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Tsuneo Morishima

Publications and source records attributed to Tsuneo Morishima.

51 records · Page 3Linked to original sources
PubMed2003

Systemic cytokine responses in patients with influenza-associated encephalopathy.

Influenza-associated encephalopathy, a severe neurologic complication of influenza, is being reported more frequently in Japan. We investigated the transcription of cytokine genes in peripheral blood leukocytes and compared patients with influenza and with encephalopathy or febrile convulsions and patients with influenza but without neurologic complications. A quantitative polymerase chain reaction (PCR) revealed that transcription of the interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha genes was up-regulated to a greater extent in patients with encephalopathy than in those without neurologic complications. Plasma IL-6 levels also were higher in patients with encephalopathy, although the difference was marginal. Viral RNA in throat swabs was quantified using a real-time quantitative PCR. The virus load was similar among patients with encephalopathy or febrile convulsions or without neurologic complications. Furthermore, virus load was not correlated with either the transcription of cytokine genes or plasma cytokine concentrations. These results suggest that influenza-associated encephalopathy might be a consequence of systemic immune responses.

Child↗
PubMed2003

Roles of anti-hemagglutinin IgA and IgG antibodies in different sites of the respiratory tract of vaccinated mice in preventing lethal influenza pneumonia.

The roles of IgA and IgG antibodies (Abs) against hemagglutinin (HA) in the prevention of lethal influenza pneumonia in vaccinated mice were examined in terms of distribution and concentration of the Abs in the mucus or the serous fluid in different sites of the respiratory tract (RT), mucosa of the nose, trachea, bronchi and bronchioli and the alveolar epithelia of pulmonary acinus. First, the surface areas of the tracheal, bronchial and bronchiolar mucosa and alveolar epithelia were measured to be 20, 260 and 217, 433 mm(2), respectively, using serial tissue sections of the trachea and lungs. Then, the volumes of the tracheal mucus, the bronchial and bronchiolar mucus and the serous fluid of alveolar epithelia were estimated to be 0.2, 2.6 and 21.7 mm(3), respectively, by calculating each from the surface area and an assumed thickness of the mucus layer (0.01 mm) or that of the serous fluid (0.0001 mm). Next, anti-HA IgA and IgG Ab responses in the nasal wash, the trachea-lung wash and the trachea wash were measured in BALB/c mice immunized intranasally with an adjuvant-combined A/PR/8/34 (H1N1) virus vaccine and challenged with a lethal dose of the virus. Then the values of Ab responses were converted to the mucus and serous fluid Ab concentration based on two premises that the serum Abs diffuse at a constant rate to the surface of the tracheal, bronchial and bronchiolar mucosa, and that the active transepithelial transport of IgA Abs does not work in the alveolar epithelia. Results showed that 21.4 microg/ml IgA Abs and 3.6 microg/ml IgG Abs in the tracheal mucus (19.1 and 0.3% of the trachea-lung wash IgA and IgG Ab amounts, respectively), 5.9 microg/ml IgA Abs and 3.6 microg/ml IgG Abs in the bronchial and bronchiolar mucus (66.0 and 3.4% of the trachea-lung wash IgA and IgG Ab amounts, respectively) and about 0.1 microg/ml IgA Abs and 12.3 microg/ml IgG Abs in the serous fluid of alveolar epithelia (14.9 and 96.3% of the trachea-lung wash IgA and IgG Ab amounts, respectively) were present in the vaccinated mice, at which concentrations influenza pneumonia was prevented. Thus, 96.3% of anti-HA IgG Abs in the trachea-lung wash work on the alveolar epithelia, whose surface area is about 800 times larger than that of tracheal, bronchial and bronchiolar mucosa and seem to play a more important role than the mucosal IgA Abs in the prevention of lethal influenza pneumonia.

Animals↗
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

Flow cytometric analysis of cytomegalovirus-specific cell-mediated immunity in the congenital infection.

