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Biomedical subjects

H Yi

Publications and source records attributed to H Yi.

At least 19 recordsLinked to original sources

Presence of functional mouse regulatory CD4+CD25+T cells in xenogeneic neonatal porcine thymus-grafted athymic mice.

Xenotransplantation with porcine thymus is emerging as a possible means to reconstitute host cellular immunity and to induce immune tolerance in rodents and large animals. However, the presence of regulatory T cells (Treg cells) in this model needs to be determined. We herein demonstrated that efficient repopulation of mouse CD4+CD25+Treg cells was achieved in Balb/c nude mice by grafting neonatal porcine thymic tissue (NP THY). Mouse CD4+CD25+T cells expressed normal levels of Foxp3 in NP THY-grafted nude mice. Furthermore, these CD4+CD25+Treg cells showed significant inhibitory effects on the cell proliferation or interleukin-2 products of syngeneic T cells to alloantigens, Con A or a peptide antigen, although the potent immunosuppressive function might be lower than CD4+CD25+Treg cells in Balb/c mice. CD4+CD25+T cells in NP THY-grafted nude mice showed significantly stronger inhibition on the response to donor porcine antigens of CD4+CD25(-)T cells than CD4+CD25+Treg cells in Balb/c mice. Both CD4+CD25+Treg cells in NP THY-grafted nude and Balb/c mice prevented the development of autoimmune disease mediated by syngeneic CD4+CD25(-)T cells in a similar efficient way in the secondary recipients. These findings provide evidence for the potential involvement of CD4+CD25+Treg cells in keeping self-tolerance and transplant tolerance in this xeno-thymus transplantation model.

Animals↗

Neuromelanin induces oxidative stress in mitochondria through release of iron: mechanism behind the inhibition of 26S proteasome.

Parkinson's disease is characterized by the selective depletion of dopamine neurons in the substantia nigra, particular those containing neuromelanin. Involvement of neuromelanin in the pathogenesis may be either cytotoxic or protective. Recently we found that neuromelanin reduces the activity of 26S proteasome. In this paper, the detailed mechanisms behind the reduced activity were studied using neuromelanin isolated from the human brain. Neuromelanin increased the oxidative stress, but synthetic melanin did not. Superoxide dismutase and deferoxamine completely suppressed the increase, indicating that superoxide produced by an iron-mediated reaction plays a central role. Iron was shown to reduce in situ 26S proteasome activity in SH-SY5Y cells and the reduction was protected by antioxidants. These results suggest that iron released from neuromelanin increases oxidative stress in mitochondria, and then causes mitochondrial dysfunction and reduces proteasome function. The role of neuromelanin is discussed in relation to the selective vulnerability of dopamine neurons in Parkinson's disease.

Acrolein↗

Overexpression of amyloid precursor protein induces susceptibility to oxidative stress in human neuroblastoma SH-SY5Y cells.

In Alzheimer's disease amyloid beta peptide (Abeta) produced from amyloid precursor protein (APP) is considered to induce cell death. To clarify the molecular mechanism underlying Abeta neurotoxicity, we established the cell line overexpressing wild or mutant (His684Arg) APP in human SH-SY5Y cells. This paper presents that overexpression of wild-APP in the cells (SH/w-APP) increased the levels of APP and Abeta(1-40) but not Abeta(1-42), and reduced Bcl-2 level and proteasome activity with increased susceptibility to oxidative stress. The intracellular levels of reactive oxygen species in SH/w-APP increased significantly by H(2)O(2) treatment. The level of Bcl-2 protein, but not mRNA, was markedly decreased in SH/w-APP cells, which was inversely correlated with APP expression among subcloned SH/w-APP cells. These results indicate that increased expression of wild type APP renders neuronal cells more vulnerable to oxidative stress leading to cell death.

Alzheimer Disease↗

N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial membrane and induction of anti-apoptotic Bcl-2.

