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Biomedical subjects

N Nakao

Publications and source records attributed to N Nakao.

At least 55 records · Page 3Linked to original sources
PubMed1999

Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington's disease.

It has been demonstrated in rats that embryonic striatal grafts placed in the excitotoxically lesioned striatum establish neuronal connections with the host globus pallidus. In order to determine whether the morphologically verified connections between the grafts and host are functional, the present study investigated the effects of embryonic striatal grafts on changes in the neuronal activity of the globus pallidus in rats with quinolinic acid-induced striatal lesions. The activity of pallidal neurons was determined by use of quantitative cytochrome oxidase histochemistry and an electrophysiological technique. Striatal lesions induced an increase in both the cytochrome oxidase activity and the spontaneous firing rate of the globus pallidus ipsilateral to the lesions. Grafts derived from the lateral ganglionic eminence, but not the medial ganglionic eminence, reversed the lesion-induced increase in the cytochrome oxidase activity of the globus pallidus with concomitant reduction of apomorphine-induced rotational asymmetry. The lateral ganglionic eminence grafts also attenuate the increase in the firing rate of pallidal neurons in rats with striatal lesions. The present results provide evidence that striatal lesions lead to the loss of a tonic inhibitory input to the globus pallidus with consequent increase in the activity of pallidal neurons, and that intrastriatal striatal grafts reverse the altered activity of pallidal neurons. The findings strongly suggest that embryonic striatal grafts functionally repair the damaged striatopallidal pathway.

Action Potentials↗
PubMed1999

Ablation of the subthalamic nucleus supports the survival of nigral dopaminergic neurons after nigrostriatal lesions induced by the mitochondrial toxin 3-nitropropionic acid.

We investigated the role of the excitatory afferents from the subthalamic nucleus (STN) in the death of nigral dopamine (DA) neurons after nigrostriatal axon terminal lesions. Nigral DA neurons were detected by use of both tyrosine hydroxylase immunolabeling or retrograde labeling of nigral cells with fluorogold. Sprague-Dawley rats were subjected to unilateral, quinolinic acid-induced destruction of the STN. Sham lesions of the STN were made by injecting phosphate-buffered saline. Two weeks after STN ablation, lesions of nigrostriatal DA neurons were induced by intrastriatal injections of either the mitochondrial toxin 3-nitropropionic acid (3-NP) or the catecholamine toxin 6-hydroxydopamine (6-OHDA). Intrastriatal injections of 3-NP or 6-OHDA caused a progressive loss of nigral tyrosine hydroxylase-positive or fluorogold-labeled DA neurons in a dose-dependent manner. Previous ablation of the STN significantly attenuates the loss of DA neurons in rats receiving 3-NP but not 6-OHDA. Sham lesions of the STN did not affect DA neuron death induced by the toxins. The results indicate that the excitatory inputs from the STN may contribute to the death of nigral DA neurons under a condition of 3-NP-induced metabolic impairment.

Animals↗
PubMed1999

[CT diagnosis of hyperdense intracranial neoplasms: review of the literature].

In contrast to typical astrocytic tumors that show hypodense areas on computed tomographic images, some intracranial tumors show hyperdense areas on CT images. The major reasons for hyperdensity on CT images are hypercellular lesions, intratumoral calcification, and intratumoral hemorrhage. Malignant lymphomas, germinomas, and medulloblastomas show homogeneous hyperdensity on CT images because of their hypercellularity. Tumorous lesions such as subependymal giant cell astrocytomas, oligodendrogliomas, ependymomas, central neurocytomas, craniopharyngiomas, and meningiomas often present with hyperdense calcified lesions on CT images. Intratumoral hemorrhage also causes hyperdensity on CT images, and is often associated with metastatic brain tumors, glioblastomas, pituitary adenomas, and rarely with any of the other intracranial tumors. Although magnetic resonance imaging is now the major diagnostic tool for diseases of the central nervous system, the first imaging studies for patients with neurologic symptoms are still CT scans. Hyperdense areas on CT images are a clue to making an accurate diagnosis of intracranial neoplasms.

Adult↗
PubMed1999

[Anatomy of intrahepatic portal branches visualized by three-dimensional imaging analysis of CT arterial portography].

