Biomedical subjects

Hong Yu

Publications and source records attributed to Hong Yu.

At least 91 records · Page 5Linked to original sources

PubMed2004

Association of genetic polymorphisms in the fibrinogen and platelet glycoprotein genes with unstable angina in Chinese patients.

BACKGROUND: Inherited predisposition has been associated with coronary artery disease (CAD) in the white population. HYPOTHESIS: The objective of this study was to investigate the association between the risk of unstable angina (UA) and genetic factors believed to be associated with an increased tendency toward thrombosis (the variable number of tandem repeats [VNTR] polymorphism of the platelet glycoprotein [GP] Ib alpha gene, Pl(A1/A2) of the platelet GP IIIa gene, 448G/A of the Bbeta fibrinogen gene and Thr312Ala of the Aalpha fibrinogen gene) in Chinese patients with UA. METHODS: We performed a case/control study evaluating 69 Chinese patients (43 men, 26 women) with UA and 69 control subjects without CAD, individually matched for age and gender. The restriction fragment length polymorphism (RFLP) method was used to determine the genetic polymorphisms. RESULTS: The frequencies of GP Ib alpha C/B genotype and Bbeta fibrinogen 448A allele were higher in patients with UA (46.4 vs. 30.4%, odds ratio [OR] 1.977, 95% confidence interval [CI] 0.98-3.97, p = 0.054, and 49.3 vs. 20.3%, OR 3.816, 95% CI 1.797-8.103, p = 0.000, respectively). Only four subjects (two cases, two controls) with GP IIIa Pl(A2) allele were found, and there was no association between Aalpha fibrinogen Thr312Ala polymorphism and UA. CONCLUSIONS: Chinese patients with UA had increased frequencies of GP Ib alpha C/B genotype and Bbeta fibrinogen 448A allele. These data suggest that some genetic factors may influence the development of UA.

Adult↗

PubMed2004

GeneWays: a system for extracting, analyzing, visualizing, and integrating molecular pathway data.

The immense growth in the volume of research literature and experimental data in the field of molecular biology calls for efficient automatic methods to capture and store information. In recent years, several groups have worked on specific problems in this area, such as automated selection of articles pertinent to molecular biology, or automated extraction of information using natural-language processing, information visualization, and generation of specialized knowledge bases for molecular biology. GeneWays is an integrated system that combines several such subtasks. It analyzes interactions between molecular substances, drawing on multiple sources of information to infer a consensus view of molecular networks. GeneWays is designed as an open platform, allowing researchers to query, review, and critique stored information.

Artificial Intelligence↗

PubMed2004

Endograft technology: a delivery vehicle for intravascular gene therapy.

PURPOSE: The purpose of this study was to determine whether vascular smooth muscle cells (SMCs) suffused into a bilayered stent graft retain and express a retrovirally transduced gene for 7 months in vivo. METHODS: SMCs harvested from dog jugular vein were retrovirally transduced to introduce genes for tissue plasminogen activator (t-PA) and beta-galactosidase. These cells were then suffused into a novel dual-layered Dacron graft and cultured for 36 to 48 hours. The grafts were mounted on a Palmaz stent and balloon- expanded in the infrarenal aorta of the SMC donor dogs (n = 6). Grafts were recovered at 1, 2, 3, 4, 5, and 7 months. A control endograft suffused with SMCs transduced with only the beta-galactosidase gene was placed in the dogs with grafts recovered at 2, 3, and 4 months. t-PA antigen concentration and expression were analyzed with an enzyme-linked immunosorbent assay. RESULTS: Retained engineered SMCs (blue nuclei) were identified in the explanted grafts, neointima, and underlying aorta with X-gal staining. The t-PA antigen concentration and t-PA activity from the SMCs recovered from the grafts remained elevated for the duration of the experiment (7 months) at levels significantly higher (3.7 +/- 0.2 ng/mL per 10(5) cells per 24 hours and 1.4 +/- 0.1 IU/mL per 10(5) cells per 24 hours) than in control endografts (0.5 +/- 0.03 ng/mL per 10(5) cells per 24 hours and 0.07 +/- 0.00 IU/mL per 10(5) cells per 24 hours; P <.001). No graft stenosis was observed. CONCLUSION: Retrovirally engineered vascular SMCs survived the implantation trauma, repopulated each graft, migrated into the underlying aorta, and expressed the transduced genes for the 7-month duration of the experiment. This bilayered Dacron endograft model provides a platform to study direct intravascular gene therapy.