Propargylamine derivatives, rasagiline and (-)deprenyl, are anti-Parkinson agents and protect neurons from cell death as shown by in vivo and in vitro experiments. The studies on the chemical structure-activity relationship proved that the propargyl moiety is essentially required for the neuroprotective function. In this paper, neuroprotective activity of free N-propargylamine was studied using SH-SY5Y cells expressing only type A monoamine oxidase (MAO) against apoptosis induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. N-Propargylamine prevented apoptosis, whereas N-methylpropargylamine and propiolaldehyde did not. N-Propargylamine stabilized mitochondrial membrane potential and induced anti-apoptotic Bcl-2 at 1 microM-10 nM. N-Propargylamine inhibited MAO-A in competition to substrate with the apparent K(i) value of 28 microM, which was significantly higher than the concentration required for neuroprotection. It indicates that MAO inhibition is not prerequisite for the protective function of N-propargylamine. The anti-apoptotic function of N-propargylamine is discussed in terms of neuroprotection by propargylamines in neurodegenerative diseases, including Parkinson's disease.

Apoptosis↗

An emerging HIV risk environment: a preliminary epidemiological profile of an MSM POZ Party in New York City.

OBJECTIVE: To develop a preliminary epidemiological description of a men who have sex with men (MSM) "POZ Party," an emerging sex environment for HIV+ MSM. METHODS: As part of a pilot study in New York City in 2003, data were collected using a brief, behavioural intercept survey at entry to POZ Party events. Domains include demographic characteristics, history of HIV infection, motivations for attending POZ parties, lifetime and recent exposure to drugs (including use during POZ Party events), and recent sexual practices (both within both POZ Party venues as well as in non-POZ Party venues). RESULTS: Predominantly white and over the age of 30, subjects in the sample include a broad range of years living with HIV infection. Motivations for using a POZ Party venue for sexual partnering include relief from burdens for serostatus disclosure, an interest in not infecting others, and opportunities for unprotected sexual exchange. High rates of unprotected sex with multiple partners are prevalent in the venue. Although the sample evidences high rates of lifetime exposure to illicit drugs, relatively little drug use was reported in these sexual environments. These reports are consistent with evidence from direct observation at the venues themselves, in which no drug use was apparent. CONCLUSION: Serosorting among HIV+ MSM may reduce new HIV infections, a stated interest of both POZ Party organisers and participants alike. However, high rates of unprotected anal intercourse within these venues signal continued risk for STIs. Additionally, unprotected sexual contact with HIV partners and status unknown partners outside POZ Party venues heightens concern for diffusion of HIV superinfection.

Adult↗

Search for pi(0)-->nu(mu)nu(mu) decays in the LSND detector.

We observe a net beam excess of 8.7+/-6.3(stat)+/-2.4(syst) events, above 160 MeV, resulting from the charged-current reaction of nu(micro) and/or nu;(mu) on C and H in the LSND detector. No beam-related muon background is expected in this energy regime. Within an analysis framework of pi(0)-->nu(mu)nu;(mu), we set a direct upper limit for this branching ratio of Gamma(pi(0)-->nu(mu)nu;(mu))/Gamma(pi(0)-->all)<1.6 x 10(-6) at 90% confidence level.

Journal Article↗

Spontaneous N incorporation onto a Si(100) surface.

Initial nitridation of the Si(100) surface is investigated using photoemission, ion-scattering and ab initio calculations. After dissociation of NO or NH3, nitrogen atoms are found to spontaneously form a stable, highly coordinated N[triple bond]Si(3) species even at room temperature. The majority of the N species is incorporated into the subsurface Si layers occupying an interstitial site, whose atomic structure and unique bonding mechanism is clarified through ab initio calculations. This unusual adsorption behavior elucidates the atomistic mechanism of initial silicon nitride formation on the surface and has important implication on the N-rich layer formation at the SiO(x)N(y)/Si interface.

Journal Article↗

Mitochondria determine the survival and death in apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, and neuroprotection by propargylamines.

