Biomedical subjects

Yanping Zhang

Publications and source records attributed to Yanping Zhang.

At least 55 records · Page 3Linked to original sources

PubMed2004

The ARF-B23 connection: implications for growth control and cancer treatment.

The tumor suppressor ARF induces a p53-dependent and -independent cell cycle arrest. Unlike nucleoplasmic localized MDM2 and p53, ARF localizes in the nucleolus. The role of ARF in the nucleolus and the molecular target and mechanism of ARF's p53-independent function remain both controversial and a fertile field of research. Recent study has identified the nucleolar protein B23 as a target of ARF for implementing its growth inhibitory function. The ability of ARF to block cell cycle progression through the MDM2-p53 pathway and to suppress ribosomal biogenesis through B23 suggest a role for ARF in coordinating inhibitions of growth and proliferation.

Animals↗

PubMed2004

Evidence of endothelial dysfunction in preeclampsia: decreased endothelial nitric oxide synthase expression is associated with increased cell permeability in endothelial cells from preeclampsia.

OBJECTIVE: The purposes of this study were to examine endothelial nitric oxide synthase expression in endothelial cells and to determine whether the inhibition of endothelial nitric oxide synthase could impair endothelial barrier function in preeclampsia. STUDY DESIGN: Messenger RNA and protein expression for endothelial nitric oxide synthase were examined in endothelial cells that were isolated from normal and preeclamptic pregnancies. Endothelial monolayer permeable response to interleukin-8 stimulation was determined. Normal endothelial cells that were treated with nitric oxide inhibitor were used to test the association of endothelial nitric oxide synthase and endothelial barrier function. Messenger RNA expression for endothelial nitric oxide synthase was determined by reverse transcription-polymerase chain reaction, and protein expression was determined by Western blot analysis. Endothelial permeability was measured by horseradish peroxidase leakage through endothelial cell filters. Interleukin-8 production was measured by enzyme-linked immunosorbent assay. Data were presented as mean+/-SE and analyzed by analysis of variance or nonparametric Mann-Whitney test. RESULTS: Relative messenger RNA expression and protein expression for endothelial nitric oxide synthase were decreased significantly in endothelial cells from preeclampsia compared with cells from normal pregnancies (messenger RNA expression, 0.191+/-0.057 vs 0.508+/-0.061 [P <.01]; protein expression, 0.225+/-0.08 vs 0.786+/-0.098 [P<.01], respectively). Horseradish peroxidase leakage in normal endothelial cells was 0.30+/-0.26 micromol/L (interleukin-8, 1 pg/mL), 3.14+/-2.45 micromol/L (interleukin-8, 5 pg/ml), and 9.08+/-2.69 micromol/L (interleukin-8, 25 pg/mL; P<.01; compared with 0.77+/-0.47 micromol/L [control endothelial cells]). Horseradish peroxidase leakage in preeclamptic endothelial cells was 6.20+/-2.19 micromol/L, 8.44+/-85 micromol/L, and 15.79+/-2.06 micromol/L (P<.05) compared with 5.23+/-1.28 micromol/L, respectively. The ratio of horseradish peroxidase leakage was >7-fold increase in normal endothelial cells, but only a 4-fold increase in preeclamptic endothelial cells in response to interleukin-8 stimulation at 25 pg/mL. The inhibition of endothelial nitric oxide synthase with N(G)-Monomethyl-L-arginine resulted in an increase in interleukin-8-induced endothelial cell permeability. No difference for interleukin-8 production was observed between normal and preeclamptic endothelial cells (1.15+/-0.21 ng/mg protein vs 1.29+/-0.23 ng/mg protein, P>.5). CONCLUSION: Increased endothelial permeability may be associated with decreased endothelial nitric oxide synthase expression and activity in endothelial cells from preeclampsia.

Case-Control Studies↗

PubMed2004

High glucose levels down-regulate glucose transporter expression that correlates with increased oxidative stress in placental trophoblast cells in vitro.

