Association of apolipoprotein J-positive β-amyloid plaques with dystrophic neurites in alzheimer’s disease brain

Apolipoprotein J (apoJ), also known as clusterin and SP-40,40, binds soluble beta-amyloid (Aβ and is up-regulated in the Alzheimer’s disease (AD) brain. In the present study we classified apoJ-immunopositive Aβ deposits in AD temporal cortex, and found apoJ-immunoreactive plaques were often associated with dystrophic neurites. Quantitative immunohistochemical analysis of five AD brains showed that 29% of Aβ deposited in the parenchyma was associated with apoJ. Of Aβ deposits with apoJ immunopositivity, 71% were associated with phospho-tau-positive dystrophic neurites in the surrounding tissue. Conversely, 64% of phospho-tau-labeled neuritic deposits were labeled with apoJ. ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S. To test the direct effects of apoJ on tau metabolism, we treated cells in culture with apoJ-containing conditioned media, and we injected apoJ-containing media into the rat hippocampus. Using both systems, we observed increases in levels of tau and phosphorylated tau. Our findings demonstrate that apoJ immunopositivity strongly correlates with the presence of amyloid and associated neuritic dystrophy in the neuropil of AD temporal cortex, and supports a model where extracellular apoJ facilitates the conversion of diffuse Aβ deposits into amyloid and enhances tau phosphorylation in neurites surrounding these plaques.     

Estrogen release from metallic stent surface for the prevention of restenosis.

For the prevention of coronary restenosis, estrogen was coupled onto a metallic stent and in vitro release of estrogen was investigated. Estrogen was introduced to the metal surface using a hydrolysable covalent bond for local sustained delivery of drug as follows: (i) the stainless steel (SS) surface was activated with silane by plasma polymerization, (ii) the activated surface (SS-Si surface) was treated with acrylic acid by plasma polymerization (SS-Si-AAc surface), and (iii) 17beta-estradiol (E2) was covalently linked to the carboxyl group on that surface (SS-Si-AAc-E2 surface). The modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and water contact angle measurement. The amount of E2 was measured by UV-visible spectrophotometry and high performance liquid chromatography (HPLC). The in vitro release profile of E2 demonstrated sustained release of E2 in aqueous buffer. In summary, a novel method of immobilizing estrogen onto a metallic stent surface using plasma polymerization has been developed. The obtained results attest to the usefulness of the estrogen-releasing stent for preventing restenosis.     

Potential role of Ca++ on the differentiation of erythroid progenitor cells

In order to gain insight into the mechanisms by which erythropoietin promotes erythropoiesis, effects of various inhibitors on the erythropoietin-promoted differentiation of erythroid progenitor cells and on the erythropoietin-promoted Ca⁺⁺ uptake in the progenitor cells were determined, and the relationship between the inhibitory activity of each inhibitor toward the differentiation and Ca⁺⁺ uptake were examined. The inhibitors used were a tyrosine kinase inhibitor (genistein), a Ca⁺⁺-channel blocker (verapamil), a Ca⁺⁺ chelator (EDTA) and a protein kinase C inhibitor (staurosporine). All of these agents inhibited both the erythropoietin-mediated differentiation of the erythroid progenitor cells, as determined by the incorporation of⁵⁹Fe into heme, and Ca⁺⁺ uptake in a concentration dependent manner. In the cases of verapamil and EDTA, the half-miximal inhibitory concentration (IC₅₀) values for differentiation of the progenitor cells may be the consequence of the inhibition of the Ca⁺⁺ uptake by the inhibitior. On the other hand, in the cases of genistein and staurosporine, the IC₅₀ values for inhibition of differentiation were significantly different from that for inhibition of Ca⁺⁺ uptake. These results suggest that the mechanism of inhibition of differentiation by these two inhibitors is complex. However, taken all together, the above results support the proposition that Ca⁺⁺ uptake may paly a role in the erythropoietin-mediated differentiation of erythoid progenitor cells.     

Validation of a driving simulator by measuring the visual attention skill of older adult drivers.

