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71.
Karl-Norbert Klotz Martin J. Lohse Ulrich Schwabe Gloria Cristalli Sauro Vittori Mario Grifantini 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):679-683
Summary The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCPA was prepared with a specific radioactivity of 1.58 TBq/mmol (43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinityK
D-value of 0.2 nmol/l. In the presence of GTP aK
D-value of 13 nmol/l was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confirmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgCl2, as has been shown for the agonist [3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A KD-value of 0.4 nmol/l and aB
max-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmol/l, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [3H]CCPA proved to be a useful agonist radioligand for characterization of A1 adenosine receptors also in tissues with very low receptor density.Abbreviations CHA
N6-cyclopenyadenosine
- CPA
N6-cy-clopentyladen,osine
- CCPA
2-chloro-N6-cyclopentyladenosine
- CCCPA
2-chloro-5-chloro-5-deoxy-N6-cyclopentyladenosine;
- CHAPS
3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate
- DPCPX
8-cyclopentyl-1,3-dipropylxanthine
- NECA
N-ethylcarboxamidoadenosine
- PEI
polyethylenimine
- PIA
N6-phenylisopropyladenosine
Send offprint requests to K.-N. Klotz at the above address 相似文献
72.
Giovanni Melioli Editta Baldini Maria Cristina Mingari Andrea De Maria Mario Roberto Sertoli Fausto Badellino Pier Luigi Percivale Alessandra Catturich Sergio Bertoglio Dario Civalleri Leonardo Santi Lorenzo Moretta 《International journal of cancer. Journal international du cancer》1989,43(2):231-234
In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine. 相似文献
73.
It has been demonstrated in transgenic mice that the overexpression of human phospholipase A2 group IIA (sPLA2), an acute-phase reactant, is associated with depressed plasma cholesterol levels, altered lipoprotein compositions, and increased lipid depositions in aortic walls. It was the aim of the present study to investigate whether the reduced plasma cholesterol levels in sPLA2-transgenic mice may be due to an increased transfer of lipids from sPLA2-modified lipoproteins to the liver and/or other nonvascular tissues. Ten sPLA2-transgenic mice and an equal number of nontransgenic littermates were fed a cholesterol-enriched (1%) diet for 13 weeks. After autopsy, cholesterol and triglyceride concentrations were measured in homogenates of liver, spleen, kidney, and myocardial tissues. Compared to the nontransgenic controls, the sPLA2-transgenic mice exhibited significantly lower plasma cholesterol levels, which was due to a reduction in both HDL and beta-lipoprotein (LDL + beta-VLDL) cholesterol. Liver tissues from the transgenic mice were found to contain significantly increased concentrations of free and esterified cholesterol, which was not associated with increased triglyceride concentrations. Spleen, kidney, and heart tissues of the two animal groups showed no significant differences in cholesterol or triglyceride concentrations. The findings suggest that the overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver. This mechanism is likely to contribute to the development of hypocholesterolemia observed in patients with inflammatory diseases. 相似文献
74.
Farilla L Tiberti C Luzzago A Yu L Eisenbarth GS Cortese R Dotta F Di Mario U 《European journal of immunology》2002,32(5):1420-1427
Autoantigenic epitope mapping represents a critical issue in autoimmune diseases. The islet tyrosine phosphatase-like protein IA-2/ICA512bdc is a major autoantigen in type 1 diabetes (IDDM), but the epitopes responsible for autoantibody binding have been only partially defined. The aim of our study was to identify ICA512bdc epitopes, and in particular mini-epitopes, utilizing a novel strategy for autoimmune diseases. The study was performed in three sequential steps: (1) construction of a lambda-phage surface-displayed ICA512bdc cDNA library with the methodology of tagged random priming with peptides displayed as a fusion to the C terminus of the capsid protein D; (2) affinity selection of the resulting library, followed by immunoscreening, enzyme-linked immunosorbent assay and sequence analysis of positive clones, and (3) radioimmunoprecipitation to detect autoantibodies to the selected clones. This strategy resulted in the identification of two epitopes (IA-2 residues 761 - 964 and 929 - 979), which were recognized by 100 % and 62.9 % ICA512bdc-positive IDDM patients, respectively. Interestingly, the larger clone was detected also by a proportion (16.7 %) of new onset ICA512bdc-negative patients, thus suggesting that this region contains not only the main autoantigenic repertoire of ICA512bdc molecule, but is able to detect IA-2 autoantibodies in even higher percentages of patients. In addition, this study showed the existence of multiple epitopes located in the C-terminal domain of the IA-2 protein, one of which is formed by the 50 C-terminal amino acids, and provided evidence that the strategy used represents a valid tool for identification of epitopes within autoantigenic molecules. 相似文献
75.
María De Los Ángeles Monclus Andreína Cesari María Eugenia Cabrillana Paola Vanina Borelli Amanda Edith Vincenti Mario Héctor Burgos Miguel Walter Fornés 《Anatomical record (Hoboken, N.J. : 2007)》2007,290(7):814-824
In many mammals, sperm associations had been observed, but not in the mouse. In this work, mouse sperm rosettes are morphologically described inside the epididymis and during its dissolution in a culture medium. Also characterized are the saccharides present in the linking material. Sperm association and other epididymal actions are supported by sperm during epididymal transit and are verified at the caudal region, suggesting a relation between epididymal transit and sperm maturation. In drops of epididymal content obtained from distal (cauda), but not from proximal (caput and corpus) regions; dissolved in culture medium, rosettes appear to be 10 to 15 motile sperm joined by their heads. After 3 min, sperm progressively detach, disassembling the rosette. These structures are studied by several techniques, including optic, electronic (scanning electron microscopy and transmission electron microscopy), and video microscopy. At the ultrastructural level, a dense network of electron‐dense material was observed between sperm heads, joining them. Based on previous works in rat, several lectins were used to characterize the type of saccharides present in this linking material. To avoid the contact between sperm and epididymal fluid from distal region—that probably exerts an influence on sperm association—a ligature was placed between caput and corpus. This epididymal content isolated from caput did not display any rosettes after 28 days. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc. 相似文献
76.
