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Biomedical subjects

S Yan

Publications and source records attributed to S Yan.

At least 73 records · Page 4Linked to original sources

Perturbation of EGF-induced MAP kinase activation by TGF-beta 1.

TGF-beta 1 regulates both cellular growth and phenotypic plasticity important for maintaining a growth advantage and increased invasiveness in progressively malignant cells. Recent studies indicate that TGF-beta-1 stimulates the conversion of epitheliod to fibroblastoid phenotype which presumably leads to the inactivation of growth-inhibitory effects by TGF-beta 1 (Portella et al. (1998) Cell Growth and Differentiation, 9: 393-404). Therefore, the investigation of TGF-beta 1 signaling that leads to altered growth and migration may provide novel targets for the prevention of increased cell growth and invasion. Although much attention has been paid to TGF-beta 1 responses in epithelial cells, the above studies suggest that examination of signal transduction pathways in fibroblasts are important as well. Data from our laboratory are consistent with the concept that TGF-beta 1 can act as a regulatory switch in density-dependent C3H 10T1/2 fibroblasts capable of either promoting or delaying G1 traverse. The regulation of this switch is proposed to occur prior to pRb phosphorylation, namely prior to activation of cyclin-dependent kinases. The current study is concerned with the evaluation of a key cyclin (cyclin D1) which activates cdk4 and p27KIP1 which in turn inhibit cdk2 in the proliferative responses of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) and their modulation by TGF-beta 1. Although the molecular events that lead to elevation of cyclin D1 are not completely understood, it appears likely that activation of p42/p44MAPK kinases is involved in its transcriptional regulation. TGF-beta 1 delayed EGF- or PDGF-induced cyclin D1 expression and blocked the induction of active p42/p44MAPK. The mechanism by which TGF-beta 1 induces a block in p42/p44MAPK activation is being examined and the possibility that TGF-beta 1 regulates phosphatase activity is being tested.

Cell Transformation, Neoplastic↗

Association of polymorphism of apolipoprotein E gene with coronary heart disease in Han Chinese.

OBJECTIVE: To investigate the association between apolipoprotein E (apoE) gene polymorphism and coronary heart disease(CHD) in Han Chinese. METHODS: Apo E genotype was examined with the methods of hot start polymerase chain reaction (PCR) and restriction isotyping in samples of 113 unrelated Chinese healthy individuals and 93 patients with CHD. The relation of the gene polymorphism of apoE and levels of serum lipids, lipoproteins, and apolipoproteins was also studied. RESULTS: The results showed that the epsilon 4/3 genotype was more frequent in CHD cases than in control subjects (31.2% vs. 11.5%, P < 0.01). The frequency of the epsilon 4 allele in CHD cases was significantly higher than in control subjects (17.2% vs 7.5%, P < 0.01). The epsilon 4 allele was associated with high concentrations of serum TC (r = 0.265, P < 0.05), LDL-C (r = 0.266, P < 0.05), and apoB (r = 0.360, P < 0.01). CONCLUSIONS: Hot start PCR assay is considered a rapid and simple technique for apoE genotyping. This method is suitable for routine laboratories and large scale population studies. Genetic polymorphism of the apoE gene might contribute to the determination of serum lipid profile and the development of CHD among Han Chinese.

Alleles↗

Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans. Identification of a common receptor for fibronectin, fibrinogen, and laminin.

Host infection by the pathogenic fungus Candida albicans is initiated by adhesion and mediated by binding to several host extracellular matrix proteins. Previously, we demonstrated that hemoglobin supplemented into a chemically defined medium significantly and specifically induced fibronectin binding to C. albicans. We now report that hemoglobin also induces binding of laminin, fibrinogen, and type IV collagen but not of thrombospondin-1 or type I collagen. The binding of each protein was inhibited by the respective unlabeled ligand in a concentration-dependent manner. Fibrinogen inhibited the binding of radiolabeled fibronectin, laminin, and fibrinogen with similar IC50 values, suggesting that a single promiscuous receptor recognizes these three proteins. Competitive binding studies indicated that a second class of receptor binds specifically to laminin. Growth of C. albicans in the presence of hemoglobin also increased cell adhesion to immobilized fibronectin, laminin, fibrinogen, and type IV collagen but not to thrombospondin-1 or type I collagen. Exposure to hemoglobin induced increased or de novo expression of several surface proteins on C. albicans. One of these proteins with a molecular weight of 55,000 recognized fibronectin, based on ligand protection and affinity chromatography on immobilized fibronectin. Thus, hemoglobin induces both promiscuous and specific receptors for extracellular matrix proteins and, therefore, may regulate matrix adhesion during dissemination of C. albicans infections.

