Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 271 records · Page 15Linked to original sources

PubMed1998

Role of CD4+ and CD8+ T cells in regulating the chronic development of liver injury induced by delayed-type hypersensitivity to picryl chloride.

In this study we first investigated the cellular immune responses in mice with chronic liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl). A continuous reduction, after week 3 of liver injury, was observed in the level of PCl-induced contact sensitivity but not in sheep red blood cell-induced footpad reaction, suggesting the presence of PCl-specific suppression. When spleen cells from mice whose liver had been injured for 1 week were systemically transferred into syngeneic recipients with the liver injury, the elevation in serum lactic dehydrogenase and the decrease in alkaline phosphatase and albumin levels in recipient mice were significantly exacerbated. However, when the liver damage in the donor mouse was allowed to proceed for 3, 5 or 7 weeks, biochemical changes in recipients were reduced to near normal levels. A flow-cytometric assay demonstrated that the number of CD4+ T cells in both spleen cells and liver nonparenchymal cells decreased dramatically during the late phase of liver injury, while CD8+ counts did not. These findings suggest that CD4+ and CD8+ T lymphocytes may contribute to the positive and negative regulation, respectively, of the early and late phases in the chronic development of liver injury.

Animals↗

PubMed1998

Functional and biochemical interactions of Wnts with FrzA, a secreted Wnt antagonist.

Wnts are highly conserved developmental regulators that mediate inductive signaling between neighboring cells and participate in the determination of embryonic axes. Frizzled proteins constitute a large family of putative transmembrane receptors for Wnt signals. FrzA is a novel protein that shares sequence similarity with the extracellular domain of Frizzled. The Xenopus homologue of FrzA is dynamically regulated during early development. At the neurula stages, XfrzA mRNA is abundant in the somitic mesoderm, but later becomes strongly expressed in developing heart, neural crest derivatives, endoderm, otic vesicle and other sites of organogenesis. To evaluate possible biological functions of FrzA, we analyzed its effect on early Xenopus development. Microinjection of bovine or Xenopus FrzA mRNA into dorsal blastomeres resulted in a shortened body axis, suggesting a block of convergent extension movements. Consistent with this possibility, FrzA blocked elongation of ectodermal explants in response to activin, a potent mesoderm-inducing factor. FrzA inhibited induction of secondary axes by Xwnt8 and human Wnt2, but not by Xdsh, supporting the idea that FrzA interferes with Wnt signaling. Furthermore, FrzA suppressed Wnt-dependent activation of the early response genes in ectodermal explants and in the marginal zone. Finally, immunoprecipitation experiments demonstrate that FrzA binds to the soluble Wingless protein in cell culture supernatants in vitro. Our results indicate that FrzA is a naturally occurring secreted antagonist of Wnt signaling.

Amino Acid Sequence↗

PubMed1998

Signal transduction in arteriosclerosis: mechanical stress-activated MAP kinases in vascular smooth muscle cells (review).

Vascular smooth muscle cell (SMC) proliferation is a key event in the development of (spontaneous) atherosclerosis, hypertension-related arteriosclerosis, angioplasty-induced restenosis and venous bypass graft arteriosclerosis. Many factors or environmental stimuli are believed to be responsible for SMC growth or hypertrophy in the vessel wall. How these environmental stimuli or signals applied onto the surface of SMCs are transduced into the cell nucleus resulting in quantitative and qualitative changes in gene expression in SMCs of arterial walls is largely unknown. Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Recent studies have focused on the signalling events in vascular tissues in vivo and in cultured SMCs in vitro. It has been demonstrated that acute hypertension and angioplasty rapidly induced MAP kinase activation in the arterial wall. Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced transcription factor AP-1 DNA-binding activity. A similar MAP kinase activation can be mimicked in in vitro cultured SMCs stimulated by either shear stress or cyclic strain stretch, suggesting direct effects of mechanical force. Interestingly, physical forces rapidly resulted in phosphorylation of platelet-derived growth factor (PDGF) receptor, an activated state, in cultured SMCs. Thus, mechanical stresses may directly perturb the cell surface or alter receptor conformation, thereby initiating signalling pathways usually used by growth factors. These findings have significantly enhanced our knowledge concerning the pathogenesis of arteriosclerosis and provide a basis for therapeutic intervention on vascular diseases.

