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R Yanagihara

Publications and source records attributed to R Yanagihara.

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

Maltol (3-hydroxy-2-methyl-4-pyrone) toxicity in neuroblastoma cell lines and primary murine fetal hippocampal neuronal cultures.

Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 -(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans.

Animals↗
PubMed1996

Sequence analysis of the complete S genomic segment of a newly identified hantavirus isolated from the white-footed mouse (Peromyscus leucopus): phylogenetic relationship with other sigmodontine rodent-borne hantaviruses.

Four Corners (FC) or Sin Nombre virus, a hantavirus harbored by the deer mouse (Peromyscus maniculatus), is the principal etiologic agent of hantavirus pulmonary syndrome (HPS). Recently, a hantavirus, designated New York (NY) virus, isolated from a white-footed mouse (Peromyscus leucopus) captured on Shelter Island, New York, was molecularly linked to a fatal case of HPS occurring in the northeastern United States. To clarify the genetic and phylogenetic relationship between NY and FC viruses and other sigmodontine rodent-borne hantaviruses, we amplified and sequenced the entire S genomic segment of NY virus. The S segment of NY virus was 2078 nucleotides long, with an open reading frame of 1284 nucleotides in the virus complementary strand, capable of encoding a protein of 428 amino acids, and with a 752-nucleotide long 3'-noncoding region, comprised of numerous imperfect repeats. Pairwise analysis indicated that NY virus was more similar to FC virus than to other sigmodontine rodent-borne hantaviruses, differing from strains of FC virus by 16.6-17.8% and 7.0-8.2% at the nucleotide and amino acid levels, respectively. As determined by the maximum parsimony and neighbor-joining methods, NY virus formed a separate lineage from FC virus and was phylogenetically distinct from hantaviruses harbored by other sigmodontine rodents. Whether or not NY and FC viruses represent distinct viral species is unclear. Further analyses of hantaviruses harbored by white-footed mice are needed to clarify the genetic diversity and evolution of Peromyscus-borne hantaviruses.

Amino Acid Sequence↗
PubMed1996

Genetic and phylogenetic analyses of hantaviral sequences amplified from archival tissues of deer mice (Peromyscus maniculatus nubiterrae) captured in the eastern United States.

The S and M segments of a hantavirus, enzymatically amplified from tissues of Cloudland deer mice (Peromyscus maniculatus nubiterrae) captured during 1985 in West Virginia, diverged from strains of Four Corners virus from the southwestern United States by more than 16% and 6% at the nucleotide and amino acid levels, respectively. Phylogenetic analysis suggested that this virus strain (designated Monongahela) forms a possible evolutionary link between the Four Corners and New York hantaviruses.

Amino Acid Sequence↗
PubMed1996

Apoptosis in glial tumors as determined by in situ nonradioactive labeling of DNA breaks.

Tumor growth depends on cell division and cell death. To investigate the role of apoptosis in tumor cell death, we examined 83 cases of glial tumors using in situ nonradioactive tailing of DNA breaks. In addition, since p53 protein may participate in the regulation of apoptosis in glioblastoma, we compared the apoptosis ratio (AR) with the labeling index (LI) of p53 protein immunopositivity. The AR in glial tumor parenchyma ranged from 0 to 1.4%: mean AR +/- standard deviation was 0.4 +/- 0.4% (range, 0-1.4) for glioblastoma, 0.3 +/- 0.3% (range, 0.01-0.83) for anaplastic astrocytoma, 0.1 +/- 0.1% (range, 0-0.41) for low-grade astrocytoma, 0.006 +/- 0.008% (range, 0-0.02) for pilocytic astrocytoma, 0.2 +/- 0.2% (range, 0-0.62) for oligodendroglioma and 0.003 +/- 0.004% (range, 0-0.01) for ependymoma. ARs were significantly higher in higher-grade astrocytic tumors than in lower-grade tumors (Mann-Whitney U test: P = 0.0003), although wide variability in each group resulted in overlapping between the groups. p53 protein immunopositivity (more than 25% of nuclei) was found in 15 of 32 glioblastoma cases, while in the remaining 17 none or only a low percentage (up to 6%) of the nuclei were positive. In p53 protein-positive cases mean AR (0.51 +/- 0.47%) was not significantly higher than that in p53 protein-negative cases (0.22 +/- 0.23%; P = 0.1681).

