Yuichiro Yamashiro

Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development

This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC‐PUFA) in maternal and child health The attending investigators involved in the majority of randomized trials examining LC‐PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base.

Dissemination of Methicillin-Resistant Staphylococci among Healthy Japanese Children

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA), regarded as a tenacious pathogen in the hospital, has recently become increasingly prevalent as a community pathogen. We evaluated the prevalence and characteristics of methicillin-resistant staphylococci in the Japanese community by testing nasal samples of 818 children of five day care centers and two kindergartens in three districts. We found that methicillin-resistant staphylococci are already prevalent among healthy children. Among 818 children, 35 children (4.3%) carried MRSA and 231 children (28.2%) carried methicillin-resistant coagulase-negative staphylococci (MRC-NS). The types of staphylococcal cassette chromosome mec (SCCmec) found among 44 MRSA isolates were as follows: type IIa, 11 isolates; type IIb, 19 isolates; and type IV, 14 isolates. The type IIb SCCmec element was a new SCCmec element found in this study. Eleven (25%) strains which belonged to clonal complex 5 (CC5) carried type IIa SCCmec, and they produced type 2 coagulase and toxic shock syndrome toxin 1. They were indistinguishable from health care-associated MRSA (H-MRSA) strains in Japan, represented by strain N315. On the other hand, 33 (75%) strains, most of which belonged to CC78 or CC91, carried small SCCmec elements, such as type IIb or type IV, and they produced type 1 or type 3 coagulase and exfoliative toxin. The data indicated that MRSA clones distinct from H-MRSA have disseminated in healthy children. The fact that MRC-NS strains were prevalent in the community suggested that they might serve as a reservoir for the SCCmec element carried by MRSA strains disseminated in the community.

Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants

Abstract Background : It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases. Because bacterial populations develop during the first day of life, the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants.

The estimated incidence of cystic fibrosis in Japan.

BACKGROUND It is believed that the incidence of cystic fibrosis (CF) among Asiatic races, including the Japanese, is very rare. This epidemiological study was carried out to investigate the incidence of CF in Japan. METHODS We collected literature describing CF cases among pure Japanese and found 124 cases reported as CF during the 43 years from 1951, when the first case was reported, to 1993. Only 104 cases (57 male and 47 female patients) of 124 cases met our diagnostic criteria. RESULTS A simple calculation based on the number of reported CF cases and of live births after 1980 suggested that the incidence of CF is about 1 in 350,000 in the Japanese population. Twenty-nine (27.9% of the total) of 30 patients diagnosed in the neonatal period presented symptoms of meconium ileus, an incidence higher than that reported for the white population. CONCLUSIONS Our study results suggest that the incidence of CF in the Japanese population is even rarer than had been estimated before and that there is a genetic difference between northern European and Japanese populations.

Effects of dietary sphingomyelin on central nervous system myelination in developing rats.

Human milk contains sphingomyelin (SM) as a major component of the phospholipid fraction. Galactosylceramide (cerebroside), a metabolite of sphingolipids, increases along with CNS myelination, and is generally considered a universal marker of myelination in all vertebrates. l-Cycloserine (LCS) is an inhibitor of serine palmitoyltransferase (SPT), a rate-limiting enzyme for sphingolipid biosynthesis that is reported to show increased activity with development of the rat CNS. The present study examined the effects of dietary SM on CNS myelination during development in LCS-treated rats. From 8 d after birth, Wistar rat pups received a daily s.c. injection (100 mg/kg) of LCS. From 17 d after birth, the animals were fed an 810 mg/100g of bovine SM-supplemented diet (SM-LCS group) or a nonsupplemented diet (LCS group). At 28 d after birth, the animals were killed and subjected to biochemical and morphometric analyses. The myelin dry weight, myelin total lipid content, and cerebroside content were significantly lower in the SM-LCS and LCS groups than in a group not treated with LCS (the non-LCS group). However, these levels were significantly higher in the SM-LCS group than in the LCS group. Morphometric analysis of the optic nerve revealed that the axon diameter, nerve fiber diameter, myelin thickness, and g value (used to compare the relative thickness of myelin sheaths around fibers of different diameter) were significantly lower in the LCS group than in the other groups, but were similar in the SM-LCS and non-LCS groups. These findings suggest that dietary SM contributes to CNS myelination in developing rats with experimental inhibition of activity.

Gut Dysbiosis and Detection of “Live Gut Bacteria” in Blood of Japanese Patients With Type 2 Diabetes

OBJECTIVE Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and “live gut bacteria” in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Using a sensitive reverse transcription–quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.

