Improving glucose tolerance by reducing weight gain in a polygenic obese mouse model: use of a high protein diet.

Diets to decrease body weight have limited success in achieving and importantly maintaining this weight loss long-term. It has recently been suggested that energy intake can be regulated by the amount of protein ingested, termed the protein leverage hypothesis. In this study, we determined whether a high protein diet would be effective in achieving and maintaining weight loss in a genetically obese model, the New Zealand Obese (NZO) mouse. NZO and C57BL/6J (C57) control mice were fed a high protein or chow diet for 5 weeks from weaning (3 weeks of age). Body weight and food intake were determined. Mice on the same diet were bred to produce offspring that were fed either a chow or high protein diet. Body weight, food intake, and glucose tolerance were determined. Feeding NZO and C57 mice a high protein diet for 5 weeks resulted in reduced food intake and consequently energy intake and body weight gain compared with mice on a chow diet. NZO mice fed a high protein diet showed a significant improvement in glucose tolerance compared with their chow-fed counterparts, while no difference was seen in C57 mice fed chow or protein diet. The offspring of NZO mice that were fed a high protein diet during gestation and weaning were also lighter and displayed improved glucose tolerance compared with chow fed animals. We conclude that a high protein diet is a reasonable strategy to reduce body weight gain and improve glucose tolerance in the NZO mouse, a polygenic model of obesity.

Insulin-sensitive targeting of the GLUT4 glucose transporter in L6 myoblasts is conferred by its COOH-terminal cytoplasmic tail.

The GLUT4 glucose transporter appears to be targeted to a unique insulin-sensitive intracellular membrane compartment in fat and muscle cells. Insulin stimulates glucose transport in these cell types by mediating the partial redistribution of GLUT4 from this intracellular compartment to the plasma membrane. The structural basis for the unique targeting behavior of GLUT4 was investigated in the insulin-sensitive L6 myoblast cell line. Analysis of immunogold-labeled cells of independent clonal lines by electron microscopy indicated that 51-53% of GLUT1 was present in the plasma membrane in the basal state. Insulin did not significantly affect this distribution. In contrast, only 4.2-6.1% of GLUT4 was present in the plasma membrane of basal L6 cells and insulin increased this percentage by 3.7-6.1-fold. Under basal conditions and after insulin treatment, GLUT4 was detected in tubulovesicular structures, often clustered near Golgi stacks, and in endosome-like vesicles. Analysis of 25 chimeric transporters consisting of reciprocal domains of GLUT1 and GLUT4 by confocal immunofluorescence microscopy indicated that only the final 25 amino acids of the COOH-terminal cytoplasmic tail of GLUT4 were both necessary and sufficient for the targeting pattern observed for GLUT4. A dileucine motif present in the COOH-terminal tail of GLUT4 was found to be necessary, but not sufficient, for intracellular targeting. Contrary to previous studies, the NH2 terminus of GLUT4 did not affect the subcellular distribution of chimeras. Analysis of a chimera containing the COOH-terminal tail of GLUT4 by immunogold electron microscopy indicated that its subcellular distribution in basal cells was very similar to that of wild-type GLUT4 and that its content in the plasma membrane increased 6.8-10.5-fold in the presence of insulin. Furthermore, only the chimera containing the COOH terminus of GLUT4 enhanced insulin responsive 2-deoxyglucose uptake. GLUT1 and two other chimeras lacking the COOH terminus of GLUT4 were studied by immunogold electron microscopy and did not demonstrate insulin-mediated changes in subcellular distribution. The NH2-terminal cytoplasmic tail of GLUT4 did not confer intracellular sequestration and did not cause altered subcellular distribution in the presence of insulin. Intracellular targeting of one chimera to non-insulin-sensitive compartments was also observed. We conclude that the COOH terminus of GLUT4 is both necessary and sufficient to confer insulin-sensitive subcellular targeting of chimeric glucose transporters in L6 myoblasts.

Behavioural clusters and predictors of performance during recovery from stroke.

We examined the patterns and variability of recovery post-stroke in multiple behavioral domains. A large cohort of first time stroke patients with heterogeneous lesions was studied prospectively and longitudinally at 1-2 weeks, 3 months and one year post-injury with structural MRI to measure lesion anatomy and in-depth neuropsychological assessment. Impairment was described at all timepoints by a few clusters of correlated deficits. The time course and magnitude of recovery was similar across domains, with change scores largely proportional to the initial deficit and most recovery occurring within the first three months. Damage to specific white matter tracts produced poorer recovery over several domains: attention and superior longitudinal fasciculus II/III, language and posterior arcuate fasciculus, motor and corticospinal tract. Finally, after accounting for the severity of the initial deficit, language and visual memory recovery/outcome was worse with lower education, while the occurrence of multiple deficits negatively impacted attention recovery.

