amyloid A (f-SAA) has been developed. Among 38 falcons with fatal AA amyloidosis, f-SAA was increased pathologically in 36, whereas f-SAA was elevated in only one of 15 apparently disease-free falcons (p < 0.001). This significant result indicates that a normal f-SAA will indicate a minimal or even absent risk of succumbing to AA amyloidosis.

  19. Protective Effects of Forskolin on Behavioral Deficits and Neuropathological Changes in a Mouse Model of Cerebral Amyloidosis.

    PubMed

    Owona, Brice Ayissi; Zug, Caroline; Schluesener, Hermann J; Zhang, Zhi-Yuan

    2016-07-01

    The production of amyloid-β peptides in the brains of patients with Alzheimer disease (AD) may contribute to memory loss and impairments in social behavior. Here, an efficient adenylate cyclase activator, forskolin, was orally administered by gavage (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, which serve as an animal model of cerebral amyloidosis. Analyses of nest construction, sociability, and immunohistochemical features were used to determine the effects of forskolin treatment. After a relatively short term of treatment (10 days), forskolin-treated transgenic mice showed restored nest construction ability (p < 0.05) and their sociability (p < 0.01). There was a reduction of Aβ plaque deposition in the cortex and in the hippocampus. Furthermore, expression of transforming growth factor β, glial fibrillary acidic protein, and Iba-1 in the cortex was reduced in the forskolin-treated group, suggesting regulation of the inflammatory response mediated by activated microglia and astrocytes in the brains of the APP/PS1 mice (p < 0.01). Taken together, these findings suggest that forskolin shows neuroprotective effects in APP/PS1 Tg mice and may be a promising drug in the treatment of patients with AD. PMID:27251043

  20. Is 18F-flutemetamol PET/CT able to reveal cardiac amyloidosis?

    PubMed

    Lhommel, Renaud; Sempoux, Christine; Ivanoiu, Adrian; Michaux, Lucienne; Gerber, Bernhard

    2014-08-01

    We report here the case of a 56-year-old man with well-documented cardiac light chain amyloidosis successfully imaged with F-flutemetamol PET/CT in 2011. A matched pair healthy volunteer was imaged in the same conditions, and no specific heart uptake could be detected. The present report suggests the potential benefit of this new pharmaceutical in this indication, as it has been recently reported for C-Pittsburgh compound B, but with the main advantage to benefit from the more practical half-life of F. Further prospective trials would, however, be required to define the potential impact of F-flutemetamol PET/CT in cardiac amyloidosis.

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

    PubMed

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

    1998-02-01

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

  2. Reactive eccrine syringofibroadenomatosis secondary to primary cutaneous amyloidosis: a novel association.

    PubMed

    Saggini, Andrea; Mully, Thaddeus

    2014-04-01

    We report the unprecedented case of reactive eccrine syringofibroadenoma (ESFA) secondary to primary cutaneous amyloidosis. A 62-year-old woman of Asian ethnicity presented with a pruritic rash on the back of long-standing duration. Physical examination revealed diffuse hyperpigmentation localized to the interscapular region; there were a multitude of hyperpigmented macules merged in a rippled pattern intermixed with scattered papules and cobblestone-like areas. A punch biopsy from a papule was taken. Histopathological examination revealed a network of epithelial strands and cords hanging from the epidermis and harboring foci of ductal differentiation. Eosinophilic collections of amorphous material were found between the epithelial strands, obscuring the superficial dermis. The microscopic picture was consistent with primary cutaneous amyloidosis associated with reactive ESFA. Results of histochemical and immunohistochemical staining confirmed the diagnosis. We speculate that pathogenetic mechanisms intrinsic to primary cutaneous amyloidosis, in addition to unknown genetic factors, resulted in clinical changes of lichen amyloidosus associated with an abnormal hyperplastic epithelial response with histopathological features of ESFA rather than the common epidermal change of acanthosis and hyperkeratosis. PMID:24325801

  3. Experience of services as a key outcome in amyotrophic lateral sclerosis (ALS) care: the case for a better understanding of patient experiences.

    PubMed

    Foley, Geraldine; Timonen, Virpi; Hardiman, Orla

    2012-08-01

    People with amyotrophic lateral sclerosis (ALS) frequently express dissatisfaction with services. Patient satisfaction with services in ALS care is not always measured and service user perspectives are not usually included when evaluating the outcomes of care. There is a lack of consensus on what constitutes satisfaction for patients in ALS care. To date, health care professionals' conceptualization of outcomes in ALS care has excluded measures of patient satisfaction with services. Exploring the context of the ALS service user experience of care will identify a conceptual framework that will include the domains of satisfaction with care for patients with ALS. An instrument that draws on the ALS patient perspective of services, developed on the basis of qualitative investigation, should be used to measure satisfaction with services. PMID:21998444

  4. Mouse model to study human A beta2M amyloidosis: generation of a transgenic mouse with excessive expression of human beta2-microglobulin.

    PubMed

    Zhang, Pengyao; Fu, Xiaoying; Sawashita, Jinko; Yao, Junjie; Zhang, Beiru; Qian, Jinze; Tomozawa, Hiroshi; Mori, Masayuki; Ando, Yukio; Naiki, Hironobu; Higuchi, Keiichi

    2010-06-01

    Patients on long-term hemodialysis can develop dialysis-related amyloidosis (DRA) due to deposition of beta(2)-microglobulin (beta(2)m) into amyloid fibrils (Abeta(2)M). Despite intensive biochemical studies, the pathogenesis of amyloid deposition in DRA patients remains poorly understood. To elucidate the mechanisms that underlie Abeta(2)M fibril formation in DRA, we generated transgenic mice that overexpress human beta(2)m protein in a mouse beta(2)m gene knockout background (hB2MTg(+/+) mB2m(+/+)). The hB2MTg(+/+)mB2m(-/-) mice express a high level of human beta(2)m protein in many tissues as well as a high plasma beta(2)m concentration (192.8 mg/L). This concentration is >100 times higher than that observed in healthy humans and >4 times higher than that detected in patients on dialysis. We examined spontaneous and amyloid fibril-induced amyloid deposition in these mice. Amyloid deposition of beta(2)m protein was not observed in aged or amyloid fibril injected animals. However, mouse senile apolipoprotein A-II amyloidosis (AApoAII) was detected, particularly in the joints of mice that were injected with AApoAII amyloid fibrils. This study demonstrates that this mouse model could be valuable in studying the components and conditions that promote DRA, and indicates that high plasma concentrations of hbeta(2)m as well as seeding with pre-existing amyloid fibrils may not be sufficient to induce Abeta(2)M.

  5. Amyloid goiter presented as a subacute thyroiditis-like symptom in a patient with hypersensitivity vasculitis.

    PubMed

    Nagai, Y; Ohta, M; Yokoyama, H; Takamura, T; Kobayashi, K I

    1998-06-01

    We present a 25-year-old woman with amyloid goiter due to hypersensitivity vasculitis, who developed transient thyrotoxicosis resembling subacute thyroiditis. She received prednisolone (20 mg/ day) for three years for hypersensitivity vasculitis, and was diagnosed as having secondary amyloidosis by biopsies of the stomach, rectum and kidneys. She noticed neck swelling with severe right neck tenderness, palpitation, hyperhidrosis and weight loss. An elastic firm diffuse goiter was palpable, and the upper pole of the right lobe was extremely tender. Her serum free T4 and T3 levels were high, and the serum TSH was suppressed to subnormal. She was positive for serum C-reactive protein. Anti-thyroidal autoantibodies were all negative. Her thyrotoxicosis subsided spontaneously within one week. Serum titers of antibodies to various viruses were unchanged during the clinical course for two weeks, but she was positive for HLA B35. Examination of a needle-biopsy specimen of the thyroid gland showed extensive amyloid deposition and no evidence of subacute thyroiditis. We considered her transient thyrotoxicosis to be associated with amyloid goiter. The clinical course of this case was similar to the subacute thyroiditis-like syndrome, first described by Ikenoue et al. When patients with primary or secondary amyloidosis have symptoms and signs of subacute thyroiditis, but develop an unusual course, amyloid goiter should be considered. PMID:9790279

  6. The full spectrum of ethical issues in the care of patients with ALS: a systematic qualitative review.

    PubMed

    Seitzer, F; Kahrass, H; Neitzke, G; Strech, D

    2016-02-01

    Dealing systematically with ethical issues in amyotrophic lateral sclerosis (ALS) care requires an unbiased awareness of all the relevant ethical issues. The aim of the study was to determine systematically and transparently the full spectrum of ethical issues in ALS care. We conducted a systematic review in Medline and Google Books (restricted to English and German literature published between 1993 and 2014). We applied qualitative text analysis and normative analysis to categorise the spectrum of ethical issues in ALS care. The literature review retrieved 56 references that together mentioned a spectrum of 103 ethical issues in ALS care. The spectrum was structured into six major categories that consist of first and second-order categories of ethical issues. The systematically derived spectrum of ethical issues in ALS care presented in this paper raises awareness and understanding of the complexity of ethical issues in ALS care. It also offers a basis for the systematic development of informational and training materials for health professionals, patients and their relatives, and society as a whole. Finally, it supports a rational and fair selection of all those ethical issues that should be addressed in health policies, position papers and clinical practice guidelines. Further research is needed to identify ways to systematically select the most relevant ethical issues not only in the clinical environment, but also for the development of clinical practice guidelines.

  7. [Radiologic and clinical aspects of osteoarticular amyloidosis caused by dialysis].

    PubMed

    Baldrati, L; Rocchi, A; Balbi, B; Bonsanto, R; Mughetti, M; Pasini, A; Feletti, C; Capponcini, C; Docci, D

    1991-06-01

    Many long-term (greater than 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 beta 2-microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1 +/- 13 years), undergoing chronic hemodialysis for 60-125 months, were examined for dialysis 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 majority 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 less than 0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p less than 0.0005) and shoulder pain (p less than 0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients and the value of diagnostic imaging in screening such patients for those lesions.

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

    PubMed Central

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

    2016-01-01

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

  9. Evaluation of 99mTc-MAMA-chrysamine G as an in vivo probe for amyloidosis.

    PubMed

    Dezutter, N A; Landman, W J; Jager, P L; de Groot, T J; Dupont, P J; Tooten, P C; Zekarias, B; Gruys, E; Verbruggen, A M

    2001-09-01

    To date, systemic amyloidosis is diagnosed histologically using Congo red staining or in vivo using iodine-123 labelled serum amyloid P component (123I-SAP) scintigraphy. We developed 99mTc-MAMA-CG, a 99mTc-labelled derivative of the lipophilic Congo red analogue chrysamine G (CG), as a possible alternative to 123I-SAP. In vivo 99mTc-MAMA-CG scintigraphy, performed in chickens with spontaneous joint amyloidosis, resulted as soon as 10 min after injection in scintigraphic images showing uptake of activity in amyloid-loaded organs (liver, joints). One of these chickens was studied also with 123I-SAP resulting in scintigraphic images revealing 123I-SAP binding to amyloid deposits in the liver. However, up to 11 h after injection no radioactivity was visible in the amyloid positive joints. In vitro autoradiography, performed on sections of chicken joints with Enterococcus faecalis induced amyloid arthropathy (chjAA), demonstrated the failure of 99mTc-MAMA-CG to bind significantly to amyloid deposits in the presence of 10 microM Congo red The specificity of 99mTc-MAMA-CG localisation was also established by the absence of 99mTc-MAMA-CG binding in non-amyloidotic organs in vitro and in vivo. 99mTc-MAMA-CG did not show any sign of acute toxicity. These findings establish the usefulness of 99mTc-MAMA-CG as a non-invasive in vivo diagnostic probe in chickens with amyloid arthropathy and suggest that it may also be applicable to human amyloidosis.

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

    PubMed

    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

  11. Patients with ALS can use sensorimotor rhythms to operate a brain-computer interface.

    PubMed

    Kübler, A; Nijboer, F; Mellinger, J; Vaughan, T M; Pawelzik, H; Schalk, G; McFarland, D J; Birbaumer, N; Wolpaw, J R

    2005-05-24

    People with severe motor disabilities can maintain an acceptable quality of life if they can communicate. Brain-computer interfaces (BCIs), which do not depend on muscle control, can provide communication. Four people severely disabled by ALS learned to operate a BCI with EEG rhythms recorded over sensorimotor cortex. These results suggest that a sensorimotor rhythm-based BCI could help maintain quality of life for people with ALS.

  12. Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and supervised counseling and exercise program. Methods/design This paper presents the study protocol: Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle, strength exercises using hand weights and relaxation exercise. Individual health counseling sessions include a self directed home walk program with a step counter. The primary endpoint is functional performance/exercise capacity (6 minute walk distance). The secondary endpoints are submaximal VO2 max test, sit to stand and bicep curl test, physical activity levels, patient reported outcomes (quality of life, anxiety and depression, symptom prevalence, intensity and interference). Evaluation of clinical outcomes will be explored including incidence of infection, hospitalization days, body mass index, time to recurrence and survival. Qualitative exploration of patients’ health behavior and experiences. Discussion PACE-AL will provide evidence of the effect of

  13. Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy.

    PubMed

    Loreth, Desirée; Ozmen, Laurence; Revel, Florent G; Knoflach, Frédéric; Wetzel, Philine; Frotscher, Michael; Metzger, Friedrich; Kretz, Oliver

    2012-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by brain accumulation of amyloid-β peptide and neurofibrillary tangles, which are believed to initiate a pathological cascade that results in progressive impairment of cognitive functions and eventual neuronal death. To obtain a mouse model displaying the typical AD histopathology of amyloidosis and tauopathy, we generated a triple-transgenic mouse line (TauPS2APP) by overexpressing human mutations of the amyloid precursor protein, presenilin2 and tau genes. Stereological analysis of TauPS2APP mice revealed significant neurodegeneration of GABAergic septo-hippocampal projection neurons as well as their target cells, the GABAergic hippocampal interneurons. In contrast, the cholinergic medial septum neurons remained unaffected. Moreover, the degeneration of hippocampal GABAergic interneurons was dependent on the hippocampal subfield and interneuronal subtype investigated, whereby the dentate gyrus and the NPY-positive interneurons, respectively, were most strongly affected. Neurodegeneration was also accompanied by a change in the mRNA expression of markers for inhibitory interneurons. In line with the loss of inhibitory neurons, we observed functional changes in TauPS2APP mice relative to WT mice, with strongly enhanced long-term potentiation in the medial-perforant pathway input to the dentate gyrus, and stereotypic hyperactivity. Our data indicate that inhibitory neurons are the targets of neurodegeneration in a mouse model of amyloidosis and tauopathy, thus pointing to a possible role of the inhibitory network in the pathophysiological and functional cascade of Alzheimer's disease.

  14. Molecular basis of a novel renal amyloidosis due to N184K gelsolin variant.

    PubMed

    Bonì, Francesco; Milani, Mario; Porcari, Riccardo; Barbiroli, Alberto; Ricagno, Stefano; de Rosa, Matteo

    2016-09-16

    Mutations in gelsolin are responsible for a systemic amyloidosis first described in 1969. Until recently, the disease was associated with two substitutions of the same residue, leading to the loss of the calcium binding site. Novel interest arose in 2014 when the N184K variant of the protein was identified as the etiological agent of a novel kidney-localized amyloidosis. Here we provide a first rationale for N184K pathogenicity. We show that the mutation induces a destabilization of gelsolin second domain, without compromising its calcium binding capacity. X-ray data combined with molecular dynamics simulations demonstrates that the primary source of the destabilization is a loss of connectivity in proximity of the metal. Such rearrangement of the H-bond network does not have a major impact on the overall fold of the domain, nevertheless, it increases the flexibility of a stretch of the protein, which is consequently processed by furin protease. Overall our data suggest that the N184K variant is subjected to the same aberrant proteolytic events responsible for the formation of amyloidogenic fragments in the previously characterized mutants. At the same time our data suggest that a broader number of mutations, unrelated to the metal binding site, can lead to a pathogenic phenotype.

  15. Molecular basis of a novel renal amyloidosis due to N184K gelsolin variant

    PubMed Central

    Bonì, Francesco; Milani, Mario; Porcari, Riccardo; Barbiroli, Alberto; Ricagno, Stefano; de Rosa, Matteo

    2016-01-01

    Mutations in gelsolin are responsible for a systemic amyloidosis first described in 1969. Until recently, the disease was associated with two substitutions of the same residue, leading to the loss of the calcium binding site. Novel interest arose in 2014 when the N184K variant of the protein was identified as the etiological agent of a novel kidney-localized amyloidosis. Here we provide a first rationale for N184K pathogenicity. We show that the mutation induces a destabilization of gelsolin second domain, without compromising its calcium binding capacity. X-ray data combined with molecular dynamics simulations demonstrates that the primary source of the destabilization is a loss of connectivity in proximity of the metal. Such rearrangement of the H-bond network does not have a major impact on the overall fold of the domain, nevertheless, it increases the flexibility of a stretch of the protein, which is consequently processed by furin protease. Overall our data suggest that the N184K variant is subjected to the same aberrant proteolytic events responsible for the formation of amyloidogenic fragments in the previously characterized mutants. At the same time our data suggest that a broader number of mutations, unrelated to the metal binding site, can lead to a pathogenic phenotype. PMID:27633054

  16. Molecular basis of a novel renal amyloidosis due to N184K gelsolin variant.

    PubMed

    Bonì, Francesco; Milani, Mario; Porcari, Riccardo; Barbiroli, Alberto; Ricagno, Stefano; de Rosa, Matteo

    2016-01-01

    Mutations in gelsolin are responsible for a systemic amyloidosis first described in 1969. Until recently, the disease was associated with two substitutions of the same residue, leading to the loss of the calcium binding site. Novel interest arose in 2014 when the N184K variant of the protein was identified as the etiological agent of a novel kidney-localized amyloidosis. Here we provide a first rationale for N184K pathogenicity. We show that the mutation induces a destabilization of gelsolin second domain, without compromising its calcium binding capacity. X-ray data combined with molecular dynamics simulations demonstrates that the primary source of the destabilization is a loss of connectivity in proximity of the metal. Such rearrangement of the H-bond network does not have a major impact on the overall fold of the domain, nevertheless, it increases the flexibility of a stretch of the protein, which is consequently processed by furin protease. Overall our data suggest that the N184K variant is subjected to the same aberrant proteolytic events responsible for the formation of amyloidogenic fragments in the previously characterized mutants. At the same time our data suggest that a broader number of mutations, unrelated to the metal binding site, can lead to a pathogenic phenotype. PMID:27633054

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

    ClinicalTrials.gov

    2016-10-06

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

  18. Chronic myopathy due to immunoglobulin light chain amyloidosis

    PubMed Central

    Manoli, Irini; Kwan, Justin Y.; Wang, Qian; Rushing, Elisabeth J.; Tsokos, Maria; Arai, Andrew E.; Burch, Warner M.; Dispenzieri, Angela; McPherron, Alexandra C.; Gahl, William A.

    2013-01-01

    Amyloid myopathy associated with a plasma cell dyscrasia is a rare cause of muscle hypertrophy. It can be a challenging diagnosis, since pathological findings are often elusive. In addition, the mechanism by which immunoglobulin light-chain deposition stimulates muscle overgrowth remains poorly understood. We present a 53–year old female with a 10-year history of progressive generalized muscle overgrowth. Congo-red staining and immunohistochemistry revealed perivascular lambda light chain amyloid deposits, apparent only in a second muscle biopsy. The numbers of central nuclei and satellite cells were increased, suggesting enhanced muscle progenitor cell formation. Despite the chronicity of the light chain disease, the patient showed complete resolution of hematologic findings and significant improvement of her muscle symptoms following autologous bone marrow transplantation. This case highlights the importance of early diagnosis and therapy for this treatable cause of a chronic myopathy with muscle hypertrophy. PMID:23465863

  19. Cardiac resynchronization therapy in a patient with amyloid cardiomyopathy.

    PubMed

    Zizek, David; Cvijić, Marta; Zupan, Igor

    2013-06-01

    Cardiac involvement in systemic light chain amyloidosis carries poor prognosis. Amyloid deposition in the myocardium can alter regional left ventricular contraction and cause dyssynchrony. Cardiac resynchronization therapy (CRT) is an effective treatment strategy for patients with advanced heart failure and echocardiographic dyssynchrony. We report a clinical and echocardiographic response of a patient with amyloid cardiomyopathy, treated with a combination of chemotherapy and CRT.

  20. Diagnostic pathway to amyotrophic lateral sclerosis (ALS): the significance of Babinski's sign in a unique patient and the necessity for a multidisciplinary approach

    PubMed Central

    Bulthuis, Vincent; Vlooswijk, Marielle; van Santbrink, Henk; Schijns, Olaf

    2013-01-01

    In this case report, we present a patient with rare diagnosis of amyotrophic lateral sclerosis (ALS). In this patient, four different neurological disorders were diagnosed in a short-time period of 8 months. The first three diagnoses, chronic low back and leg pain, a left frontal gemistocytic astrocytoma WHO grade 2 and suspected Lyme's disease, could not fully explain the signs of physical examination. Finally, the diagnosis of ALS could reduce these signs to the same denominator. PMID:23307452

  1. Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis.

