Efficacy and safety of breast milk eye drops in infants with eye discharge.

AIM: Breast milk (BM) contains various protective components, such as immunoglobulins, lactoferrin, lysozyme, oligosaccharides and immune cell subsets. We evaluated the effectiveness of BM eye drops in infants with eye discharge in a randomised controlled study. METHODS: Subjects were breastfed infants aged ≤180 days, with eye discharge. We randomly assigned patients to receive eye drops of BM or sodium azulene sulphonate hydrate 0.02% ophthalmic solution (OS). The patients received drop of BM or OS for 7 days. Improvement score of eye discharge in the groups was compared using a non-inferiority test. RESULTS: The number of patients improved eye discharge was 119/155 (76.8%) and 119/157 (75.8%) in BM and OS groups, respectively. There were no significant differences between groups. The improvement score in eye discharge was 1.76 ± 0.91 in the BM group and 1.71 ± 0.96 in the OS group. The BM group was considered non-inferior to the OS group. CONCLUSIONS: This study demonstrated that BM is no less effective than OS in infants with eye discharge aged ≤6 months. The results suggested that the use of breast milk as eye drops could be considered as a first-line treatment for infants aged ≤6 months with eye discharge.

Plasmacytoid dendritic cell dysfunction caused by heat stress is improved by administration of Lactococcus lactis strain plasma in mice.

Plasmacytoid dendritic cells (pDCs) are crucial in anti-viral immunity, acting as regulators in both adaptive and innate immunity. In this study, brief heat stress caused a decrease in splenic pDC activity in mice. Administration of Lactococcus lactis strain Plasma (LC-Plasma) significantly suppressed the decrease in pDC activity and IFN-α production. Abbreviations: LC-Plasma: Lactococcus lactis strain Plasma; LAB: lactic acid bacteria; pDC: plasmacytoid dendritic cell; IFN: interferons; mDC: myeloid dendritic cells.

Effectiveness of maternal influenza immunization in young infants in Japan.

BACKGROUND: Infants with influenza, particularly those younger than 1 year of age, are at high risk of developing a severe case or of dying. Recently, owing to the spread of pandemic influenza A (H1N1) 2009, the Advisory Committee on Immunization Practices recommended maternal immunization to reduce the risk of influenza infection in pregnant women and infants. Such reporting is rare in Japan. The aim of this study was therefore to investigate the effect on the newborn of influenza vaccination of pregnant women in Japan. METHODS: The study included 200 infants who were born to healthy mothers at Kobayashi Ladies Clinic during influenza season from November 2010 to April 2011. The incidence of fever and laboratory-confirmed influenza was assessed in the infants for the 6 months after their birth. RESULTS: Of the 200 infants, four were excluded from this study due to loss to follow up. The 106 infants in the group whose mothers received the influenza vaccine (vaccinated group) before parturition were compared with the 90 infants in the group whose mothers did not receive the influenza vaccine (non-vaccinated group). Fever was noted in 36 infants (34.0%) in the vaccinated group and in 47 infants (52.2%) in the non-vaccinated group (P < 0.007), and the incidence of influenza was 0 (0%) and 5 (5.6%), respectively (P = 0.019). The incidence of fever and influenza among infants was significantly lower in the vaccinated group compared with the non-vaccinated group. CONCLUSIONS: Maternal influenza immunization should be actively recommended in Japan to protect newborns from influenza viruses.

Effects of oral intake of plasmacytoid dendritic cells-stimulative lactic acid bacterial strain on pathogenesis of influenza-like illness and immunological response to influenza virus.

