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Biomedical subjects

W Zhou

Publications and source records attributed to W Zhou.

At least 181 records · Page 10Linked to original sources

Ubiquitous induction of p53 in tumor cells by antisense inhibition of MDM2 expression.

BACKGROUND: The MDM2 oncogene functions as a negative feedback regulator of the p53 tumor suppressor. Abnormal expression of MDM2 in tumors may attenuate the p53-mediated growth arrest and apoptosis response, resulting in increased cell proliferation and resistance to chemotherapy. MATERIALS AND METHODS: We have developed phosphorothioate antisense oligodeoxynucleotides optimized for inhibition of MDM2 expression and investigated the role of MDM2 in a large panel of tumor cell lines. RESULTS: Inhibition of MDM2 expression in 15 tumor types containing wild-type p53 results in a significant induction of nuclear p53 accumulation. The increase in p53 level is due to prolonged half-life and is associated with an increase in p53 transcriptional activity, growth inhibition, or apoptosis. Inhibition of MDM2 expression is also sufficient to induce nuclear p53 accumulation in several cell lines with cytoplasmic p53. CONCLUSIONS: The MDM2 negative feedback loop is important for maintenance of p53 at a low level by promoting p53 degradation. Nuclear export and degradation by MDM2 may contribute to the p53 nuclear exclusion phenotype. Inhibition of MDM2 expression can effectively activate p53 in most tumor types, including those without MDM2 overexpression, and may have broad anti-tumor potential.

Apoptosis↗

[Concentration of heavy elements and their compounds in the cells from BALF and pulmonary tumors in radiation-exposed subjects].

AIM: Measurement of heavy elements in alveolar macrophages (AM) of bronchoalveolar lavage (BAL) and pulmonary tumor tissue (PTT); investigation of spacial distribution of the heavy particles in the tissues. MATERIALS AND METHODS: Laser mass-spectrometry estimated quantitative and qualitative characteristics of heavy elements (Mn, Fe, Co, Cu, Zr, etc.) in diagnostic and therapeutic BAL of 6 patients exposed to radiation after the Chernobyl accident and in pulmonary tumor tissue of patients operated for central small-cell and peripheral bronchoalveolar cancer who also had been exposed to radiation after the Chernobyl. RESULTS: Heavy elements concentration in the secondary BAL was less than in the primary one. This shows effectiveness of the procedures aimed at removal of heavy particles from the respiratory organs. Heavy elements content was quite different in two histologically different tumors. CONCLUSION: Laser mass-spectrometry proved its usefulness in simultaneous study of the quantity and quality of heavy elements in AM of BAL and tumors in radiation-exposed subjects, in investigation of the elements distribution in the pulmonary tissues and changes of elements composition in the tissues in the course of tumors development.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Apoptosis in MT2 cells induced by HepG2.2.15 cells].

OBJECTIVE: To obtain the apoptosis in MT2 cells induced by HepG2.2.15 cells expressing Fas Ligand. METHODS: A human T-lymphotropic virus type I infected cell line MT2 was cultured overnight, then 0.5 ml serum contained hepatitis B virus DNA(HBV DNA), E antigen and S antigen was added to it together with 1 ml of fresh RPMI 1640 medium and incubated for 20-24 hours at 37 degrees C. The cells were washed three times with RPMI 1640 medium without serum, followed by continued incubation. The cells were harvested and Fas antigen were determined by immunohistochemistry. The cells expressed Fas antigen was added to HepG2.2.15 cells expressing Fas Ligand together with fresh RPMI 1640 medium and incubated for 48-72 hours at 37 degrees C. The apoptosis in MT2 cells was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). RESULTS: The Fas antigen was observed in MT2 cells harvested at 8-12 days post-infected, and the strong signals of apoptosis was observed in MT2 cells incubated together with HepG2.2.15 cells for 48-72 hours. CONCLUSION: MT2, a human T cell line infected with hepatitis B virus is able to express Fas antigen. The apoptosis in MT2 cells induced by HepG2.2.15 indicated that the T-lymphocyte in the quality of effective cell and the hepatocyte in the quality of target cell could be reversed in the pathogenesis of viral hepatitis.

Apoptosis↗

MDM2 oncogene as a target for cancer therapy: An antisense approach.

