Search PubMed⌕ Search

Biomedical subjects

Y Nagamine

Publications and source records attributed to Y Nagamine.

At least 55 records · Page 3Linked to original sources
PubMed1996

A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction distinguishes urokinase-type plasminogen activator induction from mitogenicity in endothelial cells.

Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase-type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM 7373 cells. In the present paper we investigated the role of the interaction of FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up-regulation in these cells. The results show that FGF-2 antagonists suramin, protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that affect growth factor binding to cell surface receptors and mitogenic activity. In contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2, indicating that FGFR and its TK activity are essential in mediating uPA induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1 mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic response. Liposome-encapsulated FGF-2 showed a limited but significant capacity, relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees C and to be internalized within the cell. uPA up-regulation by liposome-encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating that the activity of liposome-delivered FGF-2 is mediated by an extracellular action of the growth factor. Taken together, the data indicate that a distinct interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different from the one that leads to mitogenicity, is responsible for the uPA-inducing activity of the growth factor.

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

[Properties of a hemolysin produced by group B streptococci].

The hemolysin produced by group B streptococci (GBH) has an isoelectric point (pI) of 5.8 and it shows a hemolytic activity in the absence of 2-mercaptoethanol (2-ME). The hemolytic activities of GBH were compared to that of streptolysin O (SLO) and streptolysin S (SLS). These hemolysins differed with respect to the binding and release of hemoglobin (Hb). GBH was bound to phospholipids on the membranes of target erythrocytes, followed by the gentle release of K+ and slow Hb release without lag time. Incontrast SLO released Hb as rapidly as K+. GBH induced hemolysis was inhibited by the addition of 30 mM raffinose. These results indicate that the effective diameter of the pores formed by GBH was about 1.1 nm. GBH showed a lower hemolytic efficiency than SLO, reflecting the fact that these hemolysins destroy erythrocytes by a different mechanism. Intracellular K+ and Hb were released at a different rate in GBH treated cells, indicating that a colloid-osmotic process is involved in the lytic mechanism.

Bacterial Proteins↗
PubMed1996

[Transient prosopagnosia and lasting topographical disorientation after the total removal of a right occipital arteriovenous malformation].

A 32-year-old right-handed female tour guide developed a transient prosopagnosia after the total removal of an arteriovenous malformation in the right occipital lobe. Neurological examination revealed only a left homonymous hemianopsia. The ablation on the right side involved total occipital lobe, the posterior region of the parahippocampal gyrus, and a part of the precuneus and angular gyrus. Neuropsychologically she was alert and oriented in time and place. No aphasia or apraxia was observed. Visual recognition of objects, colors and letters was normal. She could match faces and insects easily, despite a close resemblance among them. Her prosopagnosia resolved in one month, while her impairment in topographical orientation and nonverbal memory continued more than eight months. These findings exclude the possibility that her prosopagnosia was derived from visual agnosia, poor discrimination of details, or nonverbal memory deficit. Excluding cases with malignant brain tumor which may affect more diffuse area of the brain, there was only one reported case who developed persistent prosopagnosia after the right occipital lobectomy. Given the rarity of prosopagnosics with only right-sided lesions, it seems that in most of humans posterior parts of both hemispheres participate in the identification of faces.

Adult↗
PubMed1995

Activation and nuclear translocation of mitogen-activated protein kinases by polyomavirus middle-T or serum depend on phosphatidylinositol 3-kinase.

Several cellular signal transduction pathways activated by middle-T in polyomavirus-transformed cells are required for viral oncogenicity. Here we focus on the role of phosphatidylinositol 3-kinase (PI 3-kinase) and Ras and address the question how these signaling molecules cooperate during cell cycle activation. Ras activation is mediated through association with SHC.GRB2.SOS and leads to increased activity of several members of the mitogen-activated protein (MAP) kinase family, while activation of PI 3-kinase results in the generation of D3-phosphorylated phosphatidylinositides whose downstream targets remain elusive. PI 3-kinase activation might also ensue as a direct consequence of Ras activation. Oncogenicity of middle-T requires stimulation of both Ras- and PI 3-kinase-dependent pathways. Mutants of middle-T incapable to bind either SHC.GRB2.SOS or PI 3-kinase are not oncogenic. Sustained activation and nuclear localization of one of the MAP kinases, ERK1, was observed in wild type but not in mutant middle-T-expressing cells. Wortmannin, an inhibitor of PI 3-kinase, prevented MAP kinase activation and nuclear localization in middle-T-transformed cells. PI 3-kinase activity was also required for activation of the MAP kinase pathway in normal serum-stimulated cells, generalizing the concept that signaling through MAP kinases requires not only Ras-but also PI 3-kinase-mediated signals.

