人々の “健康促進” のために!

人々の “健康促進” のために!
2015年春、沖縄の琉球大学キャンパス内 (産学共同研究棟) に立ち上げた “PAK研究センター” の発足メンバー(左から4人目が、所長の多和田真吉名誉教授)
For detail, click the above image.

2009年1月31日土曜日

The Bottom of Liebig's Barrel :
What Determines Our Life or Death?

The German chemist, Justus von Liebig (1803-1873), is known as the Father
of Agricultural Chemistry. For he was the first scientist who established
what are the major nutrients essential for the growth of plants: nitrogen
(N), phosphate (P), and potassium (K), by growing a plant in water. Based
on this finding, he made the first chemical fertilizer containing these
three elements. Of course two additional things are essential for the growth
of green plants, air (oxygen) and sun light. He then asked, supposed these
three environmental factors (water, air, and light) are plenty, what would
limit the growth of a plant? He found that the amount of each element would
limit the growth even if two other elements are more than sufficient. In
other words, these three elements are not inter-exchangeable. Based on this
observation, he concluded the law of the minimum, the minimum element limits
the growth, which is now called "Liebig's Barrel".

Like plants, we, human beings, need air, water, and sun light, as well as
so many nutrients including C-sources, N-sources, essential amino acids,
vitamins and minerals. In addition, unlike insects and other invertebrates,
we need special cardiovascular organs such as lung, heart and blood vessels
for taking oxygen from air, and pumping and delivering oxygen through blood
vessels to each tissues. When one of these cardiovascular systems stop working,
and in particular brain suffers from oxygen shortage, we have to die almost suddenly.
So in our Liebig's Barrel, this cardiovascular system plays the most crucial
role for our life line. The failure of cardiovascular system means a big hole
at the bottom of Liebig's Barrel. That is the major reason why cardio-
vascular diseases are among the major cause of our death, along with
cancers. In other words our life span is mainly determined by our cardio-
vascular conditions and whether we have a cancer or not. Having a cancer
also implies another big hole at the bottom of our own "Barrel".

How can we maintain our cardiovascular system healthy during our aging?
First of all, don't smoke! Otherwise, you will get lung, pancreatic or
liver cancers, soon or later. How about nutrients/diet and exercise?

The major disorders of cardiovascular system among aging people are hypertension
(high blood pressure) and arteriosclerosis (AS, hardening of arteries).
Hypertension is caused by abnormal contraction of arterial smooth muscles.
Thus, hypertension can be reduced by relaxation of this smooth muscle,
that is blocking smooth muscle actomyosin ATPase by either anti-Rock (Rho
kinase) or anti-PAK1 products. As previously mentioned, natural anti-PAK1
products such as propolis, Chinese (Sichuan) pepper called Hua Jiao, curcumin
in Indian Curry, vitamin K2 (menaquinone-7) in "Natto", a Japanese fermented
sticky soy bean product, resveratrol (trans R3) in red wine or red grapes
would be useful for the treatment of hypertension.

The AS is caused by accumulation of cholesterol along the wall of blood
vessels. Statins that block the biosynthesis of cholesterol would solve
this AS problem. Alternatively, natural approaches such as cutting calories
by 30%, IF (intermittent fast) and exercise also would prevent the accumulation
of excess fatty acids including cholesterol.

Interestingly, these natural anti-PAK1 products, CR (calorie restriction)
and exercise that prevent cardiovascular disorders are also known to suppress
or prevent cancerous growth. In other words, these natural approaches would
fill both of the two major potential holes at the bottom of our aging "Barrel",
to prolong our life span in good health, perhaps by upto 50%, as have been shown
in nematodes, Penguins and mice/rats so far.


Two Kinds of Barrels, Growing and Aging

The original Liebig's barrel for the growth of plants has a solid bottom,
and their growth solely depends on the minimum stave, either N-sources,
P-sources or K-sources as well as either water, air or sunlight. In Germany
and Japan, water is not the minimum stave, but in Australia, Sahara Desert
or other dry countries where rain falls rarely, the precious water is definitely
the No. 1 minimum stave, in particular when the global warming continues
taking place.

