Biomedical subjects

H Zeng

Publications and source records attributed to H Zeng.

At least 73 records · Page 4Linked to original sources

PubMed2000

Direct plasma sample injection in multiple-component LC-MS-MS assays for high-throughput pharmacokinetic screening.

The simultaneous dosing of numerous compounds followed by multiple-component analysis using LC-MS-MS (the N-in-1 approach) has significantly improved the throughput of the drug-screening process. However, plasma samples still need to be extracted before LC-MS-MS analysis, which frequently limits the throughput of the assay. In this work, a high-throughput on-line extraction technique has been developed for multiple-component LC-MS-MS assays using a high-flow column-switching technique. In N-in-1 LC-MS-MS assays, high sensitivity is required since the dose level is generally reduced to minimize drug-drug interactions. In addition, good chromatographic separation is essential to minimize interference and suppression effects. The direct plasma sample injection method developed in this work has successfully met the two requirements for multiple-component LC-MS-MS assays in high-throughput pharmacokinetic screening. Plasma samples containing a large number of potential drug candidates were directly injected onto an extraction column operated under a flow rate sufficiently high to exhibit a turbulent-flow profile. The extracted analytes were then eluted onto an analytical column via column switching for LC-MS-MS analysis. The use of turbulent flow resulted in a faster and more rugged extraction with reduced carryover compared with results obtained under laminar-flow conditions. Meanwhile, the use of a column-switching method maintained the chromatographic resolving power and high sensitivity of the LC-MS-MS assay. Separation efficiency, dynamic range, accuracy, and precision comparable with those of solid-phase extraction have been achieved with the turbulent-flow column-switching technique. As a result, this technique has been successfully and routinely used for high-throughput pharmacokinetic screening.

Animals↗

PubMed2000

The study of surface transformation of pulsed laser deposited hydroxyapatite coatings.

Hydroxyapatite (HA) coatings generally exhibit very good biocompatibility owing to their compositional resemblance to the natural hard tissue and to bioactive properties that are directly related to surface transformations in physiological fluids. In this study, two types of porous HA coatings produced with pulsed laser deposition were tested with respect to their dissolution/reprecipitation in a semidynamic simulated physiological solution. Coatings with higher porosity produced with a 355-nm wavelength laser exhibited significant reprecipitation earlier than those produced with a 266-nm wavelength laser. The dissolution of the non-HA phases played a major role in the reprecipitation of HA-like material as indicated by X-ray diffraction (XRD). The coatings' Ca/P ratio became closer to the theoretical value of HA. The newly formed HA had imperfect crystal structure and/or small crystal size as suggested by XRD. The reprecipitation resulted in a very dense morphology as shown by scanning electron microscopy, suggesting a mechanically strong structure after reprecipitation. Despite undergoing dissolution and reprecipitation, the coatings showed sufficient stability in the solution, as XRD and energy-dispersive X-ray studies indicated no significant loss of the coatings. The stability of these HA coatings and their ability to cause reprecipitation of HA in the simulated physiological solution showed the potential of these coatings for clinical applications.

Biocompatible Materials↗

PubMed2000

Structural and morphological study of pulsed laser deposited calcium phosphate bioceramic coatings: influence of deposition conditions, laser parameters, and target properties.

Calcium phosphate (CaP) bioceramics, especially hydroxyapatite (HA), have been used as coatings on implants owing to their biocompatible properties. The commercial practice for applying HA coating, plasma spraying, has some disadvantages which limit the long-term stability of the implants. Pulsed laser deposition (PLD) is being investigated as an alternative technique. The purpose of this research was to systematically study the effect of various parameters of the PLD process on the properties of CaP coatings. In this study, three types of HA targets and two laser wavelengths were used to make six categories of coatings. Predominantly crystalline HA coatings were produced under all six categories at optimum conditions, although small amounts of minor phases sometimes were found. Sufficient coating/substrate bond strength was also obtained. A wide variety of coating morphologies was obtained, from rather dense and uniform to rough and porous. The important factors that affected the morphology included target properties, vacuum level, deposition temperature, and laser wavelength and energy density. PLD's ability to produce both amorphous and crystalline, and both smooth/dense and rough/porous coatings may be a unique advantage.

Biocompatible Materials↗

PubMed2000

Retinoic acid selectively inhibits the vascular permeabilizing effect of VPF/VEGF, an early step in the angiogenic cascade.

