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PubMed2003

The SOS-LUX-LAC-FLUORO-Toxicity-test on the International Space Station (ISS).

In the 21st century, an increasing number of astronauts will visit the International Space Station (ISS) for prolonged times. Therefore it is of utmost importance to provide necessary basic knowledge concerning risks to their health and their ability to work on the station and during extravehicular activities (EVA) in free space. It is the aim of one experiment of the German project TRIPLE-LUX (to be flown on the ISS) to provide an estimation of health risk resulting from exposure of the astronauts to the radiation in space inside the station as well as during extravehicular activities on one hand, and of exposure of astronauts to unavoidable or as yet unknown ISS-environmental genotoxic substances on the other. The project will (i) provide increased knowledge of the biological action of space radiation and enzymatic repair of DNA damage, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation and (iii) examine the space craft milieu with highly specific biosensors. For these investigations, the bacterial biosensor SOS-LUX-LAC-FLUORO-Toxicity-test will be used, combining the SOS-LUX-Test invented at DLR Germany (Patent) with the commercially available LAC-FLUORO-Test. The SOS-LUX-Test comprises genetically modified bacteria transformed with the pBR322-derived plasmid pPLS-1. This plasmid carries the promoterless lux operon of Photobacterium leiognathi as a reporter element under control of the DNA-damage dependent SOS promoter of ColD as sensor element. This system reacts to radiation and other agents that induce DNA damages with a dose dependent measurable emission of bioluminescence of the transformed bacteria. The analogous LAC-FLUORO-Test has been developed for the detection of cellular responses to cytotoxins. It is based on the constitutive expression of green fluorescent protein (GFP) mediated by the bacterial protein expression vector pGFPuv (Clontech, Palo Alto, USA). In response to cytotoxic agents, this system reacts with a dose-dependent reduction of GFP-fluorescence. Currently, a fully automated miniaturized hardware system for the bacterial set up, which includes measurements of luminescence and fluorescence or absorption and the image analysis based evaluation is under development. During the first mission of the SOS-LUX-LAC-FLUORO-Toxicity-Test on the ISS, a standardized, DNA-damaging radiation source still to be determined will be used as a genotoxic inducer. A panel of recombinant Salmonella typhimurium strains carrying either the SOS-LUX plasmid or the fluorescence-mediating lac-GFPuv plasmid will be used to determine in parallel on one microplate the genotoxic and the cytotoxic action of the applied radiation in combination with microgravity. Either in addition to or in place of the fluorometric measurements of the cytotoxic agents, photometric measurements will simultaneously monitor cell growth, giving additional data on survival of the cells. The obtained data will be available on line during the TRIPLE-LUX mission time. Though it is the main goal during the TRIPLE-LUX mission to measure the radiation effect in microgravity, the SOS-LUX-LAC-FLUORO-Toxicity-test in principle is also applicable as a biomonitor for the detection and measurement of genotoxic substances in air or in the (recycled) water system on the ISS or on earth in general.

Cosmic Radiation↗
PubMed1999

Signal transduction in T lymphocytes--a comparison of the data from space, the free fall machine and the random positioning machine.

In this paper we discuss the effect of microgravity on T cells and we present the data of studies with two new machines for 0 g simulations. Several experiments in space show that mitogenic T cell activation is lost at 0 g. Immunocytochemistry indicates that such effect is associated with changes of the cytoskeleton. Biochemical studies suggest that the lack of expression of the interleukin-2 receptor is one of the major causes of the loss of activity. In fact, interleukin-2 is the third signal required for full activation. In order to deepen our investigations we are now working with the free-fall machine, FFM, invented by D. Mesland, and with the random positioning machine, RPM, or three-dimensional clinostat, developed by T. Hoson. The FFM produces periods of free-fall lasting approximately 800 ms followed by bounces of 15-30 g lasting 45-60 ms. The RPM eliminates the effect of gravity by rotating biological specimen randomly around two orthogonal axes. While the FFM failed to reproduce the results obtained with T lymphocytes in space, the data from the RPM are in good agreement with those in real microgravity. In fact, the inhibition of the mitotic index in the RPM is 89% compared to static controls. The RPM (as the FFM) can carry markedly larger specimen than the fast rotating clinostat and thus allows to conduct comprehensive studies to select suitable biological objects for further investigations in space.

