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Biomedical subjects

R Yanagihara

Publications and source records attributed to R Yanagihara.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fecal excretion of a novel human circovirus, TT virus, in healthy children.

The role of TT virus (TTV) as a human pathogen is unclear, as is the mode of TTV transmission. To determine the prevalence of TTV infection and the possible fecal-oral route of transmission, we analyzed fecal specimens from 67 healthy, nontransfused children for TTV DNA sequences by heminested PCR, using the NG and T primer sets. The overall prevalence of TTV fecal excretion was 22.4% (15 of 67), with the T primer set (19.4%) being more sensitive than the NG primer set (10.4%). TTV prevalence based on gender or ethnicity showed no significant differences. None of seven children in the 0- to 6-month age group had detectable TTV in feces. Of three sets of siblings, two unrelated sets of twins, ages 33 and 37 months, were negative for fecal TTV DNA, while the third set of siblings, ages 99 and 35 months, was positive. The absence of TTV in the feces of children younger than 6 months and the high prevalence (40%) in children 7 to 12 months of age is consistent with age-specific acquisition of TTV infection by the nonparenteral route. TTV genotypes 1, 3, 4, and 5 were represented in our study population. TTV-positive siblings had TTV genotypes 1 and 4, suggesting unrelated environmental sources of TTV infection. This observation suggests a possible time frame for TTV acquisition in children which coincides with increased interaction with their environment and increased susceptibility to infectious agents.

Age Factors↗
PubMed1999

Exacerbation of influenzavirus pneumonia by intranasal administration of surfactant in a mouse model.

Although surfactant-secreting type II alveolar cells have been shown to be damaged during influenzavirus pneumonia, little is known about the effects of surfactant replacement therapy. We have developed a mouse influenza model, in which viral infection can be localized to the upper respiratory tract or to both the upper and lower respiratory tract depending on the volume (rather than infectious dose) of intranasal inocula of influenzavirus. In this model, only mice infected with a large inocula die with massive infection in the lung. Using this model, we unexpectedly found that intranasal administration of surfactant dramatically exacerbated influenzavirus infection causing fatal disease even in mice inoculated with a small inocula. This exacerbation resulted from enhancement of intrabronchial and intraalveolar spread of virus, as confirmed by immunohistochemical detection of viral antigen in lungs. Assuming this experimental model in mice recapitulates naturally occurring disease in humans, extreme caution is warranted in surfactant-replacement treatment of influenzavirus pneumonia in humans.

Administration, Intranasal↗
PubMed1999

Lack of association between acquisition of TT virus and risk behavior for HIV and HCV infection in Vietnam.

BACKGROUND: The search for the cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a post-transfusion hepatitis-related DNA virus, designated TT virus (TTV), which, based on viral sequences, belongs to a new virus family. The principal modes of infection with TTV are poorly understood, and its role in human immunodeficiency virus type 1 (HIV-1) infection is unclear. OBJECTIVE: To determine if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV. METHODS: The authors analyzed DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 male; 176 female), for TTV sequences by hot-start, heminested polymerase chain reaction. RESULTS: Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences. No association was found between TTV viremia and co-infection with HIV-1 or hepatitis C virus (HCV). Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes that did not segregate according to gender, HIV-1 and HCV risk behaviors, or geographic residence. CONCLUSIONS: Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or nonparenteral route, the data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.

Adolescent↗
PubMed1999

Genotype and allele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders.

BACKGROUND: A 32-base pair (bp) deletion mutation in the beta-chemokine receptor CCR5 gene has been associated with resistance against human immunodeficiency virus type 1 (HIV-1) infection and disease. Large-scale studies conducted among Caucasians indicate that individuals who are homozygous for this deletion mutation (D32/D32) are protected against HIV-1 infection despite multiple high-risk exposures, whereas CCR5/ D32 heterozygotes have a slower progression to acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine the genotype and allele frequencies of the CCR5 gene 32-bp deletion mutation among ethnically diverse non-Caucasian populations. METHODS: DNA, extracted from blood collected between 1980 and 1997 from 1912 individuals belonging to various ethnic groups, including 363 Caucasians, 303 Puerto Rican Hispanics, 150 Africans, 606 Asians, and 490 Pacific Islanders, were analyzed for the CCR5 gene 32-bp deletion mutation by a polymerase chain reaction (PCR)-based assay, using an oligonucleotide primer pair designed to discriminate CCR5 alleles without restriction endonuclease analysis. RESULTS: The comparative frequency of CCR5/D32 heterozygosity was 61 of 363 (16. 8%) in Caucasians, 17 of 303 (5.6%) in Puerto Rican Hispanics, 9 of 490 (1.8%) in Pacific Islanders, 0 of 606 (0%) in Asians, and 0 of 150 (0%) in Africans. CONCLUSIONS: The data confirm the high frequency of CCR5/D32 heterozygosity among Caucasians. Intermediate and low-level D32 allele frequencies among Puerto Rican Hispanics and Hawaiians could be attributed to recent European Caucasian gene flow. By contrast, the inability to detect the D32 allele among Asians and other Pacific Islander groups suggests that other mechanisms are responsible for resistance to HIV-1 infection in these populations.

