Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits
RAMAEKERS, Vincent ; ; et al
in Neuropediatrics (2007), 38(6), 276-281
Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning autism with neurological abnormalities. Twenty-five patients with ... [more ▼]
Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning autism with neurological abnormalities. Twenty-five patients with early-onset low-functioning autism with or without neurological deficits, were evaluated for serum folate, cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), and serum FR autoantibodies of the blocking type to determine the significance of folate receptor (FR) autoantibodies with respect to folate transport across the blood-CSF barrier. In spite of normal serum folate, CSF 5MTHF was low in 23 of 25 patients. The reduced CSF folate in 19 of these 23 patients could be explained by serum FR autoantibodies blocking the folate binding site of the membrane-attached FR on the choroid epithelial cells. Oral folinic acid supplements led to normal CSF 5MTHF and partial or complete clinical recovery after 12 months. Serum FR autoimmunity appears to represent an important factor in the pathogenesis of reduced folate transport to the nervous system among children with early-onset low-functioning autism associated with or without neurological deficits. Early detection of FR autoantibodies may be a key factor in the prevention and therapeutic intervention among this subgroup of patients with autism. © Georg Thieme Verlag KG Stuttgart. [less ▲]Detailed reference viewed: 68 (1 ULg)
Folding and Stability of Class A beta-Lactamases
Matagne, André ;
in Frère, Jean-Marie (Ed.) Beta-Lactamases (2012)
Class A β-lactamases have proved useful as model proteins in studying a wide variety of aspects of protein folding. We review those features that have shed light on kinetic intermediates that take part in ... [more ▼]
Class A β-lactamases have proved useful as model proteins in studying a wide variety of aspects of protein folding. We review those features that have shed light on kinetic intermediates that take part in folding, including some insight into the molecular basis of the kinetic and stable molten-globule states that have been identified. The contrast between the folding behaviour of PC1 and the two lactamase mutants, P54 and P2, can be attributed in some detail to changes in molecular conformation. The early, very rapid stages of folding of β-lactamases have been shown to be multiphasic, and an interesting intermediate is described that has non-native contacts involving burial of the C-terminal tryptophan. A further feature is that the region around the disulphide bond in the TEM enzymes is formed very early in the foldingreaction. The unusual feature of class A β-lactamases, i.e. a cispeptide bond critical in the stereochemistry of the active site that usually, but not always, involves a proline residue, has been shown to be important in accounting for the slow folding reactions. The effect of substrates on the stabilization of the enzymes and on their reversible deactivation is also reviewed. [less ▲]Detailed reference viewed: 12 (1 ULg)
Folding mechanism of single domain antibody fragments (VHHs) and influence of the internal disulphide bridge on their stability and folding pathway.
Poster (2009, February)Detailed reference viewed: 15 (3 ULg)
Folding of class A beta-lactamases is rate-limited by peptide bond isomerization and occurs via parallel pathways.
Vandenameele, Julie ; Lejeune, Annabelle ; Di Paolo, Alexandre et al
in Biochemistry (2010), 49(19), 4264-75
Class A beta-lactamases (M(r) approximately 29000) provide good models for studying the folding mechanism of large monomeric proteins. In particular, the highly conserved cis peptide bond between residues ... [more ▼]
Class A beta-lactamases (M(r) approximately 29000) provide good models for studying the folding mechanism of large monomeric proteins. In particular, the highly conserved cis peptide bond between residues 166 and 167 at the active site of these enzymes controls important steps in their refolding reaction. In this work, we analyzed how conformational folding, reactivation, and cis/trans peptide bond isomerizations are interrelated in the folding kinetics of beta-lactamases that differ in the nature of the cis peptide bond, which involves a Pro167 in the BS3 and TEM-1 enzyme, a Leu167 in the NMCA enzyme, and which is missing in the PER-1 enzyme. The analysis of folding by spectroscopic probes and by the regain of enzymatic activity in combination with double-mixing procedures indicates that conformational folding can proceed when the 166-167 bond is still in the incorrect trans form. The very slow trans --> cis isomerization of the Glu166-Xaa167 peptide bond, however, controls the final step of folding and is required for the regain of the enzymatic activity. This very slow phase is absent in the refolding of PER-1, in which the Glu166-Ala167 peptide bond is trans. The double-mixing experiments revealed that a second slow kinetic phase is caused by the cis/trans isomerization of prolines that are trans in the folded proteins. The folding of beta-lactamases is best described by a model that involves parallel pathways. It highlights the role of peptide bond cis/trans isomerization as a kinetic determinant of folding. [less ▲]Detailed reference viewed: 52 (14 ULg)
