GLI1-induced mammary gland tumours are transplantable and maintain major molecular features

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-like^Ex, Class8^Ex, Claudin-Low^Ex and Erbb2-like^Ex. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.     

A role for decorin in cutaneous wound healing and angiogenesis

Decorin is known to influence tissue tensile strength and cellular phenotype. Therefore, decorin is likely to have an impact on tissue repair, including cutaneous wound healing. In this study, cutaneous healing of both excisional and incisional full‐thickness dermal wounds was studied in decorin‐deficient (Dcn^?/?) animals. A statistically significant delay in excisional wound healing in the Dcn^?/? mice occurred at 4 and 10 days postwounding and, in incisional wounds at 4, 10, and 18 days when compared with wild‐type (Dcn^?/?) controls. Fibrovascular invasion into polyvinylalcohol sponges was significantly increased by day 18 in Dcn^?/? mice relative to Dcn^+/+ mice. The 18‐day sponge implants in the Dcn^?/? mice showed a marked accumulation of biglycan when compared with the corresponding implants in Dcn^+/+ mice. Thus, regulated production of decorin may serve as an excellent therapeutic approach for modifying impaired wound healing and harmful foreign body reactions.     

Blutzuckerbestimmung bei Ekzem,Psoriasis, Lichen Vidal und Ulcus cruris

Zusammenfassung Bei Ekzem, Psoriasis, Lichen Vidal und Ulcus cruris konnte pathologische Erhöhung des Blutzuckerspiegels im allgemeinen nicht festgestellt werden, wenn eine Glykosurie nicht vorhanden war. Beim Lichen Vidal sind die Blutzuckerwerte zwar im Bereiche normaler Grenzen, aber in einer erheblichen Anzahl niedriger als bei den anderen Untersuchten.     

Sleep length and quality,sleepiness and urinary melatonin among healthy Danish nurses with shift work during work and leisure time

Background  

Sleep problems are common effects of shift work. The aim of the present study was to evaluate how different types of shift affect sleep and sleepiness, and to relate sleepiness to urinary 6-sulfatoxymelatonin.     

Diagnostic testing for inhalant allergies.

Allergic rhinitis is one of the most commonly treated disorders seen in otolaryngology office settings. It is often difficult to distinguish the symptoms associated with allergic rhinitis from other causes of rhinitis. Many times these nasal symptoms can be effectively treated using nonspecific pharmacotherapeutic agents in conjunction with general information on ways to reduce exposure to allergens or irritants in the environment. When allergic rhinitis is suspected and a targeted treatment approach is needed, allergy testing can confirm the diagnosis and guide effective treatment for the condition. This paper discusses various methods for diagnosing inhalant allergies with a special focus on a newer approach to skin testing, known as modified quantitative testing or MQT. This paper also presents an overview of the immune response as it occurs in allergic rhinitis, along with a discussion of common inhalant allergens. Finally, this paper offers a general approach to allergy testing and patient preparation.     

Use of the 90Sr applicator for intraoperative radiation therapy in a mouse tumor model

Intraoperative radiation therapy (IORT) research is limited by the lack of small-animal models. We have implanted B16 melanoma into mouse kidneys, which we subsequently operated upon and irradiated with beta rays from a ⁹⁰Sr ophthalmic applicator. The IORT has effectively prolonged survival and produced some cures. The strategy should be applicable to other murine tumors and to other internal implantation sites.     

Tardive dyskinesia in children treated with atypical antipsychotic medications.

Recent years have witnessed increased antipsychotic treatment of children despite limited long‐term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic‐naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African–American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European–American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side‐effect profile of the atypical antipsychotic drugs in children may be much different than that in adults. © 2007 Movement Disorder Society