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981.
Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor 总被引:1,自引:0,他引:1
C Ledent JM Vaugeois SN Schiffmann T Pedrazzini M El Yacoubi JJ Vanderhaeghen J Costentin JK Heath G Vassart M Parmentier 《Canadian Metallurgical Quarterly》1997,388(6643):674-678
Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors. The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR-/-) mice were viable and bred normally. Their exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety tests, and male mice were much more aggressive towards intruders. The response of A2aR-/- mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested. 相似文献
982.
This study employs both dietary and physiological studies to investigate the relationship between calcium (Ca2+) and magnesium (Mg2+) signalling in the mammalian myocardium. Rats maintained on a low Mg2+ diet (LMD; 39 mg Kg-1 Mg2+ in food) consumed less food and grew more slowly than control rats fed on a control Mg2+ diet (CMD; 500 mg Kg-1 Mg2+ in food). The Mg2+ contents of the heart and plasma were 85 +/- 3% and 34 +/- 6.5%, respectively relative to the control group. In contrast, Ca2+ contents in the heart and plasma were 177 +/- 5% and 95 +/- 3%. The levels of potassium (K+) was raised in the plasma (129 +/- 16%) and slightly decreased in the heart (88 +/- 6%) compared to CMD. Similarly, sodium (Na+) contents were slightly higher in the heart and lowered in the plasma of low Mg2+ diet rats compared to control Mg2+ diet rat. Perfusion of the isolated Langendorff's rat heart with a physiological salt solution containing low concentrations (0-0.6 mM) of extracellular magnesium [Mg2+]o resulted in a small transient increase in the amplitude of contraction compared to control [Mg2+]o (1.2 mM). In contrast, elevated [Mg2+]o (2-7.2 mM) caused a marked and progressive decrease in contractile force compared to control. In isolated ventricular myocytes the L-type Ca2+ current (ICa,L) was significantly (p < 0.001) attenuated in cells dialysed with 7.1 mM Mg2+ compared to cells dialysed with 2.9 microM Mg2+. The results indicate that hypomagnesemia is associated with decreased levels of Mg2+ and elevated levels of Ca2+ in the heart and moreover, internal Mg2+ is able to modulate the Ca2+ current through the L-type Ca2+ channel which in turn may be involved with the regulation of contractile force in the heart. 相似文献
983.
The implantable cardioverter-defibrillator (ICD) is an implantable electronic device that has been proven to be safe and effective in treating various malignant tachyarrhythmias in susceptible individuals. As the use of ICDs becomes more widespread, more individuals with the implanted devices will be encountered at autopsy. Manipulation of an activated ICD can result in electrical shock. To avoid injury, pathologists must be properly prepared to deal with bodies containing activated ICDs. These devices can also provide valuable information that may be helpful in determining the cause and mechanism of death. Herein, we present information regarding the appropriate guidelines and safeguards for pathologists confronted with an activated ICD. 相似文献
984.
MG Sunshine BW Gibson JJ Engstrom WA Nichols BD Jones MA Apicella 《Canadian Metallurgical Quarterly》1997,179(17):5521-5533
The htrB gene product of Haemophilus influenzae contributes to the toxicity of the lipooligosaccharide. The htrB gene encodes a 2-keto-3-deoxyoctulosonic acid-dependent acyltransferase which is responsible for myristic acid substitutions at the hydroxy moiety of lipid A beta-hydroxymyristic acid. Mass spectroscopic analysis has demonstrated that lipid A from an H. influenzae htrB mutant is predominantly tetraacyl and similar in structure to lipid IV(A), which has been shown to be nontoxic in animal models. We sought to construct a Salmonella typhimurium htrB mutant in order to investigate the contribution of htrB to virulence in a well-defined murine typhoid model of animal pathogenesis. To this end, an r- m+ galE mutS recD strain of S. typhimurium was constructed (MGS-7) and used in inter- and intrastrain transduction experiments with both coliphage P1 and Salmonella phage P22. The Escherichia coli htrB gene containing a mini-Tn10 insertion was transduced from E. coli MLK217 into S. typhimurium MGS-7 via phage P1 and subsequently via phage P22 into the virulent Salmonella strain SL1344. All S. typhimurium transductants showed phenotypes similar to those described for the E. coli htrB mutant. Mass spectrometric analysis of the crude lipid A fraction from the lipopolysaccharide of the S. typhimurium htrB mutant strain showed that for the dominant hexaacyl form, a lauric acid moiety was lost at one position on the lipid A and a palmitic acid moiety was added at another position; for the less abundant heptaacyl species, the lauric acid was replaced with palmitoleic acid. 相似文献
985.
