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Biomedical subjects

M Xu

Publications and source records attributed to M Xu.

At least 217 records · Page 12Linked to original sources
PubMed1998

Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice.

Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D3 receptor. This possibility was tested with mice lacking the D3 receptor as a result of gene targeting. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D3 receptor mutant and wild-type mice. The putative D3 receptor-selective agonist R(+)-trans-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin+ ++-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. In the gamma-butyrolactone (GBL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. In vivo microdialysis studies of DA release in ventral striatum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wild-type mice. These results suggest that the effects of PD 128907 on dopamine cell function reflect stimulation of D2 as opposed to D3 receptors. Although D3 receptors do not seem to be significantly involved in DA autoreceptor function, they may participate in postsynaptically activated short-loop feedback modulation of DA release.

Animals↗
PubMed1998

Images of interlayer josephson vortices in Tl2Ba2CuO6+delta

The strength of the interlayer Josephson tunneling in layered superconductors is an essential test of the interlayer tunneling model as a mechanism for superconductivity, as well as a useful phenomenological parameter. A scanning superconducting quantum interference device (SQUID) microscope was used to image interlayer Josephson vortices in Tl2Ba2CuO6+delta and to obtain a direct measure of the interlayer tunneling in a high-transition temperature superconductor with a single copper oxide plane per unit cell. The measured interlayer penetration depth, lambdac, is approximately 20 micrometers, about 20 times the penetration depth required by the interlayer tunneling model.

Journal Article↗
PubMed1998

Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast cancer in vivo.

We recently reported that a p53 encoding plasmid (BAP-p53) complexed to liposomes administered intravenously markedly attenuates the growth of a malignant human breast tumor. We now have found that systemically delivered liposomes complexed to a plasmid expressing an established antiangiogenic peptide of thrombospondin I (BAP-TSPf) decreased the growth of MDA-MB-435 tumors compared to controls in nude mice. Compared to BAP-p53, the BAP-TSPf group had a similar antitumor efficacy. More importantly, liposomes complexed with BAP-TSPf and BAP-p53 synergistically decreased the growth of MDA-MB-435 tumors when compared to either BAP-p53 or BAP-TSPf alone. Furthermore, we also determined that the combination therapy of p53 and TSPf inhibited endothelial cells in vitro more than either p53 or TSPf alone. There was also a significant decrease of the blood vessel density in the combination p53 and TSPf treatment group compared to the control groups. These results suggest that liposomes complexed to a tumor suppressor and antiangiogenic genes may be effective in treating metastatic tumors.

Animals↗
PubMed1998

In vivo gene therapy with a cationic polymer markedly enhances the antitumor activity of antiangiogenic genes.

A cationic polymer, Superfect, when complexed to the therapeutic genes, p53 and a TSP fragment, displays a much greater antitumor activity compared to cationic liposomes. At the dosages used, this polymer did not demonstrate any nonspecific antitumor effects in contrast to the liposome carriers. These in vivo findings should further stimulate the development of carrier polymers as well as expedite the evaluation of several antiangiogenic genes.

Animals↗
PubMed1998

Polyethylene glycol conjugation of recombinant methioninase for cancer therapy.

