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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 343 records · Page 19Linked to original sources
PubMed1996

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2.

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.

Breast Neoplasms↗
PubMed1996

Activation of heat shock transcription factor 1 in rat aorta in response to high blood pressure.

We have previously demonstrated that acute hypertension induces heat shock protein gene expression in rat arterial wall. Here we provide evidence that this induction is mediated through the activation of heat shock transcription factor 1 in response to high blood pressure. Rats subjected to restraint or immobilization stress displayed an acute elevation in systolic pressure accompanied by an increase in heat shock protein 70 mRNA expression. Consistent with the rapid time course of mRNA induction, an increase in binding activity to an oligonucleotide encompassing a consensus heat shock element sequence was seen in protein extracts from aorta of restrained rats as assessed with gel mobility shift assays. A similar increase in DNA binding activity was also observed in aortic extracts from rats treated with various hypertensive agents, including phenylephrine, angiotensin II, and vasopressin. That the DNA binding activity was attributed to heat shock factor 1 was shown through use of antibodies to the transcription factor that retarded the DNA-protein complexes in gel mobility supershift assays. Western blot analysis of heat shock factor 1 protein expression in aortic extracts showed a slower mobility form of the protein in hypertensive rats, indicative of an activated, presumably phosphorylated, form of the transcription factor. These findings support the view that heat shock factor 1 is responsible for induction of heat shock protein 70 in the arterial wall during acute hypertension, a response that is likely to play an important role in protecting arteries during hemodynamic stress.

Acute Disease↗
PubMed1996

Vasopressin-induced heat shock protein expression in renal tubular cells.

Heat shock proteins (HSPs), which have been shown to be induced in the kidney by a variety of stress conditions, including ischemia, inflammation, oxidative stress, and toxin exposure, are believed to protect the cells from injury. In the present study, we demonstrated that administration of vasopressin i.v. to Wistar rats leads to HSP70 induction in the kidney. The effect was specific to the kidney (i.e., absent in brain, heart, lung, muscle, etc.) and selective for the HSP70 gene family (HSP27, HSP60, and HSP90 were not induced). Western blot analysis demonstrated that HSP70 protein expression peaked between 6 and 12 hours after vasopressin administration. Immunohistochemical staining revealed that induction was localized to renal tubule lining cells, with no expression seen in glomerular or interstitial regions. The elevated protein levels were preceded by the induction of HSP70 mRNA within 30 minutes after vasopression injection. The induction of HSP70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the level of transcription. This HSP70 expression was completely blocked in the presence of both a general vasopressin receptor antagonist (V1 and V2 receptors) and an antidiuretic antagonist (V2), but not in the presence of a vasopressor antagonist (V1). These observations could be significant for understanding the possible involvement of HSP70 in physiological processes of the kidney, as well as pathophysiologic conditions associated with either elevated or deficient levels of vasopressin.

Amino Acid Sequence↗
PubMed1996

Coexpression of heat-shock protein 60 and intercellular-adhesion molecule-1 is related to increased adhesion of monocytes and T cells to aortic endothelium of rats in response to endotoxin.

Bacterial cell-wall lipopolysaccharide (LPS) is the main endotoxin contributing to local inflammation and systemic toxicity during Gram-negative infections and induces aortic endothelial injury with or without cell death and replication followed by increased leukocyte adhesion. Heat-shock protein (hsp) 60 is under study in our laboratory as a potential antigen inducing immunologic attack to endothelial cells in atherogenesis. To investigate the mechanism of LPS-induced endothelial injury and the phenotypes of adhering cells, Lewis rats were treated in vivo or, in aortic organ cultures, with LPS to determine the expression of intercellular-adhesion molecule-1 (ICAM-1) and hsp60 on aortic endothelium and to characterize phenotypes of adhering leukocytes. Increased ICAM-1 expression by aortic endothelium was observed as early as 3 hr after LPS injection and persisted up to 72 hr, whereas elevated levels of hsp60 were found between 6 and 48 hr. In vitro application of various types of stress, such as LPS, H2O2, and high temperature, not only stimulated endothelial expression of hsp60 but, concomitantly, that of ICAM-1. The number of adhering leukocytes was significantly increased on aortic endothelium 6 hr after LPS administration, and the predominant leukocytes adhering to stressed endothelium were monocytes (80%) and T lymphocytes (8 to 20%). In organ cultures of rat aortic intimal, LPS, and H2O2 evoked increased leukocyte adhesion, which proved to be selective, because adherent leukocytes were mostly Ia+ monocytes and T cells, i.e., activated. Adhering T cells were gamma/delta antigen-receptor positive in 8 to 16% after LPS stress, whereas these cells amount to only 2 to 4% of peripheral blood T cells. Blocking of adhesion molecules ICAM-1, LFA-1 alpha, and/or LFA-1 beta reduced adhesion up to 34%. Increased coordinated LPS-dependent expression of hsp60 and ICAM-1 correlates with monocyte and T-cell adhesion to aortic endothelium. These observations may be significant for elucidating the mechanism of the initiating events in the development of atherosclerosis.

