Tattoo pigment in an axillary lymph node simulating metastatic malignant melanoma

We report a case of axillary lymphadenopathy thirty years after a decorative tattoo clinically mimicking metastatic melanoma. The importance of relying on histological confirmation of metastatic disease before altering extent of surgery is discussed. The importance of recording presence of decorative tattoos is stressed.     

The cytotoxic,neurotoxic, apoptotic and antiproliferative activities of extracts of some marine algae on the MCF-7 cell line

We investigated the cytotoxic, neurotoxic, apoptotic and antiproliferative effects of extracts from Petalonia fascia, Jania longifurca and Halimeda tuna on the MCF-7 breast cancer cell line. J. longifurca extracts were more toxic than those of P. fascia and H. tuna. The algal extracts showed significant toxic effects at different dilutions. The toxic effects were due to increased oxidative stress and resulted in apoptosis. Algal toxicity may exert negative effects through the food chain or by direct interaction. Algal toxicity also has potential for cancer therapy. The toxic effects that we observed may be especially important for therapy for breast tumors.     

Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

Background

Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.

Methods

Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.

Results

Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.

Conclusions

Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.     

Postsynaptic density antigens: preparation and characterization of an antiserum against postsynaptic densities

Long-term immunization of rabbits with postsynaptic densities (PSD) from bovine brain produced an antiserum specific for PSD as judged by binding to subcellular fractions and immunohistochemical location at the light and electron microscope levels. (a) The major antigens of bovine PSD preparations were three polypeptides of molecular weight 95,000 (PSD-95), 82,000 (PSD-82), and 72,000 (PSD-72), respectively. Antigen PSD-95, also present in mouse and rat PSDs was virtually absent from cytoplasm, myelin, mitochondria, and microsomes from rodent or bovine brain. Antigens PSD-82 and PSD-72 were present in all subcellular fractions from bovine brain, especially in mitochondria, but were almost absent from rodent brain. The antiserum also contained low-affinity antibodies against tubulin. (b)Immunohistochemical studies were performed in mouse and rat brain, where antigen PSD-95 accounted for 90 percent of the antiserum binding after adsorption with purified brain tubulin. At the light microscope level, antibody binding was observed only in those regions of the brain where synapses are known to be present. No reaction was observed in myelinated tracts, in the neuronal cytoplasm, or in nonneuronal cells. Strong reactivity was observed in the molecular layer of the dentate gyrus, stratum oriens and stratum radiatum of the hippocampus, and the molecular layer of the cerebellum. Experimental lesions, such as ablation of the rat entorhinal cortex or intraventricular injection of kainic acid, which led to a major loss of PSD in well- defined areas of the hippocampal formation, caused a correlative decrease in immunoreactivity in these areas. Abnormal patterns of immunohistochemical staining correlated with abnormal synaptic patterns in the cerebella of reeler and staggerer mouse mutants. (c) At the electron microscopic level, immunoreactivity was detectable only in PSD. The antibody did not bind to myelin, mitochondria or plasma membranes. (d) The results indicate that antigen PSD-95 is located predominantly or exclusively in PSD and can be used as a marker during subcellular fractionation. Other potential uses include the study of synaptogenesis, and the detection of changes in synapse number after experimental perturbations of the nervous system.     

Comparison of methods for analysis of selective genotyping survival data

Survival traits and selective genotyping datasets are typically not normally distributed, thus common models used to identify QTL may not be statistically appropriate for their analysis. The objective of the present study was to compare models for identification of QTL associated with survival traits, in particular when combined with selective genotyping. Data were simulated to model the survival distribution of a population of chickens challenged with Marek disease virus. Cox proportional hazards (CPH), linear regression (LR), and Weibull models were compared for their appropriateness to analyze the data, ability to identify associations of marker alleles with survival, and estimation of effects when all individuals were genotyped (full genotyping) and when selective genotyping was used. Little difference in power was found between the CPH and the LR model for low censoring cases for both full and selective genotyping. The simulated data were not transformed to follow a Weibull distribution and, as a result, the Weibull model generally resulted in less power than the other two models and overestimated effects. Effect estimates from LR and CPH were unbiased when all individuals were genotyped, but overestimated when selective genotyping was used. Thus, LR is preferred for analyzing survival data when the amount of censoring is low because of ease of implementation and interpretation. Including phenotypic data of non-genotyped individuals in selective genotyping analysis increased power, but resulted in LR having an inflated false positive rate, and therefore the CPH model is preferred for this scenario, although transformation of the data may also make the Weibull model appropriate for this case. The results from the research presented herein are directly applicable to interval mapping analyses.     

A polycystin‐2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2, which encode polycystin‐1 (PC1) and polycystin‐2 (PC2), respectively. Earlier work has shown that PC1 and PC2 assemble into a polycystin complex implicated in kidney morphogenesis. PC2 also assembles into homomers of uncertain functional significance. However, little is known about the molecular mechanisms that direct polycystin complex assembly and specify its functions. We have identified a coiled coil in the C‐terminus of PC2 that functions as a homodimerization domain essential for PC1 binding but not for its self‐oligomerization. Dimerization‐defective PC2 mutants were unable to reconstitute PC1/PC2 complexes either at the plasma membrane (PM) or at PM‐endoplasmic reticulum (ER) junctions but could still function as ER Ca²⁺‐release channels. Expression of dimerization‐defective PC2 mutants in zebrafish resulted in a cystic phenotype but had lesser effects on organ laterality. We conclude that C‐terminal dimerization of PC2 specifies the formation of polycystin complexes but not formation of ER‐localized PC2 channels. Mutations that affect PC2 C‐terminal homo‐ and heteromerization are the likely molecular basis of cyst formation in ADPKD.     

SIMPLE: implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study

Background

Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).

Methods

An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.

Discussion

This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.

Trial registration

http://www.clinicaltrials.gov: NCT01261676