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Biomedical subjects

L Tian

Publications and source records attributed to L Tian.

At least 73 records · Page 4Linked to original sources

[Elevated substance P content in sputum and plasma in patients with COPD and its relationship with FEV1/FVC].

OBJECTIVE: To investigate the role of substance P(SP) of the nonadrenergic system within airways in the pathogenesis of COPD, and analyze the relationship between level of SP and FEV1/FVC in COPD patients. METHOD: SP concentration in sputum and plasma in 20 patients with COPD and 20 normal volunteers was examined and was measured by radioimmunoassay. RESULTS: The sputum SP concentration was significantly higher in patients with COPD (57.3 +/- 14.5) pmol/L than that in normal volunteers(5.9 +/- 2.6) pmol/L, P < 0.01, the plasma SP concentration was significantly higher in COPD patients (8.6 +/- 3.9) pmol/L than that in normal volunteers (3.8 +/- 2.0) pmol/L, P < 0.05. The plasma and sputum SP concentration correlated with FEV1/FVC in COPD patients (r = -0.591, r = -0.642, P < 0.05). CONCLUSION: These data suggest that neurogenic inflammation may be involved in the airway inflammation process and subsequent airway narrowing in COPD.

Aged↗

[The relationship of cellular DNA content with clinical stage and biological features of colorectal cancer].

The purpose of this study was to explore the relationship of cellular DNA content with clinical stage and biological features of cancer. Flow cytometry was performed on fresh specimens from 86 patients from 1997 to 1998. Forty-five (53.3%) specimens were found to contain cells with abnormal DNA (DNA nondiploidy). Although none of the sex, age, site, differentiation variables correlated with flow cytometric DNA ploidy, nondiploidy was associated with Dukes' stage and lymph node metastasis. Duke's A stage tumors were more frequently diploid than were more advanced tumors, but no difference between Duke's B, C and D stages were observed. These findings suggest that ploidy is associated with some pathological factors.

Aged↗

[Study on the pharmacologic effect of propolis].

Pharmacologic effects of propolis were investigated in this article. The results suggested that propolis has pharmacologic functions in many aspects. It is a new-type medicine derived from animal in pharmacology and food both. To small mouse, propolis showed the functions of anti-fatigue and endurance to lack of oxygen. To high-blood-lipid-model mouse, it prevented increase of blood-mucus and blood lipid(TC, TG, LDL-C) (P < 0.05-0.01), but there were insignificant changes to red-blood-cell proportion (HCT) and high-density lipoprotein chelesteral (HDC-C). To small immunosuppessive-model mouse, propolis could strengthen macrophagocyte phagocytosis in the abdominal-cavity (P < 0.05), and increase the thymus-index (P < 0.05), but there were insignificant changes to the spleen-index. The LD50 > 7500 mg/kg to small mouse.

Adjuvants, Immunologic↗

Perfusion of kidneys with unformulated "naked" intercellular adhesion molecule-1 antisense oligodeoxynucleotides prevents ischemic/reperfusion injury.

BACKGROUND: We have previously shown that phosphorothioate intercellular adhesion molecule (ICAM)-1 antisense oligodeoxynucleotide (oligo) IP-9125 blocks the expression of rat ICAM-1 mRNA in rat L2 cells. A single ex situ perfusion of grafts with unformulated IP-9125, suspended in Euro-Collins solution, prolonged the survival of kidney allografts in rats. The present experiments examined whether perfusion of kidneys with unformulated IP-9125 prevents ischemic/reperfusion injury. METHODS: Kidneys were perfused ex situ with 2 ml of Euro-Collins solution without or with IP-9125 and exposed to 30-min cold (4 degrees C storage time) and 30-min warm (anastomosis time) ischemia. Kidneys were then transplanted to syngeneic nephrectomized recipients. RESULTS: Within 24 hr after transplantation, the glomerular filtration rate values were reduced by almost 60% to 0.49+/-0.14 ml/min from 1.20+/-0.27 ml/min in normal kidneys (P<0.001). Kidney perfusion with 10 mg of either IP-12140 (0.41+/-0.07 ml/min) or IP-13944 (0.47+/-0.07 ml/min) control oligo was ineffective. In contrast, perfusion with 10 mg of IP-9125 significantly improved kidney function (0.8+/-0.18 ml/min; P<0.005), whereas the lower doses of 2 mg (0.47+/-0.13 ml/min; NS) or 4 mg (0.54+/-0.04 ml/min; NS) had no significant effect. The glomerular filtration rate results were confirmed by measurements of blood creatinine (CR) levels at 24 hr after grafting: untreated recipients had a twofold higher CR value (0.70+/-0.14 mg/dl) compared with normal controls (0.65+/-0.07 mg/dl; P<0.001). Although perfusion with 10 mg of control IP-12140 (0.80+/-0.14 mg/dl) or IP-13944 (0.65+/-0.07 mg/dl) did not affect CR levels, perfusion with 10 mg of IP-9125 (0.45+/-0.07 mg/dl) lowered CR levels. The Western blots or reverse transcription-polymerase chain reaction experiments performed in kidney transplants within 24 hr after grafting showed that 10 mg of IP-9125 (but not control IP-12140) reduced the expression of ICAM-1 protein and ICAM-1 mRNA, respectively. CONCLUSIONS: Perfusion of grafts with unformulated ICAM-1 antisense oligo specifically reduces intragraft ICAM-1 protein expression and prevents ischemic/reperfusion injury.