Angioplasty↗

PubMed1998

An experimental study on rat model of parkinsonism by gene therapy.

OBJECTIVE: To induce significant improvement of motor abnormalities and striatal dopamine (DA) levels in rat model of Parkinson's disease (PD), by intracerebral grafting of the genetically modified muscle cells expressing tyrosine hydroxylase (TH). METHODS: Primary myoblasts and myotubes from the rat were prepared by cell culture and a plasmid, pCMVTH, containing TH gene and a promoter of cytomegalovirus (CMV) was constructed by DNA recombination technique. The primary muscle cells were transfected with newly constructed pCMVTH DNA vector, by using lipofection. These genetically modified muscle cells were grafted into the caudate- putamen of 6-OHDA-lesioned rats, representing PD models. Before and after grafting, the rotational behaviour and the striatal levels of DA and its metabolities were tested at different postoperative survival times. In addition, the immunocytochemistry for showing TH activity was done both in vitro and in vivo. RESULTS: The newly constrcuted plasmid, pCMVTH was proved to contain TH gene and have correct direction of insertion. The cultured primary myoblasts and myotubes lipofected with pCMVTH were immunocytochemically shown to express TH activity in vitro. After grafting, these TH-expressing muscle cells showed to have a long-term survival cells in vivo and induced a marked decrease in abnormal locomotion and a increase in striatal DA levels for PD rat model. CONCLUSIONS: In experimental gene therapy for PD, the pCMVTH is a useful vector for carrying TH gene. The lipofection is a practical technique for transferring a target gene into eukaryotes and primary cultured muscle cells should be a good vehicle for DNA transfer and intracerebral grafting.

Animals↗

PubMed1998

Intra-axial tumors of the medullocervical junction: diagnosis and microsurgical treatment.

OBJECTIVE: To describe the clinical features, operative methods and postoperative management of the intra-axial tumors of medullocervical junction, and to make differential diagnosis for different subtypes. METHODS: Fifteen patients with intra-axial tumors of medullocervical junction were treated from August 1988 to June 1997. The diagnoses were confirmed by MRI and histological examinations. The tumors were divided into two subtypes according to the clinical features and the main body of the tumor. The distinctive points of the two subtypes and the appropriate surgical methods of different pathological type tumors were expounded. RESULTS: Tumors were totally removed in 10 patients and subtotally in 5. There was no death caused by operation. Postoperative complications included respiratory disturbance in six cases, upper digestive tract bleeding in one, depressed cough reflex in two, most of which recovered after proper treatment. On discharge, the nervous system status was improved in 11 cases, stable in 2 and worsened in 2. CONCLUSIONS: The intra-axial tumors of medullocervical junction can be divided into cervicomedullary and medullocervical subtypes. The MRI examination is decisive in the distinction of the diagnosis, and is important in the determination of the nature of the medullar cystic lesions and the guidance of the resection of tumor extent. The cervicomedullary tumors are more amenable to an aggressive surgical treatment, during which the surgeon should remove the tumors first in the cervical spinal cord area, then in the medullar area with the tumor resection expanding rostrally. It can make the operation safer to remove the tumors using appropriate techniques varied with pathological types of the tumors. Managing postoperative respiratory disturbances without delay is one of the important points in improving the therapeutic effect.

Adolescent↗

PubMed1998

[Influence of moderate hypothermia on the contents of 6-KETO-PGF1 alpha and TXB2 in brain tissues after cardiac arrest and resuscitation in dogs].

