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At least 163 records · Page 9Linked to original sources

Phosphoramidon inhibits the conversion of big ET-1 into ET-1 in the pithed rat and in isolated perfused rat kidneys.

Endothelin-1 (ET-1) is a powerful renal vasoconstrictor peptide that could be implicated in acute renal failure. The aim of this study was to test the effects of the endothelin-converting enzyme (ECE) inhibitor phosphoramidon on pressor responses to ET-1 and its precursor, big ET-1, in isolated perfused rat kidneys and in pithed rats. In Tyrode-perfused rat kidneys, both big ET-1 (0.2-0.4 nmol) and ET-1 (0.01-0.03 nmol) evoked dose-dependent constrictions. Phosphoramidon (10 microM) selectively inhibited the pressor responses to big ET-1 without altering those to ET-1, norepinephrine, angiotensin I (AT-I), or angiotensin II (AT-II). The metalloprotease inhibitor thiorphan, but not the angiotensin-converting enzyme (ACE) inhibitor perindoprilate, also selectively inhibited the renal constrictions caused by big ET-1 but not those induced by ET-1. In vivo, both big ET-1 and ET-1 (0.5-2 nmol/kg) evoked pressor responses that were augmented by indomethacin (15 mg/kg) and L-NNA (1 mg/kg/min). Phosphoramidon selectively inhibited the pressor responses to big ET-1 (ID50: 78 micrograms/kg/min) without affecting those to ET-1, AT-I, or AT-II. These data illustrate that the pressor responses to big ET-1 in the rat, both in vivo and in vitro, are due to its conversion into ET-1 by a phosphoramidon-sensitive ECE. In the rat, phosphoramidon selectively inhibits ECE but not ACE both in vitro and in vivo.

Angiotensin I↗

The Big-Fish-Little-Pond Effect for Academic Self-Concept, Test Anxiety, and School Grades in Gifted Children.

This study reports data extending work by Marsh and colleagues on the "big-fish-little-pond effect" (BFLPE). The BFLPE hypothesizes that it is better for academic self-concept to be a big fish in a little pond (gifted student in regular reference group) than to be a small fish in a big pond (gifted student in gifted reference group). The BFLPE effect was examined with respect to academic self-concept, test anxiety, and school grades in a sample of 1020 gifted Israeli children participating in two different educational programs: (a) special homogeneous classes for the gifted and (b) regular mixed-ability classes. The central hypothesis, deduced from social comparison and reference group theory, was that academically talented students enrolled in special gifted classes will perceive their academic ability and chances for academic success less favorably compared to students in regular mixed-ability classes. These negative self-perceptions, in turn, will serve to deflate students' academic self-concept, elevate their levels of evaluative anxiety, and result in depressed school grades. A path-analytic model linking reference group, academic self-concept, evaluative anxiety, and school performance, was employed to test this conceptualization. Overall, the data lend additional support to reference group theory, with the big-fish-little-pond effect supported for all three variables tested. In addition, academic self-concept and test anxiety were observed to mediate the effects of reference group on school grades. Copyright 1999 Academic Press.

Journal Article↗

Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension.

STUDY OBJECTIVES: Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology that is characterized by a poor prognosis. This study was undertaken to investigate possible correlations between endothelin (ET)-1 and big ET-1 plasma levels and the severity of PPH. PATIENTS: Sixteen consecutive patients with PPH were included. INTERVENTIONS: Hemodynamics of patients with PPH were measured by right-heart catheterization, and a 6-min walk test was performed. MEASUREMENTS: Plasma levels of the biologically active peptide ET-1 and its precursor big ET-1 were determined in blood samples from the pulmonary artery, peripheral artery, and peripheral vein by radioimmunoassay. RESULTS: A strong correlation was shown between pulmonary vascular resistance, mean pulmonary artery pressure, cardiac output, cardiac index, 6-min walk data, and elevated plasma levels of big ET-1 as well as mature ET-1 plasma levels at all sites of blood sampling (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Levels of circulating ET-1 might become a prognostic marker for patients with PPH and serve as a tool for the selection of patients who may benefit from treatment with ET-receptor antagonists.