3T3 Cells↗
PubMed1995

Urokinase-type plasminogen activator gene regulation by polyomavirus middle-T antigen.

Expression of polyomavirus middle-T antigen (middle-T) is involved in the formation of various tumors in vivo, e.g. hemangiomas and mammary gland tumors. Several genes have been shown to be activated in middle-T-expressing cells, but the underlying mechanisms have only been partially elucidated. Among the genes regulated by middle-T, the urokinase-type plasminogen activator (uPA) gene seems to be of primary importance for the development of the transformed phenotype. We have found that the uPA gene is highly expressed in eEnd2 cells derived from a hemangioma expressing middle-T. NIH3T3 cells show negligible levels of uPA mRNA but its expression was highly induced by infecting with a middle-T-expressing retrovirus. Middle-T did not affect uPA mRNA stability. Transient cotransfection experiments using a uPA-receptor gene construct and a middle-T expression vector showed that high uPA mRNA levels are due to increased uPA promoter activity. Analyses of various signaling molecules by transient cotransfection assays and in vitro kinase assays established that a signaling pathway involving c-Src, SOS, Ras, Raf-1 and ERK is activated by middle-T in NIH3T3 cells, resulting in the activation of the uPA gene promoter via PEA3/AP1 elements. In contrast, in eEND2 cells uPA gene induction is only partially dependent on this pathway, suggesting the involvement of additional signaling molecules in endothelial cells.

3T3 Cells↗
PubMed1995

Role of LFB3 in cell-specific cAMP induction of the urokinase-type plasminogen activator gene.

In previous work we suggested that a kidney-specific transcription factor LFB3 cooperates with cAMP-response element (CRE)-binding proteins within a cAMP regulatory unit comprised of three protein-binding domains and located 3.4 kilobase pairs upstream of the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells (Menoud, P.-A., Matthies, R., Hofsteenge, J., and Nagamine, Y. (1993) Nucleic Acids Res. 21, 1845-1852). The two domains contain a CRE-like sequence, and the third domain is recognized by LFB3. The absolute requirement of LFB3 as well as the cooperation among the three domains for cAMP regulation were confirmed by transient transfection assays in F9 teratocarcinoma cells, in which the level of LFB3 was negligible. Suspecting a possible feedback regulation of LFB3 mRNA expression during cAMP-dependent uPA gene induction in LLC-PK1 cells, we measured LFB3 mRNA levels after cAMP treatment and found a strong reduction. This reduction was not due to a change in template activity of the LFB3 gene because run-on transcription showed no significant change in LFB3 gene transcription. RNA synthesis inhibitor-chase experiments indicated that the down-regulation was post-transcriptional. Interestingly, when the inhibitor was added at the same time as cAMP, the cAMP-induced decrease in LFB3 mRNA levels was abrogated, suggesting that ongoing RNA synthesis is required for the decrease. Similar effects on LFB3 mRNA metabolism were observed with all agents that induce uPA mRNA in LLC-PK1 cells, including 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, colchicine, and cytochalasin. We discuss the significance of this regulation in uPA gene expression.

Animals↗
PubMed1995

How to treat incidental cerebral aneurysms: a review of 139 consecutive cases.

BACKGROUND: Together with current advances in neuroimaging techniques, the chance of incidental discovery of unruptured cerebral aneurysms has increased and the selection of their appropriate management remains controversial. To provide current data about management results of patients with incidental cerebral aneurysms, we have made a retrospective review of 139 consecutive patients treated either by surgical or conservative means. METHODS: The surgical indication for each patient was decided, carefully considering several factors respectively, including the surgical difficulty, aneurysm size, patient's age, and medical condition. RESULTS: Forty-nine patients were managed conservatively. Eight (16%) of those conservatively managed patients had intracranial hemorrhage due to aneurysm rupture during the follow-up period (mean, 4.3 years). Seven of these eight patients died from a fatal subarachnoid hemorrhage (SAH). The follow-up data showed that the mean size of aneurysms with late hemorrhage was significantly larger than that of aneurysms without subsequent rupture. It was also confirmed that none of the 26 tiny aneurysms smaller than 4 mm in diameter had ruptured. Ninety patients harboring 119 incidental aneurysms less than 25 mm in diameter underwent surgery. There was no surgical mortality or morbidity in this series. CONCLUSIONS: These excellent surgical results were presumably achieved due to the strict patient selection. In respect to the size of aneurysms, it seems to be justified to recommend surgery for patients with aneurysms larger than 5 mm in diameter.

