PubMed Health⌕ Search

Biomedical subjects

M Kiess

Publications and source records attributed to M Kiess.

At least 37 records · Page 2Linked to original sources
PubMed1997

Catalytic characteristics of tryparedoxin.

Tryparedoxin, a thioredoxin-related protein from Crithidia fasciculata with a molecular mass of 16 kDa catalyses the reduction of a peroxiredoxin-type peroxidase, Cf21, at the expense of trypanothione [Nogoceke, E., Gommel, D. U., Kiess, M., Kalisz, H. M. & Flohé, L. E. (1997) Biol. Chem. Hoppe-Seyler 378, 827-836]. The kinetic analysis of tryparedoxin revealed an enzyme substitution mechanism. The corresponding molecular event was elucidated to be a reversible oxidoreduction of the disulfide bridge in the thioredoxin-related motif WCPPC. The amino-proximal cysteine residue of this active site was more reactive in S-alkylation experiments than the distal residue. The natural substrates of tryparedoxin, trypanothione and Cf21, could only be substituted by glutathione and glutathione disulfide with considerable loss in activity. The pronounced specificity of tryparedoxin is further accentuated by low limiting Km values for Cf21 and trypanothione (2.2 microM and 130 microM, respectively, as compared to 990 microM for gluthathione disulfide and an infinite value for glutathione). Tryparedoxin can therefore be classified as a trypanothione: peroxiredoxin oxidoreductase. The reduction of tryparedoxin by trypanothione appears to be the rate-limiting step in the trypanothione-dependent hydroperoxide reduction because(a) the regeneration of reduced tryparedoxin from the tryparedoxin-trypanothione complex is rate limiting (k[cat] 392 min[-1]), (b) the physiological trypanothione concentrations may not always saturate tryparedoxin, and (c) the rate constants for the net forward reaction of Cf21 are faster than those of the tryparedoxin reaction. The functional characteristics of tryparedoxin explain the limited capacity of trypanosomatids in coping with oxidative stress and qualify the enzyme as a potential target for the design of specific trypanocidal compounds.

Animals↗
PubMed1997

Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration.

Macrophages are typically stimulated by components of microbial cell walls. Surprisingly, cell wall-less mycoplasmas can also very efficiently stimulate macrophages. We showed recently that mycoplasma-derived lipopeptides constitute the active principle. We have now isolated a clone of Mycoplasma fermentans expressing mainly one macrophage-stimulating lipopeptide. This lipopeptide was detergent-extracted and isolated by reversed-phase high-performance liquid chromotography, using nitric oxide release from C3H/HeJ mouse macrophages as bioassay for detection. In contrast to "conventional" bacterial lipoproteins, this lipopeptide had a free NH2 terminus. Amino acid composition, sequence, and the molecular weight of 2,163. 3 are consistent with the following structure: S-(2, 3-bisacyloxypropyl)cysteine-GNNDESNISFKEK with one mole C16:0, and a further mole of a mixture of C18:0 and C18:1 fatty acid per lipopeptide molecule. The sequence could not be found in either the protein identification resource nor the Swiss Prot data bank. We named this 2-kD lipopeptide, macrophage-activating lipopeptide-2 (MALP-2). Synthetic dipalmitoyl MALP-2 and mycoplasma-derived MALP-2 were compared with the bioassay. Both lipopeptides showed an identical dose dependency with a half-maximal response at 10(-11) M concentration. MALP-2 may be one of the most potent natural macrophage stimulators besides endotoxin.

Amino Acid Sequence↗
PubMed1997

Convenient isolation and kinetic mechanism of glutathionylspermidine synthetase from Crithidia fasciculata.

