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Biomedical subjects

L Tian

Publications and source records attributed to L Tian.

At least 109 records · Page 6Linked to original sources
PubMed1997

Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals.

1. The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/ hemidiaphragm preparations. 2. Hexamethonium (200 microM), but not MLA (0.4-2.0 microM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. 3. At low frequencies of stimulation (0.5-2 Hz), hexamethonium (200 microM) and MLA (2.0 microM) increased e.p.c. quantal content by 30-40%. At high frequencies (50-150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. 4. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. 5. At the concentrations studied, MLA and hexamethonium produced a small (10-20%) decrease in the peak amplitude of m.e.p.cs. 6. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca(2+)-activated K(+)-channels. 7. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the alpha-bungarotoxin-insensitive neuronal type.

Acetylcholine↗
PubMed1997

A cross-reactive idiotype in scleroderma.

Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.

Animals↗
PubMed1997

Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection.

The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI = 1 reflects additive, CI > 1 antagonistic, and CI < 1 synergistic, effects) analysis documented potent synergism between SRL and CsA to block allograft rejection. Combinations of the two drugs produced synergistic prolongation of heart (CI = 0.001-0.2) or kidney (CI = 0.03-0.5) allograft survival at SRL/CsA ratios ranging from 1:12.5 to 1:200. Pharmacokinetic analysis of the individual drugs showed that CsA does not affect the blood levels of SRL, and SRL mildly increases the levels of CsA in SRL/CsA-treated rats. Quantitative polymerase chain reaction analysis was used to document that both subtherapeutic (1.0 mg/kg) and therapeutic (2.0 or 4.0 mg/kg) CsA doses inhibited the expression of interferon-gamma (IFN-gamma) (P < 0.03) and IL-2 (P < 0.003) mRNA produced by T helper (Th) 1 cells, as well as IL-10 (P < 0.001), but not IL-4 (NS) mRNA produced by Th2 cells. Contrariwise, all tested SRL doses (0.02, 0.04 or 0.08 mg/kg) did not affect cytokine mRNA expression. However, heart allografts from rat recipients treated with synergistic SRL/CsA doses displayed reduced levels of IFN-gamma (P < 0.01), IL-2 (P < 0.001) and IL-10 (P < 0.001) mRNA. Thus, because subtherapeutic doses of CsA reduce Th1/Th2 activity, thereby facilitating the inhibition of signal transduction by low does of SRL, the two agents act synergistically to inhibit allograft rejection.

Animals↗
PubMed1997

Expression of immunoglobulin superfamily cell adhesion molecules on murine embryonic stem cells.

The expression of cell adhesion molecules of the Ig superfamily (Ig-CAM) were examined on embryonic stem (ES) cells during culture in vitro. ES cells maintained an undifferentiated phenotype when cultured in the presence of leukemia inhibitory factor (LIF) or with fibroblast feeder cells; > 90% of cells reacted positively to an antibody (ECMA-7) that marks undifferentiated ES cells. Using flow cytometry, high concentrations of ICAM-1, VCAM-1, and NCAM antigens were detected on undifferentiated ES cells, but their specific receptors, Mac-1, LFA-1, and VLA-4, were not detected. There was also no class I or II major histocompatibility complex (MHC) antigen expression. The ICAM-1 expressed was functional, since anti-ICAM-1 significantly (p < 0.0001) blocked ES cell-lymphocyte binding. Ig-CAM and MHC-1 expression on undifferentiated ES cells was not up-regulated by treatment of cells with interferon-gamma (IFN-gamma), tumor necrosis factor alpha, or flavivirus infection, agents that up-regulate these molecules in other embryonic cell types. Twelve hours after LIF withdrawal, ICAM-1 and NCAM expression decreased significantly, while VCAM-1 was undetectable. However, morphology and ECMA-7 expression remained unchanged. Similar patterns of expression were seen on ES cells maintained on fibroblast feeder cells. This suggests that LIF or other cytokines may maintain the expression of Ig-CAMs on undifferentiated cells. Differentiation was induced by dimethyl sulfoxide treatment for 14 days. Cells changed from a colony-forming to a monolayer morphology, and approximately 60% of the cell population no longer expressed ECMA-7. In these cells, VCAM-1 was undetectable and ICAM-1 and NCAM had declined to low levels. In these differentiated cells, ICAM-1 and MHC-1 were inducible by IFN-gamma. This study suggests that the pattern of expression of the Ig-CAMs in ES cells may have a role in defining the phenotype of differentiated and undifferentiated cells.

Animals↗
PubMed1997

Effects of modulator phase for comodulation masking release and modulation detection interference.

