JPRS ID: 9755 USSR REPORT LIFE SCIENCES BIOMEDICAL AND BEHAVIORAL SCIENCES

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JPRS L/9755
26 May 1981
~ USSR Report
,
y
LIFE SCIERICES
BIOMEDICAL AND 6EHAVIORAI SCIENCES
- cFOU o 7ia 17
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JPRS 1,/9755
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containing the major fraction of eDNA were used. As the result of the experiment
on hybridization of colonies in situlo with 125J 9S RNA and hybridization of
plasmid DNA with the fraction of eDNA enriehed by individual sequence>>, out of 20
verified clones 4 were selected. Restriction analysis of the DNA plasmids
- isolated from these clones demonstrated that one of them (pND77) has an
ineorporated fragment which contains identification for BamHI and PvuII
restrictases at one site.
_ In order to identify definitively clones bearing preproinsulin DNA, :^�:.ra1 of the
selected plasmids were investigated for the ability to stvp the syntl�sis of
preproinsulin in a protein-synthesizing system. As is well knowi, ?WA in
association with complementary DNA is not capable of participating in translation
(the me*':od of "stopping translation" is based on precisely this fact). Plasmid
DNA wa!3 denatured and centrifuged from the poly(A)-RNA, as previously described12.
Next the mixture was divided into two portions, one of which (the control) was
heated to 80 degrees Centigrade (in order to fuse the hybrid), and both
preparations were used as matrices in an cell-free system for protein synthesis.
The translates were fractioned by electrophoresis. As figure 2 shows,
hybridization of RNA with pND77 plasmid results in the disappearance of the
preproinsulin zone. Hence, this plasmid contains the insulin gene fragment. The
molecular mass of the pND77-fragment of fish DNA incorporated into the plasmid is
340,000 daltons. The restriction map of this plasmid is presented in fig 3.
The 134-209 nucleotide sequence of.the cloned DNA fragment was determined using
A.M. Maxam and W. Gilbert's method13 (fig 3a). This sequence corresponds to the
B-peptide site of fish insulin and is homologous to the B-peptide of human
insulin. As figure 3b,cshows, the amino acid sequences of the fragments of the
B-chains of human and fish insulin have only 2 conservative amino acid
substitutions: liz-arg, asp-glu. The homology of the corresponding DNA sites is
78 percent.
Preliminar�y analysis of the results of one experiment to determine the initial
sequence demonstrated that pND77 plasmids are also contained in the A-chain ef
insulin, which begins at 302 nucleotides (fig 3a).
Considering the high homology between DNA of the corresFonding sites of the
f3-chain of fish and human insulin, the cloned fragment may be used as a molecular
- probe for identifying clones containing the human insulin gene.
The study was performed in RZ [expansion unknown] conditions in conformance with
the rules for working with recombinant DNA molecules (USSR).
The authors wish to express gratitude to N. A. Shishko, the president of the USSR
Academy of Sciznces Far East Scientific Center and V. I. I1'ichev, the director of
the Pacific Ocean Oceanological Institute of the USSR Academy of Sciences Far East
Scientific Center for constant bttention and assistance in this work. We also
wish to thank Ye. D. Sverdlov (the'USSR Academy of Sciences Institute of
Bioorganic Chemistry imeni M. M. Shemyakin) and R. Sh. Bibilashvili (the USSR
Academy of Sciences Institute of Molecular Biology) for kindly supplying us with
polynucleotidekinase and terminaltransferase.
51
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BIBLIOGRAPHY
1. Lomediko, P.; Rosenthal, N.; et al. CELL. Vol 18 (1979).
_ 2. Bell, G. I.; Pictet, R. L.; et al. NATURE, Vol 284 (1980).
3. Perler, F.; Efstratiadis, A.; et al. CELL, Vol 20 (1980).
4. Liebscher, D. H.; Coutelle, C.; et al. GENE, Vol 9(1980).
5. Marcus, A.; Efron, D.; ideeks, D.P. METHODS ENZYMOL., Vol 30, Part E(1974).
6. Ullrich, A.; Chine, J.; et al. SCIENCE, Vol 196 (1977).
7. Gordon, J. I.; Burns, A. T. H.; et al. J. BIOL. CHEM.., Vol 253. (1978).
8. Roychoudhury, R.; Jay, E.; and Wu., R. NUCL,, ACIDS RES., voi 3(1976).
g. Lederberg, E.; Cohen, S. J. BACTERIOL.y Vol 199 (1974).
- 10. Grunstein, M.; Hogness, D.S. PROC. NAT. ACAD. SCI. USA, Vol 72 (1975).
- 11. Kafatos, F. C.; Jones, C.W.; and Efstradiatis. A. NUCL. ACIDS RES., Vol 7
(1979).
' 12. Villa-Komaroff, L.; Efstradiatis, A.; et al. PROC. NAT. ACAD. SCI. USA, Vol
75 (1978).
- 13. Maxam, A.M.; Gilbert, W. Ibid., Vol 74 (1977).
14. de Haen, C.; Swanson, E.; and Teller, D.C. J. MOL. BIOL., Vol 106 (1976).
COPYRIGHT: Izdatel'stvo "Nauka", "Doklady Akademii nauk SSSR", 1981
- [164-9380]
9380
CS 0: 1840
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- UDC: 612.
THE POSSIBILITIES OF USING GAS SELECTIVE MEMBRANES TO ENSURE
LIFE ACTIVITY OF BIOLOGICAL OBJECTS IN A WATER ENVIRONMENT
Moscow DOKLADY AKADE?::il NAUK SSSR in Russian Vol 255, No 2,
1980 pp 490-493
[Article by V.V. Petrash, A.R. Os'mak, N.A. Belyakov, S.A.
