Iron-Deficiency Anemia

WHAT YOU SHOULD KNOW Iron-deficiency anemia develops when the amount of iron in your blood is insufficient to make hemoglobin, the substance in red blood cells that carries oxygen from your lungs to the rest of your body. There are many other forms of anemia, all involving a shortage of red blood cells, but iron-deficiency anemia is the most common. The problem is seen most frequently in women, children, and older adults. Causes The most common cause is hidden bleeding somewhere in the digestive tract---mouth, esophagus, stomach, or intestines. You may also develop this condition if Your kidneys are not working normally. You have had surgery to remove part of your stomach. You eat too few iron-rich foods such as green leafy vegetables, beans, red meat, and liver. You follow an unbalanced, inadequate weight-loss diet. !oman are more likely to develop iron-deficiency anemia during pregnancy and menstruation. The problem is also more common in premature babies, and in children aged " months to # years, who are likely to have little iron in their diet. The condition remains a possibility from ages $ to %#, when rapid growth sparks increased demand for iron. Signs/Symptoms &uring the early stages of anemia symptoms may be lacking' and when they do appear they may be vague and confusing. (mong the typical symptoms are abdominal pain, coldness, di))iness, fainting, fatigue, headache, inability to think clearly, irritability, loss of appetite, pale blue whites of the eyes, pale skin, rapid heartbeat, shortness of breath during exercise, and weakness. *pecific signs of iron deficiency include a strong desire to eat ice, paint, or dirt, and fingernails or toenails that break easily. Care To correct the problem, it+s important to learn the cause. If blood loss is the underlying problem, your doctor will want to determine where and why you+re bleeding. If you are not eating enough iron-rich foods, you+ll need to add them to your diet, and perhaps start taking iron pills. If your baby has anemia, an iron-fortified formula may be needed. *ometimes a blood transfusion is necessary. WHAT YOU SHOULD DO If your doctor prescribes iron pills, take them with a glass of water or fruit ,uice -but not milk. at least $/ minutes before eating. If the pills upset your stomach, try taking them with a small amount of food. &on+t take the pills at bedtime' this can cause stomach upset. Your doctor may also suggest taking vitamin 0, which helps the body absorb iron. (fter taking your iron, wait at least # hours before taking other medicines. *ome drugs interfere with absorption of iron. 1iquid iron preparations may stain the teeth. 2ix the liquid with water or fruit ,uice and take it through a straw. Then brush your teeth. You should be aware that iron can turn bowel movements dark green or black, and may cause diarrhea or constipation. If constipation develops, try to eat more high-fiber foods

such as beans, vegetables, and whole grain breads and cereals. 3rune ,uice may also help---and also serves as an excellent source of iron. 4eep iron away from children. (n overdose can be poisonous. The body absorbs only a small amount of the iron in food. 5ed meat is the best source. 6ther iron-rich foods include o 7eans -lima, kidney, chickpeas, lentils. o 7lackstrap molasses o &ried fruits -prunes, raisins, apricots. o 8reen leafy vegetables -spinach and broccoli. o 9uts o !hole-grain foods -bread and cereals. &o not drink more than % pint -%" ounces. of milk a day while taking iron medicine. (ny more than this will keep the iron from being absorbed by your body. 6ther foods that prevent absorption are coffee, tea, egg yolks, and yogurt.

Call Your Doctor I !!! You develop heartburn, constipation, diarrhea, nausea, or vomiting. You feel weak or di))y. You have a fever.

See" Care Imme#iately I !!! You develop chest pain or breathing problems.

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ANXIETY - STRESS Anxiety is an abnormal apprehension and fear often accompanied by physiological signs (sweating, increased pulse). Anxiety is a Mood disorder characterized by a feeling of vague, unspecified harm, apprehension or distress, often about the future, without an apparent cause. Psychiatrists often distinguish between Anxiety which can be thought of as a reaction to an ambiguous or imagined danger, and ear, which is a response to a real threat. Prevalence Approximately !"# of adults in $estern nations have experienced an Anxiety disorder in the preceding six months. Approximately %&# of adults in $estern nations experience an Anxiety disorder during their lifetimes. These Substances Alleviate Anxiety 'ubstances that alleviate Anxiety are (nown as Anxiolytics (also (nown as 'edatives). Alcohols )imethylvinylcarbinol alleviates Anxiety (due it sedating the *+'). Amino Acids ,-.ydroxytryptophan (,-./P) alleviates Anxiety. Anxiety can be caused by .istidine imbalances. Phenylalanine alleviates some cases of Anxiety. /aurine alleviates Anxiety (by sedating the *entral +ervous 'ystem). /heanine is useful for the treatment of Anxiety (due to its ability to stimulate the generation of (relaxing) Alpha $aves in the 0rain).

