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Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 721 records · Page 40Linked to original sources
PubMed2000

c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid.

The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by UV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.

Dose-Response Relationship, Radiation↗
PubMed2000

Preliminary clinical results of window partial laryngectomy: a combined endoscopic and open technique.

Endoscopic laser resection for anterior commissure glottic carcinoma is difficult, because of inadequate exposure and close proximity to the underlying cartilage. A technique combining endoscopic carbon dioxide laser incision and an external approach creating a window in the thyroid cartilage was initially tested in a canine study and then performed in 5 patients. All patients were men, with T1 or T2 glottic or supraglottic cancer involving the anterior commissure, and had failed radiation treatment. The true or false vocal fold tumors were excised along with the paraglottic space and adjacent cartilage, with preservation of the remaining thyroid framework. The reconstruction was accomplished with placement of a sternohyoid muscle flap, by use of either a bipedicled muscle flap with overlying skin or a unipedicled muscle flap with a graft of free mucosa. The graft was secured in place with fibrin glue and laser soldering. Follow-up ranged from 11 months to 4 years and included biopsies. All patients had voice recordings before and after surgery. A tracheostomy was avoided in all patients. The hospital stays were 4 to 13 days. The voice quality was good after surgery. One patient died of unrelated causes 18 months after his surgery without evidence of recurrence. The other patients are still alive with no evidence of disease. The only complication was subcutaneous neck emphysema in 1 patient that spontaneously resolved. The results showed a satisfactory anatomic reconstruction and acceptable functions. We believe that this new combined technique is oncologically sound, may overcome the limited access seen with the endoscopic technique and the excessive cartilage resection seen with external partial laryngectomy, avoids a tracheostomy, and shortens hospital stays.

Aged↗
PubMed2000

Characterization of the murine pituitary tumor transforming gene (PTTG) and its promoter.

We recently isolated rat pituitary tumor transforming gene (PTTG) complementary DNA and showed its potent in vitro and in vivo transforming activity. We now characterize the mouse PTTG gene and its promoter. The entire gene is composed of five exons and four introns and spans about 7 kb. Northern analysis showed that PTTG was expressed in several tumor cell lines examined, but not in all normal tissues, implying a correlation between PTTG and tumorigenesis. Using rapid amplification of 5'-cDNA ends, the transcription start site was localized at -303 nucleotides upstream to the ATG codon in both F9 and AtT20 cells. An approximately 4.3-kb upstream region demonstrated promoter activity in AtT20 cells as well as other cell lines tested, and in vivo, the cloned promoter driving an enhanced green fluorescent protein transgene exhibited transcriptional activation in testis and embryo. Serial deletions showed that -313 bp of the 5'-flanking region was critical for promoter activity. Three elements contribute to promoter activity. Both element A (-313/-293) and element C (-180/-160), in an electrophoretic mobility shift assay using NIH-3T3 nuclear extract, formed three specific complexes, which were competed by a known Sp1 oligo; one complex was supershifted by Sp1 antibody, and the other two complexes were both supershifted by an Sp3 antibody. Two mutants disrupting element A resulted in up to 70% loss of promoter activity and abrogated formation of specific DNA-protein binding complexes, implying a more important role for element A. Element B (-249/-229) shows more than 80% homology to a consensus c-myb element, but formed two specific complexes that differed from that of c-myb in the electrophoretic mobility shift assay. Thus, the integrity and possible cooperation among these elements contribute to the basal promoter activity of the mouse PTTG oncogene homolog.

3T3 Cells↗
PubMed2000

Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging.

