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Biomedical subjects

X Liang

Publications and source records attributed to X Liang.

At least 145 records · Page 8Linked to original sources
PubMed1998

4-bromotiglic acid, a novel inhibitor of thiolases and a tool for assessing the cooperation between the membrane-bound and soluble beta-oxidation systems of rat liver mitochondria.

An inhibitor of long-chain 3-ketoacyl-CoA thiolase has been developed as a tool for probing the cooperation between the two fatty acid beta-oxidation systems located in the inner mitochondrial membrane and in the mitochondrial matrix, respectively. 4-Bromotiglic acid was synthesized and found to inhibit palmitoylcarnitine-supported respiration of rat liver mitochondria in concentration-dependent and time-dependent fashions. Complete inhibition of respiration was achieved after incubating coupled mitochondria with 10 microM 4-bromotiglic acid for 2 min. Uncoupled mitochondria were resistant to the toxic effect of the inhibitor. Inhibition of octanoate-supported or octanoylcarnitine-supported respiration was partially reversed when the inhibitor was removed from the incubation medium. Such reversal was not observed with either palmitoylcarnitine or 2-methyldecanoic acid as the respiratory substrate. The severity of the irreversible inhibition declined with decreasing chain length of the acylcarnitine substrate. Of all beta-oxidation enzymes, only thiolases were inactivated by the inhibitor. Under conditions at which acetoacetyl-CoA thiolase and long-chain thiolase were completely inactivated, 3-ketoacyl-CoA thiolase retained some activity. It is concluded that the degradation of palmitic acid and longer-chain fatty acids is initiated by the beta-oxidation system of the inner membrane, whereas fatty acids shorter than palmitic acid can be oxidized to a certain degree by the matrix system alone. The effectiveness of the matrix system increases with decreasing chain length of the substrate.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1.

The crystal structures of the protein-tyrosine phosphatase SHP-1 catalytic domain and the complex it forms with the substrate analogue tungstate have been determined and refined to crystallographic R values of 0.209 at 2.5 A resolution and 0.207 at 2.8 A resolution, respectively. Despite low sequence similarity, the catalytic domain of SHP-1 shows high similarity in secondary and tertiary structures with other protein-tyrosine phosphatases (PTPs). In contrast to the conformational changes observed in the crystal structures of PTP1B and Yersinia PTP, the WPD loop (Trp419-Pro428) in the catalytic domain of SHP-1 moves away from the substrate binding pocket after binding the tungstate ion. Sequence alignment and structural analysis suggest that the residues in the WPD loop, especially the amino acid following Asp421, are critical for the movement of WPD loop on binding substrates and the specific activity of protein-tyrosine phosphatases. Our mutagenesis and kinetic measurements have supported this hypothesis.

Amino Acid Sequence↗
PubMed1998

Biphasic modulatory action of the selective sigma receptor ligand SR 31742A on N-methyl-D-aspartate-induced neuronal responses in the frontal cortex.

The technique of intracellular recording was used to assess the effect of SR 31742A, a selective sigma receptor ligand, on N-methyl-d-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated responses in pyramidal cells of the rat medial prefrontal cortex in vitro brain slice preparations. Bath application of SR 31742A produced a biphasic effect on NMDA responses: SR 31742A facilitated and inhibited NMDA-induced inward current at low (0.01, 0.05 and 0.1 microM) and higher (0.5, 1 and 10 microM) concentrations, respectively. The potentiating effect reached the peak (366%) at 0.1 microM, with an estimated EC50 value of 23 nM. Correspondingly, SR 31742A also produced a similar biphasic modulatory action on excitatory postsynaptic potentials or currents (EPSPs/EPSCs) evoked by electrical stimulation of the forceps minor. In contrast, SR 31742A produced a modest potentiation of AMPA responses at the concentrations from 0.01 to 1 microM. The potentiating action of SR 31742A on NMDA-receptor mediated neurotransmission may account for, at least partially, its antipsychotic and cognitive-enhancing potential, whereas the inhibitory action on NMDA responses at higher concentrations may be related to the purported neuroprotective action of sigma receptor ligands.

