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Biomedical subjects

J Lu

Publications and source records attributed to J Lu.

At least 199 records · Page 11Linked to original sources
PubMed2000

Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma.

BACKGROUND: Hepatoma specific gamma-glutamyl transferase (HS-GGT) bands were expressed in the development of hepatocellular carcinoma (HCC) and were associated with a high incidence of HCC diagnosis. The objectives of this study were to determine the levels of HS-GGT quantitatively in the sera of patients with different liver diseases. The methylational status of GGT gene CCGG sites was analyzed in hepatoma tissues. METHODS: The HS-GGT concentrations were quantitatively analyzed in the sera of 156 HCC patients and others with liver diseases or extrahepatic tumors. In 20 hepatoma tissues, the GGT enzyme proteins were purified, the activities of GGTs of different molecular form were examined, total RNAs were extracted and amplified by using a nested polymerase chain reaction (PCR) assay, and the methylational status of CCGG site (M3) in the 5'-noncoding region of GGT genes was investigated with the restriction enzyme Hpa II. RESULTS: Total GGT activities in patients with liver diseases and extrahepatic tumors were abnormally increased. The levels of serum HS-GGT were significantly elevated (P < 0.001) in the HCC group; the incidence of HS-GGT over 5.5 IU/L was 86% in HCC patients and less than 3% in patients with other diseases. From liver cancer to distal noncancerous tissues, an increasing tendency (P < 0.05) of total RNA concentrations was found; the frequencies of amplified fragment and hypomethylated M3 site of GGT genes were 100% and 75% in HCC, 85% and 55% in paracancerous tissues, and 75% and 50% in noncancerous tissues, respectively. An inverse correlation was found between methylational degrees of GGT genes and expression levels of GGT. CONCLUSIONS: The abnormal alteration of serum HS-GGT level is a sensitive tumor marker for HCC diagnosis or differentiation, and the overexpression of GGT in HCC may be related to the hypomethylational status of CCGG sites of GGT genes.

Adult↗
PubMed2000

Two distinctive antinociceptive systems in rats with pathological pain.

A common obstacle in clinical management of pathological pain is the poor response to opioid analgesics. We now report that delta9-tetrahydrocannabinol (delta9-THC)-induced antinociception remained effective in rats with pathological pain. The selective central cannabinoid receptor antagonist SR141716A, but not the generic opioid receptor antagonist naloxone, blocked the delta9-THC antinociception. Moreover, there is no cross-tolerance between the antinociceptive effects of morphine and delta9-THC in pathological pain states. The results indicate that delta9-THC antinociception is both effective and independent of opioid receptors in rats with pathological pain. Thus, the cannabinoid analgesic system may be superior to opioids in alleviating intractable pathological pain syndromes.

Analgesics, Non-Narcotic↗
PubMed2000

Assembly of silver(I) polymers with helical and lamellar structures

The new versatile multidentate nonchelating ligand 1,2-bis[(2-pyr-imidinyl)-sulfanylmethyl]benzene (bpsb) was designed and prepared for supramolecular syntheses. Self-assembly between silver nitrate and the bpsb ligand resulted in the polymer [Ag4(bpsb)2-(NO3)4]n (1) with a single-stranded helical chain structure. Each bpsb ligand in 1 acts as a tetradentate ligand, in which two sulfur atoms and two nitrogen atoms from different pyrimidine groups coordinate to four Ag atoms in four different directions. The nitrate anions serve as a template for the formation of the helix and are either embedded in the interior of the helix or located in the flank of the helix. Self-assembly between silver perchlorate and the bpsb ligand under the same conditions gave rise to the polymer [Ag2(bpsb)3(ClO4)2]n (2) comprising a two-dimensional lamellar network containing crownlike cavities. The silver atoms in two adjacent layers are arranged staggered in 2. The two-dimensional lamellar network comprising isolated cavities of [Ag6(bpsb)6] is very different from that of usual honeycomb structures.

Journal Article↗
PubMed2000

Activation of heat shock factor 1 by hyperosmotic or hypo-osmotic stress is drastically attenuated in normal human fibroblasts during senescence.

