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Biomedical subjects

Yi Li

Publications and source records attributed to Yi Li.

At least 271 records · Page 15Linked to original sources
PubMed2002

Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats.

Marrow stromal cells (MSCs) transplantation into brain has been employed to treat experimental ischemia. However, MSCs undergo apoptosis and few survive in the ischemic brain. We test the hypotheses that coadministration of bone marrow cells (BMCs) with a cell-permeable inhibitor of caspases, Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD), into the ischemic boundary zone (IBZ) of brain promotes BMCs survival and improve outcome. Experimental groups consist of: 24 h after MCAo, either phosphate-buffered saline (PBS, n=4), dead BMC (n=4), fresh BMC (n=10), Z-VAD only (n=4), or BMC with Z-VAD (n=6) were intracerebrally injected. BMCs were harvested from donor adult rats labeled with bromodeoxyuridine (BrdU). Rats were subjected to an adhesive-removal somatosensory and motor-rotarod functional tests before MCAo and at 1 and 7 days after MCAo. Rats treated with a combination of Z-VAD and BMCs exhibited significant improvement in the adhesive-removal test at 7 days compared with the control group (combined MCAo+PBS and MCAo+dead BMC) (p<0.01), and the numbers of BrdU-BMC increased (p<0.05) and apoptotic cells decreased (p<0.05) compared with BMC alone transplantation. Our data suggest that intracerebral coadministration of BMC with Z-VAD enhances the survival of grafted BMC and improves neurological functional recovery after MCAo.

Amino Acid Chloromethyl Ketones↗
PubMed2002

Cloning a cDNA encoding an alternatively spliced protein of BRCA2-associated factor 35.

Inheritance of mutations in the breast cancer susceptibility gene, BRCA2, predisposes humans to breast and ovarian cancers. Inherited mutations in the BRCA2 gene are also known to cause susceptibility to prostate cancer. BRCA2 protein exists in a large multi-protein complex from which a novel structural DNA binding protein BRCA2-associated factor 35 (BRAF35) has been isolated. We have cloned a novel cDNA encoding an alternatively spliced protein of BRAF35, designated as BRAF25. BRAF25 transcript is present in various human cells. We have precisely mapped the BRAF25 cDNA sequence to the genomic chromosome 19 sequence. Analysis of the predicted sequence of BRAF25 identified a protein of 215 amino acids. BRAF25 contains a truncated high mobility group domain, a kinesin-like coiled-coil domain and multiple Src homology 2 (SH2) motifs. Western blot analysis using antibodies specific for BRAF25 revealed the presence of BRAF25 in human prostate cancer cells.

Alternative Splicing↗
PubMed2002

Immunohistological detection of BRAF25 in human prostate tumor and cancer specimens.

BRAF25 is an alternatively spliced protein of BRAF35 (see associated paper). We have mapped the BRAF25 gene to chromosome sub-band 19p13.3, a region where loss of chromosomal heterozygosity has been reported in about 50% of ovarian cancers. Because of the high incidence of genetic links of prostate cancer to breast and ovarian cancers, we investigated the BRAF25 expression in the prostate specimens. Immunohistochemical analysis using antibodies specific for BRAF25 revealed a strong immunostaining in sections of the benign prostatic hyperplasia (BPH). The staining was concentrated on the nuclei of cells facing the lumen of prostatic glands, even though the sporadic nuclei of cells in stromas were also stained. However, the expression of BRAF25 was dramatically reduced in intermediate prostate cancer and absent in advanced prostate cancer. Preincubation of the antibody with the immunizing peptide abolished immunostaining in BPH specimens. Therefore, the expression of BRAF25 was gradually lost in prostate cancer.

Antibodies↗
PubMed2002

4,5-diphenyltriazol-3-ones: openers of large-conductance Ca(2+)-activated potassium (maxi-K) channels.

A series of diphenyl-substituted heterocycles were synthesized and evaluated by electrophysiological techniques as openers of the cloned mammalian large-conductance, Ca(2+)-activated potassium (maxi-K) channel. The series was designed from deannulation of known benzimidazolone maxi-K opener NS-004 (2) thereby providing an effective template for obtaining structure-activity-related information. The triazolone ring system was the most studied wherein 4,5-diphenyltriazol-3-one 6d (maxi-K = 158%) was identified as the optimal maxi-K channel opener.

Animals↗
PubMed2002

Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats.

