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Biomedical subjects

S Yuan

Publications and source records attributed to S Yuan.

At least 55 records · Page 3Linked to original sources

Islet-1 marks the early heart rudiments and is asymmetrically expressed during early rotation of the foregut in the chick embryo.

Islet-1 (Isl-1), the LIM domain homeobox gene, is a well-known early marker of neuronal specification. Here, we show its spatial and temporal patterns of expression during early heart and gut development in the chick embryo. Isl-1 transcripts are first detected in the early cardiac progenitors and underlying endoderm at late stage 4. By stages 5-6, it is also expressed in the prechordal plate. From stage 6 onward, transcripts are also detected in the endoderm forming the anterior intestinal portal and floor of the caudal foregut. With progressive rostrocaudal fusion of the paired cardiac rudiments, Isl-1 expression is maintained in the cardiac mesoderm and associated endoderm. By the onset of heart beating, transcripts become restricted to the dorsal mesocardium and more caudal medial splanchnic mesoderm flanking the open gut. Within the foregut, Isl-1 is expressed in the endoderm of the oral membrane, thyroid rudiment, and second pharyngeal pouches, as well as within the second branchial grooves adjacent to the secondary pouches. Interestingly, with the onset of gut rotation, Isl-1 expression is detected unilaterally in the splanchnic mesodermal wall of the future greater curvature of the caudal stomach/rostral duodenum. Thus, Isl-1 is a novel and useful marker of the early cardiac rudiments and of the original left side of the rotating foregut. During early organogenesis, Isl-1 is also expressed in several other discrete domains as reported previously. Additionally, it is expressed at the interface between the hind limbs and trunk.

Animals↗

Heteroclite subgenomic RNAs are produced in porcine reproductive and respiratory syndrome virus infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) was shown to produce atypical subgenomic RNAs that contain open reading frame la nucleotides and are present under a wide variety of culture conditions, including high and low multiplicities of infection, in simian and porcine host cells, and during infection with cell-adapted and wild-type PRIRSV strains. Sequence analysis demonstrated that they are heterogeneous in 5-3' junction sequence and size and may code for different predicted fusion proteins. This is the first report of these novel RNA5 in arteriviruses and we have termed them heteroclite (meaning 'deviating from common forms or rules") subgenomic RNAs. The unique properties of these subgenomic RNAs include (a) apparent association with normal virus infection and stability during serial passage, (b) packaging of heteroclite RNAs into virus-like particles, (c) short, heterogeneous sequences which may mediate the generation of these RNAs, (d) a primary structure which consists of the two genomic termini with one large internal deletion, and (eJ little apparent interference with parental virus replication. These subgenomic RNA5 may be critical to, or a necessary side product of, viral replication. The expression of these novel RNA species support the template-switching model of similarity-assisted RNA recombination. In summary, PRRSV readily undergoes nonhomologous RNA recombination to generate heteroclite sub-genomic RNA5.

3' Untranslated Regions↗

Molecular mechanism of endothelial growth arrest by laminar shear stress.

This study was designed to elucidate the mechanism underlying the inhibition of endothelial cell growth by laminar shear stress. Tumor suppressor gene p53 was increased in bovine aortic endothelial cells subjected to 24 h of laminar shear stress at 3 dynes (1 dyne = 10 microN)/cm(2) or higher, but not at 1.5 dynes/cm(2). One of the mechanisms of the shear-induced increase in p53 is its stabilization after phosphorylation by c-Jun N-terminal kinase. To investigate the consequence of the shear-induced p53 response, we found that prolonged laminar shear stress caused increases of the growth arrest proteins GADD45 (growth arrest and DNA damage inducible protein 45) and p21(cip1), as well as a decrease in phosphorylation of the retinoblastoma gene product. Our results suggest that prolonged laminar shear stress causes a sustained p53 activation, which induces the up-regulation of GADD45 and p21(cip1). The resulting inhibition of cyclin-dependent kinase and hypophosphorylation of retinoblastoma protein lead to endothelial cell cycle arrest. This inhibition of endothelial cell proliferation by laminar shear stress may serve an important homeostatic function by preventing atherogenesis in the straight part of the arterial tree that is constantly subjected to high levels of laminar shearing.

Animals↗

Retinoid signaling is required to complete the vertebrate cardiac left/right asymmetry pathway.