Polyunsaturated fatty acids are enriched in the plasma membranes of mitogen-stimulated T-lymphocytes.

Plasma membranes were purified from T-lymphocytes from rabbit thymus stimulated with concanavalin A. Lipids were extracted and the fatty acid composition of the individual phospholipid species was determined by gas-liquid chromatography. Compared to the plasma membranes derived from control cells, the plasma membranes from mitogen-stimulated cells were enriched in polyunsaturated fatty acids. This increase in unsaturation was found in phosphatidylcholine, phosphatidylinositol and phosphatidylserine, while the fatty acid composition of phosphatidylethanolamine was not significantly altered. The phospholipid composition remained almost unchanged during the period of stimulation. The molar ratio cholesterol to phospholipid was decreased. These changes in the lipid composition of plasma membranes from mitogen-stimulated T-lymphocytes are discussed with regard to functional implications.

Phospholipase C in rabbit thymocytes: subcellular distribution and influences of calcium and GTP gamma S on the substrate dependence of cytosolic and plasma membrane-associated phospholipase C.

The subcellular distribution of phospholipase C (PLC) activity in rabbit thymocytes was examined by measuring the enzyme's activity in different subcellular fractions. PLC activity was determined using exogenously added [3H]PIP2 as substrate. Approx. 80% of the activity of the cell homogenate was found in the cytosolic fraction. A minor portion of PLC activity was attached to the particulate fraction. This membrane-associated PLC activity was found to be predominantly bound to the plasma membrane. Both PIP2-cleaving PLCs (the PLC associated with the plasma membrane and the PLC in the cytosol) exhibited maximum activity at pH 5. GTP gamma S stimulated the cytosolic and the membrane-bound PLC. As revealed by computer analysis of the substrate dependence of both basal and GTP gamma S-stimulated PLC activity, GTP gamma S enhanced the Vmax of the enzymes. Calcium, at a concentration of 1 mM, decreased PLC activity, as compared to a calcium concentration of 100 nM. The characteristic increase in Vmax induced by GTP gamma S was observed at a concentration of 1 mM calcium and was similar to that at 100 nM. These data suggest that the stimulatory effect of GTP gamma S is not due to an increased affinity of PLCs to calcium.

Separation of plasma membrane domains of calf thymocytes by affinity chromatography on ouabain-Sepharose.

Highly purified plasma membranes of calf thymocytes were fractionated by means of affinity chromatography on ouabain-Sepharose. By the method used two subfractions were obtained, one eluting freely from the affinity gel (MF1oua) and a second specifically retained by matrix-bound ouabain (MF2oua), with a total recovery of 95 per cent. Fractionation required the binding of matrix-bound ouabain to its plasma membrane receptor, i.e. (Na+ + K+)-ATPase. Increasing the temperature and binding time did not significantly alter the fractionation of plasma membranes into the two subfractions. Both plasma membrane subfractions separated by ouabain-Sepharose were of plasma membrane origin, as revealed by the identical specific activities of several membrane bound enzymes, gamma-glutamyl transpeptidase, alkaline phosphatase and Mg2+-ATPase in unseparated plasma membranes and in both subfractions, and by the identical amounts of the cytoskeletal protein actin in unseparated plasma membranes and subfractions. The plasma membrane subfractions MF1oua and MF2oua showed different structural and functional properties. In SDS-polyacrylamide gel electrophoresis polypeptides of 170, 150, 110, 94, 39, and 30 kDa were several-fold enriched in the adherent fraction, MF2oua. The phospholipid fatty acid composition of the plasma membrane subfractions proved to be different, as well. MF2oua contained significantly higher amounts of saturated fatty acids as compared to MF1oua. The specific activities of (Na+ + K+)-ATPase, Ca2+-ATPase and lysolecithin acyltransferase were highly enriched in the adherent fraction MF2oua, as compared to MF1oua. The data suggest that by the means of affinity chromatography on ouabain-Sepharose plasma membrane domains of the lymphocyte plasma membrane can be isolated, most probably implicated in the initiation of lymphocyte activation.

Therapeutic footwear can reduce plantar pressures in patients with diabetes and transmetatarsal amputation.