Animals↗

PubMed2004

Effect of antisense VEGF cDNA transfection on the growth of chronic myeloid leukemia K562 cells in vitro and in nude mice.

To further elucidate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of chronic myeloid leukemia (CML), we transfected K562 cells with a VEGF(121)cDNA sense vector (S), an antisense (AS) vector or vector (V) alone. The growth of transfected cells was investigated by MTT and colony-formation assays, and apoptosis was measured by flow cytometry (FCM) of Annexin-V-FITC/PI dual labeled cells. Transfected cells were subcutaneously transplanted into nude mice and the microvessel density (MVD) of tumor masses was determined by vWF immunohistochemistry staining. We tested the supernatant of different transfected K562 cells against human bone marrow endothelial cells (BMECs), and examined the synergic effects of antisense VEGF(121)cDNA and IFNalpha or STI571 on the proliferation and apoptosis of K562 cells. We found that K562/AS transfectants exhibited a 49% reduction in VEGF secretion, whereas K562/S transfectants exhibited a 3-fold increase in VEGF secretion, all in comparison to the vector controls. K562 cells transfected with antisense VEGF(121)cDNA showed growth retardation in vitro. In transplanted nude mice in vivo, transfection of implanted cells with antisense VEGF(121)cDNA resulted in decreased tumor MVD, and increased apoptosis in the presence of IFNalpha. Taken together, these results suggest that VEGF may be involved in the pathogenesis of CML through autocrine and paracrine mechanisms, and that anti-VEGF therapy alone or in combination with conventional treatment may be beneficial for CML patients.

Animals↗

PubMed2004

Arginases I and II: do their functions overlap?

Arginase, often perceived solely as the last of the now six enzymes of the urea cycle, exists in two forms and has a broad tissue distribution. A cytosolic form, AI, is highly expressed in the liver and is thought to be primarily involved in ureagenesis. A mitochondrial form, AII, has been thought to be more widely expressed and to be involved in the biosynthesis of polyamines, the amino acids ornithine, proline, and glutamate and in the inflammatory process, among others. This paper will address recent experiments that cast some doubt on the validity of these distinctions. Studies have now suggested that macrophages may express AI or AII in different experimental conditions, both in vivo and in vitro. In contrast, most studies, at least in cell culture, suggest that AII may be most highly expressed in cancers of a number of different types. Inhibition of arginase activity in vivo and in vitro has implicated this activity in maintaining ornithine levels for polyamine synthesis. In situ and "quantitative" PCR studies in mouse have demonstrated that AI and not AII is the predominant isoform expressed during development and in the majority of organs. Mouse knockout models for both AI and AII have been produced and are available to address their functions. Surprisingly, the AII knockout animal has no apparent phenotype except for some diminished fertility in homozygous males, consistent with the belief that AII, highly expressed in prostate, is important for sperm function in semen. The AI knockout animal has a more dramatic phenotype and dies at 10-12 days of life of hyperammonemia. The reason for the prolonged survival, as compared to other urea cycle knockout animals, may be due to the later occurrence of hypo-ornithinemia, a contention not yet proven. Transgenic manipulation of the AI knockout animal and breeding the AI and AII knockouts into single animals may address the ability of AII to rescue animals from some of the metabolic consequences of AI deficiency, as appears to happen in man. Newborn screening has given particular hope to patients affected by arginase (AI) deficiency. Increased arginine appears to be detectable by newborn screening with tandem mass spectrometry and the past years continue to demonstrate the therapeutic effectiveness of dietary management of the disorder, with patients treated from birth remaining normal and those treated late, ceasing to deteriorate and even improving in cognitive and physical functioning. Finally, prenatal diagnosis appears to be possible as was predicted, but never proven, some years ago.

