Biomedical subjects

G Pruijn

Publications and source records attributed to G Pruijn.

4 recordsLinked to original sources

PubMed2001

Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia.

The recessively inherited developmental disorder, cartilage-hair hypoplasia (CHH) is highly pleiotropic with manifestations including short stature, defective cellular immunity, and predisposition to several cancers. The endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins. It has at least two functions, namely, cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA. We describe numerous mutations in the untranslated RMRP gene that cosegregate with the CHH phenotype. Insertion mutations immediately upstream of the coding sequence silence transcription while mutations in the transcribed region do not. The association of protein subunits with RNA appears unaltered. We conclude that mutations in RMRP cause CHH by disrupting a function of RNase MRP RNA that affects multiple organ systems.

Alleles↗

PubMed2000

Rapid lupus autoantigen relocalization and reactive oxygen species accumulation following ultraviolet irradiation of human keratinocytes.

OBJECTIVE: In vitro treatment with ultraviolet B (UVB) induces relocalization of lupus autoantigens to the cell surface. We have addressed the relationship between autoantigen relocalization, accumulation of intracellular reactive oxygen species (ROS) and the induction of apoptosis following UVA and UVB exposure. METHODS: Human primary keratinocytes were exposed in vitro to doses of UVA and UVB equivalent to 0.01-4 times the minimal erythemal dose. The cellular locations of Ro60, Ro52, Sm, U2-B" and La were determined using monoclonal antibodies. ROS accumulation and apoptosis induction were assessed using the intracellular ROS probe 2'7'-dichlorodihydrofluorescein diacetate, and the viability stains Hoechst 33342 and propidium iodide. RESULTS: UV treatment induced the relocalization of all five autoantigens investigated and an accumulation of ROS. UVA and UVB induced necrosis and apoptosis, respectively. CONCLUSION: These data suggest that both UVA and UVB induce ROS within keratinocytes but have significantly different effects upon autoantigen relocalization and cell viability.

Antigens, Surface↗

PubMed1994

Epitope mapping with synthetic peptides of 52-kD SSA/Ro protein reveals heterogeneous antibody profiles in human autoimmune sera.

The reactivity of autoantibodies present in the sera of 489 patients with Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and other autoimmune diseases was investigated by ELISA using recombinant 52-kD SSA/Ro protein (rRo52) and 39 overlapping synthetic peptides representing the entire sequence of Ro52. We report that IgG antibodies reacting with rRo52 were present in the sera of a large number of patients with SS (67% of patients with primary SS and 46% of patients with SS associated with SLE), whereas they were less frequent (10-25%) in SLE, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and mixed connective tissue disease (MCTD), and absent in scleroderma. Among the 39 peptides tested, five were recognized by sera from 30-65% of patients with SS, namely peptides representing residues 2-11, 107-122, 107-126, 277-292 and 365-382. Patients with JCA had raised levels of IgG antibodies reacting with peptides 2-11 and 365-382, and 51% of patients with MCTD had raised levels of IgG antibodies reacting with peptide 365-382. None of the five peptides was recognized by more than 20% of sera from patients with SLE and RA. Interestingly, and of importance in the field of diagnostic tests based on peptides, the reactivity of antibodies to the Ro52 synthetic peptides varied greatly according to the origin of sera. Inhibition experiments using either patients' sera or antibodies induced in rabbits against Ro52 peptides showed that the four domains 2-11, 107-122, 277-292 and 365-382 are accessible on the surface of the Ro52 protein. These regions may thus be involved in the induction of specific antibodies in autoimmune patients.

Amino Acid Sequence↗

PubMedDate not supplied

The SS-A/SS-B autoantigenic complex: localization and assembly.

The subcellular distribution of Ro ribonucleoprotein particles (Ro RNPs) and their constituents was determined using mammalian tissue culture cells and Xenopus laevis oocytes. Cell fractionation revealed that Ro RNPs are restricted to the cytoplasm, while the Ro RNP-specific proteins were also present in the nucleus. Transport studies indicated that the protein components of Ro RNPs are actively imported into the nucleus while the RNA component accumulates in the cytoplasm. These results suggest a model for the assembly of Ro RNPs.

Animals↗