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Beta-amyloid accumulation in aged canine brain: a model of early plaque formation in Alzheimer's disease.

We characterized eight aged beagles (maintained from birth in a laboratory colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and other plaque components. All plaques within these canine brains were of the diffuse subtype and were neither thioflavine S- nor Congo red-positive. The majority of plaques in the entorhinal cortex contained numerous neurons within them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity was also present within select neurons and neuronal processes and was detected as a diffuse linear zone corresponding to the terminal fields of the perforant path. There was no significant correlation between extent of beta-amyloid accumulation and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31-immunostaining revealed dystrophic fibers, confirming the classification of these plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive immunostaining. This may explain why neuritic involvement was not detected within these canine plaques. It is possible that the beta-amyloid within the canine brain has a unique primary structure or may not be in an assembly state that adversely affects neurons.

Adolescent↗

In vitro apolipoprotein E protects human red blood cells against lysis induced by amyloid-beta (AP) fragment 25-35.

Mattson et al. (9) demonstrated lysis of human red blood cells (RBC) exposed to amyloid peptide Abeta(25-35), a new experimental model for amyloid-beta toxicity. Lysis resulted from poreformation in the RBC membranes and was completely prevented by concurrent exposure to Congo red We demonstrate that human serum, purified ApoE from human plasma, and recombinant isoforms of ApoE neutralize the Abeta(25-35) cytotoxicity: the E2 and E4 isoforms were marginally more effective than E3. Second, we demonstrate that Abeta(25-35) forms fibrils in the reaction mixtures using electron-microscopy. Together these results suggest that the RBC model might be useful in preliminary identification of natural and synthetic substances able to protect against amyloid-beta cytotoxic effects due to fibrillar Abeta(25-35). Such compounds would be candidate molecules for testing in neuronal systems.

Adult↗

CT findings in extensive tracheobronchial amyloidosis.

Primary pulmonary amyloidosis is a rare disorder that appears in three forms: tracheobronchial, nodular parenchymal, and diffuse parenchymal. We report the case of a 46-year-old women with extensive tracheobronchial amyloidosis which presented with a 2-year history of dyspnea and with signs of severe fixed obstruction in pulmonary function tests. Computed tomography of the thorax demonstrated marked thickening of the trachea and the central bronchial tree with substantial narrowing of the main, lobar, and segmental bronchi. Transbronchial specimen showed typical birefringence under polarizing microscope after staining with Congo Red. We did not find hints for systemic amyloidosis.

Amyloidosis↗

[Demonstration of amyloid using histological methods].

The authors present their personal experience with common histological methods for amyloid demonstration. For practical use, they recommend staining with Congo Red followed by differentiation in alkaline alcohol and another method using staining with a 2% solution of Saturn Red in 1% NaCl. The latter method permits to differentiate between amyloid and hyalin without employing polarized light.

Amyloid↗

Primary amyloidosis presenting as intrahepatic cholestasis.

Hepatic involvement in primary amyloidosis is not rare but is often clinically silent. A mild elevation of the serum alkaline phosphatase level and hepatomegaly are the most common findings. We report a case of primary amyloidosis in an adult male presenting with intrahepatic cholestasis where viral, drug, alcohol, and autoimmune etiologies were all excluded and the definite diagnosis was established by liver biopsy with Congo red staining. Subsequently the patient was found to have monoclonal light chain disorder.

Amyloid↗

Lympho-reticuloendothelial activity of early gastric carcinoma.

The lympho-reticuloendothelial activities of 54 cases of early gastric carcinoma were studied. Morphological blastoid transformation of lymphocyte by the addition of phytohemagglutinin-P (PHA-P) was disturbed in half of the patients. The DNA synthesizing activity of lymphocyte was not stimulated by PHA-P in the cases of advanced carcinoma but it was stimulated in the cases of early carcinoma. The tuberculin reaction was negative in 30% of the cases of early carcinoma. The reticuloendothelial system (RES) activity studied through the congo red method revealed that 86% of the cases of early carcinoma had disturbed RES function.

Adolescent↗

Pharmacological manipulation of early PrPres accumulation in the spleen of scrapie-infected mice.

In most experimental models of scrapie and in some naturally infected species, the lymphoreticular system and the spleen in particular play a major role in the pathogenesis of the disease. Previous studies demonstrated scrapie infectivity in peripheral organs from the day of infection up to the terminal stage. The discovery of the abnormal prion protein, PrPres, as a specific molecular hallmark of scrapie should permit enhanced study of scrapie pathogenesis and has some pharmacological applications. In this study, PrPres accumulation was followed day by day in peripheral organs. Four different phases were identified: the circulation of scrapie inoculum, a clearance phase, the peripheral accumulation of PrPres and a plateau phase. This kinetics was then pharmacologically modified (i) by applying the macrophage "suicide" technique to unveil the cellular types involved in scrapie pathogenesis and (ii) with anti-scrapie drugs such as polyene antibiotics, polyanions and Congo red to investigate their mode and site of action.

Amphotericin B↗

The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans.

The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.

Candida albicans↗

[A case of localized amyloidosis of the urethra].

A case of localized amyloidosis of the urethra is reported. A 42-year-old man visited with the complaint of urethral discharge and urethral tumor on May 24, 1985. A small fingertip sized, elastic hard mass was present on the left side of the external urethral meatus. Cold cup biopsy of the urethral tumor was done. Histological examination of the tumor showed amorphous eosinophilic tissue staining. Green birefringence indicating amyloidosis by Congo red staining was observed under polarized light microscope. Since the patient's symptoms were minimal, no specific therapy was instituted.

Adult↗

Coincidental amyloid nephropathy and IgA glomerulonephritis in a patient with ankylosing spondylitis.

A 43-year-old man with ankylosing spondylitis (AS) was admitted with proteinuria and renal insufficiency. Coincidental IgA nephropathy and secondary renal amyloidosis were diagnosed on renal biopsy. This is the first case reported of coincidental IgA nephropathy and renal amyloidosis as a cause of renal insufficiency in a patient with AS. Both entities should be considered in the diagnosis in a patient with AS and renal impairment. A careful study of the renal tissue including, Congo red stain and immunofluorescence studies is necessary to establish a correct diagnosis in these patients.

Adult↗

Microfluidics assisted synthesis of well-defined spherical polymeric microcapsules and their utilization as potential encapsulants.

In this article, the development of a novel technique to fabricate spherical polymeric microcapsules by utilizing microfluidic technology is presented. Atom transfer radical polymerization (ATRP) was employed to synthesize well-defined amphiphilic block copolymers. An organic polymer solution was constrained to adopt the spherical droplets in a continuous water phase at a T-junction microchannel, and the generation of the droplets was studied quantitatively. The flow conditions of two immiscible solutions were adjusted for the successful generation of the polymer droplets. The morphology of the microcapsules was examined. The efficiency of these polymer microcapsules as containers for the storage and controlled release of loaded molecules was evaluated by encapsulating the microcapsules with Congo-red dye and investigating the release performance using temperature controlled UV-VIS spectroscopy.

Capsules↗

[The antiinflammatory and immunostimulating activities of S-4001--a polysaccharide isolated from Lei Wan (Polyporus mylitiae)].

Lei Wan, Poliporus mylittae Cook et Mass (Omphalia lapidescens Schraet) is a kind of fungus used in traditional Chinese medicine, as an anthelminthic. From Lei Wan, an active component designated as S-4001 had been isolated. Preliminary results indicate that S-4001 belongs to D, beta, 1-3 glucan with some 1-6 linkages. After administration of S-4001, significant antiinflammatory activity was found in various experimental animal models, including croton oil induced ear edema in mice and agar or yeast induced ankle swelling in rats. An inhibitory action on leucocyte migration induced by intraperitoneal injection of CMC in rats was also observed. The plasma content of corticosterone was significantly increased, but the content of ascorbic acid in the adrenals did not change in rats given S-4001. Apart from these actions, S-4001 showed a number of immunostimulating actions such as increasing the clearance of Congo red from mice blood and potentiating the immunohemolysis reaction in 615 mice.

