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Biomedical subjects

C E Olsen

Publications and source records attributed to C E Olsen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Disposition of 4-methylimidazole in goats and heifers.

4-Methylimidazole (MeI) is formed when hay is ammoniated and it has been suspected of being the compound causing the 'crazy cow' syndrome. The aim of the present study was to describe the disposition of MeI in goats and heifers. The mean residence time was about five hours and the volume of distribution 0.9 litre kg-1 bodyweight in both goats and heifers. Goats metabolised MeI to a much higher extent than heifers which excreted the major part as the unchanged compound. MeI and its metabolites were excreted mainly in urine, but also in milk and faeces. In spite of administration of a dose (20 mg kg-1 bodyweight) which is much higher than the one intoxicated animals may have received through contaminated fodder none of the typical signs of intoxication were observed and it is concluded that MeI may not alone be the cause of the 'crazy cow' syndrome.

Animals↗
PubMed1993

Identification of B-cell epitopes on the S4 subunit of pertussis toxin.

The main purpose of the present study was to identify B-cell epitopes on the S4 subunit of pertussis toxin (PT) by the synthetic peptide approach. Two strategies were followed: (i) screening of two series of overlapping peptides (12- and 25-residue peptides) covering the entire S4 sequence by a panel of murine monoclonal anti-PT antibodies and various polyclonal anti-PT antisera in an enzyme-linked immunosorbent assay (ELISA), and (ii) analysis of the S4 amino acid sequence by a predictive algorithm followed by synthesis and immunization of mice with the predicted peptides coupled to diphtheria toxoid. The anti-peptide conjugate antisera were tested in an ELISA for cross-reactivity with native PT, B oligomer, and S4. Screening of the free peptides in an ELISA by the PT antisera indicated the presence of six B-cell epitope-containing domains covered by residues 18 to 32, 33 to 46, 39 to 52, 51 to 65, 71 to 84, and 91 to 106. None of the peptides, however, were recognized by the monoclonal anti-PT antibodies in an ELISA. Immunization with six computer-predicted peptides (B1 to B6) and three potential T-cell epitopes (T1 to T3) gave rise to very high antibody responses towards the homologous conjugates. With the exception of the anti-T1/diphtheria toxoid antisera, all anti-peptide conjugate antisera cross-reacted with PT in an ELISA at different levels. None of these anti-peptide conjugate antisera, however, showed any PT-neutralizing effect as measured by the Chinese hamster ovary cell assay and the leukocytosis-promoting activity test. The results of the present study suggest that discontinuous epitopes are predominant in the S4 subunit of native PT.

Amino Acid Sequence↗
PubMed1993

Antifungal macrocyclic polylactones from Penicillium verruculosum.

Three macrocyclic polylactones have been isolated from Penicillium verruculosum. Two were found to be novel and the third to be identical with NG-012(1). Their structures were elucidated by spectroscopic and chemical methods. A full assignment of 1H- and 13C-resonances in acetone-d6 are given for all three compounds. The compounds show antifungal activity.

Animals↗
PubMed1992

The biosynthesis of cyanogenic glucosides in seedlings of cassava (Manihot esculenta Crantz).

A microsomal system catalyzing the in vitro synthesis of the aglycones of the two cyanogenic glucosides linamarin and lotaustralin has been isolated from young etiolated seedlings of cassava (Manihot esculenta Crantz). A prerequisite to obtain active preparations is the complete removal of the endosperm pellicle covering the cotyledons before seedling homogenization. The rates of conversion of the parent amino acids valine and isoleucine to their cyanohydrins are 19 and 6 nmol/h/mg protein, respectively. The conversion rates for the corresponding oximes (2-methylpropanal oxime and 2-methylbutanal oxime) are 475 and 440 nmol/h/mg protein and for the nitriles (2-methylpropionitrile and 2-methylbutyronitrile) 45 and 75 nmol/h/mg protein. With the exception of 2-cyclopentenylglycine, none of the additionally tested amino acids are metabolized, whereas a broad substrate specificity is observed using oximes and nitriles as substrates. The in vitro biosynthesis is photoreversibly inhibited by carbon monoxide, demonstrating the involvement of cytochrome P450 in the hydroxylation processes. All tissues of the cassava seedling contain cyanogenic glucosides. The microsomal enzyme system responsible for their synthesis is restricted to the cotyledons and their petioles. This demonstrates that the cyanogenic glucosides are actively transported to other parts of the seedling. The enzyme activity decreases with the height of the etiolated seedling and is barely detectable in seedlings above 75 mm.

