Triploidy—Observations in 154 Diandric Cases

Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0–1,4%).     

Seasonal variation in food allergy to apple

The aim of the study was to investigate the possibility of a seasonal variation in reactivity to apples in 27 birch pollen allergic patients. Before and during the birch pollen season 1998, the patients were subjected to double-blind, placebo-controlled food challenges (DBPCFCs) with grated fresh Golden Delicious apple followed by an open food challenge with whole fresh apple. The clinical reactions elicited during the challenges were evaluated both by the patients and the investigators. Moreover, the skin reactivity and the in vitro reactivity to apple were evaluated by skin prick test (SPT), leukocyte histamine release (HR), measurement of specific IgE, and immunoblotting experiments. The sensitivity of the DBPCFC, when compared with the result of the open challenge, was 0.74 (14/19) before the season and 0.80 (16/20) during the season. None of the patients reacted to the blinded challenge without a subsequent reaction to the open challenge. One placebo reaction was registered both before and in season, but not in the same patient. The patient scores of the first positive challenges, and the maximal scores of each combined blinded and open challenge session, were significantly increased during the pollen season (P<0.05). The scores of the open challenge were significantly higher than the scores of the DBPCFC both before the season and during the in-season challenges (P<0.05). Specific IgE against Golden Delicious increased during season (P<0.05), while neither SPT, HR, nor immunoblotting experiments could confirm an increase in reactivity. In conclusion, the results of the oral challenge tests indicated an increase in clinical reactivity to apples during the birch pollen season in birch pollen allergic individuals.     

18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

BackgroundConflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of ¹⁸F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of ¹⁸F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.MethodsMice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), ¹⁸F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.ResultsAnti-VEGF monotherapy increased survival and decreased ¹⁸F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. ¹⁸F-FET SUV_max tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.Conclusion¹⁸F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of ¹⁸F-FET PET for response evaluation in future studies.     

The Circadian Clock Gene Circuit Controls Protein and Phosphoprotein Rhythms in Arabidopsis thaliana

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Investigations on the Tetranychus urticae complex in north west Europe (Acari: Tetranychidae)

Two species of spider mite occur in greenhouses in the Netherlands. Tetranychus urticae Koch is usually green, can live on many plants, but cannot build up large populations on carnations; it may have a diapausing stage which is very resistant to cold. No biological races of T. urticae were found. T. cinnabarinus Boisd. is carmine-coloured, often found on carnations, and does not have a diapause. It is not resistant to cold.The two species do not interbreed. Growers of carnations have only T. cinnabarinus to deal with, and can arrange control measures accordingly.

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Zusammenfassung Untersuchungen der Morphologie, der Wirtspflanzenwahl, der Überwinterungsweise und Kreuzingsexperimente haben gezeigt, daß in Gewächshäusern Hollands zwei Spinnmilben-Arten auftreten, nämlich Tetranychus urticae Koch und T. cinnabarinus Boids. Darüberhinaus wurde Material von Spinnmilben je einer Lokalität in Deutschland, der Schweiz und Belgien verwendet. T. urticae ist meistens grün gefärbt, lebt an einem großen Wirtspflanzenkreis, kann aber an Nelken (Dianthus caryophyllus L.) keine Populationen bilden. Diese Art geht unter dem Einfluß verschiedener biologischer Faktoren in Diapause. Während dieser Periode ist sie sehr kälteresistent. Der Winter wird an geschützten Orten verbracht. Kreuzungen zwischen Populationen verschiedener Herkunft ergaben stets eine normale Nachkommenschaft. Zucht-experimente mit diesen Populationen auf verschiedenen Wirtspflanzen ergaben keinen Hinweis für das Bestehen von biologischen Rassen bei T. urticae. T. cinnabarinus ist karminrot gefärbt und wird am häufigsten auf Nelken gefunden, obwohl in Laboratoriumsversuchen die Entwicklung an Buschbohnen (Phaseolus vulgaris L.) schneller verläuft. Diese Art tritt überhaupt nicht in Diapause ein, bleibt den Winter über an den Blättern und ist gegenüber Kältebedingungen entschieden weniger resistent als T. urticae. Kreuzungen zwischen Populationen verschiedener Herkunft ergaben immer eine normale Nachkommenschaft.Das Ausbleiben von Bastardierungen, das in Kreuzungsexperimenten zwischen den beiden Arten gefunden wurde, erbrachte den strengsten Nachweis, daß in den Gewächshäusern zwei verschiedene Arten vorkommen.Da T. cinnabarinus hauptsächlich auf Gewächshäuser mit Nelken beschränkt ist und T. urticae sich andererseits an diesen Pflanzen nicht vermehrt, haben es die Nelkenanbauer lediglich mit T. cinnabarinus zu tun, und es ergibt sich eine Möglichkeit, Nelken frei von Spinnmilbenbefall zu halten.

     

Genetic affinities between adjacent populations of spider mites (Tetranychus urticae Koch)

The interbreeding potentials of nine populations of spider mites were examined. The populations were gathered from horticultural crops in different glasshouses in a limited area of Aalsmeer. A great variety of genetic incompatibilities between these populations was found. In most crossing a partial sterility of the hybrids, as measured by egg hatchability, occurred. Some crosses showed reciprocal differences. It was suggested that genetic divergence of these adjacent populations arises especially from the haplo-diploid nature of spider mites.

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Zusammenfassung Die Kreuzbarkeit von neun Spinnmilben-Populationen wurde untersucht. Die Populationen wurden von Gartenpflanzen verschiedener Gewächshäuser in einem bestimmten Gebiet von Aalsmeer gesammelt. Es zeigte sich eine große Variabilität in der genetischen Verträglichkeit zwischen diesen Populationen. Bei den meisten Kreuzungen trat, gemessen an der Schlüpffähigkeit der Eier, eine partielle Sterilität der Hybriden auf. Einige Kreuzungen wiesen reziproke Unterschiede auf. Es wird vermutet, daß die genetische Divergenz dieser aneinandergrenzenden Populationen speziell auf der haplo-diploiden Natur der Spinnmilben beruht.

     

FDG PET scans as evaluation of clinical response to dendritic cell vaccination in patients with malignant melanoma

Background

Measurements of tumour metabolism by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) have been successfully applied to monitor tumour response after chemo- and chemo-radiotherapy and may not have the same limitations as other morphological imaging techniques. In this study it is investigated whether FDG-PET might add information on the efficacy of immune therapy.

Materials and methods

In a retrospective analysis data from patients with advanced progressive melanoma, treated with DC vaccinations and evaluated by PET/CT scans at baseline as well as after 6 vaccinations were analysed. If a patient achieved stable disease according to RECIST, additional vaccinations were given. The PET scans were evaluated according to EORTC guidelines.

Results

PET/CT scans from 13 patients were evaluated. According to RECIST 3 patients achieved stable disease and 10 patients progressed. Interestingly, when evaluated by PET scans 2 patients had partial metabolic response and 1 patient had complete metabolic response of the 2 index lesions even though a new lesion appeared simultaneously. Ten patients were seen to have stable or progressive metabolic disease.

Conclusion

By adding PET scans to the CT evaluation of patients treated with DC vaccines, a more detailed picture of the single lesions was found. This seems to improve the clinical evaluation of the treatment. The lack of correlation between the PET and CT scans suggests that some of the increases in target lesions seen in CT scans might be due to oedema or immune-infiltrates and not progression of the disease. Thus, further investigation into the contribution of PET scans to the evaluation of cancer immunotherapy is needed.