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PubMed1987

Social determinants of disease.

The primary purpose for identifying psychosocial risk factors is to prevent disease and disease complications. For 30 years, we have been doing research in this field and have been successful in identifying such risk factors as Type A behavior, social isolation, stressful life events, and various psychological patterns. However, our success in using this information to help prevent disease has been much more limited. One reason for this limited success is that we have focused virtually all of our attention on the study of individuals and almost no attention on the social environment within which people live. There are two major limitations of such a one-to-one approach: it is difficult for people to change their behavior and their life situation and even if some people do change, others enter the "at risk" population because no action has been taken to change those forces in society that stimulated the problem in the first place. In discussing the social determinants of disease, it is important that we develop a new approach that permits us to study not only individuals but also the social environment. An example of this approach is provided by researchers who were successful in preventing infectious diseases. The work of these researchers focused not on clinical entities or on individuals but on the environment. This resulted in a disease classification system that included concepts such as air-borne, food-borne, water-borne, and vector-borne diseases. We have no such system for the study of non-infectious diseases. Considerable data already are available to help us to think about such a new classification system.(ABSTRACT TRUNCATED AT 250 WORDS)

Educational Status↗
PubMed1996

Survival at high altitudes: wheel-well passengers.

There have been 10 specific "wheel-well" passenger stowaway flights (the wheel-well area was entered just before take-off) documented in the N.Y. Times between 1947-1993. Five stowaways survived flights encompassing altitudes as high as 39,000 feet, with six dying in the process (one flight had two stowaways, one fatal, one surviving). Three Douglas DC-8 and four Boeing 707 aircraft, plus a Caravelle, an unknown jet, and a piston airliner were involved. Several of the wheel-well flight stowaways were reportedly politically motivated to attempt these international flights. This paper describes the unpressurized flight environment and the physiology that enabled human survival under conditions of extreme hypoxia and cold, inducing a virtual "hibernative" state. It is likely that similar attempts will continue, and alert airport security preventive measures are indicated.

Adolescent↗
PubMed2004

Do robots need to sleep?

The present paper exposes algorithmic results providing a vision about sleep functions which complements biological theory and experiments. Derived from the algorithmic theory of information, the theory of adaptation aims at quantifying how an inherited or acquired piece of knowledge helps individuals to survive. It gives a scale of complexity for survival problems and proves that some of them can only be solved by a dynamical management of memory associating continuous learning and forgetting methods. In this paper we explain how a virtual robot "Picota" has been designed to simulate the behavior of a living hen. In order to survive in its synthetical environment, our robot must recognize good seeds from bad ones, and should take rest during night periods. Within this frame, and facing the rapid evolution of to-be-recognized forms, the best way to equilibrate the energetic needs of the robot and ensure survival is to use the nightly rest to reorganize the pieces of data acquired during the daily learning, and to trash the less useful ones. Thanks to this time sharing, the same circuits can be used for both daily learning and nightly forgetting and thus costs are lower; however, this also forces the system to "paralyse" the virtual robot, and therefore the night algorithm is reminiscent of paradoxical (REM) sleep. The algorithm of the robot takes advantage of the alternation between wakefulness or activity and the rest period. This diagram quite accurately recalls the REM period. In the future, the convergence between the neurophysiology of sleep and the theory of complexity may give us a new line of research in order to elucidate sleep functions.

Algorithms↗
PubMed2001

A comparison of the GroE chaperonin requirements for sequentially and structurally homologous malate dehydrogenases: the importance of folding kinetics and solution environment.

