Effect of guanine nucleotides and temperature on calcitonin gene-related peptide receptor binding sites in brain and peripheral tissues

Recent data have suggested the existence of at least two major classes of calcitonin gene-related peptide (CGRP) receptors in brain and peripheral tissues [Henke et al., Brain Res., 410 (1987) 404-408; Dennis et al., J. Pharmacol. Exp. Ther., 251 (1989) 718-725; ibid, 254 (1990) 123-128; Quirion et al., Ann. NY Acad. Sci., 657 (1992) 88-105]. However, little is currently known in the structure characteristics of CGRP receptors as cloning as yet to be reported. In the present study, the sensitivity of [125I]humanCGRP alpha binding to guanine nucleotides and temperature was investigated in guinea pig atria (prototypical CGRP1 tissue) guinea pig vas deferens (prototypical CGRP2 tissue) and in the rat brain and cerebellum (mixed assay). Binding isotherms of [125I]hCGRP alpha in those four tissue preparations were curvilinear and best fitted to a two-site model under most assay conditions. The high affinity binding component was highly temperature-sensitive and accounted, under experimental conditions, for up to 18% of the total population of receptors. Moreover, these high affinity sites were also highly sensitive to guanine nucleotides (Gpp(NH)p, 100 microM) in all preparations although to a different extend depending upon assay temperatures. Taken together, this suggests that the different CGRP receptor subtypes present in these tissue all belong to a G-protein coupled receptor family.     

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study

The pyrolytic behavior of inulin, a (2-->1)-linked fructofuranan, is described. Parallel investigations of the pyrolysis of glucose and of fructose were conducted to supplement the inulin results and to aid comparison with previous results from glucans. Effects of neutral and basic additives are emphasized. As with glucans, the addition of such additives (especially basic) increases the yields of the one-, two-, and three-carbon products (as well as of hexosaccharinolactones), while generally decreasing the yields of anhydro sugar and furan derivatives. The former products include glycolaldehyde, acetol, dihydroxy-acetone, acetic acid, formic acid, and lactic acid. Mechanistic speculations are made regarding the origins of these compounds, as well as of furan derivatives and saccharinic acid lactones. Parallels with alkaline degradation are considered.     

Scintillation prediction models compared to measurements on a timebase of several days

The prediction models for scintillation variance of ITU-R and Karasawa et al. (1988) are compared to measurements on a time base which is much shorter than originally considered for these models. It is shown that even after averaging over just three days, a good correlation with the measured variance is found. Both models predict higher scintillation variance than is measured at 19.8 GHz on a 12.7° elevation path in Kirkkonummi, Finland     

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Caudascopic experiences and a new patho-anatomic concept for treatment of sciatica

Osteotomy has been used in treatment of unstable intertrochanteric hip fractures in an attempt to increase the stability of the fracture fragments. We have assessed this stability in a randomised prospective study on 138 patients, all having been fixed by dynamic hip screen, comparing anatomical reduction with medialisation osteotomy. The groups were similar in terms of age, gender and fracture configuration. There was no difference in final results in both groups except that operation time was longer in osteotomy group and the blood loss was more. We found no clear benefit from osteotomy and therefore recommend anatomical reduction and fixation by a sliding hip screw in most cases. Rarely, a fracture configuration which does not allow anatomical reduction may benefit from an osteotomy.     

Net transport of cholesterol from cells of the human EA.hy 926 endothelial cell line to high density lipoproteins

EA.hy 926 cells, a human endothelial cell line, show characteristics of differentiated endothelial cells. The cells express saturable binding of apo E-free 125I-high density lipoprotein3 (HDL3). Bmax increased from 71 to 226 ng HDL3 bound/mg cell protein after cholesterol loading of the confluent endothelial cells with cationized low density lipoprotein (LDL). The affinity did not change after cholesterol enrichment (Kd was 37 micrograms HDL3 protein/ml for control cells and 31 micrograms/ml for loaded cells). Incubation of cholesterol-loaded EA.hy 926 cells with native HDL and LDL had different effects on cellular cholesterol levels. Incubation with HDL decreased both esterified and unesterified cellular cholesterol, but LDL did not change total cellular cholesterol. However, LDL tended to increase cellular cholesteryl esters, with a concomitant decrease of unesterified cellular cholesterol. Incubation of endothelial cells with both HDL and LDL also resulted in decreased total cellular cholesterol levels. These data show that cationized LDL-loaded human endothelial EA.hy 926 cells can be used to study the net transport of cellular cholesterol to HDL, the first step in reverse cholesterol transport.     

Localization of interferon-gamma and Ia-antigen in T cell line-mediated experimental autoimmune encephalomyelitis

This study reports the cellular localization of interferon-gamma (IFN-gamma) and MHC class II antigen (Ia) in the spinal cord of rats with experimental autoimmune encephalomyelitis induced by adoptive transfer of myelin basic protein-specific T cells. Numerous IFN-gamma-positive cells, stained with two different monoclonal antibodies against IFN-gamma, were present from days 3 to 7 after cell transfer. Their number was greatly reduced on day 10. A subpopulation of T cells was IFN-gamma positive. Moreover, a large number of ED1-positive macrophages contained IFN-gamma immunoreactivity. The transient presence of immune cells containing IFN-gamma immunoreactivity in experimental autoimmune encephalomyelitis suggests a pathogenic role of this cytokine in immune-mediated demyelination of the central nervous system.     

The Morris water-escape task in mice: strain differences and effects of intra-maze contrast and brightness

The Morris water-escape task is an extensively used experimental paradigm to assess the spatial discrimination performance and effects of brain lesions and drugs on this performance. In the first experiment, we compared the acquisition of this task by different strains (CFW1, BALB, NMRI, and C57BL) of mice and their performance in a probe trial. In a second experiment, C57BL mice were tested in Morris mazes where black and white tanks were combined with white or black platforms to investigate if and how the contrast between the tank and the platform affects the performance of the mice. In addition, four brightness conditions were compared to investigate whether or not the degree of brightness of the tank itself affects the learning performance. The results of these experiments indicated that 1. mice could readily learn the Morris task, 2. one of the contrast conditions affected the swimming speed, 3. the maze brightness per se did not affect water escape performance at all, and that 4. the swimming speed can strongly bias the outcome of Morris water-escape experiments in mice.