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Q Yan

Publications and source records attributed to Q Yan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Infusion of GDNF into the cerebral spinal fluid through two different routes: effects on body weight and corticospinal neuron survival.

Survival of axotomized adult rat corticospinal neurons (CSN) is supported by glial cell line-derived neurotrophic factor (GDNF). We have evaluated the trophic effects of intrathecally applied GDNF on CSN survival and rat body weight. Body weight reduction is the major side effect of intracerebral neurotrophic factor treatment. GDNF was tested at total doses of 30, 100 and 300 microg over 7 days after axotomy via different application routes: intracerebroventricularly (i.c.v.) and cisternally (cis). Animals injected i.c.v. displayed severe body weight reduction at all doses tested but CSN rescue only at the highest dose. In contrast, cis-infusion of GDNF promoted CSN survival at all doses and only the highest dose reduced the body weight. These results show that intracisternal, but not i.c.v., GDNF infusion at low doses can promote CSN survival without negatively affecting rat body weight. This finding may have implications for the clinic use of GDNF.

Animals↗
PubMed1998

Transforming growth factor-beta1 induces apoptotic cell death in cultured retinal endothelial cells but not pericytes: association with decreased expression of p21waf1/cip1.

Transforming growth factor-beta1 (TGF-beta1) regulates a variety of cellular functions. In several types of cells, for example, it acts as a growth inhibitor and an inducer of apoptotic cell death. Although one of the important modulators in retinal vascular development and retinal neovascularization, the effects of TGF-beta1 on retinal microvascular cells are not fully defined. We have found that proliferation of both bovine retinal endothelial cells (EC) and pericytes was inhibited by TGF-beta1 in a concentration-dependent manner. However, only retinal EC lost viability after exposure to increasing concentrations of TGF-beta1 (up to 10 microg/ml) in the presence of 2% fetal bovine serum. Dying EC exhibited the morphological and biochemical characteristics of apoptosis. Fragmented nuclei and chromatin condensation were apparent after staining with the fluorochrome Hoechst 33258 and the reagent ApopTag; moreover, gel electrophoresis of DNA from TGF-beta1-treated EC demonstrated degradation of chromatin into the discrete fragments typically associated with apoptosis. The addition of anti-TGF-beta1 neutralizing antibody abolished the apoptotic cell death induced by TGF-beta1. Because not all the EC in a given culture died after exposure to TGF-beta1, we separated the apoptosis-sensitive cells from those resistant to TGF-beta1 -mediated apoptosis and determined the expression of several proteins associated with this apoptotic pathway. Apoptosis of EC mediated by TGF-beta1 was associated with a decreased level of the cyclin-dependent kinase inhibitor p21waf1/cip1, compared with that observed in the apoptosis-resistant cells. In contrast, the translation product of the tumor-suppressor gene p53 was increased in the TGF-beta1-treated apoptotic cells. Thus, we propose that p21waf1/cip1 and p53 function in distinct pathways that are protective or permissive, respectively, for the apoptotic signals mediated by TGF-beta1.

Animals↗
PubMed1998

A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury.

Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme thiamine monophosphatase (TMP). Here we show that these neurons express the receptor components for glial-derived neurotrophic factor (GDNF) signaling (RET, GFRalpha-1, and GFRalpha-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFRalpha-1, GFRalpha-2, or GFRalpha-1 plus GFRalpha-2. GDNF, but not nerve growth factor (NGF), can prevent several axotomy-induced changes in these neurons, including the downregulation of IB4 binding, TMP activity, and somatostatin expression. GDNF also prevents the slowing of conduction velocity that normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GDNF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophin treatment.

Age Factors↗
PubMed1998

Response of lens epithelial cells to hydrogen peroxide stress and the protective effect of caloric restriction.

