Biomedical subjects

R Zhang

Publications and source records attributed to R Zhang.

At least 217 records · Page 12Linked to original sources

PubMed1999

Production of polyhydroxyalkanoates by Pseudomonas nitroreducens.

A strain coded AS 1.2343 was isolated from oil-contaminated soil in an oil-field in North China Tianjian City and it was identified as Pseudomonas nitroreducens. The strain demonstrated some unusual ability to synthesize polyhydroxybutyrate (PHB) homopolymer from medium-chain-length (mcl) fatty acids including hexanoate and octanoate. While polyhydroxyalkanoates (PHA) consisting of mcl hydroxyalkanoate (HA) monomers such as hydroxyoctanoate (HO) and hydroxydecanoate (HD) were the major compositions when butyrate, decanoate, lauric acid and tetradecanoic acid were used as substrates for the cell growth, respectively. PHA was accumulated up to 77% of the cell dry weight when growth was conducted in lauric acid, it appeared that the HA contents in the PHA would not be much affected by the changing of the lauric acid concentration. Varying the concentration ratio of butyrate to octanoate could change the composition of PHA accumulated by the strain. Yet PHB homopolymer was always the only polyester synthesized by the strain, regardless of the octanoate concentration change. Additionally, the ratio of carbon to nitrogen (C/N) in butyrate media was found to have effects on the PHA monomer content, as C/N increased from 2 to 100, content of HB decreased from 100% to 7%. PHA polyester synthesized by cells of Pseudomonas nitroreducens AS 1.2343 was a blend polymers consisting of acetone-insoluble HB and acetone-soluble mcl HA monomers.

Caprylates↗

PubMed1999

Effects of genistein and daidzein on membrane characteristics of HCT cells.

Genistein and daidzein are two major isoflavonoids in soybeans. They have received increasing attention because of their possible role in cancer prevention. In the present investigation, the human colon tumor (HCT) cell line was used to investigate the effect of isoflavonoids on cell growth with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. We found that genistein and/or daidzein could inhibit growth in HCT cells. The 50% inhibitory concentrations of genistein and daidzein were 15 and 40 microM, respectively. Fluorescent polarization, quasielastic light scattering, and circular dichroism were used to study the influence of isoflavonoids on membrane characteristics of HCT cells, including membrane fluidity, density of cell surface charge, and membrane protein conformation. Membrane fluidity of HCT cells was obviously reduced by genistein, but not by daidzein. The effect of genistein was time and dose dependent. In addition, genistein and daidzein could reduce the density of cell surface charge and increase the order of membrane protein conformation. All these changes may represent one of the mechanisms of the effect of isoflavonoids on growth inhibition, differentiation promotion, and transfer interference in a tumor cell line.

Anticarcinogenic Agents↗

PubMed1999

Skewed distribution of protein secondary structure contents over the conformational triangle.

A conformational triangle method is presented to analyze the secondary structure contents of 1028 structurally known proteins in the non-redundant data set of the recent 25% PDB_SELECT. The secondary structure contents of each protein are mapped on to a point in the triangle. It was found that the distribution of the 1028 points is strongly skewed in the triangle and about 42% of the whole area is empty, which is called the forbidden area. The detailed border between the allowable and forbidden areas was calculated. The possible explanation of the skewed distribution is discussed. The distributions of the mapping points for enzymes and non-enzymes in this non-redundant data set are compared. It was found that a necessary rather than a sufficient condition for an enzyme molecule is that its coil content must be >/=0.223. It is hoped that the skewed distribution observed here could be used to test the secondary structure and threading predictions.

Computational Biology↗

PubMed1999

Preparations and properties of a novel grafted segmented polyurethane-bearing glucose groups.

Novel grafted polyurethane-bearing glucose groups were synthesized through a graft copolymerization of a prefabricated polyurethane containing poly(butadiene) glycol (PBD) and hydrogenated poly(butadiene) glycol (HPBD) soft segments, and 4,4'-methylenediphenyl diisocyanate (MDI) hard segment with a hydrophilic monomer glycosylethyl methacrylate (GEMA) in solution in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) as an initiator. The bulk characteristics of the grafted polyurethanes were investigated by infra-red (IR) spectroscopy and gel permeation chromatography (GPC) measurements. The glucose groups were oriented on the surface of the cast film of grafted polyurethane with different graft-on percentages as revealed by electron spectroscopy for chemical analysis (ESCA), attenuated total reflectance infra-red spectroscopy (ATR-FTIR), and water contact angle. The grafted polyurethane surfaces which showed decreased water contact angles also indicate that hydrophilic glucose groups are present at the surface. The hemocompatibilities of these polymer surfaces were evaluated by platelet-rich plasma (PRP) contacting tests. It was found that the surface of grafted polyurethane with a graft-on percentage of 23.4% showed a good hemocompatibility in terms of platelet adhesion and shape variation. It indicates that glucose groups on the surface are effective for the improvement of hydrophilicity as well as hemocompatibility.

