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Biomedical subjects

X Yuan

Publications and source records attributed to X Yuan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Neurotransmitter receptor activation triggers p27(Kip1 )and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors.

We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors. We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining. This antiproliferative effect was specifically attributable to a beta-adrenoceptor-mediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1)and p21(CIP1), and G1 arrest. Studies with oligodendrocyte progenitor cells from INK4a-/- mice indicated that the G1 cyclin kinase inhibitor p16(INK4a) as well as p19(ARF)were not required for agonist-stimulated proliferation arrest. Our results demonstrate that beta-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of p27(Kip1) is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation.

Animals↗
PubMed1999

Essential role of caspase-3 in apoptosis of mouse beta-cells transfected with human Fas.

Several recent studies have indicated that the Fas-Fas ligand system may be critical for pancreatic beta-cell destruction in type 1 diabetes. Although the fundamental roles of caspases in the mammalian apoptotic machinery have been elucidated, it is not known which caspase or caspases play a major role in Fas-mediated apoptosis of beta-cells. In this study, we transfected human Fas cDNA into a mouse beta-cell line (betaTC1) and established a beta-cell clone expressing human Fas. This clone, designated hFas/betaTC1, underwent apoptosis when exposed to anti-Fas, showing hallmarks of apoptosis (chromatin condensation, nucleolar disintegration, internucleosomal DNA fragmentation, and annexin V staining), indicating that the mouse beta-cell line has the intact machinery of Fas-mediated apoptosis. The cross-linking of Fas by anti-Fas resulted in the elevation of caspase-3-like, but not caspase-1-like, protease activity 2-12 h after the addition of the anti-Fas. A caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, attenuated the Fas-mediated beta-cell apoptosis, while a caspase-1 inhibitor, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, failed to suppress the apoptosis. Thus the Fas-induced death signal apparently bypassed caspase-1 in the cells. Furthermore, an antisense caspase-3 construct blocked caspase-3 activation and substantially suppressed Fas-triggered apoptosis of hFas/betaTC1 cells. These observations suggest the essential role of caspase-3 in Fas-mediated apoptosis of the beta-cell line.

Amino Acid Chloromethyl Ketones↗
PubMed1999

[Heavy ion radiation induced inactivation of human bronchial epithelial cells].

OBJECTIVE: To observe the cell inactivating effects of Li, C and F ions. METHOD: Li(Z = 3), C(Z = 6) and F(Z = 9) ion beams, with LETs of 100 keV/micron, 300 keV/micron and 1000 keV/micron, respectively were produced by HI-13 tandem accelerator at the Department of Nuclear Physics, China Institute of Atomic Energy. The human bronchial epithelium cell line (BEAS-2B) was irradiated with the designed doses ranging from 0.5 Gy to 6.0 Gy. After irradiation, the cells were cultured at 1000/flask and the survival fractions were calculated. RESULT: The cell survival fraction (SF, non-unit) have negative exponential relations with dose(D, Gy) as shown by the fitted equations: SF = EXP(-D/1.28)(Li); SF = EXP(-D/1.18)(C); SF = EXP(-D/2.09)(F), respectively. The sensitive parameters (D0, Gy) of radiation were D0 = 1.28; D0 = 1.18; D0 = 2.09, respectively. The patterns of cell survival were fitted to single target model. The relative biological effectiveness (RBE) for Li, C and F ions were 2.54, 2.67, 1.55, respectively, compared with D0 of gamma-ray irradiation. The inactivation cross sections for these ions were 12.5, 40.6 and 76.5 microns2 respectively. CONCLUSION: The effectiveness of radiation induced by heavy ions of Li, C and F was more serious than that of 60Co gamma-ray, and more than one particle traversal are needed to kill a cell on the average.

Bronchi↗
PubMed1999

[Study on the induction of xenogeneic tolerance of rat to mouse bone marrow transplantation].

