Features of wound healing shown by fibroblasts obtained from the superficial and deep dermis

Dermal fibroblasts (DF) obtained from the superficial dermal layer and those from the deep dermal layer have different cellular functions. These differences are often associated with excessive scarring; they also influence early wound healing. We therefore investigated the differences between superficial and deep dermal fibroblasts with special emphasis on their contractile properties, and ability to produce connective tissue. We investigated their proliferation kinetics, ability to contract collagen lattices, and chronological mRNA expression of eight genes associated with wound healing. To estimate the changes in the differences between them during the early phase of wound healing, we investigated mRNA expression in bFGF supplemented medium because bFGF is a representative cytokine that is familiar to clinicians. Superficial DF proliferate faster than deep DF in culture, whereas deep DF are better at contracting collagen lattices than superficial ones. In realtime analysis of polymerase chain reaction, the expression of type I and III collagen, fibronectin, TGF β1 and β3, and connective tissue growth factor were higher in deep DF than in superficial DF, while the expression of TGF β2 was higher in superficial DF. After bFGF supplementation, the relative dominance of mRNA expression between superficial and deep DF remained constant except for the expression of collagenase. According to our analysis, deep DF are superior to superficial DF at promoting wound healing (particularly contraction and production of connective tissue). The intradermal distribution of DF is appropriate for efficient wound healing.     

How functions in leg development during Drosophila metamorphosis.

The Drosophila how gene encodes a KH RNA binding protein with strong similarity to GLD-1 from nematodes and QK1 from mice. Here, we investigate the function of how during metamorphosis. We show that how RNA and protein are present in a variety of tissues, and phenotypic analyses of how mutants reveal multiple lethal phases and defects during metamorphosis. In addition to previously reported abnormalities in muscle and wing development, how mutants exhibit defects in leg development. how mutant leg imaginal discs undergo cell shape changes associated with elongation, but are oriented improperly, do not evert normally, and often remain incased in peripodial epithelium longer than normal. Consequently, how mutants exhibit short, crooked legs. Our findings suggest that how functions in interactions between imaginal epithelium, peripodial epithelium, and larval epidermal cells during imaginal disc eversion.     

Autism Under Age 3 Years: A Clinical Study of 28 Cases Referred for Autistic Symptoms in Infancy

Twenty-eight children referred with a preliminary diagnosis of autistic disorder under age 3 yrs were extensively examined from the neuropsychiatric point of view and followed up for several months to several years. A diagnosis of autistic disorder was confirmed in 75% of the cases. A variety of associated medical conditions was identified. It was concluded that autism can be diagnosed in a substantial proportion of cases before age 3 yrs and that the neurobiological background is similar to that seen in older autistic children.     

Online Availability Check of Teleradiology Components

For a region-wide teleradiology network in Germany a vendor-independent Uptime-server concept was defined. The Uptime-server was realized for the availability check and prospective error-detection of the emergency teleradiology servers and clients based on encrypted digital imaging and communication in medicine (DICOM)-e-mail transfers. The concept and the experiences of 2 years of use with more than 30 clients and servers in 15 hospitals and in nine other regional partners are shown. The Uptime-server does provide automated availability checks for all servers and clients, automated checks of the download speed of the Internet lines, and a graphical user interface for the clinical user and the system administrator. A clinical user can display the availability information from all clients and servers in the network (see ). In case of malfunctions during an emergency transfer, immediate reactions are possible, often without the need for help of a hotline or a system administrator. The chosen Uptime-server concept proofed to be reliable; it worked with products from nine different manufacturers without problems. Its statistical output can be used to fulfill the legal requirements of regular availability checks for teleradiology lines.     

Differing lung function development in infants with univentricular hearts compared with healthy infants

Aim: To compare the difference in lung function development of healthy controls and patients with univentricular hearts from birth prior to surgery and during the first year of life when cardiac shunt procedures and the cavopulmonary connection are required. Methods: Tidal flow‐volume measurements and single‐occlusion tests were performed from birth serially up to 18 months of age on 28 unsedated spontaneously breathing infants with univentricular hearts and 58 healthy control infants. Results: Infants with univentricular heart physiology had low tidal volumes, low compliance of the respiratory system and high respiratory rate at birth, which over time normalized, whereas the peak expiratory flow increased during the study period. The lung function measured at birth was predictive of later lung function measurements. Conclusion: The pattern of lung function development is different in the patients with univentricular hearts compared to healthy controls. Lung function measured at birth is predictive of later lung function.     

Peptide-based immunotherapy: a novel strategy for allergic disease

The T-cell component of the antigen-specific immune response is the target of various novel interventions to modify chronic immunologic disorders, such as allergic diseases. Recent clinical trials have evaluated the safety and efficacy of therapeutic vaccines consisting of short, synthetic, allergen-derived peptides, corresponding to T-cell epitopes from the eliciting antigen. The main advantage of such an approach is the reduction in systemic, immunoglobulin E-mediated adverse events compared with existing whole allergen immunotherapy, often referred to as 'allergy shots'. T-cell peptide epitopes, although capable of inducing immunologic tolerance, are short linear structures that have reduced ability to cross-link mast cell- and basophil-bound immunoglobulin E. The precise mechanism of tolerance induction remains incompletely defined. However, recent data indicate that peptide therapy induces/expands a population of antigen-specific regulatory T-cells. A novel form of treatment combining efficacy with a substantially decreased occurrence of adverse events is likely to have a major impact on the management and prevalence of allergic diseases. Furthermore, the principles of epitope-specific therapy hold promise for the development of therapeutic vaccines for the treatment of autoimmune diseases.     

Methylation of Bone SOST,Its mRNA,and Serum Sclerostin Levels Correlate Strongly With Fracture Risk in Postmenopausal Women

Inhibition of sclerostin, a glycoprotein secreted by osteocytes, offers a new therapeutic paradigm for treatment of osteoporosis (OP) through its critical role as Wnt/catenin signaling regulator. This study describes the epigenetic regulation of SOST expression in bone biopsies of postmenopausal women. We correlated serum sclerostin to bone mineral density (BMD), fractures, and bone remodeling parameters, and related these findings to epigenetic and genetic disease mechanisms. Serum sclerostin and bone remodeling biomarkers were measured in two postmenopausal groups: healthy (BMD T‐score > –1) and established OP (BMD T‐score < –2.5, with at least one low‐energy fracture). Bone specimens were used to analyze SOST mRNAs, single nucleotide polymorphisms (SNPs), and DNA methylation changes. The SOST gene promoter region showed increased CpG methylation in OP patients (n = 4) compared to age and body mass index (BMI) balanced controls (n = 4) (80.5% versus 63.2%, p = 0.0001) with replication in independent cohorts (n = 27 and n = 36, respectively). Serum sclerostin and bone SOST mRNA expression correlated positively with age‐adjusted and BMI‐adjusted total hip BMD (r = 0.47 and r = 0.43, respectively; both p < 0.0005), and inversely to serum bone turnover markers. Five SNPs, one of which replicates in an independent population‐based genomewide association study (GWAS), showed association with serum sclerostin or SOST mRNA levels under an additive model (p = 0.0016 to 0.0079). Genetic and epigenetic changes in SOST influence its bone mRNA expression and serum sclerostin levels in postmenopausal women. The observations suggest that increased SOST promoter methylation seen in OP is a compensatory counteracting mechanism, which lowers serum sclerostin concentrations and reduces inhibition of Wnt signaling in an attempt to promote bone formation. © 2014 American Society for Bone and Mineral Research.