Escherichia coli malate dehydrogenase (EcMDH) and its eukaryotic counterpart, porcine mitochondrial malate dehydrogenase (PmMDH), are highly homologous proteins with significant sequence identity (60%) and virtually identical native structural folds. Despite this homology, EcMDH folds rapidly and efficiently in vitro and does not seem to interact with GroE chaperonins at physiological temperatures (37 degrees C), whereas PmMDH folds much slower than EcMDH and requires these chaperonins to fold to the native state at 37 degrees C. Double jump experiments indicate that the slow folding behavior of PmMDH is not limited by proline isomerization. Although the folding enhancer glycerol (<5 m) does not alter the renaturation kinetics of EcMDH, it dramatically accelerates the spontaneous renaturation of PmMDH at all temperatures tested. Kinetic analysis of PmMDH renaturation with increasing glycerol concentrations suggests that this osmolyte increases the on-pathway kinetics of the monomer folding to assembly-competent forms. Other osmolytes such as trimethylamine N-oxide, sucrose, and betaine also reactivate PmMDH at nonpermissive temperatures (37 degrees C). Glycerol jump experiments with preformed GroEL.PmMDH complexes indicate that the shift between stringent (requires ATP and GroES) and relaxed (only requires ATP) complex conformations is rapid (<3-5 s). The similarity in irreversible misfolding kinetics of PmMDH measured with glycerol or the activated chaperonin complex (GroEL.GroES.ATP) suggests that these folding aids may influence the same step in the PmMDH folding reaction. Moreover, the interactions between glycerol-induced PmMDH folding intermediates and GroEL.GroES.ATP are diminished. Our results support the notion that the protein folding kinetics of sequentially and structurally homologous proteins, rather than the structural fold, dictates the GroE chaperonin requirement.

Amino Acid Sequence↗
PubMed1986

Effect of amoxicillin-clavulanate and cephradine on the fecal flora of healthy volunteers not exposed to a hospital environment.

A 7-day course of either cephradine or amoxicillin-clavulanate treatment caused no significant change in fecal flora composition, except that staphylococci were virtually eliminated in both groups. Some amoxicillin-resistant coliforms were isolated after treatment in both groups, but cephradine- or amoxicillin-clavulanate-resistant coliforms were rarely isolated.

Amoxicillin↗
PubMed1996

Microgravity environment conditions--from Spacelab to the International Space Station.

Since the early eighties Spacelab has been the primary platform for experimentation under the state of virtually weightlessness (microgravity) in spaceflight. The International Space Station (ISS), planned to be operational by end of the century, will extend the scientific opportunities of Spacelab in many respects, e.g. by offering the opportunity for long lasting and continuous microgravity investigations. Stringent design and operational requirements have been defined for the ISS to keep residual accelerations as low as possible. These guidelines are based on investigations (Langbein, Alexander, and others) of upper allowable residual accelerations for most physical phenomena involved in space experiments. To meet these requirements, severe perturbations from operating the Station (reboosts to correct the orbit, docking maneuvers, etc.) are grouped outside dedicated microgravity-experiment phases. For the microgravity-phases, stringent criteria on upper limits of residual accelerations are specified. Recent predictions for the present ISS concept indicate that additional measures have to be taken. The results of the microgravity-studies on Spacelab missions (D-1, D-2, etc.) contain a wealth of valuable information for developing optimal design principles. Passive measures must be applied first ('perturbation reduction at the source' and timelining) before considering complex active isolation concepts which should be reserved for high sensitive investigations only.

Acceleration↗
PubMed2002

Evaluation of a virtual reality simulator in sustainment training.

Is there a better way to train and prepare our health care personnel to function in a chemical biological environment while continuing to provide for patient care in a variety of healthcare settings? The purpose of this pilot work was to compare the effectiveness and user satisfaction of the Cath-Sim Intravenous Training System to the traditional IV arm model for teaching and achieving competence at IV insertion while in Mission-Oriented Protective Posture level 4 for Army medical personnel. Grounded in adult psychomotor learning principles and in an established evaluation model, participants were tested on both the traditional IV arm and Cath-Sim models and then allowed to practice on each model while at Mission-Oriented Protective Posture level 4. One week later, participants were again tested on both models. Outcome measures included (1) a computer-generated score sheet measuring time to success and criterion success/nonsuccess on the Cath-Sim; (2) time and success rating for IV insertion on the IV arm model; and (3) satisfaction evaluations completed by the participants. There were conflicting evaluation scores for recommending one model over the other. Participants felt that there was some benefit to each model depending on user, setting, and purpose.

Biological Warfare↗
PubMed1999

Spatial- and task-dependent neuronal responses during real and virtual translocation in the monkey hippocampal formation.

