Biomedical subjects

X Zhang

Publications and source records attributed to X Zhang.

At least 217 records · Page 12Linked to original sources

PubMed2002

Boundary element method-based cortical potential imaging of somatosensory evoked potentials using subjects' magnetic resonance images.

A boundary element method-based cortical potential imaging technique has been developed to directly link the scalp potentials with the cortical potentials with the aid of magnetic resonance images of the subjects. First, computer simulations were conducted to evaluate the new approach in a concentric three-sphere inhomogeneous head model. Second, the corresponding cortical potentials were estimated from the patients' preoperative scalp somatosensory evoked potentials (SEPs) based on the boundary element models constructed from subjects' magnetic resonance images and compared to the postoperative direct cortical potential recordings in the same patients. Simulation results demonstrated that the cortical potentials can be estimated from the scalp potentials using different scalp electrode configurations and are robust against measurement noise. The cortical imaging analysis of the preoperative scalp SEPs recorded from patients using the present approach showed high consistency in spatial pattern with the postoperative direct cortical potential recordings. Quantitative comparison between the estimated and the directly recorded subdural grid potentials resulted in reasonably high correlation coefficients in cases studied. Amplitude difference between the estimated and the recorded potentials was also observed as indexed by the relative error, and the possible underlying reasons are discussed. The present numerical and experimental results validate the boundary element method-based cortical potential imaging approach and demonstrate the feasibility of the new approach in noninvasive high-resolution imaging of brain electric activities from scalp potential measurement and magnetic resonance images.

Algorithms↗

PubMed2002

Chronic treatments with tacrine and (-)-nicotine induce different changes of nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.

The present study evaluated effects of chronic treatment with tacrine and (-)-nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the brains of old rats (24-25 months) by receptor autoradiography. The nicotinic receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was observed in all of the brain regions analysed following chroinic treatment with tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in most of the brain regions analysed except for a few brain regions where a decrease was observed in tacrine treated animals compared to control animals. Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions analysed except for the hippocampus when measured by (-)-[3H]nicotine. A significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding was observed in all of the brain regions analysed following the treatment with tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine differentially interfere and regulate the subtypes of nAChRs and mAChRs in the brain of aged rat. These data differ from what have been earlier observed in the brain of young adult rat following tacrine treatment, revealing some dynamic changes in receptor properties in the brain during aging.

Aging↗

PubMed2002

Acute and chronic morphine treatments and morphine withdrawal differentially regulate GRK2 and GRK5 gene expression in rat brain.

Opioid agonist stimulates activation of G protein-coupled receptor kinase (GRK) and causes desensitization of opioid signaling, which plays an important role in opioid tolerance. The current study investigated the potential regulatory effects of acute and chronic morphine administration and withdrawal on GRK2 and GRK5 gene expression in rat brain. Our results showed that the initial morphine treatment (10 mg/kg) significantly increased GRK mRNA levels in cerebral cortex, hippocampus, and lateral thalamic nuclei. A significant decrease in GRK5 mRNA levels was observed in periaqueductal gray. In strong contrast, repeated administration of morphine for 9 days failed to cause any significant increase in GRK5 mRNA in any of these brain regions. Chronic morphine treatment resulted in 30-70% down-regulation of GRK2 expression in cerebral cortex, hippocampus, thalamus, and locus coeruleus, opposite to what observed with the single morphine administration. Moreover, spontaneous and naloxone-precipitated morphine withdrawal resulted in aberrant increases in GRK2 and GRK5 mRNA levels in these brain regions. Taken together, our study suggests that opioid not only induces rapid negative feedback regulation on opioid signals through activation of GRK but also exerts its impact, via controlling levels of GRK gene expression, on the regulatory machinery itself over a longer period of time in brain.

Analgesics, Opioid↗

PubMed2002

GABAA receptors and benzodiazepines: a role for dendritic resident subunit mRNAs.

This review is designed to describe the evolution of the seminal observation made simultaneously in 1975 by Dr. W. Haefely's laboratory (Hoffman La Roche, Basel, Switzerland) and in the Laboratory of Preclinical Pharmacology (NIH, St. Elizabeths Hospital, Washington DC), that benzodiazepine action was mediated by a modulation of GABA action at GABA(A) receptors. In fact, our suggestion was that the benzodiazepine receptor was "a receptor on a receptor" and that this receptor was GABA(A). Needless to say, this suggestion created opposition, but we did not abandon the original idea, in fact, as shown in this review, there is now universal agreement with our hypothesis on the mode of action of benzodiazepines. Hence, this review deals with the allosteric modulation of GABA(A) receptors by benzodiazepines, the role of GABA(A) receptors and benzodiazepine structure diversities in this modulation, and describes the results of our attempts to establish a benzodiazepine (imidazenil) devoid of tolerance, withdrawal symptoms, and changes in the expression of GABA(A) receptor subunits during tolerance. It also deals with the idea that the synthesis of GABA(A) receptor subunits triggered by tolerance resides in dendrites and spines where mRNAs and the apparatus for this translation is located. New analytic procedures may foster progress in the understanding of tolerance to and withdrawal from benzodiazepines.

