How Adults With Stroke Conceptualize Physical Activity: An Exploratory Qualitative Study.

IMPORTANCE: Physical activity (PA) is recommended for improving physical and cardiovascular function but can be challenging because of stroke-related impairments. A better understanding of how adults with stroke conceptualize PA could assist in developing effective interventions for increasing poststroke PA. OBJECTIVE: To explore how adults with stroke conceptualize PA. DESIGN: Phenomenological qualitative design. SETTING: Participants' homes. PARTICIPANTS: Community-dwelling adults with chronic (>6 mo) stroke (N = 15). OUTCOMES AND MEASURES: Semistructured interviews were conducted with participants. Data were analyzed by means of inductive content analysis to identify key themes. RESULTS: Three key themes emerged: (1) moderate to vigorous PA, which includes exercise-related activities (going to the gym, walking, playing sports); (2) PA necessary for performing daily activities and occupations, which includes basic and instrumental activities of daily living; and (3) avoiding sedentary behavior, which includes not wanting to sit for long periods of time, avoiding boredom, and valuing PA over being sedentary. CONCLUSIONS AND RELEVANCE: Participants broadly categorized PA, encompassing multiple activity types, which is encouraging because reducing sedentary behavior and increasing PA of any intensity can improve cardiometabolic health. Interventions that complement and enhance these conceptualizations, alone or in combination with other mechanisms of action, should be explored for their efficacy in increasing PA in adults with stroke. WHAT THIS ARTICLE ADDS: After stroke, perceptions of PA encompass exercise, daily activities and occupations, and avoiding sedentary behavior; these perceptions could be harnessed to promote PA among adults after stroke.

Evaluation of Students' Conceptual Organization of Neuroscience May Depend on the Expert Referent.

The Structural Assessment of Knowledge (SAK) is an implicit form of evaluation, which examines the organization of knowledge structures or networks. The current study investigates variability in expert knowledge structures of neuroscience concepts, and whether different expert referents affect undergraduate students' learning of neuronal physiology and structure and function relationships across different course levels. Experts and students made pairwise ratings of terms on their relatedness. Students completed the ratings before and after learning in the classroom. Using Pathfinder software, students' networks were compared to three expert networks: their individual professor, an average of neuroscience professors at their institution, and an average of neuroscience professors in the field across multiple institutions. Neuroscience experts had large variability in the number of links in their networks. Furthermore, an exploratory analysis suggests experts' training may differentiate knowledge structures for some concepts. For student knowledge structures, the type of expert referent interacted with the type of class for neuronal physiology, but not structure and function relationships. More specifically, for neuronal physiology, advanced students were more similar to their professor than professors at their institution or professors in the field, but introductory students' similarity did not vary by expert referent. These findings highlight the role factors such as type of class, type of expert referent, and type of knowledge may play in comparisons using SAK. These issues may be more complex in interdisciplinary fields like neuroscience.

The Role of Musical Experience in Hemispheric Lateralization of Global and Local Auditory Processing.

The global precedence effect is a phenomenon in which global aspects of visual and auditory stimuli are processed before local aspects. Individuals with musical experience perform better on all aspects of auditory tasks compared with individuals with less musical experience. The hemispheric lateralization of this auditory processing is less well-defined. The present study aimed to replicate the global precedence effect with auditory stimuli and to explore the lateralization of global and local auditory processing in individuals with differing levels of musical experience. A total of 38 college students completed an auditory-directed attention task while electroencephalography was recorded. Individuals with low musical experience responded significantly faster and more accurately in global trials than in local trials regardless of condition, and significantly faster and more accurately when pitches traveled in the same direction (compatible condition) than when pitches traveled in two different directions (incompatible condition) consistent with a global precedence effect. In contrast, individuals with high musical experience showed less of a global precedence effect with regards to accuracy, but not in terms of reaction time, suggesting an increased ability to overcome global bias. Further, a difference in P300 latency between hemispheres was observed. These findings provide a preliminary neurological framework for auditory processing of individuals with differing degrees of musical experience.

Use of Structural Assessment of Knowledge for Outcomes Assessment in the Neuroscience Classroom.

