Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system: a review on morphological findings and functional implications

Receptors for insulin are widely distributed in the brain and pituitary. The current hypothesis on receptor function in these regions points to a role of insulin as a mediator in the communication of the peripheral endocrine system with the brain via various steps of the neuroendocrine axis. Recent data demonstrate that receptor-positive neurons in the brain, i.e. in the hypothalamus, and secretory cells in the anterior pituitary gland possess specific proteins that are thought to be involved in key steps of post receptor signal transduction, in particular insulin receptor substrate-1 and phosphatidylinositol 3'-kinase (PI3k). PI3k is a critical enzyme of the intracellular signaling pathway that is activated by a number of receptor tyrosine kinases, including receptors for insulin and IGF-1. This information further completes the framework indicating in vivo activity of insulin receptors in central neuroendocrine cells and their involvement in one branch of several physiological mechanisms that control body metabolism and nutritional behaviour.     

Part average analysis – A tool for reducing failure rates in automotive electronics

As the complexity of technical systems increases, it is a matter of course that the quality requirements made on the assemblies, modules and components which are used increase as well. The Part Average Analysis (PAA) reveals a software-based methodical approach which can be used to improve the reliability and availability of technical functions in an efficient manner. The PAA is used to observe anomalies in functions or parameters to measure during the production process, reliably indicating a concealed defect. Components with a high risk of failure are rejected and are not installed in the vehicle (prevention). In this paper, the method will be presented, the mathematical model explained and experiences with automotive suppliers will be reported.     

Riprap Failure at Circular Bridge Piers

Riprap of bridge piers is placed to prevent scour and to secure the pier from failure. Riprap is therefore an addition to a pier to increase its performance against scour. The present research intends to present three basic scour mechanisms associated with circular-shaped bridge piers in rivers first, to introduce then a number of selected experiments for a range of hydraulic, geometric, and sedimentologic conditions, and finally to describe a novel procedure for assessing the safety of these river elements against failure. This procedure is based on the Shields diagram relating to sediment entrainment in a uniform and flat sediment bed subjected by a water flow. The Shields approach is extended for the presence of a circular-shaped pier that is protected by a circular-arranged riprap layer of equal size elements. The design procedure presented in the following thus reduces to the entrainment condition of a pier for equal riprap and the sediment sizes and to the Shields entrainment condition when the pier diameter degenerates to 0.     

Some Causes and Methods of Elimination of Aging of Asphalt Concrete

The problems that arise when the structure of asphalts contains unstable fragments and the purposeful effect of modifiers and different kinds of stone material on them are examined. The possibility of predicting some properties of asphalts and asphalt concretes and correcting these properties based on theoretical advances in studying the structure of asphalt materials and asphalt concretes is demonstrated.*     

The importance of the Doppler angle

We examined 118 infrainguinal grafts (103 patients) to determine the effect changes in the angle of theta or Doppler angle had on the accuracy of velocity measurements made with a duplex scanner. Four separate measurements of peak velocity were made on each graft. Three measurements were made with the flow toward the probe at 60 degrees, 50 degrees, 120 degrees (60 degrees the other way). The probe was then turned 180 degrees so the flow was away from the probe and measurements were made at 60 degrees. When the primary cursor was aligned with the vessel wall (Technologist A), the mean velocity at 60 degrees was 69.4 cm/sec and 57.3 cm/sec at 50 degrees, a difference of 12 cm/sec. The same measurements done by Technologist B (primary cursor non aligned with the wall), showed a 10 cm/sec difference (60.7 and 50.5). We saw a consistent difference with even this small difference in the angle of theta throughout the study. The mean velocity obtained by Technologist A when the flow was toward the probe was 61.7. When the probe was turned 180 degrees (flow away from the probe), the mean velocity was 60.5. The same measurements by Technologist B were 51.8 and 50.5. This indicates that the direction of the flow of blood towards or away from the probe does not effect the velocity measurements. Using the vessel wall to line up the primary cursor provides a consistent and easily reproducible reference point to compare measurements made on different days but is less important for single measurements.     