Animals↗

PubMed2004

The glomerulosclerosis of aging in females: contribution of the proinflammatory mesangial cell phenotype to macrophage infiltration.

Age-associated renal changes may be an important cause of renal failure. We recently found that aged female B6 mice developed progressive glomerular lesions. This was associated with macrophage infiltration, a frequent finding in glomerulosclerosis. We used these mice as a model for studying the mechanisms of glomerular aging. We compared the gene expression profile of intact glomeruli from late postmenopausal (28-month-old) mice to that of intact glomeruli from premenopausal (5-month-old) mice. We found that inflammation-related genes, especially those expressed by activated macrophages, were up-regulated in the glomeruli of 28-month-old mice, a result correlating with the histological observation of glomerular macrophage infiltration. The mechanism for macrophage recruitment could have been stable phenotypic changes in mesangial cells because we found that mesangial cells isolated from 28-month-old mice expressed higher levels of RANTES and VCAM-1 than cells from 5-month-old mice. The elevated serum tumor necrosis factor (TNF)-alpha levels present in aged mice may contribute to increased RANTES and VCAM-1 expression in mesangial cells. Furthermore, cells from 28-month-old mice were more sensitive to TNF-alpha-induced RANTES and VCAM-1 up-regulation. The effect of TNF-alpha on RANTES expression was mediated by TNF receptor 1. Interestingly, mesangial cells isolated from 28-month-old mice had increased nuclear factor-kappaB transcriptional activity. Inhibition of nuclear factor-kappaB activity decreased baseline as well as TNF-alpha-induced RANTES and VCAM-1 expression in mesangial cells isolated from 28-month-old mice. Thus, phenotypic changes in mesangial cells may predispose them to inflammatory stimuli, such as TNF-alpha, which would contribute to glomerular macrophage infiltration and inflammatory lesions in aging.

Aging↗

PubMed2004

Identification and expression analysis of EST-based genes in the bud of Lycoris longituba.

To obtain a primary overview of gene diversity and expression pattern in Lycoris longituba, 4,992 ESTs (Expressed Sequence Tags) from L. longituba bud were sequenced and 4,687 cleaned ESTs were used for gene expression analysis. Clustered by the PHRAP program, 967 contigs and 1,343 singlets were obtained. Blast search showed that 179 contigs and 227 singlets (totally 1,066 ESTs) had homologues in GenBank and 3,621 ESTs were novel.

Base Composition↗

PubMed2004

Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors.

GRP78 is a stress-inducible chaperone protein with antiapoptotic properties that is overexpressed in transformed cells and cells under glucose starvation, acidosis, and hypoxic conditions that persist in poorly vascularized tumors. Previously we demonstrated that the Grp78 promoter is able to eradicate tumors using murine cells in immunocompetent models by driving expression of the HSV-tk suicide gene. Here, through the use of positron emission tomography (PET) imaging, we provide direct evidence of spontaneous in vivo activation of the HSV-tk suicide gene driven by the Grp78 promoter in growing tumors and its activation by photodynamic therapy (PDT) in a controlled manner. In this report, we evaluated whether this promoter can be applied to human cancer therapy. We observed that the Grp78 promoter, in the context of a retroviral vector, was highly activated by stress and PDT in three different types of human breast carcinomas independent of estrogen receptor and p53. Complete regression of sizable human tumors was observed after prodrug ganciclovir treatment of the xenografts in immunodeficient mice. In addition, the Grp78 promoter-driven suicide gene is strongly expressed in a variety of human tumors, including human osteosarcoma. In contrast, the activity of the murine leukemia virus (MuLV) long-terminal repeat (LTR) promoter varied greatly in different human breast carcinoma cell lines, and in some cases, stress resulted in partial suppression of the LTR promoter activity. In transgenic mouse models, the Grp78 promoter-driven transgene is largely quiescent in major adult organs but highly active in cancer cells and cancer-associated macrophages, which can diffuse to tumor necrotic sites devoid of vascular supply and facilitate cell-based therapy. Thus, transcriptional control through the use of the Grp78 promoter offers multiple novel approaches for human cancer gene therapy.

