Biomedical subjects

Yo Hoshino

Publications and source records attributed to Yo Hoshino.

14 recordsLinked to original sources

PubMed2006

Evaluation of apoptosis in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus (EBV) is known to be a causative agent of hemophagocytic lymphohistiocytosis (HLH). To investigate association of apoptosis in the pathogenesis of EBV-associated HLH, the serum EBV loads, and serum concentrations of soluble tumor necrosis factor receptor 1 (sTNF-R1), soluble Fas ligand, and cytochrome c were examined in 15 patients with EBV-associated HLH and 24 patients with infectious mononucleosis (IM). Levels of sTNF-R1 are known to reflect the biological activity of TNF-alpha and cytochrome c is a specific marker of apoptosis. EBV loads, and concentrations of sTNF-R1 and cytochrome c were significantly higher in patients with EBV-associated HLH than in patients with IM. On the other hand, there were no statistically significant differences in the concentrations of soluble Fas ligand. In patients with EBV-associated HLH, EBV loads, concentrations of sTNF-R1, and cytochrome c were correlated with each other. These results suggest that apoptosis, which is dependent on the EBV load and could be mediated by TNF-alpha, plays a major role in the pathophysiology of EBV-associated HLH.

Apoptosis↗

PubMed2006

Clonality analysis by sequence variation of the latent membrane protein 1 gene in patients with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (EBV) infection is a severe systemic disease associated with high rates of mortality and morbidity. Recent studies suggest that the clonal expansion of EBV-infected T or natural killer cells plays a crucial role in the pathogenesis of chronic active EBV infection. However, it is not clear whether chronic active EBV infection is truly a monoclonal disorder that originates from one cell. The clonality of EBV was investigated by sequence variation of the latent membrane protein 1 (LMP1) gene, which has a high degree of sequence heterogeneity. Peripheral blood mononuclear cells were obtained from nine Japanese patients with chronic active EBV infection and four with infectious mononucleosis. A carboxyl-terminal region of the LMP1 gene was analyzed by polymerase chain reaction (PCR). The amplified PCR products were subcloned, and 18 clones from each sample were sequenced. Patients with chronic active EBV infection each had two to five different LMP1 nucleotide sequences, whereas patients with infectious mononucleosis each had one to seven different sequences. Patients with chronic active EBV infection and infectious mononucleosis both had one dominant sequence. Longitudinal analysis was performed in four patients with chronic active EBV infection, in whom the dominant strains were found to have remained unchanged for several years. The results suggest that EBV in patients with chronic active EBV infection was polyclonal, although clonal expansion may occur. Collectively, these findings are critical to clarify further the pathogenesis of chronic active EBV infection and aid in the development of effective treatment strategies.

Adolescent↗

PubMed2005

Association of virus infected-T cell in severe hepatitis caused by primary Epstein-Barr virus infection.

BACKGROUND: Infectious mononucleosis owing to primary Epstein-Barr virus (EBV) infection sometimes causes hepatitis, which is usually self-limiting with mildly elevated transaminases, but can rarely develop into severe hepatitis with jaundice. OBJECTIVE: To clarify the pathogenesis of severe hepatitis by primary EBV infection. METHODS: We experienced four cases of severe hepatitis with jaundice caused by primary EBV infection. These cases were analyzed virologically and histologically, and compared with infectious mononucleosis patients without jaundice. RESULTS AND DISCUSSION: Using real-time PCR, more EBV-DNA was detected in peripheral blood from patients with severe hepatitis, as compared to those without jaundice. Furthermore, CD3+, CD4+ or CD8+ cells contained more EBV DNA than did other cell populations, indicating that in severe hepatitis, T cells harbor most of the EBV. By contrast, mainly B cells were infected in infectious mononucleosis patients without jaundice. The liver was biopsied in three of the four cases. An in situ hybridization study showed that EBV infected lymphocytes, not hepatocytes. In addition, in one patient, it was confirmed that the infected lymphocytes were CD8+ T cells. These results suggest that a large EBV burden and T cell infection may play major roles in the mechanism of severe hepatitis caused by primary EB virus infection.

Adolescent↗

PubMed2005

Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection.

Infections of T cells and natural killer (NK) cells play a central role in the pathogenesis of chronic active Epstein-Barr virus (CAEBV) infection. To characterize the virologic and cytokine profiles of T cell-type and NK cell-type infection, 39 patients with CAEBV infection were analyzed. Patients with T cell-type infection had higher titers of immunoglobulin G against early and late EBV antigens, suggesting lytic cycle infection. However, the pattern of EBV gene expression was latency type II; BZLF1, which is a hallmark of lytic cycle infection, could not be detected in any patients, regardless of infection type. Patients with CAEBV infection had high concentrations of proinflammatory, T helper cell type 1, and anti-inflammatory cytokines. The cytokine profile in patients with NK cell-type infection was similar to that in patients with T cell-type infection, but the concentration of IL-13 was high in patients with NK cell-type infection. These findings should help to clarify the pathogenesis of CAEBV infection and facilitate the development of more-effective treatments.

