The downregulation of asparagine synthetase expression can increase the sensitivity of cells resistant to l-asparaginase.
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Animals↗
Biomedical subjects
B S Li
Publications and source records attributed to B S Li.
[Comparative study on clinical features of 215 patients with acute and subacute severe hepatitis.].
BACKGROUND: To analyze the clinical features of acute severe hepatitis (ASH) and subacute severe hepatitis (SSH) by comparison analysis. METHODS: The clinical features of 215 cases with ASH and SSH from 1995 to 2005 were retrospectively analyzed by using chi-test, t-test and regression analysis. RESULTS: The most common cause of ASH or SSH was hepatitis B virus (HBV) infection (>30%). Anti-tuberculosis therapy was the main cause of drug-induced ASH or SSH. The incidences of hepatic encephalopathy were 78.13% and 43.05% respectively (P less than 0.001). Prothrombin activity was less than 20% and less than 30%, respectively in cases with ASH and SSH. The most common complications of ASH were hepatic encephalopathy, imbalance of electrolyte and cerebral edema, and that of SSH were ascites, imbalance of electrolyte and hepatic encephalopathy. Prothrombin time, ratio of WBC and neutrophil count were positively related to case fatality of ASH or SSH. Prothrombin activity and total cholesterol (TC) were negatively correlated with fatality of ASH or SSH. Total bilirubin, blood ammonia and creatinine were also positively correlated with fatality of SSH; chlolinesterase, triglyceride, PLT, albumin were negatively correlated with fatality of SSH. CONCLUSION: ASH and SSH are two different entities because of obvious differences in the ages of suffering, the incidence and occurring time of hepatic encephalopathy, abnormality of function of blood coagulation and the marker for predicting prognosis. Severe abnormality of function of blood coagulation is an important marker with high sensitivity and specificity in ASH or SSH patients without hepatic encephalopathy.
Hepatitis↗
Survey of intestinal parasites in pigs from intensive farms in Guangdong Province, People's Republic of China.
The prevalence of intestinal parasites was investigated in intensive pig farms in Guangdong Province, China between July 2000 and July 2002. Faecal samples from 3636 pigs (both sexes and five age groups) from 38 representative intensive pig farms employing different parasite control strategies were examined for the presence of helminth ova and protozoan oocysts, cysts and/or trophozoites using standard techniques. Of the 3636 pigs sampled, 209 (5.7%) were infected with Trichuris suis, 189 (5.2%) with Ascaris, 91 (2.5%) with Oesophagostomum spp., 905 (24.9%) with coccidia (Eimeria spp. and/or Isospora suis) and 1716 (47.2%) with Balantidium coli. These infected pigs were mainly from farms without a strategic anti-parasite treatment regime. Concurrent infection of multiple parasites was common, and T. suis was the most common nematode infecting breeding, young and mature pigs. The results of the present investigation provide relevant 'base-line' data for assessing the effectiveness of control strategies against intestinal parasitism in intensively raised pigs in Guangdong Province, China.
Animals↗
Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway.
Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)-derived peptides contributes to the aetiology of Alzheimer's disease (AD) by stimulating formation of free radicals. Thus, the antioxidant alpha-lipoate, which is able to cross the blood-brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effectiveness of alpha-lipoic acid (LA) against cytotoxicity induced by Abeta peptide (31-35) (30 microM) and hydrogen peroxide (H(2)O(2)) (100 microM) with the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons of rat cerebral cortex. We found that treatment with LA protected cortical neurons against cytotoxicity induced by Abeta or H(2)O(2). In addition, LA-induced increase in the level of Akt in the neurons was observed by Western blot. The LA-induced neuroprotection and Akt increase were attenuated by pre-treatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 microM). Our data suggest that the neuroprotective effects of the antioxidant LA are partly mediated through activation of the PKB/Akt signaling pathway.
Alzheimer Disease↗
Regulation of NMDA receptors by cyclin-dependent kinase-5.
Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
Animals↗
Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt.
