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Biomedical subjects

L Tang

Publications and source records attributed to L Tang.

At least 235 records · Page 13Linked to original sources

Biocompatibility of chemical-vapour-deposited diamond.

The biocompatibility of chemical-vapour-deposited (CVD) diamond surfaces has been assessed. Our results indicate that CVD diamond is as biocompatible as titanium (Ti) and 316 stainless steel (SS). First, the amount of adsorbed and 'denatured' fibrinogen on CVD diamond was very close to that of Ti and SS. Second, both in vitro and in vivo there appears to be less cellular adhesion and activation on the surface of CVD diamond surfaces compared to Ti and SS. This evident biocompatibility, coupled with the corrosion resistance and notable mechanical integrity of CVD diamond, suggests that diamond-coated surfaces may be highly desirable in a number of biomedical applications.

Absorption↗

Expression of diverse and functional TCR gamma and Ig heavy chain transcripts in fetal liver cells cultured with interleukin-7.

We have previously shown that specific T cell receptor (TCR) gamma V regions genes (V gamma 4 and V gamma 6) are rearranged and expressed by murine fetal liver (FL) cells cultured with IL-7. The present studies determined that the sequences of the TCR V region gene transcripts expressed in response to IL-7 included diverse and functional sequences expressed by thymocyte and peripheral V gamma 4+ and V gamma 6+ T cells, indicating that the IL-7-induced expression of these genes is functionally relevant and mimics normal in vivo developmental events of gamma delta T cells. We found that more than 50% of these TCR transcripts had N region diversity. The presence of N region diversity indicates that these TCR rearrangements took place in vitro, presumably in response to IL-7, because fresh (uncultured) FL cells do not produce detectable terminal deoxynucleotidyl transferase (TdT) mRNA or protein. We also found that 100% of immunoglobulin (Ig) VH7183-JH4 transcripts from FL cells cultured with IL-7 had N region diversity at the V-DJ region, while only 40% of Ig VH7183-JH4 transcripts from FL cells cultured in the absence of IL-7 had N region diversity at this region. FL cell cultures supplemented for 7 days with IL-7 had increased TdT mRNA and protein levels. However, since 1-day culture of FL cells with or without IL-7 resulted in induction of expression of TdT, IL-7 probably does not directly stimulate TdT expression, but increases the development and expansion of TdT+ lymphoid cells. These findings implicate IL-7 as a regulator of the molecular signals involved in controlling TCR gamma rearrangement and diversity, and provide an in vitro system for studying the regulation of TdT and N region diversity in B and T lymphoid progenitors by environmental signals.

Animals↗

Detection and analysis of replicating hepatitis C virus RNA in hepatocellular carcinoma tissues.

Although persistent hepatitis C virus infection is closely associated with the development of hepatocellular carcinoma, the nature of hepatitis C virus replication in the hepatocellular carcinoma tissue has not been fully characterized. To study this, carcinoma and non-carcinoma tissues were obtained from five patients with hepatocellular carcinoma. Total RNA was recovered from each tissue, and a portion of the envelope gene of replicating hepatitis C virus was amplified by minus-strand-specific reverse transcription and nested polymerase chain reaction. The amplified cDNA was examined by single strand conformation polymorphism analysis and sequencing. Hepatitis C virus replication was detected in both carcinoma and non-carcinoma tissues in four patients who were positive for serum hepatitis C virus markers. In one patient, a single species with identical envelope 2 genome was obtained from both carcinoma and non-carcinoma tissues. In the other three patients, the replicating hepatitis C virus existed as a mixture of 2-5 species with different but highly homologous (82-99%) envelope 2 genomes (quasispecies populations). The constitution of viral populations was different between carcinoma and non-carcinoma tissues. A total of ten sequences were recovered; four sequences were found in both tissues, two were found in carcinoma tissues, and four were found in non-carcinoma tissues. The difference in the constitution of quasispecies populations between carcinoma and non-carcinoma tissues confirms the unequivocal replication of hepatitis C virus in both tissues, and may imply the presence of different biological properties among hepatitis C virus with different sequences.

