Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 325 records · Page 18Linked to original sources

PubMed2001

Effects of mild hypothermia on blood-brain barrier disruption during isoflurane or pentobarbital anesthesia.

BACKGROUND: This study was performed to determine whether mild hypothermia (32 degrees C) could attenuate the degree of blood-brain barrier (BBB) disruption caused by a hyperosmolar solution and whether the degree of disruption would vary depending on anesthetic agents. METHODS: Rats were assigned to one of four groups: normothermic isoflurane, normothermic pentobarbital, hypothermic isoflurane, and hypothermic pentobarbital. During isoflurane (1.4%; normothermic or hypothermic) or pentobarbital (50 mg/kg administered intraperitoneally; normothermic or hypothermic) anesthesia, the external carotid artery and the femoral artery and vein were catheterized. Body temperature was maintained at 37 and 32 degrees C for the normothermic and hypothermic groups, respectively. To open the BBB, 25% mannitol was infused through the right carotid artery at the rate of 0.25 ml x kg(-1) x s(-1) for 30 s. The transfer coefficient of 14C-alpha-aminoisobutyric acid was determined. RESULTS: Blood pressure was similar among the four groups of animals. The degree of the BBB disruption by hyperosmolar mannitol was less with isoflurane than pentobarbital anesthesia in the normothermic groups (transfer coefficient: 29.9 +/- 17.1 and 50.4 +/- 17.5 microl x g(-1) x min(-1) for normothermic isoflurane and pentobarbital, respectively; P < 0.05). Mild hypothermia decreased the BBB disruption during anesthesia with both anesthetic agents (hypothermic isoflurane: 9.8 +/- 8.3 microl x g(-1) x min(-1), P < 0.05 vs. normothermic isoflurane; hypothermic pentobarbital: 30.2 +/- 13.9 microl x g(-1) x min(-1), P < 0.05 vs. normothermic pentobarbital), but the disruption was less during isoflurane anesthesia (hypothermic isoflurane vs. hypothermic pentobarbital, P < 0.005). In the contralateral cortex, there were no significant differences among these four experimental groups. CONCLUSIONS: The data demonstrated that hypothermia was effective in attenuating BBB disruption by hyperosmolar mannitol during isoflurane as well as pentobarbital anesthesia. The degree of disruption appeared smaller during isoflurane than during pentobarbital anesthesia in both the normothermic as well as the hypothermic groups.

Algorithms↗

PubMed2001

Behavioral and emotional problems in Chinese adolescents: parent and teacher reports.

OBJECTIVE: This study examined behavioral and emotional problems in Chinese adolescents. METHOD: A sample of 1,694 adolescents aged 12 to 16 years participated in this study in 1997. Parents completed the Child Behavior Checklist (CBCL), and teachers completed the Teacher's Report Form (TRF). RESULTS: For both parent and teacher reports, internalizing syndromes were scored higher in girls and externalizing syndromes were scored higher in boys. Scores on most of the CBCL and TRF subscales were higher for the older adolescents. The overall prevalence rates of parent- and teacher-reported behavioral problems were 23.1% and 19.2%, respectively. The eight cross-informant syndromes were highly comorbid, with a significant association across syndromes (mean odds ratio = 16.1 for CBCL and 22.5 for TRF). Correlations between parent and teacher reports were 0.51 for eight subscales and 0.68 for Total Problems. CONCLUSIONS: These findings demonstrate that behavioral and emotional problems tend to increase with age and cluster in the same individuals. The prevalence rates of behavioral problems in Chinese adolescents are comparable to those reported in Western countries. In contrast to findings for Western samples, parent reports of behavioral problems were highly correlated with teacher reports.

Adolescent↗

PubMed2001

Effects of exposure to death in a war mortuary on posttraumatic stress disorder symptoms of intrusion and avoidance.