All-trans-retinoic acid (RA) and other retinoids modulate cell growth and differentiation, generally favoring terminal cell differentiation and inhibiting carcinogenesis. Retinoids are also reported to inhibit angiogenesis and endothelial cell migration, actions that are also anti-carcinogenic. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a multifunctional cytokine secreted by many tumors. It renders microvessels hyperpermeable to plasma and stimulates endothelial cell migration and division. To investigate further the mechanisms by which RA inhibits angiogenesis, we evaluated the effects of RA on VPF/VEGF-induced angiogenesis and microvascular permeability. RA selectively inhibited the angiogenic response induced by VPF/VEGF, but not that induced by fibroblast growth factor-2 (FGF-2), in the CAM assay. RA and two of its isomers also inhibited the vascular permeabilizing effect of VPF/VEGF but not that induced by histamine. The vascular permeabilization induced by VPF/VEGF and blocked by RA takes place within 1-15 min, too short a time frame for RA to act by modulating transcription through classic retinoid receptors. RA also inhibited VPF/VEGF-induced phosphorylation of PLC-gamma and synthesis of cGMP but actually increased VPF/VEGF binding to cultured endothelial cells. Taken together, these findings indicate that RA selectively blocks VPF/VEGF-induced microvascular permeability and angiogenesis and also identify VPF/VEGF as a major target of RA action. The selectivity of RA's action suggests that other, RA-independent pathways must exist for the angiogenesis induced by FGF-2 and the vascular permeabilizing effect of histamine.

Animals↗

PubMed2000

Cloning and expression of rat transforming growth factor beta 1 cDNA in osteoblasts.

Rat transforming growth factor beta 1 (rTGF beta 1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGF beta 1. The cloned gene was confirmed to code rat TGF beta 1 by restriction enzyme analysis. pcDNA3-TGF beta 1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGF beta 1 was detected by using immunohistochemical staining assay. It was found that the rat TGF beta 1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGF beta 1 was obtained in the rat osteoblasts in which the constructed TGF beta 1 expression vector was transfected.

Animals↗

PubMed2000

Cloning, sequencing, and function of sanF: A gene involved in nikkomycin biosynthesis of Streptomyces ansochromogenes.

A 111-bp DNA fragment related to nikkomycin biosynthesis of Streptomyces ansochromogenes 7100 was obtained with the method of reverse genetics. Then, a 2.2-kb DNA fragment was cloned from the DNA library of S. ansochromogenes 7100 by using the 111-bp fragment as a probe. Sequence analysis showed that the fragment contains one complete open reading frame (ORF) that encodes a 219-amino acid (aa) protein, and this gene was designated sanF (GenBank Accession No. AF223971). The function of the sanF gene was studied by a strategy of gene disruption, and the resulting sanF mutants lost the ability to synthesize biologically active nikkomycin, indicating that sanF is essential for nikkomycin biosynthesis.

Amino Acid Sequence↗

PubMed2000

XPS, EDX and FTIR analysis of pulsed laser deposited calcium phosphate bioceramic coatings: the effects of various process parameters.

Many techniques have been used to produce calcium phosphate, especially hydroxyapatite (HA), coatings on metallic implant surfaces for improved biocompatibility. Although some techniques have produced coatings used clinically, the long-term stability of the coating/implant is still questionable. As a new technique for making HA coatings, pulsed laser deposition (PLD) shows some advantages in controlling the coatings' crystal structure and composition. In this study, three types of HA target and two wavelengths of laser were used to produce calcium phosphate coatings. Despite PLDs ability to improve the crystal structure by incorporating water vapor into the deposition process, the characterization with EDX and XPS showed that coatings had different Ca/P ratios from that of the pure HA targets, which almost assured the presence of non-HA phases. FTIR spectra also showed differences in phosphate bands of coatings and targets although the difference in data collecting modes might have been a factor. The observed differences might be related to the differences between the surface and bulk chemistries of the coatings. Nevertheless, when evaluating the suitability of the PLD technique for making HA coatings, the possibility of the formation of non-HA phases cannot be excluded, although it may not necessarily be a negative factor.

Calcium Phosphates↗

PubMed2000

Regulated translation initiation controls stress-induced gene expression in mammalian cells.

Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis. Phenotypic analysis of targeted mutations in murine cells reveals a novel role for eIF2alpha kinases in regulating gene expression in the unfolded protein response (UPR) and in amino acid starved cells. When activated by their cognate upstream stress signals, the mammalian eIF2 kinases PERK and GCN2 repress translation of most mRNAs but selectively increase translation of Activating Transcription Factor 4 (ATF4), resulting in the induction of the downstream gene CHOP (GADD153). This is the first example of a mammalian signaling pathway homologous to the well studied yeast general control response in which eIF2alpha phosphorylation activates genes involved in amino acid biosynthesis. Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals.

