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PubMed1985

Exchangeable sodium in DOC-salt and post-DOC-salt hypertension in rats.

Eighteen male Sprague-Dawley rats were fed a sodium-free diet and given NaCl (154 mmol/l) labelled with 22Na (37 Bq/l [1 microCi/l]) to drink. Following equilibration, each had a unilateral nephrectomy; 10 days later the animals started a series of 10 injections of deoxycorticosterone (12.5 mg twice-weekly for 5 weeks). Thereafter the animals were split into two groups, one to continue with DOC injections and diet as previously (DOC-salt), the other to stop DOC injections and continue a sodium-free diet and labelled saline of lower concentration (89 mmol/l) (post-DOC). During the period of DOC injections to both groups, blood pressure and exchangeable sodium rose significantly and were significantly correlated. In the post-DOC group, hypertension persisted and was not significantly different from that in the DOC-salt group. However, in the post-DOC-salt group, exchangeable sodium fell to levels similar to those found in uninephrectomized control animals of similar age which had never been given DOC or a high salt intake and had never been hypertensive. Thus an expanded sodium space does not contribute to maintenance of hypertension in the post-DOC-salt model.

Animals↗

PubMed1989

Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep.

Augmentation of lung antiprotease levels may be an important therapeutic intervention in the prevention of pulmonary emphysema. We have administered aerosols of plasma-derived human alpha 1 proteinase inhibitor (A1PI) to the lungs of dogs and sheep to investigate (a) delivery of the protein to the distal air spaces of the lung; (b) maintenance of functional activity of the protein; and (c) flux of the protein across the components of the alveolar-capillary membrane. A1PI (26.4 mg/kg body weight) was administered as an aerosol to anesthetized animals; sheep were prepared for the chronic collection of lung lymph. Immunoperoxidase staining of lung tissue obtained 2 h after administration of A1PI demonstrated the presence of human A1PI on the surface of alveoli and distal bronchioles. Bronchoalveolar lavage fluid recovered at intervals after A1PI administration demonstrated time-dependent elevations of human A1PI levels with augmentation of lavage fluid antielastase activity in proportion to the content of human A1PI. Using radiolabeled A1PI as a tracer, we found that 32% of the aerosol was retained in the animals' lungs. Measurements of the rate of loss of A1PI from the lung and of the rate of appearance of human A1PI in plasma resulted in a calculated permeability of the alveolar-capillary membrane to A1PI of 3.49-6.39 X 10(-10) cm/s. Experiments using instrumented sheep allowed independent calculation of endothelial permeability to A1PI of 122-236 X 10(-10) cm/s and calculation of epithelial permeability of 4.70-4.81 X 10(-10) cm/s. Modeling of aerosol delivery of A1PI to humans using the results of these studies predicts that the ratio of plasma/alveolar levels of delivered A1PI will be 0.024, and that aerosolization of 175 mg A1PI/d will result in an A1PI alveolar fluid level of 1.0 mg/ml. Aerosol administration of A1PI may provide an efficient method of augmenting alveolar antiprotease levels.

Aerosols↗

PubMedDate not supplied

Treatment of chronic otitis externa with Trichophyton, Oidiomycetes, Epidermophyton antigen.

Chronic otitis externa may be a sensitivity (dermatophytid) reaction from a distant pathogenic superficial fungal infection, eg, tinea pedis and monilial vaginitis, which are often difficult to eradicate. Skin testing is done with a combined antigenic extract of TOE (Trichophyton; Oidiomycetes, ie, Monilia or Candida albicans; and Epidermophyton). The serial dilution titration method of skin testing is done, and the end point of reaction is determined. Treatment is begun on a weekly basis, with subcutaneous administration of 0.3 cc of a TOE extract two dilutions weaker than the end point. Symptomatic improvement is usually noted within two to four weeks, with objective improvement within eight weeks. After a variable maintenance period, the injections are spaced at less frequent intervals.

Antigens, Fungal↗

PubMed2004

Astronaut EVA exposure estimates from CAD model spacesuit geometry.