Bifidobacterium breve enhances transforming growth factor beta1 signaling by regulating Smad7 expression in preterm infants.

Objectives: Transforming growth factor (TGF) &bgr;1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-&bgr; signaling. Methods: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-&bgr; signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction. Results: Serum TGF-&bgr;1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28. Conclusions: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-&bgr;1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.

Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease

Background: The use of intravenous immunoglobulin (IVIG) is well established as an initial therapy for Kawasaki disease (KD), but treatment for IVIG-resistant KD remains uncertain Aim: To analyse the effects of intravenous methylprednisolone (IVMP) pulse therapy compared with additional IVIG in IVIG-resistant patients. Methods: IVMP was administered to patients with KD who had persistent or recurrent fever after a single dose of IVIG, at Juntendo University Hospital and affiliated medical institutions between May 2003 and March 2006. The effectiveness of the treatment and the incidence of coronary lesions in patients who received IVMP and those who received additional IVIG were retrospectively analysed and compared by chart review. Results: 411 patients with KD were treated with a single dose of IVIG. Of the 63 IVIG-resistant patients, 44 were then given IVMP and 19 were given additional IVIG. Treatment was successful in 34 (77%) of the patients who received IVMP and 12 (63%) who received additional IVIG. Five of the 10 patients who did not respond to IVMP and two of the seven who did not respond to additional IVIG developed coronary artery aneurysms. Although fever initially resolved faster in the IVMP-resistant group, there was a delay in fever recurrence, which ultimately delayed the final resolution of fever. Conclusions: The findings suggest that IVMP is an effective additional treatment for IVIG-resistant KD. However, there was a tendency for fever to recur later in IVMP-resistant patients, which could potentially delay the therapeutic decision-making process.

Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis.

Background n-3 Polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for ulcerative colitis (UC). However, the efficacy of n-3 PUFAs against UC has not been examined in children. Therefore, the authors investigated the effects of eicosapentaenoic acid (EPA) on fatty acid composition and leukotriene (LT) production in children with UC. Methods For 2 months the authors administered highly purified EPA ethyl ester (EPA-E) (1.8 g/d) to children with UC in remission. Colonic mucosal histology, fatty acid composition of erythrocyte membrane phospholipids, and LTB4 production by leukocytes and colonic mucosa were measured before and 2 months after the initiation of EPA-E treatment. Results No patients relapsed during the study period, and no significant differences were detected in laboratory findings obtained before and 2 months after the initiation of EPA-E ingestion. There were no significant differences in mucosal histologic scores before and 2 months after EPA-E treatment. The EPA levels in erythrocyte membranes 2 months after the initiation of EPA-E treatment were significantly higher than before treatment, but the other fatty acids showed no significant changes. LTB4 production by leukocytes and rectal mucosa after 2 months of EPA-E treatment was significantly lower than before treatment. Conclusion EPA-E treatment increased the levels of EPA in erythrocytes and decreased LTB4 levels produced by leukocytes and colonic mucosa. To assess the concomitant clinical changes, we should examine the long-term effects of EPA-E ingestion on the maintenance of remission in children with UC.

Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies

PurposeProbiotics are expected to be effective in prophylaxis of infection in cancer patient, since infections in neutropenics are mainly caused by endogenous flora through the intestinal mucosa. However, the experience with the use of probiotics in immunocompromised patients is limited, and precise fecal bacteria analysis has not been reported. The aim of the study was to evaluate the effects of the enteral administration of the probiotic, Bifidobacterium breve strain Yakult, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy.MethodsA placebo-controlled trial was performed at Juntendo University Hospital. Patients with malignancies admitted for chemotherapy (n = 42) were randomized into two groups receiving probiotic or placebo. The effects on infectious complications, natural killer cells, fecal micro flora, fecal organic acid concentrations, and fecal pH were studied.ResultsThe frequency of fever and the use of intravenous antibiotics were lower in the probiotic group than the placebo group. The probiotic administration enhanced the habitation of anaerobes. Disruption of the intestinal microbiota after chemotherapy such as the increase in the population levels of Enterobacteriaceae was observed at more pronounced manner in the placebo group in comparison to the probiotic group. The concentrations of total organic acids were maintained most of the time at the normal level, which constantly maintained the pH below 7.0 only in the probiotic group.ConclusionThese data, although based on a limited number of patients and samples, suggest that administration of B. breve strain Yakult could be an effective approach for achieving clinical benefits in immunocompromised hosts by improving their intestinal environments.