OBJECTIVE: To study glucose transporter expression and oxidative stress in placental trophoblasts under hyperglycemic conditions in vitro. METHODS: Trophoblasts were isolated from term normal human placentas and incubated with Dulbecco's modified eagle medium containing 1000, 2500, and 4500 mg/L glucose for 3 days. At the end of incubation, culture medium was collected. Trophoblast RNA was extracted and mRNA expression of glucose transporters was determined by RNase protection assay. Messenger RNA expression for copper-zinc-superoxide dismutase (CuZn-SOD) was determined by real-time polymerase chain reaction. Lipid peroxide production was determined by measuring malondialdehyde concentration in the culture supernatant. Protein expression of sodium-glucose transporter 2 (SGLT-2) was determined by Western blot analysis. RESULTS: Messenger RNA expression for glucose transporter 1 (GLUT1) and SGLT-2 were reduced in trophoblast cells incubated with 4500 mg/L glucose compared with those incubated with 1000 and 2000 mg/L glucose. mRNA expression of CuZn-SOD was also decreased in trophoblasts incubated with 4500 mg/L glucose. Malondialdehyde production was significantly increased by trophoblasts incubated with 4500 mg/L glucose compared with those by trophoblasts incubated with 1000 and 2000 mg/L glucose (4.69 +/- 0.60 versus 2.10 +/- 0.29 and 2.89 +/- 0.47 nmol/mg protein; P < .01, respectively). CONCLUSIONS: Down-regulation of gene expression of glucose transporters correlates with increased lipid peroxide production and decreased superoxide dismutase expression in placental trophoblasts cultured under hyperglycemic conditions.

Cells, Cultured↗

PubMed2004

Heme oxygenase-1 mediates up-regulation of adhesion molecule expression induced by peroxynitrite in endothelial cells.

OBJECTIVE: Endothelial cell (EC) activation with up-regulation of cellular adhesion molecule (CAM) expression is a pathophysiologic feature in preeclampsia (PE). Enhanced peroxynitrite formation in the vasculature of women with PE was also reported. This study was to test whether EC oxidative stress induced by peroxynitrite could up-regulate EC CAM expression, and whether heme oxygenase-1 (HO-1) has protective effects on this peroxynitrite-induced cellular response. METHODS: Confluent ECs were stimulated with 3-morpholinosydnonimine-HCl (SIN-1, a peroxynitrite generator) alone or combined with Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP, a peroxynitrite scavenger) up to 4 hours. EC surface protein expressions for ICAM, VCAM, P-selectin, and E-selectin were measured by colorimetric assay. ECs were also treated with Sn(IV) mesophorphyrin IX dichloride (SnMP, a HO-1 inhibitor) to determine if HO-1 was involved in the increased CAM expression in stressed cells. Protein and mRNA expressions for HO-1 were determined by Western blot analysis and reverse-transcriptase polymerase chain reaction (RT-PCR). Data are presented as the mean +/- SE and analyzed by analysis of variance (ANOVA). RESULTS: Endothelial CAM expressions for VCAM, P-selectin, and E-selectin, but not ICAM, were significantly increased in SIN-1-treated ECs. Protein and mRNA expressions for HO-1 were also up-regulated in cells treated with SIN-1. MnTMPyP blocked both mRNA and protein expressions for HO-1, whereas SnMP only blocked HO-1 protein expression. Both MnTMPyP and SnMP abolished SIN-1-induced up-regulation of VCAM, P-selectin, and E-selectin expression in ECs. CONCLUSIONS: Peroxynitrite-induced EC oxidative stress produces differential effects on CAM expression, which may be mediated by HO-1 regulation. Our results suggest that increased peroxynitrite formation in the maternal vasculature may contribute to the increased CAM expression and enhanced neutrophil-endothelial interaction associated with PE.

Cell Adhesion Molecules↗

PubMed2004

Targeting prostate cancer with conditionally replicative adenovirus using PSMA enhancer.

