Two structurally different oomycete lipophilic microbe-associated molecular patterns induce distinctive plant immune responses.

Plants recognize a variety of external signals and induce appropriate mechanisms to increase their tolerance to biotic and abiotic stresses. Precise recognition of attacking pathogens and induction of effective resistance mechanisms are critical functions for plant survival. Some molecular patterns unique to a certain group of microbes, microbe-associated molecular patterns (MAMPs), are sensed by plant cells as nonself molecules via pattern recognition receptors. While MAMPs of bacterial and fungal origin have been identified, reports on oomycete MAMPs are relatively limited. This study aimed to identify MAMPs from an oomycete pathogen Phytophthora infestans, the causal agent of potato late blight. Using reactive oxygen species (ROS) production and phytoalexin production in potato (Solanum tuberosum) as markers, two structurally different groups of elicitors, namely ceramides and diacylglycerols, were identified. P. infestans ceramides (Pi-Cer A, B, and D) induced ROS production, while diacylglycerol (Pi-DAG A and B), containing eicosapentaenoic acid (EPA) as a substructure, induced phytoalexins production in potato. The molecular patterns in Pi-Cers and Pi-DAGs essential for defense induction were identified as 9-methyl-4,8-sphingadienine (9Me-Spd) and 5,8,11,14-tetraene-type fatty acid (5,8,11,14-TEFA), respectively. These structures are not found in plants, but in oomycetes and fungi, indicating that they are microbe molecular patterns recognized by plants. When Arabidopsis (Arabidopsis thaliana) was treated with Pi-Cer D and EPA, partially overlapping but different sets of genes were induced. Furthermore, expression of some genes is upregulated only after the simultaneous treatment with Pi-Cer D and EPA, indicating that plants combine the signals from simultaneously recognized MAMPs to adapt their defense response to pathogens.

Gene and cytokine profile analysis of macrolide-resistant Mycoplasma pneumoniae infection in Fukuoka, Japan.

BACKGROUND: Recent epidemiologic data suggest that the prevalence of macrolide resistant Mycoplasma pneumoniae (MR-M. pneumoniae) is increasing rapidly worldwide. This study assessed the present status of M. pneumoniae infection in Japan and clinical end-points to distinguish children with MR-M. pneumoniae. METHODS: During an outbreak of M. pneumoniae infections in Fukuoka, Japan in 2010-11, a total of 105 children with clinically suspected M. pneumoniae infection were enrolled. M. pneumoniae was analyzed for macrolide resistance in domain V of the 23S rRNA gene. Sixty -five patients with PCR positive for M. pneumoniae were analyzed with regard to clinical symptoms, efficacy of several antimicrobial agents and several laboratory data. RESULTS: Causative pathogens were detected in 81.0% (85 of 105) and M. pneumoniae was identified 61.9% (65 of 105). The resistance rate of M. pneumoniae was 89.2% (58 of 65) in this general pediatric outpatient setting. Patients infected with MR-M. pneumoniae showed longer times to resolution of fever and required frequent changes of the initially prescribed macrolide to another antimicrobial agent. We observed three different genotypes of M. pneumoniae including the rarely reported A2063T mutation (A2063G: 31 strains, A2063T: 27 strains, no mutation: 7 strains). Drug susceptibility testing showed different antimicrobial susceptibility profiles for each genotype. Serum IFN-gamma, IL-6 and IP-10 levels were higher in patients with MR-genotypes than in those infected with no-mutation strains (p < 0.001). CONCLUSIONS: Macrolide resistance is more common than previously thought and a small epidemic of rarely reported A2063T mutation was observed in Fukuoka, Japan. Furthermore our results reveal the possibility that levels of certain inflammatory cytokines may be a candidate to predict MR-M.pneumoniae infection.

Developmental changes in crossover frequency in Arabidopsis.