    PubMed

    Brett, M; Persey, M R; Reilly, M M; Revesz, T; Booth, D R; Booth, S E; Hawkins, P N; Pepys, M B; Morgan-Hughes, J A

    1999-02-01

    We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy. PMID:10071047

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

    PubMed

    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

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

    PubMed

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

    2014-01-01

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

  4. Digitally reinforced hematoxylin-eosin polarization technique in diagnosis of rectal amyloidosis

    PubMed Central

    Doganavsargil, Basak; Buberal, Gulruh Emiroglu; Toz, Huseyin; Sarsik, Banu; Pehlivanoglu, Burcin; Sezak, Murat; Sen, Sait

    2015-01-01

    AIM: To investigate the efficacy of the digitally reinforced hematoxylin-eosin polarization (DRHEP) technique for detection of amyloidosis in rectal biopsies. METHODS: One hundred hematoxylin-eosin (HE) stained rectal biopsies with Congo-red (CR)-positive amyloid depositions and 50 control cases with CR-negative amyloid-mimicking areas were scanned blinded to the CR results for amyloid depositions under both bright and polarized light, and digitally photographed using the DRHEP technique, to accentuate the faint birefringence observed in HE slides under polarization. The results of DRHEP and HE evaluation were statistically correlated with CR polarization results with respect to presence and localization of amyloid deposits as well as amyloid types. RESULTS: Amyloid deposits showed yellowish-green birefringence by DRHEP, which allowed identification of amyloidosis in 41 HE-unsuspected cases (P = 0.016), 31 of which only had vascular deposits. True positivity was higher, and false negativity and positivity were lower by DRHEP, compared to evaluation by HE (69%, 31%, and 0.8% vs 33%, 67%, and 33%, respectively; P < 0.0001). The sensitivity, specificity, accuracy, and positive and negative predictive values for DRHEP were 69%, 98%, 78.6%, 98.5%, and 61.25%, respectively. Reasons for DRHEP false negativity were presence of extensive background birefringence in 12 cases, absence of CR birefringent vessel in 3 cases, and missing of the tiny deposits in 9 cases, which could be improved by experience, especially in the latter case. No correlation was found between age, gender, sites of deposits, or amyloid types. CONCLUSION: The DRHEP technique improves diagnostic accuracy when used as an adjunct or a prior step to CR staining, especially for cases with limited tissues for further analysis. PMID:25684948

  5. Progranulin as a candidate biomarker for therapeutic trial in patients with ALS and FTLD.

    PubMed

    Feneberg, Emily; Steinacker, Petra; Volk, Alexander Erich; Weishaupt, Jochen Hans; Wollmer, Marc Axel; Boxer, Adam; Tumani, Hayrettin; Ludolph, Albert Christian; Otto, Markus

    2016-03-01

    The loss-of-function mechanism in progranulin (PGRN) mutation carriers makes PGRN an interesting target for upregulation as a therapeutic approach in neurodegenerative diseases like frontotemporal lobar degeneration. This gives rise to several questions: (1) how stable are PGRN levels in blood and cerebrospinal fluid (CSF) in follow-up? (2) Is it necessary to measure PGRN levels in CSF to monitor a therapeutic effect? Therefore, concentrations of PGRN were measured in paired CSF and serum samples of 22 patients with behavioural variant frontotemporal dementia, including one GRN mutation carrier (c.349+1G>C), 16 patients with amyotrophic lateral sclerosis and 17 non-neurodegenerative patients, which included 22 follow-up levels. PGRN levels of 14 patients with isolated dysfunction of the blood-CSF barrier were measured and PGRN was correlated with albumin quotients as a marker for blood-CSF barrier function. The intrathecal fraction of PGRN was calculated on the basis of CSF-to-serum ratios and hydrodynamic properties. Follow-up measurements of CSF and serum PGRN levels did not show any significant change in diagnostic groups. Mean PGRN levels are 35 times higher in blood than in CSF. However, the CSF-to-serum PGRN ratio does not correlate with the albumin quotient even in patients with severe impairment of the blood-CSF barrier. The calculated intrathecal fraction of CSF PGRN levels ranged between 80 and 90 %. Assuming that CSF PGRN is either brain-derived or transported from the vascular compartment via receptor mediated mechanisms, we propose that monitoring CNS specific effects of PGRN modulating drugs should be done in CSF.

  6. Cardiac amyloidosis

    MedlinePlus

    ... the way electrical signals move through the heart (conduction system). This can lead to abnormal heartbeats ( arrhythmias ) ... due to medicine) Sick sinus syndrome Symptomatic cardiac conduction system disease (arrhythmias related to abnormal conduction of ...

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

    ClinicalTrials.gov

    2016-10-03

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  8. Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic studies.

    PubMed

    Argilés, A; Kerr, P G; Mourad, G; Mion, C M; Atkins, R C

    1993-01-01

    The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7505905

  9. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    PubMed Central

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  10. Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients.

    PubMed

    Eve, David J; Ehrhart, Jared; Zesiewicz, Theresa; Jahan, Israt; Kuzmin-Nichols, Nicole; Sanberg, Cyndy Davis; Gooch, Clifton; Sanberg, Paul R; Garbuzova-Davis, Svitlana

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA)-induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with

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

    PubMed Central

    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, cysteine protease inhibitors and kininogens. It is postulated that a point mutation has occurred, leading to the production of an unusual protein that is abnormally degraded, bound, and/or precipitated. Alternatively, gamma-trace basic protein may be genetically polymorphic, and the variant described here may represent an as-yet-undiscovered isotype or an allelic form that is linked to, but not responsible for, the deposition disease. Our data on the structure of a gamma-trace variant protein suggests that its gene expresses a polyprotein precursor in which active peptides are flanked by basic amino acid residues that permit cleavage to liberate small internal peptides. It is likely that the nucleotide sequence coding for Arg-Xaa and Lys-Xaa repeated several times in the molecule may function as alternative splicing sites for mRNA processing. Images PMID:3517880

  12. Pulmonary arterial hypertension due to pulmonary vascular amyloid deposition in a patient with multiple myeloma

    PubMed Central

    Hashimoto, Hirotsugu; Kurata, Atsushi; Mizuno, Hideaki; Nashiro, Tamaki; Hangaishi, Akira; Kuroda, Masahiko; Usuki, Kensuke; Horiuchi, Hajime

    2015-01-01

    Systemic amyloidosis is characterized by amyloid deposition throughout the body and subsequent dysfunction of various organs. Although pulmonary amyloidosis does occur, pulmonary hypertension (PH) caused by amyloidosis is extremely rare. In most of these cases, amyloid deposition occurred diffusely in alveolar septa, indicating that PH was due to lung disease and/or hypoxia. On the other hand, the mechanism of PH due to amyloid deposition in the pulmonary arteries has never been demonstrated. Here, we report the first case of PH due to amyloid deposition in pulmonary elastic arteries and muscular artery, which was complicated by multiple myeloma (MM). In the autopsy specimen of the patient, amyloid deposition was found mainly in the pulmonary arterial media, along with intimal thickening with luminal narrowing. PH thus appeared to be caused by marked decrease of pulmonary elasticity due to the amyloid deposition in the arterial media that resulted in stasis of the blood flow and subsequent luminal narrowing. Our present data demonstrates a new concept of PH caused by amyloidosis, namely, pulmonary arterial hypertension due to amyloidosis. PMID:26823900

  13. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

    PubMed Central

    Freyhult, Eva; Bodolea, Constantin; Ekegren, Titti; Larsson, Anders; Gustafsson, Mats G.; Katila, Lenka; Bergquist, Jonas; Gordh, Torsten; Landegren, Ulf; Kamali-Moghaddam, Masood

    2016-01-01

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest. PMID:26914813

  14. Case report: Maintaining and withdrawing long-term invasive ventilation in a patient with MND/ALS in a home setting.

    PubMed

    LeBon, B; Fisher, S

    2011-04-01

    Long-term home-based invasive ventilation in patients with motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) remains rare in the UK. We describe a case of an MND/ALS patient who was treated with long-term invasive ventilation at home but subsequently requested its withdrawal despite a seemingly stable period of his illness. We also discuss the impact of the delivery of this treatment and its withdrawal on his carers, primary healthcare team, community trust managers and specialist palliative care team.

  15. Role of Cholesterol and Phospholipids in Amylin Misfolding, Aggregation and Etiology of Islet Amyloidosis

    PubMed Central

    Singh, Sanghamitra; Trikha, Saurabh; Bhowmick, Diti Chatterjee; Sarkar, Anjali A.

    2015-01-01

    Amyloidosis is a biological event in which proteins undergo structural transitions from soluble monomers and oligomers to insoluble fibrillar aggregates that are often toxic to cells. Exactly how amyloid proteins, such as the pancreatic hormone amylin, aggregate and kill cells is still unclear. Islet amyloid polypeptide, or amylin, is a recently discovered hormone that is stored and co-released with insulin from pancreatic islet β-cells. The pathology of type 2 diabetes mellitus (T2DM) is characterized by an excessive extracellular and intracellular accumulation of toxic amylin species, soluble oligomers and insoluble fibrils, in islets, eventually leading to β-cell loss. Obesity and elevated serum cholesterol levels are additional risk factors implicated in the development of T2DM. Because the homeostatic balance between cholesterol synthesis and uptake is lost in diabetics, and amylin aggregation is a hallmark of T2DM, this chapter focuses on the biophysical and cell biology studies exploring molecular mechanisms by which cholesterol and phospholipids modulate secondary structure, folding and aggregation of human amylin and other amyloid proteins on membranes and in cells. Amylin turnover and toxicity in pancreatic cells and the regulatory role of cholesterol in these processes are also discussed. PMID:26149927

  16. Secondary amyloidosis in autoinflammatory diseases and the role of inflammation in renal damage

    PubMed Central

    Scarpioni, Roberto; Ricardi, Marco; Albertazzi, Vittorio

    2016-01-01

    The release of proinflammatory cytokines during inflammation represents an attempt to respond to injury, but it may produce detrimental effects. The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 (NLRP3). Once activated, inflammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 inflammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A (SAA), as acute-phase protein with also proinflammatory properties, has been shown to induce the secretion of cathepsin B and inflammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration. PMID:26788465

  17. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

    PubMed Central

    Romero-Camarero, Isabel; Jiang, Xiaoyu; Natkunam, Yasodha; Lu, Xiaoqing; Vicente-Dueñas, Carolina; Gonzalez-Herrero, Ines; Flores, Teresa; Garcia, Juan Luis; McNamara, George; Kunder, Christian; Zhao, Shuchun; Segura, Victor; Fontan, Lorena; Martínez-Climent, Jose A.; García-Criado, Francisco Javier; Theis, Jason D.; Dogan, Ahmet; Campos-Sánchez, Elena; Green, Michael R.; Alizadeh, Ash A.; Cobaleda, Cesar; Sánchez-García, Isidro; Lossos, Izidore S.

    2012-01-01

    The human germinal centre associated lymphoma (HGAL) gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that HGAL directly binds Syk in B-cells, increases its kinase activity upon B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, HGAL transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive AA amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the HGAL transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein HGAL regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation. PMID:23299888

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

    PubMed Central

    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

  19. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

    PubMed Central

    Alves, Chrystian J.; Dariolli, Rafael; Jorge, Frederico M.; Monteiro, Matheus R.; Maximino, Jessica R.; Martins, Roberto S.; Strauss, Bryan E.; Krieger, José E.; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS

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

    PubMed

    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

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

    PubMed Central

    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

  2. MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics.

    PubMed

    Scapineli, Jessica Oliboni; Ceolin, Lucieli; Puñales, Márcia Khaled; Dora, José Miguel; Maia, Ana Luiza

    2016-10-01

    Multiple endocrine neoplasia type 2A (MEN2A) may be rarely associated with cutaneous lichen amyloidosis (CLA), a skin lesion located in the interescapular region. Here, we describe 3 MEN2A-related CLA kindred and perform a systematic review (SR) of the literature on clinical, biochemical and molecular characteristics of MEN2A-related CLA patients. Thirty-eight patients with MEN2A-related CLA followed at our institution were evaluated. The median age at MEN2A diagnosis in our cohort was 25 (13-41) years, 68 % were women and all harbored codon 634 RET mutations. The literature search resulted in 20 publications that contributed with 25 MEN2A families and 214 individuals. The mean age of MEN2A diagnosis was 31 ± 17 years, with 77 % women. The mean age reported by patients to initial skin lesion suggestive to CLA was 20 ± 13 years. All but two kindred harbored mutations at codon 634: C634R 7 kindred (35 %), C634Y 5 kindred (25 %), C634W 3 kindred (15 %), C634G 1 kindred (5 %), V804M 1 kindred (5 %) and S891A 1 kindred (5 %). Most interesting, the standardized CLA prevalence was higher in women (2.3/1.0, P < 0.005). The overall reported prevalence of medullary thyroid carcinoma, CLA, pheochromocytoma and hyperparathyroidism was 94, 51, 30 and 16 %, respectively. SR of literature indicates that MEN2A-related CLA is more frequent in women and presents a high penetrance, being the second most frequent manifestation of the syndrome, preceded only by MTC.

  3. Age-related plaque morphology and C-terminal heterogeneity of amyloid beta in Dutch-type hereditary cerebral hemorrhage with amyloidosis.

    PubMed

    Maat-Schieman, M L; Yamaguchi, H; van Duinen, S G; Natté, R; Roos, R A

    2000-04-01

    The evolvement of amyloid beta (Abeta) deposition in the frontal cerebral cortex of 24 patients of increasing age with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) was studied using end-specific monoclonal antibodies to Abetax-42 (Abeta42) or Abetax-40 (Abeta40) and markers for degenerating neurites. Abeta42 immunostaining revealed parenchymal Abeta deposits with a heterogeneous morphology and distribution, i.e., clouds, fine/dense diffuse, coarse, and homogeneous plaques. Clouds and diffuse plaques were associated with glial Abeta granules. Abeta40 labeling was absent in clouds/fine diffuse plaques, inconsistent and variably intense in dense diffuse/coarse plaques and consistent in homogeneous plaques. In a subset of Abeta40-positive plaques, degenerating neurites--without tauopathy--and/or amyloid cores were observed. Electron microscopy revealed no apparent amyloid fibrils in fine diffuse plaques, small bundles of fibrils in dense diffuse/homogeneous plaques, and amyloid masses in coarse plaques. The parenchymal Abeta pathology was age-related: the ratio of fine to dense diffuse plaques decreased with age, clouds were limited to younger patients; coarse plaques to the oldest old. Homogeneous/cored plaques were present most consistently in older patients. Plaque density did not increase with age. Vascular Abeta deposits stained for both Abeta species, but exclusively Abeta42-positive, presumably recent deposits were also observed. This study suggests that HCHWA-D is a model of plaque evolution in which clouds leave fine diffuse plaques, which may become dense diffuse and ultimately coarse or homogeneous plaques.

  4. Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

    PubMed

    Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

    2015-05-01

    The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis.

  5. Validation of the German version of the extended ALS functional rating scale as a patient-reported outcome measure.

    PubMed

    Abdulla, Susanne; Vielhaber, Stefan; Körner, Sonja; Machts, Judith; Heinze, Hans-Jochen; Dengler, Reinhard; Petri, Susanne

    2013-09-01

    The revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a well-established rating instrument to assess the functional status of ALS patients. A recent innovation was the addition of three further items designed to improve its sensitivity at lower levels of physical function (ALSFRS-Extension, ALSFRS-EX). Neither the ALSFRS-R nor the ALSFRS-EX has been validated in German yet. The aim of the present study was the validation of the German version of a self-administered form of the ALSFRS-EX. Seventy-six patients participated in the study. Psychometric analysis included reliability assessment and factorial analysis. To evaluate convergent validity, correlations between ALSFRS-EX items and the MRC score, spasticity, tongue movement, pulmonary function, ALSAQ-40 and Borg dyspnoea scales (upright and supine) were performed. Internal consistency as measured by Cronbach's alpha (total scale 0.868, subscales 0.690-0.938) and corrected item to total correlations (all above 0.50) was high. Test-retest reliability assessed by Spearman's rho (0.882-0.972) and Cohen's Kappa (0.63-0.92) was also high. Principal component analysis with varimax rotation yielded a four-factor solution accounting for approximately 79% of the variance. Clinical parameters were strongly correlated with respective items and subscores of the ALSFRS-EX (muscle strength 0.568-0.833 p < 0.01; spasticity -0.236 to -0.376 p < 0.05; tongue movement 0.437-0.818 p < 0.01; pulmonary function 0.485-0.577 p < 0.01). ALSAQ-40 and Borg score correlated highly with the corresponding ALSFRS-EX items. The German self-report version of the ALSFRS-EX possesses very good psychometric properties similar to the original scale including high internal consistency and test-retest reliability as well as excellent convergent validity.

  6. Reversible pathologic and cognitive phenotypes in an inducible model of Alzheimer-amyloidosis

    PubMed Central

    Melnikova, Tatiana; Fromholt, Susan; Kim, HyunSu; Lee, Deidre; Xu, Guilian; Price, Ashleigh; Moore, Brenda D.; Golde, Todd E.; Felsenstein, Kevin M.; Savonenko, Alena; Borchelt, David R.

    2013-01-01

    Transgenic mice that express mutant amyloid precursor protein (APPsi) using tet-Off vector systems provide an alternative model for assessing short- and long-term effects of Aβ-targeting therapies on phenotypes related to the deposition of Alzheimer-type amyloid. Here we use such a model, termed APPsi:tTA, to determine what phenotypes persist in mice with high amyloid burden after new production of APP/Aβ has been suppressed. We find that 12-13 month old APPsi:tTA mice are impaired in cognitive tasks that assess short- and long-term memories. Acutely suppressing new APPsi/Aβ production produced highly significant improvements in performance short-term spatial memory tasks; which upon continued suppression translated to superior performance in more demanding tasks that assess long-term spatial memory and working memory. Deficits in episodic-like memory and cognitive flexibility, however, were more persistent. Arresting mutant APPsi production caused a rapid decline in the brain levels of soluble APP ectodomains, full-length APP, and APP C-terminal fragments. As expected, amyloid deposits persisted after new APP/Aβ production was inhibited whereas, unexpectedly, we detected persistent pools of solubilizable, relatively mobile, Aβ42. Additionally, we observed persistent levels of Aβ immunoreactive entities that were of a size consistent with SDS-resistant oligomeric assemblies. Thus, in this model with significant amyloid pathology, a rapid amelioration of cognitive deficits was observed despite persistent levels of oligomeric Aβ assemblies and low, but detectable solubilizable Aβ42 peptides. These findings implicate complex relationships between accumulating Aβ and activities of APP, soluble APP ectodomains, and/or APP CTFs in mediating cognitive deficits in this model of amyloidosis. PMID:23447589

  7. Reversible pathologic and cognitive phenotypes in an inducible model of Alzheimer-amyloidosis.

    PubMed

    Melnikova, Tatiana; Fromholt, Susan; Kim, HyunSu; Lee, Deidre; Xu, Guilian; Price, Ashleigh; Moore, Brenda D; Golde, Todd E; Felsenstein, Kevin M; Savonenko, Alena; Borchelt, David R

    2013-02-27

    Transgenic mice that express mutant amyloid precursor protein (APPsi) using tet-Off vector systems provide an alternative model for assessing short- and long-term effects of Aβ-targeting therapies on phenotypes related to the deposition of Alzheimer-type amyloid. Here we use such a model, termed APPsi:tTA, to determine what phenotypes persist in mice with high amyloid burden after new production of APP/Aβ has been suppressed. We find that 12- to 13-month-old APPsi:tTA mice are impaired in cognitive tasks that assess short- and long-term memories. Acutely suppressing new APPsi/Aβ production produced highly significant improvements in performing short-term spatial memory tasks, which upon continued suppression translated to superior performance in more demanding tasks that assess long-term spatial memory and working memory. Deficits in episodic-like memory and cognitive flexibility, however, were more persistent. Arresting mutant APPsi production caused a rapid decline in the brain levels of soluble APP ectodomains, full-length APP, and APP C-terminal fragments. As expected, amyloid deposits persisted after new APP/Aβ production was inhibited, whereas, unexpectedly, we detected persistent pools of solubilizable, relatively mobile, Aβ42. Additionally, we observed persistent levels of Aβ-immunoreactive entities that were of a size consistent with SDS-resistant oligomeric assemblies. Thus, in this model with significant amyloid pathology, a rapid amelioration of cognitive deficits was observed despite persistent levels of oligomeric Aβ assemblies and low, but detectable solubilizable Aβ42 peptides. These findings implicate complex relationships between accumulating Aβ and activities of APP, soluble APP ectodomains, and/or APP C-terminal fragments in mediating cognitive deficits in this model of amyloidosis.

  8. High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients

    PubMed Central

    Mok, Kin Y.; Koutsis, Georgios; Schottlaender, Lucia V.; Polke, James; Panas, Marios; Houlden, Henry

    2012-01-01

    An intronic expansion of a hexanucleotide GGGGCC repeat in the C9ORF72 gene has recently been shown to be an important cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in familial and sporadic cases. The frequency has only been defined in a small number of populations where the highest sporadic rate was identified in Finland (21.1%) and the lowest in mainland Italy (4.1%). We examined the C9ORF72 expansion in a series of 146 Greek ALS cases, 10.95% (n = 16) of cases carried the pathological expansion defined as greater than 30 repeats. In the 10 familial ALS probands, 50% (n = 5) of them carried a pathologically large expansion. In the remaining 136 sporadic ALS cases, 11 were carriers (8.2%). None of the 228 Greek controls carried an expanded repeat. The phenotype of our cases was spinal (13/16) or bulbar (3/16) ALS, the familial cases were all spinal ALS and none of our cases had behavioral frontotemporal dementia. Expansions in the C9ORF72 gene therefore represent a common cause of ALS in Greece and this test will be diagnostically very important to implement in the Greek population. The frequency is higher than other populations with the exception of Finland and this may be due to Greece being a relatively isolated population. PMID:22445326

  9. Novel acid-labile subunit ( IGFALS ) mutation p.T145K (c.434C>A) in a patient with ALS deficiency, normal stature and immunological dysfunction.

    PubMed

    Schreiner, Felix; Schoenberger, Stefan; Koester, Bernhard; Domené, Horacio M; Woelfle, Joachim

    2013-01-01

    We report a novel missense mutation p.T145K in the insulin-like growth factor (IGF) acid-labile subunit (IGFALS) gene identified in a Turkish patient with normal growth, transient pancytopenic episodes and signs of immunological dysfunction. Because of recurrent cutaneous mycoses and absence of pubertal development until the age of 14.75 years we determined several endocrine parameters in order to rule out autoimmune-polyendocrine syndromes. Despite a normal height between the 25th and 50th percentile we found severely decreased IGF-1 and undetectably low IGFBP-3 levels. Laboratory signs of immunological dysfunction included reduced total lymphocyte count with diminished B and T helper cell fractions, decreased serum concentrations of IgM and IgG subclass 4, and elevated antinuclear antibody and anti-dsDNA titers as well as persistently high interleukin-2-receptor levels. Further endocrine work-up revealed elevated fasting insulin and undetectably low ALS serum levels, leading to the diagnosis of ALS deficiency. Sequencing of the coding region of the IGFALS gene showed a novel homozygous missense mutation (c.434C>A; p.T145K). Since immunological abnormalities have not been reported in more than 20 ALS-deficient patients so far and our patient was born to consanguineous parents, a second autosomal recessive defect is likely to underlie the immunological phenotype, although a causative role of IGFALS p.T145K cannot be entirely ruled out. PMID:24296365

  10. The first experience of using 99mTc-Al2O3-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-08-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  11. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-06-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3- based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (TlaNxMx- T2bNxMx) treated at the Tomsk Cancer Research Institute. At 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 were injected peritumorally, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3(the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac, obturator, presacral and retrosacral regions (they amounted to 14%, respectively),and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  12. A nationwide study of acquired C1-inhibitor deficiency in France: Characteristics and treatment responses in 92 patients.

