Biomedical subjects

Yang Xiang

Publications and source records attributed to Yang Xiang.

At least 55 records · Page 3Linked to original sources

PubMed2004

The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes.

We studied arthritis-related autoantibodies in 136 patients with knee osteoarthritis (OA) and 67 age- and sex-matched healthy individuals in the Shanghai District of China. Serum antibody titers for recombinant fusion proteins of cartilage intermediate layer protein (CILP) and YKL-39 were analyzed using enzyme-linked immunosorbent assay (ELISA) and Western blot. Serum antibody titers against recombinant osteopontin (OPN) and cyclic citrullinated peptide (CCP) antibodies were measured also using ELISA. Anti-CILP antibodies were detected in 25/136 OA patients but only 1/67 controls. Anti-YKL-39, anti-OPN, and anti-CCP antibodies were detected in 9/136, 11/136, and 7/136 of the OA patients, respectively, and 0/67 controls. There was rarely overlap of these antibodies in a single patient, suggesting distinct antigen specificity in each case. The antibodies were detected in patients with OA of grades II and III but not grade IV. The prevalence of autoantibodies to various arthritis-related proteins in early-stage knee OA supports the involvement of a specific immune response in initial cartilage degeneration in OA.

Adipokines↗

PubMed2004

The protein profile of acetazolamide-treated sera in mice bearing Lewis neoplasm.

The aim of the present research is to analyze the proteome of neoplasm serum before and after treated with acetazolamide (20, 40, 80 mg kg(-1) d(-1) for 3 days p.o.). The Lewis lung carcinoma mice were used and carried out a comprehensive proteomic analysis by using the technologies of high-resolution two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and mass spectrometry (MS). The results showed that the acetazolamide could dramatically reduce the lung metastasis and primary tumor growth. Its most potent inhibition rate on lung metastases was reach to 77.7% at the dose of 80 mg kg(-1) d(-1). The two dimension electrophoresis and software analysis reveal 393 protein spots in control gel, 385 protein spots were detected in treated gel and matched 209 protein spots with control gel, indicating that intensive changes had occurred during the process of treatment. Two obviously different spots were cut off from gel and for the peptide mass fingerprinting. Data base searching showed the two proteins' peptide much more mach with Histone H2B fragment and Ubc-like protein CROC1 fragment. The results suggest that acetazolamide has a strong anti-tumor and anti-metastasis effect on Lewis-lung-carcinoma. The mechanism may be related to its regulation on plenty of proteins, in particular, on upregulation of H2B and CROC-1 expression of postreplicational DNA repair related protein in serum.

Acetazolamide↗

PubMed2004

[Fibronectin upregulates catalase gene expression in rabbit bronchial epithelial cells].

We have previously shown that the binding of integrins with extracellular matrix component fibronectin (Fn) can improve the ability of bronchial epithelial cells (BECs) in resisting oxidant injury by up-regulating the activity of catalase and increasing the content of GSH. However, the molecular mechanism or its signaling pathway of this protection is still unclear. In order to examine the intracellular signaling mechanism activated by Fn-integrin binding reaction, the present study investigated the mRNA expression of catalase in primary cultured rabbit BECs using RT-PCR based on a cell-injury model made with ozone exposure. The product bands of target gene CAT were checked with Southern blot and oligonucleotide probe hybridization. The results showed that Fn (10 microg/ml) promoted the catalase mRNA transcription (P<0.01). This effect was abolished either by protein-tyrosine kinase inhibitor genistein or calmodulin inhibitor W(7) (P<0.01). These results indicate that the promotion of catalase activity induced by Fn-integrin reaction is partly due to the elevation of catalase mRNA transcription, and that its signalling are possibly relevant to tyrosine phosphorylation or calmodulin pathway.

Animals↗

PubMed2004

Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphate isomerase as an autoantigen in patients with osteoarthritis.

