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Biomedical subjects

G Magnusson

Publications and source records attributed to G Magnusson.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of screening procedures for congenital cataracts.

AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.

Cataract↗
PubMed2002

Changes in visual acuity from 4 to 12 years of age in children operated for bilateral congenital cataracts.

AIMS: To investigate the long term effects of age at surgery on the development of visual acuity (VA) by measuring VA from preschool age to puberty. Furthermore, to report the VA levels at 12 years of age in a geographically based cohort of operated congenital bilateral cataracts. METHODS: All children born in four western counties of Sweden between January 1980 and December 1993 who were diagnosed with congenital cataracts were included in a longitudinal prospective study. The monocular VA of the better eye in 38 subjects was analysed at 4, 7, 10, and 12 years of age, with 20 total and 18 partial cataracts. The mean follow up time was 9.3 years after surgery. RESULTS: The final value of VA was 0.4 or above for approximately 50% of the subjects at 12 years of age. Visual acuity improved to a considerable extent after school age, especially in children who underwent surgery between the ages of 7 weeks and 1 year. Results for partial cataracts were favourable compared to those for total cataracts, reaching a mean of approximately 0.5 at age 12. The mean VA in the group of total congenital cataracts operated on before 7 weeks of age achieved higher values of VA at 4 years of age compared to children with total cataracts operated on between 7 weeks and 1 year of age. However, no statistically significant difference in VA results among these groups could be proved. CONCLUSION: Visual acuity improves to a considerable extent after school age in children with delayed visual development caused by congenital cataracts. Surgery within 7 weeks results in a more rapid development of VA, initially.

Age Factors↗
PubMed2001

Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor.

PapG is the adhesin at the tip of the P pilus that mediates attachment of uropathogenic Escherichia coli to the uroepithelium of the human kidney. The human specific allele of PapG binds to globoside (GbO4), which consists of the tetrasaccharide GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc linked to ceramide. Here, we present the crystal structures of a binary complex of the PapG receptor binding domain bound to GbO4 as well as the unbound form of the adhesin. The biological importance of each of the residues involved in binding was investigated by site-directed mutagenesis. These studies provide a molecular snapshot of a host-pathogen interaction that determines the tropism of uropathogenic E. coli for the human kidney and is critical to the pathogenesis of pyelonephritis.

Adhesins, Escherichia coli↗
PubMed2001

A study of the donor properties of sialyl phosphites having an auxiliary 3-(S)-phenylseleno group.

Two phosphite sialyl donors, each having an auxiliary 3-(S)-phenylseleno group, were prepared and evaluated. The phenylseleno group was introduced via a new mode of generating phenylselenenic acid ('PhSeOH'). Although the sialyl donors provided fair yields (32-76%) of the desired sialosides in glycosylations of the reactive acceptor 1,2;3,4-di-O-isopropylidene-alpha-D-galactopyranose, no sialylated products could be obtained with less reactive acceptors. The presence of a 5-N-acetylacetamido group on the phosphite sialyl donor did not appear to improve its sialylating capability. The weak C-Se bond, possibly in combination with a steric hindrance, which disfavors alpha-nitrilium ion formation, seem to explain the unsuccessful sialylations of the less reactive acceptors.

Gangliosides↗
PubMed2001

Iodine monochloride/silver trifluoromethanesulfonate (ICI/AgOTf) as a convenient promoter system for O-glycoside synthesis.

The novel promoter system iodine monochloride/silver trifluoromethanesulfonate (ICl/AgOTf) was evaluated with various thioglycoside donors and saccharide acceptors, and O-glycosides were obtained in 46-82% yield. Several practical advantages of the ICl/AgOTf system over known promoter systems were observed, such as convenient handling of the reagents and absence of byproducts related to N-succinimide.

Chlorides↗
PubMed2001

A short and practical route to 3-O-benzoyl azidosphingosine.

A short and practical route to 3-O-benzoyl azidosphingosine from D-xylose is described. The synthesis avoids the use of expensive and hazardous chemicals (i.e. mercury salts), and it is reproducible up to at least a 20 g scale. Furthermore, the synthesis proceeds to 3-O-benzoyl azidosphingosine with a minimum of protection group manipulation, by exploiting a regioselective protection of the primary HO-1 with thexyldimethylsilyl chloride.

Azides↗
PubMed2001

Comamonas denitrificans sp. nov., an efficient denitrifying bacterium isolated from activated sludge.

To find a biomarker for denitrification in activated sludge, five denitrifying strains isolated from three wastewater treatment plants were studied. These strains were selected from among 1,500 isolates for their excellent denitrifying properties. They denitrify quickly and have no lag phase when switching from aerobic to anoxic conditions. All strains have the cd1-type of nitrite reductase. The strains are Gram-negative rods and they all grow as filamentous chains when cultivated in liquid solution. The strains differ in colony morphology when grown on nutrient agar. Almost full-length 16S rDNA sequences were determined and phylogenetic analysis revealed that these strains are positioned among members of the genus Comamonas in the beta-subclass of the Proteobacteria. Signature nucleotides and bootstrap percentages were also analysed to verify this position. Strains 110, 123T, 2.99g, 5.38g and P17 were < or = 96.7% similar to known strains, but > or = 99.7% similar to each other, as judged from their 16S rDNA sequences, and grouped tightly together in the phylogenetic tree. Sequence motifs in the 16S rRNA gene were also found, suggesting the monophyletic origin of these strains. Nevertheless, some strains differed from the others, for example strain 110 branches early from the other strains and 5.38g is phenotypically more inert. Therefore, it is proposed that strains 110, 123T, 2.99g and P17 are classified into a new species, Comamonas denitrificans sp. nov., while the taxonomic status of strain 5.38g will have to await the outcome of further studies. The type strain of Comamonas denitrificans is 123T (ATCC 700936T).

Anti-Bacterial Agents↗
PubMed2001

Kilham polyomavirus: activation of gene expression and DNA replication in mouse fibroblast cells by an enhancer substitution.

The Kilham strain of polyomavirus (KV) infects vascular endothelial cells in vivo (J. E. Greenlee, Infect. Immun. 26:705-713, 1979), but no permissive cell type for growth of the virus in vitro has been identified. The failure of KV DNA to replicate in mouse fibroblast cells after transfection suggested that viral gene expression had narrow cell specificity. A KV substitution mutant having a part of the regulatory region of KV DNA replaced with a segment of the polyomavirus transcriptional enhancer was constructed. The substitution mutant was able to replicate in transfected 3T3 cells, and the newly replicated viral DNA associated with protein to form particles with the density of virions in CsCl equilibrium gradients. However, these particles were noninfectious when tested on 3T3 cells, suggesting that absorption or uptake of virus particles was defective for these cells. Analysis of early and late promoter activities by luciferase reporter gene expression showed that the enhancer substitution had a moderate positive effect on early gene expression and a large effect on the expression of the late genes. KV large T antigen inhibited the activities of both the wild-type and the substitution mutant early promoter, whereas only the mutant late promoter was activated under the same conditions. A comparison of the KV and polyomavirus large T antigens showed that they were not interchangeable in the initiation of KV and polyomavirus DNA synthesis. Furthermore, the wild-type KV origin of DNA replication was less active than the mutant structure in the presence of saturating amounts of KV large T antigen. Together, our data demonstrate several differences between the two types of large T antigen in their interactions with cellular proteins.

Animals↗
PubMed2001

Effect on polyomavirus T-antigen function of mutations in a conserved leucine-rich segment of the DnaJ domain.

The N-terminal part of the mouse polyomavirus T antigens contains a highly conserved segment (-LLELLKL-), including amino acid residues 13 to 19. The sequence motif is predicted to form alpha helix I in the DnaJ domain of the T antigens. Four mutants with conservative substitutions of amino acid residues 13 and 14 were constructed. Of the four substitutions, L13M, L13I, L13V, and L14V, only L13V resulted in a phenotypic change. In transfected mouse cells, L13V large T antigen showed a more than 100-fold-reduced viral DNA synthesis. The viral replication could not be rescued by cotransfection of the cells with DNA expressing small t antigen or a large T antigen truncated at the C terminus that would compensate for a defect in host cell stimulation. In contrast to the effect on DNA replication, the L13V substitution in large T antigen did not prevent complex formation with Hsc70 and the Rb protein. Also, the activity of the protein in transactivation of transcription from the adenovirus E2 promoter was unimpaired, showing that the transcription factor E2F was released from pRb. The L13V substitution also caused a defect in small t antigen. However, this phenotypic change was due to protein instability. In contrast, middle T antigen with the L13V substitution remained stable and functional in cellular transformation. Together, the data show that the effect of the L13V substitution did not abrogate the Hsc70 interaction of the DnaJ domain. However, it is possible that the substitution of amino acid residue 13 affected specific DnaJ functions of large T antigen.

3T3 Cells↗
PubMed2000

Galabiosyl donors; efficient synthesis from 1,2,3,4, 6-penta-O-acetyl-beta-D-galactopyranose.

1,2,3,4,6-Penta-O-acetyl-beta-D-galactopyranose was transformed into phenyl 2,3,4,6-tetra-O-benzyl-1-thio-beta-D-galactopyranoside (5) and 4-methoxyphenyl 2,3,6-tri-O-benzoyl-beta-D-galactopyranoside (8) in 73% (two steps) and 58% (three steps) yield, respectively. Glycosylation of the acceptor 8 with donor 5 using N-iodosuccinimide-trimethylsilyl trifluoromethanesulfonate as promoter furnished the galabioside 9 (8.8 g) in 95% yield. Further transformations provided in high yields anomerically-activated galabiosides (thioglycoside (1), trichloroacetimidate (2), and bromosugar (3)) suitable for use as glycosyl donors in syntheses of galabiose-containing oligosaccharides. Several of the compounds reported here are crystalline, which greatly simplified purifications.

Crystallization↗
PubMed2000

Glaucoma following congenital cataract surgery: an 18-year longitudinal follow-up.

PURPOSE: To report the occurrence of postoperative glaucoma and to evaluate risk factors. METHODS: Children born in four of the western counties of Sweden who were diagnosed with congenital cataracts formed a cohort (n=137). The following parameters were evaluated: age at cataract surgery; type of surgery; visual outcome; postoperative IOP; optic disc abnormalities; date of onset of the complication; number of reoperations, including treatment for secondary cataract; presence of systemic anomalies; microphthalmus; and eye-related anomalies. RESULTS: A diagnosis of glaucoma was recorded for 12% of the eyes. The mean follow-up time was 9.6 years. There is a relationship between surgery before the age of 10 days and development of glaucoma. Microphthalmus is an important risk factor as well. CONCLUSIONS: Despite modern surgical techniques the incidence of aphakic glaucoma is 10% or higher. No time-dependent increase in the incidence of late-onset glaucoma between the 1980s and the 1990s could be proven.

Age of Onset↗
PubMed1999

Synthesis of selected aminodeoxy analogues of galabiose and globotriose.

Six aminodeoxy 2-(trimethylsilyl)ethyl (Me3SiEt) glycoside analogues of galabiose (4'- and 6'-aminodeoxy) and globotriose (6"-, 4"-, 2"-, and 6'-aminodeoxy) were synthesized by glycosylation of protected Me3SiEt galactoside and lactoside acceptors with azido-substituted monosaccharide donors, followed by reduction of the azido groups and removal of the protecting groups.

Disaccharides↗
PubMed1999

Synthesis of some aglycon analogs of globotriosylceramide.

Seven aglycon analogs of globotriosylceramide were synthesized by glycosylation of suitable functionalized alcohols with peracetylated globotriose trichloroacetimidate, followed by further transformations of the aglycon and removal of the protecting groups.