Exposure to the dead has been an important subject for traumatic stress research, considering that such exposure is a risk factor for posttraumatic stress disorder (PTSD). Individuals required to handle the dead from war are exposed to multiple stressors. No previous studies, however, have examined pre- and post-responses to traumatic death. We studied the pre-post responses of 352 military men and women who worked in the mortuary that received the dead from the Persian Gulf War (Operation Desert Storm) in 1990 to 1991. The respondents were volunteers and nonvolunteers for assignment to the mortuary; some had prior experience in handling the dead and some did not. Symptoms of intrusion and avoidance were measured before and after exposure. Four groups were examined based on the degree of exposure to remains. Age, sex, volunteer status, and prior experience handling remains were statistically controlled. Post-exposure intrusion symptoms increased significantly for all groups exposed to the dead. Increased post-exposure avoidance symptoms were present in the two groups with the greatest exposure to remains. There were no significant increases in intrusion or avoidance in the unexposed group.

Adult↗

PubMed2001

MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity.

P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications. It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake. Individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy. To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele. The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively). The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

An analysis of multifactorial influences on the transcriptional control of ompF and ompC porin expression under nutrient limitation.

Expression of the major outer-membrane porins in Escherichia coli is transcriptionally controlled during nutrient limitation. Expression of ompF was more than 40-fold higher under glucose limitation than under nitrogen (ammonia) limitation in chemostat cultures at the same growth rate. In contrast, ompC expression was higher under N limitation. The basis of regulation by nutrient limitation was investigated using mutations affecting expression of porin genes. The influence of cyaA, rpoS, ackA and pta, as well as the two-component envZ-ompR system, was studied under glucose and N limitation in chemostat cultures. A major contributor to low ompF expression under N limitation was negative control by the RpoS sigma factor. RpoS levels were high under N limitation and loss of RpoS resulted in a 19-fold increase in ompF transcription, but little change was observed with ompC. Lack of RpoS under glucose limitation had a lesser stimulatory effect on ompF expression. Porin production was minimally dependent on EnvZ under N limitation due to OmpR phosphorylation by acetyl phosphate. Evidence obtained with pta and ackA mutants suggested that the acetyl phosphate level also regulates porins independently and indirectly via RpoS and other pathways. pta-envZ double mutants had a residual level of porin transcription, implicating alternative means of OmpR phosphorylation under nutrient limitation. Another critical factor in regulation was the level of cAMP, as a cyaA mutant hardly expressed ompF under glucose limitation but boosted ompC. In addition, the role of DNA-binding proteins encoded by hns and himA was tested under glucose limitation: the hns mutation reduced the glucose-limitation peak, but the himA mutation suppressed the hns effect, suggesting a complex web of interrelationships between the DNA-binding proteins. Indeed, multiple inputs and no single regulator were responsible for the high peak of ompF expression under glucose limitation.

Adenylyl Cyclases↗

PubMed2001

1-(Dibromomethyl)-4-methoxy-2-methylbenzene.

The title compound, C(9)H(10)Br(2)O, is a major product of the radical bromination of 4-methoxy-1,2-dimethylbenzene. Each Br atom is involved in a close contact with the O atom of a neighbouring molecule, forming a geometry that is suggestive of weak intermolecular O--> Br charge-transfer interactions.

Journal Article↗

PubMed2001

Comparison of 3-D reconstruction with 3D-OSEM and with FORE+OSEM for PET.

The combination of Fourier rebinning (FORE) and the ordered subsets expectation-maximization (OSEM), a fast statistical algorithm, appears as a promising alternative to the fully three-dimensional (3-D) iterative approach for clinical positron emission tomography (PET) data. In this paper, we evaluated the properties of FORE+OSEM and compared it with fully 3-D OSEM using both simulations and data acquired by commercial scanners. The aim is to determine to what extent the speed advantage of FORE+OSEM is paid for by a possible degradation of image quality in the case of noisy clinical PET data. A forward- and back-projection pair based on a line integral model was used in two-dimensional OSEM and 3-D OSEM (3D-OSEM) instead of a system matrix. Different variants of both approaches have been studied with simulations in terms of contrast-noise tradeoff. Two variants--FORE+OSEM with attenuation weighting (AW) [FORE+OSEM(AW)] and 3D-OSEM with attenuation-normalization weighting (ANSP) and a shifted-Poisson (SP) model [3D-OSEM(ANSP)]--were compared with measured phantom data and patient data. Based on the results from both simulations and measured data, we conclude that: 1) both attenuation (-normalization) weighting and the SP model improve the image quality but slow down the convergence and 2) despite its approximate nature, FORE+OSEM does not show apparent image degradation compared with 3D-OSEM for data with a noise level typical of a whole-body FDG scan.