Parental genomes are generally rearranged by two processes during meiosis: one is the segregation of homologous chromosomes and the other is crossing over between such chromosomes. Although the mechanisms underlying chromosome segregation and crossing over are well understood because of numerous genetic and molecular investigations, their contributions to the rearrangement of genetic information have not yet been analysed at a genome-wide level in Arabidopsis thaliana. We established 343 CAPS or SSLP markers to identify polymorphisms between two different Arabidopsis ecotypes, Col and Ler, which are distributed at an average distance of approximately 400kb between pairs of markers throughout the entire genome. Using these markers, crossover frequencies and chromosome segregation were quantified with respect to sex and age. Our large-scale analysis demonstrated that: (i) crossover frequencies during pollen formation were 1.79 and 1.37 times higher than those during megaspore formation in early and late flowers, respectively (P<0.001); (ii) the crossover frequencies during pollen formation were not significantly different between early and late flowers of main shoots (P>0.05), whereas the frequencies increased 1.30 times with shoot age during megaspore formation (P<0.001); (iii) the effect of aging depended on the developmental age of the individual shoot rather than on the age of the whole plant; and (iv) five chromosomes were randomly selected and mixed during meiosis.

Extended-stay hospitalization for childhood asthma in Japan.

BACKGROUND: While recent advances in asthma management have enabled adequate control to be frequently achieved in outpatient settings, children whose asthma remains poorly controlled despite outpatient treatment are often referred to extended-stay hospitals. The aim of the present study was to examine trends concerning extended-stay hospitalization and to evaluate the present status of this approach. METHODS: A retrospective study was conducted to assess changes in the number of admissions among 408 children with extended stays at Kamiamakusa General Hospital between 1989 and 2005. Medical and laboratory data of 236 patients admitted since 1994 were obtained from clinical records. RESULTS: The number of children with extended-stay hospitalizations since 2000 declined dramatically compared with the early 1990s, while the percentage of patients with complications of childhood asthma, such as severe atopic dermatitis, school absenteeism, and obesity, have increased significantly in the recent past. Practical benefits of extended-stay hospitalization were demonstrated by significant improvement of exercise performance and measurement of pulmonary function parameters and serum IgE concentrations by time of discharge. In addition to improvement in asthmatic symptoms, maintenance drug requirements and frequency of school absenteeism were reduced. CONCLUSIONS: The medical mission of extended-stay hospitalizations is currently limited due to the availability of improved pharmacotherapy. Some patients, however, with exceptionally severe asthma or psychological problems that interact with their medical condition still fare poorly under outpatient care and could benefit from group care. Further study is needed to identify the components of long-term programs essential to produce change.

Ghrelin and leptin modulate immunity and liver function in overweight children.

BACKGROUND: The rising prevalence of obesity represents a growing worldwide public health problem. Interactions of adipocytokines and low-grade systemic inflammation presently are considered important in the development of obesity, as well as associated chronic disease including bronchial asthma, obesity-related liver disease and type 2 diabetes mellitus. The purpose of the present study was to investigate metabolic, hormonal, immunologic and inflammatory factors in overweight children and to further clarify possible immunomodulatory effects of obesity-related hormones and cytokines. METHODS: Forty-nine prepubertal overweight children and 49 age-matched controls of normal weight without underlying disease were enrolled. Levels of plasma ghrelin and serum leptin, cytokines (interleukin [IL]-4, IL-10, IL-12, 1L-13), C-reactive protein, immunoglobulin, and insulin were measured, and liver function tests were done to better understand their status in the setting of obesity. RESULTS: Overweight subjects had significantly higher measures of adiposity (body mass indexI, % body fat) and had significantly higher serum levels of IgG, IgA and IgE than non-obese children (P = 0.038, 0.0043, 0.0034, respectively); the opposite was true for IgM (P = 0.025). The incidence of presumed non-alcoholic fatty liver disease was 28.6% in overweight children. In overweight children, serum leptin levels were associated with liver function index (aspartate aminotransferase/alanine aminotransferase ratio) and serum insulin levels. Some elevated immunoglobulin levels significantly correlated with plasma ghrelin levels and liver function index. CONCLUSIONS: It is possible that appetite-regulating hormones modulate both humoral immunity and liver function. Further studies with a larger number of subjects are needed to clarify the precise mechanisms of this association.

