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Biomedical subjects

Y Xie

Publications and source records attributed to Y Xie.

At least 397 records · Page 22Linked to original sources

The resistance of macrophage-like tumour cell lines to growth inhibition by lipopolysaccharide and pertussis toxin.

The process of tumorigenesis is frequently associated with resistance to growth inhibition by physiological regulators of normal cells. Murine macrophage-like cell lines BAC1.2F5, RAW264, J774.1A and PU5/1.8 were resistant to growth inhibition by bacterial lipopolysaccharide (LPS) and pertussis toxin, agents that blocked growth of primary bone marrow-derived macrophages (BMDM) in the presence of macrophage colony-stimulating factor (CSF-1). The resistance of the CSF-1-dependent cell line BAC1.2F5 to growth inhibition by pertussis toxin argues against the possibility that pertussis toxin-sensitive G proteins are essential for the pathway of growth stimulation by CSF-1. Conversely, these data add further weight to the argument that LPS mediates some of its biological activities by mimicking the action of pertussis toxin and inhibiting G protein function. The resistance of cell lines to LPS and pertussis toxin was not correlated with any alteration in the expression of mRNA encoding any of three pertussis-toxin sensitive G protein alpha subunits. The pattern of G protein expression was consistent between primary cells and tumour cells, suggesting that this is a differentiation marker. In particular, Gi alpha 2 mRNA was expressed at remarkably high levels in all of the cells. The specificity of LPS resistance was investigated by studying down-regulation of CSF-1 binding and induction of protooncogene c-fos and tumour necrosis factor (TNF) mRNA. BAC1.2F5 cells were LPS-resistant in each of these assays. In CSF-1 binding, RAW264 and J774.1A responded in the same way as bone marrow-derived macrophages but required higher doses of LPS, whereas c-fos and TNF mRNA were induced in these cells at concentrations that did not inhibit growth. In PU5/1.8 cells, CSF-1 binding was already very low and was not further down-regulated, but c-fos and TNF mRNA was inducible by LPS. By contrast to primary macrophages, the cell lines did not respond to LPS with down-regulation of c-fms mRNA, which encodes the CSF-1 receptor. Hence, the resistance of macrophage-like tumour cells to LPS and pertussis toxin was specific to the pathways controlling growth, and was correlated with altered regulation of the CSF-1 receptor.

Animals↗

Observation of therapeutic effect in 50 cases of chronic renal failure treated with rhubarb and adjuvant drugs.

Treatment of chronic renal failure with rhubarb and adjuvant drugs combined with other appropriate measures alleviates the suffering of the patients and improves the quality of their survival. Most patients can take care of themselves after treatment, and some can engage in half-day work. The treatment prolongs the life of the patient, and reduces medical expenses. It is of definite social and economic benefit, and conforms with China's conditions. Except for very severe cases whose blood creatinine exceeds 884 mumol/L, it can be given to all patients. It can also be used as a transitional measure before more radical therapies may be instituted.

Adolescent↗

Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon.

The effects of sodium nitroprusside (SNP) on intestinal electrolyte transport were studied in rat colon mounted in Ussing chambers. Serosal addition of SNP increases short-circuit current (Isc) in a concentration-dependent manner. The maximal change in Isc was 35.6 +/- 2.3 microA/cm2 at 1 mM SNP (ED50 approximately 81 microM). S-nitroso-N-acetylpenicillamine, a nitrosothiol which can release nitric oxide, also stimulated an increase in Isc of 13.9 +/- 3.1 microA/cm2 at a concentration of 100 microM. The response to SNP was rapid, peaking at about 4 min with partial return to baseline at 20 to 30 min. Isc responses to SNP were significantly less in the cecum and ileum as well as after mucosal addition in the distal colon. Pretreatment with serosal atropine, cimetidine, pyrilamine, ketanserin, and N omega-nitro-L-arginine and mucosal amiloride did not inhibit the SNP-stimulated Isc; iodine, methylene blue, bumetanide, piroxicam, and tetrodotoxin each significantly decreased the response and piroxicam plus tetrodotoxin abolished it. Transmural 22Na+ and 36Cl- flux studies demonstrated that the change in Isc produced by SNP was attributable to anion secretion. SNP also inhibited neutral Na+ and Cl- absorption, with the inhibition of Na+, but not Cl- absorption eliminated by tetrodotoxin and piroxicam pretreatment. In summary, SNP has several effects on intestinal electrolyte transport, suggesting that nitric oxide or other components of nitrovasodilators may be important physiological mediators of salt and water transport and may play a role in stimulated colonic epithelial electrolyte transport in inflamed tissues.

