Type Of Amyloid Protein Research Articles

Endoscopic features in amyloidosis of the small intestine: Clinical and morphologic differences between chemical types of amyloid protein

Thirty patients with amyloidosis of the small intestine were studied to determine the correlations between the chemical types of amyloid protein and endoscopic, histologic, or clinical features. Endoscopic examinations of the jejunum revealed various findings such as a fine granular appearance, erosions and mucosal friability, thickening of the valvulae conniventes, and multiple polypoid protrusions in 23 cases. Immunohistochemical study of the biopsy specimens identified the following chemical types of amyloid protein: amyloid A protein (AA) in 20 cases, light chain protein (AL) in 8, ß 2 -microglobulin (AH) in 1, and prealbumin (AF) in 1. The fine granular appearance was found significantly more often in the AA cases ( p < 0.001), whereas multiple polypoid protrusions and thickening of the valvular conniventes were observed only in the AL cases ( p < 0.001). Histologically, wide granular amyloid deposits in the propria mucosae were seen significantly more often in the AA cases ( p < 0.01), whereas massive amyloid deposits in the muscularis mucosae, submucosa, and muscularis propria were the more dominant findings in the AL cases ( p < 0.001). Clinically, a more frequent occurrence of diarrhea, malabsorption, and occult blood in stools was present in the AA cases, whereas mechanical obstruction and chronic intestinal pseudo-obstruction were evident only in the AL and the AH cases. These results suggest that clinicopathologic differences between the amyloid proteins exist in small intestinal amyloidosis and that endoscopic appearance relates to the specific accumulation pattern of each type of amyloid protein. (Gastrointest Endosc 1994;40:45-50.)

Gastrointestinal amyloidosis: radiologic features by chemical types.

To determine the correlation between the radiographic and histologic findings of amyloidosis according to chemical type of amyloid protein. The 49 patients with amyloidosis were examined radiographically, and gastrointestinal tract biopsy specimens were studied histologically. Considerable differences were found between amyloid proteins. On immunohistochemical studies, amyloid A produced a coarse mucosal pattern with innumerable fine granular elevations, which reflected expansion of the lamina propria by amyloid deposits. Polypoid protrusions and invariable thickening of the folds were evident only in light chain protein, correlating with massive amyloid deposits in the muscularis mucosae and submucosa. beta 2-Microglobulin produced marked delay in transit time and dilatation of the small and large intestines, relating to extensive amyloid deposits in the muscularis propria. The prevalence of these radiographic changes was highest in the small intestine for every chemical type. Characteristic radiographic changes of each chemical type of amyloid protein can be detected well in the small intestine.

Hepatic amyloidosis in intravenous drug abusers and AIDS patients

The clinical and pathological features of four liver biopsies and 12 autopsies from 1981-1990 with hepatic amyloidosis were reviewed. All of the patients had a history of both intravenous and subcutaneous cocaine and heroin use with chronic suppurative skin ulcers. Five patients were proven to have the acquired immunodeficiency syndrome at autopsy. Systemic amyloidosis was diagnosed in only five out of the 16 patients prior to death. Hepatomegaly was present in 12 patients. The amyloid protein was AA in 14 and AL in one case. Definitive characterization of the amyloid substance was not possible in one case. There was no evidence of multiple myeloma or a plasma cell dyscrasia in the one patient with AL amyloid. The amyloid distribution in the liver was both parenchymal and vascular in 12 cases. Cholestasis, which appeared to occur preterminally, was the only histological finding that correlated with the patient's clinical condition. The histological pattern of amyloid in the liver could not predict the type of amyloid protein that was identified. Amyloidosis should be considered in the differential diagnosis of unexplained hepatomegaly in the acquired immunodeficiency syndrome with chronic suppurative infections.

Heparan sulfate expression patterns in the amyloid deposits of patients with Alzheimer's and Lewy body type dementia.

