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Biomedical subjects

C Yun

Publications and source records attributed to C Yun.

At least 19 recordsLinked to original sources
PubMed2001

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.

Antigens, Neoplasm↗
PubMed2001

Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.

BACKGROUND/AIMS: We earlier reported that N-carbamoyl-L-glutamate (CG) plus L-arginine (Arg) protected normal and 70% hepatectomized rats from intoxication by a lethal or sub-lethal dose of ammonium acetate, respectively. In the present study, the protective effect of these compounds on cirrhotic rats was assessed. METHODS: CG plus Arg were administered prior to the injection of a sub-lethal dose of ammonium acetate into dimethylnitrosamine-induced cirrhotic rats. Control rats were given phosphate-buffered saline (PBS) instead of the mixture. The behavior of the rats was monitored until the time of sacrifice. Blood ammonia level, blood urea nitrogen (BUN) and liver carbamoylphosphate synthetase I (CPS I) activity were determined. RESULTS: Pretreatment of rats with the mixture of CG plus Arg could significantly lower the blood ammonia level (P<0.05), increase the activity of CPS I (P<0.05), improve abnormal behavior associated with ammonia intoxication (P<0.05), and increase BUN (P<0.05), as compared with the PBS-injected control group. There were significantly close correlations between (1) the increase of CPS I activity; (2) the improvement of abnormal behavior; (3) the increase of BUN; and (4) the decrease of the blood ammonia level. CONCLUSIONS: A mixture of CG plus Arg could protect rats with liver cirrhosis from acute ammonia intoxication.

Acetates↗
PubMed2001

Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases.

Hepatitis B virus X (HBx) protein is a multifunctional protein that exerts dual activity on cell proliferation and death. Although HBx is thought to be a major determinant that leads to hepatocellular carcinoma, its pathophysiological role in humans remains to be established. Attempts have been made to evaluate the role of HBx in liver specimens derived from patients with chronic B viral hepatitis and hepatocellular carcinoma. Among 25 paired liver specimens of hepatocellular carcinoma and corresponding nontumour liver tissues, HBx mRNA was hardly detected and was significantly lower than other HBV transcripts. An immunohistochemical study demonstrated that expression of HBx protein was also lower than other HBV gene products. Interestingly, however, expression of HBx protein changed with the progression of chronic hepatitis. HBx was expressed in 5.0% of patients with chronic hepatitis without cirrhosis but increased to 44.8% in chronic hepatitis with cirrhosis. In contrast, only one (3.7%) of 27 hepatocellular carcinomas showed HBx positivity whereas 29.6% of surrounding nontumour tissues was still HBx-positive. These results suggest that HBx may play a major role at the promotion stage of carcinogenesis. Noticeably, HBx-positive cells were preferentially localized in the periportal region of chronic hepatitis or periphery of cirrhotic nodules where high necroinflammatory activity was accompanied. We found a positive correlation between HBx expression and periportal inflammatory activity (P < 0.001). Thus, HBx may potentiate cell destruction and regeneration of liver that provide an opportunity for the accumulation of genetic mutations, which contribute to multistep hepatocarcinogenesis.

Carcinoma, Hepatocellular↗
PubMed2001

[Transitional pre-B-cell ALL].

An 18-month-old girl was referred to our hospital because of fever and pancytopenia. On admission, her bone marrow nuclear cell count was 45,000/microliter, being mostly blasts with cleaved nuclei. The leukemic cells were negative for peroxidase staining, expressed CD10, CD19, CD34 and sIg mu, and did not express sIg kappa and lambda, corresponding to a minor subpopulation of B cells known as transitional pre-B-cells (TPBs). Since TPB-ALL has been reported only infrequently, the incidence and clinical picture of this rare type of ALL are still uncertain. Extensive immunophenotypic studies to determine the expression of sIg mu, sIg kappa and lambda will provide accurate diagnosis, which is essential for effective management of this condition.

Antigens, CD19↗
PubMed2000

Chemotherapeutic drug, adriamycin, restores the function of p53 protein in hepatitis B virus X (HBx) protein-expressing liver cells.