Prostate cancer is the second most commonly diagnosed cancer in men and accounts for significant mortality and morbidity in the United States. Initially androgen-dependent, prostate cancer ultimately becomes androgen-independent, which makes the disease extremely difficult to cure. In this study, we examined the use of conditionally replication-competent adenovirus for the treatment of hormone-independent prostate cancer. We utilized PSME, an enhancer element for prostate-specific PSMA expression, to control viral E1A protein expression and achieve exclusive virus replication in prostate. Western blotting confirmed that PSME mediated high E1A protein expression in PSMA-positive, androgen-independent prostate cancer cells (C4-2 and CWR22rv), but was much less active in PSMA-negative cancer cells (PC-3 and A549). Consistent with E1A protein expression, the recombinant adenovirus Ad5-PSME-E1a replicated in C4-2 and CWR22rv almost as efficiently as wild type with low levels of androgen, but its replication was significantly attenuated in PSMA-negative cells. In the in vitro killing assay, Ad5-PSME-E1a lysed all C4-2 and CWR22rv cells 5 days after infection, with minimal effect on PSMA-negative cells. In addition, injections of 1.7 x 10(8) plaque-forming units in a CWR22rv xenograft model in nude mice induced significant tumor growth delay, with a substantial necrotic area. These studies suggest that PSME-driven replication-competent adenovirus may be a new therapeutic modality for prostate cancer patients after hormone ablation therapy.

Adenoviridae↗

PubMed2004

Inhibition of HDM2 and activation of p53 by ribosomal protein L23.

The importance of coordinating cell growth with proliferation has been recognized for a long time. The molecular basis of this relationship, however, is poorly understood. Here we show that the ribosomal protein L23 interacts with HDM2. The interaction involves the central acidic domain of HDM2 and an N-terminal domain of L23. L23 and L11, another HDM2-interacting ribosomal protein, can simultaneously yet distinctly interact with HDM2 together to form a ternary complex. We show that, when overexpressed, L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest. On the other hand, knocking down L23 causes nucleolar stress and triggers translocation of B23 from the nucleolus to the nucleoplasm, leading to stabilization and activation of p53. Our data suggest that cells may maintain a steady-state level of L23 during normal growth; alternating the levels of L23 in response to changing growth conditions could impinge on the HDM2-p53 pathway by interrupting the integrity of the nucleolus.

Cell Cycle↗

PubMed2004

Placental trophoblast-derived factors diminish endothelial barrier function.

Although increased vascular permeability is an important event in the pathogenesis of preeclampsia, the origin of the circulating factor(s) that elicits this endothelial barrier dysfunction is not known. In this study, we use coculture of endothelial cells and placental trophoblast cells to determine whether placental trophoblasts are a potential source of the factor(s) that mediate the increased vascular permeability of preeclampsia. Human umbilical vein endothelial cells grown in Transwell inserts or on coverslips were cocultured with trophoblast cells isolated from normal and preeclamptic placentas or placenta conditioned media. Endothelial cell barrier function was determined by: 1). measurements of electrical resistance and leakage of horseradish peroxidase, and 2). immunofluorescent staining of vascular endothelial-cadherin, pan-cadherin, and occludin. Uterine myometrium endothelial cells were also studied for comparison. We observed the following: 1). electrical resistance was significantly (P < 0.01) decreased (compared with control endothelial cells) in endothelial cell monolayers cocultured with normal trophoblast cells and further reduced in endothelial cells cocultured with preeclamptic trophoblast cells; 2). an increased horseradish peroxidase leakage that was correlated with the decreased electrical resistance in cocultured cells; and 3). disorganized tight junction proteins and an altered distribution of vascular endothelial-cadherin and occludin in monolayers of endothelial cells cocultured with preeclamptic trophoblast cells. Similar responses were noted in uterine myometrium endothelial cells. We conclude that: 1). placental trophoblast cells produce factors that diminish the barrier function of endothelial cells; 2). endothelial tight junctions are more susceptible to factors released from preeclamptic trophoblast cells than from normal trophoblast cells; and 3). these results implicate trophoblast-derived factors in the increased vascular permeability associated with preeclampsia.