Glucosides↗
PubMed1991

Monoclonal antibodies toward a stable cyclic AMP-C8 antigen.

A cyclic AMP antigen was prepared utilizing a stable thioether linkage from C8 of the purine moiety. Monoclonal antibodies were raised toward the cyclic AMP-C8-diphtheria toxoid antigen and found to be of high specificity, with only very low cross-reactivity against related compounds, less than 0.03% against cGMP being the most significant cross-reaction. The stability of the thioether linkage enabled the preparation of an enzyme tracer, which was used in an ELISA. The assay had an effective working range from 0.1 to 100 pmol cAMP. Due to the structure of the antigen, the need for sample derivatization was eliminated.

Animals↗
PubMed1991

Toxin production in Pyrenophora teres, the ascomycete causing the net-spot blotch disease of barley (Hordeum vulgare L.).

Toxin production in a large number of Pyrenophora teres isolates have been investigated. During fungal growth, the pH of the medium decreases from 6.5 to about 3.0. Aspergillomarasmine A is the major toxin excreted into the culture medium. Nonenzymatic acid-catalyzed conversion of aspergillomarasmine A to anhydroaspergillomarasmine A proceeds at low pH and is prevented by repeated titration of the culture medium to pH 6.5. The four possible stereoisomers of N-(2-amino-2-carboxyethyl)aspartic acid have been chemically synthesized and their absolute configuration determined. From circular dichroism and NMR spectroscopy and by measurements of specific optical rotation, the LL-form is identified as the stereoisomer produced by P. teres. Biosynthetic experiments using radioisotopes demonstrate that the LL-isomer of N-(2-amino-2-carboxyethyl) aspartic acid is a direct precursor of aspergillomarasmine A. Consequently, L-configuration is assigned to the two corresponding asymmetric carbon atoms of aspergillomarasmine A. This is in contrast to earlier reports which had indicated D configuration. The phytotoxicity of anhydroaspergillomarasmine A is comparable with that of L-aspartic acid, whereas LL-N-(2-amino-2-carboxyethyl)aspartic acid exerts strong phytotoxicity in the bioassays as shown previously for aspergillomarasmine A. The amount of LL-N-(2-amino-2-carboxyethyl)aspartic acid which accumulates in the P. teres cultures is low, indicating that aspergillomarasmine A is the toxin which plays the major role in the pathological changes associated with the barley net-spot blotch disease.

Ascomycota↗
PubMed1991

The potential of perturbed angular correlation of gamma rays as a tool for dynamic studies of peptides/proteins.

Four peptides and serum albumin have been derivatized with the bicyclic anydride of diethylenetriamine-pentaacetic acid. Procedures were developed to isolate the labelled species and determine the degree of derivatization. By using perturbed angular correlation of gamma-ray spectroscopy it is possible, through the determination of rotational correlation times, to decide whether labelled peptides interact with other molecules (receptors). In the case of the peptide cholecystokinin it is shown that the interaction between the peptide and its corresponding polyclonal antibody can be determined down to 1 pmol hormone. Experiments on 111In- and 111mCd-labelled Gly-Trp showed that, where the 111Cd PAC spectrum directly reflected the rotational motion of the molecule, the 111In PAC spectrum was affected by the nuclear transitions to 111mCd.

Anisotropy↗
PubMed1989

The biosynthesis of cyanogenic glucosides in higher plants. The (E)- and (Z)-isomers of p-hydroxyphenylacetaldehyde oxime as intermediates in the biosynthesis of dhurrin in Sorghum bicolor (L.) Moench.