Animals↗

Josephson persistent-current qubit

A qubit was designed that can be fabricated with conventional electron beam lithography and is suited for integration into a large quantum computer. The qubit consists of a micrometer-sized loop with three or four Josephson junctions; the two qubit states have persistent currents of opposite direction. Quantum superpositions of these states are obtained by pulsed microwave modulation of the enclosed magnetic flux by currents in control lines. A superconducting flux transporter allows for controlled transfer between qubits of the flux that is generated by the persistent currents, leading to entanglement of qubit information.

Journal Article↗

Glucocorticoid block of protein kinase C signalling in mouse pituitary corticotroph AtT20 D16:16 cells.

1. The regulation of large conductance calcium- and voltage-activated potassium (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior pituitary corticotroph cells. 2. Maximal activation of PKC using the phorbol esters, 4beta-phorbol 12-myristate, 13-acetate (PMA), phorbol 12, 13 dibutyrate (PDBu) and 12-deoxyphorbol 13-phenylacetate (dPPA) elicited a rapid, and sustained, inhibition of the outward steady-state voltage- and calcium- dependent potassium current predominantly carried through BK channels. 3. The effect of PMA was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and chelerythrine chloride (CHE; 25 microM) and was not mimicked by the inactive phorbol ester analogue 4alpha-PMA. 4. PMA had no significant effect on the 1 mM tetraethylammonium (TEA)-insensitive outward current or pharmacologically isolated, high voltage-activated calcium current. 5. PMA had no significant effect on steady-state outward current in cells pre-treated for 2 h with 1 microM of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant effect on steady-state outward current amplitude or sensitivity to 1 mM TEA and did not block PMA-induced translocation of the phorbol ester-sensitive PKC isoforms, PKCalpha and PKCepsilon, to membrane fractions. 6. Taken together these data suggest that in AtT20 D16:16 corticotroph cells BK channels are important targets for PKC action and that glucocorticoids inhibit PKC signalling downstream of PKC activation.

Animals↗

Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, immune deficiency, and a proclivity toward lymphoid malignancy. Lymphocytes of affected individuals show defects of activation, motility, and cytoskeletal structure. The disease gene encodes a 502-amino acid protein named the WAS protein (WASP). Studies have identified a number of important interactions that place WASP in a role of integrating signaling pathways with cytoskeletal function. We performed a two-hybrid screen to identify proteins interacting with WASP and cloned a proline-rich protein as a specific WASP interactor. Our clone of this protein, termed WASP interacting protein (WIP) by others, shows a difference in seven amino acid residues, compared with the previously published sequence revealing an additional profilin binding motif. Deletion mutant analysis reveals that WASP residues 101-151 are necessary for WASP-WIP interaction. Point mutant analyses in the two-hybrid system and in vitro show impairment of WASP-WIP interaction with three WASP missense mutants known to cause WAS. We conclude that impaired WASP-WIP interaction may contribute to WAS.

Animals↗

Calf sonography for detecting deep venous thrombosis in symptomatic patients: experience and review of the literature.

PURPOSE: We determined the accuracy of sonography in the detection of isolated calf deep venous thrombosis (DVT) and the rate of indeterminate ultrasound examinations in patients with physical signs or symptoms suggestive of DVT. METHODS: We reviewed the medical literature (MEDLINE) to determine the accuracy of sonography and the frequency of indeterminate studies in detecting isolated calf DVT in patients with physical signs or symptoms suggestive of DVT. A meta-analysis was used to derive summary measures of sensitivity, specificity, and accuracy from studies in which 5 or more isolated calf DVT were identified. Frequencies of indeterminate examinations were recorded for studies in which these data were provided, and we pooled these results with our own data for 196 patients. RESULTS: The meta-analysis revealed that sonography correctly identified isolated calf DVT in 49 of 53 extremities (sensitivity, 92.5%; 95% confidence interval, 81.8-97.9%) and correctly identified the absence of calf DVT in 157 of 159 extremities (specificity, 98.7%; 95% confidence interval, 95.5-99. 9%), yielding an accuracy of 97.2% (95% confidence interval, 93.9-99. 0%) for ultrasound examinations considered diagnostic. However, when evaluating our patient population and the literature, we found a substantial number of indeterminate studies (overall rate of 54.6% in 463 extremities), with a wide variation in the reported frequency of indeterminate studies (9.3-82.7%). CONCLUSIONS: Sonography is highly accurate in detecting isolated calf DVT in symptomatic patients, but indeterminate studies occur frequently, with a wide range of reported rates. Each ultrasound laboratory should evaluate its own rate of indeterminate studies.

