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B Meyer

Publications and source records attributed to B Meyer.

At least 199 records · Page 11Linked to original sources
PubMed1993

The conformations of cyclic (1-->2)-beta-D-glucans: application of multidimensional clustering analysis to conformational data sets obtained by Metropolis Monte Carlo calculations.

Sets containing up to 1.3 x 10(6) energetically accessible conformations of linear (1-->2)-beta-D-glucan oligosaccharides were obtained by Metropolis Monte Carlo (MMC) calculations performed with the GEGOP (GEometry of GlycOProteins) program. Quantitative analyses of the data sets (which were expressed in terms of the glycosidic dihedral angle coordinates) were obtained by two different clustering methods: (i) the three-distance hierarchical clustering method (3-DM), published by Jure Zupan, and (ii) a nonhierarchical clustering method (Population-Density Projection, PDP) which, through a segmentation analysis of two-dimensional projections of the population-density surface, establishes a partitioning of conformational space into a set of "cluster regions", followed by a clustering step where each conformation of the data set is assigned to one of these regions. Computer programs (MCLUST and PDPCLUST) were developed to perform the 3-DM and PDP analyses, respectively. The two types of analysis provided very similar sets of conformational families (clusters), which could be expressed as combinations of distinct conformations of the glycosidic torsional angles (phi, psi) centered at (50 degrees, 10 degrees) for conformation A, (40 degrees, 160 degrees) for conformation B, (55 degrees, -160 degrees) for conformation B', and (170 degrees, 10 degrees) for conformation C. The analysis provided the populations of the families, along with relative rates for transitions between families. Examination of the frequencies of the A, B, and C glycosidic bond conformations with respect to their relative positions in the sequence revealed the tendency of the (1-->2)-beta-D-glucan to adopt conformational repeating structures of the general form [AnB], where n = 3 or 6. These repeating structures combine in an energetically cooperative fashion to give low-energy cyclic conformations having, for example C5 symmetry [AAAB]5 for the eicosamer, and C3 symmetry [AAAAAAB]3 for the heneicosamer.

Carbohydrate Conformation↗
PubMed1993

Influence of sulfate and carboxylate groups on the conformation of chondroitin sulfate related disaccharides.

1H NMR and 13C NMR spectral parameters of eight sulfated uronic acid containing disaccharides 1-8 were used to determine the conformational preferences that depend on the pattern of sulfation. Three sulfated derivatives of benzyl beta-D-Gal-(1-->4)-beta-D-GlcA (1), its 6'-sulfate 2, 4'-sulfate 3, and 4',6'-disulfate 4 were used as models for the beta-(1-->4) glycosidic linkage of chondroitin sulfates and three sulfated derivatives of benzyl beta-D-GlcA-(1-->3)-beta-D-Gal (5), its 6-sulfate 6, 4-sulfate 7, and 4,6-disulfate 8 were used as models for the beta-(1-->3) glycosidic linkage of chondroitin sulfates. To determine the dependence of conformational preferences on the charged groups, the sulfated disaccharides 2, 3, and 4 were compared to their unsulfated parent compound 1, and 6, 7, and 8 were compared to their parent compound 5. The 3JH-5,H-6 coupling constants were determined by high-order analysis of the spin systems, and from these the preferred populations of the hydroxymethyl groups were calculated. Selective 1D NOEs and ROEs were measured from H-1' across the glycosidic linkage to obtain the average distance of the protons adjacent to the glycosidic linkage. Derivatives of beta-D-Gal-(1-->4)-beta-D-GlcA carrying a sulfate group in the 6'-position (2) and in the 4'- and 6'-position (4) show a slight repulsive effect between the 6'-sulfate groups and the carboxylate group as expressed in small changes of the preferred populations of the glycosidic linkage and the sulfonyloxymethyl group. The 4-sulfate groups in 3 and 4 do not show a significant influence on the glycosidic linkage. However, the two sulfate groups in 4 exhibit a repulsive effect leading to a very high population of the gt conformation of the sulfonyloxymethyl group. In contrast hereto, the sulfate group at C-4 of beta-D-GlcA-(1-->3)-beta-D-Gal disaccharides 7 and 8 and the carboxylate group exert an attractive interaction that leads to a change of the conformation of the glycosidic linkage in 7 and 8 by about 30 degrees. The 6-sulfate groups of the disaccharides 6 and 8 show a slight repulsive interaction with the carboxylate and/or 4-sulfate group. Changes in 13C NMR chemical shifts support the interpretation obtained from the NOE and ROE analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbohydrate Conformation↗
PubMed1993

