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991.
Pierre Boudinot Dominique Rueff-Juy Anne-Marie Drapier Pierre-Andr Cazenave Pierre Sanchez 《European journal of immunology》1995,25(9):2499-2505
The diversity of the B cell repertoire of Cx knockout mice is limited by the expression of four λ light chain types. Among the spleen B cells, λ1 is expressed by the majority (58%) of cells, and λ3 by the minority (8%), while λ2(V2) and λ2(Vx) are expressed in intermediate quantities (18% and 16%, respectively). To assess the influence of mechanistic pressures on the λ subtype distribution, the proportions of the different λ rearrangements were determined in various B cell subpopulations divided on the basis of the λ subtype expressed, and the VλJλ junction sequences were studied at different steps of B cell differentiation (pre-B, immature and mature B cells). The data show that (1) the ratio of productive/non-productive VJ junctions is determined by the nature of the λ segments that are rearranged as can be observed in the pre-B cells, (2) V1-J1 non-productive rearrangements are often found in the λ1-negative B cells in the periphery, and (3) V1J3 junctions are often non-productive regardless of the nature of the cells analyzed. Our results, therefore, suggest that a strong probability of initiating a V1-J1 rearrangement and a weak probability of giving a productive V1J3 junction are responsible for the λ1 dominance and the λ3 under-expression, respectively. The intermediate proportion of λ2(V2) subtype is most likely due to a probability of obtaining a productive joint that is better than that for V1J3 and a probability of initiating a rearrangement that is lower than that for V1J1. However, the λ2(Vx) cell proportion cannot be determined only by these parameters. 相似文献
992.
993.
Claire Corot Jean-Marc Idee Anne-Marie Hentsch Robin Santus Catherine Mallet Valrie Goulas Bruno Bonnemain Dominique Meyer 《Journal of magnetic resonance imaging : JMRI》1998,8(3):695-702
Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC50 = .016 ± .006 mmol/1) and Gd-DTPA (IC50 = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate may have deleterious biologic consequences. 相似文献
994.
M Tod F Mentré Y Merlé A Mallet 《Journal of pharmacokinetics and biopharmaceutics》1998,26(6):689-716
The expectation of the determinant of the inverse of the population Fisher information matrix is proposed as a criterion to evaluate and optimize designs for the estimation of population pharmacokinetic (PK) parameters. Given a PK model, a measurement error model, a parametric distribution of the parameters and a prior distribution representing the belief about the hyperparameters to be estimated, the EID criterion is minimized in order to find the optimal population design. In this approach, a group is defined as a number of subjects to whom the same sampling schedule (i.e., the number of samples and their timing) is applied. The constraints, which are defined a priori, are the number of groups, the size of each group and the number of samples per subject in each group. The goal of the optimization is to determine the optimal sampling times in each group. This criterion is applied to a one-compartment open model with first-order absorption. The error model is either homoscedastic or heteroscedastic with constant coefficient of variation. Individual parameters are assumed to arise from a lognormal distribution with mean vector M and covariance matrix C. Uncertainties about the M and C are accounted for by a prior distribution which is normal for M and Wishart for C. Sampling times are optimized by using a stochastic gradient algorithm. Influence of the number of different sampling schemes, the number of subjects per sampling schedule, the number of samples per subject in each sampling scheme, the uncertainties on M and C and the assumption about the error model and the dose have been investigated. 相似文献
995.
996.
997.
Magí Farré María-Teresa Terán Pere N. Roset Marta Mas Marta Torrens J. Camí 《Psychopharmacology》1998,140(4):486-495
Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males
with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized
clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam
0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple
reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects
questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales
(VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest
doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases
in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related
effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria
in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest
that it may be included in the group of benzodiazepines with a relatively high abuse potential.
Received: 13 February 1998/Final version: 1 May 1998 相似文献
998.
Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer 总被引:19,自引:6,他引:13
A. M. Lacy J. C. García-Valdecasas J. M. Piqué S. Delgado E. Campo J. M. Bordas P. Taurá L. Grande J. Fuster J. L. Pacheco J. Visa 《Surgical endoscopy》1995,9(10):1101-1105
The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.Presented at the annual meeting of the Society of American Gastrointestinal Surgeons (SAGES), Orlando, FL, USA, 11–14 March 1995 相似文献
999.
The mode of action and the structure of a herbicide in complex with its target: binding of activated hydantocidin to the feedback regulation site of adenylosuccinate synthetase. 总被引:4,自引:0,他引:4
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R Fonné-Pfister P Chemla E Ward M Girardet K E Kreuz R B Honzatko H J Fromm H P Sch?r M G Grütter S W Cowan-Jacob 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(18):9431-9436
(+)-Hydantocidin, a recently discovered natural spironucleoside with potent herbicidal activity, is shown to be a proherbicide that, after phosphorylation at the 5' position, inhibits adenylosuccinate synthetase, an enzyme involved in de novo purine synthesis. The mode of binding of hydantocidin 5'-monophosphate to the target enzyme was analyzed by determining the crystal structure of the enzyme-inhibitor complex at 2.6-A resolution. It was found that adenylosuccinate synthetase binds the phosphorylated compound in the same fashion as it does adenosine 5'-monophosphate, the natural feedback regulator of this enzyme. This work provides the first crystal structure of a herbicide-target complex reported to date. 相似文献
1000.
P Nyirády L Pirót A Altorjay A Pelényi M Merksz A Kiss A Csontai 《Acta chirurgica Hungarica》1998,37(3-4):201-204
There are recurrences and postoperative hydrocele of varicocele after any kind of surgical treatment. Laparoscopic clipping and dissection of internal spermatic vessels was performed without any complication in 73 children to treat varicocele in our department between 1995 and 1998. We have used a new method to detect etiological factors at laparoscopic surgery. The well-known Linton and Trendelenburg test was adapted to detect incidental collateral veins in 73 patients. Using these test, collateral veins were detected in 16 boys. The testicular artery identified in most of the cases as a pulsatile vessel. The operating time was 10-25 minutes. Laparoscopic varicocelectomy is a safe, effective treatment causing minimal discomfort and allowing patients an early to return to activity. These results suggest this technique a viable alternative to open ligation in paediatric urological practice. 相似文献