Outcomes assessment of undergraduate neuroscience curricula should assess the ability to think integratively about basic neuroscience concepts based on two of the core competencies established by the Faculty for Undergraduate Neuroscience. The current study investigated whether the structural assessment of knowledge (SAK) approach, which evaluates the organization of an individual's knowledge structures, is effective for demonstrating learning of basic neuroscience concepts. Students in an introductory psychology course (n = 29), an introductory neuroscience course (n = 19), or an advanced behavioral neuroscience course (n = 15) completed SAK before and after learning gross brain anatomy and neuronal physiology. All students showed improvements in their SAK after short-term dissemination for gross brain anatomy, but not for neuronal physiology, concepts. Therefore, research is needed to determine whether the effectiveness of SAK in outcomes assessment depends on the content or teaching style. Additional research using SAK should also explore effectiveness for learning over longer time frames and correlations with student performance in the course. However, the results suggest SAK is a promising technique for outcomes assessment of undergraduate neuroscience curricula.

Health Behavior Change Following Stroke: Recommendations for Adapting the Diabetes Prevention Program-Group Lifestyle Balance Program.

Objective. History of stroke increases risk for recurrent stroke, which is a significant issue faced by survivors. The Diabetes Prevention Program-Group Lifestyle Balance (DPP-GLB) program is an effective lifestyle modification intervention for ameliorating cardiovascular risk factors but has not been adapted to account for common stroke-related deficits. The purpose of this study was to determine appropriate adaptations to the DPP-GLB for adults with stroke. Design and Methods. In this phenomenological qualitative study, a total of 15 community-dwelling adults with stroke and 10 care-partners participated in 4 focus groups to review DPP-GLB curriculum materials and provide recommendations for adaptation. Focus groups were recorded and transcribed. Inductive content analysis was used to identify key themes. Results. Three themes were identified. First, physical, cognitive, sensory, and psychosocial stroke-related deficits could affect DPP-GLB participation. Second, existing DPP-GLB characteristics could facilitate participation by adults with stroke. Third, stroke-specific adaptations were recommended, including modified session content and format, adapted physical activity and dietary recommendations, and inclusion of care-partners. Conclusion. Current DPP-GLB content and structure may be insufficient to meet the unique needs of adults with stroke. The suggested adaptations should be incorporated into a stroke-specific curriculum and tested for preliminary efficacy for reducing recurrent stroke risk.

Autistic People Do Enhance Their Selves.

We investigated whether autistic people are less prone to self-enhance (i.e., portray themselves in socially desirable ways). Autistic (N = 130) and non-autistic (N = 130) participants first responded to social desirability items using the standard instruction to endorse each item as true or false about themselves. Then, all participants read an explanation of what social desirability items measure before responding again to the social desirability items. Self-enhancement was operationalized as participants endorsing more social desirability items before learning the explanation than after. All participants endorsed significantly more social desirability items before learning the explanation than after, F subjects(1,258) = 57.73, p < .001, η2 p = .183; F items(1,34) = 43.04, p < .001, η2 p = .559). However, autistic and non-autistic participants did not significantly differ in how many items they endorsed, either before or after reading the explanation, indicating that autistic people are as susceptible to social desirability and self-enhancement as non-autistic people are. Our results challenge the claim that autistic people are immune to reputation management.

Response of a concentrated monoclonal antibody formulation to high shear.

There is concern that shear could cause protein unfolding or aggregation during commercial biopharmaceutical production. In this work we exposed two concentrated immunoglobulin-G1 (IgG1) monoclonal antibody (mAb, at >100 mg/mL) formulations to shear rates between 20,000 and 250,000 s(-1) for between 5 min and 30 ms using a parallel-plate and capillary rheometer, respectively. The maximum shear and force exposures were far in excess of those expected during normal processing operations (20,000 s(-1) and 0.06 pN, respectively). We used multiple characterization techniques to determine if there was any detectable aggregation. We found that shear alone did not cause aggregation, but that prolonged exposure to shear in the stainless steel parallel-plate rheometer caused a very minor reversible aggregation (<0.3%). Additionally, shear did not alter aggregate populations in formulations containing 17% preformed heat-induced aggregates of a mAb. We calculate that the forces applied to a protein by production shear exposures (<0.06 pN) are small when compared with the 140 pN force expected at the air-water interface or the 20-150 pN forces required to mechanically unfold proteins described in the atomic force microscope (AFM) literature. Therefore, we suggest that in many cases, air-bubble entrainment, adsorption to solid surfaces (with possible shear synergy), contamination by particulates, or pump cavitation stresses could be much more important causes of aggregation than shear exposure during production.

Explicit Associations with Autism and Disability.