/hreonine alleviates Anxiety. /ryptophan alleviates Anxiety. /yrosine alleviates Anxiety. Animal-Derived Supplements 'tabilium alleviates Anxiety - the effect of 'tabilium is described as being mild. long-term and sub1ectively subtle (compared to the powerful but short-term effects of 0enzodiazepines). Enzymes Pyruvate )ehydrogenase helps to prevent Anxiety (by inhibiting the conversion of Pyruvic Acid to 2actic Acid). Hormones 'upplemental )ehydroepiandrosterone ().3A) alleviates Anxiety. 'upplemental Melatonin often alleviates Anxiety (due to its ability to bind to 0enzodiazepine 4eceptors). 'upplemental Pregnenolone may be useful for the treatment of Anxiety. Lipids Phosphatidylserine may alleviate Anxiety. Minerals Anxiety can occur as a result of 5ron deficiency. Anxiety patients are often deficient in Magnesium and supplemental Magnesium (6"" - 7"" mg per day) alleviates some cases of Anxiety. Anxiety can occur as a result of Potassium deficiency. Anxiety can occur as a result of 'elenium deficiency and supplemental 'elenium reduces Anxiety in such patients. eurotransmitters 8amma Aminobutyric Acid (8A0A) prevents Anxiety messages from reaching the motor centers of the 0rain by filling the 0enzodiazepine 4eceptors within the 0rain - 9itamin 0: and 5nositol are essential cofactors for this process. 2ow levels of .istamine can cause Anxiety. Anxiety can occur as a result of insufficient production of 'erotonin. Polyphenols Apigenin alleviates Anxiety (by binding to and activating 0enzodiazepine 4eceptors). *hrysin binds to and activates 0enzodiazepine 4eceptors - this activation of 0enzodiazepine 4eceptors helps to alleviate Anxiety. erulic Acid alleviates Anxiety. 8amma ;ryzanol alleviates Anxiety. Smart Dru!s *entrophenoxine alleviates Anxiety. )ilantin reduces Anxiety. )imethylaminoethanol ()MA3) alleviates Anxiety. 8amma-.ydroxybutyric Acid (8.0) alleviates Anxiety (by enhancing the function of 8amma Aminobutyric Acid). 8erovital (8.-:) alleviates Anxiety (especially in the elderly). +imodipine alleviates Anxiety. ;ndansetron alleviates Anxiety (by antagonizing the ,-./: 4eceptors within the 0rain, facilitating the release of Acetylcholine and preventing excessive 'erotonin activity). ;xiracetam alleviates Anxiety. Picamilon alleviates Anxiety (without producing sedation). Piracetam alleviates Anxiety. Pramiracetam alleviates Anxiety in Alzheimer<s )isease patients. Pyroglutamate alleviates Anxiety. 9inpocetine alleviates some cases of Anxiety (where Anxiety is caused by *erebral 5nsufficiency). =atosetron alleviates Anxiety (by antagonizing the ,-./: 4eceptors within the 0rain, facilitating the release of Acetylcholine and preventing excessive 'erotonin activity).