Hydrogen peroxide (H2O2) has been reported to be present at significant levels in the lens and aqueous humor in some cataract patients and suggested as a possible source of chronically inflicted damage to lens epithelial (LE) cells. We measured H2O2 effects on bovine and mouse LE cells and determined whether LE cells from old calorically restricted mice were more resistant to H2O2-induced cellular damage than those of same age ad libitum fed (AL) mice. Bovine lens epithelial cells were exposed to H2O2 at 40 or 400 microM for 2 h and then allowed to recover from the stress. The cells were assayed for DNA damage, DNA synthesis, cell viability, cell morphology, response to growth stimuli, and proliferation potential. Hydrogen peroxide-treated cells showed an increased DNA unwinding 50% greater than that for untreated controls. These DNA strand breaks appeared to be almost completely rejoined by 30 min following removal of the cells from a 2-h exposure. The 40 microM exposure did not produce a significantly lower DNA synthesis rate than the control, it responded to growth factor stimuli, and it replicated as did the control cells after removal of H2O2. The 400 microM H2O2 severely affected DNA synthesis and replication, as shown by increased cell size and by markedly reduced clonal cell growth. The cells did not respond to growth stimulation by serum or growth factors and lost irreversibly the capacity to proliferate. The responses of LE cells from old adlib diet (AL) and calorically restricted (CR) mice to H2O2 were significantly different. Exposure of LE cells to 20, 40, or 100 microM H2O2 for 1 h induces a significant loss of cellular proliferation in cells from old AL mice. LE cells from long-term CR mice of the same strain and age were more resistant to oxidative damage at all three concentrations of H2O2 than those of both old and young AL mice and showed a significantly higher proliferation potential following treatment. It is concluded that CR results in superior resistance to reactive oxygen radicals in the lens epithelium.

Age Factors↗
PubMed1998

Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist.

Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-alpha) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-alpha and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.

Animals↗
PubMed1998

Rapid alterations of BDNF protein levels in the rat brain after focal ischemia: evidence for increased synthesis and anterograde axonal transport.

Cellular localization and tissue levels of BDNF protein were studied using immunocytochemistry and enzyme immunoassay, respectively, in the cortex and striatum at different reperfusion times (0-24 h) after 2 h of unilateral middle cerebral artery occlusion (MCAO) in rats. The distribution of neuronal injury was analyzed in NeuN-, cresyl violet-, and Fluoro-Jade-stained sections. At 2 h postischemia, but not at later time points, there was a several-fold increase of the number of BDNF-immunoreactive (-ir) cells in the ipsilateral cingulate and frontal cortices outside the damaged area. Animals with cortical injury showed loss of BDNF-ir fibers in the striatum at 2-24 h, whereas rats with cell damage confined to the striatum exhibited no such change. At 2-16 h, strongly BDNF-ir fibers were observed along the myelinated fascicles medially in the striatum, in the anterior commissure, and in the corpus callosum ipsilateral to the MCAO. BDNF protein levels were increased (by 133-213%) at 2 h in the cingulate and frontal cortices and decreased (by 40%) at 24 h in the striatum. These findings show that the increased expression of BDNF mRNA in cortical neurons previously demonstrated after transient focal ischemia is accompanied by elevated levels of BDNF protein. The rapid decline of BDNF protein levels suggests a pronounced release or anterograde axonal transport in the postischemic phase. The reduction of BDNF protein in the striatum of animals with cortical damage provides further evidence for anterograde transport, which is also supported by the accumulation of BDNF protein in several preterminal fiber systems. The changes of BDNF protein after focal ischemia could play a role for survival and plasticity of cortical and striatal neurons.

Animals↗
PubMed1998

Differential regulation by MK801 of immediate-early genes, brain-derived neurotrophic factor and trk receptor mRNA induced by a kindling after-discharge.

