Biomedical subjects

S Furuya

Publications and source records attributed to S Furuya.

At least 19 recordsLinked to original sources

PubMed2005

Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis.

Accumulating evidences indicate that ceramide is closely involved in apoptotic cell death in neurodegenerative disorders and aging. We examined ceramide levels in the cerebrospinal fluid (CSF) or brain tissues from patients with neurodegenerative disorders and the mechanism of how intra- and extracellular ceramide was regulated during neuronal apoptosis. We screened the ceramide levels in the CSF of patients with neurodegenerative disorders, and found that ceramide was significantly increased in patients with Alzheimer's disease (AD) than in patients with age-matched amyotrophic lateral sclerosis (ALS) and other neurological controls. With immunohistochemistry in AD brains, ceramide was aberrantly expressed in astroglia in the frontal cortices, but not detected in ALS and control brains. To explore for the regulation of ceramide in astroglia in Alzheimer's disease brains, we examined the metabolism of ceramide during neuronal apoptosis. In retinoic acid (RA)-induced neuronal apoptosis, RA slightly increased de novo synthesis of ceramide, but interestingly, RA dramatically inhibited conversion of [14C] ceramide to glucosylceramide (GlcCer), suggesting that the increase of ceramide mass is mainly due to inhibition of the ceramide-metabolizing enzyme GlcCer synthase. In addition, a significant increase of the [14C] ceramide level in the culture medium was detected by chasing and turnover experiments without alteration of extracellular [14C] sphingomyelin levels. A 2.5-fold increase of ceramide mass in the supernatant was also detected after 48 h of treatment with RA. These results suggest a regulatory mechanism of intracellular ceramide through inhibition of GlcCer synthase and a possible role of ceramide as an extracellular/intercellular mediator for neuronal apoptosis. The increased ceramide level in the CSF from AD patients, which may be derived from astroglia, raises a possibility of neuronal apoptosis by the response to intercellular ceramide in AD.

Aged↗

PubMed2003

Shape-resonance-enhanced vibrational effects in the angular distributions of C 1s photoelectrons from fixed-in-space CO molecules.

Angular distributions of C 1s photoelectrons from fixed-in-space CO molecules have been measured with vibrational resolution. A strong dependence of the angular distributions on the vibrational states of the residual molecular ion has been found for the first time in the region of the shape resonance. Calculations in the relaxed core Hartree-Fock approximation have reproduced the angular distributions fairly well in the general shapes of the angular distributions due to the correct description of nuclear motion as an average of the internuclear-distance-dependent dipole amplitudes.

Journal Article↗

PubMed2003

Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization.

Cell surface glycoconjugates are thought to mediate cell-cell recognition and to play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of glyco-chains with an N-acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such as GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer (GM2) ganglioside, its oligosaccharide portion, GalNAcbeta4Galbeta4GlcCer (Gg(3)) Cer, GalNAcalpha3GalNAcbeta3Galalpha4Galbeta4GlcCer (Gb(5)) Cer (Forssman hapten) and alpha1-4 linked oligomers of GalNAc, induced a rapid and transient activation of cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary cultured hippocampal neurons, but not in glial cells. A cAMP-dependent protein kinase (PKA) selective inhibitor and an adenylate cyclase inhibitor blocked both PKA activation and the subsequent filopodia formation. A small GTPase cdc42 was a potential downstream target of GalNAc-S-activated PKA. These results suggest that extracellular GalNAc-S serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of PKA followed by cdc42 up-regulation via a cell surface receptor-like component. Filopodia formation induced by GalNAc-S may have a physiological relevance because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth and branch formation of primary cultured cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. These findings provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some neuronal maturation.

Acetylgalactosamine↗

PubMed2003

Ganglioside/calmodulin kinase II signal inducing cdc42-mediated neuronal actin reorganization.

