Blood rheology in acute mountain sickness and high-altitude pulmonary edema.

The role of blood rheology in the pathogenesis of acute mountain sickness and high-altitude pulmonary edema was investigated. Twenty-three volunteers, 12 with a history of high-altitude pulmonary edema, were studied at low altitude (490 m) and at 2 h and 18 h after arrival at 4,559 m. Eight subjects remained healthy, seven developed acute mountain sickness, and eight developed high-altitude pulmonary edema. Hematocrit, whole blood viscosity, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability (filtration) were measured. Plasma viscosity and erythrocyte deformability remained unaffected. The hematocrit level was lower 2 h after the arrival at high altitude and higher after 18 h compared with low altitude. The whole blood viscosity changed accordingly. The erythrocyte aggregation was about doubled 18 h after the arrival compared with low-altitude values, which reflects the acute phase reaction. There were, however, no significant differences in any rheological parameters between healthy individuals and subjects with acute mountain sickness or high-altitude pulmonary edema, either before or during the illness. We conclude that rheological abnormalities can be excluded as an initiating event in the development of acute mountain sickness and high-altitude pulmonary edema.     

Advances in bioconversion of anthracycline antibiotics

During the last decade new anthracycline-type structures with potential usefulness in cancer treatment have been supplied both by new microbial strains and by bioconversions of precursor molecules employing cells or enzymes. We highlight recent advances in bioconversion of anthracycline structures with the main focus on late transformations such as are carried out by oxidoreductases.     

Chitosan-elicited synthesis of callose and of coumarin derivatives in parsley cell suspension cultures

In suspension cultured cells of parsley (Petroselinum crispum), chitosan elicited a rapid deposition of the 1,3-ß-glucan callose on the cell wall and a slower formation of coumarins. With cells remaining in conditioned growth medium, fully N-deacetylated chitosans and partially N-acetylated chitosans were about equally active, the potency increased with the degree of polymerization up to several thousand and addition of reduced glutathione increased the sensitivity of the cells. These results indicate common initial events in the induction of callose and coumarin synthesis although two fully independent metabolic pathways are involved. When the cells were suspended in fresh growth medium, less chitosan was required, and fully N-deacetylated chitosan became the best callose elicitor.Abbreviations DP average degree of polymerization - GSH reduced glutathione - PE pachyman equivalents - Pmg Phytophthora megasperma f. sp.glycinea     

Architecture and functional aspects of the distal airways of Antarctic seals with different habits,the Weddell Seal (Leptonychotes weddellii) and the Crabeater Seal (Lobodon carcinophagus)

Summary The lung of the deep diving Weddell Seal is characterized by an unusually well developed periacinar dense collagenous connective tissue, and a thick coat of smooth musculature particularly in the distal bronchioli. Both, collagen and smooth musculature appear to be functionally interrelated, the first serving presumably as site of origin or attachment for the latter. The orientation of the bronchiolar smooth muscle cells is complex: there exists a basic pattern of two crisscrossing helical bundles that wind in opposite direction. In addition, longitudinal bundles are frequent both at the inside and the outside of the muscular coat. Furthermore, more or less complete ringshaped bundles occur as well as groups of muscle fibres running radially into the collagenous tissue of the surroundings of a bronchiolus. This complex architecture presumably allows active adjustment to various physiological needs of the Weddell Seal including as extremes both closing and widening of the bronchiolar lumen. Isometric contractions of the smooth musculature may stiffen the wall of the distal airways while diving. In the Crabeater Seal which dives for shorter durations and by far less deeply than the Weddell Seal, both periacinar collagen and bronchiolar smooth musculature are of similar arrangement, however, occur in considerably reduced amounts. A rich supply of autonomie nerve fibres with abundant varicosities controls the smooth muscle cells, which are interconnected by gap junctions and receive their innervation par distance (visceral type of smooth musculature). The majority of varicosities contains small clear vesicles, as is typical for cholinergic nerves, suggesting a strong parasympathetic influence. Other varicosities are presumably of peptidergic type. Mast cells and epithelial endocrine cells may exert additional influence on the musculature.     

Nuclear Overhauser effect and computational characterization of the beta-spiral of the polypentapeptide of elastin

The structure of the elastin polypentapeptide, poly(VPGVG), was studied by nuclear Overhauser effect experiments using perdeuterated Val1 and Val4 samples under the condition where intermolecular interactions are absent. More extensive interaction was found between the Val1 gamma CH and Pro2 beta CH protons than between the Val4 gamma CH and Pro2 beta CH protons. The Val1 gamma CH3-Pro2 beta CH interaction does not occur within the same pentamer as previously shown experimentally and as expected from steric considerations. The results are incompatible with the presence of a random chain network in poly(VPGVG) at room temperature but are readily explicable in terms of interturn interactions in a beta-spiral structure. More specifically, the results indicate that the beta-spiral conformation with 2.9 pentamers/turn is more prevalent than that with 2.7 pentamers/turn. Using conformations developed by molecular mechanics calculations, molecular dynamics simulations were carried out to compare the relative energies of these two variants of this class of beta-spiral structures. It was found in vacuo that the structure with 2.9 pentamers/turn is indeed more stable than that of 2.7 pentamers/turn by approximately 1 kcal/mole-pentamer.     