Adolescent↗

PubMed2005

Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs.

Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.

Animals↗

PubMed2004

Quantitative analysis of Epstein-Barr virus (EBV)-specific CD8+ T cells in patients with chronic active EBV infection.

To clarify the pathogenesis of chronic active Epstein-Barr virus (EBV) infection, EBV-specific CD8+ T cells were enumerated, by use of human leukocyte antigen (HLA)-A*2402-restricted tetramers, in 8 patients with chronic active EBV infection, 10 patients with infectious mononucleosis, and 16 EBV-seropositive healthy control subjects. In most of the patients with chronic active EBV infection, EBV-specific CD8+ T cells were not detected. Of note, latent membrane protein 2-specific CD8+ T cells were not detectable in any patients with chronic active EBV infection. In contrast, EBV-specific CD8+ T cells were detected in patients with infectious mononucleosis and in healthy control subjects. Low frequencies of EBV-specific CD8+ T cells may be one of the immunological features of chronic active EBV infection.

Adolescent↗

PubMed2004

Comparison of real-time and nested PCR assays for detection of herpes simplex virus DNA.

We performed a real-time PCR assay to detect herpes simplex virus (HSV) DNA, and compared it prospectively with a nested PCR assay in 164 clinical samples (109 cerebrospinal fluid and 55 sera) from patients suspected of having neonatal HSV infection or HSV encephalitis. In 25 of 164 samples, HSV DNA was detected by the nested PCR assay. All samples positive for HSV DNA in the nested PCR assay were also positive in the real-time PCR assay, and all but two samples negative for HSV DNA in the nested assay were negative in the real-time assay. The real-time PCR assay thus had a sensitivity of 100% and a specificity of 99%, when compared with the nested assay. Sequential assays in a case of disseminated HSV showed that a decrease in HSV DNA paralleled clinical improvement. Quantification of HSV DNA by real-time PCR was useful for diagnosing and monitoring patients with HSV encephalitis and neonatal HSV infection.

Cerebrospinal Fluid↗

PubMed2003

Prognostic factors for chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) is a high-mortality and high-morbidity disease. To clarify the prognostic factors, a national survey was performed in Japan, and data for 82 patients who met the criteria for CAEBV were analyzed. Of these 82 patients, 47 were alive and 35 had already died. Multivariate analysis revealed that thromobocytopenia and age at disease onset were correlated with mortality. The probability of 5-year survival was 0.45 for older patients (onset age, > or = 8 years), 0.94 for younger patients (P<.001), 0.38 for patients with thrombocytopenia (platelet count < 12 x 10(4) platelets/microL at diagnosis), and 0.76 for patients without thrombocytopenia (P=.01). Furthermore, patients with T cell infection by EBV had shorter survival times than patients with natural killer cell infection (probability of 5-year survival, 0.59 vs. 0.87; P<.009). Patients with CAEBV with late onset of disease, thrombocytopenia, and T cell infection had significantly poorer outcomes.

Adolescent↗

PubMed2003

Combination therapy with intraventricular interferon-alpha and ribavirin for subacute sclerosing panencephalitis and monitoring measles virus RNA by quantitative PCR assay.

Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the central nervous system that leads to death within a few years. Recently, it has been reported that combination therapy with intraparenchymal interferon-alpha (INF-alpha) and intraventricular ribavirin is effective. An 11-year-old SSPE patient whose clinical symptoms progressed rapidly, was treated first with intraventricular INF-alpha and then with combined intraventricular INF-alpha and ribavirin therapy. To monitor viral load over the course of the therapy, measles virus RNA was quantified using a real-time polymerase chain reaction assay. Measles virus RNA decreased rapidly after the INF-alpha therapy was started, paralleling the decrease in the measles antibody titer in the cerebrospinal fluid and the improvement in the neurological disability. After intraventricular ribavirin was combined with INF-alpha therapy, no further improvement was observed. The neurological disability gradually progressed, although the amount of virus RNA remained low.

Antiviral Agents↗

PubMed2002

Decreasing the Epstein-Barr virus load by adjusting the FK506 blood level.