Activating Transcription Factor 4↗

PubMed2000

Perk is essential for translational regulation and cell survival during the unfolded protein response.

Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation initiation. This response is believed to be mediated by increased phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and is hypothesized to reduce the work load imposed on the folding machinery during stress. Here we report that mutating the gene encoding the ER stress-activated eIF2alpha kinase PERK abolishes the phosphorylation of eIF2alpha in response to accumulation of malfolded proteins in the ER resulting in abnormally elevated protein synthesis and higher levels of ER stress. Mutant cells are markedly impaired in their ability to survive ER stress and inhibition of protein synthesis by cycloheximide treatment during ER stress ameliorates this impairment. PERK thus plays a major role in the ability of cells to adapt to ER stress.

Adaptation, Physiological↗

PubMed2000

In vivo selection using a cell-growth switch.

A major obstacle to stem-cell gene therapy rests in the inability to deliver a gene into a therapeutically relevant fraction of stem cells. One way to circumvent this obstacle is to use selection. Vectors containing two linked genes serve as the basis for selection, with one gene encoding a selectable product and the other, a therapeutic protein. Applying selection in vivo has the potential to bring a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically modified cells to be inducibly amplified, thereby averting the risks associated with cytotoxic drugs. This system provides a general platform for conditionally expanding genetically modified cell populations in vivo, and may have widespread applications in gene and cell therapy.

Animals↗

PubMed2000

Topical photodynamic therapy with 5-aminolaevulinic acid does not induce hair regrowth in patients with extensive alopecia areata.

BACKGROUND: Photodynamic therapy (PDT) is a new modality involving the administration of a photosensitizer, or photosensitizer precursor, followed by its activation with light to generate a therapeutic effect. 5-Aminolaevulinic acid (ALA) is a photosensitizer precursor that is transformed by cells into protoporphyrin IX (PpIX), which can in turn be activated by red light. OBJECTIVES: To investigate the effect of PDT in alopecia areata (AA). METHODS: In six patients with extensive AA, topical ALA lotion at 5%, 10% and 20% as well as the vehicle lotion alone were applied separately to different scalp areas, followed 3 h later by exposure to red light at each treatment session. RESULTS: No significant hair growth was observed after 20 twice-weekly treatment sessions. A significant increase in erythema and pigmentation was observed for the three concentrations of ALA lotion vs. the vehicle, implying that a phototoxic PDT effect was achieved in the skin. In vivo fluorescence spectroscopy in one patient showed an increase in red PpIX fluorescence 3 h after ALA application followed by a decrease after light exposure. On fluorescence microscopy, bright red fluorescence was present in the epidermis and sebaceous glands, but not in the inflammatory infiltrate surrounding the hair follicle following ALA application. CONCLUSIONS: PDT was ineffective in the treatment of AA.

Adult↗

PubMed2000

Deuteron NMR investigation of a photomechanical effect in a smectic-A liquid crystal

Deuteron quadrupole-perturbed NMR is used to study the perturbation of orientational order in a smectic-A liquid crystal (octylcyanobiphenyl or 8CB) caused by photoinduced trans-to-cis isomerization of a photosensitive dopant (diheptylazobenzene or 7AB). The time and temperature dependences of the orientational order were independently studied for 8CB, 7AB, and their mixtures. Upon UV irradiation that causes trans-to-cis isomerization of 7AB, the orientational order parameter of the smectic-A phase is reduced. Relaxation in the dark exponentially restores the equilibrium value of the order parameter. The characteristic time for this process closely matches the lifetimes of the 7AB excited state. While in the 8CB smectic-A matrix, the cis-isomerized 7AB molecules retain a uniaxial orientational order with the director oriented along the normal to the smectic layers. The highly bent 7AB cis molecules act as a disorienting factor, decreasing the orientational order in the layers and causing a small increase in layer spacing. This disorder-induced increase in layer spacing is much smaller than the actual increase as observed by in situ x-ray experiments on UV-irradiated mixtures of 8CB:7AB. Concomitant with the experimental observation that only a fraction of 7AB molecules are converted to the cis state, this work provides indirect evidence for a nanophase segregation with the 7AB cis-isomers arranged within the interlayer space, thus significantly increasing the smectic layer spacing.

