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Biomedical subjects

D Zhao

Publications and source records attributed to D Zhao.

At least 163 records · Page 9Linked to original sources

Short-term modulation of glutamatergic synapses in adult rat hippocampus by NGF.

Nerve growth factor promotes survival and differentiation of selected groups of neurones through long-term adaptive changes in cell function. While production of this neurotrophin in target cells in hippocampus is regulated in part by afferent glutamate neuronal input, we report now for the first time that nerve growth factor has a direct potentiating effect on spontaneous and depolarization-evoked release of glutamate from hippocampal nerve endings, accompanied by an increase in the excitatory postsynaptic potential of CA1 neurones. This correlated with increased incorporation of [32P]phosphate into synapsin I. Reciprocal positive feedback between production of trophic factors in target cells by neurotransmitter released from afferent neuronal inputs and the modulation of presynaptic neurotransmitter release by target-derived trophic factors provides a novel mechanism for short-term control over synaptic communication.

Animals↗

Persistent physiological effects caused by a single pentylenetetrazol induced seizure in neonatal rats.

A single seizure was induced by pentylenetetrazol (PTZ; 150 mg/kg i.p.) in 1-day-old and 21-day-old rats; control littermates were given saline (i.p.) injections. In vitro recordings were made in hippocampal slices derived from adult (2-3.5-month-old) rats. The population responses in CA1, CA3 and dentate gyrus (DG) were recorded following double-pulse stimulation of Schaffer collateral (CA1 stratum radiatum, for CA1 and CA3 recordings) and perforant path (for DG recordings). Paired-pulse stimuli at an interpulse interval (IPI) of 10-200 ms and intensity of 1.5, 2 or 4 times the stimulus threshold were used. PTZ given on day 1 resulted in a highly significant increase in the paired-pulse facilitation (PPF) of the population EPSP, but not of the population spike, in CA1 at all stimulus intensities. In the DG, PPF of both the population EPSP and population spike was found at 1.5 x threshold intensity. PTZ given on day 21 decreased PPF of the population EPSP and spike in CA1 and had no significant effect in the DG. No significant difference was found in CA3 responses after seizures on day 1 or day 21. The slices from seized and control animals were not different in their stimulus thresholds or response to a single pulse. It is concluded that a single neonatal PTZ-induced seizure had long-lasting physiological consequences which depend on the age of seizure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

An assessment of the precision and accuracy of protein structures determined by NMR. Dependence on distance errors.

We tested the dependence of the accuracy and precision of calculated NMR structures on the errors of the distance constraints using sequential simulated annealing and found that: (1) the accuracy of the family of structures depends mainly on the quality of the data, but is no better than about 1 A even if the errors in distance constraints are smaller than +/- 1 A. (2) The precision of the calculated structures, on the other hand, is nearly insensitive to the quality of the data. With present methods, the accuracy of NMR structures is at best of the order of 1 to 2 A, although a precision of 0.4 to 0.7 A is readily attainable. Comparisons with recent studies of this problem also brought out the importance of distinguishing between correct and incorrect definitions of accuracy when reporting numerical estimates. Using an incorrect definition of the term accuracy can lead to an artificially favorable estimate of its numerical value.

Evaluation Studies as Topic↗

The solution structures of the trp repressor-operator DNA complex.

