Search PubMed⌕ Search

Biomedical subjects

Y Huang

Publications and source records attributed to Y Huang.

At least 361 records · Page 20Linked to original sources
PubMed2000

Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in humans: preliminary analyses.

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT(1A) receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT(1A) antagonist [carbonyl-(11)C]WAY-100635 or [carbonyl-(11)C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexa necarboxamide abbreviated as [(11)C]WAY-100635. Pindolol dose-dependently decreased [(11)C]WAY-100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/- 8% at scan 3, and 44 +/- 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT(1A) receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT(1A) receptors was higher in the DRN compared to cortical regions, demonstrating a significant in vivo selectivity for DRN 5-HT(1A) autoreceptors relative to cortico-limbic postsynaptic receptors. This selectivity is necessary for the potentiation of 5-HT transmission, and this finding represents an important proof of concept in the development of 5-HT(1A) agents for this application. Early evaluation of new drugs with PET imaging will enable rapid screening of compounds based on DRN selectivity and more appropriate determination of doses for clinical trials.

Adult↗
PubMed2000

Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366.

Conversion of a nascent precursor tRNA to a mature functional species is a multipartite process that involves the sequential actions of several processing and modifying enzymes. La is the first protein to interact with pre-tRNAs in eukaryotes. An opal suppressor tRNA served as a functional probe to examine the activities of yeast and human (h)La proteins in this process in fission yeast. An RNA recognition motif and Walker motif in the metazoan-specific C-terminal domain (CTD) of hLa maintain pre-tRNA in an unprocessed state by blocking the 5'-processing site, impeding an early step in the pathway. Faithful phosphorylation of hLa on serine 366 reverses this block and promotes tRNA maturation. The results suggest that regulation of tRNA maturation at the level of RNase P cleavage may occur via phosphorylation of serine 366 of hLa.

Autoantigens↗
PubMed2000

Oxidative stability of conjugated linoleic acid isomers.

Conjugated linoleic acids (CLAs) have been shown to be a strong anticarcinogen in a number of animal models. Our previous study demonstrated that CLA as a whole was extremely unstable in air. The present study was undertaken further to examine the oxidative stability of individual CLA isomers using the combination of gas-liquid chromatography (GLC) and silver ion high-performance liquid chromatography (Ag-HPLC). It was found that CLA as a whole oxidized rapidly and more than 80% was degraded within 110 h in air at 50 degrees C. Four c,c-CLA isomers were most unstable followed by four c,t-CLA isomers. In contrast, four t,t-CLA isomers were relatively stable under the same experimental conditions. Both the oxygen consumption and the GLC analysis revealed that 200 ppm jasmine green tea catechins (GTCs) exhibited protection to CLA and were even stronger than 200 ppm butylated hydroxytoluene (BHT) when added to either CLA or canola oil containing 10% CLA. The present study emphasized that oxidative unstability of CLA should not be overlooked although CLA has many biological effects.

Antioxidants↗
PubMed2000

Intracellular free calcium concentration and cisplatin resistance in human lung adenocarcinoma A549 cells.

Human lung adenocarcinoma A549 cells sensitive and A549/DDP cells resistant to Cis-dichlorodiammine platinum[II] (cisplatin) exhibit different intracellular free calcium and calcium fluorescence images labeled with Fura-2/AM and Fluo-3/AM as judged by dual-excitation fluorescence assay, Miracal Imaging and Laser Scanning Confocal Microscopy (LSCM) of single cells. The concentration of intracellular free calcium of the resistant A549/ DDP cells is one third that of the sensitive A549 cells. The efflux of Rhodamine 123 in resistant A549/DDP cells is faster than that in sensitive A549 cells. In addition, A549/DDP cells have an increase of Phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity in the plasma membrane. So it is tentatively suggested that the increase in PtIns 4-kinase activity resulting from lower intracellular Ca2+ concentration leads to an increase of its enzymatic products--PIP and PIP2, which may stimulate the activity of P-glycoprotein.

1-Phosphatidylinositol 4-Kinase↗
PubMed2000

Changes of transmembrane Ca2+ gradient in the formation of macrophage-derived foam cells.

