Amitriptyline in migraine prophylaxis: Changes in pattern of attacks during a controlled clinical trial

A double-blind controlled clinical trial of crossover design was conducted in 26 volunteers suffering from migraine. Of 20 subjects who completed the trial, 16 had fewer attacks on amitriptyline than on placebo. Amitriptyline was found to have the greatest effect in reducing attacks with a short warning and in which no specific cause could be recognized. It had least effect in attacks with a long warning and recognized as due to fatigue. The drug was effective only in reducing those attacks with shorter duration and its effect was irrespective of severity. A dosage of between 10 and 60 mg, usually taken at night, was found to be adequate.     

The Release of Histamine,Heparin and Granule Protein from Rat Mast Cells Treated with Compound 48/80 in vitro

Fillion , G. M. B., S. A. Slorach and B. Uvnäs . The release of histamine, heparin and granule protein from rat mast cells treated with compound 48/80 i n vitro. Acta physiol. scand. 1970. 78. 547–560. The quantitative relationship between the release of histamine, heparin and granule protein from rat mast cells exposed to compound 48/80 in vitro has been investigated in order to clarify the mechanism of action of this releaser. A correlation was found between the three release curves. The ratio of heparin to granule protein was similar in extruded granules and granules remaining in the cell after compound 48/80 treatment. From these results we conclude that the principal mechanism of histamine release induced by this agent involves an initial extrusion of histamine-containing granules, followed by an exchange of histamine in the granules for cations in the extracellular medium.     

Purification and Properties of the γ-Protein Specified by Bacteriophage λ: An Inhibitor of the Host RecBC Recombination Enzyme

Previous experiments have indicated that the gam gene of bacteriophage lambda is responsible for an inhibition of the RecBC DNase-an enzyme that is essential for the major host pathway of genetic recombination. We report here experiments that define the inhibitor as the protein product of the gam gene ("gamma-protein") and that characterize the inhibition reaction with highly purified preparations of gamma-protein and RecBC DNase. Genetic characterization was performed with partially purified fractions prepared from cells infected with various lambda mutants. An activity that inhibits RecBC DNase was absent in extracts prepared after infection by phage that carry nonsense or deletion mutations in the gam gene; this activity was highly thermolabile in an extract prepared after infection by phage that carry a temperature-sensitive mutation in the gam gene. For biochemical characterization, the gamma-protein has been purified more than 800-fold. This highly purified preparation inhibited all of the known catalytic activities associated with the RecBC enzyme, but exhibited no detectable DNase or ATPase activities by itself. These findings are discussed in terms of their implications for regulation of genetic recombination and bacteriophage lambda development.     

Sigmoidovaginal and cecovaginal fistula as a complication of peridiverticulitis: Report of eight cases

Diseases of the Colon &; Rectum -     

Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer

Histone deacetylase (HDAC) 6 is a subtype of the HDAC family; it deacetylates alpha-tubulin and increases cell motility. Here, we investigate the impact of an alteration of HDAC6 expression in estrogen receptor alpha (ER)-positive breast cancer MCF-7 cells, as we identified that HDAC6 is a novel estrogen-regulated gene. MCF-7 treated with estradiol showed increased expression of HDAC6 mRNA and protein and a four-fold increase in cell motility in a migration assay. Cell motility was increased to the same degree by stably transfecting the HDAC6 expression vector into MCF-7 cells. In both cases, the cells changed in appearance from their original round shape to an axon-extended shape, like a neuronal cell. This HDAC6 accumulation caused the deacetylation of alpha-tubulin. Either the selective estrogen receptor modulator tamoxifen (TAM) or the pure antiestrogen ICI 182,780 prevented estradiol-induced HDAC6 accumulation and deacetylation of alpha-tubulin, leading to reduced cell motility. Tubacin, an inhibitory molecule that binds to the tubulin deacetylation domain of HDAC6, also prevented estradiol-stimulated cell migration. Finally, we evaluated HDAC6 protein expression in 139 consecutively archived human breast cancer tissues by immunohistochemical staining. The prognostic analyses for these patients revealed no significant differences based on HDAC6 expression. However, subset analysis of ER-positive patients who received adjuvant treatment with TAM (n = 67) showed a statistically significant difference in relapse-free survival and overall survival in favor of the HDAC6-positive group (P < 0.02 and P < 0.05, respectively). HDAC6 expression was an independent prognostic indicator by multivariate analysis (odds ratio = 2.82, P = 0.047). These results indicate the biological significance of HDAC6 regulation via estrogen signaling.