Binding, Competitive↗

Voltage- and use-dependent effect of 7-chlor-benzyltetrahydropalmatine on sodium currents in guinea pig ventricular myocytes.

The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzyltetrahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7.8 +/- 1.8 nA to 5.3 +/- 1.4 nA, P < 0.01, n = 5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V0.5 was shifted from -(82.5 +/- 2.5) mV to -(95 +/- 2.4) mV (P < 0.05, n = 4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.

Animals↗

Protective effects of extracted human-liver RNA, a known interferon inducer, against radiation-induced cytogenetic damage in male mice.

Cells in vitro or in vivo pre-exposed to low-dose radiation (LDR) or low concentrations of chemical mutagens became more resistant to large-dose radiation-induced DNA or chromosome damage. This was known as radio-adaptive response, for which the exact mechanism was unclear. However, multiple cellular and molecular responses to LDR have been documented, for instance, the induction of some cytokines such as interferon (IFN). Administration of exogenous IFN to cultured cells or mice showed marked radio-protection. In the present study, we investigated the in vivo radio-protective effects of extracted human liver RNA (HL-RNA), a known IFN inducer, indirectly to determine the radio-protective action of endogenous IFN. First, mice were administered with 6.25 mg/kg HL-RNA at different times before exposure to radiation and the 24 h pretreatment offered the optimal protective action for HL-RNA on cytogenetic effects in bone marrow cells. When the mice were treated with different concentrations of HL-RNA for 24 h, a wide dose-range (25-100 mg/kg) of HL-RNA resulted in a marked protection from X-ray-induced chromosome aberrations in both bone marrow cells and germ cells. In subsequent experiments, a protective effect of pretreatment with 25 mg/kg HL-RNA for 24 h was also found for radiation-induced micronuclei in polychromatic erythrocytes (PCE), and inhibition of DNA repair ability (unscheduled DNA synthesis, UDS). These results demonstrated that HL-RNA, an IFN inducer, is able to offer significant cytogenetic protection from radiation, implying indirectly that the induction of IFN by LDR may also play a protective role as one of the mechanisms in the induction of the cytogenetic adaptive response.

Animals↗

Irritable bowel syndrome symptom patterns: frequency, duration, and severity.

We examined symptom frequency, duration, and severity, as well as episode patterns, in 122 adult patients with irritable bowel syndrome in a 12-week study conducted in the United States, the United Kingdom, and The Netherlands. Patients used an interactive telephone data entry system daily to report symptoms. Data from 59 of the patients meeting inclusion criteria are presented, the remainder having been excluded for failing to complete at least 70 days of symptom reporting. The majority of patients experienced at least one symptom on over 50% of the reported days; however, individual symptoms were reported on less than 50% of the days, indicating that symptoms sometimes occurred sequentially rather than always simultaneously. On average, patients reported pain/discomfort on 33% of days, bloating on 28% of the days, altered stool form or stool passage on 25% and 18% of the days, respectively, and mucus on 7% of the days. The duration of symptoms was relatively short, with pain/discomfort and bloating lasting the longest, an average of five days each per episode. All symptoms but one (mucus) were moderately severe on the majority of reported days. Patients experienced an "episode" (defined as a period of days with symptoms bounded by one or more symptom-free days) on an average of 12.4 times during the study, but the duration of these episodes varied greatly among patients. These results further establish the chronic nature of irritable bowel syndrome and the burden that this condition imposes on patients.

Adult↗

Hemoglobin differentially induces binding of Candida, Trichosporon, and Saccharomyces species to fibronectin.

