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R Stanescu

Publications and source records attributed to R Stanescu.

At least 19 recordsLinked to original sources
PubMed1995

Abnormal collagen cross-linking in the cartilage of a diastrophic dysplasia patient.

The abnormal organization of the cartilage collagen in diastrophic dysplasia is not generally reflected in the levels of the major stabilizing cross-link, hydroxylysyl-pyridinoline. However, in one case there was a marked decrease in the pyridinoline concomitant with the appearance of two unknown components in the cross-link region of the chromatogram. A decrease in cross-linking of this magnitude could lead to mechanically weakened cartilage. Insufficient material was available to characterize these unknown components. The disorganization of cartilage in some cases of diastrophic dysplasia could therefore be due to post-translational modifications, including defective cross-linking.

Amino Acids↗
PubMed1994

Non-collagenous protein screening in the human chondrodysplasias: link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin.

A gel-electrophoretic screening for link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin abnormalities was performed in fetuses, newborn infants, and children with various types of chondrodysplasia. Microdissected freeze-dried sections of upper tibial growth cartilage were extracted with 4M guanidinium chloride in the presence of proteolysis inhibitors. After dialysis against 8M urea, the extracts were submitted to stepwise ion-exchange chromatography to separate the large proteoglycans (aggrecans) from the other components. The latter were analyzed by gel electrophoresis, electrotransferred onto nitrocellulose membranes, and reacted with specific antibodies. Control samples from individuals with apparently normal growth were analyzed in the same runs. Two link protein bands with abnormal electrophoretic migration were found in a sporadic case of spondylometaphyseal dysplasia, Kozlowski type. Three link protein bands with the same migration as in the control samples were found in thanatophoric dysplasia, homozygous achondroplasia, achondrogenesis type II, hypochondrogenesis, Goldblatt syndrome, Desbuquois dysplasia, pseudoachondroplasia, and diastrophic dysplasia. In several pathologic cases with normal electrophoretic pattern of the link proteins, small link protein fragments appeared after reduction. The gel electrophoretic pattern of COMP was studied in thanatophoric dysplasia, diastrophic dysplasia, homozygous achondroplasia, fibrochondrogenesis, hypochondrogenesis, Goldblatt syndrome, and Kniest dysplasia. In all these cases the pattern was the same as in the control samples. The main band of fibromodulin had a normal migration rate in fibrochondrogenesis, Desbuquois dysplasia, Kniest dysplasia, and pseudoachondroplasia. It was delayed in diastrophic dysplasia.

Carrier Proteins↗
PubMed1993

Multiple epiphyseal dysplasia, Fairbank type: morphologic and biochemical study of cartilage.

We have performed histochemical, immunohistochemical, electron microscopic, and biochemical studies on the upper tibial cartilage from a case of multiple epiphyseal dysplasia, Fairbank type. Most chondrocytes had intracytoplasmic inclusions which took the stains for proteins and were resistant to microbial collagenase digestion. The electron microscopic study showed that the inclusions are dilatations of the rough endoplasmic reticulum containing a material with alternately wide electron dense and electron lucent layers. Both in optical and in electron microscopy the inclusions fixed antibodies against the core protein of the large cartilage proteoglycans (aggrecans). They didn't stain with antibodies against type II collagen. The gel electrophoretic pattern of the large proteoglycans was different from normal controls. The morphologic and biochemical alterations found in multiple epiphyseal dysplasia are similar to those already described in pseudoachondroplasia (Stanescu et al.: Eur J Pediatr 138:121-225, 1982; Stanescu et al.: J Bone Joint Surg 66A:817-836, 1984). However, the inclusions are smaller and the growth cartilage much less disorganized in multiple epiphyseal dysplasia. The similarity of morphologic and biochemical abnormalities strongly suggests that the two diseases have a similar pathogenesis and belong to the same bone dysplasia family.

Cartilage↗
PubMed1993

Early lesions of the articular surface in a strain of mice with very high incidence of spontaneous osteoarthritic-like lesions.

Our study was designed to see if the lesions of the articular surface represent an early event in the development of some types of articular degeneration. We examined the ultrastructural appearance of the articular surface labelled in vitro with cationized ferritin in several age groups of a substrain of C57BL/6 mice that develop a high incidence of osteoarthritic-like lesions. We found that as early as the age of 2 1/2 months the articular femoral and patellar surfaces presented abnormalities that became more severe with age. Alterations of the articular surface is a precocious event in this type of osteoarthritic-like degeneration.

Aging↗
PubMed1992

Type II collagen defect in two sibs with the Goldblatt syndrome, a chondrodysplasia with dentinogenesis imperfecta, and joint laxity.

