Relationships Between Adipokine Profiles, Physique Index, and Severity of Bronchiolitis in Infancy.

INTRODUCTION: Relationships between adipokines, adiposity and severity of acute viral bronchiolitis in infancy have not been elucidated. MATERIALS AND METHODS: We investigated the relationships between three serum adipokines (leptin, adiponectin and TNF-α), physique index (Kaup index) and clinical severity in 13 bronchiolitis infants. Seven healthy infants were enrolled as the control group. We used Modified Pulmonary Index Score (MPIS) to evaluate bronchiolitis severity. RESULTS: No significant differences in adipokine levels were found between groups. In bronchiolitis infants, Kaup index negatively correlated with MPIS (r = -0.614, p = 0.03). A positive correlation was observed between the serum leptin/adiponectin ratio and MPIS (r = 0.618, p = 0.03), although correlations were not observed between respective serum adipokines levels and MPIS. Serum leptin and adiponectin had significantly negative correlations with age (r = 0.815, p = 0.001 and r = 0.566, p = 0.04, respectively), but not Kaup index. CONCLUSION: The severity of viral bronchiolitis in infancy may be related to the adipokine profile, but not adiposity.

[Safety and efficacy in two-dose vaccination using measles and rubella combined (MR) vaccine].

Measles and rubella combined (MR) vaccine and two-dose-vaccination have been used in Japan since 2006. only children undergoing monovalent measles and rubella vaccination undergo a second vaccination. We intend to administer MR vaccine twice to Japanese children from 2011, so studied the safety and efficacy of two-dose MR vaccination. Subjects were 75 pre school children undergoing MR vaccine manufactured by Biken at one year old in a clinical trial. Children were observed for adverse events for 28 days after the second MR vaccination. Efficacy was determined by measuring antibodies for measles and rubella before and after (six to eight weeks later) the second vaccination. Results showed that fever frequency decreased significantly from 27.3% to 14.9% (p < 0.05), and eruption decreased from 12.2% to 6.8% from the first to the second vaccination, whereas, the frequency of redness and swelling at the inoculation site increased from 7.3% to 10.8% and 2.9% to 8.1%. Differences are not statistically significant. Measles antibody titer determined by NT assay and rubella antibody titer measured by HI assay increased significantly from prevaccination to postvaccination (p < 0.0001). Measles antibodies measured by NT and EIA assays and rubella antibody measured by HI assay turned positive in all subjects after the second MR vaccination. In conclusion, two-dose MR vaccination should be safe and effective in eliminating measles and rubella in Japan.

HIV-2 amino acid substitutions in Gag and Env proteins occurring simultaneously with viral load upsurge in a drug-naïve patient.

It has been reported that the peptides of human immunodeficiency virus type 2 (HIV-2) most frequently recognized by cytotoxic T lymphocytes are firstly in Gag and secondly in Env proteins. In the present case study, we attempted to observe amino acid substitutions in Gag and Env proteins and related parameters possibly associated with an increase in HIV-2 load. A sudden, eightfold, increase in HIV-2 load occurred in a drug-naïve patient with human leukocyte antigen-B*5801 during the last phase of a longitudinal observation period from months 29 to 40. The genetic diversity of Gag and Env increased gradually prior to the HIV-2 load increase. The proportions of synonymous substitutions in both Gag and Env were greater than the proportions of nonsynonymous substitutions at every sampling point for 40 months, and the net charge of the V3-loop increased from months 29 to 40. Three amino acid substitutions (V2861 in Gag, K303T and N337 K/R in Env) were observed from months 29 to 40. Only one amino acid substitution (V286I) was observed with an increase in HIV-2 load in the Gag region where the clustering of epitopes was reported. These results suggest that the sites encompassing these three substituted positions are candidates for HIV-2 epitopes, although further careful examinations will be required.

Human cytomegalovirus genetic variability in strains isolated from Japanese children during 1983-2003.

The genetic variability of 74 human cytomegalovirus (HCMV) clinical isolates from 60 Japanese infants and children during 1983-2003 was investigated, and the relevance to their clinical course was studied. The patients consisted of 10 asymptomatic congenitally infected babies, 45 infected perinatally or postnatally resulting in HCMV mononucleosis/hepatitis and 5 immunocompromised hosts. The hypervariable region of the HCMV genome, that is the a sequence and UL144 region was analyzed using the polymerase chain reaction (PCR) and unrooted phylogenetic trees. HCMV glycoprotein B (gB) polymorphism was also studied. Unrooted phylogenetic trees of a sequence and UL144 allowed the isolates to be grouped to 5 and 3 clades, respectively. Three gB genotypes were also determined. However, there was no correlation between specific genotypes of these three genes and clinical forms, except for congenital infection which fell into one of three clades of the UL144 gene. In addition, the variability of the three genes had no correlation with each other. This implies that study of a single gene is insufficient for investigating the molecular epidemiology of HCMV. This study provides basic data on the genetic variability of HCMV in an Asian population and should help to determine the strains for vaccine candidates.

Etiological agents of lower respiratory tract infections in Japanese children.

