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Biomedical subjects

H Tang

Publications and source records attributed to H Tang.

At least 37 records · Page 2Linked to original sources

Preliminary X-ray crystallographic analysis of a Ca2+-binding protein human S100A1.

S100A1, a Ca(2+)-binding protein from the S100 protein family, has been crystallized by the vapour-diffusion method using polyethylene glycol 4000 as the precipitant at pH 8.5. The crystal belongs to space group P6(3). The unit-cell parameters are a = b = 57.3, c = 104.7 A. There appear to be two S100A1 molecules in the asymmetric unit. The crystals were stable during exposure to X-rays and diffract to 2.6 A resolution in-house.

Calcium-Binding Proteins↗

CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A.

Cyclophilin A (CyPA) is specifically incorporated into the virions of HIV-1 and has been shown to enhance significantly an early step of cellular HIV-1 infection. Our preliminary studies implicated CD147 as a receptor for extracellular CyPA. Here, we demonstrate a role for CyPA-CD147 interaction during the early steps of HIV-1 infection. Expression of human CD147 increased infection by HIV-1 under one-cycle conditions. However, susceptibility to infection by viruses lacking CyPA (simian immunodeficiency virus or HIV-1 produced in the presence of cyclosporin A) was unaffected by CD147. Virus-associated CyPA coimmunoprecipitated with CD147 from infected cells. Antibody to CD147 inhibited HIV-1 entry as evidenced by the delay in translocation of the HIV-1 core proteins from the membrane and inhibition of viral reverse transcription. Viruses whose replication did not require CyPA (SIV or mutant HIV-1) were resistant to the inhibitory effect of anti-CD147 antibody. These results suggest that HIV-1 entry depends on an interaction between virus-associated CyPA and CD147 on a target cell.

Animals↗

Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma.

Vascular endothelial growth factor (VEGF) is a key angiogenic molecule that plays an important role in the growth and metastasis of many types of human cancer, including pancreatic adenocarcinoma. In this study, we explored the regulation of VEGF in human pancreatic cancer cells. Over 70% of the human pancreatic cancer cell lines studied in vitro secreted constitutively high levels of VEGF. High VEGF-secreting cells also generally expressed an elevated steady-state level of VEGF mRNA. Kinetic analysis revealed that the elevated steady-state level of VEGF mRNA was due to enhanced VEGF gene transcription and increased constitutive VEGF promoter activity. Deletive mutation analyses of the VEGF promoter revealed that the region from -109 to -38 bp was essential for constitutive VEGF promoter activity. Further deletion and point mutation analyses indicated that mutation of individual or all of the putative Sp1 binding sites reduced or eliminated the constitutive VEGF promoter activity and abrogated the differential activity of the promoter in high and low VEGF-expressing cells. Consistent with the constitutive VEGF transcription activation, a high level of constitutive Sp1 expression and activity was detected in pancreatic cancer cell lines and pancreatic cancer tissue specimens overexpressing VEGF. Collectively, our data demonstrated that constitutive Sp1 activation is essential for the differential overexpression of VEGF, which in turn plays an important role in the angiogenesis and progression of human pancreatic cancer.

Adenocarcinoma↗

CaM kinase II-dependent suppression of nicotinic acetylcholine receptor delta-subunit promoter activity.

Nerve-induced muscle activity suppresses nicotinic acetylcholine receptor (nAChR) gene expression by increasing intracellular calcium levels. This suppression is mediated by nAChR promoter sequences harboring at least 1 E-box (CANNTG) that bind myogenic helix-loop-helix transcription factors. How muscle depolarization or increased calcium mediates changes in nAChR promoter activity is not well understood. In chick muscle, protein kinase C (PKC) activation is necessary for activity-dependent nAChR gene suppression. Similar effects of PKC activation have not been found in mammalian skeletal muscle. Therefore, we used rat primary muscle cultures to screen for other calcium-regulated enzymatic activities that may mediate the effects of muscle activity and calcium on nAChR promoter activity. We report here that calcium/calmodulin-dependent protein kinase II (CaM kinase II) can specifically suppress nAChR promoter activity in mammalian muscle. This regulation was mediated by a single E-box sequence residing in the previously characterized nAChR delta-subunit genes 47-base pair activity-dependent enhancer. In vitro protein/DNA interaction studies suggest that CaM kinase II inhibits binding of the myogenic factor, myogenin, to the delta-promoter 47-base pair activity-dependent enhancer. CaM kinase activity is increased in active muscle and inhibition of this enzymatic activity results in increased nAChR delta-promoter activity. Therefore, CaM kinase II may represent a previously unappreciated activity that participates in coupling muscle depolarization to nAChR gene expression.

Animals↗

The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors.

Migration is a basic feature of many cell types in a wide range of species. Since the 1800s, cell migration has been proposed to occur in the nervous and immune systems, and distinct molecular cues for mammalian neurons and leukocytes have been identified. Here we report that Slit, a secreted protein previously known for its role of repulsion in axon guidance and neuronal migration, can also inhibit leukocyte chemotaxis induced by chemotactic factors. Slit inhibition of the chemokine-induced chemotaxis can be reconstituted by the co-expression of a chemokine receptor containing seven transmembrane domains and Roundabout (Robo), a Slit receptor containing a single transmembrane domain. Thus, there is a functional interaction between single and seven transmembrane receptors. Our results reveal the activity of a neuronal guidance cue in regulating leukocyte migration and indicate that there may be a general conservation of guidance mechanisms underlying metazoan cell migration. In addition, we have uncovered an inhibitor of leukocyte chemotaxis, and propose a new therapeutic approach to treat diseases involving leukocyte migration and chemotactic factors.

Animals↗

Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody.

Systemic injection of antibodies against acetylcholinesterase (AChE) induces complement-mediated destruction of preganglionic nerve terminals in paravertebral sympathetic ganglia, but spares other AChE-rich structures, such as nerve terminals in prevertebral sympathetic ganglia, parasympathetic ganglia, and the neuromuscular junction. This pattern of differing sensitivity to "AChE immunolesion" might be explained by a differing expression of proteins that serve to protect host cells from complement activation. Two major complement regulatory proteins in rats are Crry, which interferes with the assembly of C3 convertase, and CD59, which blocks formation of the terminal cytolytic membrane attack complex. The present study used immunohistochemistry to demonstrate an inverse relation between levels of CD59 and Crry expression and sensitivity to AChE immunolesion in several AChE-rich targets. Thus, the most sensitive structures, i.e., preganglionic nerve terminals in the adrenal gland and superior cervical ganglion (SCG), expressed undetectable levels of CD59 and Crry immunoreactivities. By contrast, AChE-rich, but antibody-resistant, cholinergic nerve terminals in the inferior mesenteric ganglia (IMG) and diaphragm muscle expressed significant amounts of CD59 and Crry. Such expression was functionally important because, after membrane-anchored CD59 was removed from explanted IMG with phosphatidylinositol phospholipase C, exposure to AChE antibody and complement caused greater immunolesion. It was concluded that differential expression of regulatory proteins in different parts of the nervous system influences regional vulnerability to complement mediated damage.

Acetylcholinesterase↗

3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors block calcium-dependent tyrosine kinase Pyk2 activation by angiotensin II in vascular endothelial cells. involvement of geranylgeranylation of small G protein Rap1.

We recently reported the calcium-dependent activation of tyrosine kinase Pyk2 by angiotensin II (Ang II) in pulmonary vein endothelial cells (PVEC). Since Pyk2 has no calcium binding domain, and neither Ca(2+) nor Ca(2+)/calmodulin directly activates Pyk2, it is not clear how Ca(2+) transduces the signal to activate Pyk2, a key tyrosine kinase, in the early events of Ang II signaling. In the present study, we investigated the mechanism of the calcium-dependent activation of Pyk2 in response to Ang II by using 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors and isoprenoid intermediates in PVEC. We have obtained substantial evidence indicating that Ang II activates Pyk2 through calcium-mediated activation of the geranylgeranylated small G protein Rap1 and the Rap1 association with Pyk2. Thus, the small G protein Rap1 is an intermediary signaling molecule linking Ang II-induced calcium signal to Pyk2 activation in PVEC. In addition, our results indicate that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, a class of cholesterol-lowering drugs, could interrupt Ang II signaling independent of cholesterol lowering in endothelial cells.