Absorption↗

Nereistoxin: a naturally occurring toxin with redox effects on neuronal nicotinic acetylcholine receptors in chick retina.

Nereistoxin (NTX; 4-N,N-dimethylamino-1,2-dithiolane) is previously reported to block both muscle and neuronal nicotinic acetylcholine receptors, and reversibly inhibit radioligand binding to Torpedo nicotinic receptors. Here, we studied redox effects of NTX on neuronal nicotinic receptors in chick retinas by electrophysiological recordings and by [125I]neuronal bungarotoxin binding. NTX blocked retinal responses to the nicotinic agonist dimethylphenylpiperazinium (300 microM, 2 sec) with an IC50 of 3.5 microM. NTX inhibition was selective for nicotinic receptors, long lasting and not reversible upon washing. The nonselective oxidizing compound dithiobis(nitrobenzoic acid) (1 mM) transiently and repetitively reversed NTX (100 microM) inhibition (85% recovery). After application of the alkylating agent bromoacetylcholine (2 or 100 microM, with 2 microM neostigmine), dithiobis(nitrobenzoic acid) could no longer restore nicotinic function. d-Tubocurarine (300 microM) equally protected against alkylation with bromoacetylcholine (2 microM) after dithiothreitol (2 mM) or NTX treatment. The action of NTX differs from that of dithiothreitol because the agonist dimethylphenylpiperazinium (30 microM) protects against inactivation by dithiothreitol, but not by NTX. NTX reversibly inhibited [125I]neuronal bungarotoxin binding to chick retinal homogenates (IC50 = 16 microM). The present study suggests that nereistoxin or a metabolite is a potent antagonist as well as a selective reducing agent for nicotinic receptors in chick retina. As a dithiolane, this latter action by nereistoxin remains to be explained.

Acetylcholine↗

The importance of methionine residues for the catalysis of the biotin enzyme, transcarboxylase. Analysis by site-directed mutagenesis.

Almost all biotin enzymes contain the conserved tetrapeptide Ala-Met-Bct-Met (Bct, N epsilon-biotinyl-L-lysine). In the 1.3 S biotinyl subunit of transcarboxylase (TC), this sequence is present between positions 87 and 90. The conserved nature of these amino acids implies a critical role in the function of biotin enzymes. In order to examine the role of these conserved amino acids, point mutations in the gene encoding the 1.3 S subunit have been made by site-directed mutagenesis to generate A87G, M88L, M90L, M88T, M88C, M88A, and a double mutant A87M, M88A in the 1.3 S subunit. TC, a multisubunit enzyme containing 12 S, 5 S, and 1.3 S subunits, catalyzes the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate (overall reaction). TC can be dissociated into individual subunits and also reconstituted by assembling isolated subunits to a fully active form. The mutants of the 1.3 S subunit have been reconstituted with native 5 S and 12 S subunits from Propionibacterium shermanii. The effects of mutations on the activity of TC were compared with that of TC-1.3 S wild type (WT) prepared in a similar manner. The results show that any substitution of a residue in the conserved tetrapeptide causes impairment of the rate of TC activity. Comparison of gel filtration profiles, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron micrographs of the TC assembled with mutant 1.3 S and with wild type 1.3 S subunits showed that the impairment of the overall activity was not due to a failure of the subunits to assemble into complexes. Steady state kinetic analysis using the mutant 1.3 S subunits indicated that the Km for methylmalonyl-CoA or pyruvate did not change significantly indicating that the binding of substrates is not altered. However, the kcat values were significantly lower for mutants at positions 87 and 88 than for those at position 90. The replacement of methionine at position 88 either by hydrophobic or hydrophilic residues significantly altered the activity in the overall reaction, while similar substitution at position 90 did not dramatically alter the kcat. These results suggest that Ala-87 and Met-88 are catalytically critical in the conserved tetrapeptide.

