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PubMed2006

Neural correlates of culturally familiar brands of car manufacturers.

Brands have a high impact on people's economic decisions. People may prefer products of brands even among almost identical products. Brands can be defined as cultural-based symbols, which promise certain advantages of a product. Recent studies suggest that the prefrontal cortex may be crucial for the processing of brand knowledge. The aim of this study was to examine the neural correlates of culturally based brands. We confronted subjects with logos of car manufactures during an fMRI session and instructed them to imagine and use a car of these companies. As a control condition, we used graphically comparable logos of car manufacturers that were unfamiliar to the culture of the subjects participating in this study. If they did not know the logo of the brand, they were told to imagine and use a generic car. Results showed activation of a single region in the medial prefrontal cortex related to the logos of the culturally familiar brands. We discuss the results as self-relevant processing induced by the imagined use of cars of familiar brands and suggest that the prefrontal cortex plays a crucial role for processing culturally based brands.

Adult↗
PubMed2004

Amino acids important for ligand specificity of the human constitutive androstane receptor.

The human constitutive androstane receptor (CAR, NR1I3) is an important ligand-activated regulator of oxidative and conjugative enzymes and transport proteins. Because of the lack of a crystal structure of the ligand-binding domain (LBD), wide species differences in ligand specificity and the scarcity of well characterized ligands, the factors that determine CAR ligand specificity are not clear. To address this issue, we developed highly defined homology models of human CAR LBD to identify residues lining the ligand-binding pocket and to perform molecular dynamics simulations with known human CAR modulators. The roles of 22 LBD residues for basal activity, ligand selectivity, and interactions with co-regulators were studied using site-directed mutagenesis, mammalian co-transfection, and yeast two-hybrid assays. These studies identified several amino acids within helices 3 (Asn(165)), 5 (Val(199)), 11 (Tyr(326), Ile(330), and Gln(331)), and 12 (Leu(343) and Ile(346)) that contribute to the high basal activity of human CAR. Unique residues within helices 3 (Ile(164) and Asn(165)), 5 (Cys(202) and His(203)), and 7 (Phe(234) and Phe(238)) were found control the selectivity for CAR activators and inhibitors. A single residue in helix 7 (Phe(243)) appears to explain the human/mouse species difference in response of CAR to 17alpha-ethynyl-3,17beta-estradiol.

Amino Acid Sequence↗
PubMedDate not supplied

The monoclonal antibody-defined CAR-3 antigen is a serological marker associated with pancreatic carcinoma.

The monoclonal antibody-defined CAR-3 antigen is a new carcinoma associated marker which is expressed on a mucin-like molecule. Serum concentrations of CAR-3 were assayed in 181 patients with carcinomas of different organs, 20 patients with non-carcinomatous malignancies, 123 patients with inflammatory diseases and 150 healthy controls. Serum levels of CAR-3 were significantly increased in 51% of the patients with pancreatic carcinomas, in 60% of patients with biliary tract carcinomas and in about 15% of the patients with carcinomas of the digestive apparatus. Sera from patients with breast carcinomas were negative, as well as sera from patients with melanomas or sarcomas. CAR-3 values in samples from patients with chronic pancreatitis were constantly negative, as were samples from healthy donors. Significant concentrations of CAR-3 were detected in 20% of the sera from patients with acute pancreatitis and in 15% of the sera from patients with cirrhosis. Because of its high specificity for pancreatic carcinomas compared to chronic pancreatitis, CAR-3 seems a promising marker for distinguishing between neoplastic and chronic inflammatory diseases of the pancreas, whose differential diagnosis is difficult.

Adult↗
PubMed2001

Muscle-specific overexpression of the adenovirus primary receptor CAR overcomes low efficiency of gene transfer to mature skeletal muscle.

Significant levels of adenovirus (Ad)-mediated gene transfer occur only in immature muscle or in regenerating muscle, indicating that a developmentally regulated event plays a major role in limiting transgene expression in mature skeletal muscle. We have previously shown that in developing mouse muscle, expression of the primary Ad receptor CAR is severely downregulated during muscle maturation. To evaluate how global expression of CAR throughout muscle affects Ad vector (AdV)-mediated gene transfer into mature skeletal muscle, we produced transgenic mice that express the CAR cDNA under the control of the muscle-specific creatine kinase promoter. Five-month-old transgenic mice were compared to their nontransgenic littermates for their susceptibility to AdV transduction. In CAR transgenics that had been injected in the tibialis anterior muscle with AdVCMVlacZ, increased gene transfer was demonstrated by the increase in the number of transduced muscle fibers (433 +/- 121 in transgenic mice versus 8 +/- 4 in nontransgenic littermates) as well as the 25-fold increase in overall beta-galactosidase activity. Even when the reporter gene was driven by a more efficient promoter (the cytomegalovirus enhancer-chicken beta-actin gene promoter), differential transducibility was still evident (893 +/- 149 versus 153 +/- 30 fibers; P < 0.001). Furthermore, a fivefold decrease in the titer of injected AdV still resulted in significant transduction of muscle (253 +/- 130 versus 14 +/- 4 fibers). The dramatic enhancement in AdV-mediated gene transfer to mature skeletal muscle that is observed in the CAR transgenics indicates that prior modulation of the level of CAR expression can overcome the poor AdV transducibility of mature skeletal muscle and significant transduction can be obtained at low titers of AdV.