Recombinant methioninase (rMETase) is a homotetrameric pyridoxal 5'-phosphate enzyme of 172-kda molecular mass derived from Pseudomonas putida and cloned in Escherichia coli. rMETase has been found previously to be an effective, anti-tumor agent in vitro and in vivo. The enzyme targets the elevated minimal methionine requirement seen in all tumor types. In order to prevent immunological reactions which might be produced by multiple dosing of rMETase and to prolong the serum half-life of rMETase, the N-hydroxysuccinimidyl ester of methoxypolyethylene glycol propionic acid (M-SPA-PEG 5000) has been coupled to rMETase. Molar ratios of M-SPA-PEG-5000 (PEG) to rMETase from 10 to 40 were used for PEGylation of rMETase. PEGylation reactions were run at 20 degrees C for 30 to 60 min in reaction buffer (20 mM sodium phosphate buffer, pH 8.3). The PEGylated molecules (PEG-rMETase) were purified from unreacted PEG with Amicon 30 K centriprep concentrators or by Sephacryl S-300 HR gel-filtration chromatography. Unreacted rMETase was removed by DEAE Sepharose FF anion-exchange chromatography. The resulting PEG-rMETase subunit, from a PEG/rMETase ratio of 30/1 in the synthetic reaction, had a molecular mass of approximately 53 kda determined by matrix-assisted laser desorption/ionization mass spectrometry, indicating the conjugation of two PEG molecules per subunit of rMETase and eight per tetramer. PEG-rMETase molecules obtained from reacting ratios of PEG /rMETase of 30/1 had enzyme activities of 70% of unmodified rMETase. PEGylation of rMETase increased the serum half-life of the enzyme in rats to approximately 160 min compared to 80 min for unmodified rMETase. PEG-rMETase could deplete serum methionine levels to less than 0.1 microM for approximately 8 h compared to 2 h for rMETase in rats. Efficacy studies of PEG-rMETase on human lung cancer and kidney cancer cells in vitro demonstrated a 50% inhibitory concentration (IC50) of 0.04 and 0.06 units/ml, respectively. These IC50 values were almost identical to unmodified rMETase, thus indicating maintenance of antitumor efficacy in the PEGylated enzyme. PEG-rMETase had an IC50 for normal lung and kidney cells of 0.8 and 1.5 units/ml, respectively, similar to rMETase. The efficacy data indicated that PEG-rMETase maintained the high level tumor selectivity of rMETase. PEG-rMETase injected intravenously in mice demonstrated a tumor/blood retention ratio of approximately 1/6 compared to 1/10 of unmodified enzyme, indicating that PEG-rMETase distributes to the tumor at least as effectively as rMETase.

Animals↗
PubMed1998

High expression, purification, and properties of recombinant homocysteine alpha, gamma-lyase.

Homocysteine alpha,gamma-lyase from the anaerobic protozoan parasite Trichomonas vaginalis has been cloned from genomic DNA using PCR methods and expressed in Escherichia coli with a vector containing the T7 promoter. The recombinant homocysteine alpha,gamma-lyase (rHCYase) is expressed as the major protein in the host E. coli cells. The enzyme was purified to approximately 90% purity using heat treatment at 50 degreesC, precipitation steps with polyethyleneimine, polyethylene glycol 8000, and high sodium chloride, DEAE-Sepharose FF chromatography, and phenyl-Sepharose 6 FF chromatography. The final yield was greater than 50%, which encompassed an approximate 18-fold purification. The enzyme is a homotetramer with a monomer molecular weight of 43K and contains pyridoxal phosphate. The Trichomonas rHCYase is selective for homocysteine with respect to very low cysteinase activity in contrast to the alpha,gamma-lyase from Pseudomonas putida, which has very high cysteinase activity with respect to homocysteine. The T. vaginalis and P. putida alpha,gamma-lyases readily separate on a phenyl-Sepharose 6 FF column with the T. vaginalis enzyme eluting first. rHCYase is stable up to 50 degreesC and active over a pH range of 6-8. These properties of high recombinant expression in E. coli, a simple and effective high-yield purification procedure and high relative specificity for homocysteine with respect to cysteine, make rHCYase a promising candidate to use for the diagnosis of hyperhomocystenemia, which has been demonstrated to be a major risk factor for the onset and mortality of cardiovascular disease of all types.

Animals↗
PubMed1998

Effect of peritransplant FTY720 alone or in combination with post-transplant tacrolimus in a rat model of cardiac allotransplantation.

FTY720 is a recently discovered compound that is derived from the fungus Isaria sinclairii. Using a DA donor-to-LEW recipient rat combination, we assessed the efficacy of peritransplant FTY720 alone or in combination with post-transplant tacrolimus on the survival of cardiac allografts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days-1 and 0 prolonged graft survival from 5 to 13 days (P < 0.05). Combining peritransplant FTY720 with post-transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6%. Analysis of lymphocyte subsets by FACS revealed that FTY720 affected the total population of CD3-bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks. In conclusion, FTY720 is a powerful immunosuppressive agent when used as induction therapy and may have an additive effect--perhaps a synergistic one--with post-transplant tacrolimus.