Adult↗
PubMed1995

A case of trichorrhexis nodosa developed in winter.

A young Japanese man developed localized trichorrhexis nodosa (LTN) of the scalp hair in the winter season. To investigate the roles of shampoo, severe sunlight exposure and/or mechanical injuries, we performed the following studies. Hair was collected from the patient and from a control. The study was performed in two steps. In the first step, hair was put into shampoo, rinsed with saline water, and then exposed to ultraviolet B (UVB) radiation once a day for one week. In the second step, the hair was similarly treated, but each shaft was bent gently with forceps before UVB exposure. Scanning electron microscopic studies revealed cuticular changes when the hair was treated only with shampoo and UVB. When it was treated with shampoo, UVB, and mechanical bending, the patient's hair developed longitudinal and transverse fractures of the hair shafts, while the control hair showed only partial damage to the hair shaft. On the basis on the above findings, we conclude that mechanical bending may damage the hair shaft.

Adolescent↗
PubMed1995

Surgical removal of giant basal ganglia arteriovenous malformations through the extended transsylvian approach following preoperative embolization--two case reports.

A 12-year-old boy and a 22-year-old male presented with sudden onset of consciousness disturbance with right-sided hemiparesis and aphasia due to massive intracerebral hemorrhage from giant striocapsular arteriovenous malformations (AVMs). Angiography revealed giant AVMs located at the left basal ganglia in both patients. Large frontotemporal craniotomies were performed following staged embolization of the feeding arteries. Through an extended transsylvian approach, the lesions were totally excised with confirmation using intraoperative digital subtraction angiography. The patients showed a transient postoperative worsening of symptoms, but recovered to their preoperative status at discharge. Motor functions of the right upper and lower extremities were graded 4/5 in both patients. These cases demonstrate that combined use of preoperative embolization and intraoperative angiography allows some giant deep AVMs to be resected with encouraging results.

Adult↗
PubMed1995

[Surgical decompression for massive cerebellar infarction].

The authors report 10 patients with progressive neurological deterioration due to massive cerebellar infarctions. Computerized tomography scans confirmed obstructive hydrocephalus and brain stem compression. All 10 patients (seven men, three women; mean age, 59 years) were treated by external ventricular drainage and decompressive suboccipital craniectomy. After discharge from the hospital, they were followed up (23-101 months) and their functional independence was evaluated by the Barthel Index. The condition of three patients with brain-stem infarction had deteriorated despite decompressive surgery. Two of these died during the acute stage and one because severely disabled. The remaining seven patients showed neurological improvement during the postoperative period. Four patients with preoperative Japan Coma Scale of 100 returned to their previous jobs within the follow-up period and three patients with preoperative Japan Coma Scale of 200 required some assistance in daily activities. It is suggested that decompressive surgery may be beneficial for massive cerebellar infarction. The postoperative prognosis depends mainly on the presence or absence of coexisting brain-stem infarction. It is possible that, without brain-stem infarction, patients who remained in a "dependent" state may have recovered better if they had been operated on earlier.

Aged↗
PubMed1995

Elucidation of a signaling pathway induced by FGF-2 leading to uPA gene expression in NIH 3T3 fibroblasts.

Fibroblast growth factors (FGFs) play a role in biological processes such as cell growth and development, angiogenesis, and wound healing. Several genes have been shown to be induced by FGFs, but the underlying mechanisms have not been elucidated. We investigated the effect of FGF-2 (basic FGF) on the urokinase-type plasminogen activator (uPA) gene in NIH 3T3 fibroblasts. We found that the uPA gene is transcriptionally induced by FGF-2 as well as by 12-O-tetradecanoylphorbol-13 -acetate involving a PEA3/AP1 element located 2.4 kb upstream of the transcription initiation site; neither induction requires ongoing protein synthesis. Unlike 12-O-tetradecanoylphorbol-13-acetate induction, FGF-2 induction was not impaired by protein kinase C down-regulation. Analyses of various signaling molecules by Western blotting, extracellular signal-regulated kinase (ERK) activity assays, and transient transfection assays (cotransfection of a uPA-reporter gene construct with expression vectors for wild-type or dominant negative type of these molecules or for ERK-specific protein phosphatase MKP-1) showed that a Ras/Raf-1/MEK/ERK-2/JunD pathway is induced by FGF-2 and 12-O-tetradecanoylphorbol-13-acetate, leading to the activation of the uPA gene.

