The dynamics of intention retrieval and coordination of action in event-based prospective memory.

Event-based prospective memory requires responding to cues in the environment that are associated with a previously established intention. Some researchers believe that intentions reside in memory with an above baseline level of activation, a phenomenon called the intention superiority effect. The authors of this study predicted that intention superiority would be masked by additional cognitive processes associated with successful event-based prospective memory. These additional processes include noticing the cue, retrieving the intention, and coordinating intention execution with the ongoing activity, In 3 experiments, intention superiority was demonstrated by faster latencies to the ongoing activity on failed prospective trials and the existence of the additional processes was demonstrated by slower latencies on successful trials. This study demonstrates the importance of investigating the microstructure of the cognitive components involved with processing and responding to an event-based prospective memory cue. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of mouse CD43 in the B cell lineage of transgenic mice causes impaired immune responses to T-independent antigens

CD43 (leukosialin), a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. However, its precise physiological function remains unclear. We used mouse CD43 (mCD43)-immunoglobulin enhancer-transgenic (TG) mice to study the role of mCD43 in vivo. Previous work revealed that mCD43 expression on mature B cells in these mice resulted in immunodeficiency to T-dependent (TD) antigens (Ag), possibly by impairing B-T cell interactions. In the present study we have immunized the TG mice with the T-independent (TI) Ag fluorescein-(Fl) lipopolysaccharide (LPS) (TI type 1 Ag) and Fl-Ficoll (TI type 2 Ag). Surprisingly, the mCD43-Ig enhancer expressing mice were impaired in their ability to mount humoral responses to both Fl-LPS and Fl-Ficoll, and had decreased numbers of cells responding to Ag in vivo. Flow cytometric analysis was performed on peritoneal B-1 cells, a population which often plays a major role in humoral responses to TI Ag such as bacterial Ag. This analysis revealed similar B220, IgM and CD5 expression patterns for the TG and nontransgenic (NTG) B-1 cells. In addition, purified peritoneal B-1 cells from TG and NTG mice were able to respond to LPS. Stimulation of splenic B cells in vitro with Fl-LPS and Fl-Ficoll revealed that, in contrast to NTG B cell responses, TG B cell responses could not be enhanced by co-culture with T cells. However, soluble T cell factor enhancement of the TG B cell responses was normal. These data suggest that the mCD43 expression on B cells may inhibit cell interactions that are important for enhanced TI Ag responses. The anti-adhesive forces of mucins in general may thus be critical in regulating both TD and TI humoral responses.     

Maternal performance differences between porcine stress syndrome-normal and -carrier Landrace females

Differences between porcine stress syndrome (PSS) normal (NN) and carrier (Nn) Landrace dams were determined for adjusted number of pigs born alive, adjusted number of pigs at 21 d, adjusted 21-d litter weight, proportion of pigs surviving to 21 d, and farrowing interval. Data were analyzed from a total of 841 females, 623 normal (NN) and 218 carriers (Nn) having 2,231 and 869 records, respectively. Three susceptible (nn) females from two herds were dropped from the analysis because of their small contribution to the total number of records. Frequency of the recessive PSS allele ranged from .07 to .28 in the nine herds involved in this study. Data were adjusted using Landrace breed-specific adjustments and analyzed with mixed-model derivative-free REML procedures fitting the dams' PSS genotype as a fixed effect in the model. Only females having two or more successive parities were used in the analysis of farrowing interval, resulting in a reduction of total records analyzed to 2,201 (1,564 NN and 637 Nn records) from 632 females (445 NN and 187 Nn females). No differences between NN and Nn dams were observed for adjusted number of pigs born alive, adjusted number of pigs at 21 d, adjusted 21-d litter weight, proportion of pigs surviving to 21 d, and farrowing interval. The results of this investigation indicate no significant maternal performance differences between PSS NN or Nn Landrace dams.     

Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets

The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequivalent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each method, (3) determine metric limits that are consistent with the observed bioequivalence, and (4) rationalize the observed metric limits with respect to the role of dissolution in overall metoprolol absorption. Dissolution was performed by the USP monograph method on four formulations of metoprolol tartrate tablets (Lopressor plus fast, medium, and slow dissolving test formulations). Three general approaches to compare dissolution profiles were examined; they were ANOVA-based, model-independent, and model-dependent approaches. It is concluded that model-independent approaches and several model-dependent approaches yielded numerical results that can serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metoprolol tartrate formulations. However, these methods presented complications. Some metrics were dependent on the length of the dissolution profile and the sampling scheme. Results from the pairwise procedures also depended on the pairing assignment of individual profiles. In spite of complications, these methods suggested wide dissolution specification limits. Wide dissolution specifications were rationalized through an analysis of in vitro-in vivo relationships, which indicated metoprolol dissolution from these formulations was not the rate-limiting step; hence, a range of dissolution profiles can be expected to yield equivalent plasma profiles.     

