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Biomedical subjects

A Paulsen

Publications and source records attributed to A Paulsen.

16 recordsLinked to original sources
PubMed2000

RhoA and rho kinase regulate the epithelial Na+/H+ exchanger NHE3. Role of myosin light chain phosphorylation.

The activity of the Na(+)/H(+) exchanger NHE3 isoform, which is found primarily in epithelial cells, is sensitive to the state of actin polymerization. Actin assembly, in turn, is controlled by members of the small GTPase Rho family, namely Rac1, Cdc42, and RhoA. We therefore investigated the possible role of these GTPases in modulating NHE3 activity. Cells stably expressing NHE3 were transiently transfected with inhibitory forms of Rac1, Cdc42, or RhoA and transport activity was assessed using microfluorimetry. NHE3 activity was not adversely affected by either dominant-negative Rac1 or Cdc42. By contrast, the inhibitory form of RhoA greatly depressed NHE3 activity, without noticeably altering its subcellular distribution. NHE3 activity was equally reduced by inhibiting p160 Rho-associated kinase I (ROK), a downstream effector of RhoA, with the selective antagonist Y-27632 and a dominant-negative form of ROK. Furthermore, inhibition of ROK reduced the phosphorylation of myosin light chain. A comparable net dephosphorylation was achieved by the myosin light chain kinase inhibitor ML9, which similarly inhibited NHE3. These data suggest that optimal NHE3 activity requires a functional RhoA-ROK signaling pathway which acts, at least partly, by controlling the phosphorylation of myosin light chain and, ultimately, the organization of the actin cytoskeleton.

Animals↗
PubMed2000

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Humans↗
PubMed1995

In vitro chick pre-cardiac explant tissue differentiation during spaceflight on SpaceHab-02.

Chick precardiac tissue explants were cultured on the 8-day mission of STS-60, space shuttle Discovery. Development of in vitro cultures of precardiac chick tissue from embryo stages 5 though 8 (H-H) were initiated during orbit and were terminated after approximately fifteen hours of 37 degree C culture. Transmission electron microscopy and tritiated thymidine studies were performed postflight. No significant differences in cell proliferation were observed between flight and ground controls. Electron-microscopic studies revealed stage 8 explants were capable of differentiation during flight in a pattern which matched ground control tissues. As anticipated, stage 7 explant tissues had differentiated to a lesser extent compared to stage 8 tissues. Interestingly, stage 7 precardiac explant flight tissue differentiation was less than ground control tissue. This difference in differentiation between flight and ground cultures was enhanced in stage 6 tissues, as high levels of myofibril organization were only seen in ground controls. Other cellular components such as Golgi apparatus, junctional complexes, and mitochondria were present and appeared normal and healthy.

Animals↗
PubMed1994

Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight.

Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

Animals↗
PubMed1994

Development of the brine shrimp Artemia is accelerated during spaceflight.

Developmentally arrested brine shrimp cysts have been reactivated during orbital spaceflight on two different Space Shuttle missions (STS-50 and STS-54), and their subsequent development has been compared with that of simultaneously reactivated ground controls. Flight and control brine shrimp do not significantly differ with respect to hatching rates or larval morphology at the scanning and transmission EM levels. A small percentage of the flight larvae had defective nauplier eye development, but the observation was not statistically significant. However, in three different experiments on two different flights, involving a total of 232 larvae that developed in space, a highly significant difference in degree of flight to control development was found. By as early as 2.25 days after reactivation of development, spaceflight brine shrimp were accelerated, by a full instar, over ground control brine shrimp. Although developing more rapidly, flight shrimp grew as long as control shrimp at each developmental instar or stage.

Animals↗
PubMed1994

Clover development during spaceflight: a model system.

The development of legume root nodules was studied as a model system for the examination of gravitational effects on plant root development. In order to examine whether rhizobial association with clover roots can be achieved in microgravity, experiments were performed aboard the KC-135 parabolic aircraft and aboard the sounding rocket mission Consort 3. Binding of rhizobia to roots and the initial stages of root nodule development successfully occurred in microgravity. Seedling germination experiments were performed in the sliding block device, the Materials Dispersion Apparatus, aboard STS-37. When significant hydration of the seeds was achieved, normal rates of germination and seedling development were observed.