A method of determining the optimum beam intensities for compensation using multiple static multileaf collimator fields is presented. In this method a histogram of the number of beam pixels against beam intensity is generated for the intensity-modulated beam (IMB). The intensity of each beam to be used is chosen to minimize the mean square deviation between each bin in the histogram and the closest beam intensity. This method has been applied to sample IMBs possessing one maximum and two maxima. For both cases, the use of uniform beam intensity increments is shown to be close to optimal. In the case with two maxima, the efficacy of irradiating both peaks simultaneously, rather than separately, has been studied and shown to be of potential benefit. The optimum intensities for an IMB for breast radiotherapy are also presented. 相似文献
986.
3beta-(Iodoacetoxy)dehydroisoandrosterone (3beta-IDA), an analogue of the electrophilic substrate, Delta5-androstene-3,17-dione, as well as an analogue of several other steroid inhibitors of glutathione S-transferase, was tested as an affinity label of rat liver glutathione S-transferase, isozyme 1-1. A time-dependent loss of enzyme activity is observed upon incubation of 3beta-IDA with the enzyme. The rate of enzyme inactivation exhibits a nonlinear dependence on 3beta-IDA concentration, yielding an apparent Ki of 21 microM. Upon complete inactivation of the enzyme, a reagent incorporation of approximately 1 mol/mol of enzyme subunit or 2 mol/mol of enzyme dimer is observed. Protection against inactivation and incorporation is afforded by alkyl glutathione derivatives and nonsubstrate steroid ligands such as 17beta-estradiol-3,17-disulfate but, surprisingly, not by Delta5-androstene-3,17-dione or any other electrophilic substrate analogues tested. These results suggest that the site of reaction is within the nonsubstrate steroid binding site of the enzyme, which is distinguishable from the electrophilic substrate binding site, near the active site of the enzyme. Two cysteine residues, Cys17 and Cys111, are modified in nearly equal amounts, despite an average reagent incorporation of 1 mol/mol enzyme subunit. Isolation of enzyme subunits indicates the presence of unmodified, singly labeled, and doubly labeled subunits, consistent with mutually exclusive modification of cysteine residues across enzyme subunits; i.e., modification of Cys111 on subunit A prevents modification of Cys111 on subunit B and similarly for Cys17. Molecular modeling analysis suggests that Cys17 and Cys111 are located in the nonsubstrate steroid binding site, within the cleft between the subunits of the dimeric enzyme. 相似文献
987.
988.