Simbirtsev, All-Union Scientific Research Institute of
Pulmonology, Leningrada
[Text] The prolonged residence of man under water has been limited
by the nature of the technical agents which ensure his life ac-
tivity. Currentrapid development of technic{ues for under water
immersion has led to a search for new ways for its implementation.
One of the basic factors oi survival for the aquanaut is support
by artificial gas agents and maintenance of a microclimate. Of
interest is the possibility of producing direct gas exchange
with the surrounding water environment, through poly-permeable
membranes.
At the present time, two areas of res.earch have been formulated
- for the implementation of inembraneous gas'exehange--a method of
exchange directly with the b].ood and a method for exchange of
exhaled air with the water environment. The first method is
promising in medicine for conducting extra-pulmonary oxygenation
of the blood (1,2). However, there are definite technical and
medical complicationsin applying this method to aquanautics. A
more proauctive approach-for aquanautics is use of auxillary
syste ms of life support involving a gas chamber which communi-
cates with the water environment through a gas-permeable mem-
brane. Specific aspects of this problem are elucidated in a re-
view (3). Several theoret:ical positions on gas exchange in a
water environment are examined in an article (4). In 1966, a
system (5) was constructed which allowed a man to breathe under
water in conditions of normal baric pressure by gas exchange
_ through a millipore membrane. Progress in polymer chemistry has
resulted in production of a-yariety of new gas-permeable membranes.
Of particular relevance for gas exchange in a water environment
53
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is the use of gas selective diffusion membranes which possess
various degress of permeability for oxygen, hydrogen and nitro-
gen gases. Examples of inembranes produced in this'country are
those baseci on polyvinyltrimethylsilicone (PVTMS), polydietyl-
silicone (Sigma,) and others. .
Of significance for construction of apparatus which fulfill the
gas exchange function in a water environment are such'factors as
the properties of the membrane itsel.f, the rate of flow of the'
gas mixture. and water relative to the membrane and the degree
of their mixing.
The purpose of this study is to define the potential of gas ex-
change function of selective diffusion membranes for variaus
flows of gas mixtures and water in normal baric pressure condi-
t ions . .
Studies were conducred usirig diffusion membranes of the PVTMS r
type produced in this country. The test membrane was placed
in a special cassette, developed at the All-Union Scientific
Research Institute of Pulmorioiogy. Water was introduced from. -
one side of the memb rane using a feeder pump (Pp = 250 mm Hg; -
PC02 - 0-1 mm Hg) and a gas mixture containing 1i.3 ,percenL OZ,
5.3 percent C02 and 77.4 percent N2 (a composition analogous to
that of alveolar air) was introduced from the other side by the
same ty~pe of pump. The functioning area of the membrane measured
0.05 m. The construction of the cassette allowed mixing either
the f low of water ar the flow af gas. Control of the gas. content
of the mixture was accomplished irt the air from the cassette
with the aid of a mass spectrometer of the MKh 6202 type (USSR). _
The rate of output -of gas and -water was preset by the pumps.
~
The second group of experiments was conducted according to the
diagram shown in figure 1. In this instance, animals (rats) were
included in a system for gas exchange. The rat was given et#yl -
carbamate anesthesia (1 mg/kg of weight) and placed in a special -
air-tight chamber and immobilized in a specific position--on the -
abdomen.,To monitor the state of hemodynamics and external res- _
piration during the course of the experiment, EKG and rheoplethys-
mograms (RPG) of the thoracic cells were recorded. With the aid
of.a fee'der pump air was recirculated' through the dhamber (11 and
gas exchange device (3) which had an exchange area of 0.2 m(con-
structu.re of the exehange device was developed at the All-Union
Scientific Research Inst.itute of Pulmonology). The water was .
pumped through the exchange device at a rate of 0.6 1/min by the _
pump (2). The system was not connected to atmospheric air. Gas
ana].ysis was conducted through a meter (5) on a mass spectrometer
without disturbing the air-tight nature of the system.
54
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Figure 1. Diagram of experiment for systematic gas exchange
(explained in the text)
Key : .
_ 1. Water 3. EKG
2. Gas 4. RPG _
In the control group of experiments, the gas exchange device was _
excluded from the system.
The results. of the .first series helped to define the relatiouship
of gas transfer through the membrane to the rate of flow of gas
and water. This relationship is shown in figure 2. Given a con-
stant output of water at a rate of 40 m1/min and an output of
gas at a rate of 10 ml/min, the gas composition of the mixture
was restored to 21 percent 02 and 0.03 percent C02; tha,t is, the
composition of the mixture, for all practical purposes, was no
different from the pomposition of the surrounding air. With an
increase in the output of gas,'the gas exchange through the
membrane was reduced and given a rate of gas transfer of 70 ml/
min, the gas mixture contained 17.9 percent 02 and 2.4 percent -
C02. .
Increasing the output of water, given a constant output of gas,
increased to a lesser extent the transfer of oxygenwhile at the
same time, the elimination of C02 increased to a significant de-
- gree.
Given a.laminar flow of water through the cassette, all indices
for gas exchange'were-lower than those monitored during condi-
tions of mixing. In this case, the percentage content of 02 was
55
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- lowered by 2 percent and the content of C02 was increased by 0.3
- percent. An essential change in gas exchange was not demonstrated
when the gas was mixed.
