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R Yanagihara

Publications and source records attributed to R Yanagihara.

At least 73 records · Page 4Linked to original sources
PubMed1994

Low-incidence latent infection with variant B or roseola type human herpesvirus 6 in leukocytes of healthy adults.

Nested primer-based polymerase chain reaction was employed to determine the frequency of latent infection with human herpesvirus 6 (HHV-6) among healthy adults from Bratislava, Slovak Republic. A 592-bp region, upstream from the gene encoding the putative large tegument protein of HHV-6, was amplified from DNA extracted from peripheral blood mononuclear cells (PBMC) of only one of 29 seropositive adults, suggesting that as few as 1 in 10(5) PBMC may be infected with the virus. Direct sequencing of the 592-bp fragment indicated that the virus harbored by the seropositive Slovak subject (designated B38) differed by only 3 nucleotides from an HHV-6 variant B strain (R-147) isolated from an American infant with a roseola-like illness and by 32 bases from the variant A strain GS isolated from a patient with lymphadenopathy (5.4% sequence divergence). None of these strains had a deoxyadenosine at base position 1251, when compared to the published sequence of strain GS clone pZVH14. Although this discrepancy did not affect the large tegument protein gene, it altered the predicted amino acid sequences of two putative proteins coded by open-reading frames 1 and 2 (ORF 1 and ORF 2) located upstream from this gene.

Adult↗
PubMed1994

Cross-neutralizing antibodies against cosmopolitan and Melanesian strains of human T cell leukemia/lymphotropic virus type I in sera from inhabitants of Africa and the Solomon Islands.

The so-called cosmopolitan strains of human T cell leukemia/lymphotropic virus type I (HTLV-I) from Japan, Africa, the West Indies, and the Americas differ only slightly (< 3%) in their genomic sequence. On the other hand, the Melanesian strains of HTLV-I are somewhat more divergent, exhibiting only 93% sequence similarity with the cosmopolitan strains. Despite this difference, sera from individuals infected with Melanesian strains cross-react with T cells infected with cosmopolitan strains of HTLV-I, indicating an overall conservation of the B cell immunoprevalent epitopes. Neutralizing antibodies against HTLV-I in sera from virus-infected Africans and Melanesians were assayed by determining their ability to block the formation of syncytia in cocultures of 8166 and T cell lines harboring either cosmopolitan or Melanesian HTLV-I isolates. All six African sera blocked the formation of syncytia with cells infected with HTLV-IC91-PL, a viral isolate from the United States. Similarly, all six Melanesian sera inhibited syncytium formation with cells infected with HTLV-IMEL3, a virus isolate from the Solomon Islands. Although most of these sera inhibited syncytium formation in cell cultures carrying the cosmopolitan as well as the Melanesian HTLV-I strains, neutralizing antibody titers tended to be higher against the homologous virus. All sera failed to inhibit syncytium formation when cells were infected with HTLV-II. These data indicate the involvement of one or more epitopes in syncytial formation, some of which are conserved in all strains of HTLV-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗
PubMed1994

Genotyping of human T cell lymphotropic virus type I using Australo-Melanesian topotype-specific oligonucleotide primer-based polymerase chain reaction: insights into viral evolution and dissemination.

Sequence variants of human T cell lymphotropic virus type I (HTLV-I), genetically distinct from cosmopolitan strains of HTLV-I from Japan, the Americas, the Caribbean, and Africa, have been discovered among Melanesians in Papua New Guinea and the Solomon Islands and among Australian aboriginals. By using oligonucleotide primer pairs derived from sequences unique to the gp46- and gp21-encoding regions of the env gene of the Melanesian HTLV-I variants, HTLV-I strains from widely separated geographic regions could be grouped into either of two major geographic-specific genotypes or topotypes: Australo-Melanesian and cosmopolitan. These primers did not permit amplification of the corresponding env gene regions in strains of simian T cell lymphotropic virus type I from Asia and Africa. Phylogenetic analysis also supported two distinct lineages, consistent with evolution of HTLV-I in Australia and Melanesia independent from that in other parts of the world.

Australia↗
PubMed1994

Further ultrastructural studies of lesions produced in the optic nerve by tumor necrosis factor alpha (TNF-alpha): a comparison with experimental Creutzfeldt-Jakob disease.

