How relevant is panallergen sensitization in the development of allergies?

Panallergens comprise various protein families of plant as well as animal origin and are responsible for wide IgE cross‐reactivity between related and unrelated allergenic sources. Such cross‐reactivities include reactions between various pollen sources, pollen and plant‐derived foods as well as invertebrate‐derived inhalants and foodstuff. Here, we provide an overview on the most clinically relevant panallergens from plants (profilins, polcalcins, non‐specific lipid transfer proteins, pathogenesis‐related protein family 10 members) and on the prominent animal‐derived panallergen family, tropomyosins. In addition, we explore the role of panallergens in the sensitization process and progress of the allergic disease. Emphasis is given on epidemiological aspects of panallergen sensitization and clinical manifestations. Finally, the issues related to diagnosis and therapy of patients sensitized to panallergens are outlined, and the use of panallergens as predictors for cross‐reactive allergy and as biomarkers for disease severity is discussed.     

Neoadjuvant treatment of endometrial cancer using anastrozole: A randomised pilot study

Objective

Excessive oestrogenic stimulation is a well-known risk factor for the development and progression of endometrial cancer. Aromatase is the key enzyme which catalyses the conversion of androgens to oestrogens in postmenopausal women. Inhibition of aromatase may therefore be a useful strategy in the management of endometrial cancer. A pilot study was designed to assess the feasibility of a neoadjuvant model and understand the biological effects of anastrozole, an aromatase inhibitor, in the treatment of endometrial cancer.

Methods

Patients with endometrial cancer who consented to participate in the study were randomised to receive anastrozole or placebo for a minimum of 14 days prior to definitive surgery. Endometrial samples were obtained before and after treatment. Immunohistochemistry was performed to ascertain the expression of oestrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR), ki-67 and Bcl2 before and after treatment in glands and stroma of the endometrium.

Results

A total of 16 patients were randomised to the anastrozole arm and 8 to the placebo arm (2:1 randomisation). A significant decrease in the glandular expression of ERα and AR was observed in the anastrozole arm. There was no significant change in the expression of PR or Bcl2. Expression of ki-67, a proliferation marker, also decreased significantly following treatment with anastrozole.

Conclusions

Treatment with anastrozole caused a significant decrease in proliferation as demonstrated by decreased ki-67 expression. A large randomised controlled trial is warranted to fully assess the role of anastrozole in the neoadjuvant treatment of endometrial cancer.     

Coinheritance of two rare genodermatoses (Papillon-Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study

The co-occurrence of two rare recessive genetic conditions in apparently unrelated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultaneously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syndrome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both families were tested for polymorphisms at eight microsatellite markers spanning both CTSC and TYR loci. Independent mutations (c.318-1G-->A and c.817G-->C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chromosome bands 11q14.2-14.3, and studies with linked genetic markers suggested that the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism.     

Investigation of intercellular matrix macromolecules involved in lichen sclerosus

Dermal changes of the vulva in lichen sclerosus were compared with control vulvar samples using ultrastructural and immunofluorescence techniques. Collagen degeneration and regeneration were observed ultrastructurally in the superficial dermis of lichen sclerosus with increased amounts of ground substance. These processes appeared to alter the affinity of collagen fibres for the anticollagen antisera types I, III, IV. A decrease in elastin content was observed by electron microscopy. A loss of fibronectin was discovered at the dermo-epidermal junction, which looked normal ultrastructurally. The linear laminin pattern at the dermo-epidermal junction was also altered. These results suggested an enzymatic process in the pathogenesis of lichen sclerosus. Amidase activity could be determined in 6 normal and 6 pathological biopsies, though higher in the pathological samples (p less than 0.01).     

Evaluation of eIF4E expression in an osteosarcoma-specific tissue microarray

The ability to define osteosarcoma (OS) patients at greatest risk for metastatic progression and nonresponsiveness to conventional therapy is currently not possible. Such biomarkers are needed to predict overall prognosis, probability of metastases at diagnosis, and response to chemotherapy. The tissue microarray (TMA) serves as a powerful tool for detecting and validating protein biomarkers across a variety of patients. We constructed a novel outcome-linked TMA to add to and address shortcomings of currently available OS tissue resources. To test the use of our TMA, we surveyed the expression of eukaryotic initiation factor 4E (eIF4E) in OS patients using immunohistochemistry. Aberrant regulation of translation initiation is a feature of many cancers. eIF4E is central to initiation of protein synthesis. Its expression and activity have been implicated in tumor formation and potentially malignant and/or metastatic progression in some carcinomas. We found that eIF4E was uniformly expressed in OS patient samples. No association was found between eIF4E and outcome in OS patients. This novel OS TMA provided a facile mechanism to assess the role of a relevant protein biomarker in OS.     

Prescribed regimen intensity in diverse youth with type 1 diabetes: role of family and provider perceptions

Recent literature suggests that disparities in prescribed treatments may exist for youth with type 1 diabetes. There is limited research to date examining factors associated with prescribed regimen intensity in this population. In this study, we examined racial/ethnic differences in regimen intensity and predictors of regimen intensity in youth with type 1 diabetes. We expected that minority youth would have less intensive regimens and that caregiver and physician perceptions would be associated with regimen intensity. This cross-sectional study included 178 families of 10- to 17-yr-old youth at three endocrinology clinics. Caregivers reported perceived costs and benefits of intensive regimens. Physicians described the prescribed treatment and their perceptions of family/child competence and self-management. Analyses included analysis of covariance and hierarchical multiple linear regression. Findings indicate a disparity in regimen intensity for minority youth. Caregiver perceptions of costs associated with intensive regimens and physician perceptions of family competence are associated with prescribed regimen intensity. Interventions targeting disparities in prescribed regimen intensity should be considered. Further research is needed to understand the role of family perceptions of treatments and physician clinical decision making in addressing health disparities in type 1 diabetes.