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Biomedical subjects

X Wan

Publications and source records attributed to X Wan.

At least 37 records · Page 2Linked to original sources

Hydraulic conductance in aspen (Populus tremuloides) seedlings exposed to low root temperatures.

Low root temperatures significantly reduced root hydraulic conductivity and increased resistance to water flow through the roots of aspen (Populus tremuloides Michx.) seedlings. Increased resistance to water flow could not be fully explained by the corresponding increase in water viscosity at low temperatures. The shapes of Arrhenius plots of root water flow and the activation energies were dependent on the direction, sequence and extent of temperature change. The Arrhenius plots suggested that the effect of low root temperature on root water flow was mediated by an effect on root metabolism. The low root temperatures tested did not induce root electrolyte leakage normally associated with cell membrane injury. Although a decrease in root temperatures to 7 or 4 degrees C induced a reduction in stomatal conductance, this reduction lagged the decline in root water flow by several hours. In contrast, when soil temperatures were raised from 4 or 7 degrees C to 25 degrees C, root water flow presumably increased, and stomatal conductance responded rapidly and was temporarily higher than before the cold treatment was imposed.

Cold Temperature↗

Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation (IVF) can cause sudden death in both adults and children. One form of IVF (Brugada syndrome), characterized by S-T segment elevation (STE) in the electrocardiogram, has been linked to mutations of SCN5A, the gene encoding the voltage-gated cardiac Na(+) channel. A missense mutation of SCN5A that substitutes glutamine for leucine at codon 567 (L567Q, in the cytoplasmic linker between domains I and II) is identified with sudden infant death and Brugada syndrome in one family. However, neither the functional effect of the L567Q mutation nor the molecular mechanism underlying the pathogenicity of the mutation is known. Patch-clamp analysis of L567Q channels expressed in human embryonic kidney cells revealed a marked acceleration and a negative shift in the voltage dependence of inactivation. Unlike other Brugada mutations, this phenotype was expressed independently of temperature or auxiliary beta(1)-subunits. These results support a proposed linkage between Brugada syndrome and some instances of sudden infant death and the hypothesis that reduced Na(+) conductance is the primary cause of IVF with STE.

Cell Line↗

Modulation of T-cell responses to alloantigens by TR6/DcR3.

TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.

Animals↗

[Research on fibrotic effect of Ni-Ti and 317L alloys in esophagus].

This study was conducted to examiune the fibrotic effect of Ni-Ti and 317L alloys in esophagus. The extract fluid from Ni-Ti, 317L alloys was made according to the ASTM standards of U.S.A. The Fb of esophageal scar was cultured primarily, then incubated with alloy abstract fluid. The proliferating activity of Fb was measured by MTT at 4, 24, 48, 72 hours in the course of culturing. The esophagus embedding test of Ni-Ti, 317L alloys was made according to ASTM standards of U.S.A. The tissue around the alloys was taken at weeks 2 and 12, and the pathologic changes were analysed. The results showed that Ni-Ti, 317L extract could depress the proliferating function of Fb gently, and the depressing action increased gradually with the culturing time. The result of embedding test was in accord with the ASTM standards of U.S.A. completely; the fibrotic membrane around the NiTi, 317L alloys became thinner with embedding time. These findings suggested that the scattering composition of Ni-Ti, 317L in body fluid might not activate the proliferating and secreting function of Fb, and the two alloys could not lead to fibrosis of esophagus aroun them.

Alloys↗

Hammerhead ribozymes to modulate telomerase activity of endometrial carcinoma cells.

Telomerase is an excellent target molecule for cancer therapy, though any effective agents have never been developed in human subjects. We designed a variety of hammerhead ribozymes against human telomerase RNA (hTR) and hTERT mRNA and studied their possibility as a tool for cancer therapy. To search promising target site of hTR, the catalytic actiuity of 3 kinds of hammerhead ribozymes was studied in cell-free system. They showed equivalent catalytic activity, but only 36-ribozyme, which was designed to cleave the template region of hTR, revealed telomerase inhibitory activity in an endometrial carcinoma cell line. Among hTERT-mRNA-targeted ribozymes, the ribozyme to cleave 13 nucleotides downstream from the 5'-end of hTERT mRNA (13-ribozyme) exhibited the strongest telomerase-inhibitory activity, and the ribozyme to cleave 59 nucleotides upstream from the poly(A) tail showed clear activity. Stable transfection studies confirmed that the 36-ribozyme as well as the 13-ribozyme suppressed telomerase. These observations suggest that the template region of hTR and 5'end of hTERT mRNA are promising target sites for ribozymes to reduce telomerase activity.

