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PubMed2003

Serum amyloid A1 and tumor necrosis factor-alpha alleles in Turkish familial Mediterranean fever patients with and without amyloidosis.

The major complication of familial Mediterranean fever (FMF) is AA amyloidosis. The influence of FMF gene (MEFV) mutations and/or unknown environmental factors and other genetic modifiers are likely to affect the phenotypic variations of the disease and the development of amyloidosis. Serum amyloid A is a serum precursor of AA amyloid that is induced by inflammatory cytokines including TNF-alpha. Our analysis of SAA1.1 frequency in Turkish FMF-amyloidosis patients, revealed a higher frequency compared to non FMF-amyloidosis patients but the difference was not significant. On the other hand, the distribution of SAA1.1 homozygosity among FMF-amyloidosis patients was 55.5% compared to FMF-non-amyloidosis patients (30.8%) which was statistically significant revealing a 2.5 fold risk for the occurrence of amyloidosis. There was no significant difference between the controls and FMF patients with and without amyloidosis for the TNF-alpha-308 G-A allele. It is worth noting that all TNF-alpha-308 G-A carriers (n = 6) in FMF-amyloidosis group have SAA1.1 homozygosity compared to 2/11 in FMF-non-amyloidosis group. Further evaluation of these polymorphisms may have importance and need further study.

Alleles↗
PubMed1990

Immunohistochemical studies on fibrillin in amyloidosis, lichen ruber planus and porphyria.

The pathogenesis of macular amyloidosis and lichen amyloidosis remains unsolved and the primary amyloid fibril protein(s) has not yet been identified. Ultrastructural association of skin amyloid with elastin associated microfibrils has been noted earlier. The presence of fibrillin in conjunction with such microfibrils was recently demonstrated immunohistochemically. The presence of fibrillin immunoreactivity in the amyloid deposits in skin biopsies from 3 patients with macular amyloidosis and 3 patients with lichen amyloidosis was studied, using monoclonal anti-fibrillin antibodies. For comparison, skin specimens were studied from five patients with lichen ruber planus, four patients with erythropoietic protoporphyria and from a patient with myeloma-associated cutaneous amyloidosis. Renal specimens from two cases of the amyloid A type of renal amyloidosis also were investigated. There was no immunostaining either of the keratin bodies in specimens of lichen ruber planus, the cutaneous PAS-positive vascular deposits in patients with erythropoietic protoporphyria, or the amyloid deposits in specimens of systemic amyloidosis and it was faint or absent in amyloid deposits in the specimens from patients with lichen amyloidosis. In contrast, distinct fibrillin immunoreactivity could be demonstrated in amyloid deposits in specimens from patients with macular amyloidosis. It was sometimes absent in deposits located in the upper part of the papillary dermis, close to the dermal epidermal junction zone, while consistently strong in deposits located lower down in the dermis. The results suggest that fibrillin or part of the fibrillin molecule may be present in some of the amyloid deposits in specimens of macular amyloidosis.

Amyloidosis↗
PubMed2003

[A clinical analysis of 71 cases of amyloidosis].

OBJECTIVE: To comprehend the clinical characteristics and treatment of amyloidosis. METHODS: The clinical data of 71 patients with amyloidosis, admitted to Peking Union Medical College Hospital from February 1982 to February 2002, were analyzed. RESULTS: 57 of the 71 cases were systemic amyloidosis. Among the 57 cases, 33 were primary systemic amyloidosis, 22 secondary systemic amyloidosis and 2 familial amyloid polyneuropathy.The remaining 14 cases were localized amyloidosis.82% of the patients with systemic amyloidosis showed abnormalities in Doppler echocardiography. The positive rate of biopsy of subcutaneous fat and gingiva was 80.0% and 87.5% respectively. The treatment of systemic amyloidosis was chemotherapy, and that of localized amyloidosis was observation or localized excision. 15 systemic amyloidosis patients died during hospitalization, mainly due to congestive heart failure. CONCLUSION: As treatment and prognosis are different between local and systemic amyloidosis, the distinction between them is very important. Biopsy of abdominal fat and gingival is a useful and safe procedure to identify patients with systemic disease. Doppler echocardiography examination is also helpful for the diagnosis.

Abdomen↗
PubMedDate not supplied

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

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.