Sul"uric #ompounds Methylsulfonylmethane (M'M) (:,""" - 7,""" mg per day) alleviates Anxiety. $itamins olic Acid (especially when administered concurrently with 9itamin 0!%) alleviates Anxiety. 5nositol alleviates Anxiety (by enhancing the ability of 8A0A to bind to the 0enzodiazepine 4eceptors in the 0rain). 9itamin 0! alleviates many cases of Anxiety (by activating the Pyruvate )ehydrogenase enzyme, thereby inhibiting the conversion of Pyruvic Acid to 2actic Acid - 2actic Acid is an underlying cause of Anxiety). /he +iacinamide form of 9itamin 0: (!,""" - >,""" mg per day) alleviates Anxiety (by enhancing the ability of 8A0A to bind to the 0enzodiazepine 4eceptors within the 0rain). 9itamin 0> alleviates Anxiety. 9itamin 0!% (administered concurrently with olic Acid) alleviates Anxiety. Anxiety increases the body?s re@uirements for 9itamin *. These %oods&Herbs Alleviate Anxiety Aromatic 'ils +eroli ;il (vapors inhaled via Aromatherapy) alleviates Anxiety. ungi (Mushrooms) 4eishi Mushrooms alleviate Anxiety. Herbs Ashwagandha alleviates Anxiety. 0lac( *ohosh reputedly alleviates some cases of Anxiety (according to fol(lore). 0rahmi alleviates Anxiety. *hamomile alleviates some cases of Anxiety (by sedating the *entral +ervous 'ystem). )amiana reputedly alleviates Anxiety where Anxiety stems from sexual factors (according to fol(lore). 8in(go biloba alleviates some cases of Anxiety (especially when Anxiety is caused by *erebral 5nsufficiency). 8otu Aola alleviates Anxiety. 8reen /ea is useful for the treatment of Anxiety (due to the /heanine content of 8reen /ea stimulating the generation of (relaxing) Alpha $aves in the 0rain). .ops alleviate Anxiety by sedating the *entral +ervous 'ystem (primarily due to the )imethylvinylcarbinol content of .ops). Aava Aava (:"" mg per day) alleviates Anxiety (primarily due to the Pyrones content of Aava Aava). Passion lower alleviates Anxiety (primarily due to the 0ioflavonoids and .armala Al(aloids of Passion lower sedating the *entral +ervous 'ystem). 'aint Bohn?s $ort potently alleviates Anxiety. 9alerian alleviates Anxiety. =izyphus alleviates Anxiety. 'ther %actors that Alleviate Anxiety Exercise Moderate to intense 3xercise reduces AnxietyC - Aerobic 3xercise reduces Anxiety. research - 3xercise reduces Anxiety where Anxiety is caused by excessive consumption of *affeine. These Substances #ause&Exacerbate Anxiety Aldehydes Acetaldehyde can cause Anxiety.

Al(aloids Anxiety can occur as a result of *affeine withdrawal or from excessive consumption of *affeine (caffeinism). 3xcessive consumption of 3phedrine causes Anxiety by causing excessive stimulation of the *entral +ervous 'ystem (*+'). Anxiety can occur as a result of +icotine (i.e. /obacco 'mo(ing) withdrawal. 3xcessive dosages of Dohimbine can cause Anxiety in some persons. Amino Acids 3xcessive consumption of Aspartic Acid can cause Anxiety (by causing over-stimulation of the +-methyl-)-aspartate (+M)A) 4eceptors in the 0rain. 3xcessive consumption of 8lutamic Acid can cause Anxiety (by causing over-stimulation of the +-methyl-)-aspartate (+M)A) 4eceptors in the 0rain. Monosodium 8lutamate (M'8) can cause Anxiety (by causing over-stimulation of the +-Methyl-)-Aspartate (+M)A) 4eceptors in the 0rain. 3xcessive dosages (more than !,,"" - %,6"" mg per day) of Phenylalanine supplements can cause Anxiety. /yramine can cause Anxiety (by overstimulating the Adrenal 8lands and depleting reserves of +orepinephrine). Environmental Toxins Amalgam )ental illings can cause Anxiety (due to the Mercury component of Amalgam )ental illings). - 3pidemiological evidence indicates that young people with Mercury-containing Amalgam )ental illings have a greater incidence of Anxiety compared to young people with no Amalgam )ental illings. %ood Additives Aspartame can cause Anxiety (primarily due to its Methanol content). Hormones 3xcessive production of Adrenaline within the body causes unpleasant over-stimulation that manifests as Anxiety. 3xcessive production of *holecysto(inin (**A) can cause Anxiety. Minerals *admium can cause Anxiety. 3xcessive consumption of *opper can cause Anxiety. 3xposure to Mercury can cause Anxiety. 'r!anic Acids /he accumulation or production of excessive amounts of endogenous 2actic Acid (produced within the body during metabolism) can cause Anxiety. Pharmaceutical Dru!s 2ong-term usage of 0arbiturates causes Anxiety. Anxiety can occur as a result of the $ithdrawal 'yndrome associated with cessation of 0enzodiazepines use (despite the fact that 0enzodiazepines are usually initially used to treat Anxiety). 0upropion causes Anxiety in some persons. Anxiety is a common side effect of *lomiphene (a ertility )rug). Anxiety can occur as a result of cessation of usage of Minor /ran@uilizers. Prozac therapy can cause Anxiety (due to the increased levels of 'erotonin associated with Prozac). )ecreational Dru!s Although Alcohol (ethanol) temporarily alleviates Anxiety (by binding to the 0enzodiazepine 4eceptors in the 0rain), long-term or excessive consumption of Alcohol causes Anxiety (by damaging the 0enzodiazepine 4eceptors within the 0rain) - Alcoholics usually experience Anxiety as a result of Alcohol withdrawal. 2') can cause extreme (but temporary) Anxiety. .igh doses of Mari1uana can cause (temporary) Anxiety. Mescaline (in the dosages normally used by Psychedelic )rug users) causes Anxiety.