Animals↗
PubMed1998

The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation.

Bone morphogenetic protein 4 (BMP-4) is a vital regulatory molecule that functions throughout human development in mesoderm induction, tooth development, limb formation, bone induction, and fracture repair and is overexpressed in patients who have fibrodysplasia ossificans progressiva. The human gene encoding bone morphogenetic protein 4 (BMP-4) has been isolated and its structural organization characterized. The complete DNA sequence of an 11.2 kb region has been determined. BMP-4 mRNA is transcribed from four exons, although there is evidence that alternate first exons may be used. Transcript initiation occurs at variable positions within a GA-rich region of the DNA. The promoter region is GC-rich with no obvious TATA or CAAT consensus sequences, and contains both positive and negative transcriptional regulatory elements within the 3 kb 5' flanking region of the RNA start site. Comparison of the human and murine BMP-4 genes reveals highly conserved sequences not only in the exon-coding regions but also within the introns and 5' flanking regions. BMP-4 localizes to human chromosome 14q21 by fluorescence in situ hybridization, a location more centromeric than that recently reported. These studies provide a foundation for understanding the genetic regulation of this important gene in human development.

Animals↗
PubMed1998

In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region.

The origin of hematopoietic stem cells (HSCs) and their growth factor requirement are poorly understood. Here we describe a new in vitro culture system of the aorta-gonad-mesonephros (AGM) region, where long-term repopulating HSCs first arise. We demonstrate that oncostatin M (OSM) is expressed in the AGM and is absolutely required for the expansion of multipotential hematopoietic progenitors in vitro. In addition, OSM enhances the formation of endothelial cell clusters. Thus, OSM appears to be a key cytokine for the development of multipotential hematopoietic progenitors in the AGM, possibly acting on common precursor cells between HSCs and endothelial cells. By using the AGM culture derived from macrophage colony-stimulating factor (M-CSF)-deficient op/op mutant embryos, we also show a pivotal role for M-CSF in fetal myelopoiesis.

Animals↗
PubMed1998

Controlled release gel of ibuprofen and lidocaine in epidural use--analgesia and systemic absorption in pigs.

PURPOSE: Reduction of the frequency of injections and localization of the absorption of drug molecules to the injection site would be of great advantage in epidural pain treatment. The epidural use of a controlled release gel of lidocaine and ibuprofen was studied. METHODS: The effect of a poloxamer gel (25%) containing 2% lidocaine.HCl and 2% ibuprofen.Na on the duration of analgesia after epidural administration to pigs was compared with drug in solution. Analgesia was assessed by observing the motor function and the nociceptive reflex-withdrawal response to painful pressure stimulation on the feet. Pharmacokinetic and histological examinations were performed. RESULTS: Analgesia lasted significantly longer after epidural lidocaine gel injection in comparison with the solution. The gel prolonged the systemic absorption, thereby increasing the epidural availability of lidocaine for spinal analgesia. Although the absorption of ibuprofen was prolonged after epidural gel injection, the duration of analgesia as compared with the solution was not prolonged. After epidural injection, only slight inflammatory changes were observed in the tissue structures of the epidural space, but none in the spinal cord. CONCLUSIONS: These results demonstrate poloxamer gel to be a promising controlled-release, injectable epidural formulation for the management of pain.

Absorption↗
PubMed1998

Genetic variation and phylogenetic relationships among six populations of corn borers in China.

The genetic variation among and within six populations of the corn borer was determined by using random amplified polymorphic DNA (RAPD) markers. Extensive genetic variability was detected. Of the 802 RAPD markers obtained, 781 (97.4%) were polymorphic among populations. Genetic similarities and distances between each pair of individuals were calculated. UPGMA cluster analysis showed that the YN population (Ostrinia nubilalis Hübner) and the other five populations (Ostrinia furnacalis Guenée) made up branches of the corn borer lineage, instead of deviating; there was no significant genetic differentiation between YN and the other five corn borer populations.