In the second series of-experiments, the control group of animals,
placed in an air-tight system without gas exchange in a water en-
- vironment,died after 90 minutes. It appears that from the first
minutes of residence in the system, the composition of i;he air
was altered to a significant degree.(figure 3). Significant
changes in breathing and hemodynamics were observed in animals
after 60 minutes.
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e KaMepe c)aeoa+wM npN eunwvwHm ra3oo6tyeiotoro yerpoperet (a) H 6e3 Hero (6).4 11. - ara-
- nw 3xnepNMexIa - HcxolDiue noxaunny,l/ - yepn 30 e ll! - 4epe3 90 Mni npe6weaHxx Xa-
eonHoro s 38MxHyrop K&Mepa). e- xapaKnp xanaxewu npouexrxoro coAep~~uc O, e C0,
(urtpxxoeax H cnnouutax ntu+wt cooreercrsanto) npx noptxnwvexm ra3oo6Mexxor0 ycrpoqcrea (1)
- N 5c3 Hero (2)
Figure 2. The relationship of percentage content of 02 and C02
to the rate of flow of water and gas. a--relatior:ship
of percentage content of 02 and C02 in a gas mixture
given different rates of its flow in relation to the
membrane and given a constant flow of water at a rate
of 40 ml/min; b--relationship of percenLage content
56
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of 02 and COZ to th~: rate of flow of water in relation
to tFie membrane given a constartt output of gas at a
rate of 40 ml/min. 1---lami-nar flow of water, 2--turbu-
lent flow of water; solid line--percent C02, hatched
line--percent AZ.
Key: 1. Gas ml/min
2. Water ml/min
Figure 3. Character of changes in EKG.and rheoplethysmogram re-
cordings of the thoracic cel]s and the gas content of
- the air mixutre in the chamber containin g the animal
given connection of the gas exchange~device (a) and
_ without it (b). I, Il, III--stages of the experiment
(I--initial indices, II--after 30 minutes and III--
after 90 minutes of residence of~ the animal in the
air-tight-chamber. b--character of the changes in
percentage content of 02-and COZ (hatched and solid
lines respectively) witFi connection of the gas exchange
device (1) and witihout. it (2).
= Key:
1. RPG 3. b
2. EKG 4. minutes
Activation of the gas exchange device after the animal was in
the chamber for 90 mir_utes did not result in any observable
essential-changes in physiologic indices (EKG, RPG). The gas
content was found to be within the limits; acceptable for res-
piration. The increase in content of C02 in th'e gas composition
_ was not observed but the content of 02 was reduced to a constant
value of 18.5 percent (figure 3).
The results of our investigation confirm that Ihe usE of a gas
exchange membrane of the PVTMS type with a 1 m akea,~ given a
� flow of air at a.rate of 0,25 1/min, is'adequate to produce a
- flow of liquid volume of 0.5 1/min. In these conditions, recovery
- of a level of 02 and COZ which cor-responds to the content of al-
veolar air and to the level four~d in atmospheric air occurs in
the gas mixture.
These established principles point to the fact that for an object
placed in a state of rest, design of the surface of the membrane
must be based on the required respiratory volume and the corres-
ponding flow of water and gas relative to the membrane. For
example, in order to ensure normal life activity of rats weighing
200 g and with a volume of respiration of.80-100 ml/min, it is
necessary to have a gas exchange device with a surface area of
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of 0.4 m2 for a flow of water ai a rate of 0.2 1/min, The rela-
tionship of the content of air in the chamber should not differ
essentially from the atmospheric air.
In the second group of experiments, the area of the exchange
surface of the gas exchange device was 0.2 m2; that is, less
than necessary �or complete restoration of gas content. How-
ever, the flow of water was increased simultaneously to 0.6
_ 1/min, which ensured compYete elimination of C02.
_ Extrapolated data obtained in testing unit experiments we.r.e .
used to calculate the following: to completely restore th'e content of alveolar air to that of atmospheric air in aqua-
nauts weighing 70 kg with a volume of ventilation of b.l/mi~
it is necessary to have an area of exchange surface of 24 m
for a flow of water of 12 1/min and for transfer of water.
However, considering that the relationships are defined on
the bases of tests to restere the content of the gas mixture
to that of alveolar air and nat exhaled air, then, in order to
ensure the life activity, indices of 02 content, lower than those
used to designate atmospheric air, are adequate. One can assume
that the 2 xchange area in a concrete apparatus can be lowered
to 8-12 m .
Thus, given an optimal selection of the proportions of the
surface area of the membrane and the rate and character of the
flow of liquid and gas, gas selective membranes can produce a
v olume of oxygen and hydrogen gas between the air and water
media adquate for ensuring the life activity of biologic
_ objects.
BIBLIOGRAPHY
1. S.A. Simbirstev, G.A. Rusanov et al. Use-of a membrane
oxygen-generator for acute respiratory insufficiency in
experimental studies, 1979, p 32.
= 2. D. Birnbaum, R. Thom, E. Bucherl, World J. Surg,,, v. 3, 353
(1979).
3. J. Kylstra, Physiol, and Med. Diving and Compressed Air Work,
v. 2, 155 (1975).
4. H. Rahn, Respirat. Physiol., v. 1, 1(1966).
5. W. Ayres, U.S. Pat., 3 288 394, 1966.
COPYRIGHT: Izdatel'stvo "Nauka", "Do?clady Akademii nauk SSSR",
1980
~ [149-9139]
9139
CS O: 1840 58
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MEDICINE
SOME PROBLEMS OF SPACE MEDICINE AND SPORTS
Moscow TEORIYA I PRAKTIKA FIZICHESKOY KUL'TURY in Russian No 12, Dec 1980 pp 49-52
[Article by Al. V. Sedov, doctor of inedical sciences, Institute of Biophysics,
USSR Ministry of Health]
[Text] Barely 20 years have passed since mankind made its first step in space.