Adenoviruses, Human↗
PubMed1989

Influence of the estrous cycle, ovariectomy and estradiol replacement upon the acquisition of conditioned avoidance responses in rats.

The changes in the acquisition of conditioned avoidance responses (CARs) and the performance of some spontaneous behaviors were examined across the estrous cycle of female rats. CARs were facilitated during diestrus, impaired at proestrus and practically abolished at estrus and metestrus. Motor activity and head shaking were minimally affected with the stages of the cycle. Motor activity was increased at metestrus and head shaking decreased at estrus. At 14 days following ovariectomy, there was a significant enhancement of CARs which was antagonized by the daily administration of estradiol benzoate (10 micrograms/kg) for three days. Ovariectomy also increased grooming behavior and estradiol replacement returned grooming to its basal level. The results suggest an inhibitory control of estradiol on CARs and grooming. The involvement of other hormones which also varied across the estrous cycle and its interaction with brain catecholamine systems, particularly dopamine, are discussed.

Animals↗
PubMed2003

A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180 mg alone and with alcohol, with hydroxyzine hydrochloride 50 mg as a positive internal control, on aspects of cognitive and psychomotor function related to driving a car.

BACKGROUND: Antihistamines (H(1)-receptor antagonists) are the mainstay of symptomatic therapy for allergic disorders. Antihistamines are needed that cause no disruptive effects on cognitive and psychomotor function. It is essential that antihistamines maintain the integrity of the cognitive system, not only in ambulatory patients at increased risk of drug-induced traffic- or work-related accidents, but also in students and others whose cognitive or intellectual impairment may adversely affect their performance.Objective; The goal of this study was to investigate the acute effects of fexofenadine hydrochloride 180 mg, alone and with a "social" dose of alcohol, on subjective feelings of sedation and on a battery of objective measures related to driving a car. These measures included information processing, psychomotor speed, and reaction time in an on-the-road car-driving task. Hydroxyzine hydrochloride 50 mg was included in the study as a positive internal control to validate the sensitivity of the psychometri tests to nonspecific impairment. METHODS: In this randomized, double-blind, 6-way, crossover study conducted at the Human Psychopharmacology Research Unit, Medical Research Centre (University of Surrey, Guildford, United Kingdom), 18 healthy volunteers received fexofenadine 180 mg, hydroxyzine 50 mg, and placebo alone and with alcohol (0.3 g/kg body weight or approximately 0.43-0.50 g/L blood-alcohol concentration). Treatment periods were separated by a washout period of at least 6 days. Subjects performed tests of cognitive and psychomotor performance at 1, 3, and 5 and hours after dosing. The test battery included subjective ratings of sedation, critical flicker fusion (CFF), choice reaction time (including recognition reaction time [RRT], motor reaction time [MRT], total reaction time [TRT], and brake reaction time [BRT]. RESULTS: Eighteen healthy male volunteers (median age, 30.5 years [range, 23-44 years]) were entered into the study. Fexofenadine alone and with alcohol had no significant effect on performance compared with placebo and was not distinguishable from placebo in any of the objective or subjective tests at any point. However, impairment was evident following the administration of hydroxyzine. Hydroxyzine caused significant impairment in CFF (P < 0.05), RRT (P < 0.001), and TRT (P < 0.001) compared with placebo. Hydroxyzine with alcohol significantly disrupted performance on all of the above measures with respect to both placebo and fexofenadine (P < 0.05) as well as MRT (P < 0.001). No significant treatment effects on BRT were found. CONCLUSION: Fexofenadine 180 mg did not have disruptive effects on objective measures related to driving a car and aspects of psychomotor and cognitive function, even when combined with a dose of alcohol equivalent to 0.3 g/kg body weight, in a study in which the psychometric assessments were shown to be sensitive to impairment.

Adult↗
PubMed2005

Effects of voice technology on test track driving performance: implications for driver distraction.

