Evaluation of the indirect and IgM-capture anti-human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity.

Primary cytomegalovirus (CMV) infection during pregnancy often results in congenital CMV infection with severe clinical complications. IgM antibodies are one of the indices of primary infection. The IgG avidity index (AI) is also known to remain low for 3 months after primary infection.

Congenital cytomegalovirus in Japan: More than 2 year follow up of infected newborns.

Background: The aim of this study was to evaluate the outcome of congenital cytomegalovirus (CMV) infection identified on urine-filter screening assay at >2 years' follow up, and to observe the clinical outcomes after anti-CMV treatment.

Methods: Sixty of 72 congenital CMV patients were enrolled and clinically observed for >2 years. Forty-three were asymptomatic at birth; seven were symptomatic at birth but untreated with anti-CMV drugs; and 10 were symptomatic and treated with anti-CMV drugs.

Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

Objectives: To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences.

Study Design: Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening.

A Thr72Ala polymorphism in the NKG2D gene is associated with early symptomatic congenital cytomegalovirus disease.

The potential risk factors for congenital cytomegalovirus (cCMV) infection or development of disease remain unclear. Here, we investigated the genetic polymorphisms in natural killer (NK) group 2, member D (NKG2D), an activating receptor expressed on NK cells, and in MHC class I-related chains A, the ligand of NKG2D, in 87 cCMV cases, and found that there was a significant association between cCMV disease and a single nucleotide polymorphism, Thr72Ala, in NKG2D.

Construction of a scoring system for predicting the risk of severe gastrointestinal involvement in Henoch-Schönlein Purpura.

Objective: To evaluate the parameters associated with significant gastrointestinal (GI) involvement in Henoch-Schönlein Purpura (HSP), and construct a scoring system for the identification of patients at high risk of gross blood in stools.

Study Design: Data for HSP patients hospitalized at each of seven institutes were retrospectively analyzed. Patients were divided into four groups according to the consequent severity of GI involvement.

Cytomegalovirus (CMV) glycoprotein H-based serological analysis in Japanese healthy pregnant women, and in neonates with congenital CMV infection and their mothers.

Background: Congenital cytomegalovirus (CMV) infection is caused by maternal primary infection as well as CMV reinfection or reactivation during pregnancy, although differences in the clinical impact between these modes of infection remain to be clarified.

Objectives: To investigate the latest prevalence and risk of multiple CMV infection in healthy pregnant women, as well as the types of maternal CMV infection associated with congenital CMV infection.

Study Design: Seroprevalence against CMV and IgG subclasses were determined in 344 serum samples from healthy pregnant women in Japan.

Polymorphisms in TLR-2 are associated with congenital cytomegalovirus (CMV) infection but not with congenital CMV disease.

Background: Cytomegalovirus (CMV) is the most common cause of congenital virus infection. However, the risk factors for infection in utero and for progression to a severe clinical outcome remain uncertain. Recent studies have identified associations of specific single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes with susceptibility to infections of some viruses and with their clinical outcome.

Sequential changes in pathophysiology of systemic inflammatory response in a disseminated neonatal herpes simplex virus (HSV) infection.

Background: Disseminated neonatal herpes simplex virus (HSV) infection causes a typical systemic inflammatory response syndrome and has a high mortality rate. However, the validity of anti-inflammatory intervention against this condition remains unknown.

Objectives: We sought to demonstrate the sequential changes in the pathophysiology of disseminated neonatal HSV infections.

A novel real-time PCR method for determination and quantification of each cytomegalovirus glycoprotein H subtype in clinical samples.

To investigate reinfection in patients with congenital cytomegalovirus (CMV) infection, we established a CMV subtype-specific real-time quantitative PCR method targeting the CMV gH epitope region that can be used for evaluating pathogenic CMV strains in cases of mixed CMV infection.

Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study.

Background As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs). Objectives To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection.

Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother.

Background: Intrauterine transmission of cytomegalovirus (CMV) can occur even in CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly acquired CMV strain during pregnancy had a major role in such transmission. Although reactivation of latently infected CMV is another plausible cause, no direct evidence has been documented.

Dried umbilical cords in the retrospective diagnosis of congenital cytomegalovirus infection as a cause of developmental delays.

