原发性淀粉样变性的临床病理及电镜观察

淀粉样变性是指淀粉样蛋白在皮肤，粘膜或内脏器官的细胞外沉积引起的一种少见疾病。口腔粘膜中舌粘膜是本病的好发部位。本组４例典型地发生于口腔颌面部的原发性淀粉样变性病例，３例病变部位为舌，１例为皮肤和口腔粘膜同时受累，临床提示有必要进行全身系统检查及追踪随访。并就基临床表现，常规病理，组织化学及电镜进行研究，同时讨论了淀粉样蛋白的光镜，电镜特点，组织学类型生化组成及来源。     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Urinary dysfunction and autonomic control in amyloid neuropathy

Abstract Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves.     

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 complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered ¹²⁵I-labelled serum amyloid P component(¹²⁵I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. ¹²⁵I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of ¹²⁵I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma ¹²⁵I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis.     

The pattern of amyloidosis in a Malaysian patient population

Congo red screening of 27,052 routine biopsy specimens from 22,827 patients over a 5 1/2-year period in the Department of Pathology, University of Malaya detected 186 cases of amyloidosis. The categories of amyloidosis encountered and their prevalences in relation to each other were: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). A third of patients with systemic AL amyloidosis had coexistent immunocyte abnormality. The commonest underlying pathology for systemic AA amyloidosis was leprosy. Notable among the types of localized amyloidosis revealed by this study were isolated atrial amyloidosis, which appeared to complicate chronic rheumatic heart disease, and intratumour amyloidosis complicating nasopharyngeal carcinoma. Other tumours in which amyloid deposits were observed included basal cell carcinoma, islet cell tumour and medullary carcinoma of the thyroid. Dystrophic amyloidosis was observed in fibrotic tissues, such as damaged cardiac valves and osteoarthritic joints. Heredofamilial amyloidosis, senile systemic amyloidosis and degenerative cerebral amyloidosis were notably absent from this study.     

EXPERIMENTAL AMYLOIDOSIS INDUCED BY SAPONIN

White male rabbits, weighing about 3 kg, were injected intravenously with 5 ml of 0.1% saponin solution dissolved in physiological saline once a week for six months. The sequential histological changes in the kidneys were observed by repeated biopsies and, in addition, the animals were subjected to necropsy for light and electron microscopic examinations. Amyloid protein was purified from the animal tissues, estimated at approximately 6,300 daltons in molecular weight by SDS-PAGE and considered as an AA type protein based on its amino acid sequence study. The antibody against the purified amyloid protein was produced in guinea pigs and was used for immunohistochemical studies. The deposition of amyloid started initially in mesangial matrices and subendothelial regions of the glomeruli, but at the end the spleen, kidney and bowels were found to be frequent sites of deposition. The amyloid deposited in the tissues was specifically positive by the indirect immunohistochemistry using the prepared antibody. This antibody also reacted positively to human materials with secondary amyloidosis. These results indicate that amyloidosis induced by saponin is a good model of secondary amyloidosis.     

Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice.     

Changes in enzyme activity of leukocytes during amyloid formation experimentally and in patients with amyloidosis

In patients with secondary amyloidosis and in animals with experimental amyloidogenesis and amyloidosis (casein model) the activity of hydrolases, oxidoreductases, and myeloperoxidase was determined in neutrophils and lymphocytes of the peripheral blood. During the period of amyloid formation, hydrolase and myeloperoxidase activity in the neutrophis was reduced, especially in the stage of initial amyloid deposition. Changes in the activity of these enzymes in animals with developed amyloidosis coincided with those in the blood cells of patients with secondary amyloidosis. The results are discussed from the standpoint of the resorption theory.Presented by Academician of the Academy of Medical Sciences of the USSR E. M. Tareev.)Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 799–801, July, 1976.