Likewise, during our last war (WWII) and shortly after the end of this bloody
war, the majority of children in both Far East including Japan, Korea, and
China and the whole Europe including Germany and UK where battles actually
took place, used to suffer from starvation or malnutrition, due to the serious
food shortage. Their growing barrel did depend on the food supply (mainly
wheat and skim milk) from US under the Marshall Plan. These children had
no time to worry about the bottom of their barrel. My own generation was
among these children.

More than a half century later, these "lucky" children have fully grown
up and many of them have reached even their retirement age (over 65 or so).
Now, they have a plenty of time to worry about the "fragile" bottom of their
aging barrel, instead of the minimum staves, mainly due to overweight, hypertension,
AS and even cancers. They gradually realized that unnecessary (extra)
food intake does definitely harm the health of their aging body, by generating
extra fats and feeding their benign or malignant tumors inside. To limit
their food intake to the minimum level by CR or IF and daily exercise appear
to be the best (simplest and effective) strategy for maintain the bottom
of their aging barrel "intact". Besides this same strategy also improves
their fading memory or learning ability, delaying the onset of Alzheimer's
symptom.


Excess of Phenylalanine (PKU) Causes Mental Retardation

Of 20 natural amino acids, only 8 amino acids are generally regarded as
essential for humans: phenylalanine (Phe), valine, threonine, tryptophan,
isoleucine, methionine, leucine, and lysine. Cysteine, tyrosine (Tyr), histidine
and arginine are additionally required by infants and growing children.
Essential amino acids are so called because our body cannot synthesize them,
making it essential to include them in our diet in order to obtain them.
In addition, the amino acids arginine, cysteine, glycine, glutamine, histidine,
proline, serine and tyrosine are considered conditionally essential, meaning
they are not normally required in the diet, but must be supplied exogenously
to specific populations that do not synthesize it in adequate amounts. An
example would be with the disease phenylketonuria (PKU). PKU is caused by
deficiency of an enzyme called Phe hydroxylase, which converts Phe to Tyr
by oxidation. Individuals living with PKU must keep their intake of Phe
extremely low to prevent mental retardation and other metabolic complications.
However, Phe is the precursor for Tyr synthesis. Without Phe, Tyr cannot
be made and so Tyr becomes essential in the diet of PKU patients.

Pearl Buck (1892-1973), the first American woman Nobel laureate in literature,
and the author of the best-selling book "The Good Earth" (1931) has a daughter
called Carol. Carol was born in 1920 when Pearl and her husband stayed in China
for four decades. Carol was a perfectly healthy child, but it became evident that
she was severely (permanently) mentally retarded when Carol reached around
10. Later she was found to suffer from PKU, but it was too late to treat
her PKU by a low Phe and Tyr-rich diet, because the excess of Phe had already
poisoned her brain completely. PKU was first discovered in association with
mental retardation by the Norwegian physician Ivar Asbjorn Folling in 1934.
Since then Carol was taken care by a special school in US for the rest of
her life (six decades), and her mother, Pearl Buck, then a simple house
wife, started writing a novel in order to cover the high cost of her life-time
special care. That novel turned out to be the famous "The Good Earth",
a unique story about Chinese poor peasants, which was awarded a Pulitzer Prize
in 1932, and Nobel Prize in 1938.

It is of great interest to note that in these old days the majority of
farmers in China and other Far East countries were poor, and used/recycled
only our human waste as the natural fertilizer, instead of modern chemical
fertilizers that were invented by Liebig and other western scientists. So
their soil or earth remained very fertile, certainly rich in all three major
elements, for thousands years. The earth was the most precious treasure
for these poor farmers.