Hepatitis B virus X (HBx) protein implicated in the development of liver cancer may inhibit the function of p53 tumor suppressor protein through cytoplasmic retention of p53 protein. Here, we attempt to investigate whether the functional inhibition of p53 protein by HBx protein is reversible. First, we provide the evidence for the association of endogenous p53 protein with HBx by co-immunoprecipitation in stable Chang cells that express HBx protein in an inducible manner (ChangX-34). By immunofluorescence microscopy, the major location of p53 protein of ChangX-34 cells was confirmed at the nuclear periphery as well as in the cytoplasm where HBx protein is mainly expressed. Surprisingly, anticancer drug, adriamycin induces the nuclear translocation of p53 protein sequestered in the cytoplasm. This change is accompanied by the restoration of p53 activity, which results in increased transcriptional activity at the p53-responsive DNA elements as well as increase of p21WAF1 mRNA expression. Further, we observed the induction of cell death and G1 arrest in these cells upon adriamycin treatment regardless of HBx expression. Together, we demonstrate that functional inhibition of p53 protein through its cytoplasmic retention by HBx protein is reversible. These results may be extended into other tumors of which p53 activity is modulated by viral oncoproteins.

Antineoplastic Agents↗
PubMed2000

In vitro and in vivo studies of AT-1362, a newly synthesized and orally active inhibitor of thrombin.

AT-1362 was found to be a potent, selective, and competitive inhibitor of thrombin, with a Ki value of 6.7 nM. In a rat model of venous thrombosis induced by partial stasis and endothelial disruption, the ID(50) values (a dose required to obtain 50% inhibition of thrombus formation over each vehicle group) of AT-1362 and argatroban were 0.03 mg/kg i.v. plus 0.5 microg/kg/minute and 0. 13 mg/kg i.v. plus 8.7 microg/kg/minute, respectively, and the antithrombotic effect of AT-1362 without prolongation of bleeding time lasted for 2 hours and disappeared 4 hours after oral administration of 30 mg/kg. In the rat tail transection model, the BT(2) values (a dose causing two-fold prolongation of the bleeding time over each vehicle group) of AT-1362 and argatroban were 0.56 mg/kg i.v. plus 9.3 microg/kg/minute and 1.1 mg/kg i.v. plus 73.3 microg/kg/minute, respectively. The reduction of thrombus formation and the prolongation of bleeding time were correlated with an ex vivo activated partial thromboplastin time (APTT) for both drugs. AT-1362 at 0.3 mg/kg i.v. plus 5 microg/kg/minute and argatroban at 0.6 mg/kg i.v. plus 40 microg/kg/minute significantly (p<0.05 and p<0.01, respectively) improved the vessel patency in a FeCl(2)-induced carotid artery thrombosis model in rats. These results suggest that AT-1362 may be a potent antithrombotic agent for the treatment of thrombotic diseases.

Administration, Oral↗
PubMed2000

Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2.

Among the phospholipase C that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate, four mammalian phospholipase C-beta (PLC-beta) isotypes (isotypes 1-4) are activated through G protein-coupled receptors (GPCRs). Although the regulation of the PLC-betas by GPCRs and heterotrimeric G proteins has been extensively studied, little is known about the molecular determinants that regulate their activity. The PLC-beta isozymes carry a putative PSD-95/Dlg/ZO-1 (PDZ) binding motif (X(S/T)X(V/L)COOH) at their carboxyl terminus, which is implicated in specific interactions with anchor proteins. Using the yeast two-hybrid system, we identified Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) as a protein that interacted with a C-terminal heptapeptide of PLC-beta3. Immunoprecipitation studies revealed that NHERF2 interacts specifically with PLC-beta3, but not with other PLC-beta isotypes. Furthermore, PLC-beta3 interacted with NHERF2 rather than with other PDZ-containing proteins. This interaction required the COOH-terminal NTQL sequence of PLC-beta3 and the second PDZ domain of NHERF2. Interestingly, NHERF2 potentiated the PLC-beta activation by carbachol in COS7 and HeLa cells, while mutant NHERF2, lacking the second PDZ domain, had no such effect. Taken together, the data suggest that NHERF2 may act as a modulator underlying the process of PLC-beta3-mediated signaling.

