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Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 397 records · Page 22Linked to original sources
PubMed1996

Development of calcitonin gene-related peptide slow-release tablet implanted in CSF space for prevention of cerebral vasospasm after experimental subarachnoid haemorrhage.

The calcitonin gene-related peptide (CGRP), a known potent intrinsic cerebral vasodilator, is contained in the sensory nerves from trigeminal ganglia that inervate the cerebral arteries. We previously reported that human alpha CGRP (hCGRP) dilates spastic cerebral arteries after experimental subarachnoid haemorrhage (SAH) in rabbits. In the present study, we investigated the prophylactic potential of a sustained higher cerebrospinal fluid level of hCGRP against experimental cerebral vasospasm. An hCGRP slow-release tablet (hCGRP s-r tablet) was developed for cisternal implantation. Experimental SAH was induced by percutaneous cisternal injection of autologous arterial blood. Angiography was initiated on day 1 (before SAH) and performed everyday. The hCGRP s-r tablet was implanted into the cisterna magna on day 2 in the treated groups. The spastic response of the basilar artery was maximized on day 4 in the non-treated (80.7% of day 1) and the placebo-treated (79.3%) groups. In contrast, the arterial diameters on day 4 were 96.1% and 90.5% of day 1 in the groups implanted with hCGRP 24 micrograms and 153 micrograms s-r tablets, respectively. We also measured the concentration of hCGRP in the cerebrospinal fluid (CSF) following implantation of the hCGRP 24 micrograms s-r tablet in the cisterna magna. The hCGRP concentration before implantation was below the dectable level. Following implantation, the hCGRP level in the CSF was 23.12 nmol/L on the second day and remained at elevated levels until the fifth day. These experiments suggest that the intrathecal single implantation of the hCGRP s-r tablet could produce an elevated concentration of hCGRP in the CSF over five days and have prevented the cerebral vasospasm after SAH in the rabbit. The hCGRP s-r tablet may be clinically applicable in the treatment of patients with SAH against cerebral vasospasm.

Animals↗
PubMed1996

Surgical treatment of a sacral nerve root cyst with intermittent claudication in an 85-year-old patient: case report.

The following presents a case of an 85-year-old woman with intermittent claudication of a sacral nerve root cyst. The cyst wall was incised and oversewn while preserving the surrounding nerve fibers by microscopic procedures. All symptoms were eliminated following the operation. The syndrome of intermittent claudication may possibly arise while walking from the transient influx of cerebrospinal fluid into a cyst in a relatively narrow sacral canal. The present case may indicate that a sacral nerve root cyst is curable even in aged patients through thorough evaluation and management.

Age Factors↗
PubMed1996

Indirect revascularization for moyamoya disease: is there a beneficial effect for adult patients?

BACKGROUND: It is generally accepted that excellent development of collateral circulation can be achieved through indirect nonanastomotic bypass procedures for pediatric patients with moyamoya disease. However, there are no definitive conclusions about the effect of indirect revascularization for adult patients. To clarify the value of indirect bypass surgery for adult moyamoya disease, we have analyzed their follow-up angiographic results in comparison with those of the pediatric patients. METHODS: Between 1989 and 1993, 23 patients underwent combined direct and indirect bypass surgery. They consisted of 16 adults (mean age, 35; range, 20-59) and seven children (mean age, 10; range, 3-16). The main symptoms were those due to cerebral ischemia in all but 1 of 23 patients. Preoperative cerebral blood flow studies showed all patients to have decreased vascular reserve (misery perfusion). Postoperative follow-up angiography was done in all patients at a median of 6 months after the surgery. RESULTS: All pediatric patients showed good or moderate development of collaterals through the indirect bypass. Among the adult group, seven patients aged 20 to 29 had angiographic results similar to those of the pediatric group . On the other hand, nine patients older than 30 had results contrary to those of pediatric patients: (1) the degree of indirect revascularization declined to moderate or poor grades (especially in patients older than 40) and (2) the degree of direct bypass filling improved to high or medium grades. CONCLUSIONS: The results suggest that advancing age apparently affects the development of collateral formation through the indirect bypass. Consequently, direct bypass is thought to be the main treatment option for patients older than 40.