The MDM2 oncogene is amplified or overexpressed in human cancers. It has also been suggested that MDM2 levels are associated with poor prognosis of several human cancers. The MDM2 oncoprotein binds to the p53 tumor suppressor protein and serves as a negative regulator of p53. The p53 tumor suppressor also has an important role in cancer therapy, with p53-mediated apoptosis being a major mechanism of action for many clinically used cancer chemotherapeutic agents and radiation therapy. Therefore, the negative regulation of p53 by MDM2 may limit the magnitude of p53 activation by DNA damaging agents, thereby limiting their therapeutic effectiveness. The investigators hypothesize that, by inhibiting MDM2 expression, the MDM2 oncoprotein level will be reduced and the MDM2 negative feedback inhibition of p53 will be diminished, resulting in a significant increase of functional p53 levels that will modulate p53-mediated therapeutic effects. The overall objective of the present study was to investigate the functions of MDM2 oncogene in tumor growth and the potential value of MDM2 as a drug target for cancer therapy. The role of MDM2 in tumor growth is determined by inhibiting MDM2 expression in in vivo models of human cancers. The in vivo synergistically therapeutic effects of MDM2 inhibition and DNA damaging agents were also evaluated. Significant in vitro antitumor activities were found in cell lines, human osteosarcoma SJSA and choriocarcinoma JAR, in a time-, concentration-, and sequence-dependent manner. Following i.p. administration of anti-MDM2 antisense oligonucleotides, in vivo antitumor activity was observed in nude mice bearing SJSA and JAR xenografts in a dose-dependent manner. Moreover, in vivo synergistically therapeutic effects of MDM2 inhibition and DNA damaging agents adriamycin and 10-hydroxycamptothecin were observed. This study should provide the basis for future development of anti-MDM2 antisense oligonucleotides as cancer therapeutic agents used alone or in combination with conventional chemotherapeutics.

Animals↗

[Relationships of angiotensinogen gene M235T variant with diabetic nephropathy in Chinese type 2 diabetes mellitus].

OBJECTIVE: To investigate whether angiotensinogen(AGT) gene M235T variant is associated with type 2 diabetes mellitus without nephropathy (DM) and/or diabetic nephropathy (DN) in Chinese type 2 diabetes. METHODS: AGT genotypes of 84 cases with DM, 96 with DN and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism analysis of the region of the variant. RESULTS: Increased frequencies of T allele (0.82) and TT genotype (0.70) were observed in 96 subjects with DN, compared with those observed in 98 control subjects (0.63 and 0. 43 respectively, P = 0.003, P = 0.0004). The odds ratio associated with TT genotype was 3.47 (95% CI 1.51-7.94, P = 0.0033) for DN in analysis adjusted for several DN risk factors. There was no difference in allele distribution between 84 DM patients and the controls. CONCLUSION: TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

Adult↗

Comparison of the mutagenicity of exhaust emissions from motor vehicles using leaded and unleaded gasoline as fuel.

While unleaded gasoline has the advantage of eliminating lead from automobile exhaust, its potential to reduce the exhaust gas and particles, merits further examination. In the present studies, the concentrations of hydrocarbons (HC) and carbon mono-oxides (CO) in emissions were analyzed on Santana engine Dynamometer under a standard test cycle, and total exhaust particles were collected from engines using leaded and unleaded gasoline. It was found that unleaded gasoline reduced the emissions of CO and HC, and decreased the quantity of vehicle exhaust particulate matters by 60%. With the unleaded gasoline, only 23 kinds of organic substances, adsorbed in the particles, were identified by gas chromatography/mass spectrometer (GC/MS) while 32 components were detected using the leaded gasoline. The results of in vitro Salmonella/microsomal test and micronucleus induction assay in CHL cells indicated that both types of gasoline increased the number of histidine-independent colonies and the frequencies of micronucleus induction; no significant difference was found in their mutagenicity.

Carbon Monoxide↗

[Markov process method in analyzing longitudinal quality of life data].

