Protracted radiation-stressed primate performance.

An experimental investigation has been made of the effects of nuclear radiation on the behavior of four trained primates (rhesus monkeys) proficient in control of the primate equilibrium platform during a hypothetical 72-h aircraft mission. The radiation exposure was assumed to result from a radioactive cloud penetration at the start of the mission, with subsequent low dose rate exposure resulting from radioactive debris in and on the aircraft. Minor performance changes were detected in three of four subjects; all experienced emesis.     

Motion correction improves image quality of dGEMRIC in finger joints

Purpose

To assess motion artifacts in dGEMRIC of finger joints and to evaluate the effectiveness of motion correction.

Materials and methods

In 40 subjects (26 patients with finger arthritis and 14 healthy volunteers) dGEMRIC of metacarpophalangeal joint II was performed. Imaging used a dual flip angle approach (TE 3.72 ms, TR 15 ms, flip angles 5° and 26°). Two sets of T1 maps were calculated for dGEMRIC analysis from the imaging data for each subject: one with and one without motion correction. To compare image quality, visual grading analysis and precision of dGEMRIC measurement of both dGEMRIC maps for each case were evaluated.

Results

Motion artifacts were present in 82% (33/40) of uncorrected dGEMRIC maps. Motion artifacts were graded as severe or as rendering evaluation impossible in 43% (17/40) of uncorrected dGEMRIC maps. Motion corrected maps showed significantly less motion artifacts (P < 0.001) and were graded as evaluable in 97% (39/40) of cases. Precision was significantly higher in motion corrected images (coefficient of variation (CV = .176 ± .077), compared to uncorrected images (CV .445 ± .347) (P < .001). Motion corrected dGERMIC was different in volunteers and patients (P = .044), whereas uncorrected dGEMRIC was not (P = .234).

Conclusion

Motion correction improves image quality, dGEMRIC measurement precision and diagnostic performance in dGEMRIC of finger joints.     

History and genesis of the detailed review of thyroid hormone disruption assays

This issue presents the detailed review paper (DRP) on thyroid hormone disruption assays that was prepared for the Organization for Economic Cooperation and Development (OECD) and that exists as an OECD monograph. However, this document is now available here in one issue of Critical Reviews in Toxicology as a series of published articles. The original document has been modified in several ways. First, an overview (now article 2) was added to discuss how new data and new directions for thyroid research will play an important role in shaping thyroid assays as they evolve. Second, each of the original chapters of the thyroid DRP have been separated into individual papers. The appendices of the original DRP were removed and will be merged and published separately.     

Preserved tissue-type plasminogen activator release and endothelium-dependent vasodilation in postmenopausal women with NIDDM

We have recently shown that the net release of tissue-type plasminogen activator (t-PA) antigen can be rapidly enhanced by the muscarinic receptor stimulation in healthy males. Since diabetes mellitus has been associated with endothelial dysfunction, the aim of the present study was to compare the endothelium-derived local net release of t-PA with vasodilation in response to muscarinic receptor stimulation by metacholine (Mch) and fluid shear stress in a group of postmenopausal women with non-insulin-dependent diabetes mellitus (NIDDM), and to elucidate the influence of estrogen on this process. Six postmenopausal women with NIDDM were in randomized order exposed to step-wise intra-arterial infusions of Mch (0.1-0. 8-4.0 microg/min) and nitroprusside (SNP; 0.5-2.5-10.0 microg/min). Forearm blood flow (FBF) was assessed by plethysmography. The infusions with Mch and SNP were repeated during simultaneous intra-arterial infusion of 17-beta estradiol (E; 20 ng/min). During placebo infusion, FBF increased significantly in response to Mch and SNP (p<0.001), but no differences between Mch and SNP were found. In parallel to the blood flow increase in response to Mch stimulation, the t-PA net release was increased over 30 times (p<0.001). Estrogen did not produce any change in blood flow or net release of t-PA at baseline or in response to either drug (Mch or SNP). The present study demonstrates a preserved endothelium-dependent vasodilation and stimulated tissue-type plasminogen activator release in NIDDM postmenopausal women in response to Mch stimulation. Acute intra-arterial infusion of 17-beta estradiol did not affect the vasodilation or the t-PA net release.     

Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.