The purpose of this study was to clarify variations in intrahepatic portal branches by means of CT imaging procedures. The subjects were 73 patients, 59 men and 14 women, who ranged in age from 41 to 76 years, with a mean of 63 years. The procedures were as follows. The entire liver was scanned using helical CT during the portal and hepatic venous phases, and 3D images of the portal vein were reconstructed with the volume-rendering technique and the region-growing method. The CT unit was a HITACHI W2000, and the imaging analyzer a Sun Ultra 1. We found that the branching patterns of both the anterior (P5 and P8) and posterior segmental branches (P6 and P7) of the right lobe of the liver could be classified into four types. The caudate branch (P1) and left lateral segmental branches (P2 and P3) were classified into three types, and the interior segmental branch of the left lobe (P4) was classified into two types. The frequency of each pattern was also revealed. These branching types and their frequencies were generally the same as those described in previous reports. Thus, the portal anatomy visualized by these methods indicates that they could be very useful for preoperative examinations or IVR.

Adult↗
PubMed1999

[Fundamental and clinical study of three-dimensional compensating filters and direct dose monitoring system for total body irradiation].

We devised 3D-compensating filters to improve dose distribution during total body irradiation (TBI). This study investigated the effect of these 3D-compensating filters and related complications in patients who had undergone bone marrow transplantation (BMT) followed by TBI. The 3D-compensating filters were fabricated by CT measurement of body thickness. The effectiveness of the 3D-compensating filters in producing a homogeneous dose distribution was checked by a thermoluminescent dosimeter (TLD) and semiconductor detectors in all patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average dose distribution to each site when the 3D-compensating filter was used was 93% to the head, 97% to the neck, 99% to the thorax, and 98% to the pelvis in TLD when the scheduled dose was taken as 100%. There was no significant difference between the TBI and non-TBI groups with regard to the frequency of lung toxicity. Clinical interstitial pneumonitis occurred in 22.7% of the patients, interstitial pneumonitis with CMV in 13.6%, and idiopathic pneumonitis in 6.1% without any virus infection. Only one patient was regarded as having radiation-induced pneumonitis. 3D-compensating filters can be conveniently produced within a short time following CT measurement, and they seem to be safe and useful for dose flattening during TBI.

Adolescent↗
PubMed1998

Intrastriatal mesencephalic grafts affect neuronal activity in basal ganglia nuclei and their target structures in a rat model of Parkinson's disease.

Nigrostriatal dopamine (DA) lesions lead to changes of neuronal activity in basal ganglia nuclei such as the globus pallidus (GP, the rodent homolog of lateral globus pallidus), entopeduncular nucleus (EP, the rodent homolog of medial globus pallidus), substantia nigra pars reticulata (SNR), and subthalamic nucleus (STN). We investigated in rats whether embryonic mesencephalic DA neurons grafted in the striatum may affect the lesion-induced alterations of neuronal activity in these structures. Regional neuronal activity was determined by use of quantitative cytochrome oxidase histochemistry. It was also examined in lesioned rats whether the grafts may regulate the expression of c-Fos after systemic administration of apomorphine in the basal ganglia nuclei as well as their target structures, including the ventromedial thalamic nucleus (VM), superior colliculus (SC), and pedunculopontine nucleus (PPN). Lesioned rats exhibited an increased activity of CO in the GP, EP, SNR, and STN ipsilateral to the lesion. Intrastriatal nigral grafts reversed the increases in the CO activity in the EP and SNR, whereas the grafts failed to affect the enzyme activity in the GP or STN. Apomorphine induced an increased expression of c-Fos in the GP, STN, VM, SC, and PPN on the lesioned side. The enhanced expression of this protein in all the structures except for the STN was attenuated by nigral grafts. The present results indicate that intrastriatal DA neuron grafts can normalize the lesion-induced changes of neuronal activity in the output nuclei of the basal ganglia as well as their target structures.

Animals↗
PubMed1998

(R)salsolinol N-methyltransferase activity increases in parkinsonian lymphocytes.

