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Biomedical subjects

Y Tang

Publications and source records attributed to Y Tang.

At least 55 records · Page 3Linked to original sources
PubMed2002

Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray.

PURPOSE: To establish a hepatocellular carcinoma (HCC) cell line from lung metastatic lesions of human HCC in nude mice so as to provide a suitable model for the study of lung-metastasis-related molecular mechanisms. METHODS: HCC clone cells MHCC97-H were inoculated into BALB/c nude mice, and the pulmonary metastatic lesions were harvested and re-implanted into nude mice for the second round of in vivo selection. The same procedure was repeated twice. A new cell line from the third round of lung metastases was established. RESULTS: A human HCC cell line with unique metastatic characteristics was established by in vivo selection. This cell line, designated as HCCLM3, was polygonal epithelial cell with hypotriploid karyotype and population doubling time of 34.9 h. The cells were positive for alpha fetoprotein (AFP), albumin, cytokeratin 8 (CK8), and negative for hepatitis B surface antigen (HBsAg) by immunocytochemistry. Fluorescence polymerase chain reaction (PCR) showed HBV DNA integration in the cellular genome. When 5 x 10(6) cells were injected subcutaneously into nude mice, tumorigenicity was 100%, with a latency period of 11+/-1 days. Five weeks after s.c. injection, the pulmonary metastatic rate was 100%, the median number of lung metastases being 121 per mouse. After orthotopic implantation of tumor tissue into nude mouse liver for 35 days, widespread loco-regional and distant metastases occurred, with 100% abdominal wall metastases, 80% intra-abdominal cavity metastases, 100% intrahepatic metastases, 70% diaphragm metastases, and 100% pulmonary metastases. The median number of lung metastatic lesions was 268 per mouse. Gene expression profile of HCCLM3 was compared by cDNA microarray with MHCC97-L, a clonal cell strain from the same parental cell line but with low metastatic potential; 25 differentially expressed genes were identified, 18 of which showed decreased expression and seven increased expression in HCCLM3, including the decreased expression of cell cycle control gene Rb2, mismatch repair gene hMSH2, and signal transduction gene protein kinase C beta2, and increased expression of signal transduction gene MAP kinase, kinase 6. CONCLUSIONS: A new HCC cell line characterized by high pulmonary metastases via s.c. and orthotopic inoculation was established, which provides a new model for the study of liver cancer metastasis. Its gene expression profile could help in the understanding of the mechanism of metastasis and provide potential targets for anti-metastasis intervention.

Animals↗
PubMed2002

Itih-4, a serine protease inhibitor regulated in interleukin-6-dependent liver formation: role in liver development and regeneration.

Inter-alpha-trypsin inhibitor-4 (Itih-4) is a liver-restricted member of the serine protease inhibitor family with diverse functions as an anti-apoptotic and matrix stabilizing molecule that are important throughout development. We investigate the functional role of Itih-4 in liver formation, regeneration (LR) and examine its role in calcium and hyaluronic acid binding. Itih-4 expression is prominent in early liver development at E9 and later at E16, being restricted to hepatoblasts, immature hepatocytes, and differentiated hepatocytes. We note a marked and differential increase in Itih-4 labeling in proliferating hepatocytes, compared with bile duct cells in liver explant cultures treated with interleukin-6 (IL-6). After partial hepatectomy, maximal Itih-4 expression occurs in a bimodal manner at 30 min and at 12 hr, with a predominant centrizonal distribution. There is no detectable binding of glutathione transferase-fusion Itih-4 protein to calcium and hyaluronic acid, indicating a possible requirement for posttranslational modifications for these functions. These results suggest that in LR, Itih-4 expression corresponds to that of immediate early genes and may contribute to the entry of normally quiescent hepatocytes into the early stages of the cell cycle. The markedly high expression of Itih-4 in early liver development and in explants treated with IL-6 suggests a prominent role for Itih-4 at key points in liver formation.

Animals↗
PubMed2002

Synthesis and biological activity of novel neuroprotective diketopiperazines.