The cellular mechanisms underlying the neuroprotective effects of estrogen are only beginning to be elucidated. Here we examined the role of protein kinase B (Akt) activation in 17beta-estradiol (E2) inhibition of beta-amyloid peptide (31-35) (Abeta31-35)-induced neurotoxicity in cultured rat hippocampal neurons. Abeta31-35 (25-30 betaM) significantly decreased the total number of microtubule associated protein-2 positive cells (MAP2+). This decrease was significantly reversed by pre-treatment with 100 nM E2. Further, 100 nM E2 alone significantly increased the total number of protein kinase B and microtubule associated protein-2 positive cells compared with controls. Such E2-induced increases were inhibited by LY294002 (20 microM), a specific PI3-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate that the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation.
Alzheimer Disease↗
Activation of phosphatidylinositol-3 kinase (PI-3K) and extracellular regulated kinases (Erk1/2) is involved in muscarinic receptor-mediated DNA synthesis in neural progenitor cells.
Muscarinic acetylcholine receptor (mAChR), a member of the G-protein-coupled receptors (GPCRs) gene superfamily, has been shown to mediate the effects of acetylcholine on differentiation and proliferation in the CNS. However, the mechanism or mechanisms whereby mAChRs regulate cell proliferation remain poorly understood. Here we show that in vitro bFGF-expanded neural progenitor cells dissociated from rat cortical neuroepithelium express muscarinic acetylcholine receptor subtype mRNAs. We demonstrate that stimulation of these mAChRs with carbachol, a muscarinic agonist, activated extracellular-regulated kinases (Erk1/2) and phosphatidylinositol-3 kinase (PI-3K). This, in turn, stimulated DNA synthesis in neural progenitor cells. MEK inhibitor PD98059 and PI-3K inhibitors wortmannin and LY294002 inhibited a carbachol-induced increase in DNA synthesis. These findings indicate that the activation of both PI-3 kinase and MEK signaling pathways via muscarinic receptors is involved in stimulating DNA synthesis in the neural progenitor cells during early neurogenesis.
Animals↗
SNR versus resolution in 3D 1H MRS of the human brain at high magnetic fields.
It is commonly accepted that the signal-to-noise ratio (SNR = peak-signal/RMS-noise) per-unit-time of proton MR spectroscopy (1H-MRS) is linearly proportional to the voxel volume. Consequently, with a headcoil and 30-min acquisition, 1 cm3 is considered the SNR-limited spatial resolution barrier in the human brain. However, since local linewidths, Delta(upsilon*) = (piT2*)(-1), at high magnetic fields (B0), are dominated by regional inhomogeneities (DeltaB0), i.e., T2* << T2, reducing the voxel dimensions may increase T2*. This could compensate, in part, for signal loss with volume decrease. It is shown that for two cubic voxels of sides l1 and l2, l1 > l2, as the volume decreases by (l1/l2)3, their SNR ratio is reduced by only (l1/l2)2 due to a commensurate T2* increase of l1/l2. This is demonstrated in a phantom and the brains of volunteers, with 3D 1H-MRS in a headcoil at 4 T. It is shown that while the cubic voxels' dimensions were all halved, reducing their volume eightfold, their metabolites' SNR decreased only fourfold, due to their Delta(upsilon*s') twofold decrease. In other words, both spatial and spectral resolutions were doubled at a significantly, x2, smaller-than-expected SNR loss. This advantage was exploited to produce quality high spatial resolution, 0.75 x 0.75 x 0.75 cm3, metabolic maps in a 27-min acquisition.
Adult↗
Ethanol blocks cytosolic Ca2+ responses triggered by activation of GABA(A) receptor/Cl- channels in cultured proliferating rat neuroepithelial cells.