In 1950, Pearl Buck published a non-fiction book "The Child Who Never Grew",
a moving life-story about her own daughter Carol. So many mothers or parents
who have similar hidden children were both wept and encouraged by this book.
Among them were Rose Kennedy (the mother of John F. Kennedy) and Madam De
Gaulle (the wife of Charles De Gaulle).

PKU as an example clearly shows that not only the "minimum" stave, but also
the "excess" stave of our barrel could limit badly the growth of our body,
in particular the development of very sensitive and sophisticated organs
such as our brain.


Homeostasis for Health: "Too Little" or "Too Much" Causes Illness

To keep the normal function of any organs in our body, all essential elements
have to be kept at a certain "minimum" level (homeostasis). When this homeostasis
is broken by either too little or too much synthesis of given elements such
as Phe and PAK, the sensitive organs such as brain start suffering from
disorder or dysfunction, leading to a number of illnesses such as cancers
and mental retardation. Our body normally has a very sophisticated mechanism
to keep this delicate balance (homeostasis) of each essential element for
a good health. However, a certain genetic disorder or environmental stress
breaks this delicate balance, leading to either deficiency or overproduction
of a certain element, resulting in a severe illness.

Here I shall give you a more familiar example: PAK is an enzyme belonging
to a kinase family which is essential for a number of physiological functions
such as cell proliferation (growth) and migration, blood vessel formation
and memory/learning. If you knock out (delete) this PAK gene completely
in mice for an example, embryo fails to develop fully, and it causes the
death of this embryo in womb or mental retardation after the birth, depending
on the timing of gene deletion (and conditions of a few related genes).
If the same PAK gene is over-expressed/ over-activated, the excess of PAK
activity causes a number of severe illnesses, including more than 70% of
all cancers such as formidable pancreatic cancer, melanoma and gliomas,
NF (neurofibromatosis) tumors, mental retardation or learning deficit (LD)
often associated with NF1 and fragile X syndrome (autism), inflammation
(asthma and arthritis), epilepsy, hyper-tension, AD (Alzheimer's disease)
and HD (Huntington's diseases). To cure or treat these illness, the PAK
level has to be reduced to the basic "minimum" level by one of natural or
synthetic anti-PAK1 products. Besides CR, IF and daily exercise also would
help/boost these therapeutics synergestically, because they eventually
activate the longevity/anti-cancer protein FOXO by activating another enzyme
called AMPK (AMP-dependent kinase), as do these anti-PAK1 drugs.

In other words, fattening or overweight significantly would hamper or reduce
the therapeutic efficacy of these anti-PAK products, because the extra calorie
(=sugar) and fat continue inactivateing the FOXO, while these therapeutics
are trying to activate the FOXO. There is the international standard formula
telling you whether you are pleasantly slender/slim or over-weighted, in
order to judge the potential efficacy of these therapeutics by yourself:

S (slimness) = H (height in cm) minus W (weight in kg).

For instance, if you are 173 cm tall and weigh 63 kg, your "S" value would
be 110. If your "S" value is around 110 or higher, you are considered "slim",
clearly a splendid candidate for the "effective" therapy (if you have any
PAK-related illness such as NF). However, your "S" value is significantly
lower than 110, for instance 100 or even 90, you would definitely need to make
an extra effort to reduce your weight by 10 or even 20 kg (if you are grown-up,
and cannot increase your height any more), by CR (diet), IF (fast) or
vigorous exercise (or all of them), to make the therapeutics work more
efficiently. Clear?

Of course the recommended dose of each therapeutic is roughly proportional
of your weight, but if you are taller (or slimmer), you would get much more
benefit from the same dose!

Even in this 21st century, the Liebig's Barrel still serves as a valid model
for children suffering from starvation or malnutrition in poor African or Asian
countries. However, what the majority of people in western industrial countries
or Japan should concern more seriously would be the bottom of their own
barrel which is badly damaged by either cancers or cadio-vascular diseases,
and the belt (waist line) of their over-fed barrel, instead of the 'minimum'
stave. In the latter case, the slimmer its barrel, the longer it lasts (if not
ultra-thin cat-walk models on world fashion stages).

