Yoshihiro Ando

Exacerbation of Herpes Simplex Encephalitis after Successful Treatment with Acyclovir

Herpes simplex encephalitis (HSE) in children sometimes exacerbates after successful treatment; yet the frequency, etiology, and clinical features of exacerbation remain unclear. We report data for 27 children with HSE confirmed by polymerase chain reaction (PCR) analysis; all were successfully treated with acyclovir, but 7 (26%) had a relapse of encephalitic illness. In 2 of those 7, serial examination with a PCR assay showed that herpes simplex virus (HSV) DNA reappeared temporarily in the cerebrospinal fluid (CSF). For 5 of the 7 patients, a second course of acyclovir therapy was effective. Coxsackievirus A9 was isolated from CSF of 1 case patient during subsequent exacerbation. The total dose during initial acyclovir therapy was significantly lower in the relapse group than in the control group (P=.027). In conclusion, exacerbation of HSE in children may be more common than previously recognized. It is suggested that the replication of HSV or another viral pathogen caused a second encephalitic illness (HSE) in some cases.

Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection

We describe an experience of a specific immune transfer treatment in a patient with chronic active EBV infection. The patient had low anti‐EBV T cell‐mediated cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may have been the primary cause of the disease. An EBV‐specific cytotoxic T lymphocyte (CTL) line was established from PBMC obtained from the patient’s sister whose human leucocyte antigens (HLA) are identical to patients. The patient received three courses of intravenously administered CTL at 3‐week intervals. The number of the cells was increased with each course of treatment. After infusion of the T cell line, anti‐EBV CTL activity was detected in the patients PBMC. CTL activity increased markedly after the second course of immune transfer therapy. The amount of EBV DNA in the patients plasma showed transient but repeated decreases. Serum levels of tumour necrosis factor‐alpha (TNF‐α), which had elevated before treatment, began to decrease after initiation of treatment. No adverse effects were directly associated with CTL infusions. Despite having previously received a pneumococcal vaccine and prophylactic antibodies, the patient died of infection caused by Streptococcus pneumoniae bacteraemia 27 days after the third infusion. Although the long‐term efficacy and safety of this therapy remains to be established, our findings suggest that adoptive transfer of CTL specific for EBV obtained from an HLA‐matched donor might be a promising treatment for patients with chronic active EBV infection.

Relapse of neonatal herpes simplex virus infection

Background: Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. Recurrence of skin vesicles is common. Objective: To determine the features of relapse and identify the factors related to relapse. Design: Thirty two surviving patients with neonatal herpes virus infections were enrolled. All patients received acyclovir treatment. Clinical and virological data were analysed and compared between relapsed and non-relapsed cases. Results: Thirteen (41%) had either local skin or central nervous system relapse between 4 and 63 days after completing the initial antiviral treatment. Nine patients exhibited local skin relapses, and four developed central nervous system relapses. In one skin and two central nervous system relapse cases, neurological impairment later developed. Type 2 virus infection was significantly related to relapse (odds ratio 10.4, 95% confidence interval 1.1 to 99.0). Patients with relapse had worse outcomes than those without relapse. Conclusion: Neonates with HSV type 2 infections have a greater risk of relapse. Relapsed patients have poorer prognoses.

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.

Polymerase chain reaction-proved herpes simplex encephalitis in children

OBJECTIVE To investigate the clinical features in PCR-proved herpes simplex encephalitis (HSE) in children, excluding neonates. METHODS We studied the clinical manifestations and laboratory findings of 24 children in whom the diagnosis of herpes infection was confirmed by the PCR assay and compared them with those of 38 children with central nervous system infections other than HSE. RESULTS There were no significant differences between groups in the percentage with fever or convulsions, the initial neurologic symptoms or the level of consciousness. Analysis of cerebrospinal fluid showed no significant differences in the cell count or concentration of protein and glucose. Computerized tomography of the brain identified localized abnormalities in 18 (75%) of the 24 HSE patients and in 10 (31%) of the 32 non-HSE patients (P = 0.001). Periodic lateralized epileptiform discharges, abnormal findings on electroencephalography, were detected in 8 (36%) of 22 HSE patients and in none of the non-HSE patients (P = 0.0001). The rates of moderate to severe morbidity and death were significantly higher in the HSE patients than in the non-HSE patients. Of the 9 HSE patients with a Glasgow Coma Scale score > or = 11, all patients recovered completely. HSE patients younger than 3 years of age were more likely to develop severe sequelae or to die of the disorder than older patients (P = 0.02). CONCLUSIONS There were no specific clinical characteristics of HSE patients. The results of electroencephalography and computerized tomography were helpful, but not confirmatory, in diagnosing HSE. The Glasgow Coma Scale score and age significantly influenced the mortality and morbidity in the HSE patients.