GABA(A) receptor/Cl- channels and voltage-gated Ca2+ channels are believed to be important sites of ethanol action in the CNS. Acute exposure of ethanol potentiates GABA(A) receptor/Cl- channel activity and inhibits voltage-gated Ca2+ channels in a number of preparations, mostly post-mitotic neurons. The effects of ethanol on these channels in primary cultures of undifferentiated neural precursor cells remain unknown. To address this issue, we examined the effects of ethanol on GABA(A) agonist-activated elevation of cytosolic Ca2+ in an in vitro model of the cortical neuroepithelium derived from rat basic fibroblast growth factor-expanded neural precursor cells. We found a potent inhibition of GABA(A)-activated elevation of cytosolic Ca2+ by ethanol in actively proliferating cells. Since we had recently demonstrated that GABA(A) receptor activation depolarizes these cells and elevates their cytosolic Ca2+, we tested whether the effects of ethanol involved both GABA(A) receptors and voltage-gated Ca2+ channels. Both extracellular K+- and muscimol-induced cytosolic Ca2+ elevations were abolished by nitrendipine, indicating that both depolarizing stimuli triggered Ca2+ influx through L-type voltage-gated Ca2+ channels. Exposure of proliferating cells to different concentrations of ethanol revealed that the drug was more potent in blocking muscimol-induced compared to K+-evoked cytosolic Ca2+ elevations. These results raise the possibility that ethanol blocks GABAergic stimulation of cytosolic Ca2+ levels in proliferating precursors primarily by interacting with GABA(A) receptor/Cl- channels and secondarily with voltage-gated Ca2+ channels.
Animals↗
Integrins stimulate phosphorylation of neurofilament NF-M subunit KSP repeats through activation of extracellular regulated-kinases (Erk1/Erk2) in cultured motoneurons and transfected NIH 3T3 cells.
Integrin-mediated interactions of cells with components of the extracellular matrix (ECM) regulate cell survival, cell proliferation, cell differentiation and cell migration through activation of multiple intracellular signal transduction pathways. In this study, we have demonstrated that integrin-matrix interactions promote KSP tail-domain phosphorylation of neurofilament medium molecular weight subunits (NF-M) in cultured rat spinal cord motoneurons and NF-M transfected NIH 3T3 cells. We found that laminin and fibronectin induce NF-M tail-domain phosphorylation in motoneurons and NIH 3T3 cells transfected with NF-M, respectively. This phosphorylation was selectively inhibited by PD98059, a specific MEK1 inhibitor. This suggests that laminin and fibronectin-induced MEK1 activation and the downstream targets Erk1 and Erk2 are involved in NF-M KSP tail-domain phosphorylation. This pathway appears to represent one of the mechanisms whereby integrin-extracellular matrix interactions are involved in phosphorylation of the NF-M KSP tail domain.
3T3 Cells↗
A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis.
Adenosine accumulates to high levels in inflamed or ischemic tissues and activates A3 adenosine receptors (ARs) on mast cells to trigger degranulation. Here we show that stimulation of rat basophilic leukemia (RBL)-2H3 mast-like cells with the A3 AR agonists N6-(3-iodo)benzyl-5'-N-methylcarboxamidodoadenosine (IB-MECA; 10 nM) or inosine (10 microM) stimulates phosphorylation of protein kinase B (Akt). IB-MECA (1 microM) also causes a >50% reduction in apoptosis caused by exposure of RBL-2H3 cells to UV light. Akt phosphorylation is not stimulated by 100 nM N6-cyclopentyladenosine (A1-selective) or CGS21680 (A2A-selective) and is absent in cells pretreated with wortmannin or pertussis toxin. The KI values of the AR antagonists BW-1433 and 8-sulfophenyltheophylline (8-SPT) were determined in radioligand binding assays for all four subtypes of rat ARs: BW-1433 (A1, 5.8 +/- 1.0 nM; A2A, 240 +/- 37; A2B, 30 +/- 10; A3, 12,300 +/- 3, 700); 8-SPT (A1, 3.2 +/- 1.2 microM; A2A, 57 +/- 4; A2), 2.2 +/- 0.8; A3, >100). BW-1433 and the A3-selective antagonist MRS1523 (5 microM), but not 8-SPT (100 microM), block IB-MECA-induced protection from apoptosis, confirming the A3 AR as the mediator of the antiapoptotic response. The data suggest that adenosine and inosine activate Gi-coupled A3 ARs to protect mast cells from apoptosis by a pathway involving the betagamma subunits of Gi, phosphatidylinositol 3-kinase beta, and Akt. We speculate that activation of A3 ARs on mast cells or other cells that express A3 ARs (e.g., eosinophils) may facilitate their survival and accumulation in inflamed tissues.