To investigate the effect of moderate hypothermia of whole brain (30 degrees C to 32 degrees C) on the levels of prostacyclin and thromboxane A2 in brain tissues after cardiac arrest and resuscitation. Twenty-one dogs were divided into four groups: Group A, nonischemic controls (n = 4); Group B, 15 minute cardiac arrest without reperfusion (n = 4); Group C, 15 minute cardiac arrest and standard resuscitation (n = 6); Group D, 15 minute cardiac arrest and moderate hypothermia (30 degrees C-32 degrees C). The results showed that as compared with those in Group A, the 6-Keto-PGF1 alpha levels remained substantially unchanged in Group C and D (P > 0.05), and the levels of TXB2 and TXB2/6-Keto-PGF1 alpha ratio increased significantly in Group C (P < 0.01), but both maintained basically stable in Group D (P > 0.05). In comparison with those in Group C, the levels of TXB2 and TXB2/6-Keto-PGF1 alpha ratio decreased dramatically (P < 0.01). It is concluded that the moderate hypothermia can depress the arachidonic acid metabolism and keep a certain balance between the activities of TXA2 and PGI2 during cerebral resuscitation.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

[Effect of different prescriptions for tonifying kidney on RNA transcription activity in isolated nuclei and protein synthesis activity in free-cell extracts of the different organs of presenile mice].

OBJECTIVE: To study the anti-aging mechanism of Zuoguiyin (a prescription for tonifying Kindney Yin) and Yishenbao (a prescription for tonifying Kidney Yang) in presenile mice. METHODS: Using male, 14 months old presenile mice as a model of Kidney-Asthenia, the effects of Zuoguiyin and Yishenhao on RNA transcription activity in isolated nuclei and protein synthesis activity in free-cell extracts of the liver, brain, kidney and testes of the presenile mice were observed. RESULTS: RNA transcription activity in isolated nuclei and protein synthesis activity in free-cell extracts of the four organs of the presenile mice group were distinctly lower than those of young mice group (3 months old). After above-mentioned two prescriptions were given to the presenile mice for two months, RNA transcription activity in isolated nuclei and protein synthesis activity in free-cell extracts of the four organs of the two treated groups were obviously higher than those of control group (P < 0.05 or P < 0.01), but there was no difference between two treated groups. CONCLUSIONS: Both Zuoguiyin and Yishenbao could promote RNA transcription activity in isolated nuclei and protein synthesis activity in free-cell extracts of Kidney-Asthenia and presenile mice.

Aging↗

PubMed1998

[Application of capillary non-gel sieving electrophoresis to the analysis of short tandem repeat in phenylalanine hydroxylase gene and gene diagnosis of phenylketonuria].

OBJECTIVE: To establish a sensitive, accurate and reliable method for analysis of short tandem repeat (STR) markers for gene diagnosis, capillary electrophoresis (CE) was used for analysis of a polymorphic tetranucleotide (TCTA)n in intron 3 of the phenylalanine hydroxylase (PAH) gene. METHODS: Capillary non-gel sieving electrophoresis (CNGSE) system was used to analyze PCR products of PAH STR among 61 normal Chinese individuals and 6 phenylketonuria (PKU) families. RESULTS: The PCR fragments that differ 4 bp from each other were well separated by CNGSE. Ten alleles were identified, with a continuous distribution from 224 bp to 260 bp. The largest allele (260 bp) was first detected in Chinese population. The alleles frequencies were calculated and PIC is 0.738. The genotypes of PAH STR of total 80 Chinese people were also analyzed and the heterozygosity is 75%. We used this procedure to PAH gene linkage analysis in 6 PKU families, in which pathogenic gene could be affirmed in 3 families, including one case of prenatal diagnosis. CONCLUSIONS: In comparison with denaturing polyacrylamide gel electrophoresis, CE is an accurate, rapid, automatic and with high resolution analytical tool. CE in combination with PCR is a hopeful technique and might be widely used for gene diagnosis of genetic diseases in the future.

Alleles↗

PubMed1998

[Intrahepatic portal vein compliance in cirrhosis].

