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R Yanagihara

Publications and source records attributed to R Yanagihara.

At least 91 records · Page 5Linked to original sources

Complete nucleotide sequence of a highly divergent human T-cell leukemia (lymphotropic) virus type I (HTLV-I) variant from melanesia: genetic and phylogenetic relationship to HTLV-I strains from other geographical regions.

The high prevalences of antibodies against human T-cell leukemia (lymphotropic) virus type I (HTLV-I) reported for remote populations in Papua New Guinea and the Solomon Islands and for some aboriginal populations in Australia have been verified by virus isolation. Limited genetic analysis of the transmembrane portion (gp21) of the envelope gene of these viruses indicates the existence of highly divergent HTLV-I strains in Melanesia. Here, we report the complete nucleotide sequence of an HTLV-I isolate (designated HTLV-IMEL5) from the Solomon Islands. The overall nucleotide divergence of HTLV-IMEL5 from the prototype HTLV-IATK was approximately 8.5%. The degree of variability in the amino acid sequences of structural genes ranged between 3 and 11% and was higher (8.5 to 25%) for the regulatory (tax and rex) genes and the other genes encoded by the pX region. Since HTLV-IMEL5 was as distantly related to HTLV-II as to the other known HTLV-I strains, it could not have arisen from a reocmbinational event involving HTLV-II but rather might be an example of independent viral evolution in this remote population. These data provide important insights and raise new questions about the origin and global dissemination of HTLV-I.

Amino Acid Sequence↗

Human retroviruses in Amerindians of Colombia: high prevalence of human T cell lymphotropic virus type II infection among the Tunebo Indians.

The coexistence of infection with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) has been demonstrated recently among the Wayuu Indians from the Guajira region of Colombia. To ascertain if other Indian groups in Colombia are similarly infected, we tested 1,250 sera, collected between 1990 and 1992 from 18 culturally distinct Amerindian tribes living in widely separated regions, for IgG antibodies against HTLV-I/II using enzyme-linked immunosorbent assay (ELISA) and Western blot. Sera were also tested for antibodies against human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) to investigate the overall burden of retrovirus infection in these semi-isolated indigenous groups. A total of 33 of the 1,250 samples were repeatedly reactive to HTLV-I/II antigens by ELISA, and of these, three sera from Waunana/Noanama Indians from the Choco area and two sera from Tunebo Indians from the Santander region were found to be infected with HTLV-I and HTLV-II, respectively, as verified by Western blot and differential ELISA. Thus, despite the small sample size, the overall seroprevalences for HTLV-I and HTLV-II infection among the Waunana/Noanama and Tunebo Indians were 2.1% and 5.0%, respectively. In contrast, none of the 29 Indians who exhibited reactivity to HIV-1/2 by ELISA were seropositive by Western blot. This study adds the Tunebo to the expanding list of Amerindian groups with high prevalences of HTLV-II infection. Further intensive investigations of such indigenous populations will clarify the natural history and disease potential of HTLV-II infection.

Adolescent↗

Bovine spongiform encephalopathy in cattle mimics ultrastructurally experimental scrapie and Creutzfeldt-Jakob disease in rodents.

We report a comparison of the ultrastructural pathology of bovine spongiform encephalopathy, experimental scrapie in hamsters and a panencephalopathic model of Creuzfeldt-Jakob disease (CJD) in mice. Vacuoles in dendrites, intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages, differing in extent, were found in all three models. We conclude, that this axonal and myelin pathology is a phenomenon common to the three models of SSVE studied, and the differences between panencephalophatic CJD and polioencephalopathic BSE and scrapie are only quantitative.

Animal Diseases↗

Neuronal autophagic vacuoles in experimental scrapie and Creutzfeldt-Jakob disease.

We report the presence of autophagic vacuoles (AV) in neuronal perikarya and neuronal processes of rodents with experimental scrapie and Creutzfeldt-Jakob disease. AV were composed of sequestrated cytoplasmic areas containing ribosomes and occasionally mitochondria and small secondary vacuoles. The formation of AV may contribute to neuronal degeneration and ultimately to neuronal loss.