M Herrera-Marschitz M Goiny ZB You JJ Meana E Pettersson R Rodriguez-Puertas ZQ Xu L Terenius T H?kfelt U Ungerstedt 《Canadian Metallurgical Quarterly》1997,21(4):489-495
Experiments were designed to determine the in vivo cell-cycle phase of lymphocytes in secondary lymphoid follicles, and whether B-cell proliferation and apoptosis occur within follicular dendritic cell (FDC)-associated clusters. Using frozen serial sections of human tonsils, lymphoid follicles were stained to reveal histone H3 mRNA, as an S-phase marker, using in situ hybridization, and stained immunohistochemically with antibodies against cyclin E as a late G1 phase marker, cyclin B1 and p34cdc2 as S-G2-M phase markers, and Ki-67 as a marker of cycling cells. Each LF was divided into five zones: mantle zone, outer zone, apical light zone, basal light zone and dark zone, with the help of haematoxylin and eosin staining, and a CD23 immunostain. The rate of occurrence of positively labelled cells was calculated by dividing the number of positive cells by the number of all cells in each zone. The cells that were positive for cyclin E, histone H3 mRNA, cyclin B1, p34cdc2, and Ki-67 were found most frequently in the dark zone (54.5 +/- 6.6%, 22.0 +/- 5.7%, 36.7 +/- 14.5%, 40.0 +/- 10.2%, and 59.0 +/- 13.4%, respectively), followed by the outer zone (52.7 +/- 7.8%, 14.9 +/- 4.1%, 22.9 +/- 9.7%, 24.9 +/- 7.9%, and 44.6 +/- 12.3%, respectively), showing that both the outer zone and the dark zone contain many proliferating lymphocytes. Furthermore, FDC-associated clusters and free lymphocytes were obtained from enucleated germinal centres, using enzymatic digestion. The rates of occurrence of cells that were positive for cyclin B1 and Ki-67 within the clusters (7.2 +/- 1.9% and 37.9 +/- 10.5% respectively) were significantly lower than those of free lymphocytes outside the clusters (22.2 +/- 4.0% and 62.8 +/- 14.0%, respectively). The rates of occurrence of apoptotic bodies and cells within the clusters, as detected by in situ tailing or in situ nick translation (0.2 +/- 0.4% and 0.4 +/- 0.4%, respectively) were significantly lower than those outside the clusters (1.1 +/- 0.3, 1.6 +/- 0.5%, respectively). These results suggest that FDC-associated clusters are not the site of proliferation, and that they rarely contain apoptotic bodies and cells of B lymphocytes. 相似文献
989.
IB Shchepotin VL Valetsky VA Chorny M Shabahang RJ Nauta RR Buras SR Evans 《Canadian Metallurgical Quarterly》1997,33(9):1413-1418
Medical consequences of many nuclear accidents on humans are well studied, but the results pertaining to gastric cancer patients who were exposed to radiation as a result of the Chernobyl nuclear accident have not been analysed. In this study, the outcome of the surgical treatment of 68 gastric cancer patients who were exposed to radiation as a result of the Chernobyl nuclear accident was compared with that of 117 consecutive gastric cancer patients from uncontaminated areas of the Ukraine. Patients in the study group was significantly younger than that of the control group. Comparative analysis showed the same frequency of regional metastases (65.7% versus 71.1%, P > 0.05), but a smaller number of distant metastases (23.8% versus 38.1%, P < 0.05) in the study group. 41.2% of patients in the study group underwent total gastrectomy compared to 19.6% of patients in the control group (P = 0.002). Postoperative complications developed in 13.2% of patients in the study group, while postoperative mortality in the study group was 7.3% compared to 1.7% in the control group. A significant decrease in CD16 cells was noted in patients from the study group following the operative procedure. Young age, invasive tumours with smaller number of distant metastases, frequent necessity for total gastrectomy and combined operations with adjacent organs, a higher level of postoperative morbidity and mortality and low levels of natural killer cells (CD16+) with a tendency to decrease after surgery are characteristic of patients with carcinoma of the stomach affected by the Chernobyl accident. 相似文献
990.
G. E. Gadd P. J. Evans D. J. Hurwood S. Moricca G. McOrist T. Wall M. Elcombe P. Prasad 《Fullerenes, Nanotubes and Carbon Nanostructures》1997,5(5):871-902
Rare gas interstitial fullerenes, produced by hot isostatic pressing solid C60 in the presence of Ar, Kr or Xe, have been neutron irradiated and their behaviour investigated. The activity of the generated radionuclides was found to be in agreement with calculations and this combined with X-ray powder diffraction showed that both the activated radionuclides and the unactivated rare gas remained trapped in the solid after they have been subjected to the harsh conditions encountered in a nuclear reactor. Gamma spectroscopy of the irradiated solids and solutions of them in toluene provided strong evidence for endohedral compound formation. We estimate 1-2% of the activated rare gas atoms, which recoil as a result of prompt gamma emission, end up in the centre of what is most likely too be the C60 molecule or some other fullerene derivative. On this basis, we postulate the formation of RN@C6o where the radionuclide (RN)is 125gXe, 133gXe, I35gXe, 41Ar or85mKr. 相似文献