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71.
James F. Markmann Michael R. Rickels Thomas L. Eggerman Nancy D. Bridges David E. Lafontant Julie Qidwai Eric Foster William R. Clarke Malek Kamoun Rodolfo Alejandro Melena D. Bellin Kathryn Chaloner Christine W. Czarniecki Julia S. Goldstein Bernhard J. Hering Lawrence G. Hunsicker Dixon B. Kaufman Olle Korsgren Christian P. Larsen Xunrong Luo Ali Naji José Oberholzer Andrew M. Posselt Camillo Ricordi Peter A. Senior A. M. James Shapiro Peter G. Stock Nicole A. Turgeon 《American journal of transplantation》2021,21(4):1477-1492
72.
Cecilia Nakid-Cordero Sylvain Choquet Nicolas Gauthier Noureddine Balegroune Nadine Tarantino Véronique Morel Nadia Arzouk Sonia Burrel Géraldine Rousseau Frédéric Charlotte Martin Larsen Vincent Vieillard Brigitte Autran Véronique Leblond Amélie Guihot for the K-VIROGREF Study Group 《American journal of transplantation》2021,21(8):2846-2863
EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4+<300 cells/mm3, p < .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm3) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis. 相似文献
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76.
Milne Robert W. Jensen Rikke Holm Larsen Claus Evans Allan M. Nation Roger L. 《Pharmaceutical research》1997,14(8):1014-1018
Purpose. Humans and guinea pigs metabolise morphine extensively, forming the isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in relatively similar ratios. Both metabolites are formed in the liver, and their greater polarity relative to the parent aglycone may limit their permeability across hepatic membranes. This study compared the disposition of hepatically-generated M3G and M6G in perfused livers isolated from guinea pigs.
Methods. Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs bicarbonate buffer containing morphine (6 to 7 M). Perfusing medium, venous perfusate and bile were collected at regular intervals and concentrations of morphine, M3G and M6G determined by reversed-phase HPLC.
Results. Concentrations of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G and M6G were consistent between 20 and 50 min of perfusion. The mean (±s.d.) ratio for the rate of formation of M3G relative to M6G was 3.7 ± 1.5. A mean 33 ± 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of the M3G and M6G formed during a single passage, 19 ± 11% and 9 ± 9%, respectively, was excreted into bile; the values were significantly different (P = 0.002).
Conclusions. A greater fraction of hepatically-generated M3G excreted into bile compared to that for M6G reflects differences in their relative transport across sinusoidal and canalicular membranes of hepatocytes, possibly via carrier-mediated systems. 相似文献
77.
Esa-Pekka Pälvimäki Aki Laakso Mikko Kuoppamäki Erkka Syvälahti Jarmo Hietala 《Psychopharmacology》1994,115(4):543-546
Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg–1), fluoxetine (10 mg kg–1), or imipramine (15 mg kg–1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to 1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in 1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg–1) or fluoxetine (2.5, 10 and 20 mg kg–1) SC once daily for 14 days. The effects of citalopram and fluoxetine on 1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of 1-adrenergic receptors in the rat brain. 相似文献
78.
Rasmus W. Licht Jytte O. Larsen Donald Smith Hans Brændgaard 《Psychopharmacology》1994,115(3):371-374
The present study used stereological methods to determine whether long-term administration of lithium, with or without haloperidol, affects the number and average volume of neocortical neurons. Twenty-five rats were divided into three groups and given no treatment, lithium, or lithium combined with haloperidol. Serum lithium levels ranged from 0.5 to 0.8 mmol/l. Haloperidol was injected intraperitoneally at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the brains were prepared. Neocortical volume, density of neurons, total number of neurons and mean volume of neurons were estimated. As no differences were found between the groups, the present study provides no evidence for quantitative morphological changes in the cerebral cortex due to long-term therapeutic levels of lithium, with or without haloperidol. 相似文献
79.
The lactogen receptor has been suggested to associate with one or more G proteins despite the absence of a 7-transmembrane
spanning sequence. These studies were designed to determine whether lactogens acutely increase GTP binding to or GTPase activity
in Nb2 cell membrane. Incubation of Nb2 cell membrane with either ovine PRL (10 ng/ml) or diluent for 0–1 h resulted in a
decrease in total35S-GTP binding to both with no difference in GTP binding between PRL- and diluent-treated membranes. There was also no change
in35S-GTP binding to Nb2 cell membrane incubated with increasing oPRL concentrations (0.001–100 ng/ml) for 60 min. α-32P-GTP photoaffinity labelling was used to evaluate changes in GTP binding to specific G proteins. Photoaffinity labelling
of α-32P-GTP to no G protein was changed after preincubation with oPRL (10 ng/ml) for 0–60 min or with oPRL (0.01–10 ng/ml) for 60
min. Finally, it was determined whether oPRL had any acute effect on GTPase activity, as determined by release of32Pi from γ-32P-GTP. When Nb2 cell membrane was preincubated for 0–60 min with oPRL (10 ng/ml) or a range of oPRL concentrations (0–10 ng/ml),
no change in GTPase activity was observed. However, when Nb2 cells were incubated with lactogen for 0–7 h, GTPase activity
in equal quantities of Nb2 cell membrane prepared from those cells increased over time. Increased GTPase activity (64.9–74.4%;P<0.03 compared to 0 h) was observed after 4–7 h incubation with lactogen.
In summary, addition of lactogen to Nb2 cell membrane did not acutely increase either GTP binding or GTPase activity. Yet
when Nb2 cells were incubated with lactogen for 4 h prior to preparation of membrane, GTPase activity was significantly increased.
This evidence, in addition to our previous results showing that 4 h incubation with lactogen increased G protein β subunit
concentration and pertussis toxin-stimulated ADP-ribosylation of Gi, support a role for delayed lactogen modulation of one
or more G proteins in the Nb2 cell, requiring at least 4 h for maximal effect. 相似文献
80.
Semen quality and sex hormones among organic and traditional Danish farmers. ASCLEPIOS Study Group 总被引:3,自引:0,他引:3 下载免费PDF全文
S. B. Larsen M. Spano A. Giwercman J. P. Bonde 《Occupational and environmental medicine》1999,56(2):139-144
OBJECTIVES: To confirm or refute the hypothesis that organic farmers have higher sperm concentrations than traditional farmers. METHODS: Traditional and organic farmers were selected randomly from central registers, and 171 traditional farmers and 85 organic farmers delivered one semen sample before the start of the spraying season. The participation rate was 28.8% among traditional farmers and 42.9% among organic farmers. RESULTS: The median sperm concentration for traditional and organic farmers was 58 million/ml and 64 million/ml, respectively. After adjustment for several confounders, sperm concentration, total count, proportion of non-vital spermatozoa, sperm chromatin structure, and motility variables did not differ significantly between the two groups. The traditional farmers had a significantly lower proportion of normal spermatozoa, but this result was not confirmed in a second sample. Organic farmers had slightly higher inhibin B concentration and testosterone/sex hormone binding globulin ratio. CONCLUSION: Despite slight differences in concentrations of reproductive hormones, no significant differences in conventional measures of semen quality were found between organic and traditional farmers.
相似文献