Repression of c-fos and c-jun gene expression is not part of AT2 receptor coupled signal transduction

Recent world-wide publications were reviewed in order to determine the clinical characteristics and therapeutic relevance of the chlamydial respiratory tract infections in humans. It was emphasized that Chlamydia pneumoniae could initiate asthma and may be associated with acute asthma exacerbation. Laboratory procedures for identifying chlamydia and difficulties concerned with the diagnostics of this intracellular pathogen were also presented. In patients with evidence of chlamydial infection the casual treatment (macrolides, tetracyclines, fluoroquinolones) may induce major improvement or complete resolution of asthma.     

The Kennecott Utah Copper Refinery modernization

In early 1992, Kennecott announced plans to modernize and expand the smelter and refinery located near Salt Lake City, Utah. The project increased the smelter capacity from 150,000 tonnes per year to 280,000 tonnes per year and also increased the refinery capacity from 200,000 tonnes per year to meet smelter output. Total cost of the modernization was $882 million. Part I of this paper outlines the scope of the refinery modernization program and describes the implementation of the new technology used there. The technology is based on polymer concrete cells, thoroughly prepared anodes, stainless steel plating blanks, and highly automated materials handling. In Part II, the hydrometallurgical process chemistry employed at the new Kennecott slimes treatment facility is described. The processing philosophy incorporates three major objectives: very-high firstpass recovery of the valuable metals from the slimes with minimal in-process inventory; minimization of the return of impurity metals (e.g., Pb, Sb, As, and Bi) to the smelter circuit; and complete elimination of pyrometallurgical processing with its potential for environmental abuse and precious metals recycle. In both parts, the unit start-ups and initial operating results are presented.     

Experiences with introduction of the UNICEF program "10 steps for successful breast feeding"

Necrotizing fasciitis is a rapidly progressing, synergistic bacterial infection of fascia with a reported average mortality of about 40%. Fournier's disease, necrotizing fasciitis of the genital sphere, is also included in this study. Seven patients were studied over a one-year period between May 1991 and October 1992. Most commonly, they were infected by perineal diseases, medical procedures and cutaneous ulcers. The local clinical signs are cellulitis, oedema, blisters, necrosis and crepitus; general septic symptoms may also be present. Associated chronic diseases were present in 4 patients. Three infections were polymicrobial. Control of this potentially lethal soft-tissue infection is based on early clinical diagnosis, timely, wide surgical debridements and appropriate antibiotic treatment. The overall mortality rate was 1 of 7 (14%). Death was due to persistent wound sepsis and systemic septic complications, but mainly to delay in surgical treatment. The presence of chronic debilitating diseases (diabetes, alcohol abuse, renal insufficiency, ...) contribute to increase rate of both local and systemic infection.     

Synthesis and in vitro efficacy of transferrin conjugates of the anticancer drug chlorambucil

One strategy for improving the selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules or carrier proteins. Thus, five maleimide derivatives of chlorambucil were bound to thiolated human serum transferrin which differ in the stability of the chemical link between drug and spacer. The maleimide ester derivatives 1 and 2 were prepared by reacting 2-hydroxyethylmaleimide or 3-maleimidophenol with the carboxyl group of chlorambucil, and the carboxylic hydrazone derivatives 5-7 were obtained through reaction of 2-maleimidoacetaldehyde, 3-maleimidoacetophenone, or 3-maleimidobenzaldehyde with the carboxylic acid hydrazide derivative of chlorambucil. The alkylating activity of transferrin-bound chlorambucil was determined with the aid of 4-(4-nitrobenzyl)pyridine (NBP) demonstrating that on average 3 equivalents were protein-bound. Evaluation of the cytotoxicity of free chlorambucil and the respective transferrin conjugates in the MCF7 mammary carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence assay demonstrated that the conjugates in which chlorambucil was bound to transferrin through non-acid-sensitive linkers, i.e., an ester or benzaldehyde carboxylic hydrazone bond, were not, on the whole, as active as chlorambucil. In contrast, the two conjugates in which chlorambucil was bound to transferrin through acid-sensitive carboxylic hydrazone bonds were as active as or more active than chlorambucil in both cell lines. Especially, the conjugate in which chlorambucil was bound to transferrin through an acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were approximately 3-18-fold lower than those of chlorambucil. Preliminary toxicity studies in mice showed that this conjugate can be administered at higher doses in comparison to unbound chlorambucil. The structure-activity relationships of the transferrin conjugates are discussed with respect to their pH-dependent acid sensitivity, their serum stability, and their cytotoxicity.