The Folding Process of Hen Lysozyme: A Perspective from the 'New View'
Matagne, André ;
in Cellular and Molecular Life Sciences : CMLS (1998), 54(4), 363-71
How a conformationally disordered polypeptide chain rapidly and efficiently achieves its well-defined native structure is still a major question in modern structural biology. Although much progress has ... [more ▼]
How a conformationally disordered polypeptide chain rapidly and efficiently achieves its well-defined native structure is still a major question in modern structural biology. Although much progress has been made towards rationalizing the principles of protein structure and dynamics, the mechanism of the folding process and the determinants of the final fold are not yet known in any detail. One protein for which folding has been studied in great detail by a combination of diverse techniques is hen lysozyme. In this article we review the present state of our knowledge of the folding process of this enzyme and focus in particular on recent experiments to probe some of its specific features. These results are then discussed in the context of the 'new view' of protein folding based on energy surfaces and landscapes. It is shown that a schematic energy surface for lysozyme folding, which is broadly consistent with our experimental data, begins to provide a unified model for protein folding through which experimental and theoretical ideas can be brought together. [less ▲]Detailed reference viewed: 32 (8 ULg)
"La folie heureuse" : à propos d'un passage d'Horace (Épîtres II, 2, v. 128-140)
in Filiber, Carine (Ed.) Vertiges de la folie. Catalogue de l'exposition (Musée de la Vie Wallonne, Liège, 30/03-19/08/2012) (2012)Detailed reference viewed: 20 (7 ULg)
Folipidine, a new type quinoline alkaloid from plants of the Haplophyllum genus
; ; et al
in Chemistry of Natural Compounds (2005), 41(1, JAN-FEB), 60-64
The new quinoline alkaloid folipidine, the structure of which was established by chemical transformations and spectral data (UV, IR, mass, NMR) using APT 2D H-1-H-1 COSY, NOESY, and H-1-(13)CHSQC, HMBC ... [more ▼]
The new quinoline alkaloid folipidine, the structure of which was established by chemical transformations and spectral data (UV, IR, mass, NMR) using APT 2D H-1-H-1 COSY, NOESY, and H-1-(13)CHSQC, HMBC, was isolated from two plants of the Haplophyllum mints. Folipidine is the first representative of a new type of quinoline alkaloids that contain a heteroaromatic skeleton of [3,4-b]conjugated pyrrole and quinoline fragments. The total alkaloids of these plants exhibit antitumor activity. Folipidine does not possess such activity. [less ▲]Detailed reference viewed: 30 (0 ULg)
Follicle Stimulating Hormone -Secreting Pituitary adenomas
Beckers, Albert ; Stevenaert, Achille ; et al
in Journal of Clinical Endocrinology and Metabolism (1985), 61(3), 525-528
This retrospective study concerns 40 patients with an apparently nonsecretory pituitary adenoma who were operated on during an 11-yr period from 1971 to 1981. Among them, 6 men had elevated serum FSH ... [more ▼]
This retrospective study concerns 40 patients with an apparently nonsecretory pituitary adenoma who were operated on during an 11-yr period from 1971 to 1981. Among them, 6 men had elevated serum FSH levels. LH levels were normal in 5 and slightly elevated in 1. Testosterone levels were low in 2 patients and within normal limits in 2 others. Sexual impotency had developed from 6 months to 1 yr before surgery in all patients. Primary hypogonadism could be eliminated on clinical grounds (recent onset of hypogonadism, previous fertility of 5 of the 6, and postoperative improvement). After transsphenoidal adenomectomy, FSH levels returned to normal values in all, and clinical recovery occurred in most patients. Tumor tissue obtained at operation stained positively for the gonadotropins, but was negative for other pituitary hormones in all patients. The most probable explanation for these findings was that the tumors were responsible for the elevated FSH secretion. This explanation is supported by the immunocytochemical identification of gonadotropin-containing cells in the tumors. We conclude that these 6 men frm a series of 40 patients who presented with pituitary tumor but no GH, PRL, or ACTH hypersecretion had primary gonadotropinomas. [less ▲]Detailed reference viewed: 16 (0 ULg)
A follicle-stimulating-hormone secreting pituitary adenoma treated with long acting repeatable bromocriptine.
; Beckers, Albert ;
in Journal of Endocrinological Investigation (1990), 13Detailed reference viewed: 9 (0 ULg)
Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8.