Adolescent↗
PubMed1996

Effect of calcitonin gene-related peptide on delayed cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is an intrinsic vasodilatory substance contained in perivascular nerve fibers of intracranial arteries. It is suggested that CGRP plays a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). METHOD: An experimental SAH was produced by intracisternal injection of arterial blood in rabbits. The animals were treated with intrathecal administration of CGRP solution 3 days after SAH. The degree of vasospasm and the effect of CGRP were evaluated angiographically by measuring the basilar artery diameter. RESULTS: The basilar artery constricted to 73.0% of the pre-SAH values 3 days after SAH. Fifteen minutes after injection of 10(-10) mol/kg CGRP, the basilar artery dilated to 117.1% (n = 8), which was significantly larger than 67.1% in the vehicle group (n = 8) (p < 0.01). The significant vasodilatory effect of CGRP, compared with the vehicle group, lasted for 6 hours. CONCLUSIONS: Intrathecal administration of CGRP has therapeutic potential for treating cerebral vasospasm.

Animals↗
PubMed1996

Neuromagnetic evidence of pre- and post-central cortical sources of somatosensory evoked responses.

Somatosensory evoked magnetic fields (SEFs), corresponding with electrical median nerve stimulation, were measured using an MRI-linked, whole-head MEG system. In total 184 hemispheres, SEFs were measured, involving 22 normal volunteers and 70 patients with intracranial lesions. The first SEF peak appeared 20.2 +/- 1.5 msec (mean +/- S.D.) after stimulation. The first peak was followed by a second and third peak, 7.7 +/- 3.2 msec and 14.6 +/- 5.4 msec respectively after the first. Corresponding isofield maps suggested a single current dipole oriented in the anterior direction for the first peak, posterior for the second and either anterior or posterior for the third. Using a spherical model and a single current dipole source, the localization of each peak was estimated and superimposed on individually determined MRI images. On a grand average basis, the first-peak dipole was localized on the posterior surface of the central sulcus, "area 3b." The second-peak dipole was localized 3.7 mm medial (P < 0.001) and 2.0 mm superior (P < 0.001) to the first-peak dipole, on the anterior wall of the central sulcus, "area 4." This study with a large number of subjects was able to statistically distinguish two adjacent cortical sources, located on opposite walls of the central sulcus, and within a few millimeters of each other.

Adult↗
PubMed1996

The influence of oxygen free radicals on the permeability of the monolayer of cultured brain endothelial cells.

Free radicals have been implicated in the pathogenesis of vasogenic brain edema caused by ischemic or traumatic injury. It has been reported that in transgenic mice overexpressing the human CuZn-superoxide dismutase, brain edema is decreased in many cerebral disorders. To investigate the effects of free radicals on the permeability of the blood brain barrier, we established an in vitro model system of the blood-brain barrier using brain endothelial cells cultivated from transgenic mice and non-transgenic mice. The blood-brain barrier model is originated by a monolayer of brain endothelial cells cultured on a membrane which has 0.45-micron pores. Electrical resistance across the cell monolayer, which reflects the paracellular flux of ionic molecules, was measured. The blood-brain barrier models were incubated with menadione (vitamin K3, an intracellular O2- producing agent), and segmental changes in the electrical resistance across the monolayer were compared between the transgenic and the non-transgenic mice. Superoxide dismutase activity of the cultured brain endothelial cells was 1.7 times higher in the transgenic than in the non-transgenic mice (n = 3, P < 0.001). The electrical resistance was reduced by menadione in the transgenic but not in the non-transgenic mice (n = 7, P < 0.05) in the early stage. Moreover, desferroxamine mesylate (Fe2+ chelating agent) inhibited the menadione-induced early decrease in electrical resistance in the transgenic mice (n = 7, P < 0.05). These results suggest that the permeability of the blood-brain barrier may be affected by hydroxyl radicals and/or peroxynitrite rather than the O2- itself.

Animals↗
PubMed1996

Increased expression of the mRNA for brain- and skin-type but not heart-type fatty acid binding proteins following kainic acid systemic administration in the hippocampal glia of adult rats.

Increased gene expression for two species of cytosolic fatty acid binding proteins (FABPs) after systemic administration of kainic acid in the rat brain was demonstrated by Northern blotting and in situ hybridization histochemical analyses. The expression of brain (B)- and skin (S)- but not heart (H)-FABP mRNAs were markedly elevated in the hippocampus at 48 h after systemic kainate treatment. The elevated expression patterns of B- and S-FABP mRNAs were quite similar to that for glial fibrillary acidic protein in the normal brain, suggesting strongly that the increased expression for B- and S-FABPs occurs in dedifferentiated and proliferated astrocytes in response to kainic acid-induced seizure.

