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Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 163 records · Page 9Linked to original sources
PubMed2000

[Study on the hepatitis virus infection among medical professionals].

OBJECTIVE: In order to find out the present situation of hepatitis virus infection among medical professionals. METHODS: 140 medical professionals were studied on their serum HBsAg, anti - HBs, anti - HCV using EIA, and HEV - IgG, HGV - IgG with ELISA. RESULTS: The infection rates of HBsAg, HCV, HEV and HGV of medical professionals were 7.8%, 1.4%, 7.1% and 7.1% respectively with an overall infection rate of 23.5%. The infection rates for the clinical group and the non - clinical group were 33.3% and 12.3% respectively [with significant differences (P < 0.01)]. The infection rates of HEV and HGV for the clinical group were 8.0% and 12.0% respectively. It was found no superimposing infection in non - clinical group but was in clinical group. CONCLUSION: The result suggested that the infection rate of hepatitis virus in the medical professionals in the clinical group was higher than in the non - clinical group.

Adult↗
PubMed2000

[The morphological characteristics of desmoplastic fibroblastoma].

OBJECTIVE: To study the clinical and pathological characteristics of desmoplastic fibroblastoma. METHODS: Three cases of desmoplastic fibroblastoma were evaluated by light microscopy and immunohistochemistry. RESULTS: The patients were all adults, 2 males and 1 female, age range 46 - 62 years (mean 53 years). Clinically, the tumors presented as slowly growing painless masses, which were located in the deep soft tissue of the lower extremity, the subcutaneous tissue of the forearm and the ankle respectively. Grossly, they were well-circumscribed neoplasms with a firm consistency. Histologically, the tumors were composed of paucicellular spindle or stellate-shaped fibroblastic cells embedded in a densely fibrous or fibromyxoid stroma. The neoplastic fibroblastic cells resembled the reactive fibroblasts by containing fine chromatin and small distinct nucleoli without cellular atypia or mitotic figures. Immunohistochemically, the neoplastic cells showed diffuse and strong immunoreactivity for vimentin, focal staining for alpha-SMA, MSA and desmin. CONCLUSION: Desmoplastic fibroblastoma is a benign fibroblastic neoplasm with distinctive clinical and pathological characteristics. It should be differentiated from a variety of reactive or low-grade fibroblastic lesions.

Actins↗
PubMed2000

[Analysis of the expression of BMP-2,3,4,5 in nerve sheath tumors of maxillofacial region].

OBJECTIVE: The aim of present study is to elucidate the relationship between the members of BMP family and the neoplasms of peripheral nerve. METHODS: Eight cases of schwannoma and three cases of malignant schwannoma were collected and all samples were fixed with 10% neutral formalin and embedded in paraffin wax. Five microns thickness sections were prepared for staining with haematoxylin and eosin for histopathological assessment and processed for in situ hybridization for assessing the mRNA transcriptions of BMP-2,3,4,5. Sections of osteosarcoma that previously demonstrated consistent expression of BMP-2 mRNA were included in each batch of staining to serve as positive control. RESULTS: The results showed that all of the neoplastic lesions of nerve sheath showed a consistent expression of BMP-2,3,4,5. The positive signals of benign lesions were obviously increased in the palisading area or the area of accumulated cells. There was no detectable staining in the matrix of tumour and collagenous fiber. The staining intensity was relatively and slightly weak in cells of Antoni B tissue when compared with Antoni A tissue. Nevertheless, the tumour cells in Antoni B tissue also showed BMP-2,3,4 and 5 positively staining. The fibroblasts of schwannoma were negatively stained. The malignant lesions showed higher expression signals of BMPs than benign lesions. CONCLUSION: The results can be concluded that the selected members of BMPs may be involved in the process of growth and progression of the neoplasms of peripheral nerve.

Adult↗
PubMed2000

[The quantitative analysis of cyclin D1 expression in RA-treated and non-RA-treated ectomesenchymal cells in vitro].

OBJECTIVE: To elucidate the alteration of Cyclin D1 protein between RA-treated and the non-RA-treated ectomesenchymal cells in embryonic mice. METHODS: Ectomesenchymal cells in the developing orofacial processes were explanted from embryonic BALB/c mice on generation day 12(15) (the 15th hour of the 12th day). Primary cells were cultured using the tissue mass method. The variants of growth curves were examined in the RA-treated and normal groups. Protein of Cyclin D1 was detected using immunohistochemistry. The positive degree of Cyclin D1 staining was analyzed using image analysis. RESULTS: The findings showed that the growth of ectomesenchymal cells was inhibited dramatically. Cyclin D1 expressed strongly in normal ectomesenchymal cells. However, its expression decreased evidently after RA-treated. There was significant difference between the test group and the normal group (P < 0.01). CONCLUSION: Low expression of Cyclin D1 may contribute to the inhibition of ectomesenchymal cells. It is necessary for Cyclin D1 to express appropriately during the normal meiosis of ectomesenchymal cells.