Detection of cytomegalovirus DNA in preserved umbilical cords from patients with sensorineural hearing loss.

We performed a retrospective diagnostic study of congenital cytomegalovirus (CMV) infection in patients with sensorineural hearing loss (SNHL). CMV DNA in preserved umbilical cords was analyzed using real-time polymerase chain reaction analysis. Of 45 analyzable patients with SNHL, CMV DNA was detected in the preserved umbilical cords of 3 patients, all of whom had bilateral SNHL that lacked a clear onset period. CMV DNA was not detected in any of the patients with sudden SNHL or enlarged vestibular aqueduct-associated SNHL. The features of CMV-associated SNHL were more asymmetric than those of CMV-negative bilateral SNHL.

Variable-Range Hopping Conduction in Ion-Gel-Gated Electrochemical Transistors of Regioregular Poly(3-hexylthiophene)

Ion-gel-gated transistors enable controlled carrier doping into conjugated polymers in identical devices measurable at low temperatures. Using this technique, the carrier transport of regioregular poly(3-hexylthiophene) was investigated in a wide temperature range down to 15 K. At room temperature, carrier mobility exhibited an electrochemical behavior with a minimum at a doping level of approximately 0.4% and a subsequent sharp increase up to 0.5 cm 2 V -1 s -1 . At doping levels above ∼3%, the ohmic conductivity of the transistor channel deviated from thermal activation and showed a quasi-one-dimensional variable-range hopping behavior. This result indicates the enhanced carrier transport through the overlap of carrier wavefunctions developing toward a doping level of ∼10% under electrochemical doping in a transistor channel.

A novel exogenous mammary tumor virus encoding MHC class II H2E-independent superantigen specific foor Tcr-Vβ14

Similar to the superantigens encoded by endogenous mouse mammary tumor virus (MMTV) proviruses (Acha-Orbea et al. 1993), infectious MMTVs express superantigens, which are recognized by particular Tcrb-V in the context of MHC class II molecules (Marrack et al. 1991). Choi and coworkers (1991) and Acha-Orbea and co-workers (1991) have reported independently that MMTV(C3H) and MMTV(GR) encode superantigens which interact with T cells expressing Tcr-V~314. Both retroviral superantigens require exclusively MHC class II H2E expression for presentation and clonal deletion, and do not induce vigorous T-cell proliferation (Held et al. 1992). We injected partially purified virus particles from the milk of RIII mice or II TES mice, which had been established by the crossbreeding of DBA/2 with strains of Japanese pet mouse origin (NBCS-II and CS), into the footpad of adult BALB/c or C57BL/6(B6), and the V~3 repertoire was examined in the popliteal LN cells 4 days after injection by flowcytometry. As shown in Figure 1, the V~314 T cells in CD4 + LN cells were increased in BALB/c mice 4 days after injection with the II-TES or RIII milk, while V[36 T cells were decreased in these mice, presum-

Signature of the insulator–metal transition of a semicrystalline conjugated polymer in ionic-liquid-gated transistors

Critical behaviors indicating an insulator–metal (IM) transition are observed in poly(2,5-bis(3-hexadecylthiophene-2-yl)thieno[3,2-b]thiophene) [PBTTT] in ionic-liquid-gated transistors. At room temperature, a maximum channel conductivity of 300 S cm−1 is achieved at the doping concentration of 1021 cm−3. The conductivity shows a very weak temperature dependence; the conductivity at 5 K is only 1.6 times lower than that at 250 K. The signature of the IM transition at low temperatures is evidenced by the results of Zabrodskii plot analysis. The IM transition is benefitted by the semicrystalline lamellar structure of PBTTT enhanced by the substrate treatment with a self-assembled monolayer.

Acute retinal necrosis caused by herpes simplex virus type 2 in a 3-year-old Japanese boy

Acute retinal necrosis (ARN), which is characterized by rapidly progressing peripheral retinal necrosis, is caused mainly by herpes simplex virus type 1, herpes simplex virus type 2 (HSV-2), or varicella-zoster virus. A previously healthy 3-year-old Japanese boy developed ARN in his left eye after being bruised by a milk container. HSV-2 DNA was detected in the aqueous humor of the affected eye. Serological testing suggested that the route of infection was from mother to child, although there was no past history of apparent HSV-2 infection. Childhood ARN has not been previously reported in Japan, possibly because of the low seroprevalence of HSV-2 in Japanese women. Pediatricians must be aware of this rare disease, which can affect individuals without a previous history of HSV even in a country with a low seroprevalence of HSV-2.