Biomedical subjects
Publications and source records attributed to L Wei.
The advantages of the application of NMR imaging to the studies of enhanced oil recovery methods that include polymer slug flooding, combination slug flooding, and thermal soaking are described.
PURPOSE: Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection. METHODS: The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated. RESULTS: The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection. CONCLUSIONS: Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.
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A surface receptor complex of Mr approximately 65 000 (p65) and approximately 95 000 (p95) is expressed in cells of the central nervous system of mice. This receptor is recognized by monoclonal antibody 87.92.6 or by reovirus type 3 haemagglutinin as unnatural ligands. The p65/p95 receptor is expressed mostly in neural embryonic precursors undergoing proliferation, especially those in the S-G2 phase of the cell cycle. Receptor expression decreases progressively throughout embryogenesis to low but detectable levels in the adult brain. Biochemical characterization revealed that the neural p65/p95 receptor complex is indistinguishable from the p65/p95 receptor expressed in T cells, where receptor ligation leads to a mitogenic block. In neural and lymphoid tissues the p65/p95 receptor (or an associated protein) possesses a tyrosine kinase enzymatic activity. Receptor ligation in neural cells resulted in the rapid tyrosine phosphorylation of cellular proteins which are different from substrates phosphorylated in T cells. Differential substrate coupling to the receptor may account for differences in signal transduction and biology between neural cells and T cells. Further study of this receptor complex may help define important features of neural proliferation, differentiation and survival.
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Four flavone compounds have been separated from the mature seeds of Sophora vicii folia. By means of physico-chemical and spectroscopic analysis, their structures have been identified as 5,7,3'-trihydroxy-4'-methoxyflavone (I); 7,3'-dihydroxy-1'-methoxyflavone (II); 7,4'-dihydroxyflavone (III) and 7,3',4'-trihydroxyflavone (IV). All of them are found in S. viciifolia for the first time, and I and II are found Sophora genus for the first time.
The PCA method and NLM technology were used to study on quality of 40 Radix Sophorae Flavescentis samples collected from different regions of China. The results showed were unanimous with that of traditional appraisal.
OBJECTIVE: To study the influence of hypoxia/reoxygenation on the production and release of nitric oxide (NO), lactate dehydrogenase (LDH) and creatine kinase (CPK) from cultured newborn rat cardiomyocytes. METHODS: The rats were divided into four groups: control, hypoxia/reoxy-genation, heat shock pretreated, dexamethasone pretreated. RESULTS: After 3 hours of hypoxia and 30 minutes of reoxygenation, the content of NO in the supernatent of cardiomyocytes increased significantly (P < 0.05), which was accompanied by an increase in the release of LDH and CPK (P < 0.001, P < 0.001 respectively). When pretreated by the heat shock (exposed to 42 degrees C for 1 hour and then allowed to recover for 24 hours) or by applying dexamethasone at the onset of hypoxia, the production and release of NO, LDH, CPK decreased markedly (P < 0.05). CONCLUSIONS: Excessive release of NO may play an important role in the reperfusion injury of cardiomyocytes. Heat shock seems to provide protection for cardiomyocytes from hypoxia/reoxygenation injury. The mechanism may be related to the inhibition of excessive release of No from the cardiomyocytes.
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The effects of EGF and TGF beta 1 on onco gene expressions was studied by RT-PCR technique in an ovarian cancer cell line HO-8910. The results showed that TGF beta 1 could inhibit mRNA expression of TGF beta 1 gene and that of c-myc, EGFR and c-erbB2 genes in HO-8910 cells in vitro. However, EGF could enhance the mRNA expressions of c-myc, c-erbB2 and EGFR to various extents, but inhibit that of TGF beta 1 gene.
Spleen cells from BALB/c mice immunized with human breast cancer serum antigen were fused with murine myeloma SP 2/0 cells. After screening with ELISA and limited-dilution cloning, one hybridoma which could stably secrete specific antibody was obtained and designated McAbGB2. The titer of McAbGB2 was up to 1.2 x 10(6) after purified by ammonium sulfate and DEAE-cellulose. The McAbGB2 was defined as murine IgG1 by agarose double immunodiffusiong. Immunoblotting analysis revealed that the antigens with molecular weights of 116 kd and 45 kd recognized by McAbGB2 were distributed in human breast cancer tissue and serum.
In order to assess the relationship between seropositivity and potential infectivity caused by hepatitis C virus (HCV) and hepatitis B virus (HBV) in patients undergoing maintenance hemodialysis, 22 patients in our dialysis unit were evaluated by using nested RT-PCR to detect serum HCV RNA, ELISA to detect serum anti-HCV antibodies, dot blot to detect serum HBV DNA and RIA to detect HBV serum markers. Twenty-seven percent of the patients (6 of 22) was anti-HCV-positive. Of the 6 anti-HCV-positive patients, HCV RNA was detected in 3 (33%) patients. Among the anti-HCV-negative patients, HCV RNA was detected in one (6%) of the 16 patients. Fourteen percent (3 of 22) was HBV DNA-positive. Of the 3 HBV DNA-positive patients, HBeAG was detected in all of them. Among the nineteen HBV DNA-negative patients, no HBeAg was detected, but anti-HBc was detected in 12 (63%) of the 19 patients. Five of the seven patients with HCV infection (HCV-Ab and/or HCV RNA-positive) had evidence of additional present or past hepatitis B virus infection (4 of the 5 patients were anti-HBc-positive and one of the 5 was HBV DNA, HBeAg, HBsAg, and anti-HBc-positive). However, no HCV RNA and HBV DNA were found to coexist in the same patient in this study. These data indicate that many patients on hemodialysis have hepatitis C or B viremia and more attention should be paid to this problem.
