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Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 109 records · Page 6Linked to original sources
PubMed2002

Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats.

Interleukin-6 (IL-6) is a multifunctional cytokine that may have a role in energy regulation. Using a recombinant adeno-associated viral vector expressing murine interleukin-6 (rAAV-IL-6), we examined the chronic effects of centrally expressed IL-6 on food intake, body weight and adiposity in male Sprague-Dawley rats, and investigated the underlying mechanisms. Direct delivery of rAAV-IL-6 into rat hypothalamus suppressed weight gain and visceral adiposity without affecting food intake over a 5-week period. rAAV-IL-6 enhanced uncoupling protein 1 (UCP1) protein levels in interscapular brown adipose tissue (BAT). To investigate if the induction of UCP1 and the reduction in body weight are dependent on sympathetic innervation of BAT, we administered rAAV-IL-6 or a control vector into the hypothalamus of rats in which the interscapular BAT was unilaterally denervated. Over 21 days, there was no difference in food consumption or body weight between rAAV-IL-6- and control vector-treated rats. rAAV-IL-6 delivery increased UCP1 mRNA and protein levels in innervated BAT pads but not denervated BAT pads. Hypothalamic IL-6 signal transduction, indicated by phosphorylated signal transducer and activator of transcription 3 (P-STAT3) levels, was elevated by 2.6-fold at day 21, but returned to control levels by day 35. However, the suppressor of cytokine signaling-3 mRNA level was significantly elevated both at day 21 and day 35. These data demonstrate that chronic elevation of IL-6 in the CNS reduces body weight gain and visceral adiposity without affecting food intake. The mechanism involves sympathetic induction of UCP1 in BAT and, presumably, enhanced thermogenesis in BAT. Furthermore, chronic central IL-6 stimulation desensitizes IL-6 signal transduction characterized by reversal of elevated P-STAT3 levels.

Adipose Tissue, Brown↗
PubMed2002

Cardioprotection by breathing hyperoxic gas-relation to oxygen concentration and exposure time in rats and mice.

OBJECTIVES: Breathing a hyperoxic gas (> or =95% O(2)) protects against ischaemia-reperfusion injury in rat and mouse hearts. The present study investigated how oxygen concentration and duration of hyperoxic exposure influenced cardioprotection, and whether hyperoxia might induce delayed cardioprotection (after 24 h). METHODS: Animals were kept in normal air or in a hyperoxic environment, and their hearts were isolated and Langendorff-perfused immediately or 24 h thereafter. Global ischaemia was induced for 25 min in rats and 40 min in mice, followed by 60 min of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining. RESULTS: In rats exposure to > or =95, 80, and 60%, but not to 40% of oxygen immediately before heart isolation and perfusion improved postischaemic functional recovery. Eighty or more percent of oxygen also reduced infarct size. A preconditioning-like effect could be evoked by 60 or 180 min of hyperoxia, giving both immediate and delayed protection. In the mouse heart protection could be induced by pretreatment for 15 or 30, but not by 60 min with > or =95% oxygen. The protective effect of hyperoxia in mice could be evoked in the immediate model only. CONCLUSIONS: Hyperoxia protects the isolated rat and mouse heart against ischaemia-reperfusion injury, but some species-different responses exist. The protection depends on both oxygen concentration in inspired air, and duration of hyperoxic exposure.

Animals↗
PubMed2002

Visual linearization of the display of digital radiographs.

OBJECTIVES: To derive and test a method to linearize the visual response of the display of digital radiographs so that equal steps in gray levels will be perceived as equal steps in brightness. METHOD: A mathematical analysis was performed and expressions for visual linearization were derived. Twenty-four test images were computer generated to confirm that visual linearization may be achieved. Each image had three groups of square areas of different size placed in three rows. The left and right squares in each row were given different gray levels to simulate various contrast levels. The middle squares were initially given the same gray level value as one of the outer squares. The images were examined by ten observers who could change the gray levels of the middle squares so that the step in brightness between the middle square and the outer squares become subjectively equal. The test was performed three times employing two different monitors. RESULTS: The experimental test confirmed that visual linearization could be achieved. Linear regression analyses gave determination coefficients of 0.9926 amd 0.9942 for monitors with gamma-values of 1.93 and 2.50. respectively. The mean data from the ten observers perfectly fitted those theoretically calculated. CONCLUSION: Visual linearization of gray levels can be achieved but further clinical research is needed to determine if this improves diagnosis.

