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Tong Yin

Publications and source records attributed to Tong Yin.

14 recordsLinked to original sources
PubMed2006

Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives.

Warfarin is the most widely prescribed oral anticoagulant, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. Information from pharmacogenomics, the study of the interaction of an individual's genotype and drug response, can help optimize drug efficacy while minimizing adverse drug reactions. Pharmacogenetic analysis of two genes, the warfarin metabolic enzyme CYP2C9 and warfarin target enzyme, vitamin K epoxide reductase complex 1 VKORC1, confirmed their influence on warfarin maintenance dose. Possession of CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose. Several single nucleotide polymorphisms (SNPs) in VKORC1 are associated with warfarin dose across the normal dose range. Haplotypes based on these SNPs explain a large fraction of the interindividual variation in warfarin dose, and VKORC1 has an approximately three-fold greater effect than CYP2C9. Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic, and clinical factors to estimate the warfarin dosage, could potentially minimize the risk of over dose during warfarin induction.

Alleles↗
PubMed2006

A comparison of elderly and adult multiple organ dysfunction syndrome in the rat model.

Multiple organ dysfunction syndrome (MODS) in the elderly is the most common cause of mortality in critically ill elderly patients, and it is different from MODS in the adult in clinic. Rare studies have been done on its pathogenesis and the comparison between adult and elderly MODS animal models. This work aimed at exploring the mechanisms mediating elderly MODS and compared this with adult MODS. Male Sprague-Dawley aged and adult rats were intraperitoneally injected with zymosan for incitement of MODS. Aged rats receiving zymosan showed severer pulmonary, cardiac and renal dysfunctions than adult rats. Likewise, the tissue lesions under light microscope in major organs of zymosan treated aged rats were much worse than those of zymosan treated adult rats. Moreover, zymosan treated aged rats showed 142% and 64% greater increase in pulmonary alveolar macrophages (AMs) apoptotic rate and serum TNF-alpha level, respectively, whereas 43% smaller increase in serum IL-10 level compared to zymosan treated adult rats. Furthermore, lung injury was much worse than that in other organs in zymosan treated aged rats. Overall, these results suggest that zymosan can be used in aged rats to incite MODS in the elderly. In the animal model of elderly MODS, there are (1) severer injury in lung, heart and kidney vs adult; (2) easier to develop severe systemic inflammatory response syndrome (SIRS) instead of compensatory anti-inflammatory response syndrome (CARS) compared to the adult; and (3) severer inflammation in lung than other organs indicative of the possible roles of lung in triggering MODS in the elderly.

Aging↗
PubMed2006

Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats.

The formation of fusion genes between NUP98 and members of the HOX family represents a critical factor for the genesis of acute leukemia or acute transformation of chronic myeloid leukemia (CML). To gain insights into the molecular mechanisms underlying the leukemogenesis of NUP98-HOX fusion products, we cloned NUP98-PMX1 from a CML-blast crisis patient with t(1;11) as a secondary chromosomal translocation, and functionally studied the fusion products in detail through various molecular and protein biochemical assays. In addition to many interesting features, we have found that the NUP98-PMX1 fusion protein exerts a repressive effect on PMX1 or serum response factor-mediated c-FOS activation, probably through the recruitment of a common corepressor histone deacetylase 1 by FG domains of the NUP98-PMX1 fusion protein. Moreover, we have provided evidence that the FG domains of NUP98-PMX1 and two other NUP98-containing fusion proteins, i.e., NUP98-HOXA9 and NUP98-HOXC11, all exhibit dual binding ability to both CREB binding protein, a coactivator, and histone deacetylase 1, a corepressor. Accordingly, we have hypothesized that this dual binding activity is shared by most, if not all, NUP98-HOX-involved fusion proteins, enabling these fusion proteins to act as both trans-activators and trans-repressors, and contributing to the genesis of acute leukemia or acute transformation of CML.

Binding Sites↗
PubMed2006

PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention.

Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD). Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.

Animals↗
PubMed2006

The stem cell niches in bone.