Allosteric Regulation↗

PubMed2002

Kinetic properties of rrn promoters in Escherichia coli.

How do bacteria adapt and optimize their growth in response to different environments? The answer to this question is intimately related to the control of ribosome bio-synthesis. During the last decades numerous proposals have been made to explain this control but none has been definitive. To readdress the problem, we have used measurements of rRNA synthesis rates and rrn gene dosages in E. coli to find the absolute transcription rates of the average rrn operon (transcripts per min per operon) at different growth rates. By combining these rates with lacZ expression data from rRNA promoter-lacZ fusions, the abolute activities of the isolated rrnB P1 and P2 promoters were determined as functions of the growth rate in the presence and absence of Fis and of the effector ppGpp. The promoter activity data were analyzed to obtain the relative concentrations of free RNA polymerase, [R(f)], and the ratio of the Michaelis-Menten parameters, V(max)/K(m) (promoter strength), that characterize the promoter-RNA polymerase interaction. The results indicate that changes in the basal concentration of ppGpp can account for all growth-medium dependent regulation of the rrn P1 promoter strength. The P1 promoter strength was maximal when Fis was present and the level of ppGpp was undetectable during growth in rich media or in ppGpp-deficient strains; this maximal strength was 3-fold reduced when Fis was removed and the level of ppGpp remained undetectable. At ppGpp levels above 55 pmol per cell mass unit (OD(460)) during growth in poor media, the P1 promoter strength was minimal and not affected by the presence or absence of fis. The half-maximal value occurred at 20 pmol ppGpp/OD(460) and corresponds to an intracellular concentration of about 50 microM. In connection with previously published data, the results suggest that ppGpp reduces the P1 promoter strength directly, by binding RNA polymerase, and indirectly, by inhibiting the synthesis of Fis.

DNA, Ribosomal↗

PubMed2002

Expression of the neuropeptide Y Y1 receptor in the CNS of rat and of wild-type and Y1 receptor knock-out mice. Focus on immunohistochemical localization.

The distribution of neuropeptide Y (NPY) Y1 receptor-like immunoreactivity (Y1R-LI) has been studied in detail in the CNS of rat using a rabbit polyclonal antibody against the C-terminal 13 amino acids of the rat receptor protein. The indirect immunofluorescence technique with tyramide signal amplification has been employed. For specificity and comparative reasons Y1 knock-out mice and wild-type controls were analyzed. The distribution of Y1R mRNA was also studied using in situ hybridization. A limited comparison between Y1R-LI and NPY-LI was carried out.A widespread and abundant distribution of Y1R-LI, predominantly in processes but also in cell bodies, was observed. In fact, Y1R-LI was found in most regions of the CNS with a similar distribution pattern between rat and wild-type mouse. This staining was specific in the sense that it was absent in adjacent sections following preadsorption of the antibody with 10(-5) M of the antigenic peptide, and that it could not be observed in sections of the Y1 KO mouse. In contrast, the staining obtained with an N-terminally directed Y1R antiserum did not disappear, strongly suggesting unspecificity. In brief, very high levels of Y1R-LI were seen in the islands of Calleja, the anterior olfactory nucleus, the molecular layer of the dentate gyrus, parts of the habenula, the interpeduncular nucleus, the mammillary body, the spinal nucleus of the trigeminal, caudal part, the paratrigeminal nucleus, and superficial layers of the dorsal horn. High levels were found in most cortical areas, many thalamic nuclei, some subnuclei of the amygdaloid complex, the hypothalamus and the nucleus of the stria terminalis, the nucleus of the solitary tract, the parabrachial nucleus, and the inferior olive. Moderate levels of Y1R-LI were detected in the cornu Ammonis and the subicular complex, many septal, some thalamic and many brainstem regions. Y1R staining of processes, often fiber and/or dot-like, and occasional cell bodies was also seen in tracts, such as the lateral lemniscus, the rubrospinal tract and the spinal tract of the trigeminal. There was in general a good overlap between Y1R-LI and NPY-LI, but some exceptions were found. Thus, some areas had NPY innervation but apparently lacked Y1Rs, whereas in other regions Y1R-LI, but no or only few NPY-positive nerve endings could be detected. Our results demonstrate that NPY signalling through the Y1R is common in the rat (and mouse) CNS. Mostly the Y1R is postsynaptic but there are also presynaptic Y1Rs. Mostly there is a good match between NPY-releasing nerve endings and Y1Rs, but 'volume transmission' may be 'needed' in some regions. Finally, the importance of using proper control experiments for immunohistochemical studies on seven-transmembrane receptors is stressed.

