共查询到20条相似文献,搜索用时 15 毫秒
1.
James A. Cracknell Annemarie F. Wait Oliver Lenz B?rbel Friedrich Fraser A. Armstrong 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(49):20681-20686
In biology, rapid oxidation and evolution of H2 is catalyzed by metalloenzymes known as hydrogenases. These enzymes have unusual active sites, consisting of iron complexed by carbonyl, cyanide, and thiolate ligands, often together with nickel, and are typically inhibited or irreversibly damaged by O2. The Knallgas bacterium Ralstonia eutropha H16 (Re) uses H2 as an energy source with O2 as a terminal electron acceptor, and its membrane-bound uptake [NiFe]-hydrogenase (MBH) is an important example of an “O2-tolerant” hydrogenase. The mechanism of O2 tolerance of Re MBH has been probed by measuring H2 oxidation activity in the presence of O2 over a range of potential, pH and temperature, and comparing with the same dependencies for individual processes involved in the attack by O2 and subsequent reactivation of the active site. Most significantly, O2 tolerance increases with increasing temperature and decreasing potentials. These trends correlate with the trends observed for reactivation kinetics but not for H2 affinity or the kinetics of O2 attack. Clearly, the rate of recovery is a crucial factor. We present a kinetic and thermodynamic model to account for O2 tolerance in Re MBH that may be more widely applied to other [NiFe]-hydrogenases. 相似文献
2.
3.
Volbeda A Amara P Darnault C Mouesca JM Parkin A Roessler MM Armstrong FA Fontecilla-Camps JC 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(14):5305-5310
The crystal structure of the membrane-bound O(2)-tolerant [NiFe]-hydrogenase 1 from Escherichia coli (EcHyd-1) has been solved in three different states: as-isolated, H(2)-reduced, and chemically oxidized. As very recently reported for similar enzymes from Ralstonia eutropha and Hydrogenovibrio marinus, two supernumerary Cys residues coordinate the proximal [FeS] cluster in EcHyd-1, which lacks one of the inorganic sulfide ligands. We find that the as-isolated, aerobically purified species contains a mixture of at least two conformations for one of the cluster iron ions and Glu76. In one of them, Glu76 and the iron occupy positions that are similar to those found in O(2)-sensitive [NiFe]-hydrogenases. In the other conformation, this iron binds, besides three sulfur ligands, the amide N from Cys20 and one Oε of Glu76. Our calculations show that oxidation of this unique iron generates the high-potential form of the proximal cluster. The structural rearrangement caused by oxidation is confirmed by our H(2)-reduced and oxidized EcHyd-1 structures. Thus, thanks to the peculiar coordination of the unique iron, the proximal cluster can contribute two successive electrons to secure complete reduction of O(2) to H(2)O at the active site. The two observed conformations of Glu76 are consistent with this residue playing the role of a base to deprotonate the amide moiety of Cys20 upon iron binding and transfer the resulting proton away, thus allowing the second oxidation to be electroneutral. The comparison of our structures also shows the existence of a dynamic chain of water molecules, resulting from O(2) reduction, located near the active site. 相似文献
4.
Wang PH Blumberger J 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(17):6399-6404
[NiFe]-hydrogenases are fascinating biological catalysts with potential application in biofuel cells. However, a severe problem in practical application is the strong sensitivity of hydrogenase to gaseous inhibitor molecules such as CO and O(2). Recently, a number of successful protein engineering studies have been reported that aimed at lowering the access of diatomic inhibitors to the active site pocket, but the molecular mechanism conferring increased resistance remained unclear. Here we use a multiscale simulation approach combining molecular dynamics with a master equation formalism to explain the steady drop in CO diffusion rate observed for the mutants V74M L122A, V74M L122M, and V74M of Desulfovibrio fructosovorans [NiFe]-hydrogenase. We find that diffusion in these variants is controlled by two gates, one between residues 74 and 476 and the other between residues 74 and 122. The existence of two control points in different locations explains why the reduction in the experimental diffusion rate does not simply correlate with the width of the main gas channel. We also find that in the more effective mutation (V74M) CO molecules are still able to reach the active site through transitions that are gated by the microsecond dihedral motions of the side chain of R476 and the thermal fluctuations of the width of the gas channel defined by M74 and L122. Reflecting on the molecular information gained from simulation, we discuss future mutation experiments that could further lower the diffusion rates of small ligands inhibiting [NiFe]-hydrogenase. 相似文献
5.