Ongoing assembly and maintenance activities at the International Space Station (ISS) require much more extravehicular activity (EVA) than did the earlier U.S. Space Shuttle missions. It is thus desirable to determine and analyze, and possibly foresee, as accurately as possible what radiation exposures crew members involved in EVAs will experience in order to minimize risks and to establish exposure limits that must not to be exceeded. A detailed CAD model of the U.S. Space Shuttle EVA Spacesuit, developed at NASA Langley Research Center (LaRC), is used to represent the directional shielding of an astronaut; it has detailed helmet and backpack structures, hard upper torso, and multilayer space suit fabric material. The NASA Computerized Anatomical Male and Female (CAM and CAF) models are used in conjunction with the space suit CAD model for dose evaluation within the human body. The particle environments are taken from the orbit-averaged NASA AP8 and AE8 models at solar cycle maxima and minima. The transport of energetic particles through space suit materials and body tissue is calculated by using the NASA LaRC HZETRN code for hadrons and a recently developed deterministic transport code, ELTRN, for electrons. The doses within the CAM and CAF models are determined from energy deposition at given target points along 968 directional rays convergent on the points and are evaluated for several points on the skin and within the body. Dosimetric quantities include contributions from primary protons, light ions, and electrons, as well as from secondary brehmsstrahlung and target fragments. Directional dose patterns are displayed as rays and on spherical surfaces by the use of a color relative intensity representation.

Astronauts↗

PubMed2004

Localization of epidermal hyaluronan in the foot pads of the North American raccoon (Procyon lotor).

The localization of the epidermal hyaluronan in the digital foot pads of the North American raccoon (Procyon lotor) was examined by light and electron microscopic histochemical methods. The thick epidermis contained five epidermal layers composed of typical keratinocytes. In the stratum basale and stratum spinosum, hyaluronic acid was clearly detectable at cytoplasmic processes, in close vicinity to the surface coat of the plasma membrane, and/or in the intercellular space between the basal and spinous cells. The results suggest that epidermal hyaluronan that fills the intercellular space may particularly control water maintenance in the epidermis of the raccoon digital pads to guarantee the optimal mechanoreceptive function of the very specific and sensitive sensoric subepidermal equipment in this mammalian species.

Animals↗

PubMed1988

Metopic sutural closure in the human skull.

The present study reveals the presence in the sutural area of secondary cartilage, assuring the passive growth of the bones and undergoing an endochondral ossification, but without playing a direct role in the synostosis. The chondroid tissue is responsible for the growth of each frontal bone towards the other and constitutes the first bridge of union between the two bones. It is the most important finding in this study, which provides a description of the closure of the metopic suture and of the maintenance of an open sutural space by a process of active resorption. This new knowledge will help to understand better the whole process of suture closure and its pathology.

Cartilage↗

PubMed1989

Immune network theory.

Theoretical ideas have played a profound role in the development of idiotypic network theory. Mathematical models can help in the precise translation of speculative ideas into quantitative predictions. They can also help establish general principles and frameworks for thinking. Using the idea of shape space, criteria were introduced for evaluating the completeness and overlap in the antibody repertoire. Thinking about the distribution of clones in shape space naturally leads to considerations of stability and controllability. An immune system which is too stable will be sluggish and unresponsive to antigenic challenge; one which is unstable will be driven into immense activity by internal fluctuations. This led us to postulate that the immune system should be stable but not too stable. In many biological contexts the development of pattern requires both activation and inhibition but on different spatial scales. Similar ideas can be applied to shape space. The principle of short-range activation and long-range inhibition translates into specific activation and less specific inhibition. Application of this principle in model immune systems can lead to the stable maintenance of non-uniform distributions of clones in shape space. Thus clones which are useful and recognize antigen or internal images of antigen can be maintained at high population levels whereas less useful clones can be maintained at lower population levels. Pattern in shape space is a minimal requirement for a model. Learning and memory correspond to the development and maintenance of particular patterns in shape space. Representing antibodies by binary strings allows one to develop models in which the binary string acts as a tag for a specific molecule or clone. Thus models with huge numbers of cells and molecules can be developed and analyzed using computers. Using parallel computers or finite state models it should soon be feasible to study model immune systems with 10(5) or more elements. Although idiotypic networks were the focus of this paper, these modeling strategies are general and apply equally well to non-idiotypic models. Using bit string or geometric models of antibody combining sites, the affinity of interaction between any two molecules, and hence the connections in a model idiotypic network, can be determined. This approach leads to the prediction of a phase transition in the structure of idiotypic networks. On one side of the transition networks are small localized structures much as might be predicted by clonal selection and circuit ideas.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Reactions↗

PubMed1994

Nutrition in space: lessons from the past applied to the future.