Adherens Junctions↗

PubMed2003

Nitric oxide induces phosphorylation of p53 and impairs nuclear export.

The tumor suppressor p53 accumulates under diverse stress conditions and affects cell cycle progression and/or apoptosis. This has been exemplified for endogenously produced or exogenously supplied nitric oxide (NO) and thus accounts at least in part for pathophysiological signaling of that bioactive molecule, although detailed mechanisms remain to be elucidated. By using luciferase reporter assays, we show that NO stabilized a transcriptionally active p53 protein. Considering that p53 is targeted by murine double minute (Mdm2) for ubiquitination and subsequent proteasomal degradation and knowing that this interaction is impaired by, for example, UV-treatment with concomitant stabilization of p53 we questioned the p53/Mdm2 interaction in the presence of NO. Although p53 became phosphorylated at serine 15 under the impact of NO, coimmunoprecipitation with Mdm2 and ubiquitination remained intact, thus excluding any interference of NO with this pathway. The importance of N-terminal p53 phosphorylation was verified with p53 mutants where the first six serine residues have been converted to alanine, and which do not accumulate in response to NO. Regulation of p53 stability can be also achieved by affecting nuclear-cytoplasmic shuttling and it was presented that leptomycin B, an inhibitor of nuclear export, caused p53 accumulation. Cell fractionation and immunofluorescence staining following NO-treatment revealed predominant nuclear accumulation of p53 in close association with serine 15-phosphorylation, which suggests impaired nuclear-cytoplasmic shuttling. This was verified by heterokaryon analysis. We conclude that attenuated nuclear export contributes to stabilization and activation of p53 under the influence of NO.

Animals↗

PubMed2003

Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation.

The tumor suppressor ARF induces a p53-dependent and -independent cell cycle arrest. Unlike the nucleoplasmic MDM2 and p53, ARF localizes in the nucleolus. The role of ARF in the nucleolus, the molecular target, and the mechanism of its p53-independent function remains unclear. Here we show that ARF interacts with B23, a multifunctional nucleolar protein involved in ribosome biogenesis, and promotes its polyubiquitination and degradation. Overexpression of B23 induces a cell cycle arrest in normal fibroblasts, whereas in cells lacking p53 it promotes S phase entry. Conversely, knocking down B23 inhibits the processing of preribosomal RNA and induces cell death. Further, oncogenic Ras induces B23 only in ARF null cells, but not in cells that retain wild-type ARF. Together, our results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23, and suggest a nucleolar role of ARF in surveillance of oncogenic insults.

Cell Division↗

PubMed2003

Clinical observations of mycophenolate mofetil therapy in refractory primary nephrotic syndrome.

Mycophenolate mofetil (MMF) is an effective immunosuppressive agent in renal transplantation, and preliminary studies suggest that it may also be effective in the treatment of lupus nephritis. This study investigated the efficacy and safety of MMF therapy in patients with refractory primary nephrotic syndrome in a prospective multicentre clinical observation. Nineteen refractory nephrotic patients with minimal change disease or mesangial proliferative glomerulonephritis were enrolled in this study. Combined MMF and prednisone therapy was used for 6 months with an initial MMF dose of 1.0-2.0 g/day and a prednisone dose of 20-60 mg/day; both drugs were tapered gradually. It was found that all patients achieved clinical remission and 11 of 19 responded within 4 weeks, and 12 of 19 patients entered complete clinical remission. The prednisone dose in those patients who were previously steroid dependent could be successfully tapered. During follow up, three patients experienced transient increasing of proteinuria associated with infections and recovered without an adjustment of therapy. One patient was withdrawn from the study because of a fall in haemoglobin levels; other adverse effects did not necessitate withdrawal. Follow-up renal biopsies in two patients found no alteration in renal pathology. Mycophenolate mofetil is an effective and well-tolerated immunosuppressive agent for patients with refractory nephrotic syndrome.