We tested the hypothesis that populations of ependymal, subependymal and choroid plexus cells proliferate and differentiate after stroke in adult rats. Rats were subjected to 2 h of middle cerebral artery occlusion (n=70) and euthanized at 1, 2, 4, 7, 14, 21 and 28 days (10 per time point). Hematoxylin and eosin staining and immunostaining were performed using antibodies against bromodeoxyuridine, neuronal nuclear antigen and glial fibrillary acidic protein after stroke. In normal nonischemic rats (n=10), single layers of ependymal and choroid plexus cells do not react with bromodeoxyuridine, neuronal nuclear antigen or glial fibrillary acidic protein. Individual subependymal cells express glial fibrillary acidic protein and bromodeoxyuridine, but not neuronal nuclear antigen. After stroke, increased bromodeoxyuridine reactivity was present in multiple layers of ependymal cells and nodules of subependymal cells and in scattered choroid plexus cells from 2 to 28 days and peaked at 7 days. Bromodeoxyuridine immunoreactivity colocalized with neural phenotypes of neuronal nuclear antigen (approximately 0.1-3.5%) and glial fibrillary acidic protein (approximately 8.6%) immunoreactivity in cells in the ventricular zone and the subventricular zone, as well as in the choroid plexus of the ischemia affected hemisphere. Our data suggest that ependymal, subependymal and choroid plexus cells are potential neural precursor cells in the adult mammalian brain.

Animals↗
PubMed2002

Prediction of aqueous solubility of organic compounds using a quantitative structure-property relationship.

A quantitative structure-property relationship (QSPR) was developed for predicting the aqueous solubility of drug-like compounds from their chemical structures. A set of 321 structurally diverse drugs or related compounds, with their intrinsic aqueous solubility collected from literature, was used in this analysis. The data were divided into a training set (n = 267) for building the model and a randomly chosen testing set (n = 54) for assessing the predictive ability of the model. A series of molecular descriptors was calculated directly from chemical structures and a set of eight descriptors, including dipole moment, surface area, volume, molecular weight, number of rotatable bonds/total bonds, number of hydrogen-bond acceptors, number of hydrogen-bond donors and density, was chosen for the final model. The eight-descriptor model generated by multiple linear regression was further optimized by a genetic algorithm guided selection method. The model has a correlation coefficient (r) of 0.95 and a root-mean-square (rms) error of 0.56 log unit. It predicts the solubility of testing set compounds with a reasonable degree of accuracy (r = 0.84 and rms = 0.86 log unit). The present model can serve as a tool for medicinal chemists to guide their early synthetic efforts in arriving at appropriate analogs.

Algorithms↗
PubMed2002

Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture.

OBJECTIVE: Intravascular administration of bone marrow stromal cells (MSCs) restores function in animal models of neural injury and neurodegeneration. Adult MSCs administered intravenously to rat migrate and express neural phenotypes in ischemic brain. The aim of the present study was to investigate the mechanisms targeting MSC migration into the ischemic brain. METHODS: Monocyte chemoattractant protein-1 (MCP-1), a chemoattractant factor, was measured in rat ischemic brain at various time points after middle cerebral artery occlusion (MCAo) using a specific enzyme-linked immunosorbent assay system (ELISA). In addition, using a microchemotaxis chamber, we measured whether ischemic brain tissue extracts induce migration of MSCs and whether brain tissue extracts incubated with antibodies against MCP-1 reduce MSC migration. RESULT: Our data indicate that ischemic brain MCP-1 levels significantly increase from 6 hours, peak at 48 hours after MCAo (p < 0.05), and thereafter gradually decrease. Brain tissue extract at 6 hours, 24 hours, and 48 hours after MCAo significantly increase MSC migration across the membrane of the microchemotaxis chamber compared to normal tissue (p < 0.05). However, when the ischemic brain tissue extracts are incubated with antibody against MCP-1, MSC migration is significantly reduced at 24 hours and 48 hours after MCAo compared to extracts without this antibody (p < 0.05). CONCLUSION: Our data suggest that MCP-1 contributes to MSC migration into the ischemic brain tissue environment.

Animals↗
PubMed2002

Treatment of neural injury with marrow stromal cells.

