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Intracranial calcified deposits in neurofibromatosis.

Arts, W F; Van Dongen, K J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1986 EN
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Three patients with the central type of neurofibromatosis, who on CT showed multiple subependymal calcified deposits, are presented. The literature on intracranial non-tumourous calcifications in neurofibromatosis is briefly reviewed. On the basis of our findings and the literature, it is proposed that such intracranial calcified deposits may be part of the neurofibromatosis syndrome and are caused by calcium deposits in glial proliferations, analogous to the calcified deposits seen in tuberous sclerosis.

Mercury induced antinuclear antibodies in mice: characterization and correlation with renal immune complex deposits.

Hultman, P; Eneström, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1988 EN
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Female SJL and Balb/c mice were given subcutaneous injections of 1.6 mg HgCl2/kg body weight every third day for 2, 4, 8, or 12 weeks. Indirect immunofluorescence using HEp-2 cells as substrate showed that SJL mice developed antinuclear antibodies (ANA) with a predominantly nucleolar and a weaker, homogeneous nuclear pattern after 4 weeks treatment. The nucleolar antigen was sensitive to treatment with trypsin and RNAse, but the antibody was not absorbed by calf liver RNA. The antigen responsible for the homogeneous nuclear pattern was sensitive to treatment with trypsin, DNAse, and acid solution, but reconstitution with histones on acid treated substrate did not restore the fluorescence. The corresponding antibody was not absorbed by double-stranded or single-stranded DNA, and the Crithidia luciliae assay was negative. This suggests that the antigen responsible for the homogeneous ANA pattern is a non-histone chromatin protein. No autoantibodies were found in Balb/c mice. Electron dense immune deposits containing IgG and C3 in a mesangial-vascular pattern developed after 4 weeks mercury treatment in SJL and Balb/c mice. Acid eluate from kidneys of SJL mice with immune deposits contained tissue-bound ANA with a strictly anti-nucleolar pattern...

Chronic serum sickness glomerulonephritis: removal of glomerular antigen and electron-dense deposits is largely dependent on plasma complement.

Furness, P N; Turner, D R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1988 EN
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Chronic serum sickness glomerulonephritis was induced in 20 rats, using radio-labelled cationised bovine serum albumin (BSA) as antigen. Four days after the last dose of antigen, half the rats were given cobra venom factor (CVF) in doses sufficient to render plasma complement activity undetectable. After ten days without circulating complement, the rats had significantly more antigen in glomeruli than the control group. Subepithelial and mesangial electron dense deposits are found in this model: morphometric analysis indicated that the elimination of plasma complement had slowed the removal of deposits at both of these sites. A second experiment studied the kinetics of this effect. CVF was again given four days after the last dose of antigen, but rats were killed in small groups at intervals thereafter. The results indicate that initially decomplementation had little effect, but after seven days without complement the removal of glomerular antigen had virtually ceased. The complement depleted rats had significantly lower levels of proteinuria, despite having more antigen and larger deposits in their glomeruli. In this model therefore, complement appears to be essential for the removal of deposits, and simultaneously contributes significantly to the induction of proteinuria.

Clusterin in renal tissue: preferential localization with the terminal complement complex and immunoglobulin deposits in glomeruli.

French, L E; Tschopp, J; Schifferli, J A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1992 EN
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The membrane attack complex (MAC) of complement is activated by immune and non-immune mechanisms in the kidney. MAC has been found associated with glomerular immune deposits, but also to cell remnants, particularly along tubules and in vessel walls. Clusterin and S-protein (vitronectin) bind to MAC, rendering it cytolytically inactive. Both have been found associated with MAC in renal tissue. Here we analysed the deposition of clusterin and S-protein in 118 renal biopsies relative to the localization of the MAC using MoAbs. Statistical analysis was performed comparing no or little versus evident or strong staining by immunofluorescence (IF). In glomeruli, out of the 92 biopsies where both MAC and immunoglobulins were evaluated, deposits of MAC were found in the presence (32 out of 41) but also in the absence of immunoglobulins (20/51). Clusterin and S-protein deposits were seen, respectively, in 25 out of 61 and 36 out of 61 biopsies containing glomerular MAC, and almost never in its absence (one out of 50 for both). The association of the two inhibitors with MAC was observed mainly in glomeruli containing immunoglobulin deposits (respectively, 21 out of 32 and 25 out of 32), but not when immunoglobulins were absent (three out of 20 and seven out of 20) (coefficient of concordance...