Complications of laparoscopic paraesophageal hernia repair

The complications of laparoscopic paraesophageal hernia repair at two institutions were reviewed to determine the rate and type of complications. A total of 76 patients underwent laparoscopic paraesophageal hernia repair between December 1992 and April 1996. Seventy-one of them had fundoplication (6 required a Collis-Nissen procedure). Five patients underwent hernia reduction and gastropexy only. There was one conversion to laparotomy. Traumatic visceral injury occurred in eight patients (11%) (gastric lacerations in 3, esophageal lacerations in 2, and bougie dilator perforations in 3). All lacerations were repaired intraoperatively except for one that was not recognized until postoperative day 2. Vagus nerve injuries occurred in at least three patients. Three delayed perforations occurred in the postoperative period (4%) (2 gastric and 1 esophageal). Two patients had pulmonary complications, two had gastroparesis, and one had fever of unknown origin. Seven patients required reoperation for gastroparesis (n = 2), dysphagia after mesh hiatal closure of the hiatus (n = 1), or recurrent herniation (n = 4). There were two deaths (3%): one from septic complications and one from myocardial infarction. Paraesophageal hernia repair took significantly longer (3.7 hours) than standard fundoplication (2.5 hours) in a concurrent series (P <0.05). Laparoscopic paraesophageal hernia repair is feasible but challenging. The overall complication rate, although significant, is lower than that for nonsurgically managed paraesophageal hernia.     

Mechanism-based inactivation of human liver cytochrome P450 2A6 by 8-methoxypsoralen

The P450 2A6 catalyzed 7-hydroxylation of coumarin proceeded with a mean Km of 0.40 (+/-0.13) microM and Vmax of 6.34 nmol/nmol P450/min (36-fold variation) in microsomal preparations from a panel of 12 human livers. Substrate depletion was avoided during the kinetic determinations. 8-Methoxypsoralen (8-MOP) is a potent mechanism-based inactivator of human liver P450 2A6 and reconstituted purified recombinant P450 2A6 based on the following evidence: 1) 8-MOP causes time, concentration, and NADPH-dependent loss of P450 2A6 activity that is not reversed by potassium ferricyanide or extensive dialysis, 2) loss of P450 2A6 activity is associated with a loss of spectrally observable P450, 3) addition of nucleophiles or reactive oxygen scavengers to the incubations does not prevent inactivation of P450 2A6, and 4) 8-MOP-dependent P450 2A6 inactivation is inhibited (concentration dependent) by the addition of a competitive inhibitor (pilocarpine). Inactivation is selective for P450 2A6 at low concentrations of 8-MOP (2.5 microM) after short incubation time periods (3 min) and was characterized by a KI of 0.8 and 1.9 microM in a reconstituted and microsomal system, respectively, and a kinact of 1 min-1 and 2 min-1 in a reconstituted and microsomal system, respectively. A substrate depletion partition ratio of 21 was calculated for the inactivation of recombinant P450 2A6. Potency and selectivity suggest that 8-MOP could be a useful tool in vitro for evaluating P450 2A6 activity in various enzyme preparations.     

A Convergent-Divergent Approach to Context Processing, General Intellectual Functioning, and the Genetic Liability to Schizophrenia.

Convergent and divergent validity are critically important in developing psychological measures that reveal interpretable deficits in disordered populations. This article reports on 2 studies that evaluated the validity of context processing measures. In Experiment 1, a confirmatory factor analysis of data from 481 healthy adults established the convergent validity of 2 context processing measures and showed that context processing accounted for significant amounts of variance in standard IQ and working memory measures. In Experiment 2, 20 schizophrenia patients, 16 of their healthy siblings, and 28 controls were evaluated using a novel, short context processing measure, the dot pattern expectancy (DPX) task. The DPX was sensitive to specific deficits in schizophrenia patients and their healthy siblings. These findings support the construct validity of context processing measures, suggest context processing is a component of intellectual functioning, and demonstrate that brief context processing measures remain sensitive to psychopathological deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic ethanol consumption and withdrawal on the neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one in male and female rats

Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross-tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABA(A) receptor modulator, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP). Alterations in endogenous, cerebral cortical levels of 3alpha,5alpha-THP during alcohol withdrawal could contribute to the observed sensitization to 3alpha,5alpha-THP. Therefore, this study investigated plasma and brain levels of 3alpha,5alpha-THP, progesterone, and corticosterone during alcohol dependence and withdrawal in the rat. Plasma corticosterone, progesterone (a precursor of 3alpha,5alpha-THP) and 3alpha,5alpha-THP levels were unchanged in alcohol-dependent animals. Cerebral cortical levels of 3alpha,5alpha-THP decreased in dependent male animals, but not in dependent female rats. During alcohol withdrawal, plasma corticosterone and progesterone levels increased in male, but not female rats. However, neither plasma nor cerebral cortical 3alpha,5alpha-THP levels were altered from control levels in male or female rats during alcohol withdrawal. Plasma and brain levels of 3alpha,5alpha-THP were markedly higher in female compared with male rats. Cerebral cortical levels of 3alpha,5alpha-THP during the diestrus phase of the estrus cycle were approximately 4 to 6 ng/g, a concentration that may approach physiological relevance. These findings suggest that sensitization to 3alpha,5alpha-THP during alcohol withdrawal is not mediated by elevations in brain levels of endogenous 3alpha,5alpha-THP in male or female rats. However, elevations in circulating corticosterone and progesterone levels during ethanol withdrawal in male rats may underlie gender differences in allopregnanolone sensitivity during ethanol withdrawal.