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Biomedical subjects

Lan Yu

Publications and source records attributed to Lan Yu.

28 records · Page 2Linked to original sources

Protein kinase C betaII activation induces angiotensin converting enzyme expression in neonatal rat cardiomyocytes.

OBJECTIVE: Members of the protein kinase C (PKC) family are important mediators of cell signaling underlying multiple aspects of myocardial function. Activation of the betaII isoform of PKC is thought to be involved in the development of congestive heart failure. To investigate the biological effect of PKC-betaII, we measured gene expression of angiotensin converting enzyme (ACE) and angiotensin II (AngII) receptors AT(1A) and AT(1B) in cardiomyocytes overexpressing PKC-betaII. METHODS: An adenovirus construct expressing PKC-betaII was introduced into cultured neonatal rat ventricular myocytes (NRVMs). Western blot and in situ kinase assay was used to measure PKC-betaII level and activity in NRVMs. Real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to measure the mRNA levels of several genes following PMA stimulation of either un-infected or ad-PKC-betaII infected cells. RESULTS: Our data show that activation of PKC-betaII in cardiomyocytes leads to elevated expression of angiotensin-converting enzyme (ACE) gene. Treatment of adeno-PKC-betaII infected cardiomyocytes with phorbol 12-myristate 13-acetate (PMA) resulted in an 8-fold increase of ACE mRNA expression, whereas ACE mRNA levels only increased around 2-fold in uninfected or adeno-GFP (green fluorescent protein) infected cardiomyocytes with similar PMA treatment. The induction of ACE mRNA was blocked by the PKC-beta-specific antagonist LY379196. No significant change of angiotensin II receptors AT1a and AT1b could be detected in the cardiomyocytes expressing PKC-betaII. CONCLUSION: These data indicate that ACE is a transcription target of PKC-betaII activation in cardiomyocytes, and also suggest a mechanism for the involvement of PKC in cardiac hypertrophy and fibrosis through increased activity of angiotensin converting enzyme in the myocardium.

Angiotensin I↗

Critical role of galectin-3 in phagocytosis by macrophages.

Galectin-3 is a member of a large family of animal lectins. This protein is expressed abundantly by macrophages, but its function in this cell type is not well understood. We have studied the effect of galectin-3 gene targeting on phagocytosis, a major function of macrophages. Compared with wild-type macrophages, galectin-3-deficient (gal3-/-) cells exhibited reduced phagocytosis of IgG-opsonized erythrocytes and apoptotic thymocytes in vitro. In addition, gal3-/- mice showed attenuated phagocytic clearance of apoptotic thymocytes by peritoneal macrophages in vivo. These mice also exhibited reduced IgG-mediated phagocytosis of erythrocytes by Kupffer cells in a murine model of autoimmune hemolytic anemia. Additional experiments indicate that extracellular galectin-3 does not contribute appreciably to the phagocytosis-promoting function of this protein. Confocal microscopic analysis of macrophages containing phagocytosed erythrocytes revealed localization of galectin-3 in phagocytic cups and phagosomes. Furthermore, gal3-/- macrophages exhibited a lower degree of actin rearrangement upon Fcgamma receptor crosslinkage. These results indicate that galectin-3 contributes to macrophage phagocytosis through an intracellular mechanism. Thus, galectin-3 may play an important role in both innate and adaptive immunity by contributing to phagocytic clearance of microorganisms and apoptotic cells.

Anemia, Hemolytic, Autoimmune↗

[Maturation regulation of dendritic cells pulsed with hepatocellular carcinoma cell soluble antigens].

OBJECTIVE: To research the maturation regulation of dendritic cells (DCs) pulsed with hepatocellular carcinoma (HCC) cell soluble antigens. METHODS: BCG HSP 70 was purified by SDS-PAGE electrophoresis and its biological activity was determined with ELISA. Phenotypes of DCs pulsed with antigens or with both antigens and BCG HSP 70 were analysed with flow cytometry. MTT assay was used to estimate the proliferation of self lymphocytes and the mixed lymphocyte reaction (MLR) of BCG HSP 70 primed DCs. RESULTS: The characteristics of DCs had changed after loaded with soluble antigens of HCC. There were about 10% DCs which had lost their specific markers. The expression levels of CD54, CD83, CD86 molecules and the stimulatory ability in allogeneic MLR decreased. However, after being activated by BCG HSP 70, the DCs pulsed with antigens could keep their special markers and the expression levels of CD54, CD83, CD86 molecules increased too. The stimulatory abilities in allogeneic MLR and proliferation of self lymphocytes also improved. CONCLUSION: This study shows that BCG HSP 70 can induce DCs pulsed with antigens maturation and improve their antigen-presenting ability, which may be a useful maturation inducer for dendritic cells.

Antigen Presentation↗

[Overexpression of c-erbB-2 and hypoexpression of nm23 relating to poor prognosis of colorectal carcinoma].

OBJECTIVE: To investigate the relationship between expression of c-erbB-2, CD44v6 and nm23 gene proteins and the clinicopathological features of colorectal carcinomas. METHODS: Immunohistochemical technique was adopted to detect the protein expression of c-erbB-2, CD44v6 and nm23 genes in 92 cases of colorectal carcinomas. Of the 92 cases, 28 cases were followed up for more than 10 years, in which the prognosis was analyzed. RESULTS: Expression of c-erbB-2 and CD44v6 was correlating with UICC staging (P < 0.05), and c-erbB-2 was associated with prominent peritumoral lymphocytic infiltration (P < 0.05). In the 28 cases with followed-up data, univariant analysis revealed that the survival rate was correlated with histological grading, UICC staging, tumor growth pattern, peritumoral lymphocytic infiltration, and expression of c-erbB-2, CD44v6 and nm23. However, Cox stepwise proportional hazards analysis showed that only UICC staging, c-erbB-2 and nm23 status retained significant independently in prospecting prognosis. CONCLUSIONS: Besides UICC III and IV stage, overexpression of c-erbB-2 and decreased expression of nm23 are considered acceptable as the parameters in predicting of poor prognosis in colorectal carcinoma.

Adenocarcinoma↗

IgE-dependent mast cell activation potentiates airway responses in murine asthma models.

We have studied murine models of asthma using FcepsilonRIalpha-chain-deficient (FcepsilonRIalpha(-/-)) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcepsilonRalpha(-/-) mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcepsilonRIalpha(-/-) mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcepsilonRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.

Allergens↗

[Imaging diagnosis of hepatic alveolar echinococcosis].

OBJECTIVE: To study the characteristics of hepatic alveolar echinococcosis in B mode ultrasonography (BU), computerized tomography (CT), and magnetic resonance imaging (MRI) so as to increase the pre-operative diagnostic rate. METHODS: The data of forty-six cases with hepatic alveolar echinococcosis who underwent operation during the period January 1984 to December 2000 were analyzed and compared with the pathological findings of the resected specimens. All of the cases were examined by BU and CT, and 12 of them were examined by MIR. RESULTS: The imaging characteristics of the 46 cases were divided into three types: infiltration (41 cases, 89.1%), calcification (39 cases, 84.8%), and cavity with liqueficaction (37 cases, 80.4%). Nine imaging signs were found to be specific to hepatic alveolar echinococcosis and of diagnostic significance: halo belt sign, calcification sign, annual ring sign, invacuation sign, cavity with liqueficaction sign, grotto sign, peninsula sign, alveolar sign. With these signs, the diagnostic accuracy rate reached 97.7% in this series. CONCLUSION: There are nine imaging diagnostic signs specific to hepatic alveolar echinococcosis. They help detect the location, pathology of this disease and determine operation program. Identification of only one of them is adequate for diagnosis of hepatic alveolar echinococcosis.

Adult↗

[Imaging diagnosis and classification of hepatic cystic echinococcosis].

OBJECTIVE: To investigate the imaging characteristics of hepatic cystic echinococcosis in different imaging examinations and to formulate an imaging classification. METHODS: The data of pre-operative imaging examination of 2 039 cases with hepatic cystic echinococcosis, who underwent operation during the period January 1984 to December 2000, by B mode ultrasonograohy (all cases), X-ray computed tomography (909 cases), and magnetic resonance imaging (24 cases) were analyzed, being compared with the pathological findings of the resected specimens. RESULTS: Imaging examinations succeeded to identify not only the location, size, and form of hydatid cyst in liver, but also the typical pathomorphology of complications. The hepatic echinococcosis can be divided into seven imaging-diagnostic patterns: solitary cyst (1 625 cases, 79.70%), multiple cysts (414 cases, 20.30%), primary hydatid cyst with daughter cysts (1 114 cases, 54.63%), calcified cyst (186 cases, 9.12%), consolidated cyst (28 cases, 1.37%), cyst with infection (391 cases, 19.18%), and ruptured cyst (298 cases, 14.62%). CONCLUSION: A new diagnostic system of hepatic echinococcosis has been formulated based on imaging examination and by reference to clinical manifestation. It helps select appropriate operation program.

Adolescent↗

Aldosterone stimulates angiotensin-converting enzyme expression and activity in rat neonatal cardiac myocytes.

BACKGROUND: Members of the nuclear receptor family proteins function as transcription factors upon ligand binding and thereby regulate gene expression in host cells. Aldosterone, the high-affinity endogenous ligand for the mineralocorticoid receptor, induces cardiac hypertrophy and fibrosis in a variety of animal models, but the transcriptional targets for aldosterone in the myocardium are not well-described. METHODS AND RESULTS: Using quantitative reverse transcription-polymerase chain reaction method, we show that in cultured rat neonatal cardiomyocytes, aldosterone stimulates expression of angiotensin converting enzyme (ACE) in a concentration and time-dependent manner. Aldosterone (50 and 100 nM) increased levels of ACE mRNA by 1.8- and 2.2-fold, respectively. Aldosterone-induced ACE gene expression was blocked by spironolactone (1 microM), a mineralocorticoid receptor antagonist. In contrast, the expressions of the type I angiotensin receptor was not induced by aldosterone in either cardiac myocytes or fibroblasts. Consistent with the increased ACE mRNA level, 100 nM aldosterone also induced a 2-fold increase in ACE activity in cardiac myocytes. CONCLUSION: ACE gene expression may be a target for mineralocorticoid receptors in the myocardium, supporting the notion that at least some of the known adverse effects of aldosterone on the myocardium are mediated by increased angiotensin II.

Aldosterone↗

Current progress of China's free ART program.

China's Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China. With little experience in HIV/AIDS treatment and care and resource limitations, China's efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty. However, the Free ART Program is progressing from an emergency response to a standardized treatment and care system. The development of national guidelines, training programs, a laboratory support network, a national patient database, programs for special populations such as children and patients living with co-infections, and operational research has improved the scope and quality of the free treatment program. As of June 30, 2005, a total of 19,456 patients in 28 provinces, autonomous regions, and special municipalities had received free ART. Challenges stemming from the nature of China's health system and patient population persist, but with strong government support and a diverse set of resources, China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care.

Anti-Retroviral Agents↗