This work compares the degradation in driving performance associated with secondary tasks performed with voice-based and visual/manual interfaces, including radio tuning, phone dialing, and more complex tasks involving a sequence of interactions with an in-vehicle computer system. Twenty-one participants drove an instrumented vehicle while performing a combination of car-following, peripheral target detection, and secondary tasks on a closed test track. Drivers compensated for increased task demands associated with secondary tasks by increasing their following distance. Performing secondary tasks also resulted in significant decrements to vehicle control, target detection, and car-following performance. The voice-based interface helped reduce the distracting effects of secondary task performance. Modest improvements were observed for measures of vehicle control and target detection but not for car following. The results indicated that performing in-vehicle tasks required diversion of both peripheral (visual and manual) and attentional (cognitive) resources from driving. The voice-based interface reduced the peripheral impairment but did not appreciably reduce the attentional impairment. Actual or potential applications of this research include improvements to the design of invehicle information systems and the development of evaluation protocols to assess their distraction potential.

Adult↗
PubMed2005

Marijuana use and car crash injury.

AIMS: To investigate the relationship between marijuana use prior to driving, habitual marijuana use and car crash injury. DESIGN AND SETTING: Population based case-control study in Auckland, New Zealand. PARTICIPANTS: Case vehicles were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and control vehicles were a random sample of cars driving on Auckland roads. The drivers of 571 case and 588 control vehicles completed a structured interview. MEASUREMENTS: Self reported marijuana use in the 3 hours prior to the crash/survey and habitual marijuana use over the previous 12 months were recorded, along with a range of other variables potentially related to crash risk. The main outcome measure was hospitalization or death of a vehicle occupant due to car crash injury. FINDINGS: Acute marijuana use was significantly associated with car crash injury, after controlling for the confounders age, gender, ethnicity, education level, passenger carriage, driving exposure and time of day (OR 3.9, 95% CI 1.2-12.9). However, after adjustment for these confounders plus other risky driving at the time of the crash (blood alcohol concentration, seat-belt use, travelling speed and sleepiness score), the effect of acute marijuana intake was no longer significant (OR 0.8, 95% CI 0.2-3.3). There was a strong significant association between habitual use and car crash injury after adjustment for all the above confounders plus acute use prior to driving (OR 9.5, 95% CI 2.8-32.3). CONCLUSIONS: This population-based case-control study indicates that habitual use of marijuana is strongly associated with car crash injury. The nature of the relationship between marijuana use and risk-taking is unclear and needs further research. The prevalence of marijuana use in this driving population was low, and acute use was associated with habitual marijuana use, suggesting that intervention strategies may be more effective if they are targeted towards high use groups.

Accidents, Traffic↗
PubMed1998

The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene.

Two genes, claR and car, encoding proteins involved in clavulanic acid biosynthesis, have been found in a 2.8-kb BglII-EcoRI DNA fragment of Streptomyces clavuligerus adjacent to the region containing the cephamycin and clavulanic acid biosynthesis gene cluster. claR encoded a protein of 431 amino acids (deduced Mr 47080), that showed a significant degree of homology with several transcriptional activators of the LysR family. The ClaR protein contained two helix-turn-helix (HTH) motifs in the amino and carboxyl terminal regions. The second gene, car, encoded a protein of 247 amino acids (Mr 26629) that showed a strong similarity to oxydoreductases of the SDR family. Twelve amino acids of the amino-terminal region were identical to those previously obtained by Edman degradation of the purified clavulanic-9-aldehyde reductase of S. clavuligerus. Amplification of the claR gene in multicopy plasmids resulted in a threefold increase in clavulanic acid production and in a five- to sixfold increase of alanylclavam biosynthesis, whereas cephamycin production was significantly reduced both in defined and in complex media. By contrast, amplification of the car gene had no significant effect on clavulanic acid and alanylclavam or cephamycin production. Both claR and car are expressed as monocistronic transcripts; the level of transcript declined rapidly after 48h in complex media, but low sustained levels of both transcripts were observed in defined GSPG medium until 96h. claR and car were not significantly expressed in mutants disrupted in the ccaR gene, a regulatory gene that controls positively clavulanic acid and cephamycin biosynthesis. These results indicate that clavulanic acid and cephamycin biosynthesis in S. clavuligerus is controlled by a cascade of regulatory proteins that include CcaR and ClaR.

Alcohol Oxidoreductases↗
PubMed2002

The psychological effects of exposure to mixed organic solvents on car painters.