Fibronectin (FN) is an abundant host protein that is specifically recognized by several pathogenic yeasts. Binding of FN in solution to Candida, Trichosporon, and Saccharomyces species is increased 20- to 110-fold by growth in medium containing hemoglobin, but specific adhesion to immobilized FN is increased only in Candida albicans, Candida tropicalis, Candida krusei, and Candida glabrata. Hemoglobin induces both specific and nonspecific binding of soluble FN. Nonspecific binding accounts for all of the enhancement in Trichosporon beigelii and Saccharomyces cerevisiae, but the Candida species possess a saturable, high-affinity binding site for FN that is induced by hemoglobin. Induction of displaceable soluble FN binding correlates with the ability of hemoglobin to regulate adhesion to immobilized FN, since hemoglobin does not induce adhesion of S. cerevisiae or T. beigelii to immobilized FN. Regulation by hemoglobin of FN binding to Candida species may therefore be an important factor in the pathogenesis in these yeast infections.

Candida↗

Hemoglobin-induced binding of Candida albicans to the cell-binding domain of fibronectin is independent of the Arg-Gly-Asp sequence.

Hemoglobin specifically induces fibronectin (FN) binding to the pathogenic yeast Candida albicans. When grown in the complex medium Sabouraud broth, C. albicans expresses receptors that bind to several domains of FN. Growth in defined medium supplemented with 0.1% hemoglobin, however, enhanced the binding of FN to a single class of receptors, with a Kd = 4.6 x 10(-8) M. Competitive binding assays using recombinant and proteolytic fragments of FN revealed that the cell-binding domain mediated this interaction. A recombinant 40-kDa fragment of FN consisting of type III repeats 9 to 13 had an inhibitory activity similar to that of the entire 120-kDa cell-binding domain, indicating that the C-terminal portion of the cell-binding domain contains the binding site. A recombinant 33-kDa fragment of the cell-binding domain and a 33-kDa fragment with the RGD sequence deleted had the same inhibitory activities, demonstrating that the RGD sequence recognized by some mammalian integrins is not required. The addition of hemoglobin to the culture medium also enhanced Candida cell adhesion to immobilized FN and to 120- and 40-kDa fragments of FN but not to the collagen-binding or fibrin I domains. Using ligand protection, we identified a surface protein from C. albicans with an apparent molecular mass of 55 kDa that was protected by both FN and the 40-kDa fragment derived from the cell-binding domain. Therefore, hemoglobin both induces FN binding and changes the relative affinities of C. albicans for the cell- and collagen-binding domains of FN.

Amino Acid Sequence↗

Cellular localization of latent murine cytomegalovirus.

Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and establishing latency in various tissues. These findings provide clearly needed insight into the site of latent infection which is central to an understanding of the mechanisms of reactivation.

Animals↗

Partitioning of the elastic work of inspiration in patients with COPD during exercise.

During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with chronic obstructive pulmonary disease (COPD) increase the elastic work of inspiration (Wi) more than would be predicted from the increase in tidal volume (VT). This contributes significantly to their exertional breathlessness. In 10 stable patients with COPD, the dynamic Wi was measured during incremental bicycle exercise to exhaustion. The total Wi was then partitioned into the portion required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi). The latter is used to overcome the increase in the total respiratory system elastance during inflation. From resting breathing to peak exercise, Wi more than doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison, Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01). Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to 51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise, when expressed as a percentage of its value during resting breathing, was 25% more than that predicted from the increase in VT alone. Assuming a constant chest wall compliance, this can be attributed to the exercise-induced decrease in CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01), respectively, during resting breathing and peak exercise. In conclusion, the dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more important than the increase in tidal volume in raising the work of inspiration during exercise in patients with chronic obstructive pulmonary disease; the decrease in dynamic lung compliance plays a definite but less important role.

Adult↗

Introduction to a new inspiratory threshold loading device.

Inspiratory threshold loading is an important tool in assessing inspiratory muscle function and has been widely used in studies of respiratory mechanics. A simple system was designed to provide a pure and precise inspiratory threshold load. The inspiratory threshold loading system comprises a flow generator attached via a pressure chamber, to the inspiratory port of a Hans-Rudolph valve. By limiting the circulation of air generated by the flow generator between the room and the pressure chamber, different levels of negative pressure are produced in the pressure chamber and applied to the inspiratory valve. An inspiratory pressure equal to the negative pressure in the chamber has to be generated to open the inspiratory valve for flow. The system was tested in four subjects by measuring mouth pressure (Pm), threshold pressure (Pth) and valve resistance (R). The Pm at the beginning of inspiratory flow was defined as the opening pressure (Pop). The Pth was constant throughout inspiration. Pop was linearly related to Pth (p<0.0001), with slopes within 2% of identity and intercepts within +/-0.2 cmH2O. R was between 0.7-1.1 cmH2O x L(-1) x s(-1) under all conditions and was independent of both Pth (p=0.76) and inspiratory flow (p=0.24). The results demonstrate that this system can provide a constant inspiratory threshold load throughout inspiration with little flow resistance, and is therefore ideal for respiratory studies.