2009年1月27日火曜日

受験生諸君! 「腹七分目」にすると、記憶が向上する!

(逆にいえば、「食べ過ぎ」は記憶力を駄目にする)

細胞内の糖濃度が下がると、AMPK(AMP依存性キナーゼ)が活性化を
受け、その結果、「FOXO」と呼ばれる転写蛋白 (抗癌/養命蛋白) が
活性化される。 これが記憶の向上や癌の予防/治癒に寄与する。

同様に、プロポリスなどのPAK遮断剤を服用すると、「FOXO」が活性化を
受ける。従って、「Bio 30」などのプロポリスも、理論的には、「腹七分目」同様、
癌の予防/治癒ばかりではなく、記憶の向上にも役立つはずである。

もし、両方を同時に実行すれば、それこそ「鬼に金棒」になろう!


カロリーセーブなら記憶力Up!…ドイツで研究発表

【ワシントン=増満浩志】
健康な中高年が摂取カロリーを制限すると、記憶力が向上するという
実験結果を、独ミュンスター大学の研究チームが26日、米科学アカデミー
紀要(PNAS)電子版に発表した。

やせ過ぎていない50~79歳の男女49人を3グループに分け、19人には
カロリー摂取量をふだんより30%減らしてもらった。
別の20人は(認知症の予防に役立つという説のある)不飽和脂肪酸の摂取を
ふだんより20%増量し、残る10人は従来の食生活を続けた。

実験前と3か月後に言葉を覚えるテストを行った結果、カロリーを抑えた19
人の点数は約20%も上昇した。
他の2グループは成績に変化が見られなかった。

カロリー制限によって、体内の血糖値を調整するインスリンが効きやすくなっ
た人ほど、成績の伸びが著しかった。
こうした体質が、脳神経に何らかの良い影響を与えているとみられている。
(読売新聞「ウエッブサイト」より引用)


断食は長生きのもと? 線虫で実験、1.5倍に

断食で長生き――。土の中に住む線虫は、断食を繰り返すと最大1・5倍寿命が延びることを、京都大生命科学研究科の西田栄介教授らが突き止めた。人間にそのまま当てはまる訳ではないが、断食を繰り返し、食べる時は好きなだけ食べた方が、食事の量を減らすよりも長生きできるかもしれない。英科学誌ネイチャー電子版に15日、発表した。

西田教授らは線虫に2日間、十分に餌を与えた後、2日間断食させる、というサイクルを繰り返し、餌をずっと与え続けた場合と比較した。その結果、平均24日だった寿命は36~40日と、50%以上延びた。

モデル動物の線虫の寿命には、人間にもあるレブ(Rheb)という遺伝子が関係しており、この遺伝子の働きを止めると、断食を繰り返したり餌を制限したりしても、寿命は延びなくなった。
(2008年12月15日 読売新聞)

週に一度エサを与えない断食DAYを設定すると、ペンギンの寿命が普通のペ
ンギンの約1.5倍になる (長崎ペンギン水族館の話)。


http://plaza.rakuten.co.jp/korrida/diary/200712120000/

前身の長崎水族館時代から数多くのペンギンを飼育しているが、飼育方法に多く
の特殊なノウハウを持ち、世界的にも注目されている。
ペンギンの平均寿命は通常約20年だが、この水族館に2002年まで生存して
いたキングペンギンのぎん吉は39歳9ヶ月15日生きた世界一の長寿記録を持っ
ている (これは人間に換算すると120歳だ!!)

さらに現在、ぎん吉の娘のペペが、今年30歳で生存している。
それ以外にもフジという名前の皇帝ペンギンも、ここに来てから28年も生きた
そうで、この種の飼育世界記録を保持している。この飼育技術は「長崎方式」と
して国際的にも高い評価を得ている。

上記の線虫やペンギンばかりではなく、哺乳類のマウスでも、「断食」は寿命を
確実に伸ばしている。 従って、我々人間様も、「長崎方式」で (健康なまま) 寿命を
伸ばせる (養命する) ことができる可能性が高い。 各自それぞれ体験してみる
価値があるだろう!