Adolescent↗

PubMed2003

Increased endothelial monolayer permeability is induced by serum from women with preeclampsia but not by serum from women with normal pregnancy or that are not pregnant.

OBJECTIVE: To determine if endothelial monolayer permeability could be altered by serum from preeclampsia (PE). METHODS: Confluent normal endothelial cells (ECs) were incubated with 20% serum from nonpregnant females, normal and PE pregnancies or combined with antioxidant superoxide dismutase (SOD) for 8 hr. Confluent PE ECs were incubated with 20% serum from normal pregnancies. EC barrier function of monolayer permeability was accessed by measuring EC electrical resistance (ER) and the leakage of horseradish peroxidase (HRP) passing through EC filters. Plasma concentrations of IL-8 and lipid peroxides by MDA were also measured. We determined 1) if serum from PE could affect EC permeable function; 2) if antioxidant and serum from normal pregnancies could preserve PE EC barrier function; 3) if lipid peroxides and cytokine IL-8 were increased in PE blood samples. Data are presented as mean+/-SE. ANOVA was used for statistical analysis. A p level less than 0.05 was considered statistically different. RESULTS: 1) ER was significantly decreased and HRP passage was significantly increased in ECs incubated with serum from PE compared to serum from non-pregnant and normal pregnant females (ER: 36.30+/-2.60 vs. 51.30+/-4.00 and 53.90+/-5.80 Omega x cm2, p<0.01; HRP: 0.100+/-0.020 vs. 0.014+/-0.002 and 0.022+/-0.007 DeltaOD470 nm, p<0.01, respectively). 2) ER was improved in PE ECs incubated with serum from normal pregnancies compared to controls, 52.28+/-3.13 vs. 34.50+/-3.80 Omega x cm2, p<0.01. 3) SOD attenuated decreased EC ER induced by PE serum, 55.58+/-3.61 Omega x cm2 (SOD+PE serum) vs. 42.34+/-3.24 (control) and 35.46+/-2.44 (PE serum), p<0.01, respectively. 4) Both MDA and IL-8 concentrations were higher in plasma or serum samples from PE than those in samples from nonpregnancies and normal pregnancies, MDA: 28.65+/-1.45 vs. 22.40+/-1.47 and 25.53+/-0.89 micromol/mL, p<0.01; IL-8: 5.35+/-1.08 vs. 1.69+/-0.47 and 2.28+/-0.73 pg/mL, p<0.05, respectively. Conclusions. 1) Sera from PE but not from nonpregnant women or normal pregnancies increase EC monolayer permeability. 2) Increased lipid peroxides and IL-8 are candidates altering EC barrier function. 3) Antioxidant SOD preserves increased EC monolayer permeability induced by PE serum, suggesting that EC oxidative stress may be associated with altered EC barrier function in preeclampsia.

Adult↗

PubMed2003

Nucleocytoplasmic shuttling of p53 is essential for MDM2-mediated cytoplasmic degradation but not ubiquitination.

As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear localization signal (NLS) located at its C-terminal domain and two nuclear export signals (NES) located in its N- and C-terminal regions, respectively. The role of nucleocytoplasmic shuttling in p53 ubiquitination and degradation has been a subject of debate. Here we show that the two basic amino acid groups in the p53 bipartite NLS function collaboratively to import p53. Mutations disrupting individual amino acids in the NLS, although causing accumulation of p53 in the cytoplasm to various degrees, reduce but do not eliminate the NLS activity, and these mutants remain sensitive to MDM2 degradation. However, disrupting both parts of the bipartite NLS completely blocks p53 from entering the nucleus and causes p53 to become resistant to MDM2-mediated degradation. Similarly, mutations disrupting four conserved hydrophobic amino acids in the p53 C-terminal NES block p53 export and prohibit it from MDM2 degradation. We also show that colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation. Our data provide new insight into the mechanism and regulation of p53 nucleocytoplasmic shuttling and degradation.

Active Transport, Cell Nucleus↗

PubMed2003

Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway.

