Search PubMed⌕ Search

Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 307 records · Page 17Linked to original sources
PubMed2001

Computational design and nonlinear dynamics of a recurrent network model of the primary visual cortex.

Recurrent interactions in the primary visual cortex make its output a complex nonlinear transform of its input. This transform serves preattentive visual segmentation, that is, autonomously processing visual inputs to give outputs that selectively emphasize certain features for segmentation. An analytical understanding of the nonlinear dynamics of the recurrent neural circuit is essential to harness its computational power. We derive requirements on the neural architecture, components, and connection weights of a biologically plausible model of the cortex such that region segmentation, figure-ground segregation, and contour enhancement can be achieved simultaneously. In addition, we analyze the conditions governing neural oscillations, illusory contours, and the absence of visual hallucinations. Many of our analytical techniques can be applied to other recurrent networks with translation-invariant neural and connection structures.

Animals↗
PubMed2001

Rat osteoblast functions on the o-carboxymethyl chitosan-modified poly(D,L-lactic acid) surface.

In this study, the functions of rat osteoblasts on o-carboxymethyl chitosan-modified poly(D,L-lactic acid) (PDLLA) films were investigated in vitro. The surface characterization was measured by contact angle and electron spectroscopy for chemical analysis (ESCA). Cell adhesion and proliferation were used to assess cell behavior on the modified surface and control. The MTT assay was used to determined cell viability and alkaline phosphatase (ALP) activity was performed to evaluate differentiated cell function. Compared to the control films, cell adhesion of osteoblasts on o-carboxymethyl chitosan-modified PDLLA films was significantly higher (p < 0.05) after 6 and 8 h culture, and osteoblast proliferation was also significantly higher (p < 0.01) between 4 and 7 days. The MTT assay suggested cell viability of osteoblasts cultured on o-carboxymethyl chitosan modified PDLLA films was significantly greater (p < 0.05) than that seeded on control one, and the ALP activity of cells cultured on modified PDLLA films was significantly higher (p < 0.01) than that found on control. These results give the first evidence that o-carboxymethyl chitosan could be used to modify PDLLA surface for improving biocompatibility.

Alkaline Phosphatase↗
PubMed2001

Development and evaluation of high throughput functional assay methods for HERG potassium channel.

Three functional hERG channel assay methods have been developed and evaluated. The methods were tested against five known hERG channel inhibitors: dofetilide, terfenadine (Seldane), sertindole (Serdolect), astemizole (Hismanal), and cisapride (Propulsid). The DiBAC4(3)-based assays were found to be the most economical but had high false-hit rates as a result of the interaction of dye with the test compounds. The membrane potential dye assay had fewer color-quenching problems but was expensive and still gave false hits. The nonradioactive Rb+ efflux assay was the most sensitive of all the assays evaluated and had the lowest false-hit rate.

Animals↗
PubMed2001

Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK).

We have previously shown that the Drosophila Ste20 kinase encoded by misshapen (msn) is an essential gene in Drosophila development. msn function is required to activate the Drosophila c-Jun N-terminal kinase (JNK), basket (Bsk), to promote dorsal closure of the Drosophila embryo. Later in development, msn expression is required in photoreceptors in order for their axons to project normally. A mammalian homolog of msn, the NCK-interacting kinase (NIK) (recently renamed to mitogen-activated protein kinase kinase kinase kinase 4; Map4k4), has been shown to activate JNK and to bind the SH3 domains of the SH2/SH3 adapter NCK. To determine whether NIK also plays an essential role in mammalian development, we created mice deficient in NIK by homologous recombination at the Nik gene. Nik(-/-) mice die postgastrulation between embryonic day (E) 9.5 and E10.5. The most striking phenotype in Nik(-/-) embryos is the failure of mesodermal and endodermal cells that arise from the anterior end of the primitive streak (PS) to migrate to their correct location. As a result Nik(-/- )embryos fail to develop somites or a hindgut and are truncated posteriorly. Interestingly, chimeric analysis demonstrated that NIK has a cell nonautonomous function in stimulating migration of presomitic mesodermal cells away from the PS and a second cell autonomous function in stimulating the differentiation of presomitic mesoderm into dermomyotome. These findings indicate that despite the large number of Ste20 kinases in mammalian cells, members of this family play essential nonredundant function in regulating specific signaling pathways. In addition, these studies provide evidence that the signaling pathways regulated by these kinases are diverse and not limited to the activation of JNK because mesodermal and somite development are not perturbed in JNK1-, and JNK2-deficient mice.

Animals↗
PubMed2001

HSPPC-96: a personalised cancer vaccine.

