Behavioral activation and inhibition in everyday life.

Joint effects of daily events and dispositional sensitivities to cues of reward and punishment on daily positive affect (PA) and negative affect (NA) were examined in 3 diary studies. Study 1 showed that positive events were strongly related to PA but not NA, whereas negative events were strongly related to NA but not PA. Studies 2 and 3 examined how the dispositional sensitivities of independent appetitive and aversive motivational systems, the Behavioral Activation System (BAS) and the Behavioral Inhibition System (BIS), moderated these relationships. Participants in Study 2 with higher BAS sensitivity reported more PA on average; those with more sensitive BIS reported more NA. Also, BIS moderated reactions to negative events, such that higher BIS sensitivity magnified reactions to negative events. Study 3 replicated these findings and showed that BAS predisposed people to experience more positive events. Results demonstrate the value of distinguishing within-person and between-person effects to clarify the functionally independent processes by which dispositional sensitivities influence affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excessive activation of tyrosine kinases leads to inhibition of proliferation in a thyroid carcinoma cell line

Autocrine stimulation of growth is a hallmark of many tumor cell lines. In this work we investigated the synthesis and secretion of growth factors and the expression of their corresponding receptors in HTC-TSHr thyroid carcinoma cells. These cells synthesize epidermal growth factor (EGF) receptors and platelet-derived growth factor beta (PDGF beta) receptors and in addition transforming growth factor alpha (TGF alpha), PDGF-A and PDGF-B chains, respectively. Addition of EGF or PDGF-BB to the culture medium resulted in growth inhibition of HTC-TSHr cells. In contrast, treatment of the cells with low concentrations of neutralizing anti-TGF alpha antibodies or tyrosine kinase inhibitors led to stimulation of cell proliferation. Low concentrations of neutralizing anti-PDGF-B antibodies did not affect growth of the cells. As expected, cell proliferation was inhibited when high concentrations of either neutralizing anti-TGF alpha antibodies or anti-PDGF-B antibodies were applied. PDGF-AA did not influence growth of HTC-TSHr cells. We conclude that growth of HTC-TSHr thyroid carcinoma cells is influenced by two autocrine loops between TGF alpha and EGF receptors and between PDGF-B and PDGF beta receptors. However, our data suggest that excessive activation of tyrosine kinase receptors in these cells results in a relative inhibition rather than stimulation of growth.     

Mast cell activation and tissue cell proliferation

The effect of mast cell activation and degranulation on the proliferation in the intact mesentery was studied in Sprague-Dawley rats. Mast cell activation was achieved by a single intraperitoneal injection of Compound 48/80. The proliferation was studied using three independent methods for estimation of cell production and DNA synthesis: 1. the mitotic index, 2. the relative number of cells having a DNA content in the S and G2 regions, by Feulgen photometric measurement in individual cells, and 3. the specific DNA activity, employing a method which combines a liquid scintillation technique after an intravenous injection of 3H-thymidine and Feulgen photometric determination of the DNA content per membrane preparation. It was found that the proliferation of the normal mesenchymal cells adjacent to the activated and degranulated mast cells in the mesentery was significantly increased within 24 and 32 h, the maximum increase being more than 20-fold compared to untreated controls. The results suggest that the common type of mast cell may have a pathophysiological function related to stimulation of local cell proliferation.     

11 beta-hydroxysteroid dehydrogenases of the choriocarcinoma cell line JEG-3 and their inhibition by glycyrrhetinic acid and other natural substances

