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Biomedical subjects

L Huang

Publications and source records attributed to L Huang.

At least 37 records · Page 2Linked to original sources

Molecular tagging of a senescence gene by introgression mapping of a stay-green mutation from Festuca pratensis.

* Intergeneric hybrids between Lolium multiflorum and Festuca pratensis (Lm/Fp) and their derivatives exhibit a unique combination of genetic and cytogenetic characteristics: chromosomes undergo a high frequency of homoeologous recombination at meiosis; the chromosomes of the two species can easily be discriminated by genomic in situ hybridization (GISH); recombination occurs along the entire length of homoeologous bivalents; a high frequency of marker polymorphism is observed between the two species. * This combination of characters has been used to transfer and isolate a F. pratensis chromosome segment carrying a mutant 'stay-green' gene conferring a disrupted leaf senescence phenotype into L. multiflorum. * The genetic location within the introgressed F. pratensis segment of the senescence gene has been mapped using amplified fragment length polymorphisms (AFLPs), and F. pratensis-specific AFLP markers closely flanking the green gene have been cloned. * The use of these cloned sequences as markers for the stay-green locus in marker-assisted selection programmes has been tested. The potential application of Lm/Fp introgressions as a tool for the map-based cloning of introgressed Fp genes is discussed.

Chromosome Mapping↗

A study of active tonal noise control for a small axial flow fan.

Sound radiated by a computer cooling fan consists of tones which are phase locked with the rotation, and other less deterministic tones and broadband random noise. This paper demonstrates the feasibility of globally eliminating the rotation-locked tones by applying a very simple destructive interference to a modified cooling fan with the number of struts equal to the number of rotor blades. The rig consists of a miniature electret microphone used as a rotation sensor, an ordinary loudspeaker, and a bandpass filter with adjustable amplitude and phase delay. The microphone is located at the inlet bellmouth of the fan to pick up the fluctuating aerodynamic pressure caused by the passing rotor blades. The pressure spectrum is rich in the blade passing frequency (BPF) and its low-order harmonics. It provides much better performance than a pulse-generating tachometer. Analysis of the original fan noise shows that about 90% of the radiated tonal sound is phase locked with rotation, and this portion is almost completely eliminated in all directions. The reductions of the radiated sound power in the first two BPFs are 18.5 and 13.0 dB, respectively, and the overall sound power reduction is 11.0 dB.

Journal Article↗

Benchmark data and power calculations for evaluating disease outbreak detection methods.

INTRODUCTION: Early detection of disease outbreaks enables public health officials to implement immediate disease control and prevention measures. Computer-based syndromic surveillance systems are being implemented to complement reporting by physicians and other health-care professionals to improve the timeliness of disease-outbreak detection. Space-time disease-surveillance methods have been proposed as a supplement to purely temporal statistical methods for outbreak detection to detect localized outbreaks before they spread to larger regions. OBJECTIVE: The aims of this study were twofold: 1) to design and make available benchmark data sets for evaluating the statistical power of space-time early detection methods and 2) to evaluate the power of the prospective purely temporal and space-time scan statistics by applying them to the benchmark data sets at different parameter settings. METHODS: Simulated data sets based on the geography and population of New York City were created, including effects of outbreaks of varying size and location. Data sets with no outbreak effects were also created. Scan statistics were then run on these data sets, and the resulting power performances were analyzed and compared. RESULTS: The prospective space-time scan statistic performs well for a spectrum of outbreak models. By comparison, the prospective purely temporal scan statistic has higher power for detecting citywide outbreaks but lower power for detecting geographically localized outbreaks. CONCLUSIONS: The benchmark data sets created for this study can be used successfully for formal statistical power evaluations and comparisons. If an anomaly caused by an outbreak is local, purely temporal surveillance methods might be unable to detect it, in which case space-time methods would be necessary for early detection.

Benchmarking↗

Observation of a threshold enhancement in the plambda invariant-mass spectrum.