5' Untranslated Regions↗

[Relationship between heat stress suppression of neuroapoptosis and activation of nuclear kappa B in primary cultured rat cerebellar granule cells].

It has been well demonstrated that heat stress response (HSR) plays a crucial role in protecting cells from injury induced by various pathological stimuli. However, the protective mechanism of HSR is only poorly understood. The object of this article was to further investigate the relationship between the protective role of heat stress response and activation of NF-kappa B in primary cultured rat cerebellar granule cells. Heat stress was induced by hyperthermia (43+/-0.5 degrees centigrade), and DNA binding activity of NF-kappa B was determined with electrophoretic mobility shift assay (EMSA). Neuroapoptosis was measured by Hoechst 33258, agarose gel electrophoresis and flow cytometry (FCM) analysis. The results showed that the neurons treated with low potassium for l6 h could induce neuroapoptosis and promote the activity of nuclear kappa B. Heat stress treatment for 30, 60 and 90 min could suppress neuroapoptosis and the activity of nuclear kappa B induced by low potassium in a time-dependent manner. Activation of NF-kappa B using 100 nmol/L phorbol 12-myristate l3-acetate (PMA) could promote antiapoptotic action of heat stress response. In contrast, when NF-kappa B activation was inhibited by 10 micromol/L pyrrolidine dithiocarbamate derivatives (PDTC), heat stress did not provide protection against cell apoptosis induced by low potassium. The results suggest that the neuroprotection of heat stress has no relation to the suppression of NF-kappa B activity, and activation of NF-kappa B may promote antiapoptotic action of heat stress.

Animals↗

The 5'-end of hTERT mRNA is a good target for hammerhead ribozyme to suppress telomerase activity.

Because the expression level of hTERT, a catalytic subunit of human telomerase, is a rate-limiting determinant of telomerase activity, hTERT mRNA would be an excellent target of hammerhead ribozymes for the regulation of telomerase activity. We studied the efficiency of several hammerhead ribozymes targeting hTERT mRNA by transient and stable transfection procedures. To screen the potency of the ribozymes, transient ribozyme transfection and telomerase determination were performed. The ribozyme targeting 13 nucleotides downstream from the 5'-end of hTERT mRNA (13-ribozyme) exhibited the strongest telomerase-inhibitory activity, and the ribozyme to target 59 nucleotides upstream from the poly(A) tail showed clear activity. A stable transfection study confirmed that the 13-ribozyme suppressed telomerase. These observations suggest that the 13-ribozyme can regulate telomerase activity and may possess potential for cancer therapy.

5' Untranslated Regions↗

[Study of the fluid-percussion graded model of experimental brain injury in rats].

OBJECTIVE: To study the histopathological aspects of the fluid-percussion graded model of experimental brain injury in rats and the relationship between the fluid-percussion graded model and the clinical grades of brain injury. METHODS: The graded model of rats was set up by using the device of the improved fluid-percussion model, then we observed the changes of brain tissue of rats. RESULTS: The fluid-percussion graded model of experimental brain injury could be pathologically graded. CONCLUSION: The pathological grade of the fluid-percussion graded model can be used to evaluate the degree of brain injury in clinic and in experiments.

Animals↗

Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus.

BACKGROUND: In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates. METHODS: Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. RESULTS: The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection. CONCLUSIONS: The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.

Animals↗

B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS.

OBJECTIVES: To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection. DESIGN AND SETTING: Case-control study in Sydney, Australia. PARTICIPANTS AND METHODS: Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups. RESULTS: In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18). CONCLUSIONS: Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.

Adult↗

Functional suppression of sodium channels by beta(1)-subunits as a molecular mechanism of idiopathic ventricular fibrillation.

