PubMed Health⌕ Search

Biomedical subjects

Wei Zhu

Publications and source records attributed to Wei Zhu.

At least 91 records · Page 5Linked to original sources
PubMed2005

[Histamine release properties of human basophils in response to various stimuli].

AIM: To investigate the effects of protease activated receptor-2 (PAR-2) agonist, heparin and other stimuli on histamine release from human basophils. METHODS: Peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation. The PBMCs were then resuspended in complete Hank's balanced salt solution (HBSS) and challenged with various stimulating agents. Histamine level in samples was determined by ELISA. RESULTS: 10 mg/L trypsin could induce histamine release from basophils. However, its stimulatory effect on basophils was weaker than that of anti-IgE, calcium ionophore (CI), F-Met-Leu-Phe (FMLP), C5a and substance P. PAR-2 agonist SLIGKV-NH(2) failed to activate basophils. Heparin, C5 and adenosine did not induce any histamine release at concentrations tested, but heparin enhanced histamine release induced by C5a and substance P. CONCLUSION: Trypsin, anti-IgE, CI, FMLP, C5a and substance P can induce histamine release from baosophils, but PAR-2 agonist can not. Heparin can greatly enhance the ability of C5a and substance P to stimulate histamine release, which may be a novel mechanism of amplification of basophil activation signal.

Animals↗
PubMed2005

Comparison of monoamine oxidase a in peripheral organs in nonsmokers and smokers.

UNLABELLED: Smokers have reduced levels of brain monoamine oxidase A (MAO A) leading to speculation that MAO A inhibition by tobacco smoke may underlie some of the neurophysiologic effects of smoking. Because smoking exposes peripheral organs as well as the brain to MAO A-inhibitory compounds, we determined whether smokers would also have reduced MAO A in peripheral organs. METHODS: We measured MAO A in peripheral organs in a group of 9 smokers and compared it with a group of nonsmokers studied previously. MAO A was measured using PET and serial scans with the MAO A-specific radiotracers (11)C-clorgyline and deuterium-substituted (11)C-clorgyline ((11)C-clorgyline-D2) using the deuterium isotope effect to assess binding specificity. The time course of radiotracer in the arterial plasma was also measured and data from the tissue time-activity curves and the arterial input function were analyzed using a 3-compartment model to estimate k(3), which represents the rate-limiting step for the irreversible binding of labeled clorgyline to MAO A. RESULTS: Tracer uptake at plateau was reduced with deuterium substitution for the heart, lungs, and kidneys, indicating specificity for MAO. There was no difference in organ uptake at plateau between nonsmokers and smokers though, for the smokers, the efflux of tracer from peak uptake to plateau was slower for the lungs. The area under the time-activity curve for the arterial plasma was also significantly reduced for smokers versus nonsmokers and the reduction occurred in the first few minutes after radiotracer injection. Smokers had an approximately 50% reduction in k(3) when compared with nonsmokers; however, k(3) did not differ for nonsmokers and smokers for the heart and the kidneys. CONCLUSION: Because MAO A breaks down serotonin, norepinephrine, dopamine, and tyramine, and because the lung is a major metabolic organ in degrading some of these substances, reduced lung MAO A may contribute to some of the physiologic effects of smoking. This study also revealed that the concentration of the radiotracers in the arterial plasma is significantly lower for the smoker versus the nonsmoker and that this appears to be caused in part by retention of the radiotracer in lungs. If this is generally true for other substances that are administered intravenously, then this needs to be considered as a variable that may contribute to different short-term behavioral responses to intravenously administered drugs for nonsmokers versus smokers.

Adult↗
PubMed2005

[Interaction between ATM and radiation-activated phosphorylation of P53 and P21].