Trypanothione, the essential metabolite in the oxidant defense system of trypanosomatids, is synthesized by two distinct proteins, glutathionylspermidine synthetase and trypanothione synthetase. Glutathionylspermidine synthetase was purified to homogeneity from the trypanosomatid Crithidia fasciculata by aqueous two-phase systems and chromatography. The enzyme showed a specific activity of 38 micromol of glutathionylspermidine formed per min per mg of protein. Its molecular mass was 78 kDa in SDS-polyacrylamide gel electrophoresis, and it appeared predominantly monomeric in native polyacrylamide gel electrophoresis and gel filtration. The isoelectric point was at pH 4.6, and the pH optimum was near 7.6. Partial amino acid sequencing revealed homology with, but low similarity to, the glutathionylspermidine synthetase/amidase of Escherichia coli, and amidase activity was not detected in glutathionylspermidine synthetase of C. fasciculata. The kinetics of trypanosomatid glutathionylspermidine synthetase revealed a rapid equilibrium random mechanism with limiting Km values for Mg2+-ATP, GSH, and spermidine of 0.25 +/- 0.02, 2.51 +/- 0.33, and 0.47 +/- 0. 09 mM, respectively, and a kcat of 415 +/- 78 min-1. Partial reactions at restricted cosubstrate supply were not detected by 31P NMR, supporting the necessity of a quarternary complex formation for catalysis. ADP inhibited competitively with respect to ATP (Ki = 0. 08 mM) and trypanothione exerted a feedback inhibition competitive with GSH (Ki = 0.48 mM).

Adenosine Diphosphate↗
PubMed1997

Crystal structure of a ternary complex of D-2-hydroxyisocaproate dehydrogenase from Lactobacillus casei, NAD+ and 2-oxoisocaproate at 1.9 A resolution.

D-2-hydroxyisocaproate dehydrogenase (D-HicDH) from Lactobacillus casei is a homodimer with 333 amino acids and a molecular mass of 37 kDa per subunit. The enzyme belongs to the protein family of NAD+-dependent D-2-hydroxycarboxylate dehydrogenases and within this family to the subgroup of D-lactate dehydrogenases (D-LDHs). Compared with other D-LDHs D-HicDH is characterized by a very low specificity regarding size and chemical constitution of the accepted D-2-hydroxycarboxylates. Hexagonal crystals of recombinant D-HicDH in the presence of NAD+ and 2-oxoisocaproate (4-methyl-2-oxopentanoate) were grown with ammonium sulphate as precipitating agent. The structure of these crystals was solved by molecular replacement and refined to a final R-factor of 19.6% for all measured X-ray reflections in the resolution range (infinity to 1.86 A). Both NAD+ and 2-oxoisocaproate were identified in the electron density map; binding of the latter in the active site, however, competes with a sulphate ion, which is also defined by electron density. Additionally the final model contains 182 water molecules and a second sulphate ion. The binding of both an in vitro substrate and the natural cosubstrate in the active site provides substantial insight into the catalytic mechanism and allows us to assess previously published active site models for this enzyme family, in particular the two most controversial points, the role of the conserved Arg234 and substrate binding. Furthermore the overall topology and details of the D-HicDH structure are described, discussed against the background of homologous structures and compared with one closely and one distantly related protein.

Alcohol Oxidoreductases↗
PubMed1997

A unique cascade of oxidoreductases catalyses trypanothione-mediated peroxide metabolism in Crithidia fasciculata.

Parasitic trypanosomatids comprise causative agents of debilitating or life-threatening tropical diseases. The limited capacity of these parasites to cope with oxidative stress has been discussed as a target area for therapeutic approaches but success has been hampered by a lack of comprehension of their peculiar oxidant defense system depending on the unique redox metabolite trypanothione. Here we report that trypanothione-dependent hydroperoxide metabolism in Crithidia fasciculata is catalysed by two distinct proteins working in concert. One is Cf16, a unique protein which, apart from a WCPPC sequence that resembles the thioredoxin-type WCG(A)PC motif, only shows low similarity to thioredoxin-like proteins of bacteria and invertebrates. The second component is Cf21, which can be classified as a member of the peroxiredoxin family of proteins. The two proteins have been purified to homogeneity and shown to be essential for the trypanothione-dependent removal of hydroperoxides. By means of selective derivatisation of the substrate-reduced proteins the flux of reduction equivalents from trypanothione to Cf16, Cf21 and finally to the hydroperoxide was elucidated. Cf21 proved to be a moderately efficient peroxidase with broad specificity. The rate constants for the reaction of the reduced protein with H2O2, t-butyl hydroperoxide, linoleic acid hydroperoxide and phosphatidylcholine hydroperoxide were 1.0 x 10(5), 1.2 x 10(5), 1.0 x 10(5) and 0.4 x 10(5) M-1S-1, respectively. The apparent rate constant for the regeneration of reduced Cf21 by Cf16 was in the range of 1.5-3.5 x 10(6) M-1S-1. This newly discovered metabolic pathway adds two further candidates to the list of potential targets for trypanocidal drugs.