Cells, Cultured↗
PubMed2000

The development of international health policies--accountability intact?

International health governance as it exists today is facing major structural challenges in view of globalization, the increased transfer of international health risks and the mounting challenge of health inequalities worldwide. As a consequence the capacity of nation states to ensure population health and to address major health determinants has been weakened. This paper explores health as an exemplary field to illustrate that we have entered a new era of public policy which is defined by increasing overlaps between domestic and foreign policy, multilateral and bilateral strategies and national and international interest. Cross border spill overs and externalities of national actions need to move into the core of public policy at the national and global level within a new rules based system. A new perspective on global health governance is further necessitated through the increased number of players in the global health arena. The organizational form that is emerging is based on networks and is characterized by shifting alliances and blurred lines of responsibility. The paper explores the emerging paradox of state sovereignty and makes a set of proposals to pool state sovereignty on health and structure the myriad of networks. Particular attention is given to the role of the World Health Organization within this process of change and adjustment. In using a framework from international relations analysis the paper explores how nation states are socialized into accepting new norms, values and perceptions of interest with regard to national and international health and what challenges emerge for the WHO in "inventing" global health policy.

Global Health↗
PubMed2003

Health inequality and users' risk-taking: a longitudinal analysis in a French reproductive technology centre.

This article sets out to provide a demographic analysis of the production of social inequality through IVF trajectories in a reproductive technology centre of a French hospital. However specific this example may be, it reveals one of the paradoxes of social inequalities in health: lay experience of risk in reproductive technology shows profound inequalities related to social status, despite the fact that equality would seem to be guaranteed in France, since the social security system covers the full cost of the treatments. We will try to understand this paradox through a lifecourse approach. Thus, it will be shown that social inequality in reproductive health is deeply rooted in social scenarios of infertility that lead to differentiated medical experience: there is little benefit and even a worsening in the situation of lower class women, who were faced with unpredictable risks related to the collective testing of these new technologies. Conversely, the possibility of inventing new lifestories, which may or may not include motherhood, was given to upper class women who take calculated risks to delay the scheduling of their pregnancies. In short, this study confirms that the production of social inequality in reproductive health can only be understood in connection with the social dynamics of lifestyles, resulting in specific medical patterns. This paper also leads to the assumption that these social scenarios are related to attempts to enhance the different forms of capital: economic, cultural and social capital. In addition, the presence of risks aggravates this inequality process. This raises another question: do reproductive technologies result in reinforcing social inequality?

Adult↗
PubMed1998

Diagnosing moral disorder: the discovery and evolution of fetal alcohol syndrome.

The diagnosis of fetal alcohol syndrome (FAS) was invented in 1973. This paper investigates the process by which a cluster of birth defects associated with exposure to alcohol in utero came to be a distinct medical diagnosis, focusing on the first ten years of the medical literature on FAS. Fetal alcohol syndrome was "discovered" by a group of American dysmorphologists who published the first case reports and coined the term FAS. However, the nature of the diagnosis and its salient symptoms were determined collectively over time by the medical profession as a whole. The paper traces the natural history of the diagnosis in the U.S. through five stages: introduction, confirmation and corroboration, dissent, expansion, and diffusion. FAS serves as an example of the social construction of clinical diagnosis; moral entrepreneurship plays a key role and the medical literature on FAS is infused with moral rhetoric, including passages from classical mythology, philosophy, and the Bible. FAS is a moral as well as a medical diagnosis, reflecting the broader cultural concerns of the era in which it was discovered, including a greater awareness of environmental threats to health, the development of fetal medicine, an emphasis on "the perfect child," and a growing paradigm of maternal-fetal conflict.

Cross-Cultural Comparison↗
PubMed2001

Franz Kuhn, his contribution to anaesthesia and emergency medicine.