Animals↗
PubMed1996

Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains.

The chronological changes in the gene expression for three species of cytosolic fatty acid-binding proteins (FABPs) in the rat brain were examined by Northern and in situ hybridization analyses. The expression for heart(H)-FABP became evident after birth, with a gradual increase and confined to the gray matter, suggesting that the expression of H-FABP mRNA is neuron-specific in postnatal brain. The expression for brain(B)-FABP was very intense in the ventricular germinal zone, without expression in the cerebellar external granule cell layer, suggesting the dominant expression in the cells of glial lineage. B-FABP mRNA was transiently expressed in perinatal gray as well as white matter and the expression in glial cells persists only in the olfactory nerve fiber layer at the adult stage. On the other hand, the expression for skin type(S)-FABP was evident in the both ventricular germinal zone and cerebellar external granule cell layer, suggesting the expression in cells of neuronal lineage. The expression for S-FABP was evident in the prenatal gray matter and S-FABP mRNA was expressed in glial cells at early postnatal stage, whereafter the expression decreased to, but remained at weak levels in the adult brain. Discrete functions of the three FABPs were suggested in neurons and glia differentially at various developmental stages.

Animals↗
PubMed1996

Mutation analysis in the BRCA2 gene in primary breast cancers.

Breast cancer, one of the most common and deleterious of all diseases affecting women, occurs in hereditary and sporadic forms. Hereditary breast cancers are genetically heterogeneous; susceptibility is variously attributable to germline mutations in the BRCA1 (ref. 1), BRCA2 (ref. 2), TP53 (ref. 3) or ataxia telangiectasia (ATM) genes, each of which is considered to be a tumour suppressor. Recently a number of germline mutations in the BRCA2 gene have been identified in families prone to breast cancer. We screened 100 primary breast cancers from Japanese patients for BRCA2 mutations, using PCR-SSCP. We found two germline mutations and one somatic mutation in our patient group. One of the germline mutations was an insertion of an Alu element into exon 22, which resulted in alternative splicing that skipped exon 22. The presence of a 64-bp polyadenylate tract and evidence for an 8-bp target-site duplication of the inserted DNA implied that the retrotransposal insertion of a transcriptionally active Alu element caused this event. Our results indicate that somatic BRCA2 mutations, like somatic mutations in the BRCA1 gene, are very rare in primary breast cancers.

BRCA2 Protein↗
PubMed1996

Prognostic value of complete response after the initial treatment for malignant astrocytoma.

To evaluate prognostic value of complete disappearance of the tumor mass in contrast enhanced computerized tomography after initial treatment, 81 patients with supratentorial malignant astrocytomas (57 anaplastic astrocytomas and 24 glioblastomas) were divided into two groups. All complete response CR patients received the gross total resection (more than 95% resection). Average age of this group was significantly younger than that of noncomplete response patients (38.4 vs. 49.7 years old, p < 0.05; Student t-test). In the complete response group, median survival duration was 58 months, 2-year survival rate was 77%, and 5-year survival rate was 34% compared to 12 months, 29%, and 10%, respectively, in the noncomplete response group. The outcome of CR group was significantly better (p < 0.001; Wilcoxon test). Therefore, complete response at completion of the initial treatment is an important predictor of longer survival. Gross total resection is essential to obtain complete response and thus plays a crucial role in the initial treatment of malignant astrocytomas.

Adult↗
PubMed1996

Prolyl aminopeptidase is also present in Enterobacteriaceae: cloning and sequencing of the Hafnia alvei enzyme-gene and characterization of the expressed enzyme.

The Hafnia alvei prolyl aminopeptidase gene (hpap) was cloned and sequenced, the expressed enzyme (HPAP) was purified to homogeneity and thoroughly characterized. An open reading frame of 1,281 bp was found to code for the enzyme, resulting in a protein of 427 amino acids with a molecular weight of 48,577. HPAP resembles the Aeromonas sobria enzyme, having 45% identity and the same distinctive properties with respect to size and substrate specificities. Both enzyme show similar chromatographic behavior, and HPAP could be purified following the procedure previously described for the Aeromonas enzyme. HPAP was found to be resistant to diisopropylphosphofluoridate as are most of the prolyl aminopeptidases hitherto described. In spite of this similarity, no inhibition by 1 mM p-chloromercuribenzoate solution could be detected. Significant inhibition was, however, observed when the enzyme was incubated with 3,4-dichloroisocoumarin. This study confirms the presence of two types of prolyl aminopeptidases, of which the Hafnia and Aeromonas enzymes constitute one group and the Bacillus, Neisseria, and Lactobacillus enzymes the other, and describes the cloning of the first prolyl aminopeptidase gene from an Enterobacteriaceae.