Algorithms↗
PubMed2002

Correction for attenuation and visual response in digital radiography.

OBJECTIVES: To derive a method to correct for the exponential attenuation adding visual linearization for digital radiography and to perform an experimental test to study effects on observer performance. METHOD: A theoretical analysis was performed and expressions were derived to correct radiographic data for the attenuation. An experiment was performed exposing an aluminum step wedge with holes of increasing depths behind each step plus soft tissue simulation. Seven original images were created with a digital intraoral X-ray sensor and a further 14 transformed images produced. Ten observers examined the images in a randomized order reporting the number of holes seen per wedge step. The results were analysed by One Way ANOVA. RESULTS: It was possible to correct for attenuation and the response of the human visual system to light intensities from a computer monitor. Perception was significantly improved in all recalculated radiographs that took both attenuation and the response of the eye into account (P-values ranged from <0.0001 to <0.0286). CONCLUSIONS: The transforms may be useful for improved perception when viewing digital radiographs.

Absorptiometry, Photon↗
PubMed2002

Detection of approximal caries in digital radiographs before and after correction for attenuation and visual response. An in vitro study.

OBJECTIVE: To evaluate if digital compensation for exponential attenuation and the characteristics of the human visual system improves the diagnosis of approximal caries from digital radiographs. MATERIAL AND METHODS: Forty premolar teeth were mounted in plaster blocks. Radiographs of the teeth were exposed with the Dixi digital intraoral system employing a Prostyle Intra dental X-ray unit (Planmeca Oy, Helsinki, Finland). Thirteen radiographs were then processed to compensate for the exponential attenuation and for the characteristic of the human visual system using equations presented in the paper. Ten observers were asked to diagnose approximal caries in all radiographs. ROC analyses were performed. The teeth were subsequently sectioned for histological validation of the lesions. The areas under ROC curves of original and processed radiographs were compared and analysed using Wilcoxon's signed-ranks test. RESULTS: There were significant diagnostic differences between the two types of radiographs (all lesions P=0.005. enamel P=0.028, and dentine P=0.050). CONCLUSION: Digital radiographs processed to compensate for exponential attenuation and the characteristics of the human visual system significantly improves the diagnosis of approximal caries in vitro.

Adolescent↗
PubMed2002

The novel tumour suppressor gene ING1 is overexpressed in human melanoma cell lines.

BACKGROUND: Epidemiological evidence indicates that exposure to ultraviolet (UV) radiation is directly linked to the increase of both incidence and mortality of melanoma. However, the genetic changes caused by UV radiation that lead to melanoma formation remain poorly understood. Recently, a potential tumour suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and induce apoptosis in the presence of p53. We have demonstrated that the expression of ING1 is induced after UV irradiation and that ING1 enhances the repair of UV-damaged DNA. OBJECTIVES: To investigate if ING1 plays a role in melanoma formation. METHODS: We examined p33ING1 expression levels in 14 melanoma cell lines. RESULTS: We found that p33ING1 is overexpressed at both mRNA and protein levels in melanoma cell lines compared with normal melanocytes. Single-strand conformation polymorphism (SSCP) analysis showed band shifting in two melanoma cell lines. DNA sequencing confirmed that there were nucleotide alterations in the ING1 gene in Sk-mel-24 and Sk-mel-110 cell lines. Two silent nucleotide alterations in exon 1a were detected in Sk-mel-110. In Sk-mel-24, the A-->G nucleotide alteration at codon 260 resulted in an amino acid change from Asn to Ser, while seven other nucleotide alterations were silent. To determine if the silent nucleotide alterations in these two melanoma cell lines were due to polymorphism, SSCP analysis of ING1 gene was performed in 25 healthy volunteers. No band shift was observed in the SSCP analysis, suggesting that the nucleotide alterations in the melanoma cell lines are unlikely to be due to polymorphism. CONCLUSIONS: Taken together, our data demonstrate that ING1 is overexpressed, but infrequently mutated, in melanoma cell lines.

Cell Cycle Proteins↗
PubMed2002

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China.

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.

Case-Control Studies↗
PubMed2002

Purification of human immunoglobulin G: a new approach to plasma fractionation.