Amino Acid Sequence↗

Observations of synaptic efficacy and paired-pulse facilitation in area CA1 of hippocampal slices from coriaria lactone-kindled rats.

The changes of population spike(PS)/population excitatory postsynaptic potential (EPSP) slope relationship and paired-pulse facilitation (PPF) were primarily investigated with extracellular recording in stratum pyramidale to stimulation of Schaffer collaterals in CA1 region of hippocampal slices from coriaria lactone (CL)-kindled and control rats. The results were as follows: (1) neither spontaneous nor evoked epileptiform bursts were found in all hippocampal slices from CL-kindled and control rats; (2) the synaptic efficacy, expressed by the ratio of PS/EPSP slope, at low stimulation intensity ranging from 10-30% of its maximum was significantly increased on CL-kindled rats (P less than 0.05); and (3) although PPF was found in all slices, the PPF strength only at stimulation intensity of 10 and 20% of maximum was augmented remarkably in CL-kindled rats (P less than 0.002 and 0.024, respectively). According to the results from our previous work, we suggested that the increment of PS/EPSP slope ratio and PPF strength at low stimulation intensity may result from the potentiation of excitatory synaptic activity or/and the change of intrinsic excitability of pyramidal neurons.

Action Potentials↗

Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver.

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.

Apolipoprotein A-I↗

Age patterns of marital fertility: revising the Coale-Trussell method.

"This article revises the Coale-Trussell method for analyzing data from the World Fertility Survey by proposing and testing alternative log-linear and log-multiplicative models. The models, in one form or another, represent the structural constraint underlying the Coale-Trussell method on the variation in the age pattern of human fertility. With a Poisson distribution assumption for the number of births, several parameters of the models are simultaneously estimated via maximum likelihood. It is shown that the new approach can be adopted whenever fertility limitation is compared across multiple populations or subpopulations."

Age Factors↗

Phosphorylation regulates RNA binding by the human T-cell leukemia virus Rex protein.

The Rex protein of human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) regulates the expression of the viral structural genes and is critical for viral replication. Rex acts by specifically binding to RNAs containing sequences of the R region of the 5' long terminal repeat. Two forms of Rex detected in HTLV-II-infected cells, p26rex and p24rex, differ in the extent of serine phosphorylation. Two-dimensional phosphopeptide analysis indicates that p26rex is extensively phosphorylated at multiple sites. Using a sensitive immunobinding assay, we show that the phosphorylation state of Rex determines the efficiency of binding of Rex to HTLV-II target RNAs. Thus, the phosphorylation state of Rex in the infected cell may be a switch that determines whether virus exists in a latent or productive state. These studies also suggest that phosphorylation of RNA-binding regulatory proteins is a more general mechanism of gene regulation.

Baculoviridae↗

Effect of calcium antagonists on postischemic protein biosynthesis in gerbil brain.