    PubMed

    Gobert, Delphine; Paule, Romain; Ponard, Denise; Levy, Pierre; Frémeaux-Bacchi, Véronique; Bouillet, Laurence; Boccon-Gibod, Isabelle; Drouet, Christian; Gayet, Stéphane; Launay, David; Martin, Ludovic; Mekinian, Arsène; Leblond, Véronique; Fain, Olivier

    2016-08-01

    Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for acute attacks are variable and used off-label. Successful treatment of the associated lymphoma with rituximab seems to prevent acute attacks in subjects with AAE. The aim of this study was to describe AAE manifestations, its associated diseases, and patients' responses to treatments in a representative cohort.A retrospective nationwide study was conducted in France. The inclusion criteria were recurrent angioedema attacks and an acquired decrease in functional C1INH <50% of the reference value.A total of 92 cases were included, with a median age at onset of 62 years. Facial edema and abdominal pain were the most frequent symptoms. Fifteen patients were hospitalized in the intensive care unit because of laryngeal edema, and 1 patient died. Anti-C1INH antibodies were present in 43 patients. The associated diseases were primarily non-Hodgkin lymphoma (n = 44, with 24 splenic marginal zone lymphomas) and monoclonal gammopathy of undetermined significance (n = 24). Three patients had myeloma, 1 had amyloid light-chain (of immunoglobulin) (AL) amyloidosis, 1 patient had a bronchial adenocarcinoma, and 19 patients had no associated disease. Icatibant relieved the symptoms in all treated patients (n = 26), and plasma-derived C1INH concentrate in 19 of 21 treated patients. Six patients experienced thromboembolic events under tranexamic acid prophylaxis. Rituximab prevented angioedema in 27 of 34 patients as a monotherapy or in association with chemotherapy. Splenectomy controlled AAE in 7 patients treated for splenic marginal zone lymphoma. After a median follow-up of 4.2 years, angioedema was on remission in 52 patients.AAE cases are primarily associated with indolent lymphoma-especially splenic marginal zone lymphoma-and monoclonal gammopathy of undetermined significance but not with autoimmune diseases or other conditions. Icatibant and plasma-derived C1INH concentrate control

  13. ALS Association

    MedlinePlus

    ... toward a world without ALS! Walk to Defeat ALS® Walk to Defeat ALS® draws people of all ... We need your help. I Will Advocate National ALS Registry The National ALS Registry is a congressionally ...

  14. Creating an assistive technology clinic: the experience of the Johns Hopkins AT clinic for patients with ALS.

    PubMed

    Casey, Kelly Showalter

    2011-01-01

    For persons with Amyotrophic Lateral Sclerosis (ALS), comprehensive multidisciplinary care can effectively improve overall quality of life from diagnosis to end of life [16]. Considering the rapidly progressive loss in overall function experienced by persons with ALS, it is essential to provide comprehensive multidisciplinary care, including Assistive Technology (AT) services, in an effective and efficient manner. AT is an important adjunctive therapy for people with neurological disability. For people with complex conditions, access to a comprehensive AT clinic can be the best way to access these tools. Unfortunately, few medical centers have invested in AT clinics, and managers may not understand how to go about developing AT resources at their facility. This article chronicles the step-by-step development of The Johns Hopkins Assistive Technology Clinic for persons with ALS. It offers background evidence, the process of program development, and insight into the experience of professional accountability of one occupational therapist turned AT Director. It also details descriptions of the stakeholders and their roles in the development process, funding and ethical considerations, and barriers to implementation. It is hoped that this may provide guidance for teams who may wish to build AT facilities in their own practice settings. PMID:21558633

  15. The Relationship between Self-esteem and Quality of Life of Patients with Idiopathic Thrombocytopenic Purpura at Isfahan's Sayed Al-Shohada Hospital, Iran, in 2013

    PubMed Central

    Hemati, Zeinab; Kiani, Davood

    2016-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a chronic disease which is accompanied with hopelessness and loss of the sense of well-being due to its symptoms and treatment. It also affects patients' sense of social and spiritual well-being. This disorder decreases patients' self-esteem and their quality of life by changing their mental image and self-confidence. This study was performed to find the relationship between self-esteem and quality of life of patients with ITP. Subjects and Methods: This was a descriptive-analytical study on 64 patients with ITP who referred to Isfahan's Sayed Al-Shohada Hospital, Iran. In this study, patients with ITP were selected randomly using a random number chart. The data collection tools consisted of the World Health Organization Quality of Life (WHOQOL)-BREF and Coopersmith Self-esteem Inventory (CSEI). Data were analyzed using SPSS and chi-square and Mann-Whitney tests and the Pearson and Spearman’s rank correlation coefficients. Results: In total, 64 patients completed the questionnaires. Results showed that 32% of subjects were over 36 years of age and 59% were women. In addition, 29.7% of ITP patients had low self-esteem and quality of life. Chi-square test showed a significant relationship between self-esteem and quality of life of patients with ITP. Conclusions: The results of the present study showed that considerable attention must be paid to self-esteem, as one of the most important factors influencing the promotion of quality of life. Therefore, it is suggested that patient’s self-esteem be improved by the implementation of educational and psychological programs in order to decrease the consequences of poor quality of life. PMID:27252807

  16. Clinical evaluation of BIOXTRA in relieving signs and symptoms of dry mouth after head and neck radiotherapy of cancer patients at Seyed-al-Shohada Hospital, Isfahan, Iran

    PubMed Central

    Gookizadeh, Abbas; Emami, Hamid; Najafizadeh, Nadia; Roayaei, Mahnaz

    2012-01-01

    Background: Radiotherapy of head and neck cancers causes acute and chronic xerostomia and acute mucositis. Xerostomia increases risk of radiation caries and affects on oral comfort, fit of prostheses, speech, swallowing, and the growth of caries-producing organisms. Salivary flow rate can be measured by asking patients some questions. There are different types of commercial synthetic saliva such as BIOXTRA, but until now, no one can effectively relieve xerostomia. We tried to design a clinical research on BIOXTRA efficacy for treating xerostomia. Materials and Methods: In this research, 58 patients with head and neck cancer (except salivary gland cancers) treated in Seyed-al-Shohada Hospital. The patients received at least 40-50 GY; and after 2 months of compilation treatment, they were evaluated by asking about having xerostomia. Before and after treatment with the BIOXTRA, the PH of the oral cavity, candida albicans, and lactobacillus counts measured and documented in laboratory. We used BIOXTRA for 2 weeks, 3 times daily, and then re-evaluated patients with some questions. Results: The counts of candida albicans and lactobacilli statistically significant decreased. Conclusion: Xerostomia for most patients improved clinically during the day and night while PH of the oral cavity increased. PMID:23326802

  17. [Current aspects of the osteoarticular pathology of hemodialysis patients. Results and discussion of a rheumatological survey].

    PubMed

    Foissac-Gegoux, P; Flipo, R M; Hardouin, P; Dumont, A; Duquesnoy, B; Lecomte-Houcke, M; Delcambre, B

    1986-01-01

    In a prospective study, 80 patients undergoing long-term hemodialysis, 30% more than ten years, were evaluated for joint function and radiographic abnormalities; 58 patients (72%) had clinical symptoms; non-specific arthralgia was the most frequent; 15 patients had inflammatory pain (shoulders 9, hands 3) and diminution of finger mobility (10). Radiological examinations showed 40 abnormal findings in 23 patients (28%): erosive arthropathies of fingers (4), and multiple geodes of the carpus (8), of the humeral head (7) or of the hip (9). We also detected spondylolisthesis (4), erosive arthropathy of cervical (6) or lumbar (2) spine. Pathological study of synovial biopsies was performed in 16 cases. Amyloidosis was found in 4 samples taken routinely. In 2 other cases the biopsy was done on the basis of lesions seen on x-rays: we found amyloidosis in the synovial membrane in both patients and in the bone in one. In 8 patients we found C3 deposits positive in immunofluorescence. These results underline the role of amyloidosis in the mechanism of some arthropathies in long-term hemodialysis patients.

  18. ALS - resources

    MedlinePlus

    Resources - ALS ... The following organizations are good resources for information on amyotrophic lateral sclerosis : Muscular Dystrophy Association -- mda.org/disease/amyotrophic-lateral-sclerosis National Amyotrophic Lateral Sclerosis (ALS) Registry -- ...

  19. Extensive genetics of ALS

    PubMed Central

    Calvo, Andrea; Mazzini, Letizia; Cantello, Roberto; Mora, Gabriele; Moglia, Cristina; Corrado, Lucia; D'Alfonso, Sandra; Majounie, Elisa; Renton, Alan; Pisano, Fabrizio; Ossola, Irene; Brunetti, Maura; Traynor, Bryan J.; Restagno, Gabriella

    2012-01-01

    Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that ∼11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease. PMID:23100398

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

    PubMed Central

    Lundmark, Katarzyna; Vahdat Shariatpanahi, Aida; 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 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. PMID:24236094

  1. Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

    PubMed Central

    Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

    2016-01-01

    Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520

  2. HISTORICAL SERIES OF PATIENTS WITH VISCERAL LEISHMANIASIS TREATED WITH MEGLUMINE ANTIMONIATE IN A HOSPITAL FOR TROPICAL DISEASES, MACEIÓ-AL, BRAZIL

    PubMed Central

    Silveira, Lindon Johoson Diniz; Rocha, Thiago José Matos; Ribeiro, Sandra Aparecida; Pedrosa, Célia Maria Silva

    2015-01-01

    Introduction: Visceral leishmaniasis is an endemic protozoan found in Brazil. It is characterized by fever, pallor, hepatosplenomegaly, lymphadenopathy, and progressive weakness in the patient. It may lead to death if untreated. The drug of choice for treatment is meglumine antimoniate (Glucantime®). The aim of this study was to evaluate patients with visceral leishmaniasis according to criteria used for diagnosis, possible reactions to Glucantime® and blood pressure measured before and after treatment. Methods: 89 patients admitted to the Teaching Hospital Dr. Hélvio Auto (HEHA) in Maceió-AL, in the period from May 2006 to December 2009 were evaluated. Data were collected on age, sex, origin, method of diagnosis, adverse effects of drugs, duration of hospitalization, duration of treatment and dosage up to the onset of adverse effects. Results: There was a predominance of child male patients, aged between one and five years old, from the interior of the State of Alagoas. Parasitological diagnosis was made by bone marrow aspirate; three (3.37%) patients died, 12 (13.48%) had adverse reactions and treatment was changed to amphotericin B, and 74 (83.14%) were cured. Changes that led to replacing Glucantime® were persistent fever, jaundice, rash, bleeding and cyanosis. Conclusion: During the study, 89 patients hospitalized for VL were analyzed: 74 were healed, 12 were replaced by amphotericin B treatment and three died. Most of them were under five years old, male and came from the interior. The dosage and duration of treatment with Glucantime® were consistent with that advocated by the Ministry of Health. Persistence of fever, jaundice, rash, cyanosis and bleeding were the reactions that led the physician to modify treatment. No change was observed in blood pressure before and after treatment. This study demonstrated the work of a hospital, a reference in the treatment of leishmaniasis, which has many patients demanding its services in this area. It demonstrates

  3. Impaired attention function based on the Montréal Cognitive Assessment in vascular dementia patients with frontal hypoperfusion: The Osaki-Tajiri project.

    PubMed

    Akanuma, Kyoko; Meguro, Kenichi; Kato, Yuriko; Takahashi, Yumi; Nakamura, Kei; Yamaguchi, Satoshi

    2016-06-01

    We previously reported that the Montréal Cognitive Assessment (MoCA) was effective in the evaluation of cerebrovascular diseases. We also demonstrated that the test was effective for screening for very mild vascular dementia (VaD) in the community. Herein, we examined the effectiveness of MoCA in the assessment of patients with VaD in an outpatient clinic. Forty-four patients with VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN] criteria) and 58 patients with Alzheimer's disease (AD) (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA] criteria) were compared with 67 non-demented control subjects. All were outpatients at the Tajiri Memory Clinic, Osaki-Tajiri, northern Japan. All underwent 1.5 Tesla MRI and ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) examinations. The SPECT images were used to classify the VaD patients into two subgroups, those with frontal hypoperfusion (F-VaD) and those without frontal hypoperfusion. The frontal hypoperfusion pattern was defined as the "P2" pattern of the Sliverman classification, with or without focal hypometabolism in other areas, based on the agreement of three neurologists who were blinded to the results of the neuropsychological examinations. Total scores and attention subscores on the MoCA were lower in the F-VaD group compared with other groups. Our results suggest that the MoCA attention subscale can detect VaD participants, particularly those with frontal hypoperfusion. PMID:26778514

  4. A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low-dose methotrexate.

    PubMed

    Watanabe, Hiroshi; Suzuki, Ryoma; Asano, Tomoyuki; Shio, Kiori; Iwadate, Haruyo; Kobayashi, Hiroko; Matsuoka, Toshimitsu; Aikawa, Ken; Ohira, Hiromasa

    2010-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate. PMID:20536605

  5. [Environmental factors in ALS].

    PubMed

    Juntas-Morales, Raul; Pageot, Nicolas; Corcia, Philippe; Camu, William

    2014-05-01

    ALS is likely to be a disorder of multifactorial origin. Among all the factors that may increase the risk of ALS, environmental ones are being studied for many years, but in the recent years, several advances have pointed to a new interest in their potential involvement in the disease process, especially for the cyanotoxin BMAA. Food containing BMAA has been found on Guam, a well-known focus of ALS/parkinsonism/dementia and high levels of BMAA have been identified into the brain of these patients. The BMAA cyanotoxin is potentially ubiquitous and have also been found into the food of patients who died from ALS both in Europe and USA. BMAA can be wrongly integrated into the protein structure during mRNA traduction, competing with serine. This may induce abnormal protein folding and a subsequent cell death. Heavy metals, such as lead or mercury may be directly toxic for neuronal cells. Several works have suggested an increased risk of ALS in individuals chronically exposed to these metals. Exposure to pesticides has been suggested to be linked to an increased risk of developing ALS. The mechanism of their toxicity is likely to be mediated by paraoxonases. These proteins are in charge of detoxifying the organism from toxins, and particularly organophosphates. To date, there are insufficient scientific data to suggest that exposure to electromagnetic fields may increase the risk of having ALS. We are particularly missing longitudinal cohorts to demonstrate that risk.

  6. The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients.

    PubMed

    Collins, Mahlon; Riascos, David; Kovalik, Tina; An, Jiyan; Krupa, Kelly; Krupa, Kristin; Hood, Brian L; Conrads, Thomas P; Renton, Alan E; Traynor, Bryan J; Bowser, Robert

    2012-11-01

    RNA-binding protein pathology now represents one of the best characterized pathologic features of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration patients with TDP-43 or FUS pathology (FTLD-TDP and FTLD-FUS). Using liquid chromatography tandem mass spectrometry, we identified altered levels of the RNA-binding motif 45 (RBM45) protein in the cerebrospinal fluid (CSF) of ALS patients. This protein contains sequence similarities to TAR DNA-binding protein 43 (TDP-43) and fused-in-sarcoma (FUS) that are contained in cytoplasmic inclusions of ALS and FTLD-TDP or FTLD-FUS patients. To further characterize RBM45, we first verified the presence of RBM45 in CSF and spinal cord tissue extracts of ALS patients by immunoblot. We next used immunohistochemistry to examine the subcellular distribution of RBM45 and observed in a punctate staining pattern within nuclei of neurons and glia in the brain and spinal cord. We also detected RBM45 cytoplasmic inclusions in 91 % of ALS, 100 % of FTLD-TDP and 75 % of Alzheimer's disease (AD) cases. The most extensive RBM45 pathology was observed in patients that harbor the C9ORF72 hexanucleotide repeat expansion. These RBM45 inclusions were observed in spinal cord motor neurons, glia and neurons of the dentate gyrus. By confocal microscopy, RBM45 co-localizes with ubiquitin and TDP-43 in inclusion bodies. In neurons containing RBM45 cytoplasmic inclusions we often detected the protein in a punctate pattern within the nucleus that lacked either TDP-43 or ubiquitin. We identified RBM45 using a proteomic screen of CSF from ALS and control subjects for candidate biomarkers, and link this RNA-binding protein to inclusion pathology in ALS, FTLD-TDP and AD.

  7. Relation of clinical, echocardiographic and electrocardiographic features of cardiac amyloidosis to the presence of the transthyretin V122I allele in older African-American men.

    PubMed

    Jacobson, Daniel; Tagoe, Clement; Schwartzbard, Arthur; Shah, Alan; Koziol, James; Buxbaum, Joel

    2011-08-01

    Previous studies have shown that 3% to 4% of African Americans carry an amyloidogenic allele of the human serum protein transthyretin (TTR V122I). The allele appears to have an absolute anatomic risk for cardiac amyloid deposition after 65 years of age. In this study, a case-control comparison was performed of clinical, echocardiographic, and electrocardiographic characteristics of 23 age at risk carriers of the amyloidogenic allele and 46 age-, gender-, and ethnically matched noncarriers being evaluated for cardiac disease using standard clinical testing. The 2 groups were matched for blood pressure and the cardiac ejection fraction. None of the subjects had a prestudy diagnosis of cardiac amyloidosis. Carriers of the amyloidogenic allele were found to have statistically significant increases in the occurrence of many of the echocardiographic features of cardiac amyloidosis relative to the noncarriers and a higher frequency of congestive heart failure and atrial fibrillation. The observations suggest that TTR V122I represents a substantial risk for clinically significant cardiac amyloidosis in elderly African American men, behaving as an age-dependent autosomal dominant disease-associated allele. The diagnosis is difficult to make but can be suspected in African Americans aged >60 years on the basis of age, echocardiographic evidence of diastolic dysfunction, and interventricular septal thickening, even in the absence of more recently available sophisticated echocardiographic techniques for evaluating long-axis function and cardiac magnetic resonance imaging. Positive results for the amyloidogenic TTR V122I allele support the diagnosis and define the origin of the disease, which can be confirmed by endomyocardial biopsy. PMID:21600538

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

    PubMed

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

    2015-11-13

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

  9. [Glycogenosis type III and Crohn disease with associated ankylopoietic spondylitis and secondary amyloidosis. An unusual coincidence].

    PubMed

    Sánchez Creus, P; Martínez López de Letona, J; Ladero Quesada, J M; Gilsanz Rico, G

    1994-12-01

    We present a member of a family with glycogen deposit disease (GDD) type III (Forbes-Cori's disease) confirmed postmortem through enzymatic analysis of the hepatic and muscular tissues, coinciding with a Crohn's disease associated to ankylopoietic spondylitis, with final development of an extended secondary amiloidosis, all of these diagnosis established in life of the patient and verified in necropsy. We comment this rare finding, the absence of similar cases in the bibliography and the fortuitous nature of this association given the impossibility to suggest another relationship.

  10. An immunologic assessment of brain-associated IgG in senile cerebral amyloidosis.

    PubMed

    Goust, J M; Mangum, M; Powers, J M

    1984-09-01

    Frontal and occipital lobes were taken within four hours of death from four senile patients (77-94 years) and frozen at -70 degrees C. After thawing at room temperature, gray and white matter were separated and subjected to sequential elution at pH 7.4 and pH 2.5. The eluates were processed for isoelectric focusing on 2.5% polyacrylamide gels and stained with silver nitrate; immunoblotting was done on agarose gels and stained by immunoperoxidase for IgG and light chains. Quantitation of the amount of IgG present in neutral and acidic eluates was performed by immunonephelometry and ELISA. Only the neutral eluates contained significant amounts of IgG, which were usually polyclonal. These data indicate that IgG associated with senile cerebral amyloid are not bound to any brain or vascular component and the data do not support the occurrence of an intraparenchymal immune response. PMID:6381655

  11. Spleen and liver enlargement in a patient with rheumatoid arthritis.

    PubMed

    Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio

    2015-01-01

    We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient.

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

    PubMed Central

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

    2016-01-01

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

  13. Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis

    PubMed Central

    Mattsson, Niklas; Insel, Philip S.; Palmqvist, Sebastian; Stomrud, Erik; van Westen, Danielle; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj; Hansson, Oskar

    2016-01-01

    Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance. PMID:26948379

  14. Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.

    PubMed

    Mattsson, Niklas; Insel, Philip S; Palmqvist, Sebastian; Stomrud, Erik; van Westen, Danielle; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj; Hansson, Oskar

    2016-03-07

    Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance.

  15. Cannabinoid CB2 Receptors in a Mouse Model of Aβ Amyloidosis: Immunohistochemical Analysis and Suitability as a PET Biomarker of Neuroinflammation

    PubMed Central

    Wang, Yuchuan; Ravert, Hayden; Gao, Yongjun; Koppel, Jeremy; Lee, Deidre; Pletnikova, Olga; Cho, Eugenia; Sayyida, Nuzhat; Hiatt, Andrew; Troncoso, Juan; Davies, Peter; Dannals, Robert F.; Pomper, Martin G.; Horti, Andrew G.

