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C Faber

Publications and source records attributed to C Faber.

28 records · Page 2Linked to original sources
PubMed1998

Cultured astrocytes express regional heterogeneity of the immunoreactive phenotype under basal conditions and after gamma-IFN induction.

Cerebral astrocytes are known to show a region-specific phenotype, concerning the expression of several receptors and the synthesis of secreted substances. In order to find out whether this heterogeneity also exists for the immunological activation, we studied several parameters that are known to characterize activated astroglia on cultured primary rat astrocytes originating from cortex, hippocampus, striatum, septum and brain stem: major histocompatibility complex (MHC) class II and intercellular adhesion molecule (ICAM)-1 expression, nitric oxide (NO) production and interleukin-6 (IL-6) synthesis. Unstimulated cultures show a baseline expression of MHC class II molecules that differs from one region to another, hippocampus and brain stem showing the highest values. These differences are strongly enhanced after a 48-h incubation with gamma-interferon (gamma-IFN). NO production is also induced by a 72-h incubation with gamma-IFN, showing similar patterns of regional specialization. The baseline expressions of ICAM-1 and IL-6 also show major regional differences, with the brain stem and the striatum showing elevated values for ICAM-1, and the septum and the brain stem producing the largest amounts of IL-6. The expressions of ICAM-1 and IL-6 are not affected by an incubation with gamma-IFN. Our results demonstrate that the immunological activities of astroglial cells show regional heterogeneities. This specialization may be implicated in the pathophysiological pathways of several neurodegenerative disorders.

Animals↗
PubMed1998

Three-dimensional structure of a human Fab with high affinity for tetanus toxoid.

BACKGROUND: The wide range of antibody specificity and affinity results from the differing shapes and chemical compositions of their binding sites. These shapes range from discrete grooves in antibodies elicited by linear oligomers of nucleotides and carbohydrates to shallow depressions or flat surfaces for accommodation of proteins, peptides and large organic compounds. OBJECTIVES: To determine the Fab structure of a high-affinity human antitoxin antibody. To explore structural features which enable the antibody to bind to intact tetanus toxoid, peptides derived from the sequence of the natural immunogen and antigenic mimics identified by combinatorial chemistry. To explain why this Fab shows a remarkable tendency to produce crystals consistently diffracting to d spacings of 1.7-1.8 A. To use this information to engineer a strong tendency to crystallize into the design of other Fabs. STUDY DESIGN: The protein was crystallized in hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG) 8000. Crystals were subjected to X-ray analysis and the three-dimensional structure of the Fab was determined by the molecular replacement method. Interactive computer graphics were employed to fit models to electron density maps, survey the structure in multiple views and discover the crystal packing motif of the protein. RESULTS: Exceptionally large single crystals of this protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter was cut into six irregular pieces, each retaining the features of the original in diffracting to high resolution (1.8 A) with little decay in the X-ray beam. In an individual Fab, the active site is relatively flat and it seems likely that the protein antigen and derivative peptides are tightly held on the outer surface without significant penetration into the interior. There is no free space to accommodate even a dipeptide between VH and VL. One of the unique features of the B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site. The CDR3 of the H chain contributes significantly to this ridge, as well as to adjoining regions projected to be important for the docking of the antigen. Both the ease of crystallization and the favorable diffraction properties are mainly attributable to the tight packing of the protein molecules in the crystal lattice. DISCUSSION: The B7-15A2 active site provides a stable and well defined platform for high affinity docking of proteins, peptides and their mimotopes. The advantages for future developments are suggested by the analysis of the crystal properties. It should be possible to incorporate the features promoting crystallization, close packing and resistance to radiation damage into engineered human antibodies without altering the desired specificities and affinities of their active sites.

Amino Acid Sequence↗
PubMed1998

The structure of PurR mutant L54M shows an alternative route to DNA kinking.

The crystal structure of the purine repressor mutant L54M bound to hypoxanthine and to the purF operator provides a stereochemical understanding of the high DNA affinity of this hinge helix mutant. Comparison of the PurR L54M-DNA complex to that of the wild type PurR-DNA complex reveals that these purine repressors bind and kink DNA similarly despite significant differences in their minor groove contacts and routes to interdigitation of the central C.G:G.C base pair step. Modeling studies, supported by genetic and biochemical data, show that the stereochemistry of the backbone atoms of the abutting hinge helices combined with the rigidity of the kinked base pair step constrain the interdigitating residue to leucine or methionine for the LacI/GalR family of transcription regulators.