The biosynthesis of the tyrosine-derived cyanogenic glucoside dhurrin has been studied with a microsomal preparation obtained from etiolated seedlings of sorghum. The biosynthetic pathway involves tyrosine, N-hydroxytyrosine, and p-hydroxyphenylacetaldehyde oxime as early intermediates (Møller, B. L. and Conn, E. E. (1980) J. Biol. Chem. 254, 8575-8583). The use of deuterium-labeled tyrosine and mass spectrometric analyses demonstrate that the alpha-hydrogen atom of tyrosine is retained in the conversion of tyrosine to p-hydroxyphenylacetaldehyde oxime. This excludes p-hydroxyphenylpyruvic acid oxime as intermediate in the pathway. A high pressure liquid chromatography method was developed to separate the (E)- and (Z)-isomers of p-hydroxyphenylacetaldehyde oxime. The microsomal enzyme system was found to produce initially the (E)-isomer of p-hydroxyphenylacetaldehyde oxime. An isomerase then converts the (E)-isomer to the (Z)-isomer, which is the isomer preferentially utilized by the microsomal enzyme system in the subsequent biosynthetic reactions. The (E)-isomer produced in situ is more efficiently converted to the (Z)-isomer than exogenously added (E)-isomer and may thus be metabolically channeled.

Carbon Radioisotopes↗
PubMed1989

Preparation and Properties of Antibodies against Indoleacetic Acid (IAA)-C5-BSA, a Novel Ring-Coupled IAA Antigen, as Compared to Two Other Types of IAA-Specific Antibodies.

Two types of indoleacetic acid (IAA) antigens have been described in the literature which show marked differences with respect to antibody specificity. In this communication an alternative antigen design is described. In the so-called IAA-C5-BSA conjugate, both the acetic acid group and the pyrrole moiety are presented free, as the covalent linkage between IAA and the carrier molecule is introduced in the benzene moiety. Antibodies were elicited in rabbits against this novel antigen. Using cross-reactivity data and the strategy of successive approximation for the measurements of auxin levels in the internodes of light-grown broad bean (Vicia faba L. cv Superfine), the three types of antibodies are compared.

Journal Article↗
PubMed1987

Pharmacokinetics and metabolism of metioprim in pigs and goats.

The pharmacokinetics and metabolism of metioprim (MTP) have been studied after intravenous administration of a single dose of 5 mg/kg b.wt. to pigs (n = 4) and 10 mg/kg b.wt. to goats (n = 5). Kinetic parameters were calculated using a two-compartment open model. The elimination half-life was much shorter in goats (23 +/- 4 min.) than in pigs (169 +/- 17 min.). The apparent volume of distribution exceeded 1.0 1/kg b.wt. in both species indicating accumulation in tissues. Pigs excreted the major part of the dose (86 +/- 9%) in urine and only a small part (9 +/- 3%) in faeces, while the goats excreted almost equal amounts in urine (55 +/- 5%) and faeces (38 +/- 4%). Metabolism played the major role in elimination of MTP. Of the 80% of the dose excreted in urine within 24 hrs in pigs unchanged MTP made up 8%, metioprim sulfoxide 64% and O-desmethyl-MTP 8%. Metioprim sulfoxide was also the major metabolite in goats, but in this species another demethylated metabolite--metioprim sulfonic acid--was formed. Goats excreted 49 +/- 7% of the dose in urine within 24 hrs of which unchanged MTP made up less than 1%, while metioprim sulfoxide accounted for about 35% and metioprim sulfonic acid for approximately 14%. Metabolites isolated from urine were identified by NMR-spectroscopy combined with EI, FAB or 252Cf plasma desorption mass spectrometry.

Animals↗
PubMed1984

Pharmacokinetics and metabolism of sulphadiazine in neonatal and young pigs.

The pharmacokinetics of sulphadiazine was studied in newborn, 1 week, and 8 weeks old piglets after intravenous administration of 60 mg/kg. Kinetic parameters were calculated using a two compartment open model. Steady state volume of distribution averaged 0.62, 0.56, and 0.48 1/kg at birth, 1 week, and 8 weeks, respectively. Elimination half-life decreased from 455 min. at birth to 322 min. at 1 week and 157 min. at 8 weeks leading to a rise in body clearance from 0.99 to 2.20 ml/min./kg during the same age period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both renal function and metabolic capacity. Although renal clearance increased several times more than metabolic clearance, metabolism remained the main contributor to elimination of SDZ at all ages. Metabolism of SDZ involves two important pathways - acetylation and aromatic hydroxylation; the former being well developed at birth, while the latter increased markedly during the age period studied.

