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Biomedical subjects

B Cheng

Publications and source records attributed to B Cheng.

At least 109 records · Page 6Linked to original sources
PubMed1994

Staurosporine, K-252a, and K-252b stabilize calcium homeostasis and promote survival of CNS neurons in the absence of glucose.

Staurosporine, K-252a, and the 9-carboxylic related compound K-252b are low-molecular-weight alkaloids from microbial origin that at high concentrations are kinase inhibitors and can antagonize the effects of neuronal growth factors. Paradoxically, we have found that very low concentrations of these agents (10 fM-10 nM) prolong the survival of hippocampal, septal, and cortical neurons deprived of glucose. These agents did not prevent the depletion of ATP caused by glucose deprivation. The large elevation of intracellular calcium levels that normally mediates glucose deprivation-induced damage was attenuated by staurosporine, K-252a, and K-252b. Western blot analysis using antiphosphotyrosine antibody showed that staurosporine and the K-252 compounds (10-100 pM) stimulated tyrosine phosphorylation of several different proteins. The tyrosine kinase inhibitor genistein significantly reduced the protective effect of staurosporine and the K-252 compounds, indicating that tyrosine phosphorylation was required for neuroprotection by these compounds. Taken together, the data demonstrate that low concentrations of staurosporine and the K-252 compounds can stabilize calcium homeostasis, possibly by a mechanism involving activation of receptor tyrosine kinase transduction pathways.

Alkaloids↗
PubMed1994

[Herpes zoster keratoendotheliitis].

Herpes zoster keratoendotheliitis is related to autoimmunity or herpes zoster virus infection. It is characterised by K.P. and interstitial edema. The disease responds well to the administration of steroids and a good result is often achieved.

Adrenal Cortex Hormones↗
PubMed1994

[Comprehensive evaluation of inheritance and environmental factors in the etiology of primary liver cancer].

A1:1 matched case-control study was carried out in 152 cases with primary liver cancer (PLC) and 152 controls to identify the risk factors associated with it and its cumulative mortality in their second- and third-degree relatives. Results showed cumulative mortality of PLC in the relatives of the cases (0.46%) was significantly higher than that of controls (0.07%). Cumulative mortality of PLC in consanguineous relatives of the cases (0.55%) was significantly higher than that in non-consanguineous ones (0.08%). Cumulative mortality of PLC decreased regularly with family relation (consanguinity) drifting apart. Genetic factors still played an important role independently in the etiology of PLC with multiple regression and stratification analyses studying genetic and environmental factors as a whole. This laid a theoretical basis to study further the association between genetic factors and PLC incidence.

Case-Control Studies↗
PubMed1994

[A new diarrhea pathogen: entero-SLTs-producing and invasive Escherichia coli was over-looked as normal flora E. coli].

In clinical laboratories of Beijing, China, no known entero-pathogen but almost pure E. coli strains could be isolated from more than 60% fecal samples of diarrheal patients, which had been recognized as normal flora E. coli and dismissed. We suspected that some of the so-called normal flora E. coli strains might be virulent. To prove our idea. We collected 172 strains of E. coli isolated from diarrheal patients from whom no other enteric bacterial pathogens had been identified, including EPEC, EIEC, ETEC. With plasmid DNA analysis, Hep-2 cell adherence assay and 10 DNA probe hybridization, we found that the so-called normal flora E. coli was abnormal, 44% of them were virulent, of which 16 (9.3) were EHEC, 8 EPEC (4.7%), 11 EAggEC (6.8%). Fifty-four of 172 strains were hybridized with INV and SLT1 or SLT2 probes, which had never been reported. These strains could invade Hep-2 cells, but were lack of ipaB gene, a key gene of invasiveness gene cluster of Shigella species and EIEC. The aggregative adherence to Hep-2 cells was observed, but the strains were not hybridized with EAggEC specific DNA probe. The purified toxin protein and cell filtrate were toxic to vero cells. Based on the data obtained, we believed that this is a new category of diarrhea-genic E. coli, named as entero-SLTs-producing and invasive E.coli (ESIEC). ESIEC occupied 31.4% of the strains tested, the isolation of it was probably higher than those of ETEC, EPEC in P R China.

Adult↗
PubMed1994

Analysis of adrenal cholesteryl esters by reversed phase high performance liquid chromatography.

