Biomedical subjects

Jenny Persson

Publications and source records attributed to Jenny Persson.

6 recordsLinked to original sources

PubMed2007

Children with Down syndrome: oral development and morphology after use of palatal plates between 6 and 48 months of age.

OBJECTIVE: The aim of this study was to describe the number of erupted teeth, sucking habits, tongue morphology, facial expression and speech in children with Down syndrome (DS) aged 48 +/- 6 months and treated from 6 months of age with palatal plates in combination with speech and language therapy. METHODS: The research took the form of a multicentre, multidisciplinary, longitudinal study of children with DS followed from the age of 6 months. A total of 37 children with DS were included. One child could not cooperate at all and was excluded from the evaluations. In combination with speech and language intervention provided by speech and language therapists, the children used palatal plates provided by dentists from 6 months of age. In the evaluation, the children in the sample (n = 36) were compared with two similarly aged control groups: one group of children with DS who never had used palatal plates (n = 31) and one group of children with normal development (n = 36). The evaluation of oral parameters was performed by dentists after calibration. Registration of facial expression and speech was done by a speech and language therapist, and the evaluation was done by two speech and language therapists and one phonetician who were calibrated in joint discussions. RESULTS: In contrast to the children with DS in the control group, the subjects in the study were found to have as many erupted teeth as the children with normal development. The prevalence of sucking habits did not differ between the three groups. Only children with DS sucked their tongue, a toy or other things in addition to a thumb or dummy. The prevalence of tongue diastase in the study group with DS was of the same magnitude as in the evaluation at the age of 18 +/- 3 months. The palatal plates were used by 57-65% of the children without any larger problems. In the study sample, the possible beneficial effects of palatal plate therapy were a lower prevalence of posterior cross-bite, a higher prevalence of frontal cusp-to-cusp relation and a lower prevalence of frontal open bite. Evaluation of facial expression and speech showed a higher score for facial expression and a better communicative capacity in the children in the study group than in the control children with DS. CONCLUSIONS: In children with DS, palatal plate therapy between 6 and 48 months of age in connection with speech and language intervention had a positive effect on occlusion, oral motor function, facial expression and speech. No harmful effects were observed. Although this is a valuable method, however, it must be emphasized that palatal plate therapy puts additional demands on already burdened children and their caretakers.

Case-Control Studies↗

PubMed2006

Cytokine response to lipoprotein lipid loading in human monocyte-derived macrophages.

BACKGROUND: Macrophage foam cell formation is a prominent feature of human atherosclerotic plaques, usually considered to be correlated to uptake of and inflammatory response to oxidized low density lipoproteins (OxLDL). However, there are alternative pathways for formation of macrophage foam cells and the effect of such lipid loading on macrophage function remains to be fully characterized. In the present study we investigated basal and inducible cytokine expression in primary human macrophages either loaded with triglycerides through incubation with very low density lipoproteins (VLDL) or with cholesterol through incubation with aggregated LDL (AgLDL). We then analyzed how foam cell lipid content affected secretion of three pro-inflammatory cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and of one chemokine: interleukin-8 (IL-8), all of which are considered pro-inflammatory, pro-atherosclerotic, and are expressed by cells in atherosclerotic tissue. RESULTS: Formation of triglyceride-loaded foam cells resulted in a four-fold increase in basal IL-1beta secretion, whereas cholesterol loading lacked significant effect on IL-1beta secretion. In contrast, secretion of TNF-alpha and IL-6 decreased significantly following both cholesterol and triglyceride loading, with a similar trend for secretion of IL-8. Lipid loading did not affect cell viability or expression of caspase-3, and did not significantly affect macrophage ability to respond to stimulation with exogenous TNF-alpha. CONCLUSION: Lipid loading of primary human macrophages resulted in altered cytokine secretion from cells, where effects were similar regardless of neutral lipid composition of cells. The exception was IL-1beta, where triglyceride, but not cholesterol, lipid loading resulted in a stimulation of basal secretion of the cytokine. It is apparent that macrophage cytokine secretion is affected by lipid loading by lipoproteins other than OxLDL. As both VLDL and AgLDL have been found in the vessel wall, macrophage cytokine response to uptake of these lipoproteins may have a direct effect on atherosclerotic development in vivo. However, macrophage neutral lipid amount and composition did not affect cellular activation by exogenous TNF-alpha, making it likely that lipoprotein lipid loading can affect foam cell cytokine secretion during basal conditions but that the effects can be overruled by TNF-alpha during acute inflammation.