Objectives: Autistic people call for greater acceptance even though the general public has greater awareness of the autism spectrum. This study investigated explicit or conscious attitudes toward the autism spectrum and disability in college students and the general population. We hypothesized that both samples would associate "a person on the autism spectrum" with more negative attributes than other types of people except for "a person with a disability." Methods: In Phase 1, participants generated 10 word associations for 8 labels: a person on the autism spectrum, a person not on the autism spectrum, a person with a disability, a person without a disability, a college student, a professor, a child, and a parent. In Phase 2, participants rated the 10 most common words for each label (type of person) in Phase 1 on a 7-point Likert scale from extremely negative to extremely positive. Ninety-nine undergraduate students and 106 adults recruited through Amazon Mechanical Turk completed Phase 1. One hundred twenty-two undergraduate students and 101 adults recruited through Amazon Mechanical Turk completed Phase 2. Results: Only "a person with a disability" in the general population sample was rated as having significant negative associations. However, the associations of "a person with a disability" were rated more negatively than all other labels in both samples, and the associations of "a person on the autism spectrum" were rated as second most negative in the general population sample. Conclusion: Explicit associations toward disability and autism were somewhat mixed. Adults in the general population tended to have more negative explicit associations with disability, and to a lesser extent autism. These results underscore the need to examine attitudes in samples more representative of the general population. Furthermore, evidence of possible explicit negative associations is concerning and highlights the imperative need to confront ableism. Lay summary: Why was this study done?: The general public claims to be aware of the autism spectrum and recent research suggests that they have greater knowledge about the autism spectrum than they did in the past. However, as autistic individuals have articulated, autism awareness is not the same as autism acceptance. In order for autistic individuals to be fully included into society, we must move to autism acceptance. One way researchers examine potential discrimination is by studying attitudes.What was the purpose of this study?: This study examines people's explicit attitudes toward the autism spectrum and to disability. Explicit attitudes are attitudes that are conscious and controllable.What did the researchers do?: Two groups of adults participated in the study: a group of college students and a noncollege sample of adults designed to better represent the general population of adults. Participants completed an online study wherein they were asked to list word associations for different types of people including "a person on the autism spectrum" and "a person with a disability." In a second study, participants then rated the most common associations from extremely negative to extremely positive.What were the results of the study?: The results were somewhat mixed. Only the set of associations of "a person with a disability" were rated by participants in the noncollege group as negative. However, the associations of "a person with a disability" were rated more negatively than all other types of people in both groups, and the associations of "a person on the autism spectrum" were rated as second most negative in the noncollege sample.What do these findings add to what was already known?: The majority of research on explicit attitudes toward autism has focused on children, including how interventions may improve attitudes toward autistic children. Therefore, this research provides much needed information on the state of attitudes toward autistic individuals more generally. This research also provides a comparison of attitudes toward autism, disability, and other groups. Furthermore, research assessing attitudes toward autism in adults has largely focused on college students, whereas this research considered both college students and a noncollege sample.What are the potential weaknesses in the study?: These findings may not extend to a more diverse population as both groups had relatively high education levels, were primarily White non-Hispanic and were living in the United States. Furthermore, participants may have generated more positive associations for "a person on the autism spectrum" and "a person with a disability" because they wanted to be viewed in a favorable light. This is known as a social desirability bias.How will these findings help autistic adults now or in the future?: Unfortunately, possible explicit negative associations with the autism spectrum and with disability are concerning as they reflect people's conscious and controllable attitudes. These results highlight a need for action and also support autistic individuals' demand for actions toward autism acceptance.

The origins of insight in resting-state brain activity.

People can solve problems in more than one way. Two general strategies involve (A) methodical, conscious, search of problem-state transformations, and (B) sudden insight, with abrupt emergence of the solution into consciousness. This study elucidated the influence of initial resting brain-state on subjects' subsequent strategy choices. High-density electroencephalograms (EEGs) were recorded from subjects at rest who were subsequently directed to solve a series of anagrams. Subjects were divided into two groups based on the proportion of anagram solutions derived with self-reported insight versus search. Reaction time and accuracy results were consistent with different cognitive problem-solving strategies used for solving anagrams with versus without insight. Spectral analyses yielded group differences in resting-state EEG supporting hypotheses concerning insight-related attentional diffusion and right-lateralized hemispheric asymmetry. These results reveal a relationship between resting-state brain activity and problem-solving strategy, and, more generally, a dependence of event-related neural computations on the preceding resting state.

