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At least 1,081 records · Page 60Linked to original sources
PubMed1995

Plasma kinetics of 125I-labelled amyloid P component in beta 2M amyloidosis: a possible approach to quantitate disease activity.

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P < 0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.

Adult↗
PubMed1995

Apolipoprotein A-II gene and development of amyloidosis and senescence in a congenic strain of mice carrying amyloidogenic ApoA-II.

BACKGROUND: Apolipoprotein A-II (ApoA-II), a major apoprotein of serum high density lipoprotein (HDL) deposits as an amyloid fibril (AApoAII) in murine senile amyloidosis. Type C ApoA-II gene (Apoa2c) in the SAMP1 strain of mice, a murine model of severe senile amyloidosis and accelerated senescence was transferred on the genetic background of the SAMR1 strain, in which senile amyloidosis is rare and has a normal aging process, and a congenic strain of mouse (R1.P1-Apoa2c) was developed (Higuchi K, Kitado H, Kitagawa K, Kogishi K, Naiki H, Takeda T. FEBS Lett 1993;317:207-10). EXPERIMENTAL DESIGN: We identified AApoAII amyloid deposits in the 14-month-old congenic R1.P1-Apoa2c strain and compared these findings with the deposits in the progenitor SAMP1 and SAMR1 strains. The progression of senescence was estimated using a grading system and the age-associated changes in the metabolism of ApoA-II and HDL were investigated in the three strains of mice. RESULTS: At 14 months of age, severe amyloid deposition as compared with the donor SAMP1 strain was present in the congenic R1.P1-Apoa2c strain, but AApoAII was not evident in the progenitor SAMR1 strain which has type B ApoA-II. No obvious differences in the progression of senescence were observed between the R1.P1-Apoa2c and SAMR1 strains. In the R1.P1-Apoa2c strain, the serum HDL-cholesterol concentrations decreased in parallel with ApoA-II levels with advancing age and the decrease was much accelerated compared with the decrease seen in SAMR1 mice. CONCLUSIONS: Based on these results, we propose that the genetic type of ApoA-II plays an important role in the development of senile amyloidosis and age-associated changes in HDL metabolism. However, it has a minor role in the accelerated senescence in the mouse strains we used.

Aging↗
PubMed1994

[Difficulties in the therapy of primary amyloidosis].

The therapy of primary amyloidosis is still unsatisfactory. The response rate after the cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinaemia, brought us to the idea to test interferon alpha in the therapy of primary amyloidosis. Interferon alpha-2b was administered to the patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) daily for the treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Amyloidosis↗
PubMed1994

Haemodialysis-associated beta 2M amyloidosis: current controversies.

Beta 2M amyloidosis is a major complication of long-term haemodialysis. Beta 2M, the precursor molecule of amyloid fibrils, accumulates in renal failure because of diminished renal excretion. Whether, in addition, a minor increase of synthesis occurs in dialysed patients is still controversial. Beta 2M amyloidosis differs from most other forms of amyloid by its preferential osteoarticular location. This points to some peculiar role of the microenvironment in the synovial space, which is currently poorly defined. A finding which remains so far unexplained is the more delayed appearance of beta 2M amyloidosis in patients dialysed with polyacrylonitrile membranes. In principle, however, beta 2M amyloidosis is seen with all dialysis modalities and possibly even before maintenance dialysis. Differences between treatment modalities relate either to removal of beta 2M or some aspect of bioincompatibility, e.g. proteolytic processing. Finally, the exact chemical nature of amyloid fibrils, i.e. whether they constitute native beta 2M molecules or processed molecules, is currently controversial.

Amyloid↗
PubMedDate not supplied

[The characteristics of the nephrotic syndrome in patients with renal amyloidosis].

68 cases of histologically confirmed renal amyloidosis associated clinically with the nephrotic syndrome (NS) were studied. The age of patients (over 40 years), mounting syndrome's manifestations in developing renal failure, absence of correlation between the quantity of amyloid deposits and completeness of the syndrome's picture were characteristic of the nephrotic syndrome in amyloidosis. NS in amyloidosis was most frequently the sign of extended process in kidneys and did not differ from other nephrotic syndromes by the disorders of lipid and protein metabolism. Direct correlation between nephrotic proteinuria and severity of tubulointerstitial lesions was found. 5-year survival from the onset of NS was 48%. Vital verification of NS caused by amyloidosis is complicated, nephrobiopsy being the most informative.

Adult↗
PubMed1993

[Generalized secondary amyloidosis in rheumatoid arthritis].