Amyloidosis↗
PubMed1985

[Cardiac involvement in systemic amyloidosis: myocardial scintigraphic evaluation].

To assess the clinical significance of technetium-99m-pyrophosphate (Tc-99m-PYP), -methylene diphosphonate (Tc-99m-MDP) and thallium-201 (Tl-201) myocardial scintigraphy in the diagnosis of cardiac amyloidosis and in the differential diagnosis of cardiac diseases, 12 patients with biopsy-proved systemic amyloidosis (seven with familial amyloid polyneuropathy (FAP) and five with primary amyloidosis) were investigated. The results obtained were as follows: In 10 patients (six with FAP and four with primary amyloidosis) studied by Tc-99m-PYP scintigraphy, two (FAP one, primary amyloidosis one) had diffusely positive myocardial uptake, which was of greater intensity than that of the sternum. Six (four FAP; two primary amyloidosis) also had diffusely positive myocardial uptakes, but the intensity was less than that of the sternum. The remaining two (one FAP; one primary amyloidosis) had only equivocal myocardial uptakes. Two of these patients also had hepatic uptakes and another had both hepatic and thyroid uptakes. The intensity of myocardial uptake of Tc-99m-PYP in patients with echocardiographic left ventricular hypertrophy and/or highly refractile myocardial echoes, so-called granular sparkling appearance (GS) was slightly greater than that in patients with neither myocardial hypertrophy nor GS. FAP had slightly less intensity than primary amyloidosis. In 29 persons with other cardiac diseases and normal subjects examined by Tc-99m-PYP scintigraphy, seven (two dilated cardiomyopathy; two sarcoidosis; three hypertensive heart disease) also had diffusely positive myocardial scans of mild or moderate degree. However, none of them had marked myocardial or other tissue uptakes. Both Tc-99m-PYP and -MDP scintigraphic studies were performed in four patients (three FAP; one primary amyloidosis). In Tc-99m-MDP scintigraphy, diffusely positive myocardial uptakes were observed in two patients with FAP and the remaining two had negative scans. The intensity of Tc-99m-MDP myocardial uptake in each patient was significantly lower than that of Tc-99m-PYP uptake. Tl-201 scintigraphy was carried out in 10 patients (six FAP; four primary amyloidosis). Left ventricular hypertrophy was found in six patients and right ventricular visualization in five. Although electrocardiograms in seven of 10 patients showed QS patterns in the right to mid precordial leads, similar to that seen in antero-septal and extensive anterior myocardial infarctions, neither myocardial perfusion defect nor low uptake on Tl-201 images was detected in nine of them. The scintigrams in another one, which showed low uptake at the apical portion of the left ventricle, were considered normal.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1993

Genetic analysis of murine senile amyloidosis.

BACKGROUND: Recent studies have suggested that not only the genotypes of apolipoprotein A-II, the precursor protein of murine senile amyloid fibrils, but also other genetic factors may contribute to the pathogenesis of murine senile amyloidosis. EXPERIMENTAL DESIGN: We investigated the mode of inheritance of murine senile amyloidosis, using 12-month-old and 14-month-old F1, F2 hybrids and backcrosses between SAM-P/1 and SAM-R/1. In SAM-P/1, the senescence process is accelerated and senile amyloidosis is evident, whereas in SAM-R/1, there is a normal aging process and no evidence of senile amyloidosis. In SAM-P/1 and SAM-R/1, the genotypes of apolipoprotein A-II are Gln/Gln and Pro/Pro, respectively, identified by restriction fragment length polymorphism of the apolipoprotein A-II gene for the restriction enzyme Cfr13I. RESULTS: Among hybrids and backcrosses, no senile amyloidosis was observed histopathologically, in Pro/Pro-type strains. Mild senile amyloidosis sparing the liver and spleen was observed in a significant percentage of Pro/Gln-type strains. Practical senile amyloidosis involving the liver and spleen was observed in all of the Gln/Gln-type strains. Quantitative fluorometric analysis with thioflavine T (Naiki H, Higuchi K, Matsushima K, Shimada A, Chen W-H, Hosokawa M, et al. Lab Invest 1990;62:768-73) revealed that the degree of murine senile amyloid fibril deposition was significantly decreased in the Gln/Gln-type hybrid and backcross strains, as compared with findings in SAM-P/1 and the degree of manifestation of accelerated senescence was significantly lower in the Gln/Gln-type hybrid and backcross strains than in the SAM-P/1. CONCLUSIONS: Murine senile amyloidosis is linked to the molecular type of apolipoprotein A-II (i.e., Gln-type apolipoprotein A-II), and is transmitted as an autosomal dominant manner with incomplete penetrance. The severity of murine senile amyloidosis is far more advanced in Gln/Gln-type strains than in Pro/Gln-type strains. Other genetic factors that determine the manifestation of accelerated senescence, may significantly contribute to the degree of murine senile amyloidosis.

