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P Freisinger

Publications and source records attributed to P Freisinger.

26 records · Page 2Linked to original sources
PubMed1994

Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads.

We have used the three-dimensional culture system in alginate beads to redifferentiate human articular chondrocytes which were first expanded on a plastic support. After 15 days in alginate beads, electron microscopy showed that cells had synthesized an extracellular matrix containing collagen fibrils. Electrophoretic analysis of proline-labeled cells demonstrated that redifferentiated chondrocytes synthesized mainly type II collagen and its precursors (pro alpha 1II, pc alpha 1II, and pn alpha 1II). After pepsin digestion a small amount of collagen type XI was also detected. These results were confirmed by Northern blot analysis of total RNAs. Hybridization with collagen cDNA probes coding for the alpha 1(II) and alpha 1(I) chains of collagen types II and I showed that chondrocytes cultured in alginate expressed mainly alpha 1(II) mRNA, whereas alpha 1(I) mRNA transcripts were almost undetectable. Such a result was observed even after several passages on plastic flasks, suggesting that dedifferentiated cells were able to revert to a chondrocytic phenotype in this three-dimensional system. However, SV40-transformed chondrocytes were not able to redifferentiate in alginate as no alpha 1(II) mRNAs were detected. Total RNA was converted into cDNA by reverse transcription and amplified by polymerase chain reaction. This technique was employed to amplify mRNAs specific for collagen type II and type X and the large aggregating proteoglycan aggrecan. Two transcripts resulting from an alternative splicing of the complement regulatory protein (CRP)-like domain of aggrecan were originally identified in chondrocytes in monolayers. Like intact cartilage, chondrocytes in alginate expressed only the larger transcript with the CRP domain, whereas the two transcripts were equally expressed in SV40-transformed chondrocytes. Thus, the alginate system appears to represent a relevant model for the redifferentiation of human chondrocytes, especially when only a small cartilage biopsy is available, and could prove useful for pulse-chase studies of patients with skeletal chondrodysplasias. However it was unable to restore the chondrocytic phenotype in virally transformed cells.

Alginates↗
PubMed1993

Dysspondylochondromatosis.

We report on 3 unrelated patients with an unusual form of neonatal dwarfism with unequal limb length. Radiographs show multiple enchondromatosis of the tubular and the flat bones and severe segmentation abnormalities of the vertebral column. These observations differ from the hitherto described forms of multiple enchondromatosis with growth disorders of the spine, spondyloenchondroplasia, and others. Therefore we propose to delineate this disorder as a new entity.

Abnormalities, Multiple↗
PubMed1993

Collagen fibrils of osteoid in osteogenesis imperfecta: morphometrical analysis of the fibril diameter.

Comprehensive electron-microscopic studies showed that the structure of the collagen fibrils in the osteoid is not uniform. In 82 cases of osteogenesis imperfecta (OI), the diameter of the collagen fibrils was determined morphometrically under standardized magnification. The morphometric investigations of collagen fibrils of the osteoid in OI show clear differences in the four subtypes and in comparison with the control group.

Bone and Bones↗
PubMed1993

Dominant carpotarsal osteochondromatosis.

Dominant carpotarsal osteochondromatosis is a particular disorder of the wrist and tibiotalar joints with abnormal bone proliferation and osteochondromas. Two patients, a mother and son, are described here; a similar condition has previously been described in seven affected members of a family. The upper and the lower limbs are affected in the same patient and the lesion can be bilateral. Autosomal dominant inheritance is a further criterion allowing the diagnosis of dysplasia epiphysealis hemimelica.

Adolescent↗
PubMed1992

An atypical form of mucolipidosis III.

We report two sibs showing a very mild form of mucolipidosis III with no clinical signs but isolated involvement of the hip and very mild abnormalities of the spine. This indicates that a storage disease, in particular mucolipidosis III, should be considered in any case of isolated bilateral hip dysplasia. The differences from other reported atypical variants of mucolipidosis III are discussed.

Child↗
PubMed1991

Pachydysostosis of the fibula.

We report four patients with unilateral bowing of the lower leg, affecting only the fibula. The bone is too long with anterolateral curvature of the distal third. Because of its regressive course and the absence of cutaneous involvement, this newly described entity can be distinguished from other forms of bowing of the leg.

Child, Preschool↗
PubMedDate not supplied

Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.

Hypophosphatasia is an inherited disorder characterised by defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 13 European families affected by perinatal, infantile or childhood hypophosphatasia. Eighteen distinct mutations were found, only three of which had been reported previously in North American and Japanese populations. Most of the 15 new mutations were missense mutations, but we also found two mutations affecting donor splice sites and a nonsense mutation. A missense mutation in the last codon of the putative signal peptide probably affects the final maturation of the protein. Despite extensive sequencing of the gene and its promotor region, only one mutation was identified in two cases, one of which was compatible with a possible dominant effect of certain mutations and the putative role of polymorphisms of the TNSALP gene. In 12 of the 13 tested families, genetic diagnosis was possible by characterisation of the mutations or by use of polymorphisms as genetic markers. Hypophosphatasia diagnosis was assigned in two families where clinical, laboratory and radiographic data were unclear and prenatal diagnosis was performed in one case. The results also show that severe hypophosphatasia is due to a very large spectrum of mutations in European populations with no prevalent mutation and that genetic diagnosis of the disease must be performed by extensive analysis of the gene.

Alkaline Phosphatase↗