Generalized (systemic) secondary amyloidosis was a post mortem finding recorded in 28 patients (25.2%) by amyloid specific Congored staining according to Romhányi, from 111 randomized autopsy cases with rheumatoid arthritis. Amyloidosis was present most frequently in the gastro-intestinal tract, the heart, kidney, thyroid gland, spleen and in the suprarenal glands. The quantity of amyloid deposits is usually the highest in the organs that are most frequently have deposits. The amyloidosis is a progressive cumulative process. The conclusion is that the organs where there are frequently high quantities of amyloid is where the deposits begin and where there are infrequently any deposits or low quantities is where the deposits develop later. Biopsy of the most frequently involved organs are suggested for early diagnosis of amyloidosis. Comparing the laboratory parameters (at the last hospitalisation), the amyloidotic patients were anaemic, with low haemoglobin level (p < 0.05), the renal function significantly decreased, the carbamid (p < 0.001), and kreatinin level high (p < 0.05), with frequent proteinuria (p < 0.0001).

Adrenal Glands↗
PubMed1993

Primary systemic amyloidosis with giant hepatomegaly and portal hypertension: a case report and a review of the literature.

Amyloidosis is a manifestation of a group of diseases resulting from the variable infiltration of multiple organs by a fibrillar protein called amyloid. Hepatic involvement in amyloidosis is common both in the primary and in the secondary forms, whereas clinically-dominant liver amyloidosis is relatively rare. The authors describe a case of primary systemic amyloidosis with giant hepatomegaly, portal hypertension and renal insufficiency; the patient did not develop jaundice, ascites or gastrointestinal bleeding but died 6 months later, death being due to cerebral haemorrhage.

Adult↗
PubMed1993

[Technetium TC 99m pyrophosphate myocardial scintigraphy in amyloidosis. Correlations with Doppler echocardiography].

Technetium 99m cardiac scintigraphy as practiced at present for diagnosing amyloisodid only provides a visual semi-quantitative assessment of uptake of the isotope. To improve the diagnostic accuracy of the method, the authors evaluated prospectively a personal technique of scintigraphy quantification based on early images obtained at the 20th minute in 15 patients with neuropathic amyloidosis. Doppler echocardiographic studies indicated that 9 patients had cardiac involvement whilst 6 were free of cardiac amyloidosis. The index of isotopic uptake (ratio of cardiac/abdominal uptake) was 0.44 to 1.58 in the first group and 0.09 to 0.31 in the second group. The correlation between the scintigraphic index and interventricular septal or posterior wall thickness measured by echocardiography was poor. These results obtained in 15 patients with neuropathic amyloidosis suggest that the scintigraphic index measured at the 20th minute is discriminatory and allows identification of those patients with cardiac involvement. On the other hand, the correlations with echocardiographic wall thickness are poor. Technetium 99m cardiac scintigraphy with this technique of quantification is a useful tool for diagnosing cardiac amyloidosis, especially when echocardiography is difficult to interpret.

Adult↗
PubMed1993

Long-term complications of dialysis: pathogenic factors with special reference to amyloidosis.

Amyloidosis, caused by amyloid containing beta 2-microglobulin (beta 2m), is a frequent complication of long-term hemodialysis. The precise mechanism of its pathogenesis is not known. While beta 2m is an amyloid protein, other factors likely are involved in the pathogenesis of such amyloidosis. In treating patients with dialysis-related amyloidosis, it is essential to remove as much beta 2m from the blood as possible. In this respect, progress has been made in developing a column to adsorb beta 2m from the blood. Using a combination of a high-flux dialyzer and an adsorption column, it becomes possible to efficiently eliminate beta 2m. We have treated four patients with this column in combination with a high-flux dialyzer three times a week for periods of one month or one year. The absorbent column eliminates beta 2m from the blood, and may thus halt or slow the progression of beta 2m-related amyloidosis. However, such treatment is still in a preliminary phase; long-term studies are required to determine clinical efficacy.

Amyloidosis↗
PubMed1993

[A case of primary cardiac amyloidosis with amyloid A protein].

A case of cardiac amyloidosis in a 46-year-old male is reported. He was admitted for dyspnea. Physical examination revealed third and forth heart sound and hepatomegaly. Radiographic heart-thoracic ratio was 53%. Electrocardiogram showed first degree A-V block, rS pattern in V1-V4 leads, and ambulatory electrocardiogram showed ventricular tachycardia. Echocardiogram revealed hypertrophy and highly refractile echoes of the left ventricular wall. Endomyocardial biopsy was performed and it demonstrated amyloid fibrils, which were characterized immunohistochemically as Amyloid A (AA) protein, which is generally a constituent in secondary amyloidosis. Urine protein electrophoresis showed lambda type Bence-Jones protein, but bone marrow biopsy was normal. There was no evidence of malignancy, chronic inflammatory disease, or collagen disease. This case was diagnosed as primary amyloidosis with AA protein. It is rare that, in spite of its being a case of primary amyloidosis, its constituent protein is AA protein.