Amino Acid Sequence↗

Role of cyclic AMP in prostaglandin mediated responses in the neural retina.

Exogenous prostaglandins (PGs) have been shown to inhibit dopamine (DA) release from the rabbit retina via an effect on presynaptic EP3-receptors. In the present study, we investigated the possible involvement of cyclic AMP in DA release and in the prostanoid receptor mediated regulation of DA release from the neural retina. Both forskolin and 8-bromo-cyclic AMP enhanced field stimulation-evoked [3H]DA release from isolated, superfused rabbit retinas without affecting basal tracer efflux suggesting that presynaptic cyclic AMP may be involved in the pathway leading to DA release. Forskolin attenuated inhibition of evoked [3H]DA release caused by low but not high concentrations of PGE2. Both PGE2 and sulprostone had no significant effect on basal cyclic AMP levels but inhibited forskolin-stimulated cyclic AMP formation. Furthermore, sulprostone was more potent than PGE2 in attenuating forskolin-activated cyclic AMP production. The inhibition of forskolin-elevated cyclic AMP levels caused by PGE2 was, however, unaffected by the EP1-receptor antagonist, AH6809. We conclude that the regulation of DA release by presynaptic prostanoid EP3-receptors may be mediated, at least in part, through an inhibitory effect on adenylyl cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗

Inflammatory responses to biomaterials.

Implanted biomedical devices are of increasing importance in modern medical care. However, surprisingly little is known of the factors that determine biocompatibility of the materials used in these devices. These materials, although generally inert and non-toxic, can mediate a variety of adverse reactions, including inflammation, fibrosis, coagulation, and infection. This brief review focuses on the inflammatory responses (including fibrosis) that commonly occur around implanted biomaterials. Host proteins that spontaneously associate with implant surfaces are important determinants of the acute inflammatory response. In this regard, adsorbed fibrinogen appears particularly pro-inflammatory. Chronic inflammatory processes, in many cases in response to fragments of implanted biomaterials, may cause implant failure. In the case of silicone-filled mammary prostheses, the extravasation of silicone gel has been held responsible for a number of complications, including silicone granuloma, synovitis, connective-tissue disease, and lymphadenopathy. In some instances, material-mediated inflammatory responses may even cause degradation of the material itself (via oxidative products released by implant-associated inflammatory cells). Overall, there is insufficient knowledge of the determinants and mechanisms of host: implant responses. A clear understanding of tissue:biomaterial interactions will be required both to explain the pathogenesis of many implant-mediated complications and to aid in the development of more biocompatible materials for implantable devices.

Biocompatible Materials↗

Effects of besipirdine at the voltage-dependent sodium channel.

1. Besipirdine (HP 749) is a compound undergoing clinical trials for efficacy in treating Alzheimer's disease. Among other pharmacological effects, besipirdine inhibits voltage-dependent sodium and potassium channels. This paper presents a pharmacological study of the interaction of besipirdine with voltage-dependent sodium channels. 2. Besipirdine inhibited [3H]-batrachotoxin binding (IC50 = 5.5 +/- 0.2 microM) in a rat brain vesicular preparation and concentration-dependently inhibited veratridine (25 microM)-stimulated increases in intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) in primary cultured cortical neurones of rat. 3. Besipirdine (30-100 microM) concentration-dependently inhibited (up to 100%) veratridine-stimulated release of [3H]-noradrenaline (NA) from rat cortical slices. 4. When examined in greater detail, besipirdine was found to inhibit [3H]-batrachotoxin binding in vesicular membranes competitively. However, when examined in rat brain synaptosomes, we found that the antagonism by besipirdine was not competitive; that is, the maximal stimulation of [Ca2+]i induced by veratridine decreased with increasing concentrations of besipirdine. 5. These results show that besipirdine is an inhibitor of voltage-sensitive sodium channels and appears to bind to a site close to the batrachotoxin/veratridine binding site.