Lactococcus lactis ssp. lactis JCM5805 has been shown to be a rare lactic acid bacterium that can activate plasmacytoid dendritic cells in both murine and human species. In this study, we carried out a randomised placebo-controlled double-blind experiment to evaluate its effect on the pathogenesis of influenza-like illness during the winter season. A total of 213 volunteers were divided into two groups, which received either yogurt made with L. lactis JCM5805 or a placebo beverage daily for 10 weeks. In the JCM5805 group, the cumulative incidence days of 'cough' and 'feverishness', which are defined as major symptoms of an influenza-like illness, were significantly decreased compared with the placebo group. In addition, peripheral blood mononuclear cells prepared from volunteers were cultured in the presence of inactivated human influenza virus A/H1N1 (A/PR/8/34). IFN-α elicited by A/H1N1 tended to be higher in the JCM5805 group compared with the placebo group, and an IFN-α-inducible antiviral factor, interferon-stimulated gene 15 (ISG15), elicited by A/H1N1 was significantly higher in the JCM5805 group compared with the placebo group after the intake period. These results suggest that intake of JCM5805 is able to prevent the pathogenesis of an influenza-like illness via enhancement of an IFN-α-mediated response to the influenza virus.

Immunomodulatory effect of Lactococcus lactis JCM5805 on human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play a crucial role in anti-viral immunity through production of large amounts of interferons (IFNs). A previous study revealed the existence of lactic acid bacteria that directly stimulate pDCs in mice. In this study, we demonstrated that Lactococcus lactis JCM5805 activates human pDCs and induces IFN production in vitro. In addition, our randomized, placebo-controlled, double blind test showed that yogurt fermented with L. lactis JCM5805 activated pDC activity in vivo. This effect was greater in low pDC subjects, and their ability to produce IFNs was increased from the beginning. Furthermore, the risk of morbidity from the common cold was suppressed in the L. lactis JCM5805 group compared with the placebo group. In conclusion, intake of L. lactis JCM5805 can directly activate pDCs and increase the ability to produce IFNs in vivo. Therefore, L. lactis JCM5805 may be a beneficial tool to enhance anti-viral immunity in humans.

Increase of child car seat temperature in cars parked in the outpatient parking lot.

BACKGROUND: A guideline for the safe use of child car seats (CS) was published by the Japan Pediatric Society in 2008. There have been few studies of the increase of temperature of a CS in parked cars. The aim of this study was to determine the change in the temperature of the CS in cars parked in full sun. METHODS: The temperature of CS was measured during summer (July and August) in 2006, 2007, and 2008. The CS used in this study (n= 50) were for children (≤ 6 years old) who were taken by car to Sugimura Children's Medical Clinic. Temperatures were only measured on sunny days. Measurements were performed from 09.00 to 17.00 hours. Thermochron (Thermochron i-Button: G type, Maxim Integrated Products, CA, USA) was used to measure the temperatures. The maximum temperatures of CS were compared in time at the clinic, taking into consideration seat colors, and car colors. RESULTS: Of the 50 cars, three cars were excluded due to being in the shade while the temperature was measured. A total of 47 cars were used for this study. The temperature of the CS ranged from 38.0 to 65.5°C (47.8 ± 5.8°C). Eighteen CS (38.3%) reached a temperature of 50°C or above. The maximum temperature of the 13.00-15.00-hours group was significantly higher than that of the 09.00-11.00-hours group (P= 0.035). The CS temperatures in the black car group were significantly higher than those of the white car group (P= 0.013). CONCLUSION: CS may become very hot while a car is parked in sun, especially if the car and the CS are black, so the CS should be cooled before a young child is placed in it. Guardians of small children should be aware of this risk.

Association between the frequency of disposable diaper changing and urinary tract infection in infants.

BACKGROUND: Often diapers are not changed after infants pass urine. AIM: To define the association between the frequency of changing diapers and urinary tract infection (UTI) in infants. METHODS: Urine samples were tested in 131 infants (aged from 2 months to 2.5 years) who had a temperature > or =38 degrees C. The authors investigated the number of times diapers were changed daily. A total of 128 infants, excluding 3 cases, were divided into 2 groups: group A, without UTI (n = 96); group B, with UTI (n = 32). The number of times diapers were changed was compared between the groups. RESULTS: In group A and group B, the number of times diapers were changed daily were 7.5 +/- 1.4 and 4.7 +/- 1.4, respectively. The number of times diapers were changed was significantly lower (P < .0001) in group B than in group A. CONCLUSIONS: Among infants wearing disposable diapers, there is an increased risk of UTI as the frequency of changing diapers decreases.

Effects of recombination on hitchhiking diversity in the Brassica self-incompatibility locus complex.

