Biomedical subjects

M Siggaard-Andersen

Publications and source records attributed to M Siggaard-Andersen.

9 recordsLinked to original sources

PubMed1995

Oxygen status algorithm, version 3, with some applications.

The Oxygen Status Algorithm is a computer program which uses measurements from a pH & blood gas analyser and a hemoximeter to calculate the oxygen status and the acid-base status of the arterial blood. Version 3 features on-line data collection from the analyser; storage of up to 2000 patient cases in a Lotus 123 file format; printing of a Cumulated Patient Report in addition to the Patient Status Report; combination of arterial and mixed venous data for calculation of the shunt and the oxygen consumption rate (when cardiac output is keyed in); calculation of reference values for fetal haemoglobin for newborns (when gestational age is keyed in). Examples of applications answer the following questions: 1) Does hyperventilation improve the oxygen supply to the tissues? No, for a normal person a slight hypoventilation with a pCO2 of 8.5 kPa provides a maximal oxygen extraction tension. 2) What is the optimal hyperventilation at the top of Mt. Everest (ambient pressure 33 kPa)? Hyperventilation to a pCO2 of about 1.4 kPa provides a maximal oxygen extraction tension of 2.4 kPa for an unacclimatized person. 3) Which change in haemoglobin oxygen affinity would be equivalent to a decrease in arterial pO2 to 6.3 kPa? The oxygen extraction tension would decrease to 4.0 kPa and the same value would be caused by a decrease in half-saturation tension to 2.8 kPa, a decrease which could be due to a moderate alkalaemia (pH = 7.54) combined with a moderately decreased 2,3-diphosphoglycerate concentration (3.4 mmol/L). 4) Is temperature correction of the measured pO2 and pCO2 to the actual body temperature needed? Yes, for example, omitting temperature correction even when the patient temperature is only slightly decreased to 36 degrees C would result in a negative value for the calculated arterio-venous shunt fraction when the actual value, using temperature correction, is 11%. 5) Does the alpha-stat approach of pCO2 and pH regulation in hypothermia, where pH is allowed to rise as in blood in vitro, cause a fall in mixed venous pO2 below the critical value? No, although the mixed venous pO2 will be lower than with the pH-stat approach (constant pH at body temperature), it remains above the critical mixed venous pO2 level. The program is intended for clinical routine use as well as teaching purposes. It has context sensitive help as well as an extensive help index. A number of "demo" cases are provided with annotations in a separate file.

2,3-Diphosphoglycerate↗

PubMed1994

The fabJ-encoded beta-ketoacyl-[acyl carrier protein] synthase IV from Escherichia coli is sensitive to cerulenin and specific for short-chain substrates.

A fourth fatty acid condensing enzyme was isolated from Escherichia coli by its ability to restore elongating activity to a protein extract which had been treated with cerulenin, a condensing enzyme-specific inhibitor. The purified beta-ketoacyl-[acyl carrier protein] (ACP) synthase IV [3-oxoacyl-ACP synthase; acyl-ACP:malonyl-ACP C-acyltransferase (decarboxylating), EC 2.3.1.41] (KAS IV) is specific for short-chain acyl-ACP substrates. The enzyme is stable at 43 degrees C and very sensitive to cerulenin (50% inhibition at 3 microM), which binds covalently. A condensing enzyme-specific antibody raised to an expressed open reading frame from barley was used to identify KAS IV protein in Western blots, and the sequence obtained for 30 amino-terminal residues. This led to the isolation of the fabJ gene located in the fab cluster at 24.8 min of the E. coli chromosome. The fabJ gene encodes a polypeptide of 413 amino acids and molecular mass 43 kDa that shows 38% identity and 64% similarity to the fabB-encoded KAS I. The amino acid sequence of KAS IV, however, is more similar to all other published condensing enzyme sequences than the KAS I sequence is. A specialized putative function for this enzyme is to supply the octanoic substrates for lipoic acid biosynthesis. We predict that an analogue of KAS IV with the same function will be found in plant mitochondria. The described complementation assay can be used to detect condensing enzymes with other substrate specificities by supplementing the cerulenin-treated extract with appropriate purified KAS enzymes.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1993

The TANH-equation modified for the hemoglobin, oxygen, and carbon monoxide equilibrium.