Apolipoprotein B in Cholesterol-Containing Drusen and Basal Deposits of Human Eyes with Age-Related Maculopathy

Malek, Goldis; Li, Chuan-Ming; Guidry, Clyde; Medeiros, Nancy E.; Curcio, Christine A.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /02/2003 EN
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Lipids accumulate in Bruch’s membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share molecules and mechanisms pertaining to extracellular lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM, basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem and cryosectioned. Sections were stained with traditional lipid stains and filipin for esterified and unesterified cholesterol or probed with antibodies to apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and protein. Esterified and unesterified cholesterol was present in all drusen and basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained by traditional lipid stains and apolipoprotein antibodies than peripheral drusen. RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in sub-RPE deposits links ARM with important molecules and mechanisms in atherosclerosis initiation and progression. The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM.

Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits.

Gallo, G.; Goñi, F.; Boctor, F.; Vidal, R.; Kumar, A.; Stevens, F. J.; Frangione, B.; Ghiso, J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1996 EN
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Cardiomyopathy due to monoclonal light chain deposits is a complication of plasma cell disorders. The deposits may be either fibrillar as in light chain amyloid or nonfibrillar as in light chain deposition disease. The reasons for these structural differences are still unknown. We characterized the myocardial deposits by immunohistochemical examination of sections and extraction and biochemical analysis of the tissue deposits in a patient (MCM) who died of myeloma and systemic light chain deposition disease. Amino acid sequence analysis of the extracted nonfibrillar MCM kappa-light chain reveals that it belongs to the L12a germline subset of the kappa(I) protein and contains five distinctive amino acid substitutions (three in the framework region III and two in the complementarity-determining region III) that have not been reported previously in the same positions in other kappa(I) light chains. The theoretically determined isoelectric point (pI 8.21) of the MCM light chain is high compared with the low isoelectric point of other Bence Jones proteins from subjects without light chain deposition disease. The diffuse binding to basement membranes and the high isoelectric point of the MCM kappa-light chain suggest electrostatic interaction as a possible mechanism of tissue deposition. The spatial locations of the five distinctive residues and a sixth rare substitution of the MCM protein modeled on the backbone structure of REI...

Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits.

Cork, L. C.; Masters, C.; Beyreuther, K.; Price, D. L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1990 EN
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The evolution of senile plaques and the relationships among neuritic elements, extracellular deposits of the beta-amyloid protein (beta/A4), and vascular beta/A4 are poorly understood. Immunocytochemical methods were used to examine fixed-frozen prefrontal cortices of 14 rhesus monkeys (Macaca mulatta) (14 to 37 years of age) for the presence of abnormal fibers/neurites, alpha 1-antichymotrypsin (alpha-ACT), and beta/A4. Age-associated alterations included abnormal fibers/neurites, presence of beta/A4, and association of alpha-ACT with beta/A4 in plaques and blood vessels. Vascular amyloid was present only in the oldest monkeys. The topographic distribution of abnormal fibers/neurites was mapped with acetylcholinesterase (AChE) histochemistry, and deposits of amyloid were visualized with immunocytochemistry for beta/A4. beta/A4 often was associated with neurites, but many neurites lacked demonstrable beta/A4. Thus in aged monkeys, abnormal neurites may provide one type of focus for the accumulation of the amyloid precursor, which is subsequently abnormally processed to form beta/A4. Our data in rhesus monkeys suggest that fiber and neuritic abnormalities increase with age and that they may precede the majority of beta/A4 deposits; the initial stages of neurite formation and parenchymal amyloid deposits may be independent of the appearance of vascular amyloid; and these processes may be synergistic with advanced age.

Early extracellular and cellular lipid deposits in aorta of cholesterol-fed rabbits.