Scale properties of the Japanese version of the Strengths and Difficulties Questionnaire (SDQ): a study of infant and school children in community samples.

The Strengths and Difficulties Questionnaire (SDQ) is a short screening instrument which addresses the positive and negative behavioral attributes of infants, children and adolescents. The SDQ is widely used to evaluate child developmental disabilities, psychological and psychiatric conditions or disorders in Japan. However, we did not have normative data for the Japanese version until now. To establish the community-based data and properties for the Japanese version, we collected and evaluated parent ratings of a total of 2899 Japanese children aged 4-12 years, including 1463 boys and 1436 girls. Statistical evaluation of psychometric properties included a factor analysis verifying the proposed scale structure, an assessment of scale homogeneities, and the determination of age, gender and relationship of each difficulties scale, or prosocial scale. The total difficulties score in boys (8.70 +/- 5.03) was higher than in girls (7.86 +/- 4.88). Based on the distributions of SDQ scores observed in the Japanese community sample, recommended bandings identifying normal, borderline, and abnormal (clinical ranges) were defined for each scale, and some gender difference was found in some difficulties and prosocial SDQ scores. After evaluating parent ratings obtained in a community-based sample, the Japanese SDQ was shown to possess favorable psychometric properties. Thus, the Japanese translation of this popular and versatile instrument seems to be approximately as reliable and useful as the original English questionnaire.

Benign infantile convulsions associated with mild gastroenteritis: a retrospective study of 39 cases including virological tests and efficacy of anticonvulsants.

Benign convulsions associated with mild gastroenteritis (CwG) are a commonly observed disorder in Asia, especially in infants and seniors. Here, we describe a retrospective study about the clinical features of CwG in 62 children hospitalized at St. Mary's Hospital (Kurume City, Japan) between January 1, 2000 and March 31, 2006, and further evaluate the efficacies of various anticonvulsant treatments for patients with CwG due to either rotavirus or norovirus. Causative diarrheal viruses were detected in 71% of the fecal specimens tested; 30 patients were positive for rotavirus, nine patients were positive for norovirus, two patients were positive for sapovirus, two patients were positive for adenovirus, and one patient was positive for coxackievirus A4. The age of onset for patients with norovirus-positive CwG (16.7+/-2.7 months) was significantly lower than that of patients with rotavirus-positive CwG (23.0+/-8.7 months). The duration of the seizures due to norovirus infection (11.8+/-12.0 h) was significantly longer than that due to rotavirus infection (4.9+/-5.7 h). There were no significant differences between the two groups with regard to the results of blood chemistry analysis, including the concentrations of serum electrolytes, blood glucose levels, and liver function tests. In this preliminary study, the duration of seizures in patients with CwG due to norovirus that was treated with carbamazepine was significantly shorter than the duration of seizures in the patients treated with another anticonvulsant (phenobarbital). Further randomized controlled studies are required to clarify the efficacies of the various anticonvulsants for patients with CwG.

Temporary expression of the TAF10 gene and its requirement for normal development of Arabidopsis thaliana.

TAF10 is one of the TATA box-binding protein (TBP)-associated factors (TAFs) which constitute a TFIID with a TBP. Initially most TAFs were thought to be necessary for accurate transcription initiation from a broad group of core promoters. However, it was recently revealed that several TAFs are expressed in limited tissues during animal embryogenesis, and are indispensable for normal development of the tissues. They are called 'selective' TAFs. In plants, however, little is known as to these 'selective' TAFs and their function. Here we isolated the Arabidopsis thaliana TAF10 gene (atTAF10), which is a single gene closely related to the TAF10 genes of other organisms. atTAF10 was expressed transiently during the development of several organs such as lateral roots, rosette leaves and most floral organs. Such an expression pattern was clearly distinct from that of Arabidopsis Rpb1, which encodes a component of RNA polymerase II, suggesting that atTAF10 functions in not only general transcription but also the selective expression of a subset of genes. In a knockdown mutant of atTAF10, we observed several abnormal phenotypes involved in meristem activity and leaf development, suggesting that atTAF10 is concerned in pleiotropic, but selected morphological events in Arabidopsis. These results clearly demonstrate that TAF10 is a 'selective' TAF in plants, providing a new insight into the function of TAFs in plants.