Apoptosis↗
PubMed1995

Human T-cell lymphotropic virus type I in Iranian-born Mashhadi Jews: genetic and phylogenetic evidence for common source of infection.

High prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection and disease has been identified among Iranian-born Mashhadi Jews, an ethnically segregated, highly inbred population. To determine the origin and genetic diversity of HTLV-I in this group, 1,039 bp spanning selected regions of the HTLV-I gag, pol, env and pX genes were enzymatically amplified and sequenced directly from DNA of five Mashhadi Jews (three with spastic myelopathy and two asymptomatic carriers). Alignment and comparison of these sequences with cosmopolitan and Australo-Melanesian topotypes of HTLV-I indicated that the HTLV-I strains from Mashhadi Jews, which were > or = 99.9% identical among themselves, exhibited considerable sequence similarity (> or = 99%) to HTLV-I strains from southern India, suggesting a common source of infection. Phylogenetic analysis, using the maximum parsimony method, was consistent with a single-source introduction of HTLV-I into the Mashhadi Jewish community.

Adult↗
PubMed1995

Proliferating cell nuclear antigen immunohistochemistry in astrocytes in experimental Creutzfeldt-Jakob disease and in human kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome.

We have used immunohistochemical techniques and a monoclonal antibody against proliferating cell nuclear antigen (PCNA) to investigate the proliferative activity of glial cells in mice with experimental Creutzfeldt-Jakob disease (CJD), and in human cases of CJD, kuru and Gerstmann-Sträussler-Scheinker syndrome (GSS). Only a small proportion of hypertrophic astrocytes showed PCNA immunoreactivity (labelling index, LI: 0-4.5%). PCNA-specific immunostaining was confined entirely to cell nuclei. During the early stages of illness, with minimal CJD pathology, PCNA-immunopositive nuclei were occasionally observed in the subependymal zone of experimentally infected mice. From 18 weeks postinoculation, PCNA-immunopositive astrocytes were most frequently found in the corpus callosum and cerebellar white matter; regions which characteristically exhibit robust vacuolation. No other cells, particularly no cells of microglial morphology, showed PCNA immunoreactivity. In human cases of kuru, CJD and GSS, no PCNA-immunopositive cells were detected despite the presence of numerous microglial cells and reactive hypertrophic astrocytes. These results indicate that only a limited proportion of astrocytes proliferate in the experimental models of subacute spongiform encephalopathies and that microglia are probably postmitotic cells.

Animals↗
PubMed1995

p53 protein and epidermal growth factor receptor expression in human astrocytomas.

p53 mutations are the most frequently detected genetic alterations of gliomas, appearing in a similar proportion of low and high grade astrocytomas, while the amplification of epidermal growth factor receptor (EGFR) gene appears mainly in glioblastomas. Thus, these changes seem to delineate two subgroups of high grade astrocytomas: those originating from preexistent low grade astrocytomas and those originating de novo. Paraffin-embedded surgical specimens from 56 human astrocytomas (8 pilocytic (I.) astrocytomas, 9 low grade (II.) fibrillary astrocytomas, 9 high grade (III.) anaplastic astrocytomas and 30 glioblastomas) were analyzed immunohistochemically for the presence of p53 protein and EGFR. Approximately 41% of all cases were p53-protein-positive while 23% were EGFR-positive. Five cases (8.9%) were double-positive for p53 protein and EGFR. The p53-immunopositive nuclei were revealed in 16 cases (53.3%) of glioblastomas, 3 cases (33.3%) of high grade and 4 cases (44.4%) of low grade astrocytomas. None of pilocytic tumors was p53-positive. EGFR immunopositivity increased with the grade of malignancy (11.1%, 22.2% and 33.3%). Double EGFR-p53-positive cases occuried in similar proportions in all grades (approximately 10%) and did not show different survival rate. There were no differences between average age of patients with only-p53-positive, p53-negative (pilocytic tumors excluded) and only-EGFR-positive tumors.