OBJECTIVE: To present a method to analyze longitudinal quality of life data and discuss some relevant questions. METHOD: Based on the theories of Markov process, the Markov method was presented and used to analyze the change of quality of life status for 212 cases being detoxificated drug addicts and their influence factors. RESULTS: The intensity coefficients of status transient for 1-->2 and 2-->3 for occupation were 0.7912 and 0.6797 respectively; the coefficients for status 1-->2 for the detoxification time was 0.5663 and that for 2-->3 for the detoxification method was 0.2765. CONCLUSIONS: The Markov method is good to analyze longitudinal quality of life data for it can analyze both the transient probabilities between any two status of quality of life and their influence factors. The results showed that the occupation of drug addicts, the detoxification time and method can affect the change of quality of life.

Humans↗

Clinical study on manipulative treatment of derangement of the atlantoaxial joint.

The derangement of the atlantoaxial joint is one of main cervical sources of dizziness and headache, which were based on the observation on the anatomy of the upper cervical vertebrae, analysis of X-ray film of the atlantoaxial joint, and the manipulative treatment in 35 patients with cervical spondylosis. The clinical diagnosis of derangement consists of: dizziness, headache, prominence and tenderness on one side of the affected vertebra, deviation of the dens for 1 mm-4 mm on the open-mouth X-ray film, abnormal movement of the atlantoaxial joint on head-rotated open-mouth X-ray film. An accurate and delicate adjustment is the most effective treatment.

Adult↗

[Effects of thermal injuries on electron transport chains of rat myocardial mitochondria].

OBJECTIVE: The electron transport chain alterations of myocardial mitochondria and cardiac dysfunction were studied after severe burn injury. METHODS: Contraction properties of male Sprague-Dawley rat cardiac muscle were investigated at 2, 4, 6 hours after 30% TBSA full-thickness thermal injury. Meanwhile, changes in electron transport chains of myocardial mitochondria were measured. Mitochondria were obtained by differential centrifugation. Succinate-respiratory chains and NADH-respiratory chains were assayed polarographically and spectrophotometrically in isolated myocardial mitochondria respectively. RESULTS: The results showed that thermal injury led to decrease in the activities of two respiratory chains. At 2 h postburn, the activities of NADH-cytochrome C reductase and cytochrome oxidase declined significantly as compared with that of the sham-operated group, and at 4 h postburn, all activities of succinate-Co. Q reductase, succinate-cytochrome C reductase, NADH-Co. Q reductase were much lower than those of the sham-operated group. Along with the electron transport chain alterations of myocardial mitochondria, there were decrease in myocardial contractile function in burned rats. CONCLUSION: These results imply that weakness of myocardial contractile function resulting in the decrease in cardiac output may be associated with the impairment of utilization of oxygen in myocardial mitochondria following burn injury.

Animals↗

[Changes and significance of natural killer cell, IL-2, IL-6 and TNF alpha of heroin addicts after detoxification].

In order to find out the activity of NKC and production of IL-2 in the peripheral blood mononuclear cells and the level of IL-6 and TNF alpha in the peripheral blood serum, we investigated 51 herion addicts who were in the course of detoxification. MTT colorimetric assay and ELISA assay methods were adopted. The results showed that, in the herion addicts, NK activity was 30.11 +/- 5.2%, IL-2 activity was 8.06 +/- 1.66 IU/ml, IL-6 level was 61.17 +/- 12.07 pg/ml, and TNF alpha level was 91.83 +/- 19.19 pg/ml, whereas in the healthy controls, the results were 44.89 +/- 4.75%, 15.91 +/- 3.83 IU/ml, 22.18 +/- 9.31 pg/ml and 30.55 +/- 11.94 pg/ml respectively. When the herion addicts were subjected to detoxication, their NKC and IL-2 activities, IL-6 and TNF alpha levels gradually restored to normal, and were correlated with the time of their detoxification (NKC: r = 0.626, P < 0.001; IL-2: r = 0.684, P < 0.001; IL-6: r = -0.791, P < 0.001; TNF alpha: r = -0.703, P < 0.001).

Adult↗

Gene polymorphisms of the renin-angiotensin system in essential hypertension.

OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) gene, angiotensinogen (AGT) gene and angiotensin II receptor 1 (AT1R) gene are implicated in Chinese essential hypertension (EH). METHODS: The case-control and haplotype-based haplotype relative risk (HHRR) study consisted of 169 essential hypertensive subjects (HT), 152 normotensive controls (NT) and 62 families. The polymorphisms of insertion/deletion (I/D) allele of ACE gene and the microsatellite allele of AT1R gene were determined in DNA extracted from peripheral blood leukocytes by polymerase chain reaction (PCR). The variants of AGT gene were screened by PCR-single strand conformation polymorphism (PCR-SSCP) analysis and further identified by cloning and sequencing. RESULTS: The significant association between EH and D allele of ACE gene was found (P < 0.05). The difference of the microsatellite allele distribution of AT1R gene between HT and NT groups was statistically significant (P < 0.005). By contrast, the distribution of A-20C genotype of AGT gene was almost identical in HT and NT groups. No significant linkage disequilibrium was observed between A-20C and M235T in AGT gene. CONCLUSIONS: D allele of ACE gene might correlate with a predisposing factor for EH. The microsatellite allele of AT1R gene might be linkage disequilibrium with an unidentified variant that contributes to the development of EH. A-20C of AGT gene is not a major genetic determinant of EH.

Adult↗

[The combined use of scopolamine, naltrexone and naloxone as a rapid, safe and effective detoxification treatment for heroin addicts].

OBJECTIVE: To evaluate the efficacy of a rapid detoxification schedule for heroin addicts by scopolamine combined with opiate receptor antagonists. METHODS: The life signs such as temperature, blood pressure, ECG, heart rate, respiratory rate and blood oxygen saturation were monitored during the process of rapid detoxification treatment. The naloxone challenge test, withdrawal symptoms scale and naltrexone maintenance were used to evaluate the efficacy of the rapid detoxification. RESULTS: The withdrawal symptoms of 84 heroin addicts induced by naltrexone and naloxone were controlled completely under scopolamine administration in the 6-8 hours treatment period, although the naloxone challenge test was able to induce slight and transient withdrawal symptoms in the second day, and all patients were transferred rapidly to naltrexone maintenance. During treatment, the temperature in 19 cases elevated, and all patients showed increased heart rate, blood pressure and respiratory rate. However, the blood oxygen saturation was still stable after oral-administration of naltrexone and continuous injection of naloxone during the detoxification. Blood test in gastric fluid was positive in 3 cases during the detoxification. The follow-up data showed that the average maintenance time of naltrexone was 2.6 months, and the percentage of drug free was 21% in 6 months after the detoxification in 84 cases. CONCLUSION: The combined use of scopolamine, naltrexone and naloxone is a rapid, safe and effective detoxification treatment protocol for heroin addicts.

Adult↗

Relationship between angiotensinogen gene M235T variant with diabetic nephropathy in Chinese NIDDM.

OBJECTIVE: To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non-insulin-dependent diabetes mellitus without nephropathy (DN-), and diabetic nephropathy (DN+) in Chinese non-insulin-dependent diabetes mellitus (NIDDM). METHODS: The subjects in DN+ group, DN- group and control group were well matched with sex, age and duration of disease, and the two case groups were divided into two subgroups as with and without hypertension respectively. The M235T polymorphism of AGT gene of 84 cases with DN-, 96 patients with DN+ and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis of the region of the variant, i.e. M235T polymorphism. RESULTS: The increased frequencies of T allele (0.82) and TT genotype (0.70) were observed in 96 subjects with DN+ as compared with 98 control subjects (0.63 and 0.43, respectively, P = 0.003, P = 0.0004). The odds ratio associated with TT genotype was 3.47 (95% CI: 1.51-7.94; P = 0.0033) for diabetic nephropathy in analysis adjusted for several risk factors of diabetic nephropathy, such as body-mass index, systolic and diastolic blood pressure, serum cholesterol, low density lipoprotein and high density lipoprotein. Subgroup analysis of the 67 patients in DN+ group with hypertension revealed similar distributions of M235T genotypes and alleles to those in the DN+ without hypertension subgroup. There was no difference in allele and genotype distribution between 84 DN- patients and the controls. Similarly, frequencies of the AGT M235T genotype and allele were not different between two DN- subgroups. CONCLUSIONS: AGT gene M235T polymorphism is associated with diabetic nephropathy in NIDDM. TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese NIDDM patients.

Adult↗

[Clinical observation of the effect of shuxinsu capsule in treating angina pectoris].