Animals↗
PubMed2000

[Study on optical properties and synthesis of nanosized GeO2-SiO2 glasses].

The compound material of nm size particles GeO2-SiO2 was synthesized through hydrolysis of Si(OC2H5)4 and GeCl4 with pH-2. A heat-treatment was carried out for samples at 100-1,200 degrees C in air. Its optical property was determined by UV-Vis spectrum. We have found that the absorption edge of spectrum shifted progressively to longer wavelengths. The quantum size effect of nanocrystals appears because crystals grow and the energy of optical band gap reduces due to the influence of temperature. By the analysis of X-ray diffraction we have observed the process in which the structure of particles changed from disorder into order, and the particles with size 5-10 nm came into obviously as temperature increased until 1,100 degrees C.

Gels↗
PubMed1999

Systemic delivery of antiangiogenic adenovirus AdmATF induces liver resistance to metastasis and prolongs survival of mice.

Systemic administration of Ad5-based recombinant adenovirus leads to preferential transduction of the liver. Using this property, we have assessed the potential of venous viral injection to deliver a recombinant antiangiogenic adenovirus to treat cancer dissemination and improve survival. The results demonstrate that venous injection of adenovirus AdmATF, which encodes a secretable mouse ATF (amino-terminal fragment of urokinase) known to inhibit angiogenesis, suppressed angiogenesis induced by colon cancer metastasis growth in mice liver and improved survival. Nude mice were injected intravenously with 5 X 10(9) PFU of AdmATF and subsequently challenged after a 3-day interval by intrasplenically injected human colon carcinoma cells (LS174T, 3 x 10(6)) that home to liver. Microscopic inspection revealed that, within the AdmATF-pretreated mice (n = 8), the size and number of liver-metastasized nodules on day 30 were remarkably reduced (80% in number, p < 0.05) compared with control mice (n = 7) pretreated in parallel with a control adenovirus. Metastatic growth-related liver weight gain was also inhibited up to 90%. AdmATF-specific capability that offers liver resistance to the apparition and growth of liver metastasis was shown to correlate with the inhibition of peritumoral and intratumoral angiogenesis (reduced by 79%, p < 0.01 as shown by anti-vWF immunostaining of liver sections) and a twofold increase in tumor necrotic area and an eightfold increase in apoptotic tumor cell number. This protective effect was still observed when the mice were challenged 10 days after venous AdmATF injection (visible metastasis nodules: 6.3+/-3.1, n = 7 for control mice versus 2.7+/-2.9, n = 10 for treated mice, p < 0.05). More importantly, the mean survival has been prolonged from 45.1 days (n = 9) to 83.3 days (n = 10, p < 0.05). Altogether, the high efficacy, although transient, in this experimental mice model strongly advocates the plausibility of transforming the liver into a dissemination resistant organ by antiangiogenic gene therapy through systemic delivery approach.

Adenoviridae↗
PubMed1999

Assembly of AUF1 oligomers on U-rich RNA targets by sequential dimer association.

Many labile mammalian mRNAs are targeted for rapid cytoplasmic turnover by the presence of A + U-rich elements (AREs) within their 3'-untranslated regions. These elements are selectively recognized by AUF1, a component of a multisubunit complex that may participate in the initiation of mRNA decay. In this study, we have investigated the recognition of AREs by AUF1 in vitro using oligoribonucleotide substrates. Gel mobility shift assays demonstrated that U-rich RNA targets were specifically bound by AUF1, generating two distinct RNA-protein complexes in a concentration-dependent manner. Chemical cross-linking revealed the interaction of AUF1 dimers to form tetrameric structures involving protein-protein interactions in the presence of high affinity RNA targets. From these data, a model of AUF1 association with AREs involving sequential dimer binding was developed. Using fluorescent RNA substrates, binding parameters of AUF1 dimer-ARE and tetramer-ARE equilibria were evaluated in solution by fluorescence anisotropy measurements. Using two AUF1 deletion mutants, sequences C-terminal to the RNA recognition motifs are shown to contribute to the formation of the AUF1 tetramer.ARE complex but are not obligate for RNA binding activity. Kinetic studies demonstrated rapid turnover of AUF1.ARE complexes in solution, suggesting that these interactions are very dynamic in character. Taken together, these data support a model where ARE-dependent oligomerization of AUF1 may function to nucleate the formation of a trans-acting, RNA-destabilizing complex in vivo.

Base Sequence↗
PubMed1999

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.

Journal Article↗
PubMed1999

Mechanical unfolding intermediates in titin modules.

