Accuracy of internal dynamics models in limb movements depends on stability

This study investigated the ability to use an internal model of the environmental dynamics when the dynamics were predictable but unstable. Subjects performed goal-directed movements using a robot manipulandum while counteracting a force field, which created instability by assisting the movement in proportion to hand velocity. Subjects performance was better on the last trial than on the first trial in the force field for all four movement directions tested: out, in, right and left. Subjects adapted to the force field primarily by increasing muscle co-contraction, compared to null field movements, during all phases of movement. This co-contraction generally declined for both the deceleration and stabilization phases during the course of the first 25 movements in each direction, but tended not to decrease significantly thereafter. Catch trials at the end of the learning period suggested that increased viscoelastic impedance due to muscle co-contraction was used to counteract the force field. Only in the case of outward movements were aftereffects observed that were consistent with formation of an accurate internal model of the force field dynamics. Stabilization of the hand for outward movements required less muscle co-contraction than for movements in other directions due to stability conferred by the geometry of the arm. The results suggest that the accuracy of an internal model depends critically on the stability of the coupled dynamics of the limb and the environment.     

Neurotransmitters regulate the migration and cytotoxicity in natural killer cells

Natural killer (NK) cells and cytotoxic T lymphocytes (CTL), the functional coordination of which are governed by various signal substances, are crucial in the body’s defense of tumor and virus-infected cells. We investigated the role of various neurotransmitters and hormones on the regulation of functional parameters, including NK cell cytotoxicity, and the migration of NK cells and CTL within a three-dimensional collagen lattice. Using peripheral blood CTL and NK cells, we show that the neurotransmitters endorphin, histamine and substance P increase NK cell cytotoxicity, while norepinephrine inhibits cytotoxicity. Moreover, substance P reduces migratory activity, while norepinephrine increases NK cell and CTL migration. Furthermore, all three steroid hormones which were investigated, namely cortisone, testosterone, and estradiol, had regulatory influence on both cytotoxicity and migration of NK cells. These results further specify the functional basis of the complex interconnection between the immune and neuro-endocrine systems.     

The final demise of Rodriguez lethal acrofacial dysostosis: A case report and review of the literature

We evaluated a newborn with acrofacial dysostosis in whom a clinical diagnosis of Nager syndrome was entertained. Radiographs revealed hypoplasia of the scapulae and bilateral humeroradial synostosis, with absent ulna on the left and hypoplastic ulna on the right. The finding of bilateral humeroradial synostosis had not been seen in cases of Nager syndrome before and we considered other diagnoses. Humeroradial synostosis has been found in three cases of acrofacial dysostosis Rodriguez type, a syndrome characterized by mandibular hypoplasia, upper and lower extremity phocomelia, and oligodactyly of the upper limbs. More recently, haploinsufficiency of the SF3B4 gene has been identified as the cause of both Nager and Rodriguez syndrome, leading many to believe that Rodriguez syndrome represents a more severe end of a Nager syndrome spectrum. An SF3B4 mutation was found in our patient, prompting a review of the previous known cases of Rodriguez syndrome, which revealed no clustering of SF3B4 mutations, and four cases of Rodriguez syndrome with mutations identical to those in cases of Nager syndrome. Rodriguez syndrome was previously thought of as a lethal acrofacial dysostosis distinct from Nager syndrome. A number of more mild cases, as well as our case, intermediate between the two phenotypes, illustrate that Rodriguez syndrome is a severe manifestation of Nager syndrome, and is not lethal with aggressive medical care.     

