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Biomedical subjects

J X Wu

Publications and source records attributed to J X Wu.

At least 37 records · Page 2Linked to original sources

Establishing a reliable visual function test and applying it to screening optic nerve disease in onchocercal communities.

The computer Controlled Video Perimetry (CCVP) is a computer screening test for detecting visual function loss caused by onchocerciasis, glaucoma, etc. Installed on portable computers, the CCVP has been shown to be high acceptability in field community investigation. However, it is regarded to be difficult in obtaining reliable results from portable computer screening tests because of human behavioural variants and the lack of standard testing environment. In this paper, we propose an architecture for implementing a more reliable CCVP system. In particular, a self-organising neural network is applied to manage measurement noise caused by behavioural factors. A control unit is introduced to manage the overall behaviour of the system. The integrated test system has been used to screen optic nerve disease in onchocercal communities of rural Nigeria and the experimental results obtained from a large number of test records are very encouraging: reliable results from volatile test environments may be obtained using the proposed method.

Artifacts↗

UV activates growth factor receptors via reactive oxygen intermediates.

Exposure of mammalian cells to UV irradiation induces rapid and transient expression of early growth response-1 gene (Egr-1) encoding a transcription factor that plays a role in cell survival. These signals from the irradiated cell surface are likely to involve more than one pathway, and we show here that an essential pathway involves activation of several growth factor receptors by reactive oxygen intermediates (ROI). UVC irradiation causes the tyrosine phosphorylation of EGF receptor (EGFR) in mouse NIH 3T3 fibroblasts and HC11 mouse mammary cells. EGFR activation by irradiation of cells is abrogated by suramin, by antioxidants, and by the presence of a dominant negative EGFR. UV induces the formation of complexes between activated EGFR and SOS, Grb2, PLC gamma, and SHC that can be precipitated with antibodies to EGFR. The activation of EGFR by UV is mimicked by H2O2, suggesting that ROI may function upstream of EGFR activation. Our observations support the hypothesis that ROI and growth factor receptors operate in the early steps of the UV signal that lead to the enhanced expression and activity of Egr-1.

3T3 Cells↗

Kinase-negative mutant epidermal growth factor receptor (EGFR) expression during embryonal stem cell differentiation favours EGFR-independent lineages.

EGF receptors are expressed on most fetal and adult cells but their precise roles are not well known. We previously reported that, in P19 embryonal carcinoma cells, the expression of kinase-negative EGFR inhibits retinoic acid (RA)-induced differentiation to nervous tissue, suggesting that EGFR plays a role in differentiation (J.-X. Wu and E. D. Adamson (1993) Dev. Biol. 159, 208-222). Embryo stem (ES) cells differentiate into a wide range of tissue types after the removal of the cytokine LIF from the culture medium. We demonstrate here that the induction of some early markers of differentiation, tissue-type plasminogen activator (tPA), AFP and keratins 8 and 19 is inhibited, whilst brachyury and myosin are increased, in clones containing kinase-negative mutant EGFR. After an extended period of differentiation, the cell types present in mutant and control cultures differed. Mutant clones produced frequent cardiac and skeletal muscle as the predominant differentiated cell types in vitro; other cells types were sparse or absent. Teratocarcinomas formed by EGFR-deltakinase-expressing ES cells contained frequent skeletal and cardiac muscle as well as apoptotic nuclei, while normal ES cells produced no detectable muscle and less apoptoses. Since mutant differentiated cultures had slower growth rates and increased levels of cell death, we concluded that: (1) inactive EGFR does not allow some cell types to survive and/or proliferate; (2) tissues that do not require EGFR for their survival, development or function predominate in long-term mutant cultures; (3) EGFR activity is not necessary for cardiac and skeletal muscle or endoderm formation and (4) Impaired survival of EGF-dependent lineages leads to preferential selection of muscle in differentiating ES cells.

Animals↗

Detection and location of amphiregulin and Cripto-1 expression in the developing postnatal mouse mammary gland.