Animals↗
PubMed1999

Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4+ T-cell clone reacting to TEL/AML1 fusion protein.

The 12;21 chromosomal translocation occurs in leukemic cells from 20(30% of patients with B-lineage childhood acute lymphoblastic leukemia, the result being the TEL/AML1 fusion gene carrying a sequence different from TEL or AML1. Because the protein newly formed by TEL/ AML1 fusion is probably not tolerated by human immune system, the fusion region is a good candidate for tumor antigen expressed only in TEL/ AML1-positive leukemic cells. We established two human CD4+ alphabeta T-cell clones (T31.1 and Y41.2) reacting to the TEL/AML1 fusion region, from two unrelated healthy donors. In order to do this, we stimulated peripheral blood mononuclear cells with synthetic peptides corresponding to the TEL/ AML1 fusion region. Both T31.1 and Y41.2 proliferated in response to TEL/ AML1 fusion protein as well as to a peptide IGRIAECILGMNPSR, in the context of HLA-DP5 and DP17, respectively, and killed B lymphoblastoid cells pulsed with the peptide. Furthermore, these T-cell clones proliferated in response to several altered peptide ligands carrying a single residue substitution in the TEL/AML1 peptide, and some induced augmentation of proliferation and production of Th1-type cytokines. These superagonistic altered peptide ligands can be given consideration for anti-leukemic immunotherapy.

Adjuvants, Immunologic↗
PubMed1999

Midface distraction osteogenesis in cleft patients: a case report.

We present a case of midface distraction in a bilateral cleft lip and palate patient. The patient was a 10-year-old who underwent a high LeFort I osteotomy followed by placement of the Rigid External Distraction halo. Distraction was commenced on the fifth postoperative day at a rate of 1 to 1.5 mm per day until a total of 17 mm of maxillary advancement had been achieved. There were no complications and follow up was at 9 months post distraction. Results show that the patient had improved facial aesthetics and dental occlusion which was overcorrected to a Class III relationship. Velopharyngeal function was unaffected. Distraction osteogenesis of the midfacial skeleton in cleft patients offers the possibility to remodel not only the underlying bony skeleton but also all the soft tissues of the face and palate.

Child↗
PubMed1998

HLA-DP-associated susceptibility to the optico-spinal form of multiple sclerosis in the Japanese.

We studied polymorphism of the HLA-DP gene in 46 patients with optico-spinal form (Asian type) multiple sclerosis (MS) showing recurrent opticomyelitis and 46 patients with Western type MS with disseminated central nervous system involvement. We previously reported a significant association between an HLA-DRB1 *1501-DRB5*0101 haplotype and susceptibility to Western type but not Asian type MS. In the present study, we found that the frequencies of DPA1 *0202 and DPB1 *0501 alleles were significantly increased in patients with Asian type MS, as compared with findings in 92 healthy control subjects (91.3% vs 65.2%, P(corr)<0.05 and 89.1% vs 63.0%, P(corr)<0.05 respectively), but not in Western type MS. Our data provide further evidence that Asian and Western type MS are distinct regarding the immunogenetic background.

Alleles↗
PubMed1997

[Alteration in regional blood flow in minipigs' femur under inadequate decompression studied by isotopes washout method].