A reversed phase high performance liquid chromatographic (HPLC) method was developed for direct profiling and determination of adrenal cholesteryl ester composition. Cholesteryl adrenate and cholesteryl cervonate, which are not commercially available, were synthesized as markers. Lipid extracts of rat adrenal homogenates or lipid droplets were individually applied to a conditioned silica gel-60 column which separated cholesteryl esters from other native lipids. The eluted cholesteryl ester fraction was then analyzed by HPLC. With cholesteryl heptadecanoate as internal standard, seven adrenal cholesteryl esters were detected and quantified: cholesteryl cervonate, cholesteryl arachidonate, cholesteryl adrenate, cholesteryl myristate, cholesteryl oleate, cholesteryl palmitate, and cholesteryl stearate. Among them, cholesteryl adrenate appeared to be the major sterol ester stored in the rat adrenal.

Adrenal Glands↗
PubMed1993

Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons.

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) can protect CNS neurons against ischemic/excitotoxic insults, but the mechanism of action is unknown. Imaging of the calcium indicator dye fura-2 and whole-cell patch clamp recordings of calcium currents were used to examine the mechanisms whereby hypoglycemia damages and growth factors protect cultured rat hippocampal neurons. When cultures were deprived of glucose, massive neuronal death occurred 16-24 h following the onset of hypoglycemia. Early hypoglycemia-induced changes included calcium current inhibition and a reduction in intracellular free calcium levels ([Ca2+]i) without morphological signs of neuronal damage. Later changes included a large elevation of [Ca2+]i which was causally involved in neuronal damage. NGF and bFGF prevented or reduced both the early and later responses to hypoglycemia. The growth factors increased calcium (barium) current and [Ca2+]i to normal limits during the early stages of hypoglycemia and prevented the later elevation in [Ca2+]i and neuronal damage. Nifedipine, but not omega-conotoxin, blocked calcium currents. The increased calcium current caused by the growth factors was apparently not sufficient to protect neurons against hypoglycemic damage since K+ depolarization during the early stages of hypoglycemia did not prevent and, in fact exacerbated, the subsequent neuronal damage. In addition, exposure of neurons to K+, NGF or bFGF only during the first 1 h of hypoglycemia did not protect against hypoglycemic damage. Taken together, the data suggest that neurons initially respond to hypoglycemia with a reduction in calcium currents which may provide a means to maintain [Ca2+]i within a concentration range conducive to cell survival. Prolonged energy deprivation eventually results in a failure of calcium extrusion systems, glutamate receptor activation and a loss of neuronal calcium homeostasis. Taken together, the data indicate that the mechanism of growth factor protection against energy deprivation involves prevention of the late rise in [Ca2+]i.

Animals↗
PubMed1993

beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease.

Recent findings link altered processing of beta-amyloid precursor protein (beta APP) to disruption of neuronal Ca2+ homeostasis and an excitotoxic mechanism of cell death in Alzheimer's disease. A major pathway of beta APP metabolism results in the release of secreted forms of beta APP, APPss. These secreted forms are released in response to electrical activity and can modulate neuronal responses to glutamate, suggesting roles in developmental and synaptic plasticity. beta APP is upregulated in response to neural injury and APPss can protect neurons against excitotoxic or ischemic insults by stabilizing the intracellular Ca2+ concentration [Ca2+]i. An alternative beta APP processing pathway liberates intact beta-amyloid peptide, which can form aggregates that disrupt Ca2+ homeostasis and render neurons vulnerable to metabolic or excitotoxic insults. Genetic abnormalities (e.g. certain beta APP mutations or Down syndrome) and age-related changes in brain metabolism (e.g. reduced energy availability or increased oxidative stress) may favor accumulation of [Ca2+]i-destabilizing beta-amyloid peptide and diminish the release of [Ca2+]i-stabilizing, neuroprotective APPss.

Alzheimer Disease↗
PubMed1993

Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein.

The beta-amyloid precursor protein (beta APP) is a membrane-spanning glycoprotein that is the source of the beta-amyloid peptide (beta AP) which accumulates as senile plaques in the brains of patients with Alzheimer's disease. beta APP is normally processed such that a cleavage occurs within the beta AP, liberating secreted forms of beta APP (APPss) from the cell. The neuronal functions of these forms are unknown. We now report that APPss have a potent neuroprotective action in cultured rat hippocampal and septal neurons and in human cortical neurons. APPs695 and APPs751 protected neurons against hypoglycemic damage, and the neuroprotection was abolished by antibodies to a specific region common to both APPs695 and APPs751. APPss caused a rapid and prolonged reduction in [Ca2+]i and prevented the rise in [Ca2+]i that normally mediated hypoglycemic damage. APPss also protected neurons against glutamate neurotoxicity, effectively raising the excitotoxic threshold. APPss may normally play excitoprotective and neuromodulatory roles. Alternative processing of APPss in Alzheimer's disease may contribute to neuronal degeneration by compromising the normal function of APPss and by promoting the deposition of beta AP.