Adult↗

What is beyond the big five?

Previous investigators have proposed that various kinds of person-descriptive content--such as differences in attitudes or values, in sheer evaluation, in attractiveness, or in height and girth--are not adequately captured by the Big Five Model. We report on a rather exhaustive search for reliable sources of Big Five-independent variation in data from person-descriptive adjectives. Fifty-three candidate clusters were developed in a college sample using diverse approaches and sources. In a nonstudent adult sample, clusters were evaluated with respect to a minimax criterion: minimum multiple correlation with factors from Big Five markers and maximum reliability. The most clearly Big Five-independent clusters referred to Height, Girth, Religiousness, Employment Status, Youthfulness and Negative Valence (or low-base-rate attributes). Clusters referring to Fashionableness, Sensuality/Seductiveness, Beauty, Masculinity, Frugality, Humor, Wealth, Prejudice, Folksiness, Cunning, and Luck appeared to be potentially beyond the Big Five, although each of these clusters demonstrated Big Five multiple correlations of .30 to .45, and at least one correlation of .20 and over with a Big Five factor. Of all these content areas, Religiousness, Negative Valence, and the various aspects of Attractiveness were found to be represented by a substantial number of distinct, common adjectives. Results suggest directions for supplementing the Big Five when one wishes to extend variable selection outside the domain of personality traits as conventionally defined.

Female↗

Gender-related individual differences and the structure of vocational interests: the importance of the people-things dimension.

In 3 studies (respective Ns = 289, 394, and 1,678), males and females were assessed on Big Five traits, masculine instrumentality (M), feminine expressiveness (F), gender diagnosticity (GD), and RIASEC (Realistic, Investigative, Artistic, Social, Enterprising, Conventional) vocational interest scales. Factor analyses of RIASEC scores consistently showed evidence for D.J. Prediger's (1982) People-Things and Ideas-Data dimensions, and participants' factor scores on these dimensions were computed. In all studies Big Five Openness was related to Ideas-Data but not to People-Things. Gender was strongly related to People-Things but not to Ideas-Data. Within each sex, GD correlated strongly with People-Things but not with Ideas-Data. M, F, and Big Five measures other than Openness tended not to correlate strongly with RIASEC scales or dimensions. The results suggest that gender and gender-related individual differences within the sexes are strongly linked to the People-Things dimension of vocational interests.

Adolescent↗

[The role and place of serologic research in the system of epidemiologic surveillance of meningococcal infection].

The results of serological surveys, carried out with a view to the detection of capsular meningococcal polysaccharides in the passive hemagglutination (PHA) test and covering 1,289 patients with systemic meningococcal infection, 221 patients with bacteriologically confirmed meningococcal nasopharyngitis, 2,820 persons in organized groups of children and adults with different epidemiological situation (including 650 carriers) and 4,050 residents of 8 cities with different morbidity levels, were analyzed. The patients, the carriers and the members of organized groups underwent multiple surveys. As shown in this study, the confirmation of the meningococcal etiology of the systemic forms of meningococcal infection (meningitis, meningococcemia) in all cases with the exception of children under 1 year of age, as well as the determination of the groups of meningococci, could be achieved in the PHA test twice as frequently, i.e. in 60-70% of cases, as with the use of the bacteriological method. The same regularities were observed in nasopharyngitis. The conclusion was made on the possibility of using the PHA test for more exact determination of the group of meningococci, prevailing at the initial stage of diseases, this determination playing an essential role in the epidemiological surveillance. The data obtained as the result of serological surveys in organized groups may lead to conclusions on the circulation of meningococci and their group composition, thus showing the necessity of profound epidemiological study with ensuring epidemic-control measures. The selective serological study of some hundreds of donor sera is not expedient in big cities, as it provides no data on the circulation of meningococci there.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗

Directional biases in back trajectories caused by model and input data.