From the basic impact of nutrient intake on health maintenance to the psychosocial benefits of mealtime, the role of nutrition in space is evident. In this discussion, dietary intake data from three space programs, Apollo, Space Shuttle, and Skylab, are presented. Data examination reveals that energy and fluid intakes are almost always lower than predicted. Nutrition in space has many areas of impact, including provision of required nutrients and maintenance of endocrine, immune, and musculoskeletal systems. Long-duration missions will require quantitation of nutrient requirements for maintenance of health and protection against the effects of microgravity. Psychosocial aspects of nutrition will also be important for more productive missions and crew morale. Realization of the full role of nutrition during spaceflight is critical for the success of extended-duration missions. Research conducted to determine the impact of spaceflight on human physiology and subsequent nutritional requirements will also have direct and indirect applications in Earth-based nutrition research.

Diet↗

PubMedDate not supplied

Metabolic assessments during extra-vehicular activity.

Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha' (ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

Adult↗

PubMed1981

Comparison of daily and alternate-day prednisone during chronic maintenance therapy: a controlled crossover study.

To determine if dose spacing of low dose chronic suppressive corticosteroid therapy would result in different effects on circulating T lymphocytes and hypothalamic-pituitary-adrenal (HPA) axis suppression, a crossover trial of two maintenance steroid regimens was performed. Twenty stable renal allograft recipients were treated for 6 mo with daily prednisone (DS) and then the same patients were abruptly converted to alternate-day prednisone (ADS) for another 6 mo. Total prednisone dosage was identical during the 6-mo study periods and only dose spacing differed. Both circulating T lymphocyte numbers and responsiveness to mitogens were less on the DS regimen. Patients gained weight on DS and lost weight on ADS. Five of the 20 patients developed infections on DS. However, HPA suppression was not different on the two regimens. These findings suggest that dose spacing alters the immunosuppressive and metabolic response to prednisone, even at low dose.

Body Weight↗

PubMed1993

Earthbound applications for NASA's physician workstation.

The dream of a space probe to Mars or an astronaut colony on the moon persists. Despite years of setbacks and delays, NASA continues to lay the foundation for a new frontier in space. The necessity of a self contained health maintenance facility is an integral part of this stellar venture. As a subsystem of this health maintenance facility, the physician or astronaut workstation was envisioned as the vehicle of interface between the computer resources of the space station and the care provider. Our efforts to define and build this interface have resulted in a series of programs which can now be tested and refined using earth-based applications. The modules which have dual-use application from the NASA workstation include: patient scheduling and master patient index, pharmacy, laboratory, medical library, problem list/progress notes, and digital medical records. Our current plan is to develop these tools as objects that can be assembled in a variety of configurations. This will allow the technology to be used by the private sector where each doctor can select the starting point of his outpatient office system and add modules as he makes progress in system integration and training.

Aerospace Medicine↗

PubMed1996

Clinical aspects of the control of plasma volume at microgravity and during return to one gravity.

Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.

Adaptation, Physiological↗

PubMed2005

Pollen and seed dispersal among dispersed plants.

The ecological significance of spacing among plants in contributing to the maintenance of species richness, particularly in tropical forests, has received considerable attention that has largely focussed on distance- and density-dependent seed and seedling mortality. More recently it has become apparent that plant spacing is also relevant to pollination, which often constrains seed production. While seed and seedling survival is reduced at high conspecific densities, pollination success, by contrast, is positively correlated to local conspecific density. Distance-dependent mechanisms acting on pollination and seed production have now been described for a variety of plants, with relatively isolated plants or fragmented populations generally suffering reduced fecundity due to pollen limitation. Yet there is considerable variability in the vulnerability of plant species to pollination failure, which may be a function of breeding system, life history, the pollination vector, the degree of specialisation among plants and their pollinators, and other indirect effects of habitat change acting on plants or pollinators. As reduced tree densities and population fragmentation are common outcomes of anthropogenically altered landscapes, understanding how pollination processes are affected in such degraded landscapes can inform effective conservation and management of remaining natural areas.

Animals↗

PubMed2000

The normal distribution and projections of constitutive NADPH-d/NOS neurons in the brainstem vestibular complex of the rat.

The vestibular system is a highly conserved sensory system in vertebrates that is largely responsible for maintenance of one's orientation in space, posture, and balance and for visual fixation of objects during motion. In light of the considerable literature indicating an involvement of nitric oxide (NO) in sensory systems, it is important to determine whether NO is associated with vestibular pathways. To study the relationship of NO to vestibular pathways, we first examined the normal distribution of constitutive NADPH-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS), in the vestibular complex (VC) and then examined its association with selected vestibular projection neurons. Survey of the four major vestibular nuclei revealed that only the medial vestibular nucleus contained significant numbers of perikarya stained for NADPH-d/NOS. By contrast, all the vestibular nuclei contained a network of fine processes that stained positive for NADPH-d, although the density of this network varied among the individual nuclei. To determine whether NADPH-d/NOS neurons project to vestibular efferent targets, injections of the retrograde tracer Fluoro-Gold were made into known targets of second-order vestibular neurons. Vestibular neurons containing constitutive NADPH-d/NOS were found to project predominantly to the oculomotor nucleus. A small number of neurons also participate in vestibulothalamic and intrinsic vestibular connections. These results indicate that NADPH-d/NOS neurons are prevalent in the MVN and that a subpopulation of these neurons project to the oculomotor complex. Nitric oxide is probably released locally from axons located throughout the vestibular complex but may play a particularly important role in vestibulo-ocular pathways.