Animals↗

PubMed2002

Comparison of HPV infection, p53 mutation and allelic losses in post-transplant and non-posttransplant oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (SCC) is increasingly found in transplant recipients, although little is known of the natural history of the disease or the mechanism underlying this increase. METHODS: In this article we describe the history of development of 5 oral post-transplant SCCs (PSCCs) and compare their genetic profiles to 34 non-posttransplant SCCs (NPSCCs). RESULTS: Of the five patients with PSCCs, 3 had bone marrow transplants and two, kidney. All three PSCCs from bone marrow recipients were preceded locally by graft-vs.-host disease (GVHD). Two of the GVHD were biopsied and demonstrated dysplasia. Similar frequencies of loss of heterozygosity (LOH) occurred in PSCCs and NPSCCs at 3p, 9p, 17p and 8p, with lower frequencies in PSCCs at 4q (39% vs. 0%), 11q (53% vs. 20%) and 13q (45% vs. 20%), although the latter were not significantly different. Only 1 PSCC had a p53 mutation, compared to historical values of 40-60% for NPSCC. Interestingly, human papillomavirus (HPV) DNA was detected in 3 (60%) PSCCs, in comparison to only 4 (12%) of the 34 NPSCCs (P = 0.0346). CONCLUSIONS: Dysplasia in oral GVHD may be a strong indicator of cancer risk and should not be regarded as reactive changes to lichenoid mucosites. The low level of p53 mutation and increased HPV infection support the involvement of HPV in the development of PSCC, while the similarity in LOH patterns suggests that other aspects of carcinogenesis may be comparable in these two types of SCCs.

Adult↗

PubMed2002

A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription.

Interferon-gamma (IFN-gamma) is an important cytokine that regulates cellular immune responses to intracellular pathogens and neoplasia. Regulation of IFN-gamma expression is stringently controlled at the transcriptional level. In this report we describe two novel single nucleotide polymorphisms (SNPs); one, at -179 in the promoter, occurs in 4% of African Americans. This SNP represents a guanidine to thymidine transition and creates a potential AP-1 binding element. Electrophoretic mobility shift analysis reveals a unique complex binding to an oligonucleotide containing the variant -179T but not to the -179G using nuclear extracts from human peripheral blood T cells. In reporter gene assays, T cell lines transfected with the variant -204(179T) IFN-gamma promoter show a six to 13-fold induction of luciferase activity in response to TNF-alpha over the common -204(179G) construct. The -179T allele identified in the proximal IFN-gamma promoter confers TNF-alpha inducibility and may prove important in human immune disorders and responsiveness to pathogens.

Animals↗

PubMed2002

Regression of tumors by IFN-alpha electroporation gene therapy and analysis of the responsible genes by cDNA array.

The key to success with nonviral gene therapy as a treatment for cancer is to discover effective therapeutic genes and gene delivery methods and to understand how tumors are eradicated. We discovered that electroporation of IFN-alpha DNA into tumors in the SCCVII tumor-bearing mice led to tumor eradication in 50% of the mice and a more than two-fold increase in survival time when compared with controls (P = 0.0012). Analyses using cDNA array and Northern blot indicated that the genes responsible for the therapeutic effect of electro-IFN-alpha gene therapy included IRF-7, Granzyme A, Granzyme C, Gjb2, Krt14, Mig, IP-10 and MCP3. Because most of these genes have been known to either inhibit angiogenesis (Mig, IP-10), inhibit tumor growth (Gjb2, MCP3), kill tumor cells (Granzyme A and C), or induce expression of antitumor gene (IRF-7), they may become promising therapeutic gene candidates for a combination gene therapy approach to cancer treatment.

Analysis of Variance↗

PubMed2002

Mechanochemical ATPases and transcriptional activation.