In neurodegenerative disorders, such as Parkinson's disease, selective neuronal death characterizes clinical signs and symptoms. Recently apoptosis was reported to be a common type of cell death in some disorders, and well-controlled apoptotic cascade is proposed to be a target of neuroprotective therapy. In our studies to find endogenous neurotoxins as a pathogenic factor in Parkinson's disease, dopamine-derived N-methyl(R)salsolinol was found to induce apoptosis in dopamine neurons of rat models of Parkinson's disease. In human dopaminergic SH-SY5Y cells, apoptosis was initiated by decline in mitochondrial membrane potential, and anti-apoptotic Bcl-2 family protein regulated apoptotic signal transduction. In addition, a series of propargylamines were found to prevent apoptosis through stabilization of mitochondrial membrane potential, which also involved Bcl-2. The role of mitochondria and the involvement of Bcl-2 in apoptosis and neuroprotection were clearly demonstrated using isolated mitochondria. These results indicate that mitochondria are the site to determine the cell death induced by neurotoxins and also the neuroprotection by anti-apoptotic propargylamines.

Alkynes↗

Selective nitration of mitochondrial complex I by peroxynitrite: involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cells.

3-Nitrotyrosine (3-NT) is a specific marker of protein nitration by peroxynitrite (ONOO-) produced from nitric oxide and superoxide. Increase in 3-NT containing protein (3-NT protein) was reported in brains from patients with some neurodegenerative disorders and aging. In this paper, intracellular localization of 3-NT protein was examined in dopaminergic SH-SY5Y cells using the selective antibody against protein-bound 3-NT. 3-NT protein was detected in plasma membrane/nucleus and mitochondria fractions, and interestingly in polypeptide composition of mitochondrial complex I. ONOO--generating SIN-1 induced apoptotic cell death with concomitant increase in 3-NT protein and reduction in mitochondrial ATP synthesis. In addition, an inhibitor of proteasomes, carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal, enhanced the effects of ONOO-. These results suggest that ONOO- may induce mitochondrial dysfunction and cell death in neurons through nitration of mitochondrial complex I subunits.

Adenosine Triphosphate↗

Usefulness of silicone plate for sellar floor reconstruction.

During the transsphenoidal approach (TSA), the proper sellar floor reconstruction plays an important role in the surgical results. The authors have evaluated the usefulness of a silicone as a substitute for bone splint in sellar floor reconstruction. Silicone plates were used in 10 patients who had 7 pituitary adenomas, 2 Rathke's cleft cysts, and 1 metastatic tumor. Among the ten cases, seven underwent standard TSAs and three received extended TSAs. The silicone plate was cut to a size slightly larger than that of bone window, inserted with a three-pronged fork, and then adjusted precisely. In nine patients, complications that related to surgical repair did not occur. A postoperative cerebrospinal fluid (CSF) rhinorrhea occurred in one pituitary macroadenoma, and no infection was observed in any case. From the authors' experience, advantages of the silicone plate are its simplicity to shape for any size of defects, and the easy detectability of the previous bone window at reoperation.

Adult↗

Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen involved in angiogenesis, wound healing, and inflammation. METHODS: Rats placed on low salt diet (LSD) or normal salt diet (NSD) were treated with cyclosporine (CsA) or vehicle (VH) and killed at 7 or 28 days. We studied the expression of VEGF and its receptors Flt-1 and KDR/Flk-1 mRNA by Northern and that of VEGF protein by Western blot. RESULTS: CsA induced VEGF mRNA and protein expressions at 7 and 28 days in LSD rats. At 7 days, CsA up-regulated the expression of Flt-1 and KDR/Flk-1 receptors; however, at 28 days, Flt-1 remained unchanged whereas KDR/Flk-1 expression declined. In NSD rats, in which the lesion did not develop, the expression of VEGF and its receptors remained similar to control. CONCLUSIONS: What causes VEGF to be up-regulated remains unclear. Further studies are needed to study the role of hypoxia and other cytokines in relation to VEGF in this model.

Animals↗

[Study on telomerase activity and its clinical value in human non small cell lung cancer].