Animals↗

[Expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 in kidney of patients with lupus nephritis and membranoproliferative glomerulonephritis].

Immunohistochemical and computer-imaging analysis techniques were used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1) in the kidney of 25 patients with lupus nephritis (LN) type IV and in 15 patients with membranoproliferative glomerulonephritis (MPGN) type I. Results showed that ICAM-1 and VCAM-1 expressions were increased significantly in the kidneys of patients with MPGN and LN and that ICAM-1 in the glomeruli of LN patients correlated well with glomerular endothelial cell proliferation. ICAM-1 and VCAM-1 may well take a role in the pathogenesis of LN and MPGN.

Cell Adhesion Molecules↗

[A study on human behavior and socioeconomic factors affecting malaria transmission and control in Qiongzhong, Hainan].

This study was conducted in Heping District of Quiongzhong County, a hyperedemic mountainous area, in August-September 1992. The comparative surveys between the village and state-run farm, Li and Miao nationalities and Han nationality were carried out by using the sociological method together with the epidemiological methods. Gray relational analysis was conducted between the aforementioned 7 socioeconomic human behavioral factors and IFA rates. The result showed that their degrees of relation (r) were in the following order: (1) percentage of persons who had stayed in the mountain overnight (r = 0.8690); (2) percentage of bed net users (r = 0.7990); (3) percentage of households seeking medical service (r = 0.7990); (4) number of mosquito nets per person (r = 0.7867); (5) percentage of householders knowing malaria transmission route (r = 0.7798); (6) percentage of households with tile-roofed houses (r = 0.6767) and (7) income per capita (r = 0.6636). It indicates that staying in the mountain, using bed net and seeking medical service were three discriminating factors affecting local malaria transmission and control. Therefore, it is suggested that carrying out health education, changing the stay-in-mountain behavior, increasing the utilization of mosquito nets and reinforcing the primary health care should be taken as the fundamental measures for malaria control programme.

China↗

[The effect of hirudo on proteinuria, lipid metabolism and coagulation system in the patients with chronic glomerulonephritis].

Renal biopsy was performed in 31 cases of primary glomerulonephritis and the effect of Hirudo in these patients observed. The results revealed that proteinuria decreased significantly, serum albumin increased significantly and cholesterol, triglyceride reduced significantly 4 weeks after treatment with Hirudo (P < 0.01 or P < 0.05); Fibrinogen and platelet aggregation reduced significantly (P < 0.01). However, platelet count, partial thromboplastin time, bleeding and clotting time did not change (P > 0.05); urine NAGase decreased significantly (P < 0.01). It is concluded that Hirudo may decrease proteinuria and alleviate renal parenchymal damage.

Animals↗

[Comparative study of umbilical artery Doppler velocimetry, antenatal fetal heart rate monitoring and umbilical artery blood-gas analysis in the prediction of neonatal outcome].

One hundred and fifteen term pregnancies (62 normal pregnancies, 53 high risk pregnancies) were observed by umbilical artery Doppler velocimetry (UmA S/D ratio) and antenatal fetal heart rate monitoring (NST), and 37 of them were also observed by umbilical artery blood-gas analysis at birth. We compared the effects of these three methods to predict the neonatal outcome. The standards of the neonatal poor outcome were 5-min Apgar score < or = 7 and/or a birth weight < 2500g (SGA). The results were: (1) The neonatal poor outcome were more frequently observed in the abnormal UmA S/D ratio (> or = 3.0) group and in the UmA pH < or = 7.2 group (P < 0.005, P < 0.025, respectively), but there was no significant difference between the NST reactive or nonreactive groups (P > 0.05); (2) The neonatal acidosis at birth was also associated with the abnormal UmA S/D ratio (> or = 3.0); (3) The sensitivities of UmA S/D ratio, UmA pH, NST to predict the 5-min Apgar score < or = 7 were 60.0%, 60.0%, 20.0% respectively; the specificities 84.6%, 81.3%, 81.8% respectively. And their sensitivies to predict SGA were 100.0%, 100.0%, 40.0% respectively; the specificities 86.4%, 80.0%, 82.7% respectively. Our data show that UmA S/D ratio and UmA pH are better than NST in the prediction of neonatal outcome, and the abnormal UmA S/D ratio is closely associated with neonatal acidosis at birth.

