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Y Hirabayashi

Publications and source records attributed to Y Hirabayashi.

At least 19 recordsLinked to original sources
PubMed2006

The mildest form of acute necrotizing encephalopathy associated with influenza A.

We experienced the mildest form of acute necrotizing encephalopathy associated with influenza A. A previously healthy 13-year-old girl had mildly decreased consciousness and delirious behavior lasting for a week. Diffusion-weighted imaging showed mildly high signal intensities in the bilateral thalami, deep white matter in the centrum semiovale, and frontal lobes. Conventional T (1)- or T (2)-weighted images revealed no abnormalities.

Adolescent↗
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↗
PubMed2004

Lysis of adhesions and epidural injection of steroid/local anaesthetic during epiduroscopy potentially alleviate low back and leg pain in elderly patients with lumbar spinal stenosis.

BACKGROUND: Lumbar spinal stenosis causes various forms of back or leg pain, and is recognized with increasing frequency in elderly patients whose physical status is not always suitable for surgery. Epiduroscopy, a new, minimally invasive diagnostic and therapeutic technique, may be useful for pain relief in such patients. We investigated the epiduroscopic findings and immediate and long-term changes in back and leg pain after epiduroscopy in elderly patients with spinal stenosis. METHODS: Patients with degenerative lumbar spinal stenosis (n=58, median age 71 yr) were divided into two groups based on presenting symptoms: a monosegmental group (n=34) and a multisegmental group (n=24). Each patient underwent epiduroscopy, and the findings were evaluated using visual analogue scales for low back and leg symptoms. Epiduroscopy included breaking down adhesions in the epidural space by injections of saline, and injection of steroids/local anaesthetic. RESULTS: Epiduroscopy showed that the amount of fatty tissue and the degree of vascularity were greater in the monosegmental group than in the multisegmental group. Relief of low back pain was observed up to 12 months after epiduroscopy in both groups. Relief of leg pain was evident up to 12 months after epiduroscopy in the monosegmental group, and up to 3 months after epiduroscopy in the multisegmental group. None of the patients showed deterioration of motor or sensory deficits during follow-up. One patient was excluded from analysis because of accidental dural puncture during the procedure. CONCLUSIONS: The findings of epiduroscopy corresponded to the symptoms. Epiduroscopy may reduce low back and leg pain in elderly patients with degenerative lumbar spinal stenosis, particularly those with radiculopathy.

Aged↗
PubMed2004

Port-site metastasis after CO2 pneumoperitoneum: role of adhesion molecules and prevention with antiadhesion molecules.

BACKGROUND: Port-site metastasis is a continuing problem in laparoscopic cancer surgery. To clarify the role of adhesion molecules in the development of port-site metastasis, particularly with regard to prevention, we performed experiments in which port-site metastasis was inhibited using antibodies against extracellular matrix proteins or the active Arg-Gly-Asp (RGD) peptide after CO2 pneumoperitoneum in a murine model. METHODS: We examined the development of port-site metastasis under the following conditions: (1) CO2 pneumoperitoneum with or without hyaluronic acid and anti-integrin or anti-CD44 antibody and (2) CO2 pneumoperitoneum and a RGD peptide or pseudo-RGD sequence peptide (FC-336). BALB/c mice ( n = 130) were injected with 5 x 10(5) human gastric cancer cells (MKN45) and either antibody or peptide, treated with CO2 pneumoperitoneum, and injected intraperitoneally with antibody or peptide for 5 days. Three weeks after CO2 pneumoperitoneum, the frequency and weight of port-site metastatic tumors were determined. RESULTS: Anti-integrin antibody significantly decreased the weight of port-site metastatic tumors without hyaluronic acid (control vs anti-integrin: 8.2 +/- 7.1 vs 3.6 +/- 4.5 mg; p < 0.05) but not the frequency of port-site metastases. With hyaluronic acid, the frequency of port-site metastasis and the weight of port-site metastatic tumors were significantly decreased both by anti-integrin and by anti-CD44 antibody (control vs anti-integrin and anti-CD44; 95% and 8.5 +/- 7.2 mg vs 50% and 3.1 +/- 4.3 mg and 55% and 3.3 +/- 5.1 mg, respectively; p < 0.05). RGD peptide and FC-336 also inhibited port-site metastasis in a dose-dependent manner. CONCLUSION: Cell adhesion molecules integrin and CD44 play an important role in the development of port-site metastasis after laparoscopic cancer surgery. Intraperitoneal injection of RGD peptide or pseudo-RGD sequence peptide (FC-336) can prevent port-site metastasis.

