Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 325 records · Page 18Linked to original sources

PubMed1997

Localization of gene expression for phosphatidylinositol transfer protein in the brain of developing and mature rats.

Gene expression for alpha- and beta-isoforms of phosphatidylinositol transfer protein (PITP) was examined using in situ hybridization histochemistry in developing and mature rat brains. During embryonic and early post-natal stages, gene expression for both PITP-alpha and -beta were detected widely throughout the entire neuraxis. In the adult brain, the expression for PITP-alpha was positive in almost all neurons throughout the entire brain while the expression for PITP-beta markedly decreased in the entire gray matter regions except for the cerebellar cortex. By comparison with the previous findings on the expression for various molecules involved in the PI turnover, the present finding suggests that PITP is involved more intimately in some differentiation-related functions of immature neurons than those of mature neurons in co-operation with PI-related molecules and that PITPs exert their functions in adult brain in concert with PLCs in subtype-preferable inter-relation.

Aging↗

PubMed1997

Production and secretion of adrenomedullin from glial cell tumors and its effects on cAMP production.

The expression of adrenomedullin (ADM) and its mRNA was studied in human glial cell tumors and cultured glioblastoma cell lines, T98G and A172. Northern blot analysis showed that ADM mRNA was expressed in all brain tumors examined (three anaplastic astrocytomas and two glioblastomas multiforme) and in the glioblastoma cell lines. Immunoreactive (IR-) ADM was detectable in these brain tumors by radioimmunoassay (0.31-2.0 pmol/g wet weight), except for one anaplastic astrocytoma. Reverse phase high performance liquid chromatography of the tumor extracts showed a single peak eluting in the position of ADM-(1-52). IR-ADM concentrations in the cultured media of T98G cells were 205.5 +/- 8.4 fmol/10(5) cells/24 h (mean +/- SEM, n = 5). Treatment of T98G cells with interferon gamma or interleukin 1 beta increased the expression levels of ADM mRNA and the IR-ADM concentrations in the cultured media, whereas tumor necrosis factor alpha decreased them in a dose-dependent manner. Treatment with synthetic ADM-(1-52) (10(-8) or 10(-7) mol/l) increased the cAMP concentrations in the cultured media of T98G cells. These findings suggest that ADM is secreted from glial cell tumors and is related to the pathophysiology of these tumors.

Adrenomedullin↗

PubMed1997

Evaluation of cytokines in cerebrospinal fluid from patients with moyamoya disease.

We investigated the levels of angiogenic growth factors in cerebrospinal fluid (CSF) from patients with Moyamoya disease and from those with atherosclerotic occlusive disease to evaluate the relationship of these factors to the pathogenesis of Moyamoya disease. CSF from Moyamoya patients contained significantly higher concentrations of basic fibroblast growth factor (b-FGF) (P < 0.05). The b-FGF level was apparently elevated in patients with well developed neovascularization after indirect revascularization surgery (P < 0.01). The other angiogenic factors were not significantly elevated compared with those of the control group.

Adult↗

PubMed1997

Proton magnetic resonance spectroscopy in children with moyamoya disease.

Proton magnetic resonance spectroscopy (MRS) is an effective method to noninvasively investigate cerebral metabolism. The aim of this study was to evaluate cerebral metabolic changes in children with Moyamoya disease using proton MRS. A total of 11 patients under 15 years old were enrolled, whose main symptoms were transient ischemic attacks. In nine patients, the more and less affected hemispheres could be determined according to their symptoms and/or single-photon emission computed tomography (SPECT). A single voxel point resolved spectroscopy was performed in the frontal or parietal white matter bilaterally by using 1.5 Tesla MR system (repetition time 2000 ms and echo time 272 ms). Voxels were located within areas that were normal on T1- and T2-weighted MR imaging. Choline (Cho), creatine (Cre) and N-acetyl aspartate (NAA) were semiquantitated as a metabolite value using an external standard reference. Pre-operative Cho, Cre and NAA values were within respective normal ranges. No metabolite showed a significant difference between the more and less affected hemispheres. A total of six patients were examined before and after revascularization surgery on one side. Pre- and post-operative comparisons demonstrated that all three metabolites showed statistically significant increases following surgery. These results suggest that, although the mechanism of spectroscopic changes needs to be further investigated, proton MRS provides a valuable method to evaluate cerebral metabolism in children with Moyamoya disease.

