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Biomedical subjects

X Xi

Publications and source records attributed to X Xi.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant adenoviruses expressing TRAIL demonstrate antitumor effects on non-small cell lung cancer (NSCLC).

INTRODUCTION: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of malignant cells, but not in normal cells. This preferential toxicity to the abnormal cells renders TRAIL potentially a very powerful therapeutic weapon against cancer. However, a requirement for large quantities of TRAIL to suppress tumor growth in vivo is one of the major factors that has hindered it from being widely applied clinically. To overcome this, we constructed a replication-deficient adenovirus that carries a human full-length TRAIL gene (Ad-TRAIL) and tested its efficacy against a lung cancer model system in comparison to that of the recombinant soluble TRAIL protein. METHODS: To investigate the antitumor activity and therapeutic value of the Ad-TRAIL on the non-small cell lung cancer (NSCLC), four NSCLC cell lines, namely, YTMLC, GLC, A549, and H460 cells, were used. TRAIL protein expression was determined by Western blotting and flow cytometry. Cell viability was analyzed by proliferation assay, and DNA ladder and cell-cycle analysis were used to identify apoptosis. To further evaluate the effect of Ad-TRAIL in vivo, YTMLC cells were inoculated to the subcutis of nude mice. The Ad-TRAIL was subsequently administered into the established tumors. Tumor growth and the TRAIL toxicity were evaluated after treatment. RESULTS: YTMLC cells infected with Ad-TRAIL showed decreased cell viability and a higher percentage of apoptosis. Similar, Ad-TRAIL treatment also significantly suppressed tumor growth in vivo. CONCLUSIONS: TRAIL gene therapy provides a promising therapy for the treatment of NSCLC.

Adenoviridae↗
PubMed2001

Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase.

Activation of AMP-activated protein kinase (AMPK) has been recently demonstrated to be associated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-stimulated glucose transport mediated by both GLUT1 and GLUT4 transporters. However, signaling events upstream and downstream of AMPK are unknown. Here we report that 1) p38 mitogen-activated protein kinase (MAPK) and mitogen-activated protein kinase kinase 3 (MKK3) were activated by AICAR in Clone 9 cells, which express only the GLUT1 transporters, and 2) activation of p38 was required for AICAR-stimulated glucose transport since treatment of the cells with p38 inhibitor SB203580 or overexpression of dominant negative p38 mutant inhibited glucose transport. Moreover, we found that overexpression of the constitutively active form of AMPK mutant also resulted in a significant activation of p38, and inhibition of p38 activity by SB203580 did not affect AICAR-stimulated activation of AMPK. These findings demonstrate that AICAR-stimulated activation of p38 is indeed mediated by AMPK, and the p38 MAPK cascade is downstream of AMPK in the signaling pathway of AICAR-stimulated glucose transport in Clone 9 cells.

AMP-Activated Protein Kinases↗
PubMed2001

A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3.

We have recently shown that the platelet integrin alpha(IIb)beta(3) is activated by von Willebrand factor (vWF) binding to its platelet receptor, glycoprotein Ib-IX (GPIb-IX), via the protein kinase G (PKG) signaling pathway. Here we show that GPIb-IX-mediated activation of integrin alpha(IIb)beta(3) is inhibited by dominant negative mutants of Raf-1 and MEK1 in a reconstituted integrin activation model in Chinese hamster ovary (CHO) cells and that the integrin-dependent platelet aggregation induced by either vWF or low dose thrombin is inhibited by MEK inhibitors PD98059 and U0126. Thus, mitogen-activated protein kinase (MAPK) pathway is important in GPIb-IX-dependent activation of platelet integrin alpha(IIb)beta(3). Furthermore, vWF binding to GPIb-IX induces phosphorylation of Thr-202/Tyr-204 of extracellular signal-regulated kinase 2 (ERK2). GPIb-IX-induced ERK2 phosphorylation is inhibited by PKG inhibitors and enhanced by overexpression of recombinant PKG. PKG activators also induce ERK phosphorylation, indicating that activation of MAPK pathway is downstream from PKG. Thus, our data delineate a novel integrin activation pathway in which ligand binding to GPIb-IX activates PKG that stimulates MAPK pathway, leading to integrin activation.

Animals↗
PubMed2001

Detection of soluble urokinase receptor by immunoradiometric assay and its application in tumor patients.