Apgar Score↗

[Current malaria stratification in China].

During the past 30 years since 1958 when malaria stratification was first made, a great change in malaria situation has occurred. The original stratification can not represent the current status of malaria distribution. Therefore, it needs to be redivided so as to provide basis for future malaria control work. Taking species of mosquito vector and malaria incidence as the main indices and making reference to the natural geographical division, the current malaria endemic area in China can be divided into four regions, i.e. (1) Western region: it is mostly a natural non-endemic area, except some limited areas with sporadic cases in Xinjiang Autonomous Region; (2) Northern region: the whole north-eastern and partial northern China belong to the areas where malaria has been basically eliminated; but sporadic occurrence still exist in most part of the northern China; (3) Central region: it is mostly a hypo-endemic area, only a small part has meso-endemicity; (4) Southern region: nearly 50% has meso-endemicity and the other 50% has hypo-endemicity. The demarcation line of natural non-endemic areas and the areas where malaria has been basically eliminated has been defined.

Animals↗

[A study on behavioural characteristics of staying on the mountain and its relationship with malaria infection in Li and Miao minorities in Hainan Province].

A study of sociology combined with epidemiology was conducted in Li Minority's two villages and Miao Minority's two villages nearby the foot of mountain in a historically malaria hyperendemic area, Nanqiao Township of Wanning County in August, 1993. The results showed that malaria infection was closely correlated to the behaviour of staying overnight on the mountain of Li and Miao Minorities during farming seasons. Most of Li people stayed overnight on the mountain for planting areca were adults, accounting for 21.6% of the whole population, the duration of stay was about half a year; Miao people stayed overnight on the mountain planting and harvesting upland rice, always with their family member, so the percentage of people who had stayed on the mountain was as high as 82.1%, the duration of stay was about one and half a month. Blood smear examination showed that the malaria parasite rates in both Li and Miao villages were 11.1% and 24.1%, respectively, the positive rate of P. falciparum was 1.0% and 9.1%, respectively, the positive rate of IFA (titer >or= 1 : 40) was 31.2% and 46.5%, respectively. It is indicated that both the rate of parasitaemia and the P. falciparum infection were much higher in Miao Minority than those in Li Minority (P < 0.001). A cohort analysis showed that the malaria parasite rate of population who having not stayed, having ever stayed and being stayed on the mountain was 6.5%, 27.4% and 42.1%, respectively, of them the rate of P. falciparum infection was 0.5%, 8.8% and 18.4%, respectively. The results suggest that malaria acquired from mountainous forest referring to "up-mountain infection" is a major source of malaria infection and a significant risk factor in determining the prevalence of malaria (especially falciparum malaria) in Hainan Province. This behavioural risk factor has become the main obstacle for malaria control in Hainan Province. Therefore, controlling "up-mountain infection" and adopting appropriate anti-malaria measures to protect the risk population who have to work and stay on the mountain should be strengthened in the malaria control program.

China↗

The genetic basis of precursor supply for the biosynthesis of macrolide and polyether antibiotics.