Pandelia ME Nitschke W Infossi P Giudici-Orticoni MT Bill E Lubitz W 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(15):6097-6102
Iron-sulfur clusters are versatile electron transfer cofactors, ubiquitous in metalloenzymes such as hydrogenases. In the oxygen-tolerant Hydrogenase I from Aquifex aeolicus such electron “wires” form a relay to a diheme cytb, an integral part of a respiration pathway for the reduction of O2 to water. Amino acid sequence comparison with oxygen-sensitive hydrogenases showed conserved binding motifs for three iron-sulfur clusters, the nature and properties of which were unknown so far. Electron paramagnetic resonance spectra exhibited complex signals that disclose interesting features and spin-coupling patterns; by redox titrations three iron-sulfur clusters were identified in their usual redox states, a [3Fe4S] and two [4Fe4S], but also a unique high-potential (HP) state was found. On the basis of 57Fe Mössbauer spectroscopy we attribute this HP form to a superoxidized state of the [4Fe4S] center proximal to the [NiFe] site. The unique environment of this cluster, characterized by a surplus cysteine coordination, is able to tune the redox potentials and make it compliant with the [4Fe4S]3+ state. It is actually the first example of a biological [4Fe4S] center that physiologically switches between 3+, 2+, and 1+ oxidation states within a very small potential range. We suggest that the (1 + /2+) redox couple serves the classical electron transfer reaction, whereas the superoxidation step is associated with a redox switch against oxidative stress. 相似文献
6.
Summary From an urban population (n=9,033) of 47–49-year-old males, 6,956 participated in a multiphase screening programme, of whom 1.5% were already registered as diabetic patients, 1.7% were then found to be diabetic; of 6,325 subjects given oral glucose tolerance tests, 6.6% were found to have impaired glucose tolerance (WHO criteria, 1985). In 889 asymptomatic cases with initial capillary whole blood glucose values 6.6 mmol/l fasting and/or 2 h postload, fluctuation in oral glucose tolerance was studied at repeat tests within one month; the mean differences in glucose values between the first and second test were <–1% (fasting) and –15% (2 h post-load); there were no differences in body weight, and 62% of those with initially impaired glucose tolerance had normalised by the repeat test. Only in 109 cases (1.7%) were 2 h post-load values in the 7.8–11.0 mmol/l range both at the first and the repeat test; these cases were comparable vis-à-vis body mass index, triceps skin fold, blood pressure and initial glucose and insulin values, but had significantly lower oxygen uptake (2.34±0.54 l/min vs 2.63±0.681/min; p<0.003), as compared with subjects with initially impaired glucose tolerance but normal repeat test outcome. However, subjects with high normal first test results (2 h value in the 7.0–7.7 mmol/l range) and second test results in the 7.0–11.0 mmol/l range, resembled those with persistent impairment of glucose tolerance in all respects (including oxygen uptake). The repeat test procedure (including ergometry), is therefore to be recommended in selecting true risk cases. 相似文献
7.