; ; Heinen, Ernst et al
in Journal of Experimental Medicine (2008), 205(6), 1293-302
The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis ... [more ▼]
The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8(-/-) mice, all splenic Mfge8 was derived from FDCs rather than TBMphis. However, Mfge8(-/-) TBMphis acquired and displayed Mfge8 only when embedded in Mfge8(+/+) stroma, or when situated in lymph nodes draining exogenous recombinant Mfge8. These findings indicate a licensing role for FDCs in TBMphi-mediated removal of excess B cells. Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8(-/-) mice. Hence, FDCs facilitate TBMphi-mediated corpse removal, and their malfunction may be involved in autoimmunity. [less ▲]Detailed reference viewed: 47 (6 ULg)
Follicular Dendritic Cells Do Not Produce Tnf-Alpha nor its Receptor
; ; et al
in Advances in Experimental Medicine and Biology (1993), 329Detailed reference viewed: 12 (0 ULg)
Follicular dendritic cells in lymph nodes after x-irradiation.
; Heinen, Ernst ; Radoux, Dominique et al
in International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine (1982), 42(2), 121-30
Follicular dendritic cells (FDC), non lymphoid cells present in lymph follicles, are characterized by numerous cytoplasmic processes retaining antigen-antibody complexes. Their origin, nature and function ... [more ▼]
Follicular dendritic cells (FDC), non lymphoid cells present in lymph follicles, are characterized by numerous cytoplasmic processes retaining antigen-antibody complexes. Their origin, nature and function are unknown. Mice inguinal lymph nodes after 4.5 or 7.5 Gy X-irradiation were depleted of lymphoid cells. Ultrastructural observations during the first few days post-irradiation show that FDC are unaltered and possess dendritic processes enveloping dense material. Furthermore, they show intense metabolic activity. A lamina densa, never observed so well-developed in other lymph node cells, was detected around the nuclear envelope. The localization of junctions between FDC was analysed. FDC preserve their typical cytoplasmic processes even if lymphoid cells are rare. The latter thus seem not to be responsible for the maintenance of FDC integrity or their development. The possible role of this for antibody production is discussed. Irradiated lymph nodes of lymphoid cells are highly convenient for studying FDC. Isolation of FDC from irradiated lymph organs would seem to be possible. [less ▲]Detailed reference viewed: 22 (0 ULg)
The follicular dendritic cells in normal and pathological conditions
Book published by Springer (1995)Detailed reference viewed: 9 (0 ULg)
Follicular dendritic cells in vitro modulate the expression of Fas and Bcl-2 on germinal center B cells.
; Heinen, Ernst ;
in Cell & Tissue Research (2000), 299(3), 395-402
Germinal center (GC) B cells are highly susceptible to apoptosis. The cellular mechanism regulating this sensitivity, however, has not yet been fully delineated. To investigate whether follicular ... [more ▼]
Germinal center (GC) B cells are highly susceptible to apoptosis. The cellular mechanism regulating this sensitivity, however, has not yet been fully delineated. To investigate whether follicular dendritic cells (FDC) are capable of regulating the susceptibility to apoptosis of GC B cells, we constructed a GC model in vitro: emperipolesis of tonsillar B cells by FDC. We then analyzed the expressions of apoptosis-related proteins (Bcl-2 and Fas) on the cells by three-color flow cytometry. B cells nonentrapped by FDC decreased rapidly in number owing to early apoptosis in vitro, whereas entrapped B cells were rescued for at least 18 h and showed peculiar regulation of Fas and Bcl-2. GC founder cells (CD38+, IgD+; GCFC) and GC B cells (CD38+, IgD-) showed approximately a twofold increased expression of Fas; in contrast, mantle zone B cells (CD38-, IgD+) and memory B cells (CD38-, IgD-) showed no changes. Bcl-2 expression in mantle zone and memory B cells was reduced by approximately one-half; however, GCFC and GC B cells continued to express little Bcl-2 and this did not change. Our findings strongly suggest that FDC play a part in the modulation of the susceptibility to apoptosis on B cells within GC. [less ▲]Detailed reference viewed: 15 (0 ULg)
Follicular dendritic cells innervation within spleen of five mouse strains with different incubation periods after intraperitoneal BSE inoculation.
; ; et al
Poster (2005, February)Detailed reference viewed: 13 (1 ULg)
Follicular dendritic cells isolated from human tonsils.
; Heinen, Ernst ; et al
in Advances in Experimental Medicine and Biology (1985), 186Detailed reference viewed: 9 (0 ULg)