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beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease.

Roher, A E; Lowenson, J D; Clarke, S; Woods, A S; Cotter, R J; Gowing, E; Ball, M J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/11/1993 EN
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Reinvestigation of the chemical structure of beta-amyloid peptide (A beta) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form A beta-(1-42), rather than the more soluble A beta-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, A beta was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the A beta were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of A beta-(1-42)/A beta-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular A beta contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque A beta, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of A beta associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing A beta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.

Intraglomerular fibrin, platelet aggregation, and subendothelial deposits in lipoid nephrosis

Duffy, John L.; Cinque, Thomas; Grishman, Edith; Churg, Jacob
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1970 EN
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We have investigated the formation of fibrin, platelet aggregates, and subendothelial deposits in lipoid nephrosis. Fibrin formation was found in 10 cases of active lipoid nephrosis. Platelet aggregates were found in eight cases and subendothelial deposits in nine. Fibrin and platelets were also found in cases of nephrotic syndrome due to other causes, and in glomerulonephritis. Fibrin was generally absent in lipoid nephrosis in remission and in benign recurrent hematuria. It is suggested that what seems to be a lower incidence in females is more apparent than real and that fibrin or related material may be present in a less easily identifiable form. Steroid therapy apparently had no effect on the presence or absence of fibrin. Most instances were associated with elevated serum cholesterol and α2-globulin. It is suggested that elevated serum lipids as well as the disease process in the kidney play a role in this phenomenon. It is further suggested that intraglomerular fibrin formation could lead to irreversible renal damage in lipoid nephrosis.

In vivo interaction of antibodies with cell surface antigens. A mechanism responsible for in situ formation of immune deposits in the zona pellucida of rabbit oocytes.

Matsuo, S; Caldwell, P R; Brentjens, J R; Andres, G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1985 EN
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It was the aim of this study to test the hypothesis that the interaction of antibodies with antigens expressed on the plasma membrane of cells surrounded by a basement membrane or a basement membrane-like structure results in in situ formation of immune deposits. Ovary was chosen for the experiments because we found that a well-characterized protein, angiotensin-converting enzyme (ACE), is expressed in a diffuse pattern on the plasma membrane of mature oocytes. To investigate the events following the in vivo interaction of oolemma-ACE with its antibody, rabbits were injected with goat anti-rabbit ACE gamma-globulin or with Fab fragments of goat anti-rabbit ACE IgG in an ear vein for a maximum of 4 d; they were followed for up to 20 d thereafter. Ovary tissue was studied by immunofluorescence, and immunoelectron, light, and transmission electron microscopy. The results of this study document two new findings: First, that ACE is expressed on the oolemma of rabbit oocytes. Second, that the in vivo interaction of divalent antibodies to this cell surface antigen induces formation of granular immune deposits in the adjacent zona pellucida through a mechanism of "patching" and "shedding" of immune complexes, similar to that occurring in in vitro systems characterized by interaction of plasma membrane receptors with soluble ligands. This mechanism might have importance in the pathogenesis of Heymann glomerulonephritis and of other immunological diseases involving antigens expressed on the plasma membrane of cells.

Primary glomerular disease with extraglomerular vascular osmiophilic deposits

Nagi, A. H.; Alexander, F.; Lannigan, R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1972 EN
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The ultrastructural changes in renal arterioles and capillaries from three cases of epimembranous nephropathy, one case of minimal change, and one case of minimal change with mild focal proliferation are presented. In addition to the usual subepithelial deposits on the glomerular capillary basement membranes in the cases of epimembranous nephropathy, osmiophilic granular deposits were observed on the outer aspect of extraglomerular vascular basement membranes. No clinical history of hypertension was obtained and there was no histological evidence of renal hypertensive vascular disease.

HTLV-I associated uveitis revisited: characteristic grey-white, granular deposits on retinal vessels.