Cell Differentiation↗
PubMed1994

Embryogenesis, hatching and larval development of Artemia during orbital spaceflight.

Developmental biology studies, using gastrula-arrested cysts of the brine shrimp Artemia franciscana, were conducted during two flights of the space shuttle Atlantis (missions STS-37 and STS-43) in 1991. Dehydrated cysts were activated, on orbit, by addition of salt water to the cysts, and then development was terminated by the addition of fixative. Development took place in 5 ml syringes, connected by tubing to activation syringes, containing salt water, and termination syringes, containing fixative. Comparison of space results with simultaneous ground control experiments showed that equivalent percentages of naupliar larvae hatched in the syringes (40%). Thus, reactivation of development, completion of embryogenesis, emergence and hatching took place, during spaceflight, without recognizable alteration in numbers of larvae produced. Post-hatching larval development was studied in experiments where development was terminated, by introduction of fixative, 2 days, 4 days, and 8 days after reinitiation of development. During spaceflight, successive larval instars or stages, interrupted by molts, occurred, generating brine shrimp at appropriate larval instars. Naupliar larvae possessed the single naupliar eye, and development of the lateral pair of adult eyes also took place in space. Transmission electron microscopy revealed extensive differentiation, including skeletal muscle and gut endoderm, as well as the eye tissues. These studies demonstrate the potential value of Artemia for developmental biology studies during spaceflight, and show that extensive degrees of development can take place in this microgravity environment.

Animals↗
PubMed1994

Magnetic resonance imaging evaluation of adipose tissue and muscle tissue mass in children with growth hormone (GH) deficiency, Turner's syndrome, and intrauterine growth retardation during the first year of treatment with GH.

Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of human (h) GH in 23 GH deficiency, 8 Turner's syndrome, and 14 intrauterine growth retardation prepubertal patients. They were evaluated before and 1, 3, 6, and 12 months after the onset of hGH treatment. Seven normal children were followed longitudinally as controls. During hGH treatment, a significant increase in muscle tissue and decrease in adipose tissue cross-sectional areas was observed, leading to a dramatic increase in the muscle/adipose tissue cross-sectional area ratio in each period studied. These findings remained highly significant when corrected for the small variation observed in controls. The body mass index was correlated with muscle and adipose tissue cross-sectional area at each time point (P < 0.0001). The muscle cross-sectional area increment correlated with the first year height velocity (P < 0.01). This study indicates that in children with and without GH deficiency, hGH therapy induces rapid and intense variation of muscle and adipose tissue mass, and that magnetic resonance imaging can be used to study some aspects of the metabolic actions of GH.

Adipose Tissue↗
PubMed1993

Virus protein assembly in microgravity.

The coat of polyomavirus is composed of three proteins that can self-assemble to form an icosahedral capsid. VP1 represents 75% of the virus capsid protein and the VP1 capsomere subunits are capable of self assembly to form a capsid-like structure. Ground-based and orbiter studies were conducted with VP1 protein cloned in an expression vector and purified to provide ample quantities for capsomere-capsid assembly. Flight studies were conducted on STS-37 on April 5-9, 1991. Assembly initiated when a VP1 protein solution was interfaced with a Ca+2 buffer solution (pH 5.0). After four days a second alignment terminated the assembly process and allowed for glutaraldehyde fixation. Flight and ground-based samples were analyzed by electron microscopy. Ground-based experiments revealed the assembly of VP1 into capsid-like structures and a heterogenous size array of capsomere subunits. Samples reacted in microgravity, however, showed capsomeres of a homogenous size, but lack of capsid-like assembly.

Animals↗
PubMed1992

Scanning electron microscope observations of brine shrimp larvae from space shuttle experiments.

Brine shrimp are encysted as gastrula stage embryos, and may remain dehydrated and encysted for years without compromising their viability. This aspect of brine shrimp biology is desirable for studying development of animals during space shuttle flight, as cysts placed aboard a spacecraft may be rehydrated at the convenience of an astronaut, guaranteeing that subsequent brine shrimp development occurs only on orbit and not on the pad during launch delays. Brine shrimp cysts placed in 5 ml syringes were rehydrated with salt water and hatched during a 9 day space shuttle mission. Subsequent larvae developed to the 8th larval stage in the sealed syringes. We studied the morphogenesis of the brine shrimp larvae and found the larvae from the space shuttle experiments similar in rate of growth and extent of development, to larvae grown in sealed syringes on the ground. Extensive differentiation and development of embryos and larvae can occur in a microgravity environment.

