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Biomedical subjects

F Yin

Publications and source records attributed to F Yin.

At least 19 recordsLinked to original sources

High frequency occurrence of 1-OPRD variant of PRNP gene in gastric cancer cell lines and Chinese population with gastric cancer.

The prion protein gene PRNP encodes PrPc and PrPsc, causing a number of neurological disorders. Approximately 10-15% of human prion disease is inherited and more than 20 pathogenic mutations have been found. Most of the genetic alterations are point mutations, with the exception of genetic insertions of one to nine extra octapeptide repeats occurring in the important octapeptide-coding region. Our previous work showed that PrPc was overexpressed in gastric cancer. We wondered whether mutations of PrPc existed in human gastric cancer. DNA sequencing and gel electrophoresis were used to determine the possible mutation of PrPc in patients and cell lines of gastric cancer. We found that 1-OPRD (one octapeptide-repeat deletion) homozygosity or heterozygosity exists in several gastric cancer cell lines, e.g. MKN28 and KatoIII are homozygous for 1-OPRD, and SGC7901 and BGC-823 are heterozygous for 1-OPRD. The mutation frequency in tissues of gastric cancer cases is significantly higher than that in the common population (p<0.05). All positive cases in gastric cancer were found to be heterozygous for 1-OPRD. Further study of the variant may be helpful in understanding the mechanisms of occurrence and development of clinical gastric carcinoma as well as the biology of the mysterious gene PRNP.

Adolescent↗

Definitive experimental evidence for two-band superconductivity in MgB2.

The superconducting-gap of MgB2 has been studied by high-resolution angle-resolved photoemission spectroscopy. The results show that superconducting gaps with values of 5.5 and 2.2 meV open on the sigma band and the pi band, respectively, but both the gaps close at the bulk transition temperature, providing a definitive experimental evidence for the two-band superconductivity with strong interband pairing interaction in MgB2. The experiments validate the role of k-dependent electron-phonon coupling as the origin of multiple-gap superconductivity as well as the high transition temperature of MgB2.

Journal Article↗

Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in vascular smooth muscle cells.

The cyclin-dependent kinase inhibitor p21(Cip1) is up-regulated in response to mitogenic stimulation in various cells. PPARgamma ligands troglitazone (TRO, 10 microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1) protein by platelet-derived growth factor (PDGF) and insulin without affecting cognate mRNA levels in rat aortic smooth muscle cells (RASMC). The protein kinase Cdelta (PKCdelta) inhibitor rottlerin also blocked the induction of p21(Cip1) protein, whereas the conventional PKC isotype inhibitor Gö 6976 had no effect. Kinetic studies using the protein synthesis inhibitor cycloheximide showed that TRO, RSG, and rottlerin shortened the half-life of p21(Cip1) protein. TRO, RSG, and rottlerin inhibited PDGF-induced expression of p21(Cip1), but they did not affect insulin-induced expression of p21(Cip1). Both ligands inhibited PKCdelta enzymatic activity in PDGF-stimulated RASMC but not in insulin-stimulated cells. Adenovirus-mediated overexpression of PKCdelta rescued the down-regulation of p21(Cip1) expression both by TRO and RSG in PDGF-treated RASMC. These data suggested that the PKCdelta pathway plays a critical role in PDGF-induced expression of p21(Cip1) in RASMC and may be the potential target for PPARgamma ligand effects. Src kinase-dependent tyrosine phosphorylation of PKCdelta was decreased substantially by TRO and RSG. Tyrosine phosphorylation and activation of c-Src in response to PDGF were unaffected by either PPARgamma ligand. Protein-tyrosine-phosphatase inhibitors sodium orthovanadate and dephostatin prevented PPARgamma ligand effects on PKCdelta tyrosine phosphorylation and enzymatic activity. Both inhibitors also reversed PPARgamma ligand effects on p21(Cip1) expression in PDGF-treated RASMC. PPARgamma ligands enhanced protein-tyrosine-phosphatase activity in RASMC, which may be the mechanism for decreased PKCdelta tyrosine phosphorylation and activity. PPARgamma ligands regulate p21(Cip1) at a post-translational level by blocking PKCdelta signaling and accelerating p21(Cip1) turnover.

Acetophenones↗

Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators.

Peroxisome proliferator activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily. Ligand activation of PPARgamma has been shown to cause growth arrest in several human tumor cell types, but the underlying molecular mechanism has not been elucidated. We report here that the PPARgamma ligand troglitazone (TRO) inhibited MCF-7 cell proliferation by blocking events critical for G1 --> S progression. Flow cytometry demonstrated that TRO at 20 microM increased the percentage of cells in G1 from 51 to 69% after 24 h. Accumulation of cells in G1 was accompanied by an attenuation of Rb protein phosphorylation associated with decreased CDK4 and CDK2 activities. Inhibition of CDK activity by TRO correlates with decreased protein levels for several G1 regulators of Rb phosphorylation (cyclin D1, and CDKs 2, 4, and 6). Overexpression of cyclin D1 partially rescued MCF-7 cells from TRO-mediated G1 arrest. Targeting of G1 regulatory proteins, particularly cyclin D1, and the resulting induction of G1 arrest by TRO may provide a novel antiproliferative therapy for human breast cancer.