Pedro Dinis Daniel L. M. Suess Stephen J. Fox Jenny E. Harmer Rebecca C. Driesener Liliana De La Paz James R. Swartz Jonathan W. Essex R. David Britt Peter L. Roach 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(5):1362-1367
Hydrogenases use complex metal cofactors to catalyze the reversible formation of hydrogen. In [FeFe]-hydrogenases, the H-cluster cofactor includes a diiron subcluster containing azadithiolate, three CO, and two CN− ligands. During the assembly of the H cluster, the radical S-adenosyl methionine (SAM) enzyme HydG lyses the substrate tyrosine to yield the diatomic ligands. These diatomic products form an enzyme-bound Fe(CO)x(CN)y synthon that serves as a precursor for eventual H-cluster assembly. To further elucidate the mechanism of this complex reaction, we report the crystal structure and EPR analysis of HydG. At one end of the HydG (βα)8 triosephosphate isomerase (TIM) barrel, a canonical [4Fe-4S] cluster binds SAM in close proximity to the proposed tyrosine binding site. At the opposite end of the active-site cavity, the structure reveals the auxiliary Fe-S cluster in two states: one monomer contains a [4Fe-5S] cluster, and the other monomer contains a [5Fe-5S] cluster consisting of a [4Fe-4S] cubane bridged by a μ2-sulfide ion to a mononuclear Fe2+ center. This fifth iron is held in place by a single highly conserved protein-derived ligand: histidine 265. EPR analysis confirms the presence of the [5Fe-5S] cluster, which on incubation with cyanide, undergoes loss of the labile iron to yield a [4Fe-4S] cluster. We hypothesize that the labile iron of the [5Fe-5S] cluster is the site of Fe(CO)x(CN)y synthon formation and that the limited bonding between this iron and HydG may facilitate transfer of the intact synthon to its cognate acceptor for subsequent H-cluster assembly.The assembly of the [FeFe]-hydrogenase diiron subcluster (1, 2) requires three maturase proteins, HydE, HydF, and HydG (3), and in vitro, they can assemble an active hydrogenase (4). The sequence and structure of the maturase HydE (5) indicates that it is a member of the radical S-adenosyl methionine (SAM) superfamily, although the biochemical function of HydE has not been experimentally determined. The GTPase HydF (6, 7) has been shown to transfer synthetic (8) or biologically derived (7, 9) diiron subclusters into apo-hydrogenase, suggesting that HydF functions as a template for diiron subcluster assembly. The tyrosine lyase HydG is also a member of the radical SAM superfamily and uses SAM and a reductant (such as dithionite) to cleave the Cα–Cβ bond of tyrosine, yielding p-cresol as the side chain-derived byproduct (10) and fragmenting the amino acid moiety into cyanide (CN−) (11) and carbon monoxide (CO) (12), which are ultimately incorporated as ligands in the H cluster of the [FeFe]-hydrogenase HydA (4). Two site-differentiated [4Fe-4S] clusters in HydG have been identified using a combination of spectroscopy and site-directed mutagenesis (12–16). The cluster bound close to the N terminus ([4Fe-4S]RS) by the CX3CX2C cysteine triad motif (SI Appendix, Fig. S1) is typical of the radical SAM superfamily (17, 18) and has been shown to catalyze the reductive cleavage of SAM (11, 13). The resultant highly reactive 5′-deoxyadenosyl radical is thought to abstract a hydrogen atom from tyrosine, thereby inducing Cα–Cβ-bond homolysis with release of dehydroglycine (DHG) and the spectroscopically characterized 4-oxidobenzyl radical anion (16), which is quenched to yield p-cresol (Fig. 1A, step A). The second (auxiliary) Fe-S cluster is proposed to promote the conversion of DHG into CO and CN− (Fig. 1A, step B) (13, 16). Two intermediates have been observed by stopped-flow IR spectroscopic analysis (19): an enzyme-bound organometallic species (complex A) (Fig. 1A, 4) that converts to a species that features an Fe(CO)2(CN) moiety (complex B) (Fig. 1A, 5). These results, combined with 57Fe electron-nuclear double resonance (ENDOR) studies that showed that iron from HydG is incorporated into mature hydrogenase, led to the proposal that an organometallic synthon with a minimum stoichiometry of [Fe(CO)2CN] is synthesized at the auxiliary cluster of HydG and eventually transferred to apo-hydrogenase (19).Open in a separate windowFig. 1.Overall [FeFe]-hydrogenase H-cluster assembly and structure of TiHydG. (A) Formation of the Fe(CO)2CN synthon is proposed to occur at the auxiliary cluster of HydG (square brackets). (B) Overall fold of HydG with an end-on view of the TIM barrel showing the radical SAM core (green), the N-terminal extension (pink), and the C-terminal extension (blue). Monomer A is shown and contains a [4Fe-4S] cluster to catalyze the formation of the 5′-deoxyadenosyl radical from SAM and a [5Fe-5S] auxiliary cluster proposed to promote the conversion of DHG into cyanide and carbon monoxide. (C) The position of the two Fe-S clusters in TiHydG. The strands of the TIM barrel are shown. The orientation is rotated 90° from B.Herein, we report the crystal structure of Thermoanaerobacter italicus HydG (TiHydG) complexed with SAM (the Protein Data Bank ID code for the structure of HydG is 4WCX). The structure, which contains two HydG monomers per asymmetric unit, reveals the auxiliary Fe-S cluster in two states: one monomer contains a [4Fe-5S] cluster, and the other monomer contains a structurally unprecedented [5Fe-5S] cluster consisting of a [4Fe-4S] cubane bridged by a μ2-sulfide to a mononuclear Fe(II) center (which we term the labile iron). To supplement the crystallographic studies of TiHydG, we also report EPR spectroscopic studies of Shewanella oneidensis HydG (SoHydG) that provide solution-state characterization of the [5Fe-5S] cluster and show its conversion to a [4Fe-4S] cluster in the presences of exogenous cyanide. Taken together, these results support a proposed mechanism for [FeFe]-hydrogenase maturation in which the labile iron of the [5Fe-5S] cluster is the site for Fe(CO)x(CN)y synthon assembly. 相似文献
8.