Nakao, K; Ohba, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1996 EN
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AIMS: To elucidate whether there exists any clinical sign characteristic of HTLV-I associated uveitis. METHODS: Fifty five patients with HTLV-I associated uveitis were reviewed. These cases had serum antibodies to HTLV-I, and any other uveitis entities were carefully excluded by means of clinical and laboratory studies. RESULTS: Eight cases (14.5%) developed vascular lesions in the retina, characterised by grey-white, granular deposits scattered on the retinal veins and/or arteries in the posterior pole. The vascular changes did not accompany any haemorrhage, sheathing, or leakage of fluorescent dye on angiograms, and the retina was otherwise unremarkable. A single or clustered form of similar materials was also found to deposit on the vitreo-retinal interface of the foveolar area. These deposits resolved in a few weeks spontaneously or in response to corticosteroids together with anterior uveal inflammation. CONCLUSION: The vascular lesions described here suggest a characteristic sign for HTLV-I associated uveitis, and it may provide, if recognised, an additional clinical marker to establish diagnosis.

Acute synovitis with intra-articular apatite deposits in an osteoarthritic metacarpophalangeal joint.

Gerster, J C; Lagier, R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1985 EN
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A patient was shown to have acute arthritis in a metacarpophalangeal joint, with local calcification indicated by x-rays. Surgical and pathological examinations showed strictly intra-articular apatite crystal deposits and an erosive osteoarthritis. These crystal deposits could account for the synovial inflammation; they are thought to be related to bone fragments embedded in the synovium. The predisposing role of previous local injections of corticosteroids is debatable.

Abnormal deposits of chromium in the pathological human brain.

Duckett, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1986 EN
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Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta...

Subepithelial corneal deposits in IgG lambda myeloma.

Hill, J C; Mulligan, G P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1989 EN
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A 46-year-old female presented with disseminated IgG lambda myeloma and unusual, translucent, subepithelial deposits in the periphery of both corneas. Electrophoretic studies showed that the deposits consisted of an IgG lambda paraprotein identical to that found in the serum. Minute amounts of the papaprotein were also present in the tears.

Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers

Luibl, Volker; Isas, Jose M.; Kayed, Rakez; Glabe, Charles G.; Langen, Ralf; Chen, Jeannie
Fonte: American Society for Clinical Investigation Publicador: American Society for Clinical Investigation
Tipo: Artigo de Revista Científica
Publicado em 01/02/2006 EN
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Protein misfolding and aggregation are thought to underlie the pathogenesis of many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a stepwise protein misfolding process begins with the conversion of soluble protein monomers to prefibrillar oligomers and progresses to the formation of insoluble amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in eyes afflicted with age-related macular degeneration (AMD). Recent characterizations of drusen have revealed protein components that are shared with amyloid deposits. However, characteristic amyloid fibrils have thus far not been identified in drusen. In this study, we tested the hypothesis that nonfibrillar oligomers may be a common link in amyloid diseases. Oligomers consisting of distinct amyloidogenic proteins and peptides can be detected by a recently developed antibody that is thought to recognize a common structure. Notably, oligomers exhibit cellular toxicity, which suggests that they play a role in the pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer antibody, we came to observe the presence of nonfibrillar, toxic oligomers in drusen. Conversely, no reactivity was observed in age-matched control eyes without drusen. These results suggest that amyloid oligomers may be involved in drusen biogenesis and that similar protein misfolding processes may occur in AMD and amyloid diseases.

Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.

Charhon, S A; Chavassieux, P M; Meunier, P J; Accominotti, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/06/1985 EN
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Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.

Formation of subepithelial dense deposits in rats induced by a monoclonal antibody against the glomerular cell surface antigen.