Aging↗
PubMed1999

Long-term survival (10 years or more) in 30 patients with primary amyloidosis.

The median survival in primary systemic (AL) amyloidosis is less than 18 months. No published series of patients with AL amyloidosis have reported survival of more than 10 years. The records of all Mayo Clinic patients with a diagnosis of AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis, and localized amyloidosis were excluded. During the 21 years of the study, 841 patients with AL amyloidosis were seen. Of these, 29 were excluded because the diagnosis was made at autopsy, and 2 others were excluded because no follow-up data were available. Actuarial survival for the 810 patients was 51% at 1 year, 16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or more after the histologic diagnosis of AL amyloidosis; all received alkylating-agent therapy. In 14 patients, the monoclonal protein disappeared from the serum or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response. Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less, and the presence of peripheral neuropathy were underrepresented in the 10-year survivors and are unfavorable prognostic features. Five percent of patients with AL amyloidosis survived for 10 years or more.

Adult↗
PubMed2005

Risk stratification in cardiac amyloidosis: novel approaches.

Amyloidosis is a term for diseases with extracellular deposition of insoluble beta-fibrillar proteins in different organs. The heart is primarily involved in more than half of patients with immunoglobulin light-chain amyloidosis or hereditary amyloidosis and associated with poor prognosis. Different traditional diagnostic tools that have been described for risk stratification lack of sufficient sensitivity and specificity for patient survival. Until November 2004 in 50 consecutive patients with light chain amyloidosis and 15 patients with hereditary amyloidosis electrocardiography, echocardiography, Holter monitoring, cardiopulmonary exercise test, lung function testing, tilt-test, and laboratory investigations have been performed at our department. Cardiac amyloidosis was found in 32 patients. Interventricular septum (14.3+/-0.5 mm vs. 12.3+/-0.7 mm, P<0.05), plasma NT-proBNP (7154+/-2122 ng/l vs. 380+/-113 ng/l; P<0.01), cardiac Troponin T (0.105+/-0.030 vs. 0.019+/-0.010 microg/l; P<0.05) were increased in patients with cardiac amyloidosis as compared to patients light chain amyloidosis but no cardiac involvement. Maximal inspiratory (Pimax) and expiratory (Pemax) mouth pressure were decreased with CA compared to controls. Correlation of NT-proBNP and interventricular septum thickness (r=0.53, P=0.029) as well as and Pimax (r=0.72, P<0.01) or Pemax (r=0.69; P<0.01) was noticed. A correlation of grade of arrhythmias in Holter monitoring and syncopes was not observed. Cardiac involvement of amyloid disease carries a poor prognosis and is not well characterized by classic heart failure determinants. Heart transplantation based on novel risk markers including NT-proBNP might be a suitable therapeutic approach for patients with manifest cardiac amyloidosis, but will require alternative patient selection and listing criteria.

Amyloidosis↗
PubMed2003

Nodular amyloidosis: review and long-term follow-up of 16 cases.