Animals↗
PubMed1996

Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice.

A leukemia-selective immunotoxin was constructed by linking recombinant gelonin (rGel), a single chain ribosome inhibitory protein, to recombinant humanized M195 antibody (HuM195), which recognizes the cell-surface protein designated CD33. CD33 is an antigen found on myeloid leukemia blasts as well as myeloid progenitor cells but it is not expressed in detectable amounts on the ultimate hematopoietic progenitor stem cell. Our previous studies indicated that a non-recombinant humanized immunotoxin displayed specific, potent toxicity towards CD33-positive cells but not to CD33-negative cells in vitro. In the current study, a recombinant humanized immunotoxin, HuM195-rGel, was evaluated in vivo in a nude mouse model of human myeloid leukemias. HuM195-rGel was found to target leukemia cells rapidly in vivo and was subsequently internalized into the cells. For trials in vivo, nude mice were injected (ip) with 10(7) log-phase HL60 human leukemia cells 10 days prior to the start of i.p. HuM195-rGel treatments. HuM195-rGel demonstrated significant tumor suppressive activity in this model. While all mice treated with either saline, rGel alone, or HuM195 plus unconjugated rGel (at 10 or 14 days after transplantation) had rapid tumor growth or early deaths, 50% of mice treated with HuM195-rGel failed to develop leukemic tumors for 5 months and the 50% had significantly retarded tumor growth after treatment with HuM195-rGel. Mice treated at later times (28 days after transplantation of leukemia cells) also showed delayed leukemia cell growth, but no cures. These data show that HuM195-rGel can target leukemia cells in vivo and can result in pronounced anti-leukemic effects.

Animals↗
PubMed1996

[Histopathological and immunohistochemical studies on gliosarcoma].

Immunohistochemical staining of 5 gliosarcomas was performed. Neoplastic glial component stained positive by GFAP. Endothelial cells lining the lumina of glomeruloid vascular structures stained positively with both UEA-1 and FVIII/RAg antibodies. Mesenchymal cells of sarcomatous areas stained positively with SMSA antibody and presence of PDGFR. The staining results demonstrate that the sarcomatous component of gliosarcoma is of smooth muscle origin and suggest that the vascular smooth muscle hyperplasia is related to PDGF.

Aged↗
PubMed1996

[DNA typing for HLA-DR in donor-recipients of cadaveric transplantation].

OBJECTIVE: To accurately allocate donor-recipients of HLA-matching and improve long-term graft survival, genotyping method for HLA-DR alleles by polymerase chain reaction with sequence-specific primers (PCR-SSP) was established and applied to renal transplantation. METHODS: Thirty primers were designed and synthesized according to the HLA-DR nucleotide sequences. Genomic DNAs were prepared by a rapid salting-out method. A rapid genotyping method of PCR-SSP was set up by PCR technique and applied to HLA-DR typing in 14 cell lines DNA and 171 individuals of donor-recipients of cadaveric transplantation. The amplification was accomplished by 34 cycles consisting of denaturation at 94 degrees C for 30 seconds, annealing at 60 degrees C for 50 seconds, and extension at 72 degrees C for 40 seconds. The specificity of matching was determined against a panel of standard DNA, analysis with restriction endonucleases and Southern hybridization. RESULTS: HLA-DR alleles of all 171 samples and 14 cell line DNAs were able to be typed by PCR-SSP. The size of specific products was consistent with the size of calculation. The overall time of genotyping was only 5 hours. No false positive or false negative typing results were discovered. The typing results were confirmed by analysis with endonucleases and hybridization. The specificity and reproducibility were 100%. CONCLUSIONS: Genotyping for HLA-DR by PCR-SSP is a rapid and accurate matching technique, suitable for organ transplantation, especially allocation of donor-recipients of cadaveric transplantation.

Alleles↗
PubMed1996

Rapid HLA-DR genotyping by PCR-amplification with sequence-specific primers.

OBJECTIVE: To establish a rapid genotyping for HLA-DR alleles by polymerase chain reaction with sequence-specific primers (PCR-SSP) for clinical application. MATERIAL AND METHODS: The subjects of study included 69 recipients, 43 unrelated donors and 5 cell lines. Genomic DNA was prepared from peripheral blood leukocytes by a salting-out method. Thirty primers were designed according to the HLA-DRB nucleotide sequences, and synthesized on a 391 DNA synthesizer. Twenty separate PCR reactions were performed for each sample. The amplification was accomplished by 34 cycles consisting of denaturation at 94 degrees C for 30 seconds, annealing at 60 degrees C for 50 seconds and extension at 72 degrees C for 40 seconds. The specificity of matching was determined by standard DNAs and Southern hybridization using DIG labeling probes. RESULTS: All 112 samples and 5 cell lines were able to be typed by PCR-SSP. No false positive or false negative typing results were obtained. The reproducibility was 100%. The size of the specific product was in concordance with the size of the designed primers. The overall time for genotyping was 4 hours. The typing results were confirmed by Southern hybridization. CONCLUSIONS: Genotyping for HLA-DR by PCR-SSP is a rapid and accurate matching technique suited for clinical application.