Mineralocorticoid receptor (MR) selectivity for aldosterone is thought to be exerted by enzymes which inactivate competing glucocorticoids before they bind the receptor. Two different 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD) have been described. 11 beta-HSD-1 is NADP(+)-dependent and has a Km in the micromolar range and bidirectional activity. 11 beta-HSD-2 is NAD(+)-dependent, has a Km in the nanomolar range, exhibits only oxidase activity, and colocalizes with the MR in the kidney, so is likely to serve as the gatekeeper for the MR. We have further characterized 11 beta-HSD activity in JEG-3 cells, a cell line derived from a human choriocarcinoma which was reported to have only the high affinity, NAD(+)-dependent 11 beta-HSD-2. We found that the Km for the conversion of corticosterone to 11-dehydrocorticosterone in intact cells and homogenates was about 16 nM. NAD(+)-dependent corticosterone conversion was equal in the nuclear and mitochondrial fractions and less, but significant, in the microsomal fraction. A high affinity, Km = 40 nM, NADP(+)-dependent enzyme was also found in homogenates. The subcellular distribution of this high affinity activity was greatest in the mitochondria, less in the nuclei, and even less, but still significant, in microsomes. Because of its cofactor dependency, high affinity, and different subcellular distribution, we suggest that this enzyme is neither the 11 beta-HSD-1 nor the 11 beta-HSD-2 and have named it 11 beta-HSD-3. Conversion of 11-dehydrocorticosterone to corticosterone did not occur in intact cells or in homogenates incubated with NADH or NADPH. Enzyme activity in intact cells was inhibited by glycyrrhetinic acid, carbenoxolone, progesterone, 5 beta-dihydroprogesterone, and 5 alpha-dihydroprogesterone, but not bile acids.     

Some aspects of activation and inhibition of rat brain lipoxygenase

1. Regulatory properties of lipoxygenase activity in rat brain cytosol were studied using linoleic acid (LA) as a substrate. 2. A change in the absorbance at 234 nm was biphasic when a mixture of LA and pre-formed hydroperoxide (LA-OOH) was incubated with freshly isolated native brain cytosol. Initially, a rapid depletion of LA-OOH was observed with a concomitant formation of LA-oxo compounds. This phase was followed by LA dioxygenation. 3. Both hydroperoxidase and dioxygenase activities of lipoxygenase were inhibited by micromolar concentrations of classic lipoxygenase inhibitors (phenidone, 5,8,11-eicosatriynoic acid and nordihydroguaiaretic acid). 4. The dioxygenase activity in dialysed cytsool was stimulated by nanomolar concentrations of H2O2 and micromolar concentrations of LA-OOH and it was inhibited by serotonin, dopamine and norepinephrine (IC50 25-43 microM).     

Within-group norming and other forms of score adjustment in preemployment testing.

Various forms of score adjustment have been suggested and used when mean differences by gender, race, or ethnicity are found using preemployment tests. This article examines the rationales for score adjustment and describes and compares different forms of score adjustment, including within-group norming, bonus points, separate cutoffs, and banding. It reviews the legal environment for personnel selection and the circumstances leading to the passage of the Civil Rights Act of 1991. It examines score adjustment in the use of cognitive ability tests, personality inventories, interest inventories, scored biographical data, and physical ability tests and outlines the implications for testing practice of various interpretations of the Civil Rights Act of 1991. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of tea infusions of various varieties or different manufacturing types on inhibition of mouse mast cell activation

We investigated effects of various tea infusions on mast cell activation using mouse mast cells. Among various tea extracts, infusions from cultivar 'Benihomare' and Taiwan lineage strongly inhibited histamine release after Fc epsilon RI cross-linking. Among three types of tea (from cultivar 'Benihomare'), extract from oolong tea or black tea inhibited histamine release more strongly than green tea extract. Furthermore, 'Benihomare' oolong tea extract suppressed tyrosine phosphorylation of cellular proteins after Fc epsilon RI cross-linking, but polyvinyl polypyrrolidone treatment of the extract to remove phenolic compounds, weakened the suppressive effect.     