Heparan sulfate (HS), along with serum amyloid P component, has been identified in all types of amyloid investigated so far, regardless of the type of amyloid protein deposited. To assess whether unique or specific HS proteoglycans (HSPGs) may be involved in the formation of these lesions, we have investigated the accumulation of several distinct HSPG epitopes in the cerebra of patients with different forms of neurodegenerative disease. A panel composed of several antibodies revealed distinctive patterns of HSPG accumulation. In patients with dementia of the Lewy body type, the burned-out-type plaques and preamyloid-type plaques were strongly stained by both the anti-HS 'chain' and anti-HS 'stub' antibodies, but by none of the available anti-core protein antibodies. In Alzheimer's disease, the preamyloid-type plaques, dense-cored-type plaques, neuritic-type plaques and the neurofibrillary tangles were stained by the anti-'stub' antibody. The anti-'chain' and the anti-core protein antibodies, in contrast, failed to stain the preamyloid-type plaques and burned-out-type plaques, but stained the neuritic-type plaques in these patients. These data suggest differences in the types of HS and HSPG (fragments) that accumulate in amyloid lesions that may hallmark neurodegenerative disorders of different etiologies.

Amyloid deposition in intrahepatic large bile ducts and peribiliary glands in systemic amyloidosis

Amyloid deposition in the hepatic parenchyma and portal tracts in the liver is well known in systemic amyloidosis. We recently experienced an autopsy case of systemic amyloidosis presenting the amyloid deposits in the intrahepatic biliary tree. This experience prompted us to survey 19 autopsy cases of systemic amyloidosis. Amyloid deposition was found just under the lining epithelium of the intrahepatic large bile duct in 10 of 19 cases and around the peribiliary glandular acini in 7 of the 19 cases, respectively. Amyloid deposition in the intrahepatic large bile duct and peribiliary glands was positively correlated with the degree of amyloid deposition in the liver but not with type of amyloid protein. Double-staining of amyloid and vascular endothelium disclosed that amyloid deposition was more closely related to the inner part of the peribiliary vascular plexus and to the vascular plexus encircling the peribiliary glands than the lining biliary epithelium and peribiliary glandular acinar cells themselves. The exact pathogenesis of amyloid deposition in these anatomical components, however, remains unclear. Although our cases failed to show any overt clinical symptomatologies related to amyloid deposition in these biliary components, it seems conceivable that more massive amyloid deposition in these anatomical components could give rise to some clinical symptoms.

Cerebral amyloid angiopathy as a cause of subarachnoid hemorrhage.

Cerebral amyloid angiopathy is a pathologic condition characterized by the deposition of amyloid in the walls of small vessels in the cerebral cortex and meninges. Intracerebral hemorrhage is common in persons with this condition, but pure subarachnoid or subdural hemorrhage is rarely seen. Recently, the existence of two types of amyloid proteins related to cerebral amyloid angiopathy, beta protein and cystatin C, has been reported, and immunohistochemical methods using antisera to these proteins have become available. We describe a patient with fatal subarachnoid hemorrhage presumably caused by beta protein-type cerebral amyloid angiopathy, which was demonstrated immunohistochemically by using a monoclonal antibody to a synthetic peptide corresponding to residues 8-17 of beta protein. We suggest that beta protein-type cerebral amyloid angiopathy is a possible etiologic factor in subarachnoid hemorrhage of unknown cause.

Finnish hereditary amyloidosis: Amino acid sequence homology between the amyloid fibril protein and human plasma gelsoline

Amyloid fibrils were isolated from the kidney of a patient with Finnish hereditary amyloidosis. After solubilization of the fibrils in guanidine-HCl, fractionation by gel filtration, and purification by reverse-phase high-performance liquid chrornatography, a homogeneous amyloid protein with an apparent M r of 9000 was obtained. The protein was subjected to enzymatic digestion by trypsin and endoproteinase Lys-C. The amino acid sequences were determined for 6 of the released peptides and they were all found to be identical to the reported, deduced primary structure of human plasma gelsoline in the region of amino acids 235–269. The results show that the amyloid fibril protein in Finnish hereditary amyloidosis represents a new type of amyloid protein that shows amino acid sequence homology with gelsoline, an actin-modulating protein.

Immunoelectron microscopic classification of amyloid in renal biopsies.

