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Biomedical subjects

H Wu

Publications and source records attributed to H Wu.

At least 91 records · Page 5Linked to original sources
PubMed2001

The shorter zinc finger protein ZNF230 gene message is transcribed in fertile male testes and may be related to human spermatogenesis.

The zinc finger gene family represents one of the largest in the mammalian genome, with several of these genes reported to be involved in spermatogenesis. A newly discovered gene has been identified that is expressed abundantly in the testicular tissue of fertile men as determined by mRNA differential display. The gene encodes a C(3)HC(4)-type zinc finger protein motif (ring finger motif) consistent with a role in pre-meiotic or post-meiotic sperm development. The gene was named ZNF230 and mapped to the short arm of chromosome 11 (11p15). ZNF230 has two transcripts, of 1 kb and 4.4 kb in length. The shorter 1 kb transcript was only detected in testicular tissue whereas the longer 4.4 kb transcript was not detected in testis but was found in several other tissues. The lack of detectable ZNF230 expression in azoospermic patients by reverse transcriptase-mediated PCR analysis is interpreted to mean that this gene is involved in maintaining normal human male fertility.

Amino Acid Sequence↗
PubMed2001

Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo.

The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten-/- central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.

Animals↗
PubMed2001

Strongly UV absorbing bifunctional azoalkanes.

[structure: see text] Two new anthracene-containing azoalkanes (1 and 2) absorb UV light 600 times more strongly than simple azoalkanes. Intramolecular energy transfer from excited singlet anthracene to the azo group is nearly complete, but despite the close proximity of the two chromophores, 1 and 2 continue to exhibit anthracene fluorescence. Thermolysis of these compounds in the presence of monomers affords fluorescent labeled polymers. Compounds 1 and 2 are the first azoalkanes to undergo induced decomposition in solution.

Journal Article↗
PubMed2001

Selective sorption of cesium using self-assembled monolayers on mesoporous supports.

The synthesis of a novel nanocomposite sorbent material, copper ferrocyanide immobilized within a mesoporous ceramic matrix, and its use as a novel cesium sorbent material is reported in this paper. Complete removal of cesium was achieved in the presence of competing metal ions for solutions containing 2 ppm cesium under a variety conditions. Loading capacity of more than 1.35 mmol Cs per g of sorbent material has been achieved. The exceptionally fast binding kinetics and high loading capacity, resulting from the rigidly open pore structure and extremely high surface area of the sorbent materials, make them potentially very useful for the removal of cesium from nuclear wastes and contaminated groundwater.

Adsorption↗
PubMed2001

Infiltration of canonical Vgamma4/Vdelta1 gammadelta T cells in an adriamycin-induced progressive renal failure model.

We have previously reported an infiltration of renal interstitial gammadelta T cells in Adriamycin-induced progressive glomerulosclerosis in the rat kidney. The TCR repertoire and sequences used by these gammadelta T cells have now been studied. Two injections of Adriamycin 14 days apart caused segmental glomerulosclerosis, massive interstitial infiltration of mononuclear cells, and end-stage renal failure. Flow cytometry of lymphocyte subpopulations with Abs to CD3, the gammadelta TCR, and the alphabeta TCR showed that gammadelta T cells as a proportion of CD3(+) cells were increased in Adriamycin-treated kidneys (8.5 +/- 5.4%), but not in lymph nodes (1.3 +/- 0.4%). A semiquantitative score of glomerular damage (r = 0.65; p < 0.01) and creatinine (r = 0.62; p < 0.01) correlated significantly with the presence of gammadelta T cells. TCR Vgamma repertoire analysis by RT-PCR and Southern blotting showed that Vgamma2 was the dominant subfamily in lymph nodes, whereas Vgamma4 became the predominant subfamily in advanced stages of the rat Adriamycin-treated kidney. Sequencing of the Vgamma4-Jgamma junctional region showed an invariant sequence. The amino acid sequence of the junctional region of the Vgamma4 TCR was the same as the reported mouse canonical Vgamma4 TCR sequence. Analysis of the kidney Vdelta repertoire showed dominant expression of Vdelta1, and sequencing again revealed the selective expression of a canonical Vdelta1 gene. Semiquantitative RT-PCR for cytokine gene expression showed that gammadelta T cells from the kidneys expressed TGF-beta, but not IL-4, IL-10, or IFN-gamma. These results suggest that the predominant gammadelta T cells in the Adriamycin kidney use an invariant Vgamma4/Vdelta1 receptor.