But in this short time, the intensive development of cosmonautics has already in-
fluenced the solutions to a number of theoretical and practical problems in various
branches of science and technology. At present, it is even difficult to mention
an area of human knowledge that was not beneficially affected by the conquest of
space. More recently, there has been particularly intensive development of such
an area of natural sciences as space medicine. This field, which emerged
because of the needs of cosmonautics, has accumulated the advances in physiology,
biochemistry, pharmacology, hygiene, clinical medicine and other biomedical dis-
ciplines. Space medicine deals with a rather wide range of problems, many of
which are of definite interest to specialists in sports medicine. Since there are
many aspects to the question of ~nterrelation between space medicine and sports,
they cannot, of course, be exhaustively discussed in a single article. For this
reason, we deemed it useful to illustrate with several examples the feasibility
of using the achievements of space medicine to train highly skilled athletes.
It is known that monitoring the heart rate, which i.s an integral indicator of neuro-
humoral regulation of the body, is among the' mandatory and traditional methods of
studying the condition of an athlete in the course of a medical examination. How-
ever, it is only in recent years, in connection with development of cybernetic
conceptions in physiology of circulation, that it was established that the time
organization of heart rate is closely linked with the state of neurohumoral _
regulation of the heart and adaptive activity o� the integral organism [2].
- Mathematical analysis of series of cardiointervals was used by Soviet researchers
in experimentalphysiology, clinical practice, physiology of sports and space
medicine [1, 9].
The possibility of determining the nature of neurohuraoral regulation of circula-
tion and deriving conclusions about the state of the entire body on the basis of
the heart rate is particularly important to space medicine, where the volume of
physiological information relayed from a spacecraft to earth is limited. In view
of the fact that extraction of maximum information about a cosmonaut's functional
condition with a minimal number of parameters is an important practical task of
space biology and medicine, studies were conducted to find criteria for assessing
the regulatory systems of the organism and degree of tension thereof on the basis

1XVIt
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of analytiis of the statistical characteristics of heart rate [22]. Studies were
conducted on pilot-cosmonauts and athletes attending training meets. As a result
of these studies, some rather distinct changes were demonstrated in the structure
ot the heart rate when changing from one state to another, which justifies dis-
cussion of the feasibility of using the rate of cardiac contractions as an integral
indicator of functional activity of the body. In particular, in the course of
these studies it was established that engaging in sports causes specific changes
in the human body, which are directed toward optimum adaptation, chiefly to
physical loads. The individual values of the statistical indicators of heart rate
- are of some practical interest in medical monitoring during training. Analysis of
dynamic series of electrocardiograms revealed that the most appreciable differences
in heart rate are observed in athletes, as compared to cosmonauts and individuals
with average physical training. These differences consist of a higher daily
variational scatter and lower mean daily amplitude of mode, higher parameters of
24-h adaptability and higher Xeciprocal correlation b etween the parameters in the
circadian rhythm. On the basis of studies of regulation of function of cardiac
automatism, some important information was obtaireed about the tonus of the sym-
pachetic and parasympathetic br.anches of the autonomic nervous system, as well as
functional state of subcortical centers and cerebral cortex.
Thus, evaluation of the degree of strain on the basis of analysis of heart rate,
- which has been refined for the purposes of space biology and medicine, is of
definite importance to sports med~cine, not only with respect to theory, but
particularly practice.
There has been rather extensive introduction to space medicine of inethods that
permit determination of the degree of strain on regulatory mechanisms and functional
reserve of physiological sqstems. In particular, functional tests are used for this
purpose. For example, a physical load test is one of the most important ones in
studies of the human cardiorespiratory system 13, 17, 27]. It has been proposed that
the following method be used for complex evaluatton of reactions to exercise of the
- cardiovascular and respiratory systems 14]. The subjects perform exercises cor-
responding to 600 kg-m/min for 7 min, pedalying on a bicycle veloergometer at the
rate of 60 �5 r/min. After this there is a 1-min recovery period. There are pro-
visions for continuous recording of the heart rate on the ECG, oxygen uptake and
carbon dioxide output on a Spirolit automatic gas analyzer. During the exercise
tests, there is discrete determir.ation of duration of phases of the left ventricular
systole by the polycardiographic method, bioelectrical activity of the heart in the
three leads of Neb, arterial pressure by the tachooscillographic method. Strok.e
and cardiac indexes are calculated by the indirect Fick method 18, 23] before the
test, as well as in the 6th min of exercise and lOth min of the recovery period.
Studies conducted with the use of this test made it possible to demonstrate the
distinctions of reactions of the ,cardiorespiratory system to a physical load. Some
signs of poorer cardiorespiratory reactions ln individuals who are and are not
engaged in sports to exercise are largely related to fatigue and emotional stress
- [10, 12, 13, 15, 163, 21].
Prevention of disorders referable to circadian rhythms, as well as the possibility
- of predicting them, constitute a pressing problem of space biology and medicine.
