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Permeability of the external glial limiting membrane of rat parietal cortex.

As the relevance of previous reports demonstrating the permeability of the glia limitans appears to be not generally accepted, the problem is reinvestigated by examination of the ultrastructure of the glia limitans in combination with tracer studies using Ruthenium Red. The results clearly show that gap junctions are the only type of intercellular contact present in this layer. Measurements of the lengths of cross-sections of junctional regions reveal a decrease in size in absolute terms as well as in relation to total astrocytic surface if one proceeds from the more superficial layers into the depth of the tissue. The intercellular clefts leading from the subarachnoidal space into the interspaces of brain tissue are patent thus allowing the tracer to penetrate to a depth of 0.4-0.6 mm in one hour. Although these observations confirm the idea of an ultimate communication between the cerebrospinal fluid compartments and the extracellular space of brain the discussion shows how the particular arrangement of the intercellular channels and the cells bordering them may be suited to control the local composition of interstitial fluid independently from that of the cerebrospinal fluid.

Animals↗

Medical knowledge systems: applications to telemedicine.

The application and form of electronically stored medical knowledge has a direct impact on the design of any healthcare delivery system. For those who plan for remote medical care or who work at the disaster relief level, there are specific requirements which will dictate the type of knowledge required and the vehicle best suited to deliver that information. The PC based multimedia biomedical library developed for NASA was originally intended for long-term space missions where complete isolation from each support was a distinct possibility. The library is a combination of traditional references and secondary databases structured within a primary care physician's workstation. The integration of the library and a point-of-care system allows optimal use of both resources and provides a basic building block for telemedicine networking.

Artificial Intelligence↗

The design of silk fiber composition in moths has been conserved for more than 150 million years.

The silk of caterpillars is secreted in the labial glands, stored as a gel in their lumen, and converted into a solid filament during spinning. Heavy chain fibroin (H-fibroin), light chain fibroin (L-fibroin), and P25 protein constitute the filament core in a few species that have been analyzed. Identification of these proteins in Yponomeuta evonymella, a moth from a family which diverged from the rest of Lepidoptera about 150 million years ago, reveals that the mode of filament construction is highly conserved. It is proposed that association of the three proteins is suited for long storage of hydrated silk dope and its rapid conversion to filament. Interactions underlying these processes depend on conserved spacing of critical amino acid residues that are dispersed through the L-fibroin and P25 and assembled in the short ends of the H-fibroin molecule. Strength, elasticity, and other physical properties of the filament are determined by simple amino acid motifs arranged in repetitive modules that build up most of the H-fibroin. H-Fibroin synergy with L-fibroin and P25 does not interfere with motif diversification by which the filament acquires new properties. Several types of motifs in complex repeats occur in the silks used for larval cobwebs and pupal cocoons. Restriction of silk use to cocoon construction in some lepidopteran families has been accompanied by simplification of H-fibroin repeats. An extreme deviation of the silk structure occurs in the Saturniidae silkmoths, which possess modified H-fibroin and lack L-fibroin and P25.

Amino Acid Motifs↗

A new configuration for voltage clamp of axons used to demonstrate nerve conduction blockade by a 2,5-disubstituted pyrrolidine.

An original voltage-clamp technique on axons from crayfish Procambarus clarkii is described in this paper. Its advantages are: a fast dissection leading to the availability of several fibers of different diameters (10-500 microns) that may contain different ion channels; and use of a double-electrode voltage clamp on a chosen fiber with good clamping characteristics (short time clamp and good space clamp, small leak conductance). Because of the absence of exogenous lipidic phase in the superfusion chamber, this technique appears particularly suited to studying how liposoluble neurotoxins affect nerve conduction. This method has been successfully applied to test the effect of a synthetic derivative (2-(1non-8enyl)-5(1non-8enyl)pyrrolidine (Pyr 9)) of ant venom alkaloids from Monomorium species on nerve conduction. We present here evidence of a strong blocking effect on inward current involved in spike conduction. The resting potential of the treated axons did not change and it appears that only the inward current was affected.

Animals↗

Experimental validation of the tetrahedral skeleton model pressure drop correlation for silica monoliths and the influence of column heterogeneity.

This paper describes the use of computational fluid dynamics for the calculation of the flow resistance through computer-generated models resembling silica monoliths. This study was undertaken to determine the effect of skeleton heterogeneity on the flow resistance and, more precisely, to test the hypothesis that increased skeleton heterogeneity decreases the flow resistance. To evaluate the proposed model, 24 real silica monoliths have been prepared using the same method, covering a wide range of skeleton sizes (2.2 microm < d(s) < 8 microm) and porosities (0.47 < epsilon < 0.66). The permeability of these monoliths was determined by pressure drop measurements, and structural information was obtained by image analysis of laser scanning confocal microscopy-generated 3D images of the skeleton structure. The results indicate that the presence of preferential flow paths due to an increased heterogeneity of the flow through pore space reduces the flow resistance of monolithic media. It is also shown that the pore size is hence a much better suited scaling dimension than the skeleton size to reduce the permeability of monolithic columns.