BACKGROUND & OBJECTIVE: ATM gene is a member of PI-3K kinase family. ATM protein is capable of controlling DNA repair process and cell cycle checkpoint. In AT cells from ataxia-telangiectasia (AT) patients, ATM gene mutation leads to the deficiency of ionizing radiation-activated phosphorylation of P53 and P21. It shows ATM gene could mediate the phosphorylation of P53 and P21. This study was to explore the interaction between ATM and P53, and to observe whether ATM directly medicates the phosphorylation of P21 in a P53-independent way. METHODS: pEBS7-YZ5 vector containing ATM cDNA was transfected into AT cells by electroperforation. The cells expressing ATM protein stably were screened with hygromycin, and identified by reverse transcription-polymerase chain reaction (RT-PCR). The interaction between ATM and P53 in pEBS7-YZ5-AT cells was assessed by co-immunoprecipitation and Western blot. K562 cells served as a P53 mutation cell model to study whether ATM could interact with the phosphorylation of P21. RESULTS: pEBS7-YZ5 was transfected into AT cells successfully. RT-PCR detected fragment of ATM cDNA. After exposed to ionizing radiation, P53 of pEBS7-YZ5-AT cells was phosphorylated, and immunoprecipitation showed interaction between ATM and P53; P21 of K562 cells was phosphorylated, P21 protein was detected in the immunoprecipitation of ATM antibody-complex. CONCLUSION: Ionizing radiation-activated ATM kinase could interact with the phosphorylation of P53 and P21 in both P53 wild type and mutant type cells.

Ataxia Telangiectasia↗
PubMed2005

Tyrosine and tyramine increase endogenous ganglionic morphine and dopamine levels in vitro and in vivo: cyp2d6 and tyrosine hydroxylase modulation demonstrates a dopamine coupling.

BACKGROUND: The ability of animals to make morphine has been in question for the last 30 years. Studies have demonstrated that animals do contain morphine precursors and metabolites, as well as the ability to use some morphine precursors to make morphine. MATERIAL/METHODS: The present study uses excised ganglia from the marine invertebrate Mytilus edulis as well as whole animals. Morphine and dopamine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay. Tissues and whole animals were also exposed to morphine precursors and exposed to the CYP2D6 inhibitor quinidine and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Additionally, via RT-PCR, a cDNA fragment of the CYP2D6 enzyme in the ganglia of M. edulis was identified. RESULTS: Pedal ganglia incubated with either tyramine or tyrosine, or whole animals receiving injections, exhibited a statistically significant concentration- and time-dependent increase in their endogenous morphine and dopamine levels (2.51 +/- 0.76 ng/g for tyrosine and 2.39 +/- 0.64 ng/g for tyramine compared to approximately 1.0 ng/g morphine wet weight). Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process. We also demonstrated that CYP2D6 mediates the tyramine to dopamine step in this process, as did tyrosine hydroxylase in the step from tyrosine to L-DOPA. Furthermore, via RT-PCR, we identified a cDNA fragment of the CYP2D6 enzyme in the ganglia, which exhibits 94% sequence identity with its human counterpart. Evidence that tyrosine and tyramine were, in part, being converted to dopamine then morphine, and that this process can be inhibited by altering either or both CYP2D6 or tyrosine hydroxylase, is also provided. CONCLUSIONS: It appears that animals have the ability to make morphine. This process also appears to be dynamic in that the inhibition of one pathway allows the other to continue with morphine synthesis. Moreover, dopamine and morphine synthesis were coupled.

Animals↗
PubMed2005

[The pharmacokinetics of rhein in 12 healthy volunteers after oral administration of rhubarb extract].

OBJECTIVE: To study the pharmacokinetics of rhein in 12 healthy volunteers after oral administration of rhubarb extract. METHOD: The blood sample were obtained at 0,0.083,0.5,1,1.5,2,3,4,5,7,10 h after a single dose oral administration of rhubarb (50 mg x kg(-1)). The plasma rhein concentration was determined by HPLC. The pharmacokinetics of rhein were analysed by 3P97 program. RESULT: The absorption of rhein was very fastafter oral administration of rhubarb extract in the healthy volunteers. The main pharmacokinetic parameters of rhein were C(max) (3.20 +/- 1.08) microg x mL(-1); t(max) (1.03 +/- 0.41) h; t(1/2alpha) (0.21 +/- 0.02) h; t(1/2beta) (2.68 +/- 1.09) h; MRT(5.31 +/- 1.78) h; AUC(0-infinity) (1 573.08 +/- 366.48) microg x mL(-1) min(-1), respectively. CONCLUSION: Rhein could be absorbed rapidly and its pharmacokinetics was consistent with two-compartment model.

