PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization.
Explore the source record for details and available documents.
Algorithms↗
Biomedical subjects
K Nakai
Publications and source records attributed to K Nakai.
Inflammatory cell-mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative enzymes in murine fibrosarcoma cells.
We isolated six clones of weakly tumorigenic fibrosarcoma (QR) from the tumorigenic clone BMT-11 cl-9. The QR clones were unable to grow in normal C57BL/6 mice when injected s.c. (1x10(5) cells). However, they formed aggressive tumours upon co-implantation with a 'foreign body', i.e. a gelatin sponge, and the rate of tumour take ranged from 8% to 58% among QR clones. The enhanced tumorigenicity was due to host cell-mediated reaction to the gelatin sponge (inflammation). Immunoblot analysis and enzyme activity assay revealed a significant inverse correlation between the frequencies of tumour formation by QR clones and the levels of manganese superoxide dismutase (Mn-SOD, P<0.005) and glutathione peroxidase (GPchi, P<0.01) in the respective tumour clones. Electron spin resonance (ESR) revealed that superoxide-scavenging ability of cell lysates of the QR clone with high level of Mn-SOD was significantly higher than that with low level of the antioxidative enzyme in the presence of potassium cyanide, an inhibitor for copper-zinc superoxide dismutase (CuZn-SOD) (P<0.001). Minisatellite mutation (MSM) induced by the inflammatory cells in tumour cells were investigated by DNA fingerprint analysis after QR clones had been co-cultured with gelatin-sponge-reactive cells. The MSM rate was significantly higher in the subclones with low levels of Mn-SOD and GPchi (P<0.05) than in the subclones with high levels of both enzymes. The MSM of the subclones with low levels of both enzymes was inhibited in the presence of mannitol, a hydroxyl radical scavenger. The content of 8-hydroxydeoxyguanosine (8-OHdG) by which the cellular DNA damage caused by active oxygen species can be assessed was significantly low in the tumours arising from the QR clone with high levels of Mn-SOD and GPchi even if the clone had been co-implanted with gelatin sponge, compared with the arising tumour from the QR clone with low levels of those antioxidative enzymes (P<0.001). In contrast, CuZn-SOD and catalase levels in the six QR clones did not have any correlation with tumour progression parameters. These results suggest that tumour progression is accelerated by inflammation-induced active oxygen species particularly accompanied with declined levels of intracellular antioxidative enzymes in tumour cells.
Animals↗
A case of amnestic syndrome caused by a subcortical haematoma in the right occipital lobe.
A case of an amnestic syndrome caused by a subcortical haematoma in the right occipital lobe is reported. A 62-year-old right-handed man presented with a sudden onset of headache to the hospital. On admission, he had a left homonymous hemianopsia, disorientation and recent memory disturbance, but had normal remote memory and digit span. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a subcortical haematoma in the right occipital lobe. These findings suggest that the patient's amnesia was caused by a lesion of the retrosplenial region in the non-dominant hemisphere.
Amnesia↗
Modeling and predicting transcriptional units of Escherichia coli genes using hidden Markov models.
MOTIVATION: The hidden Markov model (HMM) is a valuable technique for gene-finding, especially because its flexibility enables the inclusion of various sequence features. Recent programs for bacterial gene-finding include the information of ribosomal binding site (RBS) to improve the recognition accuracy of the start codon, using this feature. We report here our attempt to extend the model into the total transcriptional unit, enabling the prediction of operon structures. RESULTS: First, we improved the prediction accuracy of coding sequences (CDSs) by employing the models of 'typical', 'atypical' and 'negative (false-positive)' classes as well as the models of RBS and its downstream spacer. The sensitivity of exactly predicting the 204 experimentally confirmed CDSs reached 90.2% in an objective test. Based on the prediction result of CDSs, the positions of the promoters and terminators were predicted. Our model could exactly recognize 60% of 390 known transcriptional units. Thus, the accuracy and significance of this prediction problem is far from trivial. We would like to propose this problem as an open theme in bioinformatics because the ongoing or planned post-sequencing projects will produce much data for future improvements.
Algorithms↗
Enhancement of the serotonin-mediated acetylcholine release by repeated desmethylimipramine treatment in the hippocampus of freely moving rats.
