Over-expression of the potassium channel Kir2.3 using the dopamine-1 receptor promoter selectively inhibits striatal neurons.

Dysfunction of basal ganglia circuits underlies a variety of movement disorders and neuropsychiatric conditions. Selective control of the electrical activity of striatal outflow pathways by manipulation of ion channel function presents a novel therapeutic approach. Toward this end, we have constructed and studied in vitro an adenoviral gene transfer vector that employs the promoter region of the dopamine-1 receptor to drive expression of the inward rectifier K(+) channel Kir2.3. The use of this neuronal promoter confers cell-type specificity and a physiological level of trans-gene expression in rat primary striatal cultures. The electrophysiological properties were confirmed in transfected human embryonic kidney cells, in which an inwardly-rectifying, Cs(+)-sensitive current was measured by voltage clamp. Current clamp studies of transduced striatal neurons demonstrated an increase in the firing threshold, latency to first action potential and decrease in neuronal excitability. Neurotoxin-induced activation of c-Fos, a marker of neuronal activity, was blocked in transduced neurons indicating that the decrease in electrical excitability was physiologically significant. When used in vivo, this strategy may have the potential to positively impact movement disorders by selectively changing activity of neurons belonging to the direct striatal pathway, characterized by the expression of dopamine-1 receptors.

Biphasic regulation of development of the high-affinity saxitoxin receptor by innervation in rat skeletal muscle.

Specific binding of 3H-saxitoxin (STX) was used to quantitate the density of voltage-sensitive sodium channels in developing rat skeletal muscle. In adult triceps surae, a single class of sites with a KD = 2.9 nM and a density of 21 fmol/mg wet wt was detected. The density of these high-affinity sites increased from 2.0 fmol/mg wet wt to the adult value in linear fashion during days 2-25 after birth. Denervation of the triceps surae at day 11 or 17 reduced final saxitoxin receptor site density to 10.4 or 9.2 fmol/mg wet wt, respectively, without changing KD. Denervation of the triceps surae at day 5 did not alter the subsequent development of saxitoxin receptor sites during days 5-9 and accelerated the increase of saxitoxin receptor sites during days 9-13. After day 13, saxitoxin receptor development abruptly ceased and the density of saxitoxin receptor sites declined to 11 fmol/wg wet wt. These results show that the regulation of high-affinity saxitoxin receptor site density by innervation is biphasic. During the first phase, which is independent of continuing innervation, the saxitoxin receptor density increases to 47-57% of the adult level. After day 11, the second phase of development, which is dependent on continuing innervation, gives rise to the adult density of saxitoxin receptors.

Perceiving persons and groups.

This article analyzes the similarities and differences in forming impressions of individuals and in developing conceptions of groups. In both cases, the perceiver develops a mental conception of the target (individual or group) on the basis of available information and uses that information to make judgments about that person or group. However, a review of existing evidence reveals differences in the outcomes of impressions formed of individual and group targets, even when those impressions are based on the very same behavioral information. A model is proposed to account for these differences. The model emphasizes the role of differing expectancies of unity and coherence in individual and group targets, which in turn engage different mechanisms for processing information and making judgments. Implications of the model are discussed.

Developmental regulation of the A-type potassium-channel current in hippocampal neurons: role of the Kvbeta 1.1 subunit.

The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvbeta 1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (tau(in)) of voltage-gated K+ currents: 17.9+/-1.5 ms in young neurons (5-7 days in vitro; n=53, mean+/-S.E.M.); 9.9+/-1.0 ms in mature neurons (12-15 days in vitro; n=72, mean+/-S.E.M., P<0.01). During the same developmental time, the level of Kvbeta 1.1 transcript increased more than two-fold in vitro and in vivo, determined by semi-quantitative reverse transcriptase-polymerase chain reaction for hippocampus. The hypothesis that up-regulation of Kvbeta 1.1 led to the changes in tau(in) was tested in vitro, using antisense knockdown. Kvbeta 1.1-specific antisense DNA was introduced with a modified herpes virus co-expressing enhanced green fluorescent protein and knockdown of Kvbeta 1.1 was verified by immunocytochemistry. Following transduction with the antisense virus, mature neurons reverted to tau(in) values characteristic of young neurons: 18.3+/-2.4 ms (n=20). The effect of antisense knockdown on electrical excitability was tested using current-clamp protocols to induce repetitive firing. Treatment with the antisense virus increased the interspike interval over a range of membrane depolarization (baseline membrane potential=-40 to +20 mV). This effect was most pronounced at -40 mV, where the ISI of the first pair of action potentials was nearly doubled. These data indicate that Kvbeta 1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvbeta 1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability.