Amino Acid Sequence↗
PubMed1996

A selenium-containing phospholipid-hydroperoxide glutathione peroxidase in Schistosoma mansoni.

The 100000Xg supernatant parasite platyhelminth Schistosoma mansoni exhibits a glutathione peroxidase activity with the substrate phosphatidylcholine hydroperoxide. Purification yielded a protein of 20 kDa molecular mass both on gel filtration column chromatography and SDS/PAGE, thus suggesting that S. mansoni expresses a protein similar to the mammalian selenoenzynic phospholipid-hydroperoxide glutathione peroxidase. Kinetic analysis and substrate specificity corroborated this assumption, the second-order rate constants for the oxidation of the ground-state enzyme (k+1) being higher with phosphatidylcholine hydroperoxide than with other peroxide substrates, such as cumene liydroperoxide or H2O2, and quantitatively similar to those of mammalian phospholipid-hydroperoxide glutathione peroxidase. Partial sequencing of the protein and selenium measurement by neutron activation analysis established that the purified peroxidase corresponded to the product of the S. mansoni gene previously reported and supposed to encode a selenium-containing glutathione peroxidase [Roche, C., Williams, D. L., Khalife, J., LePresle, T., Capron, A. & Pierce, R. J. (1994) Cloning and characterization of gene encoding Schistosoma mansoni glutathione peroxidase, Gene 138, 149 - 152]. S. mansoni thus contains a scienoperoxidase sharing molecular mass, catalytic efficiency and substrate specificity with phospholipid-hydroperoxide glutathione peroxidase, dismantling the concept that those enzymes are unique to vertebrate organisms.

Amino Acid Sequence↗
PubMed1996

Immunological identification of a putative precursor of the insoluble glycoprotein framework of the Chlamydomonas cell wall.

To identify precursors of the insoluble glycoprotein framework of the Chlamydomonas cell wall, a polyclonal antibody was raised against the mixture of polypeptides released from the insoluble wall fraction by chemical deglycosylation. This antibody preferentially cross-reacted with a '150 kDa' salt-soluble cell wall glycoprotein. The conclusion that this '150 kDa' glycoprotein is a putative precursor of the insoluble cell wall fraction was corroborated by the results of pulse-chase experiments and by experiments with antibodies raised against the '150 kDa' salt-soluble glycoprotein and against its 100 kDa deglycosylation product, respectively. Whereas the antibody against the '150 kDa' glycoprotein preferentially recognized carbohydrate side chains, the antibody against its 100 kDa deglycosylation product was found to have essentially the same specificity towards glycosylated and deglycosylated cell wall components as the antibody against the deglycosylation products of the insoluble wall fraction. Furthermore, the antibody against the deglycosylated, insoluble wall fraction recognized almost the same set of peptide fragments derived by V8 protease treatment from the '150 kDa' salt-soluble cell wall glycoprotein and its 100 kDa deglycosylation product, respectively, as the antibody against the 100 kDa deglycosylated cell wall polypeptide.

Amino Acid Sequence↗
PubMed1996

Activity of the retinoblastoma family proteins, pRB, p107, and p130, during cellular proliferation and differentiation.

Genetic evidence from retinoblastoma patients and experiments describing the mechanism of cellular transformation by the DNA tumor viruses have defined a central role for the retinoblastoma protein (pRB) family of tumor suppressors in the normal regulation of the eukaryotic cell cycle. These proteins, pRB, p107, and p130, act in a cell cycle-dependent manner to regulate the activity of a number of important cellular transcription factors, such as the E2F-family, which in turn regulate expression of genes whose products are important for cell cycle progression. In addition, inhibition of E2F activity by the pRB family proteins is required for cell cycle exit after terminal differentiation or nutrient depletion. The loss of functional pRB, due to mutation of both RB1 alleles, results in deregulated E2F activity and a predisposition to specific malignancies. Similarly, inactivation of the pRB family by the transforming proteins of the DNA tumor viruses overcomes cellular quiescence and prevents terminal differentiation by blocking the interaction of pRB, p107, and p130 with the E2F proteins, leading to cell cycle progression and, ultimately, cellular transformation. Together these two lines of evidence implicate the pRB family of negative cell cycle regulators and the E2F family of transcription factors as central components in the cell cycle machinery.