A change in biological rhythms is an essential and inevitable element of the pro-
cess of adaptation of the body to altered living conditions, including the conditions
of space flights. At the same time, questions of biorhythmology are becoming
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incrcasingly important as well in sports activities 119]. Numerous experimental
Studies }iave shown th at the circadian periodicity is characterized by a gradual _
ritie in level of physiological reactions of the body in the daytime (to about
1600-1800 hours) and decline at night. The lowest level is observed at 0200-0500
hours. Special stud ies also demonstrated that the nocturnal decline of physiolo-
gical reactions is ob served not only during normal sleep, but during periods of
intensive work at night. All this must, of course, be taken into consideration
when scheduling perf o rmances by athletes, especially when far from home. However, -
studies dealing with the phenomenology of alteration of circadian rhythms on the
theoretical basis of the conception of H. Selye 1241 about stress were started
relatively recently. ,
In this regard, studies of human circadian rhythms in the presence of stress fac-
- tors, which were conducCed with the problems of practical cosmonautics in mind, are
quite interesting [20]. On the basis of experimental studies, the author concluded
that desynchronosis of circadian rhythms is the biorhythmological correlate of the
alarm reaction in the general adaptation syndrome. Exercise for 1 h, constituting
up to 1200 kg-m/min, was the most intesive stress factor, with which there were
appreciable changes in heart rate, arterial pressure and maximum changes in acro-
phases of circadian rhythms. Studies of heart rate, arterial pressure and body
temperature were found to be informative enough for analysis of man's conditions
in stress situations.
The obtained experin,ental data can be used nat only in the practical support of ~
long-term space fligh ts, but for wise organization of schedules and evaluation of
the condition of ath letes.
Space flight conditions can lead to changes in functional state of the cardiovas-
cular system, impairment oCbiochemical parameters and reduction of immunob io logical
reactivity; for this reason, specialists in space medicine and biology make rather
_ wide use of pharmacological agents. A considerab le amount of research was con-
ducted in the Soviet Union and abroad to solve the special problems of space phar-
macology.
Much attention was d evoted to development of eff iciency stimulators [7, 11, 25].
Products of the phenamine type are among the most widespread and potent stimula-
tors of efficiency. These products can be recommended for intake on a one-time
basis in critical sit uations that occur during sp ace flights [26]. However, it
must be borne in mind that phenamine can induce the opposite effect in 10-15% of
the cases. Moreover, long-term intake of phenamine could deplete the nervous
- system and cause hab ituation [14].
_ However, with reference to methods of enhancing efficiency, one must take into con-
- sideration the basic difference in this matter as it relates to space and sports
medicine. For examp le, an increase in dosage or repeated intake of products of
the phenamine type in the case of considerable physical loads, against the back-
ground of depletion of catecholamine resources, could lead to acute cardiac insuf-
- ficiency and even myocardial infarction. This explains the deaths among athletes
who took phenamine and its analogues for doping purposes.
There is justification for experimental studies of stimulating properties of strych-
nine, ephedrine and caffeine. These general tonic agents are sufficiently
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pliysiological, :ind their principal action is directed at stimulating metabolism
.tnd incrcasing efficiency [fitness] of the body.
In recent years, there has been a trend toward the study and use for intensive
exercise of tonics of plant origin, or adaptogens. These substances elicit a
state of increased nonspecific resistance of the body to the most varied factors,
including physical loads. Numerous studies have confirmed that adaptogens (ginseng,
eleuterococcus, "levzeya," "rodozina," acanthopanox root) enhance efficiency
without having an appreciable stimulating effect, and they did not elicit any
adverse changes in the function of viscera and metabolism [5].
Drugs used to improve nervous and mental stability also became the subject of in-
depth medical research. It is known that emotional tension is associated, in
- particular, with excessive production of catecholamines by the adrenals. At pre-
sent, drugs have been tested that actively intervene in Che process of catechola-
- mine synthesis. In this respect, the most promising are aminazin, trioxazin,
meprotan, levopromazine and chlor.diazepoxide [18]. In therapeutic doses, these
products have a beneficial effect on neurotic states related to the feeling
of internal anxiety, impatient anticipation,.fear, restlessness and insomnia.
An important task f or space medicine is to find the means of preserving health and
maintaining high efficiency of cosmonauts. For this purpose, numerous studies were
conducted over the last 20 years, as a result of which a rather large amount of
- information was accvmulated about.the reactions of various physiological systems
and the body as a whole to the effects of the most diverse extreme factors, includ-
ing physical loads. These studies broadened appreciably the conception of reserve
capabilities of the organism.
The joint efforts of scientrists of fraternal socialist countries in experiments
conducted in the area of space biology and medicine, within the framework of the
Intercosmos Program, were instrumental in solving such a complex problem as the
reserve capabilities of the human body. A number of instruments, which were �
neeued for experimental research on the functional state of cosmonauts, were
- developed by specialists in scientific institutions of the People's Re.ublic of
Bulgaria, Hungarian People's Republic, GDR, Socialist Republic of Rumania, Polish
People's Republic and CSSR.
For example, one of the important biomedical problems is oxygenation o� tissues
when man is exposed to extreme conditions. TI'i.e impertance of knowing how tissues
are supplied with oxygen in cosmonauts and people engaged in sports is obvious.
For there are oxidative and reduction processes, as well as release of energy
required for work, in tissues. The amount of oxygen required by the body depends
on the specifics of his activities (physical work or rest), environment (air
- temperature, humidity, barometric pressure, etc.) and his state (calm, excited).
For expressly this reason, the Oxymeter instrumPnt, developed by Czech specialists,
is of considerable value to this research; it permits examination of the dynamics
of tissular oxygenation in man, both in space and on the ground.