Summary Plasma glucose, immunoreactive insulin, and growth hormone (GH) have been estimated during morning (AM) and afternoon (PM) oral glucose tolerance tests (GTT) in a group of 22 subjects, 13 of whom were young women receiving combined oestrogen-progestogen oral contraceptives. Impaired PM glucose tolerance with associated delay and impairment of insulin secretion has been confirmed, as has the inverse correlation between obesity and diurnal GTT variation. Diurnal changes in GH are unlikely to be responsible for this circadian GTT rhythm. Patients on oral contraceptives continue to show a normal GTT rhythm, so that a mildly abnormal AM test is likely to be associated with a more severely diabetic PM test. These observations indicate that while obesity and oral contraceptive use may have metabolic features in common, they differ in this respect; they support the view that, if possible, carbohydrate tolerance should be monitored in women taking oral contraceptives in whom a tendency to diabetes is suspected. 相似文献
9.
Satoshi Watanabe Takumi Kawashima Yuichi Nishitani Tamotsu Kanai Takehiko Wada Kenji Inaba Haruyuki Atomi Tadayuki Imanaka Kunio Miki 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(25):7701-7706
The Ni atom at the catalytic center of [NiFe] hydrogenases is incorporated by a Ni-metallochaperone, HypA, and a GTPase/ATPase, HypB. We report the crystal structures of the transient complex formed between HypA and ATPase-type HypB (HypBAT) with Ni ions. Transient association between HypA and HypBAT is controlled by the ATP hydrolysis cycle of HypBAT, which is accelerated by HypA. Only the ATP-bound form of HypBAT can interact with HypA and induces drastic conformational changes of HypA. Consequently, upon complex formation, a conserved His residue of HypA comes close to the N-terminal conserved motif of HypA and forms a Ni-binding site, to which a Ni ion is bound with a nearly square-planar geometry. The Ni binding site in the HypABAT complex has a nanomolar affinity (Kd = 7 nM), which is in contrast to the micromolar affinity (Kd = 4 µM) observed with the isolated HypA. The ATP hydrolysis and Ni binding cause conformational changes of HypBAT, affecting its association with HypA. These findings indicate that HypA and HypBAT constitute an ATP-dependent Ni acquisition cycle for [NiFe]-hydrogenase maturation, wherein HypBAT functions as a metallochaperone enhancer and considerably increases the Ni-binding affinity of HypA.Approximately one-half of all cellular proteins require specific metal ions for proper function, which are delivered by specific metallochaperones (1, 2). However, the mechanisms of correct acquisition and delivery to target proteins of many metallochaperones remain poorly understood. [NiFe] hydrogenases harbor a complex metal cofactor, NiFe(CN)2CO, in their active sites (3). This cofactor catalyzes reversible H2 production. The Ni atom in the NiFe(CN)2CO cofactor is bound to four thiolate groups, two of which also bridge the Fe(CN)2CO group (4, 5). NiFe(CN)2CO biosynthesis requires specific maturation machinery, in which six Hyp proteins (HypA–HypF) play key roles (6, 7). Four Hyp proteins (HypC–HypF) are involved in the biosynthesis and incorporation of the Fe(CN)2CO group (8–15). After Fe insertion, HypA and HypB insert the Ni ion into the hydrogenase large subunit (16).HypA is a Ni-metallochaperone that binds to a Ni ion with micromolar affinity (17–19), and its structure consists of a Ni-binding domain (NiBD) and a Zn-binding domain (ZnBD) (20, 21). The NiBD contains a highly conserved MHE motif that is essential for Ni binding at the N terminus (20, 22). HypB consists of a common GTPase domain and a less conserved metal-binding region (23–25). Recently, ATPase-type HypB (HypBAT, previously abbreviated as mmHypB) proteins were identified from Thermococcales (26). GTPase and ATPase types of HypB belong to the SIMIBI class NTPase family and share a similar architecture, despite their low sequence similarity (27). HypA and HypB form a transient complex in the Ni insertion process (17, 22, 28, 29). In the Escherichia coli system, Ni transfer occurs from HypB to HypA (30). However, the functional relationship between HypA and HypB or HypBAT for the maturation process is not fully understood. Here, we determined the crystal structures of the HypA–HypBAT complex from Thermococcus kodakarensis, providing the structural basis of concerted actions of these proteins for Ni insertion in the [NiFe]-hydrogenase maturation process. 相似文献
10.
