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Biomedical subjects

Lin Li

Publications and source records attributed to Lin Li.

At least 37 records · Page 2Linked to original sources

Serial cytogenetic alterations resulting in transformation of a low-grade follicular lymphoma to Burkitt lymphoma.

Follicular lymphoma (FL) is the most common indolent or low-grade non-Hodgkin lymphoma (NHL). Histologic transformation to high-grade lymphoma, generally to diffuse large B-cell lymphoma, occurs in 25-35% of cases. Although t(14;18), the cytogenetic hallmark of FL, has been found in approximately 85% of these cases, multiple secondary cytogenetic and molecular genetic changes underlie the transformation process. We report the case of a 58-year-old patient who presented with stage IVA, grade 2 FL that subsequently transformed to Burkitt lymphoma. Multiple chromosomal aberrations, including three novel translocations, were observed related to this transformation. Inversion (1)(p36.3q12) and t(3;14;18)(p23;q32;q21) occurred prior to transformation and may have contributed to the transformation process. A t(1;11)(q25;q13) was acquired simultaneously with t(8;22) and, in conjunction with other chromosomal abnormalities, coincided with an extremely aggressive clinical course. The frequent breakage of 1q observed in this case suggests that the region harbors important genomic signals for the transformation of FL.

Bone Marrow↗

Estrogen receptor-alpha phosphorylated at Ser118 is present at the promoters of estrogen-regulated genes and is not altered due to HER-2 overexpression.

Detection of estrogen receptor (ER)-alpha phosphorylated at Ser(118) (P-Ser(118)-ER-alpha) may be an indicator of an intact ligand-dependent ER-alpha in breast tumors in vivo and may predict responsiveness to endocrine therapy. The current study addresses whether P-Ser(118)-ER-alpha is functionally involved in ER target gene transcription and if this is modulated by HER-2 overexpression. Using chromatin immunoprecipitation analysis, P-Ser(118)-ER-alpha was found associated with the promoters of several estrogen-regulated genes in MCF-7 breast cancer cells 30 minutes following estrogen treatment. Coactivators AIB1 and p300 were coimmunoprecipitated with P-Ser(118)-ER-alpha following estrogen treatment. The overexpression of HER-2 protein in MCF-7 cells did not affect estrogen induction of phosphorylation of Ser(118) or its presence at the promoters of several estrogen-regulated genes. U0126, an inhibitor of mitogen-activated protein kinase (MAPK) pathway, had no effect on P-Ser(118)-ER-alpha. The lack of effect of HER-2 overexpression on P-Ser(118)-ER-alpha expression in cell models is supported by similar levels of expression of P-Ser(118)-ER-alpha in ER(+)/HER-2-overexpressing and ER(+)/HER-2(-) breast tumors in vivo. Using inhibitors of cyclin-dependent kinase 7 (Cdk7), [(5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole and 2-(R)-1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine], and IkappaB kinase-alpha (IKK-alpha; BAY-11-7082), we show that IKK-alpha, but not Cdk7, is at least in part involved in estrogen-mediated phosphorylation at Ser(118) in MCF-7 cells. Our data provide direct evidence for a functional role of P-Ser(118)-ER-alpha in estrogen-regulated signaling and do not support the hypothesis that resistance of breast tumors to tamoxifen therapy involves ligand independent activation of ER-alpha due to constitutive phosphorylation of Ser(118) by constitutive activation of MAPK pathway.

Breast Neoplasms↗

Effects of small interference RNA against PTP1B and TCPTP on insulin signaling pathway in mouse liver: evidence for non-synergetic cooperation.

Metabolic deregulation accompanying type II diabetes is characterized by insulin resistance in peripheral tissues (liver, muscle, and adipose), mediated by impairments in insulin receptor (IR) signaling. Two closely-related protein tyrosine phosphatases, PTP1B and TCPTP both showed abilities to negatively regulate insulin receptor signaling. In order to test whether these two phosphatases can act synergistically, hydrodynamic injection was applied to deliver small interfering RNA (siRNA) of PTP1B and/or TCPTP to mouse liver. By measuring insulin-sensitive reporter gene expression and plasma glucose of diabetic mice, we found siRNA of PTP1B or TCPTP alone can sensitize insulin signal transduction, but combined treatment of both siRNAs had no better effects than siRNA of PTP1B. These results suggested siRNA of PTP1B and TCPTP can strengthen insulin signaling, but their effects do not appear to be synergistic in mouse liver.

