Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “controllable CAR”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1998

[The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract].

The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C-radioactivity may be excreted into the expired air. The results suggest that Car-Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption.

Administration, Oral↗
PubMed2006

AMSH regulates calcium-sensing receptor signaling through direct interactions.

Calcium-sensing receptor (CaR) activates intracellular pathways controlling calcium homeostasis. CaR carboxyl-terminal mutants associated with metabolic diseases suggest that unidentified proteins interact with the carboxyl-terminal region of this receptor. To address this possibility, we screened for CaR-interacting proteins using the carboxyl terminus of CaR (CaRDelta895-1075 deletion mutant). We identified AMSH, an ubiquitin isopeptidase, as a CaR-interacting partner. AMSH caused a decrease on the signaling properties of wild-type and mutant CaR. Our results indicate that AMSH, which has been recently characterized as a regulator of the endosomal sorting of epidermal growth factor receptor, represents a novel modulator of CaR signaling.

Amino Acid Sequence↗
PubMed2000

Limited proteolysis of the coxsackievirus and adenovirus receptor (CAR) on HeLa cells exposed to trypsin.

Trypsin treatment of HeLa cells results in a limited proteolysis of the coxsackievirus and adenovirus receptor (CAR) after which the cleaved CAR remains cell-associated and tryptic peptides remain associated through disulfide bonds. Trypsin-treated HeLa cells remain susceptible to infection with coxsackievirus B and produce progeny virus at 8 h post-infection in amounts comparable to cells with intact CAR. HeLa cells remove the proteolysed CAR within 15 h and require over 24 h to restore intact CAR to control levels. As turnover is relatively slow, physiological functions that require intact CAR protein may be compromised for more than 24 h following trypsin treatment. Moreover, since removal of proteolysed CAR proceeds at more than twice the replacement rate, trypsin treatment disrupts the receptor-per-cell steady state for at least 24 h.

Adenoviridae↗
PubMed2003

Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and carbapenem, in Serratia via both quorum-sensing-dependent and -independent pathways.

Serratia sp. ATCC 39006 produces two secondary metabolite antibiotics, 1-carbapen-2-em-3-carboxylic acid (Car) and the red pigment, prodigiosin (Pig). We have previously reported that production of Pig and Car is controlled by N-acyl homoserine lactone (N-AHL) quorum sensing, with synthesis of N-AHLs directed by the LuxI homologue SmaI, and is also regulated by Rap, a member of the SlyA family. We now describe further characterization of the SmaI quorum-sensing system and its connection with other regulatory mechanisms. We show that the genes responsible for biosynthesis of Pig, pigA-O, are transcribed as a single polycistronic message in an N-AHL-dependent manner. The smaR gene, transcribed convergently with smaI and predicted to encode the LuxR homologue partner of SmaI, was shown to possess a negative regulatory function, which is uncommon among the LuxR-type transcriptional regulators. SmaR represses transcription of both the pig and car gene clusters in the absence of N-AHLs. Specifically, we show that SmaIR exerts its effect on car gene expression via transcriptional control of carR, encoding a pheromone-independent LuxR homologue. Transcriptional activation of the pig and car gene clusters also requires a functional Rap protein, but Rap dependency can be bypassed by secondary mutations. Transduction of these suppressor mutations into wild-type backgrounds confers a hyper-Pig phenotype. Multiple mutations cluster in a region upstream of the pigA gene, suggesting this region may represent a repressor target site. Two mutations mapped to genes encoding pstS and pstA homologues, which are parts of a high-affinity phosphate transport system (Pst) in Escherichia coli. Disruption of pstS mimicked phosphate limitation and caused concomitant hyper-production of Pig and Car, which was mediated, in part, through increased transcription of the smaI gene. The Pst and SmaIR systems define distinct, yet overlapping, regulatory circuits which form part of a complex regulatory network controlling the production of secondary metabolites in Serratia ATCC 39006.

4-Butyrolactone↗
PubMed1996

Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations.

