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Biomedical subjects

Takuya Iwasaki

Publications and source records attributed to Takuya Iwasaki.

At least 19 recordsLinked to original sources
PubMed2006

Association between severity of inflammation in CNS and development of sunset glow fundus in Vogt-Koyanagi-Harada disease.

PURPOSE: To investigate the association between central nervous system (CNS) inflammation at disease onset and the appearance of sunset glow fundus (SGF) in Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Retrospective case series. METHODS: Charts of 102 patients with VKH disease followed from from initial onset were reviewed. The frequency of cerebrospinal fluid (CSF) pleocytosis and the number of cells in the CSF were compared among the patients who eventually developed SGF and the patients who had not developed SGF as of final follow-up. RESULTS: SGF was observed in 69 (67.6%) of 102 patients. The frequency of CSF pleocytosis was 77 (82.7%) of 93 patients examined. The frequency of CSF pleocytosis and the number of cells in CSF were significantly higher in patients who eventually developed SGF (both P = .0029). CONCLUSIONS: Severe inflammatory response in CNS sites at disease onset may influence the development of SGF in VKH disease.

Adolescent↗
PubMed2006

Analysis of retinal findings of acute retinal necrosis using optical coherence tomography.

PURPOSE: To analyze the retinal findings in patients with ARN, optical coherence tomography (OCT) was performed. METHODS: Seven patients (7 eyes) with ARN were studied using OCT. RESULTS: OCT images depicted highly reflective areas in the inner layers of the retina in all seven cases, corresponding with the yellowish-white lesions of the retina in the acute phase. Disorganization of the retinal structure was also observed in these retinal lesions, especially in cases with severe inflammation. Subretinal changes including retinal exudate and/or fluid were observed in only one case. After regression of the yellowish-white lesions in the retina, a significant reduction in retinal thickness was observed on OCT. CONCLUSIONS: OCT permits the detection of full-thickness retinal necrosis in the acute phase and complete absence of retinal structure in the resolution phase, corresponding with the yellowish-white lesions seen in patients with ARN.

Adult↗
PubMed2006

Glutamate levels in aqueous humor of patients with retinal artery occlusion.

PURPOSE: We analyzed the levels of glutamate and other amino acids in aqueous humor of patients with retinal artery occlusion (RAO) to determine whether glutamate is associated with retinal ischemia in RAO. METHODS: Aqueous humor samples were obtained from nine RAO patients by paracentesis performed as an emergent therapeutic intervention and from nine cataract patients without other ocular disease who served as controls. Aspartic acid, glutamate, taurine, and alanine concentrations were determined using high-performance liquid chromatography. RESULTS: The glutamate level in aqueous humor of patients with RAO (4.46 +/- 1.62 micromol/L) was significantly higher than that in controls (2.98 +/- 1.12 micromol/L) (P < 0.05). CONCLUSIONS: Elevated glutamate levels in aqueous humor may indicate diffusion of vitreous glutamate released from the damaged retina due to acute retinal ischemia in RAO. An increase in the extracellular glutamate level may play an important role in ischemic retinal damage in RAO.

Aged↗
PubMed2006

Role of the alpha/beta interferon response in the acquisition of susceptibility to poliovirus by kidney cells in culture.

Replication of poliovirus (PV) is restricted to a few sites, including the brain and spinal cord. However, this neurotropism is not conserved in cultured cells. Monkey kidney cells become susceptible to PV infection after cultivation in vitro, and cell lines of monolayer cultures from almost any tissue of primates are susceptible to PV infection. These observations suggest that cellular changes during cultivation are required for acquisition of susceptibility. The molecular basis for the cellular changes during this process is not known. We investigated the relationship between PV susceptibility and interferon (IFN) response in primary cultured kidney and liver cells derived from transgenic mice expressing human PV receptor and in several primate cell lines. Both kidneys and liver in vivo showed rapid IFN response within 6 h postinfection. However, monkey and mouse kidney cells in culture and primate cell lines, which were susceptible to PV, did not show such rapid response or showed no response at all. On the other hand, primary cultured liver cells, which were partially resistant to infection, showed rapid IFN induction. The loss of IFN inducibility in kidney cells was associated with a decrease in expression of IFN-stimulated genes involved in IFN response. Mouse kidney cells pretreated with a small dose of IFN, in turn, restored IFN inducibility and resistance to PV. These results strongly suggest that the cells in culture acquire PV susceptibility during the process of cultivation by losing rapid IFN response that has been normally maintained in extraneural tissues in vivo.

Animals↗
PubMed2005

Mitochondrial genome sequences support ancient population expansion in Plasmodium vivax.