Franz Kuhn (1866-1929), a German surgeon, made a significant practical and scientific contribution towards the development of modern anaesthesia and emergency medicine. He developed modern, scientifically based concepts in close correlation to practical inventions for every day use. All of his studies and developments were patient orientated and led to remarkable improvements in patient safety. Kuhn was a major protagonist of endotracheal intubation, perfected his flexo-metallic endotracheal tubes, worked on different techniques of intubating the trachea, applied positive pressure to the lungs during thoracic surgery and developed anaesthesia machines. In the early 20th century, he wrote several papers on this topic including a remarkable monograph, dealing with the techniques, indications in anaesthesia and emergency medicine and his experiences of endotracheal intubation. Due to a dispute with Sauerbruch on the methods of avoiding a pneumothorax during thoracic surgery and the development of local and regional anaesthesia techniques, the value of his work and his revolutionary ideas were not appreciated until 40 years later.

Anesthesia↗
PubMed1997

Highest level automatisms in the nervous system: a theory of functional principles underlying the highest forms of brain function.

A concept that all hierarchical levels of the nervous system are built according to the same functional principles is proposed. Each level is responsible for a discrete type or set of automatisms, is a learning system, and contains two distinct functional subdivisions: (1) a controller, a subsystem providing a governing set of rules or commands-a control law-that directs the action of the recipient of these rules-the controlled object; and (2) a model, a subsystem that generates a model of object behavior, i.e. afferent information flow expected from the controlled object. A control system such as this receives two types of afferent signals-initiating and informational. The difference between these signals is that a control system minimizes initiating signals during the realization of an automatism, i.e. a control neural network utilizes informational signals to compute the proper output that minimizes the initiating input signal. A mismatch or error signal, a type of initiating signal, is responsible for learning. Both the control law and the model can be adjusted during learning. The learning process starts when the error signal increases and stops when it is minimized. A network hierarchy is structurally and functionally organized in such a way that a lower control system in the nervous system becomes the controlled object for a higher one. This hierarchy leads to a generalization of encoded functional parameters and, consequently, the working space for each higher level control system becomes more abstracted. This is the reason why each hierarchical level within the control nervous system uses detectors specific for feature of the controlled object and the environment that match the control needs in order to obtain information about the current state of the object in the environment. Movement of information toward higher hierarchical levels also is accompanied by an increase in the duration of initiating signals within each control system. The ability to store a long prehistory of preceding events is considered as the mechanism that necessitated the invention of more complex and more rapid forms of learning such as operant learning, and made possible more complex multistep computational algorithms that require memorization of the results of previous intermediate computations. The functions of the cerebellum, the limbic system and the cortico-basal ganglia-thalamocortical loops are analyzed to illustrate the utility and applicability of this theoretical concept. Basal ganglia-thalamocortical loops are described as modeling, predictive loops, and their dopaminergic innervation as an error distribution system.

Automatism↗
PubMed2002

The gynaecological-obstetrical practice of the renaissance physician Amatus Lusitanus (Dubrovnik, 1555-1557).

OBJECTIVE: A gynaecological-obstetrical causation review in Dubrovnik from 1555 to 1557. Extract from the book "Curationum Medicinalium Centuriae V et VI" Amatus Lusitanus. METHOD: A thorough life and work archive study of Amatus Lusitanus has been made and, for this review, extracted his gynaecological-obstetrical causation observations and annotations. RESULTS: Amatus Lusitanus was an undisputed, reputable and respected medical figure during the mid 16th century. He decisively focused on intern medicine, incorporating the gynaecological-obstetrical field. His work and skill, most assuredly, contributed to the better comprehension, acknowledgement and reputation of the gynaecological-obstetrical practice, thus leaving repute and respect in medical history latitude. CONCLUSION: All these cases occurred in Dubrovnik during 1555-1557 and Amatus is assuredly an excellent observer and exactist, extracting the "relevant from the non-relevant" even in Dubrovnik's gynaecological-obstetrical daily happenings. He thoughtfully concludes his inability to remedy a malignant, advanced illness of the uterus, presumes an utero-vesico-intestinal fistula and openly speaks of medical ineptness of this causation. Proud of his invention in treating "contracted nipples"; correct in his advice and recommendations of "long and difficult births". Impartial in his perception of puerperal sepsis and its unfavourable pathology outcome. His description of "hormone insufficiency" is concise and precise; the preferred procedure in an "abortus in tractu" is purposeful and meaningful. He closely works with other physicians living and working in Dubrovnik; conscientiously directing surgeons in procedures of stillborn child births. He explains and treats pyschosexual disturbances "without fault" and in concurrence with, not only, the contemporary knowledge of such sexual disturbances, but also in concurrence with contemporary psychiatric procedures that, even today, are applied in such pathology treatment.