Animals↗
PubMed1998

Gal4p-mediated chromatin remodeling depends on binding site position in nucleosomes but does not require DNA replication.

Biochemical studies have demonstrated decreased binding of various proteins to DNA in nucleosome cores as their cognate sites are moved from the edge of the nucleosome to the pseudodyad (center). However, to date no study has addressed whether this structural characteristic of nucleosomes modulates the function of a transcription factor in living cells, where processes of DNA replication and chromatin modification or remodeling could significantly affect factor binding. Using a sensitive, high-resolution methyltransferase assay, we have monitored the ability of Gal4p in vivo to interact with a nucleosome at positions that are known to be inaccessible in nucleosome cores in vitro. Gal4p efficiently bound a single cognate site (UASG) centered at 41 bp from the edge of a positioned nucleosome, perturbing chromatin structure and inducing transcription. DNA binding and chromatin perturbation accompanying this interaction also occurred in the presence of hydroxyurea, indicating that DNA replication is not necessary for Gal4p-mediated nucleosome disruption. These data extend previous studies, which demonstrated DNA replication-independent chromatin remodeling, by showing that a single dimer of Gal4p, without the benefit of cooperative interactions that occur at complex wild-type promoters, is competent for invasion of a preestablished nucleosome. When the UASG was localized at the nucleosomal pseudodyad, relative occupancy by Gal4p, nucleosome disruption, and transcriptional activation were substantially compromised. Therefore, despite the increased nucleosome binding capability of Gal4p in cells, the precise translational position of a factor binding site in one nucleosome in an array can affect the ability of a transcriptional regulator to overcome the repressive influence of chromatin.

Binding Sites↗
PubMed1998

Adipose tissue-derived tumor necrosis factor activity correlates with fat cell size but not insulin action in aging rats.

Adipose tissue-derived tumor necrosis factor (AT-TNF) protein and messenger RNA (mRNA) has been shown to correlate with insulin resistance in some studies. However, in a study using different aged Fischer 344 rats, AT-TNF activity correlated more strongly with cell size than with fasting plasma insulin. The present study was undertaken to more carefully examine the relationship among AT-TNF, adipose cell size, and insulin action using more precise measures of insulin action. Basal and hyperinsulinemic, euglycemic clamps were performed in male Sprague Dawley rats at four different ages (8, 13, 21, and 61 weeks old). [3-(3)H]glucose and 2-deoxy-D-[1-(14)C]glucose were used to assess glucose kinetics and tissue-specific glucose uptake. Because TNF activity represents the summation of TNF synthesis, secretion, and the amount of soluble inhibitors present, TNF activity was measured using a bioassay, in addition to measuring TNF protein and mRNA levels. AT-TNF activity increased significantly with age, as did the glucose infusion rate, a measure of whole body insulin resistance. However, AT-TNF activity did not correlate with any parameter of insulin action measured during the hyperinsulinemic, euglycemic clamps. In epididymal fat, AT-TNF activity correlated with: glucose infusion rate: r = -0.50, P = 0.17; rate of appearance: r = -0.19, P = 0.35; rate of disappearance: r = 0.08, P = 0.69. As was noted before, AT-TNF activity correlated well with fat cell size (r = 0.76, P < 0.001 in epididymal fat; r = 0.58, P = 0.007 in SUB fat). These data suggest that although AT-TNF activity and insulin resistance increase with age, the two are not functionally related. These data do not eliminate the potential role of nonadipose TNF in the regulation of insulin action.

Adipocytes↗
PubMed1998

[NK cell activity and subsets of truck drivers along with related factors].