Transient changes in immediate-early genes and neurotrophin expression produced by kindling stimulation may mediate secondary downstream events involved in kindling development. Recent experiments have demonstrated conclusively that both kindling progression and mossy fibre sprouting are significantly impaired by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801. To further examine the link between kindling, changes in gene expression and the NMDA receptor, we examined the effects of MK801 on neuronal induction of immediate-early genes, brain-derived neurotrophic factor (BDNF) and trk receptor mRNA expression produced by a single electrically induced hippocampal after-discharge in rats. The after-discharge produced a rapid (after 1 h) increase in Fos, Jun-B, c-Jun, Krox-24 mRNA and protein and Krox-20 protein in dentate granule neurons and a delayed, selective expression of Fos, Jun-D and Krox-24 in hilar interneurons. MK801 pretreatment produced a very strong inhibition of Fos, Jun-D and Krox-20 increases in dentate neurons but had a much smaller effect on Jun-B and c-Jun expression. MK801 did not inhibit Krox-24 expression in granule neurons or the delayed expression of Fos, Jun-D and Krox-24 in hilar interneurons. BDNF protein and trk B and trk C mRNA expression were also strongly induced in dentate granule cells 4 h following an after-discharge. MK801 abolished the increase in BDNF protein and trk B, but not trk C mRNA in granule cells at 4 h. These results demonstrate that MK801 differentially regulates the AD-increased expression of a group of genes previously identified as being likely candidates for an involvement in kindling. Because MK801 significantly retards the development of kindling and mossy fibre sprouting, it can be argued that those genes whose induction is not significantly attenuated by MK801 are unlikely to play an important role in the MK801-sensitive component of kindling and the changes in neural connectivity (mossy fibre sprouting) associated with kindling. Conversely, the role in kindling of those genes whose expression was significantly attenuated by MK801 (Fos, Jun-D, Krox-20, trkB and BDNF) requires further examination.

Animals↗
PubMed1998

Energy expenditure of Chinese infants in Guangdong Province, south China, determined with use of the doubly labeled water method.

The doubly labeled water method was used to measure the energy expenditure of a group of 41, 4- or 6-mo-old infants with a cross-sectional design. The infants were divided into two groups according to whether they were breast-fed (11 at 4 mo, 9 at 6 mo) or formula fed (11 at 4 mo, 10 at 6 mo). Anthropometric measurements were recorded at birth and at the beginning and end of the 8-d study. Anthropometric data, which were supported by the food intake and energy expenditure results, indicated that the infants were within the norms for European and American infants of the same age. Mean energy intakes of 352 kJ (84 kcal) kg(-1) x d(-1) at 4 and 6 mo were lower than the FAO/WHO/UNU recommended value of 452 kJ (108 kcal) x kg(-1) x d(-1)) and Chinese recommendations of 502 kJ (120 kcal) kg(-1) x d(-1). However, some authors believe that values of 398 kJ (95 kcal) kg(-1) x d(-1) at 4 mo and 356 kJ (85 kcal) kg(-1) x d(-1) at 6 mo are more appropriate. At 6 mo the infants' length-for-age and weight-for-age were at the National Center for Health Statistics 55th and 47th percentiles, respectively, whereas 58% were below the 50th percentile for weight-for-length. We conclude that at 4 mo infants receive sufficient energy for their requirements. However, at 6 mo energy requirements might well be greater than the revised recommendations, when infants are being weaned to alternative foods and are more prone to the influence of diet on their growth and development.

Anthropometry↗
PubMed1998

SPARC is expressed by ganglion cells and astrocytes in bovine retina.

SPARC (secreted protein, acidic and rich in cysteine)/osteonectin is a matricellular, counteradhesive glycoprotein that disrupts cell-matrix interactions, interacts with growth factors and components of extracellular matrix, and modulates the cell cycle, but appears to subserve only minor structural roles. SPARC is expressed in a variety of tissues during embryogenesis and remodeling and is believed to regulate vascular morphogenesis and cellular differentiation. Although usually limited in normal adult tissues, SPARC is expressed at significant levels in the adult central nervous system. Using a monoclonal antibody against bovine bone osteonectin, we have determined the localization of SPARC in newborn (3-day-old) and adult (4-8-year-old) normal bovine retinas. SPARC was present in the soma of ganglion cells and strong reactivity was found in ganglion cell axons. Muller cells displayed no immunoreactivity, but SPARC was present in retinal astrocytes that were identified by the astrocyte marker glial fibrillary acidic protein (GFAP). Newborn calf retina showed a staining pattern similar to that of adult retina but exhibited significantly reduced levels of SPARC. Minimal levels of SPARC protein were also detected in some capillaries of the inner retina of both newborn and adult animals, whereas large vessels were negative. The presence of SPARC in the retina was confirmed by Western blotting of retinal extracts. These data indicate that SPARC originating from bot h neurons and glia of the inner retina may be an important modulator of retinal angiogenesis. The increased expression of SPARC in adult relative to newborn retinal tissue also indicates that SPARC has an ongoing role in the maintenance of retinal functions.