Recently, an endogenous catechol isoquinoline, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol], was proved to be a neurotoxin specific for dopamine neurons by in vivo and in vitro experiments. This N-methyl(R)salsolinol was found to increase significantly in the cerebrospinal fluid of untreated parkinsonian patients, suggesting its possible involvement in the pathogenesis of Parkinson's disease. To clarify the mechanism of the increase, the activity of enzymes related to the metabolism of the neurotoxin was examined in lymphocytes prepared from parkinsonian patients and controls. In patients with Parkinson's disease, the activity of a neutral N-methyltransferase, measured by using (R)salsolinol as a substrate, was found to increase significantly (100.2 +/- 81.8 pmol/min/mg of protein) in comparison with that in controls (18.9 +/- 15.0 pmol/min/mg of protein). The distribution of the activity was bimodal in the parkinsonian patients, whereas it was singular in controls. The activity of other related enzymes, an alkaline N-methyltransferase and N-methyl(R)salsolinol oxidase, in parkinsonian lymphocytes was the same as in controls. Increase of the neutral N-methyltransferase may be an endogenous factor in the pathogenesis of Parkinson's disease.

Aged↗
PubMed1998

Changes in the mitochondrial enzyme activity in striatal projection areas after unilateral excitotoxic striatal lesions: partial restoration by embryonic striatal transplants.

It is well established that the activity of cytochrome oxidase (CO), a mitochondrial enzyme, reflects the long-term, steady-state levels of neuronal activity. The present study investigated the long-term effects of unilateral striatal lesions induced by quinolinic acid on CO activity in primary striatal targets, including the globus pallidus (GP), entopeduncular nucleus (EP), and substantia nigra pars reticulata (SNR) and a secondary striatal projection area, such as subthalamic nucleus (STN), in rats. The activity of CO was determined by measuring staining intensity on brain sections processed for CO histochemistry. We also examined whether intrastriatal transplants of embryonic striatal tissue could affect the lesion-induced changes in the CO activity of those brain structures. Unilateral striatal lesions were found to lead to increases in the CO activity of the GP, EP, and SNR ipsilateral to the lesions. By contrast, the activity of the ipsilateral STN was decreased following striatal lesions, probably due to the increased inhibitory effect of the GP on the STN. Intrastriatal implantation of the lateral ganglionic eminence (LGN), but not the medial ganglionic eminence (MGE), reversed the lesion-induced changes in the CO activity of the GP and STN with concomitant attenuation of apomorphine-induced rotational asymmetry. The grafts failed to affect the activity of either the EP or SNR. The present results indicate that striatal lesions induce changes in the functional activity of basal ganglia nuclei and that the LGE grafts placed in the damaged striatum partly reverse the alterations in the functional state of the basal ganglia circuitry.

Animals↗
PubMed1998

An increase in intracellular levels of cyclic AMP produces trophic effects on striatal neurons developing in culture.

Cyclic AMP-dependent kinases have been suggested to constitute signal transduction pathways involved in the regulation of neuronal development and survival. The present study examined whether elevated levels of cyclic AMP exhibit trophic activities on rat striatal neurons grown under serum-free culture conditions. Treatment with dibutyryl cyclic AMP, a permeable cyclic AMP, increased GABA uptake and immunocytochemically detectable levels of proteins such as c-Fos and calbindin-D28k. Neuronal survival was promoted by dibutyryl cyclic AMP only in lower density cultures. Chronic exposure of neurons to dibutyryl cyclic AMP enhanced the morphological development of calbindin-D28k-positive neurons. Furthermore, pretreatment with dibutyryl cyclic AMP afforded neuroprotection against N-methyl-D-aspartate-induced excitotoxicity. The dibutyryl cyclic AMP-induced trophic effects above were blocked by adenosine 3',5'-cyclic monophosphothioate, a specific inhibitor of cyclic AMP-dependent kinases. We also examined whether cyclic AMP is involved in trophic effects provided by membrane depolarization induced by high K+ and growth factors such as basic fibroblast growth factor and insulin-like growth factor-1. Depolarization, but not the growth factors, increased intracellular levels of cyclic AMP. Adenosine 3',5'-cyclic monophosphothioate diminished depolarization increases in GABA uptake, whereas it did not affect the trophic effect of the growth factors. Co-treatment with the growth factors and dibutyryl cyclic AMP produced additive effects on both increases in GABA uptake and neuroprotection against excitotoxicity. The present results indicate that cyclic AMP-dependent kinases play roles in mediating differentiation and survival of developing striatal neurons. Signalling pathways activated by either basic fibroblast growth factor or insulin-like growth factor-1 are independent of those involving cyclic AMP. In contrast, depolarization-induced trophic effects are mediated, at least in part, by cyclic AMP-dependent pathways. Protective actions of dibutyryl cyclic AMP against excitotoxic injury as well as the additive effects with the growth factors are of potential interest in the experimental therapy of acute or chronic neurodegenerative diseases.

