Search PubMed⌕ Search

Biomedical subjects

Y Cao

Publications and source records attributed to Y Cao.

At least 37 records · Page 2Linked to original sources
PubMed2004

Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells.

The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumour suppressor is mutated in 40-50% of human endometrial cancers. PTEN exerts its effects in part via inhibition of the antiapoptotic protein AKT. We demonstrate that two endometrial cancer cell lines that harbour PTEN mutations, Ishikawa and RL95-2, have high levels of phosphorylated AKT and high AKT kinase activity. Two additional endometrial cancer cell lines that express wild-type PTEN, Hec1A and KLE, have little phosphorylated AKT and minimal demonstrable AKT kinase activity. We tested a potential inhibitor of the AKT pathway, API-59CJ-OMe, in these four cell lines. We found that API-59CJ-OMe inhibits AKT kinase activity and induces apoptosis in the Ishikawa and RL95-2 cell lines with high AKT activity, but has little effect on Hec1A and KLE cells without AKT activity. API-59CJ-OMe may therefore have therapeutic potential for those endometrial cancers that harbour PTEN mutations and AKT activation.

Apoptosis↗
PubMed2004

An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory.

CD4+ CD45RO+ T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4+ T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4+ T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalovirus-specific memory responses of CD8+ T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8+ T cell memory responses.

Acquired Immunodeficiency Syndrome↗
PubMed2004

MRI of female genital and pelvic organs during sexual arousal.

We utilized contrast enhanced magnetic resonance imaging (MRI) to delineate the anatomy of the female genital and pelvic organs during sexual arousal. Eleven healthy pre-menopausal women and eight healthy post-menopausal women underwent MRI of the pelvis while watching an erotic video. A 1.5 Tesla MR system was used to produce T1-weighted images following administration of MS-325, a gadolinium-based blood pool contrast agent. Selected structural dimensions and enhancement were measured prior to and during sexual arousal. In both pre- and post-menopausal subjects, vestibular bulb and labia minora width increased with arousal. Enhancement measurements increased in the bulb, labia minora and clitoris in both pre- and post-menopausal subjects, and in the vagina in pre-menopausal subjects. There were no marked changes in size or enhancement of the labia majora, urethra, cervix, or rectum during sexual arousal in pre- or post-menopausal subjects. Using MRI, we observed specific changes in the female genitalia and pelvic organs with sexual arousal, in both pre- and post-menopausal women. MRI can potentially provide detailed anatomical information in the assessment of female sexual function, particularly with regard to changes in blood flow.

Adult↗
PubMed2004

A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs.

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor (VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.

Amino Acid Sequence↗
PubMed2004

Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells.

Latent membrane protein 1 (LMP1), one of the oncoproteins encoded by Epstein-Barr virus is sufficient for the development of nasopharyngeal carcinoma in vivo and nasopharyngeal epithelial cellular immortalization in vitro. It has also been shown to increase the telomerase activity in primary human nasopharyngeal epithelial cells by an unknown mechanism. We reported here that LMP1 could increase telomerase activity in coordination with LMP1-induced c-Myc expression in LMP1-transfected primary human nasopharyngeal epithelial cells or in a dual-stable LMP1 integrated nasopharyngeal carcinoma cell line with Tet-on regulatory system, named Tet-on-LMP1 HNE2 by PCR-ELISA analysis and reporter gene assay. Blocking of LMP1 expression decreased telomerase activity and c-myc transactivation. Mutagenesis of Myc-responsive E-box elements in the minimal core of hTERT promoter could inhibit the hTERT expression induced by LMP1. Moreover, blocking of c-myc transactivation could further decrease LMP1-mediated hTERT expression. It has been suggested that LMP1 can be used to aid myc control telomerase. In addition, we also found that C-terminus of LMP1, including CTAR1 and CTAR2 domains participated in telomerase activation. Together, these findings suggested that LMP1 activated telomerase via c-myc.