We report here that intraocular injection of recombinant TNF-alpha produces lesions in the optic nerve indistinguishable from those reported for the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). The lesions were patchy and confined to the injected optic nerve. Axons show variable features of degenerations. Numerous vacuoles distended the myelin sheath. Hypertrophic astrocytes were numerous and many active macrophages containing digested myelin debris and lyre-like paracrystalline bodies. At high power, myelinated axons were observed as enveloped by astrocytic processes; formation of labyrinth-like network of such processes around damaged axons were observed. In conclusions, lesions produced by TNF-alpha mimic those of the panencephalopathic type of CJD, in direct support of our previous ultrastructural, immunohistochemical and molecular data on TNF-alpha involvement in CJD pathogenesis.

Animals↗
PubMed1994

High serum antibody titers to human herpesvirus-6 in Melanesian population.

IgG antibodies to human herpesvirus-6 were found by indirect immunofluorescence in the sera of 29 out of 45 tested healthy adults from Bratislava, and in 33 out of 49 healthy Melanesians from Solomon Islands and Papua New Guinea. Although antibody seropositivity was similar in both population groups (64.5% and 67.4%, respectively), the geometric mean titer was significantly higher in the sera of Melanesians (p < 0.0001).

Adult↗
PubMed1993

Prophylaxis against a Melanesian variant of human T-lymphotropic virus type I (HTLV-I) in rabbits using HTLV-I immune globulin from asymptomatically infected Japanese carriers.

Molecular variants of human T-lymphotropic virus type I (HTLV-I), which diverge significantly from the so-called cosmopolitan prototypes, have been discovered in Melanesia. In this study, HTLV-I IgG (I-IgG) prepared from seropositive healthy Japanese carriers was evaluated for its protective effect against a Melanesian isolate, HTLV-IMEL5, in rabbits. Normal IgG (N-IgG) prepared from seronegative healthy Japanese was used as control. Both preparations contained 50 mg/mL of IgG and I-IgG had a high neutralizing antibody titer, as determined by vesicular stomatitis virus--HTLV-I pseudotype assay. Of four experimental groups (A, B, C, and D), each with three rabbits, groups A and B were infused with 10 mL of N-IgG and I-IgG, respectively, and animals were challenged immediately by transfusion of 5 mL of blood from a rabbit infected with HTLV-IMEL5. Animals in groups C and D were immunized with 10 mL of I-IgG 24 and 48 hours, respectively, after being transfused with 5 mL of blood from the virus-infected rabbit. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in all rabbits in groups A and D after 2 to 6 weeks, but in none of the animals in groups B and C. These data indicate that I-IgG is protective against HTLV-IMEL5 infection when administered before or within 24 hours of transfusion with virus-contaminated blood. Moreover, our study shows that the neutralizing domains of the so-called cosmopolitan and Melanesian strains of HTLV-I are functionally indistinguishable.

Animals↗
PubMed1993

Sequence analysis of an immunogenic and neutralizing domain of the human T-cell lymphoma/leukemia virus type I gp46 surface membrane protein among various primate T-cell lymphoma/leukemia virus isolates including those from a patient with both HTLV-I-associated myelopathy and adult T-cell leukemia.

Human T-cell lymphoma/leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. Specific regions within the outer envelope proteins of other retroviruses, e.g., human immunodeficiency virus type 1, are highly immunogenic and, because of the selective pressure of the host immune system, quite variable. Mutations in the external envelope protein gene of murine retroviruses and human immunodeficiency virus type 1 influence cellular tropism and disease pathogenesis. By contrast, no disease-specific viral mutations have been identified in HTLV-I-infected patients. However, all isolates studied thus far have originated from leukemic cell lines, peripheral blood mononuclear cells, or cerebrospinal fluid lymphocytes from patients with HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma and, therefore, may not truly reflect tissue-associated variation. The midregion of the HTLV-I gp46 external envelope glycoprotein (amino acids 190-209) induces an antibody response in 90% of infected individuals, and a hexapeptide in this region (amino acids 191-196) elicits antibodies in rabbits which inhibit syncytia formation and infection of target lymphocytes. Because of the above, we expected the neutralizing domain of the gp46 env gene of HTLV-I to possess disease or organ-associated mutations selected by the infected host's immune system. Hence, we amplified, cloned, and sequenced HTLV-I DNA directly from in vivo central nervous system, spleen, and kidney specimens, and a leukemic cell line from a patient (M. J.) with both HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma to discern the possibility of tissue- and/or disease-specific variants. In addition, we sequenced several HTLV-I isolates from different regions of the world, including Papua New Guinea, Bellona, and Liberia, and compared them to other previously published HTLV-I and related retroviral sequences. The 239-base pair sequence corresponding to amino acids 178 to 256 in gp46 displayed minor tissue-specific variation in clones derived from central nervous system tissues from patient M. J., but overall was highly conserved at both the DNA and amino acid levels. Variation was observed in this region among the other HTLV-I, simian T-cell lymphoma virus type I, and HTLV-II isolates in a pattern that was consistent with their known phylogenetic relationship. No consistent disease-related changes were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