Animals↗
PubMed1998

[Detection of minimal residual disease in acute lymphoblastic leukemia using PCR-molecule hybridization of RNA transcripts].

OBJECTIVE: To detect acute lymphoblastic leukemia's(ALL's) minimal residual disease(MRD) rapidly and effectively. METHODS: In this assay, the gamma T-cell receptor gene rearrangements serve as marker genes. The gene rearrangements are amplified from the diagnostic specimens using a consensus V segment primer and a consensus J segment primer to which the promoter T7 RNA polymerase has been appended. The PCR product from this amplification is transcribed into a radiolabeled RNA probe. The opposite DNA strand is transcribed into test RNA from the PCR product of different staged specimens. The test RNA is hybridized with the probe, and later the digestion with RNase A, Polyacrylamide gel electrophoresis and autoradiography are in progress. RESULTS: According to the mechanism, the perfectly matched RNA duplex can prevent the digestion of RNase A, and the presence of the leukemia cells in the test specimen can be determined. Logarithmical dilution experiments with DNA of a cell line from ALL have shown that this assay's sensitivity is at the 10(-5) level. Minimal residual disease was successfully detected in a case of ALL during its complete remission stage. But if the probe and test RNA are not from the same individual, the results of this kind of cross hybridization are negative. CONCLUSION: The above results suggest that this assay can become an effective measure in the detection of ALL-MRD clinically.

Child↗
PubMed1998

Agrobacterium VirD2 protein interacts with plant host cyclophilins.

Agrobacterium tumefaciens induces crown gall tumors on plants by transferring a nucleoprotein complex, the T-complex, from the bacterium to the plant cell. The T-complex consists of T-DNA, a single-stranded DNA segment of the tumor-inducing plasmid, VirD2, an endonuclease covalently bound to the 5' end of the T-DNA, and perhaps VirE2, a single-stranded DNA binding protein. The yeast two-hybrid system was used to screen for proteins interacting with VirD2 and VirE2 to identify components in Arabidopsis thaliana that interact with the T-complex. Three VirD2- and two VirE2-interacting proteins were identified. Here we characterize the interactions of VirD2 with two isoforms of Arabidopsis cyclophilins identified by using this analysis. The VirD2 domain interacting with the cyclophilins is distinct from the endonuclease, omega, and the nuclear localization signal domains. The VirD2-cyclophilin interaction is disrupted in vitro by cyclosporin A, which also inhibits Agrobacterium-mediated transformation of Arabidopsis and tobacco. These data strongly suggest that host cyclophilins play a role in T-DNA transfer.

Bacterial Proteins↗
PubMed1998

Time-resolved and nonlinear optical imaging for medical applications.

In this article, we have presented an overview of emerging novel techniques for early-light transillumination imaging as well as nonlinear optical tomography of body organs. The use of light for probing and imaging biomedical media offers the promise for development of safe, noninvasive, and inexpensive clinical imaging modalities with diagnostic ability. The strong scattering of light by biological tissues buries the shadowgram formed by forward-propatating image-bearing photons in the background noise of multiple-scattered light. Several methods for extraction of image-bearing light that capitalize on spatial, temporal and polarization characteristics of transmitted light are reviewed. More recently emerging nonlinear-optical histopathology methods for imaging subsurface structures of tissues in terms of its local spatial symmetry and molecular content are introduced. The progress made so far indicates that some of these techniques are apt to make a transition from laboratory to useful clinical modalities.

Animals↗
PubMed1998

On-probe immunoaffinity extraction by matrix-assisted laser desorption/ionization mass spectrometry.