Female↗

Leukocyte adhesion--an integrated molecular process at the leukocyte plasma membrane.

Leukocyte adhesion is of pivotal functional importance, because most leukocyte functions depend on cell-cell contact. It must be strictly controlled, both at the level of specificity and strength of interaction, and therefore several molecular systems are involved. The most important leukocyte adhesion molecules are the selectins, the leukocyte-specific beta2-integrins and the intercellular adhesion molecules. The selectins induce an initial weak contact between cells, whereas firm adhesion is achieved through integrin intercellular adhesion molecular binding. Although studies during the past twenty years have revealed several important features of leukocyte adhesion much is still poorly understood, and further work dealing with several aspects of adhesion is urgently needed. In this short essay, we review some recent developments in the field.

Carbohydrate Metabolism↗

Molecular components of large conductance calcium-activated potassium (BK) channels in mouse pituitary corticotropes.

Large-conductance calcium- and voltage- activated potassium (BK) channels play a fundamental role in the signaling pathways regulating mouse anterior pituitary corticotrope function. Here we describe the cloning and functional characterization of the components of mouse corticotrope BK channels. RT-PCR cloning and splice variant analysis of mouse AtT20 D16:16 corticotropes revealed robust expression of mslo transcripts encoding pore-forming alpha-subunits containing the mouse homolog of the 59-amino acid STREX-1 exon at splice site 2. RT-PCR and functional analysis, using the triterpenoid glycoside, DHS-1, revealed that native corticotrope BK channels are not functionally coupled to beta-subunits in vivo. Functional expression of the STREX-1 containing alpha-subunit in HEK 293 cells resulted in BK channels with calcium sensitivity, single-channel conductance, and inhibition by protein kinase A identical to that of native mouse corticotrope BK channels. This report represents the first corticotrope ion channel to be characterized at the molecular level and demonstrates that mouse corticotrope BK channels are composed of alpha-subunits expressing the mouse STREX-1 exon.

Adenosine Triphosphate↗

Leukocyte adhesion--a fundamental process in leukocyte physiology.

Leukocyte adhesion is of pivotal functional importance. The adhesion involves several different adhesion molecules, the most important of which are the leukocyte beta 2-integrins (CD11/CD18), the intercellular adhesion molecules, and the selectins. We and others have extensively studied the specificity and binding sites in the integrins and the intercellular adhesion molecules for their receptors and ligands. The integrins have to become activated to exert their functions but the possible mechanisms of activation remain poorly understood. Importantly, a few novel intercellular adhesion molecules have been recently described, which seem to function only in specific tissues. Furthermore, it is becoming increasingly apparent that changes in integrins and intercellular adhesion molecules are associated with a number of acute and chronic diseases.

Cell Adhesion↗

[The excitatory effects of histamine on cerebellar cortical Purkinje cells in the rat].

The effects of histamine on Purkinje cells (PCs) in lobule X of cerebellar cortex were investigated in rat cerebellar slices. Histamine elicited PCs' responses predominately excitatory (94.4%, 51/54), only few inhibitory (5.6%, 3/54). The excitatory response could not be abolished by perfusing the slices with low Ca2+/high Mg2+ medium. The excitatory response of PCs to histamine could be blocked by histamine H2 receptor antagonist ranitidine, but not by H1 receptor antagonist triprolidine readily. These results suggest that histamine exerts an excitatory effect on the PCs via H2 receptors. Presumably, hypothalamo-cerebellar histaminergic fibers participate in the regulation of somatic and non-somatic functions of the cerebellum.

Animals↗

[Risk state analysis on lung cancer of male in Xuanwei, China].