Guyton, J. R.; Klemp, K. F.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1992 EN
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Subendothelial accumulation of extracellular liposomes rich in unesterified cholesterol has been described as an early feature of atherosclerosis induced by cholesterol feeding in rabbits. Beta-very-low-density lipoproteins, however, the presumed source of atherogenic lipid in this animal model, contain mostly esterified cholesterol. The purpose of this study was to test for the presence of extracellular neutral lipid deposits consistent with esterified cholesterol, by employing new electron microscopic techniques. Rabbits were fed 0.5% cholesterol, 5% butter for 0, 1, 2, and 4 weeks. The lipid-preserving ultrastructural techniques showed, in control and atherosclerotic rabbit arteries, neutral lipid droplets adherent to the endothelial luminal surface. After 1 to 2 weeks, subendothelial extracellular deposits of mostly membranous lipid appeared; these deposits contained variable amounts of neutral lipid. At the same time, cytoplasmic neutral lipid droplets appeared in smooth muscle cells and in a small number of subendothelial macrophagelike cells. After 4 weeks, monocytic infiltration and macrophage foam cell development were prominent, but abundant extracellular lipid deposits also were found. Therefore, in arteries of cholesterol-fed rabbits...

Lectin binding in membranoproliferative glomerulonephritis. Evidence for N-acetylglucosamine in dense intramembranous deposits.

Nevins, T. E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1985 EN
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Type II membranoproliferative glomerulonephritis (MPGN-II) is characterized by electron-dense intramembranous deposits (DIMD) in the basal laminae of the kidney. These deposits selectively bind the lectin wheat germ agglutinin (WGA) or its succinylated derivative. In renal tissue samples from normal controls, Type I membranoproliferative glomerulonephritis, and several other renal diseases, only a normal pattern of WGA binding was observed and no membrane-oriented deposits reacted with WGA. Additional attempts to stain the DIMD with any of eight other lectins or eight antisera to renal antigens were uniformly unsuccessful. Discrete WGA reactivity indicates that the deposits contain appreciable quantities of internally linked N-acetylglucosamine and may also provide a valuable adjunct in making the histologic diagnosis of MPGN-II.

Molecular study of an IgG1κ cryoglobulin yielding organized microtubular deposits and glomerulonephritis in the course of chronic lymphocytic leukaemia

GALEA, H R; BRIDOUX, F; ALDIGIER, J-C; PARAF, F; BORDESSOULE, D; TOUCHARD, G; COGNÉ, M
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /07/2002 EN
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Glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits (GOMMID) and glomerulonephritis related to type I cryoglobulin are well-known but rare complications of B cell derived chronic lymphocytic leukaemia. In these disorders, monoclonal Ig have never been studied at the molecular level. We conducted a pathological and molecular analysis in a patient with chronic lymphocytic leukaemia, glomerulonephritis and a single circulating monoclonal Ig. Unusual IgG1κ kidney deposits were observed. The heavy and light chain variable region sequences of that cryoprecipitating monoclonal Ig were characterized. Light microscopy revealed glomerulonephritis typical of cryoglobulinaemia, with neutrophil and macrophage infiltration, endocapillary hyperplasia and few protein thrombi. Electron microscopic study clearly evidenced numerous subepithelial mixed granular and organized deposits with a unique microtubular organization, reminiscent of the GOMMID. The Ig molecule sequence revealed alterations of charge and hydrophobicity potentially promoting a crystal-like aggregation and the aggregation of microtubules.This description suggests that common mechanisms are involved in various forms of precipitation and/or deposition of complete Ig molecules...

Stimulation of mesangial phagocytes does not influence the removal of established glomerular immune complex deposits.

Furness, P. N.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1990 EN
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To test the hypothesis that mesangial phagocytes are involved in the removal of established glomerular immune complex deposits, either puromycin aminonucleoside (PAN) or polyvinyl alcohol (PVA) was given to rats as they recovered from chronic serum sickness glomerulonephritis. Both these substances increase the number and activity of mesangial macrophages. The nephritis was induced with radiolabelled cationized bovine serum albumin (BSA). After 10 days of such treatment, the animals were killed and the amount of isotope in whole renal cortex and in isolated glomeruli was measured. The volume fraction of subepithelial and mesangial electron-dense deposits was assessed by morphometric methods. Neither PAN nor PVA caused any significant alteration in any of these parameters. These results suggest that the methods by which well established glomerular immune complex deposits are removed do not involve mesangial macrophages to any major extent, and therefore differ from the systems which handle particulate matter and immune complexes as they arrive at the glomerular filter. The morphologic appearances of the deposits at the end of the experiment suggest extracellular dissolution in situ.