Nishikawa, K; Fukatsu, A; Tamai, H; Suzuki, N; Ito, Y; Sakamoto, N; Matsuo, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1991 EN
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We developed a monoclonal antibody, H5H3, of IgG1 subclass by hybridization technique using spleen cells of mice immunized with plasma membrane fraction of isolated rat glomeruli. H5H3 recognized main bands at about 220 kD by immuno-overlay technique and bound to the glomerulus as well as brush border of proximal tubules by indirect immunofluorescence (IF) microscopy on normal rat kidney frozen sections. By immunoelectron microscopy (IEM) it bound to the surface of mainly glomerular epithelial cell and weakly to the endothelial cell. After injection to Wistar rats it remained granularly in the glomerulus for more than 2 weeks seen by IF. When rats were preimmunized with murine IgG 4 days before the injection of H5H3, mouse IgG, rat IgG and C3 were strongly visible granularly in the glomerulus in 14 days by IF. Numerous dense deposits were formed at subepithelial area seen by transmission electron microscopy. Perfusion experiment of H5H3 into rat left kidney showed granular distribution of mouse IgG in 48 h, indicating that the reaction occurred in situ. H5H3 bound diffusely in fine granular pattern on the surface of cultured glomerular epithelial cells (GEC) studied by IF and IEM. Antigenic redistribution occurred on GEC after incubation of H5H3 at 37 C. These results suggested the required conditions to form subepithelial immune dense deposits...

Immune deposits in extraglomerular vessels: their correlation with circulating immune complexes.

Burden, R P; Cotton, R E; Wallington, T B; Reeves, W G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1980 EN
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Sixty-eight per cent of a consecutive series of 65 renal biopsies showed immune deposits in extraglomerular blood vessels. Although they occurred with a variety of clinical disorders and histological diagnoses, they were associated in particular with an acute nephritic syndrome, focal proliferative glomerulonephritis and non-specific mesangial changes. IgM was the commonest immunoglobulin class to be deposited and higher levels of IgM-containing complexes were detected in the serum of those patients with vascular deposits. Hitherto, immunofluorescent studies of renal biopsies have concentrated mostly on glomeruli but this study suggests that the extraglomerular vasculature deserves closer attention. The mechanisms for this pattern of localization are discussed.

Structural factors in the in vivo chelate mobilization of aged cadmium deposits.

Singh, P K; Jones, S G; Jones, M M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1990 EN
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The role of structural factors in determining the relative efficacy of dithiocarbamates as chelating agents for the in vivo mobilization of aged cadmium deposits is examined for 23 newly synthesized compounds of this type. The critical feature in determining the efficacy of the compounds in mobilizing intracellular cadmium is the balance between hydrophobic and hydrophilic groups. This balance also governs the other properties of these compounds such as the organ specificity of action and the relative propensity to carry cadmium to the brain. The transport of cadmium to the brain by dithiocarbamate can be greatly reduced by the incorporation of appropriate hydrophilic groups that prevent the formation of lipid-soluble cadmium complexes that pass readily into the brain. If the chelating agents carry an additional ionic charge, their ability to pass through cellular membranes and react with intracellular deposits of cadmium is significantly reduced, with other structural factors being equal. The structural features that optimize mobilization of cadmium from the kidney do not appear to be identical with those that optimize its mobilization from the liver. The correlation of cadmiummobilizing properties of these chelating agents with the sum of the Hansch pi constants for the parts of the molecular structures other than the dithiocarbamate grouping (sigma pi) is reasonably good for the removal of renal cadmium by derivatives of D-glucamine and D-xylamine. Another aspect of the molecular structure that appears to play a role is the presence of uncharged polar groups having the ability to form hydrogen bonds. The relevance of these factors in designing chelating agents to enhance the excretion of other toxic metals from their intracellular sites is discussed.

