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Biomedical subjects

N Nakao

Publications and source records attributed to N Nakao.

At least 37 records · Page 2Linked to original sources
PubMed2001

Unilateral spatial neglect associated with chronic subdural haematoma: a case report.

A 69-year-old right-handed man who exhibited unilateral spatial neglect in association with a chronic subdural haematoma, presented with mild left arm and leg weakness first noted 4 weeks prior to admission. Neurologic examination on admission revealed a mild left hemiparesis, including the face. Neuropsychologic examination revealed left unilateral spatial neglect, but no language disturbance. Minimal support was necessary to maintain activities of daily living. Computed tomography revealed a large right temporoparietal, extraaxial hypodense fluid collection containing scattered hypodense foci. The haematoma was evacuated via a right parietal burr hole. Following surgery, the patient dramatically improved neurologically and neuropsychologically, as well as in independent performance of daily activities. It is suggested that the improvement in ADL provides a behavioural correlate of improvement in the latter, represented a behavioural correlate of improved cerebral function, and that either direct compression by the chronic subdural haematoma or an interhemispheric pressure difference had caused unilateral spatial neglect. Such neglect is an unusual consequence of chronic subdural haematoma.

Activities of Daily Living↗
PubMed2001

An experimental study on radiation streaming through a labyrinth in a proton accelerator facility of intermediate energy.

A radiation streaming experiment has been carried out at the Takasaki Ion Accelerator Facility for Advanced Radiation Application at the Japan Atomic Energy Research Institute in a room housing a Cu target irradiated with 68 MeV protons and in a labyrinth of three-legs having a total length of 29 m. In the experiment, neutron and gamma ray energy spectra, neutron reaction rates, and neutron and gamma ray dose equivalent rates were measured using various counters and dosimeters. The experimental data show the applicability of some empirical formulas for estimating the thermal neutron flux in a room and neutrons streaming in a labyrinth designed for a proton accelerator operating in the intermediate energy region. The data suggest that it is mandatory to estimate the gamma ray dose equivalent rate in a labyrinth, which is dominated by the secondary gamma rays due to the neutron capture reaction.

Academies and Institutes↗
PubMed2001

Organization of the mouse ghrelin gene and promoter: occurrence of a short noncoding first exon.

Ghrelin is a growth hormone-releasing peptide recently discovered in the stomach of rat and human as an endogenous ligand for growth hormone-secretagogue receptor. In the present study, a full-length cDNA for mouse ghrelin has been cloned from the stomach using the oligo-capping and rapid amplification methods, and the organization of its gene and promoter has been analyzed. The mouse ghrelin cDNA was 521 bp long, consisting of 44 bp 5'-noncoding region, 354 bp coding region encoding a pre-proghrelin composed of 117 amino acid residues and 123 bp 3'-noncoding region. The genomic sequence analysis has revealed that the mouse ghrelin gene consists of 5 exons and 4 introns. The first exon was revealed to be only 19 bp long presented at the noncoding region of cDNA. The identical 19 bp sequence was also found as the first exon at the 5'-end of full-length rat ghrelin cDNA obtained from the stomach. A TATA box-like sequence, TATATAA was localized 24 bp upstream of the transcription start site of the mouse ghrelin gene. The sequence of the 5'-promoter region of mouse ghrelin gene including the TATA-like sequence and short exon 1 was highly homologous to that of reported human ghrelin gene. These findings suggest that the structure of the promoter region including the short noncoding first exon and its transcriptional regulation are conserved among the mammalian ghrelin genes.

Animals↗
PubMed2001

Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease.

OBJECT: There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. METHODS: Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the "on" or "off' phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. CONCLUSIONS: Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

Antiparkinson Agents↗
PubMed2000

Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols.

A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.

Animals↗
PubMed2000

Two novel first exons in the prolactin receptor gene are transcribed in a tissue-specific and sexual maturation-dependent manner to encode multiple 5'-truncated transcripts in the testis of the chicken.

Cloning and sequencing of the chicken prolactin receptor (PRLR) gene segment from the transmembrane domain to the box 2 motif revealed the presence of the two testis-specific first exons, TSE-1 and TSE-2, encoding the unique 5'-end sequences of the reported and newly identified multiple 5'-truncated PRLR transcripts containing only the cytoplasmic domain in the testis. TSE-1 was located downstream of the exon encoding the transmembrane domain and TSE-2 presented downstream of the exon encoding the box 1 motif. These findings indicate that the box 1-containing 5'-truncated transcripts are generated by the utilization of TSE-1 as the first exon with distinct splicing donor sites to the box 1-containing exon, and that the utilization of TSE-2 as the first exon and its splicing to the box 2-containing exon results in the generation of the box 1-lacking transcript. Three transcription initiation sites for the box 1-containing 5'-truncated transcripts and two transcription initiation sites for the box 1-lacking transcript were detected by the RNase protection assays. Reverse transcription-polymerase chain reaction analysis showed that the expression levels of all these 5'-truncated PRLR transcripts are simultaneously increased during sexual maturation, accompanying the decrease of the amount of the canonical full-length transcript for PRLR.