BACKGROUND AND OBJECTIVES: Currently, plasma fractionation involves multiple processing steps using established methods such as ethanol precipitation and column chromatography. The known limitations associated with conventional purification techniques, combined with strict regulations on safety and high demand for particular plasma proteins, have resulted in a shortage of plasma-derived therapeutics such as intravenous immunoglobulin G (IgG). MATERIALS AND METHODS: In this study, IgG was purified from human plasma using Gradiflow technology, an electrophoresis-based separation technology. RESULTS: IgG was isolated from plasma to high purity, with 94 +/- 5% recovery in a short processing time. CONCLUSIONS: The technology has been shown to be linearly scalable and has the capacity to contribute to increased production of important plasma fraction therapeutics.

Chemical Fractionation↗
PubMed2002

Obesity, coronary heart disease risk factors and diabetes in Chinese: an approach to the criteria of obesity in the Chinese population.

The aim of this work was to study the relationship between excess body weight and the risks of hypertension and diabetes in the population of northeastern China. Subsections of a cross-sectional survey in Da Qing City were used to assess the relationship of excess weight to risk factors for coronary heart disease (CHD). A 6-year prospective study also assessed the probability of developing Type 2 diabetes. A total of 2856 adults (25-70 years of age) were assessed cross-sectionally and 629 non-diabetic subjects of similar age were followed-up for 6 years. Blood pressure, plasma fasting glucose, triglycerides, high-density lipoporotein (HDL) cholesterol and fibrinogen levels were measured as well as weight, height and waist and hip circumferences. About 45% of adults had a body mass index (BMI) of > or =25.0. Risk factors increased with increasing BMI from a baseline value of 21.0: at a BMI of 23.0-24.9, the risk of hypertension and hypertriglyceridaemia doubled; the risk increased threefold at a BMI of 25.0-26.9. The prevalence of Type 2 diabetes increased progressively in women within the normal BMI range and in men from a BMI of 25.0. Type 2 diabetes was four times as common if the BMI was >27.0. Increasing waist measurements predicted 10-fold increases in hypertension and a three-to-five times increased risk of diabetes. Suitable waist cut-off points were 85cm for men and 80cm for women, with statistical analysis showing waist as the more dominant predictor of risk than age, waist-to-hip ratios or BMIs. Hence, small increases in BMI, and particularly in waist circumference, predict a substantial increase in the risk of diabetes and risk for CHD, especially hypertension, in Chinese adults.

Adult↗
PubMed2002

An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers.

MOTIVATION: MALDI mass spectrometry is able to elicit macromolecular expression data from cellular material and when used in conjunction with Ciphergen protein chip technology (also referred to as SELDI-Surface Enhanced Laser Desorption/Ionization), it permits a semi-high throughput approach to be taken with respect to sample processing and data acquisition. Due to the large array of data that is generated from a single analysis (8-10000 variables using a mass range of 2-15 kDa-this paper) it is essential to implement the use of algorithms that can detect expression patterns from such large volumes of data correlating to a given biological/pathological phenotype from multiple samples. If successful, the methodology could be extrapolated to larger data sets to enable the identification of validated biomarkers correlating strongly to disease progression. This would not only serve to enable tumours to be classified according to their molecular expression profile but could also focus attention upon a relatively small number of molecules that might warrant further biochemical/molecular characterization to assess their suitability as potential therapeutic targets. RESULTS: Using a multi-layer perceptron Artificial Neural Network (ANN) (Neuroshell 2) with a back propagation algorithm we have developed a prototype approach that uses a model system (comprising five low and seven high-grade human astrocytomas) to identify mass spectral peaks whose relative intensity values correlate strongly to tumour grade. Analyzing data derived from MALDI mass spectrometry in conjunction with Ciphergen protein chip technology we have used relative importance values, determined from the weights of trained ANNs (Balls et al., Water, Air Soil Pollut., 85, 1467-1472, 1996), to identify masses that accurately predict tumour grade. Implementing a three-stage procedure, we have screened a population of approximately 100000-120000 variables and identified two ions (m/z values of 13454 and 13457) whose relative intensity pattern was significantly reduced in high-grade astrocytoma. The data from this initial study suggests that application of ANN-based approaches can identify molecular ion patterns which strongly associate with disease grade and that its application to larger cohorts of patient material could potentially facilitate the rapid identification of validated biomarkers having significant clinical (i.e. diagnostic/prognostic) potential for the field of cancer biology. AVAILIBILITY: Neuroshell 2 is commercially available from ward systems.