Neuropsychological data in humans demonstrated a pivotal role of the medial temporal lobe, including the hippocampal formation (HF) and the parahippocampal gyrus (PH), in allocentric (environment-centered) spatial learning and memory. In the present study, the functional significance of the monkey HF and PH neurons in allocentric spatial processing was analyzed during performance of the spatial tasks. In the tasks, the monkey either freely moved to one of four reward areas in the experimental field by driving a cab that the monkey rode (real translocation task) or freely moved a pointer to one of four reward areas on the monitor (virtual translocation task) by manipulating a joystick. Of 389 neurons recorded from the monkey HF and PH, 166 had place fields that displayed increased activity in a specific area in the experimental field and/or on the monitor (location-differential neurons). More HF and PH neurons responded in the real translocation task. These neurons had low mean spontaneous firing rates (0.96 spikes/sec), similar to those of rodent HF place cells. The remaining nonresponsive neurons had significantly higher mean firing rates (8. 39 spikes/sec), similar to interneurons or theta cells in the rodent HF. Furthermore, most location-differential neurons showed different responses in different tasks. These results suggest that the HF and PH are crucial in allocentric information processing and, moreover, that the HF can encode different reference frames that are context or task-dependent. This may be the neural basis of episodic memory.

Animals↗
PubMed1969

Iodination of insulin in aqueous and organic solvents.

1. The iodination of insulin was studied under various experimental conditions in aqueous media and in some organic solvents, by measuring separately the uptake of iodine by the four tyrosyl groups and the relative amounts of monoiodotyrosine and di-iodotyrosine that are formed. In aqueous media from pH1 to pH9 the iodination occurs predominantly on the tyrosyl groups of the A chain. Some organic solvents increase the iodine uptake of the B-chain tyrosyl groups. Their efficacy in promoting iodination of Tyr-B-16 and Tyr-B-26 is in the order: ethylene glycol and propylene glycol approximately methanol and ethanol>dioxan>8m-urea. 2. It is suggested that each of the four tyrosyl groups in insulin has a different environment: Tyr-A-14 is fully exposed to the solvent; Tyr-A-19 is sterically influenced by the environmental structure, possibly by the vicinity of a disulphide interchain bond; Tyr-B-16 is embedded into a non-polar area whose stability is virtually independent of the molecular conformation; Tyr-B-26 is probably in a situation similar to Tyr-B-16 with the difference that its non-polar environment depends on the preservation of the native structure.

Chemical Phenomena↗
PubMed1992

Molecular mechanisms of genetic adaptation to xenobiotic compounds.

Microorganisms in the environment can often adapt to use xenobiotic chemicals as novel growth and energy substrates. Specialized enzyme systems and metabolic pathways for the degradation of man-made compounds such as chlorobiphenyls and chlorobenzenes have been found in microorganisms isolated from geographically separated areas of the world. The genetic characterization of an increasing number of aerobic pathways for degradation of (substituted) aromatic compounds in different bacteria has made it possible to compare the similarities in genetic organization and in sequence which exist between genes and proteins of these specialized catabolic routes and more common pathways. These data suggest that discrete modules containing clusters of genes have been combined in different ways in the various catabolic pathways. Sequence information further suggests divergence of catabolic genes coding for specialized enzymes in the degradation of xenobiotic chemicals. An important question will be to find whether these specialized enzymes evolved from more common isozymes only after the introduction of xenobiotic chemicals into the environment. Evidence is presented that a range of genetic mechanisms, such as gene transfer, mutational drift, and genetic recombination and transposition, can accelerate the evolution of catabolic pathways in bacteria. However, there is virtually no information concerning the rates at which these mechanisms are operating in bacteria living in nature and the response of such rates to the presence of potential (xenobiotic) substrates. Quantitative data on the genetic processes in the natural environment and on the effect of environmental parameters on the rate of evolution are needed.

Adaptation, Biological↗
PubMed2003

Finger-length ratios in female monozygotic twins discordant for sexual orientation.

The second to fourth finger digit ratio (2D:4D ratio) is a sex-dimorphic characteristic in humans that may reflect relative levels of first trimester prenatal sex hormones. Low interdigital ratio has been associated with high levels of androgens. It has been reported in unrelated women that low 2D:4D ratio is associated with lesbian sexual orientation, but because of the nature of those samples, it was not possible to conclude whether lower ratio (and hypothetically, higher androgen levels) in lesbians are due to differences in genetics as opposed to differences in environment. To test the hypothesis that low 2D:4D in lesbians is due to differences in environment, interdigital ratio data were analyzed in a sample of female monozygotic (MZ) twins discordant for sexual orientation (1 twin was lesbian, the other was heterosexual; n = 7 pairs). A control group of female MZ twins concordant for sexual orientation (both twins were lesbian) was used as a comparison (n = 5 pairs). In the twins discordant for sexual orientation, the lesbian twins had significantly lower 2D:4D ratios on both the right and left hands than their heterosexual cotwins. There were no significant differences for either hand in the twins concordant for sexual orientation. Because MZ twins share virtually the same genes, differences in 2D:4D ratio suggest that low 2D:4D ratio is a result of differences in prenatal environment.