Macrolide and polyether biosynthesis in actinomycetes is regulated at the level of precursor supply by effects of nutrients on the sources of the low-molecular-weight fatty acids used to build the carbon framework of these antibiotics. Ammonium ion appears to suppress the first enzymes of valine and threonine catabolism and also inhibits their activity. Disruption of the valine dehydrogenase (vdh) gene of Streptomyces coelicolor destroys its ability to grow on branched-chain amino acids as the sole nitrogen source in a minimal medium but has no effect on the biosynthesis of the acetate-derived antibiotic, actinorhodin. Expression of the vdh gene is repressed by > 25 mM ammonium ion or glucose but not by valine, glycerol, or maltose. Vdh enzyme activity is stimulated by valine induction. These results suggest that the inhibition of valine catabolism by ammonium and/or glucose could explain why macrolide production is inhibited by ammonium ion.

Amino Acid Oxidoreductases↗

Morphogenic potentials of D2, D3, and D4 dopamine receptors revealed in transfected neuronal cell lines.

Molecular cloning studies have defined a family of dopamine D2-like receptors (D2, D3, and D4), which are the products of separate genes. Our previous work has shown that stimulation of dopamine D2-like receptors in cultures of fetal cortical neurons increases the extension and branching of neurites. To determine which D2-like receptors possess morphogenic potentials, a clonal mesencephalic cell line (MN9D) was transfected with D2, D3, or D4 receptor subtypes and treated with quinpirole, an agonist of D2-like receptors, and changes in morphological characteristics were quantitated. Stimulation of D2 receptors increased the number and branching of neurites with little effect on neurite extension; stimulation of D3 and D4 receptors increased the branching and extension of neurites. Similar results were found for primary mesencephalic cultures stimulated with quinpirole. These results suggest that the known D2-like receptors have specific developmental roles in regulating neuronal morphogenesis of dopaminergic pathways.

Animals↗

Characterization of the human dopamine D3 receptor expressed in transfected cell lines.

A full-length cDNA clone of the human dopamine D3 receptor was obtained by the polymerase chain reaction (PCR) using reverse-transcribed RNA from human brain as the template. The cDNA was inserted into an expression vector which was then stably transfected into either Chinese hamster ovary (CHO), SK-N-MC human epithelioma or mouse CCL1.3 fibroblast cell lines. Post-transfection, the Bmax for D3 receptor expression was 1.9, 1.1 and 0.4 pmol/mg protein in the CHO-K1, SK-N-MC and CCL1.3 cell lines, respectively. The D3 receptor expressed in CHO-K1 and CCL1.3 cells exhibited similar radioligand binding profiles, especially for the D3-selective compound, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT). Radioligand-binding competition curves of presumed D3 agonists were shifted to the right by the addition of guanine nucleotides and Na+ to the assay buffer. Presumed D3-receptor agonists had no effect on cAMP accumulation in any of the D3-transfected cell lines although cAMP accumulation was inhibited by dopamine D2 receptor activation in D2-transfected CHO and CCL1.3 cells and by activation of the exogenously expressed neuropeptide Y receptor in SK-N-MC cells. Also, D3 receptor activation neither potentiated ATP-stimulated arachidonic acid release from CHO cells nor stimulated inositol phosphate production in CCL1.3-cells although both of these responses were elicited by D2 agonists in D2-transfected cells. We conclude that the signalling properties of the D3 receptor differ from those of its closest homolog, the D2 receptor.

Animals↗

Phenotypic change in portal fibroblasts in biliary fibrosis.

Portal fibroblasts have been considered responsible for biliary fibrosis. Since lipocytes show differentiation toward myofibroblast-like cells in hepatic fibrogenesis, we studied whether similar differentiation of portal fibroblasts could be observed in biliary fibrosis. We examined rat livers after bile duct ligation by double immunofluorescent staining of alpha-smooth-muscle actin (alpha-smA) and desmin and also by electronmicroscopy. In the portal tract of normal livers, alpha-smA-positive cells were noted only in the vessel wall, whereas desmin-positive cells were occasionally seen in the connective tissue as well. With the development of biliary fibrosis, alpha-smA was remarkably expressed in the portal connective tissue, while desmin was seen in a small portion of alpha-smA-positive cells around proliferating bile ducts. In normal livers, portal fibroblasts presented quiescent features, such as a small Golgi complex and a few cisternal profiles of endoplasmic reticulum under electron microscopy. After 7 days of bile duct ligation, portal fibroblasts proliferated, were arrayed in multilayers, and were associated with collagen bundles. Some of these fibroblasts had numerous cytoskeletal components, and developed rough endoplasmic reticulum and a dense body. These data suggest that portal fibroblasts appear to differentiate toward myofibroblasts in biliary fibrosis.

