Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice. 相似文献
Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.
Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.
Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects. 相似文献
Background: Exercise is an important strategy with potential to improve recovery in older adults following a hip fracture.Purpose: The purpose of this study was to test the impact of a self-efficacy based intervention, the Exercise Plus Program, and the
different components of the intervention, on self-efficacy, outcome expectations, and exercise behavior among older women
post-hip fracture.Methods: Participants were randomized to one of four groups: exercise plus, exercise only, plus only (i.e., motivation), or routine
care. Data collection was done at baseline (within 22 days of fracture), 2, 6, and 12 months post-hip fracture.Results: A total of 209 women were recruited with an average age of 81.0 years (SD=6.9). The majority was White (97.1%), was widowed
(57.2%), and had a high school education (66.7%). Generalized Estimating Equations were used to perform repeated measures
analyses. No differences in trajectories of recovery were observed for self-efficacy or outcome expectations. A statistically
significant difference in the overall trajectory of time in exercise was seen (p<.001), with more time spent exercising in
all three treatment groups.Conclusions: The study demonstrated that it was possible to engage these women in a home-based exercise program and that the plus only,
exercise only, and the exercise plus groups all increased exercise.
Support for this project was provided by National Institute on Aging grants R37 AG09901, R01-AG18668, R01 AG17082, and the
Claude D. Pepper Older Americans Independence Center P60-AG12583. 相似文献
The developmental courses of high-risk and resilient children were analyzed in a follow-up study of members of a 1955 birth cohort on the island of Kauai, Hawaii. Relative impact of risk and protective factors changed at various life phases, with males displaying greater vulnerability than females in their first decade and less during their second; another shift appears under way at the beginning of their fourth decade. Certain protective factors seem to have a more general effect on adaptation than do specific risk factors. 相似文献
Genetic engineering provides the opportunity for the synthesis of human proteins and derivatives thereof which are of significant value for replacement therapy. However, in addition to genetic engineering an extensive process development has to be carried out in order to establish an economic production process and to guarantee consistently high product quality from batch to batch. This includes the characterization of the production host cell vector construct, the validation of the fermentation and the protein purification process as well as the lyophilization and the reconstitution of the final product. A number of in-process and final product controls have to be established and limits for the specification have to be elaborated to provide consistent product quality. Real time stability data have to be supplied because data from accelerated conditions do not allow extrapolation of the shelf life of proteins. Data obtained from process development and validation of the production process contributes to the preparation of the chemical pharmaceutical dossier and the expert report to be submitted to the regulatory authorities. 相似文献
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
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