These *evera!es&Herbs can #ause Anxiety *affeine-*ontaining 0everages Anxiety can occur as a result of withdrawal from drin(ing *offee (this is due to *affeine withdrawal). Herbs 3xcessive consumption of 3phedra can cause Anxiety (this occurs from the 3phedrine component of 3phedra causing excessive stimulation of the *entral +ervous 'ystem). These Ailments can #ause Anxiety Di!estive System Anxiety can occur as a result of over-proliferation of *andida albicans. Metabolism Anxiety is one of the minor symptoms of ibromyalgia - >%# of ibromyalgia patients experience Anxiety, 5rritability and overconcern without any specific precipitating events causing these feelings. Anxiety can occur as a result of .ypoglycemia. Anxiety can occur as a result of .ypothyroidism. ervous System Anxiety can occur as a result of Adrenal 5nsufficiency. Anxiety can be caused by *erebral 5nsufficiency (impaired 0lood *irculation to the 0rain). ;ver stimulation of the +-methyl-)-aspartate (+M)A) 4eceptors in the 0rain can cause Anxiety. utritional Ailments Anxiety is a symptom of Pellagra. Sexual System Anxiety can occur as a result of the Male Menopause. research Anxiety can occur as a result of the PM'-A (Anxiety) form of Pre-Menstrual 'yndrome (PM'). Anxiety can #ause these Ailments #ardiovascular System Anxiety increases the ris( of .ypertension. Di!estive System )iarrhea can be caused by Anxiety. *onstant Anxiety may increase the ris( of 5rritable 0owel 'yndrome (50'). Excretory System Anxiety is a common cause of Male Erinary .esitancy in otherwise healthy men. +mmune System Anxiety causes suppression of the 5mmune 'ystem. S(in Anxiety reduces 'exual )esire. 'low healing of $ounds can occur as a result of Anxiety (due to 5mmune 'ystem suppression that occurs in con1unction with Anxiety). Types o" Anxiety Disorders 8eneral Anxiety )isorder (also (nown as 8eneralized Anxiety )isorder or 8eneralized Anxiety )isorder) involves chronic, repeated episodes of Anxiety reactions. 5t is a psychological disorder in which Anxiety or morbid ear and dread accompanied by autonomic changes are prominent features. Phobic )isorder involves 5rrational, persistent, exaggerated fear of a specific situation or ob1ect, combined with a compelling re@uirement to avoid the dreaded stimulus. Panic )isorder (also (nown as Panic Attac(s) involves severe attac(s of overwhelming Anxiety.

;bsessive-*ompulsive )isorder (;*)) involves recurrent thoughts, feelings or actions that are unpleasant and which provo(e Anxiety. Post-/raumatic 'tress )isorder (P/')) is a condition resulting from ma1or trauma such as rape, childhood abuse or wartime experiences, and including the re-experiencing of the trauma and emotional numbing.

ADHD and Iron Deficiency Anemia

0y Anthony Aane, M) Author of FG.ow to .elp /he *hild Dou 2oveFG Mental .ealth Professional Physician and 'urgeon A)) A).) Advances Anthony Aane, M) is a physician, an international lecturer, and director of special education. .e is the author of a boo(, numerous articles, and a number of online courses dealing with A).), ;)), parenting issues, and education. .is Program G.ow to 5mprove Dour *hild?s 0ehaviorG is helping parents around the world help their children. Dou may visit his website, A)) A).) Advances, at httpCHHaddadhdadvances.com and sign up there for the A)) A).) Advances online 1ournal or send an email to subscribeIaddadhdadvances.com.