11.
Tao Feng 《Gut microbes》2020,12(1)
ABSTRACT Lactic acid bacteria (LAB) are the most frequently used probiotics in fermented foods and beverages and as food supplements for humans or animals, owing to their multiple beneficial features, which appear to be partially associated with their antioxidant properties. LAB can help improve food quality and flavor and prevent numerous disorders caused by oxidation in the host. In this review, we discuss the oxidative stress tolerance, the antioxidant capacity related herewith, and the underlying mechanisms and signaling pathways in probiotic LAB. In addition, we discuss appropriate methods used to evaluate the antioxidant capacity of probiotic LAB. The aim of the present review is to provide an overview of the current state of the research associated with the oxidative stress tolerance and antioxidant capacity of LAB. 相似文献
12.
Pool DH Stewart MP O'Hagan M Shaw WJ Roberts JA Bullock RM Dubois DL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(39):15634-15639
The electrocatalytic reduction of protons to H2 by (where in the highly acidic ionic liquid dibutylformamidium bis(trifluoromethanesulfonyl)amide shows a strong dependence on added water. A turnover frequency of 43,000–53,000 s-1 has been measured for hydrogen production at 25 °C when the mole fraction of water (χH2O) is 0.72. The same catalyst in acetonitrile with added dimethylformamidium trifluoromethanesulfonate and water has a turnover frequency of 720 s-1. Thus, the use of an ionic liquid/aqueous solution enhances the observed catalytic rate by more than a factor of 50, compared to a similar acid in a traditional organic solvent. Complexes (X = H, OMe,CH2P(O)(OEt)2, Br) are also catalysts in the ionic liquid/water mixture, and the observed catalytic rates correlate with the hydrophobicity of X. 相似文献
13.
Yacoby I Pochekailov S Toporik H Ghirardi ML King PW Zhang S 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(23):9396-9401
Photosynthetic water splitting, coupled to hydrogenase-catalyzed hydrogen production, is considered a promising clean, renewable source of energy. It is widely accepted that the oxygen sensitivity of hydrogen production, combined with competition between hydrogenases and NADPH-dependent carbon dioxide fixation are the main limitations for its commercialization. Here we provide evidence that, under the anaerobic conditions that support hydrogen production, there is a significant loss of photosynthetic electrons toward NADPH production in vitro. To elucidate the basis for competition, we bioengineered a ferredoxin-hydrogenase fusion and characterized hydrogen production kinetics in the presence of Fd, ferredoxin:NADP(+)-oxidoreductase (FNR), and NADP(+). Replacing the hydrogenase with a ferredoxin-hydrogenase fusion switched the bias of electron transfer from FNR to hydrogenase and resulted in an increased rate of hydrogen photoproduction. These results suggest a new direction for improvement of biohydrogen production and a means to further resolve the mechanisms that control partitioning of photosynthetic electron transport. 相似文献
14.
15.