Certain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca(2+)-sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The present study demonstrates that the sensitivity of this receptor is modulated by physiological femtomolar concentrations of the bone-conserving hormone, calcitonin. Calcitonin was found to inhibit cytosolic Ca2+ responses to both Ca2+ and Ni2+. The latter inhibition was mimicked by amylin (10(-12) M), calcitonin gene-related peptide (10(-12) M), cholera toxin (5 micrograms/l) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (2.5 x 10(-4) or 5 x 10(-4) M) and was reversed by the protein kinase A phosphorylation inhibitor, IP-20. Finally, using a quench flow module, we showed that cellular cAMP levels rise to a peak within 25 ms of calcitonin application; this is consistent with the peptide's rapid effect on CaR activation. We conclude, therefore, that cAMP plays a critical role in the control of CaR function by calcitonin.

Animals↗
PubMedDate not supplied

Exposure, lung function, and symptoms in car painters exposed to hexamethylendiisocyanate and biuret modified hexamethylendiisocyanate.

Individuals who paint cars often complain to doctors about respiratory problems. Car painters are exposed to isocyanates, especially hexamethylendiisocyanate (HDI), and biuret modified HDI (HDI-BT). The mean exposure to HDI-BT was 115 micrograms/m3 in the air (range 10-385 micrograms/m3), which exceeds the time-weighted Swedish threshold level of 90 micrograms/m3. Exposure to HDI was about 1.0 microgram/m3 with brief peaks. This study investigated the effect of HDI and HDI-BT on lung function and included two control groups: (1) car platers, exposed to the same solvents and grinding dust as car painters, but not to isocyanates, and (2) car mechanics (controls), not exposed to the mentioned agents. Car painters and car platers were compared to car mechanics on Monday before work. Acute effects of car painting were tested by comparing the lung function values on Monday morning with those on Friday afternoon. Pulmonary function was evaluated by means of spirometry and a single breath nitrogen washout. Spirometry in painters and platers did not differ from that in controls, i.e., car mechanics. Closing volume in relation to vital capacity (CV%) was increased in car painters, suggestive of a "small airways disease" on Monday before work and tended to increase during a work week. Car platers did not differ from controls.

Adult↗
PubMed1996

Psychosocial factors in childhood pedestrian injury: a matched case-control study. Kid's'n'Cars Team.

HYPOTHESIS: Psychosocial factors--such as hyperactivity and low family cohesion--contribute to the risk for child pedestrian injury (PI), even after controlling for known demographic risk factors. PARTICIPANTS: Urban PI victims aged 5 to 12 years were recruited from one large, urban pediatric trauma center in a large city. One hundred twenty-eight cases were matched to uninjured children on age, sex, race, location of residence, and parental education. Among matched cases: 70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control comparisons on 19 psychosocial variables drawn from interviews and standardized tests, using one-tailed matched-pairs t tests and conditional logistic regression analyses. RESULTS: Cases had higher reported physical quotient [PQ] (P = .01), self-help quotient (P = .04), and family stress (P = .02), and lower family supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI) 1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26-3.61]), and that cases had lower family supportiveness (25-point decrease: OR 1.43 [1.25-1.63]). It also identified household crowding as a factor for non-black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]). CONCLUSION: Even when controlling for demographic risk, several family factors and one child factor place children at risk for PI. Clinicians may choose to use these as indicators for injury prevention counseling. Research on family effects may help clarify means to protect children who are demographically at risk for PI.

Accidents, Traffic↗
PubMed1995

Vehicle speed and risk of a severe crash.

We examined the relation between the speed of passenger cars and risk of involvement in a severe crash, in an urban setting, using a case-control study. "Cases" were 45 vehicles involved in severe crashes in the Adelaide metropolitan area; we determined their pre-crash speeds using accident reconstruction techniques. For each case, we measured the speeds of 10 controls using an amphometer; controls were cars not involved in crashes that passed through the crash location at the same time of day, day of week, and season. We found that the risk of involvement in a severe crash increased as vehicle speed increased. In particular, within 60 km per hour zones, compared with vehicles traveling at about the posted limit, vehicles traveling at 75-84 km per hour had an odds ratio of 7.8 [95% confidence interval (CI) = 1.4-38.8] for a severe crash, whereas vehicles with speeds in excess of 84 km per hour had an odds ratio of 39.0 (95% CI = 9.3-170.5).

Accidents, Traffic↗
PubMedDate not supplied

Professional exposure of drivers to carbon monoxide as a possible risk factor for the occurrence of traffic accidents in the road traffic.