A Monte Carlo method for conformational analysis of saccharides.

A Metropolis Monte Carlo (MMC) algorithm was applied to explore conformational spaces spanned by the exocyclic dihedral angles of four disaccharides alpha-D-Man(1-->3)-alpha-D-Man(1-->O)Me (1), alpha-D-Man(1-->2)-alpha-D-Man(1-->O)Me (2), methyl beta-cellobioside (3), and methyl beta-maltoside (4). The simulation method uses the HSEA force field and randomly samples the conformational space with an automatic preference for low-energy states. In comparison to a systematic grid search, MMC offers a much more convenient and efficient protocol for the computation of ensemble average values of experimentally accessible NMR parameters such as NOE effects or 3J coupling constants. Energy barriers of a few kcal/mol were found to be surmounted easily when running the simulations with the temperature parameter set at room temperature, whereas passing significantly higher barriers required elevated temperature parameters. Ensemble average NOE values were calculated using the MMC technique and a conventional systematic grid search showing that the MMC method adequately samples the conformational spaces of 1-4. Theoretical NOEs derived for global or local minimum conformations are different from ensemble average values, and it is shown that averaged NOEs agree significantly better with experimental data. Ensemble average NOEs for 1 derived from MMC/HSEA, and previously reported MM2CARB and AMBER calculations all showed good agreement with experimental data, with MMC/HSEA giving the closest fit.

Algorithms↗
PubMed1993

Bronchoalveolar lavage fluid proteins in human lung disease: analysis by two-dimensional electrophoresis.

Proteins of human bronchoalveolar lavage fluids, obtained by washing the epithelial lining fluid of the lungs with phosphate-buffered saline, were analyzed by two-dimensional electrophoresis under denaturating and reducing conditions. The two-dimensional pattern of bronchoalveolar lavage fluid proteins of healthy volunteers (controls) were compared with those of patients with idiopathic pulmonary fibrosis, sarcoidosis, and asbestosis. Particular interest was paid to the proteins present in minor amounts mainly in the low molecular weight region of the gels. Marked changes in single protein spots were observed. In idiopathic pulmonary fibrosis the spot intensity of the surfactant-associated protein, SP-A, showing isomeric forms both in charge and in molecular weight, was markedly decreased. In sarcoidosis, the immunoglobulins (IgG, IgA) and a group of protein spots at an isoelectric point of 4.5-5.0 and a molecular mass of 55 kDa were increased. An additional spot appeared at an isoelectric point of 4.5 and a molecular mass of 12 kDa. In particular in asbestosis, but also in some cases of idiopathic pulmonary fibrosis and sarcoidosis, the number and intensity of low molecular weight proteins were increased strongly.

Asbestosis↗
PubMed1993

Conformational analysis of alpha-D-Fuc-(1-->4)-beta-D-GlcNAc-OMe. One-dimensional transient NOE experiments and Metropolis Monte Carlo simulations.

