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F Du

Publications and source records attributed to F Du.

At least 73 records · Page 4Linked to original sources
PubMed1997

Right ventricular infundibular beta-adrenoceptor complex in tetralogy of Fallot patients.

Patients with tetralogy of Fallot may have episodes of paroxysmal hypoxic spells ("tet spells") or could be asymptomatic. In patients who have these episodes, treatment with a beta-adrenoceptor (betaAR) blocking agent can often ameliorate or attenuate the severity of the symptoms. Additionally, excitement, crying, and situations associated with increased sympathetic activity could provoke the occurrence of these hypoxic spells. We hypothesized that altered myocardial betaAR function may contribute to the development of paroxysmal hypoxic spells in the symptomatic tetralogy patient. Surgically excised right ventricular infundibular myocardial specimens from symptomatic (patients with spells) and asymptomatic patients were used to determine total beta1 and beta2 betaAR density and betaAR adenylyl cyclase activity. Symptomatic patients had a significantly greater number of total betaAR. The relative proportion of beta1 and beta2 receptors was comparable in both patient groups. betaAR-stimulated adenylyl cyclase activity was found to be more enhanced in the symptomatic patient group. Our results indicate that infundibular betaARs may play a role in the development of paroxysmal hypoxic spells.

Adenylyl Cyclases↗
PubMed1996

An engineered Tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression.

A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology.

Acetylcholine↗
PubMed1996

[Experimental study and clinical application of primary choledochorraphy after choledochotomy].

An animal model was established in dogs to compare primary choledochorraphy with the traditional T-tube method. Authors observed cholangic histologic changes under microscope and electron-microscope between the two groups. The result showed that primary choledochorraphy was better than the traditional method. The advantage of primary choledochorraphy lies in its simplicity, safety and reliability, which have been shown in 30 patients of cholelithiasis in clinical application. It is suggested that for patients primary choledochorraphy may clesirably be used for patients who are indicated for this approach.

Adult↗
PubMed1995

Differential neuronal vulnerability to amino-oxyacetate and quinolinate in the rat parahippocampal region.

Injection of the "indirect" excitotoxin amino-oxyacetate into the entorhinal area causes acute behavioral seizures and preferential neuronal loss in layer III of the medial entorhinal cortex in rats. We examined here whether the effects of amino-oxyacetate could be duplicated by local injections of the endogenous N-methyl-D-aspartate receptor agonist and direct excitotoxin, quinolinate. Amino-oxyacetate (685 nmol) or quinolinate (30, 45 or 60 nmol) were injected into the entorhinal cortex of rats anesthetized with choral hydrate (360 mg/kg). Separate groups of animals were co-treated with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (2 mg/kg) or given a higher dose of chloral hydrate (500 mg/kg). Rats that received amino-oxyacetate and a low anesthetic dose consistently displayed acute behavioral seizures and showed preferential loss of neurons in layer III of the medial entorhinal cortex. Animals that were given quinolinate did not display behavioral seizures, and showed preferential degeneration of neurons in layer V of the entorhinal cortex. Moreover, quinolinate-injected rats frequently exhibited neuronal loss in the superficial layers of the dorsal perirhinal cortex. The behavioral and neuropathological sequelae of amino-oxyacetate, but not quinolinate-induced neurotoxicity, were abolished by prolonged chloral hydrate anesthesia. In spite of these apparent qualitative differences between the two toxins, neurodegeneration induced by either amino-oxyacetate or quinolinate was completely prevented by dizocilpine maleate. These data suggest that a heterogeneous distribution of pharmacologically distinct N-methyl-D-aspartate receptor subtypes in the parahippocampal region may underlie the distinct neurodegenerative properties of the two toxins. Since the lesion caused by amino-oxyacetate bears remarkable similarities to neuropathological changes which have been described in this structure in temporal lobe epilepsy, further elucidation of the mechanisms of cellular toxicity of amino-oxyacetate may hold clues for the pathogenesis of this disease.