Alleles↗
PubMed1996

Microsurgery of intramedullary cervical cord tumor.

OBJECTIVE: To evaluate whether intramedullary tumor of the cervical spinal cord is amenable to aggressive surgery and to clarify surgical timing and important points for tumor removal. PATIENTS AND METHODS: Fifty-eight patients with intramedullary tumor of the cervical spinal cord were examined by magnetic resonance imaging and treated by microsurgery in Huashan Hospital between May 1988 and December 1994. The results were analysed by F or Chi square tests. RESULTS: Tumors were totally resected in 50 cases (86.2%), subtotally resected in 7 and partially resected in 1. Forty-five (77.6%) patients had their neurological status improved postoperatively. Most patients with moderate neurological deficit can recover remarkably after total tumor removal. Laser surgery is especially helpful for treating lipoma. CONCLUSIONS: Intramedullary tumor of the cervical spinal cord is amenable to total tumor removal. Operation is suitable when a patient presents moderate neurological deficit. Proficient surgical technique and standards for total tumor resection are essential for good results. Preoperative radiotherapy contributes to difficult surgery and poor prognosis, and is not recommended.

Adolescent↗
PubMed1996

[The changes of striatal dopamine levels in the brain in rat models for Parkinson's disease after gene therapy].

OBJECTIVE: To examine the levels of striatal dopamine and metabolic products in rat model of Parkinson's disease (PD) by intracerebral grafting of the genetically modified muscle cells expressing tyrosine hydroxylase (TH). METHODS: The levels of striatal dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum of rat models for PD were determined by using high performance liquid chromatography (HPLC). The tests were done in 2, 4, 12, 20 and 23 weeks after intracerebral transplantation of cultared muscle cells (myotubes) expressing TH gene. RESULTS: The levels of dopamine and its metabolites in the striatum increased significantly after transplantation of TH-expressed cultured muscle cells. For example, striatal dopamine level increased from 30.53 pg/mg to 876.25 pg/mg in brain tissue at 12 weeks after grafting. The striatal dopamine level was the highest at this time and then decreased gradually. In the control that received transplantation of muscle cells expressing LacZ gene, the striatal dopamine level showed no changes before and after grafting. CONCLUSIONS: The transplantation of TH gene-expressed cultured muscle cells is useful in the treatment of PD rat model, because it can increase striatal dopamine level.

Animals↗
PubMed1996

[Rapid genotyping for HLA-DR by PCR-amplification with sequence-specific primers and clinical practice].

Genotyping for HLA-DR alleles by polymerase chain reaction with sequence-specific primers (PCR-SSP) was first typed in 112 individuals of donor-recipients of cadaveric transplantation and 9 cell lines DNA. Twenty separate PCR reactions were performed per sample. The amplification was accomplished by 34 cycles consisting of denaturation at 94 degrees C for 30 sec, annealing at 60 degrees C for 50 sec and extension at 72 degrees C for 40 sec. HLA-DR alleles could be accurately distinguished. The overall time of genotyping was only 5 hours. The specificity of matching was determined against a panel of standard DNA, analysis with restriction endonucleases, and Southern hybridization using DIG oligonucleotide 3'- end labeling probes. The specificity and reproducibility were 100%. No false positive or false negative typing results were obtained. These showed genotyping by PCR-SSP was a rapid and accurate matching technique, suited for clinical practice.

Alleles↗
PubMed1996

[The effect of electro-acupuncture on the adrenal gland of endotoxic shocked rats].

The quantitative histochemical changes of glycogen SDH in the adrenal gland of endotoxic-shocked rat induced by electro-acupuncture were observed in this paper. The result indicates that electro-acupuncture at "Ren Zhong" or "Zusali" of endotoxic shocked animal might improve the function of adrenal cortex and achieve recovery in certain extent.

Adrenal Glands↗
PubMed1996

[An autoradiographic study of alpha 1-adrenoceptors in hepatic tissues in cirrhotic patients with portal hypertension].