The pituitary transforming gene, PTTG, is abundantly expressed in endocrine neoplasms. PTTG has recently been recognized as a mammalian securin based on its biochemical homology to Pds1p. PTTG expression and intracellular localization were therefore studied during the cell cycle in human placental JEG-3 cells. PTTG mRNA and protein expressions were low at the G1/S border, gradually increased during S phase, and peaked at G2/M, but PTTG levels were attenuated as cells entered G1. In interphase cells, wild-type PTTG, an epitope-tagged PTTG, and a PTTG-EGFP conjugate all localized to both the nucleus and cytoplasm, but in mitotic cells, PTTG was not observed in the chromosome region. PTTG-EGFP colocalized with mitotic spindles in early mitosis and was degraded in anaphase. Intracellular fates of PTTG-EGFP and a conjugate of EGFP and a mutant inactivated PTTG devoid of an SH3-binding domain were observed by real-time visualization of the EGFP conjugates in live cells. The same cells were continuously observed as they progressed from G1/S border to S, G2/M, and G1. Most cells (67%) expressing PTTG-EGFP died by apoptosis, and few cells (4%) expressing PTTG-EGFP divided, whereas those expressing mutant PTTG-EGFP divided. PTTG-EGFP, as well as the mutant PTTG-EGFP, disappeared after cells divided. The results show that PTTG expression and localization are cell cycle-dependent and demonstrate that PTTG regulates endocrine tumor cell division and survival.

Amino Acid Sequence↗
PubMed2000

Agricultural work-related injuries among farmers in Hubei, People's Republic of China.

OBJECTIVES: This population-based study evaluated patterns of and risk factors for, agricultural injuries among farmers in the People's Republic of China. METHODS: A multistage sample of 1500 Chinese farmers was selected from 14 villages. Face-to-face interviews with 1358 farmers were conducted between July 1997 and September 1997 (response rate = 91%). Agricultural work-related injuries that occurred in the previous 24 months and the associated factors were evaluated. RESULTS: A total of 33% of the farmers reported at least 1 work-related injury in the 24 months before the survey. Major external causes of the injuries were hand tools (50%), falls (26%), and heavy falling objects (10%). The statistically significant risk factors for injury were low family income, 1 to 6 school years of education, self-reported pesticide exposure, tension in relationships with neighbors, and stress in life. The most notable result was the relation between self-reported pesticide exposure and injury, with farmers with greater pesticide exposure at significantly greater risk for injury. CONCLUSIONS: The results of this study indicated that injuries occurring among Chinese farmers may have unique patterns and potential risk factors.

Accidents, Occupational↗
PubMed2000

UV-induced expression of GADD45 is mediated by an oxidant sensitive pathway in cultured human keratinocytes and in human skin in vivo.

The expression of GADD45 was examined in cultured skin keratinocytes and in human skin in vivo following UV irradiation. Northern blot analysis revealed that UV-induced the expression of GADD45 (alpha, beta, gamma) in a time- and dose-dependent manner. Messenger RNA of GADD45 (alpha, beta, gamma) increased within 30 min, peaked at 4 h and remained elevated for at least 8 h following UV irradiation in vitro and in vivo. Maximal induction of GADD45alpha was approximately 5-fold compared to the level in sham-irradiated controls. Similarly H2O2 and IL-1 also induced GADD45alpha expression in cultured human keratinocytes. The kinetics of induction of GADD45alpha by H2O2, IL-1beta and UV were very similar. Interestingly, UV-induced GADD45alpha expression was inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, and antioxidant, N-acetyl-L-cysteine (NAC), indicating the involvement of reactive oxygen species in UV signaling. Previously we have shown that EGF receptor activation by UV is prerequisite for subsequent activation of NADPH oxidase and generation of reactive oxygen species. We therefore examined the effect of EGF receptor inhibitor on UV-induced GADD45alpha expression. Our results showed that PD168393, a potent EGF receptor inhibitor, blocked UV-induced GADD45alpha expression. Collectively, our data suggest that UV-induced GADD45alpha expression occur via an EGF receptor-mediated oxidative pathway sensitive to antioxidant regulation.

Acetylcysteine↗
PubMed2000

Long-term survey of outcome in acute promyelocytic leukemia.

OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event-free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post-remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL.

Adolescent↗
PubMed2000

Novel structure having antagonist actions at both the glycine site of the N-methyl-D-aspartate receptor and neuronal voltage-sensitive sodium channels: biochemical, electrophysiological, and behavioral characterization.