In self-incompatibility, a number of S haplotypes are maintained by frequency-dependent selection, which results in trans-specific S haplotypes. The region of several kilobases (approximately 40-60 kb) from SP6 to SP2, including self-incompatibility-related genes and some adjacent genes in Brassica rapa, has high nucleotide diversity due to the hitchhiking effect, and therefore we call this region the "S-locus complex." Recombination in the S-locus complex is considered to be suppressed. We sequenced regions of >50 kb of the S-locus complex of three S haplotypes in B. rapa and found higher nucleotide diversity in intergenic regions than in coding regions. Two highly similar regions of >10 kb were found between BrS-8 and BrS-46. Phylogenetic analysis using trans-specific S haplotypes (called interspecific pairs) of B. rapa and B. oleracea suggested that recombination reduced the nucleotide diversity in these two regions and that the genes not involved in self-incompatibility in the S-locus complex and the kinase domain, but not the S domain, of SRK have also experienced recombination. Recombination may reduce hitchhiking diversity in the S-locus complex, whereas the region from the S domain to SP11 would disfavor recombination.

Administration of Lactococcus lactis strain Plasma induces maturation of plasmacytoid dendritic cells and protection from rotavirus infection in suckling mice.

Lactococcus lactis subsp. lactis JCM 5805 (LC-Plasma) is a strain of lactic acid bacteria (LAB) that activates murine and human plasmacytoid dendritic cells (pDCs) to express interferons (IFNs). Oral administration of LC-Plasma drastically decreased fatality levels caused by parainfluenza virus infection in a murine model. In this study, we investigated the anti-viral effects of oral administration of LC-Plasma using a suckling mouse model of rhesus rotavirus (RV) infection. LC-Plasma-fed mice showed improvement in retardation of body weight gain, fecal scores, and a reduction in RV titer in the feces when compared to control mice. The mechanism of anti-viral effects elicited by LC-Plasma administration was investigated using naive mice: in the LC-Plasma -fed mice, lamina propria (LP) pDCs resident in the small intestine were significantly matured and the proportion of pDCs was increased. The expression levels of anti-viral factors induced by IFNs, such as Isg15, Mx1, Oasl2 and Viperin, and an anti-bacterial factor Reg3γ, were up-regulated in the small intestinal epithelial cells (IECs) of LC-Plasma-fed mice. The specific LAB strain may affect the anti-viral immunological profile of IECs via maturation of LP pDCs, leading to protection from RV virus infection in vivo.

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice.

The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1ß gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs.

Gene conversion from SLG to SRK resulting in self-compatibility in Brassica rapa.

Self-compatible S-54 homozygotic plants were found in progenies of an F(1) hybrid cultivar in Chinese cabbage. Pollination tests revealed that this self-compatibility is controlled by the S locus and caused by the loss of the recognition function of the stigma. SRK, the gene for the recognition molecule in the stigma, was normally transcribed and translated in the self-compatible plants. The 1034-bp region in the receptor domain of SRK in the self-compatible plants was 100% identical to SLG in S-54, while that in self-incompatible S-54 homozygotic plants was 95.1% identical. These results suggest that the self-compatibility of the S-54 homozygotes is due to amino-acid changes caused by gene conversion from SLG to SRK.

Relation of the Timing of Onset of Rhinitis and Cough to Asthma Attack in Children.

If the risk of progression to asthma could be predicted in patients with rhinitis, prevention of asthma might become possible. The purpose of this study was to clarify the relationship between the duration of rhinitis symptoms and acute asthma attacks in children with a history of asthma who were not on treatment for asthma. In 94 children with a history of asthma who were asymptomatic after completing asthma treatment, we investigated the onset and duration of nasal discharge and cough related to allergic rhinitis. Then the children were followed up for 2 weeks and were classified into either an asthma attack group (Group A) or non-asthma group(Group B). A total of 78 subjects were evaluated after 16 were excluded. The duration of nasal discharge was significantly shorter in Group A than in Group B (5.5±1.9 days vs. 10.4±3.1 days, P<0.0001). The interval between the onset of cough and nasal discharge was -1.0±3.1 days in Group A and -5.7±4.1 days in Group B (P<0.0001). The risk of progression to asthma attack may be higher when the onset of cough precedes nasal discharge or when nasal discharge has a short duration and cough shows an early onset. These results may provide assistance when selecting patients for early anti-allergy therapy from among those presenting with upper respiratory tract symptoms.