OBJECTIVE: To compare how footwear (full-length shoe or short shoe), a total contact insert, a rigid rocker-bottom (RRB) sole, and an ankle-foot orthosis (AFO) affect peak plantar pressure (PPP) on the distal residuum and contralateral extremity of patients with diabetes and transmetatarsal amputation (TMA). RESEARCH DESIGN AND METHODS: Thirty patients with diabetes and TMA participated (mean age 62 +/- 4 years). In-shoe plantar pressures during walking were measured in six types of footwear. Each measurement occurred after a 1-month adjustment period. Repeated measure analysis of variance (ANOVA) was used to compare treatments. RESULTS: All five types of therapeutic footwear reduced plantar pressures compared with regular shoes with a toe-filler (P < 0.05). A full-length shoe, total contact insert, and RRB sole resulted in lower pressures on the distal residuum (222 vs. 284 kPa) and forefoot of the contralateral extremity (197 vs. 239 kPa), compared with a regular shoe and toe-filler. Footwear with an AFO showed reduced PPP on the residuum, but most patients complained of reduced ankle motion during walking. A short shoe reduced pressures on the residuum, but not on the contralateral extremity, and many patients had complaints regarding cosmesis of the shoe. CONCLUSIONS: The full-length shoe, total contact insert, and an RRB sole provided the best pressure reduction for the residuum and contralateral foot, with the optimal compromise for cosmetic acceptance and function.

TPA-induced differentiation and adhesion of U937 cells: changes in ultrastructure, cytoskeletal organization and expression of cell surface antigens.

Incubation of the human promonocytic cell line U937 with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 72 h resulted in differentiation into immature macrophage-like cells and was accompanied by marked morphological and functional changes. U937 cells which normally grow in suspension and show a smooth surface, extended pseudopodia and became adherent to each other and to the surface of the culture vessel. Concomitant with the TPA-induced adherence U937 cells ceased to proliferate. Our results show that phorbol ester-treated U937 cells exhibited markedly increased levels of fibronectin and of the cytoskeletal proteins actin, myosin and vimentin including a reorganization of actin and vimentin filaments. The induction of both cellular adherence and growth inhibition were accompanied by a significantly reduced level of cells expressing transferrin receptors and changes in cell surface antigen expression. Here, the expression of the leukocytefunction antigens (LFA-1), including CD11 and CD18 was markedly enhanced during phorbol ester-induced differentiation. TPA-treatment, however, failed to enhance the small amount of U937 cells expressing the monocyte/macrophage-specific CD14 antigen or expressing MHC class-II antigens. A detailed analysis of the CD14 cluster by 7 differential antibodies resulted in an induction of TM1, UCHM1, MEM15, My4, and 3C10, whereas the epitopes recognized by TM2 and Mo2 remained unaltered. Neither indomethacin nor interferon-gamma were capable of inducing a marked expression of these antigen epitopes in TPA-treated cells. Although these data demonstrate that during phorbol ester-induced differentiation U937 cells acquire many properties typically associated with macrophages, the failure to express marked levels of macrophage-specific cell surface antigens suggests a transition of U937 cells from a promonocytic to an immature macrophage intermediate state rather than into mature macrophage-like cells.

Differentiation and retrodifferentiation of U937 cells: reversible induction and suppression of intermediate filament protein synthesis.

Significant morphological and functional changes were observed when human monoblastoid U937 tumor cells growing in suspension were induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for 72 h to differentiate along the monocyte/macrophage pathway. These include adherence of the cells to each other and to the substratum, alterations in cell-surface antigen expression and cessation of autonomous proliferation. In this study, we show by both, hybridization analysis of RNA and immunoblotting that an enhanced expression of the intermediate filament (IF) subunit proteins vimentin, lamin A and lamin C accompanied the TPA-induced differentiation process. After long-term culture of differentiated U937 cells in the absence of TPA (more than 28 days), however, the adherent cells retracted their pseudopodia, detached and started again to proliferate. This "retrodifferentiation" process, not previously described was paralleled by a rapid down-regulation of both, IF mRNA and protein synthesis back to the level of undifferentiated U937 control cells. These data suggest a functional relationship between the expression of vimentin and lamins A and C and the differentiation process taking place in these cells.

Inhibition of the renin-angiotensin system upregulates cyclooxygenase-2 expression in the macula densa.

The expression of cyclooxygenase 2 (COX-2) in the late thick ascending limb, including the macula densa, is found to be upregulated in an activated renin-angiotensin system. How this upregulation is managed is not yet known. We therefore considered the possibility that the stimulation of COX-2 expression is triggered by the activation of the renin-angiotensin system. For this purpose, we treated male Sprague-Dawley rats with the angiotensin I-converting enzyme inhibitor ramipril (10 mg/kg per day), the angiotensin II type 1 (AT(1)) receptor blocker losartan (30 mg/kg per day), and the angiotensin II type 2 (AT(2)) receptor blocker PD123319 (6 mg/kg per day) for 4 days. We determined the expression of COX-2 mRNA and protein in the renal cortex. We found that ramipril and the AT(1) receptor blocker losartan increased COX-2 mRNA and COX-2 immunoreactivity in the macula densa approximately 4-fold, whereas the AT(2) blocker PD123319 showed no effect. A low-salt diet (0.02% wt/wt) stimulated COX-2 expression in the kidney cortex <2-fold. The combination of a low-salt diet with ramipril led to a further increase of COX-2 mRNA and COX-2 immunoreactivity compared with low salt or ramipril alone. These data indicate that endogenous angiotensin II apparently inhibits COX-2 expression in the macula densa via AT(1) receptors and can therefore not account for the stimulation of COX-2 expression associated with an activated renin-angiotensin system. Because macula densa-derived prostaglandins are considered stimulators of renin secretion and renin synthesis, inhibition of macula densa COX-2 by angiotensin II could form a novel indirect negative feedback control of the renin system.

Effect of mycophenolic acid on TNF alpha-induced expression of cell adhesion molecules in human venous endothelial cells in vitro.

1. Mycophenolic acid (MPA) is an inhibitor of inosine-5'-monophosphate dehydrogenase and therefore interferes with cellular GTP biosynthesis. Recently, MPA has been used as an antiproliferative and immunosuppressive agent. In the present study, the effect of MPA on the expression of the endothelial cell adhesion molecules (CAMs), intercellular (I) CAM-1, vascular (V) CAM-1 and endothelial (E)-selectin, was investigated in tumour necrosis factor-alpha (TNF alpha)-activated cultured human venous endothelial cells (EC). 2. Surface expression of CAMs was measured by flow cytometry and mRNA expression by Northern blot analysis. Transcriptional activation of CAMs by the nuclear factor NF-kappaB was determined by an electromobility shift assay. The function of CAMs was studied by a static adhesion assay with human monocyte-like undifferentiated U937 cells. 3. Pretreatment of TNF alpha- (5 ng ml(-1), 12 h) activated EC with MPA (10 microM, 24 h) increased the binding of U937 cells, which had not been treated with MPA, by approximately 2 fold. MPA-pretreatment of EC did not affect TNF alpha-induced surface expression of ICAM-1. However, VCAM-1 and E-selectin were increased 2-3 fold and remained elevated up to 24 h, by which time TNF alpha-activated control EC had returned to baseline levels of expression. The effect of MPA on the surface expression of CAMs was half-maximal at approximately 1 microM and required > or = 12 h of pretreatment. Guanosine (0.3 mM), a precursor of GTP, did not prevent the effect of MPA on the expression of CAMs in TNF alpha-activated EC. 4. Kinetics of mRNA expression of CAMs mirrored protein expression: mRNA for ICAM-1 was unaffected, whereas TNF alpha-induced mRNA expression for E-selectin and VCAM-1 was prolonged and increased by MPA. This effect was not due to increased transcription mediated by the nuclear transcription factor NF-kappaB. However, half-life for E-selectin mRNA was increased 10 fold by MPA, whereas ICAM-1 mRNA half-life was unchanged. 5. The data demonstrate that apart from its antiproliferative effects on lymphocytes, MPA enhances TNF alpha-induced VCAM-1 and E-selectin surface expression on EC by selectively increasing the mRNA-stability of these cell adhesion molecules. This effect of MPA on EC appears to be independent from inhibition of inosine-5'-monophosphate dehydrogenase.

Cyclosporin A suppresses proliferation of renal mesangial cells in culture.

Rat glomerular mesangial cells were isolated and grown in culture for a prolonged period of time. The proliferation of these cells was suppressed by the immunosuppressivum Cyclosporin A (CSA) up to 75%, as measured by the incorporation of radiolabeled thymidine. This was dependent on the concentration of CSA used, being in the range of 125-2000 ng/ml. This effect was specific for CSA and other immunosuppressive derivatives thereof, while a non-immunosuppressive cyclosporin was ineffective. Neither the density of the cultures, nor the time of application had any influence on the susceptibility of the cells to CSA. The suppression of MC proliferation was proliferation was reversible after removal of CSA. These studies demonstrate a suppressive effect of Cyclosporin A on the proliferation of non-lymphocytic cells, the glomerular mesangial cells. This observation may help to explain the beneficial results reported with CSA in the treatment of some kidney diseases.