Animals↗

Comparative ultrastructural neuropathology of naturally occurring bovine spongiform encephalopathy and experimentally induced scrapie and Creutzfeldt-Jakob disease.

We report the ultrastructural neuropathology of bovine spongiform encephalopathy (BSE), a recently described slow virus disease first recognized in Friesian/Holstein cattle, and compare it to that of experimental scrapie and Creutzfeldt-Jakob disease. The spongiform change, which was most pronounced in the central grey matter of the midbrain, consisted of membrane-bound vacuoles within neuronal processes, containing curled membrane fragments, secondary chambers and vesicles. Axons and dendrites accumulated whorls of neurofilaments and other subcellular organelles, such as mitochondria and dense bodies, which were entrapped within the filamentous masses. Other neurites accumulated electron-dense bodies, and still others electron-lucent cisterns and branching tubules. Membrane-bound neuronal inclusions, composed of tubules measuring 10 nm in diameter, were found in axonal terminals. Tubulovesicular structures were loosely packed and were occasionally surrounded by a common membrane, a finding previously described only in natural scrapie in sheep. Except for the intraneuronal inclusions, all of the ultrastructural features of BSE resembled those found in scrapie and Creutzfeldt-Jakob disease.

Animals↗

Ultrastructural pathology of axons and myelin in experimental scrapie in hamsters and bovine spongiform encephalopathy in cattle and a comparison with the panencephalopathic type of Creutzfeldt-Jakob disease.

We report the ultrastructural pathology of axons and myelin sheaths in bovine spongiform encephalopathy (BSE) and experimental scrapie in hamsters and compare it with that found in a panencephalopathic model of Creutzfeldt-Jakob disease (CJD). Intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages were found in all three models but to different degrees, while axons containing numerous cellular processes and concentric cisterns were observed only in experimental scrapie and CJD. We conclude that axonal and myelin pathology is a widespread phenomenon and the differences between panencephalopathic CJD and polioencephalopathic BSE and scrapie are only quantitative.

Animals↗

LTR sequence and phylogenetic analyses of a newly discovered variant of HTLV-I isolated from the Hagahai of Papua New Guinea.

A 631-bp region of the long terminal repeat (LTR) of a variant of human T-cell lymphoma/leukemia virus type I (HTLV-I), isolated from a healthy member of a remote, recently contacted group (Hagahai) in Papua New Guinea, was sequenced and compared to LTR sequences of other members of the primate T-cell lymphoma virus group (PTLV), including HTLV-I, simian T-cell lymphoma virus (STLV-I) and HTLV-II. Sequence analysis of the LTR of this New Guinean isolate, designated as HTLV-I(PNG-1), indicated a sequence divergence of 8.4% to 10.4% from prototype Japanese HTLV-I(ATK) and other HTLV-I and STLV-I isolates and 48.6% diversity from HTLV-II. Few mutations were found in the core elements of the transcriptional enhancer regions, the TATA box promoter, and the polyadenylation signal and site. Further, the observed changes did not significantly alter the inferred stability of the Rex response element, a stem loop structure critical for polyadenylation and Rex protein binding. Dendograms based on LTR sequences indicated that the strain of virus that evolved into HTLV-I(PNG-1) diverged from the other PTLV in the distant past, just after the progenitors of STLV-I from Asia, but before the ancestors of STLV-I from Africa. By contrast, other HTLV-I isolates were found to represent strains of virus that have diverged more recently and clustered primarily according to their geographical origin. These data confirm that HTLV-I(PNG-1) is a new and distinct variant of the PTLV group. Also, our analyses suggest that both HTLV-I and STLV-I may have originated in the Indo-Malay region and eventually spread to Africa and then to the New World and Japan with horizontal transmission between man and nonhuman primates possibly occurring over thousands of years.