Journal Article↗

Cerebral iron oxide distribution: in vivo mapping with MR imaging.

PURPOSE: To map the distribution of an iron oxide label in the central nervous system with in vivo magnetic resonance (MR) imaging. MATERIALS AND METHODS: Unilateral osmotic disruption of the blood-brain barrier (BBB) in rats (n = 40) was followed by injection of monocrystalline iron oxide nanoparticles (MION) into the carotid artery. MR images (1.5 T) were obtained in and ex vivo, and results were correlated with histologic section-matched iron maps. RESULTS: A mean of 0.2% of the injected MION was found in the brain 24 hours after unilateral osmotic disruption of the BBB. The spatial distribution of iron oxide within the brain correlated with areas known to have high relative perfusion. Iron was found in cell bodies and dendrites of cortical neurons and astrocytes and in the interstitial space. The threshold in concentration for detection of MION in the brain was 62.2 ng Fe/mm2. CONCLUSION: MR imaging is well suited to noninvasive in vivo mapping of the intracerebral iron oxide distribution.

Animals↗

The effect of staged decompression while breathing 100% oxygen on altitude decompression sickness.

INTRODUCTION: Space Shuttle extravehicular activity (EVA) requires decompression from sea level pressure (14.7 psia) to a 4.3 psia (30,300 ft) pressure suit. The transition currently involves altering the shuttle atmosphere to allow shirt-sleeve denitrogenation to occur during a 12 to 36-h staged decompression (SD) at 10.2 psia (9,800 ft) with an oxygen-enriched breathing gas (26.5% oxygen, 73.5% nitrogen). The denitrogenation provides protection from decompression sickness (DCS) during EVA in a 4.3 psia pressure suit. Our goal was to determine the highest altitude at which SD while breathing 100% oxygen (SD100) could provide effective protection from development of DCS symptoms after further decompression to 29,500 ft (4.5 psia). METHODS: There were 30 male subjects exposed to at least 6 of 11 conditions in random order on successive months to 29,500 ft for 4 h while performing mild exercise and being monitored for venous gas emboli (VGE) with an echo-imaging system. The subjects received 15 min of ground-level (GL) preoxygenation and an additional 60 or 120 min of SD100 at one of four altitudes between 8,000 ft (10.9 psia) and 18,000 ft (7.3 psia). Control exposures followed a 75- or 135-min ground-level preoxygenation. RESULTS: During SD100, one case of DCS occurred at 18,000 ft, but not at lower staging altitudes. Higher levels of VGE were observed during SD100 at 18,000 ft than during SD100 at any lower altitude. CONCLUSION: Staged decompression at 16,000 ft and below results in decompression risk during subsequent decompression to 29,500 ft similar to that following equivalent periods of ground-level preoxygenation.

Altitude Sickness↗

Connective tissue of the livers of newborn and adult marmosets (Callithrix jacchus).

Immunofluorescence microscopic and electron microscopic investigations revealed components of the matrix and of the basal lamina (collagen type I, III, IV and V, BL-heparan sulfate and fibronectin) in the sinus wall (Disse's space) of the livers of newborn and adult marmosets (Callithrix jacchus). Collagen type I was missing in both the two age groups. Small amounts of laminin were present in the livers of newborn and absent in those of adult animals, whereas collagen type III occurred in the form of delicate fibres. Light microscopic inspection showed a continuous distribution of all other components in the sinus wall. The amount of collagen type III and V increased depending on the age. Electron microscopic investigations revealed single or bundled fibrils (20-30 nm) and filaments (10-12 nm). After addition of tannic acid, plaques of a fine-filamentous network and incorporated granules were observed. After addition of resting Ruthenium Red, electron-dense granules (20-60 nm) were irregularly distributed in the structureless space, resting on collagenous fibrils and cell membranes. The fibrils were allocated to collagen type III, the filaments to collagen type V. The plaques were supposed to contain heparan sulfate, collagen type IV and fibronectin. The absence of a Lamina densa of the basal lamina was attributed to the absence of laminin which probably plays an important role in the formation of this layer. Differences in the distribution pattern of the matrix components and thus a functional mosaic of the permeability of Disse's space were assumed. The complete absence of collagen type I and laminin in the lobules makes the adult marmoset liver especially suited for studies on the importance of this collagen type under pathological conditions, since both components are expressed in this way.

Animals↗

Epidural morphine by continuous infusion with an external pump for pain management in oncology patients.