The model of the hemoglobin-oxygen equilibrium represented by the TANH-equation is incorporated in the Oxygen Status Algorithm, a computer program for calculating and displaying the oxygen status and the acid-base status of the blood. In the presence of carbon monoxide it is necessary to take the Haldane equation into account. We here describe the necessary equations and methods for iterative solutions. The validity of the Haldane equation has previously been demonstrated by Zwart et al. (J Appl Physiol 1984; 57: 14-20). We have performed a few experiments to confirm this. Like Zwart et al. we find a small deviation from the theory, but in the opposite direction, i.e. the measured p50 values are slightly higher than predicted. We conclude that the Haldane equation adequately accounts for the carbon monoxide effect up to 30% carboxy-hemoglobin, but further studies are needed to confirm or exclude any minor deviation from the Haldane relationship which may be significant at higher carboxy-hemoglobin fractions.

Carbon Monoxide↗

PubMed1991

Primary structure of a cerulenin-binding beta-ketoacyl-[acyl carrier protein] synthase from barley chloroplasts.

The radioactively labeled beta-ketoacyl thioester synthase inhibitor [3H] cerulenin was used to tag three dimeric barely chloroplast proteins (alpha alpha, alpha beta, and beta beta) from the stromal fraction. Oligonucleotides corresponding to amino acid sequences obtained from the purified proteins were used to generate with the polymerase chain reaction a probe for cDNAs encoding the beta subunit. cDNA sequencing revealed an open reading frame for 462 residues comprising the mature protein and a 35-amino acid transit peptide. The deduced amino acid sequence of the mature protein is homologous to the beta-ketoacyl-[acyl carrier protein] (ACP) synthase I [3-oxoacyl-ACP synthase; acyl-ACP:malonyl-ACP C-acyltransferase (decarboxylating), EC 2.3.1.41] of Escherichia coli. Under analogous experimental conditions [3H]cerulenin tagged a single dimeric protein from spinach chloroplasts.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1990

The oxygen status algorithm: a computer program for calculating and displaying pH and blood gas data.

Input parameters for the program are the arterial pH, pCO2, and pO2 (measured by a blood gas analyzer), oxygen saturation, carboxy-, met-, and total hemoglobin (measured by a multi-wavelength spectrometer), supplemented by patient age, sex, temperature, inspired oxygen fraction, fraction of fetal hemoglobin, and ambient pressure. Output parameters are the inspired and alveolar oxygen partial pressures, pH,pCO2 and pO2 referring to the actual patient temperature, estimated shunt fraction, half-saturation tension, estimated 2,3-diphosphoglycerate concentration, oxygen content and oxygen capacity, extracellular base excess, and plasma bicarbonate concentration. Three parameters related to the blood oxygen availability are calculated: the oxygen extraction tension, concentration of extractable oxygen, and oxygen compensation factor. Calculations of the 'reverse' type may also be performed so that the effect of therapeutic measures on the oxygen status or the acid-base status can be predicted. The user may choose among several different units of measurement and two different conventions for symbols. The results are presented in a data display screen comprising all quantities together with age, sex, and temperature adjusted reference values. The program generates a 'laboratory diagnosis' of the oxygen status and the acid-base status and three graphs illustrating the oxygen status and the acid-base status of the patient: the oxygen graph, the acid-base chart and the blood gas map. A printed summary in one A4 page including a graphical display can be produced with an Epson or HP Laser compatible printer. The program is primarily intended for routine laboratories with a blood gas analyzer combined with a multi-wavelength spectrometer. Calculating the derived quantities may enhance the usefulness of the analyzers and improve patient care. The program may also be used as a teaching aid in acid-base and respiratory physiology. The program requires an IBM PC, XT, AT or similar compatible computer running under DOS version 2.11 or later. A VGA color monitor is preferred, but the program also supports EGA, CGA, and Hercules monitors. The program will be freely available at the cost of a discette and mailing expenses by courtesy of Radiometer Medical A/S, Emdrupvej 72, DK-2400 Copenhagen NV, Denmark (valid through 1991). A simplified algorithm for a programmable pocket calculator avoiding iterative calculations is given as an Appendix.