Back trajectory analyses are often used for source attribution estimates in visibility and other air quality studies. Several models and gridded meteorological datasets are readily available for generation of trajectories. The Big Bend Regional Aerosol and Visibility Observational (BRAVO) tracer study of July to October 1999 provided an opportunity to evaluate trajectory methods and input data against tracer concentrations, particulate data, and other source attribution techniques. Results showed evidence of systematic biases between the results of different back trajectory model and meteorological input data combinations at Big Bend National Park during the BRAVO. Most of the differences were because of the choice of meteorological data used as input to the trajectory models. Different back trajectories also resulted from the choice of trajectory model, primarily because of the different mechanisms used for vertical placement of the trajectories. No single model or single meteorological data set was found to be superior to the others, although rawinsonde data alone are too sparse in this region to be used as the only input data, and some combinations of model and input data could not be used to reproduce known attributions of tracers and simulated sulfate.

Air Pollutants↗

Promoting successful youth mentoring relationships: a preliminary screening questionnaire.

Youth mentoring programs are an increasingly popular intervention, and although successful mentoring relationships can promote a range of positive developmental outcomes, relationships that fail can lead to decrements in a youth's functioning and self-esteem. The present research develops and validates a youth mentoring relationship quality inventory, based on data from a national evaluation of Big Brothers Big Sisters (BBBS) mentoring programs (N = 347 youth). This tool can be administered to adolescents who have been assigned mentors in order to assess the quality of the relationship as it is forming and to identify dyads that may need additional support before those relationships fail. Implications of such a tool for mentoring interventions and research are discussed. Editors' Strategic Implications: Reliability and validity data are presented for a measure of youth's perceptions of the quality of their mentoring relationship. This measure shows promise as a tool for research and evaluation of a wide array of mentoring programs due to its brevity, demonstrated psychometrics, and straightforward focus on the mentoring relationship.

Adaptation, Psychological↗

Macroprolactinemia in childhood and adolescence: a cause of hyperprolactinemia.

Human prolactin consists of multiple forms of different sizes including three major prolactin (PRL) species, termed as little, big, and big-big PRL. If serum contains big-big PRL, it is termed macroprolactinemia; no symptoms of hyperprolactinemia develop due to low biological activity of big-big PRL. There are still few data regarding macroprolactinemia in children and adolescents. In this paper we describe six patients with macroprolactinemia, one of whom was asymptomatic and the other five either had headache, menstrual disturbance, short stature, increased hair growth or early puberty, compatible with high PRL levels. Two of the cases had microadenoma. Initial mean +/- SD PRL levels of the patients were 75.2 +/- 22.8 ng/ml (range: 42.3-105.2 ng/ml). Macroprolactin analysis revealed big-big PRL levels of the patients ranging between 21.6-98.6 ng/ml. It was noteworthy that bromocriptine (BRC) therapy started in three patients caused an abrupt decrease in PRL levels. It may be concluded that macroprolactinemia should be taken into account in the differential diagnosis of hyperprolactinemia in childhood and adolescence, whether or not they have relevant clinical symptoms.

Adenoma↗

Challenges to the standard model of Big Bang nucleosynthesis.

Big Bang nucleosynthesis provides a unique probe of the early evolution of the Universe and a crucial test of the consistency of the standard hot Big Bang cosmological model. Although the primordial abundances of 2H, 3He, 4He, and 7Li inferred from current observational data are in agreement with those predicted by Big Bang nucleosynthesis, recent analysis has severely restricted the consistent range for the nucleon-to-photon ratio: 3.7 </= eta10 </= 4.0. Increased accuracy in the estimate of primordial 4He and observations of Be and B in Pop II stars are offering new challenges to the standard model and suggest that no new light particles may be allowed (N(BBN)nu </= 3.0, where Nnu is the number of equivalent light neutrinos).

Journal Article↗

Activation measurement of the 3He(alpha,gamma)7Be cross section at low energy.

