大黄素-BSA不同表位构型的免疫原性和特异性研究

目的:研究不同偶联法制备大黄素-BSA的大黄素表位构型及其免疫原性和特异性。方法:用重氮化对氨基苯甲酸偶联法和琥珀酸酐偶联法制备两种不同表位构型的大黄素-BSA1和大黄素-BSA2抗原,免疫小鼠制备抗血清,用醋酸纤维素膜双向免疫扩散法检测免疫原性及其抗体特异性。结果:大黄素-BSA1和大黄素-BSA2抗血清与大黄素反应的抗体效价分别为1∶144 0±357.771和1∶440±219.089,二者有极显著性差异(P=0.006)。分别与大黄素等五种蒽醌类化合物反应,前者对大黄素有较高特异性,抗原结合效价可达1∶1 843.2±457.947。后者对大黄素的特异性较低,结合效价仅为1∶8.8±4.382。结论:两种偶联法制备大黄素-BSA的表位构型不同,其免疫原性和特异性存在着显著差异。重氮化对氨基苯甲酸偶联法制备大黄素-BSA的免疫原性较高、大黄素特异性较强。     

罗汉果甜苷V人工抗原免疫原性检测法的建立与评价

目的制备罗汉果甜苷V(mogroside V,MogV)-载体蛋白复合物人工抗原及抗血清,建立抗血清与MogV特异性反应的检测方法,为进一步制备MogV的单克隆抗体、建立快速检测MogV的ELISA法提供技术基础。方法将MogV与丁二酸酐、载体蛋白牛血清蛋白(BSA)和人血清蛋白(HSA)反应偶联,制得半抗原-载体蛋白复合物后,通过紫外扫描光谱计算出结合的半抗原数目;以此抗原免疫Balb/c小鼠,制备抗血清,并通过ELISA法检测效价和特异性。结果合成的人工抗原MogV-HS-BSA结合比约为44∶1,MogV-HS-HSA结合比约为64∶1;通过免疫小鼠得到特异性针对MogV的抗血清,血清效价较高。结论 MogV人工抗原有较好的免疫原性,建立的免疫原性检测方法简便可行。     

百草枯人工抗原的合成及抗体的制备

目的: 制备百草枯人工抗原和抗血清, 为建立酶联免疫吸附法提供技术储备.方法: 以4, 4'-联吡啶和碘甲烷为起始原料, 于暗处通氮气保护下合成了百草枯半抗原; 混合酸酐法偶联大分子蛋白载体牛血清白蛋白(BSA)和卵清蛋白(OVA)制备免疫抗原和包被抗原; 免疫新西兰大白兔, 制备多抗.结果: 合成的半抗原经HPLC-MS、 1HNMR和IR鉴定, 初步确定合成成功; 百草枯半抗原与BSA和OVA的结合比分别为19∶ 1和14∶ 1; 抗血清经间接ELISA法检测, 效价达1∶ 2.56×104, 经饱和硫酸铵沉淀法纯化后抗体的效价达1∶ 5.12×104.结论: 合成的百草枯人工抗原具有较好的免疫原性, 为百草枯酶联免疫检测(ELISA)试剂盒的研制提供了基础.     

多菌灵人工抗原的合成及其鼠源性多克隆抗体的制备

目的 合成多菌灵人工抗原,制备多菌灵多克隆抗体并鉴定其特性。方法 利用混合酸酐法引入羧基制备多菌灵半抗原。将小分子半抗原与大分子载体牛血清白蛋白(BSA)和卵清蛋白(OVA)偶联合成多菌灵人工抗原和包被抗原,利用聚丙烯酰胺凝胶电泳(SDS-PAGE)对人工抗原进行鉴定。用制备的人工抗原免疫小鼠获得抗多菌灵多克隆抗体,利用间接ELISA对抗体效价以及特异性进行测定。结果 成功制备多菌灵人工抗原。免疫小鼠后获得的抗体效价可达1∶12 800。抗体对多菌灵的半数抑制剂量(IC₅₀)为0.107μg/mL,且与苯菌灵、噻菌灵的交叉反应率均<1%。结论 成功获得高敏感性、高特异性的多克隆抗体,为多菌灵残留快速检测方法的建立奠定了基础。     