_ Gathering diagnostic information needed to assure the safety of space flights is
an important task for space medicine. Biological radiotelemetry serves as the
principal investigative and monitoring method for this purpose. Space medicine
has gained sufficient experience with miniaturized medical instrumentation,
resistant to exogenous factors, for continuous remote monitoring of a man's
_ condition, tested by the use of biotelemetry systems during space flights. At
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prt�svnt , ~:MW rt-liable methods have been developed for recording and transmitting
via iv1vmCLry systems such physiological parnmeters as the ECG, EEG, hlood pre5surc,
seismocardiobram, kinetocardiogram, sphygomogram, electrooculogram, galvanic skin
reflex and many others. These parameters have been recorded and relayed over
telemetry channels both at rest and with graded loads [6].
Specialists in the field of space medicine developed method s for operational
medical monitoring. Thus, for dynamic medical monitoring of a cosmonaut's pulse
rate, a special device was used (cardiophone) which transf orms the electrocardio-
gram into audio signals. Transmission of pulse signals by means of the cardio-
phone is the most elementary example of coding physiological information. In this
case, the pulse rate is used as the integral indicator of intensity of the load
on the body. The objectives of current programs include not only provisions for
the minimum number of required readings, but obtaining an extensive range of
information, which makes it p.ossible to analyze the mechanism of the effects of
- space flight factors on man by means of radioelectrocardiography, radioelectro-
encephalography, radioelectromyography,.radionystagmography, etc. The obtained
biological data are processed on computers, with the use of effective diagnostic
algorithms. At the present time, rather wide use is made of short-radius telemetry
- devices for transmission of physiological data from the body cavities (endoradio-
- sonde measurements).
The problems related to the use of bioradiotelemetry in space medicine required
many years of studies, conducted by physicians and engineers. The objective was
to develop miniaturized and economical radio transmitters, small, multichannel
radiotelemetry equipment impervious to interference, that would be able to transmit :
the maximum volume of information about man's condition over long distances. The
advances of space medicinerare closely linked with continued d2velopment of biola- '
= gical radiotelemetry, development of reliable systems for medical monitoring and
- medical examination. It will become possible to make broader use of this method
in medicine when the main technical problems are solved,.with respect to transmission .
of biological information in space physiology, aimed at reducing the weight and
size of sensors, increasing economy and reliability of instrument operation.
Thus, the idea of continuous remote medical monitoring, which was brought to life
for the first time during space flights, also had practical application to a number
of branches of inedicine, including sports medicine.
Use of miniaturized biotelemetry sensors to monitor athletes during training and _
competitions increases the capabilities of a trainer and hands tothe sports _
physician a method for objective evaluation of the condition of an athlete who
is at a considerable distance from the researcher.
- In conclusion, it should be stated that the studies that are being conducted to
solve such pressing problems of space medicine as the reserve capabilities �of
the human body, on-going medical monitoring of cosmonauts and predicting their
health status on the basis of a minimal number of parameters, the search for
adequate biostimulators to enhance efficie>>.cy and development of small-sized _
biotelemetry equipment capable of transmitting extensive information about man's
reactions over long distances will, undoubtedly, have a b eneficial effect on the
continued development of inedical science as a whole and sp orts medicine in parti-
cular.
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BIBLIOGRAPHY
- 1. Bayevskiy, R. M. "Physiological Changes in Space and the Problem of Automa-
- tion There.of," Moscow, "Nauka," 1970.
2. Bayevskiy, R. M. , and Eydi, U. Ress in "Osnovy kosmich. biol. i meditsiny"
[Fundamentals of Space Biology and Medicine], Moscow, "Nauka," Vol 2, Bk 2,
1975,pp 268-305.
= 3. Beregovkin, A. V.; Baburina, Ye, B.; Georgiyevskiy, V. S.; et al. in
"Gagarinskiye chteniya. Mater." [Gagarin Lectures. Material], Moscow, 4,
1974. '
4. Beregovkin, A. V.; Vodolazov, V. S.; Georgiyevskiy, V. S.; et al. KOSMICH.
BIOL. I AVIAKOSMICH. MEDITSINA [Sp::ce Biology and Aerospace Medicine] , No 3,
1976, p 24. 5. Brekhman, I. I. "Eleuterococcus," Leningrad, "Nauka," 1968.
- 6. Burnazyan, A. I.; Vorob'yev, Ye. I.; Gazenko, 0. G.; Gurovskiy, N. N.; et al.
KOSMICH. BIOL. I AVIAKOSMICH. MEDITSINA, No 3, 1977, pp 3-4.
- 7. Vasil'ye-v, P. V.; Delay, V. Ye.; G1od, G. D.; and Razumeyev, A. N. in
"Problemy kosmich. biol." [Problems of Space Biology], Moscow, "Nauka,"
- Vol 18, 1971.
8. Vodolazov, A. S., and Pometov, Yu. D. in "Aktual'nyye voprosy kosmich. biol. ,
- i meditsiny" [Pressing Problems of Space Biology and Medicine] , Moscow,
- VYP 2, 1975, P 42. -
9. Gazenko, 0. G.; Bayevskiy, R. M.; Volkov, Yu.; et al. in "Problemy �
vychislitel'noy diagnostiki" [Problems of Computer Diagnostics], Moscow,
"Nauka," 1969, pp 7-15.
10. Georgiyevskiy, V. S.; Mikhaylov, V. M.; and Smyshlyayeva, V. V. in
"Kosmich. biol. i aviakosmich. meditsina" [Space Biology and Aerospace -
Medicine], Moscow--Kaluga, Vol 1, 1972, p 1.
- 11. Gordeycheva, N. V. ; Si:ashkov, V. S.; Kaplan, E. Ya. ; et al. KOSMICH. BIOL. I -
- AVIAKOSMICH. MEDITSINA, No 5, 1975, p 61.