Astrocytoma↗
PubMed1995

Immune recognition of genetically diverse simian T-cell lymphotropic virus type I isolates.

Nucleotide sequence analysis of selected regions of the gag, pol, env and pX genes of simian T-cell lymphotropic virus type I (STLV-I) strains indicated that African isolates were more closely related to human T-cell lymphotropic virus type I (HTLV-I) than Asian isolates. Despite these recent comparative studies on nucleotide sequence homology between HTLV-I and STLV-I isolates, only limited information is available regarding the influence of genetic differences on antigen-antibody recognition of distinct STLV-I strains. In this study, we demonstrated that sera from STLV-I-infected yellow baboons (Papio cynocephalus) reacted strongly with env gp62/68 from HTLV-I-infected cell lines MT-2 and C10/MJ. In contrast, sera from Japanese macaques (Macaca fuscata) naturally infected with Asian STLV-I had weak reactivity to env gp62/68 of these prototypic HTLV-I strains. Pst-1 restriction enzyme analysis of proviral DNA indicated that the baboon virus isolates were more closely related to HTLV-I than the Japanese isolates. These results indicate that nucleotide sequence diversity, correlates with variations in proviral restriction enzyme sites and antibody recognition of viral envelope proteins. These differences in immunoreactivity may have important implications for serologic diagnosis, as well as epidemiological and vaccine studies of STLV-I infection.

Animals↗
PubMed1995

Neuroaxonal dystrophy in experimental Creutzfeldt-Jakob disease: electron microscopical and immunohistochemical demonstration of neurofilament accumulations within affected neurites.

Neuroaxonal dystrophy is a feature of neuronal degeneration encountered in all subacute spongiform "virus" encephalopathies, including scrapie and Creutzfeldt-Jakob disease (CJD). By immunohistochemical techniques, the accumulation of 200 kDa neurofilament protein was demonstrated in affected neurites in murine CJD. These neurites exhibited the ultrastructural features of dystrophic neurites encountered in other neurodegenerative disorders, particularly Alzheimer's disease. These findings support the hypothesis that impairment of slow axoplasmic transport is a common pathogenetic mechanism for CJD and many other neurodegenerative conditions.

Animals↗
PubMed1995

Molecular linkage of hantavirus pulmonary syndrome to the white-footed mouse, Peromyscus leucopus: genetic characterization of the M genome of New York virus.

The complete M segment sequences of hantaviruses amplified from tissues of a patient with hantavirus pulmonary syndrome in the northeastern United States and from white-footed mice, Peromyscus leucopus, from New York were 99% identical and differed from those of Four Corners virus by 23%. The serum of this patient failed to recognize a conserved, immunodominant epitope of the Four Corners virus G1 glycoprotein. Collectively, these findings indicate that P. leucopus harbors a genetically and antigenically distinct hantavirus that causes hantavirus pulmonary syndrome.

Amino Acid Sequence↗
PubMed1995

Sequence and phylogenetic analyses of human T cell lymphotropic virus type 1 from a Brazilian woman with adult T cell leukemia: comparison with virus strains from South America and the Caribbean basin.

Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in South America and the Caribbean basin. To clarify the genetic and phylogenetic relationship between an HTLV-1 strain isolated from a Brazilian woman with adult T cell leukemia and viral isolates from elsewhere in South America and from other geographic regions, selected regions of the gag, pol, env, and pX genes were amplified and directly sequenced. The overall sequence similarities between the Brazil-R-1 strain and the Japanese prototype ATK strain were 98.7% based on 1,295 nucleotides and 99.1% based on 429 amino acids. Phylogenetic analysis indicated that strain Brazil-R-1 clustered with other Brazilian and South American HTLV-1 isolates and was more closely related to Caribbean isolates from Martinique and Guadeloupe than to virus strains from other geographic regions. These data suggest a common source of HTLV-1 infection in the Caribbean basin and South America.