OBJECTIVE: Autoimmunity to proteins, such as type II collagen and cartilage intermediate layer protein, that are produced by chondrocytes has been reported in patients with osteoarthritis (OA) as well as in patients with rheumatoid arthritis (RA). However, it remains to be determined whether the overall specificities of the autoimmunity differ between OA and RA patients. This study sought to clarify the differences by applying proteomic surveillance for the detection of autoantigens comprehensively. METHODS: Serum samples were obtained from 20 patients with OA, 20 patients with RA, and 20 healthy volunteers. Human chondrocyte proteins were separated from the sera by 2-dimensional electrophoresis, and antigenic protein spots were detected by Western blotting. The antigenic proteins were then identified by mass fingerprinting. The antigenicity of the identified proteins was confirmed and the prevalence of the autoantibodies in the OA, RA, and other disease groups was determined with the use of recombinant proteins. In addition, autoepitopes were mapped on the antigens. RESULTS: Nineteen protein spots were recognized only by the OA sera, but not by the RA sera. One of these proteins was identified as triosephosphate isomerase (TPI). IgG-type anti-TPI autoantibodies were detected in 24.7% of the serum samples and 24.1% of the synovial fluid samples from the patients with OA, whereas <6% of the RA and systemic lupus erythematosus samples were positive for anti-TPI. In addition, multiple autoepitopes were identified on TPI. CONCLUSION: The overall profile of autoimmunity in OA differs from that in RA, which may reflect the OA-specific pathologic role of autoimmunity. The autoantibody to TPI, detected predominantly in the OA samples and produced by the antigen-driven mechanism, has the potential to be used as a diagnostic marker for OA.

Adult↗

PubMed2004

Neoantigens in osteoarthritic cartilage.

PURPOSE OF REVIEW: Osteoarthritis has been considered a degenerative disease. However, recent evidence supports involvement of immunologic mechanisms in this pathophysiology: for example, inflammation of synovial tissue is observed in osteoarthritis. In osteoarthritis, the proinflammatory cytokine interleukin-1, which is produced by activated synoviocytes and mononuclear cells and has catabolic effects on chondrocytes, is one of the most involved. The immune reaction would require driving antigens. This review describes autoantigens in osteoarthritis and discusses their roles in triggering and/or perpetuating synovitis and joint cartilage destruction in osteoarthritis. RECENT FINDINGS: Several autoantigens/autoantibodies have been reported in osteoarthritis, such as the cartilage intermediate layer protein. Furthermore, recent comprehensive proteomic surveillance has revealed that comparable numbers of autoantigens were detected in osteoarthritis and rheumatoid arthritis, and that some of them were recognized predominantly in osteoarthritis rather than in rheumatoid arthritis. In addition, it was revealed that the cartilage intermediate layer protein immunization of mice developed calcification of tendons, thus indicating that autoimmunity modulates functions of target molecules. SUMMARY: Osteoarthritis-specific autoantigens may drive chronic synovitis and may thereby contribute to production of cytokines to upregulate proteases, which lead to chondrocyte and cartilage damage. In addition, autoimmunity may damage joint components by modulating functions of the target molecules.

Autoantibodies↗

PubMed2004

Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its relation with AQP1 water channel.

AIM: To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma. RESULTS: Treatment with topiramate (120 mg/kg/d, ig for 20 d) reduced the growth of primary tumor significantly (P<0.05). Its inhibitory rate of metastasis was 81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent manner. Topiramate apparently decreased AQP1 protein expression and immunostaining in lungs or in tumor microvessel endothelial cells of mice. CONCLUSION: Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis.

Animals↗

PubMed2004

Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA injected Xenopus oocyte.

AIM: To study the effects of acetazolamide and anordiol on osmotic water permeability in aquaporin 1 (AQP1)-cRNA injected Xenopus oocyte and their mechanisms. METHODS: AQP1 gene constructed in pBluescript was transcripted into cRNA in vitro and then the cRNA was injected in Xenopus oocytes. The effects of acetazolamide and anordiol on the water transport function of AQP1 were observed by assaying the osmotic swelling of oocytes. In addition, their effects on protein expression of AQP1 were quantitatively investigated by Western blotting method. RESULTS: After incubation for 15 min or 72 h, acetazolamide, a carbonic anhydrase inhibitor, equally reduced the water permeability of AQP1-cRNA injected oocyte in a dose-dependent manner. After incubation for 72 h, anordiol, an antiestrogen with partial estrogenic activity, reduced the osmotic water permeability dose dependently as well; however, no discernable action was observed after incubation with anordiol for 15 min. The Western blotting analysis showed that acetazolamide did not influence the protein expression of AQP1. However, after incubation for 72 h with anordiol (10 micromol/L), the quantity of AQP1 in the oocyte membrane was decreased dramatically (P<0.05). CONCLUSION: Both acetazolamide and anordiol inhibited the osmotic water permeability of AQP1-cRNA injected oocyte, but their mechanisms were different. Acetazolamide functionally inhibited the osmotic water permeability of AQP1, whereas anordiol primarily decreased the amount of AQP1 protein in the oocyte membrane.