The aim of this study was to examine the effects of increased carbon monoxide concentrations in the air of car cabin on the health status of exposed drivers and the occurrence of traffic accidents. Exposed group was comprised of 250 drivers professionally exposed to increased carbon monoxide concentrations in the car cabins. Control group was comprised of 120 professional drivers who were not exposed to increased concentrations of carbon monoxide in the air of the car cabins. Average carbon monoxide concentration in the air of the car cabins of the drivers from exposed group was 71.2 +/- 8.1 ppm, which was significantly higher compared to the controls (5.4 +/- 1.2 ppm). The drivers from the exposed group more frequently suffered from headaches, irritability, vertigo and palpitation than the drivers from the control group. The prevalence of diabetes mellitus, arrhythmia, atherosclerotic peripheral artery diseases and coronary heart diseases was more frequent in the exposed than in the control group. Drivers from the exposed had longer reaction time on acoustic and visual stimulation compared to the control group. The examined drivers statistically caused more traffic accidents than the drivers from the control group.

Accidents, Traffic↗
PubMed1969

Chemical pollution from transportation vehicles.

Recent publicity on electrically powered vehicles notwithstanding, the gasoline engine will probably be the principal power plant for passenger cars for at least the next decade. Chemical pollutants discharged by the gasoline engine are now under partial control. Motor cars of 1968 and 1969 model discharge only about 30 percent as much carbon monoxide and unburned hydrocarbons as do older models. In theory, carbon monoxide, unburned hydrocarbons and oxides of nitrogen ultimately can be completely removed from gasoline engine exhaust. In order to accomplish this it would be necessary to modify cars to operate satisfactorily on a lean mixture and perhaps to use a catalyst in the exhaust system. Present designs of gas turbines for aircraft and for future projected application to ground vehicles yield pollutants (except for smoke) at levels below those of gasoline engines for a decade to come. It has also been shown possible to eliminate smoke as well as odor from the gas turbine. Thus with proper effort it is feasible to reduce pollution of the atmosphere due to transportation to an acceptable level, even if electrically or alternatively powered vehicles cannot be developed for a decade.

Air Pollution↗
PubMed1979

The actions of dopaminergic and noradrenergic antagonists on conditioned avoidance responses in intact and 6-hydroxydopamine-treated rats.

The actions of various doses of haloperidol, pimozide, clozapine, and phenoxybenzamine were assessed on a conditioned-avoidance response (CAR) in control and 6-hydroxydopamine-treated rats, using a pole-climbing device. Haloperidol proved to be the most potent in disrupting the CAR. Pimozide was about 1.6 times less potent, and clozapine and phenoxybenzamine were approximately 52 and 155 times less potent than haloperidol, respectively. Prior treatment with 6-hydroxydopamine slightly enhanced the sensitivity to some of the doses of the DA and NE antagonists. Significantly lower levels of responding, however, were observed only after the highest dose of primozide. Clonidine was not only ineffective in reverting avoidance decrements, but also induced a further decline of the CAR. Apomorphine produced a partial, but significant, reversal of the haloperidol and pimozide-induced depression of conditioned responses. Regarding the clozapine-pretreated animals, a significant antagonism was observed only with the smaller dose of apomorphine. The highest dose induced a further decline of the CAR. The DA agonist was also ineffective in the phenoxybenzamine-injected rats. Amphetamine was effective in antagonizing the avoidance decrements produced by all the CA antagonists. Our results support the suggestion that CAR depends on both DA and NE mechanisms. DA seems to be more significant that NE, however, since the CAR was more depressed when receptors depending on the former neurotransmitter were blocked.

Amphetamine↗
PubMed2003

Pathophysiological factors affecting CAR gene expression.

The body defends itself against potentially harmful compounds, such as drugs and toxic endogenous compounds and their metabolites, by inducing the expression of enzymes and transporters involved in their metabolism and elimination. The orphan nuclear receptor CAR (NR1I3 controls phase I (CYP2B, CYP2C, CYP3A), phase II (UGT1A1), and transporter (SLC21A6, MRP2) genes involved in drug metabolism and bilirubin clearance. Constitutive androstane receptor (CAR) is activated by xenobiotics, such as phenobarbital, but also by toxic endogenous compounds such as bilirubin metabolite(s). To better understand the inter- and intravariability in drug detoxification, we studied the molecular mechanisms involved in CAR gene expression in human hepatocytes. We clearly identified CAR as a glucocorticoid receptor (GR) target gene, and we proposed the hypothesis of a signal transduction where the activation of GR plays a critical function in CAR-mediated cellular response. According to our model, chemicals or pathophysiological factors that affect GR function should decrease CAR function. To test this hypothesis, we recently investigated the effect of microtubule disrupting agents (MIAs) or proinflammatory cytokines. These compounds are well-known inhibitors of GR transactivation property. MIAs activate c-Jun N-terminal kinase (JNK), which phosphorylates and inactivates GR, whereas proinflammatory cytokines, such as IL-6 or IL1beta, induce AP-1 or NF-kB activation, respectively, leading to GR inhibition. As expected, we observed that these molecules inhibit both CAR gene expression and phenobarbital-mediated CYP gene expression in human hepatocytes.