Animals↗
PubMed1998

[A clinicopathological study on panniculitic T-cell lymphoma].

OBJECTIVE: To analyse the pathomorphology and clinical behavior of panniculitic T-cell lymphoma (PTCL) and to study the classification and name of PTCL. METHODS: Routine pathological and immunohistochemical methods were utilized to analyse 4 cases of PTCL. RESULTS: All patients presented with 1 to 3 cm diameter subcutaneous nodules accompanied by high fever. The clinical course of these patients was distinctive and progressive. All patients died within 4-9 months. Histologically, the lesions were composed of medium sized atypical cells (CD45RO+) infiltrating between fat cells, large numbers of bean bag cells (CD68+) could be observed. CONCLUSIONS: PTCL is a type of peripheral T-cell lymphoma which is highly malignant.

Adult↗
PubMed1998

[Preliminary studies on chemical constituents and pharmacological action of Eclipta prostrata L].

OBJECTIVE: To study the pharmacologically active components of Eclipta prostrata. METHOD: The components were extracted by alcohol and isolated by silica gel column and subjected to pharmacological screening. RESULT: Four compounds were isolated from E. prostrata, of which two were identified as stigmasterol and alpha-terthienyl. CONCLUSION: alpha-Terthienyl was isolated from the plant for the first time. The EtOAc part of alcoholic extraction exhibits significant hepatoprotective activity against carbon terachloride-induced liver injury in rats.

Alanine Transaminase↗
PubMed1997

Brain-derived neurotrophic factor fails to arrest neuromuscular disorders in the paralysé mouse mutant, a model of motoneuron disease.

Several new neurotrophic factors have been recently identified and shown to prevent motoneuron death in vitro and in vivo. One such agent is brain-derived neurotrophic factor (BDNF). In this study, we tested BDNF on an animal model of early-onset motoneuron disease: the paralysé mouse mutant, characterized by a progressive skeletal muscle atrophy and the loss of 30-35% of spinal lumbar motoneurons between the first and second week post-natal. The results show that subcutaneous injections of 1 or 10 mg/kg BDNF did not have any significant effect in increasing the mean survival time of mutant mice or in preventing the loss of motor function and total body weight in paralysé mice. The weight and choline acetyltransferase activity of specific muscles and the number of motoneurons in the spinal cords were identical in BDNF-treated and placebo-injected paralysé mice. These results suggest that BDNF does not act on the disease process in paralysé mice in the conditions we used. By contrast, BDNF has previously been shown to partially prevent the loss of motor function in the wobbler mouse, a suggested model of later-onset motoneuron disease. Taken together these findings suggest that BDNF acts differently on early and late-onset motoneuron diseases. It is however possible that treatment of paralysé mice with BDNF or combinations of different neurotrophic factors prior to the phenotypical expression of the paralysé mutation may prevent the loss of motor function and motoneurons in mutant mice.

Animals↗
PubMed1997

Mechanism of tubulin-colchicine recognition: a kinetic study of the binding of the colchicine analogues colchicide and isocolchicine.

