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11.
Saijo K Schmedt C Su IH Karasuyama H Lowell CA Reth M Adachi T Patke A Santana A Tarakhovsky A 《Nature immunology》2003,4(3):274-279
The nature of signals that govern the development of immunoglobulin heavy chain-dependent B cells is largely unknown. Using mice deficient for the B cell-expressed Src-family protein tyrosine kinases (SFKs) Blk, Fyn and Lyn, we show an essential role of these kinases in pre-B cell receptor (pre-BCR)- mediated NF-kappaB activation and B cell development. This signaling defect is SFK specific, as a deficiency in Syk, which controls pre-B cell development, does not affect NF-kappaB induction. Impaired NF-kappaB induction was overcome by the activation of protein kinase C (PKC)-lambda, thus suggesting the involvement of PKC-lambda in pre-BCR-mediated SFK-dependent activation of NF-kappaB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development. 相似文献
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14.
C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro 总被引:1,自引:0,他引:1
We have previously shown that activated C1s complement and activated T
cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation
of desLys58 beta2m. This process can specifically be inhibited by
C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously
added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed
lymphocyte culture (MLC) increased the endogenous production of IL-2 and
the generation of allo-specific cytotoxic T lymphocytes. C1-inh was
purified from fresh human plasma and added to human or murine MLC and
mitogen-stimulated lymphocyte cultures grown in the presence of
complement-inactivated serum. Read-outs were cell proliferation, lymphokine
production and development of T cell-mediated cytotoxicity. We found that
addition of C1-inh to MLC and mitogen- exposed murine and human lymphocyte
cultures inhibited proliferation, the development of allospecific cytotoxic
activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12
and IFN-gamma. These data clearly demonstrate a regulatory function of
C1-inh on T cell- mediated immune functions.
相似文献
15.
16.
How to use Chlamydia antibody testing in subfertility patients 总被引:1,自引:9,他引:1
Screening for tubal factor subfertility by means of Chlamydia antibody
testing (CAT) was introduced into the initial work-up of subfertile couples
several years ago. The results reported, however, are heterogeneous, and no
uniformity exists in cut-off levels of titres, or in definitions of tubal
factor subfertility. We performed a prospective cohort study to evaluate
the implications of varying the definitions of tubal pathology and of
modifying the cut-off levels on the clinical impact of CAT in predicting
tubal factor subfertility. In 227 consecutive patients who attended our
fertility clinic, the Chlamydia IgG antibody titre was determined and
related to tuboperitoneal abnormalities at laparoscopy as a reference
standard. According to received operating characteristic (ROC) curve
analysis, a titre of 16 is the optimum cut-off level. Increasing the
cut-off level improves specificity and positive likelihood ratio (LR+), at
the expense of sensitivity and negative LR (LR-). Changing the definition
of tubal factor subfertility from unspecified tuboperitoneal abnormalities
into extensive adhesions and/or bilateral distal tubal occlusion improves
LR+, LR- and kappa significantly. We conclude that CAT is more accurate in
predicting severe distal tubal pathology than unspecified tuboperitoneal
abnormalities. Although from a statistical point of view a titre of 16 is
the optimum cut-off level, from a clinical point of view 32 or 64 may be
preferable, depending on the aim of screening and the inception cohort.
相似文献
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19.
Sheldon C. Siegel M.D. Roger M. Katz M.D. Gary S. Rachelefsky M.D. Milan L. Brandon M.D. Lowell A. Borgen Ph.D. 《The Journal of allergy and clinical immunology》1985,75(6):698-705
Procaterol hydrochloride, a potent beta 2-adrenergic bronchodilator developed in Japan, was evaluated in a double-blind, placebo-controlled study for efficacy and safety in 45 patients (ages 18 to 55 yr) with chronic documented reversible airway disease. After a 1-week placebo washout period, patients were administered either 0.05 mg or 0.10 mg of procaterol or placebo twice daily for 2 wk. Spirometric determinations, vital signs, and ECGs were obtained at 1/2, 1, 2, 4, 6, and 8 hr after the first dose and at the same time intervals after 1 and 2 wk of treatment. Patients recorded on a daily basis peak flow rates, asthma symptoms, need for supplemental aerosol, concurrent medications, and side effects. Spirometry results indicated significant improvement in pulmonary function with both doses of procaterol compared with placebo (P less than 0.05). The larger dose was generally more effective. Bronchodilatation was evident 1/2 hr after dosing and peaked at 2 hr. At 8 hr after 0.10 mg of procaterol, FEV1 was still above predose values. Daily peak flow rates were significantly higher with 0.10 mg than with 0.05 mg (P less than 0.05) and placebo (P less than 0.001). Tremor and nervousness were the most frequent side effects. They occurred in a dose-related frequency, were mild and transient, and occurred early in treatment. No significant drug-related changes were noted in ECGs, heart rate, blood pressure, or clinical laboratory data. Procaterol was found to be an effective, well-tolerated oral bronchodilator with a long duration of action, especially at 0.10 mg twice daily. 相似文献
20.
Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle 总被引:1,自引:1,他引:1
Balasch J; Creus M; Fabregues F; Civico S; Reverter JC; Carmona F; Tassies D; Vanrell JA 《Human reproduction (Oxford, England)》1998,13(5):1180-1183
Increased antiphospholipid antibody prevalence has been demonstrated by a
number of recent studies in in-vitro fertilization (IVF) patients but the
potential effects of antiphospholipid antibodies on the different
components of the reproductive process and the consideration of whether to
test IVF patients for antiphospholipid antibodies are controversial. The
present study was undertaken to investigate the possible association
between the presence of circulating antiphospholipid antibodies (namely the
lupus anticoagulant and anticardiolipin antibodies), among a series of 21
consecutive IVF patients having a clinical spontaneous abortion after their
first embryo transfer. As a control group (n=42), the nearest IVF cycle
resulting in an ongoing pregnancy before and after each miscarried IVF
cycle (i.e. the closest cycles in temporal relationship to the index cycle)
was used. One patient (4.8%) in the study group and two women (4.8%) among
controls were seropositive for antiphospholipid antibodies. These low and
similar seropositivity rates found in the two groups studied lead us to
conclude that antiphospholipid antibodies testing in IVF patients should be
considered only in those women having repeated failures of
implantation/clinical abortion after embryo transfer but not in an
infertile general population reaching an IVF programme.
相似文献