Animals↗

PubMed2004

Priming with CpG-enriched plasmid and boosting with protein formulated with CpG oligodeoxynucleotides and Quil A induces strong cellular and humoral immune responses to hepatitis C virus NS3.

Cell-mediated immune responses to hepatitis C virus (HCV) proteins play a key role in recovery from infection. The NS3 protein of HCV is of special interest, since it is one of the most conserved proteins and NS3-specific immune responses are stronger and more frequently observed in patients resolving the infection than in chronically infected patients. Since these characteristics make NS3 an attractive vaccine candidate, the objective of this study was to optimize NS3-specific immune responses. Results from this group first demonstrated that a plasmid enriched with 24 CpG motifs (pBISIA24-NS3) tends to induce the strongest and most consistent Th1-biased immune response. Subsequently, it was shown that NS3 formulated with CpG oligodeoxynucleotide and Quil A (rNS3+CpG+Quil A) adjuvants induces a balanced immune response in mice, whereas rNS3 combined with either CpG or Quil A elicits a Th2-biased response. To further enhance NS3-specific cell-mediated immune responses, a vaccination regime consisting of priming with pBISIA24-NS3, followed by boosting with rNS3+CpG+Quil A, was explored in mice and pigs. When compared to immunization with rNS3+CpG+Quil A, this regime shifted the immune response to a Th1-type response and, accordingly, enhanced MHC I-restricted killing by cytotoxic T lymphocytes in mice. Although immunization with pBISIA24-NS3 also induced a Th1-biased response, including cytotoxicity in the mice, the humoral response was significantly lower than that induced by the DNA prime-protein boost regime. These results demonstrate the advantage of a DNA prime-protein boost approach in inducing a strong NS3-specific cell-mediated, as well as humoral, immune response, in both inbred laboratory and outbred large animal species.

Animals↗

PubMed2004

Angiotensin-converting enzyme inhibitor usage in patients with incidental atherosclerotic renal artery stenosis.

The efficacy of angiotensin converting enzyme (ACE) inhibitors in treatment of renovascular disease has been controversial. It has been reported that patients with incidental atherosclerotic renal artery stenosis (ARAS) are sometimes treated with ACE inhibitors before being considered for renal revascularization. This study was designed to describe the frequency and the characteristics of patients with incidental ARAS, and to examine the frequency of ACE inhibitor usage in such patients. We studied a cohort of consecutive patients undergoing abdominal aortography at the time of cardiac catheterization. Patients were stratified and compared based on the presence and severity of ARAS. ARAS (> or =50%) was present in 146 (17.0%) of 859 evaluable patients. Factors independently related to the presence of ARAS were age (odds ratio (OR)=1.07, p < 0.001), severity of coronary artery disease (OR=2.13, p < 0.001) and peripheral vascular disease (OR=1.79, p = 0.021). Among all patients with ARAS, the percentage of ACE inhibitor usage was 74.7% (109/146). Among patients with severe ARAS, moderate ARAS, mild ARAS, insignificant ARAS and normal renal arteries, the percentage of ACE inhibitor usage was 85.7% (95% confidence interval (CI): 69-100%), 82.9% (95% CI: 71-95%), 68.5% (95% CI: 59-78%), 68.6% (95% CI: 55-82%) and 53.9% (95% CI: 50-58%), respectively (contingency coefficient=0.17, p < 0.001). In patients with severe ARAS, ACE inhibitor use, calcium channel blocker use and diuretic use were shown to correlate significantly with serum creatinine levels after controlling for potential confounding factors. In this study, ACE inhibitors were used commonly in patients with incidental ARAS; the frequency of ACE inhibitor use correlated with the severity of ARAS.