The nuclear physics input from the 3He(alpha,gamma)7Be cross section is a major uncertainty in the fluxes of 7Be and 8B neutrinos from the Sun predicted by solar models and in the 7Li abundance obtained in big-bang nucleosynthesis calculations. The present work reports on a new precision experiment using the activation technique at energies directly relevant to big-bang nucleosynthesis. Previously such low energies had been reached experimentally only by the prompt-gamma technique and with inferior precision. Using a windowless gas target, high beam intensity, and low background gamma-counting facilities, the 3He(alpha,gamma)7Be cross section has been determined at 127, 148, and 169 keV center-of-mass energy with a total uncertainty of 4%. The sources of systematic uncertainty are discussed in detail. The present data can be used in big-bang nucleosynthesis calculations and to constrain the extrapolation of the 3He(alpha,gamma)7Be astrophysical S factor to solar energies.

Journal Article↗

Inhibitor potencies and substrate preference for endothelin-converting enzyme-1 are dramatically affected by pH.

Phosphoramidon has been shown to inhibit endothelin-converting enzyme-1 (ECE-1) in a remarkably pH-dependent manner (Ahn et al. Arch Biochem Biophys 1998;359:258-68). In order to determine whether this dramatic pH-dependence is a general phenomenon of ECE-1, two structurally unrelated ECE-1 inhibitors, PD 069185 and CGS 31447, were tested for ECE-1 inhibition at various pH values. Our data indicate that the potencies of these ECE-1 inhibitors are also highly affected by pH. ECE-1 is known to have a very sharp activity optimum at neutral pH which is in marked contrast to the acidic pH optimum for ECE-2. However, our results show that the pH optimum for ECE-1 activity is highly substrate-dependent. ECE-1 hydrolyzes the small peptide hormones bradykinin and substance P with acidic pH optima of 5.6-5.8, which sharply contrasts the neutral pH optimum with big ET-1 as substrate. These data suggest that the substrate preference for ECE-1 is highly affected by pH and that this pH-dependence for substrate preference might be one way of controlling the specificity of the enzyme in vivo.

Aspartic Acid Endopeptidases↗

Sandwich-type enzyme immunoassay for big endothelin-I in plasma: concentrations in healthy human subjects unaffected by sex or posture.

A sandwich-type enzyme immunoassay has been developed for measuring human big endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH-terminus fragment was used as an immobilized antibody (anti-P16). The Fab' fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase. The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1, <0.4% cross-reactivity with big endothelin-2 (big ET-2), and <0.1% with big endothelin-3 (big ET-3). We used this assay to evaluate the effect of two different postural positions (supine and standing) on plasma big ET-1 concentrations in 11 male and 11 female healthy subjects. Data analysis revealed that neither sex nor body position influenced plasma big ET-1 concentrations. This assay should thus permit the detection of possible variations in plasma concentrations of big ET-1 in certain pathologies and, in association with ET-1 assay, make possible in vitro study of endothelin-converting enzyme activity in cell models. Such studies could clarify the physiological and clinical roles of this family of peptides.

Adolescent↗

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction.

OBJECT: The central role of endothelin (ET)-1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ET(A) receptor antagonists. Clazosentan is a selective ET(A) receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ET(A) receptor-mediated contraction in the cerebrovasculature. METHODS: Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E-) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10(-9), 10(-8), and 10(-7) M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E-) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E-). CONCLUSIONS: The present data characterize clazosentan as a potent competitive antagonist of ET(A) receptor-mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Animals↗

Endothelin in septic patients: effects on cardiovascular and renal function and its relationship to proinflammatory cytokines.