Animals↗
PubMed1990

Chromosome aberrations induced in vitro in human lymphocytes by monoenergetic 2.5 MeV neutrons and 60Co gamma rays.

The aim of the present experiments was to evaluate the relative biological effectiveness (RBE) of monoenergetic 2.5 MeV neutrons, in view of the scarcity of data on the RBE of neutrons in this energy range. Human peripheral blood lymphocytes from two donors were exposed to doses of neutrons ranging from 0.005 Gy to 0.5 Gy. Gamma rays produced by a telecobalt therapy unit were used as reference radiation. RBE values were of the same order of magnitude, whatever was the model of the dose-response curve chosen for the neutrons (linear or linear-quadratic). As expected, RBE increased markedly with decreasing doses and went beyond 30 at a dose level of 0.2 Gy. The present results, compared with RBE values obtained with neutrons of higher energy (6.5, 14 and 21 MeV), confirm that low energy neutrons are more effective in producing genetic effects, especially at low doses.

Adult↗
PubMed1989

beta-Xyloside effects on basal lamina structure and anionic site distribution the embryonic mouse submandibular salivary gland.

beta-D-Xyloside is a proteoglycan biosynthesis inhibitor. Previous studies on embryonic salivary glands have demonstrated that 0.5 mM beta-xyloside (1) inhibits proteoglycan synthesis by 50%; (2) severely depresses sulphated glycosaminoglycan deposition at the basal epithelial surface, and (3) dramatically inhibits epithelial branching morphogenesis. Electron microscopy revealed a conventional three-layered basal lamina that is altered in the presence of beta-xyloside by a 35% reduction in the number of tannic acid-resolved particles in the lamina densa. Basal lamina anionic sites, resolved with ruthenium red (RR) and polyethyleneimine (PEI) cationic probes, were also reduced in the presence of beta-xyloside. PEI particles were reduced by 28%, and RR particles by 24%, per two-dimensional unit of basal lamina. These beta-xyloside effects on anionic sites are consistent with an hypothesis that sulphated glycosaminoglycans account for 50% of the basal lamina anionic sites and a predicted 25% decrease in anionic sites in the presence of beta-xyloside.

Animals↗
PubMed1986

Basal lamina anionic sites in the embryonic submandibular salivary gland: resolution and distribution using ruthenium red and polyethyleneimine as cationic probes.

The basal lamina of the embryonic submandibular epithelium is a dynamic compartment of the extracellular matrix required for branching morphogenesis. A transmission electron microscopy (TEM) structural analysis of the basal lamina, at a time of intense branching activity, was conducted, comparing standard glutaraldehyde-fixed preparations with ones that included tannic acid in the primary fixative, and comparing anionic site resolution and distribution with two cationic probes, ruthenium red (RR) and polyethyleneimine (PEI). Standard TEM revealed a conventional basal lamina structure, with a lamina densa, a lamina lucida interna and a lamina lucida externa. Fine filaments emanated from the lamina densa, traversing both lamina lucidae. Tannic acid revealed approximately 35 nm diameter electron-dense particles in the lamina densa with a spacing repeat of approximately 45 nm. Basal lamina anionic sites were resolved as approximately 26 nm diameter RR-particles and approximately 50 nm diameter PEI-particles, present in the lamina lucida interna and associated with the lamina lucida externa. RR-particle linear spacing was 70 nm in the externa and 50 nm in the interna, while the PEI-particle spacing repeat was 90 nm in both compartments. Binding of both probes was blocked by testicular hyaluronidase or chondroitinase treatment, a result suggesting that the anionic sites were chondroitin sulfate proteoglycan, hyaluronic acid, or both. The greater particle spacing observed with PEI was not simply a physical limitation resulting from the average PEI particle diameter being almost twice that of RR particles, since PEI-resolved anionic sites on interstitial collagen were much more closely spaced (approximately 60 nm) than RR-resolved sites (approximately 105 nm).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