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Biomedical subjects

L Fan

Publications and source records attributed to L Fan.

At least 55 records · Page 3Linked to original sources
PubMed2000

The role of tyrosine 15 in erythropoietin action.

The results of iodination inactivation of erythropoietin suggest that tyrosine 15 is required for biological activity. This was confirmed by site-directed mutagenesis. Substitution of tyrosine by alanine or isoleucine resulted in mutants with no biological activity, whereas substitution by phenylalanine yielded an active mutein. Protein footprinting using trypsin showed that the N-terminal residues 1 to 46 and the C-terminal residues 155 to 165 linked by the 7 to 161 disulfide bond, includes one active site of the hormone.

Antibodies, Monoclonal↗
PubMed2000

Ventricular preexcitation sensitive to flecainide in late stage chick embryo ECGs: 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs inotropic but not chronotropic or dromotropic responses to isoproterenol and confers resistance to flecainide.

ECGs free of movement artefacts were obtained without anesthesia in 16- to 18-day-old chick embryos close to hatching and used to study the effect of the environmental toxin 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on cardiac rhythm and conduction. The ECGs of normal late stage chick embryos exhibited short PR intervals, frequent nonisoelectric PR segments, delta waves, and inverted T waves. Those ECG characteristics are found in patients with the Wolff-Parkinson-White syndrome (WPW) in which they reflect ventricular preexcitation associated with the use of accessory conduction pathways and arrhythmias. Isoproterenol (30 microg/egg) did not alter the ECG preexcitation characteristics. Flecainide, a sodium channel blocker used clinically to suppress WPW accessory pathway activity, at 0.5 to 5 mg per egg diminished the preexcitation and caused atrioventricular (AV) block, supporting the use of accessory pathways together with AV-nodal conduction in normal late stage chick embryos. The findings challenge the dogma that accessory pathways are entirely replaced by AV conduction pathways in late fetal development. TCDD, at 1-2 nmol per egg for 48 h, did not affect heart rate, the increase in heart rate by isoproterenol, or the ECG characteristics, suggesting that short-term TCDD treatment did not affect sinus node function or cardiac conduction. The latter results taken together with prior findings indicate that TCDD differentially impairs the inotropic and lusitropic effects but not the chronotropic or dromotropic effects of isoproterenol. In TCDD-treated embryos, flecainide, tested at 5 mg per egg, caused much less inhibition of preexcitation or production of AV block than in the untreated or solvent-treated controls. The resistance to flecainide represents a new TCDD effect consistent with the reported increase of cardiac myocyte [Ca(2+)](i) by TCDD treatment.

Animals↗
PubMed2000

Cutting edge: ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis.

To test whether accumulation of naive lymphocytes is sufficient to trigger lymphoid development, we generated mice with islet expression of the chemokine TCA4/SLC. This chemokine is specific for naive lymphocytes and mature dendritic cells (DC) which express the CCR7 receptor. Islets initially developed accumulations of T cells with DC, with scattered B cells at the perimeter. These infiltrates consolidated into organized lymphoid tissue, with high endothelial venules and stromal reticulum. Infiltrate lymphocytes showed a naive CD44low CD25- CD69- phenotype, though half were CD62L negative. When backcrossed to RAG-1 knockout, DC were not recruited. Interestingly, islet lymphoid tissue developed in backcrosses to Ikaros knockout mice despite the absence of normal peripheral nodes. Our results indicate that TCA4/SLC can induce the development and organization of lymphoid tissue through diffential recruitment of T and B lymphocytes and secondary effects on stromal cell development.

Animals↗
PubMed2000

Inhibition of transplant vasculopathy in a rat aortic allograft model after infusion of anti-inflammatory viral serpin.