Amphiregulin (Ar) and Cripto-1 (Cr-1) are growth promoting peptides that share amino acid sequence homology with epidermal growth factor (EGF). The present study examined Ar and Cr-1 mRNA and protein expression during various stages of C57BL/6 mouse mammary morphogenesis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect transcripts for Ar and Cr-1 at all stages of mammary development. Immunocytochemical (ICC) localization demonstrated that in virgin 4-week to mature 12-week-old mouse fourth inguinal mammary gland, Ar and Cr-1 are expressed in the stromal cells, luminal epithelial cells, and myoepithelial cells of the branching ducts. Ar, and to lesser extent Cr-1, were also found in the epithelial cap cells and in the luminal epithelial cells of the advancing terminal end bud (TEB) from virgin 4-week and 6-week-old mice. Western blot analysis demonstrated that both Ar (28 and 26 kDa) and Cr-1 (90, 67, 56, and 21 kDa) proteins are expressed in virgin, 13.5 day midpregnant and in the 14 day lactating mammary gland. In addition, Ar and Cr-1 are associated with developing alveolar structures as determined by ICC. These results imply that together with EGF and transforming growth factor alpha (TGF alpha), Ar and Cr-1 may play salient roles as modifiers in the morphogenesis and differentiation of the mammary gland.

Amphiregulin↗

Identifying the measurement noise in glaucomatous testing: an artificial neural network approach.

Diagnosis of visual function losses in glaucomatous patients depends to a large extent on the analysis of the data collected from corresponding psychophysical tests. One of the main difficulties in obtaining reliable data from patients in these tests is the measurement noise caused by the learning effect, inattention, failure of fixation, fatigue etc. Using Kohonen's self-organising feature map, we have developed a computational method to distinguish between the noise and true measurement and to provide an instant assessment of reliability of the computer-based visual function test. In particular we have experimented with 270 test records from glaucoma patients and glaucoma suspects and found that this method provides a satisfactory way of locating and rejecting noise in the test data, an improvement over conventional statistical methods. This method can also provide doctors with a clear view of the patient's behaviour during the test, thus assisting in their diagnostic decision making process.

Electricity↗

Perforated amebic liver abscess: clinical analysis of 110 cases.

In this study of 503 consecutive cases of amebic liver abscess documented during a 21-year period, 110 (22%) were complicated by perforation. Perforation sites included pleuropulmonary structures (79 cases, 72%) subphrenic space (15 cases, 14%); and peritoneal cavity (11 cases, 10%). The less common sites were the thoracic and abdominal wall, pericardial sac, bile duct, kidney, mediastinum, colon, and right flank. Trophozoites were recovered in 29% of cases. For the rest of the cases, diagnosis was based on the clinical manifestations and the dramatic response to a therapeutic trial of amebicides. Open surgical drainage was done in 10 of 11 patients who had peritoneal perforation; 6 of them were cured and 5 died. Of 97 patients with perforation sites other than the peritoneal cavity, 64 were treated with metronidazole in addition to needle aspiration and/or percutaneous catheter drainage, and all achieved complete remission without relapse during subsequent follow-up. Of the 36 cases treated with metronidazole alone, 22 (61%) were cured. The mortality rate in the group with perforated abscess was 17% (19/110), compared with 5% (25/503) in the whole series. The results suggested that (1) amebic liver abscess can be difficult to diagnose, especially when the pathogen is not isolated; and (2) metronidazole combined with needle aspiration and/or percutaneous catheter drainage is the treatment of choice for amebic liver abscess with perforation.

Adolescent↗

Protective effect of tetramethylpyrazine against damages of aortic endothelial cells elicited by low-density lipoproteins.

Effects of tetramethylpyrazine (TMP) on endothelial cells damaged by low-density lipoproteins (LDL) were investigated. When endothelial cells were incubated with LDL (1.5 mg protein.ml-1) the level of malondialdehyde (MDA) was increased and the activity of superoxide dismutase (SOD) was inhibited, and levels of cGMP and epoprostenol were decreased. TMP at concentrations of both 20 and 150 mg.L-1 nullified the inhibition of SOD activity and the reduction of cGMP and epoprostenol content elicited by LDL. However, the elevation of MDA content induced by LDL was negated by TMP only at 150 mg.L-1. TMP also caused a reduction in MDA content and an increase of epoprostenol level in normal endothelial cells. This study suggests that TMP protects endothelial cells against damages elicited by LDL and that the protection of TMP might be due to reduction in lipid peroxidation through stimulation of production and/or release of epoprostenol.