Animals↗
PubMed2001

Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway.

Polo-like kinase 3 (Plk3, previously termed Prk) contributes to regulation of M phase of the cell cycle (Ouyang, B., Pan, H., Lu, L., Li, J., Stambrook, P., Li, B., and Dai, W. (1997) J. Biol. Chem. 272, 28646-28651). Plk3 physically interacts with Cdc25C and phosphorylates this protein phosphatase predominantly on serine 216 (Ouyang, B., Li, W., Pan, H., Meadows, J., Hoffmann, I., and Dai, W. (1999) Oncogene 18, 6029-6036), suggesting that the role of Plk3 in mitosis is mediated, at least in part, through direct regulation of Cdc25C. Here we show that ectopic expression of a kinase-active Plk3 (Plk3-A) induced apoptosis. In response to DNA damage, the kinase activity of Plk3 was rapidly increased in an ATM-dependent manner, whereas that of Plk1 was markedly inhibited. Recombinant Plk3 phosphorylated in vitro a glutathione S-transferase fusion protein containing p53, but not glutathione S-transferase alone. Recombinant Plk1 also phosphorylated p53 but on residues that differed from those targeted by Plk3. Co-immunoprecipitation and pull-down assays demonstrated that Plk3 physically interacted with p53 and that this interaction was enhanced upon DNA damage. In vitro kinase assays followed by immunoblotting showed that serine 20 of p53 was a target of Plk3. Furthermore, expression of a kinase-defective Plk3 mutant (Plk3(K52R)) resulted in significant reduction of p53 phosphorylation on serine 20, which was correlated with a decrease in the expression of p21 and with a concomitant increase in cell proliferation. These results strongly suggest that Plk3 functionally links DNA damage to cell cycle arrest and apoptosis via the p53 pathway.

Apoptosis↗
PubMed2001

Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy.

This exploratory analyses characterizes patterns of lymphocyte recovery in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART) and investigates their relationship with baseline indices and virologic responses. We modeled kinetics of total CD4+ lymphocytes, as well as naive (CD45RA+ CD62L+), and memory (CD45RA- CD45RO+) subsets in 48 patients treated with AZT/3TC/Ritonavir for 48 weeks in ACTG protocol 315. Cell kinetic indices were estimated by nonlinear regression methods and were correlated with baseline factors and virologic responses. Five different kinetic patterns were identified, including biphasic growth, growth-plateau, growth-depletion, decay-recovery, and biphasic decay. Although overall mean lymphocyte responses showed a biphasic increase in cell number, a careful investigation reveals that only one-third of patients actually followed the biphasic growth pattern in CD4+ cell response, while 44% of 48 patients from this study followed the growth-depletion pattern. CD4+ cell recovery during the first phase and the 48-week study period were negatively correlated with baseline CD4+ cell counts, and positively correlated with baseline viral load. Memory CD4+ cell recovery during the first phase was also negatively correlated with baseline memory CD4+ and total CD4+ cell number, but the recovery rate of memory CD4+ cells during the second phase was positively correlated with baseline CD4+ cell number. Patients with a decay in CD4+ cell count during treatment were more likely to have experienced virological rebound (58%) than patients with nondecay patterns (24%). The rate and magnitude of the absolute increase in total CD4+ and memory CD4+ cell number (but not naive CD4+ cells) during the second phase were lower in patients with viral rebound compared with patients with persistent viral suppression. These results show that the kinetics of lymphocyte reconstitution in response to potent antiretroviral therapy in individual patients vary considerably from the "classic" biphasic increase that characterizes the mean or median response pattern. Pattern analysis of lymphocyte kinetics may be useful for testing relationships among factors that modulate the response to treatment.

Anti-HIV Agents↗
PubMed2001

Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis.

