Soluble factors from neuronal cultures induce a specific proliferation and resistance to apoptosis of cognate mouse skeletal muscle precursor cells

The mechanisms or the physiological events, which control the regeneration of skeletal muscle through muscle precursor cell multiplication and differentiation, are still largely unknown. To address the question of the involvement of neurons in this process, skeletal muscle progenitors were grown in the presence of conditioned media obtained from 3-day-old cultures of embryonic neurons (derived from either the dorsal or the ventral region of 11-day-old mouse embryos) or media conditioned with satellite cells. Strikingly, only satellite cells cultured in medium conditioned from ventral embryonic neurons exhibited increased proliferation, as well as resistance to staurosporine (STS)-induced apoptosis. Our results suggest the existence of specific anti-apoptogenic neural soluble signals, which could be involved in skeletal muscle regeneration pathways.     

Immunologic response to Haemophilus influenzae type b (Hib) conjugate vaccine and risk factors for carriage among Hib carriers and noncarriers in Southwestern Alaska

Continued Haemophilus influenzae type b (Hib) carriage in rural Alaska contributes to the ongoing risk of invasive disease. Community-wide Hib carriage surveys were conducted in three villages in southwestern Alaska. Sixteen carriers and 32 age- and village-matched controls were enrolled and were vaccinated with Hib oligosaccharide-CRM(197) conjugate vaccine. Serum immunoglobulin G (IgG) concentration, antibody avidity, and serum bactericidal activity (SBA) were measured prior to Hib vaccination and 2 and 12 months after vaccination. We identified no demographic or behavioral factors associated with Hib colonization. Prior to vaccination, Hib carriers had a higher IgG geometric mean concentration than controls did (8.2 versus 1.6 microg/ml; P < 0.001) and a higher SBA geometric mean titer (7,132 versus 1,235; P = 0.006). Both groups responded to vaccination with increased IgG and SBA. These data illustrate the role of Hib colonization as an immunizing event and show that Hib carriers in communities with ongoing transmission have no evidence of reduced immune responsiveness that may have put them at risk for colonization.     

Multiple hemangiomas in a patient with a t(3q;4p) translocation: an infrequent association with Wolf-Hirschhorn syndrome

We report on the clinical phenotype of an infant with a duplication of the terminal portion of the long arm of chromosome 3(q26.3-qter) and a deletion of the terminal portion of the short arm of chromosome 4(p16.3) with multiple hemangiomas and a hamartoma. Patients with deletions of distal 4p have the characteristic features of Wolf-Hirschhorn syndrome (WHS); whereas those with the distal duplication of 3q have a well recognized syndrome with some features resembling Cornelia-de Lange syndrome (CdLS). Neither of these recognized chromosomal anomalies has been reported previously to be associated with multiple hemangiomas or other vascular malformations.     

SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model

The aim of the study was to investigate inhibitory effects of the receptor tyrosine kinase (RTK) inhibitor SU11248 against CSF-1R and osteoclast (OC) formation. We developed an in vivo model of breast cancer metastasis to evaluate efficacy of SU11248 against tumor growth and tumor-induced osteolysis in bone. The in vitro effects of SU11248 on CSF-1R phosphorylation, OC formation and function were evaluated. Effects on 435/HAL-Luc tumor growth in bone were monitored by in vivo bioluminescence imaging (BLI), and inhibition of osteolysis was evaluated by measurement of serum pyridinoline (PYD) concentration and histology. Phosphorylation of the receptor for M-CSF (CSF-1R) expressed by NIH3T3 cells was inhibited by SU11248 with an IC50 of 50-100 nM, consistent with CSF-1R belonging to the class III split kinase domain RTK family. The early M-CSF-dependent phase of in vitro murine OC development and function were inhibited by SU11248 at 10-100 nM. In vivo inhibition of osteolysis was confirmed by significant lowering of serum PYD levels following SU11248 treatment of tumor-bearing mice (P = 0.047). Using BLI, SU11248 treatment at 40 mg/kg/day for 21 days showed 64% inhibition of tumor growth in bone (P = 0.006), and at 80 mg/kg/day showed 89% inhibition (P = 0.001). Collectively, these data suggest that SU11248 may be an effective and tolerated therapy to inhibit growth of breast cancer bone metastases, with the additional advantage of inhibiting tumor-associated osteolysis.     