Macrophages from C57BL/6J mice, an animal susceptible to atherosclerosis, were chosen as target cells to study changes in the transmembrane Ca2+ gradient during the formation of macrophage-derived foam cells. The transmembrane Ca2+ gradients of single living cells were examined-using Fura-2/AM combined with Fluo-3/AM by laser scanning confocal microscopy. Exposure to Oxidized Low Density Lipoprotein, decreases the Ca2+ gradient across macrophage plasma membrane, but increases that across the nuclear membrane. The altered transmembrane Ca2+ gradients could induce the up-regulation of scavenger receptor in macrophages, resulting in the formation of foam cells.

Animals↗
PubMed2000

Regulation of phospholipase D from human hepatocarcinoma cell line by purine nucleotides and protein kinase A.

The regulation of phosphatidylcholine-specific phospholipase D by purine nucleotides and protein kinase A were studied in vitro using an enzyme preparation partially purified from the membranous fraction of 7721 hepatocarcinoma cells. It was found that the enzyme activity was elevated by low concentrations of some purine nucleotides, but the activating effects were decreased when the concentrations of the nucleotides were higher. The optimal concentrations of GTP, GTPgamma[S], GDP and ATP for maximal activation were 0.1 mM, 5 microM, 1 mM and 1 mM respectively. The activation caused by 1 mM ADP was lower. The enzyme was not activated by 1 mM AMP, but significant activation was observed by the addition of 1 mM cAMP. The latter was mediated by protein kinase A, as a specific inhibitor of protein kinase A abolished the activation. There were synergic effects between ATP and GTP, ATP and PIP2, but not between ATP and GTPgamma[S], or PIP2 and GTPgamma[S]. The activating effects of GTP and ATP were abolished by neomycin, a PIP2 scavenger. These results suggest that phospholipase D is regulated by GTP-binding protein and the presence of PIP2 is required for the activation induced by GTP. Protein kinase A may be another protein kinase in addition to protein kinase C and protein tyrosine kinase which regulate the activity of phospholipase D, when the intracellular concentration of cAMP is increased.

Adenine Nucleotides↗
PubMed2000

Study on the relationship between calcium-induced calcium release from mitochondria and PTP opening.

The permeability transition pore (PTP) is central for mitochondria function. PTP either open in low-conductance state to carry out mCICR (Ca2+-induced Ca2+ release from mitochondria) and play roles in cell phsyiological activities or open in high-conductance conformation to release harmful substances and play important roles in cell pathological responses and apoptosis. The results of study on the relationship between mCICR and PTP opening show Ca2+ concentrations but not the Ca2+ delivery mode determined the occurrence of mCICR or PTP opening. Ca2+-induced PTP opening began with and depended on mCICR. mCICR was a prerequisite for H2O2 and As2O3-induced PTP opening. The results indicated that the PTP opening was determined by Ca2+ stimulation intensity but not mode. PTP could switch from low- to high-conductance conformation and the PTP open by high-conductance began with low-conductance state. mCICR is necessary for Ca2+-dependent PTP opening. Our data suggested also that it would be possible to control cellular responses first by modulating mCICR, then by regulating PTP opening.

Animals↗
PubMed2000

Modulation of the basal activity of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in human hepatocarcinoma cells.

The modulation of GnT-V activity by signaling molecules in PI-3-K/PKB pathway in human hepatocarcinoma cell line 7721 was studied. GnT-V activity was determined after the transfection of sense or antisense cDNA of PKB into the cells, as well as the addition of activators, specific inhibitors, and the antibodies to the enzyme assay system or culture medium. It was found that the basal activity of GnT-V was up regulated by the sense and down regulated by the antisense cDNA of PKB transfected into 7721 cells. GnT-V was activated by PIP2, PIP3 or GTPgamma[S] added to the assay system, and the activation of PIP2 or GTPgamma[S] was abolished by LY2940002, a specific inhibitor of PI-3-K, but the activation of PIP3 was not attenuated by LY2940002. In addition, GnT-V activity in cultured parental or H-ras transfected cells was inhibited by the antibody against PKB or PI-3-K. These findings demonstrated the involvement of PI-3-K/PKB signaling pathway in the regulation of GnT-V. Moreover, ET18-OCH3, an inhibitor of Raf translocation and PI-PLC enzyme, which produces the activator of PKC, as well as the antibodies against Raf-1 or MEK also inhibited GnT-V activity in the parental and H-ras transfected cells. The inhibitory rates, however, were less in the transfected cells than those in the parental cells. These results reveal that in parental and H-ras transfected 7721 cells, the basal activity of GnT-V is also regulated by the Ras/Raf-1/MEK/MAPK cascade in addition to PI-3-K/PKB signaling pathway. The significance of these two pathways in the regulation of GnT-V and their relations to the activation of PKC previously reported by our laboratory (Ju TZ et al., 1995 Glyconjugate J 12, 767-772) was discussed.