Journal Article↗

PubMed2000

CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo.

Hypertrophic growth is an adaptive response of the heart to diverse pathological stimuli and is characterized by cardiomyocyte enlargement, sarcomere assembly, and activation of a fetal program of cardiac gene expression. A variety of Ca(2+)-dependent signal transduction pathways have been implicated in cardiac hypertrophy, but whether these pathways are independent or interdependent and whether there is specificity among them are unclear. Previously, we showed that activation of the Ca(2+)/calmodulin-dependent protein phosphatase calcineurin or its target transcription factor NFAT3 was sufficient to evoke myocardial hypertrophy in vivo. Here, we show that activated Ca(2+)/calmodulin-dependent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in cardiomyocytes in vitro and that CaMKIV overexpressing mice develop cardiac hypertrophy with increased left ventricular end-diastolic diameter and decreased fractional shortening. Crossing this transgenic line with mice expressing a constitutively activated form of NFAT3 revealed synergy between these signaling pathways. We further show that CaMKIV activates the transcription factor MEF2 through a posttranslational mechanism in the hypertrophic heart in vivo. Activated calcineurin is a less efficient activator of MEF2-dependent transcription, suggesting that the calcineurin/NFAT and CaMK/MEF2 pathways act in parallel. These findings identify MEF2 as a downstream target for CaMK signaling in the hypertrophic heart and suggest that the CaMK and calcineurin pathways preferentially target different transcription factors to induce cardiac hypertrophy.

Animals↗

PubMed2000

[Improvement of pulse waveform detection with autoregressive model in blood oxygen saturation measurement].

Blood oxygen saturation is an important physiological parameter of human body. The accurate measurement of it is important to both physiological research and medical application. Dual-wavelength method is widely adopted in nonivasive detection of blood oxygen saturation. In this method, the calculation of blood oxygen saturation is based on the identification of pulse waveform and the extraction of peak characteristic values. But the pulse waveform obtained from this method merely has distinctive features such as the QRS complexes in ECG, so the ratio of correct detection of pulse waveform is always low. An autoregressive model of heart-beat intervals is developed. The output of the differential method is compared with that of the AR model so as to distinguish the false or missing detection. The ratio of correct detection is improved by the use of this method.

Models, Theoretical↗

PubMed2000

[Landscape structure of Longhua area in Shenzhen City during fast urbanization process--structure and heterogeneity analysis of urban construction area].

Remotely sensed mapping information of multi-period of time and methods of landscape pattern analysis were used to study the structure and spatial distribution characteristics of two types of land use, built-up areas and new developing areas, during the fast urbanization process in Longhua area, Shenzhen City. The results indicated that from 1988 to 1996, the patch number and average size in the two types of land use increased significantly, but the fragmentation degree decreased. The increase of constructed land use could be divided into two patterns, continued expanding of big residential patches and continuous appearing of new isolated small patches, and most of the new developing area was constructed from 1990 to 1994. Under the impacts of topography and traffic, the built-up areas showed macroscopic spatial distribution with decreasing lacunarity values. Distribution difference of constructed patches was very obvious in small and moderate scales. The new developing patches, affected by the conditions as the built-up areas, were also characteristic of macroscopic heterogeneity, but the expression scale of heterogeneity was larger than the built-up areas. The fast expanding of the constructed land use produced some very negative ecological problems, which should urgently be resolved by adjusting the land use polices.

China↗

PubMed2000

Effect of intravenous nitroglycerin on hemodynamics in infants and children with congestive heart failure.