Alleles↗
PubMed1999

Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea.

RNA, extracted from peripheral blood mononuclear cells (PBMC) obtained from 81 Korean psychiatric patients (39 with schizophrenia, 33 with bipolar affective disorders and nine with major depression), was analyzed for a 391-nucleotide, highly conserved region of the p24 protein-encoding ORF II of Borna disease virus (BDV), using nested reverse transcription-polymerase chain reaction (RT-PCR). BDV genomic RNA was not detected in PBMC from any of the 81 Korean psychiatric patients. These data do not support an etiologic association between BDV infection and neuropsychiatric disorders in humans.

Adult↗
PubMed1998

IgM myeloma: case report with immunophenotypic profile.

Immunoglobulin (Ig)M myeloma is a distinct subtype of multiple myeloma (MM) displaying clinical and pathologic features of both MM and Waldenström's macroglobulinemia (WM). Although the immunophenotypic characteristics of classic MM and WM have been reported, the surface antigen expression of IgM myeloma has not been reported. We report a case of IgM myeloma and describe its immunophenotypic profile using flow cytometry. The cells showed a hybrid MM-WM phenotype, strongly expressing CD38 but lacking CD45 and DR, typical for plasma cells; however, pan-B cell antigens CD20 and FMC7 as well as weak monoclonal surface Ig also were positive, resembling B-cell lymphoproliferative malignancies. Discordant B-cell antigen expression was present, in that pan-B antigens CD19 and CD22 were absent. In addition, B-cell activation antigen CD23, early B-precursor antigen CD10, and pan-T antigen CD5 were not expressed. Although CD20 and weak surface Ig expression have been reported in MM, FMC7 positivity has not been seen. The data therefore suggest that IgM myeloma may have a unique phenotype with characteristics of both MM and WM.

Aged↗
PubMed1998

Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases.

Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.

Adult↗
PubMed1998

Progressive multifocal leukoencephalopathy (PML) and cerebral toxoplasmosis in an adult patient, with no symptoms of underlying immunosuppressing illness.

We present a case of the coincidence of progressive multifocal leukoencephalopathy (PML) and central nervous system (CNS) toxoplasmosis in an adult patient, without a detectable cause of cell-mediated immunity impairment. The proper diagnosis was made postmortem on the basis of histological changes typical of both pathological processes. PML was characterized by the presence of subcortical focal demyelination, containing enlarged, densely basophilic oligodendrocyte nuclei, often with intranuclear inclusion, and bizarre astrocytes, mimicking neoplastic cells. PML was confirmed by detecting numerous papova virus particles in oligo- and astroglial nuclei by thin-section electron microscopy. Cerebral toxoplasmosis was characterized by the presence of multiple well-circumscribed necrotizing abscesses. Numerous Toxoplasma gondii (T. gondii) cysts and free, non-encysted protozoan parasites were found among the inflammatory infiltrates. The diagnosis of cerebral toxoplasmosis was further confirmed by immunocytochemistry. In order to detect putative immunosuppressive background underlying both pathological processes, HIV infection was taken into consideration, however, no histopathological changes indicative of AIDS either in the CNS or in the peripheral organs were eventually found. Moreover no HIV provirus genome was identified in the formalin-fixed, paraffin embedded brain tissue by the polymerase chain reaction (PCR). Current view on the selected aspects of the pathogenesis of both disorders were discussed.

Antigen Presentation↗
PubMed1998

High prevalence of GB virus C/hepatitis G virus infection among homosexual men infected with human immunodeficiency virus type 1: evidence for sexual transmission.