The modular protein titin, which is responsible for the passive elasticity of muscle, is subjected to stretching forces. Previous work on the experimental elongation of single titin molecules has suggested that force causes consecutive unfolding of each domain in an all-or-none fashion. To avoid problems associated with the heterogeneity of the modular, naturally occurring titin, we engineered single proteins to have multiple copies of single immunoglobulin domains of human cardiac titin. Here we report the elongation of these molecules using the atomic force microscope. We find an abrupt extension of each domain by approximately 7 A before the first unfolding event. This fast initial extension before a full unfolding event produces a reversible 'unfolding intermediate' Steered molecular dynamics simulations show that the rupture of a pair of hydrogen bonds near the amino terminus of the protein domain causes an extension of about 6 A, which is in good agreement with our observations. Disruption of these hydrogen bonds by site-directed mutagenesis eliminates the unfolding intermediate. The unfolding intermediate extends titin domains by approximately 15% of their slack length, and is therefore likely to be an important previously unrecognized component of titin elasticity.

Biomechanical Phenomena↗
PubMed1999

Fine chemical manipulations of microscopic liquid samples. 2. Consuming and nonconsuming schemes.

Microscopic liquid particles can be manipulated chemically using a suitable diffusional microburet (DMB), whose tiny tip plugged with a diffusion membrane acts as a well-defined diffusional transfer channel. In part 1 of this work (Gratzl et al. Anal. Chem. 1999, 71, 2751-2756), we discussed the simplest DMB-based operation: addition, i.e., loading a droplet with a chemical that accumulates there without any chemical reaction occurring. Since in this process no consumption of the delivered molecules in the target droplet takes place, addition is a nonconsuming scheme. In this work, another type of nonconsuming scheme is explored, which is the subtraction of a substance from droplets via a DMB. This process has no analogy among macroscopic chemical operations. Both addition and subtraction occur according to an exponential asymptotic process when diffusion is at quasisteady state inside the DMB tip. These nonconsuming operations were characterized using the transport of microscopic quantities of Lucifer Yellow CH, a fluorescent dye, under a fluorescent microscope. The third basic type of chemical manipulation is when the substance delivered by a DMB is consumed in the target droplet instantaneously by a fast chemical reaction. This consuming scheme was studied by delivering EDTA into droplets containing Pb2+ ions and a color indicator. These microscopic titrations were monitored using gray scale transmittance images of the droplets as recorded versus time. A unified theory of the three basic DMB operations is also presented.

Chemistry Techniques, Analytical↗
PubMed1999

Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration.

To differentiate the unique and overlapping functions of LFA-1 and Mac-1, LFA-1-deficient mice were developed by targeted homologous recombination in embryonic stem cells, and neutrophil function was compared in vitro and in vivo with Mac-1-deficient, CD18-deficient, and wild-type mice. LFA-1-deficient mice exhibit leukocytosis but do not develop spontaneous infections, in contrast to CD18-deficient mice. After zymosan-activated serum stimulation, LFA-1-deficient neutrophils demonstrated activation, evidenced by up-regulation of surface Mac-1, but did not show increased adhesion to purified ICAM-1 or endothelial cells, similar to CD18-deficient neutrophils. Adhesion of Mac-1-deficient neutrophils significantly increased with stimulation, although adhesion was lower than for wild-type neutrophils. Evaluation of the strength of adhesion through LFA-1, Mac-1, and CD18 indicated a marked reduction in firm attachment, with increasing shear stress in LFA-1-deficient neutrophils, similar to CD18-deficient neutrophils, and only a modest reduction in Mac-1-deficient neutrophils. Leukocyte influx in a subcutaneous air pouch in response to TNF-alpha was reduced by 67% and 59% in LFA-1- and CD18-deficient mice but increased by 198% in Mac-1-deficient mice. Genetic deficiencies demonstrate that both LFA-1 and Mac-1 contribute to adhesion of neutrophils to endothelial cells and ICAM-1, but adhesion through LFA-1 overshadows the contribution from Mac-1. Neutrophil extravasation in response to TNF-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased.

Animals↗
PubMed1999

Use of ion chromatography for the determination of heavy and transition metals in biochemical samples.

A novel, highly sensitive method for simultaneous separation and determination of Cu2+, Ni2+, Zn2+, Cd2+, Co2+, Mn2+ and Pb2+ in biochemical samples was developed and evaluated by ion chromatography. All of these metals were well separated on a bifunctional ion-exchange column by a concentration gradient of oxalic acid and sodium chloride eluents, coupled with spectrophotometric detection after post-column derivatization with 2-[(5-bromo-2-pyridyl)azo]-5-diethylaminophenol at 560 nm. The method detection limits (signal-to-noise 3:1) were at microg l(-1) levels. The calibration graphs were linear (r2>0.999) over two-orders of magnitude. This technique was optimized and validated by analyzing five standard biochemical references.