Sequential follow-up results of catheter intervention for coronary artery lesions after Kawasaki disease: quantitative coronary artery angiography and intravascular ultrasound imaging study.

BACKGROUND: The purpose of this study was to assess the sequential follow-up results of catheter intervention in Kawasaki disease by use of quantitative coronary angiography (QCA) and intravascular ultrasound imaging. METHODS AND RESULTS: Catheter intervention was performed on 23 stenotic lesions in 22 patients (aged 2 to 24 years). Percutaneous balloon angioplasty (PBA) was performed in 4 patients, stent implantation in 7, percutaneous transluminal coronary rotational ablation (PTCRA) in 10, and a combination of PTCRA with stent implantation in 2. A total of 21 lesions (91%) were successfully dilated by catheter intervention without major or minor complications. One patient immediately underwent coronary artery bypass grafting (CABG) surgery because stent implantation failed to resolve his lesion. At 4 to 6 months after catheter intervention, 2 restenotic lesions (9%) were detected by QCA in 2 patients who had undergone PBA, and these patients subsequently underwent CABG surgery. In 6 months to 3 years after catheter intervention, no patients showed evidence of ischemic findings. At 3 to 4 years after catheter intervention, QCA and intravascular ultrasound studies were performed on 15 lesions in 14 patients. Two restenotic lesions (13%) were detected by QCA in 2 patients. One of the 2 had stent implantation and underwent CABG surgery, and the other had undergone PTCRA and underwent re-PTCRA. Thirteen patients demonstrated no ischemic findings at 3 to 8 years after catheter intervention. CONCLUSION: Catheter intervention for Kawasaki disease can be accomplished and can be effective in the short term, but the long-term efficacy should be verified by further study.

Oral administration of Lactococcus lactis subsp. lactis JCM5805 enhances lung immune response resulting in protection from murine parainfluenza virus infection.

When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer's patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo.

Spherical lactic acid bacteria activate plasmacytoid dendritic cells immunomodulatory function via TLR9-dependent crosstalk with myeloid dendritic cells.

Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-α that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-pathogenic microbiota that are in wide industrial dietary use, such as lactic acid bacteria (LAB). In this study, we screened for LAB strains, which induce pDC activation and IFN-α production using murine bone marrow (BM)-derived Flt-3L induced dendritic cell culture. Microbial strains with such activity on pDC were absent in a diversity of bacillary strains, but were observed in certain spherical species (Lactococcus, Leuconostoc, Streptococcus and Pediococcus), which was correlated with their capacity for uptake by pDC. Detailed study of Lactococcus lactis subsp. lactis JCM5805 and JCM20101 revealed that the major type I and type III interferons were induced (IFN-α, -ß, and λ). IFN-α induction was TLR9 and MyD88-dependent; a slight impairment was also observed in TLR4(-/-) cells. While these responses occurred with purified pDC, IFN-α production was synergistic upon co-culture with myeloid dendritic cells (mDC), an interaction that required direct mDC-pDC contact. L. lactis strains also stimulated expression of immunoregulatory receptors on pDC (ICOS-L and PD-L1), and accordingly augmented pDC induction of CD4(+)CD25(+)FoxP3(+) Treg compared to the Lactobacillus strain. Oral administration of L. lactis JCM5805 induced significant activation of pDC resident in the intestinal draining mesenteric lymph nodes, but not in a remote lymphoid site (spleen). Taken together, certain non-pathogenic spherical LAB in wide dietary use has potent and diverse immunomodulatory effects on pDC potentially relevant to anti-viral immunity and chronic inflammatory disease.

Effect of oral sodium cromoglycate in 2 children with food-dependent exercise-induced anaphylaxis (FDEIA).