Base Sequence↗

Coexistence of human T-lymphotropic virus types I and II among the Wayuu Indians from the Guajira Region of Colombia.

High prevalences of human T-lymphotropic virus type II (HTLV-II) infection have been found recently among certain Amerindian groups in North, Central, and South America. To determine if the Amerindians of Colombia are similarly affected, 523 sera, collected between 1987 and 1990 from nine culturally distinct Indian groups from widely separated regions, were tested for IgG antibodies against HTLV-I/II using enzyme-linked immunosorbent assay (ELISA) and Western blot. In addition, 243 sera from five non-Indian (black) and mixed-Indian (mestizo) populations were studied. Of the 766 individuals tested, 44 were ELISA positive, but of these, only four were Western blot positive. Three of the individuals confirmed positive by Western blot were infected with HTLV-II and one was infected with HTLV-I, as determined by differential ELISA. All four seropositive individuals belonged to a group of 62 Wayuu Indians, giving overall HTLV-I and HTLV-II seroprevalences of 1.6% and 4.8%, respectively. The coexistence of HTLV-I and HTLV-II in this Amerindian group provides an opportunity to study the factors governing transmission of these retroviruses.

Blotting, Western↗

Humoral responses to the immunodominant gag and env epitopes of human T-lymphotropic virus type I among Melanesians.

The immune responsiveness to the immunodominant B-cell epitopes of human T-lymphotropic virus type I (HTLV-I), derived from the external envelope glycoprotein (recombinant MTA-1(162-209), synthetic Env-1(194-214), and Env-5(242-257)) and the gag-encoded matrix protein (Gag-1a(102-117)), was analyzed in 19 HTLV-I-seropositive and 51 HTLV I-seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands. The reactivities of seropositive Melanesian specimens to MTA-1 (100%), Env-5 (89%), and Gag-1a (79%) were similar to that seen with U.S. specimens, while reactivity to Env-1 was lower in Melanesian specimens (68%). Minimal reactivity was found to the env epitopes among the 51 HTLV-I-seroindeterminate Melanesians, but 29 (57%) reacted to Gag-1a. The failure to detect HTLV-I gag, pol, env, and tax gene sequences by polymerase chain reaction among the seroindeterminate Melanesians suggests that such reactivities to the Gag-1a epitope represent cross-reacting antibodies with closely related microbial or cellular proteins.

Amino Acid Sequence↗

Failure to isolate human T cell lymphotropic virus type I and to detect variant-specific genomic sequences by polymerase chain reaction in Melanesians with indeterminate western immunoblot.

The controversy over the endemicity of human T cell lymphotropic virus type I (HTLV-I) in Melanesia has been settled recently by the isolation of genetically distinct, highly divergent sequence variants of HTLV-I from unrelated inhabitants of Papua New Guinea and the Solomon Islands. Still at issue, however, is the significance of the high frequency of indeterminate HTLV-I Western blots (defined as reactivity to only gag-encoded proteins) among Melanesians. To investigate whether this indeterminate seroreactivity reflects specific reactivity to the Melanesian HTLV-I variants, 27 seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands were studied for evidence of HTLV-I infection. Although antibodies against Melanesian variant-specific env gene products and variant-specific env gene sequences were detected by Western blot analysis and polymerase chain reaction, respectively, in all 11 HTLV-I Western blot-positive Melanesians, none of the 27 seroindeterminate Melanesians had such variant-specific antibodies or HTLV-I proviral sequences. In addition, attempts to isolate HTLV-I from seroindeterminate individuals were unsuccessful. These data indicate that HTLV-I infection is not the cause of the indeterminate Western blot reactivity seen in Melanesia.

Adolescent↗

Sensitivity and specificity of a recombinant transmembrane glycoprotein (rgp21)-spiked western immunoblot for serological confirmation of human T-cell lymphotropic virus type I and type II infections.