OBJECTIVE: To elaborate the effects of increase in portal flow on intrahepatic vein compliance with isolated perfused cirrhotic model (IPCM). METHOD: Cirrhosis was induced by CCl(4) in 80 Wistar rats, which were divided into two groups A and B, by portal with/without hepato-artery. Portal flow was increased and hemodynamic parameters were recorded and analysed. RESULT: In group A, compared with 1.65 +/- 0.28 kPa at basal control, portal pressure was elevated from 2.55 +/- 0.40 kPa to 3.96 +/- 0.67 kPa. Q(35)-Q(55) flow rates were raised from 35 to 55 ml/min, respectively. A correlation existed between portal flows and pressures (r = 0.985, P < 0.01). The low flow rate of 15 ml/min at Q(15) caused a irreversible model injury. A largest flow rate in IPCM was, less than in IPRL. In group B, no low flow-injury was found. CONCLUSION: Portal vein compliance of liver is decreased markedly in cirrhotic portal hypertension, but hepatic flow is increased. There are likely some compensative relations between portal and hepato-arterial system.

Animals↗

PubMed1998

[Supercritical fluid extraction and gas chromatographic analysis of four organochlorine pesticides in vegetable].

Supercritical fluid extraction(SFE) of pesticide residues of chlorothalonil, aldrin, dieldrin, and endrin from chives was evaluated. A mixture of vegetable sample: anhydrous magnesium sulfate(2:3) was used for extraction. The extract was analyzed by GC/ECD. The optimum SFE conditions for the pesticides in spiked samples were studied by orthogonal experiment. The chosen conditions were 30.40 MPa, 40 degrees C, 1 min static time, dynamic extraction with 15 mL of CO2, and collection in 3 mL of ethyl acetate. All the pesticides were extracted satisfactorily from their matrix.

Chive↗

PubMed1997

Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1.

Current data suggest that nitric oxide (NO) is a double-edged sword that could result in relaxation and/or cytotoxicity of vascular smooth muscle cells (SMCs) via cGMP- dependent or -independent signal pathways. Stress or heat shock proteins (hsps) have been shown to be augmented in arterial SMCs during acute hypertension and atherosclerosis, both conditions that are believed to correlate with disturbed NO production. In the present study, we demonstrate that NO generated from sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine, and spermine/nitric oxide complex leads to hsp70 induction in cultured SMCs. Western blot analysis demonstrated that hsp70 protein expression peaked between 6 and 12 h after treatment with SNP, and elevated protein levels were preceded by induction of hsp70 mRNA within 3 h. Induction of hsp70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the transcriptional level. HSF1 activation was completely blocked by hemoglobin, dithiothreitol, and cycloheximide, suggesting that the protein damage and nascent polypeptide formation induced by NO may initiate this activation. Furthermore, SMCs pretreated with heat shock (42 degrees C) for 30 min were significantly protected from death induced by NO. Thus, we provide evidence that NO induces hsp70 expression in SMCs via HSF1 activation. Induction of hsp70 could be important in protecting SMCs from injury resulting from NO stimulation.

Animals↗

PubMed1997

Topography of the photosystem I core proteins of the cyanobacterium Synechocystis sp. PCC 6803.

PsaA and PsaB are homologous integral membrane proteins that form the heterodimeric core of photosystem I. Domain-specific antibodies were generated to examine the topography of PsaA and PsaB. The purified photosystem I complexes from the wild type strain of Synechocystis sp. PCC 6803 were treated with eight proteases to study the accessibility of cleavage sites in PsaA and PsaB. Proteolytic fragments were identified using the information from N-terminal amino acid sequencing, reactivity to antibodies, apparent mass, and specificity of proteases. The extramembrane loops of PsaA and PsaB differed in their accessibility to proteases, which indicated the folded structure of the loops or their shielding by the small subunits of photosystem I. NaI-treated and mutant photosystem I complexes were used to identify the extramembrane loops that were exposed in the absence of specific small subunits. The absence of PsaD exposed additional proteolytic sites in PsaB, whereas the absence of PsaE exposed sites in PsaA. These studies distinguish PsaA and PsaB in the structural model for photosystem I that has been proposed on the basis of x-ray diffraction studies (Krauss, N., Schubert, W.-D., Klukas, O., Fromme, P., Witt, H. T., and Saenger, W. (1996) Nat. Struct. Biol. 3, 965-973). Using osmotically shocked cells for protease treatments, the N terminus of PsaA was determined to be on the n side of the photosynthetic membranes. Based on these data and available published information, we propose a topological model for PsaA and PsaB.