UNLABELLED: Food-dependent exercise-induced anaphylaxis (FDEIA) was prevented from recurring in 2 children by sodium cromoglycate (SCG) before intake of the causative food. CASE 1: A 14-year-old girl who had suffered recurrent symptoms of anaphylaxis when she exercised after lunch. Radioallergosorbent test (RAST) was 1.49 UA/mL for wheat. She was advised to take SCG before lunch. In 2007, she ate bread at lunchtime without taking SCG and developed anaphylaxis. After this, she always took SCG and did not develop anaphylaxis. CASE 2: A 9-year-old boy who had recurrent symptoms of anaphylaxis when he exercised after lunch. RAST was 0.46 UA/mL for wheat. He started taking SCG before lunch. In June 2008, he forgot to take SCG and ate fu (a food made from wheat). He exercised after lunch and developed anaphylaxis. Since then, he has always taken SCG and has not developed anaphylaxis. CONCLUSION: Our findings suggest that SCG prevents FDEIA caused by wheat allergy.

Improved antibody responses in infants less than 1 year old using intradermal influenza vaccination.

BACKGROUND: Antibody response to influenza vaccine is limited in early. Infants have poorer hemagglutination-inhibiting antibody responses than 12-month-old. Intradermal administration reportedly elicited immune responses similar to or better than a standard intramuscular dose. We hypothesized that intradermal injection could achieve a better response in infants than subcutaneous injection. METHODS: We randomized 34 healthy infants 6-12 months old to either intradermal immunization (0.1 ml of trivalent influenza vaccine containing at least 3 microg of hemagglutinin antigen per strain) or subcutaneous immunization (also 0.1 ml). Changes in hemagglutination inhibition titer were compared using Mann-Whitney U-test, changes in positivity rate, seroconversion, and seroprotection. Local and systemic adverse events were assessed. RESULTS: All 32 infants received both injections. Antibody titers on days at 42 after intradermal injection were significantly greater than subcutaneous injection (P=0.032 in A/New Caledonia (H1N1), 0.019 in A New York (H3N2) and 0.044 in B/Shanghai. Positive titers for A New York (H3N2) were attained significantly more often after intradermal (73.3%) than subcutaneous injection (23.5%) on day 28, and significantly more often 42 days after intradermal injection (93.3% for A/New Caledonia (H1N1) and 73.3% for B/Shanghai) than after subcutaneous injection. Positive rates for other stains were similar between groups on days 28 and 42. Seroconversion rates were similar between groups. Seroprotection on day 42 for A New York (H3N2) was significantly greater in the intradermal (86.7%) than in the subcutaneous group (35.3%). Seroprotection rates for other stains were similar. CONCLUSIONS: Intradermal administration to infants of two doses of influenza vaccine was more immunogenic than subcutaneous injection. Seroconversion and seroprotection rates remained insufficient. Further study of route, quantity, and frequency are needed to improve of responses in infants.

Suppression of gene expression of a recessive SP11/SCR allele by an untranscribed SP11/SCR allele in Brassica self-incompatibility.

Mutations in the S locus of a self-compatible cultivar Yellow Sarson in Brassica rapa, which has a self-compatible class-I S haplotype, S-f2, were investigated. S-28 in Brassica oleracea was found to be a member of an interspecific pair with S-f2 in B. rapa. The original S haplotype of S-f2 was identified to be S-54 in B. rapa. Sequence comparison of alleles in S-f2 with those in S-54 and B. oleracea S-28 revealed insertion of a retrotransposon-like sequence in the first intron of SRK and 89-bp deletion in the promoter region of SP11. No transcripts of SRK and SP11 were detected in S-f2 homozygotes, suggesting that the insertion and the deletion in SRK and SP11, respectively, caused the loss of the function of these genes. Promoter assay using transgenic plants indicated that the SP11 promoter of S-f2 has no activity. Heterozygotes of S-f2 and a normal class-II S haplotype, S-60, in B. rapa were found to be self-compatible. Interestingly, transcription of SP11-60 was revealed to be suppressed in the S-f2/S-60 heterozygotes, suggesting that an untranscribed class-I SP11 allele suppresses the expression of a recessive class-II SP11 allele in the anthers of S heterozygotes. Similar phenomenon was observed in heterozygotes of a self-compatible class-I S haplotype and a self-incompatible class-II S haplotype in B. oleracea.