Biomedical subjects

H Tang

Publications and source records attributed to H Tang.

At least 145 records · Page 8Linked to original sources

PubMed1999

Targeted overexpression of parathyroid hormone-related protein (PTHrP) to vascular smooth muscle in transgenic mice lowers blood pressure and alters vascular contractility.

PTH-related protein (PTHrP) and its receptor are expressed in vascular smooth muscle cells and are believed to participate in the local regulation of vascular tone. To explore the function of locally produced PTHrP in vascular smooth muscle in vivo, we developed transgenic mice that overexpress PTHrP in smooth muscle using a smooth muscle alpha-actin promoter to direct expression of the transgene. In the PTHrP-overexpressing mice, messenger RNA expression was mainly restricted to smooth muscle-containing tissues. Several founders also expressed the transgene in bone and heart and exhibited striking abnormalities in the development of these tissues. In PTHrP-overexpressing mice, blood pressure was significantly lower than that in wild-type controls (121 +/- 3 vs. 135 +/- 2 mm Hg; P < 0.01). Moreover, the magnitude of the vasorelaxant response to iv infusions of PTHrP-(1-34)NH2 was significantly attenuated in the transgenic animals. A similar desensitization to PTHrP was observed in aortic ring and portal vein preparations. Surprisingly, PTHrP-overexpressing mice were also significantly less responsive to the hypotensive action of infused acetylcholine in vivo and to the relaxant actions of acetylcholine on aortic vessel preparations in vitro. In summary, we have successfully targeted overexpression of PTHrP to the smooth muscle of transgenic mice. When expressed in its normal autocrine/paracrine setting, PTHrP lowers systemic blood pressure and decreases vascular responsiveness to further relaxation by PTHrP and other endothelium-dependent vasorelaxants such as acetylcholine. We postulate that the heterologous desensitization to acetylcholine-induced relaxation in PTHrP-overexpressing blood vessels involves desensitization of second messenger/effector signaling pathways common to PTHrP and acetylcholine.

Actins↗

PubMed1999

A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates.

The Drosophila doublesex (dsx) gene encodes a transcription factor that mediates sex determination. We describe the characterization of a novel zebrafish zinc-finger gene, terra, which contains a DNA binding domain similar to that of the Drosophila dsx gene. However, unlike dsx, terra is transiently expressed in the presomitic mesoderm and newly formed somites. Expression of terra in presomitic mesoderm is restricted to cells that lack expression of MyoD. In vivo, terra expression is reduced by hedgehog but enhanced by BMP signals. Overexpression of terra induces rapid apoptosis both in vitro and in vivo, suggesting that a tight regulation of terra expression is required during embryogenesis. Terra has both human and mouse homologs and is specifically expressed in mouse somites. Taken together, our findings suggest that terra is a highly conserved protein that plays specific roles in early somitogenesis of vertebrates.

Amino Acid Sequence↗

PubMed1999

[Detection of NV-HB/s DNA and c-myc mRNA in mice inoculated with hepatitis B nucleic acid vaccine--NV-HB/s].

OBJECTIVE: To explore the persistence period of plasmid in mice muscles injected with NV-HB/s and the possible influence on oncogene C-myc. METHODS: Anti-HBs was detected by ELISA; NV-HB/s was detected by In-situ and Southern-blot hybridization separately; C-myc mRNA was detected by In-situ hybridization. RESULTS: All mice injected with NV-HB/s were positive of anti-HBs after 1 month of immunization; NV-HB/s was negative when detected by In-situ hybridization; By Southern-blot hybridization, the positive rates of NV-HB/s were decreasing from 100% in 2 months to 25% after 6 months of inoculation. CONCLUSIONS: NV-HB/s would be disintegrated little by little after injected into mouse muscles; no C-myc activation was observed in 6 months after NV-HB/s inoculation.

Animals↗

PubMed1999

Differences between generalists and mental health specialists in the psychiatric treatment of Medicare beneficiaries.

