Masao Yoshinaga

Typical Enteroaggregative Escherichia coli Is the Most Prevalent Pathotype among E. coli Strains Causing Diarrhea in Mongolian Children

ABSTRACT Diarrhea remains one of the main sources of morbidity and mortality in the world, and a large proportion is caused by diarrheagenic Escherichia coli. In Mongolia, the epidemiology of diarrheagenic E. coli has not been well studied. A total of 238 E. coli strains from children with sporadic diarrhea and 278 E. coli strains from healthy children were examined by PCR for 10 virulence genes: enteropathogenic E. coli (EPEC) eae, tir, and bfpA; enterotoxigenic E. coli (ETEC) lt and st; enteroinvasive E. coli (EIEC) ipaH; enterohemorragic E. coli stx1 and stx2; and enteroaggregative E. coli (EAEC) aggR and astA. EAEC strains without AggR were identified by the HEp-2 cell adherence test. The detection of EAEC, ETEC, EPEC, and EIEC was significantly associated with diarrhea. The incidence of EAEC (15.1%), defined by either a molecular or a phenotypic assay, was higher in the diarrheal group than any other category (0 to 6.0%). The incidence of AggR-positive EAEC in the diarrheal group was significantly higher than in the control group (8.0 versus 1.4%; P = 0.0004), while that of AggR-negative EAEC was not (7.1 versus 4.3%). Nineteen AggR-positive EAEC strains harbored other EAEC virulence genes—aggA, 2 (5.5%); aafA, 4 (11.1%); agg-3a, 5 (13.8%); aap, 8 (22.2%); aatA, 11 (30.5%); capU, 9 (25.0%); pet, 6 (16.6%); and set, 3 (8.3%)—and showed 15 genotypes. EAEC may be an important pathogen of sporadic diarrhea in Mongolian children. Genetic analysis showed the heterogeneity of EAEC but illustrated the importance of the AggR regulon (denoting typical EAEC) as a marker for virulent EAEC strains.

Incidences of nasopharyngeal colonization of respiratory bacterial pathogens in Japanese children attending day-care centers

Background : In Japan, many younger children attending day‐care centers tend to frequently experience acute respiratory infections and prolonged otitis media.

Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.

Background—Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. Methods and Results—Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of &bgr;-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. Conclusions—Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

Prevalence of childhood obesity from 1978 to 2007 in Japan

Background:  There are few cross‐sectional and longitudinal studies on identification of the age of onset of obesity. The purpose of the present study was therefore to investigate 30 years of cross‐sectional and longitudinal changes in the prevalence of obesity from 1978 to 2007 in Japanese children and adolescents between 5 and 17 years of age, using population‐based samples.

Face immersion in cold water induces prolongation of the QT interval and T-wave changes in children with nonfamilial long QT syndrome

We investigated the relation between heart rate and the QT interval using face immersion in cold water in children with long QT syndrome (LQTS) without a family history of this condition, and in control children. The face immersion test revealed that all children with high probability of LQTS had a significantly longer QT interval than control children during face immersion, and that the test could induce T-wave alternans or a notched T-wave in all children with a high probability of LQTS.

Maternal Antibody against Toxic Shock Syndrome Toxin-1 May Protect Infants Younger than 6 Months of Age from Developing Kawasaki Syndrome

The symptoms of Kawasaki syndrome (KS) suggest a possible relationship between KS and superantigen(s). The infrequent occurrence of KS among young infants may be due to a passive maternal antibody. We investigated the antibody titers for superantigens (toxic shock syndrome toxin [TSST]-1, staphylococcal exotoxin B, and streptococcal pyrogenic exotoxins C and A) in 15 patients with KS who were <6 months of age prior to gamma globulin therapy and in 10 mothers of patients with KS <6 months of age. Significant findings were observed for only TSST-1 among the 4 anti-superantigens. The proportion of patients with KS who had high anti-TSST-1 titers was significantly higher than that among infant control subjects (33% vs. 5%, respectively; P=.031). The mean anti-TSST-1 titer for the mothers was significantly lower than that of adult control subjects (P=.021). Among infants <6 months of age, TSST-1 may be related to KS, and a maternal antibody may protect infants from developing KS.