Aged↗

PubMed2004

Ciliated hepatic foregut cyst: report of first case in China and review of literature.

OBJECTIVE: To report the first case of ciliated hepatic foregut cyst in China, and review of literature to introduce the characteristics of this disease for doctors to recognize this disease. METHOD: Report the clinical procedure of diagnosis and treatment for the first case of ciliated hepatic foregut cyst in China, and to review the embryologic genesis, incidence, clinical manifestation, radiologic features and therapeutic principle of this disease. RESULTS: We performed the resection for ciliated hepatic foregut cyst under laparoscopy; the patient recovered well after the procedure. CONCLUSION: Ciliated hepatic foregut cyst is quite rare clinically, belongs to non-parasitic, solitary and unilocular cystic lesion, is always less than 4 cm in diameter, mostly seen in the left lobe, and has the tendency of malignant change. It should be removed as soon as diagnosed.

Adult↗

PubMed2004

Nonlinear control for a class of hydraulic servo system.

The dynamics of hydraulic systems are highly nonlinear and the system may be subjected to non-smooth and discontinuous nonlinearities due to directional change of valve opening, friction, etc. Aside from the nonlinear nature of hydraulic dynamics, hydraulic servo systems also have large extent of model uncertainties. To address these challenging issues, a robust state-feedback controller is designed by employing backstepping design technique such that the system output tracks a given signal arbitrarily well, and all signals in the closed-loop system remain bounded. Moreover, a relevant disturbance attenuation inequality is satisfied by the closed-loop signals. Compared with previously proposed robust controllers, this paper's robust controller based on backstepping recursive design method is easier to design, and is more suitable for implementation.

Algorithms↗

PubMed2004

[Pathogenesis of rat mesangial proliferative glomerulonephritis induced by anti-Thy1 antibody].

OBJECTIVE: To probe into the pathogenesis of rat mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1 antibody. METHODS: Anti-Thy1 serum was produced, and then intravenously injected into Wistar rats for establishing an experimental model of MsPGN. The control group received intravenous injection of normal saline. Urinary volume and urinary protein were examined every other day. The IL-1, IL-6 and TNF contents of serum were detected by radioimmunoassay. Pathologic morphology of renal section was observed with micrscope and BI2000 Image Analysis System. The rats of model group were killed on the 1st, 3rd, 5th and 7th days. RESULTS: No significant difference was seen between the model group and control group in regard to the volume of urine and in-take water (P > 0.05). The levels of urinary protein, IL-1, IL-6 and TNF in model group were significantly higher than those in control group at all time points (P < 0.001-0.005). Glomerular mesangium cells and matrix in the model group were obviously proliferative, compared with those in control group. CONCLUSION: It is suggested that cytokine plays an important role in the onset of MsPGN.

Animals↗

PubMed2004

[Effects of growth factors and extracellular matrix on proliferation and differentiation of fetal liver progenitor cell in vitro].