Flow cytometric analysis of CD4(+) and CD8(+) T cells specific to human cytomegalovirus (CMV) was undertaken in seven patients with congenital CMV infection, six healthy infants who had acquired infection, and six CMV-seropositive adults. Intracellular cytokine assays showed that 0.03-2.23% of CD4(+) T cells in the healthy infants and adults produced interferon-gamma (IFN-gamma) in response to CMV antigens. In contrast, such CD4(+) T cells were almost undetectable in patients with congenital CMV infection who were younger than 2 years of age. Tetrameric major histocompatibility complex/peptide complex analysis demonstrated HLA*A2402-restricted phosphoprotein 65-specific CD8(+) T cells to be present in most healthy infants and adults tested, but almost absent in the patients. Interestingly, CMV-specific CD4(+) T-cell responses were observed in two patients with congenital infection beyond the age of 5 years. The present study points to impairment of CMV-specific cellular immunity in patients in single-cell levels with congenital CMV infection during the infant period and possible restoration in later childhood.

Adult↗
PubMed2003

Cerebrospinal fluid and serum levels of cytokines and soluble tumor necrosis factor receptor in influenza virus-associated encephalopathy.

This study determined the concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1) and soluble E-selectin (sE-selectin) in cerebrospinal fluid (CSF) and serum from 15 children with influenza virus-associated encephalopathy to determine the role of cytokines in the pathogenesis. Cytokines and sTNFR1 were measured by enzyme-linked immunosorbent assay. The CSF IL-6, TNF-alpha and sTNFR1 concentrations were elevated in 9, 4 and 4 of 12 children, respectively. The serum concentrations of IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in 10, 2, 5 and 7 of 13 children, respectively. Four children with elevated TNF-alpha and sTNFR1 levels in the CSF had neurological sequelae. The results suggested that cytokines not only in serum but also in CSF play a pivotal role in influenza virus-associated encephalopathy, and that the CSF TNF-alpha and sTNFR1 levels may be important for predicting neurological sequelae.

Adolescent↗
PubMed2003

Absence of associations between influenza-associated encephalopathy and human herpesvirus 6 or human herpesvirus 7.

BACKGROUND: Influenza-associated encephalopathy is a severe complication of influenza virus infection, but its pathogenesis is unknown. It was recently suggested that the neurologic complications of influenza, including encephalopathy, are associated with human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7). AIM To confirm or refute the association between influenza-associated encephalopathy and HHV-6 or HHV-7. METHODS: Cerebrospinal fluid and serum from 25 patients with central nervous system complications of influenza (18 patients with encephalopathy and 7 patients with febrile convulsions) were investigated. The specimens were examined by real time polymerase chain reaction (PCR) and nested PCR for HHV-6 and HHV-7 DNA. RESULTS: In the cerebrospinal fluid samples neither HHV-6 DNA nor HHV-7 DNA was detected by real time PCR or nested PCR. HHV-6 DNA was detected in a single serum sample from a patient with febrile convulsions. CONCLUSION: In our study there was no association with HHV-6 or HHV-7 in most patients with central nervous system complications of influenza.

Age Distribution↗
PubMed2003

Evaluation of cytomegalovirus infections transmitted via breast milk in preterm infants with a real-time polymerase chain reaction assay.

OBJECTIVE: Preterm infants are at greater risk of symptomatic cytomegalovirus (CMV) infection than term infants. Breast milk is the main source of perinatal CMV infections. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breast milk from mothers to their preterm infants. METHODS: This was a prospective study of 30 mothers and their 43 preterm infants. The infants either had a gestational age of <34 weeks or weighed <2000 g at birth. Breast milk, serum, and urine samples were collected every 2 weeks until discharge, and screened for CMV infection using a real-time PCR assay. Most of the breast milk had been preserved at -20 degrees C before feeding to the preterm infants. RESULTS: Twenty-four mothers (24 of 30, 80%), who had 34 preterm infants, were CMV immunoglobulin G positive. Twenty-one (87.5%) of the 24 seropositive mothers, who had 30 preterm infants, had detectable CMV deoxyribonucleic acid (DNA) in breast milk during the study period. Most breast milk became positive for CMV DNA 2 weeks after delivery. Viral DNA copy numbers increased until they peaked at 4 to 6 weeks. Afterward, the CMV DNA copy numbers decreased. Of the 30 infants who were fed CMV DNA-positive breast milk, CMV infection was confirmed in 3 infants. However, they had no clinical symptoms of CMV infection. CONCLUSIONS: Despite the high rate of CMV DNA in breast milk, symptomatic infections in the preterm infants did not occur. These results might be associated with the method of breast milk preservation and the population we studied. CMV infections transmitted via breast milk feeding did not have much impact on preterm infants in our institutes.

Antibodies, Viral↗
PubMed2003

Possibility of preventive treatment for EBV-associated NK cell-lineage proliferative disorders.