詳しくは、「健康長寿」の世界的権威である後藤佐多良教授の下記のネット欄を参
照されたし。

http://www.mnc.toho-u.ac.jp/v-lab/aging

今日は「リービッヒの桶」という深遠な言葉を、この欄から学んだ。早速この言葉
を拝借すると、この「命の桶」を支える一枚一枚の桶板の高さは、分子レベルで
いうと、発癌キナーゼ「PAK」の高さ (機能) に逆比例し、養命蛋白「FOXO」の
機能にほぼ比例するといえるだろう。節食や断食、運動や納豆は桶板の高さ
(健康長寿) を保つのに大いに貢献しているから、率先して実践することを是非
お勧めしたい。

2009年1月26日月曜日

山形県知事選: 民主党支援候補、
(自民推薦)現職知事を接戦で破る!

東北初の女性知事、吉村さん(57) 当選オメデトウ!


(山形県知事選の勝利で弾みを付け) 次期政権を虎視眈々と狙う「民主党内閣」の
外相候補は一体誰か?

ジョセフ・ネイ駐日米大使やヒラリー・クリントン国務長官と対等に対決出来る
人物が、日本独自の(対米追従ではない) 外交を進めるのに必要だ!

不人気だったブッシュ政権よりも、人気絶頂のオバマ政権は、我々(日本) にとって
ずっと手強い相手だ。。。(天木直人ブログ曰く)

いくら不満でも、あのスマートな青年神士に向かって、(サイズ10の) 靴をぶつ
けられないからだ。。。

さて、オバマ(大統領)を納得させ得る巧みな話術の持主が、果して日本にいるだろうか?

2009年1月14日水曜日

Trihydrophobin 1(TH1) : a Tumor Suppressor
that Directly Inhibits the Kinase PAK1

TH1 gene is a relatively ubiquitous gene that is present from Drosophila
to human beings (but absent in nematodes). In 2004 Jianxin Gu's group at
Fudan University in Shanghai found that TH1 protein inactivates the kinase
A-Raf somehow, In 2009 the same group revealed that TH1 protein directly
inhibits the kinase activity of PAK1 by binding the C-terminal kinase domain,
suggesting that TH1 protein is a tumor suppressor, as is Merlin/NF2 that
also directly inhibits the oncogenic kinase PAK1 (Hirokawa et al, 2004).

Interestingly, an E3 ubiquitin ligase of human papilloma virus (HPV) called
E6-AP was found to inactivate TH1 protein by ubiquitination (Yang et al,
2007). According to the 2008 Nobel laureate, Harald zur Hausen at German
Cancer Research Center (DKFZ), HPV is the major cause of cervical cancers.

Thus, it is likely that this virus abnormally activates PAK1 by inactivating
TH1. In other words the majority of cervical cancers are among PAK1-dependent
cancers. This notion suggests the possibility that the potent anti-PAK1
drugs such as FK228 and Bio 30 would suppress the growth of cervical cancers,
as other PAK1-dependent cancers and NF tumors.

In this context, it should be worth noting that vitamin K2, in particular
menaquinon-7, derived from "natto" (fermented sticky soy beans), a Japanese
traditional cuisine, appears to inactivate the kinase PAK1 somehow, as it
blocks the growth of PAK1-dependent cancers, metastasis and angiogenesis,
without up-regulating p27 (CDK inhibitor), down-regulation of which requires
the kinase AKT (Shibayama-Imazu et al, 2003; Liu et al, 2007). Thus, there
is a possibility that these PAK1-dependent cancers and NF tumors could be
treated at home, simply by taking "natto" every day, in near future.