OBJECTIVE: To observe the therapeutic effect of Shuxinsu capsule (SXSC) in treating angina pectoris patients. METHODS: One hundred and fifty angina pectoris patients were divided into two groups. Group A (80 cases), randomly divided into two subgroups, SXSC treated and Yixin oral liquid (YXOL) control group, each group consisted of 40 cases. Group B (70 cases) was an openly treated group (OTG). RESULTS: 17 cases were markedly effective in the SXSC treated group in relieving the symptoms, effective were 16, the total effective rate was 82.50%, while in the control group, the markedly effective cases, the effective cases and the total effective rate were 13, 16 and 72.50% respectively; there was significant difference between these two groups (u = 1.99, P < 0.05). In the treated group (SXSC and OTG) of 110 cases, the markedly effective, effective cases on ECG were 34 and 30 respectively. The total effective rate was 58.18%, higher than that of the control group, which was 55.00%, but the difference was insignificant. The activity of SOD in RBC and the amount of plasma LPO were significantly different after treatment in the SXSC group. Both of the medications had effect to reduce serum total cholesterol (TC) and triglyceride (TG), the TC was lower and high density lipoprotein-cholesterol (HDL-C) higher significantly after treatment in the SXSC group. CONCLUSION: SXSC has significant effect on angina pectoris.

Aged↗

[Clinical study on effect of xianlong capsule on senile vascular dementia].

OBJECTIVE: To assess the efficacy of Xianlong Capsule (XLC) in treating the senile vascular dementia (VD). METHODS: Forty-six cases of VD were randomly divided into two groups. The XLC group (24 patients) were treated with XLC and the control group (22 patients) were treated with Hydergine. Mini-mental state examination (MMSE), Hamilton depression scale (HDS) marks and clinical symptoms were observed in different groups. RESULTS: XLC could markedly increase MMSE and HDS marks of VD patients. XLC had the effect of improving balance and gait ability of VD patients. CONCLUSION: XLC had certain effect on VD and its effect was better than that of Hydergine.

Aged↗

[Clinical features and diagnosis of cerebral venous thrombosis].

OBJECTIVE: To investigate the clinical features and imaging diagnosis of cerebral venous thrombosis. METHODS: 65 cases of cerebral venous thrombosis (CVT) were proved by angiography (n = 34) or MR (n = 44), 30 by both procedures and 6 by pathology as well. Their age ranged from 13 to 59 years (mean age 32.5), 31 were male and 34 were female. RESULTS: The clinical manifestations were variable, but most patients had symptoms and signs of intracranial hypertension (91%)such as headache and papilledema. Nearly half of the patients had focal neurological dysfunction (49%) such as weakness of limbs and seizures and half of the patients had intracranial hypertension (51%) only. The occluded dural sinus and the clot could be visualised directly by means of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). CONCLUSION: MRI and MRA are becoming the imaging investigation of choice for the diagnosis of CVT, Anticoagulation, thrombolysis and dextran may be effective measures in the treatment of cerebral venous thrombosis.

Adolescent↗

[Reconstruction of posterior cruciate ligament using bone-patellar tendon-bone autograft].

OBJECTIVE: To introduce the surgical procedures of posterior cruciate ligament (PCL) reconstruction using bone-patellar tendon-bone autograft and to evaluate the clinical effect of treatment of posterior instability. METHODS: Twenty cases of chronic instability of knee secondary to rupture of PCL underwent reconstruction of PCL using free autograft of bone-patellar tendon-bone by isometric tibial and femoral attachment through anterior approach of knee. Larson knee function score, patient subjective evaluation and physical testing were used to evaluate the effect of this procedure. RESULTS: In this series, the average point of Larson score was 62 preoperatively. By the period of 6 - 58 month follow-up, the average point was 92. Subjectively 18 cases showed satisfactory results. Lachmann test showed negative results in all cases. The range of motion was 115 degrees on the average. CONCLUSIONS: This method can provide a strong and stable PCL replacement. But the surgical procedure is more difficult than ACL reconstruction. Some factors for a successful operation include evaluation of instability, preparation of graft material, internal fixation of graft, isometric attachment, reconstruction of other structures of knee, and bearing tension of graft.

Adolescent↗