Animals↗

PubMed1997

Discordant activation of stress-activated protein kinases or c-Jun NH2-terminal protein kinases in tissues of heat-stressed mice.

Stress-activated protein kinases (SAPK) or c-Jun NH2-terminal protein kinases (JNK) are believed to be crucial signal transducers between stress stimuli and genetic responses in mammalian cells. These kinases are activated in various types of in vitro cultured cells by heat shock, but a similar activation of SAPK/JNK in tissues in vivo has yet to be shown. In the present study, C57BL/6 mice were exposed to elevated ambient temperature for various time periods, and SAPK/JNK activities determined in protein extracts of brain, heart, liver, spleen, lung, and kidney using protein kinase assay and Western blot analyses. The time course and relative magnitude of the heat-induced SAPK/JNK activity differed among tissues of the same animal. Significant activation of SAPK/JNK was achieved in heart, liver, and kidney at 60 or 90 min of heat stress. This increased activity of SAPK/JNK kinases was demonstrated to result from activation or phosphorylation of existing proteins in tissues. The maximal activation of these kinases showed no direct relationship with the elevation in body temperature (38-40.5 degrees C). Interestingly, SAPK/JNK activation did not occur in lung, brain, or spleen of the same heat-stressed mouse. Although elevated body temperature (40.5 degrees C) did not result in SAPK/JNK activation in spleen and lung tissues, heat stress induced SAPK/JNK activation in cultured organs or fibroblasts derived from spleen or lung of C57BL/6 mice. Furthermore, activity and amount of SAPK/JNK proteins were the most abundant in brain among tissues examined. Thus, our findings demonstrated that heat shock-induced SAPK/JNK activation in vivo lacks much of the characteristic coordinate control of activation of cultured cell lines, and suggests that the mechanisms controlling SAPK/JNK activation are influenced by physiologic factors that cannot be studied in vitro.

Animals↗

PubMed1997

Macrophage-lysis mediated by autoantibodies to heat shock protein 65/60.

Macrophages in atherosclerotic lesions have been shown to express high amounts of heat shock protein 60 (hsp60), a highly conserved protein. Patients with atherosclerosis have high titers of anti-hsp65/60 antibodies (Ab) recognizing macrophages in the lesions. To elucidate the role of anti-hsp65/60 Ab in macrophage cytotoxicity, human high titer serum and purified anti-hsp65/60 Ab were tested on in vitro heat-stressed cells of a human macrophage cell line (U937) and macrophages derived from peripheral blood. Application of heat stress at 42 degrees C for 30 min resulted in marked upregulation of hsp60 mRNA, followed by increased protein expression as determined by Northern blot and FACS-analysis, respectively. Compared to unstressed cells, high titer serum and anti-hsp65/60 Ab preferentially bound to the surface of stressed U937 macrophages, but not control antibodies. Furthermore, high titer serum and anti-hsp65/60 Ab exerted significant (P < 0.01) complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) on stressed 51Cr-labelled U937 and peripheral blood derived macrophages. Thus, macrophages expressing hsp60 can be lysed by autoantibodies against hsp65/60, which may contribute to cell death in atherosclerotic plaques in vivo.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1997

Liver injury model induced in mice by a cellular immunologic mechanism--study for use in immunopharmacological evaluations.

Various drugs for clinical hepatitis were applied to a new model of liver injury induced in mice by delayed-type hypersensitivity to picryl chloride (PCI-DTH). The hepatoprotective agent, biphenyl dimethyl dicarboxylate showed a remarkable improvement against the elevation of serum transaminase levels as well as the histopathological changes when given during the induction phase but not during the effector phase of DTH reaction. Cyclophosphamide (Cy), an immunosuppressive agent, significantly inhibited the enzymatic elevation given in both induction and effector phases. However, Cy did not affect the sustaining of liver injury 4 weeks after the liver injury eliciting. Moreover, the consecutive administration of prednisolone (Pred), in both induction phase and sustaining process of liver injury, conversely caused a more severe liver damage. Such exacerbation by Pred might be resulted from its toxic action to hepatocytes. As an immunomodulatory and antiinflammatory agent, glycyrrhizin remarkably improved the sustaining process but not the acute phase of the liver injury. Krestin and malotilate also showed an improving effect on the sustaining development of liver injury. These findings that most of above drugs showed an improving action in their respective manner suggest that this model may be useful for the pharmacological evaluation of drugs especially immunomodulating agents for hepatitis.