In an effort to evaluate the importance of across-frequency comparisons of envelope patterns in comodulation masking release (CMR) experiments and to compare joint effects of target-masker frequency separation for both CMR and modulation detection interference (MDI) tasks, thresholds were measured for three tasks. These tasks were: (a) the detection of sinusoidal amplitude modulation (SAM) of a tone, (b) the detection of a reduction in the modulation depth of a fully modulated SAM tone, and (c) the detection of a tone added to a narrow band of noise. Thresholds were obtained for the target alone and for the target presented with two maskers. For the detection of SAM, thresholds did not depend on whether the modulation patterns of the target and masker elements were the same or random. For the latter two tasks, modulator phase effects were apparent for target-masker frequency separations less than 1-2 oct. In contrast, past work has shown that observers can compare modulator envelope phases across frequency separations larger than 1-2 oct [Strickland et al., J. Acoust. Soc. Am. 86, 2160-2166 (1989); Yost and Sheft, J. Acoust. Soc. Am. 85, 848-857 (1989)]. In a second experiment, thresholds for the detection of SAM were obtained after prolonged exposure to a fully modulated SAM tone. For four of the five observers, modulation-rate specific adaptation was obtained for test/adapting carrier-frequency separations approaching 2 oct below and 1 oct above the adaptor.

Auditory Perception↗
PubMed1997

[Chemical composition of Fagopyrum cymosum (Trev.) Meisn].

From the ethanolic extracts of the aerial parts of Fagopyrum cymosum, eleven compounds were isolated, of which eight have been identified as benzoic acid(1), beta-sitosterol(2),5,5'-di-alpha-furaldehyde dimethyl ether(3), p-hydroxybenzoic acid(4), rutin(5), quercetin(6), daucosterol(7), succinic acid(8) by spectroscopic methods. Compound 3 is obtained from the genus for the first time.

Drugs, Chinese Herbal↗
PubMed1997

Sirolimus in transplantation.

Although sirolimus (SRL) alone was very effective in rodents and pigs, it produced toxic side effects in dogs. Low doses of SRL combined with cyclosporine/brequinar (CsA/BQR) combinations achieved potent immunosuppression in the CsA-resistant mouse model. Similarly, SRL/CsA/BQR therapy protected kidney allografts from rejection in dogs without producing toxic side effects. In the CsA-sensitive rat model SRL/CsA combinations produced a potent synergistic interaction. In addition, recent clinical trials document the beneficial effects of low SRL doses in human kidney transplant recipients. Sirolimus, when combined with standard immunosuppressive therapy, remarkably reduces the incidence of acute rejection and permits individual drug dose reduction.

Animals↗
PubMed1996

Induction of specific allograft immunity by soluble class I MHC heavy chain protein produced in a baculovirus expression system.

Spodoptera frugiperda (Sf9) insect cells secreted a class I MHC RT1.Aa heavy chain protein when infected with baculovirus that bore a construct that contained a honeybee melittin secretion (ms) signal attached to RT1.Aa cDNA. The RT1.Aa heavy chain protein in the culture supernatant and cell lysate immunoprecipitated in the presence of 5 individual anti-RT1.Aa-specific mAb. As was revealed by densitometric analysis, the ms signal increased the production (7- to 17-fold) and secretion (20- to 47-fold) of RT1.Aa protein by Sf9 cells (compared with RT1Aa-Sf9 cells without the ms signal). Subcutaneous immunization with secreted RT1.Aa heavy chain protein of Wistar-Furth (WF; RT1u) rats (day -4) accelerated the rejection of ACI (RT1a), but not third-party Brown Norway (BN; RT1n), heart allografts from 5.9 +/- 0.5 days in controls to 4.0 +/- 0.0 days (P < 0.001); cell lysate from RT1.Aa-Sf9 or ms/RT1.Aa-Sf9 cells reduced ACI heart allograft survival to 3.8 +/- 0.4 days or 3.7 +/- 0.5 days, respectively (P < 0.001). Indirect presentation of RT1.Aa heavy chain proteins by syngeneic macrophages shortened the survival of RT1.Aa-disparate PVG.R8 (RT1.AaDuBuCu) heart allografts in PVG.1U (RT1u) hosts from 6.3 +/- 0.5 days in controls to 4.0 +/- 0.0 days (P < 0.01). Finally, RT1.Aa heavy chain proteins injected into the thymus or into the portal vein (day -14) in combination with anti-T cell receptor mAb (days -14 and -13) induced indefinite survival of ACI liver allografts in Lewis (RT1l) recipients ( > 250 days). Thus, indirect presentation of soluble class I MHC heavy chain proteins (produced in a baculovirus/Sf9 cell system) may either sensitize or induce tolerance in the same fashion as native class I MHC alloantigens expressed on donor tissues.

