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D M Gao

Publications and source records attributed to D M Gao.

At least 19 recordsLinked to original sources
PubMed2001

Time-course of changes in firing rates and firing patterns of subthalamic nucleus neuronal activity after 6-OHDA-induced dopamine depletion in rats.

The subthalamic nucleus (STN) plays a key role in motor control. Disorganization of its neuronal activity is implicated in the manifestation of parkinsonian motor symptoms. The aim of the present work was to study the time-course of changes in the firing activity of STN neurons in a rat model of parkinsonism. Electrophysiological recordings were done in normal rats and four groups of rats at different time points after 6-hydroxydopamine (6-OHDA) microinjection into the pars compacta of substantia nigra (SNc). Results showed a significant decrease in firing rate during the first and second weeks post lesion (5.53+/-0.56 and 7.66+/-0.73 spikes/s, respectively) compared to normal rats (11.13+/-0.59 spikes/s). From the 3rd week after 6-OHDA injection the firing rates returned toward baseline, with an average of 9.71+/-0.51 spikes/s during the 3rd week and 11.13+/-0.71 spikes/s during the 4th week. With regard to firing pattern, the majority of STN cells (90%) discharged regularly or slightly irregularly in normal animals. Only 4% exhibited burst activity and 6% had mixed firing patterns. After SNc-lesion, the percentage of cells exhibiting burst and mixed patterns increased progressively from 35% during the first week to 56% at week 4 post-lesion. In sum, these experiments revealed that the firing rate of STN neurons was altered only transiently following nigral lesions, whereas a progressive and stable change in the firing pattern was observed up to 4 weeks post lesion, suggesting that the persistence of bursts firing more closely relates to the motor pathologies of this rat model of parkinsonism.

Action Potentials↗
PubMed2001

Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97.

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

Albumins↗
PubMed2000

Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat.

Electrophysiological recordings were made in anaesthetized rats to investigate the mode of function of high-frequency stimulation of the subthalamic nucleus used as a therapeutic approach for Parkinson's disease. High-frequency electrical stimulation of the subthalamic nucleus (130 Hz) induced a net decrease in activity of all cells recorded around the site of stimulation in the subthalamic nucleus. It also caused an inhibition of the majority of neurons recorded in the substantia nigra pars reticulata in normal rats (94%) and in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (90%) or with ibotenic acid lesions of the globus pallidus (79.5%). The majority of cells recorded in the ventrolateral nucleus of the thalamus responded with an increase in their activity (84%). These results show that high-frequency stimulation of the subthalamic nucleus induces a reduction of the excitatory glutamatergic output from the subthalamic nucleus which results in deactivation of substantia nigra pars reticulata neurons. The reduction in tonic inhibitory drive of nigral neurons induces a disinhibition of activity in the ventrolateral motor thalamic nucleus, which should result in activation of the motor cortical system.

Adrenergic Agents↗
PubMed2000

Unilateral lesion of the nigrostriatal pathway induces a transient decrease of firing rate with no change in the firing pattern of neurons of the parafascicular nucleus in the rat.

Electrophysiological recordings of thalamic parafascicular nucleus neurons were done in normal rats and in three groups of rats at different time intervals after injection of 6-hydroxydopamine into the pars compacta of substantia nigra. In normal rats, parafascicular neurons exhibited low firing rates (3.88+/-0.80 spikes/s). Concerning the pattern, 59% of the units discharged irregularly and 41% exhibited bursty pattern. In rats with 6-hydroxydopamine lesions, the firing rate decreased significantly during the first week post-lesion (1.15+/-0.36 spikes/s, P<0.01). During the second week, the firing rate was slightly, but not significantly, lower (2.59+/-0.41 spikes/s, P>0.05) than that of normal rats to return to the basal level three weeks post-lesion (3. 66+/-0.41 spikes/s, P>0.05). In these three groups of 6-hydroxydopamine-lesioned rats, the firing pattern showed no change when compared to control animals. These results show that the lesion of nigral dopaminergic neurons induced a transient decrease of the firing rate of parafascicular neurons with no change in the firing pattern demonstrating the absence of a stable influence of the dopaminergic system on the spontaneous activity of parafascicular neurons.

Action Potentials↗
PubMed1999

High-frequency stimulation of the subthalamic nucleus suppresses experimental resting tremor in the monkey.

The effect of high-frequency stimulation of the subthalamic nucleus on parkinsonian-like resting tremor was investigated in two monkeys (Macaca fascicularis). Unilateral tremor of the arm and leg was induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. The tremor was only seen at rest condition with a very stable frequency of 4.46+/-0.59 Hz (mean+/-S.D.). Apomorphine (0.10-0.4 mg/kg, s.c.) completely blocked the tremor, suggesting that it was a dopaminergic-dependent symptom just like the parkinsonian tremor. When the stimulating frequency varied from 20 to 1000 Hz, both mono- and bipolar stimulation (square pulses, 0-5 mA, 0.06 ms) of the subthalamic nucleus suppressed resting tremor in a frequency-dependent manner but monopolar stimulation was more effective. These effects remained stable for more than two years. The present results suggest that the subthalamic nucleus is involved in the control and mechanism of resting tremor and that the high-frequency stimulation of the subthalamic nucleus can be used as an alternative therapy in parkinsonian patients with akinesia, rigidity and resting tremor.