We report on a syndrome of spondylo-epimetaphyseal dysplasia, dentinogenesis imperfecta, and ligamentous hyperextensibility in two sibs born to nonconsanguineous parents. This chondrodysplasia was characterized by severe shortness of stature and an osteoporosis without fractures. Electron microscopic examination of the cartilage documented large vacuoles of dilated rough endoplasmic reticulum within the cytoplasm of chondrocytes. Gel electrophoresis of pepsin-soluble collagen extracted from cartilage demonstrated the presence of type II collagen chains with an abnormal mobility. Prolyl and lysyl hydroxylations were slightly increased. The abnormal molecules melted at a higher temperature than the normal ones. CNBr peptide mapping of type II collagen showed an altered electrophoretic migration of peptides CB 11, CB 8, and CB 10,5 whereas CB 9,7 looked normal. In addition, two small non-collagenous proteins isolated from cartilage were not found in an age-matched control individual but were detected in a normal newborn infant. The quantitation of proline-labelled collagen synthesized by dermal fibroblasts demonstrated a 50% reduction of total collagen. This decrease essentially affected the amount of extracellular type I collagen, which was secreted less efficiently than in control cells. Nevertheless, type I collagen chains behaved normally on 5% polyacrylamide gels. The reduced mRNA levels of alpha 1I and alpha 2I chains might reflect either a transcriptional defect or a decreased stability of mRNA transcripts. We suggest that the association of both pathological chondrocytes producing altered collagen type II and decreased synthesis of type I could be responsible for this peculiar phenotype. The overmodification of alpha 1II CNBr peptides is consistent with the presence of a single-base substitution in the COL2A1 gene. Whether there is a direct causal relationship between the type II collagen defect and the underexpression of type I collagen will require clarification.

Abnormalities, Multiple↗
PubMed1992

Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe "boomerang dysplasia"?

The authors report a case of lethal neonatal dwarfism characterized by striking micromelia, fused rudimentary and supernumerary digits, large, soft head, pronounced hypertelorism, protruding eyes set laterally, enormous omphalocele and severe deficiency of tubular bone and spine ossification. Histologic examination showed lack of ossification of the cartilaginous anlage of many tubular bones. The cartilage had irregularly distributed chondrocytes. The matrix contained hypocellular and degenerated areas with scattered large chondrocytes. In a few bones a very disorganized growth cartilage was present. The case is similar to that described by Piepkorn et al. (1977) and may represent a severe form of "boomerang dysplasia" (Kozlowski et al., 1981; Tenconi et al., 1983; Kozlowski et al., 1985; Winship et al., 1990).

Abnormalities, Multiple↗
PubMed1991

Metaphyseal anadysplasia: a metaphyseal dysplasia of early onset with radiological regression and benign course.

We report on 4 boys (including 2 maternally related first cousins) with a metaphyseal dysplasia of early onset and regressive evolution. Diagnosis is possible in the first months. Distal metaphyses of long bones are very irregular. Femoral necks seem hypoplastic and the edges of the metaphyses are almost vertical; femoral shaft is bowed. Those anomalies disappear after 2 years. The main manifestations are slight shortness and a light varus deformity of the lower limbs. Stature is not affected. The upper tibial growth cartilage, studied in one case, showed wide proliferative and hypertrophic zones with an unusual appearance of the last hypertrophic cells and an abnormal zone of cartilage calcification and resorption. The name "metaphyseal anadysplasia" is suggested for this early and regressive disorder. We are aware of other forms of regressive metaphyseal dysplasia which deserve further delineation. Therefore infants whose radiological changes of metaphyseal dysplasia do not fall into one of the well-defined types should be followed and prediction of the adult height should not be made on the basis of the findings on the initial examination.

Bone Diseases, Developmental↗
PubMed1991

Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility.

The mutation fragilitas ossium (fro) was discovered in a random-bred stock of mice during an experiment aimed at detecting recessive lethal mutations after treatment of the postmeiotic germ cells of male mice with tris (1-aziridinyl)phosphine sulphide. The affected mice were moderately runted and had deformities in all four limbs. The radiological and histological findings indicate that the mutant is similar to human osteogenesis imperfecta. The ash content of long bones was lower in the mutant. A defect of type I collagen could not be detected. The electrophoretic patterns of alpha bands of type I and V collagen and CB derived peptides of type I collagen from bone and skin showed no abnormalities. The total collagen synthesis and secretion in cultures of dermal fibroblasts, as well as the gel electrophoresis of procollagen and collagen chains synthesized, and of their CB peptides, were the same as those found in the controls. The percentage of type I and type V collagen synthesized was similar; that of type III was lower in the mutants. Bone osteonectin was found to be decreased by 30% and bone sialoprotein by 5%. The mRNA level for osteonectin was decreased in the fibroblasts of the mutant by about 50%. Whether the defective expression of the osteonectin in fro/fro mice is due to a mutation in the gene itself or its regulatory site(s), or is secondary to other factors remains to be established. The fro/fro mouse may represent a model for some forms of human bone fragility without collagen abnormalities.