The solution structures of the complex between Escherichia coli trp holorepressor and a 20 base-pair consensus operator DNA were determined. The majority of proton chemical shifts of the trp holorepressor and operator DNA were assigned from homonuclear 2D NOESY spectra of selectively deuterated analog-operator DNA complexes and the 3D NOESY-HMQC spectrum of a uniformly 15N-labeled repressor-operator DNA complex. The structures were calculated using restrained molecular dynamics and sequential simulated annealing with 4086 NOE and other experimental constraints. The root-mean-squared deviation (RMSD) among the calculated structures and their mean is 0.9(+/- 0.3)A for the repressor backbone, 1.1(+/- 0.5)A for the DNA backbone, and 1.3(+/- 0.3)A for all heavy atoms. The DNA is deformed to a significant extent from the standard B DNA structure to fit the helix-turn-helix (HTH) segment of the repressor (helices D and E) into its major grooves. Little change is found in the ABCF core of the repressor on complexation in comparison to the free repressor, but changes in the cofactor L-tryptophan binding pocket and the HTH segment are observed. The N-terminal residues (2 to 17) are found to be disordered and do not form stable interactions with DNA. Direct H-bonding to the bases of the operator DNA is consistent with all of our observed NOE constraints. Hydrogen bonds from NH eta 1 and NH eta 2 of Arg69 to O-6 and N-7 of G2 are compatible with the solution structure, as they are with the crystal structure. Other direct H-bonds from Lys72, Ala80, Ile79, Thr83 and Arg84 to base-pair functional groups can also be formed in our solution structures.

Amino Acid Sequence↗

Long-lasting effects of partial hippocampal kindling on hippocampal physiology and function.

The objective of this project was to study the behavioral and physiological effects at 6-9 weeks after evoking 15 afterdischarges (ADs) in hippocampal CA1 (partial hippocampal kindling). Rats were trained on the open radial arm maze (RAM) with all eight arms baited, kindled, and then tested again on the RAM, followed by in vitro recordings at 8-9 weeks after kindling. Partial kindling was manifested by an increase in hippocampal AD duration. Enhancement of the commissural basal dendritic excitatory postsynaptic potential (EPSP) was observed for at least 1 day after the ADs. Kindled rats performed worse than control rats during the 1st but not during the 7th or 8th week after kindling. Rats that were slow in acquiring the RAM showed more RAM errors after kindling than those that showed fast acquisition. At 8-9 weeks after kindling, as shown by field potential recording in the hippocampal slice in vitro, kindled rats showed an increase in paired-pulse facilitation (PPF) of the EPSP in CA1 but a decreased PPF of the perforant path to dentate gyrus EPSP; no change in the PPF of the population spike was found in CA1 or DG. In a second group of rats that were not run on the RAM, at 6 weeks after kindling, PPF of the population EPSP and population spike were enhanced in the kindled rats compared to the control rats in CA1, but not in DG or CA3 in vitro (at 1.5, 2, or 4 times threshold intensity).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The influence of vasectomy and vasovasostomy on testicular ATPases, cAMP, ABP and androgen receptor in rabbits.

The present study was performed to further clarify the influences of vasectomy on functions of testis and to disclose the possible mechanisms of infertility after vasovasostomy (VV). Thirty-one rabbits were divided into sham-operated control group (C), vasectomy control group (V), VV fertility group (VaF) and VV infertility group (VaI). Serum testosterone (ST) level, testicular cAMP, androgen binding protein (ABP), nuclear androgen receptor (NAR) concentrations, testis cell membrane Na(+)-, K(+)-ATPase, Mg(2+)-ATPase activities, sperm density and testis weight were measured. Vasectomy resulted in significantly reduced cAMP, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase, testis weight and increased ABP; VV completely restore testis weight in VaF and VaI, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase in VaF, partly cAMP in VaF and VaI, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase in VaI, but did not restore ABP. The NAR content in VaI was significantly lower than those in C, VaF and V. No statistical differences among 4 groups were seen in Kd values for [3H]-T. ST levels in VaF, VaI and V were insignificantly different compared with C, but the value in VaF was higher than that in VaI (p < 0.05). Sperm density after VV reached 122 +/- 62 x 10(6)/ml in VaF and 10 +/- 24 x 10(6)/ml in VaI, both in VaF and VaI were significantly low compared with C (p < 0.001), and the value in VaI was remarkedly lower than that in VaF (p < 0.001). It was shown that sperm density was positively correlated with cAMP content, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase activities, but negatively with ABP. These results suggest that vasectomy gives rise to damage to the testis, and vasovasostomy does not appear completely effective in reversing testicular changes.

Adenosine Triphosphatases↗

Human c-yes-1-related proto-oncogene in clinically normal dogs.