Transcriptional activator proteins that act upon the sigma54-containing form of the bacterial RNA polymerase belong to the extensive AAA+ superfamily of ATPases, members of which are found in all three kingdoms of life and function in diverse cellular processes, often via chaperone-like activities. Formation and collapse of the transition state of ATP for hydrolysis appears to engender the interaction of the activator proteins with sigma54 and leads to the protein structural transitions needed for RNA polymerase to isomerize and engage with the DNA template strand. The common oligomeric structures of AAA+ proteins and the creation of the active site for ATP hydrolysis between protomers suggest that the critical changes in protomer structure required for productive interactions with sigma54-holoenzyme occur as a consequence of sensing the state of the gamma-phosphate of ATP. Depending upon the form of nucleotide bound, different functional states of the activator are created that have distinct substrate and chaperone-like binding activities. In particular, interprotomer ATP interactions rely upon the use of an arginine finger, a situation reminiscent of GTPase-activating proteins.

Adenosine Triphosphatases↗

PubMed2002

Phosphorus removal and greenhouse gas N2O emission in a lime-induced aerobic sludge granule process.

Aerobic sludge granulation was achieved in an activated sludge process continuously fed with lime (Ca2+ 100 mg l(-1) influent) every other day. Eighteen days after lime addition, activated sludge granules with the size of 0.5-2.2 mm were formed, which occupied 10-25% of total sludge volume. Sludge volume index (SVI) was reduced to an average of 50 ml g(-1), which increased average sludge concentration to 3.6-5.0 g VSS l(-1), 1.6-2.1 times of that of control. Greenhouse gas N2O emission was also significantly reduced: N2O concentration from the lime-addition reactor was 5-15 ppmv, 47-61% of that of control, Effluent PO4-P concentration was generally lower than 1 mg l(-1) when average influent PO4-P concentration was 6.07-6.37 mg l(-1). Total phosphorus (TP) and total nitrogen (TN) removal efficiencies were around 89.6% and 14.5-16.1%, over 3.5 and 1 times higher than those of control, respectively. COD removal rate in the lime-addition reactor was 2.05-2.48 kg COD m(-3) d(-1), higher than 1.34-1.61 kg COD m(-3) d(-1) in the control.

Air Pollution↗

PubMed2002

Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.

We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.

Aryl Hydrocarbon Hydroxylases↗

PubMed2002

Conventional and functional proteomics using large format two-dimensional gel electrophoresis 24 hours after controlled cortical impact in postnatal day 17 rats.

Conventional and functional proteomics have significant potential to expand our understanding of traumatic brain injury (TBI) but have not yet been used. The purpose of the present study was to examine global hippocampal protein changes in postnatal day (PND) 17 immature rats 24 h after moderate controlled cortical impact (CCI). Silver nitrate stains or protein kinase B (PKB) phosphoprotein substrate antibodies were used to evaluate high abundance or PKB pathway signal transduction proteins representing conventional and functional proteomic approaches, respectively. Isoelectric focusing was performed over a nonlinear pH range of 3-10 with immobilized pH gradients (IPG strips) using supernatant from the most soluble cellular protein fraction of hippocampal tissue protein lysates from six paired sham and injured PND 17 rats. Approximately 1,500 proteins were found in each silver stained gel with 40% matching of proteins. Of these 600 proteins, 52% showed a twofold, 20% a fivefold, and 10% a 10-fold decrease or increase. Spot matching with existing protein databases revealed changes in important cytoskeletal and cell signalling proteins. PKB substrate protein phosphorylation was best seen in large format two-dimensional blots and known substrates of PKB such as glucose transporter proteins 3 and 4 and forkhead transcription factors, identified based upon molecular mass and charge, showed altered phosphorylation 24 h after injury. These results suggest that combined conventional and functional proteomic approaches are powerful, complementary and synergistic tools revealing multiple protein changes and posttranslational protein modifications that allow for more specific and comprehensive functional assessments after pediatric TBI.

Age Factors↗

PubMed2002

Design of a finger ring extremity dosemeter based on OSL readout of alpha-Al2O3:C.

A finger-ring dosemeter and reader has been designed that uses OSL readout of alpha-Al2O3:C (aluminium oxide). The use of aluminium oxide is important because it allows the sensitive element of the dosemeter to be a very thin layer that reduces the beta and gamma energy dependence to acceptable levels without compromising the required sensitivity for dose measurement. OSL readout allows the ring dosemeter to be interrogated with minimal disassembly. The ring dosemeter consists of three components: aluminium oxide powder for measurement of dose, an aluminium substrate that gives structure to the ring, and an aluminised Mylar cover to prevent the aluminium oxide from exposure to light. The thicknesses of the three components have been optimised for beta response using the Monte Carlo computer code FLUKA. A reader was also designed and developed that allows the dosemeter to be read after removing the Mylar. Future efforts are discussed.