Animals↗
PubMed1990

Homozygous achondroplasia: morphologic and biochemical study of cartilage.

We have performed histochemical, immunohistochemical, electron microscopic, and biochemical studies on the upper tibial cartilage from a case of homozygous achondroplasia. The growth zone was narrow and disorganized. Columnization was absent except for a few areas with short rows of cells. Hypertrophy was reduced to scattered clusters of cells. The provisional calcification was patchy and primary trabeculae were thick and irregularly arranged. Islands of fibrous or fibrocartilagineous tissue were found along the growth zone. The matrix did not stain with safranin O and lacked metachromasia, except for pericellular rims around the hypertrophic cell clusters. Staining with antibodies against the large proteoglycan monomers and chondroitin-4-sulfate was weakly positive. Electron microscopic examination showed that only a few cells had degenerative signs. In most areas of the matrix, proteoglycan granules were absent. Areas with dense collagen fibers were seen. In contrast to the growth zone, the cartilage of the remaining epiphyses had normal histochemical, immunohistochemical, and electron microscopic appearance. The large proteoglycan monomers had a normal composition and hydrodynamic size. Type II and XI collagen, pepsin fragments of type IX collagen, and several noncollagenous proteins extracted from cartilage had a normal electrophoretic migration. It is suggested that a mutation affecting a matrix component or a regulatory pathway present only or predominantly in the growth area of the chondroepiphysis might explain the findings.

Achondroplasia↗
PubMed1990

Interaction between macrophages and articular surfaces: an in vitro transmission and scanning electron microscopy study.

Interactions between macrophages and articular surfaces were studied in an in vitro model which has been described before. Either stimulated peritoneal macrophages or a purified population of bone marrow macrophages were incubated with mice femoral heads which were either untreated or were digested with collagenase, trypsin or hyaluronidase prior to incubation. Scanning electron microscopy (EM) examination showed that macrophages attached to the surface and in their vicinity tags and fibers were visible. Transmission EM was used after labeling the surfaces with cationized ferritin employed as a sensitive marker to define the integrity of the articular surface. Alterations of the surface of various degrees of intensity were seen in all the sections examined. No adhering macrophages were found, due probably to detachment of cells during tissue processing for transmission EM. Attachment of macrophages to the surface and alterations of the latter were seen also when hyaluronic acid was added to the incubation medium or when the surfaces had been treated with hyaluronidase before incubation.

Animals↗
PubMed1988

Recessive lethal chondrodysplasia, "round femoral inferior epiphysis type".

Four cases of a sublethal form of chondrodysplasia are reported. The micromelic dwarfism is severe and on X-ray pictures the most striking feature is the shape of the lower femoral epiphysis, which is relatively well developed and rounded. The mode of inheritance is presumably autosomal recessive.

Epiphyses↗
PubMed1988

Comparative histopathology of the growth cartilage in short-rib polydactyly syndromes type I and type III and in chondroectodermal dysplasia.

The histopathology of growth cartilage of long bones was studied in two cases of chondroectodermal dysplasia (Ellis-Van Creveld syndrome), a case of short-rib polydactyly (SRP) type I (Saldino-Noonan syndrome), three cases of short-rib polydactyly (SRP) type III (Verma-Naumoff syndrome), and a case with polydactyly without other skeletal abnormalities but with visceral malformations. The lesions were qualitatively similar in chondroectodermal dysplasia and SRP I: regular concave ossification line, short, slightly irregular columns, regularly dispersed hypertrophic chondrocytes. In SRP III, the ossification line was irregular and the hypertrophic cells had a discontinuous distribution in clusters. No amylase resistant PAS intracytoplasmic inclusions were found. Short, slightly or markedly irregular primary trabeculae, some of them with wide cartilaginous cores, tongue prolongations and islands of cartilage situated along the periost were found in chondroectodermal dysplasia, SRP I and III. The case of polydactyly without other skeletal abnormalities had a normal morphology of the growth plate. These data suggest that there is a relationship between chondroectodermal dysplasia and SPR type I, and that SRP type III is distinct from SRP type I.

Ellis-Van Creveld Syndrome↗
PubMed1988

In vitro protection of the articular surface by cross-linking agents.