BACKGROUND: Transplant vasculopathy remains a difficult therapeutic problem, resulting in the majority of late cardiac graft losses. This chronic vascular disease is thought to be triggered by alloantigen-dependent and alloantigen-independent inflammatory factors. Despite improved 1-year survival, the incidence of transplant vasculopathy has not improved with current immunosuppressive protocols. Highly effective strategies have evolved in the large DNA viruses that shield infecting viruses from host inflammatory responses. Serp-1 is a secreted myxoma virus anti-inflammatory serine proteinase inhibitor. Serp-1 inhibits plasminogen activators in a manner similar to plasminogen activator inhibitor (PAI-1), a vascular protein that plays a pivotal regulatory role in vascular wound healing. In this study, we tested the ability of purified Serp-1 protein to ameliorate posttransplant vasculopathy after rat aortic allograft surgery. METHODS AND RESULTS: Serp-1 protein or controls were infused into 98 rats immediately after segmental aortic allograft transplantation. After either late (28 days, 64 rats) or early (12 to 48 hours, 24 rats) follow-up, transplanted aortic segments were harvested for morphological and immunohistochemical analysis. Significant reductions in intimal plaque growth (P<0.002) and mononuclear cell invasion (P<0.033) were detected after Serp-1 infusion at nanogram doses. Serp-1 reduced early macrophage (P<0.0016) and nonspecific lymphocyte (P<0.0179) invasion into medial and adventitial layers and inhibited associated depletion of medial smooth muscle cells (P<0.0006). CONCLUSIONS: Infusion of a viral anti-inflammatory serpin, Serp-1, significantly reduces early inflammatory responses and later luminal occlusion in a rat aortic allograft model.

Animals↗
PubMed2000

Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture.

We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 micromol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb.

Animals↗
PubMed2000

Ultrasound measurement of brachial flow-mediated vasodilator response.

Brachial artery flow-mediated vasodilation is increasingly used as a measure of endothelial function. High resolution ultrasound provides a noninvasive method to observe this flow-mediated vasodilation by monitoring the diameter of the artery over time following a transient flow stimulus. Since hundreds of ultrasound images are required to continuously monitor brachial diameter for the 2-3 min during which the vasodilator response occurs, an automated diameter estimation is desirable. However, vascular ultrasound images suffer from structural noise caused by the constructive and destructive interference of the backscattered signals, and the true boundaries of interest that define the diameter are frequently obscured by the multiple-layer structure of the vessel wall. These problems make automated diameter estimation strategies based on the detection of the vessel wall boundary difficult. We obtain a robust automated measurement of the vasodilator response by automatically locating the artery using a variable window method, which gives both the lumen center and width. The vessel wall boundary is detected by a global constraint deformable model, which is insensitive to the structural noise in the boundary area. The ambiguity between the desired boundary and other undesired boundaries is resolved by a spatiotemporal strategy. Our method provides excellent reproducibility both for interreader and intrareader analyzes of percent change in diameter, and has been successfully used in analyzing over 4000 brachial flow-mediated vasodilation scans from several medical centers in the United States.

Adult↗
PubMed2000

The viral anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury.

Chemokines and IFN-gamma function as central regulators of inflammatory responses to vascular injury. Both classes of cytokines are upregulated during restenosis, a response to vascular injury that leads to recurrent atherosclerotic plaque growth, but the relative impact of each class of cytokines remains undetermined. M-T7 is a secreted myxoma viral immunomodulatory glycoprotein that functions both as a species-specific inhibitor of rabbit IFN-gamma and as a chemokine-binding protein, interacting with a wide range of C, C-C, and C-X-C chemokines in a species-nonspecific fashion. We wished to (a) assess the efficacy of purified M-T7 protein in inhibiting intimal hyperplasia after angioplasty injury and (b) exploit unique species-specific functions of M-T7 in order to judge the relative importance of each cytokine class on plaque growth. Anesthetized New Zealand white rabbits and Sprague-Dawley rats received either M-T7 or control at the time of arterial angioplasty injury. Histological analysis at 28 days demonstrated significant reductions in intimal hyperplasia with M-T7 treatment in both models, with an associated early inhibition of inflammatory cell invasion. Purified M-T7 protein inhibits intimal hyperplasia after angioplasty injury in a species-nonspecific fashion, thus implicating the chemokine-binding activity as more critical for prevention of plaque growth after vascular injury.