Animals↗
PubMed1995

Expression of the positive regulator of cell cycle progression, cyclin D3, is induced during differentiation of myoblasts into quiescent myotubes.

L6 cells are committed skeletal muscle precursors which can be induced to differentiate into multinucleated, terminally differentiated myotubes. Upon differentiation, these immature skeletal myotubes enter a quiescent state and are unable to reenter the cell cycle. We have examined expression of a series of genes involved in regulation of progression through the G1/S boundary in undifferentiated L6 cells and during terminal differentiation of L6 myoblasts. While no change in the level of cyclin D1 transcript and a transient increase in cyclin D2 transcript were observed, a large increase in cyclin D3 expression was found. Immunohistochemistry demonstrated strong staining for cyclin D3 protein in the nuclei of the multinucleated myotubes from 4 independent myoblast cell lines; L6, L8, G8 and C2C12. Immunoprecipitation confirmed a greater than 20-fold increase in the levels of cyclin D3 protein in the differentiated L6 myotubes as well as its association with a number of proteins. Western assays demonstrated, further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and cdk4, in differentiated L6 cells. However, while kinase activity specific for a GST-pRB fusion protein was seen for cyclin D3-containing complexes isolated from undifferentiated cells, the high levels of cyclin D3 in the differentiated myotubes had no associated kinase activity. These data demonstrate that cyclin D3 may also have a function in terminally differentiated, quiescent cells. The lack of cyclin D3-associated kinase activity and its association with a number of different proteins suggest that cyclin D3 may regulate the function of other proteins by direct interaction with these factors.

Animals↗
PubMed1995

Expression of ril, a novel LIM domain gene, is down-regulated in Hras-transformed cells and restored in phenotypic revertants.

Several candidate genes involved in the maintenance of normal growth control (H-rev) were identified by differential expression cloning on the assumption that they are expressed in phenotypically normal rat cells and repressed in closely related H-ras transformed cells. Previously the genes coding for lysyl oxidase (H-rev142) and for an 18K-protein of unknown function (H-rev107) were recovered as cDNAs by subtraction cloning. Here we describe the identification and expression pattern of ril, a novel member of the heterogeneous group of genes encoding proteins with LIM/double zinc finger domains. The ril gene is expressed in normal fibroblasts and down-regulated in H-ras-transformed derivatives. Expression is restored in several independent phenotypic revertants derived from H-ras transformed cells. The predicted protein product of ril harbors a single LIM domain but lacks a homeodomain. The ril gene is highly conserved during evolution and is transcribed in various normal cell lines. Northern blot analysis and in situ hybridization studies showed that ril is expressed in meiotic spermatocytes, in somites of developing mice, and in a wide variety of tissues of adult mice.

Amino Acid Sequence↗
PubMed1995

Secondary structure prediction of adenylate kinase by circular dichroism spectroscopy of synthetic peptides.

The synthesis of 13 segments of porcine adenylate kinase (AK 1) consisting each of 15 residues and covering the whole sequence of AK 1 is reported. The peptides were obtained by multiple peptide synthesis applying Fmoc/tert. butyl strategy. For the conformational analysis by circular dichroism spectroscopy different mixtures of phosphate buffer (pH 7), trifluoroethanol and methanol were used. Ten peptides showed alpha-helical conformation in all solvents except of pure buffer. The conformation of these peptides correlated well with the secondary structure obtained by homology modelling and even more striking with the X-ray structure of adenylate kinase, which was published recently. In contrast, three peptides, which were suggested to adopt no helical conformation did not show any content of alpha-helicity in any of the solvents that we investigated. One peptide, which contains a beta-sheet according to the X-ray analysis revealed a high content of beta-conformation by CD in buffer and in mixtures with trifluoroethanol. The two other peptides revealed mainly random coil in all solvents which we investigated. Therefore, we conclude that synthetic peptides are suitable tools to investigate the secondary structure of protein segments and that this conformation is frequently preserved in the intact protein.

Adenylate Kinase↗
PubMed1995

Expression and activity of the retinoblastoma protein (pRB)-family proteins, p107 and p130, during L6 myoblast differentiation.