Recent classification of amyloidosis is based on the chemical type of amyloid protein involved. In this study, routinely embedded kidney biopsies from nine patients with generalized amyloidosis and renal involvement were tested by immunoelectron microscopy, using the protein A-gold technique, with a panel of antibodies against the following amyloid proteins: AA, A lambda, A kappa and AF. Among the antibodies, the anti-AA was monoclonal (mc1) and the others polyclonal. In all nine cases, only one type of antibody reacted with each amyloid type. Six cases were classified as AA and three cases as A lambda type. These classifications were in agreement with the clinical data and the results of serum and urine immunoelectrophoresis. The gold particles were always associated with amyloid fibrils. No reaction was evident when an amyloid type was stained by a non-corresponding antibody, or in the four control cases without amyloid. The results show that antigenic classification of amyloid is feasible on routinely processed ultra-thin epoxy sections by immunoelectron microscopy, and thus affords the possibility of retrospective studies.

Skeletal muscle amyloid deposition in AL- (primary or myeloma-associated), AA- (secondary), and prealbumin-type amyloidosis

Amyloid deposition in the quadriceps femoris muscle was investigated in 12 cases of systemic amyloidosis including 6 of AL-(primary or myeloma-associated) type, 2 of AA- (secondary) type, and 4 of prealbumin- (familial or sporadic) types. Clinically, muscle weakness was found in 7 patients. Among the 7 patients, one of the AL-type suffered from systemic myopathy showing progressive muscular stiffness, pseudohypertrophy, and weakness. The other 6 presented with polyneuropathy. Pathologically, no amyloid was found to be deposited in the AA-type. In all of the AL- and prealbumin-types, amyloid deposition was found in the blood vessels and peri- and endomysium. The degrees of amyloid deposition were marked in one case of the AL-type, which was considered to be suffering from amyloid myopathy, moderate in one of the AL-type, and slight in the rest of the AL-type and all of the prealbumin-type. Our observations and descriptions in the literature indicate that the presence and degrees of amyloid deposition in the skeletal muscles would be related to the types of amyloid proteins in amyloidosis. It seems likely that the affinity of amyloid to the skeletal muscles is variable in AL-type, probably depending on the molecular heterogeneity of AL protein, is low in prealbumin-type, and is almost absent in AA-type.

Renal amyloidosis. Correlations between morphology, chemical types of amyloid protein and clinical features.

Sixty-one autopsy cases of renal amyloidosis were reviewed to assess the relationship of renal pathology to chemical types of amyloid and clinical features. Glomerular amyloid deposition was divided on the basis of morphological characteristics, into four types: a mesangial nodular type showing nodular mesangial deposits with sparse capillary wall involvement (25 cases), a mesangio-capillary type disclosing diffuse amyloid deposition in the mesangium and along both sides of the glomerular basement membrane (19 cases), a perimembranous type principally involving the subepithelial side of the basement membrane invariably characterized by exuberant spicular arrangement (6 cases), and a hilar type showing amyloid deposits almost exclusively in hilar arterioles (11 cases). Twenty-four of 25 cases of mesangial nodular type (96%) showed amyloid protein of AA type. However, mesangio-capillary and perimembranous types were associated with deposition of AL amyloid protein in 15 of 19 (79%) and all 6 cases, respectively. Nephrotic syndrome was more frequent in patients with AL amyloidosis; notably, all patients with perimembranous type had nephrotic syndrome irrespective of the extent of glomerular amyloid deposits. Chronic renal failure and renal death appeared more common in mesangial nodular type in which the extent of glomerular amyloidosis correlated with that of vascular amyloid deposits. The results obtained suggest that the chemical type of glomerular amyloid protein (AA vs AL) is associated with significant differences in the morphological, clinical and prognostic features of the renal involvement.

上顎歯肉にみられたアミロイドーシスの１例

A case of amyloidosis appeared in gingiva of maxilla was reported. The patient was a 81-year-old man complaining of unfitness of the dentures. In the oral cavity, the tumor was oval and elastic soft with pedicle, measuring 24×36×10mm in size, and located at the right upper molar region of the alveolar ridge. The surface of the tumor was dark-reddish, containing white flecks with keratinization at the margin of the tumor, and without spontaneous pain or tenderness. Radiographic examination showed a radiolucent region with irregular margins at the alveolar bone of the lesion. The tumor was resected under local anesthesia. Histopathologically, at the upper side of pedicle, much linear and massive hyaline substances were observed in submucosal layer. A histopathologic diagnosis of amyloidosis was made by congo red staining and electromicroscopic observation. An immunohistochemical study could not identify the types of amyloid proteins of this case.