Definition of Alzheimer's disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J M Anderson.
Explore the source record for details and available documents.
Seven proteases assumed to be aminopeptidases A, B and M, dipeptidyl peptidases II and IV, esteroproteinase and gamma-glutamyltransferase were localized histochemically, using semipermeable membrane simultaneous coupling techniques, in unfixed cryostat sections of skeletal muscle removed from one healthy volunteer, six patients with disuse muscle atrophy, and 15 patients with some form of muscle disease. Normal muscle fibres showed weak reactions for aminopeptidases A and M and for the dipeptidyl peptidases, but no reactivity for gamma-glutamyltransferase or esteroproteinase. No change was detected in diseased muscle fibres except that low gamma-glutamyltransferase and esteroproteinase activities appeared in some cases. The activities of the seven enzymes were stronger in the intermyosial connective tissue than in the muscle fibres, but were also unchanged in disease. The strongest reactions were found in some interstitial cells (mast cells and macrophages) and these were much increased in diseased muscle, particularly for dipeptidyl peptidases II and IV. The findings are interpreted in terms of the release of proteases from such cells and their subsequent involvement in the breakdown of myofibrillar proteins in muscle disease.
Lysozyme was adsorbed on spin cast and lathe cut soft contact lenses of poly-2-hydroxyethylmethacrylate (PHEMA) and on poly-HEMA-methacrylic acid (PHEMA/MAA). The in vitro adsorption process was followed by ATR-FTIR. Lysozyme adsorbs both, reversibly and irreversibly, on the surfaces. While the reversible bound lysozyme experiences only minor changes in its secondary structure, conformational changes occur for the irreversibly adsorbed protein. The type and extent of structural changes depend on the degree of protein coverage on the lens surface, as well as the chemical structure and surface morphology of the lenses. PHEMA/MAA lenses adsorbed thirty times more lysozyme than either of the PHEMA lenses. Fabrication processes appear to induce different adsorption behaviour, PHEMA lathe cut lenses adsorb twice the amount of protein compared with PHEMA spin cast lenses.
Explore the source record for details and available documents.
Antibodies directed against purified cytochrome f, isolated from the cytochrome b/f complex of spinach chloroplasts, were used in on-grid immunogold labelling studies of spinach leaf tissue. Our results show unambiguously that cytochrome f, and hence the cytochrome b/f complex, is located in both appressed and non-appressed thylakoid membranes.
This article focuses on the health status of two groups of immigrant women and their experiences surrounding help-seeking. It is argued that social, economic, and political forces play a crucial role in determining the subjective experiences of immigrant women in their contacts with the health care system. Case studies of Indo-Canadian and Greek women are used to illustrate this perspective.
The effect of light quality on the composition, function and structure of the thylakoid membranes, as well as on the photosynthetic rates of intact fronds from Asplenium australasicum, a shade plant, grown in blue, white, or red light of equal intensity (50 microeinsteins per square meter per second) was investigated. When compared with those isolated from plants grown in white and blue light, thylakoids from plants grown in red light have higher chlorophyll a/chlorophyll b ratios and lower amounts of light-harvesting chlorophyll a/b-protein complexes than those grown in blue light. On a chlorophyll basis, there were higher levels of PSII reaction centers, cytochrome f and coupling factor activity in thylakoids from red light-grown ferns, but lower levels of PSI reaction centers and plastoquinone. The red light-grown ferns had a higher PSII/PSI reaction center ratio of 4.1 compared to 2.1 in blue light-grown ferns, and a larger apparent PSI unit size and a lower PSII unit size. The CO(2) assimilation rates in fronds from red light-grown ferns were lower on a unit area or fresh weight basis, but higher on a chlorophyll basis, reflecting the higher levels of electron carriers and electron transport in the thylakoids.The structure of thylakoids isolated from plants grown under the three light treatments was similar, with no significant differences in the number of thylakoids per granal stack or the ratio of appressed membrane length/nonappressed membrane length. The large freeze-fracture particles had the same size in the red-, blue-, and white-grown ferns, but there were some differences in their density. Light quality is an important factor in the regulation of the composition and function of thylakoid membranes, but the effects depend upon the plant species.
Preliminary efforts directed toward the synthesis and characterization of steroid-polyamino acid conjugates indicate that the preparation of these systems is feasible. Studies have indicated that the steroids may be released from the macromolecule resulting in long-term controlled release systems. Table 4 lists several of the variables that are important in controlling biocompatibility, biodegradation, and drug release characteristics. The biocompatibility, biodegradation, and drug release characteristics are all important in the design and preparation of a drug-polyamino acid delivery system. The variables listed in Table 4 may interact and interrelate to varying degrees when considering each of these factors independently. Although perhaps preliminary, efforts to date indicate that steroids bound to polyglutamic acid or polyglutamic acid derivatives are biocompatible, capable of undergoing biodegradation, and can release drugs at appropriate rates for extended periods of time.