3T3 Cells↗
PubMed1994

Flow Cytometric Analysis to Assess the Malignant Potential of Phyllodes Tumor.

To evaluate DNA content as a prognostic indicator in phyllodes tumor of the breast, flow cytometric DNA analyses were performed retrospectively in 13 patients who were selected, based on the availability of paraffin-embedded tumor specimens. ALL were women with an average age of 41.9 years and a mean follow-up of 51.2 months. Pathologically, 3 patients (23.0%) had malignant tumor and 10(77.7%) had benign lesions. The patients with malignant tumors tended to be older and had larger tumors. Aneuploidy was seen in one patient with malignant tumor (7.7%), with the S-phase fraction ranging from 0.8 to 12.6. This patient died of lung metastases 6 months after mastectomy. One benign tumor showing diploid, developed local recurrence 100 months after lumpectomy. DNA stem cell lines were not detected in the only patient with aneuploid tumor. There was no significant correlation between DNA content and local recurrence. In this series, the number of patients was too small to draw the certain conclusions from date. However, it appears that, compared to diploid tumors, aneuploid tumor are more often malignant and have poorer prognosis. Our study indicates that DNA content has little prognostic value, DNA aneuploidy appears to be associated with a poor prognosis.

Journal Article↗
PubMed1994

RNA synthesis inhibition stabilises urokinase mRNA in macrophages.

Urokinase-type plasminogen activator (uPA) mRNA is induced in macrophages by the lineage specific growth factor CSF-1. Upon removal of CSF-1 from bone marrow-derived macrophages (BMM), uPA mRNA decayed with a half-life of 2 h. If RNA synthesis inhibitors actinomycin D, 5,6-dichloro-1-beta-ribofuranosyl benzimidazole (DRB) or alpha-amanitin were added at the time as CSF-1 removal, the uPA message was stabilised. This was not a general effect on CSF-1 responsive mRNAs, as c-myc mRNA decayed with normal kinetics in the presence of inhibitors. The requirement for ongoing RNA synthesis for the degradation of uPA mRNA in BMM suggests that a component of the degradative pathway may be induced following removal of CSF-1.

Amanitins↗
PubMed1994

Activation of cAMP-dependent protein kinase alters the chromatin structure of the urokinase-type plasminogen activator gene promoter.

In LLC-PK1 cells, the urokinase-type plasminogen activator (uPA) gene is induced by two of the major signal transduction pathways, the protein kinase C (PKC) and the cAMP-dependent protein kinase (PKA) pathways. We have analyzed the chromatin structure of 26 kb of the uPA gene locus and have shown that PKA activation but not PKC activation induce major chromatin structural alterations in the uPA gene promoter. In uninduced cells, several DNase I hypersensitive (HS) sites were detected in the 5' and 3' flanking regions but not in the transcribed region. Two of the sites correspond to previously characterized regulatory sites: a cAMP responsive site at nucleotide position -3500 with respect to the initiation site, and the PEA3/AP1 site at -2100 that mediates PKC activation. After the activation of PKA but not PKC, a strong HS site was induced at -2600. Functional analysis of this region revealed cAMP responsive activity. Chromatin structural alterations again brought about specifically by PKA but not by PKC were were also detected in the upstream of the promoter by topoisomerase I cleavage site analysis, with two prominent sites appearing at -2800 and -3300. These results suggest that the strong cAMP induction of the uPA gene requires structural alterations that permit cooperative interactions between the multiple cAMP responsive sites.

Animals↗
PubMed1994

Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene associated with stabilization and autoregulation of c-Jun.

We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs independently of the protein kinase C- and cAMP-dependent signaling pathways. Here we show that a sequence located 2.0 kilobases upstream of the uPA gene, which resembles an AP-1-recognition sequence, mediates the action of OA. DNA-protein interaction studies, together with mRNA and protein analyses, indicate that c-Jun, but not c-Fos, is involved in OA-dependent uPA gene induction. The appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP-1-like site correspond to the appearance of c-Jun accumulation, suggesting that c-Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun protein levels increase significantly between 100 and 160 min following OA treatment, whereas c-Jun translation increases only slightly in this time frame, suggesting that post-translation mechanisms are also involved in c-Jun accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun. We discuss our results with respect to the possibility that protein phosphatase 2A maintains c-Jun in its down-regulated state in LLC-PK1 cells.

8-Bromo Cyclic Adenosine Monophosphate↗