Cell surface glycoconjugates are thought to mediate cell-cell recognition and play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of gangliosides Neu5Acalpha 8Neu5Acalpha 3Galbeta 4GlcCer, Galbeta 3GalNAcbeta 4(Neu5Acalpha 8Neu5Acalpha 3)Galbeta 4GlcCer (GD1b), Neu5Acalpha 3Galbeta 3GalNAcbeta 4(Neu5Acalpha 8Neu5Acalpha 3)Galbeta 4GlcCer (GT1b) or its oligosaccharide portion induced a rapid and transient activation of Ca2+/calmodulin-dependent protein kinase II (CaM-KII) in the subplasmalemma. Galbeta 3GalNAcbeta 4(Neu5Acalpha 3)Galbeta 4GlcCer (GM1), GalNAcbeta 4(Neu5Acalpha 3)Galbeta 4GlcCer, Neu5Acalpha 3Galbeta 4GlcCer, Neu5Acalpha 3Galbeta 3GalNAcbeta 4(Neu5Acalpha 3)Galbeta 4GlcCer (GD1a), and Neu5Acalpha 8Neu5Acalpha 3Galbeta 3GalNAcbeta 4(Neu5Acalpha 8Neu5Acalpha 3)-Galbeta 4GlcCer were ineffective. GT1b and GD1b stimulated transient elevation of bulk cytosolic Ca2+ levels while GM1 slightly elevated the levels and GD1a did not. Thus, the cytosolic Ca2+ elevation by the gangliosides may trigger the CaM-KII activation. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary hippocampal neurons, but not in glial cells. CaM-KII inhibitors blocked both CaM-KII activation and the subsequent filopodia formation. A small G-protein cdc42 was a potential downstream target of CaM-KII activated by the gangliosides. These results suggest that oligosaccharides of the gangliosides serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of CaM-KII followed by cdc42 up-regulation via a cell surface receptor-like component. The filopodia formation induced by the gangliosides may have a physiological relevance because long-term exposure of hippocampal neurons to GT1b oligosaccharide induced advanced dendritogenesis. Furthermore, exposure of cerebellar neurons to GT1b oligosaccharide facilitated CaM-KII-dependent dendritic outgrowth and branch formation of cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. Thus, the ganglioside/CaM-KII signal plays a role in modulating dendritic morphogenesis by inducing cdc42-mediated actin reorganization.

Actins↗

PubMed2001

3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain.

l-Serine is synthesized from glycolytic intermediate 3-phosphoglycerate and is an indispensable precursor for the synthesis of proteins, membrane lipids, nucleotides, and neuroactive amino acids d-serine and glycine. We have recently shown that l-serine and its interconvertible glycine act as Bergmann glia-derived trophic factors for cerebellar Purkinje cells. To investigate whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in situ hybridization and immunohistochemistry the cellular expression of 3-phosphoglycerate dehydrogenase (3PGDH), the initial step enzyme for de novo l-serine biosynthesis in animal cells. At early stages when the neural wall consists exclusively of the ventricular zone, neuroepithelial stem cells expressed 3PGDH strongly and homogeneously. Thereafter, 3PGDH expression was downregulated and eventually disappeared in neuronal populations, whereas its high expression was transmitted to the radial glia and later to astrocytes in the gray and white matters. In addition, 3PGDH was highly expressed throughout development in the olfactory ensheathing glia, a specialized supporting cell that thoroughly ensheathes olfactory nerves. These results establish a fundamental link of the radial glia/astrocyte lineage and olfactory ensheathing glia to l-serine biosynthesis in the brain. We discuss this finding in the context of the hypothesis that 3PGDH expression in these glia cells contributes to energy metabolism in differentiating and differentiated neurons and other glia cells, which are known to be vulnerable to energy loss.

Aging↗

PubMed2001

L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-Serine biosynthesis.

Microglia are well known to become activated during various kinds of neuropathological events. The factors that are responsible for the activation, however, are not fully determined. In the present study, L-Ser was shown to enhance production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) by lipopolysaccharide (LPS)-stimulated cultured rat microglial cells. L-Ser, however, did not enhance the expression of mRNAs encoding inducible NO synthase, IL-6 and TNF alpha. On the other hand, astrocytes did not depend on L-Ser for release of IL-6 and TNF alpha. The expression of an enzyme 3-phosphoglycerate dehydrogenase (3PGDH), which is essential for L-Ser biosynthesis from a glycolytic intermediate 3-phosphoglycerate, was investigated. As revealed by Western blotting and immunocytochemical staining, 3PGDH-protein expression in vitro was the highest in astrocytes, intermediate in neurons and the lowest in microglial cells. Semiquantitative RT-PCR showed that microglial cells expressed 3PGDH-mRNA at a lower level than astrocytes. In frozen sections from rat forebrain, only astrocytes were immunoreactive for 3PGDH. The present study suggested that L-Ser is able to modulate microglial function mainly at the translation level because microglial cells cannot synthesize sufficient amount of L-Ser due to the scarce expression of 3PGDH.