Antibodies, Monoclonal↗
PubMed2000

Emerging homosexual conduct during hospitalization among chronic schizophrenia patients.

OBJECTIVE: The study investigated the emerging homosexual conduct during hospitalization among chronic schizophrenia patients. METHOD: We interviewed 55 male and 58 female chronic schizophrenic patients to investigate their sexual history before and after admission. Those patients were under 45 years old, without significant deteriorated cognitive function, lived in a homogeneous gender chronic ward and did not demonstrate homosexual behaviour before admission. RESULTS: Nineteen patients (16.8%) reported having homosexual conducts during hospitalization. Their characteristics were: 1) having sexual experience before admission; 2) with younger age at first sexual experience; and 3) female patients having more sexual partners before admission. CONCLUSION: A significant proportion of patients need a sexual outlet during long-term hospitalization. Sexual education and counselling are greatly needed.

Adult↗
PubMed2000

Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.

Recent studies showed that arsenic trioxide (As2O3) could induce apoptosis and partial differentiation of leukemic promyelocytes. Here, we addressed the possible mechanisms underlying these two different effects. 1.0 microM As2O3-induced apoptosis was associated with condensation of the mitochondrial matrix, disruption of mitochondrial transmembrane potentials (DeltaPsim) and activation of caspase-3 in acute promyelocytic leukemia (APL) cells regardless of their sensitivity to all-trans retinoic acid (ATRA). All these effects were inhibited by dithiothreitol (DTT) and enhanced by buthionine sulfoximine (BSO). Furthermore, BSO could also render HL60 and U937 cells, which had the higher cellular catalase activity, sensitive to As2O3-induced apoptosis. Surprisingly, 1.0 microM As2O3 did not induce the DeltaPsim collapse and apoptosis, while 0.1 microM As2O3 induced partial differentiation of fresh BM cells from a de novo APL patient. In this study, we also showed that 0.2 mM DTT did not block low-dose As2O3-induced NB4 cell differentiation, and 0. 10.5 microM As2O3 did not induce differentiation of ATRA-resistant NB4-derived sublines, which were confirmed by cytomorphology, expression of CD11b, CD33 and CD14 as well as NBT reduction. Another interesting finding was that 0.10.5 microM As2O3 could also induce differentiation-related changes in ATRA-sensitive HL60 cells. However, the differentiation-inducing effect could not be seen in ATRA-resistant HL60 sublines with RARalpha mutation. Moreover, low-dose As2O3 and ATRA yielded similar gene expression profiles in APL cells. These results encouraged us to hypothesize that As2O3 induces APL cell differentiation through direct or indirect activation of retinoic acid receptor-related signaling pathway(s), while DeltaPsim collapse is the common mechanism of As2O3-induced apoptosis.

Antineoplastic Agents↗
PubMed2000

Mouse xenoantigens contribute to rat T-cell Vbeta repertoire generation in mixed xenogeneic bone marrow chimeras.