OBJECTIVE: To establish an effective protocol for potential clinical usage in inducing donor-specific tolerance across xenogeneic barriers. METHODS: C57BL/6 (B6) mice were conditioned with 5 Gy sublethal total body irradiation (TBI), followed by infusion of 4 x 10(7) Lewis rat bone marrow cells on day 0, then were intraperitonially administered 150 mg/kg cyclophosphamide (CP) on day 2. Recipients were characterized for engraftment with xenogeneic bone marrow cells by using fluorescence activated cell sorter (FACS) to determine the percentage of rat origin cells in the peripheral blood lymphocytes(PBL), splenic and thymic lymphoid cells on day 30, 60 and 90. Mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH) assay were performed on day 30 to examine the tolerance status. RESULTS: Rat lymphoid chimeras were reliable present in the tolerant B6 mice for more than 3 months. B6 recipients were specifically tolerant to host xenoantigens in MLR and DTH assays, but were still immunocompetent to MHC-disparate third party BALB/c mouse or DA rat stimulator cells. CONCLUSION: A durable rat to mouse xenogeneic bone marrow transplantation tolerance was achieved in this modal.

Animals↗
PubMed1999

[Surgical treatment of gastric cancer in stage T1/T2: an reevaluation of the clinical significance of early gastric cancer].

OBJECTIVE: To evaluate the clinical significance of early gastric cancer by means of an analysis of the results of surgical treatment of gastric cancer in stage T1/T2. METHODS: A retrospective review and survival analysis of 132 patients with stage T1/T2 stomach cancer treated from 1983 through 1993 was performed. RESULTS: The average tumor size, lymph node involvement, postoperative recurrence and survival rate were significantly different between gastric cancer in stage T1 and T2. It was true of both groups of patients that the survival rate of patients with and without lymph node involvement was significantly different. However, the survival rate of patients in stage T2 but without lymph node involvement was not significantly different as compared to that of patients in stage T1. CONCLUSION: For stage T1 stomach cancer, because of possible lymph node involvemnt, local mucosal excision of tumor is not recommended. For stage T2 stomach cancer without lymph node metastasis, it can be regarded as cancer still in its early stage when postoperative adjunct therapy is to be given.

Adult↗
PubMed1999

[Expression of heat shock protein 90 alpha and its effect on the growth of tumor in mice].

OBJECTIVE: To study the effect of hsp90 alpha on the growth of tumor in mice and its mechanism. METHODS: Hsp90 alpha fusion protein was expressed in E. coli. DBA/2 mice were injected with purified fusion protein, then challenged with L1210 cells. The size of tumor was measured every other day. NK cell activity was detected by 51Cr release assay. RESULTS: The tumors grew faster while activity NK cell activity of mice was lower in the test mice than that in the control mice. CONCLUSION: The results suggest that the accelerated tumor growth is probably due to the formation of anti-hsp90 alpha antibody and decreased NK cell activity of mice treated with hsp90 alpha.

Animals↗
PubMed1999

[Expression of antisense telomerase genes suppressing human cancer malignant phenotypes].

OBJECTIVE: Altering the expression of telomerase genes hTRT and hTR to induce changes in cancer cell biology and to determine their value in cancer gene therapy. METHODS: By genetic transfection of antisense hTRT into HeLa cells, and treatment of PG cells with antisenes hTR oligonucleotides, their effects on cancer cell growth and malignant phenotypes were analyzed. RESULTS: The vehicle for eukaryotic expression of hTRT antisense was constructed and transfected into HeLa cells. The obtained transfectants T4, T5 that could produce antisense hTRT stablely showed marked decrease in growth, with an arrest rate of 24%; the presence of contact growth inhibition was obvious; in nude mice transplantation, the rate for tumor induction was decreased from 100% to 25% or 0%; histologically, the tumor cells from inoculation of transfectant showed less nuclear chromatins and fewer giant tumor cells than those of the parent HeLa cells;the expression of PCNA was significantly reduced in the transfected cells. Treatment of antisense hTR oligonucleotides inhibited PG cell growth at a rate of 8%. CONCLUSIONS: Antisense expression of telomerase genes could significantly suppress cancer cell growth, decrease malignant phenotypes and histological atypia. Therefore, altering expression of telomerase genes may be a new pathway for cancer therapy.