Blotting, Western↗
PubMed2003

[Effect of transforming growth factor beta 2 on phagocytosis in cultured bovine trabecular meshwork cells].

AIM: This study was performed to investigate the effect of transforming growth factor beta 2 (TGF-beta 2) on phagocytosis in bovine trabecular meshwork cells in vitro. METHODS: After cultured bovine trabecular meshwork cells were treated for 24 h with 0 ng/ml (control), 0.32 ng/ml, 1 ng/ml, and 3.2 ng/ml TGF-beta 2, latex beads were added to the incubation medium, and the numbers of latex beads in 20 adjacent cells were then counted under a microscope after treatment with Wright's stain. RESULTS: The average numbers of latex beads in the trabecular meshwork cells treated with TGF-beta 2 of different concentrations were 53.1+/-1.7 beads/cell, 56.4+/-2.9 beads/cell, and 77.9+/-6.5 beads/cell, respectively, compared to 45.5+/-3.3 beads/cell in the nontreated control group. Thus, TGF-beta 2 significantly increased the numbers of latex beads phagocytosed by cultured bovine trabecular meshwork cells in a dose-dependent manner. CONCLUSION: TGF-beta 2 can promote the phagocytosis of bovine trabecular meshwork cells in vitro. It may be involved in the reduced cellularity of the trabecular meshwork in patients with primary open angle glaucoma by promoting the phagocytosis of these cells.

Animals↗
PubMed2003

Sickle red blood cells accumulate in tumor.

The preferential accumulation of sickle blood cells in tumor vasculature is demonstrated noninvasively using MRI and sickle red blood cells loaded with Gd-DTPA and invasively by two other techniques. The distribution of red blood cells in rat brain tumors relative to normal brains were measured using three separate techniques: MRI of Gd-DTPA loaded cells, fluorescent microscopy detection of Oregon Green 488 fluorescence conjugated to a streptavidin-biotin complex that binds to red blood cell surface proteins, and autoradiography using a technetium (99m)Tc-labeling kit. Labeled red cells were infused intravenously in rats with brain tumors. Sickle cells preferentially accumulated in tumor relative to normal brain, with highest concentrations near the tumor / normal tissue boundary, whereas control normal red cells did not preferentially aggregate at the tumor periphery. This demonstrates the potential of sickle red blood cells to accumulate in the abnormal tumor vessel network, and the ability to detect their aggregation noninvasively and at high spatial resolution using MRI. The application of the noninvasive measurement of sickle cells for imaging tumor neovasculature, or as a delivery tool for therapy, requires further study.

Anemia, Sickle Cell↗
PubMed2003

Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury.

Spinal cord injury leads to acute local ischemia, which may contribute to secondary degeneration. Hypoxia stimulates angiogenesis through a cascade of events, involving angiogenesis stimulatory substances, such as vascular endothelial growth factor (VEGF). To test the importance of angiogenesis for functional outcome and wound healing in spinal cord injury VEGF165 (proangiogenic), Ringer's (control) or angiostatin (antiangiogenic) were delivered locally immediately after a contusion injury produced using the NYU impactor and a 25 mm weight-drop. Rats treated with VEGF showed significantly improved behavior up to 6 weeks after injury compared with control animals, while angiostatin treatment lead to no statistically significant changes in behavior outcome. Furthermore, VEGF-treated animals had an increased amount of spared tissue in the lesion center and a higher blood vessel density in parts of the wound area compared with controls. These effects were unlikely to be due to increased cell proliferation as determined by bromo-deoxy-uridine-labeling. Moreover, VEGF treatment led to decreased levels of apoptosis, as revealed by TUNEL assays. In situ hybridization demonstrated presence of mRNA for VEGF receptors Flt-1, fetal liver kinase-1, neuropilin-1 and -2 in several important cellular compartments of the spinal cord. The different experiments indicate that beneficial effects seen by acute VEGF delivery was attributable to protection/repair of blood vessels, decreased apoptosis and possibly also by other additional effects on glial cells or certain neuron populations.