HSPPC-96 is a protein peptide complex consisting of a 96 kDa heat shock protein (Hsp), gp96, and an array of gp96-associated cellular peptides. Immunisation with HSPPC-96 induces T-cell specific immunity against these peptides; gp96 is not immunogenic per se. The non-covalent binding of gp96 to peptides is neither selective nor restricted to cell types. Thus, the collection of gp96-associated peptides represents the antigenic peptide pool of a cell; this is the basis of the peptide-specific immunogenicity elicited by HSPPC-96. Since the repertoire of antigenic peptides in the cell is different between normal and tumour cells and is also distinct among tumours of the same histology due to the randomness of tumour-specific mutations, a purified sample of HSPPC-96 can only effectively immunise against the tumour from which it originates. The immunisation effect is, therefore, specific to both the individual patient and the tumour type. This true custom-based vaccine has been shown to induce protective T-cell immunity against a variety of tumours in animal models. The major mechanism of action is thought to be the ability of HSPPC-96 to prime peptide-specific MHC class I-restricted CD8+ T-cells by interacting with antigen-presenting cells in a receptor-dependent manner. HSPPC-96 is now being widely tested against human malignancies for which effective therapies do not exist. The major challenges of the human studies are immunological monitoring and the determination of optimal dosing, scheduling and route of administration. HSPPC-96 has been well tolerated at all dose levels. Clinical applications are being addressed by numerous studies including an international, multi-centre, double-blind Phase III trial for the treatment of stage III renal cell carcinoma in the adjuvant setting.

Animals↗
PubMed2001

Comparison of length of hospital stay for patients with known or suspected methicillin-resistant Staphylococcus species infections treated with linezolid or vancomycin: a randomized, multicenter trial.

STUDY OBJECTIVE: To compare hospital length of stay (LOS), weekly discharges, and days of antibiotic treatment with linezolid (intravenous with oral follow-up) and vancomycin (intravenous only). DESIGN: Multinational, randomized, phase III trial. SETTINGS: Hospitals in North America, Latin America, and Europe. PATIENTS: Four hundred sixty hospitalized patients with infections of known or suspected methicillin-resistant Staphylococcus species. INTERVENTION: Administration of linezolid or vancomycin. MEASUREMENTS AND MAIN RESULTS: For linezolid recipients, median LOS was 5 and 8 days shorter (p=0.05 and 0.003) in the complicated skin and soft tissue infection intent-to-treat (230 patients) and clinically evaluable (144) samples, and slightly but not significantly shorter in the overall intent-to-treat (460) and clinically evaluable (254) samples. In all samples, linezolid recipients had more discharges in the first week of treatment and fewer days of intravenous therapy than vancomycin recipients. CONCLUSION: Our results support linezolid's ability to reduce medical resource use.

Acetamides↗
PubMed2001

Effector genes altered in MCF-7 human breast cancer cells after exposure to fractionated ionizing radiation.

Understanding the molecular mechanisms involved in the response of tumors to fractionated exposures to ionizing radiation is important for improving radiotherapy and/or radiochemotherapy. In the present study, we examined the expression of stress-related genes in an MCF-7 cell population (MCF-IR20) that has been derived through treatment with fractionated irradiation (2 Gy per fraction with a total dose of 40 Gy). MCF-IR20 cells showed a 1.6-fold increase in sensitization with dose at 10% isosurvival in a clonogenic assay, and a reduced growth delay ( approximately 15 h compared to approximately 27 h), compared to the parental MCF-7 cells treated with a single dose of 5 Gy. To determine which effector genes were altered in the MCF-IR20 cells, the expression of stress-related effector genes was measured using a filter with 588 genes (Clontech) that included major elements involved in cell cycle control, DNA repair, and apoptosis. Compared to MCF-7 cells that were not exposed to fractionated radiation, 19 genes were up- regulated (2.2-5.1-fold) and 4 were down-regulated (2.7-3.4- fold) in the MCF-IR20 cells. In agreement with the array results, 6 up-regulated genes tested by RT-PCR showed elevated expression. Also, activities of the stress-related transcription factors NFKB, TP53 and AP1 showed a 1.2-4.5-fold increase after a single dose of 5 Gy in MCF-IR20 cells compared with parental MCF-7 cells. However, when the radioresistant MCF-IR20 cell were cultured for more than 12 passages after fractionated irradiation (MCF-RV), radioresistance was lost, with the radiosensitivity being the same as the parental MCF- 7 cells. Interestingly, expression levels of CCNB1, CD9 and CDKN1A in MCF-RV cells returned to levels expressed by the parental cells, whereas the expression levels of three other genes, MSH2, MSH6 and RPA remained elevated. To determine if any of the changes in gene expression could be responsible for the induced radioresistance, CCNB1 and CDKN1A, both of which were up-regulated in MCF-IR20 cells and down-regulated in MCF-RV cells, were studied further by transfection with antisense oligonucleotides. Antisense of CCNB1 significantly reduced the clonogenic survival of MCF- IR20 cells at doses of 5 and 10 Gy, from 42% to 26% and from 5.7% to 1.0%, respectively. Antisense of CDKN1A, however, had no effect on radiation survival of MCF-IR20 cells. In summary, these results suggest that stress-related effector genes are altered in cells after treatment with fractionated irradiation, and that up-regulation of CCNB1 is responsible, at least in part, for radioresistance after fractionated irradiation.