Algorithms↗

PubMed2001

A case of cutaneous disseminated sporotrichosis.

We described a case of cutaneous disseminated sporotrichosis. The condition was diagnosed based on isolation and identification of Sporothrix schenckii from the lesions. The patient was otherwise normal, including a negative HIV test. The blood culture did not grow S. schenckii. However, spores were detected in the biopsy histological sections and stained positively with PAS staining and ConA and LCA lectin histochemistry.

Abdomen↗

PubMed2001

Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors.

The development of addiction and vulnerability to relapse following withdrawal is proposed to be the result of neuroadaptive processes within the central nervous system that oppose the acute reinforcing actions of drugs of abuse. These changes lead to impairment in the mechanisms that mediate positive reinforcement and the emergence of affective changes such as anxiety, dysphoria, and depression during withdrawal. Considerable evidence exists implicating perturbations in DA and 5-HT transmission in the nucleus accumbens--neurochemical systems that are activated by cocaine and ethanol self-administration and deficient during withdrawal--as potential substrates for these affective changes. In addition, growing evidence suggests that enhanced CRF release in the central nucleus of the amygdala represents a mechanism underlying the anxiogenic and stress-like consequences of withdrawal that are common to all drugs of abuse. A growing body of evidence also implicates dysregulation of the non-neuroendocrine CRF stress system within the central nucleus of the amygdala as a common factor in the anxiogenic and aversive consequences of withdrawal from drugs of abuse. Moreover, a possible link may exist between long-lasting abnormalities in CRF function in the CeA and vulnerability to relapse during protracted abstinence. Another presumably critical element contributing to the chronic relapsing nature of drug addiction is the learned responses to drug-related stimuli. The long-lasting efficacy of drug- and alcohol-associated contextual stimuli in eliciting drug-seeking behavior in animal models of relapse resembles the endurance of conditioned cue reactivity and cue-induced cocaine craving in humans and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. With cocaine, D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala may be important substrates for the motivating effects of drug-related environmental stimuli. With ethanol, available data suggest a role for opioid receptors in the mediation of conditioned drug-seeking behavior. Finally, conditioning factors (i.e., exposure to drug-associated stimuli) and stress can interact to augment vulnerability to relapse. This finding emphasizes that it will be important to consider the simultaneous effects of multiple environmental triggers for relapse in the development of treatment and medication strategies.

Adaptation, Physiological↗

PubMed2001

Regional improvement of signal-to-noise and contrast-to-noise ratios in dual-screen CR chest imaging--a phantom study.

The improvement of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in dual-screen computed radiography (CR) has been investigated for various regions in images of an anthropomorphic chest phantom. With the dual-screen CR technique, two image plates are placed in a cassette and exposed together during imaging. The exposed plates are separately scanned to form a front image and a back image, which are then registered and superimposed to form a composite image with improved SNRs and CNRs. The improvement can be optimized by applying specifically selected weighting factors during superimposition. In this study, dual-screen CR images of an anthropomorphic chest phantom were acquired and formed with four different combinations of standard resolution (ST) and high-resolution (HR) screens: ST-ST, ST-HR, HR-ST, and HR-HR. SNRs and their improvements were measured and compared over twelve representative regions-of-interest (ROIs) in these images. A 19.1%-45.7% increase of the SNR was observed, depending on the ROI and screen combination used. The optimal weighting factors were found to vary by only 4.5%-12.4%. Largest improvement was found in the lung field for all screen combinations. Improvement of CNRs was investigated over two ROIs in the lung field using the rib bones as the contrast objects and a 29.2%-43.9% improvement of the CNR was observed. Among the four screen combinations, ST-ST resulted in the most SNR and CNR improvement, followed in order by HR-ST, HR-HR, and ST-HR. The HR-ST combination yielded the lowest spatial variation of the optimal weighting factors with improved SNRs and CNRs close to those of the ST-ST combination.