The activity of the E2 F-family of transcription factors is tightly linked to control of the cell cycle. p107 and p130, two closely related members of the retinoblastoma protein-family of negative cell cycle regulators, modulate the activity of the E2f-family proteins by direct interaction with these factors. To understand the role of p107 and p130 in progression through or exit from the cell cycle, we have characterized the expression, phosphorylation state, cyclin-binding, and E2f-binding activity of p107 and p130 during terminal differentiation of rat myoblast cells into immature skeletal muscle (myotubes). In exponentially growing L6 myoblasts, p107 is phosphorylated in a cell cycle-dependent manner, and E2f-site binding complexes containing p107 is phosphorylated in a cell cycle-dependent manner, and E2f-site binding complexes containing p107 can be observed throughout the cell cycle. During differentiation of L6 cells, p107 levels are reduced, while p130 protein levels are increased 8-fold. Despite both p107 and p130 becoming hypophosphorylated during myogenesis, the E2F-site DNA-binding complexes containing p107 observed in exponentially growing myoblasts are quantitatively replaced in myotubes with complexes containing only p130. In myotubes, p107 is not associated with E2f-family proteins that are capable of binding DNA. The failure to observe p107-containing complexes in myotubes appears to be due to the differentiation-specific induction of both p130 and cyclin D3, p107 is found in complexes with cyclin D3 in myotubes, and the addition of exogenous cyclin D3 or p130 to lysates from undifferentiated L6 cells was able to disrupt p107-containing E2F-site binding complexes. In myotubes, p130 also forms complexes with cyclin D3 as well as cyclin E, cdk2, and cdk4. We are able to copurify cyclin D3 with cyclin E from myotubes, indicating the presence of a macromolecular complex containing both cyclin E and cyclin D3 simultaneously bound to p130. Thus, in myoblasts, p107 is normally involved in regulation of E2f-family proteins during cell cycle progression, while p130 is a differentiation-specific regulator of E2f activity. Our results also provide evidence that the apparent positive regulator of cell cycle progression, cyclin D3, has a function in terminally differentiated muscle cells.

Animals↗
PubMed1994

Phospholipid-hydroperoxide glutathione peroxidase. Genomic DNA, cDNA, and deduced amino acid sequence.

The complete amino acid sequence of the selenoprotein phospholipid-hydroperoxide glutathione peroxidase (PHGPX) from pig heart has been deduced from the corresponding genomic DNA, the cDNA covering the coding region, and by sequencing the N terminus of the protein. The maximum length of the peptide chain derived from the cDNA amounts to 170 amino acid residues. By protein sequencing the N-terminal residues methionine and cysteine of the deduced sequence were found to be cleaved. The molecular mass of 19,671 Da obtained by laser desorption mass spectroscopy, however, significantly exceeds the mean molecular mass of 19,257.09 calculated for the sequence 3-170 of PHGPX, thus indicating posttranscriptional modification. In contrast to glutathione peroxidase (GPX) the coding area of the PHGPX gene is composed of seven exons. Only the amino acid sequences encoded by the third and fifth exon are highly homologous to GPX sequences. The amino acid residues selenocysteine, tryptophan, and glutamine forming the catalytic site in bovine GPX are conserved in homologous positions of PHGPX, whereas the arginine residues presumed to bind GSH in GPX are not. Gaps in the PHGPX sequence correspond to subunit interaction sites of the tetrameric GPX. The data suggest an identical catalytic mechanism of the selenoperoxidases, a less stringent substrate specificity of PHGPX, and explain the monomeric nature of PHGPX. As in other selenoproteins, the selenocysteine residue of PHGPX is encoded by UGA. The 3'-untranslated region (UTR) of the PHGPX shows a limited consensus with that of GPX and 5'-deiodinase, where it was shown to be responsible for the decoding of UGA as selenocysteine. The 3'-UTR of PHGPX can form a stem/loop as in other mammalian selenoprotein genes. The 5'-UTR and the first intron of the PHGPX gene contain a variety of putative regulatory elements indicating hormonal control.

Amino Acid Sequence↗
PubMed1992

Morphological alterations accompanying the effect of peptaibiotics, alpha-aminoisobutyric acid-rich secondary metabolites of filamentous fungi, on Culex pipiens larvae.

The effect of different representatives of the group of peptaibiotics, alpha-amino-isobutyric acid rich secondary metabolites of filamentous fungi, on Culex pipiens larvae was studied. Light and transmission electron microscopy techniques were used to localize the intracellular damage and to determine the target organells for the mode of action of peptaibols in mosquito larvae. Though different in insecticidal activity, all tested compounds induced the same type of tissue damage, which was characterized by heavy challenge of mitochondria followed by partial swelling, crystaeolysis and destruction of mitochondrial walls. It is concluded that the mode of action of peptaibols in mosquito larvae is mediated through the damage of mitochondria. The structure-mosquitocidal effect of these compounds, their potential mode of action and role in the natural fungal entomopathogenic process are briefly discussed.