A simple and effective method has been proposed in this work for combination of immunoaffinity extraction with MALDI MS. In this method, an antibody is attached to the surface of a MALDI probe tip via a thin nitrocellulose film. This allows the corresponding antigen to be selectively captured and concentrated on the probe tip from complex plasma solution for MALDI MS analysis. The whole procedure can be completed within 1 h. This combination offers several excellent performance features in the analysis of SNX-111, a therapeutic peptide. It combines the high specificity of affinity chromatography with the high sensitivity of mass spectrometry in a rapid analysis. Direct mass detection provides unambiguous determination by the observation of signals at characteristic m/z values. This method has been used successfully to determine the therapeutic peptide at relevant doses.

Amino Acid Sequence↗
PubMed1998

Inhibition of NMDA-receptor mediated response in the rat medial prefrontal cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT: intracellular studies.

The techniques of intracellular recording and single-electrode voltage-clamp were used to study the effect of serotonin (5-HT) and the selective 5-HT3 receptor agonist SR 57227A on N-methyl-D-aspartic acid (NMDA)-evoked responses in pyramidal cells of the rat medial prefrontal cortex (mPFC) in in vitro brain slice preparations. Bath application of 5-HT or SR 57227A produced a concentration-dependent inhibition of NMDA-induced membrane depolarization, action potentials, and inward current. The depressant action of 5-HT and SR 57227A had a slow onset and showed no signs of receptor desensitization. This action was markedly attenuated or completely blocked by the selective 5-HT3 receptor antagonists granisetron and BRL 46470A, but not other receptor antagonists. In addition to inhibiting NMDA-evoked responses, SR 57227A also depressed significantly pharmacologically isolated, NMDA receptor-mediated, monosynaptic excitatory postsynaptic currents (EPSCs) elicited by electrical stimulation of the forceps minor; this inhibitory action was blocked by BRL 46470A but not other 5-HT receptor antagonists. Perfusion of Ca2+-free or low Ca2+ plus Cd2+ artificial cerebrospinal fluid prevented electrical stimulation-induced EPSCs, but did not affect the inhibitory action of 5-HT and SR 57227A. In conclusion, we demonstrate for the first time that 5-HT and SR 57227A interact with 5-HT3-like receptors to produce a direct inhibitory action on NMDA receptor-mediated response in pyramidal cells of the mPFC.

Animals↗
PubMed1998

A comparison of liver protein changes in mice and hamsters treated with the peroxisome proliferator Wy-14,643.

Interspecies differences in the liver response to Wy-14,643, a potent peroxisome proliferator in rats and mice, have been demonstrated. While both rats and mice show dramatic increases in the number of peroxisomes, the activity of peroxisomal enzymes involved in the beta-oxidation of fatty acids, and heptocyte replication, Syrian hamsters have a more moderate peroxisome proliferation response and no sustained increase in cell replication. Rats and mice, but not hamsters, develop hepatocellular carcinoma after prolonged exposure to Wy-14,643. To further characterize this species difference, two-dimensional gel electrophoresis (2-DE) has been used to compare the effect of 14-day exposure to various dietary concentrations of Wy-14,643 on liver protein expression in male mice and hamsters. Digitized images of the 2-DE protein maps were searched for significant changes. The peroxisome bifunctional enzyme (PBE) enoyl CoA hydratase/3-hydroxyacyl dehydrogenase, which migrates to the same position in mouse and hamster liver protein 2-DE patterns, increased in abundance by more than three times the control level in both mice and hamsters. In addition to the quantitative change in PBE, significant quantitative changes (P < 0.001) were found in 49 mouse liver proteins (47 decreasing and 2 increasing) and in 35 hamster liver proteins (27 decreasing and 8 increasing). There was little overlap in the mouse and hamster proteins showing quantitative changes in response to Wy-14,643, with the exception of PBE and one unidentified liver protein with an approximate molecular weight of 50,000. These results show that although peroxisome proliferation occurs in the livers of both mice and hamsters exposed to Wy-14,643, other species-specific changes in proteins occur that are independent of the peroxisome proliferation response and that could be related to species-specific susceptibility or resistance to liver tumor induction.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine-induced blockade of NMDA responses in pyramidal neurons of the rat medial prefrontal cortical slice.

