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Biomedical subjects

J C Yang

Publications and source records attributed to J C Yang.

At least 19 recordsLinked to original sources
PubMed2006

Clinical implications of neuroendocrine differentiation in prostate cancer.

The cellular signaling pathways of the prostate play a central role in the induction, maintenance, and progression of prostate cancer (CaP). Neuroendocrine (NE) cells demonstrate attributes that suggest they are an integral part of these signaling cascades. We summarize what is known regarding NE cells in CaP focusing on NE cellular transdifferentiation. This significant event in CaP progression appears to be accelerated by androgen deprivation (AD) treatment. We examine biochemical pathways that may impact NE differentiation in a chronological manner focusing on AD therapy (ADT) as a central event in inducing androgen-independent CaP. Our analysis is limited to the common adenocarcinoma pattern of CaP and excludes small-cell and carcinoid prostatic variants. In conclusion, we speculate on the future of treatment and research in this area.

Adenocarcinoma↗
PubMed2006

Cu2O island shape transition during Cu-Au alloy oxidation.

In situ transmission electron microscopy observations of the oxidation of (001) Cu-Au alloys indicate that the Cu2O islands that form undergo a remarkable transformation from an initially compact morphology to a dendritic structure as growth proceeds. Correspondingly, the surface composition becomes nonuniform and the fractal dimension associated with the islands evolves from 2.0 to a stable value of 1.87, indicating a transition in the rate-limiting mechanism of oxidation from oxygen surface diffusion to diffusion of copper through the increasingly gold-rich regions adjacent to the islands.

Journal Article↗
PubMed2004

Multiplexed analysis of polymorphisms in the HLA gene complex using bead array chips.

A novel custom bead array technology is introduced, and it is applied to multiplexed analysis of highly polymorphic human leukocyte antigen (HLA) genetic loci. Our technology combines the construction of probe libraries on color-encoded microparticles (beads) with semiconductor chip processing to produce custom-designed high-density bead array chips in large quantities. Using this novel assay format, two modes of parallel molecular typing of the HLA complex were implemented, namely direct hybridization, illustrated here for class II HLA-DR, and a novel format of on-chip polymerase-mediated primer elongation, illustrated here for class I HLA-A, HLA-B, and HLA-DR using patient and reference cell-line DNA samples. Hybridization-mediated multiplexed analysis of polymorphism method was validated with 142 samples, resulting in 100% concordance with sequence-specific oligonucleotide typing results and a concomitant average of 40% less allele ambiguity. In addition, elongation and hybridization reactions were combined to identify multiple polymorphisms on the same phase of DNA for allele identification.

HLA Antigens↗
PubMed2003

Correlations between cadmium and mineral nutrients in absorption and accumulation in various genotypes of rice under cadmium stress.

The absorption and accumulation of Cd2+, Fe3+, Zn2+, Mn2+, Cu2+ and Mg2+ in the roots and leaves of 20 rice cultivars (Oryza sativa L.) with different genotypes under cadmium (Cd) stress were investigated with pot experiments. The results showed that there existed significant differences among the rice cultivars in the contents of six mineral elements in both roots and leaves at both heading and ripening periods. The statistical analysis showed that, for their contents in roots, significant and positive correlations between Cd2+ and Fe3+, Cd2+ and Zn2+, Cd2+ and Mn2+, Cd2+ and Cu2+ existed, but no significant correlation between Cd2+ and Mg2+, at the two periods. In the leaves, Cd also showed significant and positive correlations with Fe3+, Zn2+ and Cu2+ at the both periods, but a significant and negative correlation with Mn2+ and no significant correlation with Mg2+ at heading, a significant and positive correlation with Mg2+ and no significant correlation with Mn2+ at ripening. These results suggested that there were cooperative absorption between Cd2+ and Fe3+, Mn2+, Cu2+, Mn2+ in rice plants. Genotypic differences in Cd uptake and translocation among the rice cultivars suggested that paddy field of some rice cultivars may be irrigated with partially treated sewage water.

Absorption↗
PubMed2003

Contribution of the gastrointestinal tract below the stomach to the 13C-urea breath test.