Animals↗

PubMed1999

Effective genetic therapy of established medullary thyroid carcinomas with murine interleukin-2: dissemination and cytotoxicity studies in a rat tumor model.

Replication-defective adenovirus (AdCMVmIL2) expressing murine interleukin-2 was directly injected into rat medullary thyroid carcinomas to examine antitumor activity. AdCMVmIL2 cured 42.9% of all treated tumor bearing animals. Most cured rats were protected against tumor growth after subsequent rechallenge with wild-type tumor cells, reflecting the immunity obtained from the original treatment. Studies of viral dissemination showed that the intratumoral inoculated viruses can enter the circulation, infect peripheral tissues, and express genes driven by the CMV promoter. Liver is the main target organ. In a toxicity study, AdCMVmIL2 was administered i.v. at a dose five times higher than that given directly into tumor. No detectable side effect was found. Histological studies showed variable degrees of lymphocyte infiltration in the livers of studied animals, and no functional change indicated by the normal serum level of glutamic oxalacetic transaminase and glutamic pyruvic transaminase was found in all animals studied. These data demonstrate that AdCMVmIL2 is an effective antitumor agent in this animal model, and that virus treatment can be given without significant toxicity to other organs.

Adenoviridae↗

PubMed1999

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↗

PubMed1999

Differential signatures of bacterial and mammalian IMP dehydrogenase enzymes.

IMP dehydrogenase (IMPDH) is an essential enzyme of de novo guanine nucleotide synthesis. IMPDH inhibitors have clinical utility as antiviral, anticancer or immunosuppressive agents. The essential nature of this enzyme suggests its therapeutic applications may be extended to the development of antimicrobial agents. Bacterial IMPDH enzymes show biochemical and kinetic characteristics that are different than the mammalian IMPDH enzymes, suggesting IMPDH may be an attractive target for the development of antimicrobial agents. We suggest that the biochemical and kinetic differences between bacterial and mammalian enzymes are a consequence of the variance of specific, identifiable amino acid residues. Identification of these residues or combination of residues that impart this mammalian or bacterial enzyme signature is a prerequisite for the rational identification of agents that specifically target the bacterial enzyme. We used sequence alignments of IMPDH proteins to identify sequence signatures associated with bacterial or eukaryotic IMPDH enzymes. These selections were further refined to discern those likely to have a role in catalysis using information derived from the bacterial and mammalian IMPDH crystal structures and site-specific mutagenesis. Candidate bacterial sequence signatures identified by this process include regions involved in subunit interactions, the active site flap and the NAD binding region. Analysis of sequence alignments in these regions indicates a pattern of catalytic residues conserved in all enzymes and a secondary pattern of amino acid conservation associated with the major phylogenetic groups. Elucidation of the basis for this mammalian/bacterial IMPDH signature will provide insight into the catalytic mechanism of this enzyme and the foundation for the development of highly specific inhibitors.

Amino Acid Sequence↗

PubMed1999

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↗

PubMed1999

[Gene expression profiles in squamous esophageal cancer tissues and adjacent almost normal tissues].

OBJECTIVE: To describe an esophageal cancer-specific expression profile and to identify genes that showed altered expression in squamous esophageal cancer tissues and their adjacent almost normal tissues. METHODS: The cDNA probes were synthesized from polyA(+)RNA of cancer and adjacent almost normal tissues and were differentially hybridized with two identical Atlas human cDNA expression arrays membranes containing 588 known genes. RESULTS: Autoradiographic analysis showed that of the 588 genes analyzed, 61 were found up-regulated in cancer, including cdc25B, Notch1, MMP, MET etc, and 22 down regulated in cancer, including cytokeratin4, BAD, IL-1 RECEPTOR ANTAGONIST, IL-6, etc. Expression levels of genes that associated with the regulation of cell proliferation, apoptosis, differentiation and metastasis altered most. CONCLUSION: The results for the first time provide an esophageal cancer-specific expression profile, showing that complex alterations of gene expression underlie the development of malignant phenotype of esophageal cancer cells. In addition, this line of research can lead to the identification of EC-specific genes which may be helpful for the development of diagnostic and prognostic biomarkers or therapeutic targets. The differential hybridization technique of Atlas Human cDNA expression array can be a useful method for describing the expression profiles of a tissue of cell interested.