Immunolocalization of scrapie amyloid in non-congophilic, non-birefringent deposits in golden Syrian hamsters with experimental transmissible mink encephalopathy.

Transmissible mink encephalopathy (TME), a naturally occurring subacute spongiform encephalopathy in commercially ranch-reared mink (Mustela vision), is characterized neuropathologically by spongiform changes in the neuropil, intracytoplasmic neuronal vacuolation and astrocytic hypertrophy and hyperplasia. Amyloid deposits have not been observed in brain tissue sections from animals with natural and experimental TME using conventional histochemical stains such as Congo red. To determine if amyloid deposits be visualized by immunocytochemical techniques, we stained formalin-fixed, formic acid-treated brain tissue sections from several animal species with natural and experimental TME, using a rabbit antiserum directed against scrapie amyloid (PrP27-30). Scrapie amyloid-immunoreactive deposits were found in golden Syrian hamsters experimentally infected with TME, but were absent in mink with natural and experimental TME, as well as in ferrets and squirrel monkeys with experimental TME. The scrapie amyloid-immunoreactive deposits, which were non-congophilic and non-birefringent, were distributed in the subependymal, subpial and perivascular regions of the brain, as in hamsters infected with the 263K strain of scrapie. Ultrastructurally, scrapie amyloid-immunoreactive deposits revealed a collection of degenerating neurites with numerous abnormal mitochondria and degenerating synapses. Amyloid fibrils were not observed. Anti-scrapie amyloid antibodies immunoabsorbed with scrapie amyloid abolished immunostaining. Our data indicate the presence of scrapie amyloid lacking the molecular conformation of amyloid fibrils in hamsters with experimental TME.

Animals↗
PubMed1993

Interfamilial and intrafamilial genomic diversity and molecular phylogeny of human T-cell lymphotropic virus type I from Papua New Guinea and the Solomon Islands.

To determine the interstrain genomic diversity and molecular phylogeny of the recently identified variants of human T-cell lymphotropic virus type I (HTLV-I) in Melanesia, we enzymatically amplified, then directly sequenced representative regions of the gag, pol, and env genes of HTLV-I strains from 10 members of four families, including one family from Papua New Guinea and three families from the Solomon Islands. When aligned and compared to a Japanese strain of HTLV-I (ATK), the Melanesian HTLV-I strains differed by 7.6 to 8.7% in the gag, 7.1 to 9.3% in the pol, and 7.3 to 8.2% in the env gene regions. Based on 931 nucleotides, the overall sequence divergence of the 10 Melanesian HTLV-I strains from HTLV-I ATK was 7.3 to 8.1% (68 to 75 base substitutions). The intrafamilial genetic heterogeneity among these virus strains was nil to 0.2%, while the interfamilial sequence variation between HTLV-I strains from the Solomon Islands and those from Papua New Guinea was 3.4 to 4.2%, and the genetic heterogeneity among virus strains from the three Solomon Islands families was 0.2 to 0.9%. Using the maximum parsimony and neighbor-joining methods, phylogenetic analysis indicated that the HTLV-I strains from Papua New Guinea and the Solomon Islands formed a monophyletic group and that the Melanesian and cosmopolitan strains of HTLV-I have evolved along two major geographically dependent lineages.

Base Sequence↗
PubMed1993

Neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis, parkinsonism-dementia and neurologically normal Guamanians contain a 4- to 4.5-kilodalton protein which is immunoreactive to anti-amyloid beta/A4-protein antibodies.

Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43-amino acid synthetic peptide homologous to amyloid beta/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian ALS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5-20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4- to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid beta/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid beta/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Guamanians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging.

Amyloid beta-Peptides↗
PubMed1993

Fibrils in brain of Rocky Mountain elk with chronic wasting disease contain scrapie amyloid.

