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The failure to show a necessary role for C3 in the in vitro antibody response.

The in vitro antibody response of mouse spleen cells to TNP coupled to both T-dependent and T-independent carriers as well as to sheep erythrocytes has been studied to investigate the possible role of complement activation in the induction of antibody formation. The following has been found. (1) In vitro responses of both IgM and IgG can be obtained to both T-dependent and T-independent antigens in serum-free media, although they are smaller than those found in serum-containing media. This shows that no exogenous source of complement is necessary for in vitro antibody formation by spleen cells. (2) Similarly, normal antibody responses are obtained if the cultures are grown in human serum depleted of C3b-inactivator, which contains high concentrations of C3b. (3) In the presence of antibody to mouse C3 the response to the T-independent antigen is reduced, the IgM responses being more affected than the IgG. However, purified F(ab')2 anti-C3 has no inhibitory effect and it therefore seems likely that it is the formation of intact immune complexes containing Fc rather than the interference with C3 function that is responsible for the inhibition seen. (4) The conventionally purified anti-complementary factor from cobra venom has no effect on the antibody response in serum-free culture or when human or fetal calf sera are used. In no experiment was any potentiation of T-dependent responses observed. However, the presence of quite small concentrations (2%) of cobra veno

Animals↗

Causative role of oxyradicals in myocardial stunning: a proven hypothesis. A brief review of the evidence demonstrating a major role of reactive oxygen species in several forms of postischemic dysfunction.

Whether or not ROS are the actual initiator or a downstream mediator of stunning, the theory that they play a major causative role in this phenomenon is now a proven hypothesis. ROS play a prominent role in multiple forms of stunning. Furthermore, the role of ROS is prominent not only in open-chest models but also in conscious animal preparations. The major challenge for future studies will be to identify the specific molecular targets of ROS-mediated damage and to decipher the pathways whereby ROS and calcium interact in the genesis of myocardial stunning.

Animals↗

Psychological sequelae of infertility treatment: the role of gender and sex-role identification.

Infertility has traditionally been viewed as a female problem and women have been expected to suffer greater psychological distress due to infertility. This paper investigates the nature of gender differences and sex-role identification in the psychological sequelae associated with infertility treatment. The expectation that infertile women experience higher distress levels than men was not supported by these data. No gender differences were observed in either the level of emotional strain, marital adjustment, or sexual satisfaction for the 104 couples studied. However, gender differences were apparent in factors associated with psychological distress, suggesting that while the level of strain might be comparable, the experience of infertility is different for men and women. Sex-role identification was found to have a greater relationship to the indices of distress than gender. Masculinity was associated with lower emotional strain and greater marital satisfaction for both genders and enhanced sexual satisfaction for men. Femininity was related to enhanced marital and sexual satisfaction for both genders. Gender differences and sex-role identification are discussed in the context of the unique experience of infertility.

Female↗

Role of O(2)-sensitive K(+) and Ca(2+) channels in the regulation of the pulmonary circulation: potential role of caveolae and implications for high altitude pulmonary edema.

High altitude pulmonary edema (HAPE) is a potentially fatal complication in response to exposure to low O(2) at high altitudes. Hypoxia, by causing pulmonary vasoconstriction, increases pulmonary vascular resistance and pulmonary arterial pressure, both of which are features in the pathogenesis of HAPE. Uneven hypoxic pulmonary vasoconstriction is thought to be responsible for increased capillary pressure and leakage, resulting in edema. O(2)-sensitive ion channels are known to play pivotal roles in determining vascular tone in response to hypoxia. K(+), Ca(2+) and Na(+) channels are ubiquitously expressed in both endothelial and smooth muscle cells of the pulmonary microvasculature, subfamilies of which are regulated by local changes in P(O(2)). Hypoxia reduces activity of voltage-gated K(+) channels and down-regulates their expression leading to membrane depolarization, Ca(2+) influx in pulmonary artery smooth muscle cells (by activating voltage-dependent Ca(2+) channels) and vasoconstriction. Hypoxia up-regulates transient receptor potential channels (TRPC) leading to enhanced Ca(2+) entry through receptor- and store-operated Ca(2+) channels. Altered enrichment of ion channels in membrane microdomains, in particular in caveolae, may play a role in excitation-contraction coupling and perhaps in O(2)-sensing in the pulmonary circulation and thereby may contribute to the development of HAPE. We review the role of ion channels, in particular those outlined above, in response to low O(2) on vascular tone and pulmonary edema. Advances in the understanding of ion channels involved in the physiological response to hypoxia should lead to a greater understanding of the pathogenesis of HAPE and perhaps in the identification of new therapies.