We describe our preclinical studies on the use of bone-marrow stromal cells (MSC; an uncharacterised mixed population of plastic-adherent cells) in the treatment of neural injury. These cells obtained from donor rats or human beings have been directly transplanted into brain or administered intra-arterially or intravenously. MSC selectively target injured tissue and promote functional recovery. Signals that target inflammatory cells to injured tissue probably direct MSC to injury sites. Although some MSC express proteins typical of neural cells, the possibility that benefit is derived by replacement of infarcted tissue with differentiated MSC is highly unlikely. MSC activate endogenous restorative responses in injured brain, which include angiogenesis, neurogenesis, and synaptogenesis. Given the robust therapeutic benefit of these cells in the treatment of experimental neural injury, and the fact that MSC have been used in the treatment of other human disease, there is justification for further preclinical studies leading to clinical trials for the treatment of neural injury such as stroke.

Animals↗
PubMed2002

Induction of ovarian cancer by defined multiple genetic changes in a mouse model system.

We have developed a mouse model for ovarian carcinoma by using an avian retroviral gene delivery technique for the introduction of multiple genes into somatic ovarian cells of adult mice. Ovarian cells from transgenic mice engineered to express the gene encoding the avian receptor TVA were efficiently infected in vitro with multiple vectors carrying coding sequences for oncogenes and marker genes. When target cells were derived from TVA transgenic mice deficient for p53, the addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce ovarian tumor formation when infected cells were injected at subcutaneous, intraperitoneal, or ovarian sites. We demonstrated that the ovarian surface epithelium is the precursor tissue for these ovarian carcinomas, and that introduction of oncogenes causes phenotypic changes in the ovarian surface epithelial cells. The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread.

Actins↗
PubMed2002

Optimal weight functions for marginal proportional hazards analysis of clustered failure time data.

The choice of weights in estimating equations for multivariate survival data is considered. Specifically, we consider families of weight functions which are constant on fixed time intervals, including the special case of time-constant weights. For a fixed set of time intervals, the optimal weights are identified as the solution to a system of linear equations. The optimal weights are computed for several scenarios. It is found that for the scenarios examined, the gains in efficiency using the optimal weights are quite small relative to simpler approaches except under extreme dependence, and that a simple estimator of an exchangeable approximation to the weights also performs well.

Cluster Analysis↗
PubMed2002

Over-expression of an Arabidopsis gene encoding a glucosyltransferase of indole-3-acetic acid: phenotypic characterisation of transgenic lines.

An analysis of the multigene family of Group 1 glucosyltransferases (UGTs) of Arabidopsis thaliana revealed a gene, UGT84B1, whose recombinant product glucosylated indole-3-acetic acid (IAA) in vitro. Transgenic Arabidopsis plants constitutively over-expressing UGT84B1 under the control of the CaMV 35S promoter have been constructed and their phenotype analysed. The transgenic lines displayed a number of changes that resembled those described previously in lines in which auxin levels were depleted. A root elongation assay was used as a measure of auxin sensitivity. A reduced sensitivity of the transgenic lines compared to wild-type was observed when IAA was applied. In contrast, application of 2,4-dichlorophenoxyacetic acid (2,4-D), previously demonstrated not to be a substrate for UGT84B1, led to a wild-type response. These data suggested that the catalytic specificity of the recombinant enzyme in vitro was maintained in planta. This was further confirmed when levels of IAA metabolites and conjugates were measured in extracts of the transgenic plants and 1-O-IAGlc was found to be elevated to approximately 50 pg mg-1 FW, compared to the trace levels characteristic of wild-type plants. Surprisingly, in the same extracts, levels of free IAA were also found to have accumulated to some 70 pg mg-1 FW compared to approximately 15 pg mg-1 FW in extracts of wild-type plants. Analysis of leaves at different developmental stages revealed the auxin gradient, typical of wild-type plants, was not observed in the transgenic lines, with free IAA levels in the apex and youngest leaves at a lower level compared to wild-type. In total, the data reveal that significant changes in auxin homeostasis can be caused by overproduction of an IAA-conjugating enzyme.

Arabidopsis↗
PubMed2002

Ischemic rat brain extracts induce human marrow stromal cell growth factor production.

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme-linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post-ischemia time-dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.

Animals↗
PubMed2002

18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer.