Adenosine↗
Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations.
PURPOSE: To quantify the extent of neuronal cell loss imparted to the brain by means of radiation therapy through the decline of the amino acid derivative N-acetylaspartate (NAA) by using proton (hydrogen 1) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Proton MR spectroscopy in a clinical MR imager was used to ascertain the amount of whole-brain NAA before and immediately after whole-brain radiation therapy 3-4 weeks later. Eight patients (four women, four men; median age, 55 years; age range, 39-70 years) were studied. All subjects had lung cancer (non-small cell lung cancer [n = 5], small-cell lung cancer [n = 3]) and received either palliative or prophylactic whole-brain radiation therapy. Six of them also underwent a Mini-Mental Status Examination (MMSE) for correlation with the whole-brain NAA. Two-tailed Student t tests were used to evaluate the data. RESULTS: A significant (P = .042) average decline in whole-brain NAA of -0.91 mmol per person was observed in the cohort. No corresponding changes occurred in MMSE scores. There was no significant difference in whole-brain NAA decline between prophylactic and therapeutic whole-brain radiation therapy. CONCLUSION: Since whole-brain NAA loss was detected even when MMSE scores were unchanged, the former seems to be a more sensitive measure of radiation therapy injury than is the latter.
Adult↗
Multivoxel 3D proton spectroscopy in the brain at 1.5 versus 3.0 T: signal-to-noise ratio and resolution comparison.
BACKGROUND AND PURPOSE: The new 3.0-T imagers theoretically yield double the signal-to-noise ratio (SNR) and spectral resolution of 1.5-T instruments. To assess the possible improvements for multivoxel 3D proton MR spectroscopy (1H-MRS) in the human brain, we compared the SNR and spectral resolution performance with both field strengths. METHODS: Three-dimensional 1H-MRS was performed in four 21-29-year-old subjects at 1.5 and 3.0 T. In each, a volume of interest of 9 x 9 x 3 cm was obtained within a field of view of 16 x 16 x 3 cm that was partitioned into four (0.75-cm-thick) 16 x 16-voxel sections, yielding 324 (0.75-cm3) signal voxels per examination. RESULTS: In an acquisition protocol of approximately 27 min, average voxel SNRs increased 23-46% at 3.0 versus 1.5 T in the same brain regions of the same subjects. SNRs for N-acetylaspartate, creatine, and choline, respectively, were as follows: 15.3 +/- 4, 8.2 +/- 2.2, and 8.0 +/- 2.0 at 1.5 T and 22.4 +/- 7.0, 10.1 +/- 3.5, and 10.1 +/- 3.6 at 3.0 T. Spectral resolution (metabolite linewidths) were 3.5 +/- 0.5 Hz at 1.5 T versus 6.1 +/- 1.5 Hz at 3.0 T in approximately 900 voxels. Spectral baselines were noticeably flatter at 3.0 T. CONCLUSION: Expected gains in SNR and spectral resolution were not fully realized in a realistic experiment because of intrinsic and controllable factors. However, the 23-46% improvements obtained enable more reliable peak-area estimation and an 1H-MRS acquisition approximately 50% shorter at 3.0 versus 1.5 T.
Adult↗
Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5 activity is involved in neurite outgrowth and human neurofilament protein H Lys-Ser-Pro tail domain phosphorylation.
Cellular adhesion to the extracellular matrix is mediated by a diverse class of alpha/beta heterodimeric receptors known as integrins, which transduce signals to activate multiple intracellular signal transduction pathways within the cells. The signaling pathway linking integrins to mediate neuronal process outgrowth is not well understood. Here, we have provided evidence that intracellular signaling by the alpha(1)beta(1) integrin-induced activation of cyclin-dependent kinase 5 (cdk5) is involved in neurite outgrowth and human neurofilament protein H (hNF-H) Lys-Ser-Pro (KSP) tail domain phosphorylation in differentiated human SH-SY5Y cells. The integrin alpha(1) and beta(1) monoclonal antibodies and BL-1, a specific cdk5 inhibitor, inhibited these effects. We also demonstrated that cdk5 activity and hNF-H KSP tail domain phosphorylation were increased in cdk5/p35 and hNF-H tail domain co-transfected HEK293 cells grown on laminin. This increased hNF-H tail domain phosphorylation was triggered by cdk5 activation. Taken together, these results indicated that cdk5 may play an important role in promoting neurite outgrowth and hNF-H tail KSP domain phosphorylation through the integrin alpha(1)beta(1) signaling pathway.
