慢性肾炎患者血清sIL—2R和IL—8的变化及意义

本研究用ＥＬＩＳＡ双抗体夹心法对慢性肾炎肾功能不全各期患者血清ｓＩＬ－２Ｒ和ＩＬ－８水平进行了测定。结果显示：（１）肾功能不全代偿期ｓＩＬ－２Ｒ水平显著高于健康人，提示此期存在Ｔ细胞异常活化。（２）氮质血症期ｓＩＬ－２Ｒ水平显著高于健康人和代偿期，与Ｓｃｒ呈显著正相关提示血清ｓＩＬ－２Ｒ水平可作为肾小球肾炎恶化的重要指标。     

肝硬化患者血清透明质酸含量与sIL－2R水平的观察

本文用放射免疫测定法及双抗体夹心法测定了２５例健康人，３０例肝硬化患者血清透明质酸（ＨＡ）的含量及可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平。结果表明：（１）肝硬化组血清ＨＡ含量及ｓＩＬ－２Ｒ水平均高于对照组（Ｐ值均＜０．０１）；（２）肝硬化组血清ＨＡ与ｓＩＬ－２Ｒ水平间呈正相关关系（ｒ＝０．５１９２，Ｐ＜０．０１）。提示：肝硬化组患者血清ｓＩＬ－２Ｒ水平增高与肝损害程度有关，可能是由于肝细胞受损而对ＳＩＬ－２Ｒ清除能力降低所致。     

sIL－2R释放与T细胞活化的相关性研究

本实验利用双抗体夹心ＥＬＩＳＡ、流式细胞测量术及淋巴细胞增殖试验观察了可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）释放与细胞膜ＩＬ－２受体（ｍＩＬ－２Ｒ）表达及淋巴细胞增殖反应的相关性。结果显示：①在不更换培养液的情况下，ＰＨＡ刺激的淋巴细胞培养上清中的ｓＩＬ－２Ｒ释放与ｍＩＬ－２Ｒ表达在７２ｈ内呈正相关（ｒ＝０．９４．Ｐ＜０．０５）；之后，ｍＩＬ－２Ｒ的表达逐渐减少，而ｓＩＬ－２Ｒ水平则继续缓慢增加。呈负相关（ｒ＝－０．９６．ｐ＜０．０５）；②在不同细胞浓度及不同ＰＨＡ浓度时，ｓＩＬ－２Ｒ释放与淋巴细胞增殖反应呈正相关（ｒ＝０．９６．ｐ＜０．０５；ｒ＝０９９．ｐ＜０．０１）；③１４位恶性肿瘤患者的ＰＨＡ刺激末梢血淋巴细胞培养上清中ｓＩＬ－２Ｒ水平与淋巴细胞增殖反应呈正相关（ｒ＝０．８６．ｐ＜０．０１）．上述结果提示：在培养７２ｈ内，ｓＩＬ－２Ｒ水平可反映ｍＩＬ－２Ｒ的表达状态；通过测定培养上清中ｓＩＬ－２Ｒ水平可间接了解淋巴细胞增殖情况。     

人巨细胞病毒感染对肾移植受者血清sIL－2R水平的影响

用ＰＣＲ检测ＨＣＭＶ－ＤＮＡ，ＥＬＩＳＡ法检测ＨＣＭＶ－ＩｇＭ及ＩｇＧ，以诊断肾移植受者ＨＣＭＶ感染。用双抗体夹心法ＥＬＩＳＡ检测６５例肾移植受者血清ｓＩＬ－２Ｒ水平，结果表明：ＨＣＭＶ感染后宿主血清ｓＩＬ－２Ｒ水平明显增高（Ｐ＜０．０１），且ＨＣＭＶ疾病组ｓＩＬ－２Ｒ增高程度大于无症状感染组（Ｐ＜０．０１）；６例原发性ＨＣＭＶ感染者ｓＩＬ－２Ｒ水平与ＩｇＭ水平呈正相关（ｒ＝０．９９０８），提示随感染程度增加，血清ｓＩＬ－２Ｒ水平随之增高，还发现血清ｓＩＬ－２Ｒ水平与Ｃ９４／ＣＤ８比值是负相关（ｒ＝－０．９７８９），说明ＨＣＭｖ感染后ｓＩＬ－２Ｒ水平增高与Ｔ细胞亚群改变有关，反之也说明ｓＩＬ－２Ｒ增高程度可表明体内免疫抑制状态。对于ＨＣＭＶ感染后血清ｓＩＬ－２Ｒ水平增高的机理有待进一步探讨。     

IL－2和sIL－2R在哮喘发病中的意义探讨

为了探讨ＩＬ－２和ｓＩＬ－２Ｒ在哮喘发病中的意义，对３６例哮喘患者外周血单个核细胞（ＰＢＭＣ）诱生ＩＬ－２水平和血浆ｓＩＬ－２Ｒ水平进行了检测，同时以支气管炎患者与正常人作对照。结果表明，ＰＢＭｃ诱生的ＩＬ－２活性哮喘组高于正常对照组（ｐ＜０．０５）；血浆ｓＩＬ－２Ｒ水平哮喘组高于支气管炎和正常组（ｐ＜０．０１），后两者差异无显著性。以上结果表明，哮喘发病中存在着Ｔ细胞的活化，ＩＬ－２／ＩＬ－２Ｒ在哮喘发病中起作用。     

