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Biomedical subjects

G Magnusson

Publications and source records attributed to G Magnusson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Skeletal muscle contractile characteristics and fatigue resistance in patients with chronic heart failure.

Whole muscle contractile characteristics and fatigue resistance were studied in male patients with chronic heart failure (n = 6) and in healthy control subjects (n = 6). Maximum voluntary isometric strength in the major muscle groups of leg (plantar flexors and knee extensors) and arm (elbow extensors and elbow flexors), was found to be similar for both groups of subjects. However, a faster isometric twitch time course was observed in the plantar flexor and knee extensor muscles of heart failure chronic patients. The poor resistance to fatigue in the knee extensors of chronic heart failure patients was confirmed in the present study, but using twitch interpolation this was shown not to be due to poor activation. The plantar flexors of chronic heart failure patients also showed a tendency to be less resistant to fatigue, even when the muscle was activated by direct electrical stimulation. The present study shows that independent of muscle strength, patients with chronic heart failure may possess muscles that are faster to contract and less resistant to fatigue. However, it seems this increased fatigability is not due to poor muscle activation.

Chronic Disease↗
PubMed1996

High intensity knee extensor training, in patients with chronic heart failure. Major skeletal muscle improvement.

Skeletal muscle adaptations to high intensity knee extensor strength and/or endurance training in patients with chronic heart failure were investigated. Eleven patients with chronic heart failure were randomized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks. After training, the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 (32) to 114 (40) watts (W, P < 0.05) for all 11 patients. Peak dynamic knee extensor work rate showed the greatest increase after endurance training (40%, P < 0.01). Maximal dynamic and isometric strength were elevated by 40-45% (P < 0.05) after strength training. The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs (9%, P < 0.05), and the capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58% in the endurance-trained legs (P < 0.05). The oxidative enzyme activity in m. vastus lateralis was significantly raised above 50% after endurance training, whereas glycolytic enzyme activity was unaltered. The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training. This results in a marked rise in local, and a small rise in total work capacity, indicating maintained plasticity of skeletal muscle in chronic heart failure patients.

Adaptation, Physiological↗
PubMed1996

Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle.

The knee extensor and the whole-body exercise capacities were measured in 11 chronic heart failure (CHF) patients and 11 healthy age- and sex-matched controls, and were related to ejection fraction and to biochemical and histochemical markers of the musculature. The CHF patients had a 39% lower maximal oxygen uptake measured on an ergometer cycle than the healthy controls (1.54 +/- 0.57 vs. 2.51 +/- 0.70 1 min-1, P < 0.001). The low exercise capacity was markedly related to the ejection fraction (r = 0.77, P < 0.001). The maximal strength of m. quadriceps femoris was 15% lower in the CHF patients than in the controls (P < 0.05). The cross-sectional area (CSA) of m. quadriceps femoris explained 55% (r = 0.74, P < 0.001) of the difference in strength between both groups. The endurance capacity of m. quadriceps femoris was 30% lower in CHF patients than in controls, partly as a result of the 25% lower capillary density (P < 0.05) and the 27% lower aerobic enzyme capacity (P < 0.05), as estimated by the citrate synthase activity, in the CHF patients. The citrate synthase activity correlated with the maximal oxygen uptake (r = 0.61, P < 0.05). Moreover, the ejection fraction, together with the CSA of m. quadriceps femoris, explained 75% (r = 0.86%, P < 0.01) of the difference in maximal oxygen uptake between CHF patients and controls. These results demonstrate that CHF patients have both a lower local and a lower whole-body work capacity than healthy controls. This is a function of a smaller leg muscle mass and a lower capillary density and mitochondrial enzyme capacity in the CHF patients; however, a lowered pump capacity of the heart is the factor which limits the exercise capacity the most.

Aged↗
PubMed1996

A prospective study of rapid methods of detecting cytomegalovirus in the blood of renal transplant recipients in relation to patient and graft survival.

Eighty-five renal transplant recipients were prospectively monitored for CMV infection up to 4 months post-transplantation by virus isolation from leukocytes, CMV antigen detection (pp65) in peripheral blood leukocytes (PBL), polymerase chain reaction (PCR) of alkaline treated plasma (P-PCR), PCR of extracted DNA from PBL (L-PCR) and serology. Additionally univariate and multivariate analyses of risk factors for patient and graft survival up to 4 yr post-transplantation were performed. The incidence of CMV infection was 78% and of CMV disease 33%. Antigen detection in PBL was positive before or at onset of symptoms in 23/24 (96%) evaluable patients with CMV disease. The corresponding figures for virus isolation were 22/24 (92%), P-PCR 21/24 (88%) and for L-PCR 18/24 (75%). The percentage of negative samples in patients without CMV disease was 89% for the antigen test, 92% for L-PCR and 83% for virus isolation and P-PCR. One rapid test (antigen test, P-PCR or L-PCR) was positive at a median of 16 d before the onset of symptoms. The antigen test was generally the first rapid test to become positive. CMV disease did not affect graft survival in the multivariate analysis but was associated with decreased patient survival.

Adolescent↗
PubMed1995

Major histocompatibility complex class I binding glycopeptides for the estimation of 'empty' class I molecules.

Different forms of major histocompatibility complex (MHC) class I heavy chains are known to be expressed on the cell surface, including molecules which are functionally 'empty'. Direct peptide binding to cells is obvious during sensitization of target cells in vitro for cytotoxic T lymphocyte killing and 'empty' MHC-I molecules are comparatively abundant on TAP-1/2 peptide transporter mutant cells. In the present work we have estimated the fraction of 'empty' MHC class I molecules using glycosylated peptides and cellular staining with carbohydrate specific monoclonal antibodies. Synthetic Db and Kb binding peptides were coupled at different positions with different di- or trisaccharides, using different spacing between the carbohydrate and the peptide backbone. Binding of sugar specific mAbs was compared in ELISA and cellular assays. An optimal Db binding glycopeptide was used for comparative staining with anti-Db and anti-carbohydrate monoclonal antibodies to estimate fractions of 'empty' molecules on different T lymphoid cells. On activated normal T cells, a large fraction of Db molecules were found to be 'empty'. The functional role of such 'empty' MHC class I molecules on T cells is presently unclear. However, on antigen presenting cells they might participate in the antigen presentation process.

Amino Acid Sequence↗
PubMed1995

Synthesis of disaccharide glycosyl donors suitable for introduction of the beta-D-Gal p-(1-->3)-alpha-and-beta-D-Gal pNAc groups.

2-(Trimethylsilyl)ethyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D- galactopyranoside (4) was glycosylated with phenyl 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-galactopyranoside to give 2-(trimethylsilyl)ethyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-beta-D-galactopyranoside (6) in 99% yield. Removal of the benzylidene group and acetylation gave the key intermediate 2-(trimethylsilyl)ethyl 4,6-di-O-acetyl-2-azido-2-deoxy-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-beta-D-galactopyranoside (7), which was transformed into methyl 4,6-di-O-acetyl-2-deoxy-2-phthalimido-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-1-thio-beta-D-galactopyranosid e (9) in two steps in an overall yield of 69%. Similarly, 7 was transformed in two steps into 4,6-di-O-acetyl-2-azido-2-deoxy-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-alpha-D-galactopyranosyl bromide (11) in an over-all yield of 86%. Compounds 9 and 11 are suitable glycosyl donors for introduction of the beta-D-Gal p-(1-->3)-beta- and -alpha-D-Gal pNAc groups.

Acetylgalactosamine↗
PubMed1995

Synthesis of the saccharide moiety of galactosylgloboside (SSEA-3) and its conjugation to bovine serum albumin and Sepharose.

The pentasaccharide glycoside corresponding to galactosylgloboside (SSEA-3), beta-D-Gal p-(1-->3)-beta-D-Gal pNAc-(1-->3)-alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-->4)-beta-D-Glc p-1-OCH2CH2Si-(CH3)3 (4), was synthesized via glycosylation (87%) of 2-(trimethylsilyl)ethyl 2,3,6-tri-O-benzyl-4-O-[2,3,6-tri-O-benzyl-4-O-(2,4, 6-tri-O-benzyl-alpha-D-galactopyranosyl)-beta-D-galactopyranosyl]-beta-D - glucopyranoside (2) with the glycosyl donor methyl 4,6-di-O-acetyl-2-deoxy-2-phthalimido-3-O-(2,3,4, 6-tetra-O-acetyl-beta-D-galactopyranosyl)-1-thio-beta-D-galactopyranosid e (1), followed by removal of protecting groups. Compound 4 was transformed into the spacer glycoside beta-D-Gal p(1-->3)-beta-D-Gal pNAc-(1-->3)-alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-->4)-beta-D-Glc p-1-SCH2CH2COOH (10), which was coupled to bovine serum albumin (BSA), and Sepharose beads, to give the corresponding neoglycoprotein (11, 6 mol of saccharide/mol of BSA), and glycosylated Sepharose (12, 2.7 mumol of saccharide/mL of sedimented beads), respectively. An improved synthesis of a protected globotetraoside beta-D-Gal pNAc-(1-->3)-alpha-D-Gal p-(1-->4)-beta-D-Gal p-(1-->4)-beta-D-Glc p-1-OCH2CH2SiMe3 is also reported.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1995

Preferred DNA-binding-sites of polyomavirus large T-antigen.

Polyomavirus large T-antigen is a multifunctional protein. Its essential function in virus infection is to control the synthesis of viral RNA and DNA. For this activity specific DNA binding is necessary. Large T-antigen can bind to several sites in the regulatory region of viral DNA, consisting of clustered GRGGC nucleotide motifs. Since large T-antigen also regulates the activity of cellular genes and cellular DNA synthesis, it seemed possible that there are alternative, as yet unrecognized, binding sites. To identify sites preferred by large T-antigen, double-stranded polynucleotides with random sequence were used. These polymers had a 31-bp central segment synthesized from a mixture of all four nucleotides and flanking segments of defined sequence. They were subjected to several cycles of binding to large T-antigen with intervening PCR amplification. Individual polynucleotides with affinity for large T-antigen were then isolated by cloning and their nucleotide sequences were determined. The majority of the polynucleotides contained two or three GRGGC motifs separated by between five and eight variable nucleotides. This result suggests that there are not any alternative high-affinity binding sites of large T-antigen. By comparing all the individual binding motifs an extended consensus sequence was observed. The dinucleotide TG was predominant immediately 5' to the binding pentanucleotide. On the 3'-side, at position +2, C residues were very rare. Although the pentanucleotide motif is the same as in polyomavirus DNA, the extended consensus sequence is not observed in viral DNA. In semi-quantitative experiments, binding of purified large T-antigen to a few of the selected DNA molecules was tested. Stable complexes were formed with DNA substrates containing two or three binding motifs in tandem. Binding to DNA with only one complete motif was weaker, but significantly stronger than non-specific association. This result has implications for the number of large T-antigen binding sites in cellular DNA. When mutant bc1081 large T-antigen, that is defective in specific DNA binding, was used in selection of polynucleotides, a different result was obtained. Neither bc1081 nor wild-type large T-antigen bound strongly to these polynucleotides. However, the presence of the motif TTCGGCTT, or part of it, in five of the six isolated polynucleotides suggested that the T-antigen selection was specific.

Animals↗
PubMed1995

Structural requirements for the glycolipid receptor of human uropathogenic Escherichia coli.

The binding of uropathogenic Escherichia coli to the globo series of glycolipids via P pili is a critical step in the infectious process that is mediated by a human-specific PapG adhesin. Three classes of PapG adhesins exist with different binding specificities to Gal alpha 4Gal-containing glycolipids. The structural basis for PapG recognition of the human glycolipid receptor globoside was investigated by using soluble saccharide analogues as inhibitors of bacterial haemagglutination. The minimum binding epitope was confirmed as the Gal alpha 4Gal moiety, but parts of the GalNAc beta and glucose residues, which flank the Gal alpha 4Gal in globoside (GbO4), were also shown to be important for strong binding. Furthermore, the same five hydroxyl groups of Gal alpha 4Gal in globotriasyl ceramide that were recognized by a previously characterized PapG variant were also recognized by the human-specific PapG in binding the GbO4 that dominates in the human kidney. Saccharide analogues that blocked haemagglutination also blocked the adherence of human uropathogenic E. coli to human kidney sections. Knowledge of the molecular details of the PapG-GbO4 interaction will make it possible to design antiadherence therapeutics.

Adhesins, Escherichia coli↗
PubMed1995

Neurological dysfunction above cele level in children with spina bifida cystica: a prospective study to three years.

The aim of this study was to characterize the neurological dysfunction above the cele level in children with spina bifida cystica. 22 neonates were investigated prospectively to a median age of three years. Before primary closure of the spinal malformation and at three and 18 months of age, MRI and inspection of vocal cord function were performed. The children were also assessed by a physical therapist at 12 and 24 months, 19 children had a Chiari malformation, 18 children developed neurological dysfunction above the cele level. Children with signs of isolated motor impairment stabilized or improved during the second year. Six children developed severe functional impairment of respiration, feeding and motor performance within the first three months of life. Severe neurological signs/symptoms were associated with myeloschisis, clinical signs of a tethered cord and recurrent periods of shunt dysfunction.

Child, Preschool↗
PubMed1995

Hereditary papillary renal cell carcinoma: clinical studies in 10 families.

We recently described a 3-generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Possibly family 150 is an isolated occurrence, a reflection of some as yet unknown environmental factor. Alternatively, family 150 may represent a distinct class of inherited cancer. To distinguish between these 2 possibilities we sought additional families with papillary renal cell carcinoma and we identified 9 with members affected with papillary renal cell carcinoma. There were 29 affected male and 12 affected female subjects (ratio 2.41:1), including affected members of family 150. Papillary renal cell carcinomas were often detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal cell carcinoma families. The penetrance, the proportion of obligate gene carriers that showed clinical evidence of the disease, was reduced. The median survival of affected individuals was 52 years. The results support the concept that the predisposition to develop papillary renal cell carcinomas may be inherited and that hereditary papillary renal cell carcinoma constitutes a distinct class of inherited cancer.

Adolescent↗
PubMed1994

Oligosaccharide-receptor interaction of the Gal alpha 1-4Gal binding adhesin of Streptococcus suis. Combining site architecture and characterization of two variant adhesin specificities.

The sugar binding specificities of two groups of Streptococcus suis, a pig pathogen that causes meningitis also in man, were determined. Both the group represented by a recently characterized strain inhibitable by galactose and N-acetylgalactosamine (type PN) and the group inhibitable by galactose (type PO) were found by hemagglutination and solid-phase binding inhibition experiments to recognize the disaccharide Gal alpha 1-4Gal of the P1 and Pk blood group antigens. Both types preferred the disaccharide in terminal position. PN showed some, whereas PO showed almost no, binding to the globoside oligosaccharide containing an additional GalNAc beta 1-3 residue. The complete hydrogen bonding patterns were determined by using deoxy and other synthetic derivatives of the receptor disaccharide, and the constructed models of the interactions were compared with that of Escherichia coli PapG396 adhesin. The essential hydroxyls for binding were the HO-4', HO-6', HO-2, and HO-3 hydroxyls on the beta' alpha-side of the Gal alpha 1-4Gal molecule. Type PO adhesin also formed weak interactions with the hydroxyls HO-6 and HO-3'. The mechanism differed from that of E. coli, which binds to a cluster of five hydroxyls (HO-6, HO-2', HO-3', HO-4', and HO-6') and thus to a different part of the receptor disaccharide. These results represent the first example of the comparison of the saccharide receptor hydrogen bonding patterns of two bacterial organisms of different origin and show that the same saccharide may be recognized by two different binding mechanisms.

Adhesins, Bacterial↗
PubMed1994

Synthesis of double-chain bis-sulfone neoglycolipids of the 2''-, 3''-, 4''-, and 6''-deoxyglobotrioses.

2-(Trimethylsilyl)ethyl (Me3SiCH2CH2) 2,3,6-tri-O-benzoyl-4-O-(2,3-di-O-benzoyl-6-O-p-methoxybenzyl-beta-D- galactopyranosyl-beta-D-glucopyranoside was glycosylated with different 2-, 3-, 4-, or 6-"deoxy-D-galactose" derivatives to give the corresponding deoxytrisaccharides. Removal of the protecting groups gave the Me3SiCH2CH2 2''-, 3''-, 4''-, and 6''-deoxyglobotriosides. Transformation of the protected Me3SiCH2CH2 globotriosides into the corresponding trichloroacetimidates proceeded, via the hemiacetals, in 91-96% over-all yield. Glycosylation of 3-(hexadecylsulfonyl-2-[hexadecylsulfonyl)methyl]propanol with the trichloroacetimidates, followed by removal of protecting groups, gave the title neoglycolipids.

Carbohydrate Sequence↗
PubMed1994

Lipid modulation of glycolipid receptor function. Availability of Gal(alpha 1-4)Gal disaccharide for verotoxin binding in natural and synthetic glycolipids.

Verotoxins bind to glycosphingolipids containing terminal Gal(alpha 1-4)Gal residues. Globotriaosylceramide is the most effective receptor for verotoxin-1 in vitro and is the functional plasma-membrane receptor which mediates cytopathology for most sensitive cells. Binding of verotoxin-1 to a series of galabiose-containing or globotriaose-containing synthetic glycolipids with monoalkylsulfides and bisalkylsulfides or sulfones as the lipid moiety, have been studied for toxin binding by TLC overlay and in solid phase in the presence of auxiliary lipids. The results demonstrate that for an identical carbohydrate, binding is dramatically altered according to the nature of the lipid moiety. The close proximity of the galabiose sequence and the hydrophobic species also compromised recognition. The lipid environment is also a major determinant of receptor function, since species that were effective, even preferred toxin receptors as monitored by TLC overlay, were not necessarily recognized in the presence of auxiliary lipids. Certain glycolipids, which were not recognized by TLC overlay, were nevertheless found to be effective receptors in an auxiliary lipid matrix. These results demonstrate the crucial role of the lipid moiety in verotoxin/glycolipid recognition and are discussed in relation to toxin pathogenesis and glycolipid receptor function.

Bacterial Toxins↗
PubMed1994

Nuclear magnetic resonance and conformational investigations of the pentasaccharide of the Forssman antigen and overlapping di-, tri-, and tetra-saccharide sequences.

The 1H and 13C NMR parameters, i.e., chemical shifts and coupling constants, for the pentasaccharide of the Forssman antigen and overlapping di-, tri-, and tetra-saccharide sequences thereof have been measured and assigned completely using 1D and 2D techniques, and the oligosaccharide structures have thereby been confirmed. Nuclear Overhauser effect (NOE) experiments have been carried out at three different temperatures to assess the preferred conformations of the pentasaccharide and the component oligosaccharides. The conformational preferences of the compounds mentioned above have subsequently been investigated by theoretical calculations. The flexibility and dynamics of the molecules have been studied by Metropolis Monte Carlo simulations using a modified HSEA force field, and ensemble average data have been generated and compared to data obtained experimentally.

Calorimetry↗
PubMed1994

Synthesis of the globotetraose tetrasaccharide and terminal tri- and di-saccharide fragments.

The 2-(trimethylsilyl)ethyl (TMSEt) beta-glycosides of globotetraose [beta-D-GalNAc-(1-->3)-alpha-D-Gal-(1-->4)-beta-D-Gal-(1-->4)-D-Glc] and the terminal trisaccharide, as well as the methyl alpha-glycoside 1 of the terminal disaccharide, were synthesised by silver trifluoromethanesulfonate-promoted beta-glycosylation of suitably protected galactoside, galabioside, and globotrioside alcohols with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl chloride, followed by removal of protecting groups. Removal of the anomeric TMSEt group of the globotetraoside and of the terminal trisaccharide, using trifluoroacetic acid-dichloromethane, gave the corresponding hemiacetal sugars 8 and 3. The TMSEt glycoside of the terminal trisaccharide was converted, via the 1-acetate, into the corresponding isobutyl (4) and 3-butylsulfonyl-2-[(butylsulfonyl)methyl]propyl (5) glycosides and into the TMSEt thioglycoside 6 via the glycosyl bromide.

Antigens↗