Aspartic Acid↗

PubMed1997

Assessment of encephalo-galeo-myo-synangiosis with dural pedicle insertion in childhood moyamoya disease: characteristics of cerebral blood flow and oxygen metabolism.

In the surgical treatment of childhood Moyamoya disease, we have been performing a new non-anastomotic bypass surgery using encephalo-galeo-myo-synangiosis (EGMS) with dural pedicle insertion over the brain surface. To assess the results obtained using this procedure, the long-term clinical outcome and the characteristics of cerebral blood flow and oxygen metabolism using PET were evaluated. The subjects were 19 patients with childhood Moyamoya disease admitted to our institution over 8 years from 1988 to 1996. This type of surgery was performed 39 times and the patients have been followed up from 10 months to 8 years. Preoperatively, although cerebral blood flow and oxygen metabolism were varied from individual to individual, low values of regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) with relatively high values of regional oxygen extraction fraction (rOEF) were found in the frontal region in most of the patients compared to normal children. Postoperatively, obvious improvement of cerebral blood flow and hemodynamics in all the areas in the operative site and clinical symptoms and signs ameliorated or disappeared during the follow-up period. In conclusion, the present method appeared to be useful to improve the hemodynamic in the brain and its long-term clinical outcome was satisfactory.

Age Distribution↗

PubMed1997

Direct and indirect revascularization for moyamoya disease surgical techniques and peri-operative complications.

We have performed surgical treatment for Moyamoya disease using the superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-arterio-myo-synangiosis (EDAMS). In this paper, the surgical technique of combined revascularization for Moyamoya disease as well as peri-operative complications are discussed. Craniotomy and dural opening were extensively carried out to expose the brain surface as widely as possible. Dissection of the STA, which is the most powerful resource of direct revascularization, should be carefully carried out using a surgical microscope. The temporal muscle and middle meningeal artery, which have the most potential as sources of indirect revascularization, must be preserved. STA-MCA anastomosis to the frontal branch of the middle cerebral artery is indispensable for improving cerebral circulation of the frontal lobe. A small arachnoid membrane opening and water-tight closure are also important to avoid post-operative subdural and subcutaneous fluid collection. Ischemic events disappeared immediately after surgery in most cases. However, in several cases, transient ischemic attacks recurred for several months after the surgery. Chronic subdural hematoma was seen in two cases.

Adolescent↗

PubMed1997

Localizing the central sulcus by functional magnetic resonance imaging and magnetoencephalography.

To further validate the potential of functional magnetic resonance imaging (fMRI) for localization of the sensorimotor cortex, fMRI was compared with somatosensory evoked fields (SEFs) in eight normal volunteers. A conventional 1.5 T MRI scanner and an MRI-linked 66-channel whole head magnetoencephalography system were used. fMRI activated by unilateral hand squeeze movement indicated the highest activation on the central sulci that were localized by SEFs in all 16 contralateral hemispheres. This indicates that although the fMRI signal activation may originate from a vein running along the central sulcus, fMRI is reliable to detect the central sulcus. The pre-central gyrus also indicated some signal activation on fMRI implying better visualization of spatial distribution of activation. fMRI and SEFs are complementary methods for localizing the central sulcus.

Adult↗

PubMed1997

Molecular analysis of p21 and p27 genes in human pituitary adenomas.