Vitamin A-deficient (VAD) quail embryos have severe abnormalities, including a high incidence of reversed cardiac situs. Using this model we examined in vivo the physiological function of vitamin A in the left/right (L/R) cardiac asymmetry pathway. Molecular analysis reveals the expression of early asymmetry genes activin receptor IIa, sonic hedgehog, Caronte, Lefty-1, and Fgf8 to be unaffected by the lack of retinoids, while expression of the downstream genes nodal-related, snail-related (cSnR), and Pitx2 is altered. In VAD embryos nodal expression in left lateral plate mesoderm (LPM) is severely downregulated and the expression domain altered during neurulation. Similarly, the expression of cSnR in the right LPM and of Pitx2 in the left side posterior heart-forming region (HFR) is downregulated in the VAD embryos. The lack of retinoids does not cause randomization or ectopic expression of nodal, cSnR, or Pitx2. At the six- to eight-somite stage nodal is expressed transiently in the left posterior HFR of normal quail embryos; this expression is missing in VAD embryos and may be linked to the loss of Pitx2 expression in this region of VAD quail embryos. Administration of retinoids to VAD embryos prior to the six-somite stage rescues the expression of nodal, cSnR, and Pitx2 as well as the randomized VAD cardiac phenotype. There is an absolute requirement for retinoids at the four- to five-somite developmental window for cardiogenesis and cardiac L/R specification to proceed normally. We conclude that retinoids do not regulate the left/right-specific sidedness assignments for expression of genes on the vertebrate cardiac asymmetry pathway, but are required during neurulation for the maintenance of adequate levels of their expression and for the development of the posterior heart tube and a loopable heart. Cardiac asymmetry may be but one of several critical events regulated by retinoid signaling in the retinoid-sensitive developmental window.

Activin Receptors, Type II↗

The cowpox virus serpin SPI-3 complexes with and inhibits urokinase-type and tissue-type plasminogen activators and plasmin.

The orthopoxvirus serpin SPI-3 is N-glycosylated and suppresses fusion between infected cells. Although SPI-3 contains motifs conserved in inhibitory serpins, no proteinase inhibition by SPI-3 has been demonstrated, and mutations within the serpin reactive center loop (RCL) do not affect the ability to regulate cell fusion. We demonstrate here that SPI-3 protein expressed by transcription/translation in vitro is able to form SDS-stable complexes with the serine proteinases plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA), consistent with inhibitory activity of the serpin. Weaker complexes were noted with factor Xa and thrombin. Mutation of Arg-340/Ser-341 at the predicted P1/P1' sites within the RCL prevented the formation of complexes between SPI-3 and plasmin, uPA, or tPA, suggesting that the arginine at the P1 position was required for complex formation. SPI-3 protein lacking the N-terminal signal peptide was purified by means of an N-terminal His(10)-tag and gave complete inhibition in vitro of plasmin, uPA, and tPA and partial inhibition of factor Xa. SPI-3 is therefore a bifunctional protein that acts as a proteinase inhibitor and suppresses infected cell-cell fusion. As a proteinase inhibitor, SPI-3 has similar specificity to the leporipoxvirus SERP1 protein of myxoma virus, although the two serpins are less than 30% identical overall. The inhibition constants of SPI-3 for plasmin, uPA, and tPA were determined to be 0.64, 0.51, and 1.9 nM, respectively, very similar to the corresponding K(i) values of SERP1.

Acute-Phase Proteins↗

Recording monophasic action potentials using a platinum-electrode ablation catheter.

AIMS: The monophasic action potential (MAP) is conventionally recorded using Ag-AgCl electrodes which are not suitable for delivering radiofrequency currents. To be able to use the sharp MAP upstroke for identifying the local activation, as a step towards the development of a MAP-guided catheter ablation technique, the possibility of recording MAP via platinum electrodes of an ordinary ablation catheter was explored. METHODS AND RESULTS: One hundred and forty-two MAP recordings from the endocardium were obtained via an ablation catheter in 40 patients undergoing electrophysiological study/catheter ablation. During sinus rhythm and pacing, 90% of the ventricular and 100% of the atrial MAPs had stable baselines. The amplitudes were 13 +/- 4.2 mV for ventricular and 2.4 +/- 0.8 mV for atrial MAPs. During mapping and ablation, MAPs and uni- and bipolar electrograms were recorded simultaneously using the same tip electrode in eight patients. The MAPs provided more distinct local activation than the electrograms. During 17 MAP recordings, additional MAPs were recorded simultaneously using an Ag-AgCl electrode catheter in the immediate vicinity of the ablation catheter. The MAPs taken with the ablation catheter had characteristics consistent with those taken with the Ag-AgCl catheter. CONCLUSIONS: (1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible.

Action Potentials↗

Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion.