Administration, Oral↗
PubMed2005

[Effect on apoptosis of anterior pituitary induced by cadmium chloride and its relations with p38 MAPK & ERK1/2 passway].

OBJECTIVE: To study the effects of cadmium chloride on anterior pituitary and the relation between p38 MAPK & ERK1/2 pathway and apoptosis induced by cadmium chloride. METHODS: In vivo studies, SD male rats were administered with CdCl2 at the doses of 0, 1.0, 2.0, 4.0 mg/kg bw by gavage for 6 weeks. In vitro studies, rats' anterior pituitary cells were primarily cultured and then treated with CdCl2 at doses of 0, 1.56, 3.12, 6.25, 12.50, 25.00, 50.00, 100.00 micromol/L for 6 hours. Inhabiting study, cells were incubated with SB203580 (2.65 micromol/L) or U0126 (10 micromol/L) respectively for 2 hours and then treated with CdCl2 at doses of 3.12, 100.00 micromol/L for 6 hours. The indices in above experiments included expression of TUNEL-positive cells, rate of apoptosis by Flow cytometry. RESULTS: The results showed that the apoptosis induced by CdCl2 inclined to enhance with dose dependent manner, Further more, U0126 and SB203580, the specific inhibitor of ERK1/2 and p38 MAPK respectively, could decrease the expression of TUNEL-positive cells significantly and lower apoptotic rate of primary cultured anterior pituitary cells. CONCLUSION: It was suggested that cadmium induce apoptosis of anterior pituitary both in vivo and in vitro in dose-dependent manner, ERK1/2 and p38 MAPK passways might play a role during above processes.

Animals↗
PubMed2004

[Hypoglossal neurilemmoma: current experience in diagnosis and treatment].

OBJECTIVE: To improve the diagnosis and treatment of hypoglossal neurilemmoma (HGN). METHODS: The data of 10 patients with HGN were retrospectively reviewed, 5 of 10 patients (early group) had been reported previously. A comparison of treatment strategy between early and latter group was made. RESULTS: Typical hemiatrophy of the tongue presented in all 10 patients, hypoglossal canal could be showed in the bone window of CT, which, however, might not confirm the existence of tumor if it is very small. MRI was the optical choice for diagnosis. Among the early 5 cases with HGN which were all of dumbbell type, the intracranial part and the extracranial part of the tumor in 2 cases were removed by stages, 3 cases were operated via the far-lateral approach, of which 1 was via trans-condylar approach and 2 were via trans-supracondylar approach; the 5 tumors were removed subtotally except 1 totally; CSF leakage and intra-cranial infection after operation occurred in 1 case; the rating of Karnofsky Prognosis Scale was good in 4 cases and dead in 1 case. However, among the latter 5 cases, 4 cases including 2 of dumbbell type, 1 of intra-cranial type and 1 of intracanal type were operated via the modified far-lateral approach, of which 1 was via trans-condylar approach and 3 were via trans-supracondylar approach; and the tumor of extracranial type in the last case was resected twice via transcervical approach, being removed subtotally in the first operation followed by total removal with the aid of neuronavigation and neuroendoscopy in the second operation when it failed to react to the treatment of gamma knife; the 5 tumors were removed totally except 1 subtotally.; all postoperative courses were uneventful.; follow up was performed successfully in 4 cases, the rating of Karnofsky Prognosis Scale was excellent in 3 cases and fair in 1 case. The outcomes of the latter 5 cases resected via modified approach were better than those of the early 5 cases. CONCLUSION: HGN is extremely rare and it is difficult to treat it. To achieve a good operative outcome, it is very important to design the approach individually based on its location and size and operate mini-invasively and resect tumor totally as possible as can in the primary stage.