Astrocytoma↗
PubMed2002

A versatile method for the removal of melanin from ribonucleic acids in melanocytic cells.

Melanin pigments often co-purify during preparation of nucleic acids from cells or tissues of melanocytic origin. Contaminating melanin can severely impede subsequent analyses of RNA. We attempted to eliminate melanin in RNA preparations using selected gel matrices. We show here that co-purified melanin pigments can be largely eliminated from RNA samples after passing through polyacrylamide-based beads (Bio-Gel P-60). After isolation from the pigment-containing cells or tissues, RNA was subsequently processed through batch or column purification under acidic pH conditions. The resulting RNA was devoid of contaminating melanin pigments and amenable to molecular reactions such as polymerase chain reaction and cDNA synthesis by reverse transcriptase. Although the process results in some loss of input RNA, this purification procedure is simple, robust and can easily be adopted in any laboratory for the molecular analysis of RNA that requires removal of melanin contamination.

Acrylic Resins↗
PubMed2002

Drinking histories of fatally injured drivers.

CONTEXT: About 30% of drivers killed in crashes have high blood alcohol concentrations (BACs) of 0.10+ g/dl. There is a question about whether these drivers primarily are problem drinkers who chronically drink and drive-the so-called hard core drinking drivers. OBJECTIVE: To investigate drinking histories of fatally injured drivers in relation to their BACs. DESIGN AND PARTICIPANTS: Retrospective cohort study of 818 fatally injured drivers who were included in the 1993 National Mortality Followback Survey (a national sample of US deaths in which next of kin were interviewed) and whose BACs were recorded by the Fatality Analysis Reporting System, a census of US traffic deaths. MAIN OUTCOME MEASURE: Problem drinking indicators. RESULTS: At least one indicator of potential problem drinking, primarily heavy drinking, was reported for 68% of drivers with very high BACs (0.15+ g/dl), 41% with BACs of 0.10-0.14 g/dl, 32% with BACs of 0.01-0.09 g/dl, and 7% with zero BACs. Spouses provided more credible responses than other relatives: they were more likely to report at least occasional drinking and driving among deceased drivers with high BACs. For the most direct signs of problem drinking (described as a problem drinker during the last month of life or frequently driving after having five or more drinks), spousal reports suggested the prevalence of problem drinking among drivers with very high BACs was 22% (having both indicators), 32% (frequently driving after having five or more drinks), 44% (described as problem drinker), or 57% (having either indicator). CONCLUSIONS: Drivers with BACs of 0.10+ g/dl were far more likely than sober drivers to be described as having markers of problem drinking. However, many did not have indicators suggestive of problem drinking. In addition to programs focused on repeat offenders or problem drinkers, countermeasures such as sobriety checkpoints that target a broader spectrum of drinking drivers are appropriate.

Accidents, Traffic↗
PubMed2002

Dynamics of cell interactions and communications during melanoma development.

Melanoma development not only involves genetic and epigenetic changes that take place within the cell, but also involves processes determined collectively by micro-environmental factors, including cell-cell interactions and communications. During the transition from normal cells to benign and malignant lesions, and subsequently to metastatic cancer, stepwise changes in intercellular communications provide tumor cells with the ability to overcome cell-cell adhesion and micro-environmental controls from the host and to invade surrounding tissues and disperse to distant locations. Cadherins are major cell-cell adhesion molecules involved in the development and maintenance of skin. E-cadherin expressed in normal melanocytes mediates growth and invasion control by keratinocytes. Progressive loss of E-cadherin and gain of N-cadherin during melanoma development not only free melanoma cells from control by keratinocytes, but also provide new adhesion properties, resulting in switched partnerships with fibroblasts and vascular endothelial cells. The cadherin subtype switching also dictates gap junctional specificity in melanocytic cells during tumor development. This selective intercellular communication may contribute to the regulation of cell growth, differentiation, apoptosis, and migration of melanocytic cells in both physiologic and pathologic conditions. Abnormal up-regulation of the immunoglobin repeat-containing cell adhesion molecules Mel-CAM and L1-CAM potentiates invasion and migration of melanoma. Thus, abnormal expression of intercellular adhesion receptors and dysregulated intercellular communication underlies melanoma development and progression.

CD146 Antigen↗
PubMed2001

Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53.

In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.

