Algorithm for Hypertension Therapy by Gene Expression Programming

jinksimaginaryIA et Robotique

7 nov. 2013 (il y a 7 années et 11 mois)

351 vue(s)


BMFSA(2008-13-2-13) Biomedical Soft Computing and Human Sciences, Vol.13, No.2, pp.95-100 (2008)
[Original Article] Copyright©1995 Biomedical Fuzzy Systems Association

Algorithm for Hypertension Therapy by Gene Expression Programming

Hideyasu HIRANO
, Kenichi MAKINO
and Keiichi ARASHIDANI

1) Internal Medicine, Showa Hospital, Akane Medical Corporation
2) Environmental Management, University of Occupational and Environmental Health
(received 30 September 2007, revised and accepted 19 November 2007)
Diabetes mellitus, hypertension, hyperlipidemia, and hyperuricemia are called
lifestyle related disease. Gene Expression programming might be one of the best
programming methods to reconstruct disease tissue histology. The arteriosclerosis
represents the terminal state of vascular degeneration depending on long never-ending
diabetes, hypertension, and hyperlipidemia. Histological reconstruction might induce the
better disease situation. We created 5 basic commands to control vascular atherosclerosis.
One: β-oxidation, 2:Activate PPP, and 3:Inhibition of collagen synthesis, those are
introduced from Biochemical Expression Programming (BEP). Four: digest collagen is
introduced from Gene expression Programming (GEP). Five: Suspend embolism is an
example of medicine-expression programming (MEP). We succeeded to decrease the
hypotensives by GEP programmed to clean up atherosclerotic blood vessels.

Keywords: Keywords thiamine, pantothenic acid, Glutathione, Tocopherol, Alfacalcidol
1. Introduction
Hypertension, hyperlipidemia, hyperuricemia,
stroke, ischemic heart disease, and cancer were
defined as adult ailments. While many researchers
reported those for congenital diseases, highly
controlled nutrition reduces the occurrence of such
adult ailments. So the hypertension, hyperlipidemia,
and hyperuricemia called life-style related diseases.
Hyperuricemia is an excess of uric acid in the blood
diseases. In 1996, public health council (PHC)
proposed that there are many causes of adult
ailments in our daily life, so PHC defined as those
diseases for life style diseases. Definition of
Lifestyle disease is a disease associated with the way
a person or group of people lives. Lifestyle diseases
include atherosclerosis, heart disease, stroke; obesity,
type 2 diabetes; and diseases associated with
smoking, alcohol drinking and drug abusing. Regular
physical activity helps to prevent the arteriosclerosis
that represents the terminal state of vascular
degeneration depending on long passed diabetes,
hypertension, and hyperlipidemia. Our research was
to classify the disease state, passing, therapy and
situations. After that those were collected and

Hideyasu Hirano
35-1 Shioiri Shimonoseki YG 750-0059 Japan Tel.
+81-832-31-3888, Fax. +81-832-31-7957

Figure 1. Concept of human as a computer [2].
Obesity, heart disease, hypertension, diabetes,
metastasis of cancer, and premature mortality are the
targets of histological reconstruction by GEP.

analyzed them. to cure with GEP (Gene Expression
Programming [1]). Here we created a program to
reconstruct disease’s histology and found our
program ran imaged statue in human body, and those
indicated that live human gene could control by
Fuzzy ON/OFF, Fuzzy Chaos theory. Thus our
efferts resulted in decrease no of hypotensives’
tablets. The atherosclerotic blood vessels cured well
with the created expression program almost no bugs.
2. Clean up atherosclerosis

Inside of the Arteriosclerotic blood vessel carries
fats (neutral fat =fatty acids + glycerin、cholesterol)、
thrombosis (inactivated round erythrocytes were
Biomedical Soft Computing and Human Sciences, Vol.13, No.2 (2008)


Table1.Hypertension regulatory commands and intra-human Machine Language. The commands β-oxidation
and Activate PPP were created from biochemical reactions (BEP). Digest collagens was introduced from gene
expression (GEP). Thrombolysis was chosen from medicines’ effects (MEP)

carrier of oxygen), the supporting collagens and
membrane. If those scientists analysis about blood
vessel should be true, we will be able to vanish away
those inside substances using biological, medicines
and gene expression reactions. Ideal way have to be
1) fatty acids degenerate CO
and H
O through
β-oxidation reaction using pantothenic acids and
vitamin B
, 2) components of atheroma are covered
with collagen membrane and supported with
collagen fibers. To remove these collagens we
decided to use GEP, that is, ECM (extra cellular
matrix) metallo-proteinase expressed by Vitamin D