Alloxan↗

Promoting culturally appropriate colorectal cancer screening through a health educator: a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the US. Surveys reveal low CRC screening levels among Asians in the US, including Chinese Americans. METHODS: A randomized controlled trial was conducted with Chinese patients to evaluate a clinic-based, culturally and linguistically appropriate intervention promoting fecal occult blood test (FOBT) screening. The multifaceted intervention included a trilingual and bicultural health educator, bilingual materials (a video, a motivational pamphlet, an informational pamphlet, and FOBT instructions), and three FOBT cards. Patients in the control arm received usual care. Our primary outcome measure was FOBT screening within 6 months after randomization. The proportion of FOBT completion in the intervention and control arms was compared by using a chi-square test, and logistic regression analysis was performed to adjust for the effects of sociodemographic variables and prior screening history. Potential effect modifications were also tested by using logistic regression models. RESULTS: Our intervention had a strong effect on FOBT completion (intervention group, 69.5%; control group, 27.6%), and the adjusted odds of FOBT slightly increased to over 6-fold greater in the intervention arm compared with the control arm. No effect modification by age, gender, language, insurance, or prior FOBT was found. CONCLUSIONS: The authors' multifaceted, culturally appropriate intervention significantly increased FOBT screening in a group of low-income and less-acculturated minority patients. Given the large effect size, future research should determine the effective core component(s) that can increase CRC screening in both the general and minority populations.

Aged↗

A stable and differentiable RNA positive control for reverse transcription-polymerase chain reaction.

Most RNA positive controls currently used for monitoring the quality of RT-PCR assays have some disadvantages, such as instability, inability to monitor the quality of the relevant primers and/or causing indifferentiable false positives. To avoid these disadvantages, a simple method to prepare stable and differentiable RNA positive controls is now demonstrated with a real-time RT-PCR assay for the detection of Nipah virus (NiV). A DNA sequence which was shorter than its counterpart in the NiV genome and contained the binding sites of the primers of the RT-PCR assay was designed, synthesized and inserted into a vector, and then amplified by PCR with two vector-specific primers both of which contained a T7 promoter at the 5' terminal. The RNA positive control was the dsRNA in vitro transcribed from the PCR amplicons flanked by two T7 promoters. The RNA positive control was stable and able to monitor the quality of the whole concerned RT-PCR assay. False positives caused by contaminations of the RNA positive control or its amplicons could be easily identified because the amplicons of the RNA positive control were obviously shorter than those of real positive samples. Thus, the RNA positive control reported in this study avoided some common disadvantages of current RNA positive controls.

Biotechnology↗

Concentric-ringed structures in polymer thin films.

Novel polymer crystalline structures containing micrometer-sized concentric rings (or bands) were observed in thin poly(bisphenol A hexane ether) (BA-C6) films. The origin of the banded structures was found to be different from that of traditional banded spherulites in polymer systems. Analyses based on optical microscopy (OM) and atomic force microscopy (AFM) revealed that the banded structures contained alternating ridge and valley bands of polymer crystals in the flat-on orientation. No lamellar twisting was observed within the concentric-ringed structures, which were developed as a result of the formation of a depletion zone during crystallization. The formation of a depletion zone was determined to be caused by the specific volume decrement between the crystal and the melt and by the diffusion of polymer chains to the fold surfaces of the flat-on lamellae. The height of the ridges and the interband widths could be adjusted by controlling the diffusion rate. Time-of-flight secondary ion mass spectrometry ion images showed higher concentrations of low-molecular-weight polymer chains on the surfaces of the ridges than in the valleys.

Benzhydryl Compounds↗

Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside.

OBJECTIVE: To investigate learning-memory deficit in different ages of AD-like APP transgenic mice and to observe the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities. METHODS: PDAPPV717I transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16 months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The learning-memory ability was measured by applying Morris water maze (MWM) and object recognition test (ORT). RESULTS: In the 4 months old PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency in MWM was prolonged, and the discrimination index decreased in ORT. In the 10 months old Tg mice, the learning-memory deficit was aggravated. TSG improved all spatial learning-memory impairment in MWM as well as the object recognition impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit remained to exist but abated a lot. TSG showed significant improvement in learning-memory ability in both MWM and ORT. CONCLUSION: PDAPPV717I transgenic mice with an age range 4-16 months revealed the existence of learning-memory deficit compared with the control group. Tetrahydroxystilbene glucoside not only prevents, i.e. at an early stage, the learning-memory deficit in AD-like model, but also can reverse the learning-memory deficit in the late stage of AD-like model. Thus, TSG could be considered among the future therapeutic drugs indicated for the treatment of AD.