Aminooxyacetic Acid↗
PubMed1995

Beneficial effect of oocyte activation prior to and during nuclear transfer in cattle using in vitro matured oocytes 24 h of age.

This research was designed to study in vitro development of bovine nuclear transferred embryos using enucleated young in vitro matured oocytes 24 h of age as recipient cytoplasts activated prior to nuclear transfer. The oocytes were enucleated and then activated with electric pulse at 24 h of age followed by incubation with cycloheximide for 6-7 h before nuclear transfer and membrane fusion with a blastomere of the 16-32 cell stage. This new protocol effectively improved cleavage (68 vs 17%, p < 0.05) and morula/blastocyst development of reconstructed embryos (29 vs 6%, p < 0.05), compared to similar nuclear transfer procedure without prior activation of recipient oocytes. Corresponding rates of cleavage and morula/blastocyst development for oocytes activated similarly without nuclear transfer were 49 and 19%. Factors affecting nuclear transfer were also compared. Two electric pulses for fusion increased rates of fusion (76 vs 60%, p < 0.05) and subsequent development of cloned embryos (32 vs 11%, p < 0.05). Cytochalasin B treatment following nuclear transfer manipulation seemed not to be beneficial in improving development of cloned embryos (p > 0.05). Both co-culture systems with buffalo rat liver (BRL) cells and cumulus cells promoted development of cloned embryos compared to the controls (28, 21 vs 0%, p < 0.05). The BRL cell system seemed to be better for manipulated embryos by reducing embryolysis.

Animals↗
PubMed1995

Nuclear transfer of putative rabbit embryonic stem cells leads to normal blastocyst development.

Rabbit embryonic stem-like cells, characterized by embryoid body formation and differentiation into cell types representative of all three germ layers, were studied for their ability to promote early embryonic development after nuclear transfer. After culture of the reconstructed embryos, 23% (n = 35) developed successfully into morulae or blastocysts, compared with 34% (n = 62) for cloned embryos derived from nuclear transfer with embryonic blastomeres. The cloned embryos from the embryonic stem-like cells appeared normal, with an average of 26% inner cell mass cells, similar to that of control non-manipulated embryos (25%) or cloned embryos from blastomeres (25%). Thus, nuclear transfer of rabbit embryonic stem-like cells leads to early embryonic development that is indistinguishable from blastomere fusion. These results have implications for the development of gene targeting in a species (rabbit) that may be a more suitable model for studying certain human diseases. In addition, this technique may be applicable to other species from which putative embryonic stem cells have been derived, particularly agriculturally important animals.

Animals↗
PubMed1995

Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy.

We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry. Adult male rats were either electrically stimulated in the ventral hippocampus for 90 min or injected with kainic acid or lithium/pilocarpine. Animals were observed for behavioral changes for up to 6 hr and were killed 24 hr or 4 weeks after the experimental treatments. At 24 hr, all animals that had exhibited a bout of acute status epilepticus showed a consistent pattern of neuronal loss in the EC in Nissl-stained sections. Neurodegeneration was most pronounced in layer III of the medial Ec at all dorsoventral levels. A few surviving neurons were frequently present in the lesioned area. An identical pattern of nerve cell loss was also seen in the EC of rats killed 4 weeks following the treatments. This lesion was completely prevented by an injection of diazepam and pentobarbital, given 1 hr after kainic acid administration. Immunohistochemistry demonstrated a relative resistance of parvalbumin-positive neurons in layer III of the medial EC. Taken together, these experiments indicate that prolonged seizures cause a preferential neuronal loss in layer III of the medial EC and that this lesion may be related to a pathological elevation of intracellular calcium ion concentrations.

Animals↗
PubMed1995

[A preliminary study on early development of goat (Capra hircus) reconstituted embryos].