Adenocarcinoma↗
PubMed2001

Modification by exercise training of activity and enzyme expression of hepatic branched-chain alpha-ketoacid dehydrogenase complex in streptozotocin-induced diabetic rats.

The branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex is the rate-limiting enzyme in the catabolism of branched-chain amino acids. In the present study, we examined the effects of exercise training on the activity and enzyme expression of the hepatic BCKDH complex in diabetic rats. The rats were prepared by intravenous injections of streptozotocin (50 mg/kg BW), and exercise training was accomplished by treadmill running for 45 min/d for 4 wk. The total and actual activities of hepatic BCKDH complex were significantly increased to approximately 160% by 4 wk of diabetes. On the other hand, diabetic rats in the trained group had the same level of activities as those in the normal rats, indicating that exercise training inhibited the diabetes-induced increase in the enzyme activities. The activity state (% active form) of the enzyme complex was about 100% in all groups and was not affected by diabetes or training. The protein amounts of the enzyme subunits (E1alpha and E2) and the abundance of mRNA for the E2 subunit, but not for the other subunits, in the liver had the same trend as the activities. These results suggest that the capacity for branched-chain amino acid catabolism in streptozotocin-induced diabetic rats is reduced by exercise training and that this modification is associated with the suppression of diabetes-induced BCKDH complex expression in the liver.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2001

Antitumor effect of VNP20009, an attenuated Salmonella, in murine tumor models.

VNP20009, a genetically modified strain of Salmonella typhimurium with deletions in the msbB and purI loci, exhibited antitumor activities when given systemically to tumor-bearing mice. VNP20009 inhibited the growth of subcutaneously implanted B16F10 murine melanoma, and the human tumor xenografts Lox, DLD-1, A549, WiDr, HTB177, and MDA-MB-231. A single intravenous injection of VNP20009, at doses ranging from 1 x 10(4) to 3 x 10(6) cfu/mouse, produced tumor growth inhibitions of 57-95%. Tumor volume doubling time, another indicator for tumor growth inhibition, also significantly increased in mice treated with VNP20009. Using mice with immune system deficiencies, we also demonstrated that the antitumor effects of VNP20009 did not depend on the presence of T and B cells. In addition, VNP20009, given intravenously, inhibited the growth of lung metastases in mice. Only live bacteria showed the antitumor effect.

Animals↗
PubMed2001

Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma.

Angiogenesis is essential for tumor growth and metastasis. Some angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) are involved in increased angiogenic activity and disease progression in many carcinomas. However, there is little information regarding the association between angiogenic factors and leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable it to easily receive nutrition and medicinal components, chemotherapy cannot effectively treat leiomyosarcoma. This means the resistance to anticancer drugs in leiomyosarcoma is very strong. However, the resistant mechanism is still unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF, intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The findings of this study suggest that in leiomyosarcoma, angiogenic factors, such as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis, and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation might be related to chemoresistance mechanism.

Angiogenesis Inducing Agents↗
PubMed2001

Up-regulation of transcription of smooth muscle myosin alkali light chain by ethanol in human breast cancer cells.

Both epidemiological and experimental studies indicate that ethanol is a tumor promoter and that chronic ethanol exposure enhances metastasis of breast cancer cells, and with an in vitro model (T47D human breast cancer cells), we have previously demonstrated that ethanol exposure stimulated the migration of breast cancer cells. In the present study, differential display reverse transcription polymerase chain reaction was used to identify ethanol-responsive genes in T47D cells. Three differentially displayed, ethanol-responsive gene fragments were identified, and their expression was confirmed by Northern blot hybridization. Sequence analysis revealed that one cDNA fragment represented the myosin alkali light chain (MLC 1sm) of human smooth muscle. The expression of MLC 1sm was found to be significantly higher in breast cancer cells than in normal mammary epithelial cells. With T47D cells, ethanol induced an additional duration- and concentration-dependent up-regulation of MLC 1sm. At 400 mg/dl, an ethanol-mediated increase was evident at 6 h (55% increase), peaked at 24 h (2.7-fold increase) following exposure, and diminished thereafter. At pharmacologically relevant concentrations (e.g., 100 mg/dl), ethanol produced a significant increase of MLC 1sm expression, and progressively higher ethanol concentrations resulted in more up-regulation. The half-life of MLC 1sm mRNA was not altered, however, the transcription rate of MLC 1sm was significantly increased by ethanol. MLC is a structural component of the cytoskeleton of eukaryotic cells, and it plays critical roles in the regulation of cell shaping, movement, and growth. Thus, ethanol-mediated up-regulation of MLC may be an underlying molecular mechanism for its tumor promoting effect.