Animals↗

[Protective effects of ginsenosides on oxygen free radical induced damages of cultured vascular endothelial cells in vitro].

In this study, calf aortic endothelial cells (ECs) were cultured in vitro to study the ECs damages induced by exogenous oxygen free radical (OFR), and the protective effects of ginsenosides. Exogenous OFR was generated by three methods: enzyme reaction (xanthine-xanthine oxidase), chemical reaction (Cu(2+)-ascorbate) and electrolysis. The experimental results indicated that the xanthine-xanthine oxidase method is most suitable for the study of free radical mediated ECs damages. Addition of ginsenosides (40 microliters.ml-1) reduced the concentration of MDA in the cultured ECs, while the 6-keto-PGF1 alpha content in the medium was reduced (P > 0.05) and the morphologic damages of the ECs was alleviated. It is concluded that ginsenosides exerted a protective effects on ECs damages against lipid peroxidation, and ginsenosides might play an important role in antiatherosclerosis through its protective effect on endothelial cells.

6-Ketoprostaglandin F1 alpha↗

[Experimental study on cellular electrophysiology of Viscum coloratum flavonoid in treating tachyarrhythmias].

Viscum Coloratum Flavonoid (VCF) is one of the dihydro-flavonoids isolated and purified from the stem and leaf of Viscum Coloratum. It was proved both experimentally and clinically to have the effects of anti-tachyarrhythmias. The mechanism of this effect, however, was unclear. In this study, the effects of the drug on the fast response action potentials (FAP) in canine Purkinje fibers and guinea pig ventricular myocardial cells were investigated by glass-microelectrode technique. The results indicated that 0.1 mg/ml VCF accelerated the repolarizations of 2nd and 3rd phase of FAP, shortened action potential duration (APD), and slightly shortened effective refractory period (ERP) (canine) or unchanged (guinea pig). delta ERP/delta APD ratio was increased, therefore, ERP was relatively prolonged. All effects appeared after using the drug for 2 minutes, reached stable status after 10 minutes, and disappeared after washing off the drug for 15 minutes. It was suggested that VCF was the drug which exerted effects rapidly, maintained effects shortly, and had effects reversibly. The cellular electrophysiologic mechanisms of VCF on anti-tachyarrhythmias should be attributed to prolong the ERP relatively and abolish the reentry. This drug is particularly applicable to the tachyarrhythmias due to reentry.

Action Potentials↗

[Effects of Viscum coloratum flavonoids on fast response action potentials of hearts].

The effects of the total flavonoids of Viscum coloratum (VCF) on the fast response action potentials (FAP) of canine Purkinje fibers and guinea pig ventricular papillary muscles were studied by glass-microelectrode technique. The effects of VCF on the ionic currents through cellular membrane were analysed with selective ion blockers (CsCl, verapamil, and TEA+), respectively. VCF (100 micrograms.ml-1) accelerated the repolarization of FAP and increased delta ERP/delta APD ratio, which were related to decreasing Isi and increasing Ix. It was suggested that the anti-tachyarrhythmic mechanism of VCF was attributed to prolonging ERP relatively and to abolishing reentrant excitation.

Action Potentials↗

[The preventive and curative action of fish oil compound on early atherosclerotic lesions in the aortic of diabetic rats].

250-320g male Wistar rats were divided randomly into three groups: normal control, diabetes mellitus (DM) control and fish oil compound (FOC) treatment groups. The latter two groups were induced diabetic by streptozotocin injection. At the end of the third week after injection, the treatment group was fed FOC for 9 weeks. The results showed that FOC could decrease the plasma total cholesterol, triglycerides, low density lipoprotein-cholesterol and very low density lipoprotein cholesterol levels significantly; restrain platelet aggregation; decrease blood pressure and increase atrial natriuretic polypeptide-mRNA content. It was found that the aorta in DM rats had more serious lesions than those in the FOC group. Our study found that FOC could prevent the development of atherosclerosis in DM rats.

Animals↗

Modulation of mouse preimplantation development by epidermal growth factor receptor antibodies, antisense RNA, and deoxyoligonucleotides.