Goat reconstituted embryos (REs) have been produced by electrofusion-mediated nuclear transplantation method. Single cell derived from normal embryos or REs developed to 8-cell morula stage or the inner cell mass (ICM) of early blastocyst stage was used to fuse with enucleated mature egg (26-28 hrs after injection of LRH). According to the results summarized in table 1 and 2, we decided to adopt the method to embed REs in agarose and then transfer into goat oviduct lumen of host mother for 4-6 days in vivo culture. Normal fertilized eggs seem to develop synchronously, but that of REs are not. Tables 4 and 5 reveal that REs and embryos reconstituted successively can develop normally, no significant difference was found among their development rates. All these experimental results indicate that nuclei of some blastomeres from normal embryos or REs (derived from eight cells to morula or ICM) retained their totipotency for further development. These nuclei can be reprogrammed in host ooplasm, and developed to term.

Animals↗
PubMed1995

3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum.

Glutamate, the major transmitter of the corticostriatal pathway, is present in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenase (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxin. In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level. In accordance with previous light microscopic and biochemical studies, 3HAO-i was detected exclusively in astrocytes throughout the striatum. Notably, 3HAO-i was present in fine-caliber glial processes that often surrounded or abutted synaptic profiles, both asymmetric and symmetric. Glutamate-i was heavily deposited (3-13-fold higher gold particle density than tissue average) in axon terminals forming asymmetric synapses with spines and, occasionally, dendrites. In contrast, terminals forming symmetric synapses, dendrites, neuronal somata, and glial cells contained significantly less labeling than terminals forming asymmetric synapses. In double-labeled material, 3HAO-i was observed in glial processes that partially surrounded or were adjacent to glutamate-labeled terminals forming asymmetric synapses. 3HAO-labeled glial processes were also adjacent to unlabeled terminals forming symmetric synapses. Since quinolinic acid is known to enter the extracellular compartment readily, these results suggest that astrocytic quinolinic acid may participate in the regulation of glutamatergic neurotransmission in the rat striatum.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1994

Immunocytochemical localization of the quinolinic acid synthesizing enzyme, 3-hydroxyanthranilic acid oxygenase, in the rat substantia nigra.

Quinolinic acid, an endogenous excitatory amino acid receptor agonist, may play a role in several brain diseases. In the present study, the immunocytochemical localization of 3-hydroxyanthranilic acid oxygenase (3HAO), the enzyme responsible for the synthesis of quinolinic acid, was examined in the adult rat substantia nigra at the light and electron microscopic levels. 3HAO-immunoreactivity was detected exclusively in astrocytes. Labeling was present in cell bodies and in fine glial processes, which frequently encircled capillaries and partially enveloped neuronal somata. Notably, 3HAO-labeled processes were in close contact with several types of synaptic profiles. Often, they partially engulfed asymmetric synapses, characteristic of excitatory neurotransmission. In addition, they were found in apposition to putative dopaminergic cell bodies. These data provide an anatomical basis for the idea that functional interactions may occur between glial processes which synthesize quinolinic acid, and synaptic profiles, many of which presumably utilize excitatory neurotransmitters.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1993

Delayed regional metabolic actions of phencyclidine.

Phencyclidine (PCP), a psychotomimetic drug of abuse, produces mental changes and manifestations in humans which are reminiscent of schizophrenia, though the mechanism of these actions remains unknown. We report here a biphasic time course of PCP action on regional cerebral glucose metabolism extending over 48 h. A single dose of PCP (8.6 mg/kg) produces an initial increase in glucose metabolism (at 3 h) and a later decrease in glucose metabolism (at 24 h) without a return to baseline until 48 h. A single lower dose of PCP (0.86 mg/kg), a dose which is considered selective for action at the NMDA-PCP receptor, produces no early metabolic change (at 3 h), but replicates the regional hypometabolism albeit less intense at 24 h. The delayed cerebral hypometabolism does not appear to be related to PCP-induced intracellular vacuolization, seen in the retrosplenial cortex. These metabolic changes may be associated with the psychotomimetic effects of PCP and thus may be relevant to psychosis in humans.

Animals↗
PubMed1993

gamma-Acetylenic GABA produces axon-sparing neurodegeneration after focal injection into the rat hippocampus.

