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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 271 records · Page 15Linked to original sources

Magnetic resonance angiography in patients with acute stroke treated by local thrombolysis.

Although magnetic resonance angiography (MRA) is accepted for showing chronic intracranial stenotic or occlusive lesions, the method has not been practically examined in patients with acute cerebral ischaemia. We carried out three-dimensional time-of-flight MRA in six patients with acute ischaemia treated by local thrombolysis, and compared the findings with those of digital subtraction angiography (DSA). In all patients, MRA before thrombolysis clearly demonstrated the occluded arteries, which corresponded precisely to those shown by DSA. In four patients with complete recanalisation of the occluded vessels after thrombolysis, the recanalisation could be demonstrated by postoperative MRA. In one patient with reocclusion of the recanalised artery, repeat MRA also demonstrated the reocclusion, confirmed by DSA. These results suggest that MRA may be helpful for noninvasive investigation before and after thrombolysis.

Adult↗

Neural activity of the subthalamic nucleus in Parkinson's disease patients.

The neural activity pattern of the subthalmic nucleus (STN) was investigated in five patients with Parkinson's disease who were scheduled for electrode implantation for chronic stimulation of the STN. The initial target was placed 8 mm or 10 mm lateral to the midline, 3 mm to 4 mm posterior to the midcommissural point, and 5 mm to 6 mm below the intercommissural (AC-PC) line. The STN was identified by semi-microelectrode recordings with a trajectory moving laterally in 2-mm steps. The amplitudes of multi-unit activities were relatively low at depths from 8 mm to 5 mm above and from 1 mm to 4 mm below the target, while those 4 mm to 0 mm above the target were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05), with the highest amplitude at 2 mm above the target (91.0 +/- 23.3 mu v, n = 15). In the mediolateral direction, amplitudes were relatively higher in the lateral portion, and amplitudes at 14 mm lateral to the midline were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05). The target for chronic electrical stimulation was determined to be at the midpoint of the hyperactive STN, i.e., 12 mm lateral to the midline in three patients and 13 mm lateral in two patients. Movement-related neural activity was observed at 5 sites, i.e., 3 sites responded to passive movement of the contralateral wrist and 2 sites to passive knee and/or ankle movement. In conclusion, our data show that the lateral part of the STN is hyperactive in PD, and recordings of neural activities contributed greatly to identifying the STN and determining the target for chronic stimulation within it.

Aged↗

Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes.

We report effect of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes. Generally these compounds were potent inhibitors of NADH-linked mitochondrial state 3 respiration and complex I. Presence of a phenyl group at the C1 position or oxidation of N-methylated isoquinones into N-methylisoquinolinium ion augmented the potency to inhibit mitochondrial respiration and complex I. Many of these compounds have been identified in human brains. In view of the mitochondrial and oxidative stress hypothesis, our results suggest involvement of these neurotoxins as potential causes of mitochondrial failure in Parkinson's disease.

Animals↗

Characteristic EEG findings in ring 20 syndrome as a diagnostic clue.

OBJECTIVE: To review the EEG features of ring 20 syndrome in two patients and determine the characteristic pattern of this syndrome. The features of our cases and 24 patients reported in the literature will be discussed. SUBJECTS AND METHODS: Report of two patients and review of literature. RESULTS: The two patients had intractable epilepsy since childhood. Their clinical seizures were mostly complex partial seizures. Often the patients seizures were of prolonged duration. Ictal EEG revealed characteristic slow waves, and sharp waves. The slow waves were (1) usually synchronous high-voltage slow waves with or without a spike component predominantly in the frontal and frontopolar areas, (2) sometimes showed a change in frequency every several seconds, (3) continued for a long period, and (4) easily spread diffusely. The sharp waves were 5-6 Hz irregular and diffuse discontinuous sharp waves, and sometimes appeared predominantly in the centroparietal area. The clinical seizure pattern and EEG findings were similar in the 24 published cases. CONCLUSIONS: These EEG findings may be a characteristic feature of ring 20 syndrome and thus may be useful as a diagnostic clue.

Adult↗

Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells.

Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detected in brain and urine of Parkinsonian patients on L-dopa medication, and in the urine and brain of rats after L-dopa or acute ethanol administration. Since THP is considered to be synthesized from dopamine, it may affect dopaminergic neurons through the reuptake system, i.e. dopamine transporter (DAT). To determine whether THP has affinity for DAT, we generated a cell line which stably expresses DAT and examined whether THP and its derivatives could inhibit [3H]DA uptake in these cells. Ki of THP and three derivatives (1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), 1-(3',4'-dibydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4' DHBnTIQ) and 6,7-dihydroxy-1-benzyl-1,2,3,4-tetrahydroisoquinoline (6,7 DHBnTIQ)) for inhibition of [3H]DA uptake were about 41, 35, 23 and 93 microM, respectively, which were similar to the Ki of 1-methyl-4-phenylpyridinium ion (MPP+) (28 microM). These results suggest that THP and its derivatives might be uptaken through DAT and be involved in Parkinson's disease and/or alcohol addiction.