Animals↗
PubMed1998

[Arterial infusion of SMANCS-Lipiodol for advanced hepatocellular carcinoma].

Twenty-four patients were treated with arterial infusion of SMANCS dissolved in Lipiodol. Twenty of these patients had HCC with the main trunks of portal vein occluded by tumor, and four patients had severe cirrhosis and multiple HCC. The actual dose of SMANCS administered each patient ranged from 4 to 6 mg. Side effects occurred in 50%. Severe side effects such as shock and shivering-chilliness were observed in 18%. The differences between the values of hepatic functional serum indexes obtained before and after treatment with SMANCS were small and transient. With regard to the therapeutic response of the arterial infusion of SMANCS, the mean survival time was approximately 2.8 months. It was suggested that the more effective administration of SMANCS was combination of the arterial infusion of SMANCS-Lipiodol with TAE at the level of the right hepatic artery of left hepatic artery for multiple HCC.

Antineoplastic Agents↗
PubMed1998

Tenascin-C promotes healing of Habu-snake venom-induced glomerulonephritis: studies in knockout congenic mice and in culture.

Mice without the gene for tenascin-C, a multifunctional extracellular matrix protein expressed in many important biological events, including wound healing, did not show any phenotype. However, it is now obvious that the phenotype of deletion of one gene frequently depends on the genetic background. Therefore, we have newly generated tenascin-C knockout mice (KO) by backcrossing original KO into three congenic lines: C57BL/6N, BALB/cA, and GRS/A (GR). And we investigated the disease course of reversible kidney injury, Habu-snake venom-induced proliferative glomerulonephritis. In all strains, the disease was more severe in KO, but the severity varied with the strain. The KO-GR showed irreversibility; all treated KO-GR died by the 4th month due to renal failure. The diseased KO-GR showed abnormal regenerative reactions, including reduced proliferation of mesangial cells, key players in glomerulonephritis, and reduced production of some kinds of cytokines and matrices, leading to poor formation of granulation tissue. In culture, the mesangial cells from the KO-GR had the same potential for proliferation and response to cytokines as controls, but interestingly, to achieve this potential, they required contact with tenascin-C. These reactions were blocked by an anti-tenascin monoclonal antibody. The results of the present study, the first report showing the most dramatic phenotype so far discovered, have strongly suggested the importance of tenascin-C in the resolution of the renal inflammation and that of the genetic background on which the KO was developed.

Animals↗
PubMed1998

[Evaluation by MR imaging of neoadjuvant intra-arterial infusion chemotherapy in uterine cervical cancer].

Eight patients with uterine cervical cancer received two or three courses of neoadjuvant chemotherapy, including 254-S i.v. and CDDP i.a. Transcatheter arterial embolization (TAE) was added for seven patients. The therapeutic efficacy was evaluated by MR imaging and postoperative histopathological examination. Three patients achieved a complete response (CR) and five others were evaluated as a partial response (PR) on MR imaging. On postoperative histology, three of eight showed CR or PR, which coincided with MR findings. Viable cancer cells were shown in five patients. To detect these viable tumors, dynamic MR imaging was indispensable. However, because of limited spatial resolution, the detection of small residual tumors was not easy using dynamic MR imaging.

Adenocarcinoma↗
PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.

Adult↗
PubMed1998

[Results of preoperative high-dose-rate intraluminal brachytherapy for resectable rectal cancer].

One hundred and fifteen patients with middle and lower rectal cancer were treated with preoperative High-dose-rate intraluminal brachytherapy (HDRIBT) and radical operation. Patients were divided into a middle-dose group (group A; 30-40 Gy; n = 94) and a high-dose group (group B; 60-80 Gy; n = 18). A control group of 115 rectal cancer patients who received no irradiation prior to radical surgery was used for comparison (group C). The rate of sphincter-saving resection was 71% in group A, 61% in group B, and 42% in group C (group A vs. group C; p < 0.0001). The local recurrence rate at 5 years was 10% in group A, 6% in group B, and 26% in group C (group A vs. group C; p = 0.005). The 5-year survival rate was similar among the three groups. These results suggest that preoperative HDRIBT contributed to the improvement of local control but not to survival after radical resection of rectal cancer. The application of HDRIBT might be useful to restore intestinal continuity for rectal cancer.

Adult↗