The effects of cross-linking agents on the resistance of the articular surface to digestion with clostridial collagenase were studied using a described in vitro system. Mouse femoral heads were treated with various concentrations of glutaraldehyde, with osmium tetraoxide and with dithiobis (succinimydil propionate), digested with the enzyme, labeled with cationized ferritin and examined by electron microscopy. Collagenase alone caused disruption of the articular surface with penetration of the large marker into the cartilage matrix. After treatment of the femoral heads with the cross-linking agents, no effects on the morphology and on the labeling of the articular surface and no penetration of the label into the cartilage matrix were observed. Increasing cross-linking at the articular surface might be a new route for therapeutic intervention. However, experiments would be needed to assess the effect of the procedure on the viability and nutrition of chondrocytes and on the functional properties of the tissue.

Animals↗
PubMed1987

Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of T lymphocyte lines. A light and electron microscopic study of the articular surface using cationized ferritin.

We analyzed the histopathologic findings of arthritis in 3 rat models: adjuvant arthritis induced by active immunization to Mycobacterium tuberculosis (MT) antigens, arthritis produced by passive transfer of an intrinsically arthritogenic line of anti-MT T lymphocytes, and bystander arthritis produced by intraarticular injection of a foreign antigen, ovalbumin, into rats with T lymphocyte line cells specific for the ovalbumin antigen. The histopathology of the tibiotarsal and knee joints was studied by light microscopy and the articular surface of the cartilage by electron microscopy after labeling with cationized ferritin. The lesions in the 3 models of arthritis were compared. In active adjuvant arthritis, inflammatory lesions and cartilage destruction were found as early as 9 days after immunization, and persisted for as long as 11 months. Similar, but somewhat milder, lesions were found in arthritis produced by transfer of anti-MT T lymphocytes. Inflammatory signs were present at 4 days, when there was no evidence of joint edema. Severe inflammatory lesions were found in arthritis induced by transfer of anti-ovalbumin T lymphocytes that was followed by ovalbumin injection into the knee. Pathologic changes were found to be similar in all 3 models. Thus, the changes could be attributed to the action of T lymphocytes, irrespective of whether the target antigen was intrinsic to the joint.

Animals↗
PubMed1987

Drug action on articular cartilage surface. An in vitro study using mouse femoral heads labeled with cationized ferritin.

The direct effects on the cartilage articular surface of three anti-inflammatory drugs (Diclofenac, Pirprofen and acetyl-salicylic acid) and of a polysulfated glycosaminoglycan (Arteparon), were studied using an in vitro system in which BALB-c mouse femoral heads were incubated with the drugs. After incubation and labeling of the negative charges of the articular surfaces with cationized ferritin, the femoral heads were examined by electron microscopy. In addition, the effect of the drugs on the aggressive action of collagenase on the articular surface was tested using the same in vitro system. Diclofenac, Pirprofen and the polysulfated glycosaminoglycan did not alter the structure or the charge properties of the surface. Acetyl salicylic acid produced a slight disruption of the articular surface. The drugs studied had no effect on the disruptive action of collagenase.

Animals↗
PubMed1987

Pathologic features of the femoral heads in a patient aged 14 1/2 years with spondyloepiphyseal dysplasia with osteoarthritis.

We describe a patient with spondyloepiphyseal dysplasia and precocious hip osteoarthritis. Bilateral hip arthroplasty was performed at the age of 14 1/2 years. Pathologic examination revealed severe osteoarthritic deformities: flattened and deformed femoral heads, were almost completely covered by abnormal cartilaginous, fibrocartilaginous and fibrous tissues showing intense degenerative and regenerative processes. The electron microscopic examination of chondrocytes showed large intracytoplasmic accumulations of glycogen and of microfilaments and many small vesicles suggesting intense micropinocytosis and/or microexocytosis.

Adolescent↗
PubMed1986

Acromicric dysplasia.

We describe a new type of bone dysplasia, the "acromicric dysplasia," based on the study of six patients. This dysplasia is characterized clinically by mild facial anomalies, markedly shortened hands and feet, and growth retardation that is severe in most of cases. Roentgenograms of the hands are characteristic: the metacarpals and the phalanges are short and stubby, the proximal portion of the last four metacarpals are slightly pointed with an external notch on the 2nd metacarpal and an internal notch on the 5th metacarpal, similar to pseudo-epiphysis. The shape of the epiphysis and the metaphysis of the long bones is almost normal, except for a slight deformation of the femoral heads in some patients. No signs of visceral storage were found, which rules out geleophysic dwarfism. The histological, histochemical, and electron microscopical examination of the growth cartilage in two cases showed similar lesions: disorganization of the growth zone with islands of cells, some of them degenerated; abnormal organization of collagen forming thick rims around the cells and wide fibers in the interterritorial matrix; large accumulation of glycogen in most chondrocytes. Both sexes are affected; all patients are isolated cases from normal families.

Biopsy↗