Amyloidosis↗
PubMed1995

Massive intestinal hemorrhage associated with intestinal amyloidosis. An investigation of underlying pathologic processes.

UNLABELLED: Two cases of systemic amyloidosis with massive intestinal hemorrhage necessitating bowel resection prompted an investigation of the possible pathologic processes leading to such hemorrhage, since no conclusive information about this has been published. METHODS: The two surgical specimens and, for comparison, one biopsy specimen and autopsy specimens from six cases of amyloidosis were investigated by various histologic techniques. RESULTS: Massive amyloid deposition in the muscularis mucosae was noted in both surgical specimens. The source of hemorrhage was identified as being located at the border between the muscularis mucosae and the overlying rectal or colonic mucosa. In the autopsy specimens, there was patchy or linear amyloid deposition in the muscularis mucosae, but no hemorrhage. CONCLUSIONS: Various factors could be involved in causing massive intestinal hemorrhage in systemic amyloidosis. Functional disturbances may be involved due to amyloid deposition in relation to blood vessels, lymphatics, nerves, and nerve plexuses, and, as it appeared to be the case in the two surgical specimens investigated, massive deposition in the muscularis mucosae. The reduced motility and increased rigidity of the musculature probably result in shearing forces being set up in the presence of mechanical strain (eg in coprostasis or colonoscopy) that lead to tears in the region of the muscularis mucosae and to massive hemorrhage. Intestinal hemorrhage in amyloidosis may also be related to disturbances of coagulation, which have been reported in occasional cases, and ulceration, probably resulting in some cases of ischemic colitis.

Aged↗
PubMed1996

A frame shift mutation in the fibrinogen A alpha chain gene in a kindred with renal amyloidosis.

A new American kindred with amyloidosis was found by single-strand conformation polymorphism analysis to have a mutation in the fibrinogen A alpha chain gene. Affected members in this kindred have autosomal dominant amyloid nephropathy. DNA sequencing showed a single nucleotide deletion at the third base of codon 524 of the fibrinogen A alpha chain genes (4904delG) that resulted in a frame shift and premature termination of the protein at codon 548. Antiserum was produced to a portion of the abnormal peptide predicted by the DNA sequence and amyloid deposits were immuno-histologically proven to contain this abnormal peptide. Two of the propositus' 4 children were positive for the mutant fibrinogen A alpha chain gene by restriction fragment length polymorphism analysis based on polymerase chain reaction. These two mutant gene carriers now in the second decade of life show no clinical symptoms of amyloidosis as yet but have lower plasma fibrinogen concentrations when compared with their normal siblings. This the first description of a kindred with renal amyloidosis and low plasma fibrinogen and also the first report of amyloidosis caused by a frame shift mutation.

Adult↗
PubMedDate not supplied

Familial AL-amyloidosis in three Italian siblings.

BACKGROUND AND METHODS: Familial occurrence of immunoglobulin-related (AL) amyloidosis has occasionally been reported. In this work we describe the concomitance of systemic amyloidosis and monoclonal gammopathy (one case of Waldenström's macroglobulinemia and two cases without multiple myeloma or related diseases) in three Italian siblings, two males and one female. RESULTS AND CONCLUSIONS: All of them showed a common pattern of polyneuropathy to different degrees; two presented a sicca syndrome and one also suffered from nephropathy. Two of them showed the same HLA typing with the same light chain type (k), but had different presenting symptoms. Polyneuropathy and a history of peptic disease in two cases was suggestive of type III familial amyloidotic polyneuropathy (FAP) occurring in the setting of a familial monoclonal component. However, immunohistochemical studies on different tissue specimens using anti-apolipoprotein A1 and anti-transthyretin antibodies were negative. Further screening of DNA samples for transthyretin (TTR) gene mutations was also negative. Clinical and laboratory investigations ruled out reactive or senile amyloidosis and immunohistochemical studies with anti-light chain antibodies on amyloidotic tissue specimens were positive. As a consequence, this family represents a new case of familial AL-amyloidosis.

Aged↗
PubMed1996

New aspects in the pathogenesis of dialysis-related amyloidosis: pathophysiology of advanced glycation end products in renal failure.