Two-cell mouse preimplantation embryos were cultured for 48 h in four different reagents to modulate epidermal growth factor (EGF) receptor function. These were rabbit polyclonal and mouse monoclonal antibodies to EGF receptor, EGF receptor antisense RNA, and EGF receptor antisense deoxyoligonucleotides. Embryos were scored for two endpoints: onset of cavitation as a measure of trophectoderm differentiation and mean embryo cell number as a measure of cell proliferation. The consistent observations were that cavitation was significantly accelerated by antibodies and delayed by antisense RNA and antisense deoxyoligonucleotides. None of these reagents exerted a significant effect on mean embryo cell number, with one exception, the polyclonal antibody. Our interpretation of these observations is that the antibody binding facilitated cavitation by mimicking natural ligand-receptor binding and inducing the signal transduction cascade that is typical for the EGF receptor. In the case of antisense RNA or deoxyoligonucleotide, we propose that they delayed onset of cavitation by interfering with EGF receptor production. We hypothesize that during this period of development, EGF receptor is concerned predominantly with the regulation of differentiation more than with cell proliferation.

Animals↗

Inhibition of differentiation in P19 embryonal carcinoma cells by the expression of vectors encoding truncated or antisense EGF receptor.

Murine embryonal carcinoma cells do not express detectable cell-surface epidermal growth factor receptors (EGF-R) but after 2 days of differentiation induced by retinoic acid (RA) increasingly express mRNA and protein encoded by the EGF receptor gene (Joh et al., Cell Growth and Differentiation 3, 315, 1992). The effect on morphology, growth, and differentiation of the introduction of expression vectors that produce either a truncated, kinase-negative mouse EGF receptor or an antisense mRNA was studied in P19 embryonal carcinoma (EC) cells before and after differentiation. The presence of either construct should lead to the reduction of EGF-R expression by either the dominant negative effects of a truncated protein or the inhibition of endogenous EGF-R mRNA production/translation by complementary RNA, respectively. Cells were cotransfected with the bacterial neomycin resistance gene and constitutively expressing clones were selected with G418. The cytomegalovirus LTR promoter/enhancer was found to be very inefficiently activated in P19 EC cells. After RA addition, changes in gene expression included induction of both the exogenous truncated constructs and endogenous EGF-R. Differentiation was gauged by the expression of tissue-type plasminogen activator and intermediate filament protein markers of neural tissues, as well as EGF-R. The expression of 120-kDa truncated EGF-Rs was high in four clones, but all 10 clones examined had diminished abilities to differentiate after RA induction compared to four control cell lines. Similarly, the majority of antisense transfected clones was unable to differentiate normally. The results indicate that the reduced expression of EGF-Rs in differentiating EC cells inhibits the rate, frequency, and extent of differentiation after RA induction. We conclude that the expression of EGF-Rs plays a role in the stimulation of differentiation and we speculate that the mechanism involves the tyrosine kinase activity of the receptor.

Animals↗

Epidermal growth factor receptor mRNA and protein increase after the four-cell preimplantation stage in murine development.

Epidermal growth factor receptors (EGF-Rs) are expressed at increasing levels on mouse preimplantation embryos. Immunofluorescence assays were used to show that unfertilized eggs and 2-cell embryos have a very low level of reactivity to antimouse EGF-R antibodies, but by the 4-cell stage and later the reactivity increases. The synthesis of EGF-R protein was verified at the blastocyst stage by immunoprecipitation of a 170-kDa metabolically labeled protein. The EGF-R protein is expressed on cell plasma membrane surfaces, but after compaction at the 8-cell stage concentrates on the apical cell surfaces. We also find a low level of expression of EGF-R protein on inner cell mass cells; thus, all cell lineages express receptors from the beginning of gestation. The receptor protein synthesized by the 8-cell embryo and later is probably translated from embryonic transcription, since reverse transcription-polymerase chain reaction indicates increasing levels of mRNA starting after the 4-cell stage. However, we also detected maternal mRNA in zygotes and 2-cell embryos. The pervasive nature of EGF-R expression throughout development suggests important roles for these receptors which could include autocrine and paracrine stimulation.

Animals↗

[Comparative effects of Panax notoginseng saponins, verapamil, and norepinephrine on cerebral circulation in anesthetized rats and rabbits].

