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Biomedical subjects

X Y Yang

Publications and source records attributed to X Y Yang.

At least 19 recordsLinked to original sources

Over-expression of a flower-specific transcription factor gene AtMYB24 causes aberrant anther development.

In plants, MYB transcription factors play important roles in many developmental processes and various defense responses. AtMYB24, as a member of R2R3-MYB gene family in Arabidopsis, was found mainly expressed in flowers, especially in microspores and ovules using Northern blots and in situ hybridization. It was further found that the expression of AtMYB24 was tightly regulated during anther development. Over-expression of AtMYB24 in transgenic plants resulted in pleiotropic phenotypes, including dwarfism and flower development defects, in particular, producing abnormal pollen grains and non-dehiscence anthers. Further analysis showed that the anther development of the AtMYB24-ox lines was retarded starting from the anther developmental stages 10-11. At stages 12 and 13, the septum and stomium cells of anthers would not break, and fewer or no fibrous bands were found in the endothecium and connective cells in the AtMYB24-ox plants. Similar aberrant anther phenotype was also observed in the AtMYB24-GR-ox lines treated with dexamethasone (DEX). Quantitative real-time PCR showed expression of genes involved in phenylpropanoid biosynthetic pathway, such as CHS and DFR, and AtGTP2 were altered in AtMYB24-ox lines. These results suggest an important role of AtMYB24 in the normal development of anthers in Arabidopsis.

Amino Acid Sequence↗

Thermal characteristics of microwave ablation in the vicinity of an arterial bifurcation.

PURPOSE: The objective of this research was to reveal the thermal characteristics of microwave ablations in the vicinity of an arterial bifurcation. METHODS: The temperature distribution after microwave heating of a liver-like material in the close proximity of an arterial bifurcation was simulated using the finite element method. Coupled fluid flow and solid heat transfer were taken into consideration and a three-dimensional analysis was performed. An experimentally determined SAR (specific absorption rate) generated by the absorption of microwaves in liver-like material was used in the analysis instead of utilizing electromagnetic calculations. Several different tests of time-controlled ablations with varying distances between the microwave antenna and the bifurcation were performed and detailed temperature distributions near the bifurcation were obtained. RESULTS: The interaction between the recirculation flow in the bifurcation and the heat transfer in the surrounding tissue makes the temperature distribution near the bifurcation complicated. Most importantly, after a period of continuous heating with constant microwave output power, the maximum temperatures caused by the ablation did not always increase with the distance between the antenna and the bifurcation. CONCLUSION: It can be concluded that inadequate ablations can be the result not only from a close proximity between the antenna and the blood vessel, but also from a complicated blood flow in large vessels whose structure causes recirculation flow.

Arteries↗

Diagnosis and management of uterine arteriovenous fistulas with massive vaginal bleeding.

OBJECTIVE: To study the clinical manifestations, diagnosis, management, and prognosis of uterine arteriovenous fistulas with massive vaginal bleeding. METHODS: The clinical records of 15 patients who satisfied the diagnostic criteria were retrospectively analyzed. RESULTS: All patients had massive vaginal bleeding and a history of cesarean section, curettage, or gynecologic carcinoma. The disease was diagnosed by angiography or color Doppler ultrasonography. Vaginal bleeding can be aggravated by dilation and curettage. No complications occurred in the 14 patients who were treated with uterine artery embolization. Of the 11 patients who underwent successful embolizations, all returned to a normal menstrual cycle and 5 later became pregnant. CONCLUSION: Uterine arteriovenous fistula is a rare and potentially life-threatening condition. Uterine artery embolization is a safe and effective choice of treatment for this condition, and it can preserve both uterus and ovary function.

Adult↗

Emergency craniotomy in patients with intracranial metastatic gestational trophoblastic tumor.

OBJECTIVE: To study the diagnosis, management and prognosis of intracranial metastases of gestational trophoblastic tumor (GTT) patients who had emergency craniotomy. METHODS: Sixty three intracranial metastases of GTT patients were hospitalized in Peking Union Medical College Hospital from 1985 to 2004. Thirteen of them had craniotomy that were retrospectively analyzed and all of them had a feature of raised intracranial pressure followed by intracranial hemorrhagic mass. RESULTS: Of the thirteen patients who had undergone surgery combined with multiagent chemotherapy, seven got complete remission (CR), five got partial remission (PR), and one died of progress of the disease (PD). There were three patients who died (23.1%) during or after therapy. CONCLUSIONS: Emergency craniotomy has a small but important role to play in selected patients with brain metastases who display rapidly deteriorating signs. An undetermined intracranial hemorrhage in young female patients of a reproductive age group should raise the suspicion of cerebral metastatic GTT.