The cyclic dipeptide cyclo[His-Pro] (CHP) is synthesized endogenously de novo and as a breakdown product of thyrotropin-releasing hormone (TRH), a tripeptide with known neuroprotective activity. We synthesized two isomeric compounds based on the structure of CHP, in which the histidine residue was replaced by 3,5-di-tert-butyltyrosine (DBT), a phenolic amino acid that traps reactive oxygen species. These novel diketopiperazines prevented neuronal death in an in vitro model of traumatic injury. In addition, they dose-dependently prevented death caused by the direct induction of free radicals, and by calcium mobilization through an agent that evokes rapid, necrotic death. The drugs showed activity in the latter system at picomolar concentrations. The neuroprotective profile of these compounds suggests that they may be useful as treatments for neuronal degeneration in vivo, potentially through several different mechanisms.

Animals↗
PubMed2002

Catecholaminergic projections onto spinal neurons destined to the pelvis including the penis in rat.

In rats, the spinal cord contains proerectile autonomic motoneurons destined to the penile tissue and its vasculature, and somatic motoneurons destined to the perineal striated muscles. It receives dense catecholaminergic projections issued from the medulla and pons. In adult male rats, we evidenced the catecholaminergic innervation of spinal neurons controlling lower urogenital tissues and regulating penile erection. We combined retrograde tracing techniques and immunohistochemistry against synthetic enzymes of noradrenaline and adrenaline. Both sympathetic and parasympathetic preganglionic neurons, labeled from the major pelvic ganglion or from the corpus cavernosum, were apposed by catecholaminergic immunoreactive fibers. Motoneurons, retrogradely labeled from the striated muscles, were also apposed by catecholaminergic immunoreactive fibers. Synapses between these motoneurons and fibers were suggested by confocal microscopy and confirmed by electron microscopy in some cases. The results reinforce the hypothesis of a catecholaminergic control of autonomic and somatic motoneurons regulating penile erection at the spinal level.

Animals↗
PubMed2001

Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation.

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIV-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed.

Amino Acid Sequence↗
PubMed2001

A prospective study of cerebral white matter abnormalities in older people with gait dysfunction.

OBJECTIVES: The authors previously reported cross-sectional data suggesting a relationship between cerebral white matter hyperintensities (WMH) and gait and balance dysfunction in older people. There have been no longitudinal MRI studies to address this issue. The current study compared progression of WMH in subjects with gait and balance dysfunction with that in healthy subjects. METHODS: Two brain MRI were performed on 70 healthy, ambulatory subjects (mean baseline age 79, range 74 to 88) with no identifiable neurologic disease. The mean time between MRI was 4 years. Gait and balance were quantified using the Tinetti Balance and Mobility Scale, and falls were documented each year. On T2-weighted MRI, total hyperintense volume (HV) within three periventricular levels was estimated using the Cavalieri principle, and WMH were graded (0 to 4) using an established semiquantitative scale. RESULTS: Compared with those with normal gait and balance, subjects whose Tinetti scores dropped markedly (> 4 points) between first and second MRI showed a significantly greater mean increase in HV during follow-up. The larger group of subjects with an abnormal Tinetti score (< 24) at the time of second MRI showed a significantly greater mean increase in HV, compared with those with normal gait and balance at follow-up. Subjects with marked WMH at baseline showed significantly greater increase in HV over time. Subjects with abnormal Tinetti scores had significantly more falls than subjects with normal Tinetti scores. CONCLUSIONS: Some older people develop gait and balance dysfunction that is associated with gradual onset of cerebral white matter disease.

Accidental Falls↗
PubMed2001

Total regional and global number of synapses in the human brain neocortex.

An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region of neocortex was performed. The total volume of each neocortical region was estimated using point counting according to Cavalieri's principle. The ethanolic phosphotungstic acid staining technique was modified for synapses in human autopsy brains. The numerical density of synapses in each neocortical region studied was estimated using the disector at the electron microscopical level. The total number of neocortical synapses in each region was estimated as the product of the total volume of neocortex and the numerical density of synapses. The influence of the postmortem fixation delay on the number of synapses was investigated in five large mammals (one dog, one cow, and three pigs), the brains of which were kept under conditions similar to those under which human corpses are normally kept. The apparent decrease of 3.9% in the numerical density of synapses in the large mammals following a 2-day fixation delay was not significant. The average total number of synapses in the neocortex of five young male brains was 164 x 10(12) (CV = 0.17). An analysis of the precision of the estimate of the total number of synapses in neocortex indicates that blocks represent both the major source of variation and the largest workload. Using eight blocks per brain the imprecision of the estimate is, however, only 66% of the total variance.

Adult↗
PubMed2001

Both heavy strand replication origins are active in partially duplicated human mitochondrial DNAs.