2,3-Diphosphoglycerate↗

PubMed1988

beta-Ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin binding residue.

The fabB gene of E. coli encoding beta-ketoacyl-ACP synthase I has been isolated by complementation and sequenced. The enzyme has been purified and its NH2-terminal residues sequenced. Identification of the active site was accomplished by tagging with 3H-cerulenin and radio sequencing of the region. Comparison of the deduced primary structures of the fabB gene product with the FAS2 gene product of Saccharomyces cerevisiae revealed the probable active site in chalcone synthases of higher plants.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1988

Role of Escherichia coli beta-ketoacyl-ACP synthase I in unsaturated fatty acid synthesis.

Two activities were found in E. coli extracts which could complement unsaturated fatty acid synthesis of a cerulenin treated E. coli fatty acid synthetase. One of these is beta-ketoacyl-ACP synthase I, but it is not known whether the other activity represents the previously characterized beta-ketoacyl-ACP synthase II. A mutant strain exhibiting a temperature sensitive unsaturated fatty acid synthetic activity apparently lacked an active beta-ketoacyl-ACP synthase I.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1984

A mathematical model of the hemoglobin-oxygen dissociation curve of human blood and of the oxygen partial pressure as a function of temperature.

A mathematical model is described giving the oxygen saturation fraction (s) as a function of the oxygen partial pressure (p): y - y0 = x - x0 + h X tanh [k X (x - x0)], where y = kn[s/(1-s)] and x = ln(p/kPa). The parameters are: y0 = 1.875; x0 = 1.946 + a + b; h = 3.5 + a; k = 0.5343; b = 0.055 X [T/(K - 310.15)]; a = 1.04 X (7.4 - pH) + 0.005 X Cbase/(mmol/L) + 0.07 X [[CDPG/(mmol/L)] - 5], where Cbase is the base excess of the blood and CDPG is the concentration of 2,3-diphosphoglycerate in the erythrocytes. The Hill slope, n = dy/dx, is given by n = 1 + h X k X [1 - tanh2[k X (x - x0)]]. n attains a maximum of 2.87 for x = x0, and n----1 for x----+/- infinity. The model gives a very good fit to the Severinghaus standard oxygen dissociation curve and the parameters may easily be fitted to other oxygen dissociation curves as well. Applications of the model are described including the solution of the inverse function (p as a function of s) by a Newton-Raphson iteration method. The po2-temperature coefficient is given by dlnp/dT = [A X alpha X p + CHb X n X S X (1 - s) X B]/[alpha X p + CHB X n X s X (1 - s)], where A = -dln alpha/dT approximately equal to 0.012 K-1; B = (lnp/T)s = 0.073 K-1 for y = y0; alpha = the solubility coefficient of O2 in blood = 0.0105 mmol X L-1 X kPa-1 at 37 degrees C; CHb = concentration of hemoglobin iron in the blood. Approximate equations currently in use do not take the variations of the po2-temperature coefficient with p50 and CHb into account.

Chemical Phenomena↗

PubMed1983

Donnan effect or protein interference in ionised calcium measurements?

The observation that the ionised calcium concentration is higher if measured in the original serum sample than in an ultrafiltrate is examined by means of a theoretical model. It is concluded that this difference is a predictable consequence of the Donnan equilibrium and is not a result of protein interference with the calcium-specific electrode.

Blood Proteins↗