OBJECTIVE: To investigate telomerase activity and its clinical value in human non small cell lung cancer. METHODS: Using the method of TRAP-PCR-ELISA, we measured telomerase activity in human non small cell lung cancerous, adjacent, lung benign lesion, and normal lung tissues. RESULTS: The positive rate of telomerase activity was 75%(27/36) in lung cancerous tissues; 6.25%(2/32) in adjacent tissues; 11.1%(1/9) in lung benign lesion tissues; and 0%(0/9) in normal lung tissues. There was no significant difference in telomerase activity among the pathological type, the degree of tissue differentiation, the size of tumor, lymph node metastasis, and clinical stage in the patients with lung cancer. CONCLUSION: The telomerase activity may become an important molecular marker in the diagnosis and differential diagnosis of human non small cell lung cancer.

Adult↗

[Telomerase activity in bladder cancer tissues].

OBJECTIVE: To study the correlation between telomerase and bladder cancer. METHODS: The telomerase activity was detected by telomerase PCR ELISA in 41 cases of bladder cancer tissues and 23 cases of non-cancerous bladder tissues. RESULTS: The telomerase activity was positive in 34 cases of bladder cancer tissues (82.9%) and 1 case of non-cancerous tissues (4.3%); the difference of positive rate was significant (P < 0.01). CONCLUSIONS: Telomerase activity is related with bladder cancer closely; telomerase activation may be an important molecular step in the initiation and development of bladder cancer; telomerase may be an excellent molecular biomarker in finding bladder cancer at an early stage and in postoperative following-up.

Adult↗

Voltammetric determination of cadmium(II) using a chemically modified electrode.

An 1-(pyridylazo)-2-naphthol modified glassy carbon electrode has been investigated as sensor for the measurement of trace levels of Cd2+. Cd2+ is deposited on the surface of a PAN modified glassy carbon electrode at -1.10 V (vs. SCE) via forming Cd2+-PAN and subsequent reduction at the electrode. In the following step, Cd-PAN is oxidized, and voltammograms are recorded by scanning the potential in a positive direction. Calibration plots were found to be linear in the range 2 x 10(-8) mol/L to 8 x 10(-7) mol/L. The detection limit was 5 x 10(-10) mol/L, and the coefficient of variation, determined on one single electrode at a concentration of 5 x 10(-7) mol/L, was calculated to be 3.2% (n = 5). Using this new kind of modified electrode, trace levels of Cd(II) in water samples were determined; the average recovery was calculated to be 98.78%.

Cadmium↗

Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4-reductase.

Many plant species exhibit a reduced range of flower colors due to the lack of an essential gene or to the substrate specificity of a biosynthetic enzyme. Petunia does not produce orange flowers because dihydroflavonol 4-reductase (DFR) from this species, an enzyme involved in anthocyanin biosynthesis, inefficiently reduces dihydrokaempferol, the precursor to orange pelargonidin-type anthocyanins. The substrate specificity of DFR, however, has not been investigated at the molecular level. By analyzing chimeric DFRs of Petunia and Gerbera, we identified a region that determines the substrate specificity of DFR. Furthermore, by changing a single amino acid in this presumed substrate-binding region, we developed a DFR enzyme that preferentially reduces dihydrokaempferol. Our results imply that the substrate specificity of DFR can be altered by minor changes in DFR.

Alcohol Oxidoreductases↗

A novel procedure for pre-embedding double immunogold-silver labeling at the ultrastructural level.

Pre-embedding double immunogold-silver labeling using two ultrasmall gold conjugates has not been attempted previously because a means of distinguishing labels by conjugates of identical sizes was lacking. This study investigated the feasibility of creating a particle size segregation between two ultrasmall gold conjugates through sequential immunogold incubations and silver enhancements. Two primary antibodies, mouse anti-synaptophysin and rabbit anti-glial fibrillary acidic protein (GFAP), were used in the model system. Differentiation of the double labeling was achieved by incubating with one ultrasmall gold conjugate, followed by silver enhancement, and then incubating with the second ultrasmall gold conjugate, followed by additional silver enhancement. This resulted in two groups of silver-enhanced particles: smaller particles enhanced once and larger particles enhanced twice. Electron microscopic examination revealed two readily distinguished populations of gold-silver particles within the appropriate structures, with very little size overlap. The quality of the ultrastructure permitted identification of most subcellular organelles. This procedure provides for the first time a pre-embedding immunogold-silver labeling protocol that allows the precise subcellular co-localization of multiple antigens.

Animals↗