Amino Acid Substitution↗
PubMed1996

Secondary structure and tertiary fold of the birch pollen allergen Bet v 1 in solution.

Bet v 1 is the major birch pollen allergen and therefore the main cause of type I allergies observed in early spring. It is composed of 159 amino acid residues adding up to a molecular mass of 17 kDa. We determined the secondary structure and tertiary fold of full-length Bet v 1 by NMR spectroscopy. Two- and three-dimensional NMR measurements suggest that Bet v 1 is a globular monomer in solution with a high content of well defined secondary structure. Of the total of 159 residues, 135 could be sequentially assigned, using an improved assignment strategy based mainly on heteronuclear experiments. An improved strategy for structure calculation revealed three helices and two beta-sheets as major elements of secondary structure. The globular tertiary structure is mainly stabilized by two antiparallel beta-sheets. The two helices at the C terminus are in accordance with the results from the solution structure of the chemically synthesized peptide Bet v 1-(125-154). This peptide is composed of two helices connected by a hinge. The structural features of Bet v 1 are highly similar to those found in the Ambrosia allergen Amb t V.

Allergens↗
PubMed1994

Interleukin-4 affects phenotype and proliferative response of peripheral blood lymphocytes from glioblastoma patients after specific or nonspecific in vitro stimulation.

Immunosuppressive events are often observed in glioblastoma-bearing patients. We tested the response of circulating lymphocytes from glioblastoma patients to low concentrations of interleukin (IL)-4 and IL-2 after lectin activation or specific in vitro stimulation by autologous tumor cells. In the presence of IL-2, IL-4 up-regulates the proliferation rate of phytohemagglutinin (PHA)-P-stimulated glioblastoma patients' peripheral blood lymphocytes (PBL)s. Allogeneically- and syngeneically-stimulated PBLs of these patients present an increased proliferation rate in the presence of IL-4. This specifically stimulated lymphocyte population presents a very low proportion of CD8+ cells. This proportion is slightly increased in the presence of IL-4. Our results indicate that the glioblastoma cell-imposed inhibition on T-cells can be partly overcome by low concentrations of IL-4 during in vitro stimulation. Our experiments also demonstrate that glioblastoma-bearing patients' PBLs constitute a good model in which to study the effects of IL-4.

Cells, Cultured↗
PubMed1990

[Esophagorespiratory tract fistula treated by primary suture. Apropos of 2 cases of esophago-pleural fistula and 2 cases of esophagobronchial fistula].

We describe two oesophago-pleural fistulas arriving respectively 40 months and 15 years after pneumonectomia, and two oesophago-bronchial fistulas due to perforated oesophageal diverticula. We evaluate diagnostic methods and discuss etiology of these oesophageal fistulas. Pleural fistulas treatment associate thoracic drainage, direct surgical treatment of the fistula with primary suturing of oesophagus. For oesophago-bronchial fistula treatment, we have made pneumonectomia one time and primary bronchial suturing another. In these two cases, oesophagus was only sutured without pleural or muscular flap. Transient alimentary gastrostomy was made. No fistula recidive of postoperative complication occurred. There is no operative mortality.

Adult↗
PubMed1990

[Strengthening of cryodestruction by ultrasonic energy].

The ultrasonic treatment of vital tissue with therapeutically qualified ultrasonic intensity immediate before the cryosurgery leads to a significant enlargement of the plane and the depth of the cryodestruction. This knowledge should be used in the cryosurgical treatment of inoperable carcinomas with extensive tumor mass.

Animals↗
PubMed1984

[Congenital toxoplasmosis. Tolerability of the sulfadoxine-pyrimethamine combination. 24 cases].

The pyrimethamine-sulfadoxine combination, active against acute toxoplasmosis in the mouse, was administered to 24 children with congenital toxoplasmosis in doses of 500 mg sulfadoxine and 25 mg pyrimethamine per 20 kg bodyweight once every fortnight. The drug appeared to be as effective as other sulfonamide-pyrimethamine combinations. It was generally well tolerated and was withdrawn in only 3 patients on account of minor side-effects. Giving pyrimethamine-sulfadoxine together with folinic acid is a much simpler treatment of congenital toxoplasmosis than the usual ones.

Child, Preschool↗