Croatia↗
PubMed1997

Ultrasound in ophthalmology.

The first ocular echogram was published in 1956. Since then, ophthalmic ultrasound has developed into a multifaceted diagnostic discipline, the basic methods being A-scan and B-scan, Doppler techniques and recently also three-dimensional approaches. Unique for ophthalmology is the newly invented, highly resolving equipment utilising ultrasound frequencies of 50 MHz and higher, so-called ultrasound biomicroscopy. During this development, the special ophthalmic items often kept colleagues from other fields at some distance. With a view to a fair balance between specific and more general information, the primary aim of the present overview is to provide insight for other medical branches employing diagnostic ultrasound. Regarding intraocular morphology, ultrasonic evaluation in experienced hands is superior to other imaging methods. As for orbital pathology, imaging by CT and MR appears more complete. Ultrasound is valuable, however, in particular as part of the initial clinical work-up, and for the follow-up of orbital disease. Furthermore, tissue differentiation by way of ultrasound is of great value with regard to certain entities.

Biometry↗
PubMed2003

Arithmetic inside the universal genetic code.

The first information system emerged on the earth as primordial version of the genetic code and genetic texts. The natural appearance of arithmetic power in such a linguistic milieu is theoretically possible and practical for producing information systems of extremely high efficiency. In this case, the arithmetic symbols should be incorporated into an alphabet, i.e. the genetic code. A number is the fundamental arithmetic symbol produced by the system of numeration. If the system of numeration were detected inside the genetic code, it would be natural to expect that its purpose is arithmetic calculation e.g., for the sake of control, safety, and precise alteration of the genetic texts. The nucleons of amino acids and the bases of nucleic acids seem most suitable for embodiments of digits. These assumptions were used for the analyzing the genetic code. The compressed, life-size, and split representation of the Escherichia coli and Euplotes octocarinatus code versions were considered simultaneously. An exact equilibration of the nucleon sums of the amino acid standard blocks and/or side chains was found repeatedly within specified sets of the genetic code. Moreover, the digital notations of the balanced sums acquired, in decimal representation, the unique form 111, 222...., 999. This form is a consequence of the criterion of divisibility by 037. The criterion could simplify some computing mechanism of a cell if any and facilitate its computational procedure. The cooperative symmetry of the genetic code demonstrates that possibly a zero was invented and used by this mechanism. Such organization of the genetic code could be explained by activities of some hypothetical molecular organelles working as natural biocomputers of digital genetic texts. It is well known that if mutation replaces an amino acid, the change of hydrophobicity is generally weak, while that of size is strong. The antisymmetrical correlation between the amino acid size and the degeneracy number is known as well. It is shown that these and some other familiar properties may be a physicochemical effect of arithmetic inside the genetic code. The "frozen accident" model, giving unlimited freedom to the mapping function, could optimally support the appearance of both arithmetic symbols and physicochemical protection inside the genetic code.

Amino Acid Sequence↗
PubMed1999

Synthesis of long trinucleotide repeats in vitro.