To clarify the impact of congenital cytomegalovirus (CMV) infection on developmental disabilities, 20 children with disabilities of unknown cause were analyzed. Five children were CMV positive and had no clinical manifestations at birth. Intracranial calcification was observed in 4 cases.

Genetic linkage among human cytomegalovirus glycoprotein N (gN) and gO genes, with evidence for recombination from congenitally and post-natally infected Japanese infants.

Investigation of sequence polymorphisms in the glycoprotein N (gN; gp4273), gO (gp4274) and gH (gp4275) genes of human cytomegalovirus (HCMV) strains collected from 63 Japanese children revealed that their gO genotype distribution differed slightly from that of Caucasian populations and that there was a significant linkage between the gN and gO genotypes. Linkage of these genotypes in strains obtained from Caucasian populations has been reported, so our similar findings in Japanese infants are consistent with this, and suggest generality of this linkage. Sequence analysis suggests that recombination between two strains of different linkage groups occurred approximately 200 bp upstream of the 3'-end of the gO gene.

Establishment of a cell-based assay for screening of compounds inhibiting very early events in the cytomegalovirus replication cycle and characterization of a compound identified using the assay.

To simplify the detection of infectious human cytomegalovirus (HCMV), we generated a cell line that produced luciferase in a dose-dependent manner upon HCMV infection. Using this cell line, we identified anti-HCMV compounds from a diverse library of 9,600 compounds. One of them, 1-(3,5-dichloro-4-pyridyl)piperidine-4-carboxamide (DPPC), was effective against HCMV (Towne strain) infection of human lung fibroblast cells at a 50% effective concentration of 2.

Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children.

Human cytomegalovirus (CMV) is the leading cause of intrauterine viral infection. The association of genetic polymorphisms in some particular genes with the incidence and severity of congenital infection has been controversial. To address this issue, we analyzed the genotypes of the glycoprotein B (gB), UL144 and UL149 genes of CMV clinical strains obtained from 33 congenitally and 31 postnatally infected Japanese children.

Evaluation of screening tests for congenital cytomegalovirus infection.

Although the use of dried blood spots has been proposed for screening of newborns with congenital cytomegalovirus infection, viral loads in blood were significantly smaller than those in urine (P < 0.001), and DNA recovery from dried blood spots using the thermal shock procedure was inefficient. In contrast, our urine-based screening program identified asymptomatic cases with low viral loads in blood.

Etiology of severe sensorineural hearing loss in children: independent impact of congenital cytomegalovirus infection and GJB2 mutations.

Background: Sensorineural hearing loss (SNHL) is the most common congenital disease. Longitudinal studies of infants with congenital cytomegalovirus (CMV) infection have demonstrated an association between CMV and SNHL. However, because of the lack of suitable neonatally collected specimens, the proportion of CMV-associated SNHL has not been defined, nor has the relationship between CMV and the major genetic causes of SNHL, such as mutations in the GJB2 gene.

Real-time PCR assay using specimens on filter disks as a template for detection of cytomegalovirus in urine.

Since congenital cytomegalovirus (CMV) infection causes late-onset sequelae, the identification of CMV-infected newborns is important. For this purpose, we established a simple real-time PCR assay using a filter disk. Combined with the collection of urine using filter papers placed in the diaper, this assay can make CMV screening more feasible and cost-effective.

Undetected Bacillus pseudo-outbreak after renovation work in a teaching hospital.

A 602-bed capacity hospital underwent complete renovation from 1999 to 2004. In April 2005, the Infection Control Team was informed of the occurrence of three consecutive cases of Bacillus cereus bacteremia in a ward for patients with hematologic malignancies. A retrospective analysis of patients with Bacillus isolates was initiated.

Characterization of entry mechanisms of human herpesvirus 8 by using an Rta-dependent reporter cell line.

To analyze the mechanisms of entry of human herpesvirus 8 (HHV-8), we established a reporter cell line T1H6 that contains the lacZ gene under the control of the polyadenylated nuclear RNA promoter, known to be strongly activated by a viral transactivator, Rta. We found that infection with cell-free virus, as well as cocultivation with HHV-8-positive primary effusion lymphoma cell lines, activated the lacZ gene of T1H6 in a sensitive and dose-dependent manner. Addition of Polybrene and centrifugation enhanced, but polysulfonate compounds inhibited, the HHV-8 infectivity.