Biomedical subjects

A B Shafritz

Publications and source records attributed to A B Shafritz.

3 recordsLinked to original sources

PubMed1998

Differential expression of bone and cartilage related genes in fibrodysplasia ossificans progressiva, myositis ossificans traumatica, and osteogenic sarcoma.

Fibrodysplasia ossificans progressiva, myositis ossificans traumatica, and osteogenic sarcoma are representative genetic, traumatic, and neoplastic disorders of osteogenesis, respectively. However, the pathology, pathophysiology, and natural history of the disorders differ substantially. Gene expression related to bone induction was studied in these disorders. Primary cell lines established from lesional tissues derived from each of these disorders expressed different patterns of protooncogenes, bone morphogenetic protein genes, and bone phenotype specific genes. The osteogenic sarcoma cell line expressed the entire repertoire bone morphogenetic proteins 1 to 7, c-fos and c-jun messenger ribonucleic acids. Myositis ossificans traumatica cells expressed phenotype markers similar to those of the osteogenic sarcoma cells, and expressed bone morphogenetic proteins 1, 4, and 6 and c-fos messenger ribonucleic acids, but not c-jun messenger ribonucleic acid. Fibrodysplasia ossificans progressiva early lesional cells demonstrated specific over-expression of bone morphogenetic protein 4 messenger ribonucleic acid. Differential expression of genes related to osteogenesis have important implications for understanding the earliest molecular events in normal and dysregulated osteogenesis in humans.

Adolescent↗

PubMed1996

Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva is a heritable disorder of connective tissue characterized by congenital malformation of the great toes and postnatal formation of ectopic bone. Although the disorder was first described more than 300 years ago, the genetic defect and pathophysiology remain unknown. Bone morphogenetic proteins are potent bone-inducing morphogens that participate in the developmental organization of the skeleton, and increased production of one or more of these proteins has been proposed as the cause of fibrodysplasia ossificans progressiva. METHODS: We studied lymphoblastoid cell lines established from peripheral-blood mononuclear cells of patients with fibrodysplasia ossificans progressiva and fibroblast-like cell lines derived from lesional and nonlesional tissue. We used Northern blot analysis and ribonuclease protection assays to measure the expression of messenger RNA (mRNA) of bone morphogenetic proteins 1 to 7 and immunohistochemical analysis to examine protein expression. RESULTS: Among the bone morphogenetic proteins and mRNAs examined, only bone morphogenetic protein 4 and its mRNA were present in increased levels in cells derived from an early fibroproliferative lesion in a patient with fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 mRNA was expressed in lymphoblastoid cell lines from 26 of 32 patients with fibrodysplasia ossificans progressiva but from only 1 of 12 normal subjects (P<0.001). Bone morphogenetic protein 4 and its mRNA were detected in the lymphoblastoid cell lines from a man with fibrodysplasia ossificans progressiva and his three affected children (two girls and a boy), but not from the children's unaffected mother. No other bone morphogenetic proteins were detected. CONCLUSIONS: Overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes is associated with the disabling ectopic osteogenesis of fibrodysplasia ossificans progressiva.

Bone Morphogenetic Proteins↗

PubMed1995

Vasculitis associated with antiphospholipid syndrome.

Several syndromes involving antiphospholipid antibodies have been described in the literature. Although the varied clinical manifestations have been well delineated, the vascular pathophysiology in patients with these antibodies remains unclear. Vascular damage is often described as a vasculopathy; however, several case reports have described an associated vasculitis. We report two patients with manifestations of antiphospholipid antibody syndrome (APLS) and concurrent vasculitis. The first patient, a 42-year-old man, presented with abdominal pain and fevers. The second patient, a 39-year-old man, presented with fever and testicular pain. Both were ultimately felt to have polyarteritis nodosa associated with APLS. Their complicated hospital courses and difficulties we encountered in diagnosing and treating them are discussed. The literature describing other cases of vasculitis associated with antiphospholipid antibody syndrome is reviewed. Whether the presence of antiphospholipid antibodies favors the development of vasculitis or vice versa is not clear. Further studies are needed to address this question and to determine optimal therapeutic regimens in these critically ill patients.

Adult↗