OBJECTIVES: To review the clinical presentations of nodular amyloidosis, examine these cases for evidence of plasma cell monoclonality, and obtain long-term follow-up data on progression to systemic amyloidosis. DESIGN: Retrospective case series with long-term follow-up data obtained by phone survey. SETTING: Mayo Clinic, Rochester, Minn, and Mayo Clinic, Jacksonville, Fla. PATIENTS: All patients diagnosed with nodular amyloidosis between 1971 and 2001. MAIN OUTCOME MEASURES: Clinical records and histopathologic characteristics were reviewed. Polymerase chain reaction to assess immunoglobulin gene rearrangement and immunohistochemical analysis to detect kappa and lambda light chain restriction were performed on paraffin-embedded specimens. Patients were contacted by phone to determine if progression to systemic disease had occurred. RESULTS: We identified 16 patients with nodular amyloidosis. Mean age at diagnosis was 60.8 years (range, 41-87 years). Eight (50%) of 16 patients had acral involvement. Immunohistochemical analysis demonstrated light chain restriction in 6 of 10 patients. At the time of diagnosis, no patient was known to have systemic amyloidosis. One patient, however, had a serum monoclonal lambda protein and died 4 years later secondary to systemic amyloidosis. Follow-up data were obtained in 14 of the remaining 15 patients, with a mean follow-up time of 10 years (range, 8 months to 24 years). None of the 14 patients had signs or symptoms suggesting progression to systemic amyloidosis. CONCLUSIONS: Nodular amyloidosis affects both sexes during middle age, with a tendency to affect acral sites. The relatively high rate of light chain restriction in our series provides further evidence for the presence of a local plasma cell clone. Progression to systemic amyloidosis is uncommon.

Adult↗
PubMed1996

QT interval in cardiac amyloidosis.

The aim of the study was to investigate whether cardiac amyloidosis is associated with QT interval abnormalities and ventricular arrhythmias. A controlled study of 30 patients was undertaken at a university cardiology department in a large referral hospital. Thirty patients (18 men, 12 women, mean age 56 +/- 12 years) with systemic amyloidosis verified by biopsy and strong indications of cardiac amyloidosis comprised the study group, with 30 healthy age- and sex-matched individuals serving as controls. Complete M-mode and two-dimensional echocardiographic study was undertaken and QT interval and QTc were calculated. All patients and controls underwent 24-h Holter monitoring for arrhythmias. Left ventricular (LV) wall thickening was found in all patients with cardiac amyloidosis. The LV mass in the patients with cardiac amyloidosis was significantly greater than that of the control group, as was the ratio LV mass/body surface area (p < 0.001). There was no significant difference in the max QT interval or in QTc dispersion between the two groups, although the max QTc was greater in the patients with cardiac amyloidosis. Patients with cardiac amyloidosis did not have a higher incidence of arrhythmias than the controls. Although patients with thickened cardiac walls due to cardiac amyloidosis have a prolonged QTc in comparison with controls, they do not show an increase in interlead QTc dispersion which might suggest the possibility of regional disturbances of the uniformity of repolarization. Patients with cardiac amyloidosis do not have a higher incidence of arrhythmias than controls.

Adult↗
PubMed2006

SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.

Aged↗
PubMed1989

Amyloid protein of vessels in leptomeninges, cortices, choroid plexuses, and pituitary glands from patients with systemic amyloidosis.

The cerebrum, cerebellum, and choroid plexuses from 16 patients with systemic amyloidosis, and the pituitary glands from 14 of these patients, were investigated histologically and immunohistochemically. Cerebrovascular amyloid (CVA) was found in the leptomeninges and cortices of six patients with systemic amyloidosis, including two patients with amyloid A protein (AA) amyloidosis related to serum amyloid A protein, one with AL amyloidosis related to immunoglobulin light chain (AL), two with familial type I amyloidotic polyneuropathy (FAP), and one with senile systemic amyloidosis (SSA). CVA protein from two patients with FAP reacted with anti-human prealbumin antibody similar to that of the visceral organs of these two patients. CVA in SSA reacted with anti-human prealbumin antibody and anti-beta protein antibody. Vascular amyloid was frequently noted in the pituitary glands and choroid plexuses of patients with systemic amyloidosis, and was found to be identical to that in the visceral organs (heart, kidney, and intestine) of these patients. CVA in the leptomeninges and cortices from two patients with AA amyloidosis and one with AL amyloidosis reacted with anti-beta protein monoclonal antibody but not with anti-human AA monoclonal antibody, anti-human A lambda antisera, and anti-human A kappa antisera. We suggest that amyloid proteins of AA and AL amyloidosis do not readily accumulate in the vessels in the leptomeninges and cortices even though the proteins circulate, and that beta protein is not derived from a serum precursor.

Amyloid↗
PubMed2004

Evaluation of right ventricular dysfunction in patients with cardiac amyloidosis using Tei index.