Altitude Sickness↗

Galectin-1 plays essential roles in adult mammalian nervous tissues. Roles of oxidized galectin-1.

Previous data have suggested that galectin-1 is expressed widely in nervous tissues at embryonic stages but becomes restricted mainly to peripheral nervous tissues with maturation. Though the expression is intense in adult mammalian peripheral neurons, there had been no report about functions of galectin-1 there. Recently we discovered a factor that enhanced peripheral axonal regeneration. The factor was identified as oxidized galectin-1 with three intramolecular disulfide bonds and showed no lectin activity. Oxidized recombinant human galectin-1 (rhGAL-1/Ox) showed the same nerve growth promoting activity at very low concentrations (pg/ml). rhGAL-1/Ox at similarly low concentration was also effective in in vivo experiments of axonal regeneration. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited the axonal regeneration in vivo as well as in vitro. Since galectin-1 is expressed in the regenerating sciatic nerves as well as in both sensory neurons and motor neurons, these results suggest that galectin-1 is secreted into the extracellular space to be oxidized, and then, in its oxidized form, to regulate initial repair after axotomy. The administration of oxidized galectin-1 effectively promoted functional recovery after sciatic nerve injury in vivo. Oxidized galectin-1, hence, appears to play an important role in promoting axonal regeneration, working as a kind of cytokine, not as a lectin. Recent reports indicated additional roles of cytosolic galectin-1 in neural diseases, such as ALS. Furthermore galectin-1 has been proved to be a downstream target of DeltaFosB. In hippocampus of rat brain, expression of DeltaFosB is induced immediately after ischemia-reperfusion, suggesting that galectin-1 may also play important roles in central nervous system after injury.

Animals↗

Role delineation study of pediatric nurse practitioners: a national study of practice responsibilities and trends in role functions.

INTRODUCTION: This study explored the current practice responsibilities of pediatric nurse practitioners (PNPs) from a national perspective Educational preparation, geographic region of practice, years of employment as a PNP, type of employment setting, and full-time versus part-time employment were examined. METHOD: From a randomly selected sample (N = 997), a total of 387 respondents returned their questionnaire, resulting in 325 usable questionnaires. RESULTS: Years of experience as a PNP, setting of employment, geographic region, prescriptive authority, and subspecialty practice were significantly related to various health supervision and illness-focused activities performed by PNPs, as well as level of management responsibility. Anticipatory guidance supervision continues to be an integral part of the PNP role. PNPs report that they assume major responsibility for the health assessment and management of children with common pediatric illnesses as well as chronic illnesses and conditions. DISCUSSION: The ability to prescribe prescription medications produced the greatest overall effect on PNP role activities and level of management responsibility. Years of experience exerted an interesting effect on role functions related to the overall health supervision and illness-focused activities in which PNPs engaged. Implications for the educational preparation of PNPs, the updating of national certification examinations, and planning for adequate numbers in the workforce to replace the cohort of retiring PNPs in the next 20 years are discussed.

Adult↗

ATP binding to the first nucleotide binding domain of multidrug resistance-associated protein plays a regulatory role at low nucleotide concentration, whereas ATP hydrolysis at the second plays a dominant role in ATP-dependent leukotriene C4 transport.