It has recently been found that tumor cells express large amounts of urokinase receptor (uPAR) on their surface and that the blood soluble uPAR (suPAR) level in cancer patients is increased. However, the significance of suPAR in tumor progression is still unclear. To investigate the significance of suPAR in evaluating clinical status of solid tumor patients, an immunoradiometric assay (IRMA) based on using two monoclonal antibodies (McAbs) to different epitopes of uPAR was established to determine the serum levels of suPAR in normal individuals and solid tumor patients. The detectable range of this suPAR IRMA was 1.95-500 microg/l. The affinity constant was 4.75x10(9) l/mol. The mean rate of recovery was 101.3%, and the mean coefficients of variation for intra- and interassay were 6.40+/-2.57% (mean+/-S.D., n = 11) and 10.48+/-2.65% (n = 5), respectively. The serum suPAR levels were 2.71+/-1.12 microg/l in 62 normal individuals, 3.71+/-1.69 microg/l in 30 patients with benign tumors, and 5.82+/-2.27 microg/l in 124 patients with malignant tumors. The serum suPAR levels of these two types of tumor patients were increased in comparison with that of normal individuals (P values less than.01 and.001). The extent of their increase in malignant tumors was much greater than in benign tumors (P < .001). The serum suPAR levels of patients with malignant tumors were correlated with tumor invasion, metastasis, and surgical intervention. Our data suggest that IRMA for suPAR could be a sensitive and specific assay and that the serum suPAR level would be a valuable index for evaluating the condition and prognosis of tumor patients in clinic.

Adolescent↗
PubMed2001

Dynamic photoelastic study of the transient stress field in solids during shock wave lithotripsy.

Photoelastic and shadowgraph imaging techniques were used to visualize the propagation and evolution of stress waves, and the resultant transient stress fields in solids during shock wave lithotripsy. In parallel, theoretical analysis of the wavefront evolution inside the solids was performed using a ray-tracing method. Excellent agreement between the theoretical prediction and experimental results was observed. Both the sample size and geometry were found to have a significant influence on the wave evolution and associated stress field produced inside the solid. In particular, characteristic patterns of spalling damage (i.e., transverse and longitudinal crack formation) were observed using plaster-of-Paris cylindrical phantoms of rectangular and circular cross sections. It was found that the leading tensile pulse of the reflected longitudinal wave is responsible for the initiation of microcracks in regions inside the phantom where high tensile stresses are produced. In addition, the transmitted shear wave was found to play a critical role in facilitating the extension and propagation of the microcrack.

High-Energy Shock Waves↗
PubMed2001

[Estimation of LC50 of chemicals to rainbow trout by fragment constant method].

A fragment constant model for prediction of 96 h LC50 of chemicals to rainbow trout was developed based on measured experimental data of 258 chemicals collected from the literature. The accuracy and the robustness of the model were discussed. The coefficient of determination of the model is 0.9495 and the mean residual is 0.42 log-unit. The model is robust for both individual chemical or chemical class.

Animals↗
PubMed2000

Improvement of stone fragmentation during shock-wave lithotripsy using a combined EH/PEAA shock-wave generator-in vitro experiments.

To control the collapse of cavitation bubbles induced during shock-wave lithotripsy (SWL), a piezoelectric annular array (PEAA) shock-wave generator was fabricated and combined with an experimental electrohydraulic (EH) shock-wave lithotripter with a truncated HM-3 reflector. The PEAA generator consists of eight individual transducers of 200-kHz resonant frequency. At a discharge voltage of 15 kV, the PEAA generator produces a shock wave with a peak positive pressure of 8.2 MPa, a positive half cycle duration of 2.9 micros, and a -6-dB beam width of 5 mm. The trigger of the PEAA generator was controlled via fiberoptic link with reference to the spark discharge of the EH generator. Hence, the PEAA-generated shock wave could be used to interact with cavitation bubbles induced by the EH source at various stages of their oscillation. The duration of bubble oscillation during SWL was monitored by a 2.25-MHz focused hydrophone, and this information was used to control the release timing of the PEAA generator. Stone fragmentation tests in vitro were carried out, and demonstrated that stone comminution could be significantly enhanced when the shock wave-bubble interaction occurred during the collapsing phase of the bubbles. A maximum increment of 60% to 80% in stone fragmentation was achieved when the PEAA-generated shock wave arrives near the collapse of the bubbles. Under these conditions, much intensified collapse of the bubbles near the surface of the stone, with strong secondary shock-wave emission and increased stress concentration at the impact site of the solid boundary, was observed using high-speed shadowgraph and photoelastic imaging.

Calculi↗
PubMed2000

Lipopolysaccharide effects on neuronal activity in rat basal forebrain and hypothalamus during sleep and waking.