Pituitary tumours develop at a high frequency in p27-knockout mice and retinoblastoma gene-knockout mice, which suggests that cell cycle regulatory genes, such as cyclin-dependent kinase inhibitor genes, are involved in the tumorigenesis of pituitary adenoma. Analysis of p21 and p27 gene abnormalities in human pituitary adenoma was performed in 28 pituitary adenomas by polymerase chain reaction-single-strand conformational polymorphism. No point mutations were detected in these genes. As no abnormalities of the p21 and p27genes were observed, and if these genes are indeed inactivated, it is likely to be via transcriptional or translational defects.

Adenoma↗

PubMed1997

Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow transplantation (BMT). Its prediction, diagnosis and treatment remain unclear. Examination was made of changes in hemostatic parameters in patients with or without VOD after BMT. Twenty-seven children were studied following BMT. Eight of them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin-antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC), antithrombin III (AT-III), protein C, N-terminal propeptide for type III procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG significantly fell during the post-transplant period (P < 0.05). Significantly low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD. The coagulation-fibrinolysis system following endothelial cell damage may contribute to the onset of VOD.

Adolescent↗

PubMed1997

Clinico-pathological study of Cushing's disease with large pituitary adenoma.

OBJECTIVE: To explore the biological and morphological differences between large Cushing's adenomas and small adenomas, we investigated the clinical, endocrinological, neuroradiological, and histological features of patients with large Cushing's adenomas and compared them with patients with small Cushing's adenomas. PATIENTS: Five of 250 patients with Cushing's disease undergoing trans-sphenoidal operations from 1989 to 1995 had large adenomas with maximum diameters greater than 30 mm. The clinical characteristics of these five patients were compared with the 14 patients with Cushing's disease with small adenomas in our series. RESULTS: Oedema, myopathy, and mental disturbance were more frequent and hypertension was less frequent among patients with large adenomas. The high-dose (8 mg) dexamethasone test did not suppress cortisol production in any of the five patients. Invasion into surrounding tissue was demonstrated by magnetic resonance imaging in all five cases. All five large adenomas had scarce or no periodic acid-Schiff-positive granules and were sparsely granulated ultrastructurally. Three tumours contained cells with honeycomb Golgi apparatus which rarely contained immature secretory granules. One Crooke's cell adenoma contained trapped or displaced secretory granules. The other tumour had dilated trans-Golgi network-derived vacuoles that contained reticular or circular electron-dense material. These findings were in striking contrast to those of small Cushing's adenomas, which showed strong PAS positivity, densely-packed granulation, and had prominent Golgi complex harbouring developing secretory granules. CONCLUSIONS: We found that the tumour cells in large adenomas produced only small amounts of ACTH, and showed indications of disturbances in the regulated exocytotic pathways. These factors may account for the different clinical characteristics of Cushing's disease with large pituitary adenomas.

Adenoma↗

PubMed1997

Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells.

Adrenomedullin is a potent vasodilator peptide that was originally isolated from pheochromocytoma. The production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells were studied by radioimmunoassay and northern blot hybridization. Choroid plexus carcinoma is a rare malignant tumor derived from the epithelium of the choroid plexus. Immunoreactive adrenomedullin was detected in the conditioned medium of choroid plexus carcinoma cells (40.8 +/- 7.5 fmol/10(5) cells/24 h; mean +/- SEM, n = 5). Reverse-phase HPLC of the conditioned medium showed one major peak of the immunoreactive peptide eluting in the position of synthetic human adrenomedullin and two smaller peaks eluting earlier. Addition of interleukin-1 beta (10 ng/ml) alone or in combination with three cytokines, interferon-gamma (100 U/ml), tumor necrosis factor-alpha (20 ng/ml), and interleukin-1 beta (10 ng/ml), caused significant increases in the immunoreactive adrenomedullin concentrations in the medium (approximately 175 and 293% of the control level, respectively). Northern blot analysis showed the expression of 1.6-kb adrenomedullin mRNA in the total RNA sample prepared from cultured choroid plexus carcinoma cells. Treatment with either interleukin-1 beta or the combination of three cytokines caused significant increases in levels of adrenomedullin mRNA in parallel with those in immunoreactive adrenomedullin concentrations in the conditioned medium. These findings raise a possibility that adrenomedullin is secreted from the choroid plexus and has physiological roles in the CNS via the CSF. In addition, adrenomedullin secreted from choroid plexus carcinoma may be related to the pathophysiology of the tumor.