To investigate the etiology of pediatric community-acquired pneumonia and bronchitis, we conducted a prospective, population-based study covering the total population < 15 years of age in 16 municipalities in Hokkaido, Japan, during the period of April 2000 to March 2001. Chest radiographs were available for all cases (n = 921; 398 as pneumonia and 523 as bronchitis) and paired sera for serologic assays were available for more than half of the cases. The following specimens were also collected: nasopharyngeal swabs for viral, bacteriological, mycoplasmal and chlamydial studies, blood for serology and blood culture. The children were then followed-up on days 3, 7 and 14. Specific infecting organisms were identified in a total of 853 (92.6%) out of 921 patients (398 cases of pneumonia and 523 cases of bronchitis) including 205 with mixed infection as follows: Mycoplasma pneumoniae, 252 (274%) patients; respiratory syncytial (RS) virus, 188 (20.4%); influenza A virus, 110 (11.9%); Streptococcus pneumoniae, 95 (10.3%); Haemophilus influenzae, 90 (9.8%); Haemophilus parainfluenzae, 35 (3.8%); Staphylococcus aureus, 29 (3.1%); adenovirus, 27 (2.9%); Moraxella catarrhalis, 12 (1.3%); Pseudomonas aeruginosa , 7 (0.8%); Chlamydia pneumoniae, 6 (0.7%); and other agents, 2 (0.2%). Mycoplasma infections were seen even in patients less than 5 years and RS and influenza A virus infections in patients more than 5 years of age. The importance of M. pneumoniae and RS virus in the etiology of lower respiratory infections in Japanese children was confirmed.

Frequency of human cytomegalovirus-specific T cells during pregnancy determined by intracellular cytokine staining.

The characteristics of cytomegalovirus (CMV)-specific T-cell immunity was investigated in pregnant women with primary, latent, or reactivated CMV infection, and in a comparative group of non-pregnant women. Forty-six pregnant and 8 non-pregnant women were examined based on the presence of serum antibody activity against CMV and viral excretion in urine. The frequency of CMV-specific CD4(+) T cells in peripheral blood lymphocytes was determined by staining for intracellular cytokines, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. There was no change in the frequencies of CMV-specific CD4(+) T cells in CMV-seropositive normal non-pregnant and pregnant women at any gestation. However, the frequency of CMV-specific CD4(+) T cells in pregnant women associated with CMV reactivation or reinfection was significantly higher than in CMV-seropositive normal pregnant and non-pregnant women. There were no CMV transmissions to the infants of all these women. These CMV-specific T cells responses in pregnant women may contribute some to block the intrauterine CMV infection in their infants.

Human cytomegalovirus infection during pregnancy and detection of specific T cells by intracellular cytokine staining.

OBJECTIVE: The flow cytometric assay was evaluated as a tool for real-time monitoring of human cytomegalovirus (HCMV)-specific cellular immunity in pregnant women. METHODS: We screened for HCMV infection in pregnant women in Sapporo, Japan, during the year 2000, by serologic assays, virus isolation from urine, and PCR to detect DNA in cervical swabs. The frequencies of HCMV-specific CD4+ T cells in pregnant women with serum anti-HCMV IgG antibody were detected by intracellular cytokine (ICC), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) staining. RESULTS: The levels of intracellular cytokines in pregnant women with serum anti-HCMV IgG antibody were significantly higher than those in women without anti-HCMV IgG antibody (P = 0.011 for IFN-gamma and P = 0.023 for TNF-alpha) but lower than those in non-pregnant women with serum anti-HCMV IgG antibody. Frequencies of HCMV-specific CD4+ T cells were higher in infants with symptomatic congenital infection than in infants with asymptomatic perinatal infection. CONCLUSIONS: This ICC assay may reflect immunologic activity against HCMV infection in pregnant women with immunosuppressive conditions.

Intracranial calcification with congenital rubella syndrome in a mother with serologic immunity.

We report a case of an infant with congenital rubella. The mother had received rubella vaccine at the age of 13 years. Rubella serology was performed on day 34 of pregnancy and the result was interpreted as being a positive titer. The patient was a girl born by cesarean section owing to intrauterine growth retardation and fetal distress after 37 weeks' gestation. A computed tomographic scan at 4 days of age showed several cortical low-density areas and calcifications of the periventricular area and basal ganglia. Magnetic resonance imaging (MRI) performed at 4 weeks of age showed almost similar findings. The infant had serum IgG and IgM antibodies against rubella. Rubella virus ribonucleic acid (RNA) was detected from the serum, urine, and cerebrospinal fluid of the infant. At 2 months of age, the patient showed severe bilateral hearing loss. At 12 months of age, she had mild mental retardation and developmental delay.

Immunological evaluation and clinical aspects of children with congenital cytomegalovirus infection.

To determine the ability of immunological response to human cytomegalovirus (CMV), the flow cytometric assay was evaluated as a tool for real-time monitoring of specific cellular immunity in children with congenital CMV infection. Longitudinal cohort study of 2 children with asymptomatic and 2 with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. Frequencies of CMV-specific CD4 (+) T cell in these children were detected by intracellular cytokines (ICC), interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, staining. Findings detected by CT and MRI were the most sensitive predictor for neurodevelopmental prognosis. Frequencies of CMV-specific CD4(+) T cells detected by ICC, both IFN-gamma and TNF-alpha, were higher in 2 children with symptomatic congenital CMV infection than those in 2 children with asymptomatic congenital infection. Frequencies of CMV-specific CD4(+) T cells in 2 children with symptomatic congenital infection were significantly higher than those in 6 healthy children of 1 to 5-years of age with serum anti-CMV IgG antibody without serum anti-CMV IgM antibody and viral excretion in to urine (p < 0.01). The ICC assay reflects immunological activity against CMV infection in children with asymptomatic or symptomatic congenial infection. Categorizing findings obtained by the ICC assay may helps to determine the prognosis of children with congenital CMV infection.