Membranoproliferative glomerulonephritis. Localization of early components of complement in glomerular deposits.

Davis, B. K.; Cavallo, T.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1976 EN
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A body of evidence suggests that in membranoproliferative glomerulonephritis (MPGN), complement is activated by the alternate pathway. Therefore, deposition of early components of complement should not be expected in glomeruli. The renal tissues of 16 patients--13 with classic MPGN and 3 with dense deposit disease, a variant of MPGN--were studied by light and electron microscopy and by means of elution and immunofluorescence for the localization of complement (C1q, C4, and C3), immunoglobulins (1gG, IgM, and 1gA), and other serum proteins. Variable amounts of C3, C4 and/or C1q, and IgM were detected in the glomeruli of all patients, whereas IgG and IgA were present, respectively, in 15 of 16 and 6 of 16 patients. Deposits were localized in mesangium and in peripheral capillary loops in a typical lobular distribution. The specificity of each antiserum was verified by immunodiffusion, immunoelectrophoresis, and blocking experiments utilizing unlabeled antibody. Glomerular-bound IgG was eluted with acid citrate buffer, suggesting that IgG might be complexed with antigen(s) in glomerular deposits. By light microscopy, lesions ranged from focal proliferation and lobulation to more severe involvement with typical splitting of glomerular basement membranes...

Rearrangement of immune complexes in glomeruli leads to persistence and development of electron-dense deposits

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/05/1983 EN
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Covalently, cross-linked immune complexes were prepared with multivalent 2-nitro-4-azidophenyl X human serum albumin (NAP X HSA) and antibodies to NAP at five times antigen excess. After purification with gel filtration, affinity chromatography with antigen-agarose column, and addition of the hapten, 9.5% of the antibodies dissociated from the complexes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. After injection of these cross-linked immune complexes into mice, glomeruli stained for the complexes by immunofluorescence microscopy for only a few hours and electron-dense deposits were not detected. In contrast, when the same immune complexes with comparable lattice but without covalent cross-linking were administered to a second group of mice, the initial deposition by immunofluorescence was comparable and then increased to extensive deposits that persisted to 96 h. In this second group of mice extensive electron-dense deposits evolved. These observations supported the conclusion that the immune complexes initially deposited from circulation must undergo rearrangement to persist and to form electron-dense deposits in glomeruli. The covalently cross-linked immune complexes existed in glomeruli only for a short period of time since these complexes could not rearrange.

Proteolytic enzyme treatment reduces glomerular immune deposits and proteinuria in passive Heymann nephritis

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/12/1986 EN
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26.66%
We investigated the effect of proteolytic enzyme treatment on the course of passive Heymann nephritis (PHN). PHN was induced by intravenous injection of Heymann antibody into Sprague Dawley rats. Protease-treated rats received intraperitoneal chymopapain and subtilisin. In rats given subnephritogenic doses of Heymann antibody (5 or 10 mg, insufficient to cause proteinuria), glomerular immune deposits were assessed by immunofluorescence and electron microscopy. In rats given 5 mg Heymann antibody and treated with protease in the heterologous phase of the disease (days 1-7), fewer animals were positive for rabbit IgG and rat IgG, as determined by immunofluorescence on day 12, compared with controls (p less than 0.01). Rats given 10 mg Heymann antibody and treated on days 1-5 were less frequently positive for rabbit IgG on day 5 than controls (p less than 0.05). When treatment was given on days 6-12 (autologous phase), fewer rats had glomerular rabbit and rat IgG compared with controls (p less than 0.025). Protease treatment of rats given nephritogenic doses of Heymann antibody (greater than or equal to 40 mg, causing proteinuria) did not result in significant differences in immunofluorescence deposits. However, protease treatment significantly reduced the number of electron dense deposits at all doses of antibody (p less than 0.01). Furthermore...