More than a dozen diseases have been associated with the expansion of trinucleotide repeats. Most of these expanding repeats are GC-rich (CGG/CCG or CTG/CAG), but it is difficult to amplify GC-rich repeat DNA from patient samples by the polymerase chain reaction. We invented a pair of methods to synthesize long trinucleotide repeats in vitro by polymerase extension utilizing a thermal cycler. A combination of the two methods, termed the non-template PCR method and SLIP (Synthesis of Long Iterative Polynucleotide) method, produced (CTG/CAG)190 repeat DNA. We expect that these two methods will contribute to studies of all diseases associated with tri-nucleotide repeat expansion, since they can be applied to any type of repeat DNA.

DNA↗
PubMedDate not supplied

A new cantilever system for gas and liquid sensing.

A novel setup for gas and liquid sensing was developed and tested. It is based on both detection of frequency shift and of bending of micro-cantilevers to measure mass changes as well as viscosity changes. To drive the cantilevers new electrostatic and magnetic actuations were invented with a closed feed-back loop which forces the cantilever to oscillate always at its resonance frequency. The oscillation is detected via the beam-deflection technique. By measuring the DC signal of the photodiode the static bending of the cantilever can be monitored simultaneously. The closed feed-back loop propagates a very stable oscillation at the resonance frequency and gives a strong increase in the quality factor compared to a system without such feed-back loop. Furthermore, it is possible to operate this cantilever transducer system in liquids. These cantilever sensors hence, show the potential for use in easy-to-use and highly sensitive sensor systems for gas and liquid phase chemical and biochemical sensing.

Journal Article↗
PubMed2000

Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization.

Gelonin, a type I ribosome-inactivating plant toxin, executes N-glycosidase activity on eukaryotic ribosomes. However, on intact cells, gelonin is relatively non-toxic, due to an incapability to penetrate cell membranes. Recently, a novel method, photochemical internalization (PCI), was invented for the translocation of membrane-impermeable molecules including gelonin to the cytosol [K. Berg et al., Cancer Res. 59 (1999) 1180-1183]. The combination of gelonin and photoactivation of endosomal and lysosomal localizing photosensitizers gives strong synergistic cytotoxic effects. In this study, we have evaluated the intracellular transport and stability of gelonin. By fluorescence microscopy, it was shown that gelonin co-localizes with the endosomal and lysosomal localizing photosensitizer, aluminum phthalocyanine with two sulfonate groups on adjacent phenyl rings, and both molecules re-localized to cytosol subsequently to light exposure. Gelonin accumulated in endosomal compartments by incubation at 18 degrees C was released to cytosol by PCI with concomitant inhibition of protein synthesis indicating that PCI can be executed through rupture of endosomal vesicles. The cathepsin inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanido)butane increased the cytotoxic effect of gelonin after PCI when gelonin was provided as a 2 h pulse followed by 4 h chase before PCI. Thus, although gelonin can enter the cytosol from lysosomes, lysosomal degradation is a limiting factor for the outcome of PCI of gelonin.

Cysteine Proteinase Inhibitors↗
PubMed1997

Evolution's 'missing link': a hypothesis upon neural plasticity, prefrontal working memory and the origins of modern cognition.

Many activities such as reading, mathematics and chess depend upon cognitive processes which arose after our evolution. Why could they arise if not evolved? I argue four things fortuitously came together to make our nonevolved cognitive skills possible: (i) neural plasticity; (ii) large functionally uncommitted prefrontal, temporal and parietal cerebral cortices; (iii) the ability of their neural circuits (due to neural plasticity), if trained, to take on novel symbolic and nonsymbolic skills; and (iv) a large prefrontal cortex which could use its working memory as a tuition management sketch pad in which to train them. Pre-evolved for other reasons, these four (together with invented symbolic systems and technology) together enable modern humans to 'upgrade' our already evolved cognitive skills to do new and nonevolved things.

Animals↗
PubMed1985

What's new in bronchial obstruction? Experimental pathology and clinico-pathologic correlation.