12. Yeremin, A. V.; Bazhanov, V. V.; Marishchuk, V. L.; et al. in "Problemy
kosmich. biol. Moscow, Vol 13, 1969, p 191.
13. Yeremin, A. V. ; Stepantsev, V. I. ; Sokol.ov, V. I. ; et al. in "Fizi~~log. _
_ problemy detrenirovannosti" [Physiological Problems of Deconditioning],
Moscow, 1970, p 222.
14. Isakov, P. K.; Ivanov, D. I.; Popov, I. G.; et a1. TEOR. I PRAKT. -
AVIATSIONNOY MEDITSINY [Theory an3 Practice of Aviation Medicine] , Moscow,
"Meditsina," 1975.
- 15. Kakurin, L. I.; Katkovsiciy, B. S.; Georgiyevskiy, V. S.; et al. VOPR.
KURORTOLOGII [Problems of Fsalteology] , No 1, 1970, p 19.
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16. hritkuvskiy, B. S. in "Fiziolog. probltmy detrenirovannosti," A"oscow, 1968,
p 136.
17. Katkovskiy, R. S.; Maginskiy, G. V.; Gornyago, V. A.; et al. in "hosmich.
biol. i aviakosmich. meditsina," Moscow--Kaluga, Vol 1, 1972, p 75.
18. Kosmolinskiy, F. P. "Emotional Str.r.ss During Work Under Extreme Conditions,"
Moscow, "Meditsina," 1976.
19. Makarov, V. I. in "Mater. Vses. simp. 'Bioritmy i sportivnaya deyatel`nost
jProceedings of All-Union Symposium on "n;orhtyhms and Sports Activities").
_ Kishinev, 1978.
- 20. Idem, Author abstract of dissertation, Moscow, 1979.
21. Mikhaylov, V. M.; Georgiyevskiy, V. S.; Smyshlyayeva, V. V.; et al. KOSMICH.
ISSLED. [Space Research], Vol 10, No 3, 1972, p 778.
- 22. Nikulina, G. A. Author abstract of dissertation, Moscow, 1974.
23. Pometov, Yu, D. Author abstract of dissertation, Moscow, 1972.
- 24. Selye, H. "Essays oil the Adaptation Syndrome," Moscow, 1960.
~ 25. Shashkov, V. S., and Gordeycheva, N. V. KOSMICH. BIOL. I MEDITSINA, No 2,
= 1972, p 3.
26. Shashkov, V. S., and Yegorov, B. B. FARMAKOLOGIYA I TOKSIKOLOGiYA [Pharma-
cology and Toxicologyf, No 4, 1979, p 325.
27. Berry, Ch. A. AEROSPACE MED., Vol 41, 1970, p 500.
COPYRIGHT: Izdatel'stvo "Fizkul'tura i sport". "Teoriya i praktika fizicheskoy
kul'tury", 1980
10,657
CS O: 1840/166
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UDC 615.277.4:678.046.36+616-006.6-057-02:678.046.36
- CARCINOGENIC ACTIVITY OF SYNTHETIC, ASBESTOS
Moscow GIGIYENA TRUDA I PROFESSIONAL'NYYE ZABOLEVANIYA in Russian No 10, 1975
pp 31-35
[Article by L. N. Pylev, G. D. Koval'skaya, and G. N. Yakovenko, USSR Academy of
Medical Sciences Institute of Experimental and Clinical Oiicology, Moscow, sub-
mitted 13 Feb 75]
[Text] In recent years, both in our country and in the United States, Britain,
Japan and the GDR, much attention has been given to the industrial fabrication of
synthetic f iber materials of the asbestos type.
Synthetic asbestos is used for aperation in superhigh temperature, high pressure
and vacuum conditions, and also in certain sectors of the chemical industry.
The f ibrogenic activity of synthetic asbestos has been studied by A. G. Valagov
et al. It was f ound that Na, Mg-amphibole, manganese-fluorine-amphibole and
synthetic chrysotile all display fibrogenic activity; in the last-named it was
lower than in natural chrysotile asbestos.
No research at all has been done on the blastomogenic properties of synthetic
asbestos.
Materials and Methods
We studied synthetic chrysotile and Na, Mg-hydroxyamphibole, which can be regarded
as an analog of natural magnesium arfvedsonite, obtained using the hydrothermal
method. Samples were synthetized at the USSR Academy of Sciences Institute of
Silicate Chemistry imeni I. V. Grebenshchikov.
Making synthetic asbestos by the hydrothermal method eliminates the possibility
of contamination with combustion products from the f illers. They do not even
contain the traces of such metals as Ni, Cr, A1 and others that are found in
natural asbestos as the result of ore impurities (N. I. Nesteruk et al; D. P.
Sinovskiy et al; M. V. Soboleva, A. D. Fedoseyev et al).
Asbestos materials were pulverized for 6 hours in an agate mortar; this was done
at the Sverdlovsk Scientific Research Institute of Labor Hygiene and Occupational
= Diseases. The degree of fineness of the sample was determined under an optical
microscope at 15 x 90 magnification (see table 1).
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Table 1. Particle Fineness of Synthetic Asbestos Studied
Type of asbestos
Size of particles (~m)
up to 1 1- 5 6- 10 above 10
Synthetic chrysotile asbestos
Synthetic Na,Mg-hydroxyamphibole
37.3 53.3 1.7 7.7
44.7 53.3 2.0 -
The size of the particles of the pulverized synthetic chrysotile was very close
to a sample of commercial chrysotile asbestos that we (L. N. Pylev) had studied.