In urethane-anesthetized New Zealand rabbits, mean blood pressure (MBP) and cerebrovascular resistance (CVR) fell by 27-47% and 11-17% (P < 0.05), respectively after Panax notoginseng saponins (PNS) 20-80 mg.kg-1 i.v. Verapamil (Ver) 30 micrograms.kg-1 i.v. showed similar effects, but norepinephrine (NE) 30 micrograms.kg-1 i.v. showed opposite effects. PNS and Ver reduced the MBP and CVR in sodium pentobarbital-anesthetized Wistar rats. The actions of PNS and Ver on cerebral blood flow (CBF) were related to the animal species, i.e. PNS increased CBF in rats but reduced that in rabbits, Ver increased CBF in rabbits but had no effects on that in rats. In isolated ring segments of New Zealand rabbit basilar arteries, PNS 1 and 3 mg.ml-1 non-competitively inhibited the contractions induced by KCl with the pD2' value 2.69 +/- 0.20 (-lg g.ml-1). The results indicate that PNS and Ver are vasodilators of brain blood vessel, which would be beneficial to cerebral circulation, while NE is a vasoconstrictor of brain blood vessel.

Animals↗

[Study on toxicology of a new anthelmintic "85012"].

"85012", a new anthelmintic containing amidine synthesized in our laboratory, was experimentally effective against Nippostrongylus braziliensis and Ancylostoma caninum. In acute and subacute toxicity test, it was proved lowly toxic. There was no evidence that the drug induced any damages to main organs and tissues of animals. In order to evaluate its potential mutagenicity and teratogenicity, micronucleus test, bone marrow metaphase analysis, CHL cells chromosomal aberration assay, spermatic aberration test as well as teratogenicity test were performed. No mutagenic and teratogenic effects were observed.

Amidines↗

Hemodynamic actions of guan-fu base A in anesthetized rats.

Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in this institute. GFA exhibited anti-arrhythmic effects in various experimental arrhythmia animal models, and bradycardic actions. In this paper, the hemodynamic action of GFA was investigated. GFA 20 mg.kg-1 iv decreased in heart rate from 420 +/- 51 to 305 +/- 60 bpm (P less than 0.05). The changes of SBP, DBP, LVSP, +/- dP/dtmax, and LVEDP were much smaller or insignificant. GFA (1, 3, 10, 30, 60 mg.kg-1 cumulative iv) increased the heart periods (HP) and QT-intervals in a dose-dependent manner, accompanied by a small increase in PQ-interval, but did not affect QRS complex. The increase in HP from 138 +/- 11 to 321 +/- 48 ms (P less than 0.01) was mainly due to a prolongation of the diastolic period from 22 +/- 12 ms to 156 +/- 46 ms (P less than 0.01). The triple product of HR x LVET x SBP was also decreased with every dose of GFA. This hemodynamic profile suggests that the bradycardic action of GFA can reduce myocardial oxygen consumption and improve myocardial blood supply, which may be of use in certain cardiac patients.

Alkaloids↗

Regulation of epidermal growth factor receptor gene expression in murine embryonal carcinoma cells.

The protooncogene c-erbB1 [epidermal growth factor receptor (EGF-R)] is expressed in a wide variety of cell types and in most adult tissues. The precise roles of the EGF-R in vivo are largely unknown, especially their role in growth and development of embryonic tissues. We reported earlier that EGF-Rs are not expressed on the cell surface of undifferentiated embryonal carcinoma (EC) cells, but intracellular receptor protein is detectable (A. Weller, J. Meek, and E. D. Adamson, Development, 100: 351-363, 1987). We document here that in embryonal carcinoma cells, low levels of both receptor mRNA and protein are observed, but after 4 days of retinoic acid-induced differentiation, large increases are seen. Most notable is the 35-70-fold rise in the levels of EGF-R transcripts during the differentiation of P19 embryonal carcinoma cells to neural and glial cells, and this is paralleled by a 10-fold rise in protein. Measurements of the degradation rates of EGF-R mRNA and receptor protein show that both are rather stable and may partially explain the steady-state increases during differentiation. Run-on transcription assays of the EGF-R gene show very low rates of transcriptional activity at all stages: about 2-fold changes in transcription rate can be detected. It is concluded that transcriptional mechanisms may also partially account for increased levels of gene products. We hypothesize that the appearance of EGF-Rs at the cell surface leads to the slow induction of further receptor levels by EGF/transforming growth factor alpha stimulation, and this contributes to the driving force of differentiation and to the stability of the differentiated state.

Animals↗