Animals↗
PubMed1999

[Study on the ternary complex of CPFX, copper (II) and DNA by the method of fluorescence].

Using the method of fluorescence spectrometry, the formation of binary complexes of CPFX-Cu(II) and CPFX-eucaryote DNA, and ternary complexes of CPFX-Cu(II)-eucaryote DNA was studied. The results show that the fluorescent intensity of CPFX can be quenched in the presence of Cu(II ) or DNA in CPFX system. In the presence of Cu (II), the fuorescence quenching action of DNA on CPFX was enhanced strongly. Based on the fluorescent intensity, the formation constants of CPFX-Cu (II) and CPFX-DNA in either the presence or absence were calculated,and the mechanism of interaction among CPFX,Cu(II) and DNA was presented.

Animals↗
PubMed1998

Synthetic, implantable polymers for local delivery of IUdR to experimental human malignant glioma.

PURPOSE: Recently, polymeric controlled delivery of chemotherapy has been shown to improve survival of patients with malignant glioma. We evaluated whether we could similarly deliver halogenated pyrimidines to experimental intracranial human malignant glioma. To address this issue we studied the in vitro release from polymers and the in vivo drug delivery of IUdR to experimental human U251 glioblastoma xenografts. METHODS AND MATERIALS: In vitro: To measure release, increasing (10%, 30%, 50%) proportions of IUdR in synthetic [(poly(bis(p-carboxyphenoxy)-propane) (PCPP):sebacic acid (SA) polymer discs were serially incubated in buffered saline and the supernatant fractions were assayed. In vivo: To compare local versus systemic delivery, mice bearing flank xenografts had intratumoral or contralateral flank IUdR polymer (50% loading) treatments. Mice bearing intracranial (i.c.) xenografts had i.c. versus flank IUdR polymer treatments. Four or 8 days after implantation of polymers, mice were sacrificed and the percentage tumor cells that were labeled with IUdR was measured using quantitative microscopic immunohistochemistry. RESULTS: In vitro: Increasing percentage loadings of IUdR resulted in higher percentages of release: 43.7 + 0.1, 70.0 + 0.2, and 90.2 + 0.2 (p < 0.001 ANOVA) for the 10%, 30%, and 50% loadings, respectively. In vivo: For the flank tumors, both the ipsilateral and contralateral IUdR polymers resulted in similarly high percentages labeling of the tumors versus time. For the ipsilateral IUdR polymers, the percentage of tumor cellular labeling after 4 days versus 8 days was 45.8 +/- 7.0 versus 40.6 +/- 3.9 (p = NS). For the contralateral polymer implants, the percentage of tumor cellular labeling were 43.9 +/- 10.1 versus 35.9 +/- 5.2 (p = NS) measured 4 days versus 8 days after implantation. For the i.c. tumors treated with extracranial IUdR polymers, the percentage of tumor cellular labeling was low: 13.9 +/- 8.8 and 11.2 +/- 5.7 measured 4 and 8 days after implantation. For the i.c. tumors having the i.c. IUdR polymers, however, the percentage labeling was comparatively much higher: 34.3 +/- 4.9 and 35.3 +/- 4.0 on days 4 and 8, respectively. For the i.c. tumors, examination of the percentage cellular labeling versus distance from the implanted IUdR polymer showed that labeling was highest closest to the polymer disc. CONCLUSION: Synthetic, implantable biodegradable polymers provide the local, controlled release of IUdR and result in the high, local delivery of IUdR to experimental intracranial human malignant glioma. This technique holds promise for the local delivery of IUdR for radiosensitization of human brain tumors.

Animals↗
PubMed1998

Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members.