OBJECTIVE: To examine differences between the general medical and mental health specialty sectors in the expenditure and treatment patterns of aged and disabled Medicare beneficiaries with a physician diagnosis of psychiatric disorder. DATA SOURCES: Based on 1991-1993 Medicare Current Beneficiary Survey data, linked to the beneficiary's claims and area-level data on provider supply from the Area Resources File and the American Psychological Association. STUDY DESIGN: Outcomes examined included the number of psychiatric services received, psychiatric and total Medicare expenditures, the type of services received, whether or not the patient was hospitalized for a psychiatric disorder, the length of the psychiatric care episode, the intensity of service use, and satisfaction with care. We compared these outcomes for beneficiaries who did and did not receive mental health specialty services during the episode, using multiple regression analyses to adjust for observable population differences. We also performed sensitivity analyses using instrumental variables techniques to reduce the potential bias arising from unmeasured differences in patient case mix across sectors. PRINCIPAL FINDINGS: Relative to beneficiaries treated only in the general medical sector, those seen by a mental health specialist had longer episodes of care, were more likely to receive services specific to psychiatry, and had greater psychiatric and total expenditures. Among the elderly persons, the higher costs were due to a combination of longer episodes and greater intensity; among the persons who were disabled, they were due primarily to longer episodes. Some evidence was also found of higher satisfaction with care among the disabled individuals treated in the specialty sector. However, evidence of differences in psychiatric hospitalization rates was weaker. CONCLUSIONS: Mental health care provided to Medicare beneficiaries in the general medical sector does not appear to substitute perfectly for care provided in the specialty sector. Our study suggests that the treatment patterns in the specialty sector may be preferred by some patients; further, earlier findings indicate geographic barriers to obtaining specialty care. Thus, the matching of service use to clinical need among this vulnerable population may be inappropriate. The need for further research on outcomes is indicated.

Aged↗

PubMed1999

[A study of color Doppler ultrasound on arteries of the extremities in patients with type 2 diabetes].

To investigate the changes of the arteries in extremities in patients with type 2 diabetes(DM2), fifty patients with DM2(35 women and 15 men, mean aged 57.54 +/- 14.19 years old, time of DM2 diagnosed one week-26 years, without the histories of hypertension and smoking) were studied. Radial, finger, anterior tibial and dorsum pedis arteries of all subjects were examined using color Doppler Ultrasonography, 30 of 50 patients had the symptoms of extremities (e.g., numbness, coldness and pain). The Doppler examination revealed: 1. In the patient group, arterial wall became thick, rough and rigid. The atherosclerotic plaques were found inside vascular cavities in 14/50 in patient group with one patient being asymptomatic of extremities. 2. The vascular cavities in patients remarkably narrowed compared with the control group (P < 0.05). The vascular lesion worsened along with the development of the symptoms. 3. Doppler spectra in the majority of patients displayed single-peak, whereas it displayed three peaks in normal subjects with significant differences (P < 0.05). 4. The peak flow velocities in the patients increased, and this increase was related to the development of the symptoms, but no significant differences were found. Color Doppler Ultrasound examination is valuable in the evaluation of the arterial lesion of the extremities, especially at the early stage of artery diseases in patients with DM2.

Adult↗

PubMed1999

[Early cardiac myocyte membrane changes in severely burned rats: a spin labding-ESR study].

OBJECTIVE: To demonstrate the mechanism of early cardiac myocyte membrane damage at molecular level in severely burned rats. METHODS: SD rats were randomly divided into sham-burn and burn groups. A 30% TBSA burn was created in burn group. Hearts were obtained at different time postburn. Cardiac myocytes isolated by collagenase using Langendoff perfusion apparatus were spin labeled with 5-doxylstearic acid (5NS), 16-doxylstearic acid (16NS) and 3-maleidoproxyl (3MP). The order parameters (S value), hs/hw ratio and rotational correlation time (tau c) were measured according to the spin labeling-ESR spectra. RESULTS: The S value of the polar head-group region of membrane lipid, as reported by 5NS, did not changed significantly, while that of the lipid in the hydrophobic midzone, as reported by 16NS, increased significantly. The hs/hw ratio of 2 and 6 hours postburn groups increased significantly postburn compared with that of the sham-burn group, and so did the rotational correlation time in 1 to 12 h postburn groups. CONCLUSION: There were structural and functional changes in cardiac myocyte membrane after burn injury. They were characterized by decreased fluidity in the deeper part of membrane lipid, configurational changes and motion restriction in membrane proteins. They could affect the normal performance of cardiac function.

Animals↗

PubMed1999

[Induction of potent antitumor immune response of leukemia antigen-pulsed dendritic cells by IL-2 gene modification].

OBJECTIVE: To investigate whether adenovirus-mediated IL-2 gene modification can improve antitumor immunity of the tumor antigen-pulsed dendritic cells(DC) in vivo. METHODS: DC were generated from bone marrow, then, pulsed with FBL-3 erythroleukemia cell lysates and transfected with IL-2 gene simultaneously. IL-2 secretion and T cell stimulating activity of the DC were detected. The number and cell subsets of draining lymph nodes, cytotoxic lymphocyte(CTL) activity, and the increase of protective effect for the mice s.c. vaccinated with DC were observed. RESULTS: IL-2 gene-modified, antigen-pulsed DC could secrete high level of IL-2 in vitro, stimulate proliferation of syngeneic T cells markedly. DC vaccine could increase the number of draining lymph node and induce CTL activity, which directed to FBL-3, more significantly. After the DC vaccination, the survival time of the mice challenged with wild-type FBL-3 cells were prolonged. CONCLUSION: Antitumor immune response could be induced more potently by vaccination with IL-2 gene modified, antigen-pulsed DC.