The gene encoding p53 mediates a major tumor suppression pathway that is frequently altered in human cancers. p53 function is kept at a low level during normal cell growth and is activated in response to various cellular stresses. The MDM2 oncoprotein plays a key role in negatively regulating p53 activity by either direct repression of p53 transactivation activity in the nucleus or promotion of p53 degradation in the cytoplasm. DNA damage and oncogenic insults, the two best-characterized p53-dependent checkpoint pathways, both activate p53 through inhibition of MDM2. Here we report that the human homologue of MDM2, HDM2, binds to ribosomal protein L11. L11 binds a central region in HDM2 that is distinct from the ARF binding site. We show that the functional consequence of L11-HDM2 association, like that with ARF, results in the prevention of HDM2-mediated p53 ubiquitination and degradation, subsequently restoring p53-mediated transactivation, accumulating p21 protein levels, and inducing a p53-dependent cell cycle arrest by canceling the inhibitory function of HDM2. Interference with ribosomal biogenesis by a low concentration of actinomycin D is associated with an increased L11-HDM2 interaction and subsequent p53 stabilization. We suggest that L11 functions as a negative regulator of HDM2 and that there might exist in vivo an L11-HDM2-p53 pathway for monitoring ribosomal integrity.

Amino Acid Sequence↗

PubMed2003

Antioxidant superoxide dismutase attenuates increased endothelial permeability induced by platelet-activating factor.

To study the protective effects of the antioxidant superoxide dismutase (SOD) against platelet-activating factor (PAF)-induced endothelial permeability. Endothelial cells (ECs) were isolated from human umbilical veins from normal pregnancies. The first passage (P1) ECs were grown in polycarbonate transwell filters. Confluent ECs were incubated with PAF at concentrations of 2, 5, and 10 microgram/mL for 2 hours or pretreated with superoxide dismutase. Endothelial monolayer permeability was then measured by EC electrical resistance or by the leakage of horseradish peroxide (HRP) passing through filters. Endothelial junctional protein distribution and expression of VE-cadherin and occludin were determined by fluorescent staining of endothelial monolayer and by Western blot analysis. mRNA expressions for VE-cadherin and occludin were determined by reverse transcriptase-polymerase chain reaction. Data are expressed as Omega. cm(2) for electrical resistance and DeltaOD 470 nm for HRP assay and presented as mean +/- standard error of the mean. Analysis of variance was used for statistical analysis. A P value less than.05 was considered statistically significant. Endothelial cell electrical resistance was decreased and HRP leakage was increased in ECs treated with PAF. Intercellular gaps were formed at cell contact regions in ECs treated with PAF, as evaluated by staining of junctional protein VE-cadherin and occludin. The functional changes of the EC barrier and the formation of intercellular gaps induced by PAF were concentration dependent, which could be partially attenuated by pretreatment of ECs with SOD. Total cellular junctional protein expression and mRNA expression of VE-cadherin and occludin were not affected by PAF. Increased EC monolayer permeability induced by platelet-activating factor is associated with disorganization of EC junctional protein distribution of VE-cadherin and occludin. Superoxide dismutase partially attenuated the PAF-induced increased endothelial monolayer permeability, which suggests that oxidative stress might be involved in the process of PAF-induced disturbances of endothelial barrier function.

Antigens, CD↗

PubMed2003

[Adenoid cystic carcinoma of the maxillary sinuses].

OBJECTIVE: To investigate characteristic clinical features and outcomes for patients with adenoid cystic carcinoma of the maxillary sinuses (ACC). METHOD: Thirteen patients with ACC were treated with a combination of surgery and radiation. Prognostic factors were retrospectively analyzed. RESULT: The most frequent cause of failure was local recurrence at the primary site. There was no neck node failure, 1 patient experienced distant metastases after the treatment. The overall disease-free survival rate at 5 years and 10 years were 72.5% and 54.4%, respectively. CONCLUSION: The symptoms of the ACC occurred in the maxillary sinuses are not specific. The early diagnoses are usually difficult. Surgeries combined with postoperative radiation are recommended for optimal local control and survival. The prognostic factors include the clinic stages of the tumor and the resection margins.