    2015-01-01

    In Alzheimer’s disease (AD), one of the early responses to Aβ amyloidosis is recruitment of microglia to areas of new plaque. Microglial receptors such as cannabinoid receptor 2 (CB2) might be a suitable target for development of PET radiotracers that could serve as imaging biomarkers of Aβ-induced neuroinflammation. Mouse models of amyloidosis (J20APPswe/ind and APPswe/PS1ΔE9) were used to investigate the cellular distribution of CB2 receptors. Specificity of CB2 antibody (H60) was confirmed using J20APPswe/ind mice lacking CB2 receptors. APPswe/PS1ΔE9 mice were used in small animal PET with a CB2-targeting radiotracer, [11C]A836339. These studies revealed increased binding of [11C]A836339 in amyloid-bearing mice. Specificity of the PET signal was confirmed in a blockade study with a specific CB2 antagonist, AM630. Confocal microscopy revealed that CB2-receptor immunoreactivity was associated with astroglial (GFAP) and, predominantly, microglial (CD68) markers. CB2 receptors were observed, in particular, in microglial processes forming engulfment synapses with Aβ plaques. In contrast to glial cells, neuron (NeuN)-derived CB2 signal was equal between amyloid-bearing and control mice. The pattern of neuronal CB2 staining in amyloid-bearing mice was similar to that in human cases of AD. The data collected in this study indicate that Aβ amyloidosis without concomitant tau pathology is sufficient to activate CB2 receptors that are suitable as an imaging biomarker of neuroinflammation. The main source of enhanced CB2 PET binding in amyloid-bearing mice is increased CB2 immunoreactivity in activated microglia. The presence of CB2 immunoreactivity in neurons does not likely contribute to the enhanced CB2 PET signal in amyloid-bearing mice due to a lack of significant neuronal loss in this model. However, significant loss of neurons as seen at late stages of AD might decrease the CB2 PET signal due to loss of neuronally-derived CB2. Thus this study in mouse models

  16. Al Composites

    NASA Astrophysics Data System (ADS)

    Chandanayaka, Tharaka; Azarmi, Fardad

    2014-05-01

    In the present study, cold spraying technique was used to fabricate a metal matrix composite (MMC) that consists of Ni matrix and 20 vol.% Ni3Al particles at two different particle sizes as reinforcement. This study intends to investigate the effect of reinforcement particle size on microstructural and mechanical properties of cold sprayed MMCs. Two different Ni3Al powders with nominal particle size of -45 to +5 and +45 to 100 μm were used as reinforcement in this study. Cold sprayed Ni-Ni3Al samples were subjected to the microstructural observation and characterization prior to any mechanical testing. Then, samples were tested using nano-indentation, Knoop hardness, Vickers hardness, and Resonance frequency to evaluate their mechanical properties. No significant changes were observed in microstructural characteristics due to different particle sizes. The results obtained from a variety of mechanical testings indicated that the increasing reinforcement particle size resulted in the slight reduction of mechanical properties such as elastic modulus and hardness in cold sprayed MMCs. The mechanical interlock between deposited particles defines the bonding strength in cold sprayed samples. Small size particles have a higher velocity and impact resulting in stronger interlock between deformed particles.

  17. Trientine Reduces BACE1 Activity and Mitigates Amyloidosis via the AGE/RAGE/NF-κB Pathway in a Transgenic Mouse Model of Alzheimer's Disease

    PubMed Central

    Xie, Jing-Wei; Xu, Ye; Wang, Tao; Cai, Jian-Hui; Wang, Xu; Zhao, Bao-Lu; An, Li

    2013-01-01

    Abstract Aims: There is mounting evidence that the transition metal copper may play an important role in the pathophysiology of Alzheimer's disease (AD). Triethylene tetramine dihydrochloride (trientine), a CuII-selective chelator, is a commonly used treatment for Wilson's disease to decrease accumulated copper, and thereby decreases oxidative stress. In the present study, we evaluated the effects of a 3-month treatment course of trientine (Trien) on amyloidosis in 7-month-old β-amyloid (Aβ) precursor protein and presenilin-1 (APP/PS1) double transgenic (Tg) AD model mice. Results: We observed that Trien reduced the level of advanced glycation end products (AGEs), and decreased Aβ deposition and synapse loss in brain of APP/PS1 mice. Importantly, we found that Trien blocked the receptor for AGEs (RAGE), downregulated β-site APP cleaving enzyme 1 (BACE1), inhibited amyloidogenic APP cleavage, and subsequently reduced Aβ levels. In vitro, in SH-SY5Y cells overexpressing Swedish mutant APP, Trien-mediated downregulation of BACE1 occurred via inhibition of the NF-κB signaling pathway. Innovation: In this study, we demonstrated for the first time that Trien inhibited amyloidogenic pathway including targeting the downregulation of RAGE and NF-κB. Conclusion: Trien might mitigate amyloidosis in AD by inhibiting the RAGE/NF-κB/BACE1 pathway. Our study demonstrates that Trien may be a viable therapeutic strategy for the intervention and treatment of AD and other AD-like pathologies. Antioxid. Redox Signal. 19, 2024–2039. PMID:23541064

  18. Memory deficits and retrieval processes in ALS.

    PubMed

    Mantovan, M C; Baggio, L; Dalla Barba, G; Smith, P; Pegoraro, E; Soraru', G; Bonometto, P; Angelini, C

    2003-05-01

    Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding.

  19. Memory deficits and retrieval processes in ALS.

    PubMed

    Mantovan, M C; Baggio, L; Dalla Barba, G; Smith, P; Pegoraro, E; Soraru', G; Bonometto, P; Angelini, C

    2003-05-01

    Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding. PMID:12752394

  20. The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever

    PubMed Central

    Güncan, Sabri; Bilge, N. Şule Y.; Cansu, Döndü Üsküdar; Kaşifoğlu, Timuçin; Korkmaz, Cengiz

    2016-01-01

    Objective This study aimed to investigate the frequency in which familial Mediterranean fever (FMF) coexists with other diseases and determine whether Mediterranean fever (MEFV) gene mutations are involved in such coexistence. Material and Methods In total, 142 consecutive patients with FMF investigated for MEFV mutation were enrolled in this study [Female: 87; Male: 55, mean age 32±12 years (11–62)]. All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. A previous diagnosis of inflammatory disorder other than FMF was considered true if it met the relevant criteria. MEFV mutations were divided into 2 groups, namely M694V and its subgroup (homozygous or heterozygous) (Group I) and others (Group II). Compound heterozygosity for M694V mutation was included in Group II to form a homogeneous group for Group I. Group I and Group II were compared according to phenotypical features. The presence of MEFV mutation was investigated in exons 2, 3, 5, and 10 by the multiplex-PCR reverse hybridization method. Results Concomitant disorders were found in 17 of 73 patients with FMF (23%) in Group I and 5 of 56 patients (8.9%) in Group II (p=0.04). Concomitant disorders in Group I were as follows: 7 cases of amyloidosis, 2 cases of Behcet’s disease (BD), 4 cases of ankylosing spondylitis (AS), 1 case of antiphospholipid syndrome, 1 case of Henoch–Schonlein purpura (HSP), 1 case of combination of psoriatic arthritis, HSP, and membranoproliferative glomerulonephritis, and 1 case of AS and amyloidosis. In Group II, the following disorders were found: 1 case of amyloidosis, 1 case of BD, 1 case of AS, 1 case of ulcerative colitis, and 1 case of vitiligo. Conclusion The presence of M694V mutation may predispose patients with FMF to developing other inflammatory disorders. PMID:27733942

  1. Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort.

    PubMed

    Nakamura, Ryoichi; Sone, Jun; Atsuta, Naoki; Tohnai, Genki; Watanabe, Hazuki; Yokoi, Daichi; Nakatochi, Masahiro; Watanabe, Hirohisa; Ito, Mizuki; Senda, Jo; Katsuno, Masahisa; Tanaka, Fumiaki; Li, Yuanzhe; Izumi, Yuishin; Morita, Mitsuya; Taniguchi, Akira; Kano, Osamu; Oda, Masaya; Kuwabara, Satoshi; Abe, Koji; Aiba, Ikuko; Okamoto, Koichi; Mizoguchi, Kouichi; Hasegawa, Kazuko; Aoki, Masashi; Hattori, Nobutaka; Tsuji, Shoji; Nakashima, Kenji; Kaji, Ryuji; Sobue, Gen

    2016-03-01

    We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients.

  2. Medical application of 26Al

    NASA Astrophysics Data System (ADS)

    Steinhausen, C.; Gerisch, P.; Heisinger, B.; Hohl, Ch.; Kislinger, G.; Korschinek, G.; Niedermayer, M.; Nolte, E.; Dumitru, M.; Alvarez-Brückmann, M.; Schneider, M.; Ittel, T. H.

    1996-06-01

    Accelerator mass spectrometry (AMS) measurements with 26Al as tracer were performed in order to study the aluminium metabolism and anomalies in the human body and in rats. In particular, the differences between healthy volunteers and patients with renal failure were investigated. The obtained data points of 26Al in blood and urine were described by an open compartment model with three peripheral compartments. It was found that the minimum of peripheral compartments needed to describe 26Al concentrations in blood and urine over a time period of three years is at least three.

  3. Are titanium-on-titanium TiAl6V4 modular necks safe in total hip arthroplasty for non-overweight patients? Results of a prospective series at a minimum follow-up of 7 years.

    PubMed

    Ollivier, Matthieu; Parratte, Sébastien; Galland, Alexandre; Lunebourg, Alexandre; Argenson, Jean-Noel

    2015-10-01

    Using extramedullar modularity in total hip arthroplasty has been proposed as an option to optimize the restoration of hip biomechanics. To avoid the problems that were observed with cobalt-chrome modular neck, titanium modular necks have been developed. The goals of our study were to evaluate the safety of titanium-on-titanium TiAl6V4 modular neck system. Hundred patients with a mean age of 69.6 ± 10.6 (42-86 years) and mean BMI of 25.07 ± 4.86 (17-38 kg/m(2)) suffering from primary or secondary arthritis of the hip were prospectively included. At a minimum of 7 years, no fracture of the modular neck was observed. No patient required a revision. No sign of loosening was found in the radiological analysis. Our study shows that titanium-on-titanium TiAl6V4 modular neck system can safely be used with good midterm clinical and radiological results for non-overweight patients. These results should be confirmed at longer follow-up.

  4. Multiple Myeloma: Patient Handbook

    MedlinePlus

    ... way in which these agents cross-link the DNA of myeloma cells and block cell division. Amyloidosis: ... a cancer treatment regimen. Chromosome: A strand of DNA and proteins in the nucleus of a cell. ...

  5. RAndomized Comparison of raDIal vs. femorAL Access for Routine Catheterization of Heart Transplant Patients (RADIAL-heart transplant study).

    PubMed

    Scalone, G; Brugaletta, S; Martín-Yuste, V; Seixo, F; Cotes, C; Gómez-Monterrosas, O; Alvarez-Contreras, L; Campreciós, M; Mirabet, S; Brossa, V; Sabaté, M

    2014-12-01

    Although a transradial approach (TRA) is considered feasible in many clinical situations, no data are available in patients undergoing orthotopic heart transplantation (OHT). Our goal was to randomly compare TRA versus a transfemoral approach (TFA) in this clinical setting. This single-center, prospective, randomized trial was conducted from January to November 2006, and all OHT patients scheduled for a control coronary angiography were randomized to receive TRA or TFA. The primary endpoint was the amount of contrast used during the procedure. The participating interventional cardiologists were intermediate-volume radial operators, and this was their initial experience of TRA in OHT patients. The analysis was performed according to the intention-to-treat principle. Overall, 49 patients (mean age, 55 ± 13 years; 74% male) were included in the trial: 26 patients were assigned to TRA, and 23 were assigned to TFA. A higher amount of contrast (147 mL [range, 113-175 mL] vs 105 mL [range, 86-127 mL]; P = .009), a longer fluoroscopy time (9.2 minutes [range, 6-12 minutes] vs 3.5 minutes [range, 3-5 minutes]; P < .001), a trend toward increased number of catheters used for left ostium cannulation, and a higher crossover rate (19% vs 0%; P = .03) were associated with TRA compared with TFA. Furthermore, patients treated with TRA exhibit a shorter hospital stay (6 [range 4-8]) compared with the other group (26 [range 24-28]) (P < .001). There were no significant differences between the 2 groups regarding total procedural time, and no vascular complications were reported in either group. For these operators with their first experience of TRA in OHT patients, TFA seemed to be more efficient. PMID:25498035

  6. An Unsusual Case of Lower Gastrointestinal Bleeding

    PubMed Central

    Guru, Pramod Kumar; Iyer, Vivek N.

    2016-01-01

    Patient: Female, 81 Final Diagnosis: Gastrointestinal amyloidosis Symptoms: Gastrointesinal haemorrhage • hypotension Medication: — Clinical Procedure: Endoscopy Specialty: Criitcal Care Medicine Objective: Challenging differential diagnosis Background: Amyloidosis is a multisystem disease, and can present with multitude of nonspecific symptoms. Gastrointestinal amyloidosis is common, and gastrointestinal (GI) bleeding in these patients has a wide differential diagnosis. The present case features the distinctive endoscopic finding of submucosal hematoma as a clue to immunoglobin light chain (AL) amyloid involvement of the gastrointestinal tract. Case Report: An 81-year-old woman with AL amyloidosis was transferred to the intensive care unit (ICU) for evaluation of GI bleeding. Prior to the bleeding episode, the patient had undergone paracentesis for management of her ascites related to restrictive cardiomyopathy. Initial evaluation was negative for any intra-abdominal catastrophe related to her recent paracentesis. Upper gastrointestinal endoscopy was negative for any source of bleeding. However, colonoscopy showed a ruptured submucosal hematoma, which is a rare but classical finding in patients with amyloidosis. The patient was managed conservatively and did not have any further episodes of bleeding in the hospital. She unfortunately died due to her primary illness 6 weeks after discharge from the hospital. Conclusions: The finding of submucosal hematoma on endoscopy is a rare but sentinel sign for amyloidosis involvement in the GI tract. PMID:26979633

  7. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients

    PubMed Central

    Erken, Ertugrul; Ozturk, Ozlem Goruroglu; Kudas, Ozlem; Tas, Didem Arslan; Demirtas, Ahmet; Kibar, Filiz; Dinkci, Suzan; Erken, Eren

    2015-01-01

    Background Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. Material/Methods One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. Results All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). Conclusions According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes. PMID:26574972

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

    PubMed

    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

  9. RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.

    PubMed

    Qi, Xiao-Ping; Zhao, Jian-Qiang; Chen, Zhen-Guang; Cao, Jin-Lin; Du, Juan; Liu, Nai-Fang; Li, Feng; Sheng, Mao; Fu, Er; Guo, Jian; Jia, Hong; Zhang, Yi-Ming; Ma, Ju-Ming

    2015-10-20

    There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA. PMID:26356818

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

    PubMed Central

    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

  11. RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.

    PubMed

    Qi, Xiao-Ping; Zhao, Jian-Qiang; Chen, Zhen-Guang; Cao, Jin-Lin; Du, Juan; Liu, Nai-Fang; Li, Feng; Sheng, Mao; Fu, Er; Guo, Jian; Jia, Hong; Zhang, Yi-Ming; Ma, Ju-Ming

    2015-10-20

    There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA.

  12. Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

    PubMed

    Watanabe, Yasuhiro; Beeldman, Emma; Raaphorst, Joost; Izumi, Yuishin; Yoshino, Hiide; Masuda, Michihito; Atsuta, Naoki; Ito, Satoru; Adachi, Tadashi; Adachi, Yoshiki; Yokota, Osamu; Oda, Masaya; Hanashima, Ritsuko; Ogino, Mieko; Ichikawa, Hiroo; Hasegawa, Kazuko; Kimura, Hideki; Shimizu, Toshio; Aiba, Ikuko; Yabe, Hayato; Kanba, Makoto; Kusumi, Kimiyoshi; Aoki, Tetsuya; Hiroe, Yu; Watanabe, Hirohisa; Nishiyama, Kazutoshi; Nomoto, Masahiro; Sobue, Gen; Nakashima, Kenji

    2016-08-15

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients.

  13. Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

    PubMed

    Watanabe, Yasuhiro; Beeldman, Emma; Raaphorst, Joost; Izumi, Yuishin; Yoshino, Hiide; Masuda, Michihito; Atsuta, Naoki; Ito, Satoru; Adachi, Tadashi; Adachi, Yoshiki; Yokota, Osamu; Oda, Masaya; Hanashima, Ritsuko; Ogino, Mieko; Ichikawa, Hiroo; Hasegawa, Kazuko; Kimura, Hideki; Shimizu, Toshio; Aiba, Ikuko; Yabe, Hayato; Kanba, Makoto; Kusumi, Kimiyoshi; Aoki, Tetsuya; Hiroe, Yu; Watanabe, Hirohisa; Nishiyama, Kazutoshi; Nomoto, Masahiro; Sobue, Gen; Nakashima, Kenji

    2016-08-15

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients. PMID:27423564

  14. [Radiology of osteoarticular changes in patients undergoing periodic hemodialysis for more than 15 years].

    PubMed

    Orzincolo, C; Bedani, P L; Scutellari, P N; Ghedini, M; Storari, A; Cavallari, L; Cardona, P

    1991-05-01

    Osteoarticular complications, which are characterized by osseous pain, pathologic fractures, and decreased articular mobility, represent one of the major problems affecting long-term (over 15 years) hemodialysis patients. These changes seem to have a multifactorial etiology; they include osteomalacia, secondary hyperparathyroidism, and dialysis-related amyloidosis. Ten patients (5 males and 5 females, mean age 55 +/- 7 years) on long-term (over 15 years) hemodialysis were submitted to X-ray examinations of the skull, spine, shoulders, wrists, pelvis, and knees. Serum calcium, phosphorous, parathyroid hormone, alkaline phosphatase, and basal aluminium levels were also calculated. Osteopenia was demonstrated in all patients. Seven of them had alterations due to hyperparathyroidism. Six patients exhibited signs related to dialysis spondyloarthropathy; in 9 cases amyloid lesions, geodes, and erosions were present in wrists, humeral heads, or hips. One patient exhibited osteomalacic changes. Most long-term dialysis patients presented multifactorial osteoarticular changes due to hyperparathyroidism, osteomalacia, and dialysis-related amyloidosis. Clinical symptoms and decreased articular mobility appeared to be due mainly to amyloid osteoarthropathy.

  15. The Renal Histopathology Spectrum of Elderly Patients with Kidney Diseases

    PubMed Central

    Zhu, Ping; Zhou, Fu-de; Zhao, Ming-hui

    2014-01-01

    Abstract The elderly population has significantly increased in China. However, data regarding renal histopathology in this population is lacking. The present study retrospectively analyzed renal disease spectrum of 430 elderly patients who had received renal biopsy at Peking University First Hospital between January 2003 and December 2012. Among 6049 patients receiving renal biopsies during the same period, 430 (7.10%) were elderly (≥65 years). The ratio of male (263 patients) to female (167 patients) was 1.57:1, with an age of 70.29 ± 3.99 (range 65–82) years at the time of biopsy. The most common indication for renal biopsy was nephrotic syndrome (59.53%), followed by acute kidney injury (AKI, 19.53%) and chronic glomerulonephritis (CGN, 16.05%). The most common renal histopathology in primary glomerular disease was idiopathic membranous nephropathy (iMN, 61.02%), followed by IgA nephropathy (18.22%), minimal change disease (MCD, 9.32%) and focal segmental glomerulosclerosis (6.78%). ANCA-associated vasculitis (AAV, 43.95%) was the leading secondary glomerular disease, followed by HBV-related glomerulonephritis (HBV-GN, 24.2%), and amyloidosis (14.01%). In patients with nephrotic syndrome, iMN (50%) was the leading cause, followed by HBV-GN (16.02%), MCD (7.81%), and amyloidosis (7.81%). In patients with iMN, 89.5% presented as nephrotic syndrome, 8.39% as CGN. In patients with AKI, the leading cause was AAV (48.12%), followed by acute interstitial nephritis (20.48%) and acute tubular necrosis (8.43%). In conclusion, in elderly Chinese patients, the most common renal histopathology pattern was iMN in patients with nephrotic syndrome, and AAV in patients with AKI. PMID:25526441

  16. The renal histopathology spectrum of elderly patients with kidney diseases: a study of 430 patients in a single Chinese center.

    PubMed

    Zhu, Ping; Zhou, Fu-de; Zhao, Ming-hui

    2014-12-01

    The elderly population has significantly increased in China. However, data regarding renal histopathology in this population is lacking. The present study retrospectively analyzed renal disease spectrum of 430 elderly patients who had received renal biopsy at Peking University First Hospital between January 2003 and December 2012. Among 6049 patients receiving renal biopsies during the same period, 430 (7.10%) were elderly (≥65 years). The ratio of male (263 patients) to female (167 patients) was 1.57:1, with an age of 70.29±3.99 (range 65-82) years at the time of biopsy. The most common indication for renal biopsy was nephrotic syndrome (59.53%), followed by acute kidney injury (AKI, 19.53%) and chronic glomerulonephritis (CGN, 16.05%). The most common renal histopathology in primary glomerular disease was idiopathic membranous nephropathy (iMN, 61.02%), followed by IgA nephropathy (18.22%), minimal change disease (MCD, 9.32%) and focal segmental glomerulosclerosis (6.78%). ANCA-associated vasculitis (AAV, 43.95%) was the leading secondary glomerular disease, followed by HBV-related glomerulonephritis (HBV-GN, 24.2%), and amyloidosis (14.01%). In patients with nephrotic syndrome, iMN (50%) was the leading cause, followed by HBV-GN (16.02%), MCD (7.81%), and amyloidosis (7.81%). In patients with iMN, 89.5% presented as nephrotic syndrome, 8.39% as CGN. In patients with AKI, the leading cause was AAV (48.12%), followed by acute interstitial nephritis (20.48%) and acute tubular necrosis (8.43%). In conclusion, in elderly Chinese patients, the most common renal histopathology pattern was iMN in patients with nephrotic syndrome, and AAV in patients with AKI.

  17. Clinical picture of the amyloid arthropathy in patients with chronic renal failure maintained on haemodialysis using cellulose membranes.