One-dimensional transient NOE build-up curves were measured for the synthetic disaccharide alpha-D-Fuc-(1-->4)-beta-D-GlcNAc 1 utilizing Gaussian shaped pulses. Simulated build-up curves from Metropolis Monte Carlo simulations were compared to the experimental data. Disaccharide 1 is structurally related to methyl beta-D-maltoside in that it also contains an alpha-(1-->4) linkage, and it has the same configuration of groups around the glycosidic linkage. Analysis of NOEs in methyl beta-D-maltoside is restricted to those observed upon selective excitation of H1' because of severe spectral overlap. The situation is different in 1 where 1H-NMR signals are well separated. Several interglycosidic NOEs were observed. The corresponding build-up curves allowed an accurate determination of the conformational preferences at the glycosidic linkage in 1. Comparison of experimental and theoretical NOE build-up curves showed clearly that rigid minimum-energy models cannot account for the experimental data. The best fit of experimental NOE build-up curves was obtained with theoretical curves from a 2 x 10(6) step Metropolis Monte Carlo simulation with the temperature parameter set at 1000 K. Finally, it was observed that only the interglycosidic NOE H5'/H6-pro-S significantly depends upon varying conformation distributions at the alpha-(1-->4)-glycosidic linkage, induced by choosing different temperature parameters for the Metropolis Monte Carlo simulations.

Carbohydrate Conformation↗
PubMed1993

Low-dose interferon in chronic hepatitis non-A/non-B: effects on quantitative liver function and structure in a randomized, controlled multicenter trial.

In this randomized, controlled multicenter trial we evaluated the effects of recombinant interferon-alpha 2b on galactose elimination capacity and histological activity index in 88 patients with chronic active hepatitis non-A/non-B. Forty-five patients were randomly assigned to treatment with interferon at 1.5 x 10(6) U three times per for 1 year; 43 patients were assigned to no treatment. A complete response (normalization of alanine aminotransferase) was observed, respectively, in 47% and 5% of the two groups (P < 0.006); 47% of these patients suffered a relapse. Thus 22% of patients had a sustained response. Histological activity decreased significantly in responders (P < 0.04) while the biopsy score did not change significantly in nonresponders. In contrast, galactose elimination capacity--a surrogate marker for survival in chronic active hepatitis--was not affected by response to treatment. None of the parameters evaluated, including hepatitis C virus RNA, was able to predict response or relapse. We conclude that low-dose interferon treatment for 1 year is as effective as the recommended treatment schedule.

Adolescent↗
PubMed1993

Pre-emptive renal transplantation in children and adolescents.

Forty-three out of 204 children received their first renal transplant without prior dialysis. In order to evaluate the outcome of pre-emptive transplantation, two groups were compared retrospectively. The groups consisted of 28 children who received their transplants either without prior dialysis (ND) or after a varying period of dialysis (D). They were matched by age, year of transplantation, immunosuppressive regimen, donor source, and original disease. The percentage of living related donors was 50% in each group. Patient survival was identical in both groups; one patient died in each group due to infection in the early post-transplantation period. The 5-year graft survival rates were 89% in the ND group versus 72% in the D group. The functional parameters graft function, anemia, hyperparathyroidism, hypertension, and the growth rates tended to be slightly better in the ND group than in the D group. The differences, however, were not significant. We conclude that pre-emptive transplantation is a safe procedure that shortens the period of uremia and is, therefore, recommended for children with end-stage renal failure.

Adolescent↗
PubMed1993

Preferred conformations and dynamics of five core structures of mucin type O-glycans determined by NMR spectroscopy and force field calculations.