Animals↗
PubMed2002

Development of port-site metastasis after pneumoperitoneum.

BACKGROUND: Port-site metastasis is a critical problem in laparoscopic cancer surgery; the pathogenesis and means of prevention are still unclear. The aim of this study was to clarify by scanning electron microscopy the initial morphologic changes in the development of port-site metastasis. METHODS: Fifteen nude mice were injected with human gastric cancer (MKN 45) cells. Mice were killed on days 0, 3, and 8 (n = 5 each day) after intraperitoneal injection of 5 x 105 cancer cells and carbon dioxide (CO2) pneumoperitoneum at 4-6 mmHg for 20 min. The abdominal wall with the port sites was harvested and examined under both light and scanning electron microscopy. RESULTS: Immediately after CO2 pneumoperitoneum (day 0), the abdominal peritoneum was peeled away and the muscular layer was destroyed at the port site in all mice. Several cancer cells were attached to the injured port sites. On day 3, the subperitoneal tissue and muscular layer defects were replaced by granulation tissue, and several cancer cells were observed in the subperitoneal tissue. On day 8, a small nodule was macroscopically visible at the port site; it was completely covered by mesothelial cells and consisted of numerous cancer cells. CONCLUSIONS: Free cancer cells appear to attach to the injured port sites immediately after CO2 pneumoperitoneum, and these are associated with the development of port-site metastasis after laparoscopic cancer surgery.

Animals↗
PubMed2002

Cytogenetic and cellular events during radiation-induced thymic lymphomagenesis in the p53 heterozygous (+/-) B10 mouse.

PURPOSE: Cellular and cytogenetic events in radiation-induced thymic lymphomagenesis were investigated in the p53 heterozygous (+/-) mouse following a single dose of whole-body irradiation. MATERIALS AND METHODS: The loss of the wild-type p53 allele and microsatellite markers of chromosome 11 in thymic lymphomas that developed in the p53 heterozygous (+/-) mouse after irradiation, and the stage at which prelymphoma cells appeared were analysed. RESULTS: The p53 heterozygous mouse developed thymic lymphomas in a dose-dependent manner. The loss of the wild-type p53 allele (loss of heterozygosity; LOH) occurred in almost all thymic lymphomas induced in the irradiated p53 heterozygous mouse. Cytogenetic analysis for the mechanism of LOH strongly suggested that the loss of the wild-type p53 gene in the lymphomas was caused by duplication of the disrupted allele through either homologous recombination or non-disjunctional chromosome duplication. The assay for prelymphoma cells suggested that a critical event in the development of prelymphoma cells occurred at least 3 weeks after irradiation. CONCLUSIONS: The loss of the wild-type p53 gene in thymocytes of the p53 heterozygous mouse may precede the development of prelymphoma cells after irradiation and be a valuable marker of radiation-induced leukemogenesis.

Animals↗
PubMed2001

Sustained cytomegalovirus-specific CD4+ T cell response associated with prevention of recurrence of cytomegalovirus retinitis without secondary prophylaxis after highly active antiretroviral therapy in patients with AIDS.

It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2001

Association of FcgammaRII with low-density detergent-resistant membranes is important for cross-linking-dependent initiation of the tyrosine phosphorylation pathway and superoxide generation.