Animals↗
PubMed2000

Titanium(IV) isopropoxide mediated solution phase reductive amination on an automated platform: application in the generation of urea and amide libraries.

Amine libraries and their derivatives are important targets for high throughput synthesis because of their versatility as medicinal agents and agrochemicals. As a part of our efforts towards automated chemical library synthesis, a titanium(IV) isopropoxide mediated solution phase reductive amination protocol was successfully translated to automation on the Trident(TM) library synthesizer of Argonaut Technologies. An array of 24 secondary amines was prepared in high yield and purity from 4 primary amines and 6 carbonyl compounds. These secondary amines were further utilized in a split synthesis to generate libraries of ureas, amides and sulfonamides in solution phase on the Trident(TM). The automated runs included 192 reactions to synthesize 96 ureas in duplicate and 96 reactions to synthesize 48 amides and 48 sulfonamides. A number of polymer-assisted solution phase protocols were employed for parallel work-up and purification of the products in each step.

Amides↗
PubMed2000

Detection of transfusion transmitted virus in hepatic and extra hepatic tissues using in situ hybridization.

OBJECTIVE: To investigate the location, distribution and significance of transfusion transmitted virus (TTV) in the liver and extra hepatic tissues. METHODS: A 123 bp fragment of TTV DNA within ORF(2) was amplified by PCR reaction and cloned into PCR2.1 vector. DNA sequencing revealed that the inserted fragment was highly isogenous with Japan ABO11494 strain. The inserted fragment was labeled with digoxigenin. Segment of liver, spleen, kidney, stomach and intestine tissues from 22 patients dead of liver diseases were detected by in situ hybridization with this digoxigenin labeled TTV DNA probe. RESULTS: TTV DNA was detected in 8 livers, 4 kidneys, 3 spleens, 2 intestines, and 2 stomachs. The positive cells of TTV DNA in livers were higher than that in other tissues. No obvious pathological topographical relationship of tissue inflammatory reaction with positive cells was found. CONCLUSION: TTV can infect hepatic and ex-hepatic tissues and may cause persistent infection.

Adolescent↗
PubMed2000

Study on polymorphism of MICA exon 5 microsatellite in Shanghai Han population.

OBJECTIVE: To investigate the polymorphism distribution of MICA gene exon 5 microsatellite in Shanghai Han population and study the relationship of MICA gene and its closely linked gene HLA B. METHODS: The microsatellite polymorphism of MICA exon 5 in 175 unrelated healthy individuals were investigated using PCR-heteroduplex analysis. RESULTS: (1)There are 5 alleles of the microsatellite polymorphism in exon 5 of the MICA gene in Shanghai Han population, the gene frequency of MICA*A5 is the highest(39.14%), the next is MICA*A5.1(22.29%). (2)There is strong linkage disequilibrium between the HLA-B and MICA STR loci, e.g. MICA*A5 and HLA-B15, MICA*A4 and HLA-B27. CONCLUSION: The polymorphism distribution of MICA gene and the linkage disequilibrium between MICA and HLA-B have deviations in different ethnic groups.

China↗
PubMed2000

[Study on normal pregnancy and recurrent spontaneous abortions from helper T cell 1/helper T cell 2 cytokines balance].

OBJECTIVE: To investigate the function of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4, IL-10) cytokine balance in the maternal-fetal tolerance. METHODS: The IFN-gamma, TNF-alpha, IL-4 and IL-10 mRNA were studied from PBMCs of 11 normal non-pregnancy control, 10 women in first trimester of normal pregnancy, 11 women in last trimester of normal pregnancy by semi-quantitative reverse transcriptional-polymerase chain reaction (RT-PCR) method. RESULTS: (1) The IFN-gamma mRNA decreased [(24.68 +/- 5.55)%, P < 0.05], while the IL-10 mRNA rose [(20.72 +/- 5.36)%, P < 0.01] in normal pregnancy women compared with the non-pregnancy control [IFN-gamma(30.76 +/- 5.35)%, IL-10 (13.58 +/- 3.91)%]. (2) IL-10 mRNA decreased [(9.48 +/- 2.84)%, P < 0.05], while the IFN-gamma mRNA rose [(36.08 +/- 5.75)%, P < 0.05] in RSA women compared with the non-pregnancy control. (3) The IFN-gamma mRNA rose (P < 0.01), while the IL-10 mRNA decreased (P < 0.01) in RSA women compared with women in their first trimester of normal pregnancy [IFN-gamma(27.23 +/- 5.74)%, IL-10 (18.61 +/- 5.43)%]. CONCLUSIONS: The results suggest that women in normal pregnancy had mainly the Th2 cytokines. The breakage of the Th1/Th2 balance may result in RSA. The results provide clue that Th1/Th2 balance plays a role in maternal-fetal tolerance.