Positron emission tomography (PET) imaging is not used routinely in small-cell lung cancer (SCLC) but has been proven useful in non-small-cell lung cancer. The performance of (18)F-fluorodeoxyglucose (FDG)-PET in patients with SCLC was evaluated in this study. Fifteen patients with proven SCLC were evaluated (8 men and 7 women; mean age, 68 years; range, 50-81 years). Among the 15 patients with SCLC, 3 were newly diagnosed and 12 had received chemotherapy or radiation therapy before PET. Five patients underwent surgery (3 newly diagnosed and 2 after therapy) after PET scan, and 14 received chemotherapy, radiation therapy, or both. The patient who was not treated with chemotherapy or radiation therapy underwent surgery only. All patients had computed tomographic (CT) scans before PET and had clinical follow-up for at least 2 months after PET. The patients received 3.4 to 4.15 mCi of (18)F-FDG intravenously after fasting for at least 4 hours. Whole-body PET scans were acquired approximately 50 min after injection by using an ADAC Laboratories C-PET plus scanner. Among the 12 patients treated before PET, 2 were found with solitary pulmonary nodules positive on PET. Subsequent surgical resection and pathology showed 1 true positive and 1 false positive (postradiation pneumonitis). Six of these 12 patients had extrapulmonary metastases or large intense hilar or pulmonary uptake on PET, or both. Four of these 12 had no evidence of abnormal FDG uptake and were considered true negatives. The 3 patients with newly diagnosed SCLC were all true positives on PET, confirmed by surgery. One false negative on CT scan was attributed to postradiation fibrosis. These preliminary data suggest that whole-body FDG-PET can provide the basis for determining which treatment modality would be the most appropriate during the early stages of SCLC, when surgery is still an option, and it is a useful tool to assess the effect of treatment in patients with this disease. A more accurate assessment of SCLC will be possible if FDG-PET scan is combined with CT during the early evaluation of these patients.

Aged↗
PubMed2002

Cytotoxic diterpenoids from Euphorbia pekinensis.

A new diterpenoid, named euphpekinensin, along with three known diterpenoids, was isolated from the roots of Euphorbia pekinensis for the first time and the structures were elucidated by spectral analysis. The 2D-NMR techniques such as 1H-1H COSY, HMQC, HMBC and NOESY spectra were mainly applied to determine the structure of the new diterpenoid. The four diterpenoids showed cytotoxic activity against human KB cells in vitro.

Cell Survival↗
PubMed2002

MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture.

Bone marrow stromal cells (MSCs) administered intravenously are effective in reducing neurological deficits after stroke in the rodent. These cells appear to selectively migrate and express neural phenotypes in ischemic brain. To elucidate the mechanisms targeting MSC migration into the ischemic brain, we measured, using a microchemotaxis chamber, the effect of select chemotactic factors and cytokines expressed in injured brain, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-8 (IL-8), on migration of human bone marrow stromal cells (hMSCs). In addition, we investigated whether tissue extracts prepared from rat ischemic brain at various times after middle cerebral artery occlusion (MCAo) induce migration of hMSCs. Our data indicate that MCP-1, MIP-1alpha and IL-8 enhance the migration of hMSCs. Ischemic brain tissue extracts at 24, 48 h and 1 week after ischemia significantly increase hMSC migration across the membrane compared to non-ischemic tissue (p<0.05). These data indicate that hMSCs are targeted by inflammatory chemotactic agents and cytokines and that ischemic brain attracts hMSCs.

Animals↗
PubMed2002

Removal of cyanide from dilute solution using a cell with three-phase three-dimensional electrode.

The removal of cyanide from dilute solutions containing free cyanide or cuprocyanide was experimentally investigated using a new electrochemical reactor, three-phase three-dimensional electrode cell. The experimental results were assessed in term of removal efficiency of cyanide. The results showed that the reactor could efficiently remove cyanide from the two solutions. The removal efficiency reached as high as about 93% for the two solutions by electrolysis for 10 min at 20 V cell voltage and 0.16 m3/h airflow. It was also observed that the removal efficiency depended on the applied cell voltage, airflow, interelectrode and initial pH value of the containing-cyanide solution. The former two factors have a positive effect while the latter two have a negative effect on cyanide removal in the experimental range.

Cyanides↗
PubMed2002

Bayesian automatic relevance determination algorithms for classifying gene expression data.

MOTIVATION: We investigate two new Bayesian classification algorithms incorporating feature selection. These algorithms are applied to the classification of gene expression data derived from cDNA microarrays. RESULTS: We demonstrate the effectiveness of the algorithms on three gene expression datasets for cancer, showing they compare well with alternative kernel-based techniques. By automatically incorporating feature selection, accurate classifiers can be constructed utilizing very few features and with minimal hand-tuning. We argue that the feature selection is meaningful and some of the highlighted genes appear to be medically important.

Algorithms↗