Aeromonas↗
PubMed1996

Dipeptidyl peptidase IV from Xanthomonas maltophilia: sequencing and expression of the enzyme gene and characterization of the expressed enzyme.

The dipeptidyl peptidase IV [EC 3.4.14.5] gene of Xanthomonas maltophilia, expressed in Escherichia coli, was cloned by the shotgun method. Nucleotide sequence analysis revealed an open reading frame of 2,223 bp, coding for a protein of 741 amino acids with a predicted molecular weight of 82,080. The expressed enzyme was extracted with SDS, and the solubilized enzyme was purified about 1,030-fold on columns of Toyopearl HW65C, DEAE-Toyopearl twice, and hydroxyapatite, with an activity recovery of 50%. The enzyme hydrolyzed a proline-containing peptide at the penultimate position, and was inhibited by diisopropyl phosphofluoridate. The enzyme was most active at pH 8.5, and was stable between at pH 7.0 and 9.0. The molecular weight of the purified enzyme was estimated to be 83,000 and 165,000 by SDS-PAGE and gel filtration, respectively.

Amino Acid Sequence↗
PubMed1996

Effects of nitric oxide synthase inhibition on brain infarction in SOD-1-transgenic mice following transient focal cerebral ischemia.

To investigate the role of superoxide in the toxicity of nitric oxide (NO), we examined the effect of nitric oxide synthase (NOS) inhibition on brain infarction in transgenic mice overexpressing CuZn-superoxide dismutase (SOD-1). Male SOD-transgenic mice and non-transgenic littermates (30-35 g) were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Either NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg), a mixed neuronal and endothelial NOS inhibitor, or 7-nitroindazole (7-NI; 25 mg/kg), a selective neuronal NOS inhibitor, was administered intraperitoneally 5 min after the onset of ischemia. At 24 h of reperfusion, the mice were decapitated and the infarct volume was evaluated in each group. In the nontransgenic mice, L-NAME significantly increased the infarct volume as compared with the vehicle, while 7-NI significantly decreased it. In the SOD-transgenic mice, L-NAME-treated animals showed a significantly larger infarct volume than vehicle-treated ones, whereas there were no significant differences between 7-NI- and vehicle-treated mice. Our findings suggest that selective inhibition of neuronal NOS ameliorates ischemic brain injury and that both neuronal and endothelial NOS inhibition may result in the deterioration of ischemic injury due to vasoconstriction of the brain. Since L-NAME increased infarct volume even in SOD-transgenic mice, the protective effect of SOD could result from the vasodilation by increased endothelial NO as well as the reduction of neuronal injury due to less production of peroxynitrite compared to wild-type mice. Moreover, the neurotoxic role of NO might not be dependent on NO itself, but the reaction with superoxide to form peroxynitrite, because of no additive effects of SOD and a neuronal NOS inhibitor.

Animals↗
PubMed1996

A pitfall in the surgery of a recurrent aneurysm after coil embolization and its histological observation: technical case report.

OBJECTIVE AND IMPORTANCE: This case report details the unexpected surgical difficulty encountered in treating a recurrent aneurysm after coil embolization and presents the histological findings of the resected aneurysm. This is only the second reported case of histological description of an aneurysm after coil embolization in a human. CLINICAL PRESENTATION: A 60-year-old woman experienced a 3-month history of chronic headache. Neuroimaging studies demonstrated a 2-cm anterior communicating artery aneurysm. The aneurysm was treated with a two-stage endovascular coil embolization, resulting in almost complete occlusion of the aneurysm. A cerebral angiogram at 6-month follow-up demonstrated slight refilling of the aneurysm, and angiography at 18 months showed a marked increase in the size of the small remnant. Therefore, the patient was referred for direct surgical repair of the aneurysm. INTERVENTION: The distal aneurysm dome, which had been packed with the coils and thrombus, was resected under temporary arterial trapping. An intra-aneurysmal endarterectomy was required, because the aneurysm wall developed intimal dissection that extended to the orifices of afferent and efferent arteries. The aneurysm was then obliterated with multiple clips, reconstructing the patent vessel lumen. However, the patient awoke from surgery with left hemiparesis. A postoperative angiogram disclosed occlusion of the right anterior cerebral artery. An histological study of the thrombosed aneurysm showed that the luminal surface of thrombus was not lined by endothelium. CONCLUSION: This case demonstrated not only the limited efficacy of coil embolization treatment for wide-necked aneurysms but also the potential difficulty in the direct surgical repair for such recurrent aneurysms.