Chronic wasting disease (CWD), a progressive, fatal neurological disorder of captive mule deer and Rocky Mountain elk, is characterized neuropathologically by spongiform change in the neuropil, intraneuronal vacuolation and astrocytic hypertrophy and hyperplasia. Recently, scrapie amyloid-immunoreactive plaques have been demonstrated in brain tissues of CWD-affected captive mule deer, Rocky Mountain elk and hybrids of captive mule deer and white-tailed deer. We now report on the presence of abnormal fibrils isolated from brain tissues of Rocky Mountain elk using negative-stain electron microscopy. These fibrils resemble those found in scrapie-infected hamster brain. Furthermore, protein bands with relative molecular masses of 26 to 30 kilodaltons were shown to be immunoreactive to antibodies raised against scrapie amyloid by Western immunoblotting. Immuno-dot blot showed similar reactivity. Our data support the clinical and pathological diagnosis of the disease and provide further evidence that CWD belongs to the subacute spongiform encephalopathies.

Amyloid↗
PubMed1993

Belgrade virus, a cause of hemorrhagic fever with renal syndrome in the Balkans, is closely related to Dobrava virus of field mice.

Belgrade virus is a recently described hantavirus that causes severe hemorrhagic fever with renal syndrome (HFRS) in people living in various parts of the Balkan Peninsula. Nucleotide sequencing of the G2-encoding region in the medium (M) segment of the viral genome, reverse transcribed and amplified by the polymerase chain reaction, revealed the Belgrade virus to be substantially different from Hantaan virus and other major serotypes of hantavirus but identical to Dobrava virus, a virus isolated from a field mouse (Apodemus flavicollis) in Slovenia. Belgrade virus may be an important cause of HFRS in the Balkan Peninsula, extending north toward the Alps. It poses a special danger to humans who have close contact with field rodents.

Animals↗
PubMed1993

Functional conservation of the neutralizing domains on the external envelope glycoprotein of cosmopolitan and melanesian strains of human T cell leukemia/lymphoma virus type I.

To determine if the immunodominant neutralizing epitopes on the external envelope glycoprotein of the recently identified sequence variants of human T cell leukemia/lymphoma virus type I (HTLV-I) from Melanesia are functionally conserved, sera from Japanese patients with adult T cell leukemia and from HTLV-I-infected Melanesians of Papua New Guinea and the Solomon Islands were tested for neutralizing antibodies by use of vesicular stomatitis virus pseudotypes bearing envelope antigens of Japanese and Melanesian HTLV-I strains. Neutralizing antibody titers of the Japanese and Melanesian sera and of monoclonal and polyclonal antibodies directed against a known neutralizing epitope on the external envelope glycoprotein of HTLV-I were equivalent against the Japanese and Melanesian HTLV-I pseudotypes. The demonstrated two-way cross-neutralization between Japanese and Melanesian strains of HTLV-I indicates that their antigenic determinants for neutralization are functionally indistinguishable and that HTLV-I exists as a single serotype worldwide.

Amino Acid Sequence↗
PubMed1993

Sequence analysis of human T cell lymphotropic virus type I strains from southern India: gene amplification and direct sequencing from whole blood blotted onto filter paper.

Human T cell lymphotropic virus type I (HTLV-I) infection in India has been found to be associated with adult T cell leukaemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) among life-long residents of southern India. To examine the heterogeneity of HTLV-I strains from southern India and to determine their relationship with the sequence variants of HTLV-I from Melanesia, 1149 nucleotides spanning selected regions of the HTLV-I gag, pol, env and pX genes were amplified and directly sequenced from DNA extracted from whole blood blotted onto filter paper and from peripheral blood mononuclear cells, obtained from one patient with HAM/TSP, two with ATLL and eight asymptomatic carriers from Andhra Pradesh, Kerala and Tamil Nadu. Sequence alignments and comparisons indicated that the 11 HTLV-I strains from southern India were 99.2% to 100% identical among themselves and 98.7% to 100% identical to the Japanese prototype HTLV-I ATK. The majority of base substitutions were transitions and silent. No frameshifts, insertions, deletions or possibly disease-specific base changes were found in the regions sequenced. The observed clustering of the Indian HTLV-I strains with those from Japan, as determined by the maximum parsimony method, suggested a common source of HTLV-I infection with subsequent parallel evolution. Amplification of DNA from blood specimens collected on filter paper may be useful for the study of other blood-borne pathogens.

Adolescent↗