Human c-yes-1-related canine proto-oncogene in genomic DNAs from 21 clinically normal dogs was analyzed by Southern blot hybridization. The present study indicated that this proto-oncogene was well conserved in clinically normal dogs, however, there were structural changes in some dogs. These changes were different in each individuals and detected in low frequency.

Animals↗

Canine splenic hemangiosarcoma with abdominal dissemination.

Disseminated hemangiosarcoma was encountered in a 12-year-old female Maltese dog. Tumor tissues were dispersed on the serosal surface of the liver, kidney, digestive tract, omentum and diaphragm. Metastatic lesions were not observed in the parenchyma of the lung and heart. The spleen was enlarged with rupture at the anterior region of the hilus. The disseminated protruding tumor masses could be easily peeled off from the organ surfaces. The tumor cells were round or spindle in shape, with hyperchromatic nuclei containing prominent nucleoli. Various-sized vascular spaces containing erythrocytes and serum could be identified in this tumor. This case was diagnosed as hemangiosarcoma originating from the spleen with abdominal dissemination.

Abdominal Neoplasms↗

[Protective effect of putrescine on oleic acid-induced respiratory distress syndrome (RDS)].

The effect of putrescine on oleic acid-induced RDS were studied in rat, it was found that preadministration of putrescine to rat with RDS significantly improved its hypoxemia, pulmonary edema and histologic injury; inhibited the leakage of protein from plasma; lowered increase of pulmonary lipid peroxidation products (malondialdehde, MDA). The result suggests that putrescine could have significant potential for clinical treatment of acute pulmonary injury.

Animals↗

Involvement of nitric oxide in the vasodilator and depressor effect of calcitonin gene-related peptide.

In present study, we examined the effects of NG-nitro-L-arginine (LNNA), an inhibitor of nitric oxide synthase (NOS), and/or methylene blue (MB), a blocker of guanylate cyclase on the vasodilator response of isolated rat arteries including aorta and mesenteric artery to calcitonin gene-related peptide (CGRP) by in vitro vasoconstriction experiment, and the effect of LNNA on the depressor action of CGRP by in vivo hemodynamic experiment. Furthermore, the effect of CGRP on NOS activity and cyclic guanylate monophosphate (cGMP) content were also examined by NOS activity assay and radioimmunoassay (RIA), respectively. The results showed that LNNA and/or MB significantly decreased, but not abolished, the vasodilator response of isolated rat aorta and mesenteric artery to CGRP. The depressor effect of CGRP on LNNA-induced hypertensive rats (LHR) was obviously weaker than that on spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive rats (NWR). In addition, CGRP (0.5 nmol/kg) increased the NOS activity of rat aorta tissue by 1.3 times (P < 0.05) and resulted in an increase of cGMP content of aorta (1.27 times, P < 0.05) and myocardium (1.38 times, P < 0.05). The results suggested that NO is involved in the action of CGRP.

Animals↗

[A clinic report of 54 cases of reconstruction for the anterior segment of eye].

54 cases (54 eyes) of severe injury in the anterior segment of eye with little light perception were treated by reconstruction for the anterior segment of eye. The results showed that the eyeballs in 48 cases (88.9%) were survived successfully, and 28 cases (51.9%) of the grafts were clear. The procedures included keratoplasty, iridectomy, lensectomy, anterior vitrectomy, and reconstruction of the anterior chamber to restore the cosmetic shape of the eyeball. The indications, complications of the operation, and the surgical technique are discussed.

Adolescent↗

Partial hippocampal kindling increases paired-pulse facilitation and burst frequency in hippocampal CA1 neurons.

For up to 3 weeks after 15 evoked afterdischarges (partial kindling) in the hippocampus in vivo, paired-pulse facilitation of the CA1 apical dendritic excitatory postsynaptic potentials (EPSPs), recorded from single neurons in vitro, was significantly larger in neurons of kindled than control rats. Partial kindling did not significantly affect the resting membrane potential, the threshold or size of the action potential (AP), the fast afterhyperpolarization, input resistance, time constant or the EPSP threshold. The number of APs induced within the initial 20 ms of a long-duration 0.5-nA depolarizing current was significantly higher in the kindled than control neurons. The increase in paired-pulse facilitation and intrinsic spiking in hippocampal CA1 after partial kindling may contribute to an increase in seizure susceptibility.