High density of intraepithelial γδ lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency

Borrelli, M; Maglio, M; Agnese, M; Paparo, F; Gentile, S; Colicchio, B; Tosco, A; Auricchio, R; Troncone, R
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /05/2010 EN
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The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)γδ+ intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRγδ+ IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRγδ+ IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRγδ+ IELs than controls (P < 0·05), but lower than IgAD with CD (P < 0·01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRγδ+/CD3+ ratio than the control group (P < 0·05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD...

Methotrimeprazine-induced Corneal Deposits and Cataract Revealed by Urine Drug Profiling Test

Kim, Seong Taeck; Koh, Jae Woong; Kim, Joon Mo; Kim, Won Young; Choi, Gwang Ju
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
EN
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26.66%
Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test.

Plaque and Deposits in Nine Human Stone Diseases

Coe, Fredric L; Evan, Andrew P; Lingeman, James E; Worcester, Elaine M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Data concerning nine forms of human stone disease, along with observations on normal people give new insights into formation of interstitial apatite plaque and intra-tubular crystal deposits. In general, across multiple disease states, one can reproduce the same relationships between plaque abundance as is seen among patients within individual disease states, so that the link between plaque and high urine calcium excretion, and low urine volume and pH seems increasingly secure. From this, one can propose a specific model of plaque formation, susceptible to experimental test. In many diseases, formation of inner medullary collecting duct and Bellini duct deposits is compatible with simple crystallization driven by urine supersaturations; this is expected in that these segments contain tubule fluid quite close in composition to final urine. But in ileostomy, small bowel disease and obesity bypass patients, crystals found in deposits are not those expected: apatite and urates in deposits, despite formation of highly acidic urine. Also, this discrepancy suggests the possibility of divergence between bulk urine pH and pH of focal collecting ducts, a new kind of possibility that is susceptible to experimental test.

In Situ Mass Spectrometry Imaging and Ex Vivo Characterization of Renal Crystalline Deposits Induced in Multiple Preclinical Drug Toxicology Studies

Nilsson, Anna; Forngren, Benita; Bjurström, Sivert; Goodwin, Richard J. A.; Basmaci, Elisa; Gustafsson, Ingela; Annas, Anita; Hellgren, Dennis; Svanhagen, Alexander; Andrén, Per E.; Lindberg, Johan
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 23/10/2012 EN
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Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition...

Bacteria Present in Carotid Arterial Plaques Are Found as Biofilm Deposits Which May Contribute to Enhanced Risk of Plaque Rupture

Lanter, Bernard B.; Sauer, Karin; Davies, David G.
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Artigo de Revista Científica
Publicado em 10/06/2014 EN
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Atherosclerosis, a disease condition resulting from the buildup of fatty plaque deposits within arterial walls, is the major underlying cause of ischemia (restriction of the blood), leading to obstruction of peripheral arteries, congestive heart failure, heart attack, and stroke in humans. Emerging research indicates that factors including inflammation and infection may play a key role in the progression of atherosclerosis. In the current work, atherosclerotic carotid artery explants from 15 patients were all shown to test positive for the presence of eubacterial 16S rRNA genes. Density gradient gel electrophoresis of 5 of these samples revealed that each contained 10 or more distinct 16S rRNA gene sequences. Direct microscopic observation of transverse sections from 5 diseased carotid arteries analyzed with a eubacterium-specific peptide nucleic acid probe revealed these to have formed biofilm deposits, with from 1 to 6 deposits per thin section of plaque analyzed. A majority, 93%, of deposits was located proximal to the internal elastic lamina and associated with fibrous tissue. In 6 of the 15 plaques analyzed, 16S rRNA genes from Pseudomonas spp. were detected. Pseudomonas aeruginosa biofilms have been shown in our lab to undergo a dispersion response when challenged with free iron in vitro. Iron is known to be released into the blood by transferrin following interaction with catecholamine hormones...

Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

Miklossy, Judith; Qing, Hong; Radenovic, Aleksandra; Kis, Andras; Vileno, Bertrand; Làszló, Forró; Miller, Lisa; Martins, Ralph N.; Waeber, Gerard; Mooser, Vincent; Bosman, Fred; Khalili, Kamel; Darbinian, Nune; McGeer, Patrick L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (Aβ) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated Aβ, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. Aβ was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that Aβ deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that Aβ deposits and hyperphosphorylated tau may also occur in other organs than the brain.