Acetazolamide↗

PubMed2004

Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis.

AIM: To study effects of acetazolamide on aquaporin-1 (AQP(1)) protein expression and angiogenesis. METHODS: Establishing Lewis-lung-carcinoma model, the localization of AQP(1) in tumor tissues was investigated by immunohistochemical methods; The biological activity of acetazolamide was detected by endothelial cells proliferation test (MTT) assay and chorioallantoic membrane (CAM) vascular inhibition test. RESULTS: Immunohistochemical localization of AQP(1) in mice tumor was labeled in capillaries, post capillary venules endothelial cells. After being treated with acetazolamide, the number of capillaries and post capillary venules was significantly decreased in tumor tissue. Acetazolamide showed significant inhibitory effect on angiogenesis in CAM and endothelial cell proliferation. CONCLUSION: Acetazolamide might be identified and developed as one of potential lead compounds for a new therapeutic intervention in inhibiting cancer angiogenesis.

Acetazolamide↗

PubMed2004

EMA/EP chemotherapy for chemorefractory gestational trophoblastic tumor.

OBJECTIVE: To evaluate the results of etoposide/ methotrexate/actinomycin D/etoposide/cisplatin (EMA/ EP) chemotherapy in patients with chemorefractory gestational trophoblastic tumor (GTT). STUDY DESIGN: Fifteen patients with chemorefractory GTT were treated with EMA/EP. RESULTS: Twelve of the 15 cases were choriocarcinoma, and the last 3 were metastatic placental site trophoblastic tumor (PSTT): International Federation of Gynecology and Obstetrics (FIGO) stage I, 2 cases; stage III, 10 cases; stage IV, 3 cases. Seven cases have FIGO score 7-10; the scores of the remaining 8 cases were > 10. Fifteen patients received a total of 93 cycles of the study regimen. The median number of courses for each patient was 6.2. Eleven cases (73.3%) achieved complete remission, while 3 (20%) had partial remission; 1 case (6.7%) showed no response. The main complications of EMA/EP chemotherapy were myelosuppression and gastrointestinal symptoms. CONCLUSION: The EMA/EP regimen is effective for chemorefractory GTT, and the chemotherapeutic results can be improved when combined with surgery and arterial infusion chemotherapy in selected patients. The EMA/EP regimen should be considered for primary management of metastatic PSTT.

Adult↗

PubMed2004

Floxuridine-containing regimens in the treatment of gestational trophoblastic tumor.

OBJECTIVE: To analyze the efficacy of floxuridine (FUDR)-containing regimens in the treatment of gestational trophoblastic tumor (GTT). STUDY DESIGN: Seventy-four patients with GTT, 47 with invasive mole and 27 with choriocarcinoma were treated with FUDR-containing regimens. Clinical staging of the disease was: 33 cases of stage I, 3 cases of stage II, 31 cases of stage IIIa, 6 cases of stage IIIb and 1 case of stage IV. RESULTS: The complete response rate of FUDR-containing regimens in the treatment of GTT was 91.9% (68 of 74 cases). Six patients, of whom 3 showed signs of drug resistance and 3 showed myelosuppression, had their regimens changed to non-FUDR-containing regimens, and all achieved a complete response. All 7 patients with advanced disease (>IIIb) achieved a complete response. The major adverse event with FUDR-containing regimens was myelosuppression and gastrointestinal toxicity: third- and fourth-degree neutropenia in 26% and thrombocytopenia in 6.2%, third-degree vomiting in 57.1% and third-degree diarrhea in 4.3%. CONCLUSION: FUDR-containing regimens are efficient for the treatment of GTT even for patients with advanced or drug-resistant disease.

Antimetabolites, Antineoplastic↗

PubMed2004

[Diagnosis and management of uterine arteriovenous fistula with massive vaginal bleeding].

OBJECTIVE: To study the clinical manifestation, diagnosis, management and prognosis of uterine arteriovenous fistula with massive vaginal bleeding. METHOD: The clinical records of 15 patients who satisfied the diagnostic criteria were retrospectively analyzed. RESULTS: All patients had massive vaginal bleeding, with a history of caesarean section, curettage or gynecologic carcinoma. The disease could be diagnosed by angiography or color Doppler ultrasound. Vaginal bleeding was aggravated by dilation and curettage. Fourteen patients were treated with uterine artery embolization, and no complications occurred postembolization. Of the eleven successful embolizations, all patients returned normal menstrual cycling. Five of these patients became pregnant later. CONCLUSIONS: Uterine arteriovenous fistula is a rare and potentially life threatening disease. Uterine artery embolization is a safe and effective treatment for this disease, and it can preserve normal function of uterus and ovaries.