Animals↗
PubMed2004

Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance.

During the inflammatory response, intrahepatic cholestasis and decreased drug metabolism are frequently observed. At the hepatic level, the orphan nuclear constitutive androstane receptor (CAR) (NR1I3) controls phase I (cytochrome P450 [CYP] 2B and CYP3A), phase II (UGT1A1), and transporter (SLC21A6, MRP2) genes involved in drug metabolism and bilirubin clearance in response to xenobiotics such as phenobarbital or endobiotics such as bilirubin. We investigated the negative regulation of CAR, a glucocorticoid-responsive gene, via proinflammatory cytokine interleukin 1beta (IL-1beta) and lipopolysaccharides (LPSs) in human hepatocytes. We show that IL-1beta decreases CAR expression and decreases phenobarbital- or bilirubin-mediated induction of CYP2B6, CYP2C9, CYP3A4, UGT1A1, GSTA1, GSTA2, and SLC21A6 messenger RNA. This occurs via nuclear factor kappaB (NF-kappaB) p65 activation, which interferes with the enhancer function of the distal glucocorticoid response element that we have identified recently in the CAR promoter. We demonstrate that: (1) LPSs, IL-1beta, or overexpression of p65RelA inhibit glucocorticoid receptor (GR)-mediated CAR transactivation; (2) these suppressive effects can be blocked both by pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, or by overexpression of SRIkBalpha, a NF-kappaB repressor; and (3) the GR agonist dexamethasone induces histone H4 acetylation at the proximal CAR promoter region, whereas LPSs and IL-1beta inhibit this acetylation as assessed via chromatin immunoprecipitation assay. In conclusion, GR/NF-kappaB interaction affects CAR gene transcription through chromatin remodeling and provide a mechanistic explanation for the long-standing observation that inflammation and sepsis inhibit drug metabolism while inducing intrahepatic cholestasis or hyperbilirubinemia.

Acetylation↗
PubMed2000

Motivations to control drinking behavior in abstainers, moderate, and heavy drinkers.

Motives and motivational concepts to control quantity (Q) and frequency (F) of alcohol consumption were investigated in 192 participants using a questionnaire of motives to control drinking (MCD-Q/F) developed earlier. The daily quantity of consumption was assessed by the "30 day by beverage questionnaire." Participants were grouped into heavy or moderate drinkers (limits: females 40, males 60 gram alcohol/day) and abstainers. Analyses of motives showed the importance of car driving, controlling appetite/desire, and prevention of impaired mental performance. The relative impact of motivational concepts were analyzed by cluster analysis of motives revealing three clusters: 1) emotional concepts/fear of addiction, 2) physiological sensations/interaction with concrete actual plans, 3) cognitive concepts (plans, self-control, no impairment/no desire). MANOVA of MCD-Q/F indicate highest scores for moderate drinkers and significant lower scores in heavy drinkers in controlling frequency of drinking (MCD-F). Group effect for emotional concepts failed significance, higher scores of physiological concepts were found in imbibers compared to abstainers, and scores of cognitive concepts were lower in heavy drinkers. Results indicate that for imbibers a reduced motivation to control frequency of drinking as well as low scores in cognitive concepts and a trend to high scores in emotional concepts are associated with heavy drinking.

Adult↗
PubMed1982

[Visual prevention from motion sickness in cars].