Actins↗

Extracellular and cytoplasmic CuZn superoxide dismutases from Brugia lymphatic filarial nematode parasites.

We have isolated full-length cDNAs encoding two distinct types of CuZn superoxide dismutases (SODs) from the filarial nematode parasite Brugia pahangi. The derived amino acid sequences suggested that one class of cDNAs represented a cytoplasmic form of SOD and the second class represented an extracellular (EC) variant. The predicted proteins were highly homologous to each other, but the sequence of the latter contained an additional 43 residues at the N terminus, the first 16 of which were markedly hydrophobic, and four potential sites for N-linked glycosylation. Western blotting (immunoblotting) with an antiserum to a partial SOD expressed in Escherichia coli revealed two proteins with estimated molecular masses of 19 and 29 kDa. Digestion with N-glycanase indicated that the latter protein corresponded to the EC form, as it possessed N-linked oligosaccharide chains at three sites, leaving a peptide backbone with an estimated molecular mass of 22 kDa, which was consistent with the additional 27 amino acids predicted from the cDNA sequence. Gel filtration indicated that both enzymes were dimeric in their native forms, in contrast to the human EC-SOD, which is tetrameric. Comparison of the primary structure of the parasite EC-SOD with that of the human EC enzyme revealed two major differences: the N-terminal extension of the parasite enzyme was shorter by 25 residues, and it also lacked the C-terminal charged extension which mediates binding to cell surface sulfated proteoglycans. Lavage of Mongolian jirds infected intraperitoneally with Brugia malayi resulted in the recovery of filarial CuZn SODs, principally the EC form, indicating that this form of SOD is secreted in vivo. This EC enzyme may contribute to parasite persistence by neutralizing superoxide generated by activated leukocytes, thus acting as both an antioxidant and an anti-inflammatory factor.

Amino Acid Sequence↗

Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae.

Targeted inactivation of the valine (branched-chain amino acid) dehydrogenase gene (vdh) was used to study the role of valine catabolism in the production of tylosin in Streptomyces fradiae and spiramycin in Streptomyces ambofaciens. The deduced products of the vdh genes, cloned and sequenced from S. fradiae C373.1 and S. ambofaciens ATCC 15154, are approximately 80% identical over all 363 amino acids and 96% identical over a span of the first N-terminal 107 amino acids, respectively, to the deduced product of the Streptomyces coelicolor vdh gene. The organization of the regions flanking the vdh genes is the same in all three species. Inactivation of the genomic copy of the vdh gene in S. fradiae and S. ambofaciens by insertion of a hygromycin resistance (hyg) gene caused loss of the valine dehydrogenase (Vdh) activity, and thus only one enzyme is responsible for the Vdh activity in these organisms. Analysis of the culture broth by bioassay revealed that the vdh::hyg mutants produce an approximately sixfold-lower level of tylosin and an approximately fourfold-lower level of spiramycin than the wild-type S. fradiae and S. ambofaciens strains, while maintaining essentially identical growth in a defined minimal medium with either 25 mM ammonium ion or 0.05% asparagine as the nitrogen source. The addition of the valine catabolite, propionate or isobutyrate, and introduction of the wild-type vdh gene back to each vdh::hyg mutant reversed the negative effect of the vdh::hyg mutation on spiramycin and tylosin production. These data show that the catabolism of valine is a major source of fatty acid precursors for macrolide biosynthesis under defined growth conditions and imply that amino acid catabolism is a vital source of certain antibiotic precursors in actinomycetes.

Amino Acid Oxidoreductases↗