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Biomedical subjects

H Zeng

Publications and source records attributed to H Zeng.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Diagnosing complicated congenital heart disease with two-dimensional echocardiography and three-segment concept].

OBJECTIVE: To apply three-segment heart anatomy concept to two-dimensional echocardiography (2DE) in the diagnosis of complicated congenital heart disease (CHD). METHODS: 920 cases of CHD were diagnosed with 2DE and three-segment heart anatomy concept. 822 out of the 920 cases underwent angiocardiography, and 584 cases were confirmed by operation. RESULTS: According to three-segment heart anatomy concept of atrial position, 855 cases were situs solitus (including 89 cases of left superior vena cava and 31 cases of complete anomalous pulmonary venous drainage), 53 cases were situs inversus, and 12 cases were situs ambigus. As to atrial-ventricular valve, 747 cases were both opening, 112 cases had one-side atresia, and 61 cases had one together valve; As to ventricle position, 606 cases were dextro-loop, 111 cases had levo-loop, and 203 cases had single ventricle (including 24 cases), As to cor biloculare of great artery relation, 304 cases had normal relation of great arteries, including 35 cases of pulmonary atresia, 219 cases had right-transposition of great arteries, 240 cases had left-transposition of great arteries, 32 cases were mirror to normal, and 25 cases had persistent truncus arteriosus. 823 cases were diagnosed with 2DE, with a total accurate rate of 89.5%. CONCLUSION: Applying three-segment heart anatomy concept to 2DE to diagnose complicated CHD and analyzing the heart segment by segment will make the diagnosis simple and systematic, providing a concise basis for heart surgeries.

Adolescent↗
PubMed2001

Nicotine and amyloid formation.

The major protein constituents of amyloid deposits in Alzheimer's disease (AD) are the 40-residue beta-amyloid (Abeta) (1-40) peptide and the 42-residue Abeta(1-42) peptide. The Abeta(1-42) is more pathogenic and produced in greater quantities in familial forms of AD. A major goal of research is to uncover a suitable inhibitor that either slows down or inhibits Abeta formation (beta-amyloidosis). During beta-amyloidosis, structural changes associated with the conversion of monomeric Abeta peptide building blocks into the aggregated fibrillar beta-sheet structures occur (alpha-helix-->beta-sheet or random, extended chain-->beta-sheet). In previous work, we and others established that nicotine, a major component of cigarette smoke, inhibits beta-amyloidosis of the Abeta(1-42), which may result from nicotine binding to the alpha-helical structure. These conclusions were based on solution nuclear magnetic resonance (NMR) spectroscopic studies with the nonnative 28-residue Abeta(1-28). This information suggests that, when administered therapeutically to AD patients, nicotine may not only affect cholinergic activation, but could also conceivably alter amyloid deposition. In this report, NMR studies were augmented with the naturally occurring Abeta(1-42), under conditions where the peptide folds into a predominantly alpha-helical or random, extended chain structure. The major result is that nicotine shows only modest binding to these conformations, indicating that the nicotine inhibition to beta-amyloidosis probably results from binding to a small, soluble beta-sheet aggregate that is NMR invisible.

Alzheimer Disease↗
PubMed2001

Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily.

The MRP subfamily of ABC transporters currently consists of at least six members, several of which have been demonstrated to transport amphipathic anions and to confer in vitro resistance to chemotherapeutic agents. In searching the data bases we identified the product of a cDNA sequencing project that bears significant similarity to MRP subfamily transporters. In this report the predicted coding sequence, protein product and expression pattern of this cDNA, termed MRP7, are analyzed. The MRP7 cDNA sequence encodes a 1492 amino acid ABC transporter whose structural architecture resembles that of MRP1, MRP2, MRP3, and MRP6, in that its transmembrane helices are arranged in three membrane spanning domains. However, in contrast to the latter transporters, a conserved N-linked glycosylation site is not found at the N-terminus of MRP7. Comparisons of the MRP7 amino acid sequence indicated that while it is most closely related to other MRP subfamily members, its degree of relatedness is the lowest of any of the known MRP-related transporters. The integrity of the predicted MRP7 coding sequence was confirmed by the synthesis of an approximately 158 kDa protein in reticulocyte lysates programmed with the MRP7 cDNA. While MRP7 transcript was detected in a variety of tissues by RT/PCR, it was not readily detectable by RNA blot analysis, suggesting that it is expressed at low levels in these tissues. Fluorescence in situ hybridization indicated that MRP7 maps to chromosome 6p12-21, in proximity to several genes associated with glutathione conjugation and synthesis. On the basis of these findings and evolutionary cluster analysis, we conclude that MRP7 is a member of the MRP subfamily of amphipathic anion transporters.