Antibodies↗
Testosterone and estrogen affect neuronal differentiation but not proliferation in early embryonic cortex of the rat: the possible roles of androgen and estrogen receptors.
We examined the effect of testosterone (T) and 17 beta-estradiol (E) on differentiation and proliferation of cultured neurons from the cortex of 14-day-rat embryos (E14) using immunocytochemistry. We found that the cultures receiving E had significantly more neurons with longer neurites than the control cultures, while both fewer and less differentiated neurons were seen after 24 h of incubation with T. However, neither T nor E changed the number of cells positive for BrdU, a proliferation marker. We also found that the androgen receptor (AR) was markedly expressed in the neurons, whereas the expression of estrogen (ER(alpha)) receptor was barely detectable. These results suggest that E and T differ in effect on differentiation, while neither affect proliferation in early developmental cortex. Furthermore, since the AR is expressed in the cortical neurons by E14, the inhibitory effect of T on differentiation may be receptor-mediated, while the stimulatory effects of estrogen in the cortex do not appear to involve nuclear ER(alpha) at this developmental stage.
Androgens↗
1H decoupling for in vivo (19)F MRS studies using the time-share modulation method on a clinical 1.5 T NMR system.
Time-share modulation has been implemented successfully on a clinical 1.5 T nuclear magnetic resonance (NMR) system to perform in vivo (19)F[-(1)H] decoupling. It uses commercially available radiofrequency (RF) filters, a transistor-transistor logic (TTL)-controlled attenuator, and a double-resonant RF surface coil suitable for (19)F magnetic resonance spectroscopy (MRS) studies in vivo. This decoupling scheme gives a threefold improvement in signal-to-noise ratio performance compared with the conventional WALTZ-4 decoupling scheme, when significant interaction exists between the decoupler and the receiver. It can also eliminate receiver saturation (i.e., saturation due to coupling of the strong proton decoupling pulse to the (19)F coil) without the need for a high-isolation coil system, thus allowing flexibility in coil geometry. This method has been demonstrated in vivo in patients receiving 5-fluorouracil chemotherapy. Magn Reson Med 44:5-9, 2000.
Antimetabolites, Antineoplastic↗
Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation.
Increasing evidence has shown that some neurotransmitters act as growth-regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell-derived progenitor cells during neural cell lineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU+) cells, both of which were abolished by atropine. Exposure of bFGF-deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth-stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2-bis-(O-aminophenoxy)-ethane-N,N,N', N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G-proteins, the protein kinase C inhibitor H7 and the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MAPK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth-regulatory signal during neurogenesis via pathways involving pertussis toxin-sensitive G-proteins, Ca2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis.
Acetylcholine↗
Molecular cloning, expression, and characterization of rat homolog of human AP-2alpha that stimulates neuropeptide Y transcription activity in response to nerve growth factor.
Neuropeptide Y (NPY) plays an important role in the central regulation of neuronal activity, endocrine and sexual behavior, and food intake. Although transcription activity of the NPY gene in PC12 cells is regulated by a number of agents such as nerve growth factor (NGF), the mechanism responsible for the NGF-elicited increase in the transcription of the NPY gene remains to be explored. In this study, we isolated and characterized a nuclear protein that is bound to NGF-response elements (NGFRE) that lie between nucleotide -87 and -33 of the rat NPY promoter gene. This nuclear protein is identical to the rat homolog of human transcription factor AP-2alpha. We further demonstrated that rat AP-2a promotes efficient NPY transcription activity in response to NGF. Finally, we provide direct evidence that the mice lacking transcription factor AP-2alpha exhibit reduced expression of NPY mRNA compared with wild-type mice, further supporting the hypothesis that AP-2alpha is an important transcription factor in regulating NPY transcription activity.
Amino Acid Sequence↗