The use and failure rates of protective equipment to prevent blood and bodily fluid contamination in the obstetric health care worker.

OBJECTIVE: To determine the frequency of use and the failure rate of protective equipment by obstetric staff during common obstetric procedures. METHODS: A prospective observational study was conducted of multiple obstetric procedures. The presence, area of specialty, level of training, and gender of each team member were recorded along with the use of protective equipment (cap, mask, eyewear, gown, gloves, and shoe protection). These observations were recorded by two trained observers. Blood and bodily fluid contamination of the protective equipment was quantified and recorded for each person. A forensic medicine reagent (Luminol; Cluefinders Inc., Tampa, FL) was used to detect trace amounts of blood on the inner surface of a selected subset of gowns that had gross external contamination but no obvious penetration. RESULTS: Two hundred forty-one obstetric procedures were observed involving 1022 medical personnel. The use of at least one piece of protective equipment was noted 88% of the time. Compliance with universal precautions by attending and resident physicians in all deliveries (vaginal, forceps, vacuum, cesarean) was observed in 65 (25.2%) medical personnel. The use of protective equipment varied by the type of procedure, area of specialty, and level of training of the team member. In the gowns examined with the forensic medicine reagent, 44% of the cases demonstrated laboratory evidence of penetration. The frequency of gown failure varied with the type of surgical gown used. CONCLUSION: Despite the mandate in the medical community for universal precautions, the rate of compliance remains low. However, even among the compliant medical staff, protective equipment labeled as impenetrable has a high failure rate.

The natural history of cigarette smoking: predicting young-adult smoking outcomes from adolescent smoking patterns.

Assessed the magnitude of risk that adolescent cigarette smoking carries for adult smoking. Using a longitudinal, prospective design, results indicate that even infrequent experimentation in adolescence significantly raises the risk for adult smoking and that regular (at least monthly) adolescent smoking raises the risk for adult smoking by a factor of 16 compared to nonsmoking adolescents. Relative risk was also increased by an early onset of smoking and by a stable, uninterrupted course from experimentation to regular smoking. Relative risk did not significantly vary by age or sex. The continuity of smoking behavior between adolescence and adulthood supports the importance of primary prevention programs directed at adolescent populations.

Four pathways to young-adult smoking status: adolescent social-psychological antecedents in a midwestern community sample.

Evaluated the ability of social-psychological factors, measured in adolescence, to predict young-adult smoking outcomes. Results showed substantial continuity in the antecedents of adolescent and young-adult smoking but important discontinuities as well. Beliefs in the negative social consequences of smoking and beliefs about academic success and independence were important to adolescent but not to adult smoking. Conversely, beliefs in the negative health consequences of smoking were more important to adult smoking than to adolescent smoking. Results also showed an appreciable amount of smoking onset after the high school years, as well as an appreciable amount of adolescent smoking that did not persist into young adulthood. Antecedents of late-onset smoking and of nonpersistent smoking are described.

Prospective predictors of quit attempts and smoking cessation in young adults.

This study examined prospective predictors of attempts to quit smoking and successful quitting among those who attempted to quit (n = 700), using a long-term longitudinal study of the natural history of cigarette smoking in a midwestern community sample. Participants, originally surveyed in 6th-12th grade (1980-1983), were followed up in 1987 and 1994. Results showed that amount of smoking, gender, education, health beliefs about smoking, value on healthy lifestyle, motives for smoking, reasons for quitting, and occupancy of young adult social roles were significant predictors of cessation. However, there were different predictors of attempts to quit and successful quitting among those who attempted to quit. From a public health perspective, both predictors of quit attempts and predictors of successful quitting among attempters are useful targets for intervention.

From adolescence to adulthood: age-related changes in beliefs about cigarette smoking in a midwestern community sample.

The current study used a cohort-sequential design to examine age-related changes in health-relevant beliefs from the middle school years through age 37 in a large, midwestern, community sample (N=8,556). Results suggest systematic age-related changes such that beliefs in the personalized risks of smoking declined in middle school and then increased, beliefs in generalized health risks increased beginning in the middle school years, and values placed on health as an outcome decreased in the high school years and then increased. These findings suggest that intervention programs must counter declining personalized risk perceptions among middle school students and declining values placed on health among high school age students.

The natural history of cigarette smoking from adolescence to adulthood in a midwestern community sample: multiple trajectories and their psychosocial correlates.