A multiplex methylation PCR assay for identification of uniparental disomy of chromosome 7

Uniparental disomy of chromosome 7 (UPD7) is associated with abnormal phenotypic effects because of inappropriate expression of imprinted genes on chromosome 7. Based on the differential methylation of the promoter region of the imprinted PEG1/MEST locus at 7q32, we designed a multiplex methylation PCR (mPCR) assay to rapidly distinguish UPD7 from biparental inheritance of chromosome 7. Primers were designed to produce different sized PCR amplicons based on the parent of origin-specific methylation at this locus; electrophoresis of PCR amplicons showed a 189-bp product from the methylated maternal allele and a 109-bp product from the unmethylated paternal allele. This mPCR assay correctly predicted the chromosome 7 imprinting status in normal control and UPD7 samples. Previous assays for UPD7 required genotyping of the proband and parents, or separate maternal- and paternal-specific mPCR reactions. The advantage of this assay is that parental samples are not required and that amplification of both alleles in the same reaction is simpler and provides an internal control. This multiplex mPCR assay will be useful in screening for UPD7 in patients with Silver-Russell syndrome (SRS; also Russell-Sliver syndrome, RSS), primordial growth retardation, and in patients with supernumerary marker chromosomes or chromosome rearrangements of chromosome 7 origin.     

Who's minding the shop? The role of Canadian research ethics boards in the creation and uses of registries and biobanks

Background  

The amount of research utilizing health information has increased dramatically over the last ten years. Many institutions have extensive biobank holdings collected over a number of years for clinical and teaching purposes, but are uncertain as to the proper circumstances in which to permit research uses of these samples. Research Ethics Boards (REBs) in Canada and elsewhere in the world are grappling with these issues, but lack clear guidance regarding their role in the creation of and access to registries and biobanks.     

Differential diagnosis of chronic urticaria.

OBJECTIVES: To review diseases that can present with cutaneous signs and symptoms that mimic those observed in chronic urticaria and to discuss the workup necessary to distinguish these diseases from chronic urticaria. DATA SOURCES: We performed a PubMed search using the following keywords: urticaria, cryopyrin, Sweet syndrome, subacute cutaneous lupus, urticarial vasculitis, urticaria pigmentosa, angioedema, fixed drug eruption, bullous pemphigoid, and reticular erythematous mucinosis. Appropriate chapters in general dermatology textbooks were also reviewed. STUDY SELECTION: Articles that related to disease states, which present with persistent urticarial lesions, were catalogued for use in this review. RESULTS: Besides acute, chronic, and physical urticarias, there are 2 categories of diseases that have urticarial lesions. The first group includes those in which the skin lesions are almost indistinguishable from those seen in patients with chronic idiopathic urticaria. Thus, the diagnosis relies on a careful history and physical examination, and in some cases laboratory studies are required. The second group are ones that have skin lesions that at one point in their development have an urticaria-like appearance or on rare occasion may have such lesions. These latter diseases are numerous, and we have tried to highlight the ones that most mimic chronic idiopathic urticaria or are more common. CONCLUSIONS: A working knowledge of the diseases that can present with urticarial lesions is essential to accurately diagnose and effectively treat these symptomatic and sometimes serious conditions.     

Therapist self-disclosure in cognitive-behavior therapy

Although cognitive-behavior therapy emphasizes between-session change, therapist self-disclosure within the session can be an effective tool for strengthening the therapeutic bond and facilitating client change. After noting the use of self-disclosure in other theoretical orientations, we place self-disclosure in the context of cognitive-behavioral theories of reinforcement and modeling. Clinical vignettes illustrate the use of therapist self-disclosure to provide feedback on the interpersonal impact made by the client, enhance positive expectations and motivation, strengthen the therapeutic bond, normalize the client's reaction, reduce the client's fears, and model an effective way of functioning. Therapists need to observe appropriate boundaries when self-disclosing, and in particular, should consider their own motivations for self-disclosing. Although more research is needed on the effects of self-disclosure, cognitive-behavior therapists have found that self-disclosure can be a powerful intervention.     

Aspects of social and emotional competence in adult attention-deficit/hyperactivity disorder

Social and emotional competence were evaluated using self-report and behavioral measures in adults with attention-deficit/hyperactivity disorder (ADHD) and controls. Adults with ADHD viewed themselves as less socially competent but more sensitive toward violations of social norms than controls. Films depicting emotional interactions were used to assess linguistic properties of free recall and perceived emotional intensity. Although adults with ADHD used more words to describe the scenes, they used fewer emotion-related words, despite rating the emotions depicted as more intense than did controls. In contrast, no group differences for words depicting social or cognitive processes were observed. Overall, adults with ADHD appear more aware of their problems in social versus emotional skills. Findings may have implications for improving the psychosocial functioning of these adults.     

Prostate cancer aggressiveness locus on chromosome segment 19q12-q13.1 identified by linkage and allelic imbalance studies

Whole-genome scan studies recently identified a locus on chromosome segments 19q12-q13.11 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer-scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12-q13.11 that may play a role in both familial and non-familial forms of prostate cancer.