Regulation of TNF-alpha, IL-1 and IL-6 synthesis in differentiating human monoblastoid leukemic U937 cells.

The human monoblastoid tumor cell line U937 was induced to differentiate along the monocyte/macrophage lineage by treatment with 5 x 10(-9) M 12-O-tetradecanoyl phorbol-13-acetate (TPA). Between 2 h and 4 h following TPA-treatment U937 cells started to release significant amounts of TNF-alpha which remained detectable until 8-10 days. A significant IL-1 beta release was measured 24 h-48 h post stimulation and increased levels of IL-1 beta persisted until 20-22 days of culture. In contrast no release of either IL-1 alpha or IL-6 could be detected with 5 x 10(-9) M TPA during the whole time course of the experiments. The sequential induction of TNF-alpha and IL-1 beta appeared to be independently regulated since TNF-alpha release was not required for the onset of IL-1 beta production. Northern-blot analysis confirmed the sequential induction and the long term expression of TNF-alpha and IL-1 beta mRNAs. Western-blot analysis predominantly showed a high molecular weight IL-1 beta protein of about 35 kD. Further investigations on the regulation of cytokine production and release by TPA-differentiated U937 cells revealed that TNF-alpha and IL-1 beta synthesis was not influenced by exogenously added rhTNF-alpha or PGE2, whereas rh gamma-IFN specifically enhanced the IL-1 beta production. Thus, the regulation and intracellular processing of cytokines generated by differentiating U937 cells shows some differences when compared to mature monocytes/macrophages which may be related to the tumorigenic origin of U937 cells or to an incomplete differentiation.

The immunosuppressive activities of different cyclosporins are correlated to inhibition of the early membrane phospholipid metabolism in activated lymphocytes.

Recently, it could be shown that Cyclosporin A (CsA) inhibited the activation of T and B lymphocytes by interfering with an early step of the activation, namely the stimulation of the plasma membrane-bound lysophosphatide acyltransferase. In this report, we compared three CsA-derivatives, Dihydro-Cyclosporin C (Dihydro-CsC), "C9-O-Acetyl"-CsA (CsAAC), Cyclosporin H (CsH), regarding the inhibition of proliferation and the interference with the activation of the phospholipid metabolism. At concentrations below 1 microgram/ml, CsAAC and CsH had no effect on any parameter measured. Dihydro-CsC, however, closely resembled CsA: it inhibited the induction of DNA- and RNA-synthesis in T and B lymphocytes from mesenteric lymph nodes of rabbits. Similar to CsA, Dihydro-CsC also interfered with the enhanced incorporation of arachidonic acid into plasma membrane phospholipids by inhibiting the activation of the lysophosphatide acyltransferase. The close correlation between inhibition of proliferation and interferences with the phospholipid metabolism of the plasma membrane suggested that Dihydro-CsC as well as CsA interfered with an early step of lymphocyte activation at the level of the plasma membrane.

Dietary levels of plant phenols and other non-nutritive components: could they prevent cancer?

Several non-nutritive components in fruits, vegetables, herbs and spices have been found to inhibit tumour formation in experimental animals exposed to carcinogens. The active non-nutritive components vary with respect to their chemical structures, and may be classed as phenols, terpenes, indoles, isothiocyanates, allyl sulphides or others. They also seem to work by different mechanisms, being inducers or inhibitors of various enzymes, antioxidants, scavengers of reactive metabolites, or inducers of apoptosis. The dietary levels are generally in the order of 1-100 mg/day for most classes of compounds in the Danish population, and similar levels are expected in most northern European countries. These levels are very low compared with the levels used in most animal experiments, where non-nutritive factors have individually been shown to have inhibitory actions on tumorigenesis. Human long-term intervention trials with antioxidants have generally been discouraging. In human short-term intervention studies, where increased dietary levels of specific vegetables or fruits are studied, doses are also comparatively low. Effects on important enzymes have been reported in several such studies, indicating that low levels of non-nutritive factors could influence carcinogenesis by specific mechanisms. Meta-analyses of cohort studies on specific food items rich in specific non-nutritive components, indicate that carotenoid- or glucosinolate-rich foods protect against some cancers, while flavonoid rich food items do not uniformly show protective effects.