Animals↗

PubMed2001

Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells.

cGMP is thought to play a role in cerebellar signalling yet its production within Purkinje cells has never been detected. In the present study, the hydrolysis of a fluorescent substrate analogue, 2'-O-anthranyloyl cyclic GMP, by type 5 phosphodiesterase was monitored within Purkinje cells in slices and in culture. Nitric oxide, either endogenously released from adjacent neurons or pharmacologically applied, accelerated the rate of hydrolysis in a manner that was dependent on soluble guanylyl cyclase, demonstrating that nitric oxide triggers cyclic GMP production in Purkinje cells, which in turn activates type 5 phosphodiesterase. We conclude that NO acts as an intercellular messenger in the cerebellar cortex and that parallel fibre terminals are a probable source of nitric oxide.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum.

Intense expression of mRNA of endothelin-B receptor (ETBR) has been detected in the Bergmann glia of cerebellum by in situ hybridization, but the intracellular localization has not been reported because of the absence of a useful antibody for immunohistochemical investigations. We made polyclonal antibodies against the carboxyl terminus of human ETBR (420-442) and ETAR (403-427), and performed light- and electron-microscopic immunohistochemistry of the wild-type and ETBR-deficient (sl/sl) rat cerebella. Localization of ETBR during postnatal development was examined by double-staining immunofluorescence using antibodies against ETBR and S-100 beta. In the wild-type rats, ETBR immunoreactivity appeared from postnatal day 5 (P5) and was distributed diffusely in the processes and cell bodies of S-100 beta-positive glial cells. By P14, ETBR immunoreactivity was concentrated in the Golgi apparatus of Bergmann glial cell soma and the plasma membrane of its processes. The ETBR-positive astrocytes in the granular layer decreased in number during P7-14 and had disappeared by week 3. At 3 weeks, ETBR immunoreactivity was restricted to the Golgi apparatus of Bergmann glia. In the sl/sl rats, ETBR immunoreactivity was not observed at all. In contrast to ETBR, ETAR immunoreactivity appeared transiently in the cytoplasm of all astrocytes (Bergmann glia and astrocytes in the granular layer) in the 9- to 14-day-old wild rats and 7- to 14-day-old sl/sl rats, and disappeared within 3 weeks in both. Granule cells did not express immunoreactivity for ETBR and ETAR from the neonatal stage to adulthood. Changes in the intracellular localization of ETBR and transient expression of ETAR may be correlated with the changes of glial functions and proliferation during postnatal development of rat cerebellum.

Amino Acid Sequence↗

PubMed2001

Triterpene glycosides from the roots of Sanguisorba officinalis.

Five triterpene glycosides were isolated from the MeOH extract of Sanguisorba officinalis (Rosaceae) roots, as confirmed by detailed analysis of their 1H, 13C, and two-dimensional NMR data, and by the results of hydrolytic cleavage. Three known triterpenes and six known triterpene glycosides were also isolated and identified. The isolated compounds were evaluated for their cytotoxic activities against HSC-2 cells and HGF.

Glycosides↗

PubMed2001

Symptomatic and urodynamic improvement by oral distigmine bromide in poor voiders after transurethral resection of the prostate.

UNLABELLED: OBJECTIVESz: To study the clinical and urodynamic effects of oral distigmine bromide (distigmine) by using pressure-flow studies in patients who were persistently poor voiders after transurethral resection of the prostate. METHODS: The study included 14 poor voiders after transurethral resection of the prostate who were 50 years old or older. Their poor voiding conditions were characterized by a mean International Prostate Symptom Score of 18.9 or a mean quality-of-life index of 4.6 and a mean maximum flow rate of 8.9 mL/s. All patients underwent symptomatic and urodynamic investigations before and after 4 weeks of daily treatment with 15 mg oral distigmine. RESULTS: In the baseline pressure-flow studies, all patients had weak detrusor contractility as demonstrated by Schäfer's diagram and the maximum Watts factor but did not have bladder outlet obstruction. They had symptomatic improvements after oral distigmine treatment, with the International Prostate Symptom Score reduced to a mean of less than 10 and the quality-of-life index reduced to a mean of less than 3. In the urodynamic investigations, the maximum flow rate improved significantly to a mean of more than 12 mL/s in parallel with a significant increase in the maximum Watts factor. Detrusor contractility according to Schäfer's diagram also tended to improve after oral distigmine treatment. However, no significant changes were found in any of the parameters of bladder outlet obstruction. CONCLUSIONS: Poor voiders after transurethral resection of the prostate who have weak detrusor contractility without bladder outlet obstruction may benefit clinically from treatment with distigmine because of its efficacy in increasing detrusor contractility without enhancing bladder outlet obstruction.