The aim of general pathology, which following Virchow also should be pathophysiology (and pathobiochemistry), is to elucidate general principles and main mechanisms of diseases. Conceptions like reticulo-endothelial system or coronary insufficiency, inflammations and its mediators, modes of metastasis and many comparable topics are examples of this type of scientific approach, and its tools are careful morphological analysis as well as experimental work of different kinds. In pulmonary pathology the obstruction of airways is one of the most important pathogenetical pathways. Among a broad spectrum of pulmonary diseases it is the main symptom of a developing chronic obstructive pulmonary disease (COPD) and the outstanding cause of cardio-respiratory failure. In German literature the last comprehensive survey on general respiratory pathology was written some twenty years ago and a review of the main techniques of investigation was given at about the same time. Since then - parallel to the invention of new measuring techniques and to the progress in clinical pathophysiology - a rapid further development in the understanding of the pathology of respiratory disorders has taken place, particularly in connection with research in chronic bronchitis and emphysema. Some examples of this development and of the present state of discussion will be reviewed briefly.

Airway Obstruction↗
PubMed1998

Animal electricity and the birth of electrophysiology: the legacy of Luigi Galvani.

Preceded by a companion paper on Galvani's life, this article is written on the occasion of the bicentenary of the death of Luigi Galvani. From his studies on the effects of electricity on frogs, the scientist of Bologna derived the hypothesis that animal tissues are endowed with an intrinsic electricity that is involved in fundamental physiological processes such as nerve conduction and muscle contraction. Galvani's work swept away from life sciences mysterious fluids and elusive entities like "animal spirits" and led to the foundation of a new science, electrophysiology. Two centuries of research work have demonstrated how insightful was Galvani's conception of animal electricity. Nevertheless, the scholar of Bologna is still largely misrepresented in the history of science, because the importance of his researches seems to be limited to the fact that they opened the paths to the studies of the physicist Alessandro Volta, which culminated in 1800 with the invention of the electric battery. Volta strongly opposed Galvani's theories on animal electricity. The matter of the scientific controversy between Galvani and Volta is examined here in the light of two centuries of electrophysiological studies leading to the modern understanding of electrical excitability in nerve and muscle. By surveying the work of scientists such as Nobili, Matteucci, du Bois-Reymond, von Helmholtz, Bernstein, Hermann, Lucas, Adrian, Hodgkin, Huxley, and Katz, the real matter of the debate raised by Galvani's discoveries is here reconsidered. In addition, a revolutionary phase of the 18th century science that opened the way for the development of modern neurosciences is reevaluated.

Animals↗
PubMed1998

Solid-phase microextraction (SPME) of drugs and poisons from biological samples.

Solid-phase microextraction (SPME), a new solvent-free sample preparation technique, was invented by C. Arthur and J. Pawliszyn in 1990. This method mainly was applied for the extraction of volatile and semi-volatile organic pollutants in water samples. However, since 1995, SPME has been developed to various biological samples, such as whole blood, plasma, urine, hair and breath, in order to extract drugs and poisons in forensic field. The main advantages of SPME are: high sensitivity, solventless, small sample volume, simplicity and rapidity. We have reviewed the papers published in recent years about SPME in biological samples, and sorted out main experimental conditions, such as fibers, matrixes, the extraction approaches and time, as well as the acceleration method. We would expect SPME technique to have a promising future for toxicological analysis in forensic practice.

Body Fluids↗
PubMed1986

Dissociated taste disorder.

Dissociated taste disorder is a special symptom occurring when only one or two taste qualities of the four primary taste are disturbed. Eleven % of all cases of taste disorders complain of this symptom. The subjects of this investigation were 46 patients due to be examined. We used our filter-paper disc method invented for clinical qualitative and quantitative gustometry by taste examination. True dissociated taste disorder was confirmed in 12 patients only with respect to sweetness. No dissociated taste disorder was found for the other types of taste. Sweetness differs from the other three primary tastes in that it is brought about by a protein acting as a receptor. In patients suffering from true dissociated taste disorders, the predominant cause of the condition is zinc deficiency. When zinc is not available in adequate quantities, the synthesis of the protein at the sweet-sensitive receptor site can no longer be achieved smoothly, and this may lead to the development of the complaint.

Aged↗