尿路感染患者血清和尿sIL—2R水平的变化及其意义

应用ＥＬＩＳＡ双抗体夹心法检测尿路感染（ＵＴＩ）患者血清和尿ｓＩＬ－２Ｒ水平。结果显示：①膀胱炎患者血清和尿ｓＩＬ－２Ｒ水平显著低于健康人（Ｐ〈０．０５），提示免疫细胞功能低下可能产ＵＴＩ的易感因素之一。②急性肾盂肾炎（ＡＰＮ）患者血清和尿ｓＩＬ－２Ｒ水平显著高于健康人（Ｐ〈０．０５），提示Ｔ细胞参与了ＡＰＮ机体防御。③慢性肾盂肾炎（ＣＰＮ）患者血清ｓＩＬ－２Ｒ水平显著高于ＡＰＮ组和健康人（分别为     

肝硬化患者清透明质酸含量与sIL—2R水平的观察

本文用放射免疫测定法及双抗体夹心法测定了２５例健康人，３０例肝硬化患者血清透明质酸（ＨＡ）的含量及可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平。结果表明：（１）肝硬化组血清ＨＡ含量及ｓＩＬ－２Ｒ水平间呈正相关关系（ｒ＝０．５１９２，Ｐ〈０．０１）。提示：肝硬化组患者血清ｓＩＬ－２Ｒ水平增高与肝损害程度有关，可能是由于肝细胞受损而对ｓＩＬ－２Ｒ清除能力降低所致。     

肝炎肝硬化患者血清sIL—6R和sgp130变化的研究

为了探讨肝炎肝硬化（ＨＣ）患者血清可溶性白介素６受体（ｓＩＬ－６Ｒ）和可溶性ｇｐ１３０（ｓｇｐ１３０）含量的变化及其临床意义，运用酶联免疫吸附法检测了３４例ＨＣ患者血清ｓＩＬ－６Ｒ和ｓｇｐｌ３０含量。结果表明：①活动性和静止性ＨＣ患者血清ｓＩＬ－６Ｒ和ｓｇｐ１３０水平均高于正常对照（Ｐ＜０．０１），ｓＩＬ－６Ｒ／ｓｇｐ１３０比值ＨＣ患者低于正常人，活动性ＨＣ患者低于静止性ＨＣ患者（Ｐ＜０．０１）；②血清ｓＩＬ－６Ｒ和ｓｇｐ１３０水平之间呈正相关（ｒ＝０．４１７，Ｐ＜０．０５），ｓＩＬ－６Ｒ、ｓｇｐｌ３０水平与血清Ｂｉｌ－Ｔ水平间亦呈正相关（分别为ｒ＝０．４７４，ｒ＝０．４８２，Ｐ＜０．０１），而与血清ＡＬＴ水平无明显相关性（分别为ｒ＝０．１９３，ｒ＝０．１５２，Ｐ＞０．０５）。提示：血清ｓＩＬ－６Ｒ、ｓｇｐ１３０与ＨＣ的病情演变有关     

sIL－2R在肝癌患者血清中的高度表达

本文应用ＥＬＩＳＡ双抗体夹心法检测了正常人和早期、晚期肝癌患者血清中可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平。结果表明：肝癌患者血清ｓＩＬ－２Ｒ水平明显高于正常人（Ｐ＜０．０１）．早期肝癌患者治疗前后其ｓＩＬ－２Ｒ水平差异显著（Ｐ＜０．０５），从而提示血清中ｓＩＬ－２Ｒ高表达现象可能为肝癌早期诊断、疗效判断及病情转归提供重要的参考价值；同时提供了本地区人血清中ｓＩＬ－２Ｒ水平正常参考标准。     

人胎儿脾胸腺细胞培养上清sIL－2R的分析

应用ＥＬＩＳＡ双抗体夹心法分析了不同胎龄脾、胸腺细胞培养上清和血清ｓＩＬ－２Ｒ的变化。结果显示：（１）胎儿脾、胸腺细胞体外在ｒＩＬ－２和抗ＣＤ３刺激下，上清中可产生高水平的ｓＩＬ－２Ｒ。并且随培养时间的延长显著增高（Ｐ＜０．０１）；（２）胎儿脾细胞培养上清ＳＩＬ－２Ｒ明显高于胸腺（Ｐ＜０．０１）；（３）胎儿血清ｓＩＬ－２Ｒ显著高于成人，并随胎龄的增大逐步下降．胎龄与ｓＩＬ－２Ｒ水平呈负相关。结果提示：ｓＩＬ－２Ｒ不仅是胎儿淋巴细胞活化的标志，还可能在淋巴细胞分化、成熟过程中发挥免疫调节作用。胎儿血清ｓＩＬ－２Ｒ增高并随胎龄成熟而下降，推测可能参与胚胎期免疫耐受。     

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.