DNA, Complementary↗

PubMed1999

[A study on correlation of changing proportion of L:M:S due to the variation of HBV PreS genes and liver injury].

OBJECTIVE: In order to study the correlation between the changing proportion of L:M:S due to the variation of HBV PreS genes and the liver injury. METHODS: We selected three groups of HBV-infected individuals, including acute infection with complete recovery, chronic HBV carriers and chronic severe hepatitis B, each consisting of three cases. The preS genes were amplified from serum samples with half nested PCR. The PCR products were cloned into M13 vectors, and 10 clones were randomly selected for each person and sequenced with routine methods. A total of 90 clones were sequenced and analyzed by DNA homology comparison. RESULTS: We found that there were significant characteristics in HBV-infected individuals with different clinical consequences. (1)Acute hepatitis B: normal proportion of L:M:S, Slightly higher M protein was found in one patient. (2)Chronic HBV carriers: Higher proportion of L:M:S was found by which M protein synthesis decreased. (3)Chronic severe hepatitis B: HBV and deletion of large fragment of preS1 gene may induce abnormally high immunity response, and then cause severe liver injury in these patients. CONCLUSION: These results provide some experimental facts that the possible association between changing proportion of L:M:S and liver injury could be wholly explored.

Hepatitis B↗

PubMed1999

[Clinical report of six cases of vaginal sarcomas].

OBJECTIVE: To evaluate the clinical characteristics and treatment methods of primary sarcoma of the vagina. METHOD: Retrospectively analysed the clinical data of 6 patients with vaginal sarcoma including 2 leiomyosarcoma, 1 angiosarcoma, 1 lymphoma, 1 alveolar soft tissue sarcoma and 1 rhabdomyosarcoma. RESULTS: The age of the patients was 7-52 year-old. 3 of them were treated by local resection combined with chemotherapy and radiotherapy and alive over 5-year. The rest 3 died of this disease within two years and a half after diagnosis. CONCLUSION: Local resection combined with chemotherapy and radiotherapy is the main therapeutic approach for vaginal sarcoma.

Adolescent↗

PubMed1999

[Study for the factors related to postpartum depression].

OBJECTIVE: To study the prevalence rate of postpartum depression(PD) and related factors. METHODS: 1,052 pregnant women were selected in random from our antenatal clinic from January to November, 1997 for mood study by hospital anxiety and depression (HAD), and 866 cases were further follow-up till 7 days after childbirth with Edinburgh postpartum depression scale (EPDS). RESULTS: The prevalence rate of PD was 15.01% by EPDS. Using single factor and mutifactorial stepwise regression analyses for the affected factors of PD, 7 factors were most strongly related to the onset of PD: they were women's health condition; the relationship between husband and wife; the medical workers' attitude during labor; husband's desire for boy child; the number of antenatal educational classes received; anxiety and depression mood during pregnancy. The number of educational classes received was negatively correlated with PD, while the other 6 factors were all positively correlated. CONCLUSION: The main factors related to PD are the mood of anxiety and depression during pregnancy.

Adult↗

PubMed1999

[Female malignant tumors of genital organs with pericardial effusion: report of 9 cases and review of literatures].