Angiotensin II↗

Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism.

Hepatotropism is a prominent feature of hepatitis B virus (HBV) infection. Cell lines of nonhepatic origin do not independently support HBV replication. Here, we show that the nuclear hormone receptors, hepatocyte nuclear factor 4 and retinoid X receptor alpha plus peroxisome proliferator-activated receptor alpha, support HBV replication in nonhepatic cells by controlling pregenomic RNA synthesis, indicating these liver-enriched transcription factors control a unique molecular switch restricting viral tropism. In contrast, hepatocyte nuclear factor 3 antagonizes nuclear hormone receptor-mediated viral replication, demonstrating distinct regulatory roles for these liver-enriched transcription factors.

3T3 Cells↗

Modeling the ecological impact of heavy metals on aquatic ecosystems: a framework for the development of an ecological model.

In this paper, an ecological model is proposed to predict the effects of heavy metals on aquatic ecosystems. The bioavailable concentration of metals and a concept of toxicity strength (TS) are combined. The integrated ecological model relates the transport, distribution and speciation of heavy metals and their toxicity, and the effect of environmental variability on metal toxicity. It also emphasizes the link between physical and chemical processes of heavy metals in rivers and ecological effects. Based on the data obtained from research in the CERP project (Co-operative Ecological Research Project), the ecological impact of heavy metals on the aquatic ecosystem of the Le An River (polluted by heavy metals from a copper mine) was predicted. The results show that the estimated values of toxicity strength for surface water are in agreement with the percentage inhibition for the test organism (P. phosphoreum) and that the predicted ecological effect of polluted sediment is consistent with natural variability in aquatic ecosystems.

Animals↗

Physicochemical properties and structure of large, medium and small granule starches in fractions of normal barley endosperm.

Normal barley grain was milled to flour with a machine used to polish brewers' rice from the surface layer to the center. Large (18.4 microm, median size), medium (12.3 microm) and small (2.2 microm) granule starches were isolated from classified flours. Their physicochemical properties and fine structure were investigated. The percentage (w%) of large granules decreased from the surface layer to the center, while the amounts of medium and small granules increased. Although all the starch granules were an A-type crystal, the relative crystallinity varied from 22.0 to 27.4%. The DPn of the amyloses was around 1600 and similar for all the samples. But the amylose content of the starches varied from 21.9 to 26.4%. Also, the amylopectins showed differences in DPn (around 5700-7900) and chain-length distribution between granule size or fractions. The transition temperature ranges and the enthalpy values of the starch granules differed with granule size. The gelatinization properties showed no correlation with any of the parameters, except the enthalpy value and relative crystallinity (gamma = +0.73). The findings suggested that the structural characteristics of the starches in classified flours of normal barley differed essentially from those of waxy barley.

Amylopectin↗

Conformational changes of single molecules induced by scanning tunneling microscopy manipulation: a route to molecular switching.

A detailed experimental and theoretical investigation of the processes involved in the manipulation of individual specially designed porphyrin-based molecules by scanning tunneling microscopy at low temperature is presented. On a stepped Cu(211) surface, the interaction between tip and molecule was used to locally modify in a reversible way the internal configuration of a single molecule, thus drastically changing the tunneling current passing through it. Model calculations confirm that this manipulation realizes the principle of a conformational molecular switch.

Journal Article↗

Theoretical description of transdermal transport of hydrophilic permeants: application to low-frequency sonophoresis.