It has been demonstrated that beta 2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis, a serious complication leading to bone and joint destruction in long-term hemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Several lines of evidence suggest that beta 2-microglobulin plays an active role in the development of dialysis-related amyloidosis. It is unlikely that intact beta 2-microglobulin per se contributes to the pathogenesis, because no difference in the plasma levels of intact beta 2-microglobulin has yet been found between hemodialysis patients with and without this complication. Some investigators, therefore, have focused on the modification of this molecule. Recent studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils: advanced glycation end products (AGEs) formed by a nonenzymatic reaction between aldoses and proteins. Further studies have suggested that the interaction of AGE-modified beta 2-microglobulin with monocyte/macrophage and osteoclast/osteoblast gives a plausible, albeit partial, explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This article focuses on the modification of beta 2-microglobulin with AGEs, especially on their structure and pathological role in dialysis-related amyloidosis. Furthermore, the implication of renal failure in the pathophysiology of AGEs is also discussed.

Amyloidosis↗
PubMed1996

Diffuse interstitial pulmonary amyloidosis in rheumatoid arthritis.

We describe a woman with seronegative rheumatoid arthritis (RA) who presented with diffuse septal pulmonary amyloidosis mimicking interstitial rheumatoid lung disease. Her systemic amyloidosis was diagnosed by biopsy of the kidney, stomach mucosa, and salivary glands 28 years after the onset of RA. Diffuse interstitial pulmonary infiltrates had been noted since that diagnosis, but infiltrates had been considered due to rheumatoid lung. Results of pulmonary function tests, which revealed restrictive changes and decreased diffusion capacity, were also compatible with rheumatoid lung disease. Pulmonary amyloidosis was diagnosed at autopsy. Pulmonary amyloidosis should be considered a cause of pulmonary infiltrates in patients with longstanding RA.

Amyloid↗
PubMed1996

[Amyloidosis: definition and classification].

Amyloidoses are diseases characterized by deposits of altered proteins in the tissues. The amyloid deposit is always extracellular and presents a fibrillary conformation. 85% of the amyloid protein is constituted of a specific protein of each variety of amyloidosis, while the other 15% consists of other proteins and glycoproteins common to all types of amyloidosis. The same amyloid protein can be associated with various clinical forms and, inversely, different proteins can give the same clinical expression. It is therefore preferable to adopt a biochemical classification of amyloidosis. This classification is based on the identification of the various amyloid proteins by immunohistochemical analysis. About fifteen different amyloid proteins have already been identified. Hereditary amyloidoses are the most heterogeneous forms and amyloidoses of the nervous system are still under investigation. Immunohistochemical analysis of the majority of amyloidoses (represented by amyloidosis AA and AL) can now be performed routinely on tissue samples.

Amyloid↗
PubMed1996

Brefeldin A inhibits experimentally induced AA amyloidosis.

OBJECTIVE: Brefeldin A, an antibiotic with effects on certain intracellular compartments, was tested on murine secondary AA amyloidosis. Effects on splenic proteoglycan metabolism were analyzed along with plasma serum amyloid A (SAA) levels. METHODS: Brefeldin A was administered daily to mice undergoing inflammatory stimulation with complete Freund's adjuvant to induce reactive AA amyloidosis. AA amyloid deposition was assessed using histochemistry, immunohistochemistry, and electron microscopy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting were used to detect SAA in acute phase serum. Relative (semiquantitative) measurements of total SAA levels were obtained by densitometry of stained gels. Splenic proteoglycan metabolism was analyzed in treated animals and compared to untreated individuals by in vivo 35S administration during amyloid fibrillogenesis. RESULTS: Based on (immuno)histochemistry and electron microscopy, animals undergoing drug treatment did not develop splenic amyloidosis, whereas the control animals exhibited massive amyloid fibril deposits in the spleen (p < 0.001). SAA was detected at roughly equal quantities in serum from both groups. No significant qualitative or quantitative difference in proteoglycan synthesis was found. CONCLUSION: Brefeldin A seems to exert an inhibitory action on murine AA amyloidosis. It appears that the effect does not depend on the lack of fibril protein precursor nor altered proteoglycan synthesis.

Amyloidosis↗
PubMed1996

[Primary amyloidosis complicated with chronic myelomonocytic leukemia].

A 79-year-old male was admitted to our hospital because of abnormal shadows in both lungs on chest X-ray film. He had a 5-year history of repeated bleeding episodes of unknown etiology before admission. Transbronchial lung biopsy revealed the alveolar septal type of lung amyloidosis. His serum contained a monoclonal IgA-lambda type protein but there was no evidence of multiple myeloma. A diagnosis of primary amyloidosis was made. On admission, his hematological findings revealed the coexistence of chronic myelomonocytic leukemia (CMML). Coexistence of primary amyloidosis and CMML is extremely rare. Because monocytes are known to play an essential role in the degenerative processes of serum amyloid precursor, it was suggested that his amyloidosis was accelerated by the onset of CMML through certain dysfunctions of pathological monocytes.

Aged↗