A direct enzyme immunoassay (EIA) with polyclonal antibodies was developed for detecting salmonellae in foods and feeds. Salmonella cells were attached firmly to the wells of polystyrene microtitration plates with a capture-antibody technique. Spicer-Edwards anti-H immunoglobulin G was bound to protein A-beta-D-galactosidase to serve as the signal; 4-methylumbelliferyl-beta-D-galactoside was used as the substrate. The sensitivity threshold was 10(7) cells per ml. Direct EIA, indirect EIA, and pure-culture techniques were compared by using 48 samples of naturally contaminated foods and feeds. The direct EIA was more sensitive than the indirect EIA or pure-culture technique. Food samples were analyzed within 3 working days, and 32 samples were tested simultaneously in a single 96-well microtitration plate. False-positive or false-negative results did not pose a problem. This direct EIA is sensitive, rapid, and amenable to automation.
A calcium channel agonist BAY k8644 was applied to anterior pituitary (AP) cells in vitro. BAY k8644 (0.1-10 microM) stimulated prolactin and growth hormone (GH) release from monolayer AP cultures; the calcium channel antagonist D-600 (1-10 microM) completely blocked this effect. By utilizing a perifusion system, we observed an immediate and sustained amplification of prolactin (2.9-fold), growth hormone (2.3-fold), and luteinizing hormone (LH, 1.6-fold) release during the 1-h application of BAY k8644 (3 microM). A hypophysiotrophic peptide pulse 4 h after the BAY k8644 was removed confirmed that the cells remained responsive to their natural secretagogues. In another perifusion study 10-3,000 nM BAY k8644 produced a graded increase in prolactin release that was maintained over the 30-min exposure period. Finally, individual primate mammotrophs and somatotrophs showed a marked enlargement of hemolytic plaque area, an index of hormone release, 1 h after BAY k8644 (1 microM). We conclude that this synthetic dihydropyridine enhances the rate of prolactin, GH, and LH release from AP cells of two species. Because this is the first synthetic calcium channel agonist, structure-function studies characterizing calcium channel activation and exocytosis are now feasible.
We investigated the effects of dopamine, forskolin, and maitotoxin on prolactin release from individual rat and monkey mammotrophs. Forskolin increases cAMP levels, whereas maitotoxin amplifies the influx of extracellular calcium. Prolactin secretion from single mammotrophs was visualized by the reverse hemolytic plaque assay and then quantified by measuring the proportion of plaque-forming cells and the mean plaque area. In the presence of dopamine alone both the plaque proportion and mean area of the plaques formed by rat mammotrophs decreased by 50 and 40%, respectively. This inhibition of secretion was blocked by the dopaminergic antagonist spiperone as well as forskolin and maitotoxin. Forskolin and maitotoxin alone significantly elevated both the proportion (+30%) and area (+180% for forskolin and +250% for maitotoxin) of the plaques. These actions of maitotoxin were neutralized by D-600, a calcium channel blocker. All of these agents induced similar trends with monkey prolactin cells. We conclude that single mammotrophs in culture respond to perturbations in a differential manner and in a way predicted by earlier results based on macropopulation measurements.
We have previously used a chromium-release assay to demonstrate that the cocktail of monoclonal antibodies BA-1, BA-2, BA-3, and complement can effectively lyse human leukemic cells in the presence of excess bone marrow. Using a leukemic cell colony assay, we have reinvestigated the variables influencing lysis of human leukemic cells (KM-3, HPB-NULL, NALM-6) in bone marrow using BA-1, BA-2, BA-3, and complement. Specific variables addressed included the concentration of excess bone marrow cells, the number of treatments, the presence or absence of DNase during the treatment, the combination of antibodies, and the sensitivity of different leukemic cell lines to lysis. Using the colony assay, the BA-1,2,3 cocktail was shown to be more effective than any single antibody or combination of two antibodies. We also determined that the concentration of excess bone marrow cells and number of treatments had a direct bearing on leukemic cell lysis. Although two cycles of treatment were significantly superior to one cycle, three cycles were not significantly superior to two cycles. Inclusion of DNase (10 micrograms/mL) was a critical adjunct that eliminated clumping and facilitated plating cells in the colony assay. Finally, we could show that striking differences existed in the sensitivity of the leukemic cell lines to lysis with the BA-1,2,3 cocktail and complement. NALM-6 cells were the most sensitive (approximately four logs of kill), and KM-3 cells were the most resistant (less than two logs of kill). Our results strongly support the utility of sensitive leukemic cell colony assays in the analysis of marrow treatment variables in autologous bone marrow transplantation.