Permissive hypercapnia, involving tolerance to elevated Pa(CO(2)), is associated with reduced acute lung injury (ALI), thought to result from reduced mechanical stretch, and improved outcome in ARDS. However, deliberately elevating inspired CO(2) concentration alone (therapeutic hypercapnia, TH) protects against ALI in ex vivo models. We investigated whether TH would protect against ALI in an in vivo model of lung ischemia-reperfusion (IR). Anesthetized open chest rabbits were ventilated (standard eucapnic settings), and were randomized to TH (FI(CO(2)) 0.12) versus control (FI(CO(2)) 0.00). Pa(CO(2)) and arterial pH values achieved in the TH versus CON groups were 101 +/- 3 versus 44.4 +/- 4 mm Hg and 7.10 +/- 0.03 versus 7.37 +/- 0.03, respectively. Following left lung ischemia and reperfusion, TH versus control was associated with preservation of lung mechanics, attenuation of protein leakage, reduction in pulmonary edema, and improved oxygenation. Indices of systemic protection included improved acid-base and lactate profile, in the absence of systemic hypoxemia. In the TH group, mean BALF TNF-alpha levels were 3.5% of CON levels (p < 0.01), and mean 8-isoprostane levels were 30% of CON levels (p = 0.02). Western blot analysis demonstrated reduced lung tissue nitrotyrosine in TH, indicating attenuation of tissue nitration. Finally, preliminary data suggest that TH may attenuate apoptosis following lung IR. We conclude that in the current model TH is protective versus IR lung injury and mechanisms of protection include preservation of lung mechanics, attenuation of pulmonary inflammation, and reduction of free radical mediated injury. If these findings are confirmed in additional models, TH may become a candidate for clinical testing in critical care.

Animals↗

Changes in expression of platelet-derived growth factor and its receptors in the lungs of newborn rats exposed to air or 60% O(2).

PDGF-related gene expression has been well characterized during fetal rat lung development and adult rat lung injury, but not during normal postnatal lung growth or injury. Lung expression of the mRNA for PDGF-A, -B, -alpha R, and -beta R and immunoreactive PDGF-AA, -BB, -alpha R, and -beta R were assessed in rat pups raised in air or 60% O(2) for up to 14 d after birth. Expression of mRNA and immunoreactive ligand did not correlate for pups raised in air. Immunoreactive PDGF-alpha R and -beta R, but not PDGF-AA and -BB, were evident throughout the lung at birth. Both PDGF-AA and -BB were evident in airway epithelium, PDGF-BB in alveolar epithelial cells and PDGF-AA was widely distributed in parenchymal tissue at 4 d. PDGF-alpha R was localized to airway epithelium, and PDGF-beta R to subendothelial perivascular regions and to airway and alveolar epithelium at 4 d. Immunoreactive PDGF ligands all declined after 4 d. Intraperitoneal injection of neutralizing antibodies or truncated soluble receptors to PDGF-BB reduced lung DNA synthesis in air. Exposure to 60% O(2) significantly increased mRNA for PDGF-B, -beta R, and -alpha R, but not PDGF-A, relative to air-exposed lung at various time points after birth. PDGF-A, -B, and -alpha R immunoreactivities in these lungs were reduced and delayed, consistent with a global inhibition of lung growth. Pups exposed to 60% O(2) had a similar distribution of PDGF-beta R to that seen in air, except that at 14 d PDGF-beta R was distributed throughout the lung parenchyma. We conclude that PDGF ligands and receptors are important for normal postnatal lung growth and that their expression is delayed by O(2) exposure.

Animals↗

[Experimental study on human pancreatic carcinoma treated by cytosine deaminase gene therapy].

OBJECTIVE: To explore the possibility of Escherichia coli cytosine deaminase (CD) gene on human pancreatic carcinoma gene therapy. METHODS: Recombinant adenoviruses containing a carcinoembryonic antigen (CEA) promoter were transiently introduced into SW1990, Capan-2 and Hela cells, separately. The expression of CD gene mRNA was examined by RT-PCR. CD protein level in the transduced cells was analyzed by Western blotting. The sensitivity of the cells to 5-fluorocytosine (5-FC) was determined by MTT assay. RESULTS: A specific expression of cytosine deaminase gene by adenovirus-mediated transfer exhibited only in SW1990 cells (CEA-producing). Transduction of CD gene resulted in significant sensitivity of SW1990 cells to 5-FC. The anticancer effect was seen in vivo in SW1990 xenografts nude mice with in situ CD gene transduction. CONCLUSION: The targeted expression of CD gene combined prodrug 5-FC may be a potential approach for gene therapy for human pancreatic carcinoma.