Amino Acid Sequence↗
PubMed1995

Molecular phylogeny and dissemination of human T-cell lymphotropic virus type I viewed within the context of primate evolution and human migration.

A renewed interest in the emergence and evolution of the primate T-cell lymphotropic viruses has followed the discovery of genetically distinct variants of human T-cell lymphotropic virus type I (HTLV-I) in Melanesia and Australia. Phylogenetic trees based on selected regions of the gag, pol, env and pX genes of HTLV-I from widely separated geographic regions and of simian T-cell lymphotropic virus type I (STLV-I) from African and Asian catarrhines, constructed using the neighbor-joining and maximum parsimony methods, indicated that the Australo-Melanesian and cosmopolitan strains of HTLV-I have evolved along separate geographically dependent lineages, with African STLV-I strains clustering with cosmopolitan HTLV-I strains and Asian STLV-I strains diverging from the common ancestral virus before the Australo-Melanesian HTLV-I strains. When viewed within the context of non-human primate evolution and human occupation of Australia and Melanesia, the rate of molecular change of HTLV-I and STLV-I is approximately 2.5-6.8 x 10(-7) substitutions per site per year. Overall, the sequence and phylogenetic analyses are in accord with interspecies virus transmission among non-human primates, as well as between non-human primates and humans, with independent evolution of HTLV-I in Southeast Asia and in Africa, and with dissemination of HTLV-I by forced or voluntary movements of human populations. The immunosuppressive and T-cell activation properties of HTLV-I places at added risk these Australian Aboriginal and Melanesian populations, some of which are in imminent threat of infection with human immunodeficiency virus type 1.

Africa↗
PubMed1994

Genetic evidence for a hantavirus enzootic in deer mice (Peromyscus maniculatus) captured a decade before the recognition of hantavirus pulmonary syndrome.

To determine if the emergence of hantavirus pulmonary syndrome in the United States was a consequence of recent amino-acid altering mutations and/or genetic reassortment with pathogenic hantaviruses, we examined lung and spleen tissues from seropositive deer mice trapped in August 1983 in Mono County, California, for hantaviral RNA by reverse transcriptase-directed polymerase chain reaction. Alignment and comparison of 1485 nucleotides of the S and M genomic segments enzymatically amplified from these tissues indicated that these deer mice harbored a hantavirus which was genetically similar, differing by less than 2% at the deduced amino-acid level, to the hantavirus implicated in cases of hantavirus pulmonary syndrome occurring in the Four-Corners region of New Mexico, Arizona, Utah, and Colorado in 1993. The peromyscine rodent-borne hantaviruses were, in turn, genetically distinct from other well-characterized hantaviruses, diverging by approximately 30% from Prospect Hill and Puumala viruses at the nucleotide and amino acid levels. Phylogenetic analysis using the maximum parsimony, neighbor-joining, and unweighted pair-group methods indicated that the Peromyscus-derived hantavirus shared a common ancestry with arvicolid rodent-borne hantaviruses. Overall congruency of the phylogenetic trees based on the S and M genomic sequences supported the evolutionary position of the peromyscine rodent-borne hantaviruses. Our data also establish the existence of a hantavirus enzootic in deer mice long before the recognition of hantavirus pulmonary syndrome in the United States.

Amino Acid Sequence↗
PubMed1994

Genetic analysis and molecular phylogeny of simian T-cell lymphotropic virus type I: evidence for independent virus evolution in Asia and Africa.

