Reduction in the colonization of Staphylococcus aureus on the skin surface under calcium-/magnesium-depleted conditions.

Excessive expansion of Staphylococcus aureus is associated with several skin diseases, including atopic dermatitis (AD). Recently, we have demonstrated that washing skins with ultra-pure soft water containing little bivalent metal ions improved skin conditions of atopic subjects. In this study, we investigated the roles of calcium or magnesium on the proliferation of S. aureus both in vitro and in vivo. Depletion of calcium and magnesium in the culture medium significantly suppressed the expansion of S. aureus growth. When S. aureus, diluted with water containing calcium/magnesium at the concentration of medium-hard water (83·0 mg l-1 as CaCO3 ) or the one that contains little calcium/magnesium, was applied onto the tape-stripped skin of Hos:HR-1 mice, growth of S. aureus in water without those minerals on the skin was suppressed. These results suggest that depletion of both calcium and magnesium abrogate the proliferation of S. aureus not only in the culture system but also on the skin surface of mice. Since colonization of S. aureus on the skin is well-known to exacerbate AD symptoms, usage of ultra-pure soft water containing less calcium and magnesium may improve the skin condition through the suppression of S. aureus growth on the skin of patients with skin problems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the importance of calcium and magnesium for the colonization and growth of Staphylococcus aureus by using both in vitro culture systems and in vivo experiments on the murine skin. Our results indicate that the removal of these metal ions is probably beneficial for protecting the skin from S. aureus. Thus, using ultra-pure soft water without metal ions may improve the skin condition of patients with skin problems through the protection from S. aureus colonization.

Linoleic acid salt with ultrapure soft water as an antibacterial combination against dermato-pathogenic Staphylococcus spp.

AIMS: Skin colonization of Staphylococcus spp. critically affects the severity of dermatitis in humans and animals. We examined different types of fatty acid salts for their antibacterial activity against Staphylococcus spp. when used in ultrapure soft water (UPSW). We also evaluated their therapeutic effect on a spontaneous canine model of dermatitis. METHODS AND RESULTS: UPSW, in which Ca(++) and Mg(++) were replaced with Na(+) , was generated using a water softener with cation-exchange resin. Staphylococcus aureus (Staph. aureus), Staphylococcus intermedius (Staph. intermedius), and Staphylococcus pseudintermedius (Staph. pseudintermedius) were incubated with various fatty acid salts in distilled water (DW) or UPSW and the number of bacteria was counted. Among the fatty acids, oleic acid salt and linoleic acid (LA) salt reduced the number of these bacteria. Also, UPSW enhanced the antibacterial effect of LA on Staph. spp. In spontaneously developed itchy dermatitis in companion dogs, shampoo treatment with liquid soap containing 10% LA in UPSW improved skin conditions. CONCLUSIONS: LA salt showed antibacterial activity against Staph. spp. Treatment with soap containing LA with UPSW reduced clinical conditions in dogs with dermatitis. SIGNIFICANCE AND IMPACT OF THE STUDY: Because colonization of Staph. spp. on the skin exacerbates dermatitis, the use of LA-containing soap in UPSW may reduce unpleasant clinical symptoms of the skin.

Coffin-Siris syndrome is a SWI/SNF complex disorder.

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.

Transient neonatal diabetes mellitus in an extremely preterm infant.

The present report concerns transient neonatal diabetes mellitus in an extremely preterm infant (gestational age 27 weeks, birth weight 718 g). The patient had intrauterine growth retardation and developed hyperglycaemia on the first day of life. Insulin administration was discontinued on the 89th day of life, which was 1 day before the original due date. This case suggests that (a) insufficient insulin secretion started at least from the second trimester of the pregnancy, and (b) the duration needed for recovery of insulin secretion was not dependent on the maturity.

Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome.

Mutations in the X-linked MECP2 gene cause Rett syndrome, a neurodevelopmental disorder that exclusively affects girls. Females with the MECP2 mutations exhibit a broad spectrum of clinical presentations ranging from classical Rett syndrome to asymptomatic carriers, which can be explained by differences in X chromosome inactivation (XCI). Here, we report a family with a girl with Rett syndrome in whom a novel missense mutation in the MECP2 gene was transmitted through the maternal germ line. The carrier mother was asymptomatic and presented non-random XCI in the peripheral blood cells, which resulted in the X chromosome harboring the mutant allele that was predominantly active. Thus, the presence of non-random XCI in the peripheral blood cells did not provide an explanation for the normal phenotype of the carrier mother. This result suggests that mechanisms other than XCI may contribute to the phenotypic heterogeneity associated with MECP2 mutations.

Transient neonatal diabetes mellitus in extremely preterm infant.

A report of transient neonatal diabetes mellitus in an extremely preterm infant (gestational age 27 weeks, birth weight 718 g). The patient had intrauterine growth retardation and developed hyperglycaemia on the first day of life. Insulin administration was discontinued on the 89th day of life, which was 1 day before the original due date. This case suggests that (a) insufficient insulin secretion started at least from the second trimester of the pregnancy; (b) the duration needed for recovery of insulin secretion was not dependent on the maturity.

Hutchinson-Gilford progeria syndrome with severe skin calcinosis.

We describe a case of Hutchinson-Gilford progeria syndrome (HGPS) with long-term follow-up. A 1-month-old girl with marked sclerodermatous skin changes developed various symptoms of HGPS during follow-up. These included sclerotic skin, pigmentation, skin atrophy with translucent veins, wispy hair and alopecia, nail dystrophy and decreased sweating. Marked skin calcinosis was observed over almost the entire body, a symptom that has apparently been ignored in the literature. At 16 years old, the girl underwent surgery for a skull fracture and subdural haematoma, which was followed by chronic ulceration. Wet dressing with insulin-like growth factor was used with considerable effect. Mutation of the lamin A/C (LMNA) gene mutation, which encodes nuclear lamin A and C, has been reported to be the cause of HGPS. Our case showed the mutation G608G (GGC-->GGT), which resulted in a cryptic splice site and consequently in a truncated lamin A/C protein.