A).) and 5ron )eficiency

by Anthony Aane, M) Attention Publisher, /his article is available for your website or ezine. or an ezine, send an email toC ironIaddadhdadvances.com. or an website send an email toC ironhtmlIaddadhdadvances.com About J# of children, ages 6 years and under, are deficient in iron. 0etween the ages of , and !%, the percentage rises to !:#, and then settles bac( to J# in people above the age of !,. Anemia is the best-(nown repercussion of iron deficiency. .owever, even minor deficiencies in iron may wea(en the immune system, affect the thyroid, and impair general physical performance. 5ron deficiency has also been implicated in a number of psychiatric and neurological conditions, including learning disabilities and A).). 5ron is a co-enzyme in the anabolism of catecholamines. /hat means it is essential for the creation of certain neurotransmitters. 5t helps to regulate the activity of the neurotransmitter dopamine, which probably accounts for the association of iron deficiency with neurological problems. 5t ma(es sense that supplementing A).) children, who have some level of iron deficiency, might have some effect on their A).). .owever, what ma(es sense in theory, does not always wor( in practice. Enfortunately, there have been very few studies done testing the effects of iron supplementation on A).). ;ne study, done in 5srael, evaluated !6 A).) boys for the effect of short-term iron administration on behavior. 3ach boy received iron daily for :" days. 0oth parents and teachers assessed the behavior of the children. /he parents found significant improvement in the behavior of the children. .owever, the teachers noticed no improvement. 5n a second study, :: iron-deficient, but otherwise normal, children were given an iron supplement. /he children became less hyperactive. /his study suggests that iron deficiency may cause

hyperactive behavior in some children and that hyperactive behavior is reversible when the deficiency is treated. A third study tested the affects of iron supplementation on a group of teen-aged high school girls who were determined to be iron deficient. At the end of the J-wee( study, the researchers found that girls who received iron supplementation performed better on verbal learning and memory tests than those who did not. /his is about all the evidence we have. 5t<s not a lot and it<s not very impressive. +one of the studies were double-blind studies, which means we cannot really rely on them all that much. 5f this were the only consideration, 5 would say you should definitely try to treat your child for iron deficiency. /he reason is that hyperactive children are more li(ely to be iron deficient than other children. Also, there is a possibility that your child has a higher than average iron re@uirement. /hat means that he might test normal on all the iron blood tests and still be iron deficient because he re@uires more than the average amount of iron. 'o why not 1ust give your child iron supplements and see what happensK 0ecause iron functions in the body li(e a two edged sword. 5ron exists in the body in two chemical forms. /here is the ferrous form, where the iron atom will bond to two electrons and the ferric form where the atom will bond to three electrons. 5ron can go bac( and forth between these two forms. /his is the property of iron that allows it to play a role in carrying oxygen as part of hemoglobin. .owever, it also ma(es iron an active player in oxidationreduction reactions. $hat that means is that iron has the ability to act li(e a free radical and cause significant damage to tissues. $henever iron is not bound to hemoglobin or to some other carrier protein, it travels around the body as free iron and can cause damage anywhere it goes. /o further exacerbate the problem, excess iron is not eliminated well by the body. Most of the iron in the body gets recycled. /herefore, not only is excess iron toxic, but also once you have excess iron in your body, it is going to stic( around for a long time. .igh amounts of iron have been found in the brains of people with Par(inson<s disease. 5t is very li(ely that excess iron can aggravate, if not cause, other neurological problems as well. $ith that in mind we have to approach iron supplementation with caution. My feeling is that if your child turns out to be one of the J-!:# that is deficient in iron, it is worth giving iron supplements. 5 doubt that it will help much with his A).), but it should help with his general health. /his advice applies to your non-A).) children, also. .ow should you test iron deficiencyK /he hemoglobin and hematocrit counts that come as part of the standard complete blood count (*0*) are good for diagnosing anemia. /hey do not really give you accurate information about the body<s iron status. /he best test for iron status is the serum ferritin test, which measures how much iron is stored in your body. 5t will be low if you are deficient and high if you are overloaded. 5f you find your child has an iron deficiency problem, there are several approaches to treat it. Probably the safest is by giving him more iron-containing foods. Dou can serve him red meat several times a wee(. 2iver is an excellent source, if you can get him to eat it. Dou can enhance dietary absorption by supplementing with vitamin A (about !",""" 5E) and vitamin * (about ,""mg) with the meals.