We previously demonstrated that rat bone-marrow-derived cells in mixed xenogeneic chimeras (rat + mouse --> mouse) contribute to peripheral selection of mouse T-cell receptor (TCR) variable betas (Vbetas) repertoire. In this study, we analysed rat T cells that developed in the chimeras to assess the contribution of mouse xenoantigens to the development of rat TCR repertoire. The expression of rat Vbetas was analysed using flow cytometry and a reverse transcription-polymerase chain reaction (RT-PCR) method that allows for both semiquantitative analysis of rat Vbeta gene expression and size heterogeneity of the complementarity determining region 3 (CDR3) domain. Three distinct patterns of Vbeta expression were detected. Partial deletion was observed for Vbeta5, 7, 12, 14, 16, 17 and 20 that exhibited reduced levels of peripheral expression by 3.4-, 1.8-, 8.7-, 2.0-, 7.8-, 9.5- and 1.8-fold, respectively, compared with the levels of Vbetas in naYve rats. Higher levels of peripheral expression were detected for three rat Vbeta genes; Vbeta6 (2.2-fold), Vbeta8.2 (3.2-fold), and Vbeta9 (1.7-fold). The relative expression of the other 10 known rat Vbeta families in chimeras was unchanged as compared with that of normal rats. We did not observe detectable changes in the pattern of CDR3 expression in chimeras, suggesting that the mouse xenogeneic environment exerted its influence on the development of rat T cells via the Vbeta-encoded CDR1/2 domains. Our data demonstrate that the rat T-cell repertoire in chimeras is shaped by both contractions as well as expansions of selected Vbetas and suggest that mouse xenoantigens and/or superantigens of endogenous mouse retroviruses may contribute as ligands for these selection processes

Animals↗
PubMed2000

Two independent pathways of maternal cell transmission to offspring: through placenta during pregnancy and by breast-feeding after birth.

Cell transmission from mother to offspring was demonstrated using mice with green fluorescent protein (GFP) transgenic markers. GFP transgene heterozygous (+/-) females were mated with GFP (-/-) males, and GFP(+) cells in the GFP (-/-) fetuses generated between them were analysed to assess maternal blood cell transmission to conceptuses in utero. The GFP+ maternal cells were observed throughout the body of the fetuses, as shown by fluorescence stereomicroscopy. Cell entrance into the fetal immune system was shown by histochemical and flow cytometric analyses of fetal organs such as thymus, spleen and liver. The GFP(+) maternal cells persisted in the offspring until postpartum. Next, GFP (-/-) neonates fed by GFP(+) foster mothers were examined to study the transfer of maternal milk leucocytes to offspring through breast-feeding. GFP(+) leucocytes that had infiltrated through the wall of the digestive tract were mainly localized in the livers of neonates. Their accumulation in the livers reached a maximum on days 5 or 6, and these cells became undetectable, as assessed by either histochemistry or flow cytometry, after day 9 of starting foster nursing. Collectively, the present results demonstrate two independent pathways of maternal cell transmission to offspring: transplacental passage during pregnancy and breast-feeding after birth.

Animals↗
PubMed2000

Factors associated with nocturnal hypoglycaemia among patients with type 2 diabetes new to insulin therapy: experience with insulin lispro.

AIM: To identify factors associated with nocturnal hypoglycaemia in patients with type 2 diabetes who were new (< 2 months therapy) to insulin therapy. METHODS: A randomised, multicentre, 12-month parallel open-label study compared the clinical safety and efficacy of insulin lispro with regular human insulin. A cohort of North American patients completed a health-related quality of life (HRQOL) questionnaire which included questions related to the Health Beliefs Model (HBM). Measurements of hypoglycaemia rate and short-and long-term glucose control assessed clinical safety and efficacy. Three hundred and sixty-five type 2 diabetic patients were enrolled in the study, and 195 North American patients completed the HRQOL questionnaire. RESULTS: After adjustment for demographic and psychological factors, the study population demonstrated lower nocturnal hypoglycaemia risk with insulin lispro. Higher nocturnal hypoglycaemia risk was associated with reduced body mass index (b.m.i.), lower age, and basal ultralente insulin therapy. The associated hypoglycaemia risk was lower with increased alcohol consumption. Patients who completed the HRQOL survey demonstrated higher risk for nocturnal hypoglycaemia if they: (1) had more troublesome hyperglycaemia symptoms in the week before starting insulin; (2) were more confident in their ability to control their diabetes; or (3) thought that diabetes control did not offer a clear health benefit. Nocturnal hypoglycaemia risk was inversely associated with fear of hypoglycaemia. CONCLUSIONS: Type 2 diabetic patients new to insulin therapy demonstrated lower risk of nocturnal hypoglycaemia with insulin lispro. Practitioners should consider patient characteristics and psychological factors that may predispose type 2 diabetes patients to nocturnal hypoglycaemia when initiating insulin therapy.

Aged↗
PubMed2000

Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection.