Animals↗

PubMed1996

(i, i + 4) Ion pairs stabilize helical peptides derived from smooth muscle caldesmon.

The central region of smooth muscle caldesmon contains 10 repeats of a 13-amino-acid residue motif that is rich in charged side chains. This region has been predicted to have a strong alpha-helical propensity, and the helical structure was thought to be stabilized by the interactions between oppositely charged side chains of residues at positions i and i + 4 (Wang, C.-L. A., Chalovich, J.M., Graceffa, P., Lu, R.C., Mabuchi, K, and Stafford, W.F., J.Biol. Chem. 266, 13958-13963, 1991). Two synthetic peptides corresponding to these repeats, each containing 25 and 60 amino acid residues, indeed assume an alpha-helical conformation that is stable over a wide range of salt concentration and pH, and exhibit a typical helix-coil transition upon heating. Most significantly, when the amino acid sequence of the 25-mer is randomized without losing the i-to-i + 4 ion pairs, the peptide maintains a helical content comparable to that of the wild-type peptide, whereas another peptide variant with a sequence rearranged to eliminate all i-to-(i + 4) ion pairs has much less helicity, suggesting that specific interactions between residues with (i,i + 4) spacings are important determinants for the maintenance of secondary structure in this region of caldesmon.

Amino Acid Sequence↗

PubMed1993

Cell-matrix interactions in liver.

Studies of cell-matrix interaction in liver have demonstrated the biological impact of extracellular matrix on the structure and function of liver cells, both parenchymal and mesenchymal. Much of the work involves cell culture models, in which either hepatocytes or non-parenchymal liver cells are plated on various extracellular matrix proteins and the expression of tissue-specific function is assessed. The data suggest that a basement membrane-like matrix exists within the perisinusoidal space and is critical to the maintenance of normal liver function. There are reservations concerning the accuracy of cell-culture models with respect to the intact liver, in that the precise composition and structure of this matrix still is uncertain. Nonetheless, work to date has added a new dimension to the role of the extracellular matrix of the normal liver and a new appreciation of the potential impact of pathologically altered matrix ('fibrosis') in liver disease.

Amino Acid Sequence↗

PubMed1980

The distribution of 125I-metrizamide and 125I-diatrizoate between blood, brain and cerebrospinal fluid in the rabbit.

The entry of 125I-metrizamide and of 125I-diatrizoate from blood into brain has been studied in rabbits. The blood-brain barrier is very tight to both molecules, all cerebral regions having spaces between 0.5 and 2% after maintenance of constant blood levels for 4 h. In extraneural tissues both compounds appear to distribute in extracellular fluid except for accumulation of metrizamide by the liver and perhaps the small intestine. Profiles of radioactivity through cerebral gray matter have been obtained following ventriculocisternal perfusion of artificial cerebrospinal fluid containing 125I-metrizamide. The nature of these profiles and their behavior with time suggest that metrizamide passes through gray matter by simple diffusion, that it is largely distributed in the extracellular fluid and that bake movement across the blood-brain barrier is small.

Animals↗

PubMed1981

Analysis of the ouabain-induced increase in transepithelial electrical resistance in the goldfish intestinal mucosa.

1. The ouabain-induced increase in transmural resistance of goldfish intestinal mucosa stripped free from underlying muscular layers is analysed by comparing the resistance increase in normal and in low chloride saline, the resistance increased induced by anaerobic conditions and the resistance increase provoked by hypotonicity. 2. It is concluded that the collapse of the lateral intercellular space is the prime reason for the resistance increase and that the lateral intercellular space is maintained dilated by a ouabain-sensitive solute transport mechanism. 3. This mechanism can be either a rheogenic or a neutral Na/K-pump. In the latter case additional conditions have to be specified concerning values for ion concentrations in the lateral intercellular space and in the unstirred layer adjacent to the luminal membrane. 4. There are no indications for a chloride dependent mechanism involved in the maintenance of the width of the lateral intercellular spaces in the goldfish intestinal mucosa.

Animals↗