Acetylation↗
PubMed1983

Prostaglandin-oxytocin induction of mid-trimester abortion complicated by grand mal-like seizures.

Mid-trimester therapeutic abortion is performed routinely in several clinics by using a combination of intra-amniotic instillation of prostaglandin F2 alpha, followed by intravenous infusion of oxytocin in 5% glucose. In doses as low as 10 mU/min, oxytocin has an antidiuretic action. Two cases of grand mal-like seizure in connection with this procedure of therapeutic abortion are reported and the background discussed.

Abortion, Induced↗
PubMed1983

Orotic acid sodium salt in kidney stones and urinary deposits.

Kidney stones from a plaice, Pleuronectes platessa, have been shown to consist of the sodium salt of orotic acid. Precipitation of orotic acid in human kidneys and urine samples has previously been reported but the precipitates must have been salts, most likely the sodium salt, of orotic acid and not the free acid. This reinterpretation is based on the acid strength of orotic acid and on data for the solubilities of sodium orotate and orotic acid. Sodium orotate is therefore a member on the list of compounds present in human urinary deposits and calculi. X-ray powder diagrams and d-values and IR-spectra of the sodium salt are recorded to facilitate future identifications.

Animals↗
PubMed1981

Prognostic value of human placental lactogen (HPL) in an unselected obstetrical population.

A prospective study on the value of routine HPL determination as a supplement to clinical antenatal care is presented. The HPL values in the apparently normal pregnant women were not known to the clinicians. The material comprised 1 660 pregnancies and deliveries, in 87% of which at least one HPL value was available. The results are expressed as the ability of a low HPL value to predict the birth of a distressed infant and/or an infant of low birth weight, a normal HPL value the birth of a non-distressed infant and/or an infant of normal birth weight. Moreover, the results show has many of the distressed infants and infants of low birth weight were born to mothers with low HPL values. Like a number of other authors, we found that HPL screening increases the prognostic reliability in pregnancies with complications. On the other hand, its value in normal pregnancies could not be confirmed.

Adult↗
PubMed1980

Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors.

Benzodiazepines probably exert their anxiolytic, hypnotic, and anticonvulsant effects by interacting with brain-specific high-affinity benzodiazepine receptors. In searching for possible endogenous ligands for these receptors we have purified a compound 10(7)-fold from human urine by extractions, treatment with hot ethanol, and column chromatography. The compound was identified as beta-carboline-3-carboxylic acid ethyl ester (IIc) by mass spectrometry, NMR spectrometry, and synthesis; IIc was also isolated from brain tissues (20 ng/g) by similar procedures. Very small concentrations of IIc displaced [3H]diazepam completely from specific cerebral receptors, but not from liver and kidney binding sites; the concentration causing 50% inhibition of specific [3H]diazepam binding (IC50) was 4-7 nM compared to ca. 5 nM for the potent benzodiazepine lorazepam. Specific binding sites for quinuclidinyl benzilate, naloxone, spiroperidol, serotonin, muscimol, and WB 4101 were not affected by IIc. In contrast to benzodiazepines, IIc exhibits "mixed type" competitive inhibition of forebrain benzodiazepine receptors (negative cooperativity). We surmise that an endogenous ligand for benzodiazepine receptors may be a derivative of beta-carboline-3-carboxylic acid.

Binding, Competitive↗
PubMed1980

Brain extracellular space during spreading depression and ischemia.

The change of extracellular space volume of rat brain cortex during ischemia and cortical spreading depression, CSD (Leão 1944) was evaluated by a new method. The cortical surface was irrigated with isotonic CSF containing the extracellular markers 50 mM cholin or 50 mM trimethyltris(hydroxymethyl)methyl ammonium ion (N-TRIS), and their extracellular concentrations were monitored by ion-selective microelectrodes. When steady-state for the concentration of these markers was attained, CSD evoked a reversible increase of the concentration of the markers, indicating shrinkage of the interstitial volume of distribution. During ischemia an initial slow rate of concentration increase was observed, followed a few minutes later by a rapid increase concomitant with the sharp rise in extracellular potassium concentration. During CSD and ischemia, the maximal increases of choline and N-TRIS concentration reflected a shrinkage of the extracellular space amounting to about 50% of the initial volume.

Animals↗
PubMed1980

Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate.

The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.

Animals↗