ATP-Binding Cassette Transporters↗
PubMed2001

High-speed liquid chromatography/tandem mass spectrometry using a monolithic column for high-throughput bioanalysis.

With the ever-increasing workload from a variety of in vitro and in vivo screening procedures, new analytical methodologies to perform bioanalysis in an accurate and high-throughput manner are in great demand. In this work, monolithic columns were used instead of conventional particulate HPLC columns to perform chromatographic separations. Because the pressure drop on a monolithic column was considerably lower than that on a particulate column, a high flow rate (6 mL/min) was used for a 4.6 x 50 mm monolithic column with a total backpressure of about 61 bar measured using acetonitrile/water (50:50). The capability of using a regular column length at high flow rates, combined with the extremely small dependency of separation efficiency on linear flow velocity, allowed for the generation of sufficient chromatographic resolving power in a significantly reduced runtime. As demonstrated in this work, a plasma extract of a mixture of tempazepam, tamoxifen, fenfluramine, and alprozolam were baseline separated within a total analysis time of one minute. An average peak width at half maximum of approximately one second was noted using a generic broad gradient. It was also found that the separation efficiency and signal/noise (S/N) ratios for this separation remained almost constant at flow rates of 1, 3, and 6 mL/min, respectively. The ruggedness of the separation was evaluated by injecting 600 plasma extracts containing the replicates of a standard curve of the above mixture during an overnight run. The chromatographic retention time, separation quality, peak response and sensitivity were highly reproducible throughout the run. This high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) system has been used routinely in the authors' laboratory to support drug discovery programs.

Acetonitriles↗
PubMed2001

Multiple-sprayer tandem mass spectrometry with parallel high flow extraction and parallel separation for high-throughput quantitation in biological fluids.

In this work, an on-line four-column high-flow parallel extraction device was set up and interfaced to a four-column parallel separation system with a four-sprayer tandem mass spectrometric detector. This system allowed for the direct and simultaneous sampling, extraction, separation, and detection of four samples in biological fluids, resulting in significantly increased throughput. The performance of this system was evaluated using rat plasma samples spiked with methotrexate as a test compound. The results showed that the relative standard deviation for responses across the four parallel channels was less than 10% for a concentration range from 10 to 2500 nM, resulting in comparable sensitivity (slope of curve) for the analyte on all channels. A ruggedness test was performed using a mixed set of new and used extraction columns and the relative standard deviation in analyte response was found to be below 15%. The inter-channel crosstalk was measured to be about 0.1%. A comparison between the data generated on this system and on a conventional system for a rat pharmacokinetic study showed no more than 20% difference in measured concentrations. This parallel system is a viable tool for high-throughput bioanalysis in a drug discovery environment.

Animals↗
PubMed2001

Characterization of phosphopeptides from protein digests using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray quadrupole time-of-flight mass spectrometry.