Animals↗

Brain protein kinase C assay using MARCKS substrate reveals no translocation due to profound insulin-induced hypoglycemia.

Hypoglycemia sufficient to produce EEG isoelectricity or coma leads to neuronal death by an excitotoxic mechanism due to elevated extracellular levels of glutamate, aspartate and increased intracellular calcium. Since an elevated intracellular calcium concentration is known to translocate protein kinase C (PKC) from the cytosol to the membrane (a process thought to represent the in vivo activation of the enzyme), the objective of this investigation was to determine if calcium-dependent isoforms of PKC were translocated in specific brain regions of rats subjected to 40 min of insulin-induced hypoglycemic coma. The caudate nucleus and hippocampus (regions damaged by hypoglycemia showing extensive neuronal necrosis), and cerebellum (an undamaged, control region) of hypoglycemic rats were microdissected. Soluble and detergent (Triton X-100)-solubilized particulate fractions were partially purified by DEAE-Sephacel chromatography. PKC activity in both fractions was then measured using a novel assay based on the calcium- and lipid (phosphatidylserine and diolein)-dependent phosphorylation of the specific substrate myristoylated alanine rich C kinase substrate (MARCKS). The percentage distribution of PKC in the soluble and particulate (membrane-bound) fractions of all the brain regions from hypoglycemic rats was not significantly different from that in the control brains, indicating that 40 min of hypoglycemia does not result in PKC translocation as measured in subcellular fractions from brain tissue.

Animals↗

Refined solution structures of the Escherichia coli trp holo- and aporepressor.

The solution structures of the trp-repressor from Escherichia coli in both the liganded (holo-) and unliganded (apo-) form, have been refined by restrained molecular dynamics with simulated annealing using the program XPLOR and additional experimental constraints. The ensemble of refined holorepressor structures have a root-mean-square deviation (r.m.s.d.) of 0.8 A relative to the average structure for the backbone of the dimer core (helices A, B, C, A', B', C') and 2.5 A for the helix-turn-helix DNA-binding domain (helices D and E). The corresponding values for the aporepressor are 0.9 A for the backbone of the ABC-dimer core and 3.2 A for the DE helix-turn-helix. The r.m.s.d. of the average structures from the corresponding crystal structures are 2.3 A for the holorepressor ABC core and 4.2 A for its DE region; 2.3 A for the aporepressor core and 5.5 A for its DE region. The relative disorder of the DNA-binding domain is reflected in a number of experimental parameters including substantially more rapid backbone proton exchange rates, exchange-limited relaxation times and crystallographic B-factors. The stabilizing effect of the L-Trp ligand is evident in these measurements, as it is in the higher precision of the holorepressor structure.

Amino Acid Sequence↗

Interpretation of the laser Doppler flow signal from the liver of the rat.

It has been proposed that the laser Doppler flow (LDF) signal from the surface of the rat liver is almost exclusively a measure of hepatic arterial and not of total liver blood flow and therefore that LDF is not a suitable technique for the measurement of blood flow in the hepatic microcirculation. The objective of the present study was twofold: (i) to establish that liver blood flow is homogeneously distributed and (ii) to assess the behavior of the LDF signal during changes in hepatic perfusion. When 51Cr-labeled microspheres were injected into the portal vein (n = 12), no significant differences in the relative flow (cpm/lobe to cpm/liver) to each of the liver lobes were found nor was there any difference in the ratio of flow to the outer 1-2 mm of lobe as compared to that to the "core" of the liver. Temporary occlusion of the hepatic artery and the portal vein caused approximately 13% (n = 7, P < 0.001) and approximately 74% (n = 7, P < 0.001) fall in LDF signal, respectively. Diversion of flow from the anterior to the posterior lobes (n = 5) caused a 97.9 +/- 21.1% (SD, P < 0.001) rise in LDF signal in the posterior lobes. Zero-flow LDF signal was found to represent 13.0 +/- 4.1% of maximum. Hemorrhage (in 1.5-ml aliquots) was associated with a fall in mean arterial pressure (MAP) and LDF signals. A linear relationship between MAP and the LDF signal (r > 0.9) was found. Reinfusion of blood caused both MAP and the LDF signal to return to normal. We conclude that (i) blood flow in rat liver is homogeneously distributed; (ii) the LDF signal from the liver surface responds in a manner predicted by conventional theories of hepatic hemodynamics during alteration, either independent or combined, in hepatic arterial and portal venous blood flow; and (iii) LDF may be used to measure relative changes in hepatic perfusion but problems associated with zero-flow signal and intersite variability preclude its quantification in absolute flow units.