The stem cell niche is composed of a specialized population of cells that plays an essential role in regulating adult stem cell self-renewal and differentiation. In adults, osteoblasts, responsible for osteogenesis, and hematopoietic cells, responsible for hematopoiesis, are closely associated in the bone marrow, suggesting a reciprocal relationship between the two. It was recently discovered that a subset of osteoblasts functions as a key component of the HSC niche (namely, the osteoblastic niche), controlling HSC numbers. HSCs interact not only with osteoblasts but also with other stromal cells, including endothelial cells. Sinusoidal endothelial cells in bone marrow have been revealed as an alternative HSC niche called the vascular niche. In this Review we compare the architecture of these 2 HSC niches in bone marrow. We also highlight the function of osteoblasts in maintaining a quiescent HSC microenvironment and the likely role of the vascular niche in regulating stem cell proliferation, differentiation, and mobilization. In addition, we focus on studies of animal models and in vitro assays that have provided direct insights into the actions of these osteoblastic and vascular niches, revealing central roles for numerous signaling and adhesion molecules. Many of the discoveries described herein may contribute to future clinical treatments for hematopoietic and bone-related disorders, including cancer.

Animals↗
PubMed2006

[Finite element analysis of a new shape memory alloy cervical hook for atlantoaxial instability].

The mechanics of a new shape memory alloy cervical hook for atlantoaxial instability was analyzed with finite element method on the basis of a three-dimensional model reconstructed from the images of CT scanning of an adult cadaveric upper cervical at 1-mm interval. The stress and displacement of every nodule and element in the course of deformation of the internal fixation were tested, and the results showed that the cervical hook was strong enough against tensile stress, which concentrates in the middle of the device. The pull was 237.58 N at the loading point. With such mechanical performance, this cervical hook can be reliable for correction of atlantoaxial instability.

Adult↗
PubMed2005

Application of atomic force microscopy in blood research.

AIM: To find suitable solutions having lesser granules and keeping erythrocytes in normal shapes under atomic force microscopy (AFM). METHODS: Eight kinds of solutions, 1% formaldehyde, PBS buffer (pH7.2), citrate buffer (pH 6.0), 0.9% NaCl, 5% dextrose, TAE, 1640 medium and 5% EDTA-K2, were selected from commonly used laboratory solutions, and venous blood from a healthy human volunteer was drawn and anticoagulated with EDTA-K2. Before scanned by AFM (NanoScopeIIIa SPM, Digital Instruments, Santa Barbara, CA), a kind of intermixture was deposited on freshly cleaved mica and then dried in the constant temperature cabinet (37 degrees). RESULTS: One percent formaldehyde, citrate buffer, 5% dextrose, TAE, were found to keep human erythrocytes in normal shape with few particles. Processed by these solutions, fine structures of human erythrocyte membrane were obtained. CONCLUSION: One percent formaldehyde, citrate buffer, 5% dextrose and TAE may be applied to dispose erythrocytes in AFM. The results may offer meaningful data for clinical diagnosis of blood by AFM.

Buffers↗
PubMed2005

[Apoptosis of pulmonary alveolar macrophages in aged and adult rats: a comparative study].

OBJECTIVE: To investigate the role of alveolar macrophages (AM) in the initiation of multiple organ failure in the elderly (MOFE). METHODS: Three-month-old (adult) and 24-month-old (aged) males SD rats were used as experimental animals. Zymosan 0.5 g/kg was used to establish animal model of MOFE, normal saline were used among the control rats. The rats were divided into 4 groups: aged model group, aged control group, adult model group, and adult control group. Twenty-four hours after the establishment of model, 6 surviving rats from each group were killed. The trachea, bronthi, and lungs were isolated and lavaged with normal saline. One minute later the bronchi-alveolar lavage fluid (BALF) was re-extracted. Cells were collected from the fluid and put into 24-well cell culture plate. The alveolar macrophages (AMs) adhered to the wall were collected, suspended again, cultured, re-collected, centrifuged, and isolated. Apoptosis of the enriched AM was measured by propidium staining and flow cytometry. Fluo-3.AM staining and flow cytometry were used to detect the intracellular free calcium. Mitochondrial membrane electric potential was detected by rhodamine 123 staining with flow cytometry. RESULTS: The apoptotic rate (APO) of AM in the aged rat models was 43.4% +/- 8.4%, significantly higher than that of adult model rats (24.2% +/- 3.0%, P < 0.01). Compared with the controls, the intracellular calcium increased, but mitochondrial Dgr;Psim decreased in the 2 model groups. CONCLUSION: The AM APO% of aged MOFE model increases. It may be one of the causes of difficulty to control the inflammation in the lung with MOFE and easiness to induce MOFE in elderly when their lungs are infected or injured. Changes of intracellular calcium and mitochondrial Dgr;Psim may play pivotal roles in apoptosis of AM.