Multidrug resistance-associated protein (MRP1) transports solutes in an ATP dependent manner by utilizing its two nonequivalent nucleotide binding domains (NBDs) to bind and hydrolyze ATP. The two NBDs possess different properties (Gao, M., Cui, H. R., Loe, D. W., Grant, C. E., Almquist, K. C., Cole, S. P., and Deeley, R. G. (2000) J. Biol. Chem. 275, 13098-13108; Hou, Y., Cui, L., Riordan, J. R., and Chang, X. (2000) J. Biol. Chem. 275, 20280-20287) and may play different roles during solute transport. We now report that NBD1 has moderately higher affinity for ATP than NBD2. The consequence of this difference is that the overall Kd value for wild-type MRP1 is mainly determined by ATP binding at NBD1. This conclusion is supported by the following: 1) mutation of the cysteine residue at 682 to alanine (C682A) in Walker A motif in NBD1 decreases the Kd value, indicating increased affinity for ATP; 2) mutation of the alanine residue at 1331 to cysteine (A1331C) in the Walker A motif of NBD2 does not have an effect on the Kd value; and 3) photolabeling of the protein with a cysteine residue in the Walker A motif of NBD1 is much more sensitive to N-ethylmaleimide modification than the protein with a cysteine residue in the Walker A motif of NBD2. In contrast, the Km for ATP in support of LTC4 transport is mainly determined by ATP hydrolysis at NBD2. This conclusion is supported by the following: 1) although mutation of A1331C does not have an effect on the Kd value, the Km values measured from LTC4 transport by proteins with this mutation in NBD2 are much higher than the proteins with wild-type NBD2, implying that the A1331C mutation affects ATP binding/hydrolysis at NBD2; and 2) ATP-dependent LTC4 transport by the protein with a cysteine residue in the Walker A motif of NBD2 is much more sensitive to N-ethylmaleimide modification than the protein with a cysteine residue in the Walker A motif of NBD1. Our previous results indicated that ATP binding at NBD1 at low concentration enhanced ATP binding/hydrolysis at NBD2. All of these results support the notion that ATP binding at NBD1 at low concentration plays a more important regulatory role than the binding at high ATP concentration and that ATP hydrolysis at NBD2 plays a dominant role in the ATP-dependent LTC4 transport.

Adenosine Triphosphate↗

Science-based solutions to obesity: what are the roles of academia, government, industry, and health care?

The complexity of the obesity epidemic requires the cooperation of key stakeholders in this effort. No one sector, academia, government, industry, or health care, has been successful in combating this disease to date. On March 10-11, 2004, The Harvard Medical School Division of Nutrition hosted the symposium "Science-Based Solutions to Obesity: What is the Role of Academia, Government, Industry, and Health care?" as a platform to address the role of these stakeholders, both individually and collectively, in combating the nation's epidemic of obesity. The proceedings from the symposium, included in this supplement, discuss the following: the science of obesity-related topics such as genetics, protein and weight loss, portion size, energy density, and behavior; the need for more aggressive government policies; industry's role in using research and development capabilities to promote healthier, portion-controlled products; and how to translate nutrition information from medical doctors to patients.

Academic Medical Centers↗

The role of generic and disease-specific measures of physical and role functioning in assessing patient outcomes: a longitudinal study.

Using longitudinal data from the Veterans Health Study (VHS), we extended our earlier published cross-sectional analysis in comparing the generic SF-36 physical functioning (PF) and role limitations (role-physical [RP]) scales with the disease-specific PF and RP scales using disease attributions. The present study included 569 patients with chronic lung disease (CLD) and 352 patients with chronic low back pain (LBP) who received Veterans Affairs (VA) ambulatory care between June 1993 and March 1996. Consistent with our earlier study, we found that changes in the generic PF and RP scales had higher correlations with the other generic SF-36 scales than those in the disease-specific PF and RP scales over 12 months. On the other hand, disease-specific measures of PF and RP had larger R and t statistic values in discriminating the impacts of symptom-based illness severity as well as clinical services on physical and role functioning. These results suggest that the generic and disease-specific measures of PF and RP behave distinctly different from each other over time. The generic measures of PF and RP tend to assess a broad array of health-related quality of life, whereas disease-specific attributions of PF and RP scales tend to evaluate disease progression and clinical management associated with specific disease conditions. Disease-specific attribution is an important alternative to the development of new disease-specific instruments for assessing illness severity and the impact of clinical services.