Previous research on the natural history of smoking has focused on overall group trajectories without considering the possibility of risk subgroup variation. To address this limitation, the authors of the present study aimed to identify subgroups with varying trajectories of smoking behavior. The authors accomplished this within a cohort-sequential study of a large community sample (N = 8,556) with measurements spanning ages 11-31. After removing 2 a priori groups (abstainers and erratics), the authors empirically identified 4 trajectory groups--early stable smokers, late stable smokers, experimenters, and quitters--and psychosocial variables from adolescence and young adulthood were significantly distinguished among them. Given recent advances in quantitative methods, it is now feasible to consider subgroups of trajectories within an overall longitudinal design.

The natural history of cigarette smoking from adolescence to adulthood: demographic predictors of continuity and change.

The current study examined the natural history of smoking from adolescence to adulthood in a community sample. Participants were from a longitudinal study (N = 4,035, 51.7% female, average age = 29 years). Group-level analyses showed a significant increase in smoking from adolescence to young adulthood and a nonsignificant decline after the mid-20s. Individual-level analyses showed that there was appreciable cessation and relapse but little new initiation in adulthood. Both adolescent and young adult smoking status were powerful predictors of adult smoking. Moreover, there was less cessation among less educated individuals and those with smoking parents, and more cessation among those who assumed adult social roles. The findings support the importance of prevention campaigns aimed at adolescent smoking and also suggest that those with lower educational attainment or with a family history of smoking are at heightened risk.

Hyper-reflexia without spasticity after unilateral infarct of the medullary pyramid.

Whether or not a lesion confined to the pyramidal tract produces spasticity in humans remains an unresolved controversy. We have studied a patient with an ischemic lesion of the right medullary pyramid, using objective measures of hyper-reflexia, spasticity, and weakness. Electromyographic activity (EMG) of the biceps muscles was recorded under the following conditions: (1) in response to a tendon tap with an instrumental reflex hammer, (2) in response to imposed quick stretch with motion analysis, and (3) during an isometric holding task. Hyper-reflexia of the involved arm in response to tendon tap was shown to be due primarily to an increase in the gain of the reflex arc. No velocity-dependent increase in the response to quick stretch of the involved arm was present. This was consistent with the absence of detectable spasticity on the clinical exam. These findings suggest that a lesion confined to the medullary pyramid can give rise to weakness and hyper-reflexia without causing spasticity. Moreover, these findings suggest that different anatomical substrates may underlie the clinical phenomena of hyper-reflexia and spasticity.

Detecting and identifying change: additions versus deletions.

The recognition of changes in the features of objects was examined as a function of the nature of the change (additions, deletions, no change). In two experiments we assessed both detection (noticing whether the stimulus had changed) and identification (specifying the exact nature of the change). Both detection and identification were expected to depend upon the subject's awareness of the subsequent recognition tasks while the original stimuli were encoded. In Experiment 1, subjects were not aware of subsequent detection and identification tasks while they initially viewed study slides of the to-be-changed stimuli. During the subsequent presentation of the test stimuli, detection and identification were superior for additions. On the other hand, in Experiment 2 when subjects were aware of the subsequent recognition tasks while viewing each study slide, a detection advantage for deletions obtained. Identification performance depended upon a further factor, whether the features of a stimulus were codable. Only in codable stimuli were deletions easier to identify than additions. The differences between the two experiments in detecting and identifying additions versus deletions are consistent with Tversky's (1977) research that stresses the importance of specifying which representation (the study stimulus or the test stimulus) is the subject of comparison in the comparative judgment.

Effects of initial request size and timing of a second request on compliance: the foot in the door and the door in the face.

A field experiment tested four separate procedures for influencing compliance to the second of two requests. Two factors--size of initial request and timing of the second request--were included in a 2 X 2 factorial design. Subjects were induced either to comply with a small initial request or to refuse a large initial request. They then received a moderate request either immediately (no delay) or 7--10 days later (delay). Compliance to the second request was the dependent measure. The results in the two delay conditions and the small-request--no delay condition supported a self-perception position in that the induction of one kind of behavior (compliance or noncompliance) carried over to affect subsequent behavior similarly. The large-request--no dealy condition supported a bargaining explanation, as initial refusal to comply led to an increase in subsequent compliance. Possible processes that could account for these results are discussed.

On-line and memory-based aspects of individual and group target judgments.