Annexin A5↗

Extracranial radiosurgery: immobilizing liver motion in dogs using high-frequency jet ventilation and total intravenous anesthesia.

PURPOSE: Extracranial radiosurgery requires control of organ motion. The purpose of this study is to quantitatively determine the extent of liver motion in anesthetized dogs with continuous i.v. propofol infusion with or without muscle relaxants and high-frequency jet ventilation. METHODS AND MATERIALS: Five dogs were used in the experiment. Each dog was restrained while anesthetized in the supine position using an alpha cradle. Surgical metal clips were implanted around the liver periphery so that its motion could be visualized using a fluoroscopic imaging device in a conventional simulator. Initially, two orthogonal simulation films were taken to correlate locations of implanted clips. Two orthogonal views of fluoroscopic images for each anesthetized dog were recorded on a magnetic tape and analyzed from the post-imaging data. Liver motion was documented under the following three conditions: 1) ventilated with a conventional mechanical ventilator, 2) ventilated with a high-frequency jet ventilator, and 3) ventilated with a high-frequency jet ventilator and total muscle paralysis (with vecuronium injection). The maximum liver motion for each dog was analyzed in three orthogonal directions: the inferior-to-superior direction, the anterior-to-posterior direction, and the right-to-left direction. RESULTS: When the anesthetized dogs were ventilated with a conventional mechanical ventilator, the average liver motions were 1.2 cm in the inferior-to-superior direction, 0.4 cm in the anterior-to-posterior direction, and 0.2 cm in the right-to-left direction, respectively. After the introduction of high-frequency jet ventilation, the average liver motions were reduced to 0.2 cm in the inferior-to-superior direction, 0.2 cm in the anterior-to-posterior direction, and 0.1 cm in the right-to-left direction. The maximum liver motion was dependent on ventilator settings. There was no additional measurable motion reduction with the addition of the muscle relaxant. CONCLUSION: The liver motion in each anesthetized dog was controlled under 3.0 mm in all directions with the use of high-frequency jet ventilation. No detectable advantage was identified by the injection of muscle relaxant in terms of further reducing the liver motion. The preclinical animal study indicated that the use of high-frequency jet ventilation (HFJV) would be able to limit the liver motion to an extent acceptable for the application of extracranial radiosurgery in humans. Radiosurgery for localized liver tumors warrants further investigation.

Anesthesia, Intravenous↗

Retinoids inhibit proliferation of human coronary smooth muscle cells by modulating cell cycle regulators.

Retinoids inhibit rat vascular smooth muscle cell (VSMC) proliferation in vitro and intimal hyperplasia in vivo. We examined the mechanism of the antiproliferative effect of retinoids on human coronary artery smooth muscle cells (human CASMCs). The RAR ligands all-trans-retinoic acid (atRA) and ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-propenyl]-benzoic acid (TTNPB); a pan-RXR/RAR agonist, 9-cis-retinoic acid (9cRA); and the RXR-selective ligand AGN4204 all inhibited DNA synthesis stimulated with platelet-derived growth factor and insulin (IC(50): TTNPB 63 nmol/L, atRA 120 nmol/L, AGN4204 460 nmol/L, 9cRA 1.5 micromol/L). All retinoids blocked cell cycle progression as determined by flow cytometry and inhibited retinoblastoma protein (Rb) phosphorylation. TTNPB, atRA, and AGN4204 inhibited the mitogenic induction of cyclin D1, whereas 9cRA had no effect. None of the retinoids affected the expression of CDK 2, 4, or 6 or cyclin E. All retinoids attenuated mitogen-induced downregulation of CDKI p27(Kip1), a major negative regulator of Rb phosphorylation, partly through stabilizing p27(Kip1) turnover. These data demonstrate that retinoids have antiproliferative activity by modulating G(1) --> S cell cycle regulators in human CASMCs through inhibition of Rb phosphorylation and elevation of p27(Kip1) levels.

Cell Cycle Proteins↗

[Comparison of infectious brain edema models induced by different kinds of pertussis bacilli in rats].