Adult↗

P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion.

Fexofenadine is a selective, nonsedating H(1)-receptor antagonist approved for symptoms of allergic conditions, which is mainly excreted into feces via biliary excretion. The purpose of this study is to investigate its pharmacokinetics in mice and rats to determine the role of P-glycoprotein (P-gp) in its biliary excretion. In mice, biliary excretion clearance (17 ml/min/kg) accounted for almost 60% of the total body clearance (30 ml/min/kg). Comparing the pharmacokinetics after intravenous and oral administration indicated that the bioavailability of fexofenadine was at most 2% in mice. Knockout of Mdr1a/1b P-gp did not affect the biliary excretion clearance with regard to both plasma and liver concentrations, whereas the absence of P-gp caused a 6-fold increase in the plasma concentration after oral administration. In addition, the steady-state brain-to-plasma concentration ratio of fexofenadine was approximately 3-fold higher in Mdr1a/1b P-gp knockout mice than in wild-type mice. Together, these results show that P-glycoprotein plays an important role in efflux transport in the brain and small intestine but only a limited role in biliary excretion in mice. In addition, there was no difference in the biliary excretion between normal and hereditarily multidrug resistance-associated protein 2 (Mrp2)-deficient mutant rats (Eisai hyperbilirubinemic rats) and between wild-type and breast cancer resistance protein (Bcrp) knockout mice. These results suggest that the biliary excretion of fexofenadine is mediated by unknown transporters distinct from P-gp, Mrp2, and Bcrp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cardiovascular reactivity in a simulated job interview: the role of gender role self-concept.

This study investigated the relation of gender role self-concept (G-SC) to cardiovascular and emotional reactions to an ecologically relevant stressor in a sample of graduating male and female university students. Thirty-seven men and 37 women completed the Personal Attribute Questionnaire and worked on four tasks designed to reflect common features of a job interview. Blood pressure and heart rate were measured at baseline, during, and after each task; subjective stress was measured at baseline and after each task. Subjective and objective stress scores were averaged across tasks and analyzed by sex and G-SC (i.e., instrumentality, expressiveness). Results indicated that women as a group demonstrated greater emotional reactivity, but did not differ in their physiological reactions when compared to men. Regardless of sex, participants' instrumentality scores contributed significantly to the variation in subjective stress response: those scoring high on instrumentality reported less stress, but evidenced greater blood pressure reactivity than those scoring low on instrumentality. These results suggest that gender roles, particularly an instrumental self-concept, may play an important role in both subjective and objective reactions to an ecologically relevant stressor.

Affect↗

Sex-role self-perceptions and sex-role stereotypes.

827 undergraduate students, 549 males and 278 females, responded to a set of 18 questions relating to individual self-perceptions. A second group of 35 males and 29 females responded to the questions in terms of population sex-role stereotypes for both sexes. It was hypothesized that the sexes would demonstrate convergence in self-perceptions when compared with their sex-role stereotypes. The results tended to support the hypothesis, with females demonstrating a greater deviation from the traditional sex-role stereotypes than males. The possible relationship to much publicized social movements was noted.

Behavior↗

Role reward and role stress in managerial and professional women.

The importance of balancing personal and work demands has become increasingly relevant in recent years as large numbers of women move into the labour market full time. The present study was designed to examine differences in role rewards and stress amongst a group of 163 managerial and professional women. Subjects completed a questionnaire about the stress and rewards associated with their work and family roles. Although no significant differences were found between managerial and professional women, the mean scores indicated the role of employee is both the most rewarding and the most stressful. Findings are discussed in terms of sample occupation and changing home-work patterns.

Adult↗

Sex roles and street roles.

A proposed typology of the street roles of female addicts was tested through interviews with 62 female addicts. Five role types are identified which are distinct from one another and exhaust the range of roles reported by respondents. A number of limitations to the typology are isolated and discussed.