A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes.

The main hallmark of diabetic nephropathy is elevation in urinary albumin excretion. We performed a genome-wide linkage scan in 63 extended families with multiple members with type II diabetes. Urinary albumin excretion, measured as the albumin-to-creatinine ratio (ACR), was determined in 426 diabetic and 431 nondiabetic relatives who were genotyped for 383 markers. The data were analyzed using variance components linkage analysis. Heritability (h2) of ACR was significant in diabetic (h2=0.23, P=0.0007), and nondiabetic (h2=0.39, P=0.0001) relatives. There was no significant difference in genetic variance of ACR between diabetic and nondiabetic relatives (P=0.16), and the genetic correlation (rG=0.64) for ACR between these two groups was not different from 1 (P=0.12). These results suggested that similar genes contribute to variation in ACR in diabetic and nondiabetic relatives. This hypothesis was supported further by the linkage results. Support for linkage to ACR was suggestive in diabetic relatives and became significant in all relatives for chromosome 22q (logarithm of odds, LOD=3.7) and chromosome 7q (LOD=3.1). When analyses were restricted to 59 Caucasian families, support for linkage in all relatives increased and became significant for 5q (LOD=3.4). In conclusion, genes on chromosomes 22q, 5q and 7q may contribute to variation in urinary albumin excretion in diabetic and nondiabetic individuals.

Bayesian joint prediction of associated transcription factors in Bacillus subtilis.

Sigma factors, often in conjunction with other transcription factors, regulate gene expression in prokaryotes at the transcriptional level. Specific transcription factors tend to co-occur with specific sigma factors. To predict new members of the transcription factor regulon, we applied Bayes rule to combine the Bayesian probability of sigma factor prediction calculated from microarray data and the sigma factor binding sequence motif, the motif score of the transcription factor associated with the sigma factor, the empirically determined distance between the transcription start site to the cis-regulatory region, and the tendency for specific sigma factors and transcription factors to co-occur. By combining these information sources, we improve the accuracy of predicting regulation by transcription factors, and also confirm the sigma factor prediction. We applied our proposed method to all genes in Bacillus subtilis to find currently unknown gene regulations by transcription factors and sigma factors.

Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide data.

MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis at the transcriptional level. We assess the accuracy of a fold-change analysis, Bayesian networks, dynamic models and supervised learning based on coregulation in predicting gene regulation by sigma factors from gene expression data. To improve the prediction accuracy, we combine sequence information with expression data by adding their log-likelihood scores and by using a logistic regression model. We use the resulting score function to discover currently unknown gene regulations by sigma factors. RESULTS: The coregulation-based supervised learning method gave the most accurate prediction of sigma factors from expression data. We found that the logistic regression model effectively combines expression data with sequence information. In a genome-wide search, highly significant logistic regression scores were found for several genes whose transcriptional regulation is currently unknown. We provide the corresponding RNA polymerase binding sites to enable a straightforward experimental verification of these predictions.

The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome.

A gene for Methyl-CpG binding protein 2 (MECP2), which locates Xq28, was recently found to be responsible for Rett syndrome. Although mutational analyses of MECP2 in Rett syndrome have been extensively analyzed, the mechanism(s) by which variable clinical phenotype occurred between affected monozygotic twins or sisters have not been clarified. We hypothesized that the difference of X-inactivation pattern might explain this phenomenon. With the method based on methylation-specific PCR, we analyzed polymorphic trinucleotide repeat in the human andorogen receptor gene mapped on Xq11.2-12, using DNA samples derived from previously described monozygotic twins and sisters together with their parents. Their clinical phenotypes were reported to be significantly different between siblings. We found that (1) maternally derived allele is predominantly active than paternally derived one in three out of four patients analyzed, (2) remaining one twin patient, whose ratio of active paternal allele is almost the same level as maternal allele, showed far much severe phenotype when compared with her counterpart. Together with the finding that most of the alleles with de novo mutation are from paternal X chromosome in sporadic cases, the existence of a mechanism that suppresses mutated paternal allele activation, resulting skewed X-inactivation to make clinical phenotype milder, might be speculated. Thus, when this mechanism fails to work sufficiently by an unknown reason, severer clinical phenotype could occur.

Two-generation reproductive toxicity study of tributyltin chloride in male rats.

A 2-generation reproductive toxicity study of tributyltin chloride (TBTCl) was conducted in male rats using dietary concentrations of 5, 25, and 125 ppm TBTCl to evaluate its effect on sexual development and the reproductive system. F1 males were killed on postnatal day 119 and F2 males were killed on postnatal day 91. TBTCl affected the male reproductive system of rats. The weights of the testis and epididymis were decreased and homogenization-resistant spermatid and sperm count were reduced mainly in the 125 ppm TBTCl group. Histopathologic changes were also observed in the testis of this group and included vacuolization of the seminiferous epithelium, spermatid retention, and delayed spermiation. However, the changes were minimal in nature. The weight of the ventral prostate was decreased to 84% of the control value in the 125 ppm group in the F1 generation and decreased to 84 and 69% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. The serum 17beta-estradiol concentration was also decreased to 55% of the control value in the 125 ppm group in the F1 generation and decreased to 78 and 57% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. However, the serum concentrations of luteinizing hormone (LH) and testosterone were not decreased in these groups. These changes corresponded with those caused by aromatase inhibition and therefore TBTCl might be a weak aromatase inhibitor in male rats.