We studied hepatic alpha 1-adrenoceptors of 8 hepatitis virus B-related cirrhotic patients with portal hypertension and 8 control surgical patients without liver disease by light radioautography. The density of alpha 1-adrenoceptors in various hepatic structures ("healthy" control vs. patients, per 10,000 microns 2) was as follows: on hypatocytes 1255.07 +/- 151.44/583.37 +/- 47.64 (P < 0.01); on intrahepatic artery walls 705.06 +/- 188.68/183.54 +/- 46.77 (P < 0.01); on intrahepatic portal walls 409.98 +/- 88.73/154.02 +/- 20.65 (P < 0.01); on hepatic venule walls 339.29 +/- 94.85/.... The decrease of density of alpha 1-adrenoceptors in cirrhotic liver tissues may be a result of the destruction of nomal hepatic structure by hepatitis virus B and the down-regulation of alpha 1-adrenoceptors.

Autoradiography↗
PubMed1996

[Observation on therapeutic effect of megestrol acetate on patients with chronic obstructive pulmonary disease at remission stage].

It has been reported that malnutrition is common in stable chronic obstructive pulmonary disease (COPD) patients. In order to observe the effects of Megestrol Acetate (MA) on nutritional status, respiratory muscle strength and immunological parameters in stable COPD patients, 31 stable COPD patients were divided into two groups at random--a treatment group of 16 cases and a control group of 15 cases. Before and after treatment all parameters were recorded, including food and energy intake, body weight, triceps skinfolds (TSF), pre-albumin, transferrin, albumin. Lung function, respiratory muscle and handgrip strength were examined and immunological parameters also determined. After taking MA 160 mg/day orally for two weeks, the treatment group got benefits as follows: heat energy and protein intake increased fro 6977.9 +/- 1136 kJ/d and 44.65 +/- 13.75 g/d to 9854.0 +/- 2355.3 kJ/d and 84.80 +/- 20.23 g/d respectively. With the increase of daily energy and protein intake, body weight increased from 48.27 +/- 8.61kg to 50.34 +/- 8.76 kg, TSF from 11.75 +/- 4.50 mm to 15.06 +/- 4.73 mm, serum pre-albumin from 306.6 +/- 33.7 mg/L to 332.6 +/- 1 mg/L, transferrin from 3.09 +/- 0.21 g/L to 3.46 +/- 0.32 g/L, albumin from 38.00 +/- 1.73 g/L to 42.64 +/- 3.36 g/L, MIP from 4.77 +/- 2.14 kPa (1 kPa = 7.5 mmHg) to 6.31 +/- 2.87 kPa, MEP from 6.21 +/- 2.90 kPa to 7.20 +/- 3.67 kPa and 6 minutes walking distance from 280.2 +/- 76.4 m to 370.6 +/- 81.5 m. Handgrip strength also improved. Blood lymphocyte transformation rate elevated too. (The changes of all these parameters indicated above were statistically significant, P < 0.01). However, parameters of lung function, blood gas analysis, serum immunoglobulin and complement 3 did not change significantly. In 15 control patients all the parameters did not change significantly. There were few side effects; only one case complained of nausea and vomiting. It was shown that MA can stimulate appetite and increase dietintake, improve nutritional status, elevate respiratory muscle strength, and enhance immunity. MA is a safe and effective drug which exerts a beneficial influence on stable COPD.

Aged↗
PubMed1996

[Medical imaging research on idiopathic hemifacial spasm].

In order to have a medical imaging examination for idiopathic hemifacial spasm before surgery, we designed a new method by using vertebroarterial DSA and vertebroarterial CTA based on an aired cisternapontis, 36 patients were examined since 1989 and the compression of the facial nerve from brain stem to porus acousticus internus was showed clearly in all the cases. The arteries responsible for the compression were cerebellar inferior posterior (55.6%), cerebellar inferior anterior (44.4%), auditory internus (25.0%) and vertebroarterial (11.1%), 36% of all the cases had more than one responsible arteries, 22.2% cases had only one compression point, 38.9% had two points, 25.0% had 3 and 13.9% had more. 85.7% of the compression points located in the root zone and 14.3% near the porus acousticus internus. 24 cases were treated with decompression surgery, it indicated that the compression conditions just met the medical imaging examinationg results. After surgery the symptom disappeared in 23 cases and remarkably released in one case with no death case. We believed that this method might be helpful to idiopathic hemifacial spasm decompression surgery and other surgeries in the CP angle.

Adult↗
PubMed1996

The second space experiment of protein crystallization with domestic facilities.

The second experiment of protein crystallization was performed on domestic re-entry satellite FSW-2 in 1994-07. The results are superior to the ones of the first mission in 1992: 9 of 10 different proteins were crystallized in space, and 70% of the total 48 samples yielded single crystals. Besides hen egg-white lysozyme which grew high-quality crystals on the first mission, an acidic phospholipase A2(aPLA2) from snake venom and hemoglobin from Anser Indicus produced good-quality crystals suitable for X-ray diffraction analyses. The positive effect of microgravity on protein crystal growth is verified again at this time.

Aerospace Medicine↗