Glycosyltransferases acting on O-glycans have been shown to exhibit distinct specificity for the carbohydrate and the peptide moiety of their substrates. As an approach to study the 3-dimensional interactions between enzymes and O-glycan substrates, we determined the preferred conformations of five oligosaccharide-core structures of mucin type glycoproteins by NMR spectroscopy and by static and dynamic force field calculations. Seven oligosaccharides, representing five basic core structures, were investigated: Gal beta (1-3)GalNAc alpha Bzl (1, core 1), GlcNAc beta (1-6)[Gal beta (1-3)]GalNAc alpha Bzl (2, core 2), GlcNAc beta (1-3)GalNAc alpha Bzl (3, core 3), GlcNAc beta (1-6)[GlcNAc beta (1-3)]GalNAc alpha Bzl (4, core 4), GlcNAc beta (1-6)GalNAc alpha Bzl (5, core 6), the elongated core 2, Gal beta (1-4)GlcNAc beta (1-6)[Gal beta (1-3)]GalNAc alpha pNp (6) and GalNAc alpha-Bzl (7). The dynamic behaviour of the molecules was studied by Metropolis Monte Carlo (MMC) simulations. Experimental coupling constants, chemical shift changes, and NOEs were compared with results from static energy minimizations and dynamic MMC simulations and show a good agreement. MMC simulations show that the (1-6) linkage is much more flexible than the (1-3) or the (1-4) linkages. The preferred conformations of the disaccharides (1) and (3) show only slight differences due to the additional N-acetyl group in (3). The conformational equilibrium of beta (1-3) glycosidic bonds of 1 and 3 was not affected by attaching a beta (1-6) linked GlcNAc unit to the GalNAc residue in 2 and 4. However, experimental and theoretical data show that the beta (1-6) linkages of the trisaccharides 2 and 4, which carry an additional beta (1-3) linked glycosyl residue, change their preferred conformations when compared with (5). The 6-branch also shows significant interactions with the benzyl aglycon altering the preferred conformation of the hydroxymethyl group of the GalNAc to a higher proportion of the gt conformer. The (1-6) linkage of 2, 4, and 6 can have two different families of conformations of which the lower energy state is populated only to about 20% of the time whereas the other state with a relative enthalpy of approximately 4 kcal mol-1 is populated to 80%. This fact demonstrates that the two conformational states have different entropy contents. Entropy is implicitly included in MMC simulations but cannot be derived from energy minimizations.

Carbohydrate Conformation↗
PubMed1993

A gene for familial hemiplegic migraine maps to chromosome 19.

Familial hemiplegic migraine is an autosomal dominant disorder of unknown pathogenesis in which the migrainous attacks are marked by the occurrence of a transient hemiplegia during the aura. While investigating CADASIL, mapped previously to chromosome 19, we observed that some patients had recurrent attacks of migraine with aura. Although the clinical and neuroimaging features of familial hemiplegic migraine differ markedly from CADASIL, we hypothesized that the same gene could be involved in the pathogenesis of both conditions. We chose two large pedigrees for linkage analysis of familial hemiplegic migraine. A maximum lod score > 8 was found with two markers that are also strongly linked to CADASIL. Multilocus linkage analysis suggested that the loci responsible for the two diseases reside within an interval of about 30 cM on chromosome 19.

Adolescent↗
PubMed1993

Very early analysis of graft establishment after allogeneic bone marrow transplantation using the polymerase chain reaction.

We have used minisatellite polymorphisms flanking the apolipoprotein B locus and PCR to demonstrate the emergence of donor specific alleles in peripheral blood at 3-7 d post allogeneic bone marrow transplantation (BMT). This technique affords a very early indication of the establishment of stable engraftment, and may identify patients at risk of graft failure or leukaemic relapse. Patterns of T-cell chimaerism in the first 7-14 d following transplantation may be closely associated with the development of graft-versus-host disease (GVHD), the graft versus leukaemia (GVL) effect and graft rejection and future application of this technique to the investigation of early T-cell chimaerism may give further insights into these immunologically mediated events.

Alleles↗
PubMed1993

A clinical and laboratory study to compare the addition of 0.2 mg of morphine, 0.2 mg of epinephrine, or their combination to hyperbaric bupivacaine for spinal anesthesia in cesarean section.