In exploring the recently discovered phenomenon of indirect excitotoxicity, we noted that intrahippocampal injections of the nonspecific aminotransferase inhibitor gamma-acetylenic GABA (GAG; 60-240 nmol) caused excitotoxic lesions in rats. When assessed 3 days following the injection, GAG was shown to be approximately equally toxic to CA3/hilar neurons and CA1 pyramids, while CA2 neurons and granule cells were clearly less vulnerable. Choline acetyltransferase activity, a marker of extrinsic afferents, remained unchanged in the GAG-lesioned hippocampus, indicating the axon-sparing nature of the insult. In contrast, a lesion caused by 240 nmol of GAG resulted in a significant reduction in 3H-MK-801 binding, which was used as a marker for NMDA receptor-bearing hippocampal neurons. GAG-induced lesions were blocked by the NMDA receptor antagonists MK-801 and AP7 but were not influenced by the nature of the anesthetic used during surgery. Iontophoretic application of GAG did not excite CA1/CA3 cells in the rat hippocampus. In vitro, GAG proved to be a relatively potent inhibitor (IC50: 43 microM) of kynurenine aminotransferase, the biosynthetic enzyme of the endogenous neuroprotectant kynurenic acid. GAG also inhibited the neosynthesis of kynurenic acid in hippocampal slices (IC50: 790 microM). Thus, GAG shares several characteristics of the recently described indirect excitotoxin aminooxyacetic acid (AOAA; Exp. Neurol. 113: 378, 1991). GAG and AOAA appear to belong to a new family of excitotoxic agents which produce lesions indirectly by metabolic derangement and/or inhibition of kynurenate production.

2-Amino-5-phosphonovalerate↗
PubMed1993

Kynurenine pathway enzymes in a rat model of chronic epilepsy: immunohistochemical study of activated glial cells.

The kynurenine pathway metabolites quinolinic acid and kynurenic acid have been hypothetically linked to the occurrence of seizure phenomena. The present immunohistochemical study reports the activation of astrocytes containing three enzymes responsible for the metabolism of quinolinic acid and kynurenic acid in a rat model of chronic epilepsy. Rats received 90 min of patterned electrical stimulation through a bipolar electrode stereotaxically positioned in one hippocampus. This treatment induces non-convulsive limbic status epilepticus that leads to chronic, spontaneous, recurrent seizures. One month after the status epilepticus, the rats showed neuronal loss and gliosis in the piriform cortex, thalamus, and hippocampus, particularly on the side contralateral to the stimulation. Astrocytes containing the kynurenic acid biosynthetic enzyme (kynurenine aminotransferase) and the enzymes for the biosynthesis and degradation of quinolinic acid (3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase, respectively) became highly hypertrophied in brain areas where neurodegeneration occurred. Detailed qualitative and quantitative analyses were performed in the hippocampus. In CA1 and CA3 regions, the immunostained surface area of reactive astrocytes increased up to five-fold as compared to controls. Enlarged cells containing the three enzymes were mainly observed in the stratum radiatum, whereas the stratum pyramidale, in which neuronal somata degenerated, showed relatively fewer reactive glial cells. Hypertrophied kynurenine aminotransferase- and 3-hydroxyanthranilic acid oxygenase-immunoreactive cells were comparable in their morphology and distribution pattern. In contrast, reactive quinolinic acid phosphoribosyl transferase-positive glial cells displayed diversified sizes and shapes. Some very large quinolinic acid phosphoribosyl transferase-immunoreactive cells were noticed in the molecular layer of the dentate gyrus. In the hippocampus, the number of immunoreactive glial cells increased in parallel to the hypertrophic responses. In addition, pronounced increases in immunoreactivities, associated with hypertrophied astrocytes, occurred around lesioned sites in the thalamus and piriform cortex. These findings indicate that kynurenine metabolites derived from glial cells may play a role in chronic epileptogenesis.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1993

Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy.