Animals↗

PubMed1999

[Separation and characterization of oligodeoxynucleotide by fast protein liquid chromatography].

The antisense drug synthesized by DNA synthesizer is an oligodeoxynucleotide (ODN). The purity of the drug should be determined effectively. Because the ODNs are molecules with negative charges at pH 12, they can be separated according to the quantity of charges with them on the ion-exchange column. On anion exchange column, MONO-Q, the ODNs ranged from 19 bases to 21 bases can be separated successfully by gradient elution of NaCl solution from 0 mol/L to 1.8 mol/L. The experiment proved that the fast protein liquid chromatography is a very useful tool for the determination of the antisense drug.

Chromatography, Liquid↗

PubMed1999

[HBsAg expression, anti-HBs induction and pathological observation in the mice inoculated with DNA vaccine against hepatitis B].

OBJECTIVE: To study if special humoral immunological response can be induced by DNA vaccine against Hepatitis B (NV-HB/s) and its mechanism. METHODS: The Balb/C mice inoculated with NV-HB/s by intramuscular injection were detected for HBsAg(the expressed product of NV-HB/s) by ABC immunohistochemistry or ELISA, and for anti-HBs by ELISA and also performed the routine pathological examination. RESULTS: After inoculated with NV-HB/s, HBsAg could be detected from mice muscle tissue samples of injected sites one week later and almost kept positive(75% and even more) up to 6th month, but was undetectable from all the serum samples during this period; anti-HBs could be detected from serum samples of some mice two weeks later and of all the mice detected one month later, it still kept positive at 6th month while the mice were sacrificed. Under microscope, only non-specific inflammation was found in the muscle tissues of injected sites and could completely recover within 4 weeks, no matter whether the mice were inoculated with NV-HBs, or with traditional HB vaccine derived from blood, or even with PBS as control. CONCLUSION: DNA vaccine against Hepatitis B (NV-HB/s) can successfully express HBsAg in the muscle tissue of mice by intramuscular inoculation and subsequently induce anti-HBs in vitro.

Animals↗

PubMed1999

[Analysis of Cu-O bond stretching vibration in CuO2 plane of Bi-system high temperature superconductor].

Infrared absorption spectra of Bi-system high zero resistance temperature (Tc) superconductors were measured. The relation between Cu-O bond stretching vibration in CuO2 plane and superconducting properties of Bi-system high Tc superconductors were analysed and discussed. The result of analysis indicated that the change of absorption peak strength of Cu-O bond stretching vibration was similar to the change of Tc. The reason was related to the coupling between the phonon and free carrier. And according to the theory of molecule vibration, the frequencies of Cu-O bond stretching vibration in CuO2 plane were calculated on the base of simplified model.

English Abstract↗

PubMed1999

Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases.

In addition to its well known involvement in Gq/11-mediated vasoconstriction and its key roles in the homeostasis of electrolyte balances, the angiotensin II type 1 (AT1) receptor activates mitogen-activated protein kinase (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellular signal-regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells. The mechanism for Gq-mediated activation of the tyrosine kinase pathways has not been clear. It was found that the initial release of intracellular Ca2+ results in the activation of the epidermal growth factor receptor (EGF-R), without autocrine release of epidermal growth factor. EGF-R provides a scaffold needed for the activation of p21-Ras, which leads to the activation of MAPK. MAPK plays pivotal roles in the activation of complex growth-promoting pathways. The pathway from the EGF-R involves protein tyrosine phosphorylation initiated by AT1 receptors. On the other hand, the angiotensin II type 2 (AT2) receptor counteracts the AT1 receptor-mediated tyrosine kinase activation by activating several tyrosine phosphatases and serine/threonine phosphatases, and it suppresses the cell growth process stimulated by various growth factors. The relative importance of AT1 and AT2 receptor actions depends on the levels of AT1 and AT2 receptor expression.

Animals↗

PubMed1998

The hepatitis B virus X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators.

Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements, but the mechanism has not been well elucidated. Evidence for nuclear events in HBx transactivation has been reported. Here we examine the role of HBx in modulation of transcription with a transient transfection system and an in vitro transcription assay. Reporters bearing Gal4-binding sites were applied to avoid the effects of endogenous transcription factors with or without signaling processes. The Gal4-DNA binding domain fused form of HBx exhibited no effect on Gal4-responsive reporters. However, HBx augmented activated transcription by transcriptional activators, suggesting HBx retains a co-activator but not a transcriptional activator function. The functional domain for co-activation was the same as that for HBx transactivation, and the transcription factor IIB- and RNA polymerase II subunit 5-interacting sites of HBx, which were critical for HBx transactivation, were shown to be crucial for the co-activation function. Importantly, HBx stimulated transcription on templates bearing the X responsive elements in vitro with endogenous activators. These results imply that HBx acts as a co-activator that modulates transcriptional machinery and distal-binding activators, which may explain one of the mechanisms of transactivation by HBx when localized in nuclei.

DNA-Directed RNA Polymerases↗

PubMed1998

Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.

The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vitro association and pull-down experiments, we demonstrate that Gro and its mammalian homolog TLE1 specifically interact with AML1 and AML2. In addition to the VWRPY motif, other C-terminal sequences are required for these interactions with Gro/TLE1. TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells. LEF-1 is an additional transcription factor that mediates transactivation of TCR enhancers. LEF-1 and its Drosophila homolog Pangolin (Pan) are involved in the Wnt/Wg signaling pathway through interactions with the coactivator beta-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:beta-catenin-dependent transcription. These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling.

Amino Acid Sequence↗

PubMed1998

Rotation of a single molecule within a supramolecular bearing

Experimental visualization and verification of a single-molecule rotor operating within a supramolecular bearing is reported. Using a scanning tunneling microscope, single molecules were observed to exist in one of two spatially defined states laterally separated by 0.26 nanometers. One was identified as a rotating state and the other as an immobilized state. Calculations of the energy barrier for rotation of these two states show that it is below the thermal energy at room temperature for the rotating state and above it for the immobilized state.

Journal Article↗

PubMed1998

The urokinase-type plasminogen activator receptor mediates tyrosine phosphorylation of focal adhesion proteins and activation of mitogen-activated protein kinase in cultured endothelial cells.

Urokinase-type plasminogen activator (uPA) binds to cells via a specific glycosylphosphatidylinositol-anchored receptor. Although occupancy of the uPA receptor (uPAR) has been shown to alter cellular function and to induce gene expression, the signaling mechanism has not been characterized. Urokinase induced an increase in the tyrosine phosphorylation of multiple proteins in bovine aortic endothelial cells. In contrast, low molecular weight uPA did not induce this response. Analysis by immunoblotting demonstrated tyrosine phosphorylation of focal adhesion kinase (FAK), the focal adhesion-associated proteins paxillin and p130(cas), and mitogen-activated protein kinase (MAPK) following the occupancy of the uPAR by uPA. Treatment of cells with phosphatidylinositol-specific phospholipase C, which cleaves glycosylphosphatidylinositol-linked proteins from the cell surface, blocked the uPA-induced tyrosine phosphorylation of FAK, indicating the requirement of an intact uPAR on the cell surface. The uPA-induced activation of MAPK was completely inhibited by genistein, but not by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine, a specific inhibitor of Src family kinases. Thus, this study demonstrates a novel role for the uPAR in endothelial cell signal transduction that involves the activation of FAK and MAPK, which are mediated by the receptor-binding domain of uPA. This may have important implications for the mechanism through which uPA influences cell migration and differentiation.

Animals↗

PubMed1998

IFN-gamma-deficient mice develop severe granulomatous experimental autoimmune thyroiditis with eosinophil infiltration in thyroids.

To study the role of IFN-gamma in the development of granulomatous experimental autoimmune thyroiditis (EAT), DBA1 mice with a disrupted IFN-gamma gene were used for adoptive EAT induction. Effector cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donor mice activated with mouse thyroglobulin and anti-IL-2R mAb induced severe granulomatous EAT. A predominant infiltration of the thyroid by eosinophils was observed in recipients of IFN-gamma(-/-) effector cells but not in recipients of IFN-gamma(+/+) cells. Compared with wild-type mice, thyroids of recipients of IFN-gamma(-/-) effector cells had decreased expression of mRNA for Th1 cytokines and inducible nitric oxide synthetase. Expression of Th2 cytokine mRNA was comparable to that of IFN-gamma(+/+) mice, and expression of eotaxin was increased in the thyroids of recipients of IFN-gamma(-/-) effector cells. Activation of cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donors in the presence of IL-12 also induced severe granulomatous EAT. Eosinophil infiltration in recipients of IFN-gamma(-/-) cells was unaffected when effector cells were activated with IL-12, and thyroids expressed predominantly Th2 cytokines. The extent of fibrosis of recipient thyroids was generally greater when donor IFN-gamma(+/+) and IFN-gamma(-/-) cells were activated with IL-12. Compared with IFN-gamma(+/+) mice, IFN-gamma(-/-) mice produced lower levels of mouse thyroglobulin-specific autoantibodies after immunization with MTg and LPS. These results indicate that cells from both IFN-gamma(+/+) and IFN-gamma(-/-) donors can induce severe granulomatous EAT. However, damage of thyroid follicles by IFN-gamma(-/-) and that by IFN-gamma(+/+) cells appear to involve different mediators of inflammation.