Examination of nucleotide diversity in 106 mitochondrial genomes of the most geographically widespread human malaria parasite, Plasmodium vivax, revealed a level of diversity similar to, but slightly higher than, that seen in the virulent human malaria parasite Plasmodium falciparum. The pairwise distribution of nucleotide differences among mitochondrial genome sequences supported the hypothesis that both these parasites underwent ancient population expansions. We estimated the age of the most recent common ancestor (MRCA) of the mitochondrial genomes of both P. vivax and P. falciparum at around 200,000-300,000 years ago. This is close to the previous estimates of the time of the human mitochondrial MRCA and the origin of modern Homo sapiens, consistent with the hypothesis that both these Plasmodium species were parasites of the hominid lineage before the origin of modern H. sapiens and that their population expansion coincided with the population expansion of their host.

Animals↗
PubMed2005

Organization of multisynaptic inputs from prefrontal cortex to primary motor cortex as revealed by retrograde transneuronal transport of rabies virus.

The organization of multisynaptic projections from the prefrontal cortex to the primary motor cortex (MI) was examined in macaque monkeys by retrograde transneuronal transport of rabies virus. In the first series of experiments, the virus was injected into the MI forelimb region, and the time-dependent distribution patterns of transsynaptic labeling were analyzed in the frontal lobe with various survivals (2-4 d). Two days after the viral injection, neuronal labeling emerged in the caudal aspects of the nonprimary motor-related areas that are known to project to the MI directly. At the same time, the motor thalamus contained labeled neurons. On the third day, cortical labeling extended into the rostral motor-related areas and, also, prearcuate area 8. Moreover, a number of labeled neurons were located in the internal pallidum and the cerebellar nuclei. At the 4 d postinjection period, neuronal labeling occurred widely in prefrontal areas as well as in the putamen and the cerebellar cortex. In the second series of experiments, the viral injection was made into the MI hindlimb region, and the distribution pattern of prefrontal labeling on the fourth day was compared with that in the forelimb-injection case. The labeled neurons in each prefrontal area were much fewer in the hindlimb-injection case than in the forelimb-injection case. Whereas ventral area 46 was most densely labeled from the forelimb region, only sparse labeling from the hindlimb region was observed in this prefrontal area. The present results suggest the importance of ventral area 46 in the cognitive control of forelimb movements.

Animals↗
PubMed2005

Langerhans' cell histiocytosis after living donor liver transplantation: report of a case.

We report a case of Langerhans' cell histiocytosis (LCH) occurring after a living donor liver transplantation (LDLT) for fulminant hepatitis. A 9-month-old girl underwent an LDLT for fulminant hepatitis of an unknown cause. The histology of the native liver did not show any findings of LCH. On postoperative day 42, her Epstein-Barr virus (EBV)-DNA and cytomegalovirus antigenemia were both found to be positive. As a result, she was treated with antiviral agents and a reduction of the immunosuppression dosage. On postoperative day 98, acute rejection occurred, and she was treated with FK506, methylprednisolone, and finally, anti-CD3 murine monoclonal antibody was added. Subsequently, the EBV was re-activated. Thereafter, skin eruptions, swelling of the systemic lymph nodes, and pancytopenia appeared on postoperative day 127. LCH was diagnosed based on the typical histological findings as LCH, CD1a, and S-100-positive cells in her skin and a lymph nodes biopsy. She was treated by chemotherapy. The symptoms disappeared a few weeks after the start of the chemotherapy, and a clinical remission of LCH was obtained. We could not detect any evidence of EBV infection in the tumor cells. In spite of the fact that her LCH lesions thereafter remained in remission, she died of hepatic failure at 22 months after undergoing the liver transplantation. In conclusion, we discuss the factors influencing the occurrence of LCH in our patient after LDLT, while also evaluating the relationship between LCH and the immunosuppressive therapy administered to this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Imaging polarimetry in central serous chorioretinopathy.

PURPOSE: To evaluate a noninvasive technique to detect the leakage point of central serous chorioretinopathy (CSR), using a polarimetry method. DESIGN: Prospective cohort study. METHODS SETTING: Institutional practice. PATIENTS: We examined 30 eyes of 30 patients with CSR. MAIN OUTCOME MEASURES: Polarimetry images were recorded using the GDx-N (Laser Diagnostic Technologies). We computed four images that differed in their polarization content: a depolarized light image, an average reflectance image, a parallel polarized light image, and a birefringence image. Each polarimetry image was compared with abnormalities seen on fluorescein angiography. RESULTS: In all eyes, leakage area could be clearly visualized as a bright area in the depolarized light images. Michelson contrasts for the leakage areas were 0.58 +/- 0.28 in the depolarized light images, 0.17 +/- 0.11 in the average reflectance images, 0.09 +/- 0.09 in the parallel polarized light images, and 0.11 +/- 0.21 in the birefringence images from the same raw data. Michelson contrasts in depolarized light images were significantly higher than for the other three images (P < .0001, for all tests, paired t test). The fluid accumulated in the retina was well-visualized in the average and parallel polarized light images. CONCLUSIONS: Polarization-sensitive imaging could readily localize the leakage point and area of fluid in CSR. This may assist with the rapid, noninvasive assessment of CSR.