The transliminal brain at rest: baseline EEG, unusual experiences, and access to unconscious mental activity.

Transliminality reflects individual differences in the threshold at which unconscious processes or external stimuli enter into consciousness. Individuals high in transliminality possess characteristics such as magical ideation, belief in the paranormal, and creative personality traits, and also report the occurrence of manic/mystic experiences. The goal of the present research was to determine if resting brain activity differs for individuals high versus low in transliminality. We compared baseline EEG recordings (eyes-closed) between individuals high versus low in transliminality, assessed using The Revised Transliminality Scale of Lange et al. (2000). Identifying reliable differences at rest between high- and low-transliminality individuals would support a predisposition for transliminality-related traits. Individuals high in transliminality exhibited lower alpha, beta, and gamma power than individuals low in transliminality over left posterior association cortex and lower high alpha, low beta, and gamma power over the right superior temporal region. In contrast, when compared to individuals low in transliminality, individuals high in transliminality exhibited greater gamma power over the frontal-midline region. These results are consistent with prior research reporting reductions in left temporal/parietal activity, as well as the desynchronization of right temporal activity in schizotypy and related schizophrenia spectrum disorders. Further, differences between high- and low-transliminality groups extend existing theories linking altered hemispheric asymmetries in brain activity to a predisposition toward schizophrenia, paranormal beliefs, and unusual experiences.

L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest.

Hematogenous carcinoma metastasis is supported by aggregated platelets and leukocytes, forming tumor cell emboli. Early tumor cell-platelet interactions can be mediated by P-selectin binding to tumor cell surface ligands and this process is blocked by heparin. We previously showed that L-selectin deficiency also attenuates experimental metastasis. However, the mechanisms and timing of L-selectin action remained unknown. Here, we study how L-selectin facilitates establishment of pulmonary metastatic foci in syngeneic mice by using experimental metastasis to time events following entry of tumor cells into the bloodstream. Although L-selectin deficiency did not affect platelet aggregation or initial tumor cell embolization, the association of leukocytes with tumor cells was reduced and tumor cell survival was diminished 24 hours later. Temporal inhibition of L-selectin by a function-blocking antibody reduced metastasis. Moreover, although selectin blockade by heparin 6 to 18 hours after tumor cell injection was synergistic with P-selectin deficiency in reducing metastasis, there was no further effect in L-selectin-deficient animals. Thus, heparin apparently works at these time points primarily by blocking L-selectin. Endogenous L-selectin ligands were concomitantly induced adjacent to established intravascular tumor cell emboli in a similar time window when leukocytes were also present. Metastasis was attenuated in mice missing these induced endogenous L-selectin ligands due to fucosyltransferase-7 deficiency. Thus, L-selectin facilitation of metastasis progression involves leukocyte-endothelial interactions at sites of intravascular arrest supported by local induction of L-selectin ligands via fucosyltransferase-7. These data provide the first explanation for how leukocyte L-selectin facilitates tumor metastasis.

Gender differences in mental rotation strategy depend on degree of autistic traits.

Participants with low, medium, and high autistic traits completed a mental rotation task while their eye movements were recorded. Men were more accurate than women (F(1, 102) = 4.36, P = 0.04, η2p = 0.04), but there were no group differences in reaction time. In terms of eye movements, all participants tended to rely on top corners of cube figures for most angles of rotation, and bottom corners of cube figures for 0 and 90 degree rotations (duration: F(8, 816) = 21.70, P < 0.001, η2p = 0.18; count: F(8, 816) = 24.42, P < 0.001, η2p = 0.19) suggesting a shift in strategy with rotation angle. Eye movements to corners of cube figures also varied by autistic traits group and gender (duration: F(4, 204) = 2.44, P = 0.05, η2p = 0.05; count: F(4, 204) = 2.47, P = 0.05, η2p = 0.05). Participants with low and medium autistic traits tended to rely more often on the top corners, whereas women with high autistic traits relied on both the top and bottom corners and men with high autistic traits relied on all corners equally. These results suggest mental rotation strategies may vary by both gender and autistic traits. Autism Res 2018, 11: 1024-1037. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The current study looked at eye movements to assess adults' strategies when mentally rotating three-dimensional cube figures. Adults with varying levels of autistic traits differ in their mental rotation strategies. In addition, gender differences in strategies are observed in adults with the highest level of autistic traits.

Do puzzle pieces and autism puzzle piece logos evoke negative associations?