Amyloid beta-Protein Precursor↗
PubMed1993

Lacrimal secretion stimulants: sigma receptors and drug implications.

3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to sigma-receptors (25 nM) in the presence of 25 nM spiperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10(-9) to 10(-2)M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N,N'-dimethyl-2-phenyl-ethylamine), yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50 = 900 nM). Applying the technic of Bromberg [Exp. Eye Res., 40:313-320, 1985], in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds. In vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10(-8) to 10(-4) M for various derivatives of bromhexine and 10(-4) M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50 microliters) to the right eye of New Zealand white rabbits (n = 20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10(-4) M), with haloperidol (10(-4) M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a dose-response curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.

Animals↗
PubMed1993

Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons.

Basic fibroblast growth factor (bFGF) was recently found to modulate the outgrowth-regulating effects of glutamate, and protected neurons from several brain regions against excitotoxi/ischemic damage. We provide evidence that the excitoprotective mechanism of bFGF involves suppression of the expression of a 71 kDa NMDA receptor protein (NMDARP-71). NMDARP-71 protein and mRNA levels were reduced in neurons in bFGF-treated hippocampal cell cultures. The levels of the NMDARP-71 were not reduced by NGF or epidermal growth factor, and bFGF did not reduce the level of mRNA for the GluR1 kainate/AMPA receptor, demonstrating the specificity of the effect of bFGF on the NMDARP-71. The reduction in NMDARP-71 expression in bFGF-treated neurons was correlated with reduced vulnerability to NMDA neurotoxicity. A major role for NMDARP-71 in calcium responses to NMDA and excitotoxicity was demonstrated using antisense oligonucleotides directed against NMDARP-71. Northern and Western blot analysis and immunocytochemistry showed that NMDARP-71 antisense oligonucleotides caused a selective suppression of NMDARP-71 mRNA and protein levels during 12-44 hr exposure periods. Elevations in intracellular calcium levels normally caused by glutamate and NMDA were attenuated in neurons exposed to NMDARP-71 antisense oligonucleotide; calcium responses to kainate were relatively unaffected. NMDARP-71 antisense oligonucleotides protected the neurons against excitotoxicity. Thus, NMDARP-71 is a necessary component of an NMDA receptor mediating calcium responses and neurotoxicity in hippocampal neurons. Taken together, these data identify a mechanism whereby bFGF can modify neuronal responses to glutamate, and suggest that regulating the expression of excitatory amino acid receptors may provide a means for growth factors to influence the plasticity and degeneration of neural circuits.

Animals↗
PubMed1993

[Separation and purification of human apolipoproteins A-I and C-III by chromatofocusing].

Human very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were isolated and purified by a process of combined dextran sulfate precipitation and density gradient ultracentrifugation. Chromatofocusing, which separates protein based on differences in isoelectric point, was used to separate apolipoprotein A-I (apoA-I) and apolipoprotein C-III from human HDL and VLDL, respectively. Discontinuous SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and analytical isoelectric focusing (IEF) were used to study the purity of different fractions. Both purified apoA-I and apoC-III showed single bands on SDS-PAGE at molecular weights of 28183 and 9400 Daltons, respectively. As determined by IEF in the presence of 8 mol/L urea, apoA-I had eight isoforms with pI of 5.66-5.87. The pI's of the three isoproteins of apoC-III (C-III0, C-III1 and C-III2) were 5.06, 4.88 and 4.72, respectively. Chromatofocusing, a new simple technique combining the high resolving power of IEF with the high capacity of ion-exchange column chromatography, is extremely valuable for large-scale purification of the major apolipoproteins of VLDL and HDL.

Apolipoprotein A-I↗
PubMed1993

Growth factors protect neurons against excitotoxic/ischemic damage by stabilizing calcium homeostasis.