GB virus C/hepatitis G virus (GBV-C/HGV), a recently discovered orphan flavivirus, is distantly related to hepatitis C virus (HCV). Although both GBV-C/HGV and HCV can be transmitted by the parenteral route, their principal modes of transmission and associated risk behaviors may differ. Using reverse transcription-polymerase chain reaction, the 5'-noncoding regions of GBV-C/HGV and HCV were amplified from plasma or sera of 209 individuals infected with human immunodeficiency virus type 1 (HIV-1). As verified by Southern blot analysis, GBV-C/HGV and HCV infection were detected in 37 (17.7%) and 22 (10.5%) of 209 HIV-1-infected individuals, respectively. GBV-C/HGV infection was significantly associated with homosexual sex (P = 0.044) and was more common than HCV infection among HIV-1-infected homosexual men (P = 0.006). The prevalence of GBV-C/HGV infection was nearly equal in women infected with HIV-1 via high-risk heterosexual sex (14.0%) or injection drug use (IDU) (17.5%). By contrast, HCV infection was associated significantly with women reporting IDU when compared to women reporting high-risk heterosexual sex (P < 0.0001). Alanine aminotransferase levels were elevated in HIV-1-infected individuals who were co-infected with HCV (P = 0.009), but not with GBV-C/HGV (P = 0.9). The high prevalence of GBV-C/HGV infection in HIV-1-infected nondrug-injecting homosexual men and among women engaging in high-risk heterosexual sex is consistent with transmission by the mucosal route and with acquisition of infection by the receptive rather than insertive partner.

Adult↗
PubMed1998

Gradual loss of IgG antibodies against GB virus C/hepatitis G virus in a patient with AIDS.

GB virus C/hepatitis G virus (GBV-C/HGV) is a positive-sense, single-stranded RNA virus belonging to the family Flaviviridae and is distantly related to hepatitis C virus (HCV). GBV-C/HGV can be transmitted by the parenteral and the sexual route. Among individuals infected with human immunodeficiency virus type 1 (HIV-1) by the sexual route, we and others have demonstrated a high prevalence of GBV-C/HGV infection. Recently, Woolley and colleagues reported that AIDS patients co-infected with GBV-C/HGV had a significantly lower mean CD4 cell count than AIDS patients without GBV-C/HGV infection, suggesting that GBV-C/HGV antibody may be lost with progression to AIDS. To our knowledge no data are available on the loss of antibody against GBV-C/HGV in AIDS patients. We now report on an HIV-infected patient who exhibited gradual loss of IgG antibodies against GBV-C/HGV, as well as HCV, with progression of HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Asian genotypes of JC virus in Native Americans and in a Pacific Island population: markers of viral evolution and human migration.

The human polyomavirus JC (JCV) causes the central nervous system demyelinating disease progressive multifocal leukoencephalopathy. Previously, we showed that 40% of Caucasians in the United States excrete JCV in the urine as detected by PCR. We have now studied 68 Navaho from New Mexico, 25 Flathead from Montana, and 29 Chamorro from Guam. By using PCR amplification of a fragment of the VP1 gene, JCV DNA was detected in the urine of 45 (66%) Navaho, 14 (56%) Flathead, and 20 (69%) Chamorro. Genotyping of viral DNAs in these cohorts by cycle sequencing showed predominantly type 2 (Asian), rather than type 1 (European). Type 1 is the major type in the United States and Hungary. Type 2 can be further subdivided into 2A, 2B, and 2C. Type 2A is found in China and Japan. Type 2B is a subtype related to the East Asian type, and is now found in Europe and the United States. The large majority (56-89%) of strains excreted by Native Americans and Pacific Islanders were the type 2A subtype, consistent with the origin of these strains in Asia. These findings indicate that JCV infection of Native Americans predates contact with Europeans, and likely predates migration of Amerind ancestors across the Bering land bridge around 12,000-30,000 years ago. If JCV had already differentiated into stable modern genotypes and subtypes prior to first settlement, the origin of JCV in humans may date from 50,000 to 100,000 years ago or more. We conclude that JCV may have coevolved with the human species, and that it provides a convenient marker for human migrations in both prehistoric and modern times.

Biomarkers↗
PubMed1997

Molecular analysis of prion protein (PrP) and glial fibrillary acidic protein (GFAP) transcripts in experimental Creutzfeldt-Jakob disease in mice.

Prion protein (PrPsc) which accumulates in the brains affected with subacute spongiform encephalopathies (SSE) is altered isoform of normal, cellular isoform (PrPc), and PrP deposition is accompanied with spongiosis and astrogliosis. To find the amounts of PrP and GFAP transcripts during progression of experimental Creutzfeldt-Jakob disease we performed comparative RT-PCR on the terminally sick mice brains, 22 weeks following inoculation with Fujisaki strain of CJD agent, and on control brains. The intensity of bands for PrP-mRNA and control beta-actin were similar for infected and uninfected brains, while amounts of transcripts for GFAP increased as for cytokines released by glial cells-TNF-alpha and IL-1 alpha. This study supports thesis that PrPc to PrPsc conversion is post-translational process not related to PrP overproduction. Increased amounts of GFAP-mRNA during the course of the disease correlated with astrocytosis estimated by immunohistochemistry with anti-GFAP antibody.