Adult↗
PubMed2005

Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid.

OBJECTIVES: Clinical studies have shown that administration of eicosapentaenoic acid (EPA) to patients who have unresectable pancreatic cancer induces marked attenuation of cachexia. However, the exact mechanisms of the beneficial effect of EPA on pancreatic cancer are unknown. This examined the effect of EPA on proliferation of human pancreatic cancer cell lines and sought to clarify its mechanisms. METHODS: The effects of EPA on proliferation of three human pancreatic cancer cell lines (SW1990, AsPC-1, and PANC-1) were assessed. Induction of apoptosis and expressions of apoptosis-related proteins were measured. The effect of EPA on cyclo-oxygenase-2 expression in these cell lines was determined. RESULTS: EPA inhibited proliferation of all three human pancreatic cancer cell lines in a dose-dependent fashion. Simultaneously, EPA treatment induced apoptosis and this was associated with caspase-3 activation. EPA treatment was also associated with a decrease in intracellular levels of cyclo-oxygenase-2 protein. CONCLUSION: We have demonstrated that EPA inhibits human pancreatic cancer cell growth due at least in part to the induction of apoptotic cell death. Such apoptosis is associated with activation of caspase-3 and suppression of cyclo-oxygenase-2 expression. Greater understanding of the molecular events associated with the biological activity of EPA should enhance the therapeutic potential of administration of EPA to patients who have pancreatic cancer.

Apoptosis↗
PubMed2005

Spectral imaging of the area of internal limiting membrane peeling.

PURPOSE: To evaluate a spectral imaging technique to detect the area of internal limiting membrane (ILM) peeling after vitrectomy for idiopathic macular hole. MATERIALS AND METHODS: In a prospective study, 15 eyes of 15 patients with idiopathic macular holes were tested. After vitrectomy with ILM peeling, retinal images were taken with color fundus photography, red-free fundus photography, and scanning laser ophthalmoscope imaging at 488 nm, 514 nm, 633 nm, and 780 nm. We calculated the Michelson contrast at the margin of ILM peeling, and each image was rank ordered for the ability to discern the margin of ILM peeling. RESULTS: The Michelson contrasts in scanning laser ophthalmoscope images at 488 nm and 514 nm were significantly larger than those in images at 633 nm and 780 nm and in the red-free fundus photograph. The scanning laser ophthalmoscope images at 488 nm and 514 nm were rated superior to images at 633 nm and 780 nm, the color fundus photograph, and the red-free fundus photograph. CONCLUSION: The scanning laser ophthalmoscope images at 488 nm and 514 nm provide a better tool than some of the common clinical means for detection of the area of ILM peeling. This may assist with rapid, noninvasive assessment of ILM peeling.

Aged↗
PubMed2005

Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys.

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease and is sometimes associated with serious neurological disorders. In this study, an attempt was made to identify molecular determinants of EV71 attenuation of neurovirulence in a monkey infection model. An infectious cDNA clone of the virulent strain of EV71 prototype BrCr was constructed; temperature-sensitive (ts) mutations of an attenuated strain of EV71 or of poliovirus (PV) Sabin vaccine strains were then introduced into the infectious clone. In vitro and in vivo phenotypes of the parental and mutant viruses were analysed in cultured cells and in cynomolgus monkeys, respectively. Mutations in 3D polymerase (3D(pol)) and in the 3' non-translated region (NTR), corresponding to ts determinants of Sabin 1, conferred distinct temperature sensitivity to EV71. An EV71 mutant [EV71(S1-3')] carrying mutations in the 5' NTR, 3D(pol) and in the 3' NTR showed attenuated neurovirulence, resulting in limited spread of virus in the central nervous system of monkeys. These results indicate that EV71 and PV1 share common genetic determinants of neurovirulence in monkeys, despite the distinct properties in their original pathogenesis.

3' Untranslated Regions↗
PubMed2005

Molecular determinants for subcellular localization of hepatitis C virus core protein.