We have previously reported that osmotic stress prominently induces the DNA binding activity of the heat shock transcription factor 1 (HSF1). In the present study, we examined the effects of medium osmolarity on both the activation of HSF1 and the programmed cell death in normal human fibroblasts during cellular senescence. The activation of HSF1 occurred rapidly in presenescent (early passage) IMR-90 cells when exposed to either hypo-osmotic or hyperosmotic stress. In contrast, the activation of HSF1 was significantly attenuated in senescent cells. Western blot analysis indicated that equal amounts of HSF1 were present as monomers in the cytoplasm of both presenescent and senescent cells in normal growth medium. Under either hypo-osmotic or hyperosmotic stress, trimerization and nuclear localization of HSF1 occurred in presenescent cells but not in senescent cells. More than 80% of HSF1 in senescent cells remained as monomers in the cytoplasm under osmotic stress, suggesting a defect in the signal transduction pathways that lead to HSF1 trimerization or a dysfunction in the HSF1 protein itself. Possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways in the activation HSF1 was investigated by monitoring the activation of the three MAPKs, ERK1/2, JNK1/2, and p38, in cells exposed to hypo-osmotic or hyperosmotic stress. All three MAPKs were activated by hyperosmotic stress but not hypo-osmotic stress, suggesting that the MAPK signal transduction pathways may not be directly linked to the osmotic stress-induced activation of HSF1. In contrast to the rapid heat shock transcription factor (HSF) activation, apoptosis occurred only after long-term exposure to hypo-osmotic or hyperosmotic stress. Despite the prominent induction of HSF1 activation, the presenescent cells were more sensitive than the senescent cells to the osmotic stress-induced apoptosis.

Apoptosis↗
PubMed2000

Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations.

Germline mutations in the BRCA1 and BRCA2 genes predispose women to breast and ovarian cancer. An incidence of 5% and 3.3% respectively has been reported of BRCA1 and BRCA2 mutations in women with ovarian cancer unselected for family history. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Chinese women is unknown. A total of 60 samples of ovarian cancer diagnosed in Chinese unselected for age or family history were analyzed for BRCA mutations using the protein truncation test. The entire coding exon of BRCA1 of 53 cases and that of exon 11 of BRCA2 of 43 cases were successfully screened. Six germline (11.3%) mutations (633C>T, 1080delT, 1129delA, 2371-2372delTG, 3976-3979delGTGA, and IVS 22+7 A>G) were detected in BRCA1. One germline mutation (3337C>T) (2.1%) was detected in BRCA2. None of these seven cases were associated with strong family history of breast and/or ovarian cancer. Five out of our six BRCA1 mutations and the one BRCA2 mutation identified are novel. Our 11.3% incidence of BRCA1 mutations in ovarian cancer found amongst Chinese with insignificant family history is apparently higher than that previously reported in other populations. It suggests that BRCA1 mutation may play a significant role in the development of sporadic ovarian cancer in Chinese women.

Adult↗
PubMed2000

Monomethyl selenium--specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation.