Animals↗

PubMed1998

Role of cytoplasmic tail of the type 1A angiotensin II receptor in agonist- and phorbol ester-induced desensitization.

To investigate mechanisms underlying the agonist-induced desensitization of the type 1A angiotensin II receptor (AT1A-R), we have stably expressed in Chinese hamster ovary (CHO) cells the wild-type receptor and truncated mutants lacking varying lengths of the cytoplasmic tail. Assay of inositol 1,4,5-trisphosphate (IP3) formation in response to agonist demonstrated that the truncated mutants T318, T328, and T348 lacking the last 42, 32, or 12 amino acid residues, respectively, couple with Gq protein with an efficiency similar to that of full-length receptors, whereas coupling of Gq protein was abolished in the T310 truncated mutant devoid of the carboxyl-terminal 50 amino acids. Exposure of CHO/AT1A-R cells expressing the wild-type AT1A-R to angiotensin II resulted in rapid and dose-dependent homologous desensitization of receptor-mediated IP3 formation, which was independent of the receptor internalization. Mastoparan, an activator of G protein-coupled receptor kinase (GRK), induced desensitization of the AT1A-R. The agonist-induced desensitization of the receptor was largely prevented by heparin, a potent inhibitor of GRK, whereas it was only partially attenuated by a protein kinase C (PKC)-specific inhibitor. The homologous or heterologous desensitization of the receptor was greatly impaired in the truncated mutants T318 and T328, lacking the Ser/Thr-rich (13 or 12 Ser/Thr residues) cytoplasmic tail of the AT1A-R. Deletion of the last two Ser residues, including one PKC consensus site in the receptor tail, prevented only phorbol 12-myristate 13-acetate-induced desensitization by 30%. Moreover, we found an agonist-induced translocation of a heparin-sensitive kinase activity. The angiotensin II-stimulated heparin-sensitive kinase could phosphorylate a thioredoxin fusion protein containing the entire AT1A-R cytoplasmic tail (N295 to E359), which lacks consensus phosphorylation sites for GRK1, GRK2, and GRK3. The heparin-sensitive kinase may not be GRK2, GRK3, or GRK6 expressed in CHO/AT1A-R cells, since angiotensin II did not induce translocation of these receptor kinases. Potential Ser/Thr phosphorylation sites located between S328 and S347 in the cytoplasmic tail of AT1A-R seem to play a critical role in the heterologous and homologous desensitization of the receptor. A heparin-sensitive kinase other than GRK2, GRK3, or GRK6 may be involved in the agonist-induced homologous desensitization of the AT1A-R.

Amino Acid Sequence↗

PubMed1998

Effects of 2-amino-7-phosphonohepatanoic acid, melatonin or NG-nitro-L-arginine on cyanide or N-methyl-D-aspartate-induced neurotoxicity in rat cortical cells.

When cortical neuronal cells were exposed to potassium cyanide (0.01, 0.05, 0.1, 0.5, or 1.0 mM) or N-methyl-D-aspartate (NMDA: 0.005, 0.01, 0.05, 0.1, or 0.2 mM) for 24 h at 37 degrees C in a 95% air and 5% CO2 environment, lactate dehydrogenase (LDH) efflux into the extracellular fluid from the cortical cells was significantly increased in a concentration dependent manner and morphological changes were observed. The increased LDH efflux and the morphological changes in cortical cells induced by potassium cyanide or NMDA were blocked by co-exposure to 2-amino-7-phosphonoheptanoic acid (AP7: 1.0 mM), a selective antagonist of the NMDA receptor, melatonin (1.0 mM), a potent hydroxyl and peroxyl radical scavenger, or NG-nitro-L-arginine (1.0 mM), an inhibitor of nitric oxide (NO) synthase. These results suggest that activation of NMDA receptor and NO synthase and/or free radical formation may contribute to the development of neurotoxicity induced by cyanide or NMDA.

2-Amino-5-phosphonovalerate↗