might digest collagens [3-5]. 3) The third is to inhibit
clotting of erythrocytes by activating pentose
phosphate pathway. This procedure regenerates
erythrocytes from stomacyte shape to normal
discocyte shape (biconcave discoid shape).
Regenerated discocytes might re-circulate blood
vessel. 4) Atorvastatin inhibits HMG-CoA reductase,
which is the key enzyme of cholesterol synthesis.
Ursodeoxycholic Acid increases cholesterol
excretion into feces, these two reactions may work
for histological reconstruction.
Gene expression mechanism of vitamin D
illustrated in Figure 3 Binding after the receptor on
plasma membrane, the vitamin D
internalized into cellular plasma. Then the formed
spherical particle move to the surface on the nuclear
membrane, thereafter fused into inside-out forming
to release receptor complex of vitamin D
, which
moved again in the nuclear plasma to bind vitamin
binding element at the promoter of ECM
metalloprotease genes, that switch on to transcribe
mRNAs [7-9].
Making a program to run in human

The program to run must clean up atherosclerosis,
and then we defined 3 months (12 weeks) as 1 Kur.
The initial step took for 2 weeks to digest collagens

‘Clean up arteriosclerosis [CLEANUPAS.BAS]
*Start - - - - - 1 Kur
‘Cleanup blood vessels with arteriosclerosis
For repeat=1 to 3
For week_a=1 to 2
For day=1 to 7
Digest collagens
Activate PPP
Suspend embolism
Next day
Next week_a
‘Cover with vascular end membrane
For week_b=1 to 2
For day=1 to 7
Suspend embolism
Inhibit collagen synthesis
Next day
Next week_b
Next repeat :*END
and β-oxidize fatty acids, next step of waiting
endothelium membrane growth inside blood vessel
needed 2 weeks. It was possible to change this
waiting step to inhibit collagen synthesis with
vitamin E that inhibits collagen synthesis after
re-circulate erythrocyte and peeling off atheroma
little by little with Vitamin D

H. HIRANO et al.: Algorithm for Hypertension Therapy by Gene Expression Programming


Figure 2. The pathway for catabolism of fatty acids is referred to as the β-Oxidation
Pathway, because oxidation occurs at the β-position of carbon (C3).[6]

Figure 3. ECM metalloproteinase gene expression
mechanism of vitamin D

4. Measuring age of the blood vessel by
Pulse wave velocity (PWV) is an index of arterial
stiffness, and a simple device for measuring
brachial-ankle PWV (baPWV) by measuring 4
inflatable (Riva-Rocci) cuffs with round metal panel
placed around the both upper arms and lower
extremities on 2 cm upper ankles. The pulse wave
velocity indicates the age of arterial blood vessel.
We defined 6 arteriosclerotic statuses as for
5: Very dangerous is for more than 115 years,
4: Dangerous is for more than 85,

Figure 4A, FORM data is shown. The highest double
line box 1 is the data of patient. Box 3 described
patient's blood pressure of 4 extremities and of ABIs.
Box 4. Left graph shows plotted data. Abscise: ABI,
ordinate baPWV. Right graph shows mean (line) and
-SD (dotted line) of blood vessel ages. Triangles:
Actual patient data. Abscise: year’s olds, ordinate:
A fatty acid oxidation occurs
at β-position of carbon atom,
formed acetyl-CoA was
oxidized at mitochondrial TCA
cycle to CO
and H

Biomedical Soft Computing and Human Sciences, Vol.13, No.2 (2008)


3: Relatively dangerous is for 20 years over the
actual age,
2: Need to control nutrition, and
1: the rest of them are safety.
6: Out of normal ABI index (<0.9, 1.3<) indicates
the existence of arteriosclerosis obliterans, in this
status no reliable baPWVs obtain, need
immediate div (drip infusion in vein) therapy.
The case 6, 5, 4, and 3 need GEP therapy we
describing here.
Figure 4 shows FORM data of 86 years, the blood
vessel age was over 115 years old while after the
GEP therapy the age showed 95 years, 20 yeas had
pull backed
We focused the effect of GEP therapy on carotid
artery. The echograms of figure 5 shows before and
after the GEP therapy of carotid artery. The pulsation
was very limited before GEP, while clear pulsation

observed after GEP. Inside and outside of the
membrane fat disappeared after GEP.