Biophysical Phenomena↗

PubMed2001

Comparison of an amorphous silicon/cesium iodide flat-panel digital chest radiography system with screen/film and computed radiography systems--a contrast-detail phantom study.

Flat-panel (FP) based digital radiography systems have recently been introduced as a new and improved digital radiography technology; it is important to evaluate and compare this new technology with currently widely used conventional screen/film (SF) and computed radiography (CR) techniques. In this study, the low-contrast performance of an amorphous silicon/cesium iodide (aSi/Csl)-based flat-panel digital chest radiography system is compared to those of a screen/film and a computed radiography system by measuring their contrast-detail curves. Also studied were the effects of image enhancement in printing the digital images and dependence on kVp and incident exposure. It was found that the FP system demonstrated significantly better low-contrast performance than the SF or CR systems. It was estimated that a dose savings of 70%-90% could be achieved to match the low-contrast performance of the FP images to that of the SF images. This dose saving was also found to increase with the object size. No significant difference was observed in low-contrast performances between the SF and CR systems. The use of clinical enhancement protocols for printing digital images was found to be essential and result in better low-contrast performance. No significant effects were observed for different kVps. From the results of this contrast-detail phantom study, the aSi/CsI-based flat-panel digital chest system should perform better under clinical situations for detection of low-contrast objects such as lung nodules. However, proper processing prior to printing would be essential to realizing this better performance.

Cesium↗

PubMed2001

Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus.

Cell-mediated immunity appears to be critical for the prevention and control of varicella-zoster virus (VZV) infection and complications arising from zoster. Current assays of VZV-specific cell-mediated immunity are cumbersome or lack sensitivity. We have developed a gamma interferon ELISPOT assay that provides a direct measure of the number of T cells secreting a cytokine following stimulation with antigen. This assay is extremely sensitive and specific, with the ability to detect gamma interferon spot-forming cells (SFC) in the range of 10 to 1,000 SFC per million peripheral blood mononuclear cells (PBMCs). This assay has been validated by demonstrating the following: (i) the response detected is mediated almost entirely by CD4+ T cells, (ii) ELISPOT responses from fresh-frozen PBMCs are equivalent to those from freshly isolated cells, (iii) frozen PBMCs can be shipped on dry ice for up to 48 h without loss of activity, (iv) frozen PBMC samples can be stored in liquid nitrogen over long periods (>22 months) without any significant change in response, and (v) the numbers of ELISPOTs counted using a computer-based imaging system are equivalent to those counted by humans but have lower variability. The ability to use frozen cells is facilitated by the use of a recombinant nuclease (Benzonase) that can prevent cell clumping when samples are thawed. Frozen PBMC samples can be cycled through multiple changes in storage between liquid nitrogen and dry ice without any change in response being detected. This facilitates collection of samples at one site and testing performed at a remote location. This VZV ELISPOT assay provides a new versatile tool for monitoring cellular immune responses either during a herpes zoster disease outbreak or following vaccination.

Antibodies, Monoclonal↗

PubMed2001

Combinatorial use of antibodies to secreted mycobacterial proteins in a host immune system-independent test for tuberculosis.