Animals↗

Successful treatment of progressive myoclonus epilepsy with TRH.

Thyrotropin-releasing hormone (TRH) is sometimes used for the treatment of neurologic disorders such as intractable epilepsy and spinocerebellar degeneration. A 14-year-old girl with progressive myoclonus epilepsy was treated with intravenous TRH for 12 months. Clinical symptoms, such as cortical myoclonus and cerebellar signs, were improved, and P25-N33 amplitudes of somatosensory-evoked potentials decreased after TRH therapy. P100 amplitudes on flash visual-evoked potentials and photosensitivity on electroencephalograms also decreased but only temporarily. Changes in neurophysiologic findings after TRH therapy indicate that TRH inhibits hyperexcitability in the sensorimotor cortex and the visual cortex. Therefore, intravenous TRH therapy is recommended as an alternative therapy in the treatment of progressive myoclonus epilepsy.

Adolescent↗

Panosialins, inhibitors of an alpha1,3-fucosyltransferase Fuc-TVII, suppress the expression of selectin ligands on U937 cells.

Panosialins A and B were isolated as inhibitors of an alpha1,3-fucosyltransferase, Fuc-TVII, which is a key enzyme in the biosynthesis of selectin ligands, from culture broth of Streptomyces sp. Panosialins A and B inhibited the Fuc-TVII activity with IC50 values of 4.8 and 5.3 microg/ml, respectively. Panosialin A suppressed expression of selectin ligands on U937 cells, and inhibited the cell adhesion to immobilized E-selectin-immunoglobulin. Panosialins are the first reported Fuc-TVII inhibitors which can suppress the biosynthesis of selectin ligands and then inhibit selectin-mediated cell adhesion.

Benzene Derivatives↗

Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism.

We designed as candidate metabolites and synthesized two 1-benzyl-1,2,3,4-tetrahydroisoquinoline derivatives containing a dopamine moiety: 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4'DHBnTIQ) and 1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (6,7DHBnTIQ). Both were detected in mouse brain as endogenous amines by gas chromatography/mass spectrometry. 3',4'DHBnTIQ induced parkinsonism in mice when chronically administered intraperitoneally, whereas 6,7DHBnTIQ did not despite the structural similarity of the two compounds. This difference may be related to cellular uptake: In rat striatal synaptosomes, these compounds were intracellularly transported by the dopamine transporter with Km values of 6.14 and 7.82 microM and Vmax values of 214.3 and 112.2 pmol/min/mg of protein, respectively. Thus, endogenous 3',4'DHBnTIQ may be actively transported into dopaminergic neurons and accumulated there, contributing at least in part to the induction of idiopathic Parkinson's disease.

Animals↗

Regrowth of the residual tumour after acoustic neurinoma surgery.

Ideally, acoustic neurinomas should be completely removed without neurological deficit. In some cases, however, removal is subtotal in order to preserve anatomical continuity of the facial nerve. In this report we discuss the regrowth of residual tumour in these patients and the difference between regrowing and dormant tumours. Eight of 81 patients with acoustic neurinomas where the facial nerve was anatomically preserved leaving tumour overlying it were investigated and followed-up. Only one case with residual tumour along the 7th nerve from the intrameatal portion to its entry to the brainstem showed regrowth 3.5 years after the operation. In the other seven cases with residual tumour along the nerve from the porus to the brainstem, the tumour remained dormant during a follow-up period of 4.5-8.5 years. Removal of tumour in the internal auditory meatus may make regrowth unlikely.

Adult↗

Massive haemorrhage into acoustic neurinoma related to rapid growth of the tumour.

Massive haemorrhage into a acoustic neurinoma is very rare. A large size, mixed Antoni type and secondary vascular changes are thought to be causative factors. We describe a patient with a rapidly growing acoustic neurinoma which led to a massive haemorrhage. Rapid growth of the tumour seems to be another risk factor for haemorrhage.

Adult↗

Reductive dechlorination of DDT to DDD by rat blood.

The present study provides evidence that the reductive dechlorination of DDT (p, p'-dichlorodiphenyltrichloroethane) to DDD (p, p'-dichlorodiphenyldichloroethane) mediated by rat blood proceeds in the presence of both a reduced pyridine nucleotide and a flavin. The reduction appears to proceed in two steps. The first step is reduction of a flavin such as FAD, FMN or riboflavin by NADPH or NADH, either enzymatically or nonenzymatically. The second step is nonenzymatic reductive dechlorination of DDT by the reduced flavin, catalyzed by the heme group of hemoglobin.