IgG immune complexes trigger humoral immune responses by cross-linking of FcRs for IgG (FcgammaRs). In the present study, we investigated role of lipid rafts, glycolipid- and cholesterol-rich membrane microdomains, in the FcgammaR-mediated responses. In retinoic acid-differentiated HL-60 cells, cross-linking of FcgammaRs resulted in a marked increase in the tyrosine phosphorylation of FcgammaRIIa, p58(lyn), and p120(c-cbl), which was inhibited by a specific inhibitor of Src family protein tyrosine kinases. After cross-linking, FcgammaRs and tyrosine-phosphorylated proteins including p120(c-cbl) were found in the low-density detergent-resistant membrane (DRM) fractions isolated by sucrose-density gradient ultracentrifugation. The association of FcgammaRs as well as p120(c-cbl) with DRMs did not depend on the tyrosine phosphorylation. When endogenous cholesterol was reduced with methyl-beta-cyclodextrin, the cross-linking did not induce the association of FcgammaRs as well as p120(c-cbl) with DRMs. In addition, although the physical association between FcgammaRIIa and p58(lyn) was not impaired, the cross-linking did not induce the tyrosine phosphorylation. In human neutrophils, superoxide generation induced by opsonized zymosan or chemoattractant fMLP was not affected or increased, respectively, after the methyl-beta-cyclodextrin treatment, but the superoxide generation induced by the insoluble immune complex via FcgammaRII was markedly reduced. Accordingly, we conclude that the cross-linking-dependent association of FcgammaRII to lipid rafts is important for the activation of FcgammaRII-associated Src family protein tyrosine kinases to initiate the tyrosine phosphorylation cascade leading to superoxide generation.

Cells, Cultured↗
PubMed2001

Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex.

Although glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.

Animals↗
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

Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta.

We have isolated a cDNA encoding a splice variant of ASIC (acid-sensing ion channel)-beta from the rat trigeminal ganglion. This clone, designated ASIC-beta2, showed a 342 base deletion just after the first transmembrane domain in ASIC-beta. RT-PCR experiments revealed that ASIC-beta2 was expressed exclusively in the trigeminal ganglion and dorsal root ganglion. In situ hybridization showed that ASIC-beta2 mRNA was concentrated in both small diameter and large diameter neurons and co-localized with ASIC-beta mRNA within single sensory neurons in the trigeminal ganglion. When expressed in Xenopus oocytes, ASIC-beta2 was inactive by itself. However, it associated with ASIC-beta to form heteromers, which display lower affinity for protons than ASIC-beta alone.

Acid Sensing Ion Channels↗
PubMed2001

Developmental patterns of ceramide glucosyltransferase (GlcT-1) expression in the mouse: in situ hybridization using DIG-labeled RNA probes.

Glycosphingolipids (GSLs) play significant roles in a variety of cell membrane events, including cellular interactions, signaling, and trafficking. Ceramide glucosyltransferase (glucosylceramide synthase, GlcT-1, EC 2.4.1.80) catalyzes the initial step in GSL synthesis, the transfer of glucose from UDP-glucose to ceramide. The reaction product of glucosylceramide serves as a core structure for over 400 species of GSLs. The enzyme is a key regulatory factor controlling intracellular levels of ceramide and GSLs. Appearance and differential distribution of GlcT-1 mRNA during mice postimplantation embryogenesis [embryonic (E) days; E9, E11, E13, E15] were investigated by in situ hybridization with digoxigenin-labeled RNA probes, coupled with alkaline phosphatase detection. On E9, tissues of the mesencephalon, myelecephalon, diencephalons, and telencephalon expressed GlcT-1. On E11, it was expressed to a detectable extent in various tissues including mesencephalon, myelecephalon, diencephalon, telencephalon, nose, lung, liver, vertebra, tail, spinal cord, and tongue. The expression patterns of E13 were similar to those of E11, except that the heart and stomach became positive. On E15, a specific signal for GlcT-1 was detected in all organs of the embryo. These results provide the first evidence that GlcT-1 is differentially expressed during postimplantation embryogenesis.