Effect of total adipose weight and systemic hypertension on left ventricular mass in children

To investigate the effect of obesity and hypertension on left ventricular (LV) mass in children, we performed echocardiography and measured the height, weight, and blood pressure of 267 healthy children (145 boys and 122 girls) aged 12 years. The percentage of body fat was estimated using bioelectric impedance to derive the total adipose weight and lean body weight. End-diastolic measurements of LV parameters were obtained from M-mode echocardiograms. The LV mass was calculated by using the formula of Devereux et al. A strong positive correlation was demonstrated between non-normalized LV mass and height or other measures of body size. Systolic blood pressure was weakly correlated with non-normalized LV mass in boys. The impact of height on LV mass differed between boys and girls. Thus, different allometric formulas to normalize the LV mass for height were determined, using the height to the 3.1 and 1.9 powers for boys and girls, respectively. Regression analysis revealed that only total adipose weight affected the normalized LV mass, and that the effect of total adipose weight was greater in girls than in boys. The obese children had a significantly greater normalized LV mass than the nonobese children. The increase in the LV mass due to obesity appeared to be eccentric, because of the lack of an association between the indices of obesity and relative wall thickness. Our data indicate that appropriate normalization of LV mass is necessary for each study population, and that LV hypertrophy due to obesity begins in childhood.

Effect of obesity on echocardiographic parameters in children

We studied the effect of obesity on echocardiographic parameters in Japanese children. The subjects were 341 children: 106 first graders (age 6 years), 166 seventh graders (age 12 years), and 69 tenth graders (age 15 years). They were assigned to six groups according to school grade and sex. Echocardiographic parameters included thickness of the interventricular septum and of the posterior wall, end diastolic left ventricular internal dimension, and left ventricular mass. Left ventricular parameters were normalized for height, and for height to the power of 2.7. The obesity index as well as the body mass index were used to estimate obesity, because the obesity index is frequently used in Japan. There were significant correlations between the indices of obesity and left ventricular internal dimension or left ventricular mass in each group. The obesity index was more strongly correlated than the body mass index with posterior wall thickness and left ventricular internal dimension. For normalization of left ventricular parameters, correction for height was better for the first graders, whereas correction for height to the power of 2.7 was better for seventh and tenth graders. The most important finding was that the effect of obesity on left ventricular parameters was evident at 6 years of age.

A Kir3.4 mutation causes Andersen–Tawil syndrome by an inhibitory effect on Kir2.1

Objective: To identify other causative genes for Andersen–Tawil syndrome, which is characterized by a triad of periodic paralysis, cardiac arrhythmia, and dysmorphic features. Andersen–Tawil syndrome is caused in a majority of cases by mutations in KCNJ2, which encodes the Kir2.1 subunit of the inwardly rectifying potassium channel. Methods: The proband exhibited episodic flaccid weakness and a characteristic TU-wave pattern, both suggestive of Andersen–Tawil syndrome, but did not harbor KCNJ2 mutations. We performed exome capture resequencing by restricting the analysis to genes that encode ion channels/associated proteins. The expression of gene products in heart and skeletal muscle tissues was examined by immunoblotting. The functional consequences of the mutation were investigated using a heterologous expression system in Xenopus oocytes, focusing on the interaction with the Kir2.1 subunit. Results: We identified a mutation in the KCNJ5 gene, which encodes the G-protein–activated inwardly rectifying potassium channel 4 (Kir3.4). Immunoblotting demonstrated significant expression of the Kir3.4 protein in human heart and skeletal muscles. The coexpression of Kir2.1 and mutant Kir3.4 in Xenopus oocytes reduced the inwardly rectifying current significantly compared with that observed in the presence of wild-type Kir3.4. Conclusions: We propose that KCNJ5 is a second gene causing Andersen–Tawil syndrome. The inhibitory effects of mutant Kir3.4 on inwardly rectifying potassium channels may account for the clinical presentation in both skeletal and heart muscles.

Antigenic specificity of lymphocytes isolated from valvular specimens of rheumatic fever patients

T cell lines were established from both valvular specimens and peripheral blood lymphocytes from seven patients with well documented rheumatic heart disease. These cell lines were stimulated with either PHA or streptococcal antigens. Proliferation assays revealed that both valvular and peripheral blood T cell lines reacted to cell wall (CW) and cell membrane (CM) antigens obtained from rheumatic fever associated group A streptococci and not to nephritogenic strains. None of the cell lines reacted to M protein, myosin or other mammalian cytoskeletal proteins. The unique reactivity of rheumatic fever T cell lines only to cellular structures obtained from rheumatogenic strains suggests that these lines react to epitopes specific for antigens obtained from these strains.