Lack of effect of coumarin in women with lymphedema after treatment for breast cancer

BACKGROUND: Lymphedema of the arms can be a serious consequence of local and regional therapy in women with breast cancer. Coumarin has been reported to be effective for the treatment of women with lymphedema; we undertook a study in which we attempted to replicate those findings. METHODS: We studied 140 women with chronic lymphedema of the ipsilateral arm after treatment for breast cancer. The women received 200 mg of oral coumarin or placebo twice daily for six months and then the other treatment for the following six months. The end points of the study consisted of the volume of the arm (calculated from measurements of hand and arm circumference) and the answers on a questionnaire completed by the patient about symptoms potentially related to lymphedema. RESULTS: The volumes of the arms at 6 and 12 months, were virtually identical, regardless of whether coumarin or placebo was given first. After six months, the average volume of the affected arm increased by 21 ml during placebo treatment and 58 ml during coumarin treatment (P=0.80). In addition, answers to patient-completed questionnaires were similar in the two treatment groups. After six months only 15 percent of the women in the coumarin group and 10 percent of those in the placebo group reported that the study medication had helped a moderate or large amount (P=0.19). Coumarin was well tolerated, except that it resulted in serologic evidence of liver toxicity in 6 percent of the women. CONCLUSIONS: Coumarin is not effective therapy for women who have lymphedema of the arm after treatment for breast cancer.     

Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after i.m. injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by i.v. injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.     

Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation

Erythropoietin receptor (EPOR) is thought to be activated by ligand-induced homodimerization. However, structures of agonist and antagonist peptide complexes of EPOR, as well as an EPO-EPOR complex, have shown that the actual dimer configuration is critical for the biological response and signal efficiency. The crystal structure of the extracellular domain of EPOR in its unliganded form at 2.4 angstrom resolution has revealed a dimer in which the individual membrane-spanning and intracellular domains would be too far apart to permit phosphorylation by JAK2. This unliganded EPOR dimer is formed from self-association of the same key binding site residues that interact with EPO-mimetic peptide and EPO ligands. This model for a preformed dimer on the cell surface provides insights into the organization, activation, and plasticity of recognition of hematopoietic cell surface receptors.     

Molecular structure of the amyloid-forming protein kappa I Bre

The molecular structure of the amyloid-forming Bence-Jones protein kappa I Bre has been determined by X-ray crystallography at 2.0 A resolution. The fragment from the kappa chain of immunoprotein contains 107 amino acid residues, and polymerizes in the crystal form into a giant helical spiral, surrounding a cylinder of water 50 A in diameter with a repeat of 77.56 A, containing 12 kappa molecules, plus another 12 molecules from neighboring parallel spirals. The resulting structure has many features which have been found or suggested from studies on the protein fibrils found in amyloid deposits. From the results of the X-ray crystal structure a hypothesis is presented for the structure and formation of the amyloid fibril.     

Comments on "Inversion of multivariable linear systems"

The purpose is to give a simple algebraic proof to the necessary part of the criterion of functional reproducibility of multivariable linear systems given by Silverman and to incorporate a slight correction to his criterion. Furthermore, the criteria of the functional reproducibility of Silverman and Sain and Massey [1] are shown to be equivalent.