Peripheral administration of lipopolysaccharide (LPS) is associated with alterations in sleep and the electroencephalogram. To evaluate potential neuronal mechanisms for the somnogenic effects of LPS administration, we used unanesthetized rats to survey the firing patterns of neurons in various regions of rat basal forebrain (BF) and hypothalamus during spontaneous sleep and waking and during the epochs of sleep and waking that occurred after the intraperitoneal administration of LPS. In the brain regions studied, LPS administration was associated with altered firing rates in 39% of the neurons examined. A larger proportion of LPS-responsive units showed vigilance-related alterations in firing rates compared with nonresponsive units. Approximately equal proportions of LPS-responsive neurons showed increased and decreased firing rates after LPS administration, with some units in the lateral preoptic area of the hypothalamus showing particularly robust increases. These findings are consistent with other studies showing vigilance-related changes in neuronal activity in various regions of BF and hypothalamus and further demonstrate that peripheral LPS administration alters neuronal firing rates in these structures during both sleep and waking.

Animals↗
PubMed2000

[An experiment on disinfection using high power microwave].

This experimental disinfection was intended to examine the effect of high power microwave on bacteria, and the putative nonthermal effect. The bacteria of the experimental groups were irradiated by high power microwave in different intensities and time and were compared with the controls--bacteria heated only. The principles of disinfection by means of high power microwave were studied. The results showed that the temperature did not change after the dry bacteria were irradiated by high power microwave in different intensities and time, but the number of bacteria alive decreased significantly(P < 0.05). The high power microwave's effect of disinfection was greater in the wet bacteria group than in the dry bacteria group and the bacteria heated group. These data indicate that the disinfection effect of high power microwave is higher than that of heating. High power microwave can kill dry bacteria, and it has the nonthermal effect in addition to its thermal effect.

Disinfection↗
PubMed1999

Analysis of the roles of 14-3-3 in the platelet glycoprotein Ib-IX-mediated activation of integrin alpha(IIb)beta(3) using a reconstituted mammalian cell expression model.

We have reconstituted the platelet glycoprotein (GP) Ib-IX-mediated activation of the integrin alpha(IIb)beta(3) in a recombinant DNA expression model, and show that 14-3-3 is important in GPIb-IX signaling. CHO cells expressing alpha(IIb)beta(3) adhere poorly to vWF. Cells expressing GPIb-IX adhere to vWF in the presence of botrocetin but spread poorly. Cells coexpressing integrin alpha(IIb)beta(3) and GPIb-IX adhere and spread on vWF, which is inhibited by RGDS peptides and antibodies against alpha(IIb)beta(3). vWF binding to GPIb-IX also activates soluble fibrinogen binding to alpha(IIb)beta(3) indicating that GPIb-IX mediates a cellular signal leading to alpha(IIb)beta(3) activation. Deletion of the 14-3-3-binding site in GPIbalpha inhibited GPIb-IX-mediated fibrinogen binding to alpha(IIb)beta(3) and cell spreading on vWF. Thus, 14-3-3 binding to GPIb-IX is important in GPIb-IX signaling. Expression of a dominant negative 14-3-3 mutant inhibited cell spreading on vWF, suggesting an important role for 14-3-3. Deleting both the 14-3-3 and filamin-binding sites of GPIbalpha induced an endogenous integrin-dependent cell spreading on vWF without requiring alpha(IIb)beta(3), but inhibited vWF-induced fibrinogen binding to alpha(IIb)beta(3). Thus, while different activation mechanisms may be responsible for vWF interaction with different integrins, GPIb-IX-mediated activation of alpha(IIb)beta(3) requires 14-3-3 interaction with GPIbalpha.

14-3-3 Proteins↗
PubMed1999

Recent developments in SWL physics research.

Two projects in our laboratory highlight some recent developments in shockwave lithotripsy (SWL) physics research. In the first project, we developed a prototype of a piezoelectric annular array (PEAA) shockwave generator that can be retrofitted on a Dornier HM-3 lithotripter for active control of cavitation during SWL. The PEAA generator, operating at 15 kV, produces a peak positive pressure of approximately 8 MPa with a -6-dB beam diameter of 5 mm. The shockwave generated by the PEAA was used to control and force the collapse of cavitation bubbles induced by a laboratory electrohydraulic shockwave lithotripter with a truncated HM-3 reflector. With optimal time delay between the lithotripter pulse and the PEAA-generated shockwave, the collapse of cavitation bubbles near the stone surface could be intensified, and the resultant stone fragmentation in vitro could be significantly improved. In the second project, high-speed shadowgraph imaging was used to visualize the dynamics of lithotripter-induced bubble oscillation in a vascular phantom. Compared with the free bubble oscillation in water, the expansion of cavitation bubble(s) produced in silicone tubes and a 200-microm cellulose hollow fiber by either a Nortech EHL or a Dornier XL-1 lithotripter was found to be significantly constrained. Rupture of the cellulose hollow fiber was observed consistently after about 20 shocks from the XL-1 lithotripter at an output voltage of 20 kV. These results confirm experimentally that SWL-induced cavitation in vivo can be significantly constrained by the surrounding tissue, and large intraluminal bubble expansions could cause rupture of capillaries and small blood vessels.