OBJECTIVE: Chronic active EBV infections (CAEBV) are often causative of malignant lymphoproliferative disorders, such as natural killer (NK) cell-lineage granular lymphocyte proliferative disorders (NK-GLPD), which are refractory to several conventional chemotherapies and usually show a poor prognosis. To explore the possibility of preventive treatment for Epstein-Barr virus (EBV)-infected NK-GLPD, we examined the effect of antiviral drugs on EBV-infected pre-malignant NK cells. METHODS: EBV-infected pre-malignant NK cells (P-NK cells) were isolated from the periphery of a patient suffering from severe hypersensitivity to mosquito bites (SHMB). Abnormal oligoclonal expansion of EBV-infected CD56(+)/CD3(-) NK cells was observed in her periphery. Effects of several antiviral drugs were examined both on the proliferation and on EBV-replication of P-NK cells. RESULTS: Vidarabine and foscarnet, but not acyclovir nor gancyclovir, significantly suppressed both the proliferation and EBV-DNA replication of P-NK cells in a dose-dependent manner, whereas these drugs did not suppress the proliferation of YT, which is an EBV-infected malignant NK cell line. The combination of vidarabine and foscarnet had an additive effect and almost completely suppressed the proliferation of P-NK cells. CONCLUSION: The present results indicate that vidarabine and/or foscarnet may be effective for preventive treatment of EBV-associated NK-GLPD.

Adolescent↗
PubMed2003

[Treatment of influenza-associated encephalopathy].

Recently, the number of reports of encephalopathy associated with influenza has increased in Japan. The abrupt onset of seizure and coma after development of high-grade fever is a prominent indicator of CNS involvement. Approximately 600 patients have been reported during 1999-2002. 78% of them are younger than 6 yr old, and the mortality was 30% in 1999 and 2000 seasons. The pathogenicity of brain dysfunction is still unknown. However, elevation of cytokines(TNF-alpha and IL-6) and the damage of vascular endothelial cells were demonstrated. Thus, the prognosis of this illness was extremely poor. Intensive care trial in combination with (1) anti-virals, (2) high dose gamma-grobulin, (3) steroid pulse therapy. (4) high dose AT III, (5) head cooling and (6) plasma exchange has started since 2001, that could reduce the mortality from 30 to 15% in 2001 and 02. In order to establish more effective treatment, further investigation will be necessary.

Antithrombin III↗
PubMed2002

Encephalitis and encephalopathy associated with an influenza epidemic in Japan.

During the winter of 1998-1999, there was an outbreak of encephalitis/encephalopathy in Japan that appeared to be associated with influenza. We conducted a national survey of the prevalence and clinical features of disease and the associated outcomes and prognostic factors related to this outbreak. A total of 202 cases were analyzed, of which 148 were diagnosed as influenza-associated encephalitis/encephalopathy on the basis of virologic analysis. Of the 148 cases studied, 130 (87.8%) were type A influenza and 17 were type B. Encephalitis/encephalopathy developed mainly in children age <5 years, either on the day that influenza signs appeared or on the next day. The major signs included altered consciousness or loss of consciousness, convulsions, cough, and vomiting. In many patients, multiple-organ failure developed, and rates of mortality (31.8%) and disability (27.7%) were high. Thrombocytopenia and severely elevated transaminase levels were factors associated with a poor prognosis. Thus, influenza-associated encephalitis/encephalopathy progressed rapidly and was associated with poor outcomes.

Aspartate Aminotransferases↗
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

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↗
PubMedDate not supplied

Fatal natural killer cell lymphoma arising in a patient with a crop of Epstein-Barr virus-associated disorders.

Natural killer (NK) lymphoma in Asia is frequently associated with latent Epstein-Barr (EBV) infection. Unlike the adult cases, EBV-associated NK/T cell lymphomas in children are often preceded by various EBV-related disorders, including chronic active EBV infection (CAEBV), hypersensitivity to mosquito bites (HMB), virus-associated haemophagocytic syndrome (VAHS), and hydroa vacciniforme (HV)-like eruptions. Here, we report a 14-year-old Japanese girl who sequentially developed all the symptoms related to EBV-associated NK/T cell lymphoproliferative disorders in a 12-year clinical course. Our observations confirm the spectrum of EBV-associated cutaneous disorders and indicate the importance of long-term follow-up.

Adolescent↗