A novel series of N-substituted 4-ureido-5,7-dichloro-quinolines were synthesized to contain pharmacophores directed at voltage-sensitive sodium channels (VSNaCs) and N-methyl-D-aspartate (NMDA) receptors. These compounds were shown to act in a use-dependent manner as antagonists of VSNaCs and to act as selective competitive antagonists at the strychnine-insensitive glycine recognition site of NMDA receptors. These agents had little or no effect on alpha-adrenergic receptors, other glutamate receptors, or sites other than the glycine site on the NMDA receptor, and did not block voltage-sensitive calcium channels in vitro. In vivo, the compounds were active in preventing or reducing the signs and symptoms of neurohyperexcitability and had anxiolytic properties. Unlike benzodiazepines, N-substituted 4-ureido-5, 7-dichloro-quinolines showed little interaction with the sedative effects of ethanol, but were effective in controlling ethanol withdrawal seizures. The combined actions of these compounds on VSNaCs and NMDA receptors also impart properties to these compounds that are important for preventing and reducing excitotoxic neurodegeneration, but these compounds lack the undesirable side effects of other agents used for these purposes.

Animals↗
PubMed2000

Inhibition of the mitogen activated protein kinase pathway potentiates radiation-induced cell killing via cell cycle arrest at the G2/M transition and independently of increased signaling by the JNK/c-Jun pathway.

The ability of low dose ionizing radiation (2 Gy) to modulate the activities of the mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK1) cascades in human monocytic leukemia (U937/pREP4) cells and in cells over-expressing dominant negative c-Jun (TAM67) (U937/TAM67) was investigated. Radiation exposure caused prolonged ( approximately 1 h) MAPK activations in U937 cells. In contrast, low dose irradiation weakly modulated JNK1 activity in these cells. Inhibition of the MAPK pathway by use of the specific MEK1/2 inhibitor (10 microM PD98059) in both U937/pREP4 and U937/TAM67 cells prior to radiation exposure permitted strong prolonged radiation-induced activations of JNK1. Expression of TAM67 decreased the ability of radiation to cause apoptosis compared to control transfected cells. However, combined MEK1/2 inhibition and radiation exposure in both cell types caused a large decrease in suspension culture growth and a large increase in apoptosis, when compared to either treatment alone. Reduced proliferation after combined irradiation and PD98059 treatment in both cell types correlated with prolonged cell cycle arrest in G2/M phase. Prolonged growth arrest was abolished when MEK1/2 inhibitor was removed 6 h following irradiation, which was associated with a reduction in apoptosis. The ability of MEK1/2 inhibition to cause prolonged G2/M growth arrest was reduced in U937 cells stably transfected with a p21Cip-1/WAF1 antisense construct (U937/p21AS). This data correlated with an enhancement of radiation-induced apoptosis and a reduced ability of MEK1/2 inhibition to potentiate apoptosis. Collectively our data demonstrate that inhibition of MEK1/2 function increases the radiation sensitivity of U937 cells, independently of c-Jun function, and decreases the ability of these cells to recover from the radiation-induced G2/M cell cycle checkpoint arrest. In addition, our data also demonstrate that the ability of MEK1/2 inhibition to potentiate radiation-induced cell death in U937 cells in part requires an ability of cells to express low levels of p21Cip-1/WAF1.

Apoptosis↗
PubMed2000

Bucillamine suppresses human Th1 cell development by a hydrogen peroxide-independent mechanism.