PURPOSE: Interest in diseases of the nervous system resulting from occupational exposure to mixed organic solvents has greatly increased. The aim of our study was to identify preclinical effects of low-level chronic solvent exposure on the central nervous system in car painters by assessing their cognitive performance. METHODS: This psychological study involved 169 clinically healthy male volunteers (84 car painters and 85 controls) and is part of a comprehensive study investigating effects of solvent exposure. The test battery included paper-pencil tests (vocabulary test, block design test, c.i., d2 test), computer-based tests (digit span test, simple-choice reaction time test), and a questionnaire to assess the participants' mental state. RESULTS: Car painters with long-term exposure to solvents showed psychological deviations such as deficits in concentration, memory and reaction time compared to unexposed subjects. The significant differences between the two groups were confirmed by multivariate statistical analysis. CONCLUSIONS: Our study displayed psychological effects associated with long-term solvent exposure in concentrations below German threshold limit values. These findings emphasize the necessity to promote the resolute compliance with occupational safety and health regulations in affected companies.

Adult↗
PubMed2003

Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells.

Coxsackie and adenovirus receptor (CAR) is not only a high-affinity receptor for adenovirus, but also a tumor inhibitor in both prostate and bladder cancer lines. Decreased CAR gene expression is often detected in cancer specimens; however, the mechanism(s) is still unknown. In this study, we cloned the entire CAR gene and characterized the core promoter sequence of the CAR gene. The CAR gene promoter activity correlated with the differential expression of CAR mRNA levels from several urogenital cancer cell lines, indicating that the down-regulation of CAR gene expression is mediated by transcriptional regulation. It is known that epigenetic control, such as DNA methylation and histone acetylation of chromatin structure, dictates gene expression. Data from this study indicate that the activation of the CAR gene promoter is modulated by histone acetylation, but not by DNA methylation, in urogenital cancer cells. Also, a potent cancer chemotherapeutic agent (FR901228), a histone deacetylase inhibitor, was able to induce endogenous CAR gene expression in several urogenital cancer cells. Taken together, epigenetic control of CAR gene underlies the down-regulation of this gene in urogenital cancers.

Base Sequence↗
PubMed1996

[DNA damage induced by fotemustine in cultured HL60 cells].

AIM: To detect DNA damage caused by fotemustine (Fot). METHODS: DNA damage in HL60 cells was evaluated by modified alkaline elution technique. DNA interstrand crosslink (ISC) and DNA-protein crosslink (DPC) were determined. Carmustine (Car) was used as control. Drug treatment time was 1 h. RESULTS: After treatment with Fot 300 mumol.L-1, ISC and DPC index were 5.4 and 6.1 at 6 h, 2.7 and 1.2 at 12 h, respectively. ISC reached the maximum at about 6 h. For Fot 100 mumol.L-1, ISC and DPC index at ISC peak time were 2.1 +/- 0.9 and 3.55 +/- 0.23, 5.0 +/- 0.5 and 7.7 +/- 1.1 for Car 100 mumol.L-1, respectively. Single strand break (SSB) was induced by Fot. CONCLUSION: Fot caused HL60 cell DNA ISC, DPC, and SSB. ISC was formed more quickly by Fot than that by Car.

Antineoplastic Agents↗
PubMed1995

The canary androgen receptor mRNA is localized in the song control nuclei of the brain and is rapidly regulated by testosterone.

Singing in canaries is an androgen-inducible behavior, under the control of an identified motor pathway, which includes several discrete "song nuclei" in the telencephalon. To determine whether the mRNA for the canary androgen receptor (cAR) is expressed in these song control nuclei, we synthesized probes from the recently cloned cAR cDNA and used in situ hybridization to examine spring male canary brain sections. Concentrations of cAR mRNA are detectable in several of the song control nuclei of the forebrain, including high vocal center (HVC), lateral magnocellular nucleus of the anterior neostriatum and robust nucleus of the archistriatum. In addition, we also show that testosterone treatment rapidly induces a significant reduction of cAR mRNA levels in nucleus HVC of females. Since the effects of androgen on singing behavior occur much more slowly, the behavioral effects are probably a secondary or independent result of androgen's primary and immediate action on target gene transcription.

Animals↗
PubMed1986

Effects of long-term administration of buspirone and diazepam on driver steering control.

The effects of buspirone, diazepam, and placebo on tracking control were investigated over a nine-day period, using three groups of subjects, each with eight females and eight males. Subjects were tested using an interactive, computer-based driving simulator on days one, eight, and nine of the treatment period. On day nine, subjects received alcohol with their drug treatment. Measures of steering control were derived from car-driver transfer functions. Tracking performance was also measured. Diazepam was found to adversely affect steering control measures in comparison with placebo. This was true both after doses on the first as well as the eighth day of treatment. Thus, there was no evidence of behavioral tolerance to diazepam. In contrast, buspirone was not found to have any adverse effects on steering control; in fact, some evidence of improved tracking control was found. When alcohol was added to each treatment on the ninth day, differences between the drug treatment groups were less pronounced but in the same direction as on the first and eighth days.