BACKGROUND: Graham et al. [Lancet, I (1987) 1174] found a late increase of 13C enrichment in the 13C-urea breath test 120 min after administration of labeled urea to patients without Helicobacter pylori infection. This may give false positive results. AIM: We designed this study to elucidate the contribution of the gastrointestinal tract below the stomach to the 13C-urea breath test. PATIENTS: Twenty-eight patients with dyspeptic symptoms who gave their consent were enrolled. METHODS: Patients underwent the 13C-urea breath tests both via the mouth (as usual) and the duodenum (labeled urea introduced to the second portion). Breath samples were collected at baseline, 5, 15, 30, 45, 60, 90, 120, 150 and 180 min for analysis. H. pylori status was defined by the CLOtest and by histological examination. RESULTS: There was no late increase in 13C enrichment of 13C-urea breath test for eight H. pylori negative patients either via the mouth or the duodenum. For those H. pylori positive patients, seventeen had no late rise 13C enrichment of the 13C-urea breath test via the duodenum and three patients had a rise after 15 min. CONCLUSIONS: No late rise in 13CO2 excretion to cause a positive 13C-urea breath test up to 180 min after the administration of labeled urea was found in the present study.

Adult↗
PubMed2003

Angiogenesis is not mediated by prostate cancer neuropeptides.

Once metastatic, prostate cancer (CaP) treatment options are limited to androgen withdrawal. In this environment, the cells often develop an androgen independent state resulting in patient demise. It has been shown that during this transition, CaP cells transdifferentiate to neuroendocrine cells, which produce neuropeptides. These neuropeptides have a mitogenic effect on surrounding CaP cells. Previous observations suggest that endothelial cells may show a similar mitogenic response to neuropeptides, implicating angiogenesis in the progression of CaP. We stimulated human umbilical endothelial cells (HUVECs) with the neuropeptides bombesin and neurotensin and measured proliferation, migration, cell tube formation, and tyrosine kinase activation. In our studies, neurotensin and bombesin did not stimulate HUVEC proliferation, migration, nor tube formation. Although HUVECs express the non-receptor tyrosine kinases Fak, Src, and Etk which mediate neuropeptide signaling in CaP, they are not activated by neuropeptides in HUVECs.

Blotting, Western↗
PubMed2003

Understanding charge transport in molecular electronics.

For molecular electronics to become a viable technology the factors that control charge transport across a metal-molecule-metal junction need to be elucidated. We use an experimentally simple crossed-wire tunnel junction to interrogate how factors such as metal-molecule coupling, molecular structure, and the choice of metal electrode influence the current-voltage characteristics of a molecular junction.

Computer Simulation↗
PubMed2002

Metal-molecule contacts and charge transport across monomolecular layers: measurement and theory.

Charge transport studies across molecular length scales under symmetric and asymmetric metal-molecule contact conditions using a simple crossed-wire tunnel junction technique are presented. It is demonstrated that oligo(phenylene ethynylene), a conjugated organic molecule, acts like a molecular wire under symmetric contact conditions, but exhibits characteristics of a molecular diode when the connections are asymmetric. To understand this behavior, we have calculated current-voltage (I-V) characteristics using extended Huckel theory coupled with a Green's function approach. The experimentally observed I-V characteristics are in excellent qualitative agreement with the theory.

Journal Article↗
PubMed2001

Signal transduction-mediated regulation of urokinase gene expression in human prostate cancer.

Urokinase-type plasminogen activator (u-PA) contributes to tumor progression in prostate cancer (CaP). We have previously shown that u-PA expression is upregulated through the AP-1 and PEA3 sites and repressed by androgen. However, signaling pathways mediating u-PA gene expression in CaP are not delineated. We hypothesized that MAPK pathways mediate u-PA in CaP, and thereby studied specific ERK, JNK, and P38-MAPK pathway mutant constructs and inhibitors in vitro. Human, androgen insensitive CaP PC3 cells stably transfected with the androgen receptor expression vector and vector alone were used. A u-PA promoter CAT vector transiently expressed with dominant negative mutant signaling constructs was studied. All mutants drastically reduced u-PA promoter activity. Furthermore, inhibition of PI3K, an upstream regulator in the JNK/SAPK pathway, decreased u-PA promoter transcription. Collectively, these results show that MAPK pathways ERK, JNK/SAPK, and P38-MAPK represent a significant component in the regulation of u-PA expression in human CaP.