Adult↗
PubMed2004

Endogenous morphinergic signaling and tumor growth.

The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune down regulating activities parallels those actions formerly attributed to nitric oxide. We have now identified the mu3 receptor at the molecular level and sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene (MOR). Furthermore, using Northern blot, reverse transcription coupled to polymerase chain reaction (RT-PCR) and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells. The presence of this mu splice variant, adds to the growing body of evidence supporting the hypothesis that morphine is an endogenous signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth, with emphasis on immuno-regulatory and antiproliferative mechanisms.

Alternative Splicing↗
PubMed2004

Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model.

UNLABELLED: To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer. INTRODUCTION: Although clinical bone morphogenetic protein (BMP) therapy is effective, required doses are very high. Previous studies have suggested that the co-expression of two different BMP genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP2 and BMP7 gene transfer was performed to test whether this approach improves osteoblastic differentiation and bone formation compared with single BMP gene transfer. MATERIALS AND METHODS: A producer cell (A549) was co-transfected with adenovirus vectors encoding BMP2 (AdBMP2) and BMP7 (AdBMP7) or, as controls, each vector alone, AdNull (with no transgene) or no virus. Supernatants were compared for their ability to stimulate osteoblastic differentiation of C2C12 myoblasts and MC3T3-E1 pre-osteoblasts. In a rat posterolateral spine fusion model, co-administration of AdBMP2 and AdBMP7 was compared with treatment with each vector alone, AdNull or no virus in 78 rats. The spines were assessed 8 weeks after surgery for radiographic and mechanical fusion, bone formation, and mineralization. RESULTS: BMP2 and BMP7 were co-precipitated from supernatants of cells co-transfected with AdBMP2 and AdBMP7, indicating the presence of BMP2/7 heterodimer. Supernatants of co-transfected cells containing relatively low doses (7-140 ng/ml) of BMPs induced osteocalcin expression and alkaline phosphatase activity in both C2C12 and MC3T3-E1 cells, that were up to 6- and 40-fold higher, respectively, than levels induced by maximal doses (200-1000 ng/ml) of either BMP2 or BMP7 alone. In the spine fusion model, co-administration of AdBMP2 and AdBMP7 resulted in a significantly greater number of mechanically stable fusions and also 2-fold higher mineralization rate and bone volume in the fusion mass versus single BMP gene transfer (p < 0.02, all comparisons). CONCLUSION: Combined BMP2 and BMP7 gene transfer is significantly more effective in inducing osteoblastic differentiation and spine fusion than individual BMP gene transfer.

3T3 Cells↗
PubMed2004

[Transplantation of gene-transfected neural stem cells for transient cerebral ischemia in rats].

