Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

White and brown adipose tissue functionality is impaired by fine particulate matter (PM2.5) exposure

Journal of Molecular Medicine - Chronic exposure to high levels of particulate matter (PM) is correlated to a higher prevalence of cardio-metabolic disturbances. Adipose tissue represents a pivotal...     

Association of the calcitonin gene (CA) polymorphism with bone mass and bone responsiveness to hormone therapy in postmenopausal Korean women

OBJECTIVE: To evaluate the relationship between cytosine-adenine (CA) polymorphism of the calcitonin gene, serum calcitonin levels, bone mineral density (BMD) and bone responsiveness to hormone therapy (HT). DESIGN: Calcitonin (CA) polymorphism, serum calcitonin, and BMD at the lumbar spine and proximal femur were determined in 430 postmenopausal Korean women. In all, 181 women were treated with sequential HT for 2 years. RESULTS: Four major calcitonin alleles were present with a frequency greater than 5%: 122 base pair (bp) 61.3%, 108 bp 25.1%, 110 bp 7.0%, and 124 bp 6.2%. There were no differences in the BMD at the lumbar spine and proximal femur in postmenopausal women with zero, one, or two copies of major alleles. Serum calcitonin levels in women with two copies of the 108 bp allele were significantly higher than those in women with zero or one copy of the 108 bp allele. The annual rate of positive change of BMD at the femoral neck after HT was significantly higher in women homozygous for the 108 bp allele than in women with zero or one copy of the 108 bp allele, but the number of copies of the major calcitonin alleles was not significantly associated with HT-responsiveness. CONCLUSION: The calcitonin (CA) polymorphism is one of the genetic factors that may affect BMD changes at the femoral neck after HT in Korean women.     

Gentamicin-releasing urethral catheter for short-term catheterization

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization.     

Interleukin-1 beta gene polymorphism related with allergic pathogenesis in Iris constitution

Iridological constitution has a strong familial aggregation and is implicated in heredity. The aetiology of inflammatory bowel disease is still unknown. However, from genetic epidemiological studies there is considerable evidence that genetic factors are associated with both Crohn's disease and ulcerative colitis. We investigated the relationships between Iridological constitution and interleukin 1 beta (IL-1β) gene polymorphism. IL-1β is a major proinflammatiry cytokine, and the polymorphisms of this gene have been shown to be of importance in a number of diseases. Especially, IL-1 has been suspected of involvement in allergic pathogenesis. Also, IL-1β genotype is one of the genetic markers of gastric cancer. Therefore, we classified 166 individuals according to Iris constitution, and determined IL-1β genotype. The frequencies of Iris constitutions as follows: neurogenic type, 41 (24.7%); abdominal connective tissue weakness type, 53 (31.9%); cardio-renal connective tissue weakness type, 50 (30.1%); the others type, 22 (13.3%). Especially, the frequency of abdominal connective tissue weakness type was higher in C/T genotype than in the remaining constitutions although the statistical power was very weak. Furthermore, we first attempted to explore possible involvement of the IL-1β polymorphism and the Iris constitution.     

Modulation of differentiation and mineralization of marrow stromal cells cultured on biomimetic hydrogels modified with Arg-Gly-Asp containing peptides

We synthesized biomimetic hydrogels modified with an osteopontin-derived peptide (ODP) and used them as a substrate for in vitro culture of marrow stromal cells (MSCs) to investigate the effect of the biomimetic surface on differentiation of MSCs into osteoblasts. Proliferation and biological assays for 16 days proved that MSCs became differentiated into osteoblasts secreting osteogenic phenotypic markers such as alkaline phosphatase (ALP), osteopontin, and mineralized calcium. In addition, there was an additive effect of the cell-binding peptide on differentiation and mineralization of MSCs cultured in the presence of soluble osteogenic supplements in cell culture media. For example, calcium content at day 16 on peptide-modified hydrogels was significantly higher than on tissue culture polystyrene. Two general trends were observed: (1) proliferation of MSCs decreased as the amount of differentiation markers increased, and (2) higher peptide concentrations accelerated the differentiation of MSCs. On the hydrogel modified with ODP, ALP activity exhibited a maximum value of 36.7 +/- 4.2 pmol/cell/h at day 10 for the concentration of 2 micromol/g while the culture time needed for maximum ALP activity occurred on day 13 for the lower concentrations. On the same hydrogel, the calcium content at day 10 was 21.4 +/- 2.3 ng/cell for the peptide concentration of 2 micromol/g and 1.0 +/- 0.3 ng/cell for 1.0 micromol/g. We used Gly-Arg-Gly-Asp-Ser (GRGDS) for modification of the hydrogel as a comparison to the results with ODP. However, osteoblast development was not significantly affected by the nature of the binding peptide sequences. These results suggest that MSC function can be modulated by variation of the peptide concentration in biomimetic hydrogels used for scaffold-based bone tissue engineering.     

Successful liver transplantation following veno-arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: A case report

Son SK, Oh SH, Kim KM, Lee YJ, Jhang WK, Park SJ, Shin HJ, Park J‐J, Kim TH, Kim DY, Hwang S, Park K‐M, Lee Y‐J, Lee S‐G. Successful liver transplantation following veno‐arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: A case report.
Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract: Massive pulmonary hemorrhage and other serious cardiopulmonary diseases in patients with fulminant hepatitis result not only in graft failure but also mortality after LT. ECMO is used to treat children with cardiorespiratory failure refractory to conventional intensive care. We describe a five‐yr‐old girl with genetically confirmed fulminant Wilson disease and severe pulmonary hemorrhage who underwent successful primary LT following veno‐arterial ECMO. To our knowledge, this is the first report of successful primary LT in a patient using veno‐arterial ECMO. The present case demonstrates that ECMO, as a bridging modality to LT, may be necessary to manage both massive pulmonary hemorrhage and possible graft loss because of hypoxemia.     

Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.     

Phenotype–genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties

Inherited GPI (glycosylphosphatidylinositol) deficiencies (IGDs), a recently defined group of diseases, show a broad spectrum of symptoms. Hyperphosphatasia mental retardation syndrome, also known as Mabry syndrome, is a type of IGDs. There are at least 26 genes involved in the biosynthesis and transport of GPI‐anchored proteins; however, IGDs constitute a rare group of diseases, and correlations between the spectrum of symptoms and affected genes or the type of mutations have not been shown. Here, we report four newly identified and five previously described Japanese families with PIGO (phosphatidylinositol glycan anchor biosynthesis class O) deficiency. We show how the clinical severity of IGDs correlates with flow cytometric analysis of blood, functional analysis using a PIGO‐deficient cell line, and the degree of hyperphosphatasia. The flow cytometric analysis and hyperphosphatasia are useful for IGD diagnosis, but the expression level of GPI‐anchored proteins and the degree of hyperphosphatasia do not correlate, although functional studies do, with clinical severity. Compared with PIGA (phosphatidylinositol glycan anchor biosynthesis class A) deficiency, PIGO deficiency shows characteristic features, such as Hirschsprung disease, brachytelephalangy, and hyperphosphatasia. This report shows the precise spectrum of symptoms according to the severity of mutations and compares symptoms between different types of IGD.     

Placenta hominis protects osteoporosis in ovariectomized rats

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T₄) level was stimulated in OVX rats. The extracts inhibited the T₄ level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.