The best "natto" brand (from Mizkan) contains 1700 micro g of menaquinone-7
per 100 g, and probably 40 g (the minimum package) of this "natto" daily
would be sufficient for the treatment. This small package costs only 40
cents in Japan which is even less expensive than 5 ml of Bio 30 costing
around US$1.00. If "natto" is not available at your local oriental shop,
you could make "natto" at home, by mixing steamed/boiled soy beans with
spores of Bacillus subtilis var natto, and incubating at 42oC for a few days.


J Biol Chem. 2009 Jan 9.

Trihydrophobin 1(TH1) interacts with PAK1 and regulates ERK/MAPK activation
and cell migration.

Cheng C, Kong X, Wang H, Gan H, Hao Y, Zou W, Wu J, Chi Y, Yang J, Hong
Y, Chen K, Gu J.

Gene Research Center, Shanghai Medical College of Fudan University, Shanghai,
Shanghai 200032.

PAK activity has been shown to be required for maximal activation of the
oncogenic RAF-MEK-MAPK signaling cascade, due to PAK co-activation of RAF
and MEK.

Trihydrophobin 1 (TH1), previously identified as a negative regulator of
the kinase A-RAF, also interacted with PAK1 in cultured cells. Confocal
microscopy assay indicated that TH1 colocalized with PAK1 in both cytoplasm
and nucleus. GST-pull down and coimmunoprecipitation experiments demonstrated
TH1 directly interacted with PAK1 and bound selectively to the carboxyl
kinase domain of PAK1 and the ability of the binding was enhanced along
with activation of PAK1. The binding pattern of PAK1 implied that this interaction
was mediated in part by the PAK1 kinase activity.

TH1 inhibited PAK1 kinase activity and negatively regulated MAPK signal
transduction.

2009年1月3日土曜日

納豆菌が生産する「抗癌」ビタミン 「K2 」 (メナキノン-7)

アルピニストなら「K2 」と言えば、ヒマラヤ山脈にあるエベレストに次ぐ世界第
二の高山 (海抜 8611メートル) をすぐ想起するだろう。山頂が鋭く切り立っ
たこの山の登頂はエベレストよりもテクニカルにずっと困難で、1954年(エ
ベレスト征服の翌年)にイタリヤ遠征隊によって、初めて征服された。

さて、もう1つ我々にとって興味深い 「K2 」がこの世に存在する。 それは、
我々日本人の日常生活に大変身近な (なじみ深い) ビタミンの一種である。

納豆には抗癌作用を持つビタミン 「K2」 (化学名メナキノン-7) がタップリ含れ
ている。その理由は、(大豆を発酵させて納豆を作る) 「納豆菌」がそれをせっせ
と生産するからである。さて実際に、どの位含れているのかを知りたいわけだが、
例えば、あなたが食べている納豆には、ビタミンK2の含量の表示がありますか?

参考までに、国立健康栄養研からの情報を紹介すれば、例えば、 糸ひき納豆には、
870 micro g/100 g、 ひき割り納豆には、1300 micro g/100 g も含れている。

http://hfnet.nih.go.jp/contents/detail17.html

さて、次に我々が知りたいのは、毎日どれぐらいの量の納豆を食べたら、あるい
はビタミンK2を摂取したら、癌の予防あるいは治療効果があるかを算出できる具体的な
動物実験データである。目下文献で調査中なので、しばらくお待ち下さい!


ビタミンK2の抗癌作用メカニズム?

