Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation.

The alpha angle alpha (degrees) is a thrombelastographic measure of clot propagation. A parametric measurement of clot propagation [maximum rate of thrombus generation (MRTG), dynes/cm2 per s], however, has recently been utilized. Thus, the relationship of changes in alpha with changes in MRTG were determined. alpha and MRTG values obtained from 859 thrombelastograms was collected from nine studies. Data were analyzed and the relationship between alpha and MRTG defined with commercially available software. Additional comparisons were made retrospectively from whole-blood and plasma data obtained from 33 normal individuals. Data from the nine studies demonstrated that MRTG increased in an exponential fashion compared with increases in alpha (R2 = 0.88, P < 0.001). Whole-blood alpha values were in the range 66.7-74.7 whereas MRTG values were 5.5-10.8, and plasma alpha values were 65.1-77.9 with corresponding MRTG values of 3.5-12.0. Assessment of clot propagation utilizing MRTG provides a more parametric evaluation than the determination of alpha. While normal alpha values may vary by only 12-20%, MRTG values vary by approximately 200-300%. The MRTG should be progressively utilized to a greater extent in both laboratory and clinical settings to parametrically quantify clot growth kinetics with thrombelastography.     

Gastrulation in the spider Zygiella x-notata involves three distinct phases of cell internalization.

The cell movements of gastrulation were analyzed in embryos of the spider Zygiella x-notata, using time-lapse video, cell tracing, and improved histology. Cells are internalized near the center of the germ disc in three distinct phases. First, cumulus mesenchyme cells ingress and migrate as a group beneath the superficial layer. Second, mass internalization through a blastopore yields a diffusely organized deep layer. Third, superficial cells accumulate at the center of the germ disc to form the caudal bud. The floor is internalized, and the caudal bud moves over the nascent dorsal field to form the caudal lobe. This pattern of gastrulation differs from the canonical pattern described in the historical literature: (1) the cumulus of Z. x-notata is completely formed before any other cells internalize; and (2) the caudal lobe is formed by means of the caudal bud, which is a locus of cell internalization.     

Replication of a type I avian adenovirus (CELO) mutant in the chicken embryo

Summary Replication of a CELO large plaque (LP) mutant and that of its wild type small plaque (SP) parent was studied in the chorioallantoic membrane (CAM) and in the amnion of 11-day-old embryos. Although both strains produced essentially the same amount of virus in the tissue fluids, they differed in their rates of replication. Replication of the SP parent was maximal in the CAM 24 to 48 hours before that of the LP mutant. Whereas inclusions were observed in SP inoculated CAM 48 hours PI and were present during the course of study; LP inclusions were rare at 72 hours PI and thereafter; LP inclusions were seen at 72 hours PI. Fewer SP than LP particles were required to produce inclusions. No inclusions were seen in sections of the trachea and liver removed at 96 hours PI from embryos inoculated via the amniotic sac with LP and SP virus.Contribution 1466 of the Rhode Island Agriculture Experimental Station.     

Relationship between shock attenuation and stride length during running at different velocities

The purpose of the study was to investigate the characteristics of shock attenuation during high-speed running. Maximal running speed was identified for each subject [n=8 males, 25 (SD 4.6) years; 80 (8.9) kg; 1.79 (0.06) m] as the highest speed that could be sustained for about 20 s on a treadmill. During testing, light-weight accelerometers were securely mounted to the surface of the distal antero-medial aspect of the leg and frontal aspect of the forehead. Subjects completed running conditions of 50, 60, 70, 80, 90, and 100% of their maximal speeds with each condition lasting about 20 s. Stride length, stride frequency, leg and head peak impact acceleration were recorded from the acceleration profiles. Shock attenuation was analyzed by extracting specific sections of the acceleration profiles and calculating the ratio of head to leg power spectral densities across the 10–20 Hz frequency range. Both stride length and stride frequency increased across speeds (P<0.05) and were correlated with running speed (stride length r=0.92, stride frequency r=0.89). Shock attenuation increased about 20% per m·s^–1 across speeds (P<0.05), which was similar to the 17% increase in stride length per m·s^–1. Additionally, shock attenuation was correlated with stride length (r=0.71) but only moderately correlated with stride frequency (r=0.40) across speeds. It was concluded that shock attenuation increased linearly with running speed and running kinematic changes were characterized primarily by stride length changes. Furthermore, the change in shock attenuation was due to increased leg not head peak impact acceleration across running speeds. Electronic Publication     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Modification of T-cell receptor Vbeta repertoire in response to allergen stimulation in peanut allergy

BACKGROUND: Peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis. Little is known of the immunologic mechanisms that underlie peanut allergy. OBJECTIVES: In this study we examined clonality of the T-cell response (TCR) to peanut in MHC class II identical, peanut allergy-discordant sibling pairs. METHODS: Four sibling pairs were investigated. The TCR repertoire was analyzed before and after in vitro stimulation of PBMCs with crude peanut or PHA, as control for general/nonspecific reactivity. Eighteen TCR-Vbeta families were examined by flow cytometry. Where significant differences in incidence of particular TCR-Vbeta families were observed, PCR familyspecific cDNA amplification and gene scanning were performed. RESULTS: After stimulation with peanut, no selective expansion of any TCR-Vbeta subpopulation was observed with flow cytometry, in either the peanut-allergic or nonallergic siblings, with the exception of 1 peanut-allergic subject who demonstrated a significant increase of TCR-Vbeta11(+) cells (0.3%-5.9% of the total CD3(+) cells). However, gene scanning revealed predominant single-size PCR products for TCRBV11 in all peanut-allergic subjects after peanut stimulation. TCRBV11 polyclo-nality was observed in allergic and nonallergic subjects before peanut stimulation and in nonallergic subjects after peanut stimulation. In comparison, all subjects, before and after stimulation with peanut, showed polyclonality for TCRBV2. CONCLUSIONS: Our results argue for clonal or oligoclonal TCRs to crude peanut and indicate that changes in the TCRBV11 subpopulation are restricted to peanut-allergic subjects after stimulation with crude peanut allergen.     

An investigation of visuospatial memory impairment in children with attention deficit hyperactivity disorder (ADHD), combined type

BACKGROUND: Memory impairment is not considered a core cognitive feature of attention deficit hyperactivity disorder, combined type (ADHD-CT), although it is associated with impairments in attentional and executive functions. This study investigates visuospatial memory impairment, in particular encoding and retrieval aspects, in children with ADHD-CT who are stimulant-medication naive and medicated with stimulant medication. METHOD: A cross-sectional study of visuospatial memory in 6- to 12-year-old children with stimulant-medication-naive ADHD-CT (n = 62) and medicated ADHD-CT (n = 58) compared to an age- and gender-matched healthy control group (n = 39) was completed. RESULTS: Both medication-naive and medicated ADHD-CT groups demonstrated subtle yet significant impairment in visuospatial memory. The memory impairment was delay-independent, which, along with other factors, suggest dysfunction of the encoding rather than retrieval phase of visuospatial memory. CONCLUSIONS: Careful study of large ADHD-CT samples does detect deficits in a visuospatial memory task, but these reflect attentional deficits rather than being specifically due to dysfunction of the medial temporal lobe explicit memory system. Children with ADHD-CT may benefit from cognitive and behavioural strategies focused on improving encoding of relevant information rather than retrieval strategies.