We studied the alteration in regional blood flow in minipigs' femur under inadequate decompression after hyperbaric air exposure. The animals were placed in the hyperbaric chamber and exposed to the pressure of 0.5 MPa for 1.5 h, which was reduced to atmosphere at an ascent rate of 0.03-0.04 MPa/min. Regional blood flow in the femur was measured by the isotopes washout method of inhaling 133Xe. The radioactivity was monitored by a multifunctional blood flowmeter interfaced to a minicomputer. Before exposure, the values of average blood flow (F) of femur on the left and right were 15.4 +/- 1.8 and 16.9 +/- 2.0 ml/100 g.min respectively. The values of blood flow (f1) of hematopoietic marrow were 19.1 +/- 2.0 and 21.3 +/- 2.0 ml/100 g.min (n = 7). After inadequate decompression, F values were reduced to 10.3 +/- 1.8 and 11.1 +/- 1.6 ml/100 g.min and f1 values reduced to 13.9 +/- 1.4 and 13.8 +/- 1.0 ml/100 g.min (n = 7), which were obviously lower than those before exposure (P < 0.05). This experiment showed that significant reduction in blood flow in the femur region occurred under inadequate decompression after the exposure of minipigs hyperbaric environment, suggesting that ischemia is a causative factor of osteonecrosis.

Animals↗
PubMed1994

Identification of genes affecting production of the adhesive holdfast of a marine caulobacter.

Caulobacters are stalked bacteria that produce a structure termed a holdfast which enables firm attachment to surfaces. Tn5 insertion mutagenesis was used to identify genes affecting holdfast production or function in the marine strain MCS6. Twelve thousand Tn5 insertion mutants were screened for adhesion defects by an assay involving the attachment of cells to polystyrene microtiter dish wells. Among adhesion-defective mutants, those with multiple polar (pleiotropic) defects were excluded and the remainder were examined for the presence of holdfast. Forty-one mutants that produced no detectable holdfast or a significantly reduced amount were found. Southern blot and pulsed-field gel electrophoresis analyses indicated that 11 unique Tn5 insertions were clustered in three regions of the genome. In addition, 71 mutants that adhered poorly or not at all to polystyrene, yet still produced a holdfast, were found. Southern blot and pulsed-field gel electrophoresis analyses of 15 of these mutants showed eight unique Tn5 insertion sites clustered in two additional regions of the genome. An assay involving attachment to glass treated with siloxane chemicals (producing surfaces with varying degrees of hydrophobicity or hydrophilicity) was used to attempt characterization of this phenotype. Unexpectedly, no simple pattern of differences in binding between the mutants and wild-type caulobacters was found. In particular, no reduction in the ability of the mutants to bind to hydrophobic surfaces was noted. Complementation with cosmid clones was successful in nearly all cases and confirmed the designation of five genomic regions of holdfast-related genes. No detectable cross-hybridization was observed with several holdfast-related gene regions from a freshwater caulobacter, providing further evidence that the marine and freshwater caulobacters are genetically distinct.

Bacterial Adhesion↗
PubMed1992

[Feasibility of the new WHO Trachoma Grading System in China].

The New WHO Trachoma Grading System is found feasible in China by an epidemiological survey of trachoma using the two trachoma grading systems, the new WHO system and the Chinese conventional system, especially for large scale examination and treatment and for epidemiological survey. However, the New System regards the proportion of active trachoma amongst children under 10 years as the index of the scope and severity of the disease in a community, while the authors opine that the trachoma prevalence in teenagers, especially in middle school students, better reflects the situation of trachoma infection in a Chinese community.

Adolescent↗
PubMed1987

Proton and sodium 23 magnetic resonance imaging of human ocular tissues. A model study.

Clinical evaluation of uveal melanomas by magnetic resonance imaging (MRI) techniques depends on developing an understanding of the appearance of these tumors in magnetic resonance (MR) images. We have determined MR characteristics of uveal melanomas by proton (1H) and sodium 23 MRI of freshly enucleated human eyes at 1.5 tesla. The MR images were obtained using two-turn proton and 23Na surface coils, designed to both transmit and receive the radiofrequency signal. Proton MRI techniques included saturation recovery and spin echo; the gradient-recalled echo technique was used for 23Na MRI. Proton and 23Na MR images provide complementary information; contrast between intraocular tumors and vitreous, lens, or subretinal hemorrhage may be varied by using MR pulse sequences that emphasize tissues based on T1, T2, proton, or sodium density values. A combination of proton and 23Na MRI provides differentiation between normal ocular structures and intraocular tumors, as well as associated complications, such as retinal detachments and subretinal hemorrhages.

Eye↗