An enhancement near the m(p)+M(Lambda) mass threshold is observed in the combined pLambda and pLambda invariant-mass spectrum from J/psi-->pK(-)Lambda;+c.c. decays. It can be fit with an S-wave Breit-Wigner resonance with a mass m=2075+/-12(stat)+/-5(syst) MeV and a width of Gamma=90+/-35(stat)+/-9(syst) MeV; it can also be fit with a P-wave Breit-Wigner resonance. Evidence for a similar enhancement is also observed in psi(')-->pK(-)Lambda;+c.c. decays. The analysis is based on samples of 5.8x10(7)J/psi and 1.4x10(7)psi(') decays accumulated in the BES II detector at the Beijing Electron-Positron Collider.

Journal Article↗

Microemulsification of triglyceride sebum and the role of interfacial structure on bicontinuous phase behavior.

A unique triblock surfactant is reported that allows for the efficient microemulsification of triglycerides. Unlike the results of all previous efforts, these triglyceride microemulsions can be formed without the use of cosurfactants or dilution with co-oils and follow the classical patterns of surfactant phase behavior exhibited by mixtures of water, alkane oils, and nonionic oligoethylene glycol surfactants, i.e., progression from oil/water emulsions to one-phase microemulsions to water/oil emulsions with increasing temperature. Lamellar phases that usually dominate the aqueous phase behavior of surfactant/triglyceride mixtures are suppressed, allowing for the formation of single-phase microemulsions containing equal amounts of triglyceride and water. These isotropic and low-viscous fluids are particularly useful for cleansing and delivery of functional ingredients in skin care products. The effects of mixing a variety of typical skin care ingredients and components of sebum (skin oil) were also explored. Fatty acids significantly reduce the average microemulsion temperature, while other ingredients and oils, which do not partition at the oil/water interface, have less impact on the phase behavior. In all cases, one-phase microemulsions containing equal amounts of oil and water can be formed even at high additive concentrations. Indeed, partial replacement oftriglyceride with any of the additives examined consistently reduced the amount of surfactant necessary to form single-phase microemulsions. However, the greatest boost in surfactant efficiency was found with the addition of medium molecular weight amphiphilic block copolymers.

Emulsions↗

Ethical consideration of incidental findings on adult brain MRI in research.

OBJECTIVE: To characterize the frequency and severity of incidental findings in brain MRIs of young and older adult research volunteers, and to provide an evaluation of the ethical challenges posed by the detection of such findings. METHODS: The authors reviewed 151 research MRI scans obtained retrospectively from subjects recruited to studies as healthy volunteers. Incidental findings were classified into four categories: no referral, routine, urgent, or immediate referral. p Values for significance were computed from chi(2) tests of contingency. RESULTS: Of 151 studies, the authors found an overall occurrence of incidental findings having required referral of 6.6%. By age, there were more findings in the older cohort (aged >60 years) than in the younger cohort (p < 0.05) and in more men than women in the older cohort (p < 0.001). Three of four (75%) findings in the younger cohort were classified in the urgent referral category; 100% of the findings in the older cohort were classified as routine (p < 0.05). CONCLUSION: The significant presence but different characteristics of incidental findings in young and older subjects presumed to be neurologically healthy suggest that standards of practice are needed to guide investigators in managing and communicating their discovery.

Adolescent↗

Observation of the decay psi(2S)-->K0SK0L.

The decay psi(2S)-->K(0)(S)K(0)(L) is observed using psi(2S) data collected with the Beijing Spectrometer at the Beijing Electron-Positron Collider; the branching fraction is determined to be B(psi(2S)-->K(0)(S)K(0)(L))=(5.24+/-0.47+/-0.48)x10(-5). Compared with J/psi-->K(0)(S)K(0)(L), the psi(2S) branching fraction is enhanced relative to the prediction of the perturbative QCD "12%" rule. The result, together with the branching fractions of psi(2S) decays to other pseudoscalar meson pairs (pi(+)pi(-) and K+K-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.

Journal Article↗

Observation of many coherent oscillations for MeV protons transmitted through stacking faults.

High spatial resolution, high-contrast transmission channeling images of stacking faults in silicon have been produced using a beam of 2 MeV protons focused to a spot size of 60 nm. Over a narrow range of beam tilts to the (011) planes, up to ten periodic intensity oscillations are observed, providing evidence of a long-range coherency of the planar channeled trajectories. This behavior is characterized using Monte Carlo computer simulations, and a phase-space model of planar channeled ion interactions with stacking faults is developed which incorporates all observed channeling and blocking phenomena.