Ten patients with advanced malignancies and severe pain were given epidural morphine (EDM) by continuous infusion. The pain had been treated previously with large doses of oral or parenteral narcotics, without success. The pain was disabling in all the cases. The total dose of morphine administered was 10-90 mg per day; median dose was 25 mg. Treatment lasted from 9 to 400 days. Pain relief was complete in seven patients, near complete in two, and moderate in one. Five patients became fully ambulatory. Two patients were treated as outpatients and resumed work activities. No central nervous system or gastrointestinal adverse effects, respiratory depression, or pruritus were noted. One patient developed urinary retention. EDM by continuous infusion produced constant pain relief for prolonged periods. This technique is safe for analgesia in oncology patients and suited for outpatient management.

Aged↗

Continuous distributions of specific ventilation recovered from inert gas washout.

We describe a new technique for recovering continuous distributions of ventilation (V) as a function of tidal ventilation/volume ratio (V/V0) from the nitrogen washout. The analysis yields a continuous distribution of V as a function of V/V0 represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: a) the distributions of young, normal subjects were narrow and unimodal with a mean ln standard deviation of 0.56 plus or minus 0.13; b) those of subjects over age 40 were broader (ln SD 0.86 plus or minus 0.19) with more poorly ventilated units; c) patients with pulmonary disease of all descriptions showed enlarged dead space; d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and e) patients with obstructive lung diseases fell into several classes, three of which are illustrated. These results suggest that our approach is well suited for clinical investigation.

Adult↗

Russian system of countermeasures on board of the International Space Station (ISS): the first results.

The system of countermeasures used by Russian cosmonauts in space flights on board of International Space Station (ISS) was based on the developed and tested in flights on board of Russian space stations. It included as primary components: physical methods aimed to maintain the distribution of fluids at levels close to those experienced on Earth; physical exercises and loading suits aimed to load the musculoskeletal and the cardiovascular systems; measures that prevent the loss of fluids, mainly, water-salt additives which aid to maintain orthostatic tolerance and endurance to gravitational overloads during the return to Earth; well-balanced diet and medications directed to correct possible negative reactions of the body to weightlessness. Fulfillment of countermeasure's protocols inflight was thoroughly controlled. Efficacy of countermeasures used were assessed both in- and postflight. The results of studies showed that degrees of alterations recorded in different physiological systems after ISS space flights in Russian cosmonauts were significantly higher than those recorded after flights on the Russian space stations. This phenomenon was caused by the failure of the ISS crews to execute fully the prescribed countermeasures' protocols which was as a rule excused by technical imperfectness of exercise facilities, treadmill TVIS particularly.

Aerospace Medicine↗

Membrane-protein crystallization in cubo: temperature-dependent phase behaviour of monoolein-detergent mixtures.

The lipidic cubic phase of monoolein has proved to be a matrix well suited to the production of three-dimensional crystals of membrane proteins. It consists of a single continuous bilayer, which is contorted in three-dimensional space and separates two distinct water channels. It has previously been proposed that on the addition of precipitants, membrane proteins embedded in the cubic phase migrate through the matrix to nucleation sites and that this process is dependent upon the stability of the lipidic cubic phase. Here, the effect of detergent type (C(8)-C(12) glucosides, C(8)-C(12) maltosides and C(7) thioglucoside) and concentration (1-3x the critical micelle concentration; CMC) on cubic phase stability are reported in the form of the temperature-dependent phase behaviour (268-313 K) in 40% aqueous solution. The results are tabulated to show the best monoolein (MO)-detergent mixtures, mixing temperatures and crystallization temperatures identified. Monoolein-detergent mixtures suited for low-temperature in cubo crystallization of temperature-sensitive proteins are also reported for the first time. These mixtures can be prepared at low temperatures (mixed at <or=288 K) and remain stable at 277 K for a period of at least one Month. They include MO-heptyl thioglucoside (1x and 3x CMC), MO-nonyl glucoside (3x CMC), MO-octyl maltoside (3x CMC), MO-nonyl maltoside (1x CMC) and MO-decyl maltoside (1x CMC).

Crystallization↗

Hindlimb suspension and hind foot reversal in Varecia variegata and other arboreal mammals.

The foot, perhaps more than any other region of the primate body reflects the interaction of positional behaviors with the geometric properties of available supports. The ability to reverse the hind foot during hindlimb suspension while hanging from a horizontal support or descending a large diameter vertical trunk has been noted in many arboreal mammals, including primates. Observations of Varecia variegata in the wild and under seminatural conditions document hindlimb suspension in this lemurid primate. The kinematics and skeletal correlates of this behavior are examined. Analogy is made with the form and function exhibited by nonprimate mammalian taxa employing this behavior. Examples of carnivores and rodents display very similar adaptations of the tarsals while other mammals, such as the xenarthrans, accomplish a similar end by means of different morphologies. However, a suite of features is identified that is shared by mammals capable of hind foot reversal. Hindlimb suspension effectively increases the potential feeding space available to a foraging mammal and represents a significant, and often unrecognized, alternative adaptive strategy to forelimb suspension and prehensile-tail suspension in primates.