Puzzle pieces have become ubiquitous symbols for autism. However, puzzle-piece imagery stirs debate between those who support and those who object to its use because they believe puzzle-piece imagery evokes negative associations. Our study empirically investigated whether puzzle pieces evoke negative associations in the general public. Participants' ( N = 400) implicit negative associations were measured with an Implicit Association Task, which is a speeded categorization task, and participants' explicit associations were measured with an Explicit Association Task, which is a standard task for assessing consumers' explicit associations with brands (and images of those brands). Puzzle pieces, both those used as autism logos and those used more generically, evoked negative implicit associations ( t(399) = -5.357, p < 0.001) and negative explicit associations ( z = 4.693, p < 0.001, d = 0.491). Participants explicitly associated puzzle pieces, even generic puzzle pieces, with incompleteness, imperfection, and oddity. Our results bear public policy implications. If an organization's intention for using puzzle-piece imagery is to evoke negative associations, our results suggest the organization's use of puzzle-piece imagery is apt. However, if the organization's intention is to evoke positive associations, our results suggest that puzzle-piece imagery should probably be avoided.

Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects.

Heparin and low molecular weight heparin (LMWH) are widely used for treatment of cancer patients with thrombosis, a common complication of malignant disease. Several recent prospective clinical studies indicate that heparin might improve outcomes of human cancer. Meanwhile, experimental evidence from mouse models consistently demonstrates that heparin efficiently inhibits metastasis. We have previously shown that P- and L-selectin play independent roles in supporting the initial stages of hematogeneous metastasis. Heparin is a known potent inhibitor of such selectin-mediated interactions. Here we provide evidence that the absence of both P- and L-selectin (PL -/- mice) dramatically improved survival in an experimental metastasis model. The use of clinically acceptable amounts of heparin did not further aff5ct metastasis rates in such mice. However, a non-anticoagulant derivative of heparin with P- and L-selectin inhibitory properties reduced metastasis to similar levels as observed in PL -/- mice. The virtual elimination of metastasis by a single treatment with a modified heparin without anticoagulant activity strongly suggests that heparin primarily reduces metastatic disease by inhibiting P- and L-selectin interactions. However, such heparins could have further effects at higher doses.

Psychometric Properties of the Autism-Spectrum Quotient for Assessing Low and High Levels of Autistic Traits in College Students.

The current study systematically investigated the effects of scoring and categorization methods on the psychometric properties of the Autism-Spectrum Quotient. Four hundred and three college students completed the Autism-Spectrum Quotient at least once. Total scores on the Autism-Spectrum Quotient had acceptable internal consistency and test-retest reliability using a binary or Likert scoring method, but the results were more varied for the subscales. Overall, Likert scoring yielded higher internal consistency and test-retest reliability than binary scoring. However, agreement in categorization of low and high autistic traits was poor over time (except for a median split on Likert scores). The results support using Likert scoring and administering the Autism-Spectrum Quotient at the same time as the task of interest with neurotypical participants.

Retrospectively Assessed Early Motor and Current Pragmatic Language Skills in Autistic and Neurotypical Children.

Autistic individuals often struggle developmentally, even in areas that are not explicit diagnostic criteria, such as motor skills. This study explored the relation between early motor skills, assessed retrospectively, and current pragmatic language skills. Caregivers of neurotypical and autistic children, matched on gender and age, completed assessments of their child's early motor development and current language abilities. Early motor skills were correlated with later pragmatic language skills, and autistic children exhibited fewer motor skills than neurotypical children. In fact, motor skills were a better predictor of an autism spectrum diagnosis than were scores on a measure of current pragmatic language. These results highlight the important role of motor skills in autism spectrum disorders.

Specificity, contexts, and reference groups matter when assessing autistic traits.