Adult↗

PubMed2003

The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic.

PACS-1 is a cytosolic sorting protein that directs the localization of membrane proteins in the trans-Golgi network (TGN)/endosomal system. PACS-1 connects the clathrin adaptor AP-1 to acidic cluster sorting motifs contained in the cytoplasmic domain of cargo proteins such as furin, the cation-independent mannose-6-phosphate receptor and in viral proteins such as human immunodeficiency virus type 1 Nef. Here we show that an acidic cluster on PACS-1, which is highly similar to acidic cluster sorting motifs on cargo molecules, acts as an autoregulatory domain that controls PACS-1-directed sorting. Biochemical studies show that Ser278 adjacent to the acidic cluster is phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN. These results suggest that coordinated signaling events regulate transport within the TGN/endosomal system through the phosphorylation state of both cargo and the sorting machinery.

Amino Acid Sequence↗

PubMed2003

Sequential binding of agonists to the beta2 adrenoceptor. Kinetic evidence for intermediate conformational states.

The beta2 adrenoreceptor (beta2AR) is a prototypical G protein-coupled receptor (GPCR) activated by catecholamines. Agonist activation of GPCRs leads to sequential interactions with heterotrimeric G proteins, which activate cellular signaling cascades, and with GPCR kinases and arrestins, which attenuate GPCR-mediated signaling. We used fluorescence spectroscopy to monitor catecholamine-induced conformational changes in purified beta2AR. Here we show that upon catecholamine binding, beta2ARs undergo transitions to two kinetically distinguishable conformational states. Using a panel of chemically related catechol derivatives, we identified the specific chemical groups on the agonist responsible for the rapid and slow conformational changes in the receptor. The conformational changes observed in our biophysical assay were correlated with biologic responses in cellular assays. Dopamine, which induces only a rapid conformational change, is efficient at activating Gs but not receptor internalization. In contrast, norepinephrine and epinephrine, which induce both rapid and slow conformational changes, are efficient at activating Gs and receptor internalization. These results support a mechanistic model for GPCR activation where contacts between the receptor and structural determinants of the agonist stabilize a succession of conformational states with distinct cellular functions.

Adrenergic beta-Agonists↗

PubMed2003

The PDZ-binding motif of the beta2-adrenoceptor is essential for physiologic signaling and trafficking in cardiac myocytes.

beta1- and beta2-adrenergic receptors (AR) regulate cardiac myocyte function through distinct signaling pathways. In addition to regulating cardiac rate and contractility, beta1AR and beta2AR may play different roles in the pathogenesis of heart failure. Studies on neonatal cardiac myocytes from beta1AR and beta2AR knockout mice suggest that subtype-specific signaling is determined by subtype-specific membrane targeting and trafficking. Stimulation of beta2ARs has a biphasic effect on contraction rate, with an initial increase followed by a sustained Gi-dependent decrease. Recent studies show that a PDZ domain-binding motif at the carboxyl terminus of human beta2AR interacts with ezrin-binding protein 50/sodium-hydrogen exchanger regulatory factor, a PDZ-domain-containing protein. The human beta2AR carboxyl terminus also binds to N-ethylmaleimide-sensitive factor, which does not contain a PDZ domain. We found that mutation of the three carboxyl-terminal amino acids in the mouse beta2AR (beta2AR-AAA) disrupts recycling of the receptor after agonist-induced internalization in cardiac myocytes. Nevertheless, stimulation of the beta2AR-AAA produced a greater contraction rate increase than that of the wild-type beta2AR. This enhanced stimulation of contraction rate can be attributed in part to the failure of the beta2AR-AAA to couple to Gi. We also observed that coupling of endogenous, wild-type beta2AR to Gi in beta1AR knockout myocytes is inhibited by treatment with a membrane-permeable peptide representing the beta2AR carboxyl terminus. These studies demonstrate that association of the carboxyl terminus of the beta2AR with ezrin-binding protein 50/sodium-hydrogen exchanger regulatory factor, N-ethylmaleimide-sensitive factor, or some related proteins dictates physiologic signaling specificity and trafficking in cardiac myocytes.

Amino Acid Motifs↗

PubMed2003

Myocyte adrenoceptor signaling pathways.