BACKGROUND: Cardiac amyloidosis is an infiltrative disease causing predominant diastolic dysfunction and systolic dysfunction at its advanced stage. Right ventricular (RV) dysfunction is an independent predictor of poor prognosis in congestive heart failure and cardiomyopathies. However, the assessment of RV function is still technically difficult because of the complicated geometry of the RV. The recently proposed Tei index, obtained from the cardiac time interval analysis, allows noninvasive and quantitative estimation of global ventricular function without geometric evaluation. Therefore, this study was designed to assess RV function for patients with cardiac amyloidosis. METHODS: Study patients consisted of 30 consecutive patients with biopsy specimen-proven cardiac amyloidosis and 50 control subjects. Patients were classified as having early or advanced stage of cardiac amyloidosis on the basis of mean left ventricular wall thickness < 15 mm or >/= 15 mm. Tei index, defined as the sum of isovolumetric contraction and relaxation time divided by ejection time, was obtained from tricuspid and pulmonary Doppler flow velocity. RESULTS: RV Tei index was significantly increased for patients with cardiac amyloidosis (0.54 +/- 0.16 vs 0.28 +/- 0.05, amyloidosis vs control, P <.001). The incidences of abnormal RV isovolumetric contraction time, ejection time, isovolumetric relaxation time, and Tei index in all patients with cardiac amyloidosis were 63%, 43%, 73%, and 83%, respectively. The same incidences were 50%, 13%, 63%, and 75% in the early stage and 68%, 54%, 77%, and 86% in the advanced stage, respectively. CONCLUSION: Patients with cardiac amyloidosis frequently have RV dysfunction even in its early stage. Tei index allows simple, noninvasive, and nongeometric estimation of RV dysfunction in patients with cardiac amyloidosis.

Adult↗
PubMed2000

Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis.

PURPOSE: Obstructive intramural coronary amyloidosis is an unusual complication of systemic amyloidosis. SUBJECTS AND METHODS: We review the characteristics of 11 patients seen at the Mayo Clinic (Rochester, Minnesota) from January 1, 1960, to June 1, 1999, with intramural cardiac amyloidosis diagnosed at autopsy or after examination of an explanted heart. RESULTS: Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis was found in 11 patients (8 men, 3 women). The mean (+/-SD) age at the diagnosis of primary amyloidosis was 62 +/- 12 years. All patients had angina pectoris; angina was the presenting symptom of primary amyloidosis in 6 patients. Unstable coronary syndromes occurred in 7 patients and congestive heart failure in 8. New electrocardiographic abnormalities after the development of angina were common and included ischemic changes, bundle branch block, and dysrhythmias. Low voltage was seen in only 2 patients. All 7 patients who underwent coronary angiography had normal or clinically insignificant findings. Endomyocardial biopsy was performed on 4 patients; amyloid was found in 3 patients, none of whom had obstructive intramural coronary amyloidosis. The diagnosis of obstructive intramural coronary amyloidosis with associated myocardial injury was established only at autopsy or after examination of the explanted heart after cardiac transplantation. The mean time to death or cardiac transplantation after symptoms of cardiac ischemia developed was 18 +/- 20 months. CONCLUSIONS: The diagnosis of ischemic heart disease resulting from obstructive intramural coronary amyloidosis is difficult to establish before death or cardiac transplantation. Although the condition has a poor prognosis, its accurate recognition may have therapeutic implications, because some patients may benefit from treatment, including systemic chemotherapy or cardiac transplantation.

Adult↗
PubMed2000

MEFV mutations in multiplex families with familial Mediterranean fever: is a particular genotype necessary for amyloidosis?

Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.

Adolescent↗
PubMed2002

A family with gastrointestinal amyloidosis associated with variant lysozyme.