Aluminum Oxide↗

PubMed2002

Genetic diversity of Chinese native chicken breeds based on protein polymorphism, randomly amplified polymorphic DNA, and microsatellite polymorphism.

Genetic diversity of Chinese native chicken breeds was investigated using protein polymorphism, randomly amplified polymorphic DNA (RAPD), and microsatellite polymorphism. Imported broiler and layer breeds were also included in the analysis. The results from protein polymorphism did not show distinct differences between Chinese native chicken and imported broilers; however, there were small significant differences between these two types of chickens. The results from RAPD indicated that gene diversity within a population was large in Chinese native chickens, intermediate in broilers, and low in layers and that there were small differences between Chinese native chickens and both broilers and layers. A great difference between broilers and layers was observed. Microsatellite polymorphism data showed that genetic diversity was high in the Chinese native chickens and low in layers and that there was a close relationship between Chinese native chickens and broiler but a remote relationship between Chinese native chickens and layers. The wide genetic diversity of Chinese native breeds can meet different requirements of breeding for chicken quality in China.

Alkaline Phosphatase↗

PubMed2002

Comparative analysis of allozyme, random amplified polymorphic DNA, and microsatellite polymorphism on Chinese native chickens.

Allozyme, random amplified polymorphic DNA (RAPD), and microsatellite polymorphisms were examined and compared among five native populations of Chinese chickens, two fast-growing broiler lines, and one layer line. Three assay systems resulted in a different average heterozygosity or gene diversity in each of the eight populations. The lowest average heterozygosity was obtained with allozyme analysis (0.2209), intermediate heterozygosity was obtained with RAPD (0.2632), and the highest heterozygosity was observed with microsatellite analysis (0.7591). The genetic distances among all populations measured by three methods were also different. Allozyme data showed close relationships between Chinese native chickens and the two broiler lines, but they were both remotely related to the layer line. Microsatellite polymorphism analysis was similar to the allozyme analysis but genetic distances from RAPD showed a close relationship between Chinese native chickens and broiler and layer chickens.

Albumins↗

PubMed2002

Epidemiology survey of rhegmatogenous retinal detachment in Beixinjing District, Shanghai, China.

PURPOSE: To investigate the recent incidence and related risk factors of rhegmatogenous retinal detachment (RRD) in Chinese people. METHODS: This study was an incidence survey based on data for 108,132 persons in Beixinjing District, Shanghai, China. Patients with RRD were inpatients, outpatients, and patients from the local health network. Patients with RRD were compared with control subjects who were matched by sex, age, and block of residence. Previous population data were used to estimate the whole and specific incidence of RRD. Some factors relevant to the incidence of RRD were found by comparing the patients with RRD with the control subjects. RESULTS: Between January 1996 and December 1999, 61 cases of RRD occurred. The annual incidence of RRD was 11.3 cases per 100,000 population in 1996, 14.1 cases per 100,000 population in 1997, 14.1 cases per 100,000 population in 1998, and 17.9 cases per 100,000 population in 1999. The average annual incidence was 14.4 cases per 100,000 population (95% confidence interval, 10.0-18.6). There were 29 males and 32 females with RRD. The incidence of RRD among persons older than 40 years was high, especially among those between 40 and 59 years of age. The proportion of individuals with high myopia (more than -6 diopters) was significantly higher in the patient group than in the control group (P < 0.001). CONCLUSION: The annual incidence of RRD among a local Chinese population increased over 4 years. This disease is strongly associated with high myopia and age.

Adolescent↗

PubMed2002

Modeling sound transmission through the pulmonary system and chest with application to diagnosis of a collapsed lung.

A theoretical and experimental study was undertaken to examine the feasibility of using audible-frequency vibro-acoustic waves for diagnosis of pneumothorax, a collapsed lung. The hypothesis was that the acoustic response of the chest to external excitation would change with this condition. In experimental canine studies, external acoustic energy was introduced into the trachea via an endotracheal tube. For the control (nonpneumothorax) state, it is hypothesized that sound waves primarily travel through the airways, couple to the lung parenchyma, and then are transmitted directly to the chest wall. In contradistinction, when a pneumothorax is present the intervening air presents an added barrier to efficient acoustic energy transfer. Theoretical models of sound transmission through the pulmonary system and chest region to the chest wall surface are developed to more clearly understand the mechanisms of intensity loss when a pneumothorax is present, relative to a baseline case. These models predict significant decreases in acoustic transmission strength when a pneumothorax is present, in qualitative agreement with experimental measurements. Development of the models, their extension via finite element analysis, and comparisons with experimental canine studies are reviewed.

Acoustic Stimulation↗