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Space medicine is fundamental to the human exploration of space. It supports survival, function and performance in this challenging and potentially lethal environment. It is international, intercultural and interdisciplinary, operating at the boundaries of exploration, science, technology and medicine. Space medicine is also the latest UK specialty to be recognized by the Royal College of Physicians in the UK and the General Medical Council. This review introduces the field of space medicine and describes the different types of spaceflight, environmental challenges, associated medical and physiological effects, and operational medical considerations. It will describe the varied roles of the space medicine doctor, including the conduct of surgery and anaesthesia, and concludes with a vision of the future for space medicine in the UK.Space medicine doctors have a responsibility to space workers and spaceflight participants. These 'flight surgeons' are key in developing mitigation strategies to ensure the safety, health and performance of space travellers in what is an extreme and hazardous environment. This includes all phases from selection, training and spaceflight itself to post-flight rehabilitation and long-term health. The recent recognition of the speciality provides a pathway to train in this fascinating field of medicine and is a key enabler for the UK Government's commercial spaceflight ambition.

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OBJECTIVES: To investigate the cellular distribution and relative intensity of the immunoreactivity associated with the expression of sodium, potassium-adenosine triphosphatase (Na, K-ATPase) in cells of the olfactory mucosa. Second, changes in the activity of this enzyme in the olfactory mucosa are correlated with changes in the circulating corticosteroid aldosterone. METHODS: Combination of immunohistochemical and biochemical techniques were employed to examine the olfactory Na, K-ATPase. RESULTS: Within the olfactory epithelium, the Na, K-ATPase immunoreactivity was greatest at the supranuclear region of sustentacular cells and/or dendrites of olfactory receptor neurons (ORNs). Cell bodies of ORNs demonstrated moderate immunoreactivity, whereas the duct cells of Bowman's gland exhibited moderate to intense immunoreactivity. Acinar cells of the Bowman's gland were the most intensely stained components of the lamina propria, exhibiting strong immunoreactivity at the basolateral plasma membrane domains of the acinar cells and less within the cytoplasm. Binding of ouabain, a specific inhibitor of Na, K-ATPase, was significantly elevated for aldosterone-injected versus sham-injected controls. CONCLUSION: These results suggest that olfactory Na, K-ATPase is regulated by the systemic corticosteroid aldosterone. The results are consistent with the hypothesis that corticosteroids regulate olfactory secretion.

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OBJECTIVES: Define the presence and distribution of glucocorticoid receptors (GRs) within the olfactory mucosa in order to assess potential physiologic and pathophysiologic effects of these hormones on olfaction. STUDY DESIGN: The olfactory mucosa was harvested from adult male rats and guinea pigs. Kidney tissue was utilized as a known positive control. METHODS: The techniques of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry were utilized to examine the expression of GR mRNA and protein. To assure the presence of olfactory mucosa in the nasal tissue samples, RT-PCR was utilized to identify the olfactory marker protein (OMP). RESULTS: The presence of GR mRNA was confirmed in both the olfactory mucosa and kidney. GR-like immunoreactivity associated with the olfactory epithelium was greatest at the apical surface, a position corresponding to the dendrites, knobs, and cilia of olfactory receptor neurons, as well as the supranuclear region of sustentacular cells. Weaker GR-like immunoreactivity was associated with the region of the cell bodies of the olfactory receptor neurons. Within the lamina propria, acinar cells of the Bowman's glands and olfactory nerve bundles were intensely immunoreactive. CONCLUSIONS: The presence of GR mRNA and protein within the olfactory mucosa is consistent with a functional role for glucocorticoid hormones in the systemic regulation of olfaction. Furthermore, these studies suggest that corticosteroid medications may have direct effects on the cells of the olfactory mucosa in the pathologic state. The potential mechanisms whereby these hormones may act are discussed.

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The lipoprotein Lp(a), a major inherited risk factor for atherosclerosis, consists of a low density lipoprotein-like particle containing apolipoprotein B-100 plus the distinguishing component apolipoprotein(a) (apo(a)). Human apo(a) contains highly repeated domains related to plasminogen kringle four plus single kringle five and protease-like domains. Apo(a) is virtually confined to primates, and the gene may have arisen during primate evolution. One exception is the occurrence of an Lp(a)-like particle in the hedgehog. Cloning of the hedgehog apo(a)-like gene shows that it is distinctive in form and evolutionary history from human apo(a), but that it has acquired several common features. It appears that the primate and hedgehog apo(a) genes evolved independently by duplication and modification of different domains of the plasminogen gene, providing a novel type of "convergent" molecular evolution.

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Since mammalian cells vary widely in their intrinsic thermoresistance, we have investigated the genetic basis underlying this phenomenon in human and rodent cell lines. Typically, human cells are considerably more resistant to killing by heat than rodent cell lines. To determine whether the heat-resistant phenotype is dominant or recessive and to locate the chromosome(s) bearing determinants for heat resistance, we have prepared hybrids of heat-resistant human HT1080 cells and heat-sensitive Chinese hamster ovary (CHO) cells to test their response to heat. For both mass hybrid cultures and individual clones, the heat response of the hybrids was similar to that of the CHO parent. Analysis by in situ hybridization revealed the presence of five to 20 human chromosomes per cell in the mass hybrids and four to eight intact chromosomes plus some fragments in individual clones isolated from the hybrid cell population. A similar result was obtained using a different human cell line, AG1522. These data suggest that heat resistance is a recessive trait. Consistent with this conclusion are the results from a study of a fusion of HT1080 to a CHO mutant, BL-10, which was found to be hypersensitive to heat-induced killing. These hybrids had a normal CHO heat response and not the more heat-resistant phenotype of HT1080 cells. Two hybrid clones, H2 and H4, from the HT1080/BL-10 fusion were studied in more detail. Both clones possess similar amounts of Mr 70,000 heat shock protein (HSP70), despite the fact that H4 contains three human chromosomes (Nos. 6, 14, and 21) which carry HSP70 genes while H2 contains only one (chromosome 6). Both hybrid cell lines have the same response to heat. Although we found a wide range of sensitivities to heat, all cell lines contained a similar amount of constitutive HSP70, suggesting that HSP70 levels per se are not the critical determinant of intrinsic heat resistance.

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Rotavirus gastroenteritis is a leading cause of infant mortality in developing countries and an important cause of morbidity in children under 2 yr of age in the United States. Vaccine programs have evaluated animal rotavirus strains that are attenuated in humans but antigenically similar to some human strains. Whether a single vaccine strain can elicit protective immunity in humans to rotaviruses of the same or different serotypes is an important question in determining vaccine efficacy. We used characterized serotype-specific monoclonal antibodies directed at VP7 in a competitive solid-phase immunoassay to measure epitope-specific immune responses to serotypes 1, 2, and 3 in sera of children who received a candidate serotype-3 rotavirus vaccine. Antibodies to serotype 3 were detected in 72% of sera samples, and to serotype 1 and 2 in only 11% each. Also, a VP3-specific monoclonal antibody which neutralizes three serotypically distinct strains of rotavirus was used to detect the presence of similar antibodies in 56% of the test sera. This finding suggests a mechanism of heterotypic immunity.

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