OBJECTIVE: To understand the difference of infectious brain edema models induced by varied kinds of pertussis bacilli in rats and to look for a new infectious brain edema model. METHODS: Sprague-Dawley rats were randomly divided into 3 groups: normal saline group(NS); rude pertussis bacilli(PBR); purified pertussis bacilli(PBP). After infectious brain edema model was induced by rude pertussis bacilli or purified pertussis bacilli, the water content(WC), Evan's blue content(EB), Na+ and K+ content in brain tissues were measured. RESULTS: The WC, EB and Na+ contents in brain tissues in PBR and PBP groups were significantly increased than those in NS group; K+ content was significantly decreased in PBR and PBP groups than that in NS group(P < 0.01). Evan's blue discoloration was demonstrated in all rats of PBR group, but 6 rats of PBP group showed bluish discoloration. EB content in brain tissues was significantly increased in PBR group than that in PBP group. CONCLUSIONS: The infectious brain edema model can be induced by rude pertussis bacilli or purified pertussis bacilli in rats, the former gives priority to mixed brain edema, and the latter mainly avails cytotoxin brain edema.

Animals↗

Peroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1--> S transition in vascular smooth muscle cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily that is activated by binding certain fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZD). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell proliferation and migration both in vitro and in vivo. The precise mechanism of its antiproliferative activity, however, has not been elucidated. We report here that PPARgamma ligands inhibit rat aortic vascular smooth muscle cell proliferation by blocking the events critical for G(1) --> S progression. Flow cytometry demonstrated that both TRO and another TZD, rosiglitazone, prevented G(1) --> S progression induced by platelet-derived growth factor and insulin. Movement of cells from G(1) --> S was also inhibited by the non-TZD, natural PPARgamma ligand 15-deoxy-(12,14)Delta prostaglandin J(2) (15d-PGJ(2)), and the mitogen-activated protein kinase pathway inhibitor PD98059. Inhibition of G(1) --> S exit by these compounds was accompanied by a substantial blockade of retinoblastoma protein phosphorylation. TRO and rosiglitazone attenuated both the mitogen-induced degradation of p27(kip1) and the mitogenic induction of p21(cip1). 15d-PGJ(2) and PD98059 inhibited both the degradation of p27(kip1) and the induction of cyclin D1 in response to mitogens. These effects resulted in the inhibition of mitogenic stimulation of cyclin-dependent kinases activated by cyclins D1 and E. These data demonstrate that PPARgamma ligands are antiproliferative drugs that act by modulating cyclin-dependent kinase inhibitors; they may provide a new therapeutic approach for proliferative vascular diseases.

Animals↗

Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia.

Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.

Adolescent↗

[Changes of glutamate and gamma-aminobutyric acid contents in brain tissue of brain edema and effects of baicalin on them in rats].

OBJECTIVE: To observe the changes of glutamates (Glu) and gamma-aminobutyric acid (GABA) contents in brain tissue of infectious brain edema, and effects of baicalin on them in rats. METHODS: The high performance liquid chromatography (HPLC) was used to determine the Glu and GABA contents in homogenized brain tissue after baicalin was injected intraperitoneally on infectious brain edema induced by pertussis bacilli in rats. RESULTS: Glu contents of homogenized brain tissue in blank control group (C), normal saline group (NS), pertussis bacilli group (PB) and baicalin group (BC) had no significant difference (P > 0.05). The concentration of GABA was more significantly increased in the BC group (4.06 +/- 0.52) than that in the PB group (2.71 +/- 0.29) (P < 0.05). Water content of brain was reduced in the BC group (79.8 +/- 0.4) as compared with the PB group (82.2 +/- 0.3)(P < 0.01). CONCLUSION: Baicalin has a protective effect against the pertussis bacilli-induced brain edema in rats, and protective effect was correlated to the increased content of GABA in the brain tissue in rats.

Animals↗

Growth inhibitory effects of flavonoids in human thyroid cancer cell lines.

Previous studies have indicated that flavonoids exhibit antiproliferative properties on some hormone-dependent cancer cell lines, such as breast and prostate cancer. In the present study, the effects of some selected flavonoids, genistein, apigenin, luteolin, chrysin, kaempferol, and biochanin A on human thyroid carcinoma cell lines, UCLA NPA-87-1 (NPA) (papillary carcinoma), UCLA RO-82W-1 (WRO) (follicular carcinoma), and UCLA RO-81A-1 (ARO) (anaplastic carcinoma) have been examined. Among the flavonoids tested, apigenin and luteolin are the most potent inhibitors of these cell lines with IC50 (concentration at which cell proliferation was inhibited by 50%) values ranging from 21.7 microM to 32.1 microM. The cells were viable at these concentrations. Using NPA cells known to be estrogen receptor positive (ER+), it was shown that no significant [3H]-E2 displacement occurred with these flavonoids at the IC50 concentration. In WRO cells that are known to have an antiestrogen binding site (AEBS), biochanin A caused a stronger inhibitory growth effect (IC50 = 64.1 microM) than in NPA and ARO cells. In addition, it was observed that biochanin A has an appreciable binding affinity for the AEBS as indicated by the displacement of [3H]-tamoxifen from the WRO cells. In summary, flavonoids have potent antiproliferative activity in vitro against various human thyroid cancer cell lines. The inhibitory activity of certain flavonoid compounds may be mediated via the AEBS and/or type II EBS. The observation that ARO cells that lack both the AEBS and the ER are effectively inhibited by apigenin and luteolin suggest that other mechanisms of action are operative as well. The present study suggests that flavonoids may represent a new class of therapeutic agents in the management of thyroid cancer.