Androgens↗
PubMed2001

Regulation of u-PA gene expression in human prostate cancer.

u-PA contributes to CaP progression, especially in the metastatic androgen-insensitive state. In vitro, u-PA is expressed by androgen-insensitive, but not androgen-sensitive, CaP cell lines. We hypothesized that in androgen-sensitive CaP an activated ARE represses u-PA expression but in androgen-insensitive CaP this repression is lost and u-PA is upregulated through MAP kinase signaling pathways. To determine whether binding of the DHT-AR complex to AREs in the u-PA promoter region represses u-PA transcription in androgen-sensitive CaP, we studied 2 PC3 androgen-insensitive human CaP cell lines stably transfected with AR [PC3(AR)(2) and PC3(AR)(13)] and 1 mock-transfected cell line [PC3(M)]. In the presence of the synthetic androgen mibolerone, both PC3(AR)(2) and PC3(AR)(13), but not PC3(M), cells showed decreased u-PA expression as assayed by Western and Northern blotting. The AR inhibitor flutamide abrogated mibolerone's effect. Androgen regulation of a second gene, PSA, was also demonstrated in the PC3(AR)(2) cell line. To explore the pathway stimulating u-PA expression in CaP, we performed transient transfections in PC3(AR)(2) cells using u-PA promoter-regulated CAT reporter constructs. Compared to full-length u-PA promoter-CAT constructs, either deletion or mutation of the 5' AP-1 or PEA3 site reduced CAT expression. The location of androgen responsiveness in the u-PA promoter was not identified through the combination of promoter search and transient transfection assays, indicating that a more complicated mechanism is involved in the AR-mediated downmodulation of u-PA expression.

Blotting, Northern↗
PubMed2001

Immunization against endogenous retroviral tumor-associated antigens.

Endogenous retroviral gene products have been found in some human tumors, and therefore, may serve as antigens for immunotherapy approaches. The murine colorectal carcinoma CT26 and melanoma B16 have recently been found to express the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there has been no demonstration of tumor treatment using an endogenous retroviral protein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L(d)-restricted minimal determinant were protected from CT26 tumor challenge. Splenocytes from mice immunized with vaccinia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to investigate the treatment of established CT26 or B16 lung metastases, mice were treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E peptide. Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs. The ability to immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers.

Animals↗
PubMed2001

Cellular characterization of leukotoxin diol-induced mitochondrial dysfunction.

Leukotoxin, a cytochrome P450-derived epoxide of linoleic acid, has been implicated as a causative factor in acute respiratory distress syndrome. Conversion of this fatty acid epoxide to leukotoxin diol by epoxide hydrolase has been hypothesized as the critical activation step in leukotoxin-induced cellular toxicity. In both human and insect cells, we observed that leukotoxin diol causes acute cellular toxicity and that cyclosporin A, an inhibitor of the mitochondrial permeability transition, ameliorates leukotoxin diol-associated toxicity. To evaluate mitochondria as a target of leukotoxin diol, multiple aspects of mitochondrial integrity were evaluated in both cell- and organelle-based assays. Leukotoxin diol specifically activated the mitochondrial permeability transition, resulting in release of cytochrome c and subsequent cell death. Pretreatment with cyclosporin A inhibited these effects and, furthermore, limited in vivo toxicity. While the mechanisms underlying leukotoxin-mediated toxicity remain to be fully elucidated, the observation that leukotoxin diol disrupts mitochondrial function specifically through activation of the mitochondrial permeability transition suggests at least one mechanism through which leukotoxin diol may exert its activity in physiological contexts.

Animals↗
PubMed2001

Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas.