Administration, Oral↗
PubMed2005

Quantitative assessment of driving performance in Parkinson's disease.

OBJECTIVES: The primary aim of this study was to determine how Parkinson's disease (PD) affects driving performance. It also examined whether changes in driver safety were related to specific clinical disease markers or an individual's self rating of driving ability. METHODS: The driving performance of 25 patients with idiopathic PD and 21 age matched controls was assessed on a standardised open road route by an occupational therapist and driving instructor, to provide overall safety ratings and specific driving error scores. RESULTS: The drivers with PD were rated as significantly less safe (p<0.05) than controls, and more than half of the drivers with PD would not have passed a state based driving test. The driver safety ratings were more strongly related to disease duration (r = -0.60) than to their on time Unified Parkinson's Disease Rating Scale (r = -0.24). Drivers with PD made significantly more errors than the control group during manoeuvres that involved changing lanes and lane keeping, monitoring their blind spot, reversing, car parking, and traffic light controlled intersections. The driving instructor also had to intervene to avoid an incident significantly more often for drivers with PD than for controls. Interestingly, driver safety ratings were unrelated to an individual's rating of their own driving performance, and this was the case for all participants. CONCLUSIONS: As a group, drivers with PD are less safe to drive than age matched controls. Standard clinical markers cannot reliably predict driver safety. Further studies are required to ascertain whether the identified driving difficulties can be ameliorated.

Aged↗
PubMed1996

Legionellosis linked with a hotel car park--how many were infected?

An outbreak of legionellosis associated with a hotel in Sydney, Australia, and the subsequent epidemiological and environmental investigations are described. Four cases of Legionnaires' disease were notified to the Public Health Unit. A cross-sectional study of 184 people who attended a seminar at the hotel was carried out. Serological and questionnaire data were obtained for 152 (83%) of these. Twenty-eight (18%) respondents reported symptoms compatible with legionellosis. Thirty-three subjects (22%) had indirect fluorescent antibody (IFA) titres to Legionella pneumophila serogroup 1 (Lp-1) of 128 or higher. The only site which those with symptoms of legionellosis and IFA titre > or = 128 were more likely to have visited than controls was the hotel car park (adjusted odds ratio [OR] 14.7, 95% confidence interval [CI]: 1.8-123.1). Those with symptoms compatible with legionellosis, but whose IFA titres were < 128 were also more likely to have visited the hotel car park (adjusted OR 4.4, 95% CI: 1.5-12.9). Seroprevalence of Lp-1 antibodies was higher in those who attended the seminar than in a population sample of similar age. Findings suggested that the 4 cases represented a small fraction of all those infected, and highlighted difficulties in defining illness caused by Lp-1 and in interpreting serology.

Adult↗
PubMed2001

Association of polymorphic alleles of the calcium-sensing receptor gene with the clinical severity of primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is a heterogeneous disease in its clinical course and severity. Previous studies have suggested an association between the clinical severity of pHPT and the genotypes of vitamin D receptor, oestrogen receptors and PTH molecules. The Ca-sensing receptor (CaR) is activated by an extracellular calcium ion and controls PTH secretion, and thus polymorphisms of CaR might be associated with the magnitude of PTH secretion and the clinical severity of pHPT. In this study, we examined the relationship between CaR polymorphisms and biochemical markers in pHPT patients. METHODS: We analysed 105 Japanese pHPT patients (85 females and 20 males; mean age 55.6 +/- 14.0 years). We determined the CaR genotypes of G990R and intron 5 polymorphisms with genomic DNA extracted from peripheral lymphocytes. The intron 5 polymorphism was defined as T/T, T/C and C/C. RESULTS: In the G990R polymorphism, serum levels of both intact PTH and alkaline phosphatase (ALP) were significantly higher and the serum level of phosphorus was significantly lower in the RR group than in the GG group. In the intron 5 polymorphism, the T/T group showed significantly lower serum levels of intact PTH and Ca. Furthermore, patients with both the codon 990 RR and the intron 5 C allele (the RRC(+) group) had significantly higher serum levels of intact PTH and ALP than did the other patients. CONCLUSIONS: The present study is the first to show that CaR polymorphisms of G990R and intron 5 were closely associated with the magnitude of PTH secretion and/or PTH degradation as well as the clinical severity in pHPT patients.

Adolescent↗