Animals↗
PubMed2001

Morphology of the murine peritoneum after pneumoperitoneum vs laparotomy.

BACKGROUND: Although there have been studies of the effects of pneumoperitoneum on the peritoneal cavity, we still do not know whether the morphologic changes to the peritoneum are different for pneumoperitoneum vs laparotomy. Using scanning electron microscopy, we examined the murine peritoneum after pneumoperitoneum vs laparotomy and compared the changes. METHODS: Forty-five mice were anesthetized with diethyl ether and divided into seven groups. Pneumoperitoneum was established at 5 mmHg for 30 min with carbon dioxide (CO(2)) (n = 9), helium (n = 9), and air (n = 9). One group underwent laparotomy for 30 min (n = 9), and a control group underwent anesthesia only (n = 3). CO(2) pneumoperitoneum was further established at 10 mmHg for 30 min (n = 3) and at 5 mmHg for 60 min (n = 3). After the procedures, the peritoneum was resected from the mesenterium of the small intestine in each animal and examined by scanning electron microscope for morphologic changes of the mesothelial cells. RESULTS: Bulging up of the mesothelial cells was evident immediately after pneumoperitoneum, whereas detachment of the mesothelial cells was present immediately after laparotomy. Bulging up of the mesothelial cells was reduced at 24 h after CO(2) pneumoperitoneum and fully resolved at 72 h in all pneumoperitoneum groups, whereas the mesothelial cells remained detached at 72 h in the laparotomy group. Intercellular clefts were found immediately after helium pneumoperitoneum and were present at 24 h and 72 h after helium pneumoperitoneum, but they were not seen after air pneumoperitoneum and were only evident after CO(2) pneumoperitoneum at 10 mmHg. Depression of the mesothelial cell surface was observed when pneumoperitoneum lasted 60 min. CONCLUSION: Morphologic peritoneal alterations after pneumoperitoneum differed from those after laparotomy and were influenced by the type of gas, amount of pressure, and duration of insufflation. These peritoneal changes after pneumoperitoneum may be associated with a specific intraperitoneal tumor spread after laparoscopic cancer surgery.

Air↗
PubMed2001

A new phosphoglycerolipid, 'phosphatidylglucose', found in human cord red cells by multi-reactive monoclonal anti-i cold agglutinin, mAb GL-1/GL-2.

Cord red cell membranes express many differentiation-related molecules. To study such molecules, we have established human cell lines, termed GL-1 and GL-2, by the Epstein-Barr virus transformation method, both of which produce monoclonal anti-i cold agglutinin [Y. Nagatsuka et al., Immunol. Lett. 46 (1995) 93-100]. Thin layer chromatography immunoblotting analysis revealed that these antibodies had broad specificities reacting with a variety of glycolipid antigens. Of the immunoreactive lipid antigens, a new phosphoglycerolipid containing glucose from human cord red cells was found. The isolated lipid was unstable to alkaline hydrolysis and contained glucose as a sole sugar. Secondary ion mass spectrum-collision-induced dissociation mass spectrometric analysis of this lipid gave the main molecular ion peak at m/z 885 corresponding to phosphatidylhexose. This antigen was susceptible to phospholipases A2, C and D but resistant to phosphatidylinositol-specific phospholipase C. Two-dimensional nuclear magnetic resonance spectroscopy confirmed that glucose is linked to the sn-glycerol 3-phosphate residue with a beta-anomeric configuration. Based upon these combined results, we identified this lipid as phosphatidyl-beta-D-glucose. This is the first report showing the presence of the glucosylated glycerophospholipid in mammalian sources.

Agglutinins↗
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↗