Type C retroviruses, designated simian T-cell lymphotropic virus type I (STLV-I), have been isolated from several genera of Old World monkeys and apes, but not from New World monkeys and prosimians. To determine the genomic diversity and molecular evolution of STLV-I and to clarify their genetic relationship to human T-cell lymphotropic virus type I (HTLV-I), we enzymatically amplified, then directly sequenced selected regions of the gag, pol, env, and pX genes of STLV-I strains from Asia and Africa. STLV-I strains Si-2, Matsu, and JM86 from Japanese macaques, which exhibited sequence similarities ranging from 98.5 to 99.8% among themselves, diverged by 12.9 to 13.3% from STLV-I strain MM39-83 from a naturally infected rhesus macaque, by 9.7 to 11.2% from STLV-I strains from Africa, and by 8.8 to 11.2% from HTLV-I strains originating in Japan, India, Africa, the Caribbean, the Americas, Polynesia, and Melanesia. By contrast, the interspecies nucleotide sequence similarity among African STLV-I strains from green monkey, yellow baboon, sooty mangabey, and common chimpanzee was remarkably high, ranging from 96.9 to 97.4%, and these STLV-I strains diverged by only 2.2 to 2.8% from HTLV-I strain EL from equatorial Zaire. Phylogenetic trees constructed by using the neighbor-joining and maximum parsimony methods indicated that the Asian STLV-I strains diverged from the common ancestral virus prior to African STLV-I and cosmopolitan and Melanesian HTLV-I strains. Thus, our data are consistent with an archaic presence of STLV-I in Asia, probably predating macaque speciation, with subsequent independent virus evolution in Asia and Africa.

Africa↗
PubMed1994

The Cu/Zn superoxide dismutase gene in ALS and parkinsonism-dementia of Guam.

Guam is one of three endemic foci whose indigenous (Chamorro) people have an unusually high incidence of fatal neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia (PD). Recently, mutations in the Cu/Zn superoxide dismutase (SOD-1) gene have been identified in some familial cases of ALS. To investigate if mutations in the SOD-1 gene are also involved in the pathogenesis of ALS and PD of Guam, we analyzed the SOD-1 gene in Chamorros. No mutations were found in Chamorros with ALS or PD, indicating that mutations in the SOD-1 gene do not underlie the high-incidence neurodegenerative disorders of Guam.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Dose-dependent selective suppression of light (NFL) and medium (NFM) but not heavy (NFH) molecular weight neurofilament mRNA levels in acute aluminum neurotoxicity.

We inoculated 5- to 6-week old New Zealand white rabbits intracisternally with either 100, 250, 500, 750, or 1000 micrograms of AlCl3 or 0.9% NaCl and correlated the extent of cervical motor neuron neurofilamentous inclusion formation at 48 h postinoculation with alterations in neurofilament (NF) mRNA levels. RNA was isolated from cervical spinal cord by the guanidine isothiocyanate method and individual RNA samples were normalized for poly(A+) content. Northern blot analysis was performed with cDNA probes for light (NFL), medium (NFM), and heavy (NFH) neurofilament subunit protein or with oligonucleotide probes for alpha-tubulin or actin. No significant alteration in the levels of alpha-tubulin, actin, or NFH mRNA were observed, regardless of the aluminum dose. In contrast, dose-dependent reductions in NFL and NFM mRNA levels occurred in direct proportion to the extent of neurofilamentous inclusion formation. While inoculums of NaCl or 100 or 250 micrograms AlCl3 induced neither inclusion formation or alterations in mRNA levels, both inclusion formation and reductions in the levels of NFL and NFM mRNA occurred thereafter, becoming maximal with inoculums of 1000 micrograms AlCl3. These experiments indicate that intracisternally administered AlCl3 acutely suppresses NFL and NFM mRNA levels without affecting those of NFH. This pattern is in distinct contrast to the uniform reductions of all NF mRNA transcript levels during neurogenesis or following axotomy, indicating a specific effect of aluminum upon steady-state levels of NF mRNA that correlates with the induction of neurofilamentous aggregates.

Aluminum Chloride↗