A two-step mass spectrometric method for characterization of phosphopeptides from peptide mixtures is presented. In the first step, phosphopeptide candidates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) based on their higher relative intensities in negative ion MALDI spectra than in positive ion MALDI spectra. The detection limit for this step was found to be 18 femtomoles or lower in the case of unfractionated in-solution digests of a model phosphoprotein, beta-casein. In the second step, nanoelectrospray tandem mass (nES-MS/MS) spectra of doubly or triply charged precursor ions of these candidate phosphopeptides were obtained using a quadrupole time-of-flight (Q-TOF) mass spectrometer. This step provided information about the phosphorylated residues, and ruled out nonphosphorylated candidates, for these peptides. After [(32)P] labeling and reverse-phase high-performance liquid chromatography (RP-HPLC) to simplify the mixtures and to monitor the efficiency of phosphopeptide identification, we used this method to identify multiple autophosphorylation sites on the PKR-like endoplasmic reticulum kinase (PERK), a recently discovered mammalian stress-response protein.

Amino Acid Sequence↗
PubMed2001

Induction of heme oxygenase-1 by Ginkgo biloba extract but not its terpenoids partially mediated its protective effect against lysophosphatidylcholine-induced damage.

In this study, we examined whether Ginkgo Biloba Extract and its terpenoid constituents protect against oxidative stress through actions on heme oxygenase (HO) gene expression and activity. HO-1 and glutathione peroxidase (GPx) gene expressions were examined by reverse transcription polymerase chain reaction (RT-PCR) analysis, HO activity and GPx enzyme activity were analysed by spectrophotometric assay. Pretreatment of H9c2 myocytes with 100-500 microgml(-1)Ginkgo Biloba Extract caused induction of HO-1 gene expression and a significant increase in HO activity; 30 microgml(-1)ginkgolide B and 30 microgml(-1)bilobalide had little effect. Treatment with Ginkgo Biloba Extract for 24 h also significantly increased GPx gene expression and GPx enzyme activity. Pretreatment with Ginkgo Biloba Extract, ginkgolide B and bilobalide protected myocytes against lysophosphatidylcholine (LPC)-induced damage. The protective effect of Ginkgo Biloba Extract against LPC-induced damage was partially suppressed by a HO inhibitor, Zinc protoporphyrin-IX (ZnPP-IX), while ZnPP-IX did not suppress the protective effect of ginkgolide B or bilobalide. Furthermore, pretreatment with hemin, biliverdin or bilirubin reduced cytotoxicity induced by LPC. These results suggest that induction of HO-1 by Ginkgo Biloba Extract but not its terpenoid constituents may play a beneficial role in oxidative stress. The mechanism of Ginkgo Biloba Extract-induced HO-1 gene expression and the increase in HO activity may be related to alteration of intracellular glutathione levels.

Animals↗
PubMed2001

Ultrasonographic diagnosis of bone tumor of the knee and its clinical implication.

In order to evaluate the value of the ultrasonography in the diagnosis of tumor of the knee and its clinical implication, 67 patients with clinically suspected bone tumor of the knee were examined by ultrasound. The ultrasonographic characteristics of different bone tumors were studied and compared with the results of pathologic characters after operation. Ultrasonography can readily visualize the bony destruction and the pathologic change of the periosteum and the soft tissue related to bone tumor. Fifty-two cases of malignant bone tumors and 15 cases of giant cell tumors were diagnosed by ultrasonography. Pathologically, there were 54 cases of malignant bone tumor and 13 cases of giant cell tumor. It was concluded that ultrasonographic examination might be a useful method for the diagnoses of bone tumor of the knee and play an important role in guiding needle biopsy and electing operative method and approach.

Adolescent↗
PubMed2001

Cell surface glypicans are low-affinity endostatin receptors.

Endostatin, a collagen XVIII fragment, is a potent anti-angiogenic protein. We sought to identify its endothelial cell surface receptor(s). Alkaline phosphatase- tagged endostatin bound endothelial cells revealing two binding affinities. Expression cloning identified glypican, a cell surface proteoglycan as the lower-affinity receptor. Biochemical and genetic studies indicated that glypicans' heparan sulfate glycosaminoglycans were critical for endostatin binding. Furthermore, endostatin selected a specific octasulfated hexasaccharide from a sequence in heparin. We have also demonstrated a role for endostatin in renal tubular cell branching morphogenesis and show that glypicans serve as low-affinity receptors for endostatin in these cells, as in endothelial cells. Finally, antisense experiments suggest the critical importance of glypicans in mediating endostatin activities.