Journal Article↗

Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains.

The results of recent studies suggest that the mouse Sac (saccharin preference) locus is identical to the Tas1r3 (taste receptor) gene. The goal of this study was to identify Tas1r3 sequence variants associated with saccharin preference in a large number of inbred mouse strains. Initially, we sequenced approximately 6.7 kb of the Tas1r3 gene and its flanking regions from six inbred mouse strains with high and low saccharin preference, including the strains in which the Sac alleles were described originally (C57BL/6J, Sac(b); DBA/2J, Sac(d)). Of the 89 sequence variants detected among these six strains, eight polymorphic sites were significantly associated with preferences for 1.6 mm saccharin. Next, each of these eight variant sites were genotyped in 24 additional mouse strains. Analysis of the genotype-phenotype associations in all 30 strains showed the strongest association with saccharin preference at three sites: nucleotide (nt) -791 (3 bp insertion/deletion), nt +135 (Ser45Ser), and nt +179 (Ile60Thr). We measured Tas1r3 gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different Tas1r3 haplotypes and saccharin preferences. The results of these experiments suggest that the polymorphisms associated with saccharin preference do not act by blocking gene expression, changing alternative splicing, or interfering with protein translation in taste tissue. The amino acid substitution (Ile60Thr) may influence the ability of the protein to form dimers or bind sweeteners. Here, we present data for future studies directed to experimentally confirm the function of these polymorphisms and highlight some of the difficulties of identifying specific DNA sequence variants that underlie quantitative trait loci.

Animals↗

Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor of childhood. Significant proportions of these patients eventually develop pulmonary metastases and succumb to their disease even after conventional multi-agent chemotherapy and surgical excision. Matrix metalloproteinase (MMP)-2 induced degradation of blood vessel basement membranes is an important pre-requisite for tumor invasion and metastasis. Bisphosphonates (BPs) have been known to inhibit tumor growth and metastasis in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer, and may do so through inhibition of MMP secretion. We, therefore, tested the effect of BPs on tumor cell invasion, MMP-2 secretion, and apoptosis of osteosarcoma cell lines. PROCEDURE: Two osteosarcoma cell lines (SaOS-2, U(2)OS) were treated with alendronate (50, 100, and 150 microM) for 24 and 48 hr. Matrigel invasion assay was used to investigate the invasive potential of osteosarcoma cell lines before and after alendronate treatment. Real-time quantitative RT-PCR was used to determine the mRNA level of MMP-2 with and without alendronate treatment. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the cytokine level of MMP-2 secreted in the condition medium. BP-induced cell apoptosis was evaluated by fluorescent flow cytometric analysis. RESULTS AND CONCLUSIONS: The results showed that alendronate inhibited cell invasion of both osteosarcoma cell lines in a dose-dependent manner. Alendronate reduced the mRNA level and cellular level of MMP-2 in both cell lines in a time and dose-dependent manner. Alendronate also induced significant apoptosis in both cell lines. Our finding suggests that alendronate downregulates MMP-2 secretion and induces apoptosis in osteosarcoma cells, which may both contribute to the reduction of invasive potential of the tumor cells.

Alendronate↗

Bisphosphonates induce apoptosis of stromal tumor cells in giant cell tumor of bone.