Analysis of Variance↗
PubMed2002

Functional MRI-BOLD of brainstem structures during visually triggered migraine.

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.

Adult↗
PubMed2002

[Insulin-like growth factor 1 (IGF-1) mRNA and IGF-1 protein. Expression in cells of the trabecular meshwork of the bovine eye].

BACKGROUND: The purpose of the study was to determine whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin-like growth factor-1 (IGF-1) mRNA and protein. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of IGF-1 mRNA. To detect the protein on the cells an IGF-1-specific immunohistochemical stain was used on trabecular meshwork cells. RESULTS: A single 240 bp RT-PCR product was obtained, the RT-PCR product was verified by sequencing and the derived sequence was homologous to the known bovine sequence. IGF-1 immunostaining was positive in the cytoplasm of trabecular meshwork cells. CONCLUSIONS: We conclude that trabecular meshwork cells produce IGF-1 mRNA and contribute to the presence of IGF-1 protein in the trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF-1 not only through paracrine but also through autocrine action. Whether regulations in IGF-1 production may contribute to the pathogenesis of primary open-angle glaucoma and the possibility of promoting the autocrine action of IGF-1 by trabecular meshwork cells to treat the disease is worth further investigation.

Animals↗
PubMed2002

The complete nucleotide sequence of Beet black scorch virus (BBSV), a new member of the genus Necrovirus.

The complete nucleotide sequence of Beet black scorch virus (BBSV) was determined. The BBSV genome is composed of 3641 nucleotides and has similar organization with Tobacco necrosis virus D of 61% nucleotide identity. The 5'-proximal open reading frame (ORF) encodes a putative 23 kDa protein and a 82 kDa protein by reading-through of an amber termination codon. Three small ORFs located in the center of the genome may encode for a 4.2 kDa protein and two 7 kDa proteins. The 3'-proximal ORF encodes a 24.5 kDa protein equivalent in mass to the viral coat protein. Considering biological and molecular similarities with TNV, it is concluded that BBSV is a new member of the genus Necrovirus.

Base Sequence↗
PubMed2002

Dorsal-enhanced sutures improve tension resistance of tendon repair.

Thirty-six fresh pig flexor tendons were repaired using either the modified Kessler method or the Tang method. Nine tendons from each group were tested in an Instron tensile testing machine with the tendons passing 90 degrees around a pulley. The other nine tendons from each group were pulled linearly by the testing machine. The 2 mm gap formation force of the tendons repaired with the modified Kessler and Tang methods and pulled at 90 degrees were 64%+/-5% and 79%+/-9% respectively of those forces recorded during linear testing. The ultimate strengths of tendons repaired by the modified Kessler and Tang methods and pulled at 90 degrees were 76%+/-6% and 81%+/-8% respectively of the forces measured during linear testing. The percentage gap formation and ultimate strength of the Tang method was significantly higher than that of the modified Kessler suture when the tendons were pulled around a pulley. This demonstrates that the Tang suture, with its main components in the dorsal part of the repaired tendon, has greater tension resistance capacity than conventional tendon sutures which are placed in the middle of the tendon. This study suggests that dorsally-enhanced multiple tendon sutures are better placed to sustain the tension generated during active finger flexion.

Animals↗
PubMed2001

Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists.

Selective muscarinic agonists could be useful in the treatment of neurological disorders such as Alzheimer's disease, schizophrenia, and chronic pain. Many muscarinic agonists have been developed, yet most exhibit at best limited functional selectivity for a given receptor subtype perhaps because of the high degree of sequence homology within the putative binding site, which appears to be buried within the transmembrane domains. Bivalent compounds containing essentially two agonist pharmacophores within the same molecule were synthesized and tested for receptor binding affinity and muscarinic agonist activity. A series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine linked by an alkyloxy moiety exhibited very high affinity (K(i) < 1 nM) and strong agonist activity. The degree of activity depended on the length of the linking alkyl group, which could be replaced by a poly(ethylene glycol) moiety, resulting in improved water solubility, binding affinity, and agonist potency.