Adenocarcinoma↗

[Genes of micrometastasis in bone marrow of patients with colorectal cancer].

OBJECTIVE: To detect the gene of micrometastasis in bone marrow of patients with colorectal cancer. METHODS: PCR-SSCP/silver stain technique was used to find out the metastatic cancer cells in 51 bone marrow samples in different time. RESULTS: The total positive rate of mutations of p53 and K-ras in bone marrow was 37.25% before operation. The incidence of mutations was obviously correlated with Duke's stage and lymphatic metastasis. After postoperative chemotherapy mutation in 11 patients turned to be negative. CONCLUSIONS: Detection of micrometastasis in bone marrow may contribute to early diagnosis of blood stream metastasis of colorectal cancer.

Bone Marrow Neoplasms↗

[Expression of thymidylate synthase gene and recurrence of colorectal carcinoma: their relation and clinical significance].

OBJECTIVE: To study the relationship between expression of thymidylate synthase (TS) gene and recurrence of colorectal carcinoma and its effect on clinical treatment. METHODS: RT-PCR was used to detect the expression of TS gene in primary foci, para-tumoral intestine mucosa, local recurrence, abdominal-pelvic dissemination and hepatic metastasis in 68 cases of colorectal carcinoma, and TS protein was examined with western blot. RESULTS: In 68 cases of colorectal carcinoma, the expression of TS gene in primary foci was 22.1% (15/68); and the positive rates of TS gene expression in local recurrence, abdominal-pelvic dissemination and hepatic metastasis were 88.5% (23/26), 85.0% (17/20), 40.9% (9/20) respectively. The rates of TS protein expression in primary foci, local recurrence, abdominal-pelvic dissemination and hepatic metastasis were 22.1% (15/68), 84.6% (22/26), 80.0% (16/20), 36.4% (8/22) respectively. The negative expression of TS gene and TS protein was detected in paratumoral intestinal mucosa. The results of TS gene and TS protein expression were identical with those the two methods. The positive rates of TS gene and TS protein expression in diversified recurrence foci and metastasis were higher than those in primary foci (P < 0.01). The differences of TS gene and TS protein expression rates between recurrence and hepatic metastasis were significant (P < 0.01). The expression rates of TS gene and TS protein in local recurrence and abdominal-pelvic dissemination tissues were higher than those in hepatic metastasis. CONCLUSION: Overexpression of TS gene plays an important role in the process of local recurrence and abdominal-pelvic dissemination of colorectal carcinoma.

Adult↗

[Acute promyelocytic leukemia cell differentiation induced by tanshinone II A and its molecular mechanism].

OBJECTIVE: To investigate APL cell differentiation induced by tanshinone II (Tan II A) and its molecular mechanism. METHODS: In vitro incubation of NB4 cells with Tan II A at the concentration of 0.5 microg/ml for 5 days, the cell differentiation was observed by cytomorphology, and nitroblue tetrazolium (NBT) test. Cell cycle, membrane CD(33), CD(11b) antigens and gene expressions (c-myc, c-fos, p53 and bcl-2) were analysed by flow cytometry. RESULTS: (91.3 +/- 2.1)% of NB4 cells were induced into morphologically and functionally more differentiated cells including 0.26 of myelocytes and metamyelocytes, and 0.68 of band form and neutrophils. Cell growth curve showed that growth of NB4 cells were inhibited. NBT reduction was significantly increased. Expression of CD(33) decreased and CD(11b) increased. The degrees of cell differentiation and growth inhibition induced by Tan II A or ATRA were no difference. Flow cytometry analysis showed that Tan II A arrested NB4 cell in G(0)/G(1) phase, inhibited cellular DNA synthesis, down-regulated c-myc and bcl-2 genes expression, and up-regulated c-fos and p53 genes expression. CONCLUSION: Tan II A can induce differentiation and growth inhibition of NB4 cells. Its possible molecular mechanism might relate to modulation of gene expressions associated proliferation and differentiation, and to inhibition of DNA synthesis.

Abietanes↗

[Study on the regulatory effect of Chinese herbal medicine on peritoneal lymphatic stomata and in enhancing drainage of ascites in mice with liver fibrosis].

