Clinical relevance of sensitization to lupine in peanut-sensitized adults

Background: The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanutsensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). Methods: Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. Results: Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. Conclusion: In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only five fold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness

Food allergy in the Netherlands: differences in clinical severity, causative foods, sensitization and DBPCFC between community and outpatients

Background: It is unknown whether food allergy (FA) in an unselected population is comparable to those from an outpatient clinic population. Objective: To discover if FA in a random sample from the Dutch community is comparable to that of outpatients. Methods: This study was part of the Europrevall-project. A random sample of 6600 adults received a questionnaire. Those with symptoms to one of 24 defined priority foods were tested for sΙgE. Participants with a positive case history and elevated sIgE were evaluated by double-blind placebo-controlled food challenge (DBPCFC). Outpatients with a suspicion of FA were evaluated by questionnaire, sIgE and DBPCFC. Results: In the community, severe symptoms were reported less often than in outpatients (39.3% vs. 54.3%). Participants in the community were less commonly sensitized to any of the foods. When selecting only those with a probable FA (i.e. symptoms of priority food and elevation of sIgE to the respective food), no major differences were observed with respect to severity, causative foods, sensitization and DBPCFC between the groups. Conclusion: In the Netherlands, there are large differences in self-reported FA between community and outpatients. However, Dutch community and outpatients with a probable FA do not differ with respect to severity, causative foods, sensitization and DBPCFC-outcome

USF-1 Is Critical for Maintaining Genome Integrity in Response to UV-Induced DNA Photolesions

An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations. This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents. To protect against this, cells have evolved effective mechanisms to recognize DNA damage, signal its presence, and mediate its repair. While these responses are expected to be highly regulated because they are critical to avoid human diseases, very little is known about the regulation of the expression of genes involved in mediating their effects. The Nucleotide Excision Repair (NER) is the major DNA–repair process involved in the recognition and removal of UV-mediated DNA damage. Here we use a combination of in vitro and in vivo assays with an intermittent UV-irradiation protocol to investigate the regulation of key players in the DNA–damage recognition step of NER sub-pathways (TCR and GGR). We show an up-regulation in gene expression of CSA and HR23A, which are involved in TCR and GGR, respectively. Importantly, we show that this occurs through a p53 independent mechanism and that it is coordinated by the stress-responsive transcription factor USF-1. Furthermore, using a mouse model we show that the loss of USF-1 compromises DNA repair, which suggests that USF-1 plays an important role in maintaining genomic stability

Dissociation of CAK from Core TFIIH Reveals a Functional Link between XP-G/CS and the TFIIH Disassembly State

Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation

Novel HIV-1 Knockdown Targets Identified by an Enriched Kinases/Phosphatases shRNA Library Using a Long-Term Iterative Screen in Jurkat T-Cells

HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA) library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies

Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

Circadian Rhythms

Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the Suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation — its organization, mechanism and consequences — unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Étude du Systéme Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on ‘Circadian Rhythms’, Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60639/1/circadian_rhythms.pd

Clustering analyses in peptidomics revealed that peptide profiles of infant formulae are descriptive

Contains fulltext : 154788.pdf (publisher's version ) (Open Access)Prompted by the accumulating evidence on bioactive moieties of milk-derived peptides, novel methods were applied to compare the peptide composition among commercially available hydrolysate formulations and to determine batch-to-batch variations of protein hydrolysate products. Despite the availability of general methods to measure, for example, the degree of hydrolysis and peptide mass distribution at a high level, the objective of this study was to more qualitatively compare peptide sequences and composition. By a comprehensive approach combining peptidomics technologies and multivariate clustering analyses, the peptide profiles of different hydrolyzed milk protein formulations were compared. Moreover, peptide profiles of various hydrolysate batches that had been produced over a period of 5 years were included. Coupling of identified peptide sequences to the position in their corresponding milk proteins produced numerical datasets that subsequently were utilized for multivariate data analyses. These analyses revealed that batch-to-batch variation in the peptide profiles of a specific extensively hydrolyzed casein preparation was low. Moreover, extensive multivariate evaluations revealed that the peptide profiles of different commercially available hydrolyzed milk protein formulations provided a descriptive and distinct signature. Overall, the described methodology may contribute to the field of peptide research as observed dissimilarities in peptide profiles of similar products may be related to differences in their overall functionality

Health effects of holistic housing renovation in a disadvantaged neighbourhood in the Netherlands:a qualitative exploration among residents and professionals

Background: Holistic housing renovations combine physical housing improvements with social and socioeconomic interventions (e.g. referral to social services, debt counselling, involvement in decision-making, promoting social cohesion). In a deprived neighbourhood in Utrecht, the Netherlands, this paper examined residents’ and professionals’ experiences, ideas, and perceptions regarding holistic housing renovation, its health effects, and underlying mechanisms explaining those effects. Methods: Semi-structured in-depth interviews were conducted with 21 social housing residents exposed to holistic housing renovation, and 12 professionals involved in either the physical renovation or social interventions implemented. Residents were interviewed in various renovation stages (before, during, after renovation). Transcripts were deductively and inductively coded using qualitative software. Results: Residents experienced and professionals acknowledged renovation stress caused by nuisance from construction work (noise, dust), having to move stuff around, and temporary moving; lack of information and control; and perceived violation of privacy. Involvement in design choices was appreciated, and mental health improvement was expected on the long term due to improved housing quality and visual amenity benefits. Social contact between residents increased as the renovation became topic for small talk. Few comments were made regarding physical health effects. The interviews revealed a certain amount of distrust in and dissatisfaction with the housing corporation, construction company, and other authorities. Conclusions: Renovation stress, aggravated by lack of information and poor accessibility of housing corporation and construction company, negatively affects mental health and sense of control. Potential stress relievers are practical help with packing and moving furniture, and increased predictability by good and targeted communication. Social interventions can best be offered after renovation, when residents live in their renovated apartment and the nuisance and stress from the renovation is behind them. Social partners can use the period leading up to the renovation to show their faces, offer practical help to reduce renovation stress, and increase residents’ trust in their organization and authorities in general. This might also contribute to residents’ willingness to accept help with problems in the social domain after renovation.</p