A possible involvement of serotonin-mediated cholinergic activation in the antidepressant effect of desmethylimipramine (DMI) was investigated by determination of the effects of a single or repeated DMI administration on acetylcholine (ACh) release in the hippocampus using an in vivo microdialysis technique and a radioimmunoassay for ACh. Rats were administered DMI (10 mg/kg, i.p.) acutely or repeatedly for 21 days. A single or repeated DMI administration did not cause any significant effects on the basal ACh release compared with the respective controls. Atropine perfusion in the acutely DMI-treated or control rats increased the ACh release to the same degree. In repeatedly DMI-treated rats, serotonin (5-HT) (1 to 10 microM) perfusion enhanced significantly the ACh release. However, 5-HT in acutely DMI-treated rats enhanced significantly the ACh release only at 10 microM. 5-HT did not cause any changes in ACh release in control rats. Hippocampal 5-HT content of acutely DMI-treated rats was significantly higher than that of saline-treated control rats, while no difference was observed between the repeatedly DMI- and saline-treated rats. These findings suggest, for the first time, that DMI induced a facilitation of cholinergic neurotransmission in the rat hippocampus through the activation of 5-HT-receptor function.
Acetylcholine↗
[Construct validity of a new computer-assisted cognitive assessment battery in normal adults].
A computer-assisted battery for neuropsychological tests (CNT) has been designed to screen adults for cognitive impairment. The aim of this study was to gather evidence for the construct validity of CNT and also investigate the relationship between CNT and conventional neuropsychological tests. Subjects were 45 healthy adults (21 men and 24 women), who ranged in age from 20 to 70 years (mean = 33.5, SD = 1.9) with no history of substance abuse, or of psychotic or neurological disorders. The CNT in our study consists of six subtests designed to assess various components of driving, such as digit span, visual scanning, visual and verbal memory, complex reaction time, and vigilance. Mini-mental state test, Kana-hiroi test, word fluency, the auditory-verbal learning test and Raven's colored progressive matrices were also performed as conventional neuropsychological tests. Results showed there were high correlations between each CNT subtests and conventional neuropsychological tests. A factor analysis (with varimax rotation) identified 4 factors with eigen values greater than 1, which accounted for over 70% of the variance. CNT was able to estimate each factor related to cognitive function such as learning and memory, attention, judgment, and visual scanning selectively. CNT may thus be a useful tool for detection of cognitive impairment, although this test has important limitations. Broader applications of these tests will require extensive population-based validation.
Adult↗
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↗
[Choroid plexus papilloma in the posterior third ventricle in infancy: a case report].
Choroid plexus papillomas represent approximately 0.5% of all intracranial tumors, but they are found in the third ventricle only infrequently. We report a case of choroid plexus papilloma in the third ventricle which is difficult to differentiate from a pineal region tumor. A 4-month-old female presented with bulging fontanelle and sunset phenomenon. A CT scan and MRI showed marked hydrocephalus caused by a tumor extending from the posterior third ventricle to the peneal body. Preoperatively, we diagnosed the lesion as a pineoblastoma. The tumor was totally removed through the occipital transtentorial approach. Pathological examination of the tumor revealed a typical choroid plexus papilloma. The operation was uneventful, and she has grown normally without recurrence of the tumor for three years since the operation. A sagittal gadolinium-enhanced MRI was useful in our case to differentiate a choroid plexus papilloma from a pineal region tumor, because the former extended into the aqueduct forming the shape of the letter V while the latter compressed the aqueduct downward.
Cerebral Ventricle Neoplasms↗
Application of low-intensity ultraviolet irradiation to the treatment for pharmacological vasoconstriction via a percutaneous transluminal approach.
We applied low-power ultraviolet (UV) laser irradiation via a thin flexible optical fiber to an in vivo model of vasospasm using an intravascular transluminal approach. The surgically exposed left femoral arteries of a rabbit were constricted by norepinephrine. A quartz fiber of 400 microm in diameter was introduced into the artery via the right common carotid artery through a 2.5F catheter. The femoral artery lumen was then irradiated with a helium-cadmium laser (wavelength 325 nm, output power 8 mW) through the fiber for 30 s. The UV irradiation increased the mean luminal diameter by 85% in comparison to the precontracted state, while the increase was only 45% in a sham operation. A histopathologic examination revealed no thermal damage and an intact internal elastic lamina. These results suggest that intravascular transluminal irradiation with a low-power UV laser may thus have potentially clinical applications to reverse acute arterial vasospasm.
Angiography↗
[Serum nuclear matrix proteins (NMPs)].
Explore the source record for details and available documents.
Antigens, Nuclear↗
Cell cycle dependency of porphyrin uptake in a glioma cell line.
We used a two-color analysis system to assess the porphyrin uptake and DNA content in four established cell lines of glioma employing flow cytometry (FCM). The FCM study revealed porphyrin uptake in all cells, regardless of the phase of the cell cycle they were in. However, those in the G0/G1 phase showed moderate uptake of porphyrin and those in the G2/M phase showed a higher uptake. These results indicated the advantage of using porphyrin as the carrier of tumor targeting agents as a therapeutic strategy for malignant tumors.