3T3 Cells↗
PubMed2001

Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival.

The protein kinase PERK couples protein folding in the endoplasmic reticulum (ER) to polypeptide biosynthesis by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha), attenuating translation initiation in response to ER stress. PERK is highly expressed in mouse pancreas, an organ active in protein secretion. Under physiological conditions, PERK was partially activated, accounting for much of the phosphorylated eIF2alpha in the pancreas. The exocrine and endocrine pancreas developed normally in Perk-/- mice. Postnatally, ER distention and activation of the ER stress transducer IRE1alpha accompanied increased cell death and led to progressive diabetes mellitus and exocrine pancreatic insufficiency. These findings suggest a special role for translational control in protecting secretory cells from ER stress.

Animals↗
PubMed2001

MRP subfamily transporters and resistance to anticancer agents.

The MRP subfamily of ABC transporters from mammals consists of at least seven members, six of which have been implicated in the transport of amphipathic anions. MRP1, MRP2, and MRP3 bear a close structural resemblance, confer resistance to a variety of natural products as well as methotrexate, and have the facility for transporting glutathione and glucuronate conjugates. MRP1 is a ubiquitously expressed efflux pump for the products of phase II of xenobiotic detoxification, while MRP2, whose hereditary deficiency results in Dubin-Johnson syndrome, functions to extrude organic anions into the bile. MRP3 is distinguished by its capacity to transport the monoanionic bile constituent glycocholate, and may function as a basolateral back-up system for the detoxification of hepatocytes when the usual canalicular route is impaired by cholestatic conditions. MRP4 and MRP5 resemble each other more closely than they resemble MRPs 1-3 and confer resistance to purine and nucleotide analogs which are either inherently anionic, as in the case of the anti-AIDS drug PMEA, or are phosphorylated and converted to anionic amphiphiles in the cell, as in the case of 6-MP. Given their capacity for transporting cyclic nucleotides, MRP4 and MRP5 have also been implicated in a broad range of cellular signaling processes. The drug resistance activity and physiological substrates of MRP6 are unknown. However, its hereditary deficiency results in pseudoxanthoma elasticum, a multisystem disorder affecting skin, eyes, and blood vessels. It is hoped that elucidation of the resistance profiles and physiological functions of the different members of the MRP subfamily will provide new insights into the molecular basis of clinical drug resistance and spawn new strategies for combating this phenomenon.

Amino Acids↗
PubMed2001

Complement-mediated T-cell depletion of bone marrow: comparison of T10B9.1A-31 and Muromonab-Orthoclone OKT3.

BACKGROUND: T10B9.1A-31 (T(10)B(9)) and Muromonab-Orthoclone OKT3 (OKT3) are both murine MAb with a narrow specificity for T lymphocytes. Over the past 10 years, we have used each for T-cell depletion (TCD) of BM. In this report we describe similarities and differences using these antibodies, as well as their effects on patient outcome. METHODS: We compared BM mononuclear cells (BMMC) prepared using a Cobe Spectra apheresis machine with density gradient (DG) separation to remove RBC and enrich for CD34(+) cells prior to TCD. FACS and limiting dilution assays (LDA) were used to measure the efficiency of TCD, the subsets of cells removed and CD34 content. Univariate statistics were used to assess graft outcome, including GvHD, graft failure, post-transplant lymphoproliferative disease (PTLD), relapse, DFS, and TRM. RESULTS: BMMC preparation on the Cobe Spectra resulted in superior recovery of CD34(+) cells. However, this method could not be used with OKT3 due to inhibition of T-cell lysis. Optimal TCD required two rounds of complement at room temperature for OKT3, compared with one or two rounds for T(10)B(9). TCR(gamma delta)(+) T-cells, but not natural killer cells, were spared to a greater degree with T(10)B(9). Further T-cell loss occurred during culture with T(10)B(9) but not with OKT3. Overall efficiency of TCD was superior using T(10)B(9). The risk of acute GvHD was higher with OKT3-mediated TCD, independent of T-cell content, and may have led to a higher incidence of PTLD. A decreased risk of relapse for patients with high-risk disease was seen with OKT3-treated grafts, but engraftment, TRM and DFS did not significantly differ. DISCUSSION: TCD using OKT3 results in higher T-cell content and higher rates of acute GvHD and PTLD compared with T(10)B(9). Cobe Spectra cannot be used for BMMC processing with OKT3, fewer CD34(+) are therefore infused. Technical, as well as biological, differences between narrow specificity MAbs can affect graft outcome.

