Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Affect intensity and cardiac arousal.

Investigated in 3 experiments the relationships between affect intensity and basal, evoked, and perceived cardiac arousal. Affect intensity was assessed using R. J. Larsen and E. Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (J. Blascovich, 1990). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement of adenovirus-mediated gene transfer to human bone marrow cells

Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on the multiplicity of infection (MOI), time of incubation, the volume in which the co-incubation occurs and the presence or absence of growth factors. Studies revealed that a brief co-incubation (1-8 hours), resulted in low levels of transgene expression, suggesting that adenovirus infection of CD34+ cells occurs slowly, and optimal transduction requires a 24 hour exposure to adenovirus. Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction efficiency but inhibited hematopoietic function. However, treatment at a MOI of 50-100 resulted in efficient transduction (10.7-15.7% positive) without detectable toxicity. Secondary proof of adenovirus transgene expression was demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta-gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has no significant effect on hematopoietic function. Adenovirus-mediated transduction of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with improved gene delivery and maintenance of hematopoietic function. In summary, adenovirus vectors can be used to transiently transduce stem cells, and conditions have been defined to maximize expression and limit inhibitory effects on CD34+ cells. These data support continued investigation of this vector for local cytokine delivery and purging of stem cell products.     

Phytotoxic properties of cnicin,a sesquiterpene lactone fromcentaurea maculosa (spotted knapweed)

Water and solvent extracts from the aerial tissues ofCentaurea maculosa, spotted knapweed, inhibited the root growth of lettuce. Column chromatography and lettuce bioassay of a chloroform extract led to the isolation of cnicin, a sesquiterpene lactone. Pure cnicin was bioassayed at 0, 1, 2, 4, 6, 8, and 10 mg/5 ml water with lettuce, created wheatgrass, bluebunch wheatgrass, rough fescue, western larch, lodgepole pine, and spotted knapweed. Germination was inhibited at one or more concentrations for all species except lodgepole pine and spotted knapweed. Growth, particularly of the roots, was retarded between 1 and 4 mg of cnicin. Lettuce, bluebunch wheatgrass, and spotted knapweed were inhibited significantly at all concentrations tested.     

Application of virtual reality for peritoneal dialysis exchange learning in patients with end-stage renal disease and cognitive impairment

Virtual Reality - Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own....     

The effect of breed,parity, and stage of lactation on conjugated linoleic acid (CLA) in milk fat from dairy cows

Dairy products are the main source of conjugated linoleic acid (CLA), a functional food component with health benefits. The major source of cis-9, trans-11 CLA in milk fat is endogenous synthesis via delta9-desaturase from trans-11 18:1, with the remainder from incomplete rumen biohydrogenation of linoleic acid. Diet has a major influence on milk fat CLA; however, effects of physiological factors have received little attention. Our objectives were to examine milk fat content of CLA and the CLA-desaturase index with regard to: 1) effect of breed, parity, and stage of lactation, and 2) variation among individuals and the relationship to milk and milk fat. Holstein (n = 113) and Brown Swiss (n = 106) cows were fed a single diet and milk sampled on the same day to avoid confounding effects of diet and season. Frequency distributions demonstrated that milk fat content of CLA and CLA-desaturase index varied over threefold among individuals, and this needs to be considered in the design of experiments. Holsteins had a higher milk fat content of CLA and CLA-desaturase index, but breed differences were minor. Parity and days in milk also had little or no relationship to the individual variation for these two CLA variables. Breed, parity, and days in milk accounted for < 0.1, < 0.3, and < 2.0% of total variation in CLA concentration in milk fat, respectively. Milk fat content of CLA and CLA-desaturase index were essentially independent of milk yield, milk fat percent, and milk fat yield. We speculate that the basis for the genetic variation among individuals is related to rumen output of trans-11 18:1 and to a lesser extent cis-9, trans-11 CLA, and to the tissue amount and activity of delta9-desaturase.     

Charge Density Influences C1 Domain Ligand Affinity and Membrane Interactions

The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure–activity relations for C1 domain ligands. Coexpressing pairs of C1‐containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain.     

Monte Carlo Simulation of Massive Absorbers for Cryogenic Calorimeters

There is a growing interest in cryogenic calorimeters with macroscopic absorbers for applications such as dark matter direct detection and rare event search experiments. The physics of energy transport in calorimeters with absorber masses exceeding several grams is made complex by the anisotropic nature of the absorber crystals as well as the changing mean free paths as phonons decay to progressively lower energies. We present a Monte Carlo model capable of simulating anisotropic phonon transport in cryogenic crystals. We have initiated the validation process and discuss the level of agreement between our simulation and experimental results reported in the literature, focusing on heat pulse propagation in germanium. The simulation framework is implemented using Geant4, a toolkit originally developed for high-energy physics Monte Carlo simulations. Geant4 has also been used for nuclear and accelerator physics, and applications in medical and space sciences. We believe that our current work may open up new avenues for applications in material science and condensed matter physics.     

Piperidine Alkaloids in Nitrogen Fertilized Pinus ponderosa

We fertilized individual, pole-size ponderosa pine trees at two low-quality sites and pine saplings at a relatively high-quality site, with ammonium nitrate. Six to 12 months later, we measured total %N and 2,6-disubstituted piperidine alkaloids in the foliage. The N additions raised foliar %N above deficiency levels (i.e., from 1.0–1.1% to 1.4–1.6%) at the low-quality sites, but did not elevate foliar %N in saplings at the higher quality site, where it was already (1.9%) well above critical levels. In control trees with foliar N below a threshold of 1.1%, we detected no more than trace levels of alkaloids, indicating that alkaloid production is highly constrained by N deficiency. The N additions increased mean concentrations of the predominant alkaloid, pinidine, at all three sites. Mean total alkaloid concentrations for fertilized trees at the two low-quality sites were 12 and 155 g/g dry wt higher than controls (relative increases of 12× and 4.5×, respectively). For saplings at the high-quality site, the mean total increased by 584 g/g dry wt (1.6×) with the N additions. Allocation of foliar N to alkaloids was highest in fertilized saplings (0.81%) compared to control saplings (0.53%). These findings demonstrate that foliar alkaloid concentrations can be increased by nitrogen fertilization of forest trees growing on both low- and high-quality sites. Fertilizing for the purpose of inhibiting potential herbivores may be more successful at higher quality sites where alkaloid levels are enhanced relative to food quality (foliar %N).