Animals↗
PubMed1996

Metal-induced modulation of nitric oxide production in vitro by murine macrophages: lead, nickel, and cobalt utilize different mechanisms.

Macrophages (M phi) can be induced to produce nitric oxide (NO), which has been suggested to be important for macrophages to exercise various functions. We have previously reported that an environmental toxicant, lead (Pb), can significantly inhibit NO production by murine splenic M phis. Herein, eight additional metal ions, gold (Au), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), and zinc (Zn), were assessed. In addition to Pb, Hg and Cd significantly suppressed NO production by cytokine (interferon-gamma and tumor necrosis factor-alpha)-stimulated murine M phis. Au and Cu also were inhibitory, but less than Pb, Hg, and Cd. In contrast, Cr and Zn were not modulatory, and Ni and Co significantly enhanced NO production by cytokine-stimulated M phis. The enhancement by Ni and Co was inhibited by the arginine analog N-monomethylarginine. The metals showed different activating/inhibiting profiles when added to a cell-free (activated M phi lysate) NO-producing-system in which inducible NO synthase (iNOS) is already expressed. Cr, Cu, Pb, and Zn moderately suppressed iNOS, which suggests that they may directly modify enzyme or cofactor activity. Cd, Hg, Mg, Ni, or Co did not produce any significant effect on NO production by the cell-free system. Inhibition of NO production by Pb-exposed M phis was not due to decreased expression of iNOS nor limited to its modest direct inhibition of iNOS; thus, other mechanism(s) must be accountable for the efficient Pb-induced inhibition of NO production by M phi. Ni or Co did induce a substantial increase of iNOS protein. Overall, these observations provide additional insight into the means by which metals via inhibition or enhancement of NO production may be pathogenic, by suppression of defense mechanisms or induction of hypersensitivity, respectively.

Animals↗
PubMed1996

Immunohistochemical analysis of growth factor expression and localization in gastric coronary vein of cirrhotic patients.

This study was designed to investigate the expression and localization of PDGF, bFGF, EGF, and TGF alpha in gastric coronary vein of cirrhotic (n = 30) and non-cirrhotic patients (n = 10) using immunohistochemical technique. The strongly positive immunostaining rate were 93%, 89%, 70% and 68% respectively in cirrhotic patients. The immunostaining was negative in non-cirrhotic patients. The damage to endothelium, hypertrophy and hyperplasia of vascular smooth muscle cells and vascular remodeling were seen in gastric coronary vein of cirrhotic patients. These results suggested that gastric coronary vein could produce growth factor during cirrhosis, the growth factor can act on the vascular function and/or structure via autocrine-paracrine mechanism.

Adult↗
PubMed1996

[CD4-CD8- to CD4-CD8+ transition induced by anti-CD3 mAb in vitro cell culture system].

In our experiments, we have observed the effect of anti-CD3 mAb in inducing the differentiation of CD4-CD8- (double negative, DN) thymocytes into CD4+ CD8+ (double positive, DP) cells in an in vitro cell culture system including IL-7 for maintaining the growth of TN thymocytes. When TN thymocytes were stimulated by immobilized anti-CD3 mAb for 3 days, CD4-CD8+ cells generated, which were mostly immediate precursors of CD4+CD8+ thymocytes according to their surface TCR beta expression. The transition from DN to DP thymocytes accompanied with downregulation of interleukin 2 receptor (IL-2 R) alpha chain, and the TCR alpha beta-CD3 expression induced by IL-7 was also inhibited. Anti-CD3 mAb was effective only before the appearance of functional TCR-alpha beta-CD3 complex. Taking together, the results strongly suggest that anti-CD3 mAb induced DN thymocyte defferentiation is through the pre-TCR complex.

Animals↗
PubMed1996

Kinetics of in vitro immune responses of T and B cells during tolerance induction by sirolimus.