Adrenoceptors (ARs), members of the G protein-coupled receptor superfamily, form the interface between the sympathetic nervous system and the cardiovascular system, with integral roles in the rapid regulation of myocardial function. However, in heart failure, chronic catecholamine stimulation of adrenoceptors has been linked to pathologic cardiac remodeling, including myocyte apoptosis and hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling to different G proteins and induction of specific signaling pathways, which is partly regulated by the subtype-specific distribution of receptors in plasma membrane compartments containing distinct complexes of signaling molecules. The Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways bring into focus the specific signaling pathways of individual AR subtypes and their relevant functions in vivo.

Animals↗

PubMed2003

The third intracellular loop and the carboxyl terminus of beta2-adrenergic receptor confer spontaneous activity of the receptor.

It is well established that the beta2-adrenergic receptor (beta2-AR) exhibits a robust ligand-independent activity, whereas this property is considerably weaker in the closely related beta1-AR subtype. To identify the potential domain(s) of beta2-AR responsible for the spontaneous receptor activation, we created three chimeras in which the third intracellular loop (beta1/beta2-Li3) or the carboxyl terminus (beta1/beta2-CT) or both domains (beta1/beta2-Li3CT) of beta1-AR are replaced by the corresponding parts of the beta2-AR. Using adenoviral gene transfer, we individually expressed these beta1/beta2-AR chimeras in mouse cardiomyocytes lacking both native beta1-AR and beta2-AR (beta1/beta2 double knockout), and examined their possible spontaneous activities. Overexpression of these beta1/beta2-AR chimeras markedly elevated basal cAMP accumulation and myocyte contractility in the absence of agonist stimulation compared with those infected by a control adenovirus expressing beta-galactosidase or an adenovirus expressing wild type beta1-AR. These effects were fully reversed by a beta2-AR inverse agonist, (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551; 5 x 10-7 M), regardless of inhibition of Gi with pertussis toxin, but not by a panel of beta1-AR antagonists, including [2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluormethyl-2-imidazolyl)-phenoxy]-2-propanolmethanesulfonate (CGP20712A), betaxolol, bisoprolol, and metoprolol. Furthermore, we have shown that the C-terminal postsynaptic density 95/disc-large/ZO-1 (PDZ) motif of beta1-AR is not responsible for the lack of beta1-AR spontaneous activation, although it has been known that the beta1-AR PDZ motif prevents the receptor from undergoing agonist-induced trafficking and Gi coupling in cardiomyocytes. Taken together, the present results indicate that both the third intracellular loop and the C terminus are involved in beta2-AR spontaneous activation and that either domain seems to be sufficient to confer the receptor spontaneous activity.

Adrenergic beta-Antagonists↗

PubMed2003

[Study on Realgar inducing apoptosis in T lymphocytic cell line CEM].

OBJECTIVE: To study the Realgar induced T lymphocytic leukemia cell line CEM apoptosis in vitro. METHODS: CEM cells were incubated with Realgar. Cell proliferation inhibition was determined by MTT. Cell cycle, apoptosis, Apo2.7 and Fas were measured by cytometer. RESULTS: Realgar inhibited the proliferation of CEM cell line. The cells treated with Realgar showed a Sub-G(0)/G(1) apoptotic peak in DNA distribution histogram, increment of Apo2.7 protein expression, and arrested cells in G(2)/M phase, but ineffectiveness on Fas expression. CONCLUSION: The Realgar can induce CEM cell apoptosis in vitro.

Apoptosis↗

PubMed2003

[Clinical analysis of 17 cases of nongestational choriocarcinoma].

OBJECTIVE: To evaluate the diagnosis, treatment and prognosis of nongestational choriocarcinoma. METHODS: Retrospective analysis was done on 17 cases (11 female patients and 6 male patients) of nongestational choriocarcinoma treated in Peking Union Medical College Hospital from 1985 to 2001. RESULTS: All cases received operation as well as chemotherapy. The mean courses of chemotherapy for each patient is 8.6. Correct diagnosis at the first administration was seen in only 3 cases. Nine female and 2 male patients obtained complete remission after the treatment and no recurrence was seen during the 8 to 118 months of follow up. CONCLUSIONS: The diagnosis of nongestational choriocarcinoma is expected to be promoted. Optimal prognosis can be gained for the female patients after treatment by operation as well as chemotherapy, but the prognosis for the male patients is poor.

Adolescent↗