Adult↗

Ventilation performance in the operating theatre against airborne infection: numerical study on an ultra-clean system.

A laminar airflow study was performed in a standard operating theatre in Hong Kong, the design of which followed the requirements of the UK Health Technical Memorandum. The study of the ultra-clean ventilation system investigated the effectiveness of the laminar flow in: (i) preventing bioaerosols released by the surgical staff from causing postoperative infection of the patient; and (ii) protecting the surgical team against infection by bacteria from the wound site. Seven cases of computer simulation are presented and the sensitivity of individual cases is discussed. Air velocity at the supply diffuser has been identified as one of the most important factors in governing the dispersion of airborne infectious particles. Higher velocity within the laminar regime is advantageous in minimizing the heat-dissipation effect, and to ensure an adequate washing effect against particulate settlement. Inappropriate positioning of the medical lamps can be detrimental. Omission of a partial wall may increase the infection risk of the surgical team due to the ingression of room air at the supply diffuser periphery. This paper stresses that a successful outcome in preventing airborne infection depends as much on resolving human factors as on overcoming technical obstacles.

Air Microbiology↗

Novelty-seeking behavior and stress-induced locomotion in rats of juvenile period differentially related to morphine place conditioning in their adulthood.

The relationship between motor responses in a novel environment and susceptibility to place conditioning effect of psychostimulants has been reported in adult rats. However, it is in question whether this correlation could be generalized to motor activity in rats of juvenile period and place conditioning effect in their adulthood for narcotic morphine. In the present study, we tested locomotor activity in an arena open-field and the subsequent novelty-seeking behavior after adaptation process in juvenile rats (P42) and morphine (2 mg/kg) place conditioning effect 56 days later in the same rats' adulthood (P98). Our results showed that rats with high response to novelty (HRN) spent more prolonged duration in the drug-paired compartment in the place conditioning test compared with their low response counterparts (LRN), with the latter group no salient change on this measure. Moreover, rats with high response to the open-field test (HRS) expressed equally elevated duration in drug-paired side relative to their low response counterparts (LRS). The present research demonstrated that novelty-seeking behavior and locomotor activity in the open-field in rats of juvenile period differentially related to morphine place conditioning in their adulthood, with slow acquisition of morphine place conditioning effect in LRN animals.

Age Factors↗

Ventilation performance in operating theatres against airborne infection: review of research activities and practical guidance.

Surgical site infection risk due to airborne bacteria is a key area of consideration in developing operating theatre ventilation design and monitoring procedures. This paper reviews the recent extensive research into operating theatre ventilation development in relation to the design concepts in operating theatre layout, pressurization and ventilation, particularly the evolvement of ultra-clean ventilation. The findings that led to the current technical standards and the developments of microbial measurements and numerical techniques are discussed. Since the late 1980s, computational fluid dynamics has been a fast developing tool used in the prediction of room air distribution and contaminant dispersion. The basic principles and current practice applying to operating theatre ventilation studies are introduced.

Air Microbiology↗

Serum lysophosphatidic acid concentrations measured by dot immunogold filtration assay in patients with acute myocardial infarction.

In this study the relation between lysophosphatidic acid (LPA) and myocardial infarction was investigated, the typical and simplified methods for measuring serum LPA concentration by dot immunogold filtration assay (DIFA) based on a polyclonal antibody to LPA were developed, and serum LPA concentrations were measured in 31 patients with acute myocardial infarction (AMI) and 12 controls (blood donors) by DIFA. Serum LPA levels were raised more than twofold 8 h after the onset of AMI. Maximal elevation (10.43 mg/L) was found at 48-72 h following onset and remained higher than the control concentration (1.66 mg/L) 7 days after AMI. The rise in serum LPA concentration in AMI patients suggests that LPA might be involved in AMI-related pathophysiology in the cardiovascular system. The simplified DIFA developed in the present study for measuring serum LPA concentration is convenient and highly sensitive.

Adolescent↗

Transgenic twin lambs cloned by granulosa cells.

