Effects of high oxygen concentrations on microbial biosensor signals. Hyperoxygenation by means of perfluorodecalin

Amperometric biosensors register oxygen depletion in response to analyte catabolism, and thus are limited by the availability of dissolved oxygen. Microbial sensors containing immobilized cells of Gluconobacter oxydans were hyperoxygenated to 400% of control levels and the effects on sensor responses to glucose were determined. Oxygenated perfluorodecalin (a completely fluorinated organic substance) was as effective in hyperoxygenation as direct sparging with O2, increasing sensor base medium oxygen concentrations from 9.3 to 37 mg/l. Hyperoxygenation enhanced maximal biosensor response amplitudes, particularly at high cell loading densities. Maximal response rates were also improved, although less dramatically. Results suggest that hyperoxygenation may be a new general approach for modulating biosensor responses.     

Neurobiological basis of creativity

We have used a previously described model of bilateral radiation-induced lung disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the role of hyaluronan in this process. Hyaluronan was measured in the bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma irradiation or sham irradiation. Four weeks after irradiation, during peak alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was in the intra-alveolar edema fluid but was not increased in the alveolar walls; hyaluronan, measured by high-performance liquid chromatography, also was not elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis (6 to 20 weeks). The administration of methylprednisolone significantly decreased the alveolitis, including the increase in hyaluronan in the alveolar space and serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of inflammation and cannot be used as a serum marker to predict the onset of radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does not appear to be a necessary precursor in the evolution of radiation fibrosis.     

Parvovirus B19 infection in AIDS patients

We report a 16-year-old boy, born to consanguineous parents, with mental retardation, gait disturbances and dysarthria; brain magnetic resonance showed features consistent with rhombencephalosynapsis. This condition is characterised by a hypoplastic single-lobed cerebellum. The interest of this case is the presence of common ancestors, pointing to an autosomal recessive inheritance of the malformation.     

Towards a consolidated model for a collaborative courseware authoring system

Abstract In an effort to reduce the expensive resource requirements in courseware production and to allow effective management of, and communication and collaboration between authors, a model is needed to harmonize the diverse theoretical backgrounds such a process requires. To this end we look at five abstract models which where chosen for their apparent appropriateness within the general area of collaborative authoring and reuse of multimedia courseware. These models consist of a functional model of hypertext, an infrastructure model for an open collaborative authoring system, two object-oriented communication models, and a courseware production model. We attempt a consolidation of these models and ultimately make several conclusions, which are exposed during a conceptual harmonisation. The principal conclusion is that a hypermedia logical model is not by itself adequate to support collaboration and reuse. Our modeling conclusions have driven the design of a system which will be implemented and tested.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

The affinity of an oligodeoxynucleotide-peptide conjugate for an RNA hairpin loop depends on stereochemistry at the DNA-peptide junction

Molecular models of an oligodeoxynucleotide-peptide conjugate complexed to an RNA hairpin loop were constructed to assess the effect of stereoisomerism at the point of attachment of the peptide to the oligodeoxynucleotide on the affinity of the conjugate for an RNA target. The peptide portion of the oligodeoxynucleotide-peptide conjugate, (L-lysine)8, was covalently attached to the N-allyl group of (D)- or (L)-aspartic alcohol that was incorporated into the interior of an antisense oligodeoxynucleotide. The stereocenter in the oligodeoxynucleotide interior originates from either (D)- or (L)-aspartic alcohol. The oligodeoxynucleotide portion of the oligodeoxynucleotide-peptide conjugate forms Watson-Crick base pairs with the single-stranded RNA that flanks the RNA hairpin loop. The positively charged peptide makes specific electrostatic contacts with the negatively charged phosphate backbone of the RNA hairpin loop when attached to the N-allyl of (D)-aspartic alcohol but does not have the proper orientation to make these electrostatic contacts when attached to the N-allyl of (L)-aspartic alcohol. This modelling study emphasizes the importance of stereocontrol at the point of branching in synthesizing oligodeoxynucleotide-peptide conjugates for binding of RNA hairpin loops.     

Neuromuscular activation patterns during treadmill walking after space flight

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.     

Nephrotic syndrome. What is new since the 1988 study?

Hormone-refractory prostate cancer (HRPC) patients often have nonmeasurable disease. In such patients, predictive biomarkers other than tumor response may be required to compare therapeutic effects. We examined the predictive value for survival of various clinical and laboratory parameters, including prostate-specific antigen (PSA), in HRPC patients treated with suramin. Data from 103 HRPC patients were analyzed using various survival analyses, the likelihood ratio approach, and logistic regression analyses. When pretreatment factors, percentage decrease in PSA at 4 weeks from start of treatment (deltaPSA), and updated survival data were fit by a multivariate Cox proportional hazards model, acid phosphatase, lactate dehydrogenase, and deltaPSA were significant, with risk ratios close to 1. There was a decrease in likelihood ratio with increasing APSA. A logistic regression model was developed to predict the probability of <1 year of survival from the start of treatment. Hemoglobin and deltaPSA were found to be significant variables. However, in view of the complexities involving the relationship between PSA expression and prostate cancer growth and possible selective effect of treatment on PSA, further prospective testing is necessary. Therefore, deltaPSA cannot necessarily be used as a biomarker for survival response in individual patients during the evaluation of the therapeutic response of HRPC to new antineoplastic drugs.     

Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter

Calmodulin (CaM) has been reported to have affinity for the estrogen receptor (ER). Observations reported here reveal a direct physical interaction between purified CaM and ER. This direct ER-CaM interaction may be an initial event preceding the assembly of ER plus auxiliary proteins into the active ER complex with its DNA motif, the estrogen response element. We demonstrate that CaM is an integral component of this complex by using a system reconstituted from purified ER and nuclear extract from ER-negative breast cancer cells and also with ER-depleted nuclear extract of an ER-positive breast cancer cell line. Although CaM is essential for formation of this complex, it is not sufficient, suggesting roles also of auxiliary proteins. CaM also is functionally required for activation of an ER-responsive promoter, in the 17beta-estradiol-ER pathway of hormone action and regulation of 17beta-estradiol-responsive gene expression that is associated with proliferation of mammary epithelial cells.