T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

Acute Disease↗
PubMed2000

A protein kinase G-sensitive channel mediates flow-induced Ca(2+) entry into vascular endothelial cells.

The hemodynamic force generated by blood flow is considered to be the physiologically most important stimulus for the release of nitric oxide (NO) and prostacyclin (PGI(2)) from vascular endothelial cells (1). NO and PGI(2) then act on the underlying smooth muscle cells, causing vasodilation and thus lowering blood pressure (2, 3). One critical early event occurring in this flow-induced regulation of vascular tone is that blood flow induces Ca(2+) entry into vascular endothelial cells, which in turn leads to the formation of NO (4, 5). Here we report a mechanosensitive Ca(2+)-permeable channel in vascular endothelial cells. The activity of the channel was inhibited by 8-Br-cGMP, a membrane-permeant activator of protein kinase G (PKG), in cell-attached membrane patches. The inhibition could be reversed by PKG inhibitor KT5823 or H-8. A direct application of active PKG in inside-out patches blocked the channel activity. Gd(3+), Ni(2+), or SK&F-96365 also inhibited the channel activity. A study of fluorescent Ca(2+) entry revealed a striking pharmacological similarity between the Ca(2+) entry elicited by flow and the mechanosensitive Ca(2+)-permeable channel we identified, suggesting that this channel is the primary pathway mediating flow-induced Ca(2+) entry into vascular endothelial cells.

Alkaloids↗
PubMed2000

Potentiating effects on contractions by purified baicalin and baicalein in the rat mesenteric artery.

The effects of purified baicalin and baicalein from the traditional Chinese herb, Huangqin, on contractions induced by phenylephrine, U46619, and high extracellular K+ were investigated in isolated rat mesenteric arteries. Both baicalin (1-100 microM) and baicalein (1-50 microM) potentiated the contractile response to phenylephrine in a concentration-related manner. Both flavonoids (10 microM) also enhanced the U46619- or 40 mM K+-induced contractions. Baicalein (100-300 microM) reduced the phenylephrine-induced tone. Prazosin at 1 microM did not affect U46619-induced contraction in the absence and presence of baicalein or baicalin. Neither baicalin (1-100 microM) nor baicalein (1-100 microM) affected the basal tension. Removal of the functional endothelium abolished the potentiating effects of baicalin and baicalein in arteries preconstricted by both constrictors. Pretreatment of endothelium-intact rings with 100 microM N(G)-nitro-L-arginine also potentiated phenylephrine- or U46619-induced contraction but completely inhibited the effects of baicalin and baicalein. Pretreatment with 1 mM L-arginine reversed the enhancing effect of baicalin but not of baicalein on phenylephrine-evoked contraction. Pretreatment with 10 microM baicalin or 10 microM baicalein significantly reduced the endothelium-dependent relaxation induced by acetylcholine or ionomycin. These results indicate that both baicalin and baicalein potentiated the evoked contractile response, likely through inhibition of nitric oxide formation and/or release in the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Sixty-four cases of thumb and finger reconstruction using transplantation of the big toe skin-nail flap combined with the second toe or the second and third toes.

The purpose of this article is to introduce the results of thumb and finger reconstruction using transplantation of the big toe wraparound flap combined with the second toe or the second and third toes. Between August of 1981 and December of 1998, in a series of 64 cases involving 58 patients with digitless hands, either (1) the thumb and index fingers were reconstructed by transplantation of a big toe wraparound flap combined with the adjacent second toe harvested from the ipsilateral foot; or (2) the thumb, index, and long fingers were reconstructed by transplantation of an ipsilateral big toe wraparound flap combined with the adjacent second and third toes. The phalanx of the new thumb was usually an iliac block. The success rate of this series was 92.2 percent. At long-term follow-up, the average static 2-point discrimination was less than 10 mm. The distance between the tip of the new thumb and the new index finger ranged from 6 to 10 cm (average, 8 cm). Opposition action was nimble and forceful. The patients could lift a 6- to 12-kg weight with their reconstructed digits. All patients were satisfied with their new hands and were able to use them in their daily activities. The transplants for reconstructing the thumb and fingers are harvested from the same foot in a procedure known as one-foot donation. Function of the bilateral digitless hand can be recovered with this procedure.

Adolescent↗