Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein(a) production

Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors regulating plasma concentrations of Lp(a) are poorly understood. Apo(a), the protein that distinguishes Lp(a) from LDL, is highly polymorphic, and apo(a) size is inversely correlated with plasma Lp(a) level. Even within the same apo(a) isoform class, however, plasma Lp(a) concentrations vary widely. A series of in vivo kinetic studies were performed using purified radiolabeled Lp(a) in individuals with the same apo(a) isoform but different Lp(a) levels. In a group of seven subjects with a single S4-apo(a) isoform and Lp(a) levels ranging from 1 to 13.2 mg/dl, the fractional catabolic rate (FCR) of 131I-labeled S2-Lp(a) (mean 0.328 day-1) was not correlated with the plasma Lp(a) level (r = -0.346, P = 0.45). In two S4-apo(a) subjects with a 10-fold difference in Lp(a) level, the FCR's of 125I-labeled S4-Lp(a) were very similar in both subjects and not substantially different from the FCRs of 131I-S2-Lp(a) in the same subjects. In four subjects with a single S2-apo(a) isoform and Lp(a) levels ranging from 9.4 to 91 mg/dl, Lp(a) concentration was highly correlated with Lp(a) production rate (r = 0.993, P = 0.007), but poorly correlated with Lp(a) FCR (mean 0.304 day-1). Analysis of Lp(a) kinetic parameters in all 11 subjects revealed no significant correlation of Lp(a) level with Lp(a) FCR (r = -0.53, P = 0.09) and a strong correlation with Lp(a) production rate (r = 0.99, P < 0.0001). We conclude that the substantial variation in Lp(a) levels among individuals with the same apo(a) phenotype is caused primarily by differences in Lp(a) production rate.     

Conformity behavior of schizophrenic subjects with maternal figures.

4 groups of 10 Ss each were used: (a) a group of Nondrug Poor Premorbid schizophrenic Ss, (b) a group of Drug Poors, (c) a group of hospitalized Alcoholics, and (d) a group of Normal control Ss. S was placed in a 2-choice situation, and asked to indicate his preference, over a number of trials, after having learned the preference of a cold, domineering, maternal figure. Conformity was measured in terms of 3 relatively independent response attributes. The results indicate that, as compared to the Nondrug schizophrenics: (a) the Drug schizophrenics manifested less conformity, (b) the Normals were uninfluenced, and (c) the Alcoholics tended to disagree with the negative mother. All groups were equally accurate in their perception of the 2 mothers. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men

Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P = 0.05). Lp(a) was highest in the apoE genotypes epsilon 2 epsilon 3 and epsilon 3 epsilon 3 and lowest in genotype epsilon 3 epsilon 4, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P = 0.04) in apoE genotype epsilon 2 epsilon 3 than in genotype epsilon 3 epsilon 3. Lp(a) concentrations did not differ among the XbaI (P = 0.65) or SP 24/27 (P = 0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P < 0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors.     

Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic patients from Romania

Several studies suggested that lipoprotein (a)-Lp(a) is an independent atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is characterized by an increased risk of coronary heart disease (CHD) as related to the general population, the main purpose of our study was to compare the plasma levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our department, and in 20 non-diabetic controls from Timi?oara. Apo (a) values were similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for microalbuminaria with the MICRAL-test and we compared apo (a) levels in those having albumin excretion values above and under the cut-off point (20 mg/l). Apo (a) concentrations were similar in both samples. We found no association between apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have similar apo (a) concentrations to non-diabetic subjects and they do not seem to be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid values Apo (a) and apo B are significantly correlated, both in diabetic and non-diabetic subjects.     

Apolipoprotein(a) binds to low-density lipoprotein at two distant sites in lipoprotein(a)

Lipoprotein(a) [Lp(a)] consists of low-density lipoprotein (LDL) and apolipoprotein(a) [apo(a)] linked with a disulfide bond. Scanning force microscopy (SFM) of Lp(a) showed, for the first time, a belt-like structure of apo(a) with both ends attached to a spherical LDL. The two ends of apo(a) were bound to the LDL sphere at two distant sites. Occasionally, the ends were attached to two touching spheres. Under the same imaging conditions, LDL appeared as individual spheres. Electron microscopy (EM) studies of Lp(a) by several groups over the past decade failed to reveal this belt-like structure of apo(a). Images of isolated apo(a) in air or in phosphate buffer showed apo(a) as individual belts, and these belts tended to crowd together. Lp(a) formed leaf-like aggregates; apo(a) aggregates were fishnet-like, whereas LDL aggregates were less characteristic. Quantitative analysis of Lp(a) showed the diameter of the LDL to be 24.8 +/- 8.7 nm (n = 46), which is close to the reported value of 24.2 +/- 4.2 nm found with EM. The length of the belts attached to the spheres was measured to be 173.5 +/- 6.6 nm (n = 15). I also found, by using a functionalized tip, that the interaction force between apo(a) and its ligand, lysine, was related to the ionic strength of the bulk solution. This force can be reduced by the presence of epsilon-aminocaproic acid.     

Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect

Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of 20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.     

The development of a goal to become a teacher.

The purpose of this project was to investigate how the goal of becoming a teacher emerges. The study used interviews to develop goal histories for 8 preservice teachers. There tended to be 4 sources of influence for their goal to become a teacher: (a) family influences, (b) teacher influences, (c) peer influences, and (d) teaching experiences. The categories developed from the interviews to describe the types of influences those sources provided were (a) suggesting that the person become a teacher, (b) encouraging the person to become a teacher, (c) modeling teaching behavior, (d) exposing the person to teaching experiences, and (e) discouraging the person from becoming a teacher. In addition, influences such as critical incidents, emotions, and social-historical factors, such as the status and pay of teachers, were prominent in the goal histories of the participants. Finally, the results of the study are discussed within the context of goals and self-directed behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinguished teaching in psychology: Benton J. Underwood.

The Distinguished Teaching in Psychology award, which includes a check for $1,000, is given to the recipient for his or her contributions to the teaching of psychology. The following guidelines are used to determine the recipient: (a) demonstrated influence as a teacher of students who become outstanding psychologists, (b) development of effective teaching methods and/or teaching materials, (c) engagement in significant research on teaching, (d) development of innovative curricula and courses, (e) outstanding performance as a classroom teacher, (f) being an especially effective trainer of teachers of psychology, and (g) being responsible for administrative facilitation of outstanding teaching. This article provides a citation and a biography for Benton J. Underwood, who received the award for Distinguished Teaching in Psychology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protecting the integrity of Rorschach expert witnesses: A reply to Grove and Barden (1999) re: The admissibility of testimony under Daubert/Kumho analyses.

The Rorschach Comprehensive System has been considered by W. M. Grove and R. C. Barden (1999) as inadmissible for expert psychological testimony according to the guidelines from the Daubert (1993), Joiner (1997), and Kumho (1999) decisions. This article refutes W. M. Grove and R. C. Barden's conclusions, arguing that the Rorschach Comprehensive System is (a) testable, (b) valid and reliable, (c) extensively peer reviewed, (d) associated with a reasonable error rate, (e) standardized, (f) accepted by a relevant and substantial scientific community, and (g) appropriate for a wide range of forensic issues. In drawing their negative conclusions, W. A Grove and R. C. Barden overlooked or minimized a substantial body of empirical data supporting the reliability and validity of the Rorschach Comprehensive System and misinterpreted the language and intent of the Supreme Court decisions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Report of the Treasurer, 1975: Light at the end of the tunnel.

Presents the American Psychological Association's (APA's) treasurer's report for 1975. This financial overview includes (a) our audited report of the 1974 results from operations; (b) a look at APA's financial condition as of December 31, 1974; (c) a prediction for 1975; (d) a glance at the 1976 approved budget; and (e) a peek at the association's prospects for 1977. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic mouse urinary tract

Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human apoB. Steady-state and pulse-chase labeling experiments demonstrated that newly synthesized human apo(a) had a prolonged residence time (approximately 60 min) in the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was inefficiently secreted by the hepatocytes and a large portion of the protein was retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex folding pathway in the ER, which included incorporation of apo(a) into high molecular weight, disulfide-linked aggregates. These folding characteristics could account for long ER residence time and inefficient secretion of apo(a). Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before appearing in the culture medium. Apo(a) could be released from the cell surface by apoB-containing lipoproteins. These studies are consistent with a model in which the efficiency of post-translational processing of apo(a) strongly influences human plasma Lp(a) levels, and suggest that cell surface assembly may be one pathway of human Lp(a) production in vivo. Transgenic mouse hepatocytes thus provide a valuable model system with which to study factors regulating human Lp(a) biogenesis.     

Defining a complex intervention: The development of demarcation criteria for “meditation”.