Administration, Oral↗

PubMed2001

Flavonol glycosides and steroidal saponins from the leaves of Cestrum nocturnum and their cytotoxicity.

Phytochemical analysis of the leaves of Cestrum nocturnum (Solanaceae) resulted in the isolation of two new flavonol glycosides (1, 2) and seven steroidal saponins (3-9), including four new ones (4, 6, 7, and 9). The structures of the new compounds were determined by spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage. Cytotoxic activities of the isolated compounds against human oral squamous cell carcinoma-(HSC-2) cells and normal human gingival fibroblasts are reported.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal.

Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported in association with the use of cysteinyl leukotriene receptor antagonists, including zafirlukast, montelukast, and pranlukast, in asthmatic patients. The case of a 26 year old woman with a three year history of asthma, rhinitis, and nasal polyps is reported in whom eosinophilia, pulmonary infiltrates, and fulminant eosinophilic endomyocarditis accompanied by cardiogenic shock developed during pranlukast treatment after corticosteroid withdrawal. Acute necrotising eosinophilic endomyocarditis was confirmed by endomyocardial biopsy. The patient recovered after intensive treatment, including mechanical assistance involving intra-aortic balloon pumping and steroid pulse therapy, along with the discontinuation of pranlukast. It is recommended that careful attention must be paid to signs of a systemic eosinophilic condition or even fulminant eosinophilic myocarditis in asthmatic patients who have begun treatment with antileukotriene drugs following withdrawal of steroids.

Adult↗

PubMed2001

[Transurethral endoscopic treatment for chronic hematospermia caused by müllerian duct cyst and ejaculatory duct obstruction].

Between June 1997 and September 1999, we performed transurethral unroofing (TUUR) in three patients with hematospermia that recurred repeatedly for one year or more. Patient 1 (48 years old) and Patient 2 (59 years old) were diagnosed as having müllerian duct cysts that communicated with the left ejaculatory duct, and Patient 3 (36 years old) as an ejaculatory duct obstruction with the right ejaculatory duct dilation. A mixture of water-soluble contrast medium and indigocarmine blue dye was injected into the cysts and the ejaculatory duct cavity after incision of the vas deferens in Patients 1 and 3, and by cyst puncture under transrectal ultrasound (TRUS) guidance in Patient 2. Then the urethra was incised between the bladder neck and the verumontanum using a Collins' hot knife electrode, and spouting of the dye from the incision was judged to indicate successful unroofing. In Patient 2, safe and simple TUUR was possible by identifying the cyst location and its distance from the knife electrode under TRUS guidance. Hematospermia resolved after surgery in all three patients and there has been no recurrence for 1.3-3.5 years (mean: 2.6 years). Thus, TUUR was effective for treating chronic hematospermia caused by müllerian duct cyst and ejaculatory duct obstruction. For safe and reliable performance of this treatment, TRUS guidance and injection of the dye into the cyst and ejaculatory duct cavity can be recommended.

Adult↗

PubMed2001

[The prediction of bladder outlet obstruction with prostate volume, maximum flow rate, residual urine and the international prostate symptom score in patients with lower urinary tract symptoms].

We determined whether prostate volume (PV), maximum flow rate (Qmax), residual urine (RU) and the International Prostate Symptom Score (I-PSS) predicted bladder outlet obstruction in patients having lower urinary tract symptoms (LUTSs). The study consisted of 114 patients aged 50 years or older with LUTSs who had scores of 8 or more on the I-PSS and 2 or more for the quality of life index. All patients received transrectal ultrasonography for estimation of PV and pressure-flow study (PFS). When PFS showed an obstruction grade of 2 or more in Schäfer's p/Q diagram, the result was defined as bladder outlet obstruction. When we examined which criteria indicated that 90% of patients had bladder outlet obstruction (positive predictive value: 90%), we found that PV of 35 ml or more, Qmax of 8 ml/sec or less, RU of 110 ml or more, and I-PSS of 30 or more did so. Fifty-nine percent of patients met at least one of these criteria. The results suggested that 59% of patients with LUTSs had bladder outlet obstruction with a 90% positive predictive value based on the value of PV, Qmax, RU or I-PSS.

Aged↗

PubMed2000

A reliable method for culture of dissociated mouse cerebellar cells enriched for Purkinje neurons.

