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

1. Download : Download high-res image (147KB)
2. Download : Download full-size image

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.

     

Entry of [(1,2-13C2)acetyl]-L-carnitine in liver tricarboxylic acid cycle and lipogenesis: a study by 13C NMR spectroscopy in conscious, freely moving rats.

The biochemical pathways involved in acetyl-L-carnitine utilization were investigated in conscious, freely moving rats by 13C NMR spectroscopy. Following 4-h [(1,2-13C2)acetyl]-L-carnitine infusion in fasted animals, the free carnitine levels in serum were increased, and an efflux of unlabelled acetyl-L-carnitine from tissues was observed. [(1,2-13C2)Acetyl]-L-carnitine was found to enter biosynthetic pathways in liver, and the acetyl moiety was incorporated into both cholesterol and 3-hydroxybutyrate carbon skeleton. In accord with the entry of [(1,2-13C2)acetyl]-L-carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the 13C label was also found in liver glutamate, glutamine, and glutathione. The analysis of the 13C-labelling pattern in 3-hydroxybutyrate and cholesterol carbon skeleton provided evidence that the acetyl-L-carnitine-derived acetylCoA pool used for ketone bodies synthesis in mitochondria was homogeneous, whereas cholesterol was synthesized from two different acetylCoA pools located in the extra- and intramitochondrial compartment, respectively. Furthermore, cholesterol molecules were shown to be preferentially synthesized by the metabolic route involving the direct channelling of CoA-activated mitochondria-derived ketone bodies into 3-hydroxy-3-methylglutarylCoA pathway, prior to equilibration of their acyl groups with extramitochondrial acetylCoA pool via acetoacetylCoA thiolase.     

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.