Adjuvants, Immunologic↗

Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis?

Immunotactoid glomerulopathy (IT), or alternatively, microtubular glomerulopathy, is a term that has been used by some investigators to encompass those glomerulopathies characterized by the presence of fibrillar or microtubular deposits which are distinguished from amyloid principally by their larger size and lack of reactivity with the Congo red reagent. A case is presented here of IT as it was initially described. The present case, and a review of the literature, suggest that the diagnosis of IT be restricted to those glomerulopathies associated with large, at times organized, microtubular deposits. Terms such as fibrillary glomerulonephritis, or alternatively Congo red-negative amyloidosis-like glomerulopathy, could then be used to describe those patients with smaller, fibrillar glomerular deposits having an appearance closely resembling amyloid. We believe it is possible to separate the entities fibrillary glomerulonephritis and IT on morphological grounds. This is a potentially useful distinction that identifies patients who are likely to have or develop clinical evidence of a lymphoplasmacytic disorder or dysproteinemia, which are associated with deposits of IT, and distinguishes them from patients with fibrillary glomerulonephritis, of whom only a single case has been linked to such clinical findings.

Biopsy↗

Effect of iron restriction on the outer membrane proteins of Actinobacillus (Haemophilus) pleuropneumoniae.

The outer membrane protein profile of Actinobacillus (Haemophilus) pleuropneumoniae grown under iron-restricted and iron-replete conditions was studied by polyacrylamide gel electrophoresis and immunoblotting. A virulent serotype 1 isolate synthesized a novel protein with an apparent molecular weight of 105,000 (105K) and increased the synthesis of a 76K protein under iron-restricted conditions. Both proteins were synthesized within 15 min of establishment of iron-restricted conditions. Proteins of equivalent molecular weights could also be induced by iron restriction in serotype 2, 3, 4, 5, and 7 isolates of A. pleuropneumoniae. Convalescent-phase sera from serotype 1-infected pigs contained antibodies which recognized both the 105K and 76K proteins from all six serotypes examined, indicating that these proteins were expressed in vivo and were immunologically conserved. Cells expressing the 105K and 76K proteins also displayed an enhanced ability to bind Congo red and hemin, suggesting that one or both of these proteins functioned to acquire complexed iron during in vivo growth.

Actinobacillus↗

Pharmacodynamic parameters of gentamicin and their effect on biological properties of gram-negative bacteria.

The in vitro postantibiotic effect (PAE) and the postantibiotic effect of subinhibitory concentrations (PA SME) of gentamicin were investigated on clinical isolates of Salmonella typhimurium, Salmonella enteritidis and Pseudomonas aeruginosa. The PAE was induced by 2 x MIC and 4 x MIC of gentamicin for 0.5 h. The PA SME were studied by the addition of 0.1, 0.2 and 0.3 x MIC during the postantibiotic phase of the bacteria. The S. enteritidis strain did no regrow after affecting of supra-subinhibitory concentrations for 24 h with exception of the concentration 2 x MIC + 0.1 x MIC. The PAEs against P. aeruginosa were nearly identical for all the suprainhibitory concentrations tested (4.4-4.6 h) and no regrowth after PA SME was observed. The studied pharmacodynamic parameters decreased the surface hydrophobicity of Salmonella sp., mainly of S. enteritidis, evaluated by the ability to bind Congo red and by the aggregation in solutions of ammonium sulphate (SAT). Gentamicin in suprainhibitory concentrations expressively decreased the phospholipase C production--an important virulence factor of P. aeruginosa.

Anti-Bacterial Agents↗