Laboratory diagnosis of tuberculosis is often difficult. Immunodetection of circulating Mycobacterium tuberculosis proteins shed during active infection would not depend on an intact host immune response and could take advantage of the speed and low costs afforded by antibody-based assays. We previously showed that patients with active tuberculosis had increased levels of circulating antigen 85 (Ag85) proteins independent of their tuberculin skin test status (S. I. Bentley-Hibbert, X. Quan, T. Newman, K. Huygen, and H. P. Godfrey, Infect. Immun. 67:581-588, 1999). To extend these observations to a Mycobacterium bovis BCG-vaccinated population and to another secreted mycobacterial protein, Ag85 and PstS-1 (protein antigen B, p38 antigen) were quantified in sera from 97 Chilean tuberculosis patients and healthy controls (many of whom had received BCG as children) using dot immunobinding, mouse monoclonal anti-BCG Ag85 complex antibody, and chicken antipeptide antibodies reactive with M. tuberculosis Ag85B and PstS-1. The latter antibodies had been raised to peptide-derived immunogens expressed on a novel proprietary protein carrier in Escherichia coli. Median serum Ag85 levels measured by using either anti-Ag85 antibody were significantly higher in patients with active tuberculosis than in healthy controls (P, <0.001 to 0.01); the median serum PstS-1 levels were similar in patients and controls. The sensitivity of significantly elevated circulating Ag85 levels in patients with pulmonary tuberculosis measured by anti-Ag85 complex or anti-Ag85B antibodies was 60 and 55%, respectively, but increased to 77% when results obtained with both anti-Ag85 antibodies were considered jointly (P < 0.02). The corresponding specificities for individual and joint consideration were 95, 85, and 80%, respectively. These results indicate that elevated Ag85 levels can be detected in patients with active tuberculosis even after BCG vaccination and suggest that combinatorial use of antibodies directed at different epitopes of this protein could provide a viable strategy for developing new host immune response-independent diagnostic tests for tuberculosis.

Adolescent↗

PubMed2001

p53 Stimulates TFIID-TFIIA-promoter complex assembly, and p53-T antigen complex inhibits TATA binding protein-TATA interaction.

Simian virus 40 large T antigen has been shown to inhibit p53-mediated transcription once tethered to p53-responsive promoters through interaction with p53. In this study we report that p53 stimulates transcription by enhancing the recruitment of the basal transcription factors, TFIIA and TFIID, on the promoter (the DA complex) and by inducing a conformational change in the DA complex. Significantly, we have demonstrated that T antigen inhibits p53-mediated transcription by blocking this ability of p53. We investigated the mechanism for this inhibition and found that DA complex formation was resistant to T-antigen repression when the TFIID-DNA complex was formed prior to addition of p53-T antigen complex, indicating that the T antigen, once tethered to the promoter by p53, targets TFIID. Further, we have shown that the p53-T antigen complex prevents the TATA binding protein from binding to the TATA box. Thus, these data suggest a detailed mechanism by which p53 activates transcription and by which T antigen inhibits p53-mediated transcription.

Antigens, Polyomavirus Transforming↗

PubMed2001

Role of gut flora on intestinal group II phospholipase A2 activity and intestinal injury in shock.

We previously showed that group II phospholipase A2 (PLA2-II), a secretory, bactericidal, and proinflammatory protein in intestinal crypts, is upregulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF) challenge. Here we examined whether germ-free environment (GF) or antibiotic treatment (ABX) affects the pathophysiological responses and intestinal PLA2-II activity after PAF (1.5 microg/kg) or LPS (8 mg/kg) injection. We found that LPS and PAF induced hypotension and mild intestinal injury in conventionally fed (CN) rats; these changes were milder in ABX rats, whereas GF rats showed no intestinal injury. PLA2-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA2-II activity, which was abrogated in GF and ABX rats. Recolonization of GF rats by enteral contamination restituted their PLA2-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA2-II activity are dependent on gut bacteria, and ABX and GF rats are less susceptible to LPS-induced injury than CN rats.

Animals↗

PubMed2001

Effect of short-term cyclic stretch on sodium pump activity in aortic smooth muscle cells.