We report a characteristic pattern of neuropathological change in the entorhinal cortex (EC) from four patients with temporal lobe epilepsy. Specimens of the EC were obtained during the surgical treatment of intractable partial seizures and were studied by light microscopy in Nissl-stained sections. A distinct loss of neurons was observed in the anterior portion of the medial EC in the absence of apparent damage to temporal neocortical gyri. Cell loss was most pronounced in layer III, but also noticed in layer II, particularly in the rostral field. A similar pattern of neurodegeneration in the EC was found in all specimens examined though the degree of neuronal loss varied between cases. These observations provide neuropathological evidence for an involvement of the EC in temporal lobe epilepsy. Since the EC occupies a pivotal position in gating hippocampal input and output, our results further support previous suggestions that dysfunction of this region may contribute, either independently or in concert with Ammon's horn sclerosis, to epileptogenesis in humans.

Adult↗
PubMed1993

Red blood cell Na-Li countertransport, hypertensive heredity, and cardiovascular risk in young adults.

The erythrocyte Na-Li countertransport (CT) has been considered as a marker of genetic propension to essential hypertension, but also to be linked to atherosclerosis risk factors. We have evaluated these relationships by measuring the Na-Li CT, blood pressure levels, the family predisposition to hypertension, body mass index, subscapular skin-fold thickness, waist/hip ratio, and plasma lipids in 43 young adults (22 to 23 years; 13 with a positive family history of hypertension), followed since adolescence (+/- 10 years) to analyze the natural history of blood pressure in this period of life. The Na-Li CT was negatively correlated with the HDL cholesterol (r = -0.37) and the HDL cholesterol/total cholesterol ratio (r = -0.44). This transport system was positively correlated to family history of hypertension (r = 0.38), waist/hip ratio, and the diastolic blood pressure. When the family history of hypertension was present, Na-Li CT and diastolic blood pressure were higher (P < .05), but the HDL cholesterol was lower (P < .01). After separating people according to the blood pressure level during adolescence in two groups, one lower than the 75th percentile (P75), and one higher, we notice that the latter remains characterized by a higher systolic blood pressure. But neither the Na-Li CT nor family history of hypertension and plasma lipids could explain the difference in the blood pressure behavior during this period. Thus, an increase of RBC Na-Li CT activity in young adults would suggest a higher cardiovascular risk rather than to be a simple marker of a hypertensive risk.

Adult↗
PubMed1993

Intracellular cation concentrations in essential hypertension and chronic renal failure.

The aim of this study was to test basal and after treatment erythrocyte sodium and calcium concentrations, and calcium-ATPase activity and platelet cytosolic free calcium and pH in 20 normotensive controls, 20 hemodialysis-dependent chronic renal failure patients and in 18 essential hypertensives. Prior to treatment, essential hypertensive and uremic patients presented similar higher platelet calcium concentrations and lower pH than the normotensive control group. The erythrocyte sodium, calcium, and magnesium concentrations were only significantly elevated in chronic renal failure, with a significant decrease in the calcium-ATPase activity in the latter population. Hemodialysis partially reversed these intracellular ionic abnormalities with normalization of platelet pH. Significant correlations have been noted between weight loss and decreases in platelet calcium concentration (r = 0.60, p < 0.01) or in erythrocyte sodium (r = 0.50, p < 0.05). The systolic blood pressure decrease was only correlated to the increase in calcium-ATPase activity (r = 0.57, p < 0.05). Antihypertensive treatment (captopril and nifedipine) only tended to normalize the intracellular calcium concentration with correlation between the decrease of the latter and blood pressure decrease (r = 0.64 for the systolic blood pressure and 0.68 for the diastolic blood pressure, p < 0.01). Thus, in essential hypertension and in uremia, some cellular ionic abnormalities exist in platelets in baseline condition. Moreover, in uremia, erythrocyte presents abnormal ionic pattern. Some, but not all of these abnormalities could be corrected by treatment affecting blood pressure (cellular calcium) in essential hypertension or by hemodialysis (cellular sodium, calcium, and pH). In the latter treatment, the changes are linked to extracellular fluid modification. In essential hypertension, the intracellular calcium reduction was linked to blood pressure decrease.

Adult↗