Humans↗
PubMed1999

Shock wave-inertial microbubble interaction: methodology, physical characterization, and bioeffect study.

A method of generating in situ shock wave-inertial microbubble interaction by a modified electrohydraulic shock wave lithotripter is proposed and tested in vitro. An annular brass ellipsoidal reflector (thickness = 28 mm) that can be mounted on the aperture rim of a Dornier XL-1 lithotripter was designed and fabricated. This ring reflector shares the same foci with the XL-1 reflector, but is 15 mm short in major axis. Thus, a small portion of the spherical shock wave, generated by a spark discharge at the first focus (F1) of the reflector, is reflected and diffracted by the ring reflector, producing a weak shock wave approximately 8.5 microseconds in front of the lithotripter pulse. Based on the configuration of the ring reflector (different combinations of six identical segments), the peak negative pressure of the preceding weak shock wave at the second focus (F2) can be adjusted from -0.96 to -1.91 MPa, at an output voltage of 25 kV. The preceding shock wave induces inertial microbubbles, most of which expand to a maximum size of 100-200 microns, with a few expanding up to 400 microns before being collapsed in situ by the ensuing lithotripter pulse. Physical characterizations utilizing polyvinylidene difluoride (PVDF) membrane hydrophone, high-speed shadowgraph imaging, and passive cavitation detection have shown strong secondary shock wave emission immediately following the propagating lithotripter shock front, and microjet formation along the wave propagation direction. Using the modified reflector, injury to mouse lymphoid cells is significantly increased at high exposure (up to 50% with shock number > 100). With optimal pulse combination, the maximum efficiency of shock wave-induced membrane permeabilization can be enhanced substantially (up to 91%), achieved at a low exposure of 50 shocks. These results suggest that shock wave-inertial microbubble interaction may be used selectively to either enhance the efficiency of shock wave-mediated macromolecule delivery at low exposure or tissue destruction at high exposure.

Acoustics↗
PubMed1999

Morbidity and mortality attributable to alcohol, tobacco, and illicit drug use in Canada.

OBJECTIVES: This study estimated morbidity and mortality attributable to substance abuse in Canada. METHODS: Pooled estimates of relative risk were used to calculate etiologic fractions by age, gender, and province for 91 causes of disease or death attributable to alcohol, tobacco, or illicit drugs. RESULTS: There were 33,498 deaths and 208,095 hospitalizations attributed to tobacco, 6701 deaths and 86,076 hospitalizations due to alcohol, and 732 deaths and 7095 hospitalizations due to illicit drugs in 1992. CONCLUSIONS: Substance abuse exacts a considerable toll on Canadian society in terms of morbidity and mortality, accounting for 21% of deaths, 23% of years of potential life lost, and 8% of hospitalizations.

Adult↗
PubMed1999

Studies on biosensor to determine diacetyl.

We studied the purification of diacetyl reductase, the preparation of a biosensor, and its performance. With diacetyl reductase and reduced coenzyme I (NADH) co-immobilized as working membrane, NAD+/NADH produced in the course of diacetyl reduction was connected with Fe2+/Fe to build a biosensor. The biosensor could be used to determine diacetyl concentration within the range from 0.1 microgram/mL to 0.5 microgram/mL and the response time was less than two minutes, and its performance was stable within 9 days. The experiments showed that typical metal ions and organics in nominal concentration did not affect the performance of the biosensor, meanwhile, the interference of dissolved oxygen on the performance of biosensor and regeneration of coenzyme I (NADH) were solved to some extent.

Acetoin Dehydrogenase↗
PubMed1999

[Influence of drug compatibility on extractive retes of chlorogenic acid and isochlorogenic acid in simiaoyonglan tang decoction].

OBJECTIVE: To study the influence of drug compatibility on the extractive rates of chlorogenic acid and isochlorogenic acid in Simiaoyonglan Tang (SMYAT) decoction. METHOD: The contents of chlorogenic acid and isochlorogenic acid in SMYAT decoction, Flos Lonicerae and Flos Lonicerae in combination with other single drugs were determined by TLC-UV spectrophotometry respectively. The data from this experiment were treated statistically. RESULTS: The contents of chlorogenic acid in other five prescriptions of different compatibilities decreased markedly in comparison with those in Flos Loniceraés decoction (P < 0.01). The content of isochlorogenic acid in SMYAT decoction as a whole was about the same as thar in Flos Loniceraés decoction, but decreased significantly in other prescriptions of different compatibilities (P < 0.01). CONCLUSION: Drug compatibility is one of the main causes for changes of chlorogenic acid and isochlorogenic acid contents in SMYAT decoction.

Angelica sinensis↗