Adaptation, Physiological↗

Use of the direct linear plot to estimate, in an immunoglobulin solution, the proportion which is specific monoclonal antibody against an unknown cell surface antigen.

A Cornish-Bowden direct linear plot was used to assess the level of specific monoclonal antibody in a protein A preparation from mouse ascitic fluid. With this method, experimental observations are plotted directly as lines in parameter space and estimates of kinetic parameters are read directly from the plot without need for further calculation. This method is particularly well suited for the analysis of systems, such as the one outlined here, where conventional kinetic analysis is not possible because the preparation contains both specific and non-specific antibody. Results obtained with the direct linear plot showed that estimates of the level of specific immunoglobulin present in a given protein A preparation are consistent, not only within individual experiments, but also throughout a series of experiments using more than one labelled antibody preparation.

Antibodies, Monoclonal↗

Radiation situation determining the possibility of a manned flight to Mars and back.

Possible manned flights toward Mars are discussed from the viewpoint of radiation hazard. A standard situation is considered for the fast two times crossing of the Earth radiation belts. The flight to Mars is shown to be practically impossible without a special system of radiation shelters, because of the effect of penetrating galactic and solar radiations which are responsible for almost maximum permissible doses. But even in case there were radiation shelters on board the spacecraft their flights are undesirable in the periods of maximum and minimum solar activity. It would obviously be worthwhile to schedule Martian flights for intervals in between minima and maxima of 11-year cycles of solar activity when primary cosmic rays levels are considerable reduced and flare activity is not yet sufficiently high. It should be mentioned that it would not be easy to select such allowed intervals. Further studies of that aspect are discussed.

Astronauts↗

Distribution-based descriptors of the molecular shape.

A rational design of economically cost-effective chemical libraries as well as successful data mining during a process of drug discovery employs a vast array of the molecular descriptors. Despite the huge importance of this area of the research there is still a need for the further development of the simple, intuitive, easily calculable, specific and size-invariant parameters of the molecular shape. Here we present ab initio calculation of the molecular volumes and expectations for the molecular areas of projection. These molecular size parameters were used as a basis to define a group of novel descriptors of the molecular shape. A set of molecular descriptors was developed: ovality, roughness, size-corrected parameters, and the parameters derived from the higher central momenta of the distributions of the size descriptors-skewness and kurtosis. The rationale for the construction of the descriptors was first to calculate the descriptors of the molecular size along many directions in the space and second to use the statistical parameters of the distribution of those descriptors as the shape descriptors. The size descriptors well suited for the above purpose and discussed in this paper are generalized molecular radii and the molecular areas of projection. Molecular volume and projection area-derived descriptors were calculated and their applicability as shape descriptors was illustrated using exploratory methods (factor analysis and hierarchical cluster analysis). The shape descriptors appear to be promising in their ability to discriminate and classify the molecular shapes e.g. spheroids, disklike, rodlike, starlike, crosslike, anglelike, etc.

Journal Article↗

Definitive control of bleeding from severe pelvic fractures.

Forty patients with severe pelvic fracture and extraperitoneal hemorrhage were reviewed. Eighteen patients seen prior to 1975 (group I) were clinically similar to 22 patients seen subsequently (group II). Major pelvic fracture hemorrhage was defined as bleeding in excess of 2,000 ml over and above initial resuscitation volumes. Ten of 22 group II patients met the criteria for continued extraperitioneal bleeding and were immobilized in an inflatable G-suit after surgically remediable lesions had been excluded. Ventilator support and hemodynamic monitoring were instituted and clinical response recorded. Prompt cessation of bleeding was observed in nine of ten patients. One patient required selective catheterization of a bleeding artery with subsequent embolic occlusion. Significant reductions in overall mortality and the frequency of shock related death were observed in group II patients. Sepsis was the leading cause of late death in survivors. Immobilization of pelvic fracture patients in the G-suit is recommended as a means of controlling continuing retroperitoneal hemorrhage when surgically correctable bleeding points have been dealt with. Failure of patients to respond promptly to the G-suit strongly suggests arterial bleeding amenable to selective catheterization and embolic occlusion.

Adolescent↗

Towards deterministic equations for Lévy walks: the fractional material derivative.

Lévy walks are random processes with an underlying spatiotemporal coupling. This coupling penalizes long jumps, and therefore Lévy walks give a proper stochastic description for a particle's motion with broad jump length distribution. We derive a generalized dynamical formulation for Lévy walks, in which the fractional equivalent of the material derivative occurs. Our approach is expected to be useful for the dynamical formulation of Lévy walks in an external force field or in phase space, for which the description in terms of the continuous time random walk or its corresponding generalized master equation are less well suited.

Journal Article↗