Animals↗
PubMed2001

Metabolism of S-nitrosoglutathione by endothelial cells.

S-nitrosoglutathione (GSNO) is an inhibitor of platelet aggregation and has also been shown to protect the ischemic heart from reperfusion-mediated injury. Although GSNO is often used in cell culture as a source of nitric oxide, the mechanisms of GSNO metabolism are not well established. We show here that GSNO decomposition by bovine aortic endothelial cells has an absolute dependence on the presence of cystine in the cell culture medium. In addition, GSNO decay is inhibited by diethyl maleate, an intracellular glutathione scavenger, but not by buthionine sulfoximine, a glutathione synthesis inhibitor. This indicates that thiols in general, rather than specifically glutathione, are the major factors that influence GSNO decay. Only 40% of the nitroso group of GSNO could be recovered as nitrite/nitrate, suggesting that the primary route of GSNO decay is reductive and that nitric oxide is only a minor product of GSNO decay. We conclude that the intracellular thiol pool causes the reduction of extracellular disulfides to thiols, which then directly reduce GSNO.

Animals↗
PubMed2001

Magnetic and structural properties of electrochemically self-assembled Fe1-xCox nanowires.

Fe1-xCox (0 < or = x < or = 1) nanowires have been self-assembled by electrodeposition in porous alumina films. The crystal structure is bee at the Fe end. With increased addition of Co, the crystal structure remains bcc until about 67% addition of Co. At the Co end, the structure is a mixture of hcp and fcc. Magnetic studies show very high coercivities for the Fe-Co alloys in the bcc phase. For Fe0.67Co0.33 nanowires of diameter 9 nm, the coercivity is about 2900 Oe, whereas for Fe0.33Co0.67 nanowires, it is about 2850 Oe. Temperature and size dependence of magnetic properties show no indication of superparamagnetic effects down to wire diameters of 9 nm.

Aluminum Oxide↗
PubMed2001

Arsenic suppresses necrosis induced by selenite in human leukemia HL-60 cells.

Selenium, an essential trace element for humans, has been shown to have anticancer effects. Arsenic, a possibly essential ultratrace element for humans, has been used in the treatment of leukemia. Anticancer effects of selenium and arsenic have been related to their ability to induce apoptosis. Because humans are exposed to diverse trace elements simultaneously, it is important to learn their interrelationship. In this study, we demonstrate that sodium selenite (Na2SeO3) causes apoptosis at 3 microM and necrosis at high concentrations (> 3 microM) in HL-60 cells. Similarly, both sodium arsenite (NaAsO2) at 50 microM and sodium arsenate (Na2HAsO4) induce apoptosis at 500 microM and necrosis at higher concentrations (> 50 microM and > 500 microM, respectively) in HL-60 cells. Arsenite/arsenate, but not selenite, enhances AP-1 DNA-binding activity. This finding indicates different mechanisms through which apoptosis is induced by these two elements. Interestingly, we observed that HL-60 cell necrosis induced by a high concentration (> 3 microM) of selenite was essentially inhibited by arsenic (50 microM of NaAsO2 or 500 microM of Na2HAsO4), which resulted in a net effect of apoptosis. Because AP-1 DNA-binding activity was not induced in the presence of a combination of necrotic amount of selenite and apoptotic amount of arsenite/arsenate, the observed apoptosis apparently was through the mechanism used by selenite. Our results suggest, for the first time, that the toxic necrotic effect of selenite can be neutralized by arsenite/arsenate at the cellular level.