最近の色々な研究結果をまとめてみてわかったことは、どうやらビタミンK2も、
面白いことには、抗癌性のキナーゼ「PAK」を遮断しているらしいということ
である。 まず、サイクリンD1 の発現を抑えると共に、p21 (CDK 阻害蛋白)
の発現を高め、、癌細胞の分裂を抑える。 さらに、細胞死ももたらす。固形癌の
増殖に必要な血管新生ばかりではなく、癌の転移も抑える。

これらの一連の作用は、「PAK」遮断剤と非常に良く似ている。さらに、ビタミンK2は、
「PAK」依存性の癌であるすいぞう癌や卵巣癌の増殖を選択的に抑えるが、正常な
細胞の増殖には全く影響を及ぼさない。将来チャンスがあったら、ビタミンK2が実際に
「PAK」を遮断していることを確かめてみたい。


納豆は、喘息などのアレルギー症にも効く!

http://www.takenokoshinryojo.com/soudan/index5-6.htm

喘息を抑えるのは納豆中のメナキノンー7である。1975年ごろ、岡山大学医学
部第二内科の高橋 清らの研究結果によれば、このビタミンK2による一年間以上
の治療 (治験) によって、喘息患者の大部分が「喘息持ち」から解放されたそう
である (発作を即座に止めるというのではなく、発作を予防する)。

さて、メナキノンー7が喘息を抑える分子メカニズムらしいものが、この正月明
けに判明した。実は、喘息は気管支にアレルギー性の炎症を起こることによるわ
けだが、この炎症 (発作) には、マスト (肥満) 細胞が脱顆粒し、ヒスタミンな
どが放出されることが必要である。このマスト細胞の機能には、なんと「PAK」
が必須であることが、米国のインディアナ大学の小児科医ウエード・クラップの
研究室によって、直接 (動物実験で) 証明された (詳しくは、下記の論文要旨を
参照されたし)。

前述したが、PAK遮断剤「FK228」により、動物の喘息症状やリュウマチ性
関節炎が抑えられることが既に確認されている。

逆にいえば、メナキノンー7が「PAK」遮断剤であることを、間接的に裏付け
ているわけだ。こうして、「納豆はPAK遮断剤である」という我が自説に、さ
らなる自信を深めた! あとは実験で直接証明するだけだ。。。

Blood. 2009 Jan 5.

PAK1 regulates mast cell degranulation via effects on calcium mobilization
and cytoskeletal dynamics.


Allen JD, Jaffer ZM, Park SJ, Burgin S, Hofmann C, Sells MA, Chen S, Derr-Yellin
E, Michels EG, McDaniel A, Bessler WK, Ingram DA, Atkinson SJ, Travers JB,
Chernoff J, Clapp DW.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis,
IN, United States.

Mast cells are key participants in allergic diseases via activation of high
affinity IgE receptors (FcepsilonRI) resulting in release of pro-inflammatory
mediators. The biochemical pathways linking IgE activation to calcium influx
and cytoskeletal changes required for intracellular granule release are
incompletely understood.

We demonstrate, genetically, that PAK1 is required for this process. In
a passive cutaneous anaphylaxis experiment, W(sh)/W(sh) mast cell-deficient
mice locally reconstituted with PAK1(-/-) bone marrow-derived mast cells
(BMMCs) experienced strikingly decreased allergen-induced vascular permeability
as compared to controls. Consistent with the in vivo phenotype, PAK1(-/-)
bone marrow-derived mast cells (BMMCs) exhibited a reduction in FcepsilonRI-induced
degranulation.

Further, PAK1(-/-) BMMCs demonstrated diminished calcium mobilization and
altered depolymerization of cortical filamentous actin (F-actin) in response
to FcepsilonRI stimulation. These data implicate PAK1 as an essential molecular
target for modulating acute mast cell responses that contribute to allergic
diseases.


納豆は「家庭でも」容易に手作りが可能!

材料として、煮た大豆と(煮沸した) 稲藁があれば、中学生にでもできる。
(耐熱性の「納豆菌」は、藁に棲息している)。
だから、「納豆屋」さんの存在しない「海外」でも手作りが可能!
早速、実験をしてみよう。詳しくは、下記のネット欄を参照されたし:

http://www.aichi-c.ed.jp/contents/rika/syotou/syo10/nattou/nattou.htm


Methods for Making "Natto" in North America:

http://www.gaia21.net/natto/making.htm

続く