Hereditary nonneuropathic systemic lysozyme amyloidosis is a very rare form of amyloidosis, and only 4 families with this condition have been detailed until now in the literature. Clinical manifestations of lysozyme amyloidosis observed until now mainly concerned the kidneys, liver, and digestive tract. We report here a new family with hereditary lysozyme amyloidosis who presented predominantly with gastrointestinal involvement. The proband, a middle-aged woman, underwent partial gastrectomy for a hemorrhagic "gastric peptic ulcer" in 1984. Gastrointestinal amyloidosis was diagnosed in 1998 on biopsies performed on the gastroduodenal anastomosis, which appeared to be very congestive at presentation. Immunohistochemical stainings in tissue sections were positive for lysozyme. Amyloid was also observed in the colonic mucosa. The patient had a mutation in the lysozyme gene characterized by substitution of the amino acid at position 64 in the mature protein from tryptophan to arginine, previously described in only 1 French family with prominent nephropathy. It is interesting to note that her father had died many years before with an uncharacterized digestive amyloidosis. Our observation shows that a search for gastrointestinal amyloidosis is important, particularly when physicians are faced with congestive mucosa, unexplained abdominal hemorrhage, or abdominal symptoms. When gastrointestinal amyloidosis is diagnosed, it is important to determine with precision the nature of the amyloid fibril proteins, because various types of amyloidosis can involve the gastrointestinal tract.

Amyloidosis↗
PubMed1997

Decreased excretion of urine glycosaminoglycans as marker in renal amyloidosis.

BACKGROUND: The diagnosis of renal amyloidosis is normally established by kidney biopsy. In order to advance the determination of the diagnosis and the initiation of the therapy, fast and cheap, non-invasive diagnostic techniques are required. METHODS: Urine excretion of glycosaminoglycans (GAG) was measured in 10 patients with AA amyloidosis and 5 patients with AL amyloidosis and compared to 25 controls with primary glomerular diseases and 22 healthy controls. The subjects with primary glomerular disease were matched with regard to their renal function and the degree of albuminuria. RESULTS: The median urine GAG to creatinine ratio and the median fractional GAG excretion were significantly decreased (P < 0.05) in both AA amyloidosis (0.21 mg/mmol and 0.053 respectively) and AL amyloidosis (0.33 mg/mmol and 0.077 respectively) compared to control patients with primary glomerular disease (1.73 mg/mmol and 0.336 respectively) and healthy controls (2.67 mg/mmol and 0.226 respectively). The urine GAG to creatinine ratio did not correlate to age, sex, serum creatinine, urine albumin, or to the plasma levels of acute phase proteins. CONCLUSIONS: The decreased GAG excretion in renal amyloidosis is probably caused both by diminished number of functioning nephrons, decreased GAG synthesis in functioning glomeruli, and the trapping of GAG by amyloid fibrils. Urinary GAG excretion may serve as an independent marker of renal amyloidosis. It may be used in diagnostic work-up of renal amyloidosis in patients with glomerular diseases and in screening of amyloidosis in patients with chronic inflammatory disorders, with or without signs of renal disease.

Adult↗
PubMed2002

Vascular involvement and cell damage in experimental AA and clinical beta(2)-microglobulin amyloidosis.

BACKGROUND: Amyloidosis is a highly prevalent disease characterized by the deposition of amyloid fibrils. Although several types of amyloidosis can be identified according to their protein constituents and suggest putative aetiological factors, the causes of amyloidosis remain unknown. Furthermore, the cellular participation and the ultrastructural particularities of amyloidosis have received little attention. The aim of our study was to evaluate the vascular participation in amyloidosis and the cellular consequences of this disease. METHODS: Two forms of amyloidosis were studied: experimental amyloid A (AA) and clinical beta(2)-microglobulin amyloidosis. We studied kidney, liver, and spleen in a mouse model, and examined surgically obtained carpal deposits from dialysis patients. We used light and electron microscopy with immunogold labelling for anti-beta(2)-microglobulin and anti-AA protein antibodies. RESULTS: AA amyloid fibril accumulation was associated with membrane lesions in basal, cytoplasmic organelle (endoplasmic reticulum, mitochondria), and nuclear membranes. Amyloid fibrils from beta(2)-microglobulin amyloidosis were also closely associated with elastic fibres and endothelial basement membrane. We observed proliferation of endothelial cells as well as basement membrane enlargement and disruption. CONCLUSIONS: Vascular abnormalities, including endothelial enlargement, basement membrane modifications, and vascular proliferation were associated with amyloidosis. Amyloid fibrils have a high avidity for elastic fibres and are able to contact and damage the basement membrane, the cell and intracellular organelle membranes, as well as the nuclear envelope, suggesting a toxic effect of amyloid fibrils on cells.

Amyloidosis↗