Lysyl oxidase initiates the covalent cross-linking of elastin and collagen by oxidizing lysine residues in these proteins to alpha-aminoadipic-delta-semialdehyde. Sequences surrounding susceptible lysines in elastin are considerably different from those in collagen and yet the same enzyme can oxidize both substrates. Possible bases of the specificity have been explored assaying for H2O2 release accompanying the oxidation of synthetic peptide and protein substrates. Rates of oxidation of random co-polymers were maximal with (Ala,Lys)n and decreased in the order (Val,Lys)n greater than (Leu,Lys)n greater than (Lys)n greater than (Phe,Lys)n greater than (Tyr,Lys)n. The ordered polymer (Ala-Lys-Glu)n was oxidized at only 3% of the rate of (Ala,Lys)n, implying inhibition by peptidyl glutamate. Consistent with this conclusion, kinetic analyses using ordered oligopeptides revealed that, relative to Ala-Ala-Lys-Ala-Ala, Km is increased 9.3-fold for lysine in Ala-Ala-Lys-Glu-Ala-Ala, 2.5-fold in Ala-Ala-Lys-Arg-Ala-Ala, and 1.8-fold in Ala-Ala-Glu-Lys-Ala-Ala. Tyrosine C-terminal to lysine in such peptides also increases Km 5-fold. In addition, lysyl oxidase oxidized lysine in various proteins with basic isoelectric points and was much less or not active against various acidic proteins. Lysyl oxidase was inactive against native bovine serum albumin but effectively oxidized albumin if albumin carboxyl functions were first amidated by chemical modification. These results suggest that peptides bind to lysyl oxidase in a preferred directional sense and indicate-that net anionic character as well as the specific position of anionic residues in substrates can selectively effect substrate potential. Implications of these results for the oxidation of elastin and collagen are discussed.
Explore the source record for details and available documents.
An infra- red approach has been developed to characterize hydrophilic biomaterials, particularly contact lenses. Water was utilized as the optical coupling agent between the sample and the ATR element. This method enables the study of hydrophilic polymers in their natural aqueous environment and simultaneously solves the optical contact problem that usually arises when the ATR technique is used. Some studies were made utilizing this approach: dry and hydrated samples were structurally compared; also, a depth profiling study and a surface comparison were made on soft contact lenses fabricated by different industrial processes. Finally, the three dimensional orientation of one hydrated structure was characterized.
Adsorption of human serum albumin on three different soft contact lens surfaces (lathe cut and spin cast crosslinked PHEMA and spin cast PHEMA/MAA) was studied. Using ATR--FTIR spectroscopy the spectra of the adsorbed protein were obtained at different times of adsorption. Structural changes were detected, initially characterized by an increase in hydrogen bonding and after that by involvement of the protein hydrophobic side chain residues. At long adsorption times, the protein becomes denatured, its alpha-helix content is drastically reduced and the amounts of random coil and beta-sheet conformations are increased. ATR-FTIR and circular dichroism studies of albumin solutions reveal similar conformational changes to those experienced by the adsorbed protein. Differences in the adsorption behaviour for the hydrogel surface, indicate the importance of the hydrophilicity, surface regularity and the chemical composition of the contact lens surfaces as the controlling parameters in the protein adsorption phenomena.
The biocompatibility of biomaterials at implant sites is controlled by the tissue/material interaction. A major cell in the tissue reaction is the macrophage. A summary is presented on macrophage mediation of cellular and humoral regulatory pathways in inflammatory and immune responses.
When cultures of Candida albicans which had entered stationary phase due to the depletion of zinc (zinc-limiting conditions) were compared with cultures which had entered stationary phase due to the depletion of another growth-limiting component (zinc-excess conditions), at least two cellular characteristics were found to differ: (i) zinc-limited cells appeared more homogeneous and larger on the average than zinc-excess cells, and (ii) zinc-limited cells evaginated on the average of 40 min later than zinc-excess cells. In the present study, it is demonstrated that the distribution of volumes for a stationary-phase culture of zinc-excess cells is skewed towards very small volumes, but even the smallest cells contain nuclei; in contrast, the volumes of zinc-limited cells are evenly distributed around a much larger mean value; the evagination kinetics of zinc-excess cells released into fresh medium are far less synchronous than are those of zinc-limited cells, and the smaller cells in the population take much longer to evaginate than do the larger cells; the onset of net RNA accumulation and achievement of a maximum rate of [3H]uridine incorporation occur significantly earlier in zinc-excess cells than in zinc-limited cells released into fresh medium; and the onset of net protein accumulation and [3H]leucine incorporation occur significantly earlier in zinc-excess cells than in zinc-limited cells released into fresh medium. These results indicate that although zinc-excess cells are extremely heterogeneous in volume, they may still be homogeneously blocked in the nuclear division cycle, and that the later average evagination time of released zinc-limited cells may be due to a delay in the onset of protein synthesis, which in turn may be due to the time necessary to reaccumulate zinc to levels sufficient for the reinitiation of RNA synthesis.