Animals↗
PubMed2000

Dephosphorylation-induced decrease of anti-apoptotic function of Bcl-2 in neuronally differentiated P19 cells following ischemic insults.

It is known that Bcl-2 has a protective effect against neuronal ischemia. Some reports speculate anti-apoptotic function of Bcl-2 depends not on the expression level but on the phosphorylation state. We found induction of apoptosis and CPP32 activation by energy impairment (3-nitropropionic acid (3-NP)-treatment or glucose-deprivation) in the neuronally differentiated P19 cells. Time course study of cell viability following ischemic insults showed that the number of viable cells decreased along with the increase in the amount of dephosphorylated Bcl-2 without obvious quantitative alteration of the protein. Then, we generated differentiated P19 cells overexpressing wild-type Bcl-2 (P19/wt. Bcl-2) or phosphorylation-negative Bcl-2 mutant (P19/mut.Bcl-2), in which alanine was substituted for serine 70. When the cell viability was examined within 24 h, P19/mut.Bcl-2 was more vulnerable to energy impairment as compared with P19/wt.Bcl-2. In addition, overexpression of wild-type Bcl-2 inhibited DNA laddering and CPP32 activation induced by the insults, while that of mutant Bcl-2 did not. These findings suggest that the phosphorylation state, as well as the expression level, of Bcl-2 plays an important role to modulate its protective effect against ischemic insults.

Animals↗
PubMed2000

Human amniotic epithelial cells produce dopamine and survive after implantation into the striatum of a rat model of Parkinson's disease: a potential source of donor for transplantation therapy.

We have recently found that human amniotic epithelial (HAE) cells synthesize catecholamines including dopamine (DA). The present study was designed to explore the possibility of HAE cells to serve as a donor for transplantation therapy of Parkinson's disease (PD). Thus, we investigated their ability to produce DA in vitro and the survival and function of HAE cells grafted into a rat model of PD. RT-PCR and Western blotting revealed that HAE cells express tyrosine hydroxylase (TH) mRNA and protein, respectively. TH-immunohistochemistry on cultured HAE cells demonstrated that around 10% of the total cells are immunopositive for this protein. The production of DA by HAE cells was increased with time in the presence of L-tyrosine and BH(4), and was abolished with a specific TH inhibitor, alpha-methyl-rho-tyrosine. Dissociated HAE cells transduced with the Escherichia coli LacZ marker gene (beta-gal) were implanted into the previously DA-depleted striatum of immunosuppressed rats. Two weeks postgrafting HAE grafts were demonstrated to survive without overgrowth, as evidenced by the presence of beta-gal-positive cells and TH-immunoreactive cells within the grafts. The grafts also provided partial amelioration of apomorphine-induced rotational asymmetry. The results clearly indicate that HAE cells capable of producing DA can survive and function in the brain of a rat model of PD. Although DA replacement therapy of PD could possibly be achieved with implantation of HAE cells, further studies are needed to develop strategies to enhance the ability of HAE cells to produce DA as well as the graft survival.

Amniotic Fluid↗
PubMed2000

Fetal tissue transplants in animal models of Huntington's disease: the effects on damaged neuronal circuitry and behavioral deficits.

Accumulating evidence indicates that grafts of embryonic neurons achieve the anatomical and functional reconstruction of damaged neuronal circuitry. The restorative capacity of grafted embryonic neural tissue is most illustrated by studies with striatal tissue transplantation in animals with striatal lesions. Striatal neurons implanted into the lesioned striatum receive some of the major striatal afferents such as the nigrostriatal dopaminergic inputs and the gluatmatergic afferents from the neocortex and thalamus. The grafted neurons also send efferents to the primary striatal targets, including the globus pallidus (GP, the rodent homologue of the external segment of the globus pallidus) and the entopeduncular nucleus (EP, the rodent homologue of the internal segment of the globus pallidus). These anatomical connections provide the reversal of the lesion-induced alterations in neuronal activities of primary and secondary striatal targets. Furthermore, intrastriatal striatal grafts improve motor and cognitive deficits seen in animals with striatal lesions. Since the grafts affect motor and cognitive behaviors that are critically dependent on the integrity of neuronal circuits of the basal ganglia, the graft-mediated recovery in these behavioral deficits is most likely attributable to the functional reconstruction of the damaged neuronal circuits. The fact that the extent of the behavioral recovery is positively correlated to the amount of grafted neurons surviving in the striatum encourages this view. Based on the animal studies, embryonic striatal tissue grafting could be a viable strategy to alleviate motor and cognitive disorders seen in patients with Huntington's disease where massive degeneration of striatal neurons occurs.