Bacterial Toxins↗
PubMed1999

Synthesis of selected aminodeoxy analogs of globotriosylceramide.

Four aminodeoxy analogs of globotriosylceramide (6"-, 4"-, 2"-, and 6'-aminodeoxy) were synthesized by glycosylation of 3-O-benzoylated azidosphingosine with the corresponding aminodeoxy-globotriose trichloroacetimidate, followed by reduction of the azido group, N-acylation with 1-adamantaneacetic acid, and removal of the protecting groups.

Magnetic Resonance Spectroscopy↗
PubMed1999

Comparative 1H NMR study of hydroxy protons in galabioside and its S-linked 4-thiodisaccharide analogue in aqueous solution.

The NMR data obtained from hydroxy protons have been used to investigate the presence and absence of intramolecular hydrogen bonding in aqueous solutions of 2-(trimethylsilyl)ethyl galabioside (alpha-D-Galp-(1-->4)-beta-D-Galp-O(CH2)2SiMe3) and the S-linked 4-thiodisaccharide analogue. The data show that there is a weak hydrogen bond interaction between O-6H and O-2'H in galabioside, but not in the thio-analogue. The results are in good agreement with those reported for the substances in a Me2SO-d6 solution. It is also shown that the existence of a hydrogen bond can be quite easily monitored by comparing the NMR data of the hydroxy protons.

Carbohydrate Conformation↗
PubMed1999

Use of bacteriophage T7 displayed peptides for determination of monoclonal antibody specificity and biosensor analysis of the binding reaction.

A heptapeptide library displayed by bacteriophage T7 was used to characterize epitopes of the monoclonal antibodies F4, F5, and LT1 directed against mouse polyomavirus large T-antigen. Phage selected by biopanning was cloned by plaque isolation, and the binding specificity of individual clones was confirmed by enzyme-linked immunosorbent assay. In phage reacting with the F5 antibody the deduced amino acid sequence of the displayed peptides corresponded to a segment of large T-antigen. In phage reacting with the antibodies F4 and LT1, no such similarity was observed. The kinetics of phage particle-monoclonal antibody complex formation and dissociation was analyzed in an optical biosensor instrument. Sensor chips of standard quality were useful for binding analysis of T7 phage in crude lysates of infected Escherichia coli. We synthesized peptides corresponding to selected consensus sequences and showed by biosensor analysis that these peptides (linear NH3-CPNSLTPADPTMDY-COOH and NH3-NSLTPCNNKPSNRC-COOH with an intramolecular S--S bridge) were able to compete with large T-antigen in binding to the corresponding antibodies (LT1 and F4). These synthetic peptides were also used for gentle and specific dissociation of large T-antigen-antibody complexes. The results demonstrate the potential of phage T7 for display of peptides and for rapid analysis of interactions of these peptides with ligands.

Amino Acid Sequence↗
PubMed1999

Determination of the cell adhesion specificity of Streptococcus suis with the complete set of monodeoxy analogues of globotriose.

Streptococcus suis causes meningitis and other serious infections in pigs and humans, and binds to host cell globotriosylceramide. In order to determine the essential hydroxyls involved in binding, the complete set of monodeoxy derivatives of the receptor trisaccharide Gal alpha1-Gal beta1-4Glc were tested as inhibitors of bacterial hemagglutination. Removal of the 4''-, 6'', 2' or 3'-hydroxyls abolished inhibitory activity, which indicated that they were critically involved in binding. The same results were obtained using synthetic lipid-linked monodeoxy derivatives of the trisaccharides in a thin-layer overlay assay. The P(N) and P(O) subtypes of the S. suis adhesin showed similar binding patterns. The hydroxyls of the glucose moiety were not critical for binding, although the adhesin binds better to the trisaccharide Gal alpha1-4Gal beta1-4Glc than the disaccharide Gal alpha1-4Gal.

Animals↗