ART1 and ART2 models of adaptive resonance theory network have been employed in quality evaluation of 40 Radix Sophorae Flavescentis samples collected from different regions of China. Based on the UV data of MeOH extract and IR data of CHCL3 extract, Shannon information theory has been used for feature selection. The results consist with those of traditional appraisal.
Treatment of HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1-5 nM) induced inhibition of cell growth and the appearance of an adherent monocyte-like cell type in a dose- and time-dependent manner. The extent of TPA-induced monocytic differentiation was found to be markedly reduced by okadaic acid (OA) (35 nM). OA had to be present for the early 12 h during treatment with TPA to reduce the induction of monocytic differentiation. The majority of cells (80%) were non-adherent but morphologically resembled mature myelocytes or granulocytes after treatment with TPA (5 nM) in the presence of OA (35 nM). Vanadate (VD), on the other hand, enhanced the extent of monocytic differentiation induced by low-dose of TPA (1 nM). These results indicated that dephosphorylation by tyrosine protein phosphatase and serine-threonine protein phosphatase may play an important role in the induction of monocytic and granulocytic differentiation.
The deduced primary sequence of the cytoplasmic protein-tyrosine kinase domain of the insulin receptor contains a conserved kinase homology region (receptor residues 1002-1257) flanked by a juxtamembrane region and a C-terminal tail. A soluble 48-kDa derivative (residues 959-1355) containing these regions but lacking the first six residues of the juxtamembrane region had earlier been synthesized in Sf9 cells using a baculovirus expression system. The catalytic core of the kinase domain was studied first by proteolytic analysis of the 48-kDa kinase and then by expressing a series of truncated kinase domains in transiently transfected COS cells. Based on these studies, two core kinases of 34 (residues 985-1283) and 35 (residues 978-1283) kDa, respectively, were overexpressed in Sf9 cells. Biochemical characterization of the 35-kDa kinase revealed that the core kinase conserved the major functional properties of the native receptor kinase domain. Activity of the 35-kDa kinase toward a synthetic peptide increased more than 200-fold upon autophosphorylation, which occurred exclusively at Tyr-1158, Tyr-1162, and Tyr-1163; the largest increase was observed between bis- and trisphosphorylation of the kinase. The activated 35- and 48-kDa kinases were similar with respect to specific activity and ATP and Mg2+ requirements for peptide phosphorylation. Moreover, autophosphorylation appeared to initiate predominantly at Tyr-1162, immediately followed by phosphorylation at Tyr-1158 and then at Tyr-1163. The rate of autophosphorylation was dependent on enzyme concentration, consistent with a trans-phosphorylation mechanism. Finally, the 35-kDa kinase was crystallized, making possible elucidation of its three-dimensional structure by x-ray crystallography.
Small monomeric cyclic analogs that mimic the beta-turn regions of nerve growth factor (NGF) were designed and synthesized. Potent competitive antagonists were derived from the NGF beta-turn C-D, which inhibited [125I] NGF binding to TrkA receptors and specifically inhibited optimal NGF-mediated neurite outgrowth in PC12 cells. The cyclic beta-turn A'-A" analog also inhibited NGF binding to TrkA receptors but with lower potency. These data indicate that beta-turns C-D and A'-A" are critical for TrkA binding and may confer neurotrophin receptor specificity. Furthermore, structural requirements for binding are absolute, because unconstrained analogs derived from the same regions had no effect. Compounds that mimic NGF will be useful in deciphering the interactions of NGF and its receptors and in rational drug design.
Polyamines (PA) have been shown to be critical mediators of estradiol-induced breast cancer cell proliferation. This finding suggests that constitutive activation of the PA pathway may promote tumor progression, possibly leading to hormone independence. To test this hypothesis, we transfected hormone-responsive MCF-7 breast cancer cells with a complementary DNA coding for ornithine-decarboxylase (ODC), the first rate-limiting enzyme in PA biosynthesis. Marked ODC overexpression observed in stably transfected clones was associated with a selective increase in cellular putrescine content, while spermidine and spermine levels were not altered. ODC-overexpressing MCF-7 cells were resistant to the antiproliferative effects of low but not high concentrations of the enzyme inhibitor, alpha-difluoromethylornithine. In agreement with our hypothesis, sensitivity to the growth-promoting action of estradiol was reduced by approximately one third (P < 0.001) in ODC-overexpressing MCF-7 cells compared with vector-only transfected clones. Basal growth under anchorage-dependent conditions was only marginally increased by ODC overexpression (P = 0.048), while clonogenicity in soft agar was actually reduced. These data suggest that activation of PA biosynthesis may contribute in part to the acquisition of estrogen independence by breast cancer cells. Since only putrescine content was increased as a result of ODC overexpression, these data may underestimate the overall influence of the PA pathway on breast cancer phenotype.
To determine the direct influence of the polyamine (PA) pathway on breast cancer phenotype, we employed a transfection approach to induce overexpression of the PA biosynthetic enzyme ornithine decarboxylase (ODC) in the hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overexpression of ODC resulted in a consistent but modest increase in [3H]thymidine incorporation into DNA which was similar in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence of serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was inconsistent, possibly as a result of subtle differences in culture conditions. Overall, our results support the hypothesis that activation of the PA biosynthetic pathway may confer a growth advantage to breast cancer cells.