Animals↗
PubMed2000

Fetal striatal transplants reinstate the electrophysiological response of pallidal neurons to systemic apomorphine challenge in rats with excitotoxic striatal lesions.

Previous studies with single-unit recording and 2-[14C]deoxyglucose quantitative autoradiography have shown that systemic administration of apomorphine increases the functional activity of pallidal neurons, and that the enhancement in the globus pallidus (GP) activity is abolished by striatal lesions. The present study employing electrophysiological techniques tested whether embryonic striatal tissue implanted in the excitotoxically damaged striatum of rats may affect the lesion-induced alteration in the neuronal response of GP to apomorphine. Systemically administered apomorphine significantly increased spontaneously firing rates of GP cells. The blockade of dopamine receptors with haloperidol reversed the increased rate to baseline levels. Quinolinate-induced striatal lesions attenuated the rate-increasing effect of apomorphine. Embryonic striatal grafts placed in the lesioned striatum restored the response of GP cells to systemic apomorphine. The graft-mediated restoration of the GP neuron response to apomorphine were accompanied by an improvement in the motor asymmetry induced by this drug. Considering previous anatomical data to demonstrate extensive innervation of the GP by embryonic striatal grafts, the present results suggest that the grafts reconstruct the functional striatopallidal pathway which is capable of transmitting apomorphine-induced changes in the neuronal activity.

Action Potentials↗
PubMed2000

Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson's disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor.

OBJECT: The P19 embryonal carcinoma-derived cell line consists of undifferentiated multipotential cells, which irreversibly differentiate into mature neurons after exposure to retinoic acid (RA). In the present study, the authors genetically engineered P19 cells to produce glial cell line-derived neurotrophic factor (GDNF), and grafted the cells in a rat model that had been rendered parkinsonian. METHODS: Undifferentiated P19 cells were grown in vitro and transduced with GDNF complementary DNA. The level of GDNF released from the transduced cells was measured using an enzyme-linked immunosorbent assay, and its neurotrophic activities were assessed by testing the effects on rat embryonic dopamine (DA) neurons in culture. After having been exposed to RA for 48 hours and allowed to differentiate into postmitotic neurons, the GDNF gene-transduced cells were implanted into the midbrain of immunosuppressed rats. A unilateral nigrostriatal lesion was then induced by intrastriatal infusions of 6-hydroxydopamine. Immunohistochemical analyses performed 4 weeks postgrafting revealed that the GDNF-producing cells expressed several neuronal markers without evidence of overgrowth. The grafts expressed GDNF protein and prevented the death of nigral DA neurons. Furthermore, the GDNF-producing cells implanted 4 weeks after nigrostriatal lesions restored the expression of tyrosine hydroxylase in injured DA neurons and induced their dendritic sprouting. CONCLUSIONS: The results indicate that the P19 cell line transduced with the GDNF gene can stably secrete functional levels of GDNF, even after being converted to postmitotic neurons. Because it is has been established that GDNF exerts trophic effects on DA neurons, the means currently used to deliver GDNF into the brain could be a viable strategy to prevent the death of nigral DA neurons in cases of Parkinson's disease.

Analysis of Variance↗
PubMed2000

[Evaluation of hepatic toxicity following high-dose 5-FU arterial infusion chemotherapy: analysis of 42 cases of colorectal liver metastases].

The regional toxicity of an anticancer agent for normal liver tissue following hepatic arterial infusion chemotherapy (HAI) was evaluated in terms of morphology, function, and histopathology. Forty-two patients(M:F = 30:12; mean age, 59.9 years) with liver metastases from colorectal cancer were treated with HAI using a totally implantable vascular access port system from July 1994 to March 1999. The regimen used here was so-called weekly high-dose 5-fluorouracil(5-FU) infusion(5-FU, 1,000 mg/m2/week). Volume measurement of the liver demonstrated not only whole liver atrophy including the tumor but also volume reduction of the non-tumorous lobe. Atrophic change of the liver was seen in patients who were administered over 20 g/m2 of 5-FU(p < 0.01). The CT attenuation values of the liver were examined, and fatty infiltration was seen in six patients. Histologic examination of liver biopsies from the non-tumorous part revealed steatosis and infiltration of inflammatory cells in the portal triad, which were not seen in specimens prior to HAI. On clinical laboratory findings, enzymes representing bile duct, including alkaline phosphatase, leucine amino peptidase, and gamma-glutamyltranspeptidase, were increased in 22 patients. In terms of regional toxicity for long-term HAI, 20 g/m2 of 5-FU, is the key dose at which to consider temporary cessation or dose reduction.