Ss were given instruction sets to induce either on-line or memory-based processing while reading behavioral statements about individual and group targets. Impression-set instructions induced online judgments, and comprehensibility-set (comp) instructions induced memory-based judgments regardless of target type. More important, with nondirective instructions (memory set), natural differences in processing information about individuals and groups were observed, with more online judgments for individuals. As expected, illusory correlations between minority targets and infrequent behaviors (a memory-based product) emerged with comp instructions (which induced memory-based judgments for both target types) and in the memory-set condition for group targets only. These data provide insights into the differences in impression formation for groups and individuals and furnish direct evidence of the processes responsible for illusory correlations.

Illusory correlation in the perception of groups: an extension of the distinctiveness-based account.

The prevailing explanation for illusory correlation in the stereotyping of groups is that distinctive information (minority groups' infrequent behaviors) is salient, receives enhanced encoding, and becomes highly accessible, thus biasing subsequent judgments. This distinctiveness-based explanation (DBE) depends on information distinctiveness at the time of its encoding. Information distinctiveness at encoding was manipulated, while ultimate distinctiveness was kept constant. Experiment 1, contrary to the DBE, found illusory correlations emerge regardless of distinctiveness at encoding. Experiment 2 collected process data that showed that ultimately distinctive behaviors were highly accessible at the time of judgment even when they were not distinctive at encoding. Experiments 3-5 ruled out an alternative account. A basis for illusory correlation that depends on postpresentation, but prejudgment, encoding of distinctive information is suggested.

Inferring traits from behaviors versus behaviors from traits: the induction-deduction asymmetry.

It is argued that inductive inferences from behaviors to traits are performed more frequently than deductive inferences from traits to behaviors-a phenomenon referred to as the induction-deduction asymmetry. Two experiments are reported in which behavior-to-trait inferences and trait-to-behavior inferences were compared within the same paradigm: Participants learned a series of descriptions of a target person, half of which were presented in trait form, half in behavior form. A subsequent recognition task was constructed so that some of the items (traits and behaviors) had actually been seen, some were entirely new, and some were new but had been implied by the information given. The 2 experiments provide clear evidence for the hypothesis that traits implied by a behavior are more frequently misidentified as already seen than behaviors implied by a trait. Response-time data in Experiment 2 further suggest that inferences from behaviors to traits are made on-line, whereas inferences from traits to behaviors appear to be memory based.

Target entitativity: implications for information processing about individual and group targets.

It is hypothesized that perceptions of entitativity (i.e., seeing social targets as possessing unity and coherence) have important implications for how one organizes information about, and forms impressions of, individual and group targets. When perceivers expect entitativity, they should form an integrated impression of the target, resulting in on-line judgments. However, when perceivers expect little entitativity, they should not process target-relevant information in an integrative fashion, resulting in memory-based judgments. Although many factors affect perceptions of entitativity, the current study focused on expectations of similarity and behavioral consistency. It was predicted that in general, perceivers expect greater entitativity for individual than group targets. However, when explicitly provided with similar expectancies of entitativity, information processing would be similar for both individual and group targets. Two experiments supported these predictions, using recall, memory-judgment correlation, and illusory correlation measures.

Within-target illusory correlations and the formation of context-dependent attitudes.

Two experiments explored the formation of context-dependent attitudes about a single social target. One such mechanism for the development of differential attitudes toward a target in different contexts is illusory correlation formation. It was proposed that within-target illusory correlations (i.e., perceiving unwarranted associations between salient target behaviors and distinctive domains in which the target is observed) can result in biased evaluations of a social target in different domains (e.g., home vs. work). When memory-based (vs. on-line) judgments were induced, perceivers formed context-dependent attitudes for both group (Experiment 1) and individual (Experiment 2) targets. These findings are consistent with theories regarding multiply categorizable attitude objects. Further, they suggest that some apparent discrepancies between attitudes and behavior may reflect holding multiple context-dependent attitudes about social targets.

Varieties of groups and the perception of group entitativity.

Three studies examined perceptions of the entitativity of groups. In Study 1 (U.S.) and Study 2 (Poland), participants rated a sample of 40 groups on 8 properties of groups (e.g., size, duration, group member similarity) and perceived entitativity. Participants also completed a sorting task in which they sorted the groups according to their subjective perceptions of group similarity. Correlational and regression analyses were used to determine the group properties most strongly related to entitativity. Clustering and multidimensional scaling analyses in both studies identified 4 general types of groups (intimacy groups, task groups, social categories, and loose associations). In Study 3, participants rated the properties of groups to which they personally belonged. Study 3 replicated the results of Studies 1 and 2 and demonstrated that participants most strongly valued membership in groups that were perceived as high in entitativity.