The cerebellar Purkinje neuron (PN) serves as an important model in studies of neuronal development in the mammalian central nervous system. Dissociated PN preparations maintained in an in-vitro environment with simplified cellular and biochemical conditions can facilitate molecular analyses of neuronal development. Here we describe a reliable method to prepare dissociated cultures of mouse cerebellar neurons maintained with a serum-free, Dulbecco's modified Eagle's medium/F-12 nutrient-based medium, which facilitates PN survival and dendritic differentiation. The survival of mouse PNs in this culture was maximized when cerebellar cells were (1) taken from prenatal animals, (2) dissociated with papain, and (3) seeded at a density of 5 000 000 cells/ml or higher. Dissociated PNs prepared by our method from mice of embryonic day 18 (E 18) reproduced several morphological and electrophysiological changes seen in intact postnatal rodents with similar time-courses. Therefore, our culture method offers a useful model for investigating molecular mechanisms underlying postnatal neuronal development.

Action Potentials↗

PubMed2000

L-serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons.

Glial cells support the survival and development of central neurons through the supply of trophic factors. Here we demonstrate that l-serine (l-Ser) and glycine (Gly) also are glia-derived trophic factors. These amino acids are released by astroglial cells and promote the survival, dendritogenesis, and electrophysiological development of cultured cerebellar Purkinje neurons. Although l-Ser and Gly are generally classified as nonessential amino acids, 3-phosphoglycerate dehydrogenase (3PGDH), a key enzyme for their biosynthesis, is not expressed in Purkinje neurons. By contrast, the Bergman glia, a native astroglia in the cerebellar cortex, highly expresses 3PGDH. These data suggest that l-Ser and Gly mediate the trophic actions of glial cells on Purkinje neurons.

Animals↗

PubMed2000

Localization of endothelin A receptors in the rat pituitary TSH cells: light- and electron-microscopic immunohistochemical studies.

Endothelins modulate hormonal secretion in the pituitary gland. Intense signaling of endothelin A receptors (ET(A)R) has been detected by in situ hybridization, binding assay and receptor autoradiography. We used light- and electron-microscopic immunohistochemistry of ET(A)R with polyclonal antibody against a synthetic peptide corresponding to the carboxyl terminus (403-427) of human ET(A)R. Immunoreactivity was observed in 6-8% of anterior pituitary cells, which were rather large polygonal or stellate cells. These cells were often clustered. Double-staining immunofluorescence showed that the ET(A)R-positive cells immunoreacted with antibody against the beta-subunit of thyroid-stimulating hormone (TSH), but not adrenocorticotropic hormone (ACTH) or lutenizing hormone beta (LHbeta). Pre- and postembedding electron-microscopic immunohistochemistry showed that ET(A)R-positive cells had vacuolated or parallel-lined rough endoplasmic reticulum (rER) and numerous round granules in their periphery and the elongated processes. By pre-embedding immunohistochemistry, diaminobenzidine tetrahydrochloride (DAB) products were shown to be mostly located around the granules and occasionally underneath the plasma membrane. By postembedding immunohistochemistry, granules in the ET(A)R-positive cells were 90-150 nm in diameter, and colloidal gold particles due to ET(A)R were associated with about 10% of these granules. These results indicate that ET(A) receptors are associated mostly with the secretory granules of TSH cells.

Adrenocorticotropic Hormone↗

PubMed2000

Ultrastructural study on calcification of cartilage: comparing ICR and twy mice.

Twy mice are autosomal recessive mutant mice that develop multiple progressive abnormal calcification, mainly of the cartilage or tendons of the spine and limbs. They finally succumb to severe deformation and ankylosis. We carried out an ultrastructural study on the growth plate as well as the articular and spinal disc cartilage of twy mice and control ICR mice. Knee and spinal specimens were obtained from the animals, then prepared using standard procedures. Ultrastructural observations were made on uranyl lead-stained sections and elemental analysis was carried out on unstained sections. In both twy and ICR mice, linked granules (chain granules) were observed at the pericellular matrix, but there was no remarkable difference between their presence in the growth cartilage. In the twy mice, however, chain granules were observed in the pericellular matrix, cytoplasm, and nucleus of the articular and spinal disc cartilage. These chain granules disappeared after decalcification. Elemental analyses revealed significant amounts of calcium and phosphorus in these granules. It may be significant for abnormal calcification that such chain granules were observed in the articular and spinal disc cartilage of twy mice.

Animals↗