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Amyloidotic Polyneuropathy (amyloidotic + polyneuropathy)
Kinds of Amyloidotic Polyneuropathy Selected AbstractsPAINFUL NEUROPATHY, MONOCLONAL GAMMOPATHY AND AMYLOID DEPOSITS: RESPONSE TO THERAPY IN 3 CASESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002Article first published online: 11 MAR 200 Siciliano G.1, D'Avino C.1, Panichi V.2, Azzarà A.3, Del Corona A.1, Pollina L.3, Murri L.1 1Department of Neuroscience, 2Department of Internal Medicine and 3Department of Oncology,University of Pisa-Italy Amyloidosis is a systemic disease with a wide organic involvement. Amyloidotic polyneuropathies may be genetic in their origin or present in association with a number of chronic inflammatory dysimmune disorders. We report on three patients affected by predominantly sensitive polyneuropathy, monoclonal gammopathy and amyloidosis. Patient 1. Woman, 72 years old, with a one year history of painful paraesthesias, ataxic gait and demyelinating predominantly sensitive polyneuropathy at 4 limbs also with involvement of sympathetic fibres. Blood protein electrophoresis showed a monoclonal gammopahty (IgG-k) with normal bone marrow biopsy and positivity for amyloid at fat biopsy. The patient has been treated with melphalan 0.2 mg/Kg/day+prednisone 100 mg/day for 7 days each month for 6 months with good efficacy and only a transient reduction in platelet and white blood cells count. Patient 2. Man, 60 years old, new diagnosis of diabetes with a 9 month history of painful paraesthesias and hyposthenia, a demyelinating sensory-motor polyneuropathy at 4 limbs. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow biopsy, fat biopsy but not sural nerve biopsy positive for amyloid. The patient underwent melphalan+prednisone therapy, with insulinic control of glycemia. He presented a clear-cut improvement in sensitive-motor symptomatology. Patient 3. Man, 72 years old, with a 15 year history of ulcerous rectocolites. Since 1998 started complaining of paraesthesias and disaesthesias at four limbs associated with gait disturbances. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow aspiration and elevated serum Interleukin-6 levels, fat biopsy positive for amyloid, and high anti-MAG antibodies titer (1:100000). Because of RCU, melphalan therapy was excluded and the patient is at the moment under fludarabine (25 mg/m2/day) ev for 5 days each 6 weeks for 6 bouts. [source] Polyacrylamide gel electrophoresis followed by sodium dodecyl sulfate gradient polyacrylamide gel electrophoresis for the study of the dimer to monomer transition of human transthyretinELECTROPHORESIS, Issue 14 2003Klaus Altland Abstract Familial amyloidotic polyneuropathy (FAP) is caused by mutations which destabilize transthyretin (TTR) and facilitate the aggregation into extracellular amyloid fibrils preferentially in peripheral nerve and heart tissues. Therapeutic and preventive trials for FAP at the plasma TTR level require a careful study of the destabilization of TTR under variable conditions. We have developed a simple double one-dimensional (D1-D) electrophoretic procedure with polyacrylamide gel electrophoresis (PAGE) followed by sodium dodecylsulfate (SDS) gradient PAGE to study the dimer to monomer transition. TTR is first isolated by PAGE from other plasma proteins. The gel strip containing the TTR fraction is incubated in 2% SDS under varying conditions of temperature, buffer composition, pH, and additives like urea and/or a sulfhydryl-reactive agent, followed by SDS-gradient PAGE for the separation of TTR dimers and monomers. We demonstrate that an unidirectional dimer to monomer transition of normal TTR is achieved at 70,80°C in neutral to mild alkaline buffers or at 37°C and slightly acidic pH (6,7). Addition of urea favors the transition into monomers. Amyloidogenic mutations like amyloidogenic TTR (ATTR)-V30M or ATTR-I107V favor the transition into monomers in buffer systems close to the physiological pH of human plasma. We conclude that this finding has to be considered by any hypothesis on ATTR-derived amyloidogenesis. [source] Misfolded transthyretin causes behavioral changes in a Drosophila model for transthyretin-associated amyloidosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Malgorzata Pokrzywa Abstract Familial amyloidotic polyneuropathy is an autosomal dominant neurodegenerative disorder caused by accumulation of mutated transthyretin (TTR) amyloid fibrils in different organs and prevalently around peripheral nerves. We have constructed transgenic flies, expressing the clinical amyloidogenic variant TTRL55P and the engineered variant TTR-A (TTRV14N/V16E) as well as the wild-type protein, all in secreted form. Within a few weeks, both mutants but not the wild-type TTR demonstrated a time-dependent aggregation of misfolded molecules. This was associated with neurodegeneration, change in wing posture, attenuation of locomotor activity including compromised flying ability and shortened life span. In contrast, expression of wild-type TTR