We previously demonstrated that expression of both the alpha1- and alpha2-subunits of Na+-K+-ATPase is elevated after a 2- to 4-day cyclic stretch in aortic smooth muscle cells. In this study, we determined the effect of short-term (2-30 min) cyclic stretch on the activity of the Na pump and investigated possible mechanisms that may be involved in the action of stretch. Na pump activity was significantly increased above the baseline activity between 2 and 30 min of stretch. This effect of stretch was reversible within 1 h. Intracellular Na was also elevated at corresponding time points. Blocking the entry of Na with Gd and amiloride did not affect the stretch-induced increase in Na pump activity. Inhibition of protein kinase A (PKA) activity attenuated the effect of stretch on the Na pump. Furthermore, inhibition of polymerization of actin and phosphatidylinositol 3-kinase (PI3K) activity prevented the action of stretch on Na pump activity. We conclude that the stimulation of the Na pump in response to cyclic stretch requires the integrity of the actin cytoskeleton as well as the activity of PI3K, which has a role in intracellular vesicular trafficking. PKA may also be involved in this effect of stretch on Na pump.

Actins↗

PubMed2001

Bradykinin augments fibroblast-mediated contraction of released collagen gels.

Bradykinin is a multifunctional mediator of inflammation believed to have a role in asthma, a disorder associated with remodeling of extracellular connective tissue. Using contraction of collagen gels as an in vitro model of wound contraction, we assessed the effects of bradykinin tissue on remodeling. Human fetal lung fibroblasts were embedded in type I collagen gels and cultured for 5 days. After release, the floating gels were cultured in the presence of bradykinin. Bradykinin significantly stimulated contraction in a concentration- and time-dependent manner. Coincubation with phosphoramidon augmented the effect of 10(-9) and 10(-8) M bradykinin. A B2 receptor antagonist attenuated the effect of bradykinin, whereas a B1 receptor antagonist had no effect, suggesting that the effect is mediated by the B2 receptor. An inhibitor of intracellular Ca2+ mobilization abolished the response; addition of EGTA to the culture medium attenuated the contraction of control gels but did not modulate the response to bradykinin. In contrast, the phospholipase C inhibitor U-73122 and the protein kinase C inhibitors staurosporine and GF-109203X attenuated the responses. These data suggest that by augmenting the contractility of fibroblasts, bradykinin may have an important role in remodeling of extracellular matrix that may result in tissue dysfunction in chronic inflammatory diseases, such as asthma.

Animals↗

PubMed2001

C/EBPbeta contributes to cAMP-activated transcription of phosphoenolpyruvate carboxykinase in LLC-PK(1)-F+ cells.

Phosphoenolpyruvate carboxykinase (PEPCK) is a key regulatory enzyme in renal gluconeogenesis. Activation of various PEPCK(-2300)Luc reporter constructs in LLC-PK(1)-F+ cells, a gluconeogenic line of porcine renal proximal tubule-like cells, by protein kinase A (PKA) is mediated, in part, through the cAMP-response element (CRE)-1 of the PEPCK promoter. Incubation of a CRE-1 containing oligonucleotide with nuclear extracts from LLC-PK(1)-F+ cells produced multiple bands, all of which were blocked by antibodies that are specific for C/EBPbeta but not for C/EBPalpha or C/EBPdelta. Treatment of cells with cAMP did not affect the expression of C/EBPbeta, but the observed binding activity was increased nearly threefold. Mutation of CRE-1 to a Gal-4 binding site reduced the PKA-dependent activation of PEPCK(-2300)Luc to 40% of that observed with the wild-type construct. Coexpression of a chimeric protein containing a Gal-4 binding domain and the transactivation domain of C/EBPbeta, but not of C/EBPalpha or CRE binding protein (CREB), restored full activation by PKA. A deletion construct that lacks the activation domain of C/EBPbeta functions as a dominant negative inhibitor. Thus the binding of C/EBPbeta to the CRE-1 may contribute to the cAMP-dependent activation of the PEPCK promoter in kidney cells.

Animals↗