OBJECTIVE: To understand the effect of intravenous nitroglycerin (NTG) on hemodynamics in infants and small children with congestive heart failure secondary to congenital cardiac defect of left to right shunt. METHODS: Heart rate, blood pressure and total peripheral resistance were monitored continuously. Echocardiography was used to measure ejection fraction, fractional shortening, end-diastolic volume index of left ventricle, pulmonary capillary wedge pressure, pulmonary artery mean pressure and left ventricular wall stress before the use and during 0.5, 1.0, 1.5, 2.5, and 5.0 micrograms.kg-1.min-1 dosages of nitroglycerin (NTG). RESULTS: There was no significant difference in the indexes of heart rate, blood pressure, ejection fraction and fractional shortening of left ventricle, stroke volume index, cardiac output index, end-diastolic volume index before the use and after the use of NTG. Pulmonary capillary wedge pressure decreased from 15.5 +/- 2.3 mm Hg before the use of NTG to 14.3 +/- 2.2 mm Hg after the use of 0.5 microgram.kg-1.min-1 NTG (P < 0.05), minimum to 12.3 +/- 2.4 mm Hg; left ventricular wall stress I, II and III decreased from 407 +/- 65 dyn.cm-2.10(3), 166 +/- 48 dyn.cm-2.10(3), 255 +/- 52 dyn.cm-2.10(3) to 357 +/- 75 dyn.cm-2.10(3), 136 +/- 48 dyn.cm-2.10(3), 218 +/- 52 dyn.cm-2.10(3) (P < 0.05), minimum to 321 +/- 50 dyn.cm-2.10(3), 114 +/- 42 dyn.cm-2.10(3), 187 +/- 42 dyn.cm-2.10(3), respectively. Total peripheral resistance and pulmonary artery mean pressure were decreased when the dosage of intravenous NTG was increased to above 2.5 micrograms.kg-1.min-1 (P < 0.05). There was no statistical difference in the above indexes of the different dosages. CONCLUSION: Congestive heart failure secondary to congenital cardiac defect of left to right shunt in infants and small children is the indication of using intravenous NTG which could improve hemodynamics. There was different selectivity in dosage between arterial and venous vasodilatation, and the change in hemodynamics was independent of dosage. The dosages of 0.5-1.0 microgram.kg-1.min-1 NTG are recommended when the decrease of cardiac preload is the main point of therapy of heart failure.

Dose-Response Relationship, Drug↗

PubMed2000

[Infusion chemotherapy and chemoembolization of liver metastases from cancer of the alimentary tract].

OBJECTIVE: To evaluate the efficacy of hepatic artery infusion chemotherapy and chemoembolization in the treatment of liver metastases from alimentary tract cancer. METHODS: A total of 92 patients with unresectable liver metastases from alimentary tract cancer was treated 316 times by hepatic artery infusion chemotherapy and chemoembolization. Of the 92 patients, only infusion chemotherapy was performed in 29 patients, and infusion chemotherapy and chemoembolization in 63 patients. Chemotherapy was carried out with a combination of epirubicin and/or cisplatin, mitomycin-C, calcium folinate and 5-fluorouracil. Embolization was accomplished with lipiodol ultra-fluid or lipiodol ultra-fluid and gelatin sponge. Response rates were assessed by CT scanning. RESULTS: An overall response rate (CR + PR) of the cases was 45.7%. The mean survival period of 92 patients was 19.6 months. The 0.5-, 1-, 2-, 3- and 5-year survival rate was 95.7%, 73.8%, 30.9%, 17.6% and 9.9%, respectively. Best therapeutic results were obtained in 9 cases with single metastatic focus in the liver, with a mean survival period of 31.2 months. There was no severe side effect or complication. CONCLUSION: Treatment by transcatheter hepatic artery infusion chemotherapy and chemoembolization is beneficial to patients with metastatic cancer of the liver.

Adult↗

PubMed2000

[A clinicopathological study of hepatic focal nodular hyperplasia].

OBJECTIVE: To study the clinicopathological features of focal nodular hyperplasia (FNH). METHODS: The clinicopathological characteristics of 25 cases of FNH were studied retrospectively. 20 cases followed for 6 to 47 months. All were evaluated by use of paraffin-embedded sections, special and immunohistochemical staining (EnVision method) and electron microscope. RESULTS: 17 female and 8 male FNH patients aged 14 to 58 (median 38) years of age, all alpha-fetoprotein negative, asymptomatic and normal biochemical liver tests in most cases. The macroscopic hallmark is a central stellate fibrotic scar, composed of fibrous connective tissue and tortuous blood vessels, the fibrous tissue radiated peripherally, dividing the mass into multiple, variably sized nodules, simulating the pattern of cirrhosis. Microscopically, multinodular proliferation of benign-appearing hepatocytes separated by bile-duct-containing fibrous septae that radiate from the central scar. Internodular bile duct proliferation is abundant and merge imperceptibly with the hepatocyte elements near the fibrous septa. Immunohistochemically, the keratin expessed by hepatocytes and by the proliferated bile ducts were similar. Electron microscopic examination found that the ultrastructure of tumor cells were similar to normal hepatocytes. 20 cases were followed for 6-47 months, all survived with no recurrence. CONCLUSION: FNH is a benign hepatocytic lesion, i.e. a reactive proliferation of hepatic cells to local blood vessel anomalies.

Adolescent↗