Animals↗

The functional residues and their representation by a hypothetical 3D model of silkworm eclosion hormone.

We have previously reported that an insect neuropeptide, eclosion hormone contained an alpha-helix in the N-terminal region and the helix was likely to play an important role in constructing an active globular structure. Furthermore, Met24 and Phe25 were found to be indispensable for the biological activity. On the other hand, no strict structure at the C-terminal side was found. In this paper, we predicted the secondary structure in the C-terminal side and analyzed the functional residues by a Gly-substitution technique. As a result, we speculated that the eclosion hormone contains three alpha-helices throughout the molecule which are essential for an active peptide structure. Moreover, we found four residues important for the biological activity of silkworm eclosion hormone: Phe29, Ile55, Phe58 and Leu59. In order to understand these results stereochemically, we have constructed a 3D structure using computer aided molecular modelling. The hypothetical 3D model showed that Phe25 and Phe58 interact together in a hydrophobic manner to keep a globular form. Met24, Phe29, and Ile55 are exposed to solvent to have a hydrophobic interaction with an eclosion hormone receptor. Leu59 can also play an important role by forming a functional conformation with Phe29 and Ile55.

Amino Acid Sequence↗

Inhibitory effects of propofol on intracellular signaling by endothelin-1 in aortic smooth muscle cells.

BACKGROUND: Blood pressure decreases when propofol is administered. However, the exact mechanism underlying the vascular effects of propofol has not yet been elucidated. Endothelin produced by vascular endothelial cells is a potent vasoactive peptide that elicits prolonged contraction of vascular smooth muscle cells. The effects of propofol on endothelin-1-induced intracellular signaling in an aortic smooth muscle cell line, A10 cells, were examined. METHODS: Cultured A10 cells were pretreated with propofol for 20 min and then stimulated with endothelin-1. The effect of propofol on the endothelin-1-induced Ca2+ influx into A10 cells was evaluated by measuring intracellular 45Ca2+. The effects of propofol on the endothelin-1-induced activation of phosphatidylinositol-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D were evaluated by measuring the formation of inositol phosphates and choline, respectively. The effect of propofol on endothelin-1 binding to its receptor was determined by an [125I] endothelin-1-binding assay. RESULTS: Propofol inhibited the endothelin-1-induced Ca2+ influx, but this was significant only at supuraclinical concentrations. The endothelin-1-stimulated formation of inositol phosphates was significantly suppressed by propofol. However, propofol had no effect on the formation of inositol phosphates induced by NaF, an activator of heterotrimeric guanosine triphosphate (GTP)-binding proteins. Propofol inhibited the endothelin-1-induced formation of choline. Propofol had no effect on the binding of endothelin-1 to its receptor. CONCLUSIONS: These results suggest that propofol inhibits endothelin-1-induced intracellular signaling in vascular smooth muscle cells. The inhibitory effect of propofol might be exerted at a point between the endothelin-1 receptor and its GTP-binding protein. However, because all significant effects are observed at high concentrations, clinical relevance is unclear.

Anesthetics, Intravenous↗

Changes in protein synthesis and calcium homeostasis in the thalamus of spontaneously hypertensive rats with focal cerebral ischemia.

The thalamus has been shown to undergo secondary degeneration after cerebrocortical ischemia. However, little is known about the time course of the retrograde thalamic degeneration. The present study was designed to investigate time-dependent changes in the morphology, protein synthesis and calcium metabolism of thalamic neurons in middle cerebral artery (MCA)-occluded spontaneously hypertensive stroke-prone rats that showed primary focal ischemia in the temporoparietal cortex after permanent occlusion of the left distal MCA. In the histologic study by light and electron microscopy, swelling of the nucleus and shrinkage of the perikarya were seen in some neurons of the ventroposterior (VP) thalamic nucleus on the lesioned side at 5 days after ischemia. At the same time, the incorporation of radiolabeled leucine in VP thalamic neurons began to decrease significantly with concomitant a decrease in the number of polyribosomes in the neurons. Conspicuous 45Ca accumulation was noted at 3 days after ischemia and persisted up to 1 month in the VP thalamic nucleus on the lesioned side. These findings suggest that the secondary thalamic degeneration after cortical infarction starts with disruption of calcium homeostasis in situ at the third day after MCA occlusion, followed by a decrease in polyribosomes but not by disaggregation of polyribosomes as seen in hippocampal CA1 neurons subjected to transient forebrain ischemia.