To prevent post-transplant lymphoproliferative disease (PTLD), the viral load must be diminished before the symptoms of Epstein-Barr virus (EBV) infection appear. Twenty-three consecutive liver transplant recipients were entered into our study to identify the characteristics of post-transplant EBV-infected patients and to clarify the correlation between the FK506 blood level and EBV load. After transplantation, EBV-DNA appeared more frequently in patients who had been seronegative before transplantation than in seropositive patients (10/13 versus 1/10; P=0.0014). As for rejection, resistance to steroid pulse therapy, and FK506 trough level, there were no significant differences between patients with and without EBV infection. In patients with primary EBV infection after transplantation, there was a strong correlation ( r=0.681) between the FK506 level and the viral load. In liver transplant recipients, especially in those seronegative for EBV, it is necessary to check the viral load by polymerase chain reaction (PCR) carefully after liver transplantation, before any symptom appears.

Adolescent↗

PubMed2002

Quantitation of viral load in neonatal herpes simplex virus infection and comparison between type 1 and type 2.

Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity in spite of the development of effective anti-viral therapies. The viral load in neonatal herpes simplex virus (HSV) infection was measured retrospectively in 37 patients. HSV DNA copy numbers in serum and cerebrospinal fluid (CSF) were quantified using a real-time PCR assay. Patients with disseminated infection had a higher viral load in their sera. whereas patients with central nervous system (CNS) infection exhibited a higher viral load in the CSF. The viral load was significantly higher in the serum of patients who died later. Interestingly, patients with HSV type-2 infection exhibited more CNS involvement and neurological impairment, together with a high viral load in the CSF, than did HSV type-1 patients. These results suggest that quantitation of HSV viral load may be useful for assessing the prognosis, and may provide additional information for the management of neonatal HSV infection.

Central Nervous System Viral Diseases↗

PubMed2002

Epstein-Barr virus-specific T-cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation.

The in vivo cytotoxic mechanism of Epstein--Barr virus (EBV)-specific cytotoxic lymphocytes was examined in a patient who suffered with EBV-associated lymphoproliferative disease (LPD) after bone marrow transplantation (BMT). His peripheral CD8+ T-cell count was significantly increased and >70% of these cells were EBV-specific by fluorescence-activated cell sorter (FACS) analysis for interferon-gamma production. Intracellular perforin expression was markedly increased in CD8+ T cells by FACS analysis. The lymphocytes from this patient had cytotoxic activity against autologous EBV+ lymphoblastoid cell lines which were completely inhibited by concanamycin A, an inhibitor of perforin, and a anti-human leucocyte antigen (HLA)-class I monoclonal antibody. These results suggest that the cytotoxicity was mediated by the perforin, in an HLA-class I-restricted manner. We performed serial intracellular perforin analyses in another patient who also showed endogenous expansion of EBV-specific CD8+ T cells that coincided with an increased EBV-DNA load. Perforin expression in the CD8+ and CD4+ T cells paralleled the EBV-specific CD8+ T cells and EBV-DNA load, which also suggests that perforin mediates EBV-specific cytolysis in vivo and is responsible for effective immunosurveillance against EBV reactivation after BMT. Evaluation of host immunity against EBV by determining perforin expression in lymphocytes and EBV-specific lymphocytes along with quantification of EBV-DNA may be useful for predicting the clinical course of patients with EBV-associated LPD after BMT.

Biomarkers↗

PubMed2002

Detection of herpesvirus DNA in the serum of immunocompetent children.

The DNA of herpesviruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV6), and human herpesvirus-7 (HHV7) has been detected in the serum of patients with primary infection or with immunosuppression. However, it is unknown how frequently herpesvirus DNA can be detected in the serum of immunocompetent children, or whether the detection of herpesvirus DNA indicates an active infection or virus-related diseases. Using a real-time polymerase chain reaction assay, attempts were made to detect herpesvirus DNA in the serum of 176 ambulatory children who visited a hospital for various reasons. EBV was detected in 4 (2.2%), HHV6 in 4 (2.2%), and HHV7 in 2 (1.1%) of 176 children, but CMV was not detected. Of the 10 positive patients, only 4 were considered, by virtue of clinical and serological characteristics, to have primary infections. The other 4 positive patients had other infections, such as mycoplasma and salmonella. Although herpesvirus DNA could be detected in the serum of immunocompetent children, there was not always a relationship between clinical manifestations and the detection of virus DNA. When herpesvirus DNA is detected in the serum, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease.

Antibodies, Viral↗

PubMed2002

Viral load in Epstein-Barr virus-associated hemophagocytic syndrome.

The viral load in peripheral blood from patients with Epstein-Barr virus (EBV)-associated hemophagocytic syndrome was measured by real-time quantitative PCR and compared with that in infectious mononucleosis. Patients with EBV-associated hemophagocytic syndrome generally had larger viral burdens, although it was difficult to differentiate EBV-associated hemophagocytic syndrome from infectious mononucleosis simply by viral load. The difference in viral load seemed to be clearer in peripheral blood mononuclear cells than in plasma.

Adult↗