Previous work suggested that antiangiogenic activity may be a novel mechanism contributing to the cancer chemopreventive activity of selenium (Se). Because methylselenol has been implicated as an in vivo active chemopreventive Se metabolite, experiments were conducted to test the hypothesis that this metabolite pool might inhibit the expression of matrix metalloproteinase-2 (MMP-2) by vascular endothelial cells and of vascular endothelial growth factor (VEGF) by cancer epithelial cells, two proteins critical for angiogenesis and its regulation. In human umbilical vein endothelial cells (HUVECs), zymographic analyses showed that short-term exposure to methylseleninic acid (MSeA) and methylselenocyanate (MSeCN), both immediate methylselenol precursors, decreased the MMP-2 gelatinolytic activity in a concentration-dependent manner. In contrast, Se forms that enter the hydrogen selenide pool lacked any inhibitory effect. The methyl Se inhibitory effect on MMP-2 was cell dependent because direct incubation with Se compounds in the test tube did not result in its inactivation. Immunoblot and enzyme-linked immunosorbent assay analyses showed that a decrease of the MMP-2 protein level largely accounted for the methyl Se-induced reduction of gelatinolytic activity. The effect of MSeA on MMP-2 expression occurred within 0.5 h of exposure and preceded MSeA-induced reduction of the phosphorylation level of mitogen-activated protein kinases (MAPKs) 1 and 2 (approximately 3 h) and endothelial apoptosis (approximately 25 h). In addition to these biochemical effects in monolayer culture, MSeA and MSeCN exposure decreased HUVEC viability and cell retraction in a three-dimensional context of capillary tubes formed on Matrigel, whereas comparable or higher concentrations of selenite failed to exert such effects. In human prostate cancer (DU145) and breast cancer (MCF-7 and MDA-MB-468) cell lines, exposure to MSeA but not to selenite led to a rapid and sustained decrease of cellular (lysate) and secreted (conditioned medium) VEGF protein levels irrespective of the serum level (serum-free medium vs. 10% fetal bovine serum) in which Se treatments were carried out. The concentration of MSeA required for suppressing VEGF expression was much lower than that needed for apoptosis induction. Taken together, the data support the hypothesis that the monomethyl Se pool is a proximal Se for inhibiting the expression of MMP-2 and VEGF and of angiogenesis. The data also indicate that the methyl Se-specific inhibitory effects on these proteins are rapid and primary actions, preceding or independent of inhibitory effects on mitogenic signaling at the level of MAPK1/2 and on cell growth and survival.

Apoptosis↗
PubMed2000

In-situ monitoring of protein labeling reactions by matrix-assisted laser desorption/ionization mass spectrometry.

Taking the labeling reaction of horse heart cytochrome c or ubiquitin with biotinamidocaproate N-hydroxysucchinimide ester (biotin-NHS) as test cases, this report demonstrates the usefulness of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry for in-situ monitoring of the labeling process and for determining the composition of the labeled products without the need for prior separation. The effects of pH and starting materials concentration on the labeling process were investigated in detail. Our MALDI MS results show that: (1) labeled products are always mixtures of different conjugates, which may explain peak broadening found in chromatographic studies of labeling reactions; (2) the higher conjugate fractions become more prominent as the labeling reaction proceeds, with a concomitant exponential decline of the lower conjugate fractions; (3) biotin-NHS can be incorporated into peptides and protein in a stepwise and controlled manner simply by adjusting the molar ratio of the starting materials.

Aminocaproates↗
PubMed2000

Grazing incidence X-ray diffraction of highly aligned phospholipid membranes containing the antimicrobial peptide magainin 2.

We present the first study of grazing incidence X-ray diffraction on a model system of phospholipid membranes and antimicrobial peptides. For this purpose, highly oriented multilamellar samples have been prepared on solid substrates. By this technique, the short-range order of the lipid chains in the fluid L(alpha) phase can be investigated quantitatively, including not only the mean distance between acyl chains, but also the associated correlation length. The short-range order in lecithin is found to be severely affected by the amphiphilic peptide magainin 2.

Amino Acid Sequence↗
PubMed2000

Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.

Osteoprotegerin ligand (OPGL) targets osteoclast precursors and osteoclasts to enhance differentiation and activation, however, little is known about OPGL effects on osteoclast survival. In vitro, the combination of OPGL + colony-stimulating factor-1 (CSF-1) is required for optimal osteoclast survival. Ultrastructurally, apoptotic changes were observed in detached cells and culture lysates exhibited elevated caspase 3 activity, particularly in cultures lacking CSF-1. DEVD-FMK (caspase 3 inhibitor) partially protected cells when combined with OPGL, but not when used alone or in combination with CSF-1. CSF-1 maintained NF-kappaB activation and increased the expression of bcl-2 and bcl-X(L) mRNA, but had no effect on JNK activation. In contrast, OPGL enhanced both NF-kappaB and JNK kinase activation and increased the expression of c-src, but not bcl-2 and bcl-X(L) mRNA. These data suggest that aspects of both OPGL's and CSF-1's signaling/survival pathways are required for optimal osteoclast survival. In mice, a single dose of OPG, the OPGL decoy receptor, led to a >90% loss of osteoclasts because of apoptosis within 48 hours of exposure without impacting osteoclast precursor cells. Therefore, OPGL is essential, but not sufficient, for osteoclast survival and endogenous CSF-1 levels are insufficient to maintain osteoclast viability in the absence of OPGL.