Erythropoiesis occurs in 2 distinct waves during embryogenesis: the primitive wave in the extra-embryonic yolk sac (YS) followed by the definitive wave in the fetal liver and spleen. Even though progenitors for both cell types are present in the YS blood islands, only primitive cells are formed in the YS during early embryogenesis. In this study, it is proposed that erythropoietin (Epo) expression and the resultant EpoR activation regulate the timing of the definitive wave. First, it was demonstrated that Epo and EpoR gene expressions are temporally and spatially segregated: though EpoR is expressed early (embryonic days 8.0-9.5) in the yolk sac blood islands, no Epo expression can be detected in this extra-embryonic tissue. Only at a later stage can Epo expression be detected intra-embryonically, and the onset of Epo expression correlates with the initiation of definitive erythropoiesis. It was further demonstrated that the activation of the EpoR signaling pathway by knocking-in a constitutively active form of EpoR (R129C EpoR) can lead to earlier onset of definitive erythropoiesis in the YS. Thus, these results provide the first in vivo mechanism as to how 2 erythroid progenitor populations can coexist concurrently in the YS yet always differentiate successively during embryogenesis.

Animals↗
PubMed2001

Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR.

Recent evidence places the FRAP/mTOR kinase downstream of the phosphatidyl inositol 3-kinase/Akt-signaling pathway, which is up-regulated in multiple cancers because of loss of the PTEN tumor suppressor gene. We performed biological and biochemical studies to determine whether PTEN-deficient cancer cells are sensitive to pharmacologic inhibition of FRAP/mTOR by using the rapamycin derivative CCI-779. In vitro and in vivo studies of isogenic PTEN(+/+) and PTEN(-/-) mouse cells as well as human cancer cells with defined PTEN status showed that the growth of PTEN null cells was blocked preferentially by pharmacologic FRAP/mTOR inhibition. Enhanced tumor growth caused by constitutive activation of Akt in PTEN(+/+) cells also was reversed by CCI-779 treatment, indicating that FRAP/mTOR functions downstream of Akt in tumorigenesis. Loss of PTEN correlated with increased S6 kinase activity and phosphorylation of ribosomal S6 protein, providing evidence for activation of the FRAP/mTOR pathway in these cells. Differential sensitivity to CCI-779 was not explained by differences in biochemical blockade of the FRAP/mTOR pathway, because S6 phosphorylation was inhibited in sensitive and resistant cell lines. These results provide rationale for testing FRAP/mTOR inhibitors in PTEN null human cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A novel deletion mutation of the EXT2 gene in a large Chinese pedigree with hereditary multiple exostosis.

Hereditary multiple exostoses (EXT) is an autosomal dominant disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxta-epiphyseal regions of the long bones. 3 genes are known to be involved in the formation of exostoses. Among them, EXT1 and EXT2, which encode enzymes that catalyse the biosynthesis of heparan sulfate, an important component of the extracellular matrix, are responsible for over 70% of the EXT cases. A large Chinese family with hereditary multiple exostoses has been analysed and the disease-causing mutation has been found. Blood samples were obtained from 69 family members, including 23 affected individuals. The EXT phenotype was shown to be linked to the EXT2 gene by using 2-point linkage analysis. After polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and DNA sequencing, a previously unreported deletion of a G in exon 3 of EXT2 gene was observed. This deletion co-segregated with the disease phenotype, suggesting that it is the disease-causing mutation in this family. Furthermore, in at least 4 members chondrosarcoma occurred after either an operation or injury of the exostosis and 3 of them died of the malignancy in the family. Whether the operation or injury was responsible for the malignant transformation still needs further study.

Base Sequence↗
PubMed2001

Prognostic value of cardiac troponin I re-elevation following percutaneous coronary intervention in high-risk patients with acute coronary syndromes.