Many of the personality and behavioral traits (e.g., social imperviousness, directness in conversation, lack of imagination, affinity for solitude, difficulty displaying emotions) that are known to be sensitive to context (with whom?) and reference group (according to whom?) also appear in questionnaire-based assessments of autistic traits. Therefore, two experiments investigated the effects of specifying contexts and reference groups when assessing autistic traits in autistic and non-autistic participants. Experiment 1 (124 autistic and 124 non-autistic participants) demonstrated that context matters when assessing autistic traits (F(1,244) = 267.5, p < .001, η2p = .523). When the context of the Broad Autism Phenotype Questionnaire was specified as the participants' out-group (e.g., "I like being around non-autistic people" or "I like being around autistic people"), both autistic and non-autistic participants self-reported having more autistic traits; when the context was specified as the participants' in-group, participants reported having fewer autistic traits. Experiment 2 (82 autistic and 82 non-autistic participants) demonstrated that reference group matters when assessing autistic traits (F(2,160) = 94.38, p < .001, η2p = .541). When the reference group on the Social Responsiveness Scale was specified as the participants' out-group (e.g., "According to non-autistic people, I have unusual eye contact"), autistic participants reported having more autistic traits; when the reference group was their in-group, autistic participants reported having fewer autistic traits. Non-autistic participants appeared insensitive to reference group on the Social Responsiveness Scale. Exploratory analyses suggested that when neither the context nor the reference group is specified (for assessing autistic traits on the Autism-Spectrum Quotient), both autistic and non-autistic participants use the majority ("non-autistic people") as the implied context and reference group.

Differential metastasis inhibition by clinically relevant levels of heparins--correlation with selectin inhibition, not antithrombotic activity.

PURPOSE: Unfractionated heparin reduces metastasis in many murine models. Multiple mechanisms are proposed, particularly anticoagulation and/or inhibition of P-selectin and L-selectin. However, the doses used are not clinically tolerable and other heparins are now commonly used. We studied metastasis inhibition by clinically relevant levels of various heparins and investigated the structural basis for selectin inhibition differences. EXPERIMENTAL DESIGN: Five clinically approved heparins were evaluated for inhibition of P-selectin and L-selectin binding to carcinoma cells. Pharmacokinetic studies determined optimal dosing for clinically relevant anticoagulant levels in mice. Experimental metastasis assays using carcinoma and melanoma cells investigated effects of a single injection of various heparins. Heparins were compared for structural relationships to selectin inhibition. RESULTS: One (Tinzaparin) of three low molecular weight heparins showed increased selectin inhibitory activity, and the synthetic pentasaccharide, Fondaparinux, showed none when normalized to anticoagulant activity. Experimental metastasis models showed attenuation with unfractionated heparin and Tinzaparin, but not Fondaparinux, at clinically relevant anticoagulation levels. Tinzaparin has a small population of high molecular weight fragments not present in other low molecular weight heparins, enriched for selectin inhibitory activity. CONCLUSIONS: Heparin can attenuate metastasis at clinically relevant doses, likely by inhibiting selectins. Equivalent anticoagulation alone with Fondaparinux is ineffective. Clinically approved heparins have differing abilities to inhibit selectins, likely explained by size distribution. It should be possible to size fractionate heparins and inhibit selectins at concentrations that do not have a large effect on coagulation. Caution is also raised about the current preference for smaller heparins. Despite equivalent anticoagulation, hitherto unsuspected benefits of selectin inhibition in various clinical circumstances may be unwittingly discarded.

Cross-resistance to cisplatin in cells with acquired resistance to copper.

PURPOSE: Cells selected for resistance to cisplatin (DDP) demonstrate cross-resistance to copper (Cu) suggesting one or more common mechanisms of cellular defense. We sought to determine whether cells selected for resistance to Cu are cross-resistant to DDP. MATERIALS AND METHODS: Parental HuH7 human hepatoma cells and the CuR27 Cu-resistant subline were compared for sensitivity to Cu and DDP by clonogenic assay, and with respect to drug uptake and efflux by measuring cellular Cu and Pt content. RESULTS: CuR27 cells were found to be 1.8-fold resistant to Cu and 8.6-fold cross-resistant to DDP. Changes in the cellular pharmacokinetics of Cu in the CuR27 cells were paralleled by changes in the kinetics of DDP. The accumulations of Cu and DDP measured at 1 min were, respectively, 36% and 26% of those in the parental HuH7 cells. The initial rate of efflux from the CuR27 cells was 6.2-fold faster for Cu and 2.5-fold faster for DDP than from the HuH7 cells. Cu reduced the accumulation of DDP in the HuH7 cells in a concentration-dependent manner and vice versa. DDP also reduced the efflux of Cu. Western blot analysis demonstrated that expression of the Cu exporter ATP7B was increased 3.9-fold in the CuR27 cells. CONCLUSIONS: In this model system, cross-resistance between Cu and DDP was bidirectional and accompanied by parallel changes in the cellular pharmacokinetics of both compounds. The results are consistent with the idea that transporters and chaperones that normally mediate Cu homeostasis also directly or indirectly modulate the accumulation of DDP.