Blotting, Northern↗
PubMed2001

[Cloning of cNDAs involved in malignant transformation induced by glycidyl methacrylate].

The malignant transformation of human embryonic lung fibroblasts (HELF) induced by glycidyl methacrylate (GMA) in vitro was used as a model for comparing gene expression between the transformed cells and controls. Using mRNA differential display PCR(DD-PCR) technique, the three cDNA fragments up-regulated in the transformed cells were identified and highly homologous to human breast cancer transcription factor(ZABC1), Tbx3 and mouse ubiquitin conjugating enzyme(E2) gene. These results suggest that activation or inactivation of genes including ZABC1, Tbx3 and E2 may be involved in GMA-induced transformation.

Air Pollutants, Occupational↗
PubMed2001

[Effects of methyl mercury chloride on nuclear factor-kappa B DNA binding activities of nuclear protein extracts from developing rat cerebra and cerebella].

The effects of methyl mercury chloride (MMC) on DNA binding activities of nuclear factor kappa B(NF-kB) in developing rat cerebella and cerebra were investigated with electrophoretic mobility shift assays(EMSAs). The bindings of NF-kB in nuclei of rat cerebra and cerebella to kB probes showed two bands on gel shift in both control and experiment groups. NF-kB I and NF-kB II DNA binding activities of nuclear protein extracts from rat cerebra exposed to MMC in uterus, was lower than control groups on postnatal day 3 and 7, while that from rat cerebella was higher than control groups. The results suggested that the reactive abilities of neural cell to MMC between cerebra and cerebella were different. In binding reaction mixture, the quantities of MMC increased with the increase of NF-kB DNA binding activities of nuclear protein extracts.

Animals↗
PubMed2001

Comparison of single- versus double-bolus treatments of O(6)-benzylguanine for depletion of O(6)-methylguanine DNA methyltransferase (MGMT) activity in vivo: development of a novel fluorometric oligonucleotide assay for measurement of MGMT activity.

Previous studies have demonstrated that optimal reversal of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance requires complete inactivation of the DNA repair protein O(6)-methylguanine DNA methyltransferase (MGMT) for at least 24 h following BCNU administration. In preparation for clinical trials at this institution, this study was undertaken to compare the efficacy of a conventional single-bolus dose versus double-bolus dose treatments with O(6)-benzylguanine (BG) in depleting MGMT activity in vivo. In xenograft human glioma SF767 tumors, a single 30-mg/kg bolus dose of BG completely inhibited MGMT activity for at least 8 h, but approximately 50% of the basal MGMT activity recovered within 24 h. To sustain the MGMT depletion for 24 h, a second bolus injection of BG at escalating doses was administered 8 h after the first dose. Second bolus doses of 5, 10, and 15 mg/kg BG attenuated the MGMT recovery in a dose-dependent manner compared with the single 30-mg/kg BG dose alone. When the 15-mg/kg BG dose was administered 8 h after the 30-mg/kg initial dose, MGMT activity was completely inactivated in the tumor xenografts for 24 h. This double-bolus BG treatment also depleted MGMT activity in normal murine tissues, including the liver, kidney, lung, brain, spleen, and bone marrow; and the kinetics of MGMT recovery varied among these tissues. When combined with BCNU treatment, the double-bolus BG treatment would be expected to produce greater antitumor activity in future trials than the conventional single-bolus BG treatment.

Animals↗
PubMed2001

Efficacy of nonwoven fabric bioreactor immobilized with porcine hepatocytes for ex vivo xenogeneic perfusion treatment of liver failure in dogs.

We have developed a new bioartificial liver bioreactor filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF). In this study, we investigated the efficacy of our hybrid bioartificial liver system incorporating the NWF bioreactors and an immunoglobulin adsorbent column for perfusion treatment in a canine liver failure model. Xenogeneic perfusion treatment for operative canine liver failure models were performed for 3 h, and survival time, intracranial pressure, and blood and cerebrospinal fluid data were documented. Treatment was carried out without obstruction by immunological rejection when immunoglobulin adsorbent columns were used with the NWF bioreactors in combination. Dogs treated with this system exhibited a restricted increase of intracranial pressure and significant compensatory effects on blood and cerebrospinal amino acid imbalances as shown by a significant improvement of Fischer's ratio. On the other hand, relatively low capacity for ammonia elimination was shown as compared with homologous direct hemoperfusion.

Animals↗