目的探讨去卵巢大鼠血清中活性氧及抗氧化体系的变化,为临床早期诊断及治疗骨质疏松提供依据。方法选用4月龄清洁级SD大鼠20只,随机分为正常对照组和模型组。模型组行双侧卵巢切除术,对照组行假手术。三个月后测量两组大鼠体重、子宫湿重、左侧股骨及腰椎骨密度、左侧股骨生物力学及血清生化指标Ca2 、肌酐(Cr)、碱性磷酸酶(ALP)、抑制OH能力、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的水平。结果模型组与对照组相比,体重明显增加,股骨及腰椎骨密度均降低,股骨生物力学特性最大载荷降低,子宫湿重降低,血清Ca2 、ALP、MDA、Cr水平升高,抑制OH能力、SOD、GSH-Px水平降低,差异有统计学意义(P<0.05)。结论血清中活性氧及抗氧化成分羟自由基、SOD、MDA及GSH-Px等可能参与了绝经后骨质疏松的病理进程。 相似文献
16.
From the Cover: A [Cu2O]2+ core in Cu-ZSM-5, the active site in the oxidation of methane to methanol
Julia S. Woertink Pieter J. Smeets Marijke H. Groothaert Michael A. Vance Bert F. Sels Robert A. Schoonheydt Edward I. Solomon 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(45):18908-18913
Driven by the depletion of crude oil, the direct oxidation of methane to methanol has been of considerable interest. Promising low-temperature activity of an oxygen-activated zeolite, Cu-ZSM-5, has recently been reported in this selective oxidation and the active site in this reaction correlates with an absorption feature at 22,700 cm−1. In the present study, this absorption band is used to selectively resonance enhance Raman vibrations of this active site. 18O2 labeling experiments allow definitive assignment of the observed vibrations and exclude all previously characterized copper-oxygen species for the active site. In combination with DFT and normal coordinate analysis calculations, the oxygen activated Cu core is uniquely defined as a bent mono-(μ-oxo)dicupric site. Spectroscopically validated electronic structure calculations show polarization of the low-lying singly-occupied molecular orbital of the [Cu2O]2+ core, which is directed into the zeolite channel, upon approach of CH4. This induces significant oxyl character into the bridging O atom leading to a low transition state energy consistent with experiment and explains why the bent mono-(μ-oxo)dicupric core is highly activated for H atom abstraction from CH4. The oxygen intermediate of Cu-ZSM-5 is now the most well defined species active in the methane monooxygenase reaction. 相似文献
17.
Summary Daily physical activity, work capacity, relative body weight and glucose tolerance were studied in 115 normoglycaemic 48 year old men selected from a health screening programme. In contrast to the reported physical activity at work, leisure time activity was significantly related to maximal oxygen uptake (p < 0.05), glucose (p < 0.05) and insulin values (p < 0.05) during OGTT, but not to relative body weight. The number of men with impaired glucose tolerance (glucose at 120 min > 6.9mmol) was significantly higher among those who were physically inactive during their leisure time. The insulin glucose ratio at 0 and 120 min during the OGTT was significantly higher in the obese unfit as compared to the obese fit subjects thus suggesting an influence of moderate leisure time physical activity on glucose tolerance. 相似文献
18.
目的 探讨65岁以上病人冠状动脉搭桥术中局部脑氧饱和度(regional cerebral oxygen saturation,rSO2)的变化与术后神经功能障碍的关系.方法 随机选择择期冠状动脉搭桥手术病人358例,按年龄分为≥65岁组和<65岁组.术中应用经颅脑氧饱和度仪(transcranial cerebral oximetry,TCCO)和经颅多普勒超声,对所有病人的rSO2变化和大脑中动脉的栓子数量进行了持续监测,将术中rSO2<50%定为低rSO2.术后3~4 d进行神经功能评估.结果 两组主动脉阻断时间、体外循环时间、栓子数量和rSO2基础值无明显差异.≥65岁组低rSO2和术后神经功能障碍发生率明显高于<65岁组.两组中低rSO2者术后神经功能障碍发生率明显高于正常rSO2者.结论 65岁以上病人冠状动脉搭桥术中易发生低tSO2,这可能与术后神经功能障碍发生率较高有关. 相似文献
19.
20.
Achievement of immune tolerance in a patient with haemophilia B and inhibitory antibodies, complicated by an anaphylactoid reaction 总被引:1,自引:1,他引:0
Summary. We describe a young boy with severe haemophilia B who developed inhibitory antibodies and an anaphylactoid reaction to factor IX. Immune tolerance was achieved by desensitisation with escalating doses of factor IX followed by the Malmö regimen. 相似文献