In the present study, we demonstrate that, in a concentration-dependent manner, M100907 (formerly MDL 100907, a highly selective 5-HT2A receptor antagonist and a purported atypical antipsychotic drug [APD]), but not its much less active stereoisomer M100009, completely prevents or markedly reverses the phencyclidine (PCP)-induced blockade of N-methyl-D-aspartate (NMDA) responses in pyramidal neurons of the medial prefrontal cortex (mPFC). Furthermore, the atypical APD clozapine, but not the typical APD haloperidol or raclopride (a selective dopamine D2,3 receptor antagonist), mimicked the action of M100907, preventing the PCP-induced effect. These results suggest that M100907 might be an antidote for treating the PCP-induced psychotomimetic state that closely resembles schizophrenia; they could also account for the antipsychotic potential of M100907. Furthermore, our results suggest that the prototype (clozapine) and a candidate (M100907) atypical APDs might be effective in ameliorating schizophrenic symptoms including cognitive and neuropsychological deficits, which are induced in humans who abuse PCP. We hypothesize that the ability of M100907 and clozapine to prevent or reverse the PCP-induced blockade of the NMDA receptor channel is attributed to their 5-HT2A receptors antagonizing property. Therefore, with further systematic studies, the ability of compounds to prevent or reverse PCP's blockade of NMDA responses may prove to be an effective electrophysiological model for screening potential atypical APDs and predicting their therapeutic efficacy in cognitive deficits.

Animals↗
PubMed1998

Polyamine inhibition of estrogen receptor (ER) DNA-binding and ligand-binding functions.

Polyamines are known to inhibit sequence specific DNA-binding activity of several zinc-finger transcription factors, including estrogen receptor (ER) binding to its cognate estrogen response element (ERE). The mechanism accounting for this disruption of protein-DNA interaction is unknown, although polyamine induction of DNA conformational changes has been suggested. To determine if polyamines can directly impair ER action, we compared the effects of putrescine (Putr), spermidine (Spd), and spermine (Spm) on ER DNA-binding (ER-ERE complex formation), ER ligand-binding (estradiol), ER structure (circular dichroism and sucrose gradient sedimentation), and the capacity of ER to transactivate an ERE-tk-CAT reporter in transient transfection assays. Polyamine concentrations causing 50% inhibition of ER-ERE formation (IC50 values) were found to be 1 mM for Putr, 4 mM for Spd, and 3 mM for Spm. This loss of ER DNA-binding was associated with a direct and irreversible effect on the ER DNA-binding domain (ER-DBD). Additionally, polyamines were observed to inhibit ER ligand-binding with IC50 values of 10 mM for Putr, 2 mM for Spd, and < 0.1 mM for Spm; and this correlated with a measureable change in higher-order ER structure (5S to 3.5S sedimentation) and inhibition of intracellular ER transactivation. These findings suggest that in ER-positive human breast tumors with increased polyamine (especially Spm) content, ER structure and function may be directly altered by tight-ion polyamine complexing that results in loss of ER-mediated gene regulation.

Breast↗
PubMed1998

Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Adleptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/- standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.

Adenoviridae↗
PubMed1998

Pulmonary capillary hemangiomatosis: radiographic appearance.

Pulmonary capillary hemangiomatosis is a rare disorder that is characterized pathologically by formation of capillaries along alveolar walls that may ultimately invade the pulmonary parenchyma and pulmonary arteries. The clinic presentation overlaps that of primary pulmonary hypertension, but the natural history of pulmonary capillary hemangiomatosis is one of rapid deterioration. The typical radiographic appearance is a diffuse bilateral reticulonodular pattern associated with enlarged central pulmonary arteries.

Adult↗
PubMed1998

Aldosterone overproduction and CYP11B2 mRNA overexpression in vessels of spontaneously hypertensive rats.