Antineoplastic Agents↗
PubMed2001

Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells.

Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) has been shown in previous studies to improve psoriasis. However, topical ALA-PDT may not be practical for the treatment of extensive disease. In order to overcome this limitation we have explored the potential use of oral ALA administration in psoriatic patients. Twelve patients with plaque psoriasis received a single oral ALA dose of 10, 20 or 30 mg/kg followed by measurement of protoporphyrin IX (PpIX) fluorescence in the skin and circulating blood cells. Skin PpIX levels were determined over time after ALA administration by the quantification of the 635 nm PpIX emission peak with in vivo fluorescence spectroscopy under 442 nm laser excitation. Administration of ALA at 20 and 30 mg/kg induced preferential accumulation of PpIX in psoriatic as opposed to adjacent normal skin. Peak fluorescence intensity in psoriatic and normal skin occurred between 3 and 5 h after the administration of 20 and 30 mg/kg, respectively. Ratios of up to 10 for PpIX fluorescence between psoriatic versus normal skin were obtained at the 30 mg/kg dose of ALA. Visible PpIX fluorescence was also observed on normal facial skin, and nonspecific skin photosensitivity occurred only in patients who received the 20 or 30 mg/kg doses. PpIX fluorescence intensity was measured in circulating blood cells by flow cytometry. PpIX fluorescence was higher in monocytes and neutrophils as compared to CD4+ and CD8+ T lymphocytes. PpIX levels in these cells were higher in patients who received higher ALA doses and peaked between 4 and 8 h after administration of ALA. There was only a modest increase in PpIX levels in circulating CD4+ and CD8+ T lymphocytes. In conclusion oral administration of ALA induced preferential accumulation of PpIX in psoriatic plaques as compared to adjacent normal skin suggesting that PDT with oral ALA should be further explored for the treatment of psoriasis.

Administration, Oral↗
PubMed2001

[The apolipoprotein E gene polymorphism in children with steroid-resistant idiopathic nephrotic syndrome].

OBJECTIVE: To study apolipoprotein E gene polymorphism in children with steroid- resistant idiopathic nephrotic syndrome (SRINS). METHODS: Sixty children with SRINS (including 9 children with focalsclerosing glomerulonephritis) were observed in comparison with 80 age-sex-matched healthy children. Seven lipoprote in metabolism parameters including serum total-cholesterol(TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI(apoAI), apolipoprotein B (apoB), lipoprotein (a)[Lp (a)] were detected by enzyme method, and single-strand conformation polymorphism(PCR-SSCP) was used to determine the apoE genotypes in the two groups. RESULTS: Serum TC, TG, HDL-C, LDL-C, apoAI, apoB, Lp(a) in the observation group were significantly higher than those in the healthy controls (P<0.01). After 6 months, the levels of serum TC, TG, LDL-C,apoB,Lp(a) were 81.25%, 78.13%, 84.38%, 87.50% and 78.13% respectively in 32 SRINS cases of the observation group. The apo epsilon 2 allele gene frequence was higher in the observation group than in the controls (11.66% vs 5.00%, P<0.05). The apo apsilon 2 allele gene frequence in the cases of focalsclerosing glomerulonephritis was significantly higher than that in the controls (22.22% vs 5.00%, P<0.01). CONCLUSION: The above results indicate the obvious and long term abnormalities of serum lipoprotein metabolism in the children with SRINS. The apo apsilon 2 allele gene frequence is higher in the children with SRINS. There are risk factors for atherosclerosis and cardiovascular diseases in the children with SRINS. The antilipemic drugs should be considered in use for the children with SRINS.

Apolipoprotein A-I↗