Aging↗
PubMed2005

AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec.

To explore the genetic abnormalities that cooperate with AML1-ETO (AE) fusion gene to cause acute myeloid leukemia (AML) with t(8;21), we screened a number of candidate genes and identified 11 types of mutations in C-KIT gene (mC-KIT), including 6 previously undescribed ones among 26 of 54 (48.1%) cases with t(8;21). To address a possible chronological order between AE and mC-KIT, we showed that, among patients with AE and mC-KIT, most leukemic cells at disease presentation harbored both genetic alteration, whereas in three such cases investigated during complete remission, only AE, but not mC-KIT, could be detected by allele-specific PCR. Therefore, mC-KIT should be a subsequent event on the basis of t(8;21). Furthermore, induced expression of AE in U937-A/E cells significantly up-regulated mRNA and protein levels of C-KIT. This may lead to an alternative way of C-KIT activation and may explain the significantly higher C-KIT expression in 81.3% of patients with t(8;21) than in patients with other leukemias. These data strongly suggest that t(8;21) AML follows a stepwise model in leukemogenesis, i.e., AE represents the first, fundamental genetic hit to initiate the disease, whereas activation of the C-KIT pathway may be a second but also crucial hit for the development of a full-blown leukemia. Additionally, Gleevec suppressed the C-KIT activity and induced proliferation inhibition and apoptosis in cells bearing C-KIT N822K mutation or overexpression, but not in cells with D816 mC-KIT. Gleevec also exerted a synergic effect in apoptosis induction with cytarabine, thus providing a potential therapeutic for t(8;21) leukemia.

Adolescent↗
PubMed2004

Combined effects of As4S4 and imatinib on chronic myeloid leukemia cells and BCR-ABL oncoprotein.

Imatinib (STI571, Gleevec) is a tailored drug for chronic myelogenous leukemia (CML), whereas arsenic compounds were used as ancient remedies for CML with certain efficacy. The aim of this study was to investigate the potential benefit of combination therapy with imatinib and arsenic sulfide (As(4)S(4)). Analysis of cell proliferation and clonogenic ability showed that As(4)S(4) and imatinib exerted synergistic effects on both K562 cells and fresh CML cells. The effective concentrations on fresh CML cells were pharmacokinetically available in vivo but had much less inhibitory effect on CD34(+) cells from the nonleukemic donors. Examination of cell cycles showed that As(4)S(4) induced G(2)/M arrest whereas imatinib induced G(1) arrest. Using a number of parameters such as morphology, annexin V/propidium iodide (PI), mitochondrial transmembrane potential, caspase-3 activity, and Fas/Fas-L, the synergistic effects were revealed on induction of cell apoptosis, largely through the mitochondrial pathway. The 2 drugs also exhibited a synergistic effect in targeting BCR-ABL protein. While As(4)S(4) triggered its degradation and imatinib inhibited its tyrosine kinase activity, combined use of the 2 led to lower protein/enzymatic activity levels of BCR-ABL. Our in vitro data thus strongly suggest a potential clinical application of imatinib and As(4)S(4) combination on CML.

Antineoplastic Agents↗
PubMed2003

Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer.