The development potential of transgenic adult cells after nuclear transfer (NT) was evaluated. Primary ovine granulosa cells (GC(S)) from a slaughter ovary were transfected with pEGFP-N1 plasmid DNA. Three G418-resistance cell lines (A2, B2 and B4) were used as donor cells in NT. A total of 162 NT blastocysts were then frozen with ethylene glycol solution and stored for five months before transplanted into recipients. Twenty-nine frozen thawed NT blastocysts were transferred into 15 synchronized recipients. Twin lambs (6.9%) derived from B2 line were delivered by cesarean section on day 143 but died after birth. A tumor consisting of lung tissues was found on the surface of left lung of the 4-kg lamb and histological analysis indicated that it resembles a hamartoma. DNA analysis confirmed that two lambs were genetically identical to B2 donor cells. Gene insertion and expression have been detected in fibroblasts cells derived from muscle tissues of the lambs. This study indicates that granulosa cell is a suitable cell type for producing transgenic animals by nuclear transfer. Offspring were produced after long-term storage of NT blastocysts.

Animals↗

Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial.

BACKGROUND: Herpes simplex facialis/labialis (HSFL) is a common infectious skin disorder, caused mainly by herpes simplex virus (HSV) type 1, for which the topical application of a cream containing an antiviral agent for treatment of the disease has been widely utilized. OBJECTIVE: To explore the efficacy of the topical application of 1% penciclovir cream in the treatment of HSFL, and to compare its efficacy and safety with 3% aciclovir cream. METHODS: A total of 248 patients with a diagnosis of HSFL were randomly allocated to one of the two treatment groups (n = 124 each), using stratified randomization based on a table of random numbers. Before treatment (day 0) and at every visit (days 3, 5 and 7) during the study, the sign and symptom scores were recorded by the same doctor. RESULTS: Excluding 23 patients (10 in the penciclovir and 13 in the aciclovir groups), 225 completed the study, and no severe adverse events were noted with any of the treatment regimens. Results show that an encouraging improvement in the clinical course was found simultaneously for patients with each episode type and each treatment assignment. There were no significant differences in terms of efficacy endpoint, clinical cure rate, and safety between the two treatment arms, but there was a trend towards a shorter time to resolution of all symptoms, cessation of new blisters, and loss of crust (p <or= 0.08) in penciclovir-treated primary patients. In addition, the clinical scores in penciclovir-treated primary patients were significantly lower than those in the respective aciclovir-treated patients on treatment day 5 (p < 0.01) and day 7 (p < 0.05). CONCLUSION: Topical 1% penciclovir cream is as convenient and as effective as 3% aciclovir cream for the treatment of HSFL. Penciclovir cream may provide a good topical alternative to other types of therapy in the future.

Acyclovir↗

Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3.

Estrogen receptors (ERs)(1) highly expressed by multiple myeloma (MM) cells and stimulation of estrogenic ligands leads to cell apoptosis. Interleukin (IL)-6 is a major growth factor in the pathogenesis of MM. However, little is known concerning the molecular consequences of ER activation on IL-6-regulated MM cell growth. Here we show that the ER agonist 17 beta-estradiol completely abolished IL-6-inducible MM cell proliferation. By contrast, the ER antagonist ICI 182,780 overcame the inhibitory effect of estrogen. Estrogen blocked STAT3 DNA binding and transactivation but failed to affect the mRNA expression of IL-6 receptor chains or activation of JAK2 and STAT3. Estrogen-activated ER did not associate directly with STAT3. Estrogen induced the mRNA expression of PIAS3 (protein inhibitor of activated STAT3) and increased PIAS3 physical association with STAT3, suggesting a possible mechanism of STAT3 inhibition requiring PIAS3 as a co-regulator modulating the cross-talk between ER and STAT3. These data directly demonstrate STAT3 to be a molecular participant in ER inhibition of the IL-6 signaling pathway in human MM cells and provides the molecular basis for the potential use of estrogenic ligands in the treatment of MM or other tumors where IL-6 has an autocrine or paracrine role.

Base Sequence↗

Organization of human ACAT-2 gene and its cell-type-specific promoter activity.

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis. Two ACAT genes exist in mammals. We report here the genomic organization of human ACAT-2 gene and analysis of its promoter activity in various cell lines. The human ACAT-2 gene spans over 18 kb and contains 15 exons. Three transcription start sites and one poly(A) site are identified by the 5'/3'-RACE. In addition, the human ACAT-2 gene is linked to the insulin-like growth factor binding protein 6 (IGFBP-6) gene in a head-to-tail manner with a small intergenic region of about 1.2 kb. The 5'-flanking region of human ACAT-2 gene contains many potential cis-acting elements for multiple transcriptional regulatory factors but lacks TATA and CCAAT boxes. Using promoter-luciferase reporter assays, we demonstrate the transcriptional activity of ACAT-2 gene promoter is high in Caco-2 cells, especially after these cells become postconfluent and behave as intestinal enterocytes.