Animals↗
PubMed2000

Dextran sulfate sodium-induced colonic histopathology, but not altered epithelial ion transport, is reduced by inhibition of phosphodiesterase activity.

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function.

Animals↗
PubMed2000

Statistical power for a long-term survival trial with a time-dependent treatment effect.

A time-dependent treatment effect is often observed in cancer clinical trials with survival endpoints, especially in long-term studies. This article evaluates the statistical power of the log-rank test when change point(s) in treatment effect are given. Following the work of Schoenfeld, we derive the asymptotic properties of the log-rank test statistics with time-dependent step-function alternatives. We show that the statistical power for such an alternative hypothesis is determined by the distribution of the number of events for given time intervals. Then, the relationship between the statistical power and the sample size, accrual, and minimum follow-up period can be established. Aided by the examples of two prostate cancer trials conducted by the Radiation Therapy Oncology Group, we demonstrate the changes in statistical power under various alternative hypotheses such as prolonged lag time and a declining treatment effect in long-term studies. Having examined the loss in statistical power by the interim analyses under the alternative hypothesis with a lag time, we recommend that the lower sequential boundary not be used in a long-term survival clinical trial. Control Clin Trials 2000;21:561-573

Clinical Trials as Topic↗
PubMed2000

The immune responses to diabetes in BB rats supplemented with vitamin A.

A substantial amount of evidence suggests that in type I diabetes, vitamin A and zinc status could be of concern because of their impaired metabolic availability. Because both vitamin A and zinc play important roles in the regulation of immune function, the present study was undertaken to examine the immune responses to vitamin A and zinc supplements in diabetic-prone Bio-Breed rats (BBdp), and if the supplements increase the incidence of diabetes. Weanling BBdp rats were fed a NIH-07 diet supplemented with vitamin A either alone or in combination with zinc up to 120 days of age. A greater percentage of rats developing diabetes was found in rats that had supplements of vitamin A and zinc (67%) than those on the basal diet (55%) or with vitamin A supplementation alone (50%). The B cells and macrophages were all markedly increased, whereas CD(4)(+) and CD(8)(+) T cells were decreased at the onset of diabetes. However, this immune status was not changed by vitamin A and zinc supplements. The plasma vitamin A levels were significantly decreased in the presence of diabetes and the vitamin A status did not improve when the rats were given vitamin A and zinc supplements. The Natural Killer cell cytotoxicity on a per-cell basis was significantly decreased in the presence of diabetes, irrespective of supplements with vitamin A and zinc. Overall, results indicated that vitamin A and immune status are both affected by type I diabetes; these effects, however, are not responsive to supplemental intakes of vitamin A either alone or in combination with zinc.

Journal Article↗
PubMed2000

Synthesis and pharmacology of a hybrid cannabinoid.

A pentacyclic hybrid cannabinoid (4) has been synthesized, which combines structural elements of traditional cannabinoids and cannabmimetic indoles. Cannabinoid 4 contains a 1-pentylindole structure fused to the 2,3-positions of the partially reduced hydroxydibenzopyran system of THC. The successful approach to 4 employed 9-benzoyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole (17) as the starting material. Dehydrogenation to carbazole 18, followed by demethylation and condensation with trans-p-menthadienol gave N-benzoyl hybrid cannabinoid 22, N-alkylation of which afforded target cannabinoid 4. The hybrid cannabinoid had affinity for the CB1 receptor approximately equal to that of delta8-THC (Ki = 19.3+/-3 nM), and shows comparable potency in vivo.