Adenocarcinoma, Follicular↗

[Effect of pertussis bacilli on the release of excitatory amino acids in brain slice of rats].

OBJECTIVE: To investigate the effect of pertussis bacilli on the release of excitatory amino acids (EAAs) in rat-brain slice and to know whether MK-801(dizocipine) protects brain tissue from excitotoxicity. METHODS: SD rats were randomly divided into 3 groups: 1. Normal slice cultured group(NC); 2. 10% pertussis bacilli(PB) slice cultured group(PBC); 3. 10% PB slice cultured group after pretreatment with MK-801. The release of EAAs from brain slices was measured by high performance liquid chromatography. RESULTS: The concentrations of glutamate(Glu 29.53 +/- 8.00), aspartate(Asp 23.74 +/- 5.79) and LDH(38.03 +/- 8.45) were significantly higher in PBC group than those(Glu 16.46 +/- 4.00, Asp 15.27 +/- 5.31, LDH 23.10 +/- 5.11) in MPBC group and (Glu 16.09 +/- 3.74, Asp 11.47 +/- 2.51, LDH 25.82 +/- 4.50) NC group. CONCLUSION: Pertussis bacilli may elicit a large increase of extracellular EAAs and LDH in vitro, while MK-801 protects brain tissue from excitotoxicity.

Animals↗

Detection of hepatitis C virus RNA sequences in hepatic portal cholangiocarcinoma tissue by reverse transcription polymerase chain reaction.

OBJECTIVE: To detect hepatitis C virus (HCV) RNA sequences in the hepatic portal cholangiocarcinoma tissues and their relationship. METHODS: RNA was extracted from paraffin-embedded cholangiocarcinoma tissues of 6 patients by guanidinium method, subjected to reverse transcription and then amplified by double PCR technique using nested primers from the highly conserved 5' noncoding region of HCV genome. RESULTS: HCV RNA of 5' NT sequences was found in the hepatic portal cholangiocarcinoma tissues of 5 out of 6 (83%) patients. CONCLUSIONS: HCV RNA sequences present with high infectious rate in cholangiocarcinoma, and reverse transcription polymerase chain reaction (RT-PCR) assay using primers derived from 5' NT region of HCV sequence is most useful in detecting HCV infection. The development of cholangiocarcinoma awaits further studies.

Adenocarcinoma↗

[Detection of thyroid stimulating antibodies and TSH binding inhibitor immunoglobulins in patients with thyroid diseases and its clinical applications].

Thyroid stimulating antibodies (TSAb) and TSH binding inhibitor immunoglobulins (TBII) were assessed in patients with thyroid diseases. The activity of TSAb and TBII was significantly higher in patients with untreated Graves' disease (GD) as compared with that in patients with remitted GD and Hashimoto's thyroiditis, while the latter two groups had higher TSAb and TBII activity than patients with thyroid adenoma or control subjects. Of 24 patients with untreated GD, TSAb and TBII were detected in 22 and 19 respectively. The positive rates of TSAb and TBII in patients with remitted GD or Hashimoto's thyroiditis were 0.48 and 0.44 or 0.231 and 0.615. Both TSAb and TBII were negative in patients with thyroid adenoma or controls. No statistical correlation was found between TSAb and TBII activity, suggesting the coexistence of heterogeneous populations of TSH receptor antibodies.

Adenoma↗

[Evaluation of surgical resection for gastric cancer extending to adjacent organs].

From June 1972 to December 1993, 280 patients underwent surgical resection for their gastric cancer extending to adjacent organs. The patients were divided into three groups. Group A, 93 patients, were treated with gastrectomy plus complete removal of the invaded organs. Group B, 55 patients, underwent gastrectomy with incomplete removal of the invaded organs. Group C, 132 patients underwent gastrectomy only. The 5 year survival rate of each group was 32.7%, 7.7% and 4.4%, respectively. The 5 year survival rate in the group A was significantly higher than that in two other 2 groups (P < 0.05). The 5 year survival rate in the group B and C was similar (P > 0.05). The patients without incurable factors (liver metastasis, peritoneal dissemination and widespread nodal involvement) underwent gastrectomy with complete excision of invaded organs, irrespective of the number or site of invaded organs. On the other hand, the patients with incurable factors should be given palliative gastrectomy only. Because symptoms are alleviated, the quality of life is improved and the survival time is prolonged.

Adult↗