    PubMed

    Muñoz-Gómez, J; Gómez-Pérez, R; Llopart-Buisán, E; Solé-Arqués, M

    1987-08-01

    The clinical picture of 15 patients (10 male, five female) with amyloid arthropathy secondary to chronic renal failure treated with haemodialysis has been studied. The average period of haemodialysis was 10.8 years. Joint symptoms appeared between three and 13 years after starting haemodialysis. No patient had renal amyloidosis. Early symptoms were varied and often overlapped: knee swelling (seven patients), painful and stiff shoulders (seven), and carpal tunnel syndrome (six) were the most prominent. Follow up showed extension to other joints. Joint effusions were generally of the non-inflammatory type. Radiologically, geodes and erosions of variable sizes were seen in the affected joints, which can develop into a destructive arthropathy. Amyloid was found in abdominal fat in three of the 12 patients on whom a needle aspiration was performed. Four of 12 patients showed changes compatible with amyloid infiltration in the echocardiogram. One patient had amyloid in the gastric muscular layer, another in the colon mucus, and two of four in rectal biopsy specimens. Amyloid deposits showed the presence of beta 2 microglobulin in 10 patients. The clinical and radiological picture was similar to the amyloid arthropathy associated with multiple myeloma. These patients can develop systemic amyloidosis.

  18. The transthyretin amyloidoses: advances in therapy.

    PubMed

    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. [Peritoneal implants in patients affected by chronic renal failure in hemodialysis programme].

    PubMed

    Saurina, A; Pou, M; Fulquet, M; Ramírez de Arellano, M; Chiné, M; Esteba, M D; de las Cuevas, X

    2006-01-01

    The presence of peritoneal implants detected by computered axial tomography (CT) is usually related to mesothelial primary neoformative processes or, more frequently to peritoneal metastasis or peritoneal carcinomatosis. Although the higher prevalence of neoplastic processes in the chronic renal failure population, the association of peritoneal implants and constitutional syndrome is not always correlated to peritoneal carcinomatosis. We present the case of two patients with chronic renal failure in hemodialysis programme, with abdominal insidious clinical, constitutional syndrome and similar peritoneal implants seen by CAT: the histologic analysis of peritoneal implants gave the definitive diagnostic of secondary amyloidosis and peritoneal tuberculosis respectively.

  20. Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation

    PubMed Central

    Cohen, D. J.; Cheng, A.; Kahn, A.; Aviram, M.; Whitehead, A. J.; Hyzy, S. L.; Clohessy, R. M.; Boyan, B. D.; Schwartz, Z.

    2016-01-01

    Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants. PMID:26854193

  1. Bunina bodies in motor and non-motor neurons revisited: a pathological study of an ALS patient after long-term survival on a respirator.

    PubMed

    Kimura, Tadashi; Jiang, Haishan; Konno, Takuya; Seto, Makiko; Iwanaga, Keisuke; Tsujihata, Mitsuhiro; Satoh, Akira; Onodera, Osamu; Kakita, Akiyoshi; Takahashi, Hitoshi

    2014-08-01

    Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72 mutation, of 12 years duration in a 75-year-old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non-motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP-43 inclusions. PMID:24444375

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

    PubMed Central

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

    2009-01-01

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

  3. In vivo seeding and cross-seeding of localized amyloidosis: a molecular link between type 2 diabetes and Alzheimer disease.

    PubMed

    Oskarsson, Marie E; Paulsson, Johan F; Schultz, Sebastian W; Ingelsson, Martin; Westermark, Per; Westermark, Gunilla T

    2015-03-01

    Several proteins have been identified as amyloid forming in humans, and independent of protein origin, the fibrils are morphologically similar. Therefore, there is a potential for structures with amyloid seeding ability to induce both homologous and heterologous fibril growth; thus, molecular interaction can constitute a link between different amyloid forms. Intravenous injection with preformed fibrils from islet amyloid polypeptide (IAPP), proIAPP, or amyloid-beta (Aβ) into human IAPP transgenic mice triggered IAPP amyloid formation in pancreas in 5 of 7 mice in each group, demonstrating that IAPP amyloid could be enhanced through homologous and heterologous seeding with higher efficiency for the former mechanism. Proximity ligation assay was used for colocalization studies of IAPP and Aβ in islet amyloid in type 2 diabetic patients and Aβ deposits in brains of patients with Alzheimer disease. Aβ reactivity was not detected in islet amyloid although islet β cells express AβPP and convertases necessary for Aβ production. By contrast, IAPP and proIAPP were detected in cerebral and vascular Aβ deposits, and presence of proximity ligation signal at both locations showed that the peptides were <40 nm apart. It is not clear whether IAPP present in brain originates from pancreas or is locally produced. Heterologous seeding between IAPP and Aβ shown here may represent a molecular link between type 2 diabetes and Alzheimer disease.

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

    DOE PAGES

    Wall, Jonathan; Martin, Emily B.; Richey, Tina; Stuckey, Alan C.; Macy, Sallie; Wooliver, Craig; Williams, Angela; Foster, James S.; McWilliams-Koeppen, Penney; Uberbacher, Ed; et al

    2015-04-27

    Amyloid is a complex pathologic matrix comprised principally of para-crystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloidoses are rare (~3500 new cases per year in the US); thus, routine diagnosis is often challenging, and effective treatment options are limited, resulting in high morbidity and mortality rates. Glycosaminoglycans contribute inextricably to the formation of amyloid fibrils and foster the deposition of amyloid in tissues. Those present in amyloid deposits are biochemically and electrochemically distinct from glycosaminoglycans found in the plasma membrane and extracellular matrices of healthy tissues due to the presence of a high degree of heparin-like hypersulfation. We havemore » exploited this unique property and evaluated heparin-reactive peptides, such as p5+14. Herein we show efficacious detection of murine systemic amyloid in vivo by using molecular imaging, and the specific targeting of the peptide to major forms of human amyloid in tissue sections. 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; thus, providing a novel technique for prognostication, patient stratification, and monitoring response to therapy.« less

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

    SciTech Connect

    Wall, Jonathan; Martin, Emily B.; Richey, Tina; Stuckey, Alan C.; Macy, Sallie; Wooliver, Craig; Williams, Angela; Foster, James S.; McWilliams-Koeppen, Penney; Uberbacher, Ed; Cheng, Xiaolin; Kennel, Stephen J.

    2015-04-27

    Amyloid is a complex pathologic matrix comprised principally of para-crystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloidoses are rare (~3500 new cases per year in the US); thus, routine diagnosis is often challenging, and effective treatment options are limited, resulting in high morbidity and mortality rates. Glycosaminoglycans contribute inextricably to the formation of amyloid fibrils and foster the deposition of amyloid in tissues. Those present in amyloid deposits are biochemically and electrochemically distinct from glycosaminoglycans found in the plasma membrane and extracellular matrices of healthy tissues due to the presence of a high degree of heparin-like hypersulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14. Herein we show efficacious detection of murine systemic amyloid in vivo by using molecular imaging, and the specific targeting of the peptide to major forms of human amyloid in tissue sections. 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; thus, providing a novel technique for prognostication, patient stratification, and monitoring response to therapy.

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

    PubMed

    Devi, L; Ohno, M

    2015-05-05

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

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

    PubMed

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

    1996-06-25

    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 manifestations. So far, more than 40 distinct amino acid substitutions distributed throughout the TTR sequence over 30 positions have been found to be correlated with an increased amyloidogenicity of TTR. Most of these amyloidogenic amino acid substitutions are suspected to alter the conformation and stability of the monomer. Here we identify and characterize by protein and DNA analysis a novel amyloidogenic Val-20 to Ile mutation in a German three-generation family. The index patient suffered from severe amyloid cardiomyopathy at the age of 60. Conformational stability and unfolding behavior of the Ile-20 monomer in urea gradients was found to be almost indistinguishable from that of wild-type TTR. In contrast, tetramer stability was significantly reduced in agreement with the expected change in the interactions between the two opposing dimers via the side chain of Ile-20. Our observations provide strong evidence for the view that amyloidogenic amino acid substitutions in TTR facilitate the conversion of tetrameric TTR complexes into those conformational intermediates of the TTR folding pathway that have an intrinsic amyloidogenic potential.

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

    PubMed Central

    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 manifestations. So far, more than 40 distinct amino acid substitutions distributed throughout the TTR sequence over 30 positions have been found to be correlated with an increased amyloidogenicity of TTR. Most of these amyloidogenic amino acid substitutions are suspected to alter the conformation and stability of the monomer. Here we identify and characterize by protein and DNA analysis a novel amyloidogenic Val-20 to Ile mutation in a German three-generation family. The index patient suffered from severe amyloid cardiomyopathy at the age of 60. Conformational stability and unfolding behavior of the Ile-20 monomer in urea gradients was found to be almost indistinguishable from that of wild-type TTR. In contrast, tetramer stability was significantly reduced in agreement with the expected change in the interactions between the two opposing dimers via the side chain of Ile-20. Our observations provide strong evidence for the view that amyloidogenic amino acid substitutions in TTR facilitate the conversion of tetrameric TTR complexes into those conformational intermediates of the TTR folding pathway that have an intrinsic amyloidogenic potential. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8692810

  9. The association of nephrotic syndrome and renal vein thrombosis: a clinicopathological analysis of eight pediatric patients.

    PubMed

    Tinaztepe, K; Buyan, N; Tinaztepe, B; Akkök, N

    1989-01-01

    Cases with a pathological diagnosis of renal venous thrombosis (RVT) associated with nephrotic syndrome (NS) were studied retrospectively for clinicopathological evaluation. The material consisted of 21 RVT cases which were diagnosed in 2000 consecutive pediatric necropsies, with an overall incidence of about one percent. Eight of the 21 RVT cases were associated with nephrotic syndrome (34%), and this group formed 0.4 percent of the total necropsies in our pediatric center. The glomerulopathies of these nephrotic patients consisted of three cases of Finnish-type congenital NS (FCNS), three cases of renal amyloidosis secondary to familial Mediterranean fever, and two cases of membranoproliferative glomerulonephritis (MPGN). The presence of sepsis associated with disseminated intravascular coagulation, and the morphological age of the thrombi suggested that the RVT was secondary to sepsis in the FCNS cases. In the MPGN and secondary renal amyloidosis cases, the long duration of both the nephrotic state and the administration of diuretics along with glucocorticoid treatment and also the newly formed thrombi without infarction are strong evidences, although not definite, that the RVT developed as a complication of the glomerulopathy. Even though there were no definite clinical criteria for the diagnosis of most of the RVT cases, we would like to emphasize the importance of flank pain, the rapid deterioration of renal functions in a stable nephrotic patient, as well as the hypercoagulable state in the consideration of the development of RVT which indicate the need for appropriate radiological studies for confirmation of this condition during life.

  10. [Oral status and oral mucosa blood circulation changes in patients with chronic heart failure].

    PubMed

    Orekhova, L Iu; Rybakova, M G; Barmasheva, A A; Kuznetsova, I A; Semernin, E N; Shirshova, N A; Shliakhto, E V; Gudkova, A Ia

    2013-01-01

    The objective of this study was to characterize dental status and oral mucosa blood flow in patients with chronic heart failure and amyloid deposits in oral mucosa. Histological and immunohistochemical analysis of 80 oral mucosa biopsies taken from patients aged 32-72 years with chronic heart failure I-IV NYHA functional class was carried out. It detected a systemic amyloidosis in 15.7% of cases; a local amyloid deposition in oral mucosa was found in 58.5% of cases. Amyloid deposition in oral mucosa was associated with severe chronic generalized periodontitis in more than a half of cases. Amyloid deposits in oral mucosa were revealed more often in patients with metabolic syndrome (63.5%). The article describes dental status and oral mucosa blood flow in patients with heart failure.

  11. Immunoglobulin-free light chain monomer-dimer patterns help to distinguish malignant from premalignant monoclonal gammopathies: a pilot study.

    PubMed

    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

  12. Genetics Home Reference: transthyretin amyloidosis

    MedlinePlus

    ... a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body ... peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments in bodily ...

  13. Clearance and synthesis rates of beta 2-microglobulin in patients undergoing hemodialysis and in normal subjects

    SciTech Connect

    Floege, J.; Bartsch, A.; Schulze, M.; Shaldon, S.; Koch, K.M.; Smeby, L.C. )

    1991-08-01

    Retention of {beta} 2-microglobulin in patients undergoing hemodialysis is associated with a {beta} 2-microglobulin-derived amyloidosis. Removal of {beta} 2-microglobulin by renal replacement therapy has been proposed for the prevention of this amyloidosis. Currently, however, data on the {beta} 2-microglobulin synthesis rate in patients undergoing hemodialysis are scarce, and consequently it remains speculative how much removal would be necessary to counterbalance synthesis. The plasma kinetics of iodine 131-labeled {beta} 2-microglobulin were therefore examined in 11 patients with anuria who were undergoing long-term hemodialysis. Five healthy persons served as controls. Kinetic modeling of the plasma curves showed that the data fitted a two-pool model (r2 greater than 0.96) consisting of a rapid 2 to 4 hour distribution phase followed by a less steep curve, described by the plasma (metabolic) clearance (Clp). Synthetic rates were calculated from Clp and the {beta} 2-microglobulin steady state plasma concentration (plus {beta} 2-microglobulin removal during hemodialysis in the case of high flux hemodialysis). The results showed a significantly higher Clp in normal controls as compared with patients undergoing hemodialysis (65.5 {plus minus} 12.8 ml/min (mean {plus minus} SD) versus 3.4 {plus minus} 0.7 ml/min). In contrast, the {beta} 2-microglobulin synthesis rate in the patient group (3.10 {plus minus} 0.79 mg/kg/day) was not significantly different from that of normal controls (2.40 {plus minus} 0.67 mg/kg/day), which was due to markedly elevated {beta} 2-microglobulin plasma concentrations in the patients (37.6 {plus minus} 14.1 mg/L vs 1.92 {plus minus} 0.27 mg/L). These findings suggest that the presence of end-stage renal disease does not have a significant impact on the beta 2-microglobulin generation rate.

  14. Amyotrophic Lateral Sclerosis (ALS)

    MedlinePlus

    ... Pictures of ALS Mutant Proteins Support Two Major Theories About How the Disease is Caused May 2003 ... All NINDS-prepared information is in the public domain and may be freely copied. Credit to the ...

  15. Genetic Testing for ALS

    MedlinePlus

    ... Involved Donate Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing By Deborah Hartzfeld, MS, CGC, Certified Genetic ... guarantee a person will develop symptoms of ALS. Genetic Counseling If there is more than one person ...

  16. All About ALS

    MedlinePlus

    ... External link, please review our exit disclaimer . Subscribe All About ALS Understanding a Devastating Disorder In the ... a coffee pot, or button a shirt. Eventually, all muscles under voluntary control are affected, and people ...

  17. What Is ALS?

    MedlinePlus

    ... scarring or hardening ("sclerosis") in the region. Motor neurons reach from the brain to the spinal cord ... the body. The progressive degeneration of the motor neurons in ALS eventually leads to their demise. When ...

  18. ALS superbend magnet system

    SciTech Connect

    Zbasnik, J.; Wang, S.T.; Chen, J.Y.; DeVries, G.J.; DeMarco, R.; Fahmie, M.; Geyer, A.; Green, M.A.; Harkins, J.; Henderson, T.; Hinkson, J.; Hoyer, E.H.; Krupnick, J.; Marks, S.; Ottens, F.; Paterson, J.A.; Pipersky, P.; Portmann, G.; Robin, D.A.; Schlueter, R.D.; Steier, C.; Taylor, C.E.; Wahrer, R.

    2000-09-15

    The Lawrence Berkeley National Laboratory is preparing to upgrade the Advanced Light Source (ALS) with three superconducting dipoles (Superbends). In this paper we present the final magnet system design which incorporates R&D test results and addresses the ALS operational concerns of alignment, availability, and economy. The design incorporates conduction-cooled Nb-Ti windings and HTS current leads, epoxy-glass suspension straps, and a Gifford-McMahon cryocooler to supply steady state refrigeration. We also present the current status of fabrication and testing.

  19. Modulus measurements in ordered Co-Al, Fe-Al, and Ni-Al alloys

    NASA Technical Reports Server (NTRS)

    Harmouche, M. R.; Wolfenden, A.

    1985-01-01

    The composition and/or temperature dependence of the dynamic Young's modulus for the ordered B2 Co-Al, Fe-Al, and Ni-Al aluminides has been investigated using the piezoelectric ultrasonic composite oscillator technique (PUCOT). The modulus has been measured in the composition interval 48.49 to 52.58 at. pct Co, 50.87 to 60.2 at. pct Fe, and 49.22 to 55.95 at. pct Ni for Co-Al, Fe-Al, and Ni-Al, respectively. The measured values for Co-Al are in the temperature interval 300 to 1300 K, while those for the other systems are for ambient temperature only. The data points show that Co-Al is stiffer than Fe-Al, which is stiffer than Ni-Al. The data points for Fe-Al and Ni-Al are slightly higher than those reported in the literature.

  20. Genetic counselling in ALS: facts, uncertainties and clinical suggestions.

    PubMed

    Chiò, Adriano; Battistini, Stefania; Calvo, Andrea; Caponnetto, Claudia; Conforti, Francesca L; Corbo, Massimo; Giannini, Fabio; Mandrioli, Jessica; Mora, Gabriele; Sabatelli, Mario; Ajmone, Clara; Mastro, Enza; Pain, Debora; Mandich, Paola; Penco, Silvana; Restagno, Gabriella; Zollino, Marcella; Surbone, Antonella

    2014-05-01

    The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.

  1. Al Shanker Remembers.

    ERIC Educational Resources Information Center

    American Educator, 2000

    2000-01-01

    In a 1996 interview shortly before his death, Al Shanker, longtime president of the American Federation of Teachers, discussed such topics as: his own educational experiences; how he learned about political fighting in the Boy Scouts; the appeal of socialism; multinational corporations and the nation state; teaching tough students; and John Dewey…

  2. Fosetyl-al

    Integrated Risk Information System (IRIS)

    Fosetyl - al ; CASRN 39148 - 24 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  3. ALS renewal moves forward

    NASA Astrophysics Data System (ADS)

    Falcone, R. W.; Feinberg, B.; Hussain, Z.; Kirz, J.; Krebs, G. F.; Padmore, H. A.; Robin, D. S.; Robinson, A. L.

    2007-11-01

    As the result of an extensive long-term planning process involving all its stakeholders—management, staff, and users—the ALS has seen its future and is aggressively moving ahead to implement its vision for keeping the facility at the cutting edge for the next 2-3 decades. The evolving strategic plan now in place aims to renew the ALS so it can address a new generation of fundamental questions about size dependent and dimensional-confinement phenomena at the nanoscale; correlation and complexity in physical, biological, and environmental systems; and temporal evolution, assembly, dynamics and ultrafast phenomena. The renewal spans three areas: (1) increased staffing at beamlines to support the growing user community and safety professionals to keep an increasingly complex facility hazard free; (2) implementing advances in accelerator, insertion device, beamline, and detector technology that will make it possible for ALS users to address emerging grand scientific and technological challenges with incisive world-class tools; and (3) construction of a user support building and guest housing that will increase the safety and user friendliness of the ALS by providing users office, meeting, experiment staging, and laboratory space for their work and on-site accommodations at reasonable rates.

  4. Complementary and Alternative Therapies in ALS

    PubMed Central

    Bedlack, Richard S.; Joyce, Nanette; Carter, Gregory T.; Pagononi, Sabrina; Karam, Chafic

    2015-01-01

    Synopsis Given the severity of their illness and lack of effective disease modifying agents, it is not surprising that most patients with ALS consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation and energy healing. This chapter reviews these in detail. We also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy and shared decision making. Finally, we review a program called ALSUntangled which using shared shared decision making to review alternative therapies for ALS. PMID:26515629

  5. Characterization of human sporadic ALS biomarkers in the familial ALS transgenic mSOD1(G93A) mouse model.

    PubMed

    Lilo, Eitan; Wald-Altman, Shane; Solmesky, Leonardo J; Ben Yaakov, Keren; Gershoni-Emek, Noga; Bulvik, Shlomo; Kassis, Ibrahim; Karussis, Dimitrios; Perlson, Eran; Weil, Miguel

    2013-12-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1(G93A) transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1(G93A) and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1(G93A) mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS.

  6. Common ground: stem cell approaches find shared pathways underlying ALS.

    PubMed

    Matus, Soledad; Medinas, Danilo B; Hetz, Claudio

    2014-06-01

    The development of curative therapies for genetically complex diseases such as ALS has been delayed by the lack of relevant disease models. Recent advances using induced-pluripotent-stem-cell-derived motoneurons from patients harboring distinct ALS mutations have recapitulated essential disease features and have identified some common pathways driving disease pathogenesis. PMID:24905158

  7. 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

    PubMed Central

    Yamanaka, Keiichi; Nakanishi, Takehisa; Saito, Hiromitsu; Maruyama, Junko; Isoda, Kenichi; Yokochi, Ayumu; Imanaka-Yoshida, Kyoko; Tsuda, Kenshiro; Kakeda, Masato; Okamoto, Ryuji; Fujita, Satoshi; Iwakura, Yoichiro; Suzuki, Noboru; Ito, Masaaki; Maruyama, Kazuo; Gabazza, Esteban C.; Yoshida, Toshimichi; Shimaoka, Motomu; Mizutani, Hitoshi

    2014-01-01

    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. PMID:25119884

  8. Ausbildung als zentrale Aufgabe

    NASA Astrophysics Data System (ADS)

    Krämer, Walter; Schmerbach, Sibylle

    Anders als Lesen und Schreiben zählen Grundkenntnisse in Statistik heute noch nicht zu den Voraussetzungen einer sinnvollen Teilhabe am Sozialgeschehen. Und auch in der akademischen Statistik-Ausbildung gibt es noch einiges zu tun. Das vorliegende Kapitel zeichnet die Geschichte dieser akademischen Ausbildung an deutschen Universitäten nach dem zweiten Weltkrieg nach, stellt aktuelle Defizite vor und weist auf mögliche Verbesserungen hin.

  9. Prospective study of cost of care at multidisciplinary ALS centers adhering to American Academy of Neurology (AAN) ALS practice parameters.