Animals↗
PubMed1997

Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma.

The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97 +/- 0.34 g compared to 2.04 +/- 0.34 g, P < 0.001) and alpha-Fetoprotein value (93 +/- 59 micrograms/L compared to 769 +/- 282 micrograms/L, P < 0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 micrograms/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.

Animals↗
PubMed1996

Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues.

A highly metastatic LCI-D20 model of human hepatocellular carcinoma (HCC) was obtained via orthotopic implantation of a histologically preserved metastatic tumour selected from 1 of 30 surgical specimens, and had been maintained for 18 passages in nude mice. All mice with transplanted tumours exhibited 100% transplantability and metastatic ability, as well as various manifestations reminiscent of tumour behaviour in HCC patients. These included: local growth, regional invasion, spontaneous metastasis to liver, lymph nodes and lungs, and peritoneal seeding. Histological characteristics of the LCI-D20 tumour were similar to those of the original tumour. Karyotypic analysis revealed heteroploid cells. Immunohistochemically, expression of AFP and HBxAG was shown. Our nude mouse model with its high metastatic rate and short latency period could be an interesting tool for the study of human HCC.

Animals↗
PubMed1996

Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens.

In this study of orthotopic implantation of histologically intact surgical specimens, the authors constructed metastatic models of human hepatocellular carcinoma (HCC) in nude mice. Histologically intact human liver cancer specimens, derived from patients, were implanted directly into the liver of nude mice, and their orthotopic growth and metastases were observed. The transplantability and metastatic rate of two specimen groups (primary and metastatic lesions) were analysed. alpha-Fetoprotein (AFP) was also determined in transplanted tumours by an immunohistochemical method. Orthotopic growth was observed in 14 of 30 transplanted specimens and formation of metastases in 7 cases, which exhibited the variety of clinical behaviours seen in patients with HCC. These behaviours included local growth, regional invasion, spontaneous intrahepatic, lymph node and lung metastasis and peritoneal seeding. In two groups the growth rate of metastatic lesions following implantation was clearly higher than that of primary tumours. Chromosome analysis from locally growing tumours confirmed their morphologically human origin. An immunohistochemical study showed that implanted tumours originating from AFP-positive specimens maintained AFP expression. These results indicated that the animal models should prove valuable for developing new treatment modalities and studying the mechanism of metastasis of human HCC.

Animals↗
PubMed1996

Simultaneous recording of spontaneous activities and nociceptive responses from neurons in the pars compacta of substantia nigra and in the lateral habenula.

Using simultaneous extracellular single-unit recording in the pars compacta of the substantia nigra and in the lateral habenula of rats, 45 pairs of neurons responding to peripheral nociceptive stimulation were recorded. In 41 of these pairs, nigral dopaminergic neurons were inhibited by peripheral nociceptive stimulation, while lateral habenula neurons were excited. Moreover, in 14 pairs, when sweeps were triggered randomly by spontaneous spikes from lateral habenula neurons the spontaneous firing rate of the dopaminergic neurons during the first 250 ms after the sweep was much lower than rates after this time period. In this case, the sweep was often triggered by burst-firing of lateral habenula neurons. Our results indicate a cross-correlation between the spontaneous activities of these two nuclei, suggesting that the excitation of lateral habenula neurons induced by peripheral nociceptive stimulation might be directly responsible for inhibition of nigral dopaminergic neurons.

Action Potentials↗
PubMed1994

Structure of the nucleocapsid protein gene of rice yellow stunt rhabdovirus.

The complete nucleotide sequence of the N protein gene of rice yellow stunt rhabdovirus (RYSV) was determined by sequencing of cDNA clones derived from the viral genomic RNA. The 3' end of the N gene (messenger sense) was defined by sequence analysis of cDNA clones generated from the N protein mRNA by 3'RACE. The 5' end sequence of the gene was putatively assigned as 5'-AACAC-3'; this sequence is found in the presumed 3' leader/N gene junction region. The mRNA encoding the RYSV N protein is 1714 nt comprising a 15-nt untranslated 5' leader sequence followed by an open reading frame (ORF) of 1563 nt and a 136-nt untranslated 3' region. The calculated molecular mass of the N protein encoded by the ORF is 58,400 Da, which is larger in size than N proteins of other rhabdoviruses. Amino acid composition analysis shows that the RYSV N protein is rather basic with a predicted isoelectric point of 10.04; indeed, a large highly basic region could be found at the carboxy terminal portion of the protein. Amino acid sequence comparison between N proteins of RYSV and sonchus yellow net virus, both of which belong to the same genus Nucleorhabdovirus, revealed an overall 30% identity, with three relatively conserved blocks of 14-20 amino acid residues. Moreover, the hydropathy profiles of the two proteins are generally similar. The structural similarities between the N protein of RYSV and that of lettuce necrotic yellows virus, the type member of the genus Cytorhabdovirus, and those of animal rhabdoviruses, are less significant. Nucleotide sequence determination of 5' and 3' regions flanking the RYSV N gene identified a 14-nt common sequence that is very similar to the consensus gene junction sequences of other plant and animal rhabdoviruses.