The differential effects of vision on motion sickness in cars were tested under real road conditions using linear accelerations, in order to confirm earlier laboratory results on visual modulation of vestibular nausea induced by angular accelerations of the body. The 18 voluntary subjects were exposed to repetitive braking maneuvers (linear accelerations: 0.1-1.2 g) on a highway. The simultaneous visual stimulus conditions for the 3 separate days were: I) eyes open, visual control of car motion; II) eyes closed; III) eyes open, artificial stationary visual field (reading). The severity of motion sickness (magnitude estimation 1-10) was a function of the visual stimulus condition with significant differences among these conditions: I) moderate nausea (less than 1) with adequate visual motion perception; II) medium nausea (approximately equal to 2) with eyes closed and somatosensory-vestibular excitation only; III) strong nausea (greater than 5) with conflicting sensory input, when vestibular acceleration is in disagreement with the visual information of no movement. Providing ample peripheral vision of the relatively moving surround is the best strategy to alleviate car sickness.

Acceleration↗
PubMedDate not supplied

[Traumatic heart rupture or infarct?].

A 70-year-old motorist driving on the wrong side of the road caused a car-to-car head-on collision and died some minutes later. The autopsy revealed a lethal rupture of the right heart ventricle. The insurance company argued that driving on the wrong side was an act of gross negligence so that the damage was not covered by the full comprehensive insurance. Surprisingly, the microscopic examination of the myocardium performed by a clinical pathologist brought to light a severe myofibrillar degeneration (MFD) which was interpreted as diagnostic of acute myocardial infarction. It was supposed that this could have caused an incapacity of the driver to control his car, which in turn would commit the insurance to payment. A critical re-evaluation of the heart tissue material, however, revealed the pattern of trauma-induced hypercontraction banding of the myocardium along the cleft edges but no findings suggestive of myocardial infarction. Thus, the accident was not the result of a cardiac attack. But there was a severe preexisting pathology including cardiac hypertrophy, scarring of the myocardium, siderophages of the lungs, and an infarction of the pons, so that a cerebral dysfunction was the most plausible explanation for the accident. Thus, gross negligence had to be denied, and the insurance company was obliged to pay. This observation points to the existence of two different variants of MFD: Clinical pathologists are familiar with "tyical" MFD occurring in reperfusion after ischemia, in catecholamine toxicity, and around infarct necroses. But hypercontraction banding, regularly found along penetrating heart lesions and well known to forensic pathologists, is uncommon in clinical pathology.

Accidents, Traffic↗
PubMed2004

The M170 is selective for faces, not for expertise.

Are the mechanisms for face perception selectively involved in processing faces per se, or do they also participate in the processing of any class of visual stimuli that share the same basic configuration and for which the observer has gained substantial visual expertise? Here we tested the effects of visual expertise on the face-selective "M170", a magnetoencephalography (MEG) response component that occurs 170 ms after stimulus onset and is involved in the identification of individual faces. In Experiment 1, cars did not elicit a higher M170 response (relative to control objects) in car experts compared to controls subjects. In Experiment 2, the M170 amplitude was correlated with successful face identification, but not with successful car identification in car experts. These results indicate that the early face processing mechanisms marked by the M170 are involved in the identification of faces in particular, not in the identification of any objects of expertise.

Adult↗
PubMed1996

Children and cycle helmets -- the case against.

Much of the literature on child cycling accidents appears to blame the child as a victim, as though children's activities of playing and travelling were somehow wrong and that children are at fault when an adult drives a car over them. This adult-centred approach then leads to the idea that children should protect themselves with helmets, and that they are to blame if they are injured. However, adults who continue to hold the fantasy that helmets might be of value should know that the British Standard for cycle helmets protects only in a vertical fall of 1 m -- certainly not motor vehicle crashes. Thicker motor cycle helmets would give better protection but, of course, are heavier (and therefore unsaleable). Yet even with compulsory wearing helmets, more motor cyclists still die of head injuries than pedal cyclists. In the Newcastle study, five times as many child pedestrians died of road accidents as child cyclists. Convinced helmeteers should recommend all children playing or travelling in the streets to wear helmets (presumably heavy motor-cycle helmets). Slightly more sceptical proponents might prefer half of them -- in a randomized controlled trial. Car driving appears to have as serious health consequences as tobacco, alcohol and drugs, and to be as addictive (McCarthy 1992). Helmets are similar to filters in cigarettes -- they give the illusion of safety to both consumer and producer of the product, but the illusion is fatal. Yet, for their cardiovascular and mental health, children should have the freedom to cycle in safety around where they live. A profound change in the habits of adults is needed, rather than suits of armour for children.

Bicycling↗