Animals↗

Impairment in biochemical level of arterial dilative capability of a cyclic nucleotides-dependent pathway by induced vasospasm in the canine basilar artery.

The authors investigated the changes and the potential of cyclic nucleotide-dependent signal transduction, which induces smooth muscle relaxation, in the basilar artery with severe vasospasm in dogs with double experimental subarachnoid hemorrhage (SAH) to explore at which biochemical level the arterial dilative capability was impaired. The amount of cyclic adenosine and guanosine monophosphates (cAMP and cGMP) decreased significantly in the basilar artery after SAH. The activities of adenylate and guanylate cyclases also were decreased significantly in the smooth muscle cells of the basilar artery 4 days after SAH. In addition to the failure of the pathways to produce cyclic nucleotides, the activities of cAMP- and cGMP-dependent protein kinases, which are representative actual enzymes that amplify the signal for vascular dilation, also significantly decreased together with the almost total loss of activation by cyclic nucleotides in the same basilar artery after SAH. It was revealed that the system for smooth muscle relaxation was impaired severely in the cerebral arteries with severe vasospasm after SAH, on the biochemical basis of significantly less vasodilative capability and in several of the steps to produce the cyclic nucleotides of intracellular signal transduction.

Adenylyl Cyclases↗

Hyperechoic appearance of hepatic parenchyma on ultrasound examination of patients with blunt hepatic injury.

OBJECTIVE: To study the significance of a geographic hyperechoic liver parenchyma pattern on ultrasound (US) examination of patients with blunt abdominal injury. DESIGN: Prospective clinical study with double-blind evaluation of images and clinical data. METHODS AND MAIN RESULTS: We performed US examinations in 831 consecutive patients admitted to our hospital for blunt abdominal trauma and identified 33 with a geographic hyperechoic pattern in the liver. We correlated the appearance with computed tomographic images and with clinical, angiographic, and scintigraphic data. All patients with a geographic hyperechoic pattern showed mild computed tomographic evidence of hepatic injury (Mirvis grade 2, 69%; Mirvis grade 3, 31%). Excluding patients who required urgent surgery for other reasons and patients in shock, patients with the geographic hyperechoic pattern were managed conservatively with no complications. CONCLUSION: The geographic hyperechoic pattern of liver parenchyma on US examination of trauma patients is a mild injury that, of itself, does not require surgical therapy.

Adolescent↗

Cerebral blood flow measurement as an indicator for an indirect revascularization procedure for adult patients with moyamoya disease.

OBJECTIVE: Some adult patients with moyamoya disease have been treated successfully by indirect revascularization alone, although surgical indications and hemodynamic changes for these patients have not been fully explored. To examine surgical indications for this procedure, we studied the regional cerebral blood flow (rCBF) and angiographic findings in adult patients with moyamoya disease preoperatively and postoperatively. METHODS: On 17 hemispheric sides of 12 adult patients with moyamoya disease treated surgically with a combination of various indirect procedures, mainly by encephaloduroarteriosynangiosis, we retrospectively evaluated changes in rCBF using xenon-133 single photon emission computed tomography, angiographic collateral formation, and clinical results. RESULTS: Preoperatively, the rCBF values in the cortices at the bypass site at rest and after acetazolamide loading were lower than normal. The rCBF values were significantly increased after revascularization, approaching normal, except for incomplete recovery of vascular reactivity. The extent of postoperative neovascularization from implanted tissues fed by the external carotid artery system was more developed, in parallel with the preoperative decrease in resting and loading rCBF values. One-third of the operated sides exhibiting both a low rCBF at rest and impaired vascular reactivity in the noninfarcted cortices achieved good revascularization over two-thirds of the middle cerebral artery territory, accompanied by rCBF improvement and moyamoya vessel regression. Enough potential for neovascularization in the noninfarcted cortices was indicated that the resting rCBF was lower than 50 ml/100 g per minute (below the normal value by 2 standard deviations) and did not increase more than that value after loading, even in a 40-year-old patient who presented with a hemorrhage. Clinically, 11 patients (92%) had good results at the 4-year follow-up, whereas 1 patient (8%) with unsatisfactory neovascularization and a lesser extent of moyamoya vessel reduction experienced rebleeding. CONCLUSION: We conclude that for the surgical treatment of adult patients with moyamoya disease, indirect procedures, mainly encephaloduroarteriosynangiosis, are recommended for patients with lower rCBF and no or negative vascular reactivity in the noninfarcted cortices, as well as for those who have no indication for the direct procedure. It is possible to determine these indications by a xenon-133 inhalation single photon emission computed tomographic study including an acetazolamide challenge test.

Adolescent↗