Age Factors↗

Air quality impacts of power plant emissions in Beijing.

The CALMET/CALPUFF modeling system was applied to estimate the air quality impacts of power plants in 2000 and 2008 in Beijing, and the intake fractions (IF) were calculated to see the public health risks posed. Results show that in 2000 the high emission contribution induced a relatively small contribution to average ambient concentration and a significant impact on the urban area (9.52 microg/m(3) of SO(2) and 5.29 microg/m(3) of NO(x)). The IF of SO(2), NO(x) and PM(10) are 7.4 x 10(-6), 7.4 x 10(-6) and 8.7 x 10(-5), respectively. Control measures such as fuel substitution, flue gas desulfurization, dust control improvement and flue gas denitration planned before 2008 will greatly mitigate the SO(2) and PM(10) pollution, especially alleviating the pressure on the urban area to reach the National Ambient Air Quality Standard (NAAQS). NO(x) pollution will be mitigated with 34% decrease in concentration but further controls are still needed.

Air Pollutants↗

Magnetoresistance effects evidencing the pi-d interaction in metallic organic conductors, (EDT-DSDTFVO)2*MX4 (M = Fe, Ga; X = Cl, Br).

The 2:1 salts of a new donor molecule, EDT-DSDTFVO with MX4- (M = Fe, Ga; X = Cl, Br) ions, were prepared. The crystal structures of the donor molecules had a beta-type packing motif. All the salts essentially exhibited metallic behaviors despite the small upturns in the resistances below 30-70 K. A large negative magnetoresistance (MR) effect [-14.7% (rho(perpendicular)) at 4.0 K and 5 T] was observed in the FeCl4- salt, while a positive MR effect [+4.0% (rho(perpendicular)) at 4.0 K and 5 T] was observed in the GaCl4- salt, suggesting that there is a pi-d interaction in the FeCl4- salt. The pressure application suppressed the resistivity upturns, increased the negative MR effect (-17.7% at 9.5 kbar) in the FeCl4- salt, and decreased the positive MR effect (+3.3% at 15 kbar) in the GaCl4- salt.

Journal Article↗

Proteomic identification of AP2 gamma as a rat placental lactogen II trophoblast cell-specific enhancer binding protein.

The factors that regulate the developmental expression of the rodent prolactin gene family in placenta remain poorly defined. We previously identified an enhancer element in the 5' flanking region of one family member, rat placental lactogen II (rPLII), which could target reporter gene expression to the placenta in transgenic mice; this enhancer functioned in the Rcho rat trophoblast cell line but not in the rat pituitary GC cell line. In further experiments to identify the factors that bind this element, we have selectively enriched for DNA binding proteins in nuclear extract from Rcho cells using magnetic beads coupled to a 43-bp enhancer oligonucleotide. Tryptic peptides of bound proteins were analyzed by HPLC coupled off-line to matrix-assisted laser desorption ionization time of flight mass spectrometry. Several peptides of AP2 gamma, a key trophoblast cell-specific transcription factor, were identified. Gel mobility shift assays using AP2 gamma-specific antiserum and mutant enhancer oligonucleotides demonstrated binding specifically to the FP2 DNase I-protected region of the element, identifying an atypical binding site for this factor. In cotransfection assays in rat pituitary GC cells, AP2 gamma transactivated the enhancer via this region. Chromatin immunoprecipitation assays confirmed AP2 gamma occupancy of the enhancer region in situ in the nuclei of Rcho giant cells. These data support a role for AP2 gamma in the placental giant cell-specific expression of the rPLII gene and provide the first direct evidence for the involvement of a placental-specific transcription factor in the regulation of a member of this gene family.

Animals↗

Solid-state conversion of fly ash to effective adsorbents for Cu removal from wastewater.