Adult↗
PubMed1996

Toward virtual anatomy: a stereoscopic 3-D interactive multimedia computer program for cranial osteology.

Advances in computer visualization and user interface technologies have enabled development of "virtual reality" programs that allow users to perceive and to interact with objects in artificial three-dimensional environments. Such technologies were used to create an image database and program for studying the human skull, a specimen that has become increasingly expensive and scarce. Stereoscopic image pairs of a museum-quality skull were digitized from multiple views. For each view, the stereo pairs were interlaced into a single, field-sequential stereoscopic picture using an image processing program. The resulting interlaced image files are organized in an interactive multimedia program. At run-time, gray-scale 3-D images are displayed on a large-screen computer monitor and observed through liquid-crystal shutter goggles. Users can then control the program and change views with a mouse and cursor to point-and-click on screen-level control words ("buttons"). For each view of the skull, an ID control button can be used to overlay pointers and captions for important structures. Pointing and clicking on "hidden buttons" overlying certain structures triggers digitized audio spoken word descriptions or mini lectures.

Adult↗
PubMed1998

The virtual anatomy practical: a stereoscopic 3D interactive multimedia computer examination program.

Continuing advances in computer visualization and interface technologies have enabled development of "virtual reality" programs that allow users to perceive and to interact with objects in artificial three-dimensional environments. Such technologies were used to create an image database and program for administering a practical examination in human gross anatomy. Stereoscopic image pairs of prepared laboratory dissections were digitized from multiple views of the thorax, abdomen, pelvic region, and upper and lower extremities. For each view, the stereo pairs were interlaced into a single, field-sequential stereoscopic picture using an image processing program. The resulting color-corrected, interlaced image files were organized in a database stored on a large-capacity hard disk. Selected views were provided with structural identification pointers and letters (A and B). For each view, appropriate two-part examination questions were spoken by a human narrator, digitally recorded, and saved as universal audio format files on the archival hard disk. Images and digital narration were organized in an interactive multimedia program created with a high-level multimedia authoring system. At run-time, 24-bit color 3D images were displayed on a large-screen computer monitor and observed through liquid crystal shutter goggles. A 90-second interval timer and tone were provided to give student users a time limit for each question comparable to that of a conventional practical examination. Users could control the program and select regional "subexams" using a mouse and cursor to point-and-click on screen-level control words ("buttons").

Anatomy, Regional↗
PubMed1991

Sensitive and vulnerable periods in the development of the visual system.

In advanced mammals the visual system consists of a number of parallel channels for the efficient processing of different aspects of the visual scene. Much of the basic anatomical structure of the visual pathway is constructed before birth. A wave of maturation sweeps through the system, from the eye to the visual cortex, the correct formation of connections depending on precisely timed interactions between axons and their targets. Competition between growing axons (apparently dependent on spontaneous impulse activity in those axons), cell death (partly influenced by competition between those cells' axons), axon withdrawal, trophic interactions--these and other mechanisms play a part in constructing the visual pathway and laying down basic 'maps' of the visual field before birth. Disturbances in such processes might underlie disorders of the genesis of the nervous system. At the level of the visual cortex, synaptic plasticity continues after birth and may permit cortical neurons to refine their processing capacities on the basis of information provided by the visual environment. This makes the young animal vulnerable to disturbances of visual experience early in life, which can cause virtually irreversible deficits in stereoscopic vision, visual resolution and sensitivity to contrast (amblyopia) in adult life.

Animals↗
PubMed1979

Structure and conformation of glucocorticoids.