Base Sequence↗

Expression, purification, and characterization of active recombinant prostate-specific antigen in Pichia pastoris (yeast).

BACKGROUND: Prostate-specific antigen (PSA), a member of the kallikrein family of serine proteases, is a chymotrypsin-like glycoprotein produced by the prostate epithelium. Elevated serum PSA (> 4 ng/ml) is a tumor marker for prostatic cancer and benign prostatic hypertrophy; increasing serum PSA over time is indicative of metastatic disease. It has been suggested that PSA may contribute to tumor metastasis through degradation of extracellular matrix glycoproteins, as well as cleavage of IGF binding protein-3, a modulator of IGF-1. To elucidate the role of PSA in the development and progression of prostatic cancer, it is necessary to have a reliable, cost-effective source of enzymatically active protein. Previous efforts to express recombinant PSA (rPSA) produced inactive proPSA, or mixtures of active and inactive PSA requiring activation by removal of the propeptide. We describe the expression of active recombinant mature PSA in yeast. METHODS: Stable chromosomal integration of a construct consisting of the yeast alpha-factor signal sequence preceding the mature PSA sequence resulted in secretion of rPSA. The rPSA was purified from the yeast cell culture supernatant to homogeneity by strong cation-exchange chromatography, and characterized by SDS-PAGE, Western analysis, electrospray mass spectrometry, N-glycanase digestion, N-terminal amino acid sequencing, and inactivation by a PSA-specific inhibitor. RESULTS: We report the production of active, mature rPSA in Pichia pastoris. Two forms of rPSA varying slightly in glycosylation were identified. The specific activity of the rPSA was equal to that of human seminal plasma PSA (0.56 micromol/min mg) as determined using a chromogenic substrate. CONCLUSIONS: Large-scale production of active rPSA will be useful in the exploration of PSA effects on tumor cell proliferation, migration and metastasis. In addition, a large supply of enzyme should facilitate the discovery of novel inhibitors for in vitro and in vivo evaluation, and may provide a reproducible source of rPSA for use as a standard in diagnostic testing.

Amidohydrolases↗

Synergistic transcriptional activation of human Acyl-coenzyme A: cholesterol acyltransterase-1 gene by interferon-gamma and all-trans-retinoic acid THP-1 cells.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation. Human ACAT-1 gene contains two promoters (P1 and P7), each located in a different chromosome (1 and 7) (Li, B. L., Li, X. L., Duan, Z. J., Lee, O., Lin, S., Ma, Z. M., Chang, C. C., Yang, X. Y., Park, J. P., Mohandas, T. K., Noll, W., Chan, L., and Chang, T. Y. (1999) J. Biol Chem. 274, 11060-11071). Interferon-gamma (IFN-gamma), a cytokine that exerts many pro-atherosclerotic effects in vivo, causes up-regulation of ACAT-1 mRNA in human blood monocyte-derived macrophages and macrophage-like cells but not in other cell types. To examine the molecular nature of this observation, we identified within the ACAT-1 P1 promoter a 159-base pair core region. This region contains 4 Sp1 elements and an IFN-gamma activated sequence (GAS) that overlaps with the second Sp1 element. In the monocytic cell line THP-1 cell, the combination of IFN-gamma and all-trans-retinoic acid (a known differentiation agent) enhances the ACAT-1 P1 promoter but not the P7 promoter. Additional experiments showed that all-trans-retinoic acid causes large induction of the transcription factor STAT1, while IFN-gamma causes activation of STAT1 such that it binds to the GAS/Sp1 site in the ACAT-1 P1 promoter. Our work provides a molecular mechanism to account for the effect of IFN-gamma in causing transcriptional activation of ACAT-1 in macrophage-like cells.

Base Sequence↗

Urea signaling to ERK phosphorylation in renal medullary cells requires extracellular calcium but not calcium entry.

The renal cell line mIMCD3 exhibits markedly upregulated phosphorylation of the extracellular signal-regulated kinase (ERK) 1 and 2 in response to urea treatment (200 mM for 5 min). Previous data have suggested the involvement of a classical protein kinase C (cPKC)-dependent pathway in downstream events related to urea signaling. We now show that urea-inducible ERK activation requires extracellular calcium; unexpectedly, it occurs independently of activation of cPKC isoforms. Pharmacological inhibitors of known intracellular calcium release pathways and extracellular calcium entry pathways fail to inhibit ERK activation by urea. Fura 2 ratiometry was used to assess the effect of urea treatment on intracellular calcium mobilization. In single-cell analyses using subconfluent monolayers and in population-wide analyses using both confluent monolayers and cells in suspension, urea failed to increase intracellular calcium concentration. Taken together, these data indicate that urea-inducible ERK activation requires calcium action but not calcium entry. Although direct evidence is lacking, one possible explanation could include involvement of a calcium-dependent extracellular moiety of a cell surface-associated protein.