Solid-state conversion of fly ash to an amorphous aluminosilicate adsorbent (geopolymer) has been investigated under different conditions and the synthesised material has been tested for Cu2+ removal from aqueous solution. It has been found that higher reaction temperature and Na:FA ratio will make the adsorbents achieving higher removal efficiency. The adsorbent loading and Cu2+ initial concentration will also affect the removal efficiency while the adsorption capacity exhibits similarly at 30-40 degrees C. The adsorption capacity of the synthesised adsorbent shows much higher value than fly ash and natural zeolite. The capacity is 0.1, 3.5 and 92 mg/g, for fly ash, natural zeolite, and FA derived adsorbent, respectively. The kinetic studies indicate that the adsorption can be fitted by the second-order kinetic model. Langmuir and Freundlich isotherms also can fit to the adsorption isotherm.

Adsorption↗

The role of Sp1 and Sp3 in the constitutive DPYD gene expression.

Dihydropyrimidine dehydrogenase (DPD), the initial and rate-limiting enzyme in the 5-fluorouracil (5-FU) catabolic pathway, has been implicated as one of the factors determining the efficacy and toxicity of the anticancer agent 5-FU. Studies have attributed variation in DPD activity partially to alterations at the transcriptional level of DPYD gene. We investigated the transcription factors implicated in the constitutive expression of DPYD by utilizing a 174-bp fragment of the DPYD promoter region in which three consensus Sp protein binding sites (SpA, SpB and SpC) were predicted. The binding of Sp1 and Sp3 transcription factors to this region was detected by electrophoretic mobility shift and chromatin immunoprecipitation assays. By ectopically expressing human Sp1 and Sp3 in Sp-deficient Drosophila S2 cells, we demonstrated that Sp1 is a strong activator, while Sp3 by its own is a weak activator of the DPYD promoter. Moreover, Sp3 may serve as a competitor of Sp1, thus decreasing the Sp1 induced promoter activity. SpA, SpB and SpC sites are all Sp1 inducible. In the full activation of the DPYD promoter in human cell lines, the SpB site is essential; the SpC site works cooperatively with SpB, while SpA has minor promoter activity. These studies provide further insight into the molecular mechanisms underlying the heterogeneity of DPD activity, and may facilitate the efficacy and safety of 5-FU-based chemotherapy.

Base Sequence↗

Absence of alpha3 (Cx46) and alpha8 (Cx50) connexins leads to cataracts by affecting lens inner fiber cells.

Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(-/-) alpha8(-/-) double knockout mice and characterized their lens phenotypes. Without gap junctions between lens fiber cells, alpha3(-/-) alpha8(-/-) lenses displayed severe cataracts resulting from cell swelling and degeneration of inner fibers while normal peripheral fiber cells continued to form throughout life. Neither an increase of degraded crystallins nor an increase of water-insoluble crystallins was found in alpha3(-/-) alpha8(-/-) lenses. However, a substantial reduction of gamma-crystallin proteins, but not alpha- and beta-crystallins, was detected. These results suggest that gap junction communication is important for maintaining lens homeostasis of inner fiber cells and that a loss of gap junctions leads to cataract formation as well as reductions of gamma-crystallin proteins and transcripts.

Animals↗

Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome.

BACKGROUND: The aims of this study were to analyse the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (NIDDM) in Chinese polycystic ovary syndrome (PCOS) patients and to assess the ability of screening tests to predict these abnormalities within this population. METHODS: A total of 102 PCOS patients were evaluated. All patients underwent oral glucose tolerance tests (OGTTs) with blood samples taken at 0, 1 and 2 h. The 2-h plasma glucose level was used to categorize subjects as having IGT or NIDDM. RESULTS: The prevalence of IGT was 20.5% and that of NIDDM was 1.9%. There was no significant relationship between BMI and 2-h plasma glucose levels. The areas under the receiver operating characteristic (ROC) curve for glucose to insulin ratio (G:I), homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were 0.702, 0.734 and 0.733 respectively. ROC analysis suggested a threshold value of 10.7 in G:I ratio (73.9% sensitivity and 59.5% specificity), a value of 2.14 in HOMA (73.9% sensitivity and 73.4% specificity) and a value of 0.34 in QUICKI (73.9% sensitivity and 73.4% specificity) for the prediction of abnormal glucose tolerance (IGT and NIDDM). CONCLUSIONS: Chinese women with PCOS are at increased risk of IGT and NIDDM. Even though G:I, HOMA and QUICKI are easier than OGTT, they could not replace the role of 2-h post-challenge plasma glucose level in the screening of IGT and NIDDM in PCOS women.

