A complex program of striatal gene expression induced by dopaminergic stimulation

Dopamine acting in the striatum is necessary for normal movement and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these effects are thought to involve alterations in gene expression. Using the 6-hydroxydopamine lesion model of Parkinson's disease and differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of striatal dopamine D1 receptors. The induced mRNAs include both novel and previously described genes, with diverse time courses of expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more after stimulation. Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a homeostatic response to excessive stimulation. Others may be part of a genetic program involved in cellular and synaptic plasticity. A very similar set of genes is induced in unlesioned animals by administration of the psychostimulant cocaine or the antipsychotic eticlopride, although in distinct striatal cell populations. In contrast to some previously described early genes, most of the novel genes are not induced in cortex by apomorphine, indicating specificity of induction. Thus we have identified novel components of a complex, coordinated genetic program that is induced in striatal cells in response to various dopaminergic manipulations.     

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer

Thirteen postmenopausal women with advanced breast cancer were enrolled in an open randomized Phase I trial of a new p.o. active aromatase inhibitor, CGS 20267 (letrozole). The primary aim of the trial was to assess the impact of two doses of letrozole (0.5 and 2. 5 mg/day) on the peripheral aromatization of androstenedione to estrone. An in vivo isotopic technique was used to measure peripheral aromatization in each patient before treatment. The patients were then randomly assigned to one of the two doses, and measurements of aromatization were repeated after 6 weeks. At 0.5 mg and 2.5 mg/day, letrozole inhibited aromatization by 98.4% (97.3 to >99.1) and >98.9% (98.5 to >99.1; geometric means and ranges), respectively. Plasma estrogen levels were also measured before and during treatment. At the dose of 0.5 mg/day estrone and estradiol levels fell by 82.0% and 84.1% (geometric means), respectively. At the dose of 2.5 mg/ day, the estrogens fell by 80.8% and 68.1%, respectively. There were no significant differences between the doses in aromatase inhibition. No formal statistical analysis was performed on the estrogen data. Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated. The falls in estrogen levels were greater than those seen with earlier generation aromatase inhibitors.     

Theoretical conformational investigation of thrombin-fibrinogen recognition complex

Theoretical conformational investigation of the thrombin-fibrinogen recognition complex was fulfilled. At first preliminary study was carried out using space-filling molecular models. At the next stage computer simulation was conducted. For this purpose a package of programs for the theoretical conformational analysis of two interacting molecules has been developed in the framework of atom-atom potentials. The package contains an original algorithm for constructing initial approximation based on assumption that the structure of the complex is determined mainly by the ligand-ligand attraction and Van-der-Vaals repulsion. Complex structure with considerable binding energy was obtained. Molecules of that structure are bound mainly by four oppositely charged pairs of side chain groups. The beta -loop of thrombin in the complex is shown to undergo essential structural transformations. A hypothesis is suggested that this transformation may influence active sites allosterically. Some ways and mechanisms of this influence are discussed as well as an approach to its calculation.     

The influence of splinting procedures on the periodontal and peri-implant tissue damping characteristics. A longitudinal study with the Periotest device

The aim of the present study was to evaluate the capability of the Periotest device in detecting and monitoring functional changes in the periodontal as well as in the pari-implant damping characteristics. In the first part of this study, 107 teeth were splinted by means of 40 full acrylic fixed prostheses (AFP) and another 37 teeth were splinted by means of 14 ceramometallic fixed prostheses (C-MFP). The Periotest measurements of individual teeth were done the day the fixed prostheses were cemented temporary (PTV 1), and again after a mean observation period of 27.4 days (PTV 2). In the 2nd part, 78 osseointegrated two-stage implants were splinted by means of 23 full acrylic fixed prosthesis (AFP) and other 18 implants were left without it. Using the same abutment length, Periotest measurements were performed, at abutment connections and before installation of the final prosthesis. In a 3rd part, using both implants and teeth as abutments, 29 osseointegrated implants were connected with 25 abutment teeth by means of 7 AFP. The measurements were performed at the beginning of the prosthetic treatment and 2, 4 and 6 weeks later. After splinting teeth by means of AFP for the observation period, no statistically significant reduction in PTVs was found. When on the other hand, a C-MFP was used, PTV 2 showed a significant reduction. The PTVs at abutment connection went down after a period of time, during which some implants were interconnected by means of an AFP and others were not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute appendicitis in early childhood

1728 appendectomies were performed in our institution between the years 1973 and 1978, only 18 of them below the age of 5 years. Acute appendicitis in this age is characterized by a very low incidence (1%); an overwhelming male predominance (8:1), a short history, and a rapid progress of the disease. In 72% perforation of appendix and peritonitis were present at operation. The triad of fever, abdominal pains and vomiting was present in all cases. A high leucocyte count was noted in all cases except one. All patients were operated upon within 16 h of admission. No mortality, a low morbidity and a short hospital stay were recorded.     

Parasitic lumbar arterial blood supply in renal angiomyolipoma

A young woman with azotemia was found to have an angiomyolipoma which had parasitic blood supply from a lumbar artery. Parasitic lumbar arterial blood supply from a lumbar artery. Parasitic lumbar arterial blood supply has previously been considered a strong indication of malignancy. Since this benign lesion had not invaded the adjacent retroperitoneal structures, the phenomenon tends to confirm the postulate that parasitic blood supply to a lesion may occur through hypertrophy of small anastomotic channels normally present between adjacent vessels but not normally seen in angiography.     

Investigation of multiple solutions for gas cooled current leads and results of survey information on current leads

This paper is divided into two distinct sections. In the first section, we investigate the possible existence of multiple steady state solutions for a gas cooled lead. In the second section, we summarize calculated values of the runaway and recovery times for 31 current leads in use throughout the world.