Colchicide (IDE) is a colchicine (COL) analogue in which the C-10 methoxy group is replaced by a hydrogen atom. Its binding to tubulin is accompanied by a quenching of the protein fluorescence. The fluorescence decrease shows a monoexponential time dependence. The observed rate constant increases in a non-linear way with the total concentration of IDE, allowing the determination of a binding constant for an initial binding site (K1=5300+/-300 M-1) and the rate constant for the subsequent isomerization (k2=0.071+/-0.002 s-1) at 25 degrees C. The rate constant, k-2, for the reversed isomerization can be determined by displacement experiments. Despite the minor alteration of the C-ring substituent, the kinetic and thermodynamic parameters of binding are substantially different from those of COL itself, for both steps. In isocolchicine (ISO) the carbonyl oxygen atom and the methoxy groups of the C-ring have been interchanged. Its binding to tubulin only results in small fluorescence and absorbance changes. Therefore competition experiments with MTC [2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4, 6-cycloheptatrien-1-one] were performed. ISO competes rapidly and with low affinity with MTC. Fluorimetric titrations of tubulin with MDL (MDL 27048 or trans-1-(2,5 dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2-methyl-2-propen-1 -one) in the presence and absence of ISO give evidence for the existence of a second, slow-reacting low-affinity site for ISO that is not accessible to MTC or MDL. The relevance of these results for the recognition of COL is analysed.

Animals↗
PubMed1997

Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord.

Using immunocytochemistry and in situ hybridization, we have examined the expression of brain-derived neurotrophic factor (BDNF) and of neurotrophin receptors in dorsal root ganglion cells. In the adult rat, BDNF mRNA and protein were found mainly in the subpopulation of cells that express the nerve growth factor (NGF) receptor trkA and the neuropeptide calcitonin gene-related peptide (CGRP). NGF increased BDNF within the trkA/CGRP cells to the extent that almost 90% of trkA cells contained BDNF mRNA after intrathecal NGF treatment, and 80-90% of BDNF-expressing cells contained trkA. Non-trkA cells that expressed BDNF included some trkC cells and some small cells that labeled with the lectin Griffonia simplicifolia IB4, a marker for cells that do not express trks. However, very few trkB cells expressed either BDNF mRNA or protein, and NGF did not increase BDNF expression in non-trkA cells. BDNF protein was anterogradely transported both peripherally and centrally. The central transport resulted in BDNF immunoreactivity in CGRP containing terminal arbors in the dorsal horn of the spinal cord, and this immunoreactivity was increased by NGF treatment. Electron microscopic analysis revealed that the BDNF immunoreactivity was present in finely myelinated and unmyelinated axons and in axon terminals, where it was most concentrated over dense-cored vesicles. Our data do not support an autocrine or paracrine role for BDNF within normal dorsal root ganglia, but indicate that BDNF may act as an anterograde trophic messenger. NGF levels in the periphery could influence dorsal horn neurons via release of BDNF from primary afferents.

Afferent Pathways↗
PubMed1997

Brain-derived neurotrophic factor is reduced in Alzheimer's disease.

Alzheimer's disease may be due to a deficiency in neurotrophin protein or receptor expression. Consistent with this hypothesis, a reduction in BDNF mRNA expression has been observed in human post-mortem Alzheimer's disease hippocampi. To further investigate this observation, we examined whether the alteration in BDNF expression also occurred at the protein level in human post-mortem Alzheimer's disease hippocampi and temporal cortices using immunohistochemical techniques. We observed a reduction in the intensity and number of BDNF-immunoreactive cell bodies within both the Alzheimer's disease hippocampus and temporal cortex when compared to normal tissue. These results support and extend previous findings that BDNF mRNA is reduced in the human Alzheimer's disease hippocampus and temporal cortex, and suggest that a loss of BDNF may contribute to the progressive atrophy of neurons in Alzheimer's disease.

Adult↗
PubMed1997

Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy.

Glial cell-line derived neurotrophic factor (GDNF) has survival promoting effects on axotomized neonatal motoneurons. We examined how long it could sustain motoneurons after postnatal day O (PND) facial nerve axotomy. GDNF, or cytochrome c as a negative control, were locally administered by Gelfoam implants at the time of axotomy and some were re-implanted on PND 14. The surviving motoneurons were quantified on PND 14 and 28. GDNF completely rescued lesioned motoneurons from axotomy-induced cell death at 14 days and was still effective (about 40%) at PND 28. GDNF also prevented axotomy-induced atrophy at both PND 14 and 28, indicating that the neurotrophic effects of GDNF on neonatal motoneurons are long-term.

Animals↗