Leukocyte apoptosis and its significance in sepsis and shock 总被引:12,自引:0,他引:12
Sepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute to the apoptotic changes, their effects are tissue- and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis. 相似文献
77.
Mario T. Philipp Gary P. Wormser Adriana R. Marques Susan Bittker Dale S. Martin John Nowakowski Leonard G. Dally 《Clinical and Vaccine Immunology : CVI》2005,12(9):1069-1074
C6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C6 negative or had a ≥4-fold decrease in C6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis. 相似文献
78.
A comparison of the sniff magnitude test and the University of Pennsylvania Smell Identification Test in children and nonnative English speakers 总被引:1,自引:0,他引:1
The sniff magnitude test (SMT) is a reliable and rapid clinical test of olfactory function that is minimally dependent on cognitive and linguistic abilities. In this study, we compared performance on the SMT and University of Pennsylvania Smell Identification Test (UPSIT) in samples of children and nonnative English speakers. Previous research has shown that these populations perform poorly on the UPSIT as compared with young, healthy U.S. adults. Such performance differences may reflect variations in memory/cognition and language/culture rather than olfactory abilities. The UPSIT scores of children and of Indian and Chinese graduate students were found to be lower than those of young U.S. adults. By contrast, these groups did not perform more poorly than U.S. adults did on the SMT. The results are consistent with findings from our studies, with the elderly showing that performance on the UPSIT, but not the SMT, is significantly correlated with measures of memory, language and other cognitive abilities. The findings highlight the utility of the SMT when evaluating the olfactory ability of the very young, older adults and people with diverse linguistic and cultural backgrounds. 相似文献
79.
Cristofori P Crivellente F Campagnola M Pasini AF Garbin U Rigoni A Tosetti M Turton J Faustinelli I Cominacini L 《International journal of experimental pathology》2004,85(2):105-114
A study has been carried out in the apolipoprotein (apo) E-deficient mouse to investigate the activity of lacidipine (a calcium antagonist with antioxidant properties) in inhibiting the development of atherosclerotic lesions; of particular interest were changes in the susceptibility of low-density lipoproteins (LDL) to oxidation. Mice receiving a Western-type diet to accelerate the development of atherosclerosis were treated orally with vehicle or lacidipine at 3 or 10 mg/kg/day for 8 weeks. Lacidipine treatment (at 3 or 10 mg/kg) had no effect on the plasma lipid profile. However, a significant (P < 0.01) dose-related reduction of 43 and 50% of the aortic lesion area in respect to vehicle-treated mice was observed. Moreover, the resistance of mouse plasma LDL to undergo lipid peroxidation was significantly (P < 0.01) increased in apo E-deficient mice treated with lacidipine. The native LDL-like particle, derived from apo E-deficient mice treated with lacidipine, contained significantly lower concentrations of malonyldialdehyde than the vehicle-treated control group (P < 0.01). After exposure to human umbilical vein endothelial cells, LDL-like particle vitamin E levels (expressed as area under the curve; AUC), were significantly higher (P < 0.01) in both the 3 and 10 mg/kg lacidipine-treated groups, in comparison with the vehicle-treated control animals. We conclude that lacidipine reduced the extent of the atherosclerotic area in hypercholesterolaemic apo E-deficient mice, and that this reduction may be associated with the capacity of the drug to decrease the susceptibility of LDL to oxidation. 相似文献
80.
Mario Sánchez-Borges Fernan Caballero-Fonseca Arnaldo Capriles-Hulett 《Annals of allergy, asthma & immunology》2005,94(1):34-38
BACKGROUND: Selective inhibitors of cyclooxygenase 2 (COX-2) are generally tolerated by patients sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1. Valdecoxib is a new sulfonamide-containing COX-2-specific inhibitor indicated for the treatment of acute pain, osteoarthritis, and rheumatoid arthritis. OBJECTIVE: To compare the clinical tolerance to rofecoxib and valdecoxib in patients who previously developed urticaria and angioedema while taking classic NSAIDs. METHODS: Patients with challenge-proven NSAID cutaneous sensitivity were submitted to single-blinded controlled oral challenges with rofecoxib, 50 mg, and valdecoxib, 40 mg. RESULTS: Twenty-eight patients (19 females and 9 males; mean +/- SD age, 28.6 +/- 15.0 years; age range, 10-61 years) participated in this study. Twenty-two (85%) of 26 patients who underwent skin tests were atopic, as demonstrated by a clinical history of rhinitis and/or asthma plus positive immediate-type skin hypersensitivity test results. A previous exclusive cutaneous reaction pattern (urticaria and/or angioedema) had occurred in 10 patients (36%), whereas a mixed pattern of skin and respiratory symptoms had occurred in 18 patients (64%). Twenty patients (71%) were multiple reactors, and 8 patients (28%) were single reactors. In this current study, 2 patients (7%) taking rofecoxib experienced angioedema, and 1 patient (4%) taking valdecoxib experienced urticaria. CONCLUSIONS: Rofecoxib and valdecoxib can be safely used by most NSAID-sensitive patients with cutaneous reactions. Our findings suggest that isolated cross-reactions may occur in these patients, and for this reason, controlled oral provocation may be prudent when prescribing valdecoxib or rofecoxib for patients who have previously had urticaria or angioedema triggered by NSAIDs. 相似文献