AIM: To elucidate the relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. METHODS: Routine autopsy was carried out in the randomly selected 102 patients (among them 100 patients died of various diseases, and 2 patients died of non-diseased reasons), their superficial lymph nodes locating in bilateral necks (include supraclavicle), axilla, inguina, thorax, and abdomen were sampled. Haematoxylin-Eosin staining was performed on 10 % formalin-fixed and paraffin-embedded lymph node tissue sections (5 um). The histological patterns of the lymph sinuses containing blood were observed under light microscope. The expression of CD31, a marker for endothelial cell, was detected both in blood and non-blood containing lymph node sinuses with the method of immunohistochemistry. RESULTS: Among the 1 322 lymph nodes sampled from the autopsies of 100 diseased cases, lymph node sinuses containing blood were found in 809 lymph nodes sampled from 91 cases, but couldn't be seen in the lymph nodes sampled from the non-diseased cases. According to histology, we divided the blood containing lymph node sinuses into five categories: vascular-opening sinus, blood-deficient sinus, erythrophago-sinus, blood-abundant sinus, vascular-formative sinus. Immunohistochemical findings showed that the expression of CD31 was strongly positive in vascular-formative sinuses and some vascular-opening sinuses while it was faint in blood-deficient sinuses, erythrophago-sinuses and some vascular-opening sinuses. It was almost negative in blood-abundant sinus and non-blood containing sinus. CONCLUSION: In the state of disease, the phenomenon of blood present in the lymph sinus is not uncommon. Blood could possibly enter into the lymph sinuses through the lymphaticovenous communications between the veins and the sinuses in the node. Lymph circulation and the blood circulation could communicate with each other in the lymph node sinuses. The skipping and distal lymphatic metastasis of gastric cancer may have some connection with the blood containing lymph node sinuses.

Adolescent↗
PubMed2002

Application of catalytic wet air oxidation for the treatment of H-acid manufacturing process wastewater.

Four types of powder catalysts whose main active components are copper (Cu), cerium (Ce), cadmium (Cd) and cobalt-bismuthide (Co-Bi) are prepared with the method of the co-deposition and are evaluated through the catalytic wet air oxidation (CWAO) treatment of H-acid solution. The comparison of the efficiencies of different catalysts shows that Ce3Cu1 (3:1) catalyst is the best one. When the reaction temperature is 200 degrees C, oxygen partial pressure is 3 MPa, pH value is 12, and reaction time is 30 min, the COD removal rate is over 90%. All the H-acid is decomposed in 5 min and is oxidized into NH4+, SO4(2-) formic acid, acetic acid and other end products. The pH value can greatly affect the COD removal and the production of organic acid. CWAO process not only can get a high reaction rate, but also can oxidize the short-chain organic acid.

Catalysis↗
PubMed1999

Cyclosporin A protects Balb/c mice from liver damage induced by superan tigen SEB and D-GalN.

AIM:To investigate the pathogenic effect of SEB and D-GalN on liver and the protection of cyclosporin A, the relationship between hepatic apoptosis and necrosis and the possible mechanism of acute hepatic necrosis.METHODS:After staphylococcal enterotoxin B (SEB) mixed with D-galactosamine (D-GalN) were injected intraperitoneally into Balb/c mice and those previously treated with cyclosporin A, blood samples were collected and livers were isolated at 2, 6, 12, 24h. Patterns of hepatocellular death were studied morphologically and biochemically, circulating cytokines (TNF-alpha, IFN-gamma) and mice mortality within 24h was assessed.RESULTS: The SEB could induce the typical apoptotic changes of hepatocytes, the D-GalN could induce hepatocytes apoptosis and degeneration at the same time, and the mice having received the SEB+D-GalN injections developed apoptosis at 2 and 6h, but after 12h hepatocytes were characterized by severe injury, whereas all the examinations in the cyclosporin A treated mice were normal.CONCLUSION:Hepatic cell apoptosis might be related to necrosis, and massive hepatocyte apoptosis is likely the initiating step of acute hepatic necrosis in mice. The effects induced by SEB and D-GalN on hepatocytes might be mediated by T cells, and could be prevented by cyclosporin A.

Journal Article↗