The polymorphic marker DXS304 is within 5 centimorgans of the fragile X locus

The fragile X syndrome, which is the most common cause of inherited mental retardation, poses important diagnostic problems for genetic counseling. The development of diagnostic strategies based on DNA analysis has been impaired by the lack of polymorphic markers very close to the disease locus. Here we report that the polymorphic probe U6.2 (locus DXS304) is much closer to the fragile X locus than all the previously reported markers. A recombination fraction of 0.02 between DXS304 and the fragile X locus was estimated by multipoint linkage analysis (confidence interval 0.002 to 0.05). Our data suggest that DXS304 is distal to the fragile X locus. This marker thus represents a major improvement for carrier detection and prenatal diagnosis in fragile X families.     

Genetic and physical mapping of a novel region close to the fragile X site on the human X chromosome

We report the isolation and characterization of a novel DNA marker (1A1) in Xqter in the region of the fragile X. Genetic studies in families segregating for the fragile X syndrome suggest that 1A1 lies between the disease mutation and the distal locus, DXS52. Studies in normal and fragile X families show that 1A1 is tightly linked to DXS52 (Zmax = 17.20; theta max = 0.03) and F8 (Zmax = 7.01; theta max = 0.08). Multipoint mapping of families supports the order Xcen-DXS105-FRAXA-1A1-DXS52-(F8, DXS115)-Xqter. Pulsed-field gel electrophoresis (PFGE) studies demonstrate that 1A1 defines a new region of at least 2 Mb of DNA not physically linked to DXS52 or F8, thus extending the physical map of Xq27-qter to over 4 Mb. Complex partial digestion PFGE patterns, probably due to differing degrees of methylation, are observed with 1A1 in unrelated normal and fragile-X-positive individuals, whereas other distal markers give uniform digestion profiles. Physical data suggest that 1A1 lies in a region less CpG rich than other distal markers in Xq27-qter.     

Age-related difference in bioenergetics of lung and heart mitochondrial from rats exposed to ozone

Bioenergetics of isolated lung and heart mitochondria from adult and aged rats were examined in the presence of glutamate (NAD-linked substrate) or succinate + rotenone (FAD-linked substrate) following ozone exposure (3.0 ppm, 8 hr). In controls, several differences were observed between adults and aged in both organ preparations. Following exposure, all bioenergetic parameters were decreased significantly in lung preparations from both adult and aged rats. In heart mitochondria, the respiration rates in state 3 and in uncoupled state, and the ADP/O ratio were decreased significantly in both exposed age groups. The respiratory control ratio (RCR) was decreased significantly only in the aged exposed rats. These results suggest that acute exposure to high levels of ozone alters energy production in both lung and heart mitochondria of adult and aged rats.     

Guanine nucleotide-dependent, pertussis toxin-insensitive regulation of phosphoinositide turnover by bradykinin in bovine pulmonary artery endothelial cells

In this paper we examine the effect of the vasodilator peptide bradykinin on endothelial cell regulation of phosphoinositide (PI) turnover. The data show that the activation of PI turnover by bradykinin in bovine pulmonary artery endothelial cells is insensitive to pertussis toxin, which ADP ribosylates a membrane protein of mol wt 40,000. However, this effect of bradykinin can be potentiated by guanosine 5'-O-(3-thio)triphosphate (GTP gamma S), an activator of G proteins, and depressed by guanosine 5'-O-(2-thio)diphosphate (GDP beta S), an inhibitor of G proteins. After endothelial cells were preincubated for 1 h with GTP gamma S, there was a three- to fourfold increase in PI turnover. Preincubation of cells with GDP beta S did not affect the basal level of PI turnover, but completely prevented activation of PI turnover by bradykinin. 4 beta-Phorbol-12 beta-myristate-13 alpha-acetate can block the bradykinin-stimulated inositol monophosphate formation in cultured endothelial cells. The effects of bradykinin on PI turnover were blocked by B2 antagonists but not by B1 antagonists. Taken together, these results indicate that in endothelial cells the bradykinin B2 receptor is coupled to phospholipase C via a G protein (or proteins) that is not a substrate for pertussis toxin (neither Gi nor Go).