Serum specimens (n = 2,712) obtained from individuals residing in diverse geographic regions and categorized as seropositive (n = 122), seroindeterminate (n = 523), or seronegative (n = 2,067) for human T-cell lymphotropic virus (HTLV) infection in accordance with U.S. Public Health Service guidelines were retested by recombinant transmembrane protein (rgp21)-spiked Western immunoblotting. Of the 122 HTLV-positive specimens, those from 85 of 85 (100%) U.S. blood donors, 2 of 2 (100%) Brazilians, 1 of 2 (50%) Indonesians, 14 of 14 (100%) Solomon Islanders, and 18 of 19 (95%) Papua New Guineans reacted with rgp21, yielding an overall sensitivity of 98% (120 of 122). Specimens from individuals whose infections were confirmed to be HTLV type I or HTLV type II by the polymerase chain reaction assay reacted equally well with rgp21. Of the 523 HTLV-indeterminate specimens, those from 21 of 379 (5.5%) U.S. blood donors, 3 of 6 (50%) Brazilians, 10 of 23 (44%) Ugandans, 8 of 49 (16%) Indonesians, 4 of 36 (11%) Solomon Islanders, and 5 of 30 (17%) Papua New Guineans reacted with rgp21. None of these 51 specimens reacted with native gp46 and/or gp61/68 in a radioimmunoprecipitation assay, suggesting a false-positive reaction (9.75%). Of the 2,067 HTLV-negative specimens, 12 reacted with rgp21, yielding a false-positivity rate of 0.6%. These data indicate that while detection of rgp21 is highly sensitive, it can yield false-positive results. Thus, specimens exhibiting reactivity with rgp21 in the absence of reactivity with native gp46 and/or gp61/68 by Western blot should be tested further by a radioimmunoprecipitation assay to verify HTLV type I or type II infection.

Blotting, Western↗

Evolutionary insights on the origin of human T-cell lymphoma/leukemia virus type I (HTLV-I) derived from sequence analysis of a new HTLV-I variant from Papua New Guinea.

Recent studies have established the presence of human T-cell lymphoma/leukemia virus type I (HTLV-I) in Melanesia. An HTLV-I strain, PNG-1, has now been isolated from a healthy member of the Hagahai, a remote, recently contacted group in Papua New Guinea. To further characterize PNG-1, we employed polymerase chain reaction amplification with subsequent cloning and sequencing of amplified products. Sequence analyses of amplified regions of pol, env, and pX genes of this variant indicate marked heterogeneity (approximately 7%) from prototype HTLV-I. Based on available sequence data, PNG-1 is distinct from all other known HTLV-I strains and diverges from the common ancestor of HTLV-I prior to prototype isolates. The data also suggest, therefore, that HTLV-I originated in the Indo-Malay region rather than Africa.

Amino Acid Sequence↗

Human T-cell lymphotropic virus type I infection and disease in the Pacific basin.

Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is widespread in the Pacific basin. Modes of virus transmission include blood transfusion (and intravenous drug use), breast milk, and sexual intercourse. High prevalences of HTLV-I infection and disease occur among the inhabitants of southwestern Japan and among first- and second-generation (issei and nisei) Japanese-Americans in the Hawaiian Islands. Other Pacific populations with high prevalences of HTLV-I infection include several remote groups in West New Guinea, Papua New Guinea, the Solomon Islands, and Vanuatu, which have had no contact with Japanese or Africans. By contrast, Micronesian and Polynesian populations, even those with prolonged contact with Japanese, exhibit low prevalences or no evidence of HTLV-I infection. Low prevalences of infection are also found in Australia, except among some aboriginal populations. Changing patterns of HTLV-I infection and disease are no better exemplified than in Japan, where striking reductions in transfusion-acquired infection and subsequent development of HAM/TSP have followed the institution of nationwide screening of blood donors for HTLV-I infection. Furthermore, virus transmission from mother to infant by means of infected breast milk has been markedly curtailed in HTLV-I-hyperendemic regions in Japan by interrupting the practice of breast feeding by HTLV-I-infected mothers. The next frontier of HTLV-I research is in Melanesia, where highly divergent sequence variants of HTLV-I have been discovered.