OBJECTIVE: To detect the expression and the role of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in rat brain subjected to ischemia. METHODS: Fetal NSCs were cultured from E14 days SD rats and transfected with VEGF121 gene by using lipofectAMINE technique. The gene expression of transfected cells was detected by RT-PCR and immunofluorescent staining in vitro. Temporary middle cerebral artery occlusion (tMCAO) model was established in 40 SD rats and then rate were randomly divided into (1) control group (n = 10), (2) PBS transplantation group (n = 10), (3) neural stem cells transplantation group (n = 10), and (4) VEGF-secreting neural stem cells transplantation group (n = 10). BrdU-labelled NSCs and VEGF-secreting NSCs were transplanted into the penumbra zones respectively 3 days after the tMCAO model was established. Neurological Severity Score (NSS) was checked in all groups 2, 4, 6, 8, 10, 12 weeks respectively after transplantation. One and 12 weeks after the transplantation, 10 rats in the group (4) were killed and then brains taken out respectively. By using immunofluorescent staining, the VEGF expression of transplanted cells 1 week after transplantation, differentiation and migration of transplanted neural stem cells 12 week after transplantation were detected respectively. RESULTS: VEGF-transfected neural stem cells could continuously express gene products during the first 2 weeks. Both transfected NSCs and their progeny expressed VEGF gene products, which was demonstrated by fluorescence study. There were no significant differences in NSS in groups 4 when tMCAO models were just established. However, the values of NSS in (4) group were 5.8 +/- 1.5, 5.0 +/- 1.0, 4.6 +/- 1.0, 4.0 +/- 0.7, 4.0 +/- 1.0, 3.8 +/- 0.4 from 2 approximately 12 weeks after transplantation, significantly lower than those in groups (1) and (2) 8 weeks (P = 0.008) and those in groups (1), (2) and (3) 12 weeks (P = 0.000) after transplantation. NSS in group (3) was also lower than that in groups (1) and (2) 8 and 12 weeks after transplantation. One week after transplantation, immunofluorescent staining showed that VEGF-transfected NSCs migrated and expressed VEGF into hosts' brains. Twelve weeks after transplantation, transplanted NSCs survived and migrated, some of them differentiated to neurons and integrated well with hosts' cytoarchitectural components. CONCLUSION: VEGF-transfected NSCs express gene products during the early time after transplantation, which reduce brain injury through protecting the vascular system against ischemia and reperfusion injury. Transplantation of VEGF-transfected NSCs might be a novel method for treatment of cerebral ischemia.

Animals↗
PubMed2004

Commonalities in the central nervous system's involvement with complementary medical therapies: limbic morphinergic processes.

BACKGROUND: Currently, complementary and alternative medicine (CAM) are experiencing growing popularity, especially in former industrialized countries. However, most of the underlying physiological and molecular mechanisms as well as participating biological structures are still speculative. Specific and non-specific effects may play a role in CAM. Moreover, trust, belief, and expectation may be of importance, pointing towards common central nervous system (CNS) pathways involved in CAM. MATERIAL/METHODS: Four CAM approaches (acupuncture, meditation, music therapy, and massage therapy) were examined with regard to the CNS activity pattern involved. CNS commonalities between different approaches were investigated. RESULTS: Frontal/prefrontal and limbic brain structures play a role in CAM. Particularly, left-anterior regions of the brain and reward or motivation circuitry constituents are involved, indicating positive affect and emotion-related memory processing--accompanied by endocrinologic and autonomic functions--as crucial components of CAM effects. Thus, trust and belief in a therapist or positive therapy expectations seem to be important. However, besides common non-specific or subjective effects, specific (objective) physiological components also exist. CONCLUSIONS: Non-specific CNS commonalities are involved in various CAM therapies. Different therapeutic approaches physiologically overlap in the brain. However, molecular correspondents of the detected CNS analogies still have to be specified. In particular, fast acting autoregulatory signaling molecules presumably play a role. These may also be involved in the placebo response.

Acupuncture↗
PubMed2004

Music alters constitutively expressed opiate and cytokine processes in listeners.

BACKGROUND: Listening to music as a means of inducing a sense of calm and relaxation has been known for some time. Although these effects are robust, little research has been conducted into exploring the underlying neurochemical changes, which must occur to provide an individual with these objective sensations. MATERIAL/METHODS: In the current report we utilize an AB design to explore observed differences in blood plasma signaling molecules in pre- and post music listening groups when compared with controls. We focus chiefly on cytokines, as well as peripheral blood mononuclear cells and polymorphonuclear cells. We utilized reverse transcription followed by real-time polymerase chain reactions to determine relative mRNA expression for the mu opiate receptor gene. Using high pressure liquid chromatography coupled to electrochemical detection as well as nano electrospray ionization double quadrupole orthogonal acceleration time of flight-mass spectrometry we determined opiate alkaloid levels. RESULTS: Our findings are two-fold: with regard to mu opiate receptor expression, mononuclear cells showed a statistically significant increase in subjects in the music group compared to the control. Plasma morphine levels were found to be non-significantly lower in subjects after listening to music when compared to control subjects whereas morphine 6 glucuronide levels increased slightly, suggesting morphine's conversion to morphine 6 glucuronide. IL- 6 levels were significantly lower as well whereas IL-1b, IL-10 and cortisol values were unchanged. CONCLUSIONS: Taken together, it appears that music-listeners exhibit plasma signal molecule changes consistent with the physiological changes associated with the reported actions of music, i.e, lower blood pressure.