The aim of this prospective, randomized, double-blind study was to compare the effects of adding either preservative-free morphine, 0.2 mg (n = 20), epinephrine, 0.2 mg (n = 21), or a combination of both (n = 29) to hyperbaric bupivacaine in parturients having elective cesarean sections during spinal anesthesia. Ten additional patients receiving spinal bupivacaine alone were studied as the Control Group. High-pressure liquid chromatography with a sensitivity of 20 micrograms/mL was used to measure serum bupivacaine in all subjects. The results showed that the spread and regression of the sensory and motor blocks were similar among the study groups. However, the intraoperative analgesia was superior in patients receiving bupivacaine combined with morphine and epinephrine, whereas there was no difference between those given an addition of either morphine or epinephrine. Postoperative analgesia was the shortest and opioid requirement in the first 24 h the most with epinephrine alone. No respiratory depression occurred. The neonatal condition was excellent in all groups. Serum concentrations of bupivacaine at 10 min, at delivery (25 +/- 1.4 min), and at 60 min after the intrathecal injection were similar among the groups including the Control Group. The concentrations of bupivacaine in umbilical arterial and venous sera were less than the sensitivity level of the analytical method. We conclude that the addition of 0.2 mg of morphine plus 0.2 mg of epinephrine to hyperbaric bupivacaine improves the intra- and postoperative analgesia without an added risk. This improvement is not due to vasoconstriction and a reduction in the absorption of bupivacaine from the subarachnoid space.

Adult↗
PubMed1993

[Surgery for bleeding peptic ulcer: short- and long-term results].

Thirty-one patients operated on for bleeding peptic ulcer were reviewed. The basic concept was to make an early decision to operate and proceed as soon as the patient was haemodynamically stable. In addition to haemostasis, a definitive operation was performed. The procedure was a proximal gastric vagotomy (PGV) for duodenal ulcers (DU), combined with an antrectomy for pre-pyloric ulcers, and either a PGV with ulcer excision or a Billroth I for gastric (GU) or combined (GU + DU) ulcers. Twenty-four patients (77%) were operated on within the first 24 hours. Nine patients could not be operated according to the basic protocol because of anatomical reason, additional ulcer complication or severe co-existing systemic disease. During the hospital stay, 2 deaths (6%) occurred and 4 patients (13%) rebled postoperatively, all of them were reoperated. During a mean follow-up of 44 months, 12 deaths unrelated to peptic disease and one recurrent bleeding occurred. PGV for DU could be used in 70% of cases without any hospital mortality; one patient rebled after the operation and another during the long-term follow-up. These results support the views that early surgery has a low hospital mortality and that PGV gives good results when performed as an emergency procedure.

Adolescent↗
PubMed1993

Contamination of transplantable tumors, cell lines, and monoclonal antibodies with rodent viruses.

Different biological materials were tested for murine viral contamination by using the mouse/rat antibody production test. Of 297 tumors examined, 75 (25.3%) were contaminated. Considerable differences in the contamination rate became evident when transplantable tumors from in vitro and from in vivo passages were compared. Of 186 tumors that had been propagated in animals, 36.6% were positive, whereas only 7 of 111 (6.3%) tumors propagated in vitro were contaminated. The highest rate of contamination was detected in mouse tumors. Testing of 135 specimens of mouse origin revealed 46.7% were contaminated, and 57 (70.4%) of 81 samples propagated in mice were positive for murine viruses. Moreover, 6.7% of 90 human tumors that had been passaged in athymic nude mice and 3.5% of 57 rat tumors were positive. Lymphocytic choriomeningitis virus was detected in 4 of 14 hamster tumors. The most frequent contaminant was lactic dehydrogenase elevating virus followed by reovirus 3, lymphocytic choriomeningitis virus, minute virus of mice, mouse hepatitis virus, rat coronaviruses, Kilham rat virus, and Mycoplasma pulmonis. Contamination with reovirus 3 and minute virus of mice was found in 4 (3.7%) of 109 cell lines tested, and 2 of 60 monoclonal antibody preparations or hybridoma cells contained lactic dehydrogenase virus. Contamination with two pathogens was detected in four mouse tumors and in one cell line.

Animals↗