与脂质体有关的半抗原-载体复合物的免疫原性

作者研究了脂质体包被的半抗原-载体复合物在豚鼠体内的免疫原性,以了解抗原存在形式对载体的细胞免疫和对半抗原的体液免疫的影响。根据Eisen技术将人γ球蛋白(HGG)和牛血清白蛋白(BSA)二硝基苯化,形成半抗原-载体复合物DNP_(62)HGG、DNP_(55)HGG、DNP_(34)BSA和DNP_(29)BSA(DNP后的数值是一定浓度半抗原-载体复合物溶液在360nm的吸收光值)。实验根据抗原存在形式不同分为三组:溶于生理盐水的S组、包被在脂质体内的E组和与脂质体(不包被)混合的M组。结果在静脉注射200μgI)NP_(62)HGG后,12天或20天皮内注射10μgDNP_(29)BSA,E组出     

甲氰菊酯人工抗原的合成和鉴定

目的 合成与鉴定甲氰菊酯的人工抗原.方法 通过水解、酰化、酯化等反应合成了甲氰菊酯的半抗原2,2,3,3.四甲基环丙烷羧酸-a-(N-丁酸基)-甲酰氨-3-苯氧基苄酯(Ⅳ)和2,2,3,3-四甲基环丙烷羧酸-a-羧基-3-苯氧基苄酯(Ⅲ).通过碳二亚胺法将半抗原Ⅳ与牛血清蛋白(BSA)偶联制备免疫抗原,通过混合酸酐法将半抗原Ⅲ与卵清蛋白(OVA)偶联制备包被抗原.结果 用质谱和核磁共振对Ⅲ和Ⅳ进行结构表征,合成产物为目标物.紫外光谱法鉴定结果表明,免疫抗原和包被抗原都发生了有效偶联,偶联比38:1和15:1,免疫抗原通过免疫新西兰大白兔得到的抗体效价为5.12×105.结论成功的合成了甲氰菊酯的人工抗原,为其免疫方法的建立奠定了基础.     

PCB77人工抗原的合成及多克隆抗体的制备

目的:制备PCB77人工抗原和多克隆抗体,为建立其免疫学检测方法提供技术准备。方法:以3,4-二氯苯基乙酸为半抗原,在低温和弱碱性条件下,采用N-羟基琥珀酰亚胺活性酯法将其与载体BSA偶联,制备PCB77的人工抗原,计算结合比为23∶1,免疫家兔获得了PCB77的多克隆抗体。采用混合酸酐法将半抗原与OVA偶联,结合比为8∶1,用作ELISA检测包被原。间接ELISA检测结果表明,2只兔子的抗血清效价均达1∶20 000以上。抗血清经辛酸-硫酸铵沉淀法纯化后通过ELISA检测验证了PCB77人工抗原的有效性,通过方阵滴定法确定ELISA的最佳工作浓度,建立标准曲线。在0.75~300 ng/L范围内,抑制率与PCB77的质量浓度对数呈显著的线性关系,检测限达到4.44μg/L。结论:合成的PCB77人工抗原具有较好的免疫效果,纯化后的抗体符合后续实验的条件要求,为研制和开发PCB77免疫检测试剂盒奠定了基础。     

甲基对氧磷人工抗原的合成及鉴定

目的 合成甲基对氧磷（M1600）人工抗原。方法 用醋酸-锌粉盐酸还原对氧磷，制备氨基甲基对氧磷，重氮化法使氨基甲基对氧磷与牛血清白蛋白（BSA）及中国鲎血蓝蛋白（TTH）偶合，合成人工抗原M1600-BSA、M1600TTH。结果M1600-BSA免疫新西兰兔10周后，双向琼脂扩散试验和间接ELISA检测，证明得到了高价且具有较好特异性的多抗血清，结论 成功地合成了甲基对氧磷人工抗原，为其免疫分析法的建立提供了条件。     