The approaches currently available for determining the structure and conformation of glucocorticoids are reviewed. We discuss the optimization of steroid geometry based on the relative molecular energy calculated by a Westheimer equation. This method permits an extensive description of steroid molecules in a state free of external constraints and which can be assumed to correspond to the minimum internal energy. The structures, conformations, surface areas, and volumes of fifteen steroid molecules that interact with the glucocorticoid receptor have been studied. The basic structure of the A ring is a 1 alpha,2 beta-half-chair, whatever the substitutions. Rings B and C are semi-rigid chairs virtually uninfluenced by substituent groups. In contrast, the shape of the D ring depends on the nature and environment of the substituents. As to the fundamental conformation of the side chain, the steroids fall into two categories, depending on the pressure of a 17-hydroxyl group. For a given molecule, the energy changes associated with conformations of the side chain other than that corresponding to the minimum energy have also been explored. The hypothesis is formulated that receptor binding requires a particular conformation of the side chain. Finally, the overall shape of the molecule can be influenced by the summation of minor but numerous changes brought about by various substitutions, such as 11 beta-hydroxyl, which increases the convexity of the molecule. These investigations should help in elucidating structure-activity relationships for glucocorticoids. They may improve our knowledge of the interaction between these hormones and their receptor and of the molecular mechanism of glucocorticoid action.

Glucocorticoids↗
PubMed1986

Differentiation of osteoid-producing cells in vitro: possible evidence for the requirement of a microenvironment.

Periostea were dissected from 17-day-old chicken embryo calvariae, placed on millipore filters, and cultured on fluid media containing serum or on serum and plasma containing "plasma clots," in three ways: 1) with the osteogenic layer facing the filter, 2) with the osteogenic layer away from the filter, 3) folded such that the osteogenic layer was in apposition with itself within the fold. The cultures were studied histologically as well as biochemically. Periostea that were cultured folded showed differentiation of osteoblastlike cells after 2 days, and production of osteoid at day 4. Tissues cultured with the osteogenic layer away from the filter demonstrated similar osteoblastic differentiation and osteoid production. Both types of cultures exhibited an increase in histochemically detectable alkaline phosphatase activity over the 4 day culture period that was associated with osteoblasts and the osteogenic area. Periostea cultured with the osteogenic layer facing the filter produced no osteoid. In these cultures, histochemically detectable alkaline phosphatase activity decreased and virtually disappeared over the 4 day culture period. The possibility that the creation of a suitable micro-environment is required for osteodifferentiation in this culture system is discussed.

Acid Phosphatase↗
PubMed2005

Cross-modal activation of visual cortex during depth perception using auditory substitution of vision.

Previous neuroimaging studies identified multimodal brain areas in the visual cortex that are specialized for processing specific information, such as visual-haptic object recognition. Here, we test whether visual brain areas are involved in depth perception when auditory substitution of vision is used. Nine sighted volunteers were trained blindfolded to use a prosthesis substituting vision with audition both to recognize two-dimensional figures and to estimate distance of an object in a real three-dimensional environment. Using positron emission tomography, regional cerebral blood flow was assessed while the prosthesis was used to explore virtual 3D images; subjects focused either on 2D features (target search) or on depth (target distance comparison). Activation foci were found in visual association areas during both the target search task, which recruited the occipito-parietal cortex, and the depth perception task, which recruited occipito-parietal and occipito-temporal areas. This indicates that some brain areas of the visual cortex are relatively multimodal and may be recruited for depth processing via a sense other than vision.

Acoustic Stimulation↗
PubMed1985

Nuclear magnetic resonance observation and dynamics of specific amide protons in T4 lysozyme.

We have produced T4 lysozyme using a bacterial expression system which allows efficient incorporation of isotopically labeled amino acids in lysozyme. By using conditions that repress the expression of various transaminases, we have incorporated 15N-labeled amino acid into the five phenylalanine residues of the protein. The relatively large spin--spin coupling (87 +/- 3 Hz) between the 15N nucleus and the phenylalanine amide protons may then be exploited in a variety of ways to selectively observe the five phenylalanine amide proton resonances. These include a simple "echo difference" technique which displays the amide proton resonances in one dimension and a "forbidden echo" technique [Bax, A., Griffey, R. H., & Hawkins, B.L. (1983) J. Magn. Reson. 55, 301-335] which gives two-dimensional information allowing the proton and 15N chemical shifts of each amide to be determined. With these approaches, all five phenylalanine amide protons give resolved resonances. Deuterium exchange experiments demonstrate that three of the five resonances are slow to exchange (half-times of about 1 week at pH 5.5 and 4 degrees C) while the other two are rapid with complete exchange in hours or less. These observations correlate well with the secondary structure of the protein which shows three residues in alpha-helical regions and two residues in surface-exposed environments. This approach of isotopic substitution on nitrogen or carbon atoms is of general utility and should allow virtually any proton on a protein of molecular weight 20 000 or thereabout to be selectively observed.

Amides↗