OBJECTIVE: Liver development needs a number of growth factors and components of the extracellular matrix. The study is to explore how growth factors and extracellular matrix regulate proliferation and differentiation of fetal liver progenitor cell. METHODS: We demonstrate isolation of hepatic progenitor/stem cells from ED 14.5 SD rat liver, which contains a large number of hepatoblasts. Proliferation assay-3H thymidine incorporation was used to detect the effect of growth factors on proliferation of hepatic progenitor cell. Growth factor and extracellular matrix were added and stem cell clone formation was counted. Mark of bile duct and hepatocyte were detected with double-marker immunocytochemistry. RESULTS: Progenitor liver cells displayed clonogenic capacity, expressed markers of hepatocytes and bile duct cells and G-6-P. HGF, EGF can accelerate DNA synthesis and stem cell clone formation of hepatic progenitor cell. Extracellular matrix collagen I, collagen IV or laminin were essential for formation of stem cell clone. Single cell culture needed HGF, EGF, extracellular matrix and supernatant of mix cell (which contained fetal parenchymal cells, mesenchymal cells and hematopoietic cells) culture. CONCLUSION: Growth factors especially HGF and EGF play crucial role in proliferation and differentiation of liver progenitor cell. Some factors secreted from mesenchymal cell and hematopoietic cells may be involved.

Animals↗

PubMed2004

[The retrospect and analysis of the clinical diagnosis and therapy for congenital cholesteatoma of temporal bone].

OBJECTIVE: To discuss the diagnosis and the therapy methods of congenital temporal bone cholesteatoma. METHOD: Reviewing and analyzing the clinical data and information about 16 cases of congenital temporal bone patients from 1980 to 2002. RESULT: The surgery were proceeded for removing cholesteatoma focus in all patients and the diagnosing were made by histopathologic investigation. Following for half to three years, 6 cases of facial nerve paralysis got partially or totally healing, hearing function improved in 5 cases, 2 cases relapsed and operation were made again for resecting, recrudescent cholesteatoma. There were no any subsequent symptoms happened. CONCLUSION: The diagnosis of congenial temporal bone cholesteatoma mainly base on the patient's clinical symptoms and manifestation, and imaging examination. MRI can clearly show cholesteatoma focus and other organs or tissues (including some encephalic frameworks) around it, which also is one of important inspection techniques for discriminating from congenital encephalic cholesteatoma near rock part of temporal bone. The drum integrity is not necessary condition for diagnosing this disease, the surgery approaches are selected by the size and position of focus. The key for preventing recrudescence is to drastically eliminate cholesteatoma tissues.

Adolescent↗

PubMed2004

[Effect of lumbar protective belt on prevention of low back fatigue in personnel during simulated driving].

OBJECTIVE: To observe low back fatigue of subjects before and after simulated driving, and to study the role of the belt used in prevention of low back fatigue of drivers during driving. METHODS: To assess the changes in median frequency (MF), mean power frequency (MPF) of surface electromyogram (SEMG), and flicker frequency, visuognosis persistence of drivers with and without protective belt in simulated driving. RESULTS: There were significant differences in MF [(47.35 +/- 6.07), (39.26 +/- 5.79), (47.21 +/- 6.02), (43.44 +/- 6.26) Hz respectively], MPF [(69.86 +/- 7.08), (59.12 +/- 7.19), (69.86 +/- 7.08), (63.88 +/- 7.49) Hz respectively] between before and after simulated driving without or with the special belt (P < 0.01). But no differences in MF or MPF between without and with the belt before simulated driving were found (P > 0.05). The flicker frequency [(35.64 +/- 2.82), (42.31 +/- 4.68), (35.96 +/- 3.05), (39.79 +/- 3.36) Hz], visuognosis persistence (65.77% +/- 3.94%, 56.83% +/- 5.68%, 65.88% +/- 3.92%, 62.27% +/- 2.91%) had some changes too. CONCLUSION: Simulated diving could induce fatigue of back muscle in drivers. However, the protective belt can effectively prevent low back fatigue of drivers in simulated driving.

Adult↗

PubMed2004

[Quantitative detection of telomerase activity and its association with clinicopathological characteristics in breast cancer].