Abortion, Habitual↗
PubMed2000

[A study on the deficiency of anticoagulant proteins in Chinese patients with deep venous thrombosis].

OBJECTIVE: To investigate the incidence of anticoagulant proteins deficiency in Chinese patients with venous thrombosis. METHODS: Eighty-seven patients with otherwise unexplained venous thrombophilia were studied. Both the antigen and antivitity of PC, PS, and antithrombin III (ATIII) were determined using commercial kits (Stago, or IL) activated PC, sensitivity ratio (APC-SR) by Coatest chromogenix, and factor V gene mutation by polymerase chain reaction with restriction fragments long polymorphism (PCR-RFLP). RESULTS: Of all the patients twenty-five were found to be abnormal. These consisted of 3 ATIII deficiencies, 5 PC deficiencies, 10 PS deficiencies, 2 resistance of activated protein C (APC-R), 1 combined ATIII and PC deficiency, 1 combined ATIII and PS deficiency, 1 combined PC and PS deficiency, 1 combined APC-R and PC deficiency and 1 combined APC-R and PS deficiency. The overall prevalence of ATIII, PC and PS deficiencies was 26.4%. The patients with anticoagulant proteins deficiency had earlier onset (35.2 +/- 9.7 vs 42.1 +/- 10.9; P < 0.01) and more recurrent thrombosis (P < 0.05), as well as more pulmonary embolism (44.0% vs 16.1%; P < 0.01) than those of without anticoagulant protein deficiency. CONCLUSION: The overall prevalence of ATIII, PC, and PS deficiency in Chinese venous thrombosis patients was higher than that of Western patients. It suggests that the etiology of thrombophilia may be different between Chinese and Western.

Adolescent↗
PubMed2000

[Endometrial stromal sarcoma with multi-differentiation: a study of 17 cases].

OBJECTIVE: To investigate the clinical and pathomorphological features of multi-differentiated endometrial stromal sarcoma of the uterus and to discuss their behaviour and differential diagnosis. METHODS: The histological characteristics of all cases were observed by pathological examination, some of them have been studied by immunohistochemical and/or ultrastructural techniques. RESULTS: Multi-differentiation was present in 13 cases of low grade and 4 cases of high grade endometrial stromal sarcoma, of which, 13 cases had sex-cord differentiation, 10 cases had smooth muscle differentiation, osseous differentiation in 2 cases and striated muscle differentiation in 1 case. Two types of multi-differentiation was present in 9 cases. CONCLUSIONS: Both low-grade and high-grade endometrial stromal sarcoma of uterus can display multi-differentiation. Sex-cord and smooth muscle differentiation are the most common types. Osseous and striated muscle differentiation are very rare. There is no definite correlation between prognosis and the amount or types of multi-differentiation components.

Adult↗
PubMed2000

[Evaluation of hearing thresholds of 40Hz auditory event related potential and auditory brainstem response].

Recordings of pure tone response, 40 Hz auditory event-related potential (40 Hz AERP) and auditory brainstem response (ABR) were obtained for 74 ears of 42 cases (32 normal ears, 42 injured ears). 40 Hz AERP (0.5-2 kHz) of 20 ears was tested under natural sleep and awake conditions. The results showed that the threshold of 40 Hz AERP was higher than that of tone pip, with the difference of 12.7 +/- 6.4 dBnHL at 0.5 kHz, 14.7 +/- 6.3 dBnHL at 1 kHz, and 15.6 +/- 5.6 dBnHL at 2 kHz respectively. The threshold of 40 Hz AERP increased in natural sleep compared with that in awake state. The threshold of ABR was higher than the behavioral. The data suggests that jointly using several tests get more accurate and objective results in evaluating hearing loss.

Adolescent↗
PubMed1999

Construction and characterization of polycistronic retrovirus vectors for sustained and high-level co-expression of apolipoprotein A-I and lecithin-cholesterol acyltransferase.

Apolipoprotein A-I (apo A-I) and lecithin-cholesterol acyltransferase (LCAT) are constituents of circulating high-density lipoprotein (HDL) particles and play an important role in 'reverse cholesterol transport', the process by which cholesterol in peripheral tissues is transferred to the liver for excretion. Enhancing levels of apo A-I, as well as LCAT, in plasma may promote the removal of excess cholesterol from the arterial wall and thus reduce the formation of atherosclerotic lesions. Indeed, both apo A-I and LCAT genes have been identified as therapeutic targets to prevent or limit atherogenesis. Here, we have constructed two retroviral vectors, one containing LCAT cDNA and the neomycin phosphotransferase (NEO) gene (pLLEN), the other apo A-I cDNA, LCAT cDNA and the NEO gene (pLAPLEN) linked by internal ribosome entry sites (IRES). Both bi- and tricistronic retroviral vectors efficiently co-expressed their two or three genes when transfected into cultured mouse C2C12 muscle cells or human 293 cells. After 30 days, the retroviral vector sequences were retained by the host cells, whereas those of a conventional plasmid vector were lost. Moreover, transduced C2C12 mouse myoblasts maintained the ability for heterologous expression of human LCAT and apo A-I even after differentiation into myotubes. Stably-transduced clones of C2C12 cells were selected by neomycin (G418) resistance and continued to efficiently express human LCAT for 60 days. These findings indicate that the use of polycistronic retrovirus vectors to genetically modify myoblasts, which can be transplanted back into skeletal muscle, might be a safe and feasible strategy to express human apo A-I and LCAT and hence have therapeutic potential to regress atherosclerotic lesions.

Animals↗
PubMed1999

Smoking in China: findings of the 1996 National Prevalence Survey.

CONTEXT: As the world's largest producer and consumer of tobacco products, China bears a large proportion of the global burden of smoking-related disease and may be experiencing a tobacco epidemic. OBJECTIVE: To develop an evidence-based approach supporting tobacco control initiatives in China. DESIGN AND SETTING: A population-based survey consisting of a 52-item questionnaire that included information on demographics, smoking history, smoking-related knowledge and attitudes, cessation, passive smoke exposure, and health status was administered in 145 disease surveillance points in the 30 provinces of China from March through July 1996. PARTICIPANTS: A nationally representative random sample of 128766 persons aged 15 to 69 years were asked to participate; 120298 (93.8%) provided data and were included in the final analysis. About two thirds of those sampled were from rural areas and one third were from urban areas. MAIN OUTCOME MEASURES: Current smoking patterns and attitudes; changes in smoking patterns and attitudes compared with results of a previous national survey conducted in 1984. RESULTS: A total of 41187 respondents smoked at least 1 cigarette per day, accounting for 34.1% of the total number of respondents, an increase of 3.4 percentage points since 1984. Current smoking continues to be prevalent among more men (63%) than women (3.8%). Age at smoking initiation declined by about 3 years for both men and women (from 28 to 25 years). Only a minority of smokers recognized that lung cancer (36%) and heart disease (4%) can be caused by smoking. Of the nonsmokers, 53.5% were exposed to environmental tobacco smoke at least 15 minutes per day on more than 1 day per week. Respondents were generally supportive of tobacco control measures. CONCLUSION: The high rates of smoking in men found in this study signal an urgent need for smoking prevention and cessation efforts; tobacco control initiatives are needed to maintain or decrease the currently low smoking prevalence in women.

Adolescent↗