The analysis of lung cancer risk factors among male population was based on the data of a retrospective cohort study conducted during 1976-1996 in Xuanwei, China. The results verified that the indoor air pollution from burning smoky coal was the main cause of high lung cancer mortality, and found that cigarette smoking was also significantly related with the lung cancer mortality. Using risk state analysis theory, fuel types(including household stove improvement), smoking and the history of chronic bronchitis were selected as the covariance for the analysis. A risk state analysis model for male lung cancer in Xuanwei was established. The model can be used to quantitatively estimate the risk of lung cancer and to determine high risk population and individuals. The model is helpful for the prevention of lung cancer in Xuanwei.

Adult↗

Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation.

Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/- mice yielded an abnormally low number of LCAD +/- and -/- offspring, indicating frequent gestational loss. LCAD -/- mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD -/- males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/- mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo.

Acyl-CoA Dehydrogenase, Long-Chain↗

Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via In utero or postnatal transfer.

Although in utero transplantation (IUT) has been shown to be effective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared with postnatal bone marrow transplantation (BMT) for SCID is unknown. Therefore, comparative studies were undertaken in mice to determine the engraftment outcome in these two settings. Because T-cell depletion (TCD) reduces graft-versus-host disease (GVHD) severity but compromises alloengraftment, studies were performed with TCD or non-TCD BM and GVHD risk was assessed using a tissue scoring system and by the adoptive transfer of splenocytes from engrafted mice into secondary recipients. Non-SCID recipients received pre-BMT irradiation to simulate those circumstances in which conditioning is required for alloengraftment. IUT recipients of non-TCD and especially TCD BM cells in general had higher levels of donor T-cell and myeloid peripheral blood (PB) engraftment than nonconditioned SCID recipients. Increased TCD or non-TCD BM cell numbers in adult SCID recipients resulted in similar levels of PB engraftment as IUT recipients. However, under these conditions, mean GVHD scores were higher than in IUT recipients. The majority of adoptive transfer recipients of splenocytes from IUT recipients were GVHD-free, consistent with the in vitro evidence of tolerance to host alloantigens. Total body irradiation (TBI)-treated mice that had the highest engraftment had evidence of thymic damage as denoted by a higher proportion of thymic and splenic T cells with a memory phenotype as compared with IUT recipients. IUT mice had vigorous thymic reconstitution by 3 weeks of age. Our data indicate that IUT has a number of advantages as compared with postnatal BMT. Future studies examining the fine specificity of immunoreconstitution in IUT versus postnatal BMT are indicated.

Adoptive Transfer↗

Protection against allograft rejection with intercellular adhesion molecule-1 antisense oligodeoxynucleotides.

BACKGROUND: We designed an antisense phosphorothioate oligodeoxynucleotide (oligo) to specifically inhibit the expression of rat intercellular adhesion molecule-1 (ICAM-1) mRNA (IP-9125). METHODS: IP-9125 oligo was delivered intravenously by osmotic pump alone or in combination with cyclosporine (CsA) to recipients in order to prevent the rejection of kidney or heart allografts. In additional experiments, kidney allografts were perfused with IP-9125 before grafting. RESULTS: IP-9125 inhibited ICAM-1 mRNA and ICAM-1 protein expression in rat aortic endothelial cells; scrambled controls IP-12140 and IP-13944 were ineffective. Untreated ACI (RT1a) recipients rejected Lewis (RT1l) kidney allografts at a mean survival time of 8.5+/-1.1 days. A 14-day intravenous administration of 2.5 mg/kg/day IP-9125 prolonged the survival of kidney allografts to 39.2+/-16.4 days; 5.0 mg/kg/day, to 43.0+/-17.5 days; and 10.0 mg/kg/day, to 50.4+/-21.6 days. In contrast, a scrambled control IP-12140 was not effective. A combination of 10 mg/kg/day IP-9125 and 1.0 mg/kg/day CsA delivered for 14 days synergistically extended kidney allograft survival times 88.5+/-7.5 days. In contrast, the combination of 10.0 mg/kg/day control IP-12140 with CsA was ineffective (20.7+/-3.2 days) when compared with CsA alone (20.2+/-4.0 days). Similar results were obtained for heart transplants in recipients treated with IP-9125 alone or in combination with CsA. Furthermore, in situ immunostaining showed that IP-9125 significantly reduced the expression of ICAM-1 protein in kidney allografts. Finally, perfusion of kidney grafts alone with 20.0 mg per 2 ml of IP-9125 protected kidney allografts from rejection (37.5+/-7.5 days; P < 0.001), whereas perfusion with 20 mg per 2 ml of control IP-12140 was ineffective (12.6+/-5.0 days). CONCLUSIONS: Rat ICAM-1 IP-9125 oligo inhibits ICAM-1 protein expression in vitro and in vivo as well as blocks allograft rejection when used for pretreatment of donors, graft perfusion, or postoperative treatment of recipients.

Animals↗