The replication of human mitochondrial DNA (mtDNA) is initiated from a pair of displaced origins, one priming continuous synthesis of daughter-strand DNA from the heavy strand (OH) and the other priming continuous synthesis from the light strand (OL). In patients with sporadic large-scale rearrangements of mitochondrial DNA (i.e., partially-deleted [Delta-mtDNA] and partially-duplicated [dup-mtDNA] molecules), the dup-mtDNAs typically contain extra origins of replication, but it is unknown at present whether they are competent for initiation of replication. Using cybrids harboring each of two types of dup-mtDNAs-one containing two OHs and two OLs, and one containing two OHs and one OL-we used ligation-mediated polymerase chain reaction (LMPCR) to measure the presence and relative amounts of nascent heavy strands originating from each OH. We found that the nascent heavy strands originated almost equally from the two OHs in each cell line, indicating that the extra OH present on a partially duplicated mtDNA is competent for heavy strand synthesis. This extra OH could potentially confer a replicative advantage to dup-mtDNAs, as these molecules may have twice as many opportunities to initiate replication compared to wild-type (or partially deleted) molecules.

Cell Line↗
PubMed2001

[Schizophrenia and dopamine D4 gene polymorphism in Chinese population: association analysis].

OBJECTIVE: To investigate the association of the 48 bp variable number tandem repeat (VNTR) polymorphism in the dopamine D4 receptor (DRD4) gene exon III with schizophrenia in Chinese Han population. METHODS: Case-control association study was adopted to analyze the association between the 48 bp VNTR polymorphism of DRD4 gene exon III in 510 DSM-IV schizophrenics and 171 psychiatrically normal controls. RESULTS: (1) The DRD4 gene 48 bp VNTR polymorphism was manifested as 2-7 repeats, with the 4 repeats the most common (78.6% in schizophrenics and 76.9% in controls respectively). The frequency of 2 repeats was 16.2% and 19.3% in the schizophrenics and controls respectively. (2) The genotypic frequency was statistically significantly different between the schizophrenics and the controls. The genotypic frequency of short tandem repeats (2/2 and 2/3 genotype) was lower in patients (3.3%) than in controls (10.5%) (chi 2 = 14.88, df = 2, P = 0.00). (3) the frequency of the genotype with 4-repeat allele in patients was higher (95.9%) than in controls (88.3%) (chi 2 = 13.00, df = 1, P = 0.000). CONCLUSION: The most common allele in Chinese schizophrenics was 4 repeats in the 48 bp VNTR polymorphism of DRD4 gene exon III. The repeat number of 48 bp is probably associated with schizophrenia. Lack of 2-3 repeats or excess of genotype with 4-repeat allele may be associated with increased vulnerability to schizophrenia.

Adult↗
PubMed2001

Highly diastereoselective synthesis of vinylcyclopropane derivatives with (-)-8-phenylmenthol as chiral auxiliary.

The silylated telluronium allylide 4, generated in situ from the corresponding telluronium salt in the presence of LiTMP, reacted with (-)-8-phenylmenthyl alpha,beta-unsaturated esters to afford trans-2-silylvinyl-trans-3-substituted cyclopropyl esters with high diastereoselectivity in high yields. The absolute configuration was determined by chemical transformation. A mechanistic rationale is proposed.

Cyclohexanes↗
PubMed2001

Insulin-like growth factor-I induces renal cell hypertrophy via a calcineurin-dependent mechanism.

Insulin-like growth factor-I (IGF-I) may play an important role in the development of renal hypertrophy. In this study we determined the effect of IGF-I on cultured mesangial cells (MCs) and examined activation of key signaling pathways. IGF-I induced hypertrophy as determined by an increase in cell size and an increase in protein to DNA ratio and increased accumulation of extracellular matrix (ECM) proteins. IGF-I also activated both Erk1/Erk2 MAPK and phosphatidylinositol 3-kinase (PI3K) in MCs. Inhibition of either MAPK or PI3K, however, had no effect on IGF-I-induced hypertrophy or ECM production. Next, we examined the effect of IGF-I on activation of the calcium-dependent phosphatase calcineurin. IGF-I treatment stimulated calcineurin activity and increased the protein levels of calcineurin and the calcineurin binding protein, calmodulin. Cyclosporin A, an inhibitor of calcineurin, blocked both IGF-I-mediated hypertrophy and up-regulation of ECM. In addition, calcineurin resulted in sustained Akt activation, indicating possible cross-talk with other signaling pathways. Finally, IGF-I treatment resulted in the calcineurindependent nuclear localization of NFATc1. Therefore, IGF-I induces hypertrophy and increases ECM accumulation in MCs. IGF-I-mediated hypertrophy is associated with activation of Erk1/Erk2 MAPK and PI3K but does not require either of these pathways. Instead, IGF-I mediates hypertrophy via a calcineurin-dependent pathway.