OBJECTIVE: To observe the regulatory effect of Chinese herbal medicine on peritoneal lymphatic stomata in carbon tetrachloride induced mouse model of liver fibrosis and its significance in treating ascites. METHODS: (1) To form the mouse model of liver fibrosis by intragastric administration of carbon tetrachloride. (2) Two kinds of Chinese herbal compound prescriptions were given separately by gastrogavage to observe their effect on prevention and treatment of liver fibrosis. (3) Hematoxylin and eosin and van Gieson staining were used in the observation of pathology and histology. (4) Scanning electronmicroscope and computer image processing were used. (5) urinary volume and sodium ion concentration were measured. RESULTS: The fibrotic change of the mouse models was alleviated with using both the prevention or treatment groups of the two compound prescriptions. The diameter of lymphatic stomata enlarged with increased number of opening and density of distribution. Urinary volume and sodium ion excretion increased after treatment. The effects displayed more significant in the group treated by compound prescription. CONCLUSION: Both kinds of Chinese herbal compound prescriptions have marked effect in alleviating liver fibrosis, regulating peritoneal lymphatic stomata, improving the drainage from the peritoneal cavity, causing increase of urinary volume and sodium ion excretion to reduce the water and sodium retention, and thus have favorable therapeutic effect in treating ascites.

Animals↗

[Study on sensitivity of neuroglioma to chemotherapeutic drugs].

In this study, the chemosensitivity of 36 cases' fresh neuroglioma specimens was examined in vitro with MTT assay. The separation method for single tumor cell, the number of planting of cells, and the dosage and acting time of drugs, which have effects on the results of MTT assay, were studied systematically. On the basis of this experiment, we established a screening method for the chemosensitivity of neuroglioma; it is accurate, rapid, and simple. At the same time, the results showed that neuroglioma was more sensitive to the chemotherapeutic drugs Vm26, DDP and MMC, and the sensitivity varied with not only the drugs but also the individuals.

Antineoplastic Agents↗

[Terminal differentiation of human acute promyelocytic leukemia (APL) cells induced by Tanshinone II A in primary culture].

The aim of this study was to investigate whether Tanshinone II A (Tan II A) can induce human acute promyelocytic leukemia (APL) cells to differentiate or not in primary culture. The APL cells from 5 cases were cultured respectively with Tan II A at the concentration of 0.5 microgram/ml for 7 days in vitro. The differentiations of these leukemia cells were observed cytomorphologically and examined by nitroblue tetrazolium (NBT) test. The cell DNA cycle and membrane cluster differentiation (CD) antigens (CD33, CD11b) were analyzed by flow cytometry. The results showed that 82.5% +/- 4.8% of APL cells were induced into morphologically and functionally differentiated cells. The cell growth curve showed that the growth of APL cells was inhibited. The degree of differentiation and growth inhibition induced by Tan II A was not different from that by ATRA (P > 0.05). Flow cytometry analysis showed that Tan II A arrested APL cells in G0/G1 phase and inhibited cellular DNA synthesis. This study demonstrates that Tan II A can induce differentiation of APL cells in vitro, and hence it is worthy of further studies for clinical use.

Abietanes↗

[Relationship of p53 gene mutation with pathological characteristics and prognosis of thyroid carcinoma].

This study was directed to the role of p53 gene in the carcinogenesis of thyroid carcinomas and to the correlation between p53 gene and the clinicopathological characteristics of the cancer. Single-stranded conformation polymorphism of PCR was used in detecting p53 gene point mutations in exons 7, 8. The result showed that ten of thirty-one thyroid carcinomas had mutations in exons 7 and 8 (32.3%). The frequency of p53 gene mutations was significantly higher in relapse group than in no relapse group (P < 0.01). No statistically significant differences in p53 mutation were found relating to metastasis, histological type and differentiation (P > 0.05). These data suggest that the mutation of p53 gene may play an important role in thyroid carcinoma and the mutations of p53 gene be associated with the prognosis of thyroid carcinoma.

Adenocarcinoma, Follicular↗

[Study on chemosensitivity assay in vitro in the peripheral blood lymphocyte and the tumor cells].

In this study, the MTT method was used to test the sensitivity of the peripheral blood lymphocyte and the tumor cells of 35 patients with neuroglioma to 15 kinds of anti-cancer drugs. The results showed that the peripheral blood lymphocyte and the tumor cells were more sensitive to chemotherapeutic drugs Vm26 and TAX, and sensitive to DDP, Me-CCNU, EADM, ADM, MMC, HCPT, but not sensitive to MTX, ACR, VP-16, VCR and BLM. There were no statistical differences in the rate of sensitivity to the above-mentioned drugs between the peripheral blood lymphocyte and the tumor cells. These results prompt that the chemosensitivity test of the peripheral blood lymphocyte may take the place of the tumor cells for reference to choosing chemotherapeutic drugs in clinical practice.

Antineoplastic Agents↗