Methodology for identifying tumor-associated antigens recognized by T cells has been successfully used to clone antigens from melanoma cells. Similar efforts for nonmelanoma tumors have had limited success with few antigens identified. To identify potentially relevant tumor-associated antigens expressed in renal cell carcinoma cell lines, a tumor-specific CTL clone was established from tumor-infiltrating lymphocytes from a regressing pulmonary lesion. This CTL recognized nonmutated fibroblast growth factor-5 (FGF-5). Quantitative real-time reverse transcription PCR revealed that FGF-5 was overexpressed in the majority of renal cell carcinomas, as well as in some prostate carcinoma and breast carcinoma lines. FGF-5 expression by quantitative real-time reverse transcription PCR in normal tissues was below the recognition threshold for this CTL. As a normal protein with significant overexpression by multiple adenocarcinomas and little normal tissue expression, FGF-5 represents an immunotherapy target with potential utility against a broad array of nonmelanoma cancers.

Adenocarcinoma↗
PubMed2001

Solution structure of a C-terminal coiled-coil domain from bovine IF(1): the inhibitor protein of F(1) ATPase.

Bovine IF(1) is a basic, 84 amino acid residue protein that inhibits the hydrolytic action of the F(1)F(0) ATP synthase in mitochondria under anaerobic conditions. Its oligomerization state is dependent on pH. At a pH value below 6.5 it forms an active dimer. At higher pH values, two dimers associate to form an inactive tetramer. Here, we present the solution structure of a C-terminal fragment of IF(1) (44-84) containing all five of the histidine residues present in the sequence. Most unusually, the molecule forms an anti-parallel coiled-coil in which three of the five histidine residues occupy key positions at the dimer interface.

Amino Acid Sequence↗
PubMed2001

Serum endostatin levels are elevated in patients with soft tissue sarcoma.

BACKGROUND: Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor-derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma. METHODS: The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age-matched and gender-matched volunteer blood donors. RESULTS: Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log-rank test). CONCLUSIONS: Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study.

Adult↗
PubMed2001

Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice.

The possible analgesic effect of melatonin was investigated in young male ICR mice. The formalin test which elicits typically 2 phases of pain response, the acute (first) phase and tonic (second) phase, was used. The test was performed in the late light period when the mice have been reported to be more sensitive to pain. Compared to control mice, no significant difference in nociceptive response was observed when melatonin was injected intraperitoneally at doses of 0.1, 5, and 20, mg/kg body weight. The combined effects of melatonin with diazepam and/or morphine, were also investigated. Melatonin, injected at 20 mg/kg 15 min before formalin test, significantly increased the antinociceptive response of diazepam (1 mg/kg) or morphine (5 mg/kg) in the second phase. In addition, when melatonin was given at 20 mg/kg together with diazepam and morphine, antinociceptive responses in both the first and second phase were increased. These data indicate the synergistic analgesia effect of melatonin with morphine and diazepam and suggest the possible involvement of melatonin as an adjunct medicine for pain patients.

Analgesics↗
PubMed2001

Effect of mouth washing on the.

BACKGROUND: Mouth washing is often mentioned as a possible method to eliminate the interference of urease activity in the oral cavity before the [13C]-urea breath test (UBT). However, the effectiveness of mouth washing prior to testing has not been demonstrated clearly in the literature. Thus, the present study was designed to examine the consistency of the [13C]-UBT and the effects of mouth washing on it. METHODS: A total of 101 healthy volunteers underwent the [13C]-UBT three times. The first and second tests used a standard protocol and collected samples at 5, 10, 15 and 30 min. In the third test, the procedure was the same except that mouth washing was omitted. RESULTS: We used 5 permil (/1000) as the cut-off value and there were 21 (20.8%) positive cases. The kappa values for the samples collected at 5, 10, 15 and 30 min between the first and second tests were 0.68, 0.97, 1 and 1, respectively, and all showed good consistency, except for the sample collected at 5 min. Judging from the mean value of the [13C] enrichment of the first and second tests (with mouth washing) and the third test (without mouth washing), 50 (63.3%), 15 (18.8%), 0 and 0 cases at 5, 10, 15 and 30 min, respectively, changed from negative to positive. There were 14 (17.5%) and six (7.5%) cases at 15 and 30 min, respectively, whose [13C] enrichment changed from less than 3 (negative) to between 3 and 5 (border zone). CONCLUSIONS: These results indicate that mouth washing had an important effect on samples obtained at 5 and 10 min, while this influence decreased at 15 min and was lowest at 30 min.

Adult↗