Autonomic Correlates of Sensation Seeking and Monoamine Oxidase Activity: Using Confirmatory Factor Analysis on Psychophysiological Data

A negative relationship between platelet monoamine oxidase (MAO) activity and Sensation Seeking (SS) has been reported in several studies. This study evaluates the possible contribution of autonomic nervous system (ANS) activity to this relationship. Additionally, confirmatory factor analysis was used to create models of ANS concepts from a larger number of psychophysiological variables. Skin conductance (SC) and heart rate (HR) were recorded from 46 men and 49 women during a two-session protocol that included rest periods, a balloon stress, a series of tones, and two tasks: two-flash threshold and tachistoscopic recognition. Results showed that the best-fitting models for both rest and task periods included concepts of SC base levels (“arousal”), SC lability, and HR, and were quite similar for men and women. MAO activity correlated positively with SC concepts, most strongly for women. Women showed negative relationships between sensation seeking and both SC arousal and HR concepts. In contrast, men showed evidence of positive relationships between SC concepts and an active life style. The sex differences and response specificity in these relationships make it unlikely that ANS activity mediates the negative MAO-SS relationship.     

The hypotransferrinaemic mouse: Ultrastructural and laser microprobe analysis observations

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2- and 12-month-old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month-old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providing in situ documentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.     

Effects of Beta-Adrenergic Activity on T-Wave Amplitude

This study addresses the hypothesis that electrocardiographic T-wave amplitude is influenced by beta-adrenergic stimulation of the heart. Beta-adrenergic activity was manipulated both pharmacologically and through behavioral challenge. Under resting conditions, 12 healthy men underwent infusion of placebo and then the beta-agonist, isoproterenol, and the beta-blocker, propranolol, in a counterbalanced, crossover design. During infusion of placebo, subjects also underwent two behavioral challenges, a structured interview and mental arithmetic. Analysis of the resting data indicated that propranolol produced a significant increase in T-wave amplitude, and isoproterenol produced significant T-wave amplitude attenuation. As previously reported, drug effects were also in evidence for heart rate. Behaviorally-induced reduction of T-wave amplitude was observed for mental arithmetic but not structured interview, which again paralleled heart rate data. Both pharmacological and behavioral data reported in this study support the hypothesis that the T-wave is significantly affected by beta-sympathetic influence on the heart. However, a nonspecific effect of heart rate change on T-wave amplitude would also account for these results. The findings are discussed in terms of their implications for the utility of T-wave amplitude in psychophysiological research.     

Analytical technique for quantification of selected resorbable calcium phosphate bone void fillers with the use of polarized-light microscopy

Synthetic calcium phosphate bone void fillers promote varying rates of bone formation and material resorption depending on chemistry, porosity, pore structure, and implant site. The objective of this study was to quantify the resorption of a novel ultraporous beta-tricalcium phosphate cancellous bone void filler with simultaneous quantification of bone formation in a canine humerus model. Potential measurement error involved in conventional histomorphometry using Von Kossa stains inspired the development of a new technique. This technique utilizes bright-field and polarized-light microscopy in conjunction with image analysis software, allowing more accurate histomorphometry. This technique was validated with two separate controlled experiments. Scanning electron microscopy further supported the results. The findings suggest that the use of polarized-light microscopy combined with image analysis software can be an effective tool in simultaneously quantifying calcium phosphate resorption and bone formation.     

The Lipofuscin-Iron Association in Pigmentosis Tubae

Pigmentosis tubae (PT) is a rare condition characterized by the presence of numerous lipofuscin-laden macrophages in the lamina propria of the fallopian tube. Two women, who also had endometriotic ovarian cysts, showed polypoid pigmented tubal mucosae. In addition to lipofuscin, occasional cells showed spotty positivity for iron. Ultrastructural examination of the tubal mucosa showed the lipofuscin-containing bodies, which were similar to lipofuscin-containing lysosomes found in other pigmented conditions. Cytoplasmatic ferritin and hemosiderin in siderosomes were observed in macrophages and endothelial cells of the lamina propria. The present study is the first to demonstrate the presence of iron-containing particles and lipofuscin in the residual bodies of PT. The origin of the excess iron is not clear, but erythrophagocytosis and an abnormal tubal environment could play a role. Iron-promoted lipid peroxidation may alter the lysosomal membranes and contribute to the excessive accumulation of lipofuscin in these cells.