Binding, Competitive↗
PubMed2001

IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development.

To identify functions of the IKKalpha subunit of IkappaB kinase that require catalytic activity, we generated an Ikkalpha(AA) knockin allele containing alanines instead of serines in the activation loop. Ikkalpha(AA/AA) mice are healthy and fertile, but females display a severe lactation defect due to impaired proliferation of mammary epithelial cells. IKKalpha activity is required for NF-kappaB activation in mammary epithelial cells during pregnancy and in response to RANK ligand but not TNFalpha. IKKalpha and NF-kappaB activation are also required for optimal cyclin D1 induction. Defective RANK signaling or cyclin D1 expression results in the same phenotypic effect as the Ikkalpha(AA) mutation, which is completely suppressed by a mammary specific cyclin D1 transgene. Thus, IKKalpha is a critical intermediate in a pathway that controls mammary epithelial proliferation in response to RANK signaling via cyclin D1.

Animals↗
PubMed2001

Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58.

Agrobacterium tumefaciens is a plant pathogen capable of transferring a defined segment of DNA to a host plant, generating a gall tumor. Replacing the transferred tumor-inducing genes with exogenous DNA allows the introduction of any desired gene into the plant. Thus, A. tumefaciens has been critical for the development of modern plant genetics and agricultural biotechnology. Here we describe the genome of A. tumefaciens strain C58, which has an unusual structure consisting of one circular and one linear chromosome. We discuss genome architecture and evolution and additional genes potentially involved in virulence and metabolic parasitism of host plants.

Agrobacterium tumefaciens↗
PubMed2001

Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening.

Bcl-2 belongs to a growing family of proteins which regulates programmed cell death (apoptosis). Overexpression of Bcl-2 has been observed in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer. Thereby, Bcl-2 is an attractive new anti-cancer target. Herein, we describe the discovery of novel classes of small-molecule inhibitors targeted at the BH3 binding pocket in Bcl-2. The three-dimensional (3D) structure of Bcl-2 has been modeled on the basis of a high-resolution NMR solution structure of Bcl-X(L), which shares a high sequence homology with Bcl-2. A structure-based computer screening approach has been employed to search the National Cancer Institute 3D database of 206 876 organic compounds to identify potential Bcl-2 small-molecule inhibitors that bind to the BH3 binding site of Bcl-2. These potential Bcl-2 small-molecule inhibitors were first tested in an in vitro binding assay for their potency in inhibition of the binding of a Bak BH3 peptide to Bcl-2. Thirty-five potential inhibitors were tested in this binding assay, and seven of them were found to have a binding affinity (IC(50) value) from 1.6 to 14.0 microM. The anti-proliferative activity of these seven active compounds has been tested using a human myeloid leukemia cell line, HL-60, which expresses the highest level of Bcl-2 protein among all the cancer cell lines examined. Compound 6 was the most potent compound and had an IC(50) value of 4 microM in inhibition of cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Five other compounds had moderate activity in inhibition of cell growth. Compound 6 was further evaluated for its ability to induce apoptosis in cancer cells. It was found that 6 induces apoptosis in cancer cells with high Bcl-2 expression and its potency correlates with the Bcl-2 expression level in cancer cells. Furthermore, using NMR methods, we conclusively demonstrated that 6 binds to the BH3 binding site in Bcl-X(L). Our results showed that small-molecule inhibitors of Bcl-2 such as 6 modulate the biological function of Bcl-2, and induce apoptosis in cancer cells with high Bcl-2 expression, while they have little effect on cancer cells with low or undetectable levels of Bcl-2 expression. Therefore, compound 6 can be used as a valuable pharmacological tool to elucidate the function of Bcl-2 and also serves as a novel lead compound for further design and optimization. Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2.

Amino Acid Sequence↗