OBJECTIVE: To study the clinical characteristics and the management of malignant tumors of genital organs with pericardial effusion. METHODS: Nine cases of gynecologic malignant tumors with pericardial effusion were analyzed retrospectively. RESULTS: Nine cases of gynecologic malignant tumors were separated into 4 cases of epithelial ovarian carcinoma, 2 cases of diffuse ovarian granulosa cell tumor, 2 cases of cervix carcinoma and 1 case of endometrial carcinoma. The mean age was 41.6 years, the intervals from primary tumors to pericardial effusions were 2-49 months. The clinical symptoms were mainly severe shortness of breath. Nine cases were diagnosed by chest X-rays, 6 of them were confirmed by B ultrasonography simultaneously. Three cases were given pericardiocentesis and their cytologic examinations were positive. Two cases of ovarian malignant tumors have been surviving for 49 and 12 months respectively after pericardiocentesis with local chemotherapy and effective systemic chemotherapy, 1 case was survived for 5 months by hormone therapy, but 6 untreated cases were died of cardiac tamponade within one month. CONCLUSIONS: Malignant tumors of genital organs with pericardial effusion could be definitely diagnosed by X-ray, B ultrasonography and cytology. The surviving period may be prolonged by pericardio centesis combined with systemic effective chemotherapy.

Adolescent↗

PubMed1999

[Expression of prolactin, TGF alpha and TGF beta 1 genes in estrogen-induced eutopic and ectopic pituitary prolactin-secreting tumors of rats].

The Sprague-Dawley (SD) rat bearing a heteroplasted pituitary underneath renal capsule was used to observe differential expression of prolactin (PRL), transforming growth factor alpha (TGF alpha) and transforming growth factor beta 1 (TGF beta 1) genes during the formation of pituitary prolactin-secreting tumor (prolactinoma) induced by 17 beta-estradiol (E2). Our results indicated that in both eutopic and ectopic pituitaries disconnected from hypothalamus formed simultaneously PRL-secreting tumors after the rats treated with E2 for 120 days in vivo, which was accompanied by overexpression of PRL gene (P < 0.05-0.01). The PRL mRNA level was higher in eutopic prolactinoma than that in ectopic prolactinoma (P < 0.05). Overexpression of TGF alpha and TGF beta 1 genes were also detected in eutopic prolactinoma. However, the expression of TGF alpha and TGF beta 1 genes in ectopic prolactinoma was similar to that in normal pituitary. It is suggested that TGF alpha and TGF beta 1 may be involved in prolactinoma tumorigenesis of eutopic pituitary. However, the mechanism mediating eutopic and ectopic prolactin-secreting tumor formation seems different.

Animals↗

PubMed1999

Aldosterone biosynthesis in extraadrenal tissues.

OBJECTIVE: To determine whether extraadrenal tissues synthesize aldosterone in addition to vascular tissue and brain. METHODS: Ex vivo kidney perfusion was performed in normal Wistar rats, ACEI pretreated and adrenalectomized rats prior to the perfusion experiment. After equilibration for 30 minutes, 120 ml of perfusate was collected and subjected to reverse-phase HPLC and then aldosterone was measured by RIA. By RT-PCR and Southern blot the expression of aldosterone synthase gene-CYP11B2 mRNA was studied in both kidney tissue and cultured renal tubular epithelial cell, lung and liver tissues. In situ hybridization was used to identify the cell types of liver and lung expressing CYP11B2 mRNA. RESULTS: Production of aldosterone in the kidney perfusate was not changed in adrenalectomized rats although it was decreased in the group pretreated with ACEI perindopril. By RT-PCR and Southern blot the expression of CYP11B2 mRNA was demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We have also identified CYP11B2 mRNA expression in liver and lung of rats. In situ hybridization showed that CYP11B2 mRNA was localized in the endoplasm of liver fat-storing cell (Ito cells) and type II alveolar cells of lung. CONCLUSIONS: These studies prove that kidney, liver and lung are able to produce aldosterone.

Aldosterone↗

PubMed1999

Medulloblastoma.

OBJECTIVE: To elucidate the diagnosis, treatment and prognosis of medulloblastoma in both children and adults. METHODS: A retrospective review was conducted in 80 patients with medulloblastoma confirmed pathologically during the period of 1984 and 1995. Multivariate analysis and comparison were made of the therapeutic effects of operation, radiotherapy and chemotherapy as well as the survival period. RESULTS: There were 42 males and 38 females with average age at diagnosis being 9.1 years in children and 25.1 years in adults. All patients were operated on to remove the tumour. Cerebral aqueduct re-opening was got through in 54 cases (67.5%), and Torkilsen's shunt was carried out at the same time for the rest patients. Seventeen patients had ventriculoperitoneal shunt, and 13 of them were performed after surgical excision of the tumour. Complete follow-up information was obtained in 61 patients (76%) for a period of 6 months to 14 years. During the follow-up, 27 patients received postoperative craniospinal irradiation, and 27 local radiation. Fourteen patients were subjected to adjuvant chemotherapy. The overall 5-year and 10-year survival rates were 50.5% and 27.89% respectively. The 5-year survival rate was higher in adults than in children (P < 0.05), whereas the 10-year survival rate was similar. Thirty-two patients died of relapse or metastasis between 6 months and 10 years after initial surgical therapy, and the mean recurrence time was 3.5 years. CONCLUSIONS: Operation and postoperative regular radiotherapy were important therapeutic modalities for medulloblastoma. Total or subtotal removal of the tumour combined with craniospinal radiotherapy can improve patients' survival rate. The survival period of medulloblastoma patients is consistent with Collins' law, that is, the period of risk for survival is the age at initial diagnosis plus 9 months. Only few patients can gain long-term survival.