    PubMed

    Boylan, Kevin; Levine, Todd; Lomen-Hoerth, Catherine; Lyon, Mary; Maginnis, Kimberly; Callas, Peter; Gaspari, Celeste; Tandan, Rup

    2015-01-01

    Multidisciplinary care in ALS is associated with longer survival, improved quality of life, and reduced hospital admissions, but there are no published data on institutional costs associated with multidisciplinary ALS care at U.S. centers. We prospectively examined institutional costs, adherence to AAN Practice Parameters and patient satisfaction in multidisciplinary ALS clinics at 18 U.S. ALS centers. Centers reported patient volumes; direct costs for staff salary/benefits, supplies and equipment; and institutional non-salary and overhead costs over a three-month period. In 1117 patients seen during this period, mean age was 61.5 years (range 25-91 years), 56% were male, and mean ALSFRS-R score was 29. Mean total salary/benefit cost per clinic day for all providers was $2964 (range $1692-$5236 across centers). Mean salary/benefit cost per patient per clinic was $507 (range $258-$806 across centers). Differences among centers in reporting non-salary costs prevented meaningful analysis. Practice parameter adherence and patient satisfaction were high. This prospective collaborative study demonstrates the direct financial burden of evidence-based multidisciplinary ALS care in the U.S.; more refined non-salary and overhead cost data are needed to evaluate the full cost impact of care. These data may be useful in supporting evidence-based models of patient centered care for ALS. PMID:26462131

  10. Destructive Spondyloarthropathy in Patients on Long-Term Peritoneal Dialysis or Hemodialysis.

    PubMed

    Hayami, Noriko; Hoshino, Junichi; Suwabe, Tastuya; Sumida, Keiichi; Mise, Koki; Hamanoue, Satoshi; Sawa, Naoki; Kitajima, Izuru; Hirota, Yutaka; Oohashi, Kenichi; Fujii, Takeshi; Okuda, Itsuko; Takaichi, Kenmei; Ubara, Yoshifumi

    2015-08-01

    Destructive spondyloarthropathy (DSA) is the most serious spinal complication of dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we could not find any information about DSA in patients on peritoneal dialysis (PD) for over 10 years. We retrospectively evaluated factors contributing to DSA in HD and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were compared between a PD group (n = 23) or a HD group (n = 44). In the PD group, nine patients (39%) developed DSA. The mean age of DSA patients was significantly higher than that of non-DSA patients (66.2 ± 10.0 vs. 51.0 ± 12.8 years, P = 0.03). The frequency of cervical spine DSA did not show any difference between the PD and HD groups, but the frequency of lumbar spine DSA showed a significant difference (22% vs. 5%, P = 0.04). The serum beta-2 microglobulin (B2MG) level was significantly higher in PD patients than in HD patients (38.4 mg/L vs. 27.4 mg/L, P = 0.0025). Mechanical stress such as elevation of the intra-abdominal pressure due to infusion of PD fluid (1500 mL to 2000 mL) for over 10 years might contribute to lumbar DSA in patients on long-term PD.

  11. Cancer Patients and Fungal Infections

    MedlinePlus

    ... mould-related diseases in immunocompromised patients. Journal of Antimicrobial Chemotherapy 2011;66:i5-i14. Ribaud P. Fungal ... al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update ...

  12. Environmental Risk Factors and Amyotrophic Lateral Sclerosis (ALS): A Case-Control Study of ALS in Michigan

    PubMed Central

    Yu, Yu; Su, Feng-Chiao; Callaghan, Brian C.; Goutman, Stephen A.; Batterman, Stuart A.; Feldman, Eva L.

    2014-01-01

    An interim report of a case-control study was conducted to explore the role of environmental factors in the development of amyotrophic lateral sclerosis (ALS). Sixty-six cases and 66 age- and gender-matched controls were recruited. Detailed information regarding residence history, occupational history, smoking, physical activity, and other factors was obtained using questionnaires. The association of ALS with potential risk factors, including smoking, physical activity and chemical exposure, was investigated using conditional logistic regression models. As compared to controls, a greater number of our randomly selected ALS patients reported exposure to fertilizers to treat private yards and gardens and occupational exposure to pesticides in the last 30 years than our randomly selected control cases. Smoking, occupational exposures to metals, dust/fibers/fumes/gas and radiation, and physical activity were not associated with ALS when comparing the randomly selected ALS patients to the control subjects. To further explore and confirm results, exposures over several time frames, including 0–10 and 10–30 years earlier, were considered, and analyses were stratified by age and gender. Pesticide and fertilizer exposure were both significantly associated with ALS in the randomly selected ALS patients. While study results need to be interpreted cautiously given the small sample size and the lack of direct exposure measures, these results suggest that environmental and particularly residential exposure factors warrant close attention in studies examining risk factors of ALS. PMID:24979055

  13. An epidemiological study of cutaneous leishmaniasis in Al-jabal Al-gharbi, Libya.

    PubMed

    Abdellatif, Manal Z M; El-Mabrouk, Khamis; Ewis, Ashraf A

    2013-02-01

    Cutaneous leishmaniasis (CL) is an endemic parasitic infection in the Mediterranean region, including Libya and its Al-jabal Al-gharbi province. We aimed at studying the occupational relevance as well as other epidemiological aspects of CL. We investigated 140 CL cases who attended at Gharyan outpatient polyclinic during a period of 6 months in 2009. CL infection was clinically diagnosed and confirmed by demonstration of Leishmania parasites on smears from lesions. Our findings showed that males were more affected than females (P=0.04), and people above 10-years were more affected than younger ones (P=0.0001). A significant percent of CL cases belonged to Al-Kawasem subprovince (P=0.0001). Farm-related activities were the most frequent occupations among CL cases (P=0.04). In addition to farm workers, housewives and students are at risk groups since they are engaged at farm activities. Moreover, those who have occupations that require staying outdoors for a part of night, e.g., policemen, are also at risk. Compared to children, adult CL patients had multiple lesions (P=0.001) that were more prevalent in their upper and lower extremities than the face (P=0.0001). We conclude that CL is a major health problem in Al-jabal Al-gharbi province of Libya. The presence of rodents and sandflies makes it a suitable environment for Leishmania to spread in an endemic epidemiological pattern. Being engaged in farming activities or outdoor occupations increases the risk of infection. Various clinical patterns of CL suggest the presence of more than 1 species of Leishmania at Al-jabal Al-gharbi province. We propose that the 2 species responsible for CL in this area are L. major and L. tropica. Further investigations to identify the leishmanial species responsible for CL at Al-jabal Al-gharbi together with adoption of preventive and control programs are needed.

  14. An Epidemiological Study of Cutaneous Leishmaniasis in Al-Jabal Al-Gharbi, Libya

    PubMed Central

    Abdellatif, Manal Z. M.; El-Mabrouk, Khamis

    2013-01-01

    Cutaneous leishmaniasis (CL) is an endemic parasitic infection in the Mediterranean region, including Libya and its Al-jabal Al-gharbi province. We aimed at studying the occupational relevance as well as other epidemiological aspects of CL. We investigated 140 CL cases who attended at Gharyan outpatient polyclinic during a period of 6 months in 2009. CL infection was clinically diagnosed and confirmed by demonstration of Leishmania parasites on smears from lesions. Our findings showed that males were more affected than females (P=0.04), and people above 10-years were more affected than younger ones (P=0.0001). A significant percent of CL cases belonged to Al-Kawasem subprovince (P=0.0001). Farm-related activities were the most frequent occupations among CL cases (P=0.04). In addition to farm workers, housewives and students are at risk groups since they are engaged at farm activities. Moreover, those who have occupations that require staying outdoors for a part of night, e.g., policemen, are also at risk. Compared to children, adult CL patients had multiple lesions (P=0.001) that were more prevalent in their upper and lower extremities than the face (P=0.0001). We conclude that CL is a major health problem in Al-jabal Al-gharbi province of Libya. The presence of rodents and sandflies makes it a suitable environment for Leishmania to spread in an endemic epidemiological pattern. Being engaged in farming activities or outdoor occupations increases the risk of infection. Various clinical patterns of CL suggest the presence of more than 1 species of Leishmania at Al-jabal Al-gharbi province. We propose that the 2 species responsible for CL in this area are L. major and L. tropica. Further investigations to identify the leishmanial species responsible for CL at Al-jabal Al-gharbi together with adoption of preventive and control programs are needed. PMID:23467624

  15. A fruitful endeavor: modeling ALS in the fruit fly.

    PubMed

    Casci, Ian; Pandey, Udai Bhan

    2015-05-14

    For over a century Drosophila melanogaster, commonly known as the fruit fly, has been instrumental in genetics research and disease modeling. In more recent years, it has been a powerful tool for modeling and studying neurodegenerative diseases, including the devastating and fatal amyotrophic lateral sclerosis (ALS). The success of this model organism in ALS research comes from the availability of tools to manipulate gene/protein expression in a number of desired cell-types, and the subsequent recapitulation of cellular and molecular phenotypic features of the disease. Several Drosophila models have now been developed for studying the roles of ALS-associated genes in disease pathogenesis that allowed us to understand the molecular pathways that lead to motor neuron degeneration in ALS patients. Our primary goal in this review is to highlight the lessons we have learned using Drosophila models pertaining to ALS research. This article is part of a Special Issue entitled ALS complex pathogenesis.

  16. Modeling neuronal vulnerability in ALS.

    PubMed

    Roselli, Francesco; Caroni, Pico

    2014-08-20

    Using computational models of motor neuron ion fluxes, firing properties, and energy requirements, Le Masson et al. (2014) reveal how local imbalances in energy homeostasis may self-amplify and contribute to neurodegeneration in ALS.

  17. Effect of Orem Self-Care Program on the Life Quality of Burn Patients Referred to Ghotb-al-Din-e-Shirazi Burn Center, Shiraz, Iran: A Randomized Controlled Trial

    PubMed Central

    Hashemi, Fatemeh; Rahimi Dolatabad, Fatemeh; Yektatalab, Shahrzad; Ayaz, Mehdi; Zare, Najaf; Mansouri, Parisa

    2014-01-01

    Background: Advances in treatment and critical care have largely improved the survival following burns; therefore, the importance of quality of life in burn patients is an issue beyond question. The aim of this study was to determine the effects of Orem self-care program on Quality of Life of burn patients. Methods: A randomized clinical trial study was conducted on 110 eligible burn patients who were selected using easy sampling method and allocated randomly into two groups of experiment and control. The instrument for data collection was a questionnaire, containing demographic and burn information and burn-specific health scale–brief (BSHS-B) questionnaire. For the experiment group, 5 sessions of theoretical training and 75-90 minutes of practical training were accomplished. The quality of life of the patients with burns was assessed in three phases by the BSHS-B questionnaire. The data were analyzed in SPSS-17 using Chi-square test, Fisher’s exact test, Independent t-test and repeated measurement multivariate test. Results: After one month and two months of the use of self-care model, the quality of life of the cases improved from 73.33% to 83.78% and 98.12%, respectively (P<0.001). But the changes in the quality of life of the patients in the control group were not statistically significant (P>0.05). Conclusion: Based on the obtained results of this study, designing and implementing a self-care program based on Orem’s model and the needs of burn patients will improve their quality of life. Therefore, it is recommended that this program should be considered as a part of treatment program for these patients. Trial Registration Number: 2013042112129N1 PMID:25349844

  18. Diagnosing Multiple Myeloma from Test Results

    MedlinePlus

    ... does not need to be treated right away. Light chain amyloidosis A diagnosis of light chain amyloidosis is made when the patient has ... A biopsy that shows amyloid made up of light chains, PLUS any of the following: Elevated free ...

  19. Al Jazirah, Sudan

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Al Jazirah (also Gezira) is one of the 26 states of Sudan. The state lies between the Blue Nile and the White Nile in the east-central region of the country. It is a well populated area suitable for agriculture. The area was at the southern end of Nubia and little is known about its ancient history and only limited archaeological work has been conducted in this area. The region has benefited from the Gezira Scheme, a program to foster cotton farming begun in 1925. At that time the Sennar Dam and numerous irrigation canals were built. Al Jazirah became the Sudan's major agricultural region with more than 2.5 million acres (10,000 km) under cultivation. The initial development project was semi-private, but the government nationalized it in 1950. Cotton production increased in the 1970s but by the 1990s increased wheat production has supplanted a third of the land formerly seeded with cotton.

    The image was acquired December 25, 2006, covers an area of 56 x 36.4 km, and is located near 14.5 degrees north latitude, 33.1 degrees east longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  20. Examining the evidence about treatment in ALS/MND.

    PubMed

    Miller, R G

    2001-03-01

    The application of evidence-based medicine to the treatment of patients with amyotrophic lateral sclerosis (ALS) is just beginning. A small number of systematic reviews analyzing the pertinent evidence, grading the methodology and formulating recommendations to guide clinical decision-making have begun to appear. The American Academy of Neurology practice parameters for informing the patient and managing nutritional and respiratory issues and palliative care are discussed. In addition, the first systematic review in the field of ALS/MND from the Cochrane collaboration concerns riluzole treatment and this meta-analysis is also described. Some of the most important recommendations that have the potential to significantly prolong survival and enhance quality of life are the early institution of percutaneous endoscopic gastrostomy for patients with significant dysphagia, and the initiation of non-invasive positive pressure ventilation for patients with symptoms of early respiratory insufficiency. Assertive treatment of pain and dyspnea are also strongly recommended for patients with ALS. The North American ALS patient database, ALS C.A.R.E., is also described as a methodology for measuring clinical outcomes, and some early results are presented. The evidence on riluzole indicates effectiveness in prolonging survival with a good safety profile. PMID:11465930

  1. ALS Performance Summary - Update

    SciTech Connect

    Waters, A M; Brown, W D; Martz, Jr., H E

    2004-09-30

    High Energy Density Physics (HEDP) experiments play an important role in corroborating the improved physics codes that underlie LLNL's Stockpile Stewardship mission. Conducting these experiments, whether on the National Ignition Facility (NIF) or another national facility such as Omega, will require not only improvement in the diagnostics for measuring the experiment, but also detailed knowledge of the as-built target components and assemblies themselves. To assist in this effort, a defined set of well-known reference standards designed to represent a range of HEDP targets have been built and are being used to quantify the performance of different characterization techniques [Hibbard, et al. 2004]. Without the critical step of using reference standards for qualifying characterization tools there can be no verification of either commercial or internally-developed characterization techniques and thus an uncertainty in the input to the physics code models would exist.

  2. A yeast functional screen predicts new candidate ALS disease genes

    PubMed Central

    Couthouis, Julien; Hart, Michael P.; Shorter, James; DeJesus-Hernandez, Mariely; Erion, Renske; Oristano, Rachel; Liu, Annie X.; Ramos, Daniel; Jethava, Niti; Hosangadi, Divya; Epstein, James; Chiang, Ashley; Diaz, Zamia; Nakaya, Tadashi; Ibrahim, Fadia; Kim, Hyung-Jun; Solski, Jennifer A.; Williams, Kelly L.; Mojsilovic-Petrovic, Jelena; Ingre, Caroline; Boylan, Kevin; Graff-Radford, Neill R.; Dickson, Dennis W.; Clay-Falcone, Dana; Elman, Lauren; McCluskey, Leo; Greene, Robert; Kalb, Robert G.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Ludolph, Albert; Robberecht, Wim; Andersen, Peter M.; Nicholson, Garth A.; Blair, Ian P.; King, Oliver D.; Bonini, Nancy M.; Van Deerlin, Vivianna; Rademakers, Rosa; Mourelatos, Zissimos; Gitler, Aaron D.

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery. PMID:22065782

  3. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy

    PubMed Central

    Palma, Eleonora; Reyes-Ruiz, Jorge Mauricio; Lopergolo, Diego; Roseti, Cristina; Bertollini, Cristina; Ruffolo, Gabriele; Cifelli, Pierangelo; Onesti, Emanuela; Limatola, Cristina; Miledi, Ricardo; Inghilleri, Maurizio

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. By microtransplanting muscle membranes from selected ALS patients into Xenopus oocytes, we show that PEA reduces the desensitization of acetylcholine-evoked currents after repetitive neurotransmitter application (i.e., rundown). The same effect was observed using muscle samples from denervated (non-ALS) control patients. The expression of human recombinant α1β1γδ (γ-AChRs) and α1β1εδ AChRs (ε-AChRs) in Xenopus oocytes revealed that PEA selectively affected the rundown of ACh currents in ε-AChRs. A clear up-regulation of the α1 subunit in muscle from ALS patients compared with that from non-ALS patients was found by quantitative PCR, but no differential expression was found for other subunits. Clinically, ALS patients treated with PEA showed a lower decrease in their forced vital capacity (FVC) over time as compared with untreated ALS patients, suggesting that PEA can enhance pulmonary function in ALS. In the present work, data were collected from a cohort of 76 ALS patients and 17 denervated patients. Our results strengthen the evidence for the role of skeletal muscle in ALS pathogenesis and pave the way for the development of new drugs to hamper the clinical effects of the disease. PMID:26929355

  4. Theoretical studies of AlF, AlCl, and AlBr

    NASA Technical Reports Server (NTRS)

    Langhoff, Stephen R.; Bauschlicher, Charles W., Jr.; Taylor, Peter R.

    1988-01-01

    Spectroscopic constants have been obtained for the lowest six singlet and lowest five triplet states of AlF and AlCl. The results suggest that the correct ordering of the triplet manifold in these molecules is: a 3Pi, b 3Sigma(+), c 3Sigma(+), d 3Pi, and e 3Delta. Radiative lifetimes have been determined for the excited states, and the A 1Pi to X 1Sigma(+) transition in AlF, AlCl, and AlBr has been examined in detail. A-X transition moment functions, Einstein coefficients, and A 1Pi vibrational lifetimes have been obtained for AlF and AlCl.

  5. A Fruitful Endeavor: Modeling ALS in the Fruit Fly

    PubMed Central

    Casci, Ian; Pandey, Udai Bhan

    2014-01-01

    For over a century Drosophila melanogaster, commonly known as the fruit fly, has been instrumental in genetics research and disease modeling. In more recent years, it has been a powerful tool for modeling and studying neurodegenerative diseases, including the devastating and fatal amyotrophic lateral sclerosis (ALS). The success of this model organism in ALS research comes from the availability of tools to manipulate gene/protein expression in a number of desired cell-types, and the subsequent recapitulation of cellular and molecular phenotypic features of the disease. Several Drosophila models have now been developed for studying the roles of ALS-associated genes in disease pathogenesis that allowed us to understand the molecular pathways that lead to motor neuron degeneration in ALS patients. Our primary goal in this review is to highlight the lessons we have learned using Drosophila models pertaining to ALS research. PMID:25289585

  6. Alexandria (Al Iskandariya), Egypt

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This image of Alexandria was taken by astronauts on board the International Space Station in December 2000 using an Electronic Still Camera. A wider-angle view (STS088-739-90) taken from the Space Shuttle in December 1998 is available for context. Alexandria (Al Iskandariya) occupies a T-shaped peninsula and strip of land separating the Mediterranean from Lake Mariout. Originally the town was built upon a mole (stone breakwater) called Heptastadium, which joined the island of Pharos (see referenced website, below) to the mainland. Since then sedimentary deposits have widened the mole. Since 1905, when the 370,000 Alexandrians lived in an area of about 4 sq km between the two harbors, the city (population 4 million; see referenced website, below) has grown beyond its medieval walls and now occupies an area of about 300 sq km. The Mahmudiya Canal, connecting Alexandria with the Nile, runs to the south of the city and, by a series of locks, enters the harbor of the principal port of Egypt (note ships). The reddish and ochre polygons west of Lake Mariout are salt-evaporation, chemical-storage, and water-treatment ponds within the coastal lagoon. Reference Youssef Halim and Fatma Abou Shouk, 2000, Human impacts on Alexandria's marine environment: UNESCO, Coastal Regions and Small Islands Unit (CSI), Coastal Management Sourcebooks 2 (accessed December 20, 2000) Additional photographs taken by astronauts can be viewed at NASA-JSC's Gateway to Astronaut Photography of Earth. Image ISS001-ESC-5025 provided by the Earth Sciences and Image Analysis Laboratory, Johnson Space Center.

  7. Promoting excellence in end-of-life care in ALS.

    PubMed

    Mitsumoto, Hiroshi; Bromberg, Mark; Johnston, Wendy; Tandan, Rup; Byock, Ira; Lyon, Mary; Miller, Robert G; Appel, Stanley H; Benditt, Josh; Bernat, James L; Borasio, Gian Domenico; Carver, Alan C; Clawson, Lora; Del Bene, Maura L; Kasarskis, Edward J; LeGrand, Susan B; Mandler, Raul; McCarthy, Jane; Munsat, Theodore; Newman, Daniel; Sufit, Robert L; Versenyi, Andrea

    2005-09-01

    The type and quality of end-of-life care varies greatly in ALS; the time to initiate end-of-life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end-of-life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end-of-life care in ALS; and 3) identify areas needed for new prospective clinical research. The ALS Peer Workgroup reviewed the literature and 1) identified the current state of knowledge, 2) analysed the gaps in care, and 3) provided recommendations for standard of care and future research. It was shown that areas of investigation are needed on the incorporation of an interdisciplinary approach to care in ALS that includes: psychosocial evaluation and spiritual care; the use of validated instruments to assess patient and caregiver quality of life; and the establishment of proactive caregiver programs. Several public policy changes that will improve coverage for medical care, hospice, and caregiver costs are also reviewed. More clinical evidence is needed on how to provide optimal end-of-life care specifically in ALS.

  8. Scavenger treatment of free radical injury in familial amyloidotic polyneuropathy: a study on Swedish transplanted and non-transplanted patients.

    PubMed

    Suhr, O B; Lång, K; Wikström, L; Anan, I; Ando, Y; El-Salhy, M; Holmgren, G; Tashima, K

    2001-02-01

    Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.

  9. Electrical impedance myography as a biomarker to assess ALS progression

    PubMed Central

    Rutkove, Seward B.; Caress, James B.; Cartwright, Michael S.; Burns, Ted M.; Warder, Judy; David, William S.; Goyal, Namita; Maragakis, Nicholas J.; Clawson, Lora; Benatar, Michael; Usher, Sharon; Sharma, Khema R.; Gautam, Shiva; Narayanaswami, Pushpa; Raynor, Elizabeth M.; Watson, Mary Lou; Shefner, Jeremy M.

