Muscle and femoral vein temperatures during short-term maximal exercise in heart failure

Core temperature decreases throughout short-term maximal exercise in heart-failure patients. To investigate possible causes for this unusual response to exercise, we studied core (pulmonary arterial blood), femoral vein, muscle, and skin temperatures in eight patients with severe heart failure who performed maximal upright incremental bicycle exercise to 50 W. A normal group (n = 4) was exercised for comparison. In the heart-failure patients, core temperature was 36.95 +/- 0.37 degrees C at rest, significantly (P less than 0.05) decreased at 25 W of exercise to 36.59 +/- 0.40 degrees C, and at 50 W remained decreased to 36.57 +/- 0.40 degrees C. In comparison, we found that the resting core temperature in the normal subjects was 37.28 +/- 0.34 degrees C, was the same at 25 W (37.29 +/- 0.41 degrees C), and increased significantly (P less than 0.05) to 37.50 +/- 0.32 degrees C at 50 W of exercise. Femoral vein temperature in heart-failure patients (n = 6) was below core temperature throughout exercise to 25 and 50 W (36.22 +/- 0.62 and 36.34 +/- 0.65 degrees C, respectively). Muscle temperature (n = 7) was significantly (P less than 0.05) lower in the heart-failure patients (34.8 +/- 1.1 degrees C) at rest compared with the normal subjects (36.2 +/- 1.0 degrees C). During exercise, muscle temperature increased above core temperature in only four of the heart-failure patients and was significantly (P less than 0.05) lower (36.5 +/- 1.3 degrees C) compared with the normal subjects (38.0 +/- 0.2 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

The bias due to incomplete matching

Observational studies comparing groups of treated and control units are often used to estimate the effects caused by treatments. Matching is a method for sampling a large reservoir of potential controls to produce a control group of modest size that is ostensibly similar to the treated group. In practice, there is a trade-off between the desires to find matches for all treated units and to obtain matched treated-control pairs that are extremely similar to each other. We derive expressions for the bias in the average matched pair difference due to the failure to match all treated units--incomplete matching, and the failure to obtain exact matches--inexact matching. A practical example shows that the bias due to incomplete matching can be severe, and moreover, can be avoided entirely by using an appropriate multivariate nearest available matching algorithm, which, in the example, leaves only a small residual bias due to inexact matching.     

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Characterization of A units released from the poly(A) tract of rabbit globin mRNA during protein synthesis: possible role of the released ATP in synthesizing protein

1. Rabbit globin mRNA poly(A) was translated in two cell-free synthesizing systems, rabbit reticulocyte lysate and wheat germ extract, to characterize the product released from the poly(A) tract during globin synthesis. 2. Kinetic studies indicate that the size of the cleaved nucleotide proves to be a monomer, as revealed by column chromatography on Sephadex G-100 or G-25. 3. Characterization of the monomer was accomplished by chromatography on DEAE-cellulose. Initially, 5 min post-translation, the monomer was ATP only; however, at later times ATP, ADP, AMP and adenosine were detected. 4. The two synthesizing systems differed in that globin mRNA poly(A) was translated at a faster rate in the wheat germ extract as revealed by the appearance of ATP, whereas AMP was detected sooner in the rabbit reticulocyte lysate. 5. The results indicate that the A unit released from the poly(A) tract during mRNA poly(A) translation is a monomer, and that these metabolites may play a role in controlling protein initiation via the released ATP.     

Application of a photosystem II model for analysis of fluorescence induction curves in the 100 ns to 10 s time domain after excitation with a saturating light pulse

A mathematical model of photosystem II (PSII) events was used to analyze chlorophyll fluorescence transients in the time domain from 100 ns to 10 s after excitation with a saturating 10-ns flash, applied as a part of specialized illumination protocol, using preparations of a thermophilic strain of the unicellular green alga, Chlorella pyrenoidosa Chick (using both intact and diuron-treated cells). Analysis of simulation results has proven that particular attention should be given to flash-induced recombination processes, including nonradiative recombination in PSII, while subsequent charge transfer along the electron transport chain of thylakoid membrane can be adequately described by a single reaction of quinone reoxidation. The PSII model was extended by taking inhibition by diuron of the electron transport in the acceptor side of PSII into account, which allowed simulation of fluorescence induction curves observed in the presence of this inhibitor. The model parameters were determined (stromal pH, rate constants of nonradiative recombination, and the initial reduction state of the quinone pool) which provided adequate simulation of experimentally observed ratios of the maximal and initial fluorescence levels (F _m/F ₀).     

Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase

The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites.