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排序方式: 共有339条查询结果,搜索用时 15 毫秒
1.
吡酮酸类抗菌药物的研究Ⅷ.1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其类似物的合成和构效关系 总被引:1,自引:0,他引:1
为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。 相似文献
2.
Van de Velde H; De Vos A; Joris H; Nagy ZP; Van Steirteghem AC 《Human reproduction (Oxford, England)》1998,13(11):3160-3164
In human in-vitro fertilization (IVF), the oocytes are surrounded by
cumulus and corona cells at the time of insemination so that their maturity
cannot easily be evaluated. The best IVF results are obtained if the
oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic
sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and
mechanical treatment in order to be able to perform the injection. As a
consequence, the nuclear maturity of the oocytes can be evaluated and only
those that have extruded the first polar body are injected. However,
metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot
be recognized. The purpose of this study was to investigate the effect of
different timing of cumulus- corona cell removal and injection on the
outcome of ICSI. For this we allowed the oocytes to complete in-vitro
cytoplasmic maturation in two different culture conditions: (i) surrounded
by their cumulus and corona cells or (ii) totally denuded. We performed
three different studies on sibling oocytes obtained after a standardized
buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated
the effect of early (1-2 h after retrieval) and late (5-6 h after
retrieval) oocyte denudation and injection on the survival and
fertilization of the injected oocytes and on embryo cleavage after
fertilization. We found no statistically significant differences between
early and late injection, indicating that after a standardized
buserelin/HMG protocol the metaphase-II oocytes do not need time for
further cytoplasmic maturation. Furthermore, a different timing of
cumulus-corona cell removal has no effect on the outcome of ICSI,
suggesting that the surrounding cells are not necessary for survival,
fertilization and cleavage after ICSI.
相似文献
3.
Percoll gradient centrifugation can be omitted in sperm preparation for intracytoplasmic sperm injection 总被引:4,自引:3,他引:4
De Vos A; Nagy ZP; Van de Velde H; Joris H; Bocken G; Van Steirteghem A 《Human reproduction (Oxford, England)》1997,12(9):1980-1984
Prior to intracytoplasmic sperm injection (ICSI), seminal fluid is
currently washed out from the ejaculated semen and further sperm selection
is carried out by a discontinuous Percoll gradient. Possible deleterious
effects from the sperm-separating substance Percoll on sperm function or
embryo cleavage after in-vitro fertilization (IVF) have, to our knowledge,
not yet been reported and the use of Percoll has been widely accepted in
IVF. In this study, we examined whether the omission of the Percoll step in
the sperm preparation has any influence on the outcome of the ICSI
procedure. Two methods of sperm preparation for ICSI were compared in a
controlled study on sibling oocytes: washing the semen sample once,
followed by a Percoll gradient centrifugation versus washing the sperm
sample twice without a Percoll gradient centrifugation. The mean
fertilization rates were similar for the two sperm preparation methods:
78.2 +/- 21.4 and 75.0 +/- 24.1% respectively of the intact oocytes
displaying two pronuclei. Cleavage rates did not differ statistically
between the two groups. Whereas in both groups similar percentages of
excellent, good and poor quality embryos were obtained, the percentage of
fair quality embryos was significantly higher in the group without Percoll
(16.3 +/- 20.1 versus 9.1 +/- 15.7%). However, no statistical differences
were observed in either the percentage of transferable embryos or in the
percentage of embryos actually transferred or frozen in the two groups. In
conclusion, spermatozoa from ejaculates that are washed out from the
seminal fluid without any further selection can be used for ICSI without
any adverse effect on fertilization and embryo cleavage.
相似文献
4.
5.
Targeted inactivation of αi2 or αi3 disrupts activation of the cardiac muscarinic K+ channel, IK+Ach, in intact cells
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Margaret O. Sowell Chianping Ye Dennis A. Ricupero Sherry Hansen Stephen J. Quinn Peter M. Vassilev Richard M. Mortensen 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(15):7921-7926
Cardiac muscarinic receptors activate an inwardly rectifying K+ channel, IK+Ach, via pertussis toxin (PT)-sensitive heterotrimeric G proteins (in heart Gi2, Gi3, or Go). We have used embryonic stem cell (ES cell)-derived cardiocytes with targeted inactivations of specific PT-sensitive α subunits to determine which G proteins are required for receptor-mediated regulation of IK+Ach in intact cells. The muscarinic agonist carbachol increased IK+Ach activity in ES cell-derived cardiocytes from wild-type cells, in cells lacking αo, and in cells lacking the PT-insensitive G protein αq. In cells with targeted inactivation of αi2 or αi3, channel activation by both carbachol and adenosine was blocked. Carbachol-induced channel activation was restored in the αi2- and αi3-null cells by reexpressing the previously targeted gene and guanosine 5′-[γ-thio] triphosphate was able to fully activate IK+Ach in excised membranes patches from these mutants. In contrast, negative chronotropic responses to both carbachol and adenosine were preserved in cells lacking αi2 or αi3. Our results show that expression of two specific PT-sensitive α subunits (αi2 and αi3 but not αo) is required for normal agonist-dependent activation of IK+Ach and suggest that both αi2- and αi3-containing heterotrimeric G proteins may be involved in the signaling process. Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of IK+Ach or the expression of αi2 or αi3. 相似文献
6.
7.
Polyspecificity is defined as the ability of a given antibody molecule to bind a large panel of structurally diverse antigens. A fraction of circulating IgG in all healthy individuals acquires promiscuous antigen-binding activity only after a transient exposure to certain protein destabilizing factors. The molecular mechanisms of this phenomenon are not well understood. Exposures to protein destabilizing agents are common steps in immunoglobulin isolation and purification processes. We performed kinetic and thermodynamic analyses using surface plasmon resonance-based technique in order to characterize the interactions of a single mouse monoclonal antibody to its cognate antigen before and after induction of promiscuous antigen-binding activity. The obtained results, suggest that enhanced antigen binding activity induced by exposure to mild denaturing condition resulted from an increase in the structural flexibility of the antigen-binding site. Further pH and ionic strength-dependence analyses of the antibody/antigen interactions demonstrated that the transition to promiscuous antigen-binding was accompanied by a change in the type of non-covalent forces involved in the complex formation. Moreover, from this study, it is evident that an antibody molecule could use two distinct thermodynamic pathways for binding to the same antigen while retaining the same value of the binding affinity. The obtained results may contribute to the understanding of the molecular mechanisms that lay behind natural antibody polyspecificity. 相似文献
8.
Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice 总被引:1,自引:0,他引:1
Tchorbanov AI Voynova EN Mihaylova NM Todorov TA Nikolova M Yomtova VM Chiang BL Vassilev TL 《European journal of immunology》2007,37(12):3587-3596
The pathological DNA-specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross-links their surface immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG antibody-producing cells. Intravenous infusions with the DNA-peptide antibody chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA-peptide chimeric antibody to 18 wk-old mice with full-blown disease resulted in the maintenance of a flat level of IgG anti-DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease-associated B cells in autoimmune diseases. 相似文献
9.
The process of incorporating insulin pumps into the everyday lives of people with Type 1 diabetes: A critical interpretive synthesis
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Claire Reidy MSc Mike Bracher PhD Claire Foster PhD Ivaylo Vassilev PhD Anne Rogers PhD 《Health expectations》2018,21(4):714-729
Background
Insulin pump therapy (IPT) is a technological advancement that has been developed to help people manage Type 1 diabetes (T1D). However, ways of managing diabetes requiring the implementation of health technologies bring new complexities and a need to understand the factors which enable people with T1D to incorporate a novel device. This new comprehension could provide an exemplar for people with long‐term conditions to incorporate new technologies more generally.Objective
To determine what influences the incorporation, adaptation and use of IPT into the everyday lives of people living with diabetes.Design
Critical interpretive synthesis (CIS) using systematic searches undertaken in 7 electronic databases of literature, published 2008 onwards.Results
A total of 4998 titles were identified, 274 abstracts reviewed, 39 full articles retrieved and 22 papers selected for analysis. Three themes emerged which were of relevance to the introduction and use of IPT; Tensions between expectations and experiences in adoption and early adaptation; Negotiation of responsibility and accessing support; Reflexivity, active experimentation and feedback.Conclusions
This CIS builds on earlier reviews on lived experiences of IPT. Novel insights are offered through examination of the experiences of pump users from children through to adults, their families and health‐care professionals. Expectations of what the device can do to improve self‐management impacts on the early stages of adoption as the reality of the technology requires substantial thought and action. Areas for intervention to improve IPT incorporation include establishing who is responsible for management tasks of the device and enabling navigation to further means of support and resources. 相似文献10.