Animals↗

Selective disruption of interleukin 4 autocrine-regulated loop by a tyrosine kinase inhibitor restricts activity of T-helper 2 cells.

Interleukin (IL) 4 is a potent immunomodulatory cytokine secreted by T-helper 2 (Th2) cells and Th2 mast cells that promotes the commitment of cells. However, unregulated production and release of IL-4 can exacerbate allergic reactions and increase susceptibility to infectious organisms and viruses. Here, we present evidence that AG-490, a Janus tyrosine kinase (JAK) 2-JAK3 inhibitor, effectively blocked IL-4 gene expression and secretion in the Th2 cell line D10 that was not occurring after anti-CD3 antibody stimulation, whereas AG-490 had no inhibitory effect on production of other Th2 cytokines or cytokines synthesized by the corresponding Th1 cell line clone 29. AG-490 potently inhibited IL-4-mediated proliferation of both D10 and the IL-4-dependent cell line CT.4S. Moreover, AG-490 markedly inhibited IL-4 activation of JAK3 and blocked the downstream activation of signal transducer and activator of transcription 6, as judged by tyrosine phosphorylation, DNA binding, and transcription assays. In contrast, AG-490 did not affect tumor necrosis factor alpha activation of NF-kappaB at similar concentrations of drug. These data suggest that tyrosine kinase inhibitors that inhibit JAK3 may have previously unrecognized and selective clinical potential as immunotherapeutic drugs to treat Th2-mediated diseases driven by IL-4. (Blood. 2000;95:3816-3822)

Animals↗

Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma co-association with transcription factor NFAT.

T lymphocyte activation is highlighted by the induction of interleukin-2 (IL-2) gene expression, which governs much of the early lymphocyte proliferation responses. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. PPARgamma mRNA expression was found in human peripheral blood T lymphocytes, raising the possibility of PPARgamma involvement in the regulation of T cell function. Here we show that PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14) prostaglandin J(2), but not PPARalpha agonist Wy14643, inhibited IL-2 production and phytohemagglutinin-inducible proliferation in human peripheral blood T-cells in a dose-dependent manner. This inhibitory effect on IL-2 was restricted to the PPARgamma2-expressing, not the PPARgamma-lacking, subpopulation of transfected Jurkat cells. The activated PPARgamma physically associates with transcriptional factor NFAT regulating the IL-2 promoter, blocking NFAT DNA binding and transcriptional activity. This interaction with T-cell-specific transcription factors indicates an important immunomodulatory role for PPARgamma in T lymphocytes and could suggest a previously unrecognized clinical potential for PPARgamma ligands as immunotherapeutic drugs to treat T-cell-mediated diseases by targeting IL-2 gene expression.

Base Sequence↗

Targeted disruption of stat6 DNA binding activity by an oligonucleotide decoy blocks IL-4-driven T(H)2 cell response.

The transcription factor, signal transducer and activator of transcription (Stat) 6, regulates T(H)2-lymphocyte activity by controlling the expression and responsiveness to interleukin (IL)-4, which plays a key role in numerous allergic maladies. Therefore, we sought to use a phosphorothiolate cis-element decoy to target disruption of Stat6 transcriptional activity. Here we showed that the Stat6 decoy potently ablated the messenger RNA expression and production of IL-4, but not of several other cytokines. The Stat6 decoy functionally disrupted IL-4-inducible cell proliferation of murine T(H)2 cells and primary human CD4(+) T lymphocytes. Specificity of the decoy was demonstrated by its ability to directly block Stat6 binding to a cis-element probe and transactivation, but not affect Stat6 tyrosine phosphorylation or expression of the IL-4 receptor chains. Moreover, the decoy failed to inhibit non-Stat6-dependent signaling pathways since IL-2 was competent to induce cell proliferation and activation of Stats 1, 3, and 5a/b. With the use of laser scanning confocal microscopy, fluorescently tagged Stat6 decoy was detectable in the cytoplasm and nucleus; however, greater levels of oligonucleotide were present in the latter following IL-4 treatment. Taken together, these data suggest that IL-4-driven T(H)2 cell activity can be preferentially restricted via targeted disruption of Stat6 by a novel and specific decoy strategy that may possess gene therapeutic potential. (Blood. 2000;95:1249-1257)

Base Sequence↗