Giant cell tumour of bone (GCT) is an aggressive primary neoplasm that results in the production of osteolytic lesions. Stromal cells, which form the main neoplastic component of this tumor, regulate the formation of osleoclast-like giant cells that are ultimately responsible for bone destruction. Bisphosphonates prevent bone resorption by inhibiting osteoclast activity and promoting osteoclast apoptosis, and they have been known to induce apoptosis of primary neoplastic cells such as those in breast and prostate cancers. We hypothesized that in bisphosphonates may induce apoptosis not only in osteoclast-like giant cells but also in neoplastic stromal cells of GCT both in vitro and in vivo. Twelve patients with GCT were treated with weekly injections of pamidronate for a period of 6 weeks prior to surgery. GCT specimens were collected at the time of biopsy and during definitive surgery. TUNEL assay was used to evaluate apoptotic DNA fragmentation in cells. In addition, twelve GCT primary cultures from these patients were treated with zoledronate, pamidronate, or alendronate for 48 hours at different doses (3, 30, or 150 microM) and subjected to apoptosis assay by flow cytometry following fluorescent Annexin-V labeling. The results showed that pamidronate significantly induced apoptosis in both osteoclast-like giant cells and stromal tumor cells, in vivo. All three bisphosphonates caused substantial apoptosis of stromal tumor cells in cultures. Zoledronate was the most potent reagent, resulting in an average cell death of 27.41% at 150 microM, followed by pamidronate (22.23%) and alendronate (15.3%). Our observations suggest that these drugs may be considered as potential adjuvants in the treatment of GCT.

Alendronate↗

Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone.

In giant cell tumour of bone (GCT), mononuclear stromal cells, which represent the neoplastic component of this lesion, regulate the formation of multinucleated osteoclast-like giant cells which are the characteristic hallmark of this tumour. However, the origin of stromal tumour cells has not yet been clearly defined. In this study, we evaluated several osteoblast markers including collagen type I, bone sialoprotein (BSP), osteonectin and osteocalcin in GCT using immunohistochemical techniques. Amongst the 13 GCT specimens and 7 GCT stromal cell (GCTSC) cultures studied, majority of the GCTSC synthesized type I collagen, BSP and osteonectin proteins but did not produce the differentiated osteoblast marker, osteocalcin. We further examined the regulation of several important osteogenic genes such as Cbfa-1, osterix and osteocalcin, and regulation of ALP activity in GCTSC in culture by bone morphogenetic protein 2 (BMP-2). Real-time PCR analysis indicated that Cbfa-1, osterix and osteocalcin mRNA were present in primary cultures of GCTSC. The addition of BMP-2 upregulated Cbfa-1 and osterix gene expression within 12 h and the enhancement was still observed at 24 h. ALP activity was minimal in untreated GCTSC in cultures. The number of ALP-positive GCTSC was significantly increased following treatment with BMP-2 or combinations with beta-glycerophosphate and ascorbic acid. In contrast, BMP enhancement of osterix mRNA level and ALP activity was also seen in SaOS2 osteoblast-like cells, but not in the primary culture of normal human skin fibroblasts. In summary, our data suggest that GCT stromal tumour cells may have an osteoblastic lineage and retain the ability to differentiate into osteoblasts.

Analysis of Variance↗

A tumour vaccine of fixed tumour fragments in a controlled-release vehicle with cytokines for therapy of hepatoma in mice.

BACKGROUND: Cytokines can be strong potentiators for a tumour vaccine, but they have very short life in vivo when administered as a solution. AIMS: To evaluate the slow release of interleukin 2 from a cytokine-vehicle in vitro and in vivo and to evaluate the anti-tumour activity of a new tumour vaccine in vivo. METHODS: The tumour vaccine was composed of formalin-fixed Hepa 1-6 hepatoma tissue fragments, tuberculin and a lipid based vehicle containing granulocyte-macrophage colony-stimulating factor and interleukin 2. The quantity of interleukin 2 release from the cytokine-vehicle in vitro and in vivo was determined by a proliferation assay with CTLL-2 cell line. Hepa 1-6 hepatoma model system with C57BL/6J mice was used to examine protective and therapeutic anti-tumour effect of the vaccine. RESULTS: Release of interleukin 2 from the cytokine-vehicle lasted 5 days in vitro and 3 days in vivo. The vaccine protected 67% of mice from a Hepa 1-6 cell challenge and had a therapeutic effect by prolonging the life span of mice bearing established Hepa 1-6 tumours of 5 mm in diameter. Of the treated mice, 20% became completely tumour-free. CONCLUSIONS: Formalin-fixed tumour fragments and cytokines in controlled-release vehicle are useful in the rational design of tumour vaccines.

Animals↗

Orientation bias of the extraclassical receptive field of the relay cells in the cat's dorsal lateral geniculate nucleus.