Two distinct forms of human mast cell chymase--differences in affinity for heparin and in distribution in skin, heart, and other tissues

Chymase, a chymotrypsin-like protease secreted by human mast cells, is generally considered to be a single enzyme. However, by heparin-agarose chromatography of high-salt extracts of human skin, we have consistently resolved three peaks of chymotryptic activity, eluting at 0.4 M NaCl (peak A), 1.0-1.2 M NaCl (peak B) and 1.8-2.0 M NaCl (peak C), with peak B containing 75-90% of the recovered activity. Each peak retained its identity upon rechromatography. The three peaks of activity were similar in substrate specificity and inhibitor profile and distinctly different from other chymotryptic enzymes, including cathepsin G and the stratum corneum chymotryptic enzyme. Examination of different tissues revealed that peak C was virtually absent from synovial tissue, was present as a minor component in skin and heart, but constituted the predominant chymotryptic activity in lung. Peaks B and C from skin tissue were further purified by chromatography on Sephacryl S-200. Both had a molecular mass of 28-29 kDa, yielded the N-terminal sequence reported for chymase, and on western blots reacted with a panel of polyclonal, monoclonal and antipeptide antibodies against chymase. Chymase C required higher concentrations of NaCl to overcome the stimulatory effects of heparin than did chymase B, but had a similar pH profile. Thus, human chymase exists in at least two distinct but similar forms, and the differences in heparin binding and tissue distribution could have important consequences for enzyme function.     

Separation of inhibition and activation of the allosteric yeast chorismate mutase

Yeast chorismate mutase (EC 5.4.99.5) shows homotropic activation by the substrate, allosteric activation by tryptophan, and allosteric inhibition by tyrosine. In this study mutants of chorismate mutase have been found that remain sensitive to one allosteric effector (tryptophan) but insensitive to the other (tyrosine). These mutations are located in the catalytic domain: loop 220s (212-226) and helix 12 (227-251). The first example starts with the Thr-266 --> Ile mutant that had previously been shown to be locked in the activated R state. The additional mutation Ile-225 --> Thr unlocks the R state and restores the activation by tryptophan but not the inhibition by tyrosine. The second example refers to a molecular trigger for the switch between the T and R state: a hydrogen-bonded system, which stabilizes only the T state, from Tyr-234 to Glu-23 to Arg-157. Various mutants of Tyr-234, especially Tyr-234 --> Phe, are unresponsive to tyrosine but are activated by tryptophan. This separation of activation from inhibition may indicate a pathway for activation that is independent of the allosteric transition and may also be consistent with an intermediate structure between T and R states.     

Gitelman's syndrome is genetically distinct from other forms of Bartter's syndrome

In the past the term Bartter's syndrome has been used to describe a spectrum of inherited renal tubular disorders with hypokalemic metabolic alkalosis and overlapping and additional clinical and biochemical features. Pathogenesis remained uncertain until recently Gitelman's syndrome, the hypokalemic-hypomagnesemic variant with hypocalciuria, was linked to the gene encoding the thiazide-sensitive Na-Cl-cotransporter (TSC) located on chromosome 16q. Various mutations in the TSC gene were identified in patients with Gitelman's syndrome. To clarify whether different forms of hypokalemic tubular disorders (HTD) represent variable phenotypes of a common genetic defect, we performed linkage analyses in 17 families with different symptoms of HTD with four highly polymorphic chromosome 16 DNA markers closely linked to the TSC gene. Linkage of Gitelman's syndrome to the TSC locus was confirmed in our families with a maximum two-point Lod score Z = 4.70 (theta = 0.001) for marker locus D16S526. Highly negative LOD scores were obtained at this locus in our families with classic Bartter's syndrome (Z = 9.89, theta = 0.001) and hyperprostaglandin E syndrome (Z = -11.24, theta = 0.001). Our data prove that Gitelman's syndrome is genetically distinct from classic Bartter's syndrome and hyperprostaglandin E syndrome. It remains unknown if classic Bartter's syndrome and hyperprostaglandin E syndrome are caused by a common genetic defect.     