OBJECTIVE: To clarify the effect of bucillamine, an antirheumatic drug related to D-penicillamine, on the development of human Th1 and Th2 cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) or purified CD4+ T cells were subjected to the priming culture in which cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies for 3 days and expanded for 4 days in the presence of interleukin-2. Cytokine production by the generated cells was determined on a flow cytometer using intracellular cytokine staining. The effects of bucillamine were determined by adding it for the first 3 days of the priming culture. RESULTS: Bucillamine decreased the frequency of interferon-gamma (IFN-gamma) producing CD4+ T cells among generated CD4+ T cells after the priming culture of PBMC, although D-penicillamine did not. This effect of bucillamine was independent of hydrogen peroxide since it was not reversed by a catalase treatment. One of the bucillamine metabolites, SA981, which exerts its effects by a hydrogen peroxide-independent mechanism, decreased the frequency of IFN-gamma producing CD4+ T cells more potently than bucillamine. Bucillamine reduced the frequency of Th1 cells after the priming culture of purified CD4+CD45RO- T cells, indicating that bucillamine exerts the effect in the absence of monocytes or B cells. CONCLUSION: Bucillamine directly acts on CD4+CD45RO- T cells to suppress Th1 cell development by a hydrogen peroxide-independent mechanism. This previously unknown action may explain the in vivo effect of bucillamine in the treatment of rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

[Short-term memory performance of German and Chinese probands with verbal and figural items: on the function of the phonological loop and visual-spatial sketchpad].

In a computer-controlled experiment using n = 48 German and n = 48 Chinese subjects we established the memory span for simple geometrical figures and their names in the subjects' respective native language. Half of the subjects replied verbally, the other half nonverbally via a touch screen. In addition, verbal reproduction times were measured. Significant differences in memory span between the two language groups were found only under nonverbal report conditions: here, the Chinese subjects achieved better results than their German contemporaries. There were no differences in oral reproduction times between the two groups. The results are discussed within the framework of Baddeley's working memory model.

Adolescent↗
PubMed2000

Experimental diabetes-induced regression of the rat prostate is associated with an increased expression of transforming growth factor-beta.

PURPOSE: Transforming growth factor-beta (TGF-beta), a potent inhibitor of cell growth, plays an important role in the androgen-dependent processes of the prostate through a complex network of growth factors. TGF-beta expression in the prostate is under negative regulatory control of androgen. As experimental diabetes causes a regression of the prostate and decrease in serum testosterone levels in rats, we examined TGF-beta alterations at the mRNA and protein levels in the diabetic rat prostate. MATERIALS AND METHODS: The expression of TGF-beta1 and TGF-beta2 and their respective mRNAs in prostates from streptozotocin (STZ)-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using relative multiplex RT-PCR, semi-quantitative Western blotting, and immunohistochemistry. RESULTS: Induction of diabetes caused a significant reduction in prostatic weight and in serum testosterone levels in rats. Both mRNA and protein levels of TGF-beta1, and mRNA level of TGF-beta2 were up-regulated in the diabetic rat prostate. Insulin-treatment normalized changes observed in prostatic weight and serum testosterone levels, and reversed the alterations in the TGF-beta1 and TGF-beta2 expression at the gene transcript and protein levels to control levels. Immunohistochemical studies demonstrated that TGF-beta1 is localized to prostatic stromal cells, whereas TGF-beta2 is located in both epithelial and stromal cells. CONCLUSION: These results suggest that TGF-beta1 and TGF-beta2 may be involved in the diabetes-induced regression of the prostate gland.

Animals↗
PubMed2000

A trial of ademetionine in the treatment of intrahepatic biliary stasis viral hepatitis.

OBJECTIVE: To observe the efficacy and safety of ademetionine in the treatment of viral hepatitis with intrahepatic biliary stasis. METHODS: In this series, 110 patients with viral hepatitis associated intrahepatic biliary stasis were randomly divided into Groups A and B. Patients in Group A received ademetionine for four weeks. Patients in Group B received potassium magnesium aspartate for four weeks. RESULTS: In Group A, at the end of treatment, the effective rate for skin pruritus in patients with cholestatic hepatitis was 86.67% (13/15), and the effective rate for skin pruritus and anorexia were 88.24% (15/17) and 82.35% (14/17), respectively in patients with chronic hepatitis combining intrahepatic cholestasis, which were significantly higher than that in Group B (P<0.05). STB, SCB, TBA, ALT and AST were lower in Group A than Group B (P<0.05). The decrease of ALP and the increase of albumin after treatment were more significant in Group A than in Group B (P<0.05). CONCLUSION: Ademetionine has better efficacy than potassium magnesium aspartate in the treatment of patients with cholestatic viral hepatitis.