Adolescent↗
PubMed2004

Synthesis, structure-activity relationships, and mechanism of drug resistance of D- and L-beta-3'-fluoro-2',3'-unsaturated-4'-thionucleosides as anti-HIV agents.

Various D- and L-2',3'-unsaturated 3'-fluoro-4'-thionucleosides (D- and L-3'F-4'Sd4Ns) were synthesized for the studies of structure-activity relationships. The synthesized D-2',3'-unsaturated 3'-fluoro-4'-thionucleosides did not show any significant antiviral activity against HIV-1, while unnatural L-nucleosides such as cytosine 34 (EC(50) = 0.13 microM; EC(90) = 1.7 microM) and 5-fluorocytosine 35 (EC(50) = 0.031 microM; EC(90) = 0.35 microM) derivatives exhibited potent anti-HIV activity without significant toxicity. Molecular modeling study shows that the 3'-fluorine atom of the d-2',3'-unsaturated cytidine triphosphate (D-3'F-4'Sd4CTP) experiences unfavorable electrostatic interaction with its own triphosphate moiety, resulting in the decreased binding affinity to wild-type HIV-1 reverse transcriptase (RT), which may be one of the reasons for the insensitivity of HIV-1 RT to these compounds. On the other hand, L-3'F-4'Sd4CTP binds to the active site of wild-type HIV-1 RT without steric hindrance and there is a possible hydrogen bonding between the 3'-fluorine atom and Asp185, which correlates with its potent anti-HIV activity. However, L-3'F-4'Sd4C 34 and L-3'F-4'Sd4FC 35 showed high cross-resistance to 3TC-resistant mutant (M184V) RT. Like other unnatural L-nucleosides, the unfavorable steric hindrance of the sugar moiety of L-3'F-4'Sd4CTP with the side chain of Val184 explains its significant cross-resistance to the M184V mutant.

Anti-HIV Agents↗
PubMed2004

Gene structure prediction from consensus spliced alignment of multiple ESTs matching the same genomic locus.

MOTIVATION: Accurate gene structure annotation is a challenging computational problem in genomics. The best results are achieved with spliced alignment of full-length cDNAs or multiple expressed sequence tags (ESTs) with sufficient overlap to cover the entire gene. For most species, cDNA and EST collections are far from comprehensive. We sought to overcome this bottleneck by exploring the possibility of using combined EST resources from fairly diverged species that still share a common gene space. Previous spliced alignment tools were found inadequate for this task because they rely on very high sequence similarity between the ESTs and the genomic DNA. RESULTS: We have developed a computer program, GeneSeqer, which is capable of aligning thousands of ESTs with a long genomic sequence in a reasonable amount of time. The algorithm is uniquely designed to tolerate a high percentage of mismatches and insertions or deletions in the EST relative to the genomic template. This feature allows use of non-cognate ESTs for gene structure prediction, including ESTs derived from duplicated genes and homologous genes from related species. The increased gene prediction sensitivity results in part from novel splice site prediction models that are also available as a stand-alone splice site prediction tool. We assessed GeneSeqer performance relative to a standard Arabidopsis thaliana gene set and demonstrate its utility for plant genome annotation. In particular, we propose that this method provides a timely tool for the annotation of the rice genome, using abundant ESTs from other cereals and plants. AVAILABILITY: The source code is available for download at http://bioinformatics.iastate.edu/bioinformatics2go/gs/download.html. Web servers for Arabidopsis and other plant species are accessible at http://www.plantgdb.org/cgi-bin/AtGeneSeqer.cgi and http://www.plantgdb.org/cgi-bin/GeneSeqer.cgi, respectively. For non-plant species, use http://bioinformatics.iastate.edu/cgi-bin/gs.cgi. The splice site prediction tool (SplicePredictor) is distributed with the GeneSeqer code. A SplicePredictor web server is available at http://bioinformatics.iastate.edu/cgi-bin/sp.cgi