Amino Acid Sequence↗
PubMed1994

Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.

In animal models of Parkinson's disease (PD), it is postulated that the excessive output from the subthalamic nucleus (STN) plays a critical role. Selective lesions or high frequency electrical stimulation of the STN can alleviate parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN stimulation in patients suffering from severe akinetic forms of PD. After approval of the institutional ethical committee, we operated on a parkinsonian patient aged 51, suffering for 8 years from a strongly disabling akinetorigid form of PD, complicated by an on-off effect (Hoehn and Yahr stage 5 in the worst-off motor phase). Stereotactic surgery was done on one side under local anesthesia. The theoretical target was chosen according to stereotactic atlases, based on ventriculographic landmarks such as anterior and posterior commissures (AC and PC). The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs. A spontaneous increase in neuronal activity was recorded in an area located 2-4 mm under the level of the intercommissural plane, 10 mm from the midline, at mid-distance between AC and PC. Within the same place, a 130-Hz stimulation induced acute and reversible akinesia alleviation mainly on the contralateral limbs, comparable to that obtained with dopaminergic drugs. No dyskinesia, such as hemiballism, was induced by introduction of electrodes or by stimulation. Then a long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies of the effects of chronic stimulation were extensively performed to determine the best spatiotemporal and electrical stimulation variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Stimulation Therapy↗
PubMed1993

[Effects of the stimulation of the subthalamic nucleus in Parkinson disease].

In Parkinson's disease, experimental studies favour a neuronal hyperactivity of the subthalamic nucleus. We carried out a subthalamic nucleus electrical stimulation in a patient aged 51, suffering for 8 years from a severe akineto-rigid form of Parkinson's disease, complicated with an on-off effect. Stereotaxic surgery was done under local anaesthesia on one side. Within the theoretical target, a 130 Hz stimulation induced akinesia alleviation mainly on the contralateral limbs. No abnormal movement was noticed. Then a long-term quadripolar DBS Medtronic electrode was inserted in that area. The study of the effects of chronic stimulation is in progress to determine the best temporal and electrical stimulation variables.

Electric Stimulation Therapy↗
PubMed1991

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.

Aged↗
PubMed1990

Intensity-dependent nociceptive responses from presumed dopaminergic neurons of the substantia nigra, pars compacta in the rat and their modification by lateral habenula inputs.

The characteristics of nociceptive responses from presumed dopaminergic (DAergic) neurons in the SN were investigated in the anesthetized rat with extracellular recordings. 194 presumed DAergic neurons were recorded. A majority of these neurons (78%) were inhibited by intensive electrical stimulation performed at the tail (PNS) and 15% were excited. Both inhibitory and excitatory responses were intensity-dependent. Single shock stimulation of the lateral habenula (LHb) inhibited 89% of the tested DAergic neurons, most of which (83.8%) were also inhibited by PNS. LHb stimulation increased PNS-induced inhibition of DAergic neurons and electrical destruction of ipsilateral LHb depressed their nociceptive responses. Our results strongly suggest that DAergic neurons encode the nociceptive stimulation intensity and that the LHb shares a step in nociceptive projection to the SN.

Animals↗
PubMed1990

Direct vision controlled gastric coronary vein embolization for the treatment of portal hypertension.

Complications of gastric mucosal bleeding and ectopic embolism occurred in gastric coronary embolization under direct vision in treating hemorrhage from ruptured esophageal varices though it has been widely used with satisfactory results. 40 patients with portal hypertension were treated by splenectomy and gastric coronary vein embolization under direct vision in this hospital. On the basis of Liu's operative method, 20 of the 40 patients underwent controlled embolization of the gastric coronary vein with satisfactory results. The technic not only occluded the predicted bleeding sites of the veins at the esophageal and gastric fundic regions but also blocked its communication with surrounding veins. Thus serious complications were reduced or prevented. The effectiveness of devascularization derived from the technic in question, the detailed maneuver of the procedure, and prevention of complications are discussed.

Adult↗
PubMed1990

[A technic of limited gastric coronary vein embolization under direct vision for treatment of portal hypertension].

Venous embolism of the gastro-cardiac area for the purpose of controlling hemorrhage, as suggested at Liu Xiougong in 1984, was adopted widely by some institutes in our country with a satisfactory outcome although some complications did happen. Forty cases of portal hypertension was treated in this institute since May 1985 with coronary vein embolism plus splenectomy under direct vision. Based on modified Liu's technique and animal experiment, the authors practiced limited gastric coronary vein embolism in 20 cases with a satisfactory result. This procedure may not only block the veins where bleeding may incidentally occur, but also cut off the communications between the veins of the lower esophagus, the fundus of the stomach and the adjacent venous system to minimize the possibility of postoperative complications. The mechanism of blockade and technique of this procedure were described and the ways to prevent complications presented in detail.

Adult↗