OBJECTIVE: The purpose of this study was to validate a laboratory-based driving simulator as an off-road screening tool for older adult drivers by measuring their visual attention skill, and to determine how the visual attention skill changes across time in a 45-minute simulated driving test. METHOD: One hundred and twenty-nine community-dwelling older drivers volunteered to take part in the study. A range of driving scenarios was devised and implemented in a simulator setting to assess the driving skills of the participants. Visual attention skill, an important contributing factor to motor vehicle crashes, was assessed by the participant's reaction times to a sequence of 14 visual stimuli during the primary task of sustained driving. Repeated measures of analysis of variance (ANOVA) were undertaken to determine the effects of age and gender on the visual attention skill. Trend analysis was performed to investigate how repeated exposures to the visual stimulus affected the reaction time. RESULTS: The visual attention skill of older drivers was found to decline with age (F(1,126)) = 42.52, p value = 0.002), whereas the effect of gender was not significant. Participants increased their speed of reaction times for the first half of the testing then slowed down during the second half. CONCLUSION: That visual attention skill declined with age was consistent with the literature, and validated the driving simulator as an effective screening tool for older adult drivers. With rapid advancements in computer technology, the driving simulator will likely play an important role in assisting occupational therapists with off-road assessment of older drivers.     

Potential role of protein kinase C on the differentiation of erythroid progenitor cells

The effect of protein kinase C inhibitors, staurosporine and 1-(5-isoquinolinyl sulfonyl)-2-methyl piperazine(H7) onin vitro differentiation of erythroid progenitor cells which were isolated from spleens of mice infected with the anemia-inducing strain of Friend virus were examined. Erythropoietin-mediated differentiation of erythroid progenitor cells, as determined by the incorporation of⁵⁹Fe into protoporphyrin, was inhibited by staurosporine and H7 in a concentration-dependent manner. Scatchard analysis of the³H-phorbol-12, 13-dibutyrate binding to erythroid progenitor cells revealed that at the high affinity sites the dissociation constant was 22nM and the maximum number of³H-phorbol-12,13-dibutyrate binding sites per cell was approximately 3.7×10⁵. Cytosolic protein kinase C was isolated from erythroid progenitor cells and then purified by sequential column chromatography. Two isoforms of protein kinase C were found. Photoaffinity labeling of the purified protein kinase C samples with³H-phorbol 12-myristate 13-acetate followed by analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autofluorography showed radiolabeled 82-KDa peptides. Radiolabeling of the 82-kDa peptides with³H-phorbol 12-myristate 13-acetate was almost completely blocked by excess unlabeled phorbol 12-myristate 13-acetate. Results of phorbol 12-myristate 13-acetate-promoted phosphorylation with the purified protein kinase C samples showed that the phosphorylation of 82-kDa peptides was increased as the concentration of phorbol 12-myristate 13-acetate was increased from 10⁻⁸ M to 10⁻⁴M. In light of the findings that erythroid progenitor cells possessed an abundance of protein kinase C and that staurosporine and H7 inhibited erythroid differentiation, it seemed likely that protein kinase C would play a role in the erythroid progenitor cell development.     

A practical guide to reading CT coronary angiograms—How to avoid mistakes when assessing for coronary stenoses

There are now many physicians, both radiologists and cardiologists who are reporting CT coronary angiography (CTCA) scans who may not be aware that there are many pitfalls present. For the inexperienced reader a significant stenosis in a coronary artery can be easily missed or a moderate stenosis overcalled as significant. Artifacts can also be misinterpreted as representing a significant lesion. It is important that the studies are correctly interpreted, especially as the reported high negative predictive value of CTCA scans is a major strength of this imaging technique. The learning curve of reading these scans is steep and access to conventional coronary catheterisation results is essential for feedback and to improve the readers results. We have developed some rules to aid beginners avoid some of the pitfalls that can occur as these studies are not as easy to read as they may appear initially.     

Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.     

Epithelioid hemangioendothelioma of the liver

Epithelioid hemangioendothelioma of the liver is a rare vascular tumor with intermediate malignant potential. On imaging studies, the lesion has a solid appearance and may mimic metastatic disease. We present a case in which the morphologic features (multifocal aspect, peripheral location, and capsular retraction) and the clinical history aided in including this entity in the differential diagnosis.