Ventricular fibrillation leading to sudden cardiac death can occur even in the absence of structural heart disease. One form of this so-called idiopathic ventricular fibrillation (IVF) is characterized by ST segment elevation (STE) in the electrocardiogram. Recently we found that IVF with STE is linked to mutations of SCN5A, the gene encoding the cardiac sodium channel alpha -subunit. Two types of defects were identified: loss-of-function mutations that severely truncate channel proteins and missense mutations (e.g. a double mutation, R1232W and T1620M) that cause only minor changes in channel gating. Here we show that co-expression of the R1232W+T1620M missense mutant alpha -subunits in a mammalian cell line stably transfected with human sodium channel beta(1)-subunits results in a phenotype similar to that of the truncation mutants. In the presence of beta(1)subunits the expression of both ionic currents and alpha -subunit-specific, immunoreactive protein was markedly suppressed after transfection of mutant, but not wild-type alpha -subunits when cells were incubated at physiological temperature. Expression was partially restored by incubation at reduced temperatures. Our results reconcile two classes of IVF mutations and support the notion that a reduction in the amplitude of voltage-gated sodium conductance is the primary cause of IVF.

Animals↗

The effects of [K+]o on regional differences in electrical characteristics of ventricular myocytes in guinea-pig.

Altering [K+]o might have different effects on action potential duration (APD) in myocytes from different regions. Therefore, the effects of [K+]o on regional differences in action potential characteristics were investigated in sub-endocardial, mid-myocardial and sub-epicardial myocytes isolated from the base of guinea-pig left ventricular free wall using three different [K+]o (2.7, 5.4 and 8.1 mM KCl). Action potentials were recorded using the switch-clamp technique at 0.5 Hz. Increasing [K+]o from 2.7 to 8.1 mM shortened the action potential duration to 90 % repolarization (APD90; mean APD90 values in sub-endocardial, mid-myocardial and sub-epicardial myocytes were, respectively, 295 +/- 9, 286 +/- 9 and 266 +/- 8 ms in 2.7 mM [K+]o, 270 +/- 7, 255 +/- 7 and 215 +/- 7 ms in 5.4 mM [K+]o, 234 + 7, 212 +/- 10 and 155 +/- 8 ms in 8.1 mM [K+]o), depolarized the resting potential, and reduced the amplitude of the action potential. The effect of increasing [K+]o on action potential characteristics was more pronounced in sub-epicardial myocytes than in sub-endocardial and mid-myocardial myocytes. The regional differences in APD90 in 5.4 mM [K+]o were increased in 8.1 mM [K+]o and abolished in 2.7 mM [K+]o. In conclusion, changing [K+]o produces more pronounced effects on action potentials in sub-epicardial myocytes than in sub-endocardial myocytes, modifying the normal heterogeneity of action potentials. The differences in the response of sub-epicardium and sub-endocardium to [K+]o may contribute to the flattening or inversion of the T wave commonly seen in patients presenting with hypokalaemia and the upright and tall T waves observed in electrocardiograms recorded during hyperkalaemia, although the underlying ionic currents remain to be determined.

Action Potentials↗

Expression of PTEN and PTEN pseudogene in endometrial carcinoma.

PTEN is a tumor suppressor gene and its mutation is frequently found in endometrial carcinoma. Recently, the pseudogene of PTEN has been reported to be actively transcribed in a number of cells and tissues and a potential for translation is suggested. For further understanding of the involvement of PTEN in endometrial carcinogenesis, we analysed the expressions of PTEN and the pseudogene in 36 endometrial carcinomas with special reference to the genetic status of PTEN. Mutations of PTEN were found in 42% (15/36) of the endometrial carcinomas. The transcript of the pseudogene was expressed in 6 samples (17%) of 36 endometrial carcinomas, but in none of the normal endometria. Western blot analysis showed no translated protein of the pseudogene in any of the cases. Steady level of PTEN protein expression was observed in all the cases examined. Expression level was consistent among the proliferative endometria, secretory endometria and endometrial carcinomas as long as PTEN protein was not truncated. These results indicate that PTEN is a constitutive protein in the endometrium, so that the somatic mutation of PTEN exerts a crucial effect on the endometrial carcinogenesis. In addition, the presence of the PTEN pseudogene transcript urges us caution for the mutational analysis of PTEN as well as careful choice of the probe for the detection of PTEN transcript.