Aldosterone is synthesized in extra-adrenal tissues such as blood vessels and brain. Damage to blood vessels could play a crucial role in perpetuating hypertension. In this study, we determined both aldosterone production and aldosterone synthase gene-CYP11B2 mRNA expression in vessels of spontaneously hypertensive rats (SHR). The results showed that aldosterone was overproduced in the vasculature of SHR, by means of ex vivo mesenteric artery perfusion, HPLC, and RIA, and that CYP11B2 mRNA expression was upregulated in aortas of SHR, confirmed by RT-PCR and Southern blot.

Aldosterone↗
PubMed1998

Applications of micro-CT and MR microscopy to study pre-clinical models of osteoporosis and osteoarthritis.

There is a tremendous unmet therapeutic need for the treatment of osteoporosis and osteoarthritis. The ovariectomized rat and the guinea pig are widely used animal models for the evaluation of new therapeutics for osteoporosis and osteoarthritis, respectively. We have utilized X-ray micro-CT techniques to quantitatively evaluate the differences in trabecular bone in the rat proximal tibia following ovariectomy and treatment with estrogen (17-B-estradiol). Results demonstrate a loss of trabecular bone and architecture following ovariectomy (p < 0.001), and a marked inhibition of trabecular bone loss in the estrogen treated group (p < 0.001). A similar change in architecture can be visualized in images obtained by high resolution MR microscopy. In addition, a good correlation was observed between the values of trabecular bone fraction (BV/TV) in the rat tibiae as obtained from 3-dimensional micro-CT data and 2-dimensional static histomorphometry (r = 0.89, 0.73, 0.79 for sham, OVX, and treated groups, respectively). Micro-CT images were also obtained from a set of lumbar vertebrae from sham operated and ovariectomized rats. Significant bone loss can be measured as early as 8 weeks following ovariectomy (p < 0.005). Micro-CT and MR images were also obtained to study age related changes in the stifle joint of the guinea pig. Significant boney changes can be seen in the tibia and femur from the animals at various ages. Changes in cartilage and joint space can also be visualized in the images. The utility of micro-CT imaging in evaluating the mouse skeletal system is illustrated by obtaining morphological and architectural details from high resolution images of the mouse hind limb and proximal tibia, respectively. The results demonstrate the advantages that multi-dimensional imaging techniques can offer in evaluating bone and joint related changes in animal models of osteoporosis and osteoarthritis.

Animals↗
PubMed1998

Study on hydroxyapatite-coated titanium implants used as orthodontic anchorage--an experimental investigation of implant stability and peri-implant neck tissue in dogs.

OBJECTIVE: Hydroxyapatite-coated titanium endosseous implants as orthodontic anchorage were studied. METHODS: These implants, installed in the mandibles of two dogs, were loaded with the orthodontic force of 150 g for 3 months. The stability of the implant and peri-implant neck tissue were investigated with radiograph and index evaluation. RESULTS: No implants were mobile, loosened or dislocated at the 3-month follow-up. The soft tissue around the cervical part of the implants had slight inflammation because of poor oral hygiene and stimulation of residual foods attached to the stainless steel spring. However, no resorption of marginal alveolar bone was found under sustained orthodontic force. CONCLUSIONS: The HA-coated titanium implant can be used as anchorage for short-term orthodontic treatment.

Alveolar Bone Loss↗
PubMed1998

[HA-coated titanium implants used as orthodontic anchorage. An experimental investigation of implant stability and peri-implant neck tissue in dogs].

This study was aimed at the feasibility of using HA-coated titanium endosseous implants as orthodontic anchorage. These implants installed in dog's mandibles were loaded with the orthodontic force of 150 g for 3 months. The stability of the implant and the peri-implant neck tissue were investigated with radiograph and index evaluation. The findings demonstrated that no implant was mobile or loose or dislocated. The soft tissue around the cervical part of the implants had a slight inflammation because of bad oral hygiene and the stimulation of residual food attached to the stainless string. However, no resorption of marginal alveolor bone was found under sustained orthodontic force. The above results suggest that the HA-coated titianium implant can be used as anchorage for short-term orthodontic treatment.

Animals↗