An aberrant elevation in intraneuronal calcium levels resulting from energy failure and excitatory amino acid receptor activation is believed to play a major role in the neuronal damage and death that occur in stroke. We have found that several growth factors can protect cultured rat hippocampal and septal neurons and human cortical neurons from excitotoxic damage caused by glucose deprivation or hypoxia. Using the calcium indicator dye fura 2 and whole-cell patch-clamp recording, we found that glucose deprivation initially results in calcium current inhibition and a reduction in intraneuronal free calcium levels without morphological signs of cell damage. After 12 to 16 hours of glucose deprivation, a large elevation in intraneuronal calcium levels occurred that involved N-methyl-D-aspartate receptor activation and mediated the cell damage and death. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each prevented, in a dose-dependent manner, glucose deprivation-induced loss of calcium homeostasis and neuronal damage. The growth factors were effective to varying degrees when added up to 12 hours after the onset of glucose deprivation. NGF, bFGF, and IGFs also protected neurons against damage caused by exposure to a hypoxic environment. By stabilizing intraneuronal calcium levels within a window of concentrations conducive to neuronal survival, growth factors can protect neurons against the damaging effects of ischemia-like insults. Because ATP levels are expected to be reduced under ischemia-like conditions, we determined whether the growth factors would protect neurons against a more selective reduction in ATP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Intraoperative explosive choroidal hemorrhage (report of four cases)].

Intraoperative explosive choroidal hemorrhage (ECH) is a rare, but severe complication of intraocular surgery. This complication often occurs during or after intraocular surgery. We report four cases that developed this complication during surgery. Once the complication occurs, we should use the dehydration medicine intravenously, suture the incision, application of pressure directly to the eye and incise the postsclera. If the bleeding can't be stopped, enucleation is the indication.

Aged↗
PubMed1992

Glucose deprivation elicits neurofibrillary tangle-like antigenic changes in hippocampal neurons: prevention by NGF and bFGF.

A decrement in glucose utilization in brain was previously demonstrated in Alzheimer's disease (AD) and this abnormality has been proposed to play a role in the process of neuronal degeneration. We now report that glucose deprivation in cultured hippocampal neurons can result in antigenic alterations similar to those seen in AD neurofibrillary tangles (NFT) and, ultimately, cell death. Hypoglycemia caused an increase in neuronal immunoreactivity toward tau and ubiquitin antibodies. The antigenic alterations resulted from hypoglycemia-induced elevations in intracellular calcium levels as measured using the calcium indicator dye fura-2. The increased intraneuronal calcium levels, increased tau and ubiquitin immunoreactivities, and neuronal damage resulted from influx through the plasma membrane since they were not observed when cells were incubated in calcium-deficient medium. Neuronal damage and NFT-like antigenic changes were completely prevented by nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), but not by epidermal growth factor (EGF). NGF and bFGF, but not EGF, prevented the aberrant rise in intracellular calcium levels that normally resulted from glucose deprivation. These data are consistent with the possibility that reduced glucose availability to neurons may contribute to the neuronal degeneration that occurs in AD. They also suggest that growth factors may normally protect neurons against hypoglycemic damage.

Animals↗
PubMed1992

Degenerative and axon outgrowth-altering effects of phencyclidine in human fetal cerebral cortical cells.

Babies born to mothers abusing the psychotomimetic drug phencyclidine (PCP), often show profound deficits in CNS function. It is now reported that PCP can cause progressive degeneration and death in human fetal cerebral cortical neurons in culture and sublethal levels of PCP can inhibit axon outgrowth. In cerebral cortical cell cultures established from 14 week fetuses, exposure to 500 microM PCP resulted in a progressive degeneration of neurons over a 2-8 day period, characterized by early reversible vacuolation of the soma and later irreversible neurite fragmentation and cell death. A sublethal concentration of PCP (100 microM) suppressed axon outgrowth. The adverse effects of PCP on neurons were apparently not due to actions on N-methyl-D-aspartate (NMDA) receptors because: the neurons were not responsive to NMDA during the first 3 weeks in culture; concentrations of PCP that should block NMDA receptors maximally (1-50 microM) did not affect axon outgrowth or cell survival; and another NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) did not cause neurodegeneration or affect axon outgrowth. Exposure of cultures to the sigma receptor ligand, pentazocine (10 microM), did not significantly affect the survival of neurons and haloperidol did not reduce PCP-induced neurodegeneration, indicating that the effects of PCP were not mediated by sigma receptors. Degenerative effects, similar to those elicited by PCP, were observed in cortical neurons exposed to the K+ channel blockers, 4-aminopyridine and tetraethylammonium, a finding consistent with the possibility that the degenerative actions of PCP were mediated by its known inhibitory effects on K+ channels. In support of the latter possibility, it was found that PCP caused a progressive elevation in intracellular levels of calcium during several days of exposure. In addition to affecting neurons, PCP and K+ channel blockers caused vacuolation and degeneration of astrocytes. Taken together with previous data, indicating that PCP can be concentrated and retained in the fetal CNS, the present data suggest that high levels of PCP can disrupt the normal development of neural circuitry in the human fetus, which would be expected to result in profound functional impairments.

Astrocytes↗