had no discernible effect on either longevity or behavior. These results suggest that Drosophila can be used as a disease-model to study TTR amyloid formation, and to screen for pharmacological agents and modifying genes. [source] Advanced glycation end product in familial amyloidotic polyneuropathy (FAP)JOURNAL OF INTERNAL MEDICINE, Issue 4 2000N. Nyhlin Abstract. Nyhlin N, Ando Y, Nagai R, Suhr O, El Sahly M, Terazaki H, Yamashita T, Ando M, Horiuchi S (Umeå University Hospital, Umeå, Sweden and Kumamoto University School of Medicine, Kumamoto, Japan). Advanced glycation end product in familial amyloidotic polyneuropathy (FAP). J Intern Med 2000; 247: 485,492. Objectives. Advanced glycation end products (AGE) are present in amyloid deposits in ,2 -microglobulin amyloidosis, and it has been postulated that glycation of ,2 -microglobulin may be involved in fibril formation. The aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP). Setting. Department of Medicine, Umeå University Hospital and First Department of Internal Medicine, Kumamoto University School of Medicine. Design. The presence of AGE was sought immunohistochemically and biochemically in amyloid-rich tissues from patients with FAP. Subjects. Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous samples from three FAP patients were used. Results. Immunohistochemical studies using a polyclonal anti-AGE antibody revealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non-amyloid associated immunoreactivity was also observed in a few regions of the specimens, although the AGE-positive structures were situated in areas containing amyloid deposits. Western blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils. Conclusion. The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP. [source] Familial amyloidotic polyneuropathy (ATTR Val30Met) with widespread cerebral amyloid angiopathy and lethal cerebral hemorrhagePATHOLOGY INTERNATIONAL, Issue 6 2001Naomi Sakashita We report an autopsy case of familial amyloidotic polyneuropathy (FAP) with cerebral hemorrhage. A 38-year-old woman with a typical FAP pedigree started developing severe diarrhea and sensori-motor polyneuropathy at the age of 28 years; autonomic nervous system, heart and renal dysfunction manifested themselves in the following years. Genetic analysis revealed a single amino acid substitution at codon 30 of transthyretin (ATTR Val30Met). Ten years after her initial symptoms, the patient died of a sudden convulsive attack and respiratory failure. Autopsy revealed lethal cerebral hemorrhages and uremic lungs. Histochemical and immunohistochemical analyses revealed TTR-derived amyloid protein in every tissue examined, particularly in glomeruli and peripheral vessels. Severe meningo-cerebrovascular amyloidosis was also detected. Because uremia causes oxidative damage to the vascular system and amyloid formation is closely associated with oxidative stress, it is possible that uremic endothelial damage facilitated an unusual cerebral amyloid deposition. In typical FAP (ATTR Val30Met), cerebral amyloid angiopathy does not usually have clinical manifestations. However, cerebral amyloid angiopathy should be considered to explain FAP symptoms when some risk factors such as uremic vascular damage are accompanying features. [source] A non-invasive method based on saliva to characterize transthyretin in familial amyloidotic polyneuropathy patients using FT-ICR high-resolution MSPROTEOMICS - CLINICAL APPLICATIONS, Issue 6-7 2010Gonçalo da Costa Abstract Purpose: To identify, characterize and perform a relative quantification of human transthyretin (TTR) variants in human saliva. Experimental design: Serum and saliva samples were collected from healthy and familial amyloidotic polyneuropathy (FAP) patients, proteins separated by SDS-PAGE, TTR bands excised, in-gel digested and analyzed by MALDI-FTICR. Results: We identified and performed a relative quantification of mutated and native TTR forms in human saliva, based on FTICR-MS. The results are quantitatively identical to the ones obtained with human serum. In FAP patients subjected to cadaveric liver transplant, the TTR mutant form is no longer detected in saliva, while in patients receiving a domino liver from a FAP donor the mutant form of TTR becomes detectable in saliva, thus demonstrating the serum origin of TTR in saliva. Conclusions and clinical relevance: Saliva TTR originates in serum and the ratio of mutant to native TTR is preserved. The method provides a non-invasive detection of mutated TTR and a relative quantification of TTR forms. Diagnostic and disease prognosis of FAP is crucial at early stages of the disease and after liver transplantation, the only curative therapy. A suitable non-invasive method was developed for monitoring the most important FAP biomarker in human saliva. [source] Diagnosis of familial amyloidotic polyneuropathy by bone marrow biopsyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2007Kit-Fai Wong No abstract is available for this article. [source] | |||||||||||||