Glucocorticoid regulation of eicosanoid production by glial cells under basal and stimulated conditions

We measured the production of two eicosanoids, prostaglandin E₂ and thromboxane-B₂, by rat glial cell cultures under basal conditions, following stimulation with phorbol-12-myristate-13-acetate and the bacterial endotoxin lipopolysaccharide, and following treatment with synthetic glucocorticoids. Stimulation of rat glial cells in culture with either phorbol-12-myristate-13-acetate or lipopolysaccharide caused a 1.5–5.0-fold increase in prostaglandin E₂ production, but did not affect thromboxane production. Pretreatment of the cultures with dexamethasone markedly inhibited the stimulated production of prostaglandin E₂ but had only a modest effect on basal production. Dexamethasone did not affect the activity of the enzyme protein kinase C, a putative regulator of eicosanoid synthesis. Our findings show that glucocorticoids have the potential to modulate central nervous system eicosanoid production particularly under conditions of stimulated production, such as inflammatory and demyelinating disorders. This mechanism may explain, at least in part, the therapeutic benefit of glucocorticoids in patients with multiple sclerosis.     

Enchondroma of the hand – clinical evaluation of diagnosis, surgical treatment, and outcome

Summary Enchondroma are benign cartilaginous tumors and are localized most often at the site of the phalanges. Between 1982 and 1993 73 patients with monostotic enchondroma and 5 patients with polyostotic enchondroma were operated at our clinic. Clinical signs of monostotic tumors were pathological fracture (38.4 %), pain or swelling. Eleven percent of cases were accidental findings. Surgical treatment was performed by complete removal of the tumors and filling the bone cavity with autologous spongiosa taken from the pelvic bones, the elbow, or the radius. Three patients (4.1 %) had to be operated a second time due to wound infections and hematoma. In one case Sudeck's dystrophy was diagnosed. One patient (1.4 %) developed a recurrent tumor. Our follow-up examination of 65 patients showed that 77 % of the patients with monostotic enchondroma achieve very good or good functional long-term results after this operation, but only 40 % of the patients with polyostotic enchondroma.      

Alternative Treatments for Asthma: Assessing the Need

Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be “steroid-dependent.”     

Separation of rare cell subpopulations with the aid of biotin-labelled ligands

A universal method for selection of surface marker-positive cells is described. The cells, admixed with an excess of surface marker-negative cells, are In-st labelled with a specific biotinylated ligand and then isolated with the aid of monoclonal, anti-biotin coated beads. The method enables selection and isolation of cells with a frequency as low as 10^-4. The ligand can be an antigen (for selection of infrequent antibody-producing cells), an antibody (for selection of surface antigen-positive cells) or other molecules (for selection of specific receptor-positive cells).     

Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta.

Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.     

Lambda foo: a lambda phage vector for the expression of foreign proteins.

This work describes a lambda phage expression system, lambda foo, that produces foreign proteins fused to the surface of the virus particle. The lambda foo vector has multiple cloning sites for the insertion of a foreign DNA fragment and color selection for recombinants. Foreign proteins are fused to the C terminus of a truncated phage tail protein, pV, by a peptide linker. Conditional chain termination allows the assembly and fusion of multisubunit proteins. We have attached the complete Escherichia coli beta-galactosidase and the plant Bauhinia purpurea agglutinin by cloning their genes into the vector. The constructs express functionally active proteins on the phage particle surface and have been purified by affinity chromatography with an antibody for beta-galactosidase and a mucin as a ligand for Bauhinia purpurea agglutinin.     

Fulminant subacute sclerosing panencephalitis in association with pregnancy

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.     

Osteogenesis imperfecta: A clinical study of the first ten years of life

Summary One hundred twenty-seven children with osteogenesis imperfecta (O.I.) were studied during the first 10 years of life. According to Sillence, 40 patients were assigned to type I, 39 to type III, and 48 to type IV O.I. Centiles for height, weight, and the annual number of fractures could be established for the different types of O.I. The development of the skeletal changes could be documented for the different forms of the disease. At birth, the skeletal changes were significantly more severe in type III than in type IV patients. During the first 10 years of life the number of fractures, extent of skeletal deformities, and growth retardation did not differ between types III and IV. Only fracture nonunion, dentinogenesis imperfecta, and congenital cardiac malformations were more frequent in type III than in type IV. Papillary calcifications of the kidney and kidney stones were diagnosed in 4 type III and 2 type IV patients. Hemihypertrophy of the body developed, in 2 type I patients. Although types III and IV patients suffered from severe short stature, serum insulin-like growth factor (IGF) I was in the normal range.