OBJECTIVES: The purpose of the study presented herein was to examine immune performances of rat heart allograft recipients immunosuppressed with sirolimus (SRL, rapamycin; Rapamune, Wyeth-Ayerst, Princeton, NJ). METHODS: The immune performances of lymphocytes harvested from SRL-treated Wistar Furth (WF; RT1u) recipients of Buffalo (BUF; RT1b) heart allografts were examined on days 7, 14, and 90 postgrafting. RESULTS: Whether derived from normal WF rats, SRL-treated WF heart recipients, or SRL-untreated WF heart recipients, pan-T cell population purified from the lymph nodes or spleens on day 7 or 14 displayed similar responses to phytohemaglutinin, anti-T cell receptor R73 monoclonal antibody, donor-type BUF, or third-party Brown Norway alloantigenic stimulators. There was no in vitro evidence of suppressor T cells in SRL-treated recipients. The frequencies of anti-BUF-specific cytotoxic T cells, as shown by limiting dilution analysis, were similar in the short- (days 7 or 14) and in the long- (day 90) term surviving recipients. SRL treatment did not affect the expression of interleukin-2 (IL-2) messenger RNA (mRNA) by T helper 1 (Th1) or of IL-4 and IL-10 mRNA by Th2 cells on days 7 and 14 postgrafting, but did induce selective activation of Th2 cells on day 60 postgrafting. Administration of SRL induced the production of non-complement (C')-fixing IgG2c BUF-specific alloantibodies that appeared in the sera of unresponsive recipients on day 14 postgrafting and reached a peak concentration on day 120 postgrafting. In contrast to untreated recipients that rejected BUF heart allografts, all SRL-treated WF recipients failed to produce C'-fixing BUF-specific alloantibodies. CONCLUSIONS: SRL promotes long-term selective activation of Th2 cells and the production of non-C'-fixing IgG2c blocking antibodies.

Animals↗
PubMed1996

Nucleotide sequences of three H-2K and three H-2D complementary DNA clones coding mouse class I MHC heavy chain proteins.

OBJECTIVES: The polymerase chain reaction (PCR)-based method was used to obtain and sequence three H-2K and three H-2D mouse complementary DNAs (cDNA) of class I major histocompatibility complex (MHC) molecules. METHODS: Messenger RNA was isolated from Conconavalin A-activated splenocytes of C57BL/10 (H-2b), C3H (H-2k), and Balb/c (H-2d) mice. We designed H-2K- and H-2D-specific primers as well as a common downstream primer based on previously published mouse class I MHC sequences. Using the PCR method and selective primers we isolated and sequenced H-2Kb and H-2Db cDNAs of C57BL/10, H-2Kk and H-2k cDNAs of C3H, as well as H-2Kd and H-2Dd cDNAs of Balb/c strains. RESULTS: Analysis of the nucleotide sequences documented similarity between our three H-2K cDNA sequences and all mouse MHC class I sequences available in the GenBank. Similarly, our three H-2D sequences were homologous with all mouse class I MHC sequences deposited in the GenBank. Our H-2K and H-2D sequences were also identical to numerous published sequences. CONCLUSIONS: Using these mouse cDNAs, we plan to determine the localization of polymorphic in vivo immunogenic amino acids in class I MHC H-2K and H-2D alloantigens.

Amino Acid Sequence↗
PubMed1995

Activated T cells enhance nitric oxide production by murine splenic macrophages through gp39 and LFA-1.

Macrophages can be stimulated to produce a relatively large amount of nitric oxide, which is an important component in macrophage-mediated defense mechanisms and regulation of T cell activities. It has been known that T helper (Th) cell activation requires intimate physical interaction between T helper cells and macrophages and that cytokines from activated Th cells regulate macrophage activities including nitric oxide production. The current study indicates that surface molecules on activated Th cells also can synergize with cytokines to substantially enhance nitric oxide production by macrophages through cell-cell contact. The CD40 ligand (gp39) and LFA-1 appear to be two major contributors for T cell dependent nitric oxide production.

Animals↗
PubMed1995

Lead inhibits nitric oxide production in vitro by murine splenic macrophages.

The heavy metal lead is an environmental toxicant that can compromise host defense systems and induce pathophysiological changes in many organ systems. We report herein that low levels of lead can efficiently block nitric oxide production in vitro by murine splenic macrophages, which could contribute to lead's inhibition of pathogen killing by macrophages. We observed that lead was able to suppress nitric oxide production by concanavalin A-stimulated murine splenocyte cultures. Since splenocyte cultures contain macrophages, lymphocytes, and other cell types, we further delineated the target(s) of the inhibition. High- and low-dose interferon-gamma and tumor necrosis factor-alpha-induced nitric oxide production by macrophages was readily blocked by low levels of lead (ID50 = 0.35-0.95 microM or 0.07-0.19 ppm); however, activated T cell membrane-enhanced nitric oxide production by macrophages was less sensitive to inhibition by lead. Since lead has been reported to preferentially enhance the activation of T helper-2 cells, which produce interleukin-4, a regulator of macrophage activities, the role of interleukin-4 in the inhibition by lead also was assessed. Interleukin-4 did not mediate the inhibition; instead, interleukin-4 appeared to be an enhancing factor for nitric oxide production in vitro. The observed effects of lead on nitric oxide production may provide an explanation for some of the lead-induced abnormalities associated with host defense and organ systems in addition to the immune system.

Animals↗