    2012-01-01

    Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM’s potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique’s correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials. PMID:22670883

  10. Thermal Modeling of Al-Al and Al-Steel Friction Stir Spot Welding

    NASA Astrophysics Data System (ADS)

    Jedrasiak, P.; Shercliff, H. R.; Reilly, A.; McShane, G. J.; Chen, Y. C.; Wang, L.; Robson, J.; Prangnell, P.

    2016-07-01

    This paper presents a finite element thermal model for similar and dissimilar alloy friction stir spot welding (FSSW). The model is calibrated and validated using instrumented lap joints in Al-Al and Al-Fe automotive sheet alloys. The model successfully predicts the thermal histories for a range of process conditions. The resulting temperature histories are used to predict the growth of intermetallic phases at the interface in Al-Fe welds. Temperature predictions were used to study the evolution of hardness of a precipitation-hardened aluminum alloy during post-weld aging after FSSW.

  11. Thermal Modeling of Al-Al and Al-Steel Friction Stir Spot Welding

    NASA Astrophysics Data System (ADS)

    Jedrasiak, P.; Shercliff, H. R.; Reilly, A.; McShane, G. J.; Chen, Y. C.; Wang, L.; Robson, J.; Prangnell, P.

    2016-09-01

    This paper presents a finite element thermal model for similar and dissimilar alloy friction stir spot welding (FSSW). The model is calibrated and validated using instrumented lap joints in Al-Al and Al-Fe automotive sheet alloys. The model successfully predicts the thermal histories for a range of process conditions. The resulting temperature histories are used to predict the growth of intermetallic phases at the interface in Al-Fe welds. Temperature predictions were used to study the evolution of hardness of a precipitation-hardened aluminum alloy during post-weld aging after FSSW.

  12. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease.

    PubMed

    Sung, Chih-Chien; Hsu, Yu-Chuan; Chen, Chun-Chi; Lin, Yuh-Feng; Wu, Chia-Chao

    2013-01-01

    Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  13. Philosophieren als Unterrichtsprinzip im Mathematikunterricht

    NASA Astrophysics Data System (ADS)

    Meerwaldt, Diana

    Philosophieren und Mathematik scheinen zunächst gegensätzliche Bereiche zu sein, die sich kaum vereinbaren lassen. Dies trifft für eine Auffassung zu, die Philosophieren als "Gerede" disqualifiziert und Mathematik als eine reine "Formelwissenschaft" begreift. Beide Auffassungen werden den Gegenständen nicht gerecht.

  14. The Advanced Launch System (ALS)

    NASA Astrophysics Data System (ADS)

    Eldred, Charles H.

    The Advanced Launch System (ALS) is an unmanned vehicle that will achieve low hardware cost by using a reusable booster stage which flies back to the launch site, and a core stage in which the rocket engines and redundant avionics are in a module that is returned to earth and recovered for reuse. The booster's utilization of liquid propellant instead of solid propellant will help lower the consumable costs. The ALS also includes launch processing and flight control facilities, necessary support equipment, and ground- and flight-operations infrastructure. The ALS program studies show that, through the ALS, the United States can launch a major Mars initiative economically and with confidence. It is estimated that the objective ALS can be operational in the late 1990s.

  15. Quantum dots formed in InSb/AlAs and AlSb/AlAs heterostructures

    NASA Astrophysics Data System (ADS)

    Abramkin, D. S.; Rumynin, K. M.; Bakarov, A. K.; Kolotovkina, D. A.; Gutakovskii, A. K.; Shamirzaev, T. S.

    2016-06-01

    The crystal structure of new self-assembled InSb/AlAs and AlSb/AlAs quantum dots grown by molecularbeam epitaxy has been investigated by transmission electron microscopy. The theoretical calculations of the energy spectrum of the quantum dots have been supplemented by the experimental data on the steady-state and time-resolved photoluminescence spectroscopy. Deposition of 1.5 ML of InSb or AlSb on the AlAs surface carried out in the regime of atomic-layer epitaxy leads to the formation of pseudomorphically strained quantum dots composed of InAlSbAs and AlSbAs alloys, respectively. The quantum dots can have the type-I and type-II energy spectra depending on the composition of the alloy. The ground hole state in the quantum dot belongs to the heavy-hole band and the localization energy of holes is much higher than that of electrons. The ground electron state in the type-I quantum dots belongs to the indirect X XY valley of the conduction band of the alloy. The ground electron state in the type-II quantum dots belongs to the indirect X valley of the conduction band of the AlAs matrix.

  16. Telomere shortening leads to earlier age of onset in ALS mice

    PubMed Central

    Linkus, Birgit; Wiesner, Diana; MeΔner, Martina; Karabatsiakis, Alexander; Scheffold, Annika; Rudolph, K. Lenhard; Thal, Dietmar R.; Weishaupt, Jochen H.; Ludolph, Albert C.; Danzer, Karin M.

    2016-01-01

    Telomere shortening has been linked to a variety of neurodegenerative diseases. Recent evidence suggests that reduced telomerase expression results in shorter telomeres in leukocytes from sporadic patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. Here, we have characterized telomere length in microglia, astroglia and neurons in human post mortem brain tissue from ALS patients and healthy controls. Moreover, we studied the consequences of telomerase deletion in a genetic mouse model for ALS. We found a trend towards longer telomeres in microglia in the brains of ALS patients compared to non-neurologic controls. Knockout of telomerase leading to telomere shortening accelerated the ALS phenotype in SOD1G93A–transgenic mice. Our results suggest that telomerase dysfunction might contribute to the age-related risk for ALS. PMID:26978042

  17. Psychosocial adjustment to ALS: a longitudinal study

    PubMed Central

    Matuz, Tamara; Birbaumer, Niels; Hautzinger, Martin; Kübler, Andrea

    2015-01-01

    For the current study the Lazarian stress-coping theory and the appendant model of psychosocial adjustment to chronic illness and disabilities (Pakenham, 1999) has shaped the foundation for identifying determinants of adjustment to ALS. We aimed to investigate the evolution of psychosocial adjustment to ALS and to determine its long-term predictors. A longitudinal study design with four measurement time points was therefore, used to assess patients' quality of life, depression, and stress-coping model related aspects, such as illness characteristics, social support, cognitive appraisals, and coping strategies during a period of 2 years. Regression analyses revealed that 55% of the variance of severity of depressive symptoms and 47% of the variance in quality of life at T2 was accounted for by all the T1 predictor variables taken together. On the level of individual contributions, protective buffering, and appraisal of own coping potential accounted for a significant percentage in the variance in severity of depressive symptoms, whereas problem management coping strategies explained variance in quality of life scores. Illness characteristics at T2 did not explain any variance of both adjustment outcomes. Overall, the pattern of the longitudinal results indicated stable depressive symptoms and quality of life indices reflecting a successful adjustment to the disease across four measurement time points during a period of about two years. Empirical evidence is provided for the predictive value of social support, cognitive appraisals, and coping strategies, but not illness parameters such as severity and duration for adaptation to ALS. The current study contributes to a better conceptualization of adjustment, allowing us to provide evidence-based support beyond medical and physical intervention for people with ALS. PMID:26441696

  18. In memory of Al Cameron

    NASA Astrophysics Data System (ADS)

    Cowan, John; Truran, James W.

    Al Cameron, who died recently (October 3, 2005) at 80, was one of the giants in astrophysics. His insights were profound and his interests were wide-ranging. Originally trained as a nuclear physicist, he made major contributions in a number of fields, including nuclear reactions in stars, nucleosynthesis, the abundances of the elements in the Solar System, and the origin of the Solar System and the Moon. In 1957, Cameron and, independently, Burbidge, Burbidge, Fowler and Hoyle, wrote seminal papers on nuclear astrophysics. Most of our current ideas concerning ele- ment formation in stars have followed from those two pioneering and historical works. Al also made many contributions in the field of Solar System physics. Particularly noteworthy in this regard was Cameron's work on the formation of the Moon. Al was also a good friend and mentor of young people. Al Cameron will be missed by many in the community both for his scientific contributions and for his friendship.

  19. The internet for self-diagnosis and prognostication in ALS.

    PubMed

    Chen, Zhongbo; Turner, Martin R

    2010-12-01

    Persons with ALS, and those close to them, may use the internet to explore symptoms prior to formal diagnosis, and as a source of information about prognosis and treatment thereafter. We used an internet search engine to rank the sensitivity of a variety of symptom search terms a patient might use for the diagnosis of ALS/MND. We also studied search engine responses to questions about life expectancy and possible 'cure'. An internet search engine in relation to ALS currently lacks sensitivity, and results varied greatly with only minor differences in the search terms used. The prognostic information did not reflect the inherent heterogeneity. Results in relation to 'cure' were misleading and may promulgate false hopes. There is a need to guide those with ALS (and particularly their children) to sources of reliable web-based information in addition to open discussion.

  20. Comparing the Thermodynamic Behaviour of Al(1)+ZrO2(s) to Al(1)+Al2O3(s)

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2004-01-01

    In an effort to better determine the thermodynamic properties of Al(g) and Al2O(g). the vapor in equilibrium with Al(l)+ZrO2(s) was compared to the vapor in equilibrium with Al(l)+Al2O3(s) over temperature range 1197-to-1509K. The comparison was made directly by Knudsen effusion-cell mass spectrometry with an instrument configured for a multiple effusion-cell vapor source (multi-cell KEMS). Second law enthalpies of vaporization of Al(g) and Al2O(g) together with activity measurements show that Al(l)+ZrO2(s) is thermodynamically equivalent to Al(l)+Al2O3(s), indicating Al(l) remained pure and Al2O3(s) was present in the ZrO2-cell. Subsequent observation of the Al(l)/ZrO2 and vapor/ZrO2 interfaces revealed a thin Al2O3-layer had formed, separating the ZrO2-cell from Al(l) and Al(g)+Al2O(g), effectively transforming it into an Al2O3 effusion-cell. This behavior agrees with recent observations made for Beta-NiAl(Pt) alloys measured in ZrO2 effusion-cell.

  1. The distinct genetic pattern of ALS in Turkey and novel mutations.

    PubMed

    Özoğuz, Aslıhan; Uyan, Özgün; Birdal, Güneş; Iskender, Ceren; Kartal, Ece; Lahut, Suna; Ömür, Özgür; Agim, Zeynep Sena; Eken, Aslı Gündoğdu; Sen, Nesli Ece; Kavak, Pınar; Saygı, Ceren; Sapp, Peter C; Keagle, Pamela; Parman, Yeşim; Tan, Ersin; Koç, Filiz; Deymeer, Feza; Oflazer, Piraye; Hanağası, Haşmet; Gürvit, Hakan; Bilgiç, Başar; Durmuş, Hacer; Ertaş, Mustafa; Kotan, Dilcan; Akalın, Mehmet Ali; Güllüoğlu, Halil; Zarifoğlu, Mehmet; Aysal, Fikret; Döşoğlu, Nilgün; Bilguvar, Kaya; Günel, Murat; Keskin, Özlem; Akgün, Tahsin; Özçelik, Hilmi; Landers, John E; Brown, Robert H; Başak, A Nazlı

    2015-04-01

    The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population. PMID:25681989

  2. Ab initio modeling of zincblende AlN layer in Al-AlN-TiN multilayers

    NASA Astrophysics Data System (ADS)

    Yadav, S. K.; Wang, J.; Liu, X.-Y.

    2016-06-01

    An unusual growth mechanism of metastable zincblende AlN thin film by diffusion of nitrogen atoms into Al lattice is established. Using first-principles density functional theory, we studied the possibility of thermodynamic stability of AlN as a zincblende phase due to epitaxial strains and interface effect, which fails to explain the formation of zincblende AlN. We then compared the formation energetics of rocksalt and zincblende AlN in fcc Al through direct diffusion of nitrogen atoms to Al octahedral and tetrahedral interstitials. The formation of a zincblende AlN thin film is determined to be a kinetically driven process, not a thermodynamically driven process.

  3. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

    PubMed

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

    2014-06-01

    Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

  4. A de novo nonsense mutation of the FUS gene in an apparently familial ALS case

    PubMed Central

    Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Brunetti, Maura; Barberis, Marco; Traynor, Bryan J.; Carrara, Giovanna; Valentini, Consuelo; Restagno, Gabriella; Chiò, Adriano

    2014-01-01

    Mutations in C9ORF72, SOD1, TARDBP and FUS genes account for approximately two third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) in a young patient with an apparently familial ALS. This mutation cause a phenotype characterized by a young age at onset, a rapid course (<24 months) and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes. PMID:24439481

  5. C-src Enriched Serum Microvesicles Are Generated in Malignant Plasma Cell Dyscrasia

    PubMed Central

    Zendrini, Andrea; Radeghieri, Annalisa; Caimi, Luigi; Ricotta, Doris

    2013-01-01

    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. PMID:23940647

  6. ALS: A bucket of genes, environment, metabolism and unknown ingredients.

    PubMed

    Zufiría, Mónica; Gil-Bea, Francisco Javier; Fernández-Torrón, Roberto; Poza, Juan José; Muñoz-Blanco, Jose Luis; Rojas-García, Ricard; Riancho, Javier; de Munain, Adolfo López

    2016-07-01

    The scientific scenario of amyotrophic lateral sclerosis (ALS) has dramatically changed since TDP-43 aggregates were discovered in 2006 as the main component of the neuronal inclusions seen in the disease, and more recently, when the implication of C9ORF72 expansion in familial and sporadic cases of ALS and frontotemporal dementia was confirmed. These discoveries have enlarged an extense list of genes implicated in different cellular processes such as RNA processing or autophagia among others and have broaden the putative molecular targets of the disease. Some of ALS-related genes such as TARDBP or SOD1 among others have important roles in the regulation of glucose and fatty acids metabolism, so that an impairment of fatty acids (FA) consumption and ketogenic deficits during exercise in ALS patients would connect the physiopathology with some of the more intriguing epidemiological traits of the disease. The current understanding of ALS as part of a continuum with other neurodegenerative diseases and a crossroads between genetic, neurometabolic and environmental factors represent a fascinating model of interaction that could be translated to other neurodegenerative diseases. In this review we summarize the most relevant data obtained in the ten last years and the key lines for future research in ALS.

  7. ALS: A bucket of genes, environment, metabolism and unknown ingredients.

    PubMed

    Zufiría, Mónica; Gil-Bea, Francisco Javier; Fernández-Torrón, Roberto; Poza, Juan José; Muñoz-Blanco, Jose Luis; Rojas-García, Ricard; Riancho, Javier; de Munain, Adolfo López

    2016-07-01

    The scientific scenario of amyotrophic lateral sclerosis (ALS) has dramatically changed since TDP-43 aggregates were discovered in 2006 as the main component of the neuronal inclusions seen in the disease, and more recently, when the implication of C9ORF72 expansion in familial and sporadic cases of ALS and frontotemporal dementia was confirmed. These discoveries have enlarged an extense list of genes implicated in different cellular processes such as RNA processing or autophagia among others and have broaden the putative molecular targets of the disease. Some of ALS-related genes such as TARDBP or SOD1 among others have important roles in the regulation of glucose and fatty acids metabolism, so that an impairment of fatty acids (FA) consumption and ketogenic deficits during exercise in ALS patients would connect the physiopathology with some of the more intriguing epidemiological traits of the disease. The current understanding of ALS as part of a continuum with other neurodegenerative diseases and a crossroads between genetic, neurometabolic and environmental factors represent a fascinating model of interaction that could be translated to other neurodegenerative diseases. In this review we summarize the most relevant data obtained in the ten last years and the key lines for future research in ALS. PMID:27236050

  8. Andalusian astronomy: al-Zij al-Muqtabis of Ibn al-Kammâd.

    NASA Astrophysics Data System (ADS)

    Chabás, J.; Goldstein, B. R.

    1994-12-01

    In the twelfth century the Arabic astronomer Ibn al-Kammâd, living in Islamic Spain, composed three sets of astronomical tables, called "zijes". The zijes were largely based on the work of predecessors, going back to Ptolemy on the one hand, and Hindu astronomers on the other. None of his zijes survived in the original Arabic, but a Latin manuscript contains a translation of an apparently complete zij, the "al-Zij al-Muqtabis". This paper examines the body of astronomical knowledge contained in this zij. Specifically, it is shown that one can gain valuable information on the solar theory of the Islamic astronomers from this translation. Furthermore, the theory of lunar and solar eclipses in the work is analyzed, and tables of mean planetary and solar motions are discussed. In addition, tables for the motion of the vernal equinox, star tables, and several topics of Islamic spherical astronomy are examined.

  9. Microstructure Evolution and Mechanical Properties of Al/Al-Mg/Al composite sheet metals

    NASA Astrophysics Data System (ADS)

    Cho, Jaehyung; Kim, Su-Hyeon; Kim, Hyoung-Wook; Lim, Cha-Yong; Kim, Eun-Young; Choi, Shi-Hoon

    2011-08-01

    Two different types of aluminum alloys of AA1050 and AA5182 were used to manufacture Al/Al-Mg/Al composite sheet metals by roll bonding technology at room temperature. The composite sheet metals were annealed at 400 °C and carried out uniaxial tension tests to investigate mechanical properties. Macroscopic mechanical properties are strongly dependent on the volume (or thickness) fraction of two component layers. Microstructure and texture evolution were also investigated during roll bonding process. The AA1050 sheets located in the outer layer mainly consist of shear texture components and the AA5182 sheet located in the center layer consists of plane strain texture components. With differential speeds of the top and bottom rolls, roll bonding was also carried out. Elongation along the RD and TD was improved at a speed difference of approximately 10%-20%.

  10. Dynamic Modeling of ALS Systems

    NASA Technical Reports Server (NTRS)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  11. [Motor nerve hyperexcitability in ALS: its pathophysiology and treatment].

    PubMed

    Shibuya, Kazumoto; Misawa, Sonoko; Kuwabara, Satoshi

    2014-01-01

    Wide-spread fasciculations are prominent clinical features in patients with amyotrophic lateral sclerosis (ALS), specifically seen in ALS among disorders with neurogenic muscle atrophy. Fasciculations frequently arise from the motor nerve terminals, and the hyperexcitability of motor axons appears to constitute the pathophysiology of the disease. Neurophysiologic investigations of the upper and lower motor neurons/axons have shown increased excitability. The altered excitability is supposed to relate to motor neuron death. Based on these findings, a clinical trial of mexiletine (non-selective sodium channel blocker) is ongoing. PMID:25672715

  12. Absence of split hand in the flail arm variant of ALS.

    PubMed

    Sun, Xian; Zhang, Zhecheng; Liu, Na

    2016-04-01

    Flail arm syndrome (FAS), a variant of amyotrophic lateral sclerosis (ALS), has many similarities with upper limb onset ALS (UL-ALS). This study analyzed the compound muscle action potentials (CMAPs) recorded from abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles in patients presenting these two types of ALS variants, compared to normal controls. The APB/ADM CMAP amplitude ratio was lower in the UL-ALS group (mean±SEM: 0.56±0.37), consistent with a split hand, compared to the FAS (1.05±0.29) or control (1.11±0.30) groups. An abnormally reduced APB/ADM CMAP amplitude ratio (<0.6) was found in 40% of UL-ALS patients and 11% of FAS patients. However, absent CMAP in the APB or extremely low APB/ADM CMAP amplitude ratio (<0.25) were observed only in UL-ALS patients (27%) and could be used as diagnostic criteria to differentiate UL-ALS from FAS variant. PMID:27157380

  13. Response to Pagano et al.

    PubMed

    Rezende, Flávia; Löwe, Oliver; Helfinger, Valeska; Prior, Kim-Kristin; Walter, Maria; Zukunft, Sven; Fleming, Ingrid; Weissmann, Norbert; Brandes, Ralf P; Schröder, Katrin

    2015-11-20

    In their letter, Pagano et al. appreciate the development of the Nox1, Nox2, and Nox4 triple (3N(-/-)) knockout mouse. They also agree on the view that chemiluminescence assays in general have severe limitations. However, they criticize the fact that the membrane assays in the particular study were restricted to chemiluminescence techniques. Moreover, Pagano et al. got the impression that statements concerning membrane assays of Nox activity in general were made. In addition to a lack of some technical details, Pagano et al. also found the characterization of the 3N(-/-) incomplete and some of the results to be incomprehensible. Although we are grateful for the interest of Pagano et al. in our work, we realized that basically each observation of our study was questioned. This is certainly an excessive rejection of the study in total and fails to appreciate the clear chain of evidences presented. Our work focused on chemiluminescence, and thus, any conclusions are restricted to this technique. Moreover, the 3N(-/-) mice were never developed to study the physiology of Nox enzymes, but rather to validate Nox specificity of NADPH-stimulated chemiluminescence assays. We are convinced that our findings are a valid demonstration that chemiluminescence-based assays in membrane preparations stimulated with NADPH do not measure Nox activity. This conclusion is based on both overexpression studies as well as genetic deficient mouse models. The criticisms of Pagano et al. thus might be justified in some aspects; they, however, cannot disprove the conclusions of our work. Antioxid. Redox Signal. 23, 1247-1249.