Adolescent↗
PubMed2000

Selecting anti-HBsAg fab phage antibodies from the phage antibody library.

OBJECTIVE: Selecting Fab phage antibodies to HBsAg from the phage antibody library. METHODS: The phages displaying antibody fragments were subjected to three rounds of panning with HBsAg coated in solid phase. RESULTS: The eluted phages were enriched nearly 80-fold, and the percentage of recombinant clones increased from 17% to 100% after the third round of panning. The HBsAg specific monoclonal antibodies were determined by ELISA. These antibodies combined specifically with HBsAg, but not with BSA and HAV antigens. CONCLUSION: Our work on constructing human immunoglobulin combinatorial library and selecting anti-HBsAg Fab phage antibodies would be beneficial to the further study on the production of soluble Fab antibodies.

Bacteriophages↗
PubMed2000

[Induction of apoptosis in human hepatocellular carcinoma cells by adenoviral-mediated transfer of human multigenes].

OBJECTIVE: To investigate the apoptosis induced by adenovirus-mediated transduction of human genes (p53, B(7-1), GM-GSF, IL-2) in liver cancer cells and the effects of tumorigenicity in nude mice. METHODS: Using light microscopy and electron microscopy and TUNEL assay, apoptosis in Ad-multigenes-transduced liver cancer cell lines was detected. The tumorigenicity of HepG(2) cells transduced with Ad-multigenes was detected. RESULTS: Ad-multigenes could induce apoptosis, and elevated sensitivity of human liver cancer cells to chemotherapy drugs. After cells with transduced Ad-multigenes were treated with 10mg/L cisplatin for 24 h, apoptosis was seen in nearly 30% of them. The tumorigenicity of Ad-multigenes-transduced was reduced. CONCLUSION: Apoptosis induced by adenovirus-mediated multigenes acts synergetically with cisplatin in promotion of inducing apoptosis in liver cancer cell lines.

Adenoviridae↗
PubMed2000

Tetraethylammonium-evoked oscillatory contractions of rat tail artery: a K-K model.

Spontaneously rhythmic contraction of peripheral blood vessels actively modulates the peripheral circulation and blood pressure. However, the underlying mechanisms for the complex rhythmic contraction patterns of various vascular tissues are not yet fully understood. In the present study, the tetraethylammonium (TEA)-induced spontaneously oscillatory contractions of isolated rat tail artery tissues were examined. It was found that TEA evoked arterial oscillatory contractions in a concentration-dependent, but endothelium-independent manner. The voltage-dependent K+ (Kv) channel specific blocker, 4-aminopyridine (4-AP), induced a sustained, but not oscillated, vascular contraction. The presence of 4-AP had no effect on the TEA-induced oscillatory contractions. The blockade of KCa channels with charybdotoxin or apamin did not affect the basal force of vascular tissues. Neither the TEA-induced oscillatory contraction was affected by these blockers. The opening of KATP channels by levcromakalim or their blockade by glybenclamide ceased or increased, respectively, the oscillation of TEA-induced contractions. The absence of Ca2+ or the presence of nifedipine in the bath solution completely abolished the effects of TEA. The inhibition of Ca2+-ATPase in the sarcoplasmic reticulum with micromolar concentrations of thapsigargin or cyclopiazonic acid either abolished or enhanced, respectively, the TEA-induced oscillatory contractions. Ryanodine did not affect the TEA-induced oscillatory contraction. In conclusion, the TEA-induced oscillatory contraction may be initiated by the blockade of the TEA-sensitive delayed rectifier K+ channels and maintained by the TEA-insensitive but ATP-sensitive K+ channels. This K-K model presents a novel mechanism for the depolarization-induced rhythmic contractions of small arteries.

Animals↗