Application of ultrasound enhances transdermal transport of drugs (sonophoresis). The enhancement may result from enhanced diffusion due to ultrasound-induced skin alteration and/or from forced convection. To understand the relative roles played by these two mechanisms in low-frequency sonophoresis (LFS, 20 kHz), a theory describing the transdermal transport of hydrophilic permeants in both the absence and the presence of ultrasound was developed using fundamental equations of membrane transport, hindered-transport theory, and electrochemistry principles. With mannitol as the model permeant, the role of convection in LFS was evaluated experimentally with two commonly used in vitro skin models- human cadaver heat-stripped skin (HSS) and pig full-thickness skin (FTS). Our results suggest that convection plays an important role during LFS of HSS, whereas its effect is negligible when FTS is utilized. The theory developed was utilized to characterize the transport pathways of hydrophilic permeants during both passive diffusion and LFS with mannitol and sucrose as two probe molecules. Our results show that the porous pathway theory can adequately describe the transdermal transport of hydrophilic permeants in both the presence and the absence of ultrasound. Ultrasound alters the skin porous pathways by two mechanisms: (1) enlarging the skin effective pore radii, or (2) creating more pores and/or making the pores less tortuous. During passive diffusion, both HSS and FTS exhibit the same skin effective pore radii (r = 28 +/- 13 A). In contrast, during LFS, r within HSS is greatly enlarged (r > 125 A), whereas r within FTS does not change significantly (23 +/- 10 A). The observed different roles of convection during LFS across HSS and FTS can be attributed to the different degrees of structural alteration that these two types of skin undergo during LFS.

Administration, Cutaneous↗

Recovery of underwater resonances by magnetization transferred NMR spectroscopy (RECUR-NMR).

A method for detecting small molecule NMR resonances under a water peak in biological samples is presented. After high-efficiency solvent suppression using double WATERGATE, either a TOCSY- or ROESY-based coherence transfer sequence is applied to reestablish the resonances close to, or under, water through magnetization transfer using scalar or dipolar coupling, respectively. The use of the TOCSY and ROESY methods ensures an in-phase magnetization transfer, which makes the new approach readily extended for the measurement of transverse relaxation times, internuclear ROEs, and ROE buildup rates. An extension of the new approach for J-resolved spectroscopy is also presented and tested using a sample of human blood plasma.

Blood Glucose↗

Apoptosis and Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

To investigate the roles of apoptosis and the Fas system (Fas, Fas ligand, soluble Fas) in the process of liver cirrhosis (LC) converting into hepatocellular carcinoma (HCC), expression of Fas and Fas ligand (FasL) in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Serum soluble Fas (sFas) levels in 28 cases of LC and 27 cases of HCC were measured by enzyme-linked immunosorbent assay (ELISA) method. Compared with LC, apoptotic indices (AI) in HCC tissues were significantly reduced (P < 0.001), expression of Fas was decreased (P < 0.05), and that of FasL was increased (P < 0.05). Serum sFas levels in HCC patients were significantly higher than those in normal controls. Down-regulation of Fas expression, up-regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

Adult↗

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.

Adolescent↗

Modified inorganic polymer flocculant-PFSi: its preparation, characterization and coagulation behavior.

As a new kind of water and wastewater treatment reagents, inorganic polymer flocculants (IPFs) are in a trend of rapid development. Among them, iron-based IPF without any toxic problems is greatly expected. In this paper, a new protocol for preparation of iron-based IPF is investigated. Three kinds of silica, named silicaA, silicaB and silicaC, are prepared and used as modifiers to tailor-make polyferric silicate (PFSi), denoted PFSiA. PFSiB and PFSiC, respectively, in accordance to the above silica. Based on several direct and indirect speciation methods, the species distribution and characteristic of three kinds of PFSi are investigated in detail. The experiment results show that the species distribution of PFSi is mainly decided by the kinds of silica introduced and Si/Fe ratio adopted. SilicaA and silicaB function as precipitation preventing reagents during the hydrolysis of Fe(III). At certain amount of basicity, Fe(a) (monomers) increases with increase of Si, Fe ratio, while Fe(c) (colloidal species) decreases markedly. Although the formation of Fe(c) is inhibited, the stabilization of Fe(b) (oligomers or polymers) can still not be achieved. SilicaC on the other hand exhibits little effect on the species distribution of modified Fe(III) solutions. The coagulation behavior of above PFSi is also examined. The different effect of silica is then discussed with respect to the chemical species.

Flocculation↗