Adrenomedullin↗

PubMed1997

Hirudin suppresses the invasion of inflammatory cells and the appearance of vimentin-positive astrocytes in the rat cerebral ablation model.

Hirudin is a specific and direct-acting thrombin inhibitor superior to heparin as an anticoagulant. Thrombin is a multifunctional molecule that acts as a serine protease locally generated from prothrombin during blood coagulation related to injury and/or inflammation. We previously reported that thrombin might be involved in the inflammatory response, glial reaction, and scar formation that occurred in central nervous system (CNS). Here we studied the suppressive effects of hirudin on the inflammation, vimentin-positive astrocytes, and glial fibrillary acidic protein (GFAP)-positive astrocytes using rat cerebral ablation models. Hirudin and vehicle solution soaked in Gelform were administered to the cavity of the traumatic brain defect. Brains were examined by conventional histologic and immunohistologic technique. Antibodies for monocytes/macrophages, GFAP, and vimentin were used to assess the infiltration of inflammatory cells and reaction of astrocytes. The number of the inflammatory cells, vimentin-positive astrocytes, and GFAP-positive astrocytes were quantitatively analyzed. Hirudin suppressed the infiltration of inflammatory cells and the increase in vimentin-positive astrocytes, but had no effects on the increase in GFAP-positive astrocytes. These data suggest that thrombin may play an important role in inflammatory and glial responses to CNS injury, and that hirudin can be a candidate for the therapeutic agent that minimizes the secondary brain damage following the inflammation, and the glial reaction mediated by vimentin-positive astrocytes near the lesion site.

Animals↗

PubMed1997

Prolyl aminopeptidase from Serratia marcescens: cloning of the enzyme gene and crystallization of the expressed enzyme.

We cloned and sequenced the Serratia marcescens prolyl aminopeptidase (SPAP) gene. Nucleotide sequence analysis revealed an open reading frame of 951 bp, encoding a protein of 317 amino acids with a predicted molecular weight of 36,083. The expressed enzyme was purified about 90-fold on columns of Toyopearl HW65C and DEAE-Toyopearl, with an activity recovery of 30%. The apparent molecular weight of the purified enzyme was 36,000 and 38,000 as estimated by SDS-PAGE and gel filtration, respectively. The enzyme was not inhibited by diisopropyl phosphofluoridate (DFP) or phenylmethylsulfonyl fluoride (PMSF), but was markedly inhibited by 3,4-dichloroisocoumarin (DCIC). Crystals of the enzyme were grown by the hanging drop vapor diffusion method using PEG6000 as a precipitant at pH 6.5. The crystals are tetragonal with cell dimensions a= b =65.6 A, and c=169.8 A, a space group P4(1)2(1)2 or P4(3)2(1)2, and probably contain one monomer in the asymmetric unit. They diffract to at least 2.22 A resolution.

Amino Acid Sequence↗

PubMed1997

Cine magnetic resonance imaging of spinal intradural arachnoid cysts.

OBJECTIVE: The diagnostic value of cine magnetic resonance imaging (CMRI) that visualizes fluid and tissue movement was evaluated in patients with spinal intradural arachnoid cysts, a rare but increasingly detected cause of spinal cord dysfunction. METHODS: Four patients with thoracic spinal intradural arachnoid cysts were investigated with conventional T1- and T2-weighted and cardiac-gated CMRI. Four normal volunteers also underwent CMRI for comparison. RESULTS: Sagittal T1- and T2-weighted imaging showed lesions as an abnormal widening of the posterior spinal subarachnoid space, but mixed high- and low-signal intensities on T2-weighted imaging suggested cystic lesions. CMRI, using 16 to 20 sagittal gradient echo images during the cardiac cycle of normal volunteers, indicated synchronous signal changes along the subarachnoid space, suggesting a smooth cerebrospinal fluid flow. CMRI of patients detected that the caudal or cranial direction of the high-signal propagation suddenly reversed at some locations (as if rebounding) in an asynchronous fashion along the lesion (asynchronous rebound phenomenon), which was well demonstrated by the closed-loop video mode. Cystectomy revealed that the cysts consisted of multiple lobules and that the asynchronous rebound phenomenon corresponded with some boundaries of cyst lobules. CMRI also visualized dynamic spinal cord compression by the cyst. CONCLUSION: CMRI can demonstrate abnormal fluid flow and spinal cord compression caused by a spinal intradural arachnoid cyst.