Algorithms↗
PubMed2004

Anti-cytokine autoantibodies in experimental autoimmune neuritis in Lewis rats.

Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated, inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain-Barre syndrome (GBS) in humans. Cytokine production has been suggested to act a pathogenic role for EAN. To study the potential role of cytokines in context with cytokine autoantibodies (Aabs) in EAN, we used in situ hybridization to detect mRNA expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-4, IL-10, and transforming growth factor (TGF)-beta in lymph node mononuclear cell (MNC) and in sciatic nerve sections, as well as ELISA for detection of their autoantibodies in sera and cerebrospinal fluid (CSF) over the course of EAN. Increased mRNA expression for IFN-gamma and TNF-alpha was registered correlating with the peak of clinical signs of EAN, and high levels of mRNA expression for IL-4, IL-10, and TGF-beta were associated with EAN recovery. The levels of cytokine mRNAs were generally inversely correlated to their autoantibodies in serum and CSF, whereby the CSF levels were equal to or lower than the serum levels. Autoantibodies to IFN-gamma dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages proving a neutralizing biological effect of these autoantibodies. Our data demonstrate the existence of the anti-cytokine autoantibodies in the sera and CSF of rats with EAN; however, the role of anti-cytokine autoantibodies in the disease process of EAN remains to be resolved.

Animals↗
PubMed2004

Exposure to appetitive food stimuli markedly activates the human brain.

OBJECTIVE: The increased incidence of obesity most likely reflects changes in the environment that had made food more available and palatable. Here we assess the response of the human brain to the presentation of appetitive food stimuli during food presentation using PET and FDG. METHOD: Metabolic changes in response to food presentation were done in 12 healthy normal body weight subjects who were food deprived before the study. RESULTS: Food presentation significantly increased metabolism in the whole brain (24%, P < 0.01) and these changes were largest in superior temporal, anterior insula, and orbitofrontal cortices. The increases in the right orbitofrontal cortex were the ones that correlated significantly with the increases in self-reports of hunger and desire for food. DISCUSSION: The marked increase in brain metabolism by the presentation of food provides evidence of the high sensitivity of the human brain to food stimuli. This high sensitivity coupled with the ubiquitousness of food stimuli in the environment is likely to contribute to the epidemic of obesity. In particular, the activation of the right orbitofrontal cortex, a brain region involved with drive, may underlie the motivation to procure food, which may be subjectively experienced as "desire for food" and "hunger" when exposed to food stimuli.

Adult↗
PubMed2004

Comparison of the binding of the irreversible monoamine oxidase tracers, [(11)C]clorgyline and [(11)C]l-deprenyl in brain and peripheral organs in humans.

The monoamine oxidase A and B (MAO A and B) radiotracers [(11)C]clorgyline (CLG) and [(11)C]L-deprenyl (DEP) and their deuterium labeled counterparts (CLG-D and DEP-D) were compared to determine whether their distribution and kinetics in humans are consistent with their physical, chemical and pharmacological properties and the reported ratios of MAO A:MAO B in post-mortem human tissues. Irreversible binding was consistently higher for DEP in brain, heart, kidneys and spleen but not lung where CLG >DEP and not in thyroid where there is no DEP binding. The generally higher DEP binding is consistent with its higher enzyme affinity and larger free fraction in plasma while differences in regional distribution for CLG and DEP in brain, heart, thyroid and lungs are consistent with different relative ratios of MAO A and B in humans.

Adult↗