BACKGROUND AND PURPOSE: Prolonged inhibition of protein synthesis precedes delayed neuronal death in the CA1 sector of the hippocampus after transient cerebral ischemia. Organic calcium antagonists have been recommended for alleviation of ischemic neuronal damage. The present study was undertaken to investigate whether these drugs improve the recovery of protein biosynthesis after interruption of cerebral blood flow. METHODS: Cerebral protein synthesis was measured biochemically and autoradiographically in gerbils submitted to 5 minutes of bilateral occlusion of the common carotid arteries followed by 2 hours or 2 days of recirculation. Flunarizine (25 mg/kg) or nimodipine (1.5 mg/kg) were applied intraperitoneally shortly after ischemia. RESULTS: Treatment with either calcium antagonist did not markedly influence postischemic recovery of protein synthesis in the resistant regions of the brain and did not prevent the persisting inhibition in the vulnerable stratum pyramidale of the CA1 sector of the hippocampus. CONCLUSIONS: The postischemic application of the organic calcium antagonists nimodipine and flunarizine does not promote postischemic recovery of protein synthesis. The beneficial effects of these drugs must, therefore, be based on other mechanisms.

Amino Acids↗

[Correlation among electrocardiogram, important risk factors of coronary artery diseases and coronary lesion in patients with chest pain].

Clinical and angiographic data from 103 patients with chest pain were evaluated to determine their correlation with ST-T abnormality in resting electrocardiogram. Univariate analysis suggested that male sex, hypertension, old myocardial infarction, severe coronary lesion, multiple vessel lesion and left ventricular wall motion abnormality significantly increase the likelihood of ST-T abnormality. Multivariate analysis suggested that male sex, hypertension and left ventricular wall motion abnormality were significant independent predictors of abnormal ST-T. It is essential to improve the electrocardiographic accuracy of diagnosing CAD so as to help clinical doctors in preventing and treating this disease.

Adult↗

[Effects of adrenergic agonist on population spike in CA1 region of hippocampal slices from partial and full kindled rats].

Effects of adrenergic agonist on population spike (PS) amplitude were studied extracellularly at CA1 region of hippocampal slices from partial and full kindled rats with coriaria lactone (1-1.25 mg/kg, two days a time, i.m.) and compared with those from control rats. 5 mumol/L norepinephrine (NE) increased PS; 50 mumol/L NE decreased it slightly. 5 mumol/L isoproterenol (ISO) increased PS. 100 mumol/L phenylephrine (PE) decreased it. The effects of increasing and decreasing PS could be antagonised by beta and alpha adrenergic antagonists, respectively. The effects of NE and PE on PS amplitude showed no significant difference between the control and kindled rats. The effect of beta-adrenergic agonist ISO on PS amplitude in hippocampal slices from partial kindled rats was less than that of control (P < 0.01). The effect of ISO on PS of full kindled rats was partially recovered.

Animals↗

[Effects of calcium channel blocker verapamil on hippocampal kindled seizures induced by coriaria lactone in rabbits].

Eighteen fully kindled rabbits, whose epilepsy had been produced by intrahippocampal (i.h.) injections of 2 microliters of diluted solution containing 0.32 or 0.55 micrograms of coriaria lactone (CL), were separated into three groups. One of them was used as the control group. For seizure, all animals were given CL (0.6-1 micrograms/2 microliter i.h.). Ten minutes later, the verapamil (VR) group of six rabbits was treated with VR (1.5 or 2 mg/kg i.m. 2.5 or 5 micrograms/2 microliters i.h.); the normal saline (NS) group (six rabbits) received 0.8 ml/kg (i.m., in the same volume as that of the VR 2 mg/kg injection) or 2 microliters (i.h.) of NS; the control group of six received neither VR nor NS. The experiments were made once every eight days. Hippocampal EEGs of all animals were recorded by telemetric method and their behavior after injection was observed continuously in 4-7 hours. The results of the experiment indicated that the i.h. administration of 2.5 or 5 micrograms/2 microliters of VR is effective on hippocampal kindled seizures induced by CL in rabbits, but the curative effects of the i.m. administration of 1.5 or 2 mg/kg of VR were less notable than those of the i.h. administration.

Animals↗

Effects of oxidizing and reducing analogs of acetylcholine on neuronal nicotinic receptors.