Adult↗

PubMed1997

Induction of macrophage migration inhibitory factor messenger ribonucleic acid in rat forebrain by reperfusion.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a cytokine that has the potential to immobilize and activate monocytes/macrophages. To examine whether MIF may potentially be involved in the pathogenesis of reperfusion injury of the brain, we investigated the expression of MIF in a rat model of reperfusion. METHODS: A four-vessel occlusion procedure was performed for 30 minutes using male Wistar rats to obtain a moderate reperfusion in the forebrains. Semiquantitatively calibrated reverse-transcription polymerase chain reaction analysis was conducted to examine temporal profiles of messenger ribonucleic acid (mRNA) expression for MIF and macrophage chemoattractant protein 1. MIF protein assays expression was assessed with specific Western blot analysis. For anatomic mapping of MIF, an immunohistochemical study was performed. RESULTS: Reverse-transcription polymerase chain reaction demonstrated that the mRNA level of MIF increased depending on the duration of reperfusion (< or = 24 h) subsequent to global ischemia. The macrophage chemoattractant protein 1 mRNA was also observed to increase after reperfusional stress, but its maximum expression was reached earlier (1 h after the stress) than was MIF mRNA. Increase of MIF protein was also shown by Western blot. MIF-positive staining was observed in the neuronal processes (neuropil) in the cortex and basal growth ganglia of a rat forebrain. CONCLUSION: This protein is up-regulated and may modulate immunological reaction in secondary brain damage after ischemia and reperfusion stress.

Animals↗

PubMed1997

Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats.

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Animals↗

PubMed1997

Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy.

We performed volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain with a 1.5 T magnet in 28 patients with autism, and compared the results with those from 28 age-matched patients with unclassified mental retardation and 25 age-matched healthy children. Peaks for N-acetylaspartate, choline and creatine, but not lactate, were observed in each group on 1H-MRS. The N-acetylaspartate/choline ratio was lower in patients with mental retardation than in patients with autism and controls (P = .05, respectively). However, there were no differences in the N-acetylaspartate/ choline ratios between patients with autism and controls, and the N-acetylaspartate/creatine and choline/creatine ratios did not differ among the three groups. These results suggest that N-acetylaspartate is decreased in patients with mental retardation and that a disorder or dysfunction of neurons in the brain exists. There also appear to be differences in the brain lesions or dysfunctions found in patients with autism and mental retardation.

Aspartic Acid↗

PubMed1997

Cloning and expression of the cDNA encoding prolyl oligopeptidase (prolyl endopeptidase) from bovine brain.

Prolyl oligopeptidase (EC 3.4.21.26, prolyl endopeptidase) cDNA from bovine brain was cloned by PCR, and the amplified fragment was used as a probe to screen the cDNA library from bovine brain. The obtained clone contained a 2.7 kb DNA fragment with an open reading frame of 2130 nucleotides, and encoded a protein of 710 amino acids with a deduced molecular weight of 80640 Da. The deduced amino acid sequence is 95, 94, 51 and 48% homologous to those of human T-cell, porcine brain, Aeromonas hydrophila, and Flavobacterium meningosepticum prolyl endopeptidases, respectively. The bovine brain prolyl endopeptidase-encoding cDNA was expressed using an expression vector bearing a tac promoter, with an approximate yield of 20 micrograms/ml of cell culture.

Amino Acid Sequence↗