Acute Disease↗

PubMed1997

Anti-inflammatory activity of the aqueous extract from Rhizoma smilacis glabrae.

Our previous paper has reported that the aqueous extract from Rhizoma smilacis glabrae (RSG) (RSG ext) selectively inhibited the effector phase of delayed-type hypersensitivity (DTH) without suppressing humoral immune response. In the present study, a remarkable inhibitory activity was exhibited by the extract against both primary and secondary hind paw swelling of adjuvant arthritis in rats. RSG ext also significantly reduced the inflammatory edema induced by carrageenan in either naive or bilaterally adrenalectomized rats, suggesting the independence of the anti-inflammatory action on the function of pituitary-adrenal axis. The PGE2 content in the carrageenan-induced inflammatory tissue was also decreased remarkably by the extract. Furthermore, RSG ext showed a distinct inhibition on the formation of cotton-induced granuloma formation. However, as compared with a steroidal agent, prednisolone, the extract did not affect the vitamin C content in adrenal gland as well as the weights of some organs. These results suggest that RSG ext may act as a therapeutic agent of immunoinflammatory diseases through a selective suppression on the cellular immune response involved in inflammations as well as through a direct anti-inflammatory mechanism including inhibiting PGE2.

Adrenal Glands↗

PubMed1997

A new strategy for regulating the immunological liver injury--effectiveness of DTH-inhibiting agents on DTH-induced liver injury to picryl chloride.

Aqueous extracts from various crude drugs showing a selective inhibition on the induction or effector phase of delayed-type hypersensitivity (DTH) reaction were applied to the new model of liver injury induced in mice by picryl chloride(PCl)-induced DTH. The inhibiting drugs to the induction phase of DTH, Fructus Triburi (FT) and Er-Miao-San (EMS), showed a remarkable improvement against the elevation in serum transaminase levels as well as in histopathological changes when given during this phase. The administration in the effector phase by Rhizoma Smilacis Glabrae (RSG) and Cortex Dictamni (CD), selectively inhibiting the phase of DTH, also significantly improved the liver damage. In addition, RSG and CD showed an almost complete recovery of serum alkaline phosphatase from a persistent decrease in the sustaining process of liver injury when given consecutively for 4 weeks after the elicitation of liver injury. Cyclophosphamide, an immunosuppressive agent, significantly inhibited the enzymatic elevation given in either phase, while it did not affect the ability to sustain liver injury. When the above extracts were given in a combined manner to the same mouse during these two phases, respectively, FT with RSG and EMS with CD showed a distinct synergism against the liver injury. RSG or CD also enhanced the activity of prednisolone in suppressing PCl-induced ear contact sensitivity. These findings suggest that this immunological liver injury may be regulated by a set of selective suppressants to DTH reaction and the suitable application of such agents may pave the way for a new strategy in treating liver damage.

Animals↗

PubMed1997

Eph-related receptors and their ligands: mediators of contact dependent cell interactions.

Recent studies of the large families of Eph-related receptor tyrosine kinases and their ligands suggest that they have key roles in embryonic development. These receptors mediate cell contact dependent signalling by binding to membrane-bound ligands, and certain ligands may themselves transduce signals. Functional studies indicate that in a number of tissues the receptors and ligands are expressed in complementary domains and mediate repulsive interactions that restrict cell and axon migration. In addition, they can also stimulate cell migration. Eph-related receptors and their ligands are therefore mediators of cell interactions required for tissue patterning and neuronal pathfinding during development. The potential clinical implications of these findings are discussed.

Animals↗