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P Straehl

Publications and source records attributed to P Straehl.

9 recordsLinked to original sources
PubMed1991

Structures of mucin-type sugar chains of the galactosyltransferase purified from human milk. Occurrence of the ABO and Lewis blood group determinants.

The mucin-type sugar chains of human milk galactosyltransferase samples purified from two donors with different blood types were released by alkaline borohydride treatment and quantitatively labeled by N-[3H]acetylation. The radioactive oligosaccharides thus obtained were fractionated by high performance liquid chromatography and immobilized lectin chromatography, and their structures were studied by sequential digestion with endo- or exoglycosidases, methylation analysis, and periodate oxidation. It was revealed that the structures of the mucin-type sugar chains of galactosyltransferase are extremely various, and many blood group determinants are expressed on more than 13 different backbone sugar chains. The characteristic features of the sugar chains could be summarized as follows. 1) The sugar chains of both samples are composed of core 1, Gal beta 1----3GalNAc, and core 2, GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 2) One or two N-acetyllactosamine repeating units extend from the core through GlcNAc beta 1----6Gal and GlcNAc beta 1----3 Gal linkages. 3) Blood group determinants are expressed in accord with the blood types of the donors: sample 1 from a donor of blood type O, Lea+b- contains oligosaccharides with Lea and X determinants, and sample 2 from a donor of B, Lea-b- contains those with H, X, Y, and B determinants.

ABO Blood-Group System↗
PubMed1991

Brefeldin A induces endoplasmic reticulum-associated O-glycosylation of galactosyltransferase.

Recent data from several laboratories show that Brefeldin A (BFA) induces a microtubule-dependent back-flow of Golgi components to the endoplasmic reticulum (ER) thereby causing disassembly of the Golgi apparatus and its fusion with ER membranes. In order to delineate the effect of BFA on resident Golgi proteins, we investigated its effect on biosynthesis, maturation and intracellular transport of galactosyltransferase (gal-T), an established trans-Golgi enzyme. Using a protocol of metabolic labeling/immunoprecipitation followed by electrophoretic/fluorographic analysis, we show that in the presence of BFA, gal-T matures to a molecular form of 48.5 kD, a size intermediate between the 2 precursor forms of 44 and 47 and the mature form of 54 kD (Strous and Berger: J. Biol. Chem., 257:7623-28, 1982). Little mature form was detectable in the presence of BFA even after prolonged chase times of up to 28 hr. The intermediate form was sensitive to O-glycanase and endoglycosidase H, indicating early O-glycosylation without sialylation and lack of complex N-glycosylation, respectively. In order to define the compartment responsible for O-glycosylation in the presence of BFA, a temperature block of 25 degrees C was applied which inhibited recovery of Golgi elements from BFA-induced fusion with ER. At this temperature and in absence of BFA, biosynthesis of gal-T was not appreciably affected, while maturation was completely inhibited as indicated by the presence of unmodified precursor forms of gal-T. After 60 min preincubation with BFA, a time period sufficient to demonstrate complete fusion of Golgi with ER, subsequent biosynthesis of gal-T at 25 degrees C in absence of BFA led to the intermediate form, while precursor forms were not detectable. These data provide direct evidence for BFA-induced redistribution to the EF of Golgi enzymes involved in O-glycosylation and their early functional involvement in biosynthesis of newly synthesized gal-T.

Acetylglucosaminidase↗
PubMed1990

Brain development: 1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods.

We compared in vitro 1H magnetic resonance spectroscopy (MRS) measurements of rat brain extracts (rats: 2-56 days old) with chromatographic measurements and in a further step also with results of in vitro MRS. The following substances can be reliably measured in brain extracts by in vitro MRS: N-acetylaspartate (NAA), total creatine (Cr), phosphorylethanoloamine (PE), taurine (Tau), glutamate (Glu), glutamine (Gln), gamma-aminobutyrate (GABA) and alanine (Ala). Two different methods of MRS data evaluation compared with chromatographic data on Cr and NAA are shown. During development of the rat from day 2-56 brain concentrations of PE, Tau and Ala decrease, those of NAA, Cr, Glu and Gln increase, while GABA does not change. The developmental patterns of these substances are the same, whether measured by in vitro MRS or by chromatographic methods. Quantification of NAA, Cr, Tau, GABA and PE leads to the same results with both methods, while Glu, Gln and Ala concentrations determined by in vitro MRS are apparently lower than those measured chemically. The NAA/Cr ratios of 7 to 35-day-old rats were determined by in vivo 1H MRS. These results correlate with chromatographic and in vitro data. Using appropriate methods in the in vivo and in vitro MR-technique, the obtained data compare well with the chromatographic results.

Aging↗
PubMed1988

Correlation between 31P NMR phosphomonoester and biochemically determined phosphorylethanolamine and phosphatidylethanolamine during development of the rat brain.

Phosphomonoesters were measured in the developing rat brain by in vivo and in vitro 31P nuclear magnetic resonance (NMR) spectroscopy and by classical biochemical methods. In vitro NMR showed that the main component of the phosphomonoester peak is phosphorylethanolamine. Phosphomonoesters measured by in vivo NMR decreased during development at the same rate as the biochemically estimated phosphorylethanolamine. Phosphorylethanolamine, a precursor of the membrane lipid phosphatidylethanolamine, decreased during development parallel to an increase of the lipid phosphatidylethanolamine, which was measured biochemically. These studies show that 31P NMR can be used to monitor brain development in vivo.

Aging↗
PubMed1985

[Hemodynamic effects of a new long-acting isosorbide dinitrate].