5. GEP therapy effective to decrease
Patients with hypertension have to take
hypotensives all their lives, our GEP therapy,
however, succeeded to decrease their tablets taken.
The name of the used tablets were Valsartan
(40)(angiotensin II receptor blocker), amlodipine
(2.5)(calcium channel antagonist), nifedipineL(10)
(L-type calcium channel blockade), Imidapril (5)
(Angiotensin-converting enzyme inhibitor),
doxazosin(1) (α1-blocker), prazosin(0.5) (α-1
adrenergic blocker), DiltiazemR(100) (L-type Ca2+
channel blocker Diltiazem) and Aspirin(100)
(long-term aspirin use irreversibly blocks the
formation of thromboxane A2 in platelets).
All 4 patients decreased their hypotensives within
330 days. A rapid case spent 90 days, and a slow
case needed 330 days. Main reason of this difference
was the body weight control. The best case was
hospitalized and controlled nutritionally. The longest
case no visit our clinic from 49
day to 153
Long days difference of this might be induced from
Niacin, which is the key vitamin to synthesize fatty
acids. A patient suffered from fatty liver or diabetes
mellitus and whose compliance was bad, it was
difficult to peel off atheroma in the course of
increasing bodyweight.

Figure4B. Blood vessel age. upper graph: before GEP, down graph: after GEP. FORM data indicated that her
blood vessel age was changed from115 yeas old to 95 years, this meant more than 20 years off her pre GEP
therapy of blood vessel age. Both of Abscises ABI, Ordinates baPWV. ▲is right lower extremity, △is left
lower extremity
H. HIRANO et al.: Algorithm for Hypertension Therapy by Gene Expression Programming


Figure 5. Echograms of before and after GEP therapy of carotid artery arteriosclerosis. Fatty generated inside
and outside of carotid artery had almost cleared and recovered pulsation.

Figure 6. Four line graphs show individual patients. All 4 patients decreased their
hypotensives‘ tablets by GEP therapy.

6. Conclusions

1. BEP: β-oxidation, Activate PPP
2. GEP: Digest collagen
3. MEP: Suspend embolism
We have defined 4 main GEP (BEP, GEP and
MEP) commands to control arteriovenous histology.
We used these command on the program mode
against human body that induced artheriosclerotic
restoration of vessels, and decreased their

[1] Hirano-H, Makino-K, Tomonaga-K,
Arashidani- K, Kunugita-K. Yoshimizu-T.,
(2006) “Gene Expression Programming to
Biomedical Soft Computing and Human Sciences, Vol.13, No.2 (2008)


Envelop Metastasized Cancer Cells by
Commanding Adjacent Fibroblasts,” J. Showa
Hsp, Vol. 3, No. 1, pp. 89-99
[3] Thomson B. M, Atkinson S. J., Reynolds J. J.,
Meikle M.C., (1987) “Degradation of type I
collagen films by mouse osteoblasts is
stimulated by 1,25 dihydroxyvitamin D3 and
inhibited by human recombinant TIMP (tissue
inhibitor of metalloproteinases),” Biochem
Biophys Res Commun, Vol. 148, No. 2, pp.
[4] Uchida M., Shima M., Chikazu D., Fujieda A.,
Obara K., Suzuki H., Nagai Y., Yamato H.,
Kawaguchi H., (2001) “Transcriptional
induction of matrix metalloproteinase-13
(collagenase-3) by 1alpha,25-dihydroxyvitamin
D3 in mouse osteoblastic MC3T3-E1 cells,” J
Bone Miner Res., Vol. 16, No. 2, pp. 221-230.
[5] Grumbles R. M., Shao L., Jeffrey J. J., Howell
D. S., (1996) “Regulation of rat interstitial
collagenase gene expression in growth cartilage
and chondrocytes by vitamin D3, interleukin-1
beta, and okadaic acid,” J Cell Biochem, Vol.
63, No. 4, pp. 395-409.
[6] Sergio MARCHESINI, Professor of Bioche-
mistry / University of Brescia / Italy,
ml, Biochemistry Course, Fatty Acid
Oxidation and ketone bodies.
[7] Wecksler W. R, Norman A. W., “Measurement
of kinetic rate constants for the binding of 1
alpha, 25-dihydroxyvitamin D3 to its chick
intestinal mucosa receptor using a
hydroxyapatite batch assay”.
[8] Danan J. L., Delorme A. C., Cuisinier-Gleizes
P., (1981) “Biochemical evidence for a cyto-
plasmic 1 alpha,25-dihydroxyvitamin d3 recep-
tor-like protein in rat yolk sac.”, J Biol Chem.,
Vol. 256, No. 10, pp. 4847-50.
[9] Lawson D. E., Wilson P. W., (1974) “Intra-
nuclear localization and receptor proteins for
1,25-dihydroxycholecalciferol in chick intes-
tine”, J Biol Chem., Vol. 144, No. 3, pp. 573-

Hideyasu Hirano
Internal Medicine Fukuoka
Kieikai Hospital,
Special Therapeutic Skills
Suppress Metastasis
Arteriosclerosis obliterans
Hypertention, Athopic dermatitis, Allergie etc.