The synthesis and pharmacological characterization of dithiobisacetylcholine and dithiobis-N,N-dimethyl-4-acetylpiperazinium (two oxidizing analogs of acetylcholine), as well as those of their reduced counterparts, are described. Both the oxidizing and reducing analogs stimulate nicotinic receptors in the chick retina and block the binding of 125I-labeled neuronal bungarotoxin to retinal homogenates (IC50 values of 2 x 10(-6) to 6 x 10(-5) M). Both oxidizing compounds reverse the physiological effects of reduction by dithiothreitol on nicotinic function in intact chick retina, when applied for 2 sec (EC50 values of about 10(-5) M). This effect is selective, insofar as neither agent alters the effects of dithiothreitol treatment on receptors for N-methyl-D-aspartate. Reoxidation takes place at the disulfide located near the nicotinic receptor agonist binding site, inasmuch as reoxidation by these agents prevents affinity alkylation by bromoacetylcholine, and occupation by the competitive antagonist d-tubocurarine prevents reoxidation. Unlike thiocholine, a weak agonist with a free sulfhydryl that, paradoxically, is reported to oxidize nicotinic receptors in electroplax, the reduced forms, mercaptoacetylcholine and N,N-dimethylamino-4-mercaptoacetylpiperazinium, have no direct redox effects on retinal receptors, but they do protect the receptors against reduction by dithiothreitol.

Acetylcholine↗

[Observation of paired-pulse depression in CA1 region of hippocampal slices from coriaria lactone-kindled rats].

Paired-pulse depression (PPD) technique was used to investigate the potency of recurrent synaptic inhibition mediated by GABA in area CA1 of 54 hippocampal slices from coriaria lactone (CL)-kindled and control rats. When paired stimuli were sent to the axon of CA1 pyramidal cell and Schaffer collaterals, the effect of population spike PPD lasted about 40-60ms; no significant change was observed on PPD potency between kindled and control groups (P = 0.06, 2-way ANOVA). The results indicate that the GABA-ergic synaptic inhibition seemed not to play a key role in the maintenance of the chemical kindling induced by CL.

Animals↗

[Ca2+ channels and the abnormal electrical activity of demyelinated nerve].

Peripheral nerve demyelination was produced in adult rats by placing loosely-constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and possible spontaneous pain were produced. In the meantime, abnormal spontaneous afferent activities (ectopic firings)originating from the demyelinated region were recorded. Evidence showed that the application of Ca2+ and Ca2+ channel blockers modulated the abnormal activity of the injured nerve. Ca2+ facilitation was dependent on its concentration (in the range of 10-20 mol/L), while 40mol/L Ca2+ always abolished firing. Verapamil, as well as La3+, applied locally or i. v. (for verapamil) not only strongly inhibited the spontaneous ectopic firings, but also blocked discharges elicited by tetraethylammonium. It is suggested that newly formed Ca2+ channels on the naked axolemma are largely responsible for the abnormal afferent activities following demyelination of the nerve.

Animals↗

[Ultrastructural observation of SC1001-sodium on brain neurons kindled seizures by coriaria lactone in rabbits].

The ultrastructural changes of hippocampus and cerebral cortex neurons were derived from the rabbits kindled by coriaria lactone and from the kindled rabbits after treatment with SC1001 Na. The results of experiment showed that the hippocampus and cerebral cortex neurons in the kindled group had some degenerative changes, such as the swelling mitochondria, dilated rough endoplasmic reticulum and Golgi complexes when the injuries of neurons were not serious, but the seriously injured neurons were subjected to rupture of the cell membrane and solution of most organella, with only a small amount of degenerative organella. In the group treated with SC1001 Na, the ultrastructure of brain neurons demonstrated a tendency of recreation to normal which showed that SC1001 Na had cured many of the degenerative brain cells. This suggested that active treatment is very important for the epileptic patients.

Animals↗