Cross-Cultural Comparison↗

Expression of tumor necrosis factor-alpha cachectin in primary brain tumors of astrocytic lineage.

The tumor necrosis factor alpha (TNF-alpha) is a cytokine released within central nervous system from activated astrocytes and macrophages and involved in several pathologic processes including AIDS-myelopathy, multiple sclerosis and myelin dilatation in panencephalic type of Creutzfeldt-Jakob disease. We studied the expression of the TNF-alpha in brain tumors. Only tumors of astrocytic lineage like astrocytomas and glioblastomas, or tumors of mixed lineage as oligo-astrocytomas and multipotential primitive neuroectodermal tumors (PNET) expressed TNF-alpha-like immunoreactivity. We conclude that this lymphokine is expressed in neoplastic astrocytes. We postulate that TNF-alpha may participate in neoplastic transformation of astrocytes via cascade of interactions with receptor for TNF-alpha.

Astrocytoma↗

Highly divergent molecular variants of human T-lymphotropic virus type I from isolated populations in Papua New Guinea and the Solomon Islands.

To determine the molecular genetic relationship between Melanesian strains of human T-lymphotropic virus type I (HTLV-I) and cosmopolitan prototype HTLV-I, we amplified by PCR, then cloned, and sequenced a 522-base-pair region of the HTLV-I env gene in DNA extracted from uncultured (fresh) and cultured peripheral blood mononuclear cells obtained from six seropositive Melanesian Papua New Guineans and Solomon Islanders, including a Solomon Islander with HTLV-I myeloneuropathy. Unlike isolates of HTLV-I from Japan, the West Indies, the Americas, and Africa, which share greater than or equal to 97% sequence homology, the Melanesian strains of HTLV-I were only 91.8%-92.5% identical with a prototype Japanese HTLV-IATK-1. The nucleotide sequence of proviral DNA from the Solomon Islander with HTLV-I myeloneuropathy also diverged markedly from that of HTLV-I isolated from Japanese patients with HTLV-I-associated myelopathy and from Jamaican patients with tropical spastic paraparesis, suggesting that these variant viruses are capable of causing disease. The HTLV-I variants from Papua New Guineans, in turn, differed by nearly 4% from the Melanesian variants from Solomon Islanders, indicating the existence of another HTLV-I quasi-species. By contrast, HTLV-I strains from two residents of Bellona Island, a Polynesian Outlier within the Solomon Islands, were closely related to cosmopolitan prototype HTLV-I (greater than or equal to 97% sequence identity), suggesting recent introduction, possibly during this century. These findings are consistent with a proto-Melanesian HTLV-I strain of archaic presence, which evolved independently of contemporary cosmopolitan strains, and pose new questions about the origin and global dissemination of HTLV-I.

Adult↗

Immunolocalization of scrapie amyloid (PrP27-30) in chronic wasting disease of Rocky Mountain elk and hybrids of captive mule deer and white-tailed deer.

Scrapie amyloid-immunoreactive plaques are present in brain tissues of captive mule deer with chronic wasting disease (CWD), a progressive neurological disorder characterized neuropathologically by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and astrocytic hypertrophy and hyperplasia. We report here the immunolocalization of scrapie amyloid (PrP27-30) in plaques observed in brain tissues of Rocky Mountain elk (Cervus elaphus nelsoni) and hybrids of mule deer and white-tailed deer (Odocoileus virginianus) naturally affected with CWD. Similar findings have been shown in kuru, Creutzfeldt-Jakob disease, and Gerstmann-Sträussler syndrome in humans. Our data corroborate that CWD in Rocky Mountain elk and hybrids of mule deer and white-tailed deer belongs to the subacute spongiform virus encephalopathies (transmissible cerebral amyloidoses).

Animals↗