The spatial properties of the extraclassical receptive fields (ECRF) of neurons responding to a stimulus restricted to it and its interaction with the classical receptive field (CRF) in visual information processing were investigated in 74 relay cells in the dorsal lateral geniculate nucleus (LGNd) of anesthetized cats. The results demonstrate that the ECRF of most relay cells in the LGNd responded preferentially to a grating stimulus of low spatial frequency through a mechanism of spatial summation. These biased cells showed a significant orientation bias which was relatively smaller than that of the CRF. The preferred orientations of the ECRF were not correlated with those of the CRF in most relay cells. The orientation biased ECRFs and CRFs interacted with each other in a non-linear way, resulting in a great diversity of response properties. Overall, the CRF played a more significant role than the ECRF in determining a cell's orientation bias and preferred orientation. The ECRF mostly showed a modulatory role mainly in suppressing and/or in partially facilitating the neural response to stimulation in the CRF although in some cases, the ECRF did determine a cell's responsiveness and orientation sensitivity. These results suggest that the ECRF might contribute to the ability of the LGNd neurons to detect some complex features such as texture segmentation and provide a subcortical contribution to the integrative field of visual cortical cells through receiving inputs from retinal ganglion cells with similar orientation biased extended surrounds [Neuroscience 98 (2000) 207].

Action Potentials↗

Inhibition of human non-small cell lung tumors by a c-Met antisense/U6 expression plasmid strategy.

c-Met is a receptor tyrosine kinase whose activation by hepatocyte growth factor (HGF) can lead to transformation and tumorigenicity in a variety of tumors. We investigated the effects of suppressing c-Met protein expression in human non-small cell lung tumors. Expression plasmids containing either sense or antisense sequences of the human c-met gene were constructed under control of the U6 snRNA promoter. A U6 control plasmid was also constructed that did not contain any c-met sequence. These constructs have been examined both in vitro and in an in vivo tumor xenograft model. The c-Met protein was downregulated by 50-60% in two lung cancer cell lines that were transiently transfected with the c-Met antisense versus U6 control. Tumor cells treated with the c-Met antisense construct also show decreased phosphorylation of c-Met and MAP kinase when exposed to exogenous HGF. Lung cancer cells were grown as xenografts in mice and treated by intratumoral liposome-mediated transfer of the c-Met sense, antisense or U6 control plasmids. The treatment of lung tumors with c-Met antisense versus U6 control plasmid resulted in the downregulation of the c-Met protein expression, a 50% decrease in tumor growth over a 5-week treatment period and an increased rate of apoptosis. These results suggest that targeting the HGF/c-Met pathway may be an effective novel strategy to treat lung cancer patients.

Animals↗

Restoration of dystrophin expression in mdx mice by intravascular injection of naked DNA containing full-length dystrophin cDNA.

Duchenne muscular dystrophy (DMD) is a lethal, X-linked, recessive disease caused by a defect in the dystrophin gene. No effective therapy is available. Dystrophin gene transfer to skeletal muscle has been proposed as a treatment for DMD. However, successful treatment for DMD requires restoration of dystrophin in the affected muscle fibers to at least 20% of the normal level. Current gene transfer methods such as intramuscular injection of viral vector or naked DNA can only transfect a small area of muscle, and therefore is of little clinical utility. We have developed a semisystemic method for gene transfer into skeletal muscle of mdx mice, an animal model for DMD. Naked DNA was injected through the tail artery or vein of mice, in which the aorta and the vena cava were clamped at the location just below the kidneys. The DNA solution was thus forced into the blood vessels of both legs. Luciferase gene expression was detected in all muscle groups in both legs. The effects of injection speed, injection volume, and ischemia time on gene expression were also optimized. LacZ staining was used to check the spread of gene expression in muscle. Although the percentage of transfected fibers was modest (approximately 10%), beta-galactosidase was found in all muscle groups of both legs. Finally, plasmid DNA encoding full-length dystrophin gene was injected into mdx mice and widespread restoration of dystrophin protein was observed in all muscles of both hind limbs. In conclusion, these results demonstrate that the semisystemic delivery of naked DNA is a potential approach towards the long-term goal of gene therapy for DMD.

Animals↗