Adult↗
PubMed2000

[Regional differences of in vivo proton MR spectroscopy in developing human brain].

The purpose of this study was to clarify regional differences in proton MR spectroscopy (1H-MRS) in the developing human brain. Proton MR spectra were obtained from 24 infants aged 0 to 24 months old. Proton MR spectroscopy was performed on a 1.5 Tesla clinical MR unit using a 3D-chemical shift imaging sequence (3D-CSI). MR spectra obtained from voxels in frontal white matter and those in parietal white matter were compared. The NAA/Cho ratios of the frontal region were lower than those of the parietal region at birth but increased rapidly during the first six months of life. The rate of increase was reduced in the second year of life. In contrast, NAA/Cho ratios in paracentral areas were already high at birth but increased slowly through the first two years of life. Cho/Cr ratios of the frontal region were stable during the first year of life and started to decrease in the second year of life. In the parietal region, Cho/Cr ratios were decreased throughout infancy. Regional differences in 1H-MRS spectra were apparent during infancy, and these differences were suggested to reflect regional differences in the maturation of the developing human brain.

Adult↗
PubMed2000

[Cell transplantation therapy for Parkinson's disease].

We found that Parkinson's disease(PD) patients receiving autotransplants of the cervical sympathetic ganglia show a significant improvement in the parkinsonian symptoms with a consequent reduction in the daily intake of levodopa. The grafting procedure have recently been modified to further enhance the efficacy of the transplantation. Thus, in order to increase the amount of donor tissue we opted for the endoscopically excised thoracic sympathetic ganglia as a donor. With the aid of CT-guided stereotaxic surgery, we unilaterally placed one transplant deposit in the caudate head and three deposits in the putamen. Four patients that had received the grafts were followed with antiparkinsonian medication being unchanged at least one year postgrafting. Although no patients exhibited a substantial improvement in motor performance rated in either "on" or "off" phase, the awake time spent in "off" phase was reduced by 30-40% in all the patients. In two patients, dyskinesia in "on" phase was also attenuated. Our new transplantation paradigm is encouraging and deserves further investigation.

Cell Transplantation↗
PubMed2000

[A case of myasthenia gravis following sarcoidosis and Hashimoto's thyroiditis].

Here, we report on an elderly woman with sarcoidosis and Hashimoto's disease who later developed myasthenia gravis. She was 68-year-old with a long history of Hashimoto's disease who had a clinical diagnosis of sarcoidosis with uveritis at the age of 66 years. On laboratory examination, angiotensin-converting enzyme, lysozyme and gamma-globulin were elevated and there was bilateral hilar lymphoadenopathy. She was admitted to our hospital because of left blepharoptosis and mild fatigability in the proximal muscles at the age of 68 years. Myasthenia gravis, type IIa, was confirmed by elevated titer of anti-acetylcholine receptor antibody in serum (0.8 nmol/l, normal < 0.6), positive edrophonium test and decremental EMG response. Oral prednisolone therapy was effective. Her muscle biopsy revealed HLA ABC-positive fibers in all fascicles, and HLA-DR positive fibers in the perifascicular areas. Myasthenia gravis complicated by sarcoidosis and Hashimoto's thyroiditis is extremely rare, suggesting that the common underlying immunological abnormalities for the three disorders such as a certain defective cellular immunity are responsible for the pathomechanism to induce the patient condition.

Aged↗
PubMed2000

[A case of LGMD2A identified with both western blot analysis and immunostaining of calpain 3 in biopsied muscle].

A 45-year-old housewife had proximal dominant limb muscle weakness from around 25 years of age. Her parents were cousins. None of family members was affected. Progressive muscle weakness and atrophy were prominent at the posterior compartments of legs and trunk. Serum CK was moderately elevated. Muscle pathology revealed variation in fiber size, moderate increase in numbers of internal nuclei and abundant lobulated fibers. On immunostaining using by monoclonal antibody against human calpain 3 (NCL-CALP-2 C4; Novocastra) to the biopsied muscle, calpain 3 was completely absent in the sarcoplasm, while granular debris and in part positive striation were noted in control muscle. By Western blot analysis, a band corresponding to 94 kDa of calpain 3 was not detected. A genetic analysis of calpain 3 revealed homozygous C-565-G mutation (Leu189Val). From the present study. Western blot analysis and immunostaining by using calpain 3 antibody were suggested to be useful to diagnose LGMD2A in LGMD patients.

Biomarkers↗