Animals↗
PubMed1997

Sequence and phylogenetic analyses of HIV-1 infection in Vietnam: subtype E in commercial sex workers (CSW) and injection drug users (IDU).

More than 4,000 persons with human immunodeficiency virus type 1 (HIV-1) infection have been identified in Vietnam through sentinel surveillance since 1990, when the first case of HIV-1 infection was diagnosed in a young woman in Ho Chi Minh City. Currently, the estimated HIV-1 seroprevalences of 10% for injection drug users (IDU) and 3% for female commercial sex workers (CSW) in Vietnam are comparable to those observed in the same risk groups in Thailand five years ago. To clarify if concurrent epidemics with different HIV-1 subtypes (or clades) are occurring among different high-risk behavior groups in Vietnam, we conducted a genotypic analysis of HIV-1 by amplifying and sequencing a 325-nucleotide region spanning the principal neutralizing domain, or V3 loop, of the gp120-encoding env gene from genomic DNA extracted from dried, filter paper-blotted blood samples, collected in April/May and August/September 1995 from 8 HIV-1-seropositive CSW in Ho Chi Minh City, Can Tho and An Giang provinces and from 16 IDU in Ho Chi Minh City, Hanoi, Nha Trang and An Giang province. Sequence alignment and comparison with other HIV-1 subtypes indicated that the HIV-1 strains from CSW and IDU in Vietnam were genetically most similar to subtype E strains from Cambodia. The interstrain genetic variation among the Vietnam HIV-1 env sequences ranged from 0.3% to 9.0% (mean, 4.6%). Phylogenetic analysis verified that some of the Vietnam HIV-1 strains formed discrete clusters and were indistinguishable from other Southeast Asian strains. The demonstration of subtype E in both CSW and IDU in Vietnam contrasts sharply with the previously observed HIV-1 clade restriction in these high-risk behavior groups in nearby Thailand.

Adolescent↗
PubMed1996

Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice.

The ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus is characterized by myelin sheath vacuolation that closely resembles that induced in murine spinal cord organotypic cultures by tumor necrosis factor alpha (TNF-alpha), a cytokine produced by astrocytes and macrophages. To clarify the role of TNF-alpha in experimental CJD, we investigated the expression of TNF-alpha in brain tissues from CJD virus-infected mice at weekly intervals after inoculation by reverse transcription-coupled PCR, Northern and Western blot analyses, and immunocytochemical staining. Neuropathological findings by electron microscopy, as well as expression of interleukin 1 alpha and glial fibrillary acidic protein, were concurrently monitored. As determined by reverse transcription-coupled PCR, the expression of TNF-alpha, interleukin 1 alpha, and glial fibrillary acidic protein was increased by approximately 200-fold in the brains of CJD virus-inoculated mice during the course of disease. By contrast, beta-actin expression remained unchanged. Progressively increased expression of TNF-alpha in CJD virus-infected brain tissues was verified by Northern and Western blot analyses, and astrocytes in areas with striking myelin sheath vacuolation were intensely stained with an antibody against murine TNF-alpha. The collective findings of TNF-alpha overexpression during the course of clinical disease suggest that TNF-alpha may mediate the myelin sheath vacuolation observed in experimental CJD.

Animals↗
PubMed1996

Microwave treatment enhances the immunostaining of amyloid deposits in both the transmissible and non-transmissible brain amyloidoses.

The immunolocalization of amyloid deposits containing either protease-resistant prion protein (PrP) or amyloid beta protein (A beta) in the brains of patients with transmissible or non-transmissible cerebral amyloidoses has been greatly facilitated by the pretreatment of tissue sections with concentrated formic acid. We have investigated whether microwave processing of formalin-fixed tissue sections would obviate the need for formic acid pretreatment. Exposure of brain sections to microwaves, even for periods as brief as 1 sec, greatly enhanced the immunostaining of PrP and A beta amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. Microwaving for 1 min yielded staining intensities similar to that following pretreatment with concentrated formic acid for 10 min. Moreover, the combination of formic acid pretreatment and microwave processing resulted in an even more intense staining of amyloid deposits. Microwave processing, which is easy to perform and comparatively inexpensive, makes exposure to the potentially toxic fumes of formic acid unnecessary.

Alzheimer Disease↗