25-羟基维生素D3人工完全抗原的合成与鉴定

目的:合成25-羟基维生素D3人工完全抗原,并制备抗25-羟基维生素D3的特异性抗体。方法:将25-羟基维生素D3进行化学修饰加入羧基活性基团,合成具有半抗原结构特征的25-羟基维生素D3-半琥珀酸酯。采用碳二亚胺法,将25-羟基维生素D3-半琥珀酸酯,分别与牛血清白蛋白(BSA)和卵清蛋白(OVA)偶联,合成人工完全抗原25-羟基维生素D3-半琥珀酸酯-BSA和25-羟基维生素D3-半琥珀酸酯-OVA。通过紫外吸收光谱,SDS-PAGE和MALDI-TOF进行偶联鉴定。用25-羟基维生素D3-半琥珀酸酯-BSA免疫小鼠,获得抗25-羟基维生素D3抗体免疫血清。结果:25-羟基维生素D3-半琥珀酸酯与BSA的偶联比为(12±0.16)∶1,免疫小鼠后获得高效价(效价为6.25×10-4)的抗体,且标准品浓度在37.5～600 ng/mL范围具有显著的竞争性线性关系,检测的灵敏度为37.5 ng/mL。结论:成功合成了25-羟基维生素D3人工完全抗原,制备出25-羟基维生素D3的抗体且其线性关系显著,灵敏度较高,为进一步研制检测25-羟基维生素D3的试剂盒奠定了基础。     

玉米赤霉烯酮半抗原及全抗原的合成与鉴定

目的:合成玉米赤霉烯酮(ZEN)半抗原及全抗原,并鉴定其是否合成成功,为制备ZEN抗体奠定基础.方法:将ZEN与羧甲氧基胺半盐酸盐(0-( carboxymethyl)hydroxylamine hemihydrochloride)反应,合成半抗原ZEN-6-羧甲氧基胺(ZEN-oxime),采用TLC、HPLC和液相-质谱联用技术进行半抗原的纯化、鉴定;通过活泼酯法将半抗原与载体蛋白偶联制备ZEN全抗原,采用紫外光谱法、TNBS法结合比的测定以及免疫学方法进行全抗原鉴定.结果:鉴定结果表明目标半抗原及全抗原合成成功.结论:本研究采用多种方法进行半抗原及全抗原的鉴定,结果皆表明目标半抗原及全抗原合成成功,说明本研究合成ZEN半抗原及人工抗原的技术路线是可行的,为进一步研制ZEN的抗体奠定良好基础.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.     

Platelet-activating factor receptor and respiratory and metabolic responses to hypoxia and hypercapnia

Activation of the platelet-activating factor receptor (PAFR) regulates neural transmission. A PAFR blocker reduced the peak hypoxic (pHVR) but not hypercapnic ventilatory (HCVR) responses in rats [Am. J. Physiol. 275 (1998) R604]. To further examine the role of PAFR in respiratory control, genotype-verified PAFR -/- and PAFR +/+ adult male mice underwent hypoxic and hypercapnic challenges. HCVR was similar in the two groups (p-NS). However, pHVR was significantly reduced in PAFR -/- mice (38 +/- 13% baseline [S.D.]) compared to PAFR +/+ mice (78 +/- 16% baseline; P < 0.001, ANOVA), with reduced tidal volume recruitments during pHVR. In addition, hypoxic ventilatory depression was attenuated in PAFR -/- mice (P < 0.01), and was primarily due to attenuation of the time-dependent decreases in oxygen consumption during sustained hypoxia (P < 0.01). Thus, PAFR expression/function modulates components of the acute ventilatory and metabolic adaptations to hypoxia but not to hypercapnia. Imbalances in PAFR activity may lead to maladaptive regulation of the tightly controlled metabolic-ventilatory relationships during hypoxia.