Adolescent↗

Chromatin modification of the trefoil factor 1 gene in human breast cancer cells by the Ras/mitogen-activated protein kinase pathway.

Histone H3 phosphorylation is a downstream response to activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. This modification is thought to have a role in chromatin remodeling and in the initiation of gene transcription. In MCF-7 breast cancer cells, we observed that phosphorylated histone H3 (phospho-H3) at Ser(10) but not Ser(28) increased with phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) treatment. Although phosphorylated extracellular signal-regulated kinase 1/2 levels in these cells cultured under estradiol deplete and replete conditions displayed no change, a significant induction was observed after TPA treatment. Furthermore, whereas both estradiol and TPA increased trefoil factor 1 (TFF1) mRNA levels in these cells, only TPA-induced and not estradiol-induced TFF1 expression was inhibited by the H3 kinase mitogen and stress activated protein kinase (MSK) inhibitor H89 and MAPK kinase inhibitor UO126, showing the involvement of the Ras/MAPK following TPA induction. Mutation of the activator protein 1 (AP-1) binding site abrogated the TPA-induced transcriptional response of the luciferase reporter gene under the control of the TFF1 promoter, showing the requirement for the AP-1 site. In chromatin immunoprecipitation assays, estradiol treatment resulted in the association of the estrogen receptor-alpha (ERalpha) and acetylated H3 with the TFF1 promoter. The levels of phospho-H3 and MSK1 associated with the TFF1 promoter were moderately increased. In the presence of TPA, whereas ERalpha was not bound to the promoter, a strong association of acetylated and/or phospho-H3, MSK1, and c-Jun was observed. These results show that although both stimuli lead to TFF1 gene activation, estradiol and TPA exert their effects on TFF1 gene expression by different mechanisms.

Binding Sites↗

Application of a methylation gene panel by quantitative PCR for lung cancers.

Detection of lung cancer at early stages could potentially increase survival rates. One promising approach is the application of suitable lung cancer-specific biomarkers to specimens obtained by non-invasive methods. Thus far, clinically useful biomarkers that have high sensitivity have proven elusive. Certain genes, which are involved in cellular pathways such as signal transduction, apoptosis, cell to cell communication, cell cycles and cytokine signaling are down-regulated in cancers and may be considered as potential tumor suppressor genes. Aberrant promoter hypermethylation is a major mechanism for silencing tumor suppressor genes in many kinds of human cancers. Using quantitative real time PCR, we tested 11 genes (3-OST-2, RASSF1A, DcR1, DcR2, P16, DAPK, APC, ECAD, HCAD, SOCS1, SOCS3) for levels of methylation within their promoter sequences in non-small cell lung cancers (NSCLC), adjacent non-malignant lung tissues, in peripheral blood mononuclear cells (PBMC) from cancer free patients, in sputum of cancer patients and controls. Of all the 11 genes tested 3-OST-2 showed the highest levels of promoter methylation in tumors combined with lowest levels of promoter methylation in control tissues. 3-OST-2 followed by, RASSF1A showed increased levels of methylation with advanced tumor stage (P<0.05). Thus, quantitative analysis of 3-OST-2 and RASSF1A methylation appears to be a promising biomarker assay for NSCLC and should be further explored in a clinical study. Our preliminary data on the analysis of sputum DNA specimens from cancer patients further support these observations.

Adenocarcinoma↗

Identification of key residues in proteins by using their physical characters.

Key residues in proteins are important to their stability, folding, and functions. They usually are highly conserved and can be identified by sequence or structure alignments. However, these methods can only determine the locations of key residues in sequences and structures and give less information about their physical characters. In this paper, we try to identify key residues by analyzing their inter-residue interactions. The model we study is the protein domain from transducin. We show that the usual Gaussian network analysis and distance-based contact analysis have difficulty identifying the key residues in this protein, but the contact energies can do it well. We find that most key residues can be located by the lowest contact energies. This enables us to predict and analyze the key residues in other proteins. Our results suggest that contact energy analysis may provide an alternative approach to investigating the folding and stability of proteins.

Amino Acid Sequence↗