Brain Neoplasms↗
Detection and isolation of a novel human gene located on Xp11.2-p11.4 that escapes X-inactivation using a two-dimensional DNA mapping method.
Using a two-dimensional DNA mapping method, we detected four NotI restriction sites that escape chromosome X-specific methylation in humans. Two genes corresponding to two of these sites that lie in the region of Xp11.2-p11.4 were cloned and their properties studied. One of the genes matched a known gene, but the other, termed EXLM1, is novel and is predominantly expressed in cultured lymphocytes and skeletal muscle.
Amino Acid Sequence↗
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↗
Isolation of full-length cDNA of mouse PAX4 gene and identification of its human homologue.
Recent genetic studies have suggested that PAX4, a member of the paired box (PAX) gene family, is involved in the mechanism regulating the fate of pancreatic islet endocrine progenitor cells. Murine PAX4 was originally identified by genomic screening and, to date, only a partial sequence of PAX4 has been reported. In this study, we cloned the full-length cDNA of mouse PAX4 by RACE (rapid amplification of cDNA ends) using RNA from MIN6 cells, a mouse insulinoma cell line. The full length of cDNA was 1.38 kb, consistent with the estimated size of the transcript by Northern blot. The deduced mouse PAX4 protein was 349 amino acids and had the predicted molecular weight of 38 kDa. Two DNA binding motifs, a 128-amino acid paired domain and a 61-amino acid paired-type homeodomain exhibit the highest amino acid homology with PAX6 (71.2%, 65.0%, respectively), another member of the PAX gene family. However, the sequence of the C-terminal segment of PAX4 diverged and showed no significant homology with any other known PAX genes. As to the genomic DNA, the coding region of the mouse PAX4 gene spanned approximately 5.5 kb and was composed of 10 exons. In the public DNA database, a human cosmid (g1572c264), which was localized on human chromosome 7q31.3, was found to contain a gene homologous to PAX4. The nucleotide and protein sequence homologies between mouse PAX4 and its human homologue were 83.1% and 80.0%, respectively. Interestingly, the ARP5 (ADP-ribosylation factor 5) gene was also found in the same cosmid g1572c264, suggesting the ARP5 gene to be adjacent to the human PAX4 homologue. The human cosmid g1572c264 contains at least four SSRPs (simple sequence repeat polymorphism), which could be used for genetic linkage studies of the locus. The results of this study, i.e. isolation of the full-length cDNA sequence of PAX4 and identification of the homologous human gene, will facilitate further functional and genetic studies of the PAX4 gene.
Alternative Splicing↗
[Prevention of sudden death and the countermeasures--cardiac sudden death and acute myocardial infarction--ideal emergicenters].
Explore the source record for details and available documents.
Cardiopulmonary Resuscitation↗
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↗
Magnetic resonance signal intensity and volume changes after endovascular treatment of intracranial aneurysms causing mass effect.
To determine when and how intracranial aneurysms causing mass effect change following endovascular treatment, we used MRI to assess patients for 2-3 years after the interventional procedure. Nine patients who had aneurysms compressing the surrounding structures underwent endovascular treatment. Proximal occlusion of the parent artery was performed in seven cases, and in two the aneurysm was embolised with microcoils. After embolisation, signal intensity within aneurysms tended to be high on both T1- and T2-weighted images. When there was rapid reduction in size high-signal zones within aneurysms became isointense or gave low signal on T1-weighted images. On T2-weighted images, isointense or low-signal foci appeared within high-signal areas in the aneurysm, giving mixed intensity. In typical cases, the mean volume of the aneurysm fell to approximately 30% of its initial value 2-12 months after treatment. After this, no additional reduction was observed. The aneurysms which showed little signal intensity change tended to shrink more slowly and to a lesser degree than the more typical cases. Aneurysms which gave high signal on both T1- and T2-weighted images early following embolisation shrank more quickly than those showing little signal change.
Adult↗
Carotid endarterectomy and simultaneous percutaneous transluminal angioplasty for tandem internal carotid stenoses.
We treated three patients with tandem internal carotid stenoses in single procedures including carotid endarterectomy (CEA) for the proximal stenosis and percutaneous transluminal angioplasty (PTA) for the distal stenosis. We devised a Y-shaped shunt tube for the CEA, through which a balloon catheter was introduced to perform PTA guided by mobile digital subtraction angiography. No cerebrovascular events occurred during follow-up. Our approach avoids the risk of a second procedure while effectively treating tandem stenoses.
Aged↗