Adolescent↗

PubMed1999

A comparative study on the effects of low dose of tPA and different regimens of intravenous urokinase in acute myocardial infarction.

OBJECTIVE: To compare the effects of low dose of recombinant tissue-type plasminogen activator (tPA) with those of conventional dose of urokinase (UK) and assess the influence of different regimens of intravenous UK in patients with acute myocardial infarction (AMI). METHODS: Eighty patients with AMI were randomized to 50 mg of tPA (Group I; n = 26) using an accelerating approach or 1.0-1.5 million U of UK (Group II; n = 54). UK was administered as a single bolus injection of whole dose (Group IIa; n = 26) or half dose bolus injection followed by half dose infusion (Group IIb; n = 28). All patients underwent coronary arteriography 90 min after the initiation of intravenous thrombolysis, and the infarct-related coronary artery (IRA) patency was evaluated. Cardiac events during hospitalization were recorded and predischarge left ventricular function was determined by two-dimensional echocardiography. RESULTS: The IRA patency rate was significantly higher in Group I (88.4%) than in Group II (53.7%) (P < 0.01). Group I patients had less cardiac events during hospitalization (11.5% vs 33.3%) and greater improvement in left ventricular function than Group II patients. However, these angiographic, left ventricular functional and prognostic parameters did not significantly differ between Group IIa and Group IIb. CONCLUSIONS: Thrombolysis after AMI with low dose of intravenous tPA exerts better angiographic and clinical effects than that with conventional dose of UK. The thrombolytic effects of UK were not affected by different regimens of intravenous administration of the agent.

Aged↗

PubMed1999

The surgical treatment of lung cancer: a retrospective analysis of 2004 cases.

OBJECTIVE: To summarise the clinical results of surgical treatment of 2004 cases of lung cancer over a period of 33 years and to evaluate the main influencing factors for long-term results. METHODS: 2004 patients treated at our department were included in this study. The pathological classification proposed and revised by WHO in 1982 was used. The TNM (tumour, nodes, and metastasis classification) system of staging proposed and modified by UICC (International Union Against Cancer) in 1987 was followed. Pearson's Chi-square test was used in comparing variables. RESULTS: There were 1571 men and 433 women, with a man to woman ratio of 3.6:1. The pathological findings were squamous cell carcinoma (944 cases, 47.1%), adenocarcinoma (694, 34.6%), small cell carcinoma (167, 8.3%), adenosquamous cell carcinoma (78, 3.9%), large cell carcinoma (22, 1.1%), alveolar cell carcinoma (17, 0.8%) and miscellaneous carcinoma (82, 4.1%). The p-TNM staging in 1721 resected cases was: stage 0 (2 cases, 0.1%), stage I (860, 50%), stage II (407, 23.6%), staging IIIa (396, 23.0%), stage IIIb (35, 2.0%) and stage IV (21, 1.2%). The overall resection rate was 85.9% (1721/2004) and the complication rate was 15.7% (271/1721). The 30-day mortality was 1.3% (22/1721). The 5-, 10- and 15-year survival rates were 38.8%, 31.6% and 21.8%, respectively. Factors influencing the long-term survival rate included the nature of resection, the mode of resection, presence or absence of lymph gland metastasis, tumour size and degree of extension, pathological type and p-TNM staging. CONCLUSIONS: Surgery is recommended for stage I, II and IIIa non-small cell lung cancer and for stage I and II small cell lung cancer. Meticulous preoperative staging process is important. Bronchoplastic resection is recommended to replace pneumonectomy whenever the conditions are permissible.

Adenocarcinoma↗