Animals↗
PubMed2001

[Comparative effects of carvediol in large, middle, and small dose in preventing left ventricular remodeling after acute myocardial infarction in rats].

OBJECTIVE: To compare the effects of carvedilol in large, middle, or small dose in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats. METHODS: AMI were conducted by ligating left coronary artery in female SD rats. Twenty-four hours after the procedure, 142 surviving rats were randomly assigned to one of the following groups: AMI control (n = 35), large dose carvedilol (10 mg.kg-1.d-1, n = 37), middle dose carvediol (1 mg.kg-1.d-1, n = 35), and small dose carvediol(0.1 mg.kg-1.d-1, n = 35) Sham-operated rats (n = 16) were selected randomly as non-infarction control. Carvedilol was administered by direct gastric gavage for four weeks. Then hemodynamic studies were performed, and the hearts of the rats were taken out and fixed with 10% formalin and pathologic analysis was performed. Exclusive of the rats with infarct size < 35% or > 55%, complete experimental variables were obtained in 58 rats. RESULTS: No significant difference was found in MI size (44.5-46.3%, all P > 0.05) among the four AMI groups. Compared with the sham-operated group, a significant increase could be seen in left ventricular end diastolic pressure (LVEDP, 24.5 mm Hg +/- 5.3 mm Hg), left ventricular volume (LVV, 0.92 ml +/- 0.11 ml), left ventricular absolute weight (LVAW, 730 mg +/- 79 mg) and left ventricular relative weight (LVRW) (LVEDP: vs.; LVV: vs.; LVAW: vs. 730 mg +/- 79 mg; P < 0.05-0.001), and a significant decrease could be seen in sphericity index and LV pressure maximal rate of rise and fall (+/- dp/dt) as well as their corrected values (+/- dp/dt/LVSP) among AMI groups (P < 0.01-0.001). In comparison with AMI groups, a dose-dependent and significant decrease could be seen in LVEDP (7.7 mm Hg +/- 1.9 mm Hg, 12.1 mm Hg +/- 2.0 mm Hg, 14.5 mm Hg +/- 4.6 mm Hg), LVV(0.72 ml +/- 0.10 ml, 0.79 ml +/- 0.08 ml, 0.82 ml +/- 0.10 ml), LVAW (589 mg +/- 57 mg, 622 mg +/- 70 mg, 666 mg +/- 57 mg) and LVRW among large, middle, and small dose carvediol groups (all P < 0.01), while a significant increase could be seen in +/- dp/dt and +/- dp/dt/LVSP (all P < 0.05-0.01) among the three carvedilol groups without significant difference among different doses. The sphericity index was significantly increased only in large-dose carvedilol group (1.71 +/- 0.19 vs 1.96 +/- 0.25, P < 0.05). CONCLUSION: Carvedilol in no matter what dose effectively and dose-dependently prevent LV remodeling after AMI and improve hemodynamics and LV function in rats.

Adrenergic beta-Antagonists↗
PubMed2001

Evolution and transmission of stable CTL escape mutations in HIV infection.

Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.

Adult↗
PubMed2001

Crystal structure of alpha-momorcharin in 80% acetonitrile--water mixture.

Crystals of alpha-momorcharin (MMC) were cross-linked and soaked in an 80% acetonitrile--water mixture and X-ray data were collected to 2.2 A resolution. MMC is a ribosome-inactivating protein with a sugar chain on Asn-227. In previous studies, the whole conformation of the sugar chain could not be obtained in the aqueous system. Here the structure of MMC in a low water system is shown to be similar to the native one, but the sugar chain on Asn-227 is defined by the electron density map. Several oxygen atoms of the oligosaccharide formed intramolecular hydrogen bonds to the protein moiety. The conformation of the residues in the active center is similar to that in the aqueous system. Our results show conformational alteration of the tetrasaccharide of MMC in organic media. They indicate that the oligosaccharides are more rigid in organic solvents. X-ray determination in organic media may be used to solve some structures of oligosaccharides linked to glycoproteins.

Acetonitriles↗