Tuberous sclerosis (TSC) is a genetic disorder that results in the development of hamartomatous lesions in a variety of organ systems. Both the prevalence of the disease and the often devastating consequences of these tumors pose a serious health and medical care problem. The disease has been mapped to two distinct genetic loci in humans, and although the genes (TSC1 and TSC2) for both loci have recently been cloned, their function remains an enigma. Data presented here demonstrates that TSC2 protein can bind and selectively modulate transcription mediated by members of the steroid receptor superfamily of genes. These data place TSC2 into a growing list of nuclear receptor coregulators and strengthen the expanding body of evidence that these coregulators may play critical roles in cellular differentiation.

Amino Acid Sequence↗
PubMed1998

Cloning and expression of Staphylococcus aureus and Treptococcus pyogenes murD genes encoding uridine diphosphate N-acetylmuramoyl-L-alanine:D-glutamate ligases.

Bacterial UDP-N-acetylmuramyl-L-alanine:D-glutamate ligase (MurD), a cytoplasmic peptidoglycan biosynthetic enzyme, catalyzes the ATP-dependent addition of D-glutamate to an alanyl residue of the UDP-N-acetylmuramyl-L-alanine precursor, generating the dipeptide. The murD gene was cloned from both Staphylococcus aureus and Streptococcus pyogenes. Sequence analysis of the S. aureus murD gene revealed an open reading frame of 449 amino acids. The deduced aa sequence of S. aureus MurD is highly homologous to MurD from Escherichia coli, Haemophilus influenzae, Bacillus subtilis and St. pyogenes. Recombinant MurD protein from both S. aureus and St. pyogenes was separately overproduced in E. coli and purified as His-tagged fusion. Both recombinant enzymes catalyzed the ATP-dependent addition of D-glutamate to the precursor sugar peptide.

Amino Acid Sequence↗
PubMed1998

Identification of a tumor-specific methylation site in the Wilms tumor suppressor gene.

Malignant mesothelioma is one of the very few extrarenal neoplasms in which the Wilms tumor suppressor gene (wt1) is expressed. We examined wt1 for alterations in rat mesotheliomas, a well characterized animal model for the human disease. Southern analysis revealed a 3.5 kb EcoRI wt1 fragment readily detectable in majority of mesothelioma cell lines and primary mesotheliomas but not in normal rat tissues. Cloning and sequencing of this fragment revealed that the presence of this EcoRI fragment resulted from an inability of this enzyme to cut at a EcoRI site in intron 1 of wt1. This site contains potential motifs for cytosine methylation and treatment of mesothelioma cells with 5-azadeoxycytosine restored the normal EcoRI digestion pattern of wt1 in these cells indicating that cleavage was inhibited by methylation at this site. Southern analysis using HpaII/MspI digestion revealed no differences in methylation between mesothelioma cell lines and normal mesothelium at other CpG sites in wt1 5' region. Renal cell carcinoma lines which did not express wt1 were also methylated at this EcoRI site. Our identification of a site frequently methylated in malignant cells, independent of gene expression, provides a new model system to study determinants of site-specific methylation in tumors.

Animals↗
PubMed1998

Clinical characterization of polymorphisms in the sulphonylurea receptor 1 gene in Japanese subjects with Type 2 diabetes mellitus.

To assess the association of polymorphisms at the sulphonylurea receptor (SUR1) gene with the development of Type 2 diabetes mellitus, 456 subjects, 236 with Type 2 diabetes and 220 non-diabetic controls, were analysed for variants at exon 7, exon 22 and intron 24 of the SUR1 gene by the polymerase chain reaction and restriction fragment length polymorphism. The T761T substitution in exon 22 of the SUR1 gene was not found in either diabetic patients or non-diabetic controls. Both the exon 7 variant and the intron 24 variant were present in both groups at similar frequencies. No significant association was seen between either variant and obesity. Diabetic patients homozygous for the -3C allele of intron 24 had a higher ratio of positive family history than patients homozygous for the -3T allele (p = 0.03). We conclude that these polymorphisms are not major determinants of diabetes and obesity in the Japanese population.

ATP-Binding Cassette Transporters↗
PubMed1998

Protracted exposure radiosensitization of experimental human malignant glioma.