Case reports and literature review: the association between reactivation of human herpes virus-6 and peripheral white blood cell count in patients with carbamazepine-induced hypersensitivity syndrome.

Eruptions induced by anticonvulsants can often be experienced clinically, and the clinical diagnosis of "drug induced hypersensitivity syndrome (HS)" was proposed to characterize these drug eruptions. Reactivation of human herpes virus-6 seems to be an integral component of HS. Previously, we experienced two cases of carbamazepine (an anticonvulsant) induced HS and both cases did not show a reactivation of human herpes virus-6 infection (no elevation of anti-human herpes virus-6 IgG titres). The features of these two cases were compared with other reported cases that presented HS with the reactivation of human herpes virus-6. In the early phase of HS, a change in peripheral white blood cell count seems to be important and could be used as an indicator to predict whether late phase HS with reactivation of human herpes virus-6 will occur, since the increase in white blood cell count is seen before the increase in anti-human herpes virus-6 titres. Reactivation of human herpes virus-6 may cause severe clinical symptoms such as encephalitis. When an increase in white blood cells are observed in HS cases at onset, immediate discontinuation of cause drug and intensive care are necessary to avoid the more severe symptoms of HS.

Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the response.

BACKGROUND: Mouse monoclonal IgE antibodies can promote the survival of mouse bone marrow-derived cultured mast cells and induce the cells to secrete mediators in the absence of known specific antigen. OBJECTIVE: To determine whether human IgE, in the absence of known specific antigen, had effects on the mediator secretion or survival of human mast cells. METHODS: We tested whether human IgE induced human cord blood-derived mast cells to secrete mediators or enhanced their survival on withdrawal of stem cell factor. RESULTS: Exposure to IgE, but not IgG, at concentrations as low as 2.5 microg/mL significantly enhanced the release of IL-8 and monocyte chemoattractant protein 1, but not histamine or cysteinyl leukotrienes. However, under the conditions tested, chemokine production in response to IgE alone was significantly less than that induced when aliquots of the same IgE-sensitized populations of human mast cells were stimulated with anti-IgE. The production of IL-8 and monocyte chemoattractant protein 1 in response to either IgE alone or IgE and anti-IgE was enhanced by preincubation of the cells in IL-4 and was inhibited by preincubation of the cells with dexamethasone. By contrast, we did not detect any ability of IgE to enhance mast cell survival on withdrawal of stem cell factor. CONCLUSION: Exposure to human IgE in vitro in the absence of known specific antigen can enhance chemokine production by human mast cells, and this secretory response can be enhanced by preincubation of the mast cells with IL-4 and can be suppressed by dexamethasone.

Transient Haemophilus influenzae type b bacteremia in a healthy child.

Occult bacteremia with Streptococcus pneumoniae (S. pneumoniae) is sometimes experienced in general clinics, while that with Haemophilus influenzae type b (Hib) is less common and mostly develops to serious central nervous infection. Recently we encountered a patient with bacteremia due to Hib, in whom bacteremia recovered spontaneously without intravenous antibiotic therapy. A previously healthy 17-month-old girl was brought to our hospital with the complaint of high fever. Although her clinical condition did not present any of meningeal signs, the laboratory data on the first day showed prominent leukocytosis and sepsis work-up was done. Two days later (third day of illness), blood culture grew Haemophilus influenzae sensitive to ampicillin and the strain isolated from blood was identified as Hib. The febrile condition soon disappeared and bacteremia resolved with the negative result of the next blood culture. It is not clear about the precise mechanisms of this phenomenon, however, it is an extremely rare case for Hib bacteremia to resolve spontaneously.

Transcriptional response of human mast cells stimulated via the Fc(epsilon)RI and identification of mast cells as a source of IL-11.

BACKGROUND: In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (Fc(epsilon)RI). RESULTS: One to two hours after Fc(epsilon)RI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2-200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130-529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE. CONCLUSION: Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the Fc(epsilon)RI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the Fc(epsilon)RI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma.