The Hotel Dieu in Paris has been one of the first pediatric hospital in the world (see my photo of the hospital entrance). I recall from the detailed history of allergic diseases by Schadewaldt that at the beginning of the last century it was difficult to presen the students a case of the Bostock hayfever.
The disease was so rare that it took more than one week to find a child with the typical symptoms. Yea, yea.
I am detailing in a forthcoming paper in “Allergy”, that the contradicting results found with ADAM33 (the first positionally cloned asthma gene) probably results from a rather poor design of all follow-up studies.
It does not make so much sense to repeat over and over the same few SNP marker; instead a full resquencing of the linkage region would be necessary. From the analysis of public LD maps it is even possible that neighboring genes may be responsible for the observed associations.
I have also doubts if the SNP-centric view is always leading to success. BTW there is a new database of over 400,000 non-reduandt indels of which 280,000 are validated by comparison with other human or chimpanzee genomes (see Mills et al., the indels are available in dbSNP under the “Devine_lab” handle).
Folllowing up numerous emails to my recent review about allergy and vitamin D exposure, I wonder if there could be a quantitative relationship if we look at the vitamin D system as a major biological hub. This is not so much about connecting different playgrounds but of integrating signals (as shown in the hourglass blog). The East-West German difference, the farming studies as well as numerous other studies would even allow a quantitative effect. Yea, yea.
Biospektrum will publish in their next issue a summary of the vitamin D story.
4-07-2007 The list of vitamin D dependent genes that are associated with allergy (IL12B, IL12RB, SPP/OPN, CD14, CD23, VDR, TNF, GC, IFN, IL1RN, IL8, ADRB2, CARD15, IL4R, ALOX5, FLG, SOCS3) is expanding: TSLP and CD86
A new study now shows directly that personal exposure of particles is linked to asthma symptoms. Children carried pollution monitors in their backpacks on the way to school where PM2.5 ranged from 20 to 50 micrograms per cubic meter. Although only around 10 percent of the total mass of particles was diesel soot, it was this that was most closely linked to the children’s asthma. This nicely complements results of our study in Munich in 1989/1990 which was the first survey indirectly linking car exhaust and airway symptoms in children. Mechanisms how this happens are not very well known – for a discussion of the biphasic response see our paper of a mouse model, yea, yea.
Having read again Beutlers 2004 TLR review, I am always fascinated by the flexible response and the hourglass response effect. On the outside there is the microbial universe and inside are the many strategies to fight infection, but all goes through a single bottleneck. What is the reason behind? To calm down but strike when necessary?
Asthma in Africa: I will touch this issue in more detail in a forthcoming editorial in PLos Medicine. Africa has fascinated me since childhood when I read books of Paul White, Albert Schweitzer and tried to get everything our library had about David Livingstone and Morton Stanley. Here is a further link that we couldn’t place in the editorial – a 2 month helicopter trip from Hamburg to Kapstadt including daily GPS data to watch a heli flying in Google Earth, simply the best, I have seen in the internet this year, yea.
-moblog- A new nature medicine paper describes a deficient induction of interferon beta (gene is on chr 9) and interferon lambda (gene is on chr 19). The author concludes that genetic polymorphisms are an unlikely cause as genes are on different chromosomes. What a misunderstanding – does the author really believe in a single asthma gene? Yea, yea.
If you are invited to a party just mention genetically modified (GM) food and you will be center of the crowd. There are many national and internationally bodies that deal with GM food (see the dissertation of Scholderer). As far as we do not know what makes and allergen and allergen, I would always care when introducing any modification. There is a way round, however, that GM food can also have less allergen content – just found a preprint of a gene-silenced tomato. This German-Spanish group managed by RNAi silencing to reduce protein Lyc e 3 with led to reduced skin reactivity of tomato allergic probands. BTW – do you renember our fake food hypothesis? Yea, yea. BTW The best tomato bread can be found in Barcelona.
The CD14 / allergy story never ends – after many years and numerous contradictory reports. A new comment in the AJRCCM concludes that “further research is required” – at this time “research into the area of gene-by-environment interaction where large-scale studies, advanced assessment of environmental exposure of and experimental investigations of interactions are needed”. Is there any sense with neverending loops (except playground for hamster)? Nay, nay.
JCI has a paper about resurrection of vitamin D deficiency (more about the author at 1, 2 and 3). The author uses references 46-59 to underpin his opinion that rickets has again become an epidemic. These references are from 1992, 1984, 2005, 2000, 1987, 1987, 1989, 1994, 1989, 2001, 1998, 2001, 1987, 2006. So nothing really new – no prospective study, no systematic survey, just a few isolated reports. Sure, that there might be a rickets problem in a selected areas or in minority groups, but there is no world-wide epidemic. He argues also that many (if not all) studies show “low” serum 25-OH-D3 values. Is this chasing a phantom? A more systematic study concludes that rickets in Africa is more a disease of calcium deficiency. The JCI article is particular poorly written when it comes to immunological effects; asthma is misquoted from the Camargo study (which is subject of my review at Pediatric Allergy. Nay, nay.
German news magazine SPIEGEL ONLINE writes of an ongoing trial in Berlin where 1 to 6 month year old newborns are given some kind of “oral LPS vaccination”. You might know my opinion about LPS and will therefore understand my hope that newborn gastric acid pH will prevent them from any LPS side effect. Yea, yea.
… was the title of a recent editorial in JCI. Clearly that’s not true for vitamin D as you may know of the many immunological functions. A new study now shows, that mice get atopic dermatitis by applying vitamin D ointment. A EJCN paper published on the same day concludes that “the national fortification of fluid milks and margarines with vitamin D safely improved the vitamin D status of children”. Nay, nay.
You can probably find hundreds of times the argument in the medical literature that the main cause of asthma is the environment – as genes can not spread within 1 or 2 generations. While this might be true for de novo mutations it is certainly not true with pre-existing variations and recent population dynamics. In a review how asthma came into live, I argued that introduction of antibiotics and improved child care extremely shaped our genome by suppressing purifying selection. In developing countries respiratory infections are among the main killers. Who can help with 1,000 unbiased 100 year old DNA samples to prove this hypothesis? I have an excellent dentist to punch holes in bones.