Cells, Cultured↗

PubMed2006

Extreme sequence divergence but conserved ligand-binding specificity in Streptococcus pyogenes M protein.

Many pathogenic microorganisms evade host immunity through extensive sequence variability in a protein region targeted by protective antibodies. In spite of the sequence variability, a variable region commonly retains an important ligand-binding function, reflected in the presence of a highly conserved sequence motif. Here, we analyze the limits of sequence divergence in a ligand-binding region by characterizing the hypervariable region (HVR) of Streptococcus pyogenes M protein. Our studies were focused on HVRs that bind the human complement regulator C4b-binding protein (C4BP), a ligand that confers phagocytosis resistance. A previous comparison of C4BP-binding HVRs identified residue identities that could be part of a binding motif, but the extended analysis reported here shows that no residue identities remain when additional C4BP-binding HVRs are included. Characterization of the HVR in the M22 protein indicated that two relatively conserved Leu residues are essential for C4BP binding, but these residues are probably core residues in a coiled-coil, implying that they do not directly contribute to binding. In contrast, substitution of either of two relatively conserved Glu residues, predicted to be solvent-exposed, had no effect on C4BP binding, although each of these changes had a major effect on the antigenic properties of the HVR. Together, these findings show that HVRs of M proteins have an extraordinary capacity for sequence divergence and antigenic variability while retaining a specific ligand-binding function.

Amino Acid Sequence↗

PubMed2005

Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor.

Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.

Amino Acid Sequence↗

PubMed2005

Single-step purification of human C4b-binding protein (C4BP) by affinity chromatography on a peptide derived from a streptococcal surface protein.

Many Gram-positive bacteria express surface proteins that bind human plasma proteins. These bacterial proteins, and derivatives of them, are of interest for analysis of bacterial pathogenesis and as immunochemical tools. Well-characterized examples include the IgG-binding reagents staphylococcal protein A and streptococcal protein G, and the recently described streptococcal IgA-binding peptide Sap. Here, we show that a peptide derived from the streptococcal M22 protein can be used for single-step affinity purification of the human complement regulator C4b-binding protein (C4BP). Binding of C4BP was strongly enhanced by dimerization of the peptide via a C-terminal cysteine residue not present in the intact M22 protein. The purified C4BP had the expected binding characteristics, and acted as a cofactor for factor I in the degradation of C4b. Passage of serum through a peptide column under non-saturating conditions resulted in binding of >99.5% of serum C4BP, implying that such a column can be used to deplete serum of C4BP. These data indicate that the C4BP-binding peptide is a versatile tool that can be used for simple and rapid purification of biologically active human C4BP or for removal of C4BP from serum.

Amino Acid Sequence↗

PubMed2002

Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells.

Laminins are alphabetagamma heterotrimeric extracellular proteins that regulate cellular functions by adhesion to integrin and nonintegrin receptors. Laminins containing alpha4 and alpha5 chains are expressed in bone marrow, but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 (alpha5beta1gamma1/alpha5beta2gamma1), laminin-8 (alpha4beta1gamma1), laminin-1 (alpha1beta1gamma1), and fibronectin. About 35% to 40% of CD34(+) and CD34(+)CD38(-) stem and progenitor cells adhered to laminin-10/11, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-8 and laminin-1. Adhesion of CD34(+)CD38(-) cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by 12-tetradecanoyl phorbol-13-acetate (TPA). Fluorescence-activated cell-sorting (FACS) analysis showed expression of integrin alpha6 chain on most CD34(+) and CD34(+)CD38(-) cells. Integrin alpha6 and beta1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineage-committed myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated stromal-derived factor-1alpha (SDF-1alpha)-stimulated transmigration of CD34(+) cells, by an integrin alpha6 receptor-mediated mechanism. In conclusion, we demonstrate laminin isoform-specific adhesive interactions with human bone marrow stem, progenitor, and more differentiated cells. The cell-adhesive laminins affected migration of hematopoietic progenitors, suggesting a physiologic role for laminins during hematopoiesis.

Antigens, CD34↗