Adult↗

Analysis of the characteristics of folate binding proteins and its relationship with expression of multidrug resistance P-glycoprotein in myelodysplastic syndromes.

OBJECTIVE: To observe the characteristics of folate binding proteins (FBP) in myelodysplastic syndromes (MDS) and leukemia and to study the clinical significance of reduced folate carrier (RFC) present in MDS and its relationship with multidrug resistance (MDR). METHODS: The features of FBP on bone marrow cells were analyzed using radiolabeled 3H-folic acid (3H-FA) binding membrane proteins and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). In the same time, P-glucoprotein and mRNA of MDR gene were detected using immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively in patients with MDS and leukemia. RESULTS: Two kinds of FBP, folate receptor (FR) and reduced folate carrier (RFC), were found on the leukemic cells. The same results were presented on mononuclear cells of bone marrow in 5 out of 14 MDS patients, and MDR positive was seen in 4 patiens of them. In normal control and other 9 cases of MDS FRs were only found on the mononuclear cells of bone marrow. CONCLUSION: Reduced folate carrier, which is present in the leukemic cell, is a product of neoplastic cell. It might reveal preleukmic state and have the same significance with MDR that RFC is found in MDS patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Clinical and experimental study on using Cassia angustifolia extract as enema after abdominal operation].

OBJECTIVE: To investigate the curative effect and mechanism of using Cassia angustifolia extract (CAE) in treating gastrointestinal tract dysfunction after abdominal operations. METHODS: Enema administration of CAE (Clyster method) was used. RESULTS: The result of 130 patients was very effective in reducing the rate of gastrointestinal decompression, accelerating the restitution of borborygmi and the time of exhaustion. Animal experiment showed the CAE function is very obvious in enhancing the bowel movement of rats (P < 0.05). It can enhance peristalsis and contraction amplitude of vibration in the isolated ileum of rats (P < 0.05). It can push on the charcoal powder in intestinal tract of mice obviously (P < 0.05). CONCLUSION: CAE could regulate disordered function of gastrointestinal tract after abdominal operations.

Abdomen, Acute↗

[Effect of RNA against hepatic fibrosis in rabbits infected with Schistosoma japonicum].

AIM: To study the effect of ribonucleic acid (RNA) against schistosomal hepatic fibrosis in rabbits. METHODS: 54 rabbits were randomly and equally divided into normal group, infected group, and RNA group. On the 40, 70, 100th day after RNA i.m. injection, 6 rabbits from each of the above 3 groups were killed and their plasma and liver were examined by way of biochemistry and pathology. RESULTS: Compared with the infected group the collagen fiber of liver in RNA group was less produced, the hepatic cellular nucleolus was enlarged, the number of rough endoplasmic reticulum (RER) and the granules on the RER were increased, the collagen fiber around fat-storing cell was decreased, the content of hyaluronic acid in plasma, the hydroxyproline level in liver tissue, the percentage of collagen fiber distribution and the collagen fiber level in liver tissue of RNA group were significantly reduced. CONCLUSION: RNA might play a role in the prevention of schistosomal hepatic fibrosis.

Animals↗

Cathepsin B and human tumor progression.

Cathepsin B has been implicated in progression of various human tumors. Overexpression of cathepsin B mRNA, increased cathepsin B staining and elevated cathepsin B activity have been found in different human cancers. These occur especially at the invasive edges of cancers, suggesting a role for cathepsin B in tumor invasion. In some tumors, mRNA expression and protein staining for cathepsin B correlate with clinical progression. Cathepsin B can facilitate tumor progression directly through degradation of components of the basement membrane and extracellular matrix. In vitro studies show that cathepsin B may exert its degradative effects intracellularly or extracellularly, depending on the cell type and location of cathepsin B. Cathepsin B can also facilitate tumor progression indirectly through activation of other latent proteases and/or degradation of protein inhibitors of other proteases. Thus cathepsin B may be an integral component of the proteolytic cascade linked to malignant progression of human tumors.

Animals↗