We investigated the immunity and the main factors that affect the immune system of 19 truck drivers as the experimental group and 27 office workers as the control group at a transit corporation in Tokyo; all subjects in both groups were examined through an assay of NK activity and NK subsets before and after work. At the same time, they were asked to complete a questionnaire on their working hours per day (WHPD) and driving hours per day (DHPD), in addition to the Health Practice Index (HPI), Self-Rating Depression Scale (SDS), Stress Tolerance Check List (STCL), and Symptom Checklist (SCL). The results obtained were as follows: 1. Before work, no difference was seen in NK activity between the experimental group and the control group, with both groups showing E:T ratios 5:1 to 20:1. After work, the NK activity (E:T = 20:1) of the experimental group was significantly lower than that of the control group. 2. In the experimental group, the NK activity and NK subsets (CD3-CD16+CD56+, CD3-CD56+, CD3-CD16+) of the peripheral blood lymphocytes after work were significantly lower than before work (p < 0.05, p < 0.01, p < 0.01). After more than five driving hours, the value of the CD3-CD16+CD56+ subset was significantly lower than that after fewer driving hours. 3. Correlation coefficients were calculated based on the average value of NK activity (E:T = 20:1), CD3-CD16+CD56+ subset, and WHPD, DHPD, and HPI in the driving group. NK activity (E:T = 20:1) and DHPD were found to be negatively correlated (r = -0.28), as were the CD3-CD16+CD56+ subset and WHPD (r = -0.43) and the CD3-CD16+CD56+ subset and DHPD (r = -0.63). On the other hand, NK activity (E:T = 20:1), the CD3-CD16+CD56+ subset and HPI were found to be positively correlated (r = 0.41 and 0.33).

Adult↗
PubMed1998

Nuclear matrix as a target for hyperthermic killing of cancer cells.

The nuclear matrix organizes nuclear DNA into operational domains in which DNA is undergoing replication, transcription or is inactive. The proteins of the nuclear matrix are among the most thermal labile proteins in the cell, undergoing denaturation at temperatures as low as 43-45 degrees C, i.e. relevant temperatures for the clinical treatment of cancer. Heat shock-induced protein denaturation results in the aggregation of proteins to the nuclear matrix. Protein aggregation with the nuclear matrix is associated with the disruption of many nuclear matrix-dependent functions (e.g. DNA replication, DNA transcription, hnRNA processing, DNA repair, etc.) and cell death. Heat shock proteins are believed to bind denatured proteins and either prevents aggregation or render aggregates more readily dissociable. While many studies suggest a role for Hsp70 in heat resistance, we have recently found that nuclear localization/delocalization of Hsp70 and its rate of synthesis, but not its amount, correlate with a tumor cell's ability to proliferate at 41.1 degrees C. These results imply that not only is the nuclear matrix a target for the lethal effects of heat, but it also is a target for the protective, chaperoning and/or enhanced recovery effects of heat shock proteins.

Cell Death↗
PubMed1998

Diagnosis and classification of hepatic echinococcosis by ultrasonography.

OBJECTIVE: To make an early and correct diagnosis of hepatic echinococcosis. METHODS: A total of 1092 patients with hepatic echinococcosis underwent operation in our hospital between 1984 and 1995. Of these patients, 427 (39.1%) were cases with complications, including secondary infection, rupture, obstructive jaundice, anaphylactic shock, disseminated implantation with resultant multiple echinococcosis and portal hypertension. The ultrasonic examination has been generally used in clinical practice for comprehensive evaluation which can dectedct the preoperative diagnostic accuracy rate. RESULTS: B-mode ultrasonography can be used not only to detect the location, dimension and pathological characteristics of hydatid cyst but also to show the pathological changes of various complications caused by echinococcosis. Seven patterns specific ultrasonic scanning images were revealed. In this series the diagnostic accuracy rate reached 98.8%. CONCLUSIONS: Ultrasonic examination is harmless to human body, and has been widely used in combination with immunological tests in clinical and epidemiological studies to detect the asymptomatic parasite carriers in early stage and to improve the preoperative diagnostic accuracy rate.

Echinococcosis, Hepatic↗