Clinical modulation of radiosensitivity via combined fractionated high dose rate and continuous ultra-low dose rate irradiation (ULDR) holds promise for the radiosensitization of human malignant gliomas. We measured both the in vitro and in vivo responses of a human malignant glioma cell line to combined continuous ULDR and high dose rate treatments. For in vitro ULDR treatments, U251 human malignant glioma cells were cultured in media containing tritiated water to yield a continuous dose rate of 0.03 Gy/hr. After exposures of 24, 48, or 72 hr, cells were acutely (1.1 Gy/min) irradiated, replated, and scored for colony formation. In vivo, U251 flank xenografts in nude mice had 125-iodine (125-I) seed brachytherapy at a dose rate of 0.05 Gy/hr. For whole-body continuous ULDR (0.03 Gy/hr), a 137-Cs source was mounted a fixed distance above the cages of animals bearing xenografts. After 3 days' continuous exposure, xenografts were acutely irradiated (2 Gy x 8 vs. 5 Gy x 2 daily fractions), and the regrowth delay in tumors was measured. In vitro, exposure to ULDR (0.03 Gy/hr) alone caused only modest killing and reduced the surviving fraction by approximately 0.2 logs after 72 hr exposure. The highest (10 Gy) dose of acute irradiation alone reduced survival by 1 log. However, U251 cell killing increased to 2.5 logs after combined HDR and ULDR treatments. Linear-quadratic modeling showed comparatively greater increase in the beta than the alpha coefficients of the linear-quadratic model for cell killing. In vivo, the 125-I seed brachytherapy treatments delayed tumor growth but resulted in no regression. The HDR treatments (5 Gy x 2 or 2 Gy x 8 daily fractions) caused growth delays (in days) of 17+/-2 or 16+/-2 (P=NS) days, respectively. The combined seed and 5 Gy x 2 or 2 Gy x 8 daily fractions regimen resulted in striking prolongation of regrowth delay (52.3+/-8.7 vs. 59.5+/-7.7 days) (P < 0.001 vs. HDR treatments alone). External ULDR alone caused no regression and minimal growth delay. Combined continuous external ULDR and the 5 Gy x 2 vs. 2 Gy x 8 daily fraction regimens resulted in prolongation of growth delay (33+/-0.9 (P=0.01 vs. 5 Gy x 2 daily fractions alone) vs. 35+/-0.7 (P=0.049 vs. 2 Gy x 8 daily fractions alone). We conclude that continuous ULDR increases the effect of HDR treatments of experimental malignant glioma. This increased effect may prove clinically important in the treatment of human malignant brain tumors.

Animals↗
PubMed1998

Effects of proline cis-trans isomerization on TB domain secondary structure.

The transforming growth factor beta (TGF-beta) binding protein-like (TB) domain is found principally in proteins localized to extracellular matrix fibrils, including human fibrillin-1, the defective protein in the Marfan syndrome. Analysis of the nuclear magnetic resonance (NMR) data for the sixth TB module from human fibrillin-1 has revealed the existence of two stable conformers that differ in the isomerization states of two proline residues. Unusually, the two isoforms do not readily interconvert and are stable on the time scale of milliseconds. We have computed independent structures of the major and minor conformers of TB6 to assess how the domain fold adjusts to incorporate alternatively cis- or trans-prolines. Based on previous observations, it has been suggested that multiple conformers can only be accommodated in flexible regions of protein structure. In contrast, P22, which exists in trans in the major form and cis in the minor form of TB6, is in a rigid region of the domain, which is confirmed by backbone dynamics measurements. Overall, the structures of the major and minor conformers are similar. However, the secondary structure topologies of the two forms differ as a direct consequence of the changes in proline conformation.

Fibrillin-1↗
PubMed1998

Identification of a single nucleotide insertion polymorphism in the upstream region of the insulin promoter factor-1 gene: an association study with diabetes mellitus.

Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35%) and lower in NIDDM patients (17%) than in normal control subjects (28%, p=0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene.

Adolescent↗