Control of ecdysteroidogenesis: activation and inhibition of prothoracic gland activity

The ecdysteroid hormones, mainly 20-hydroxyecdysone (20E), play a pivotal role in insect development by controlling gene expression involved in molting and metamorphosis. In the model insect Manduca sexta the production of ecdysteroids by the prothoracic gland is acutely controlled by a brain neurohormone, prothoracicotropic hormone (PTTH). PTTH initiates a cascade of events that progresses from the influx of Ca2+ and cAMP generation through phosphorylation of the ribosomal protein S6 and S6-dependent protein synthesis, and concludes with an increase in the synthesis and export of ecdysteroids from the gland. Recent studies indicate that S6 phosphorylation probably controls the steroidogenic effect of PTTH by gating the translation of selected mRNAs whose protein products are required for increased ecdysteroid synthesis. Inhibition of S6 phosphorylation prevents an increase in PTTH-stimulated protein synthesis and subsequent ecdysteroid synthesis. Two of the proteins whose translations are specifically stimulated by PTTH have been identified, one being a beta tubulin and the other a heat shock protein 70 family member. Current data suggest that these two proteins could be involved in supporting microtubule-dependent protein synthesis and ecdysone receptor assembly and/or function. Recent data also indicate that the 20E produced by the prothoracic gland feeds back upon the gland by increasing expression and phosphorylation of a specific USP isoform that is a constituent of the functional ecdysone receptor. Changes in the concentration and composition of the ecdysone receptor complex of the prothoracic gland could modulate the gland's potential for ecdysteroid synthesis (e.g. feedback inhibition) by controlling the levels of enzymes or other proteins in the ecdysteroid biosynthetic pathway.     

Cell activation mediated by glycosylphosphatidylinositol-anchored or transmembrane forms of CD14

CD14 is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein which functions as a receptor on myeloid cells for ligands derived from microbial pathogens such as lipopolysaccharide (LPS). We have studied the importance of the GPI tail of CD14 in signalling with the promonocytic cell line THP-1 expressing recombinant CD14 in a GPI-anchored form (THP1-wtCD14 cells) or in a transmembrane form (THP1-tmCD14). We found that, like other GPI-anchored molecules, GPI-anchored CD14 was recovered mainly from a Triton X-100-insoluble fraction, whereas transmembrane CD14 was fully soluble in Triton X-100. LPS induced cell activation of THP1-wtCD14 and of THP1-tmCD14 (protein tyrosine kinase phosphorylation, NF-kappaB activation, and cytokine production) in a very similar manner. However, anti-CD14 antibody-induced cross-linking caused a rapid calcium mobilization signal only in GPI-anchored CD14 cells. Studies with pharmacologic inhibitors of intracellular signalling events implicate phospholipase C and protein tyrosine kinases in the genesis of this antibody-induced calcium signal. Our results suggest that GPI anchoring and CD14 targeting to glycolipid-rich membrane microdomains are not required for LPS-mediated myeloid cell activation. GPI anchoring may however be important for other signalling functions, such as those events reflected by antibody cross-linking.     

Behavioral inhibition and activation systems: Differences in substance use expectancy organization and activation in memory.

We used multidimensional scaling to model the semantic network of alcohol and marijuana expectancies (N = 897). Preference mapping was used to estimate vectors representing patterns of activation through the network as a function of levels of behavioral inhibition (BIS) and behavioral activation (BAS). Individuals with low BIS combined with high BAS levels exhibited patterns of activation emphasizing behavioral activation similar to heavier drug users in previous research. High BIS, low BAS individuals exhibited activation patterns with greater emphasis on inhibitory expectancies similar to low-level users. Differences in expectancy activation patterns were maintained after controlling for substance use and gender. Individual differences in BIS/BAS are associated with the organization of semantic networks and patterns of activation of expectancies contributing to differences in substance use behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Homicide–suicide and other forms of co-occurring aggression against self and against others.

Assessing the risk of harm to self and the risk of harm to others usually are distinct clinical processes. Yet these forms of aggression frequently coexist, occasionally with lethal outcomes. The author summarizes the literature on co-occurring aggression against self and others. Studies of homicide-suicide are reviewed first. Studies investigating the risk of co-occurring aggression against self and against others are reviewed next. The studies show a strong link between the 2 forms of aggression, etiologically implicating depression and other factors. Both types of risk assessment should occur jointly. Guidelines for combined risk assessment, prevention, and treatment are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral activation and inhibition systems and the severity and course of depression.