The following hemodynamic parameters were measured at rest and 1, 2, 4, 6, 8, 12 and 24 hours after 100 mg of ISDNSR p.o. in 10 patients with dilated cardiomyopathy (NYHA class III-IV): mean pulmonary artery, pulmonary capillary wedge (PCW) and arterial pressures (AP), and cardiac output (thermodilution). Plasma levels of ISDN were determined by capillary gas chromatography at the same intervals and correlated with the hemodynamic changes. PCW fell from 24 +/- 1.5 (SE) to 18 +/- 1.8 mm Hg after 1 hour (p less than 0.05) and after 2 hours to 16.9 +/- 1.6 mm Hg. This change was sustained for 8 hours. At 12 hours PCW had increased again to 21 +/- 1.5 mm Hg and at 24 hours to 22 mm Hg. AP dropped from 89 +/- 5 to 81 +/- 4 mm Hg at 1 hour (p less than 0.2) and remained 80-84 mm Hg for 8 hours. It returned to baseline levels at 12 hours. Heart rate, cardiac index, systemic vascular resistance, stroke index and left ventricular work index did not change significantly during the observation period. Plasma levels of ISDN remained between 3 and 12 ng/ml for 16 hours. Thus, ISDNSR is an effective long-acting nitrate preparation which reduces preload for 8-12 hours. After this interval, nitrate tolerance starts to develop.

Blood Pressure↗
PubMed1985

Isosorbide dinitrate bioavailability, kinetics, and metabolism.

We studied the kinetics of isosorbide dinitrate (ISDN) after a dose of 5 mg iv and the bioavailability of a sublingual and an oral preparation of ISDN. Plasma levels of isosorbide 5-mononitrate (IS-5-MN), isosorbide 2-mononitrate (IS-2-MN), and ISDN were determined by GLC. After intravenous and sublingual dosing, ISDN plasma levels declined biexponentially and could adequately be described by an open two-compartment body model. Distribution was rapid; the t1/2 was 4.7 minutes after intravenous injection and 8.7 minutes after sublingual dosing. The volume of distribution at steady state was 90 L. The terminal disappearance t1/2 was 54.7 minutes after intravenous injection, 48.8 minutes after sublingual dosing, and 47.7 minutes after oral dosing. Total plasma clearance was 136 L/hr, exceeding normal liver plasma flow and indicating extrahepatic metabolism of ISDN. ISDN bioavailability after oral (10 mg) or sublingual dosing (10 mg) was similar (about 29%), indicating that the first-pass effect cannot be avoided by sublingual ISDN dosing. After intravenous ISDN, mononitrate plasma levels could be adequately described by another two-compartment body model. The terminal t1/2 was 4.33 hours for IS-5-MN and 1.83 hours for IS-2-MN. Noncompartmental calculations of the mononitrate levels revealed 100% systemic availability after oral and sublingual ISDN. We assume that ISDN was completely absorbed from the gastrointestinal tract, but 70% was metabolized during the first pass through the liver. After 5 mg iv ISDN, 16 mumol IS-5-MN and 5.3 mumol IS-2-MN reached systemic circulation. The entire dose of ISDN was converted to its two metabolites in a ratio of 3:1 (i.e., 75% IS-5-MN and 25% IS-2-MN).

Administration, Oral↗
PubMed1984

Isosorbide 5-mononitrate and isosorbide 2-mononitrate kinetics after intravenous and oral dosing.

Isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN) kinetics were studied in two groups of young healthy subjects after intravenous injection of 5 mg of both and after oral doses of 20 mg of IS-2-MN and 10, 15, and 20 mg of IS-5-MN. Mononitrate plasma levels were measured by GLC with capillary columns. After intravenous injection, IS-5-MN and IS-2-MN plasma levels declined biexponentially and could be described by an open two-compartment body model. Distribution t 1/2 was rapid; 8.6 min for IS-5-MN and 12.5 min for IS-2-MN. Substances were distributed throughout body water; volume of distribution at steady state (Vd ss) was 48 l for IS-5-MN and 55 l for IS-2-MN and elimination t 1/2 was 4.15 hr for IS-5-MN and 1.9 hr for IS-2-MN. Total plasma clearance was 8.5 l/hr for IS-5-MN and 23.2 l/hr for IS-2-MN. After oral doses the mononitrates were rapidly and completely absorbed (absorption t 1/2 ranged from 2.5 to 5 min) from the gastrointestinal tract without first-pass metabolism, i.e., absolute systemic availability was 100%. In the dose range studied, kinetics of the two mononitrates were linear. Compared with isosorbide dinitrate, mononitrate kinetics are different because of greater systemic availability, slower clearance, and smaller Vd ss.

Absorption↗
PubMedDate not supplied

Single-dose pharmacokinetics of intravenous sulbactam in pediatric patients.

The pharmacokinetics of intravenously administered sulbactam were studied in 17 pediatric patients two to 14 years of age. Single doses of 12.5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 micrograms/ml, respectively. Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters. Linear pharmacokinetics were found in the concentration range studied. The mean terminal-phase half-life was 1.75 hr, the mean total plasma clearance was 180 ml/min per 1.73 m2, and the mean apparent volume of distribution was 340 ml/kg. Approximately 70%-80% of an intravenous dose was excreted unchanged in the urine. In children with cystic fibrosis, both total plasma clearance and apparent volume of distribution were significantly increased. The data support the intravenous administration of 12.5-25 mg of sulbactam/kg every 6 to 8 hr for assessing the adequacy of this drug as an adjunct to beta-lactam therapy for various bacterial infections in children.

Adolescent↗