Animals↗
PubMed1999

The p38MAPK inhibitor SB203580 alleviates ultraviolet-induced phosphorylation at serine 389 but not serine 15 and activation of p53.

Phosphorylation of p53 at serine 389 has been shown to be responsive uniquely to UV but not gamma irradiation. This report describes identification of the UV-responsive p38MAPK protein as a serine 389 kinase. The immunoprecipitated p38MAPK from UV-irradiated murine embryonic testicular carcinoma F9 cells phosphorylated the serine 392 residue but not serine 15 of the human p53 protein in vitro and this phosphorylation was inhibited by a p38MAPK-specific chemical inhibitor SB203580. The inhibitor also remarkably alleviated the UV-caused induction and serine 389 but not serine 15 phosphorylation of the murine p53 protein in vivo. Subsequently, this compound suppressed transcriptional activity of p53 and partially retarded UV-induced apoptosis. Moreover, p53 bound to p38 as revealed by immunoprecipitation with anti-p53 antibodies from UV-treated F9 cells. Thus, these results suggest that UV-stimulated p53 phosphorylation at serine 389 is mediated by the stress-responsive p38MAPK.

Animals↗
PubMed1999

Fine chemical manipulations of microscopic liquid samples. 1. Droplet loading with chemicals.

Physically and chemically stable microscopic aqueous droplets of nano-, pico-, and femtoliter volumes were made and kept under heptane. Such droplets can contain chemicals of interest in pico-, femto-, and attomole amounts or less. Their fine chemical manipulation was achieved by a diffusional microburet (DMB), which consists of a pulled glass capillary whose microscopic tip is filled with a tiny diffusion membrane of agar or polyacrylamide gel. Once this tip is moved into a target droplet by a fine micromanipulator under a microscope, diffusional reagent delivery from the DMB body begins, driven by the concentration gradient within the tip. This system was tested in this work by delivering an inert fluorescent dye, Lucifer Yellow CH, into buffer droplets while fluorescence intensity in each droplet was recorded. An exponential decay of delivery rate was observed corresponding to an exponential saturation process for the accumulation of the delivered chemical inside the target droplet.

Chemistry Techniques, Analytical↗
PubMed1999

Monitoring drug efflux from sensitive and multidrug-resistant single cancer cells with microvoltammetry.

Multidrug resistance (MDR) is the eventual cross-resistance of certain cancer cells to a series of chemically unrelated drugs. It is attributed to a number of possible biophysical processes, one of them being increased drug efflux from resistant cells which leads to a decreased intracellular drug accumulation and retention. In this work, a carbon fiber microdisk electrode was used to monitor directly doxorubicin efflux from single preloaded cancer cells. Electrochemical cleaning, adsorptive preconcentration, and an electrocatalytic effect due to ambient oxygen made it possible to detect eventually very low drug concentrations (down to 1 nM) at good temporal resolution (down to 30 s/measurement) very close (< or = 1 micron) to single cancer cells for the first time. The results from a sensitive (AUXB1) and a drug-resistant (CHRC5) version of Chinese hamster ovarian cancer cells show that resistant cells exhibit a much higher initial efflux rate and shorter efflux time constant when both cell lines are preloaded up to the same intracellular drug concentration. These observations are consistent with results obtained from populations of the same cells by conventional techniques, proving that microvoltammetry can be used to monitor doxorubicin efflux at the single-cell level. Compared with existing methodologies, however, whose data represent only average cell behavior at typically low temporal resolution, the technique described here can provide information on the microheterogeneity of cancer cell populations in terms of drug efflux at high temporal resolution. The actual driving force of efflux is obtained since concentrations are measured directly at individual cells. This approach may lead to important new information on the mechanisms and prospective treatments of MDR.

Animals↗
PubMed1999

p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage.

The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents and contributes to the induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms. Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage.

Animals↗
PubMed1999

Steered molecular dynamics simulations of force-induced protein domain unfolding.

Steered molecular dynamics (SMD), a computer simulation method for studying force-induced reactions in biopolymers, has been applied to investigate the response of protein domains to stretching apart of their terminal ends. The simulations mimic atomic force microscopy and optical tweezer experiments, but proceed on much shorter time scales. The simulations on different domains for 0.6 nanosecond each reveal two types of protein responses: the first type, arising in certain beta-sandwich domains, exhibits nanosecond unfolding only after a force above 1,500 pN is applied; the second type, arising in a wider class of protein domain structures, requires significantly weaker forces for nanosecond unfolding. In the first case, strong forces are needed to concertedly break a set of interstrand hydrogen bonds which protect the domains against unfolding through stretching; in the second case, stretching breaks backbone hydrogen bonds one by one, and does not require strong forces for this purpose. Stretching of beta-sandwich (immunoglobulin) domains has been investigated further revealing a specific relationship between response to mechanical strain and the architecture of beta-sandwich domains.

Computer Simulation↗