The authors used a 5-round Delphi study with a panel of 7 experts in meditation research to achieve agreement on a set of criteria for a working definition of “meditation” for use in a comprehensive systematic review of the therapeutic use of meditation. Participants agreed that essential to a meditation practice is its use of (a) a defined technique, (b) logic relaxation, and (c) a self-induced state. Participants also agreed that a meditation practice may (d) involve a state of psychophysical relaxation somewhere in the process; (e) use a self-focus skill or anchor; (f) involve an altered state/mode of consciousness, mystic experience, enlightenment or suspension of logical thought processes; (g) be embedded in a religious/spiritual/philosophical context; or (h) involve an experience of mental silence. The results of this study provide insight into the challenges faced by researchers who want to demarcate meditative practices from nonmeditative practices, and they describe an approach to this problem that may prove useful for researchers trying to operationalize meditation in the context of comparative research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpretational confounding is due to misspecification, not to type of indicator: Comment on Howell, Breivik, and Wilcox (2007).

R. D. Howell, E. Breivik, and J. B. Wilcox (2007; see record 2007-07830-006) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dream reports and creative tendencies in students of the arts, sciences, and engineering.

105 students of arts, sciences, and engineering were asked to report a dream and to take a test which measures independence of judgment and relates to creativity. 4 predictions were stated: (a) (confirmed)—the proportion of dream recallers would be greatest among art students and least among engineering students; (b) (partially confirmed)—dream imaginativeness would be greatest among art students and least among engineering students; (c) (not confirmed)—dream recallers would have higher test scores than Ss who failed to recall a dream; (d) (confirmed)—there would be a positive relation between dream imaginativeness and test scores. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The lactose transporter of Staphylococcus aureus--overexpression, purification and characterization of the histidine-tagged domains IIC and IIB

Epidemiological studies have shown lipoprotein(a) (Lp(a)) to be an independent risk factor for cardiovascular disease. Lp(a) is a cholesterol-rich, low-density lipoprotein (LDL)-like particle to which a large glycoprotein, apolipoprotein(a) (apo(a)) is attached. Plasma Lp(a) levels are highly genetically determined and influenced to a minor degree by environmental factors. In an effort to determine whether Lp(a) might be associated with longevity, we have evaluated Lp(a) levels and apo(a) isoform sizes in a population of French centenarians (n = 109) compared to a control group (n = 227). The mean age of centenarians was 101.5 +/- 2.4 years while the control group was 39.4 +/- 7.2 years. Plasma levels of total cholesterol and triglyceride were within the normal range in both centenarian and control subjects. Lp(a) levels were higher in centenarians (both male and female) than in the normolipidemic control group (mean Lp(a) level = 0.33 +/- 0.42 and 0.22 +/- 0.27 mg/ml, respectively, P < 0.005). The distribution of apo(a) isoforms was significantly shifted towards small isoform size in the centenarian population as compared to the controls (54.4 and 41.4% of isoforms < or = 27 kringles (kr), respectively, P = 0.04). Nonetheless, the apo(a) size distribution in centenarians did not entirely explain the high Lp(a) levels observed in this population. Factors other than apo(a) size, and which may be either genetic or environmental in nature, appear to contribute to the elevated plasma Lp(a) levels of our centenarian population. We conclude therefore that high plasma Lp(a) levels are compatible with longevity.     

(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).     

Influence of anxiety on the relationship between self-acceptance and acceptance of others.

Tests of general and test anxiety were administered with a self-acceptance (SA)-acceptance of others (AO) questionnaire to 92 Ss to test the prediction that anxiety increased the usual SA-AO correlation. Results indicate that (a) anxiety is significantly associated with both lowered self-acceptance and lowered acceptance of others, (b) anxiety disrupts the SA-AO relationship by lowering self-acceptance at a greater rate than acceptance of others, (c) low anxiety permits the usual SA-AO correlation to exist. Conclusions were that (a) learning theory from which the prediction was derived is inadequate in self-theory areas of personality, (b) anxiety has a disruptive, yet systematic influence on the self-acceptance-acceptance of others relationship. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of scenery, lighting, glideslope, and experience on timing the landing flare.

This study examined three visual strategies for timing the initiation of the landing flare based on perceptions of either: (a) a critical height above ground level; (b) a critical runway width angle (Ψ); or (c) a critical time-to-contact (TTC) with the runway. Visual displays simulated landing approaches with trial-to-trial variations in glideslope, lighting, and scene detail. Twenty-four participants (8 private pilots, 8 student pilots, and 8 nonpilots) were instructed to initiate the flare when they perceived that their TTC with the runway (30 m wide by 840 m long) had reached a critical value of 2 seconds. Our results demonstrated a significant effect of flight experience on flare timing accuracy and dominance of the height-based strategy over the runway-width-angle and TTC-based strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)