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51.
G. Mathé F. De Vassal L. Schwarzenberg M. Delgado R. Weiner M. A. Gil J. Pena-Angulo D. Belpomme P. Pouillart D. Machover J. L. Misset J. L. Pico C. Jasmin M. Hayat M. Schneider A. Cattan J. L. Amiel M. Musset C. Rosenfeld 《Cancer immunology, immunotherapy : CII》1977,2(4):225-232
Summary Protocol ICIG-ALL 9 with only nine months' remission chemotherapy followed by active immunotherapy has given a proportion of about 50% of the patients on the plateau of the first remission curve, while 60% of the children are on the plateau of survival curve.These results do not differ from those of another protocol (ICIG-ALL 10) conducted on an identical population of patients and comprising a 25 month remission chemotherapy before immunotherapy.This observation, confirmed by a randomized trial of the EORTC Haemopathy Working Party, suggests that between the 9th and the 25th month, active immunotherapy is as efficient as maintenance chemotherapy.The overall results of this protocol with short chemotherapy followed by active immunotherapy have been compared with those of another prolonged maintenance chemotherapy before immunotherapy protocol (ICIG-ALL 11), and with published protocols comprising only long maintenance chemotherapy: protocol 9 is, as far as the first remission plateau and the survival plateau are concerned, superior to most of these protocols (if not all their branches).Lethal toxicity of active immunotherapy is nil, in contrast to the proportion of deaths (4–28%) occurring during remission in the patients submitted to maintenance chemotherapy.However, not all patients with so-called acute lymphoid leukaemias should be treated identically: our early prognosis parameters (WHO cytological types and volume of the tumour, in this study) allow us to distinguish a good prognosis group in which protocol 9 gave an 80% cure expectancy.The patients with a poor prognosis should be the object of further research for a more efficient therapy. Even if this should be more intensive, the risk is justified in this group, while it is not so for the good prognosis group. 相似文献
52.
G. Mathe F. de Vassal M. Delgado P. Pouillart D. Belpomme R. Joseph L. Schwarzenberg J. L. Amiel M. Schneider A. Cattan M. Musset J. L. Misset C. Jasmin 《Cancer immunology, immunotherapy : CII》1976,1(1-2):77-86
Summary The first 100 acute lymphoid (and undifferentiated) leukemias, (of which the smears at the first presentation of the disease are still available for typing), treated successively with remission induction chemotherapy, complementary cell-reducing chemoradiotherapy and then active immunotherapy with irradiated pooled allogeneic leukemic cells and fresh Pasteur Institute BCG applied on scarifications, have been reviewed, especially in connection with BCG application.Tolerance of BCG has been good. Its application had to be stopped due to a side effect (choroiditis) in only one patient. This toxic cost is negligible compared to that of so-called maintenance chemotherapy.No subject of our first control trial started in 1963 has relapsed between 3 and 13 years.In the overall group of the 100 patients studied, no relapse has been observed after 48 months, which is quite different to the observations of frequent relapses after that time in patients submitted to maintenance chemotherapy.Moreover, second remissions are obtained in 94% of the patients who relapsed early under immunotherapy, and their life expectancy after a second remission is as high as it is after the first remission.The median of survival is longer than 5 years.The action of active immunotherapy on the immune machinery has been followed by several assays, of which the increase of null cells (which include K-cells) may be the most interesting.Several prognostic factors have been demonstrated among which are sex, the volume of the neoplasia, meningeal localizations, and the cytological types. Age has no prognostic value in immunotherapy patients, contrary to maintenance chemotherapy patients. Also the cytological types behave differently under immunotherapy and under maintenance chemotherapy. The disease-free survival of more than 85% of the microlymphoblastic patients submitted to immunotherapy is not observed in J. Bernard's patients submitted to maintenance chemotherapy, which suggests that this high cure rate is due to active immunotherapy. Hence, these prognostic factors are probably factors of sensitivity to active immunotherapy. A statistical computerized study has shown that there is a link between the cytological types and other prognostic factors and that they all depend on the cytological type.Hence, our present protocol is adapted to this immunotherapy sensitivity factor. It comprises a nonrisk preimmunotherapy chemotherapy for the microlymphoblastic type, and a longer and more intensive chemotherapy for less immunotherapy sensitive types. 相似文献
53.
A modular treatment of molecular traffic through the active site of cholinesterase 总被引:1,自引:0,他引:1
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We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products. 相似文献
54.
哈尔滨西郊赤狐冬季巢区的初步研究 总被引:5,自引:2,他引:3
本文利用雪地跟踪方法对哈尔滨西郊5只赤狐在1985-1986年冬季的巢区做了观察。结果表明,5只狐对巢区内各部分使用的强度是不等的,对巢区中部的某些地块使用强度要高于对外围的使用,并具有明显的方向性。5个巢区的平均活动半径为320±68米至557±82米,面积为1.44-4.O9平方公里,线性指数为1.079至2。5只狐相邻距离约1000米。 相似文献
55.
Nonglucosylated oligosaccharides are transferred to protein in MI8-5 Chinese hamster ovary cells 总被引:3,自引:2,他引:1
A CHO mutant MI8-5 was found to synthesize Man9-GlcNAc2-P-P-dolichol rather
than Glc3Man9GlcNAc2-P-P-dolichol as the oligosaccharide-lipid intermediate
in N-glycosylation of proteins. MI8-5 cells were incubated with labeled
mevalonate, and the prenol was found to be dolichol. The mannose-labeled
oligosaccharide released from oligosaccharide-lipid of MI8-5 cells was
analyzed by HPLC and alpha-mannosidase treatment, and the data were
consistent with a structure of Man9GlcNAc2. In addition, MI8-5 cells did
not incorporate radioactivity into oligosaccharide- lipid during an
incubation with tritiated galactose, again consistent with MI8-5 cells
synthesizing an unglucosylated oligosaccharide-lipid. MI8-5 cells had
parental levels of glucosylphosphoryldolichol synthase activity. However,
in two different assays, MI8-5 cells lacked dolichol-
P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase activity. MI8-5 cells
were found to synthesize glucosylated oligosaccharide after they were
transfected with Saccharomyces cerevisiae ALG 6, the gene for
dolichol-P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase. MI8-5 cells
were found to incorporate mannose into protein 2-fold slower than parental
cells and to approximately a 2-fold lesser extent.
相似文献
56.
57.
58.
Fran?ois Philippart Ga?lle Bouroche Jean-Fran?ois Timsit Maité Garrouste-Orgeas Elie Azoulay Michael Darmon Christophe Adrie Bernard Allaouchiche Claire Ara-Somohano Stéphane Ruckly Anne-Sylvie Dumenil Bertrand Souweine Dany Goldgran-Toledano Lila Bouadma Beno?t Misset Outcomerea study group 《PloS one》2015,10(9)
Rationale
Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection.Objectives
To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP).Methods
We used data entered into the French prospective multicenter Outcomerea database in 1997–2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included.Measurements and Main Results
Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P<0.01) and longer time to VAP (5.0 vs.10.5 days; P<0.01). After adjustment on independent risk factors for VAP and previous antimicrobial use, IAI was associated with a decreased risk of VAP (hazard ratio, 0.62; 95% confidence interval, 0.46–0.83; P<0.0017). The pathogens responsible for VAP were not different between the groups with and without IAI (Pseudomonas aeruginosa, 345 [42.8%] and 24 [42.8%]; Enterobacteriaceae, 264 [32.8%] and 19 [34.0%]; and Staphylococcus aureus, 215 [26.7%] and 17 [30.4%], respectively). Crude ICU mortality was not different between the groups with and without IAI (81 [27.9%] and 747 [32.0%], P = 0.16).Conclusions
In our observational study of mechanically ventilated ICU patients with severe sepsis and/or septic shock, VAP occurred less often and later in the group with IAIs compared to the group with infections at other sites. 相似文献59.
Margrete Solheim Mari C Brekke Lars G Snipen Rob JL Willems Ingolf F Nes Dag A Brede 《BMC microbiology》2011,11(1):3
Background
Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40). 相似文献60.
Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10