Theorists have proposed that depression is associated with abnormalities in the behavioral activation (BAS) and behavioral inhibition (BIS) systems. In particular, depressed individuals are hypothesized to exhibit deficient BAS and overactive BIS functioning. Self-reported levels of BAS and BIS were examined in 62 depressed participants and 27 nondepressed controls. Clinical functioning was assessed at intake and at 8-month follow-up. Relative to nondepressed controls, depressed participants reported lower BAS levels and higher BIS levels. Within the depressed group, lower BAS levels were associated with greater concurrent depression severity and predicted worse 8-month outcome. Levels of both BIS and BAS showed considerable stability over time and clinical state. Overall, results suggest that BAS dysregulation exacerbates the presentation and course of depressive illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Asymmetric switch cost and backward inhibition: Carryover activation and inhibition in switching between tasks of unequal difficulty.

Asymmetric switch cost, observed when switching between tasks varying in difficulty, shows that the difference between repeat and switch trials is greater when switching to the easier task. Early explanations of this effect attributed this pattern to both positive priming of the difficult task and negative priming of the easier task, but more recent models have focused only on activation processes. The role of inhibition in asymmetric switch cost was examined using backward inhibition, a more direct measure of task-set inhibition. The results indicated asymmetric backward inhibition, with greater sequential inhibition of the easier task (i.e., easy-difficult-easy sequences). Switch costs, however, showed both typical and reversed asymmetry (greater cost when switching from the easy to the difficult task), depending on the relative difficulty of task pairs. This pattern of results indicates that switch costs are attributable to both activation and inhibition processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Ras antagonist S-farnesylthiosalicylic acid induces inhibition of MAPK activation

Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhibitors that block Ras membrane anchorage is limited due to alternative prenylation of Ras. Here we demonstrate that inhibition of the Ras-dependent Raf-1-MAPK (mitogen activated protein kinase) cascade is achieved by S-farnesylthiosalicylic acid (FTS) which affects Ras membrane association but not Ras farnesylation. FTS interferes with the activation of Raf-1 and MAPK and inhibits DNA synthesis in Ras-transformed EJ cells at concentrations similar to those at which it inhibits EJ cell growth (5-25 microM). FTS also inhibits MAPK activity and DNA synthesis stimulated by serum, EGF or thrombin in serum-starved untransformed Rat-1 cells, demonstrating the generality of its effects on Ras-dependent signaling. The effects of FTS on MAPK activity developed relatively rapidly (within 2-6 h) consistent with its rapid effect on Ras membrane anchorage. FTS represents a new class of Ras antagonists that may be useful for the inhibition of various types of oncogenic Ras isoforms independently of their prenylation.     

Diabetes complications and their potential prevention: aldose reductase inhibition and other approaches

Despite recent advances both in the chemistry and molecular pharmacology of antidiabetic drugs, diabetes still remains a life-threatening disease, which tends to spread all over the world. The clinical profile of diabetic subjects is often worsened by the presence of several long-term complications, namely neuropathy, nephropathy, retinopathy, and cataract. Several attempts have been made to prevent or at least to delay them. The most relevant are reported in this review, including the development of compounds acting as aldose reductase inhibitors, anti-advanced glycation end-product drugs, free radical scavengers, vasoactive agents, essential fatty acid supplementation, and neurotropic growth factors.     

Physical violence and other forms of marital aggression: Links with children's behavior problems.

Two studies examined whether physical marital violence and other forms of marital aggression (e.g., threats, throwing objects) correlate with children's behavior problems in families marked by recent spousal violence. Study 1 included 55 families seeking marital therapy. Study 2 included 199 families at battered women's shelters. In the marital therapy sample, both physical marital violence and other forms of marital aggression correlated positively with children's externalizing problems. In the women's shelter sample, physical violence and other forms of marital aggression correlated positively with children's externalizing and internalizing problems. After accounting for the frequency of physical marital violence, forms of marital aggression other than physical violence still related to children's externalizing problems in the marital therapy sample and to children's internalizing problems in the women's shelter sample. (PsycINFO Database Record (c) 2010 APA, all rights reserved)