Adult↗

PubMed2002

Risk factors for suicide in China: a national case-control psychological autopsy study.

BACKGROUND: Suicide is the fifth most important cause of death in China, but the reasons for the high rate and unique pattern of characteristics of those who kill themselves are unknown. METHODS: We pretested, and then administered a comprehensive interview to family members and close associates of 519 people who committed suicide and of 536 people who died from other injuries (controls) randomly selected from 23 geographically representative sites in China. FINDINGS: After adjustment for sex, age, location of residence, and research site, eight significant predictors of suicide remained in the final unconditional logistic regression model. In order of importance they were: high depression symptom score, previous suicide attempt, acute stress at time of death, low quality of life, high chronic stress, severe interpersonal conflict in the 2 days before death, a blood relative with previous suicidal behaviour, and a friend or associate with previous suicidal behaviour. Suicide risk increased substantially with exposure to multiple risk factors: none of the 265 deceased people who were exposed to one or fewer of the eight risk factors died by suicide, but 30% (90/299) with two or three risk factors, 85% (320/377) with four or five risk factors, and 96% (109/114) with six or more risk factors died by suicide. INTERPRETATION: Despite substantial differences between characteristics of people who commit suicide in China and the west, risk factors for suicide do not differ greatly. Suicide prevention programmes that concentrate on a single risk factor are unlikely to reduce suicide rates substantially; preventive efforts should focus on individuals exposed to multiple risk factors.

Adolescent↗

PubMed2002

Expression of creatine kinase isoenzyme genes during postnatal development of rat brain cerebellum: evidence for transcriptional regulation.

Transcription and accumulation of brain-type creatine kinase (CKB) mRNA and its protein was examined during postnatal development of rat brain cerebellum, the brain region containing highest CKB mRNA in the adult. CKB protein was extremely low at day 1, increased about 10-fold until week 4 and remained constant until week 10. This time course was paralleled by cerebellar CKB mRNA, which was also extremely low at day 1 and increased 5-fold during the first 3 weeks and then remained constant. High levels of CKB protein were also detected in cultured primary cerebellar granular neurons. Nuclear run-on assays directly showed that CKB mRNA accumulation during postnatal cerebellar development was due to increased transcription. When compared with cerebrum and whole brain, cerebellar CKB mRNA accumulation during postnatal development was temporally delayed. Analysis of myocyte enhancer factor (MEF)-2 and Sp1, factors known to initiate or sustain CKB transcription in tissues other than brain, revealed that MEF-2 in cerebellum was low at week 1 but increased 3.5-fold by week 7, while Sp1 remained unchanged. The increase in CKB protein during cerebellar postnatal development was coincident with that of the ubiquitous mitochondrial CK protein and mRNA, indicating that a functional phosphocreatine energy shuttle probably exists for efficient ATP regeneration in the cerebellum. This should be beneficial for the many energy-demanding requirements during cerebellar development, as indicated by the observed temporal co-expression of CKB with myelin basic protein, which is involved in axon myelination by oligodendrocytes.

Animals↗

PubMed2002

Effect of Vitreoscilla hemoglobin biosynthesis in Escherichia coli on production of poly(beta-hydroxybutyrate) and fermentative parameters.

In order to attain high cell density and low cost production of poly(beta-hydroxybutyrate) (PHB), the Vitreoscilla globin gene (vgb) was introduced into a novel recombinant strain, Escherichia coli VG1 (pTU14). Experiments showed that the expression of vgb was under the regulation of dissolved oxygen (DO) in broth and the introduction of vgb in VG1 (pTU14) induced the parent promotion effect on cell growth and PHB accumulation, especially under low DO conditions. Further experiments indicated that the introduction of vgb in VG1 (pTU14) not only decreased the critical oxygen concentration, but also affected the volumetric oxygen transfer coefficient of the recombinant strain.

3-Hydroxybutyric Acid↗