BACKGROUND & OBJECTIVE: Telomerase is a ribonucleoprotein enzyme, which plays an important role in cell immortalization and carcinogenesis. Recent studies on the association of telomerase activity with prognostic factors of breast cancer were controversial due to different methods. This study was to establish a feasible assay of quantitative detection of telomerase activity based on silver staining, and investigate possible association between telomerase activity and clinicopathological prognostic factors in primary breast cancer. METHODS: Highly sensitive silver-staining telomeric repeat amplification protocol assay (SS-TRAP) was used to quantify telomerase activity in 52 frozen human breast cancer samples and their adjacent breast tissues, 32 benign lesions, and 14 normal mammary gland lesions. The association between telomerase activity and clinicopathological data was analyzed. RESULTS: Telomerase activity was detected in 47 of the 52 breast cancer samples (90.38%), and in 10 of the 32 benign lesions, whereas no activity was detected in 37 of 52 adjacent nonmalignant breast tissues, and all 14 normal mammary gland tissues. The telomerase activity levels were 36.91+/-15.35, 8.27+/-4.37, 14.10+/-5.28, 0 (unit: TPG) in breast cancer, adjacent tissue of cancer, benign lesion, and normal tissue, respectively. The difference of telomerase activity was significant between breast cancer and the other 3 groups by using ANVOA (all P< 0.01). A strong correlation was found between telomerase activity and pathological category, and differentiation degree by logistic regression analysis, i.e. with ongoing tumor progression, telomerase activity appeared to increase in primary breast cancer (P=0.003, and P=0.004). No correlation was seen between telomerase activity and disease course, age, and menopause status of patients (all P >0.05). Telomerase activity level of invasive non-special cancer was higher than that of invasive special cancer(P< 0.05). Telomerase activity level of moderately/poorly differentiated carcer was higher than that of highly differentiated cancer (P< 0.05), while no obvious difference was found between moderately and poorly differentiated cancer (P >0.05). CONCLUSIONS: The activation of telomerase might occur early in breast cancer,and plays a critical role in carcinogenesis and tumor development. Telomerase may serve as a specific marker of early diagnosis and prognosis in mammary gland neoplasm.

Adenofibroma↗

PubMed2004

[The experimental study on the expression of toll-like receptor 2 in fulminant hepatic failure].

OBJECTIVE: In order to explore the role of toll-like receptors 2 (TLR2) in initiating inflammatory response, the expression of TLR2 of the liver and IL-18, TNF-alpha and IFN-gamma of plasma in fulminant hepatic failure was analysed. METHODS: D-galactosamine (D-Gal, 900 mg/kg) and lipopolysaccharide (LPS, 10 microg/kg) were administered intraperitoneally into the BALB/C mice. To evaluate the hepatic injury, serum transaminase (ALT and AST) and plasma IL-18, TNF-alpha and IFN-gamma were determined and the mortality was observed at various time points following the intraperitoneal injection. The level of TLR2 mRNA was measured by semiquantitative RT-PCR. The protein expression of TLR2 in the liver was detected by immunohistochemistry. The data was analyzed by SAS software. RESULTS: After 4 hours of intraperitoneal injection of D-Gal/LPS, the serum transaminase and plasma IL-18, TNF-alpha and IFN-gamma levels were elevated. The treated mice began to die at 7 hours. The mortality reached up to 80% at 10 h. TLR2 mRNA was expressed at a low level in liver tissues of normal mice, while it was significantly increased and maintained at a higher level following intraperitoneal injection with D-Gal/LPS. The expression of TLR2 protein was similar to that of the TLR2 mRNA, and the expression of TLR2 mRNA was positively correlated with the concentration of plasma IL-18, TNF-alpha and IFN-gamma (r=0.36, P=0.02; r = 0.48, P 0.003; r = 0.72, P<0.001) at different time points. CONCLUSIONS: Our results showed that TLR2 was involved in initiating and inducing the expression of proinflammation cytokines in this model of fulminant hepatic failure. The results suggest that adjusting the expression of TLR2 might be a new strategy in preventing the development of infectious diseases

Animals↗