OBJECTIVE: To determine the time course of big-endothelin (big-ET) and its relationship to proinflammatory cytokines and organ function in sepsis. DESIGN: Prospective analysis in patients meeting criteria of severe sepsis as part of a multicenter study (RAMSES) with an anti-tumor necrosis factor monoclonal antibody F(ab')2 fragment (afelimomab). SETTING: University hospital intensive care unit. PATIENTS: A total of 23 nontrauma patients with severe sepsis or septic shock and ten multiple trauma patients. Septic patients were randomized for additional experimental treatment when initial interleukin (IL)-6 serum level was above 1000 pg/mL. INTERVENTIONS: Randomized patients received 1.0 mg/kg afelimomab or placebo three times daily over 3 days in addition to standard treatment. In each patient, serial blood samples for plasma big-ET and cytokine determination as well as clinical data were collected over 28 days. MEASUREMENTS AND MAIN RESULTS: Significantly increased concentrations of circulating big-ET were found in patients with severe sepsis as compared with healthy subjects. In septic patients, big-ET plasma levels were higher than in multiple trauma patients, and were more elevated in randomized than in nonrandomized patients. At study entry (day 0), big-ET reached a peak concentration and significantly correlated with IL-6 (r2 = .43) and IL-8 (r2 = .44) in patients with severe sepsis. Moreover, big-ET levels in septic patients, pooled over all observation days, correlated positively with pressure-adjusted heart rate, central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance and correlated inversely with creatinine clearance (r2 = .54, .54, .59, .40, and .51, respectively, p = .0001). In all randomized septic patients, pressure-adjusted heart rate decreased from day 0 to day 2 in parallel with big-ET; however, a significant decrease in big-ET (day 0 to day 2) was only found in patients additionally treated with afelimomab. CONCLUSIONS: In patients with severe sepsis, big-ET plasma levels are markedly increased, even above those of multiple trauma patients, in close relationship to IL-6 and IL-8, and with significant correlation to renal function and pulmonary vascular tone.

Adult↗

[Digital archiving of imaged heart catheter studies on CD-R. Detection of irreversible CD damage].

The digital archiving has great advantages compared to the standard 35-mm X-ray cinefilm documentation. The data are immediately available and quantitative coronary angiography possible. In addition the technical progress is enhancing the availability of data. The loss of films is nearly eliminated, as only copies of the digital archive data are delivered. In addition a big advantage concerning pollution is present, when CD Rs are used. We report about the damage of CD Rs after 89, 162, 181 and 252 days when they were stored in polypropylene material containing envelopes. The damaged CD Rs all belonged to the provider Verbatim, whereas CD Rs of the provider Rank Xerox or Kodak were never damaged. In contrary to the Verbatim company, Rank Xerox gave written confirmation for 10-year storage and a written confirmation, that the storage in the polypropylene envelopes is possible. Mechanical, thermal damage and damage by humidity have to be discussed as well as chemical interactions of the CD Rs surface with the polypropylene material. As the digital storage for X-ray images has to be provided for 10 years in Germany, it is concluded, that the storage in polypropylene envelopes has to be avoided, when a written confirmation by the company is not given. These observations should stimulate to better control and analyze the real storage availabilities of digital data and provide in the future other media than CD R for long-term archiving.

CD-ROM↗

Personality in proportion: a bipolar proportional scale for personality assessments and its consequences for trait structure.

Trait structures resulting from personality assessments on Likert scales are affected by the additive and multiplicative transformations implied in interval scaling and correlational analysis. The effect comes into view on selecting a plausible alternative scale. To this end, we propose a bipolar bounded scale ranging from -1 to +1 representing an underlying process in which the assessor would review and discount positive and negative behavioral instances of a trait. As an appropriate index of likeness between variables X and Y, we propose LXY = SigmaXY/N, the average of the raw scores cross products. Using this index, we carried out a raw scores principal component analysis on data consisting of 133 participants who had each been rated by 5 assessors including self on 914 items. Contrary to the Big-Five structure that was found in these data on standard analysis, the results showed a relatively large first principal component F1 and 2 very small ones, F2 and F3. The sizes LFF=SigmaF2/N, the averages of the squared component scores, were modest to small. It thus appears that the scale, bipolar proportional versus standard, has a profound impact on the size and structure of personality assessments. The dissimilarity remains on analyzing self-ratings rather than averaged (over the 5 assessors) ratings.

Humans↗