Troponin I is a predictive marker of short- and intermediate-term adverse cardiac events in patients with acute coronary syndromes (ACS). These high-risk patients may benefit from early percutaneous coronary intervention. However, whether additional myocardial injury, defined as postprocedural troponin I elevation, may be associated with adverse short- and intermediate-term outcomes has not been fully explored. Accordingly, we studied 132 consecutive patients with non-ST-elevation ACS (62% with non-Q-wave myocardial infarction) and elevated troponin I levels at admission (>0.15 ng/ml) who underwent percutaneous coronary intervention > or =48 hours after admission. Troponin I levels were routinely measured at 6 and 18 to 24 hours after intervention and patients were stratified according to the presence or absence of troponin I re-elevation, defined as postprocedural troponin I levels >1 times the admission levels. In-hospital and cumulative 6-month clinical outcomes were compared between groups. Patients with troponin I re-elevation (n = 51) were older (68 +/- 13 vs 64 +/- 12 years, p = 0.05) and had experienced prior myocardial infarction more frequently (92.5 vs 82.1, p = 0.09), but otherwise had similar baseline clinical characteristics. Patients with troponin I re-elevation had significantly higher in-hospital mortality (9.8% vs 0%, p = 0.016) and a higher 6-month cumulative death rate (24% vs 3.7%, p = 0.001). There was a trend for an increased 6-month myocardial infarction rate in patients with troponin I re-elevation (13.7% vs 3.7%, p = 0.11) and target vessel revascularization was similar between groups (16.7% vs 17.4%, p = 0.92). By multivariate analysis, troponin I re-elevation (odds ratio [OR] 6.2, p = 0.011) and diabetes mellitus (OR 5.7, p = 0.014) were the strongest independent predictors for increased 6-month cumulative mortality, whereas creatine kinase MB-fraction re-elevation had no prognostic value. We conclude that troponin I re-elevation after percutaneous coronary intervention in high-risk patients with ACS is associated with a substantial increase in mortality and reduced event-free survival at 6-month follow-up.

Aged↗
PubMed2001

Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3.

Upon exposure of cells to hydrogen peroxide (H(2)O(2)) phosphorylation of p53 was rapidly induced in human fibroblast GM00637, and this phosphorylation occurred on serine 9, serine 15, serine 20, but not on serine 392. In addition, H(2)O(2)-induced phosphorylation of p53 was followed by induction of p21, suggesting functional activation of p53. Induction of phosphorylation of p53 on multiple serine residues by H(2)O(2) was caffeine-sensitive and blocked in ATM(-/-) cells. Polo-like kinase-3 (Plk3) activity was also activated upon H(2)O(2) treatment, and this activation was ATM-dependent. Recombinant His(6)-Plk3 phosphorylated glutathione S-transferase (GST)-p53 fusion protein but not GST alone. When phoshorylated in vitro by His(6)-Plk3, but not by the kinase-defective mutant His6-Plk3(K52R), GST-p53 was recognized by an antibody specifically to serine 20-phosphorylated p53, indicating that serine 20 is an in vitro target of Plk3. Also serine 20-phosphorylated p53 was coimmunoprecipitated with Plk3 in cells treated with H(2)O(2). Furthermore, although H(2)O(2) strongly induced serine 15 phosphorylation of p53, it failed to induce serine 20 phosphorylation in Plk3-dificient Daudi cells. Ectopic expression of a Plk3 dominant negative mutant, Plk3(K52R), in GM00637 cells suppressed H(2)O(2)-induced serine 20 phosphorylation. Taken together, our studies strongly suggest that the oxidative stress-induced activation of p53 is at least in part mediated by Plk3.

Cell Cycle Proteins↗
PubMed2001

A multiple imputation method for missing covariates in non-linear mixed-effects models with application to HIV dynamics.

We propose a three-step multiple imputation method, implemented by Gibbs sampler, for estimating parameters in non-linear mixed-effects models with missing covariates. Estimates obtained by the proposed multiple imputation method are compared to those obtained by the mean-value imputation method and the complete-case method through simulations. We find that the proposed multiple imputation method offers smaller biases and smaller mean-squared errors for the estimates of covariate coefficients compared to other two methods. We apply the three missing data methods to modelling HIV viral dynamics from an AIDS clinical trial. We believe that the results from the proposed multiple imputation method are more reliable than that from the other two commonly used methods.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Surface Patterson function by inversion of low-energy electron diffraction I-V spectra at multiple incident angles.

An accurate Patterson function, free of artifacts, is obtained by transforming low-energy electron diffraction I-V spectra at multiple incident angles. The demonstration is carried out using normal incidence measured spectra and calculated spectra at three angles of incidence. The errors between intensity spots in the Patterson function and known interatomic distances are less than 0.01 A in the horizontal direction and 0.09 A in the vertical direction. The reason for the high accuracy in the horizontal direction is given.

Journal Article↗
PubMed2001

Topical transfection using plasmid DNA in a water-in-oil nanoemulsion.