Pitfalls in a method for assessment of total antioxidant capacity.

A relatively simple and widely applied method for quantitating the total antioxidant capacity of body fluids and drug solutions based on the absorbance of the ABTS radical cation was evaluated. In this assay, the end-point is an antioxidant-induced decrease in absorbance at a fixed time. This decrease is used as an index of total antioxidant capacity. It is shown that Trolox, potassium cyanide and quercetin all decrease the absorbance of ABTS radical cations at a fixed time, but by different mechanisms. Trolox scavenges the ABTS radical, potassium cyanide inhibits radical formation, while quercetin acts by both mechanisms. Using this method antioxidant capacity may be overestimated, due to both a scavenger effect and an effect on the rate of ABTS oxidation. To distinguish between these effects, a post-addition assay was used in which the sample is added when the formation of radicals is stable. Using post- addition assay conditions enables discrimination between effects on radical scavenging and on the radical formation, two major mechanisms for antioxidant action. In extrapolating the results to an in vivo situation it should be questioned: (i) whether the peroxidase process does indeed mimic the process of radical formation in vivo, and (ii) whether the ABTS radicals do resemble the radical species involved in an in vivo situation. Results obtained in the ABTS radical-based methods should therefore be reviewed critically before the antioxidant capacity can be assessed.

Small sample failure of random assignment: a further examination.

The purpose of random assignment is to produce equivalence on nuisance variables across experimental groups, even when the nuisance variables are unmeasured or of uncertain number. The effectiveness of random assignment, however, depends on sample size; as sample size increases, the likelihood of equivalence also increases. This article demonstrates that, although nonequivalence on a nuisance variable may be quite likely for small samples, the probability is quite low that nonequivalence will produce erroneous inferences. In fact, the probability of an erroneous inference in the absence of a true treatment effect is generally no greater than the nominal Type I error rate. Accordingly, it is unlikely that small samples have biased inferences drawn from past psychotherapy outcome research. However, small samples cause other problems that argue against their routine use.

Differential effects of hypnotic suggestion on multiple dimensions of pain.

Within the framework of multidimensional pain assessment, this study extended an earlier finding that hypnotic analgesia and relaxation suggestions have differential effects on pain reduction by evaluating these strategies in subjects undergoing a cold pressor protocol. Thirty-two highly susceptible subjects were randomly assigned to an analgesia or a relaxation suggestion treatment group. Six pain reports were taken at 10-sec intervals for each experimental condition. The baseline measures served as covariates. A 2 x 2 x 2 x 6 repeated-measures analysis of covariance (ANCOVA) revealed a significant group (analgesia, relaxation) by pain dimension (intensity, unpleasantness), by condition (suggestion alone, hypnotic induction plus suggestion) interaction. Analysis of the simple-simple main effects, holding both group and condition constant, revealed that application of hypnotic analgesia reduced report of pain intensity significantly more than report of pain unpleasantness. Conversely, hypnotic relaxation reduced pain unpleasantness more than intensity. The clinical implications of the study are discussed.

Attributional style and the type A coronary-prone behavior pattern.

The present two studies examined the attributional styles of Type A and B individuals. Past research suggests that Type A's exhibit greater performance deficits than Type B's following exposure to extended, salient uncontrollable stimuli. The reformulated learned helplessness model suggests that individuals most prone to such performance deficits should exhibit an attributional style characterized by internal, stable, and global attributions for negative outcomes, but external, unstable, and specific attributions for positive outcomes. However, a self-esteem protection explanation of learned helplessness findings predicts an opposite, self-serving attributional style. Results from both studies indicated that Type A's are more self-serving than Type B's in their attributions for positive and negative outcomes.

Type A behavior pattern and the judgment of noncontingency: mediating roles of mood and perspective.

Past research indicates that Type A's and B's differ in their behavioral responses to lack of control. The present study examined perceptual judgments of noncontingency in an attempt to clarify further the role of a control dynamic in Type A-B differences. Type A's and B's assumed the role of either an actor or an observer on a standard contingency judgment task. Consistent with previous research, both Type A's and B's exhibited an illusion of control when in the role of actor. Only Type B's exhibited an illusion of control when observing another person perform the task. Additional analyses indicated that the absence of an illusion of control by Type A observers reflected accuracy rather than a motivational distortion. Mood was also found to mediate control judgments, but only for actors. The plausibility of a memory-based interpretation for the mood effects is discussed.