/he most li(ely the reason that your child is deficient is because he is a poor eaterL so, dietary intervention may not be practical. A second and far inferior source of iron is through supplements. /he primary difficulty of iron supplements is that they do not get into the body. ortifying foods with iron in general does not wor(. Many foods bind iron and, as a result, the iron is excreted rather than absorbed. /he best form of supplemental iron is errochel. errochel is an amino acid chelated iron, which is highly bio-available and is not affected by foods that bind iron. Most iron supplements have a ten percent absorption rate. /hat means if you ta(e !" mg of the supplement, your body absorbs ! mg. errochel is different. errochel has a &,# absorption rate. /hat means !., mg of errochel provides more iron to your body than !" mg of other supplements. /hat is an interesting fact, but it is not why 5 am recommending it. /he more important property of errochel is that since it is already amino acid bound, it does not become free iron in the body. /hat means it does not have the dangers and side effects of other iron supplements. /he )A has given errochel the designation of 84A', (generally regarded as safe). +o other iron supplement has this designation. /he ta(e home message is that iron deficiency may be the cause of hyperactivity in some children. 5t is worth your while to have your child tested. 5f for some reason you suspect your child is iron deficient, the best approach is to increase your child<s iron inta(e through his diet. 5f that doesn<t wor( and you need to use supplements, the best supplemental iron is errochel. 8ood luc(. Anthony Aane, M) A)) A).) Advances Anthony Aane, M) is a physician, an international lecturer, and director of special education. .e is the author of a boo(, numerous articles, and a number of online programs dealing with A).) treatment, ;)), child behavior issues, and education. Dou may visit his website, A)) A).) Advances, and sign up for the A)) A).) Advances online 1ournal. M %""!-%""& Anthony Aane. All 4ights 4eserved.

B. 0iochem, !77,, 9ol. !!&, +o. 6 -./---0 M !77, Bapanese 0iochemical 'ociety

researcharticle

+nvolvement o" Peripheral-Type *enzodiazepine )eceptors in the +ntracellular Transport o" Heme and Porphyrins1
Shi!eru Ta(etani23 Hirao 4ohno3 Ta(a(o %uru(a5a and )i(io To(una!a

Department of Hygiene, Kansai Medical University Moriguchi, Osaka 570

%

/o whom correspondence should be addressed

/o investigate the involvement of peripheral-type benzodiazepine receptors (P04) in heme metabolism, we examined the interaction of N,, eOheme with P04. /ransfection of the cloned mouse P04-iso@uinoline carboxamide-binding protein (P04H50P) c)+A into mon(ey (idney *os-! cells resulted in a %.,-fold increase in N,, eOhemin binding sites, concomitant with the increase in N:.OPA!!!7, binding sites, as compared with those seen in antisense P04H50P c)+A-transfected cells. /he binding of hemin to the transfected receptors exhibited a relatively high affinity with a Kd of !% nM, and was inhibited by several benzodiazepine ligands, including PA!!!7,, 4o ,-6J>6, diazepam and protoporphyrin 5P. $hen mouse liver mitochondria were incubated with N,, eOhemin, the binding to P04 had a Kd of !,Q!.JnM. /he max of N,, eOhemin binding to the mitochondria was >.JJQ".&> pmolHmg of protein, a value consistent with that of N:.OPA!!!7, binding, with a lower affinity. *oproporphyrinogen 555, a precursor porphyrin produced in the cytosol, is translocated into mitochondria, then is converted to protoporphyrinogen 5PL this conversion decreased in the presence of benzodiazepine ligands. /o examine whether this decrease was related to a decrease in the binding of coproporphyrinogen to the mitochondria, the effects of benzodiazepines on the binding of coproporphyrinogen were examined. As the binding was dose-dependently inhibited by PA!!!7,, 4o ,-6J>6, and diazepam, porphyrins are li(ely to be endogenous ligands for P04. $e propose that P04 play a role in the intracellular transport of porphyrins and heme.
!

/his study was supported in part by 8rands-in-Aid for 'cientific 4esearch from +issan 'cience oundation, from the 'cientific 4esearch Promotion und of the Bapan Private 'chool Promotion oundation and from the Ministry of 3ducation, 'cience and *ulture of Bapan