Aortic Dissection↗
PubMed1996

Prevention of cerebral vasospasm by calcitonin gene-related peptide slow-release tablet after subarachnoid hemorrhage in monkeys.

OBJECTIVE: The goal of this work was to investigate the efficacy of a calcitonin gene-related peptide (CGRP) slow-release tablet (CGRP tablet) for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: Experimental SAH was produced in 10 cynomolgus monkeys by placing a clot around the internal carotid artery bifurcation (Day 0). In five animals, CGRP tablets (1200 micrograms of CGRP) were then placed in the cerebrospinal fluid space (CGRP group). In two animals, placebo tablets were similarly placed (placebo group). The remaining three animals were treated with no tablets after SAH (SAH group). A series of angiographic analyses were performed, before SAH and on Days 7 and 14, to examine changes in the diameters of the ipsilateral internal carotid artery, middle cerebral artery, and anterior cerebral artery. The CGRP concentration in the cerebrospinal fluid taken before each angiogram was also determined. RESULTS: In the SAH and placebo groups, cerebral vasospasm developed on Day 7 (54.8% of the pre-SAH value at the internal carotid artery, 62.3% at the middle cerebral artery, 51.3% at the anterior cerebral artery, and 56.1% as an average of the three arteries). In the CGRP group, vasospasm was significantly ameliorated at the middle cerebral artery, at the anterior cerebral artery, and on average (81.7, 81.1, and 75.7%, P < 0.05, 0.03, and 0.02, respectively). The CGRP concentration was positive only on Day 7 for the CGRP group (6.5 nmol/L). CONCLUSION: The CGRP tablet prevented cerebral vasospasm after SAH and may have significant potential for the treatment of patients with SAH.

Animals↗
PubMed1996

Deletion mapping of chromosome 10 in human glioma.

We analyzed DNAs from 35 gliomas (27 malignant, grades III and IV; 8 less malignant, grades I and II) for loss of heterozygosity (LOH) using microsatellite sequences on chromosome 10 as polymorphic markers. An LOH was found in 8 of 11 (73%) glioblastomas (grade IV) and 4 of 16 (25%) grade III gliomas, but not in the less malignant types. We detected three commonly deleted regions. One was located in a telomeric region of 10p and the others were relatively large regions of 10q. Our results suggested that three putative tumor suppressor genes on chromosome 10 are involved in the malignant progression of gliomas.

Alleles↗
PubMed1996

Angiogenic factors in moyamoya disease.

BACKGROUND AND PURPOSE: We previously reported that the level of basic fibroblast growth factor (bFGF) is high in cerebrospinal fluid (CSF) taken from patients with moyamoya disease. The present study investigated the levels of other angiogenic growth factors in the CSF of moyamoya patients and the clinical significance of bFGF in moyamoya disease. METHODS: The levels of bFGF, interleukin-8, platelet-derived growth factor, transforming growth factor-beta, endothelial growth factor, and vascular endothelial cell growth factor in CSF, taken from 38 patients with moyamoya disease and 16 patients with atherosclerotic occlusive disease (control group), were measured by an enzyme-linked immunosorbent assay. We analyzed the correlation between the level of bFGF and the clinical factors of age, onset pattern, development of neovascularization, and cerebral circulation. RESULTS: The CSF of moyamoya patients contained a high concentration of bFGF to a significant (P < .05) extent. The bFGF level was apparently elevated in the patients in whom neovascularization from indirect revascularization, such as encephaloduroarteriosynangiosis, was well developed (P < .01). A linear correlation between the values of bFGF and cerebral vascular response to acetazolamide (r = .7; P < .05) was revealed. The other angiogenic factors were not significantly high compared with the control group. CONCLUSIONS: The elevation of bFGF in moyamoya disease seems to be specific and is not related simply to cerebral ischemia. Clinically, the bFGF level is a useful indicator to predict the efficacy of indirect revascularization after surgery.

Adult↗