Alamethicin↗
PubMed1992

Reduced lymphocyte activation in space: role of cell-substratum interactions.

We investigated the effect of substratum adhesiveness on stimulated lymphocyte blastogenesis by reducing and blocking cell adhesion with poly (2-hydroxyethyl methacrylate) (poly-HEMA) in a simple on-ground system. Cells grown on medium-thick and thick poly-HEMA films were rounded in shape and displayed no signs of spreading. By contrast, on tissue culture plastic and very thin poly-HEMA films, they showed clear signs of spreading. The mitogenic response of lymphocytes grown on thick poly-HEMA films was reduced by up to 68% of the control (tissue culture plastic). Interferon-gamma production was near zero when the cells were grown on the least adhesive substratum. On uncoated plastic, activated lymphocytes subjected to high gravity (20g) exhibited an increased proliferation rate (40%) compared with 1g. By contrast, on poly-HEMA, high gravity did not improve lymphocyte responsiveness. These results show that activated lymphocytes need to anchor and spread prior to achieving an optimal proliferation response. We conclude that decreased lymphocyte adhesion could contribute to the depressed in vitro lymphocyte responsiveness found in the microgravity conditions of space flight.

Cell Adhesion↗
PubMed1990

A ground-based model to study the effects of weightlessness on lymphocytes.

The mitogenic response of human lymphocytes was found to be markedly reduced in weightlessness conditions as compared to normal gravity. One possible explanation is that due to the non-existent sedimentation in space the lymphocytes could not adhere and spread on a substratum. Thus, we investigated the effect of substratum adhesiveness on lymphocyte responsiveness by reducing and blocking cell adhesion with poly-HEMA in a simple on-ground system. Lymphocyte adhesiveness was assessed by measuring the proportion of non-adhesive, slightly, and strongly adhesive 51Cr-radiolabelled cells on uncoated and poly-HEMA coated plastic. The amount of cell spreading on surfaces with varying adhesiveness was determined by measuring the area of cells. Cells grown on medium and thick poly-HEMA films were rounded in shape. By contrast, on tissue culture plastic, they showed clear signs of spreading. The mitogenic response of lymphocytes grown on thick poly-HEMA films was reduced by up to 68% of the control (tissue culture plastic). Interferon-gamma production was virtually nil when the cells were grown on the least adhesive substratum. These results show that activated lymphocytes need to anchor and spread prior to achieving an optimal proliferation response. We conclude that decreased lymphocyte adhesion could contribute to the depressed in vitro lymphocyte responsiveness found in the microgravity conditions of space flight.

Cell Adhesion↗
PubMed1990

Oxygen delivery and consumption and ventricular preload are greater in survivors than in nonsurvivors of the adult respiratory distress syndrome.

In patients with adult respiratory distress syndrome (ARDS), oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Because of alterations in ventricular function, DO2 may be inadequate to satisfy oxygen demand and may contribute to multiple-system organ failure (MSOF). To determine whether there are differences in DO2, VO2, ventricular function, and MSOF, between survivors and nonsurvivors of ARDS, we studied 29 patients without cardiac disease early in the course of ARDS (hypoxemia, diffuse bilateral pulmonary infiltrates, and pulmonary artery occlusion pressure less than 18 mm Hg). Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen transport measurements were made within 24 h of onset of ARDS. Thirteen survivors had greater DO2 and VO2 than did 16 nonsurvivors (p = 0.004 and 0.001, respectively). MSOF developed in no survivors and in 63% of nonsurvivors. In four survivors and in six nonsurvivors in whom DO2 was changed acutely, VO2 was dependent on DO2 (p = 0.014). Survivors had greater stroke volume index and right and left ventricular end-diastolic volume indices than did nonsurvivors despite similar right atrial and pulmonary artery occlusion pressures. There were no differences between survivors and nonsurvivors in biventricular ejection fractions. We conclude that survivors of ARDS have greater DO2 and VO2 than do nonsurvivors. Survival may be explained by the strong inverse relation between DO2 and development of MSOF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