Animals↗
PubMed2000

Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases.

Skeletal muscle differentiation is controlled by associations between myogenic basic-helix-loop-helix and MEF2 transcription factors. We show that chromatin associated with muscle genes regulated by these transcription factors becomes acetylated during myogenesis and that class II histone deacetylases (HDACs), which interact with MEF2, specifically suppress myoblast differentiation. These HDACs do not interact directly with MyoD, yet they suppress its myogenic activity through association with MEF2. Elevating the level of MyoD can override the repression imposed by HDACs on muscle genes. HDAC-mediated repression of myogenesis also can be overcome by CaM kinase and insulin-like growth factor (IGF) signaling. These findings reveal central roles for HDACs in chromatin remodeling during myogenesis and as intranuclear targets for signaling pathways controlled by IGF and CaM kinase.

Amino Acid Sequence↗
PubMed2000

Vibrational spectroscopic studies on ion solvation of lithium perchlorate in propylene carbonate + N,N-dimethylformamide mixtures.

The infrared (IR) and Raman spectra are reported for solutions of lithium perchlorate in propylene carbonate (PC), N,N-dimethylformamide (DMF) and PC + DMF mixtures. The band splittings of symmetric ring deformation for PC and O=CN deformation for DMF suggest that there is a strong interaction between lithium cations and solvent molecules. The solvent molecules have been assigned to two types, the free and complexed molecules. By a comparison of the intensity for the corresponding bands, it has been concluded that Li+ cations are preferentially solvated by DMF molecules in the LiClO4/PC-DMF solutions. This has been explained by the difference in values of donor number.

Carbonates↗
PubMed2000

Changes in ganglioside contents, plasma sialic acid and cAMP levels in experimental hepatoma in mice.

The present study was designed to assess whether changes in glycolipids and cyclic AMP contents might serve as markers for the diagnosis of malignancy in the liver. The experimental model was a transplantable murine hepatoma. Experimental mice were divided into three groups: (1) a therapeutic group, which had been transplanted with hepatoma and treated with the antimetabolism drug 5-fluorouracil (0.2 mg/day i.p.), (2) a control group, which had been transplanted with hepatoma and treated with 0.2 ml 0.9% NaCl/day and (3) a normal group of mice. The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP, total- and lipid-bound sialic acid levels and red blood cell membrane sialic acid levels were determined. Results showed that the ganglioside content, total and lipid-bound sialic acid levels in the control group were significantly higher than those in the livers of normal mice (p < 0.01) while these respective values in the therapeutic group were significantly lower than those in the control group (p < 0.01). The cAMP levels of tumor tissues and plasma in the control group were lower than those in normal mice. No significant difference in red blood cell membrane sialic acid content was observed between the therapeutic and control groups though levels for both were higher than those in normal mice. These results indicate that ganglioside content and sialic acid levels in hepatoma tissues were significantly elevated, and cAMP levels in hepatoma tissues were significantly decreased during proliferation and abnormal differentiation.

Animals↗
PubMed2000

A study of the process and kinetics of electrochemical deposition and the hydrothermal synthesis of hydroxyapatite coatings.

Hydroxyapatite (HAp) coatings were prepared using electrochemical deposition and post-hydrothermal synthesis. The composition and morphology of coatings at each processing step was studied through the application of scanning electron microscopy (SEM), X-ray diffraction (XRD) and infra-red spectroscopy (IR). The mechanism and kinetics of hydrothermal synthesis were considered in particular, and the influence of the temperature and time on the HAp formation rate was also investigated. The results show that the electrochemical deposition coatings are composed of CaHPO42H2O crystals which are converted into needle-like HAp crystals after post-hydrothermal treatment. The HAp content of the coatings increases with the treatment temperature and time. The synthesis rate also increases with the pH value of the water. The formation of HAp coatings is considered to be a combination of several reactions. An Arrhenius relationship was found between the HAp formation rate and the temperature, and an apparent activation energy of 94.4 KJ/mol was obtained by calculation.

Journal Article↗