  14. Response to Pagano et al.

    PubMed

    Rezende, Flávia; Löwe, Oliver; Helfinger, Valeska; Prior, Kim-Kristin; Walter, Maria; Zukunft, Sven; Fleming, Ingrid; Weissmann, Norbert; Brandes, Ralf P; Schröder, Katrin

    2015-11-20

    In their letter, Pagano et al. appreciate the development of the Nox1, Nox2, and Nox4 triple (3N(-/-)) knockout mouse. They also agree on the view that chemiluminescence assays in general have severe limitations. However, they criticize the fact that the membrane assays in the particular study were restricted to chemiluminescence techniques. Moreover, Pagano et al. got the impression that statements concerning membrane assays of Nox activity in general were made. In addition to a lack of some technical details, Pagano et al. also found the characterization of the 3N(-/-) incomplete and some of the results to be incomprehensible. Although we are grateful for the interest of Pagano et al. in our work, we realized that basically each observation of our study was questioned. This is certainly an excessive rejection of the study in total and fails to appreciate the clear chain of evidences presented. Our work focused on chemiluminescence, and thus, any conclusions are restricted to this technique. Moreover, the 3N(-/-) mice were never developed to study the physiology of Nox enzymes, but rather to validate Nox specificity of NADPH-stimulated chemiluminescence assays. We are convinced that our findings are a valid demonstration that chemiluminescence-based assays in membrane preparations stimulated with NADPH do not measure Nox activity. This conclusion is based on both overexpression studies as well as genetic deficient mouse models. The criticisms of Pagano et al. thus might be justified in some aspects; they, however, cannot disprove the conclusions of our work. Antioxid. Redox Signal. 23, 1247-1249. PMID:26173053

  15. Clinical and radiological features of bone disease in long-term (15 or more years) hemodialysis patients.

    PubMed

    Bedani, P L; Orzincolo, C; Storari, A; Perini, L; Soffritti, S; Gilli, P

    1993-10-01

    Fifteen patients on regular dialytic treatment for more than 15 years were given X-rays of the skull, spine, shoulders, wrists, pelvis and knees with the purpose of studying the principal skeletal and articular alterations due or not due to the uraemic status. Serum calcium, phosphorus, parathyroid hormone, alkaline phosphatase and basal aluminium were recorded. Osteopenia was evident in all the patients. Ten of whom (67%) showed alterations due to hyperparathyroidism. Nine patients presented the marks of dialysis spondyloarthropathy; in 14/15 cases geodes were present in the wrists, humeral heads or hip-joints; in ten patients there were multiple amyloid lesions. Two patients with serum basal aluminum above 100 micrograms/L showed the typical radiographic marks of osteomalacia. The majority of the long-term survivors showed multifactorial osteo-articular alterations resulting mainly from the combination of hyperparathyroidism and dialysis-related amyloidosis. The less frequent joint alterations were represented by arthrosis, enthesopathy and chondrocalcinosis. Disability and decreased articular mobility resulted in being mainly due to amyloid osteo-arthropathy.

  16. The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy

    PubMed Central

    Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.

    2009-01-01

    With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications. PMID:19052538

  17. [Destructive cervical amyloidotic spondyloarthropathy in patients undergoing periodic dialysis. Personal experience].

    PubMed

    Madia, G; Mughetti, M; Muratore, F; Mignani, R; Leurini, R; Boccadoro, R; Denicolò, M

    1990-12-01

    The accumulation of amyloid (beta 2-microglobulin) in several organs and tissues of patients in chronic dialysis is a recent pathologic condition. A wide range of cases, supported by specific tests for amyloid on bioptic and autoptic samples, showed a radiographic semiology of osteostructural alterations in various areas which allows amyloidotic condition of bone to be diagnosed with high reliability. In 11 of 62 patients (17.74%) we observed destructive cervical amyloidotic spondyloarthropathy (DCAS). The radiological patterns common to all patients were subchondral sclerosis, erosions of vertebral body plates, widening/narrowing of intervertebral spaces, no/poor osteophytosis. Over-hanging was present in 54.5% of cases, and deformation of vertebral bodies in 45.4%. CT was useful in improving the definition of the various alterations, and in locating others, such as cavitations in vertebral bodies and involvement of apophyseal joints. Constant factors were the association with extravertebral osseous amyloidosis, dyalitic age over 60 months, and the use of Cuprophan membranes for dialysis. The frequent (72.72%) association with alterations involving the lumbar rachis (subchondral sclerosis, erosions and geodes) was suggestive of amyloidotic condition.

  18. Large rectification magnetoresistance in nonmagnetic Al/Ge/Al heterojunctions.

    PubMed

    Zhang, Kun; Li, Huan-Huan; Grünberg, Peter; Li, Qiang; Ye, Sheng-Tao; Tian, Yu-Feng; Yan, Shi-Shen; Lin, Zhao-Jun; Kang, Shi-Shou; Chen, Yan-Xue; Liu, Guo-Lei; Mei, Liang-Mo

    2015-09-21

    Magnetoresistance and rectification are two fundamental physical properties of heterojunctions and respectively have wide applications in spintronics devices. Being different from the well known various magnetoresistance effects, here we report a brand new large magnetoresistance that can be regarded as rectification magnetoresistance: the application of a pure small sinusoidal alternating-current to the nonmagnetic Al/Ge Schottky heterojunctions can generate a significant direct-current voltage, and this rectification voltage strongly varies with the external magnetic field. We find that the rectification magnetoresistance in Al/Ge Schottky heterojunctions is as large as 250% at room temperature, which is greatly enhanced as compared with the conventional magnetoresistance of 70%. The findings of rectification magnetoresistance open the way to the new nonmagnetic Ge-based spintronics devices of large rectification magnetoresistance at ambient temperature under the alternating-current due to the simultaneous implementation of the rectification and magnetoresistance in the same devices.

  19. Thermodynamic modeling of Pt-Al and Pd-Al

    NASA Astrophysics Data System (ADS)

    Carr, Derek

    2011-03-01

    Pure platinum and pure palladium are too soft for typical jewelry applications. Adding small amounts of other metals can significantly increase their performance. However, international hallmarking standards require the alloys to be 95% pure by weight. How does one achieve significant improvements in performance adding only small amounts (5 wt-%) of other metals? Significant improvements are possible even with small additions if precipitate hardening can be induced. Using a combination of first-principles, cluster expansion, and Monte Carlo modeling, we have identified new Pt-rich/Pd-rich phases in Pt-Al and Pd-Al that should be useful in precipitate hardening. Thermodynamical modeling indicates that the phases are experimentally feasible (not kinetically inhibited).

  20. Large rectification magnetoresistance in nonmagnetic Al/Ge/Al heterojunctions

    NASA Astrophysics Data System (ADS)

    Zhang, Kun; Li, Huan-Huan; Grünberg, Peter; Li, Qiang; Ye, Sheng-Tao; Tian, Yu-Feng; Yan, Shi-Shen; Lin, Zhao-Jun; Kang, Shi-Shou; Chen, Yan-Xue; Liu, Guo-Lei; Mei, Liang-Mo

    2015-09-01

    Magnetoresistance and rectification are two fundamental physical properties of heterojunctions and respectively have wide applications in spintronics devices. Being different from the well known various magnetoresistance effects, here we report a brand new large magnetoresistance that can be regarded as rectification magnetoresistance: the application of a pure small sinusoidal alternating-current to the nonmagnetic Al/Ge Schottky heterojunctions can generate a significant direct-current voltage, and this rectification voltage strongly varies with the external magnetic field. We find that the rectification magnetoresistance in Al/Ge Schottky heterojunctions is as large as 250% at room temperature, which is greatly enhanced as compared with the conventional magnetoresistance of 70%. The findings of rectification magnetoresistance open the way to the new nonmagnetic Ge-based spintronics devices of large rectification magnetoresistance at ambient temperature under the alternating-current due to the simultaneous implementation of the rectification and magnetoresistance in the same devices.

  1. Reality versus fantasy: reply to Lynn et al. (2014).

    PubMed

    Dalenberg, Constance J; Brand, Bethany L; Loewenstein, Richard J; Gleaves, David H; Dorahy, Martin J; Cardeña, Etzel; Frewen, Paul A; Carlson, Eve B; Spiegel, David

    2014-05-01

    We respond to Lynn et al.'s (2014) comments on our review (Dalenberg et al., 2012) demonstrating the superiority of the trauma model (TM) over the fantasy model (FM) in explaining the trauma-dissociation relationship. Lynn et al. conceded that our meta-analytic results support the TM hypothesis that trauma exposure is a causal risk factor for the development of dissociation. Although Lynn et al. suggested that our meta-analyses were selective, we respond that each omitted study failed to meet inclusion criteria; our meta-analyses thus reflect a balanced view of the predominant trauma-dissociation findings. In contrast, Lynn et al. were hypercritical of studies that supported the TM while ignoring methodological problems in studies presented as supportive of the FM. We clarify Lynn et al.'s misunderstandings of the TM and demonstrate consistent superiority in prediction of time course of dissociative symptoms, response to psychotherapy of dissociative patients, and pattern of relationships of trauma to dissociation. We defend our decision not to include studies using the Dissociative Experiences Scale-Comparison, a rarely used revision of the Dissociative Experiences Scale that shares less than 10% of the variance with the original scale. We highlight several areas of agreement: (a) Trauma plays a complex role in dissociation, involving indirect and direct paths; (b) dissociation-suggestibility relationships are small; and (c) controls and measurement issues should be addressed in future suggestibility and dissociation research. Considering the lack of evidence that dissociative individuals simply fantasize trauma, future researchers should examine more complex models of trauma and valid measures of dissociation.

  2. AlSb/InAs/AlSb quantum wells

    NASA Technical Reports Server (NTRS)

    Kroemer, Herbert

    1990-01-01

    Researchers studied the InAs/AlSb system recently, obtaining 12nm wide quantum wells with room temperature mobilities up to 28,000 cm(exp 2)/V center dot S and low-temperature mobilities up to 325,000 cm(exp 2)/V center dot S, both at high electron sheet concentrations in the 10(exp 12)/cm(exp 2) range (corresponding to volume concentrations in the 10(exp 18)/cm(exp 2) range). These wells were not intentionally doped; the combination of high carrier concentrations and high mobilities suggest that the electrons are due to not-intentional modulation doping by an unknown donor in the AlSb barriers, presumably a stoichiometric defect, like an antisite donor. Inasmuch as not intentionally doped bulk AlSb is semi-insulating, the donor must be a deep one, being ionized only by draining into the even deeper InAs quantum well. The excellent transport properties are confirmed by other observations, like excellent quantum Hall effect data, and the successful use of the quantum wells as superconductive weak links between Nb electrodes, with unprecendentedly high critical current densities. The system is promising for future field effect transistors (FETs), but many processing problems must first be solved. Although the researchers have achieved FETs, the results so far have not been competitive with GaAs FETs.

  3. Identification of Candida albicans ALS2 and ALS4 and Localization of Als Proteins to the Fungal Cell Surface

    PubMed Central

    Hoyer, L. L.; Payne, T. L.; Hecht, J. E.

    1998-01-01

    Additional genes in the growing ALS family of Candida albicans were isolated by PCR screening of a genomic fosmid library with primers designed from the consensus tandem-repeat sequence of ALS1. This procedure yielded fosmids encoding ALS2 and ALS4. ALS2 and ALS4 conformed to the three-domain structure of ALS genes, which consists of a central domain of tandemly repeated copies of a 108-bp motif, an upstream domain of highly conserved sequences, and a domain of divergent sequences 3′ of the tandem repeats. Alignment of five predicted Als protein sequences indicated conservation of N- and C-terminal hydrophobic regions which have the hallmarks of secretory signal sequences and glycosylphosphatidylinositol addition sites, respectively. Heterologous expression of an N-terminal fragment of Als1p in Saccharomyces cerevisiae demonstrated function of the putative signal sequence with cleavage following Ala17. This signal sequence cleavage site was conserved in the four other Als proteins analyzed, suggesting identical processing of each protein. Primary-structure features of the five Als proteins suggested a cell-surface localization, which was confirmed by indirect immunofluorescence with an anti-Als antiserum. Staining was observed on mother yeasts and germ tubes, although the intensity of staining on the mother yeast decreased with elongation of the germ tube. Similar to other ALS genes, ALS2 and ALS4 were differentially regulated. ALS4 expression was correlated with the growth phase of the culture; ALS2 expression was not observed under many different in vitro growth conditions. The data presented here demonstrate that ALS genes encode cell-surface proteins and support the conclusion that the size and number of Als proteins on the C. albicans cell surface vary with strain and growth conditions. PMID:9765564

  4. Al-Anon and recovery.

    PubMed

    Cermak, T L

    1989-01-01

    The history of Al-Anon and its current demographics are reviewed. In order to understand 12-step recovery and psychotherapy for family members of alcoholics, the concept of codependence is defined with a set of diagnostic criteria consistent with the DSM-III-R definition of personality traits and disorders. At the core of codependence are denial and an unrealistic relationship to willpower. The therapeutic implications of considering codependence as a personality disorder are explored, as are the characteristics that make codependence unique among personality disorders: the central role of denial and the existence of a self-help organization to facilitate recovery. The dynamics of working the 12 steps on codependent characteristics are outlined. A synergistic relationship between psychotherapy and the 12 steps is described. Special attention is given the emergence of Al-Anon adult children of alcoholic meetings, and the future of codependence is discussed.

  5. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): The study methodology, recruitment, and baseline demographic and disease characteristics

    PubMed Central

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R.; Andrews, Leslie; Rabkin, Judith G.; McElhiney, Martin; Nieves, Jeri; Santella, Regina M.; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S.; Miller, Robert G; Katz, Jonathan S.; Forshew, Dallas; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Bjorn; Filho, J Americo M. Fernandes; Kasarskis, Edward J.; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Shefner, Jeremy M.; Andrews, Jinsy A.; Koczon-Jaremko, Boguslawa A.

    2015-01-01

    Objective In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods An extensive structured telephone interview ascertained environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3 to 6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Results 355 patients were recruited. Subjects were enrolled over a 36 month-period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, with the only difference being type of health insurance among enrolled patients. Sites were divided into 3 groups by the number of enrolled subjects. Comparing these 3 groups, the Columbia site had fewer “definite ALS” diagnoses. Conclusion This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and was accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized. PMID:24564738

  6. Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients.

    PubMed

    Lavelle, Lisa P; McEvoy, Sinead H; Ni Mhurchu, Elaine; Gibney, Robert G; McMahon, Colm J; Heffernan, Eric J; Malone, Dermot E

    2015-01-01

    Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the white population. Mutation of the CF transmembrane conductance regulator gene on chromosome 7 results in production of abnormally viscous mucus and secretions in the lungs of patients with CF. A similar pathologic process occurs in the gastrointestinal tract, pancreas, and hepatobiliary system. Inspissated mucus causes luminal obstruction and resultant clinical and radiologic complications associated with the disease process. Pancreatic involvement can result in exocrine and endocrine insufficiency, pancreatic atrophy, fatty replacement, or lipomatous pseudohypertrophy. Acute and chronic pancreatitis, pancreatic calcification, cysts, and cystosis also occur. Hepatic manifestations include hepatic steatosis, focal biliary and multilobular cirrhosis, and portal hypertension. Biliary complications include cholelithiasis, microgallbladder, and sclerosing cholangitis. The entire digestive tract can be involved. Distal ileal obstruction syndrome, intussusception, appendicitis, chronic constipation, colonic wall thickening, fibrosing colonopathy, pneumatosis intestinalis, gastroesophageal reflux, and peptic ulcer disease have been described. Renal manifestations include nephrolithiasis and secondary amyloidosis. The educational objectives of this review are to reveal the abdominal manifestations of CF to facilitate focused analysis of cross-sectional imaging in adult patients. Life expectancy in patients with CF continues to improve because of a combination of aggressive antibiotic treatment, improved emphasis on nutrition and physiotherapy, and development of promising new CF transmembrane conductance regulator modulators. As lung function and survival improve, extrapulmonary conditions, including hepatic and gastrointestinal malignancy, will be an increasing cause of morbidity and mortality. Awareness of the expected abdominal manifestations of CF may assist radiologists in identifying

  7. Emerging mechanisms of molecular pathology in ALS.

    PubMed

    Peters, Owen M; Ghasemi, Mehdi; Brown, Robert H

    2015-05-01

    Amyotrophic lateral sclerosis (ALS) is a devastating degenerative disease characterized by progressive loss of motor neurons in the motor cortex, brainstem, and spinal cord. Although defined as a motor disorder, ALS can arise concurrently with frontotemporal lobal dementia (FTLD). ALS begins focally but disseminates to cause paralysis and death. About 10% of ALS cases are caused by gene mutations, and more than 40 ALS-associated genes have been identified. While important questions about the biology of this disease remain unanswered, investigations of ALS genes have delineated pathogenic roles for (a) perturbations in protein stability and degradation, (b) altered homeostasis of critical RNA- and DNA-binding proteins, (c) impaired cytoskeleton function, and (d) non-neuronal cells as modifiers of the ALS phenotype. The rapidity of progress in ALS genetics and the subsequent acquisition of insights into the molecular biology of these genes provide grounds for optimism that meaningful therapies for ALS are attainable. PMID:25932674

  8. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

    2015-08-01

    Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge. PMID:25842074

  9. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

    2015-08-01

    Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge.

  10. Observational Study of a French and Belgian Multicenter Cohort of 23 Patients Diagnosed in Adulthood With Mevalonate Kinase Deficiency

    PubMed Central

    Durel, Cécile-Audrey; Aouba, Achille; Bienvenu, Boris; Deshayes, Samuel; Coppéré, Brigitte; Gombert, Bruno; Acquaviva-Bourdain, Cécile; Hachulla, Eric; Lecomte, Frédéric; Touitou, Isabelle; Ninet, Jacques; Philit, Jean-Baptiste; Messer, Laurent; Brouillard, Marc; Girard-Madoux, Marie-Hélène; Moutschen, Michel; Raison-Peyron, Nadia; Hutin, Pascal; Duffau, Pierre; Trolliet, Pierre; Hatron, Pierre-Yves; Heudier, Philippe; Cevallos, Ramiro; Lequerré, Thierry; Brousse, Valentine; Lesire, Vincent; Audia, Sylvain; Maucort-Boulch, Delphine; Cuisset, Laurence; Hot, Arnaud

    2016-01-01

    Abstract The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission. PMID:26986117

  11. Observational Study of a French and Belgian Multicenter Cohort of 23 Patients Diagnosed in Adulthood With Mevalonate Kinase Deficiency.

    PubMed

    Durel, Cécile-Audrey; Aouba, Achille; Bienvenu, Boris; Deshayes, Samuel; Coppéré, Brigitte; Gombert, Bruno; Acquaviva-Bourdain, Cécile; Hachulla, Eric; Lecomte, Frédéric; Touitou, Isabelle; Ninet, Jacques; Philit, Jean-Baptiste; Messer, Laurent; Brouillard, Marc; Girard-Madoux, Marie-Hélène; Moutschen, Michel; Raison-Peyron, Nadia; Hutin, Pascal; Duffau, Pierre; Trolliet, Pierre; Hatron, Pierre-Yves; Heudier, Philippe; Cevallos, Ramiro; Lequerré, Thierry; Brousse, Valentine; Lesire, Vincent; Audia, Sylvain; Maucort-Boulch, Delphine; Cuisset, Laurence; Hot, Arnaud

    2016-03-01

    The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission. PMID:26986117

  12. FTD and ALS--translating mouse studies into clinical trials.

    PubMed

    Ittner, Lars M; Halliday, Glenda M; Kril, Jillian J; Götz, Jürgen; Hodges, John R; Kiernan, Matthew C

    2015-06-01

    Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are related neurodegenerative disorders, which are characterized by a rapid decline in cognitive and motor functions, and short survival. Although the clinical and neuropathological characterization of these diseases has progressed--in part--through animal studies of pathogenetic mechanisms, the translation of findings from rodent models to clinical practice has generally not been successful. This article discusses the gap between preclinical animal studies in mice and clinical trials in patients with FTD or ALS. We outline how to better design preclinical studies, and present strategies to improve mouse models to overcome the translational shortfall. This new approach could help identify drugs that are more likely to achieve a therapeutic benefit for patients.

  13. [Have ALS centers changed the care and management of amyotrophic lateral sclerosis?].

    PubMed

    Pouget, J

    2013-02-01

    The multidisciplinary care of amyotrophic lateral sclerosis (ALS) patients in clinics with expertise in the disease was created in the 1980s and 1990 s specifically to manage the severe functional impairment caused by the disorder. This specialized care for both diagnosis and management led to the creation of the ALS centers. To facilitate the continuity of care through close liaisons between primary-care physicians and community-based services, a specialized network was also developed. French ALS centers are now 10 years old, and their efficient national coordination has provided an improved and homogeneous care delivery in our country, while their recommendations for care have been published both nationally and internationally. Several studies have indicated positive effects on ALS patients'survival after attending ALS centers and receiving such specialized palliative treatments as assisted ventilation.

  14. Synthesis of AlN/Al Polycrystals along with Al Nanoparticles Using Thermal Plasma Route

    SciTech Connect

    Kanhe, Nilesh S.; Nawale, A. B.; Kulkarni, N. V.; Bhoraskar, S. V.; Mathe, V. L.; Das, A. K.

    2011-07-15

    This paper for the first time reports the (200) oriented growth of hexagonal Aluminum nitride crystals during synthesis of aluminum nanoparticles in dc transferred arc thermal plasma reactor by gas phase condensation in nitrogen plasma. The structural and morphological study of as synthesized AlN crystal and aluminium nanoparticles was done by using the x-ray diffraction method, scanning electron microscopy and transmission electron microscopy.

  15. The National ALS Registry: A Recruitment Tool for Research

    PubMed Central

    Malek, Angela M.; Stickler, David E.; Antao, Vinicius C.; Horton, D. Kevin

    2014-01-01

    Introduction Subject recruitment is critical for understanding fatal diseases like ALS, however linking patients with researchers can be challenging. The US population-based National ALS Registry allows recruitment of persons with ALS (PALS) for research opportunities. Methods The Registry’s Research Notification Mechanism was used to recruit PALS aged ≥21 years; participants completed a web-based epidemiologic survey. PALS (n=2,232) were sent an email describing the study, and 268 surveys were completed. Results The mean age (± SD) of eligible participants was 57.7 ± 9.3 years for men and 61.5 ± 8.9 for women. Most were men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n=96) returned an authorization to disclose protected health information. ALS was confirmed for 94% (83/88) from physician responses. Discussion This analysis demonstrates the National ALS Registry’s usefulness in recruiting PALS for research. This recruitment source can potentially foster the discovery of better treatment options and therapies, and of prevention strategies. PMID:25111654

  16. Ab initio modeling of zincblende AlN layer in Al-AlN-TiN multilayers

    DOE PAGES

    Yadav, S. K.; Wang, J.; Liu, X. -Y.

    2016-06-13

    An unusual growth mechanism of metastable zincblende AlN thin film by diffusion of nitrogen atoms into Al lattice is established. Using first-principles density functional theory, we studied the possibility of thermodynamic stability of AlN as a zincblende phase due to epitaxial strains and interface effect, which fails to explain the formation of zincblende AlN. We then compared the formation energetics of rocksalt and zincblende AlN in fcc Al through direct diffusion of nitrogen atoms to Al octahedral and tetrahedral interstitials. Furthermore, the formation