Mostly Separate Distributions of CLAC- versus Aβ40- or Thioflavin S-Reactivities in Senile Plaques Reveal Two Distinct Subpopulations of β-Amyloid Deposits

Kowa, Hisatomo; Sakakura, Tomoko; Matsuura, Yusuke; Wakabayashi, Tomoko; Mann, David M.A.; Duff, Karen; Tsuji, Shoji; Hashimoto, Tadafumi; Iwatsubo, Takeshi
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /07/2004 EN
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Collagenous Alzheimer amyloid plaque component (CLAC) is a unique non-Aβ amyloid component of senile plaques (SP) derived from a transmembrane collagen termed CLAC-precursor. Here we characterize the chronological and spatial relationship of CLAC with other features of SP amyloid in the brains of patients with Alzheimer’s disease (AD), Down syndrome (DS), and of PSAPP transgenic mice. In AD and DS cerebral cortex, CLAC invariably colocalized with Aβ42 but often lacked Aβ40- or thioflavin S (thioS)-reactivities. Immunoelectron microscopy of CLAC-positive SP showed labeling of fibrils that are more loosely dispersed compared to typical amyloid fibrils in CLAC-negative SP. In DS cerebral cortex, diffuse plaques in young patients were negative for CLAC, whereas a subset of SP became CLAC-positive in patients aged 35 to 50 years, before the appearance of Aβ40. In DS cases over 50 years of age, Aβ40-positive SP dramatically increased, whereas CLAC burden remained at a constant level. In PSAPP transgenic mice, CLAC was positive in the diffuse Aβ deposits surrounding huge-cored plaques. Thus, CLAC and Aβ40 or thioS exhibit mostly separate distribution patterns in SP, suggesting that CLAC is a relatively early component of SP in human brains that may have inhibitory effects against the maturation of SP into β-sheet-rich amyloid deposits.

Lipoproteins accumulate in immune deposits and are modified by lipid peroxidation in passive Heymann nephritis.

Exner, M.; Susani, M.; Witztum, J. L.; Hovorka, A.; Curtiss, L. K.; Spitzauer, S.; Kerjaschki, D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1996 EN
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Proteinuria in passive Heymann nephritis is primarily caused by reactive oxygen species that are produced by glomerular cells. Reactive oxygen species apparently exert their damaging effects on the glomerular filter by lipid peroxidation and subsequent adduct formation on matrix proteins of glomerular basement membranes. This raised the question as to the source of polyunsaturated fatty acids required as substrates for lipid peroxidation. Here we have localized by immunocytochemistry rat apolipoprotein E and apolipoprotein B within subepithelial immune deposits. Moreover, apolipoprotein B extracted from isolated glomeruli of proteinuric passive Heymann nephritis rats shows degradation and lipid peroxidation adduct formation, similar to apoproteins of oxidized lipoproteins in atherosclerotic lesions. These data provide evidence that lipoproteins accumulate within immune deposits and suggest that their lipids generate lipid-peroxidation-derived reactive compounds.

The "normal" brain. "Abnormal" ubiquitinilated deposits highlight an age-related protein change.

Pappolla, M. A.; Omar, R.; Saran, B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1989 EN
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Known morphologic changes that characterize "normal" brain senescence are insufficient to explain the widespread, age-related decline of psychomotor functions. We report that the heavily ubiquitinilated deposits can be consistently detected by immunohistochemistry in the normal senescent brain. Immunostaining of hippocampal sections from aged brains with an anti-ubiquitin antibody was unrelated to neurofibrillary degeneration or senile plaque formation. In contrast, ubiquitin deposits were not detectable in brain sections from neurologically and neuropathologically normal young individuals who had died of nonneurological causes. This finding shows an unrecognized protein change in the normal aged brain.

Ultrastructural localization of DNA in immune deposits of human lupus nephritis.

Malide, D.; Londoño, I.; Russo, P.; Bendayan, M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1993 EN
Relevância na Pesquisa
26.47%
DNA molecules were revealed in the glomerular wall of lupus nephritis patients by applying two specific colloidal gold cytochemical approaches at the electron microscope level: immunocytochemistry using a monoclonal anti-DNA antibody in conjunction with protein A-gold and enzyme-gold cytochemistry using DNAse-gold complexes. Application of both techniques has demonstrated that DNA molecules are preferentially located over the electron-dense deposits found in the glomerular basement membrane and mesangial matrix of SLE patients, as well as over the nuclei. Their distribution within the glomerular wall was correlated with electron-dense immune deposits revealed by anti-light chain antibodies. In normal control kidney, DNA labeling was restricted to the cell nuclei. Several control experiments have demonstrated the high specificity of the results. These data thus suggest a possible role for DNA as an antigenic component in the formation of immune complexes.

Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex.

Martin, L. J.; Pardo, C. A.; Cork, L. C.; Price, D. L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1994 EN
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26.47%
The cerebral cortices of macaques (ranging in age from 10 to 37 years; n = 17) were analyzed by immunocytochemistry and electron microscopy to determine the cellular and subcellular localizations of the amyloid precursor protein and beta-amyloid protein, the cellular participants in the formation of senile plaques and parenchymal deposits of the beta-amyloid protein, and the temporal/spatial development of these lesions. Amyloid precursor protein was enriched within the cytoplasm of pyramidal and nonpyramidal neuronal cell bodies in young and old monkeys. In the neuropil, amyloid precursor protein was most abundant within dendrites and dendritic spines; few axons, axonal terminals, and resting astrocytes and microglia contained the amyloid precursor protein. At synapses, amyloid precursor protein was found predominantly within postsynaptic elements and was enriched at postsynaptic densities of asymmetrical synapses. The earliest morphological change related to senile plaque formation was an age-related abnormality in the cortical neuropil characterized by the formation of dense bodies within presynaptic terminals and dendrites and an augmented localization of the amyloid precursor protein to astrocytes and microglia. In most monkeys > 26 years of age...

Renal and systemic kappa light chain deposits and their plasma cell origin identified by immunoelectron microscopy.

Silver, M. M.; Hearn, S. A.; Ritchie, S.; Slinger, R. P.; Sholdice, J. A.; Cordy, P. S.; Hodsman, A. B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1986 EN
Relevância na Pesquisa
26.47%
Kappa light chain determinants were identified by immunoelectron microscopy in nodular glomerulosclerotic lesions and systemic interstitial deposits from a man who died several years after the onset of proteinuric renal failure treated by hemodialysis. He developed adrenal and hepatic failure preterminally but not overt malignant myeloma. Specific labeling was most concentrated over the inner aspect of glomerular basement membrane and the mesangium, which suggested that the protein was nonfiltrable. Tubular basement membrane labeling was densest over the outer aspect, which suggested that the protein perfused from the interstitium rather than from the tubular lumen. We identified the source of the protein as a population of plasma cells present within bone marrow and renal interstitium; these showed specific immunogold labeling for kappa light chain protein over organelles concerned with protein synthesis, secretion, and storage. This appears to be the first identification of light chain determinants in human interstitial para-amyloid deposits with the use of immunogold ultrastructural techniques in tissues prepared for electron microscopy by standard methods and stored as epoxy resin blocks.

Redistribution of amyloid deposits.

Shirahama, T.; Cohen, A. S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1980 EN
Relevância na Pesquisa
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After 21 daily subcutaneous injections of 0.5 ml 10% casein, CBA/J mice were left untreated and evaluated periodically for 6 months for the development of amyloid in spleens, livers, and kidneys. At the end of the amyloid-inducing regimen, the mice developed moderate to heavy splenic amyloid, trace to light hepatic amyloid, and virtually no renal amyloid. Renal amyloid appeared about 2 months after cessation of the casein and then increased steadily, while splenic and hepatic amyloid gradually diminished. Six months after the cessation of casein, moderate amyloid deposits were observed in the kidneys whereas no, or only traces of, amyloid remained in spleens and livers. This renal amyloid was localized predominantly in the peritubular area and differed from the renal amyloid seen in rapidly induced disease, when it localizes dominantly in glomeruli. This phenomenon is interpreted in the light of possible redistribution of amyloid deposits from organ to organ, and the clinical and investigative significances of this possibility and others are discussed.