Animals↗

Effect of orthotopic transplantation and chemical denervation of the liver on hepatic hemodynamics in the rat.

The involvement of the sympathetic nervous system in the control of basal hepatic hemodynamics was investigated. Hepatic denervation was achieved by orthotopic transplantation or chemical denervation of the organ. In male Lewis rats, transplantation with rearterialization of the graft was performed. Chemical denervation was achieved by intraportal injection of 6-hydroxydopamine (75 mg/kg). Normal liver physiology was confirmed by histology and liver function tests. Four weeks post-transplantation and 7 days post-denervation, histological examination revealed no differences between transplanted, denervated and untreated or sham-operated control animals. Liver function measured by standard tests (e.g., plasma SGOT, bilirubin) was normal in all groups. The rate constants for aminopyrine breakdown in transplanted (0.015 +/- 0.005 min-1), denervated (0.015 +/- 0.0012 min-1) and control rats (0.015 +/- 0.001 min-1) were not significantly different. No significant difference in the rate of galactose breakdown was found. Total liver blood flow (measured by the 133Xe clearance technique in the anesthetized animal) was unaffected by transplantation (rate constant, 0.245 +/- 0.062 min-1; control 0.279 +/- 0.011 min-1). The interlobular distribution of portal blood flow was tested by intraportal injection of 51Cr-labelled microspheres. A linear relationship between flow to lobe and lobe size was confirmed in control (r = 0.95), denervated, (r = 0.99) and transplanted rats (r = 0.97) and the 'relative' flow to each lobe was not significantly different in the 3 groups. No significant differences in the 'core' to 'periphery' distribution of portal blood flow were found in the 3 groups. A small but significant portal systemic shunt was found in transplanted but not denervated or control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of orthotopic liver transplantation and chemical denervation of the liver on the activities of hepatic monoamine oxidase and catechol-O-methyltransferase.

The denervation of some tissue is associated with a fall in the activities of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Here we report on the effect of orthotopic liver transplantation and chemical denervation of the liver on the enzymes. Liver transplantation was performed on Lewis rats (n = 7). Denervation (n = 8) was by intraportal injection of 6-hydroxydopamine (75 mg/kg). A control group (n = 8) was also included. The norepinephrine content of the transplanted and denervated livers was reduced by greater than 99% (P < 0.001) and 95% (P < 0.001), respectively. The activity of hepatic COMT (substrate: catechol [5 mM] was not affected by transplantation or denervation. The activity of MAO with 0.1 mM 5-hydroxytryptamine (5-HT) (substrate for MAO-A) and with 0.01 mM 2-phenylethylamine (substrate for MAO-B) were not affected by denervation. In the transplanted liver, the activity of MAO with 5-HT and 2-phenylethylamine was increased by 26% (P < 0.05) and by 53% (P < 0.001), respectively. The ratios of the activities of the A to B forms of MAO (approximately 70% A to 30% B) was not affected by either procedure. Enzyme sensitivity for MAO inhibitors clorgyline and deprenyl were not significantly altered by transplantation. The concentration of plasma norepinephrine in the transplantation group was significantly lower than either the control (P < 0.001) or denervation groups (P < 0.05). We conclude from our results that the metabolism of circulating catecholamines by the liver is unlikely to be impaired after liver transplantation.

Animals↗