Antineoplastic Agents↗
PubMed2001

Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development.

During melanoma development, transformed cells evade keratinocyte-mediated control by downregulating cell adhesion molecules. This study investigated the regulation of cell adhesion by hepatocyte growth factor (HGF) in melanoma. Melanocytes and two melanoma lines, WM164 and WM35, expressed normal level E-cadherin and Desmoglein 1, whereas most melanomas (18 out of 20) expressed no E-cadherin and significantly reduced Desmoglein 1. Overexpression of dominant negative E-cadherin and Desmoglein in melanocytes demonstrated that both molecules contribute to adhesion between melanocytes and keratinocytes. In contrast to melanocytes, most melanomas expressed HGF. All melanocytic cells expressed the HGF receptor c-Met, and autocrine HGF caused constitutive activation of c-Met, MAPK and PI3K. When autocrine activation was induced with HGF-expressing adenovirus, E-cadherin and Desmoglein 1 were decreased in melanocytes, WM164 and WM35. MAPK inhibitor PD98059 and PI3K inhibitor wortmannin partially blocked the downregulation, suggesting that both pathways are involved in this process. c-Met was coimmunoprecipitated with E-cadherin, Desmoglein 1 and Plakoglobin, suggesting that they form a complex (es) that acts to regulate intercellular adhesion. Together, the results indicate that autocrine HGF decouples melanomas from keratinocytes by downregulating E-cadherin and Desmoglein 1, therefore frees melanoma cells from the control by keratinocytes and allows dissemination of the tumor mass.

Autocrine Communication↗
PubMed2001

No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits.

OBJECTIVES: We tested the hypothesis that cardioprotection with ischemic preconditioning (PC) is lost in the aging, or senescent, heart. BACKGROUND: Although infarct size reduction with PC has been documented in virtually all models, a purported exception to this paradigm is the aging heart, the population in which cardioprotection is most relevant. However, no previous studies have assessed the concept of an age-associated loss in the efficacy of PC in an in vivo model of acute myocardial infarction in which definitive hallmarks of cardiovascular aging were demonstrated and a reduction of infarct size, the "gold standard" of PC, served as the primary end point. METHODS: Using the in vivo rabbit model, three cohorts of animals were studied: adult (4 to 6 months old), middle-aged ( approximately 2 years old) and old ( approximately 4 years old) rabbits. Within each cohort we assessed: 1) infarct size (measured by tetrazolium staining and expressed as percent myocardium at risk) in control and PC groups; and 2) morphologic and functional hallmarks of cardiovascular aging (progressive myocyte hypertrophy, increased myocardial fibrosis and attenuated responsiveness to beta-adrenergic stimulation). RESULTS: In adult animals, infarct size was significantly smaller in the PC group than in the control group (29 +/- 4% vs. 57 +/- 2%; p < 0.01). Although middle-aged and old rabbits exhibited all three archetypal indexes of cardiovascular aging, a comparable (approximately 50%) reduction in infarct size with PC was evident in both cohorts. CONCLUSIONS: These data provide the first in vivo evidence that infarct size reduction with PC is not precluded by increased cardiovascular age, per se.

Aging↗
PubMed2001

Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and beta-catenin pathways.

Melanoma cells produce growth factors for autocrine growth control and for stimulating fibroblasts and endothelial cells in the tumor stroma. Activated stromal fibroblasts can in turn secrete growth factors that support tumor growth. We studied this feedback from fibroblasts to melanoma cells by overexpressing insulin-like growth factor 1 (IGF-1) with an adenoviral vector. Melanoma cells do not produce IGF-1. IGF-1 enhanced survival, migration, and growth of cells from biologically early lesions, but not from biologically late primary or metastatic lesions. Early melanoma cells were activated by IGF-1 to phosphorylate Erk1 and -2 of the mitogen-activated protein kinase pathway. IGF-1 also activated Akt, inhibited its down-stream effector GSK3-beta, and stabilized beta-catenin. Late primary and metastatic melanoma cells did not respond to growth stimulation by IGF-1 because of a constitutive activation of the mitogen-activated protein kinase pathway and a higher level of stabilized beta-catenin. These studies demonstrate that fibroblast-derived growth factors from the tumor environment can provide the malignant cells with a positive feedback through multiple mechanisms but that this stimulation is required only for cells from early and not late stages of tumor progression.

Cell Division↗