Expression plasmids encoding chloramphenicol acetyltransferase (CAT) or human interferon-alpha2 cDNA were formulated in water-in-oil nanoemulsions and applied to murine skin. The histological location of transfected cells was assessed by in situ DNA PCR and showed that the deposition of plasmid DNA was primarily in follicular keratinocytes. Transgene expression in the skin was monitored for 24-72 h, following topical application of either single or multiple daily doses by quantitative RT-PCR and ELISA. It was found that transgene expression was optimal at 24 h following topical application of a single dose of water-in-oil nanoemulsion containing plasmid DNA. Dose-response studies using a total dose of 3, 10 or 30 microg of plasmid DNA suggested that topical transfection using nanoemulsions is subject to both threshold and saturation effects. None of the cationic liposome formulations tested as controls mediated transgenic protein expression at levels higher than background values of the ELISAs used to assay transgenic protein. Single and multiple dose experiments using human interferon-alpha2 as a transgene indicated that the efficiency of nanoemulsion mediated transfection was most effective in the context of normal versus atrophic hair follicles. In addition, the total amount of human interferon-alpha2 present in skin appeared to accumulate as a consequence of multiple dosing. Histologic evaluation of treated skin showed no overt signs of toxicity or irritation associated with the short-term application of the nanoemulsions. The results suggest that water-in-oil nanoemulsions can be used to facilitate transfection of follicular keratinocytes in vivo.

Administration, Topical↗
PubMed2001

Creatine kinase-MB fraction elevation after percutaneous coronary intervention in patients with chronic renal failure.

We evaluated the short- and long-term clinical outcomes of 326 consecutive patients with chronic renal failure, not on dialysis, who had creatine kinase (CK)-myocardial band (MB) fraction elevation after successful percutaneous coronary intervention in a native coronary artery. Based on peak CK-MB levels measured after intervention, patients were divided into 3 groups: no elevation (group 1, n = 184), 1 to 3 x upper normal levels (group 2, n = 72), and >3 x upper normal levels (group 3, n = 70). Baseline clinical and angiographic characteristics were similar among the 3 groups. Angiographic success was similar among the 3 groups, although there was a significantly higher use of intra-aortic balloon pump in patients who had postprocedural CK-MB >3 x normal values and a higher rate of in-hospital complications, i.e., repeat catheterization, repeat target lesion intervention, pulmonary edema, renal function deterioration, emergency dialysis, and major bleeding complications. At 1-year follow-up, mortality rates were significantly higher in these patients (35.4% vs 22.0% for patients with CK-MB 1 to 3 x normal values and 16.7% for patients without CK-MB elevation, p = 0.007). Multivariate analysis showed that CK-MB >3 x normal (odds ratio 3.04; 95% confidence interval 1.41 to 6.57, p = 0.005) and intra-aortic balloon pump (odds ratio 1.49; confidence interval 1.15 to 1.93, p = 0.002) were independent predictors of late mortality. Therefore, patients with chronic renal failure who had CK-MB elevation >3 x the upper normal limit after a successful percutaneous coronary intervention had a higher incidence of in-hospital complications and a significantly higher mortality rate at 1-year follow-up than patients without CK-MB elevation or with <3 x normal CK-MB elevation.

Aged↗
PubMed2001

Topical transport of hydrophilic compounds using water-in-oil nanoemulsions.

A variety of water-in-oil nanoemulsions were prepared using sorbitan monooleate (Span80), polyoxyethylene 20 sorbitan monooleate (Tween80), olive oil and water. The nanoemulsions were tested for their ability to facilitate transport of a model hydrophilic solute, inulin, across hairless and hairy mouse skin and hairy rat skin following topical in vitro application. The transport of inulin incorporated in water-in-oil nanoemulsions was found to be significantly higher (5- to 15-fold) than that obtained with micellar dispersions or aqueous controls. The rate and extent of inulin transport across hairy mouse skin was found to be highly dependent on the hydrophile-lipophile balance (HLB) of the surfactant mixture in the nanoemulsion. Nanoemuslions prepared using mixtures with lower HLB exhibited significantly higher rate and extent of transport. It was also found that nanoemulsion-mediated transport was independent of molecular size of the hydrophilic solute and the nature of the aqueous phase. More importantly, transport of inulin from nanoemulsions was independent of animal skin characteristics such as stratum corneum thickness and follicle-type. The combined results suggest that water-in-oil nanoemulsions that are compatible with the lipophilic sebum environment of the hair follicle facilitate efficient transport of incorporated hydrophilic solutes and imply that such transport is predominantly transfollicular in nature.

Administration, Topical↗