Adult↗

The mutation of insulin receptor substrate-1 gene in Chinese patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700-(+)4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. RESULTS: Two amino acid variations [GGG-->AGG (G971 R) and CCT-->TCT (P1079 S)] and 3 silent mutations [GAT-->GAC(D422D), CCA-->CCC(P737 P) and GCA-->GCG (A804 A)] were identified, among which the CCA-->CCC(P737 P) and CCT-->TCT(P1079S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA-->GCG(A804A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, chi 2 = 18.42, P < 0.01). The most common polymorphism in the Chinese population was GCA-->GCG (A804A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, chi 2 = 8.84, P < 0.01). The homozygotes of the variation in patients with NIDDM and control subjects were 8.8% and 1.5%, respectively (chi 2 = 2.41, P > 0.05). CONCLUSION: These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM.

Adult↗

Comparison of Botox with a Chinese type A botulinum toxin.

OBJECTIVE: To confirm and compare the therapeutic efficacies and remote effects of a Chinese type A botulinum toxin (CBTX-A, Lanzhou Biological Products Institute, China) and Botox (Allergan Inc., USA) for focal dystonia and muscle spasm. METHODS: Prospective open study was conducted over 4 years for focal dystonia and muscle spasm. We enrolled 785 patients: 192 were injected with Botox and 593 with CBTX-A. They were followed for 3 to 48 months. Meanwhile single fiber electromyography (SFEMG) was performed in a subset of 40 patients before, 2-3 weeks, 5-8 weeks and 4-5 months after injection of Botox or CBTX-A. RESULTS: There were no significant differences in clinical effects from two preparations, including the latency of response, maximal benefit and duration of improvement. The dose of the Chinese preparation which produced effects similar to Botox was higher. A significant increase in jitter was demonstrated 2-3 weeks after injection in both groups and fiber density values increased at the same time or later and remained 4-5 months after injections. CONCLUSION: Both preparation are safe and effective treatments for patients with focal dystonia and muscle spasm. They both have subclinical effects on neuromuscular transmission of remote uninjected muscles. The Chinese preparation is a little less powerful but much cheaper than Botox.

Adolescent↗

[Carcinogenesis effects of gastric and duodenal refluxate on esophageal mucosa].

OBJECTIVE: To investigate the effects of different refluxant on esophageal carcinogenesis in rats. METHODS: The animal models of gastroesophageal reflux (G), duodenoesophageal reflux (D) and duodenogastroesophageal reflux (DG) and no reflux as control (C) were made by operations. The rats in all of the groups were given carcinogen (methyl-n-amyl nitrosamine, MANA). They were killed at 4, 20, 26, 40-week, then their esophagi were taken to the morphologic study and the expression of p53, cyclinD(1), CDK(4) studied with immunohistochemical studies. RESULTS: At 4-week without carcinogen, most of rats in reflux groups displayed evidence of esophageal mucosal injury. The degree of mucosal injury in D group was greater than that in DG which was greater than that in G; and became severity with the time. At 40 weeks, the incidences of papillomas in group D, DG, G were 94.7%, 95.2%, 70.5%, respectively. All of them compared to the group C (38.5%) were significant difference. Only in both D and DG group, there were 24 with esophageal columnar metaplasia, 20 with dysplasia and 11 with cancer. The overexpression of p53, CDK(4), cyclin D(1) was seen in D and DG groups, while in G group, the overexpression of p53 and cyclin D(1) were seen only. CONCLUSION: Both of gastric juice and duodenal contents reflux can promote tumourgenesis of MANA on esophagi by changing the expression of cell cycle-related protein. The effect of duodenal contents is stronger. It may play an important role in tumourgenesis of gastroesophageal reflux disease.

Animals↗

[Color Doppler ultrasound and quantitative histologic study of angiogenesis in ovarian tumors].

OBJECTIVE: To investigate whether there is any correlation between minimum resistance index (RImin) and microvessel density (MVD) in ovarian tumors. METHODS: The intratumor artery RImin of 61 patients with ovarian tumor was measured by color doppler ultra-sound (CDU) preoperatively. MVD identified by von Willebrand factor was evaluated postoperatively. The relationship between RImin and MVD was analyzed. RESULTS: Compared with the RImin of benign ovarian tumors, the RImin in ovarian cancers was significantly lower (P < 0.001). MVD of ovarian cancer was significantly higher than that of benign tumor both at a 100 magnification (P < 0.01) and a 400 magnification (P < 0.03). There was a significant negative correlation between RImin and MVD at a 100 magnification in benign group (r = -0.67, P < 0.01), in malignant group (r = -0.91, P < 0.01), and in both of groups (r = -0.84, P < 0.01). CONCLUSION: Low RImin reflects high MVD in ovarian tumor.

Female↗