Crime↗

Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response.

The mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), and p38, are activated in response to infectious agents and innate immune stimulators such as CpG DNA, and regulate the subsequent initiation and termination of immune responses. CpG DNA activates p38 and ERK with slightly different kinetics in monocytic cells. The present studies investigated the roles of these two key mitogen-activated protein kinases in regulating the CpG DNA-induced production of pro- and anti-inflammatory cytokines in the macrophage-like cell line RAW264.7. p38 activity was essential for the induction of both IL-10 and IL-12 expression by CpG DNA. In contrast, CpG DNA-mediated ERK activation was shown to suppress IL-12 production, but to be essential for the CpG DNA-induced IL-10 production. Studies using rIL-10 and IL-10 gene-deficient mice demonstrated that the inhibitory effect of ERK on CpG DNA-mediated IL-12 production is indirect, due to the role of ERK in mediating IL-10 production. These results demonstrate that ERK and p38 differentially regulate the production of pro- and anti-inflammatory cytokines in APCs that have been activated by CpG DNA. CpG DNA-induced p38 activity is required for the resulting innate immune activation. In contrast, ERK plays a central negative regulatory role in the CpG DNA-mediated Th1 type response by promoting production of the Th2 type cytokine, IL-10.

Adjuvants, Immunologic↗

[The 3 palatine fibromucous membranes. Their role in maxillary growth. Therapeutic role in surgery of the palatine shelves].

The palatine fibromucosa is not the same throughout the various regions of the palatine vault and its role differs in maxillary growth. On can in fact distinguish: --the fibromucosa of the "palatine lamellae", thin and smooth, which occupies only the median and posterior portion of the vault, opposite the nasal fossae. Its importance derives from the fact that it covers the medio-palatine and palatino-vomerian suture complex, which has an essential role in transverse, vertical and also sagital maxillary growth; --the palatine maxillary fibromucosa, thick and striated, which surrounds the above as far as the gingiva. It plays a major role in transverse and vertical maxillary growth. In fact, it would appear that it possesses autonomous growth potential; --the "gingival" fibromucosa, smooth, which is located at the alveolar level (from the palatine maxillary to the gingivo-dental border) and is involved in the structure of the latter. A good understanding of the anatomical and physiological aspects of these three fibromucosae has a therapeutic relevance, in particular, in subjects suffering from congenital velo-palatine defects (isolated or associated with a labio-maxillary defect).

Cleft Lip↗

Antithrombotic therapy: role of platelet-inhibitor drugs. I. Current concepts of thrombogenesis: role of platelets. (first of three parts).

Definite evidence has confirmed that platelets play a major role in thrombus formation and embolization, especially in the arterial system. In addition, increasing evidence has now shown that platelet deposition and thrombus formation can contribute to the growth and progression of atherosclerotic plaques. For these reasons, considerable attention has been focused recently on the question of whether drugs that inhibit certain platelet functions can prevent or modify the course of arterial thromboembolic disease and atherosclerotic disease in humans. In this first part, we review the current understanding of the role of platelets in thrombus formation, especially in the arterial system. This section comprises (1) the phases of arterial thrombus formation and its ultrastructural and biochemical basis, (2) the clinicopathologic presentation and fate of the arterial thrombus, and (3) the role of laboratory tests in its detection.

Animals↗

Ideal sex roles for children and acceptance of variation from stereotypic sex roles.

In a sample of 50 child psychology students, 40% preferred that there be no differences between male and female children on 14 personality characteristics, while 60% preferred differences resembling current sex role stereotypes. For the latter students there was some preference for dominance, aggression, autonomy, exhibition, heterosexuality, and achievement to be more characteristic of males, and order, succorance, deference, nurturance, and abasement to be more characteristic of females. Both groups observed male and female peers describing themselves in a manner appropriate or not appropriate to current stereotypes. The students with a stated preference for no sex role difference among children did in fact express a more equal attraction to male or female peers whether they depicted sex appropriate or inappropriate roles.

Achievement↗