Effects of the M1 agonist xanomeline on processing of human beta-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells

1. Three experiments were conducted to investigate the diurnal variation of blood viscosity in broilers. In experiment 1 food and water were supplied freely at 20 degrees C (20-FW). In experiment 2 food and water were withdrawn at 20 degrees C (20-NFW), while in experiment 3 food and water were withdrawn at 30 degrees C (30-NFW). 2. Blood sampling time points were 09.00 h, 15.00 h, 21.00 h, 03.00 h and 09.00 h the next day in each experiment. 3. In all experiments, whole blood viscosity (WBV), red blood cell count (RBC) and haematocrit (HCT) were greater during the dark (21.00 h and 03.00 h) than during the light period. During the dark period, there were no differences in WBV, RBC and HCT between 20-FW and 20-NFW, or between 20-NFW and 30-NFW. At 09.00 h, WBV and HCT were higher in 20-FW than in 20-NFW. At 15.00 h and 09.00 h (day 2), WBV and HCT were greater in 20-NFW than in 30-NFW. 4. There were no light-dark differences in plasma viscosity (PV), plasma protein concentration (PPC) or mean corpuscular volume (MCV) in any experiment. However, 20-NFW birds had a lower PPC and higher MCV compared with 20-FW, and a higher PPC and lower MCV compared with 30-NFW, while no difference was found in PV. 5. WBV increased linearly with RBC and HCT. PV increased with PPC, while MCV decreased. 6. These results indicate that there is diurnal variation in whole blood viscosity, which is greater during the dark than during the light period. During the light period it is strongly influenced by high environmental temperature and food and water withdrawal.     

Bradycardia and hypotension associated with severe hemorrhage are reversed by morphine given centrally or peripherally in anesthetized rats

It has been shown that G proteins are potential regulatory molecules in the transmembrane signaling cascade. The aim of this study was to examine the possibility of equivalent G-protein redistribution and/or down-regulation in a target cell upon agonist stimulation. Short-term (0-80 min) incubation of rat pituitary GH4C1 cells with vasoactive intestinal peptide (VIP, 0.1 microM) induced a decrease in the levels of Gsalpha in the membrane fraction, whereas immunoblot analysis and reconstitution assay of adenylyl cyclase clearly showed an increase in the amount of Gsalpha in the supernatant (cytosolic) fraction. The VIP-induced release of G proteins alpha subunits from membranes was specific for Gsalpha. The VIP-dependent release of Gsalpha from membranes was blocked by a VIP-receptor antagonist, (N-Ac-Tyr,D-Phe)-GRF(1-29)-NH2 (10 microM). Pituitary adenylate cyclase-activating polypeptide (PACAP) also stimulated the release of Gsalpha from membranes of GH4C1 cells. Furthermore, prolonged exposure of cells to VIP (0.1 microM) for 2-24 h caused a 21-40% decrease in Gsalpha from membranes and a 6% increase in total Gsalpha in the cytosolic fraction. The effect of VIP was dose-dependent with ED50 values of 81.6+/-20.0 nM for down-regulation and 2.5+/-0.3 nM for translocation of Gsalpha. Concurrent treatment of GH4C1 cells with VIP and cycloheximide indicated that suppression of protein synthesis de novo did not mimic the effect of VIP. Moreover, the chase experiment of 35S-labeled Gsalpha clearly demonstrated a more rapid rate of decay in the cells maintained in the presence of the agonist. These data indicate that VIP-receptor activates Gsalpha protein and induces the release of Gsalpha from membranes along with its down-regulation in cellular levels.     

Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques

The authors examined the efficacy of Bacillus anthracis protective antigen (PA) combined with adjuvants as vaccines against an aerosol challenge of virulent anthrax spores in rhesus macaques. Adjuvants tested included i) aluminum hydroxide (Alhydrogel), ii) saponin QS-21 and iii) monophosphoryl lipid A (MPL) in squalene/lecithin/Tween 80 emulsion (SLT). Animals were immunized once with either 50 micrograms of recombinant PA plus adjuvant, or with Anthrax Vaccine Adsorbed (AVA), the licensed human anthrax vaccine. The serological response to PA was measured by enzyme linked immunosorbent assay. Lymphocyte proliferation and serum neutralization of in vitro lethal toxin cytotoxicity were also assayed. In all vaccine groups, anti-PA IgM and IgG titers peaked at 2 weeks and 4-5 weeks postimmunization, respectively. Five weeks postimmunization, animals in all vaccine groups demonstrated PA-specific lymphocyte proliferation and sera that neutralized in vitro cytotoxicity. Six weeks after immunization, the animals were challenged by aerosol with approximately 93 LD50 of virulent anthrax spores. Animals were bled daily for 1 week to monitor bacteremia, and deaths were recorded. Anti-PA ELISA titers in all groups of immunized animals were substantially increased 2 weeks after challenge. One dose of each vaccine provided significant protection (> 90%) against inhalation anthrax in the rhesus macaques.     

CD45 isoform expression on human haemopoietic cells at different stages of development

Modified retroperitoneal lymph node dissection for stage I testicular tumors has been described by Weissbach. For performing laparoscopic retroperitoneal lymphadenectomy within these boundaries, we have developed a two-step procedure. In the first step, a ventral approach is used. The colon is dissected free, then the spermatic vein is excised, and the borders of dissection are defined. Removal of retroaortic and retrocaval nodal tissue is technically not feasible from the ventral approach. Therefore, in the second step, a lateral approach is employed, which is the key to success since it allows for easy transection of the lumbar vessels. Thus complete lymph node dissection can be realized. Between August 1992 and June 1993 this procedure was performed in 11 patients. In 7 patients, the tumor was on the right side and in 4 on the left. Conversion to open surgery was necessary in two patients because of uncontrollable bleeding and a large metastasis, respectively. Microscopic metastases were detected in two other patients. No major complications occurred; no blood transfusions were required. So far, the results have been encouraging.     

Species differences in regional patterns of 3H-8-OH-DPAT and 3H-zolpidem binding in the rat and human brain

A series of brief office counseling interventions for the prevention and treatment of violence is reviewed in this article. Primary prevention strategies throughout the pediatric age span cover topics from gun storage to nonviolent handling of a potential street fight. Secondary prevention strategies deal with patients who have been injured by violence or patients who engage in street violence, weapon carrying, or dating violence.     

Intensity-induced stopband bending in periodic nonlinearmultilayers

A simple and physically appealing theory is developed to describe the intensity-induced “bending” of the stopband region of nonlinear multilayered devices. The theory is subsequently used to graphically map the general response of devices as a function of input intensity and phase detuning. Deeper insight into conventional (known) phenomena is obtained, while new phenomena are revealed, such as “hard” optical limiting, intensity discrimination, and a new arrangement for bistability     

A high-efficiency 200 W average power copper HyBrID laser

The high-power, high efficiency copper HyBrID laser has been scaled to large bore (6 cm), with an active length of 200 cm, to generate, as an oscillator, an average output power of 201 W at 1.9% efficiency (based on stored energy) in the green (510.6 nm) and yellow (578.2 nm). For an output power of 120 W, the efficiency reached 3.2%, when the pulse recurrence frequency was 17 kHz. The factors which make the interacting circuit superior to conventional capacitor transfer circuits for the excitation of copper lasers are discussed     

Collapse analysis of plates with strain hardening

A theoretical method is described for predicting the collapse behaviour of thin, simply supported, rectangular plates of light alloy, subjected to in-plane compressive loading. The material behaviour of light alloy is assumed to follow a smooth, rounded, stress-strain curve with a plastic range exhibiting continuous strain hardening, in the manner prescribed, e.g. by the Ramberg-Osgood formula. Isotropic hardening is assumed and plastic flow is calculated from the Prandtl-Reuss equations. A normalised formulation of the standard governing equations is shown to have significant computational advantages.     

Regional hip blockade. A simplified technique for the relief of intractable osteoarthritic pain

A regional anaesthetic technique is described using a blind anatomical approach to the obturator nerve and nerve to quadratus femoris, as a means of alleviating the disabling pain of chronic osteoarthritis of the hip, when arthroplasty is not available.