Hepatitis C virus (HCV) core protein is a putative nucleocapsid protein with a number of regulatory functions. In tissue culture cells, HCV core protein is mainly located at the endoplasmic reticulum as well as mitochondria and lipid droplets within the cytoplasm. However, it is also detected in the nucleus in some cells. To elucidate the mechanisms by which cellular trafficking of the protein is controlled, we performed subcellular fractionation experiments and used confocal microscopy to examine the distribution of heterologously expressed fusion proteins involving various deletions and point mutations of the HCV core combined with green fluorescent proteins. We demonstrated that a region spanning amino acids 112 to 152 can mediate association of the core protein not only with the ER but also with the mitochondrial outer membrane. This region contains an 18-amino-acid motif which is predicted to form an amphipathic alpha-helix structure. With regard to the nuclear targeting of the core protein, we identified a novel bipartite nuclear localization signal, which requires two out of three basic-residue clusters for efficient nuclear translocation, possibly by occupying binding sites on importin-alpha. Differences in the cellular trafficking of HCV core protein, achieved and maintained by multiple targeting functions as mentioned above, may in part regulate the diverse range of biological roles of the core protein.

Amino Acid Sequence↗
PubMed2005

The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus.

Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to poliovirus. After intravenous inoculation, severe lesions positive for the poliovirus antigen were detected in the liver, spleen, and pancreas in addition to the central nervous system. These results suggest that the alpha/beta IFN system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection. We subsequently examined the expression of IFN and IFN-stimulated genes (ISGs) in the PVR-transgenic mice. In the nontarget tissues, ISGs were expressed even in the noninfected state, and the expression level increased soon after poliovirus infection. On the contrary, in the target tissues, ISG expression was low in the noninfected state and sufficient response after poliovirus infection was not observed. The results suggest that the unequal IFN response is one of the important determinants for the differential susceptibility of tissues to poliovirus. We consider that poliovirus replication was observed in the nontarget tissues of PVR-transgenic/Ifnar knockout mice because the IFN response was null in all tissues.

Animals↗
PubMed2005

CCR5-deficient mice develop experimental autoimmune uveoretinitis in the context of a deviant effector response.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an organ-specific, Th1-cell-mediated disease that targets the neural retina. CCR5 is a chemokine receptor expressed on Th1 cells that promotes their migration. In CCR5-deficient mice, we examined the role of CCR5 in the development of EAU induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide. METHODS: Wild-type or CCR5-deficient B6 mice were immunized with human IRBP peptide 1-20 (hIRBP-p), and the severity of EAU was assessed clinically and histologically. Splenocytes and cells of regional lymph nodes near the eye were collected and their proliferation and production of IL-6, IL-10, IFN-gamma, and CCL2 (MCP-1) in response to hIRBP-p stimulation were measured. Moreover, the intraocular levels of these cytokines were analyzed. RESULTS: Immunization with hIRBP-p induced EAU in CCR5-deficient mice with a severity comparable to that in wild-type mice. Histologically, T-cell infiltration of the eye was reduced, but granulocyte infiltration was augmented in CCR5-deficient mice. Although splenic T cells from CCR5-deficient mice produced IFN-gamma but not IL-10 on stimulation by hIRBP-p, T cells from the regional lymph nodes failed to produce both cytokines. IL-6 production in the eye and IL-6 and CCL2 production by splenic T cells were predominantly augmented in CCR5-deficient mice. CONCLUSIONS: The development of EAU is not prevented in CCR5-deficient mice. Although T-cell infiltration into the eye is apparently reduced in CCR5-deficient mice, the defect is compensated for by granulocyte infiltration, supposedly mediated by augmented intraocular production of IL-6.

Animals↗
PubMed2004

Productive infection in the murine central nervous system with avian influenza virus A (H5N1) after intranasal inoculation.

The H5N1 type of influenza A virus isolated from human patients in 1997 has a characteristic hemagglutinin and was considered to be directly transmitted from birds. Although neuropathogenicity of this virus was not demonstrated in human autopsy cases, some experimental studies using mice have disclosed that this virus infects the central nervous system (CNS) after intranasal inoculation. In this study we focused on the topographical localization of virus-infected cells in the murine CNS after intranasal inoculation. We immunohistochemically examined virus-infected cells in mouse tissues using a rabbit antiserum recognizing the nucleoprotein of influenza A virus. The virus-infected cells appeared initially in the respiratory tract. Thereafter, the virus antigen-positive cells appeared in the olfactory system and the cranial nerve nuclei innervating the facial region. This suggests that this virus is principally transmitted from the nasal cavity to CNS through the cranial nerves. Neurons were frequently infected and glial and ependymal cells were also infected. Transneuronal transmission of the virus might play the important role of viral spread within the CNS.

Administration, Intranasal↗