More than 90 percent of the particles were smaller than 5 microns. The degree of
fineness for the pulverized Na,Mg-hydroxyamphibole was somewhat greater than for
commercial magnesium arfvedsonite. Whereas in the former, 98 percent of particles
were smaller than 5 microns, the,number of particles of this size in the natural
asbestos was about 50 percent; in both samples, however, most particles were
smaller than 10 microns. Some 125 mongrel rats (63 females and 62 males) weighing about 100 grams were
used in the experiments. A total of 64 animals (33 females and 31 males) was
administered 3 intrapleural 20-mg doses of synthetic chrysotile asbestos in the
form of a suspension of physiologic solution. The interval between administra-
tion of the doses was 1 month. Using the same method, synthetic Na,Mg-hydroxy-
amphibole was administered to 61 rats (30 females and 31 males).
Only animals that died were studied, and the histologic processing of material was
the same as that used in the study of natural asbestos.
Experimental Results and Discussion
Pretumor changes and tumors found in the rats that received the synthetic asbes-
tos materials are shown in table 2.
~ When 60 mg of synthetic chrysotile were adminstered, premesothelioma changes were
found in the animals and diffuse, uneven hyperplasia of the pleural mesothelium
was found more often.
A single, dense node was found in the pleural cavity in only one case, in a
male that had died 24 months and 25 days later. Histologic studies showed that
it was a benign f ibrous mesothelioma.
In the experiment with Na,Mg-hydroxyamphibole, when 60 mg of the substance were
- administered premesothelioma changes were found at a level several percentage
points higher than in the experiment with chrysotile (see table 2). Moreover, in
a number of animals, pleural tumors were found. The first pleural mesothelioma
-i was found in a rat that had died after 330 days of observation. As the time
period of the experiment was prolonged, the percentage of tumors increased. Of
the 24 animals that died 200 to 400 days after the start of the experiment, pleural
mesothelioma was found in 6(25 percent), while of the 22 rats that died after
_ 400 to 600 days pleural mesothelioma was found in 14 (63.64 percent). Mesotheli-
omas were found in a total of 54.5 percent of cases and there was no difference
between males and females in the f requency of tumors.
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Tab]e 2. Morphologic Changes Found in Rats After 3 20-mg Doses of Synthetic
Asbestos Administered Intrapleur-ally at 1-Month Intervals
Period of
death (in
Period of death (in
months) wh
e-n synthetic
months) when syn-
chrysotile
was admin-
thetic Na,Mg-hydroxy-
istered
amphibole was
- Chan es
administered
uptol
1-9 10-29
1-9 11-21.5
(n=6)
(n=17) (n=41)
(n=17) (n=44)
- Localized hyperplasia and
epithelial proliferation in
the bronchi without flat-cell
metaplasia
1
Diffuse uneven hyperplasia of
the pleural mesothelium
6 12
6 17
Localized hyperplasia of the
pl.eural mesothelium
5 9
1 16
Fibrous pleural mesothelioma
1
Adenomatous pleural meso-
thelioma
2
Sarcoma-like pleural meso-
thelioma
11
Carcinoma-like pleural meso-
thelioma
5
Mixed-structure pl.eural meso-
6
thelioma
Pulmonary reticulosarcoma
1
1
Suprarenal adenama
1
ribroadenoma of the breast
3
Total of pleural tumors
1
24 (54.54% m�7.5)
Females
52.170% :at10.4
Males
57.14 % mt10.8
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Resultsfrom the experiments conducted indicate that synthetic chrysotile asbestos
possesses very weak blastomogenic properties. Whereas in experiments with natural
chrysotile, tumors have been found in 65.5 percent of cases (L. N. Pylev), in
experiments with the synthetic analog, a benign fibrous p3.eural mesothelioma was
_ found in only one rat.
Synthetic Na,Mg-hydroxyamphibole also turned out to be considerably less blasto-
mogenic than natural asbestos. When 3 20-mg doses of cdmmercial magnesium
arfvedsonite were administered to rats intrapleurally at 1-month intervals,
pleural mesothelioma was found in 77 percent plus or minus 5.4 cases.
As we have already indicated, the degree of fineness of these dusts was about the
same. However, the mixtures differed in regard to chemical composition. In the
_ chrysotile we studied there were more iron oxides (1.25-5 percent by weight) than
in the synthetic analog (0.53 percent). In the natural asbestos there was also
- a mixture of the oxides of various other metals (Ni, A1, Cr, Mn). There were
also substantially greater numbers of iron oxides in the natural magnesium
arfvedsonite (12.5 percent) than in the synthetic Na,Mg-hydroxyamphibole (2 per-
cent).
A number of writers (Cralley; Morgan and Cralley; Morgan and Holmes) link the
blastomogenic nature of asbestos with contamination by various metals, in particu-
lar, Ni, Cr and Fe. The carcinogenic activity of Ni and Cr is well known (Ya. M.
Grushko, P. P. Dvizhkov and V. I. Fedorova; A. V. Saknyn and N. K. Shabynina;
V. I. Fedorova; Hueper and Conway). Et-idently iron itself is not carcinogenic,
but in complexes with dextran, dextrin, sugars and glutamic acid it acquires
carcinogenic properties (Hueper and Conway). The idea has also been suggested
that the relationship between trivalent and bivalent iron plays an important
role in the mechanism of blastomogenic action in asbestos, and moreover, car-
cinogenicity is linked with a low relationship (Harington and Roe).
Evidently the idea that metallic impurities have a role in asbestos blastomo-
genesis is not without foundation, as our experiments show. However, it is
- hardly possible to use this alone to explain the malignant action of asbestos on
the mesothelium. Synthetic Na,Mg-hydroxyamphibole still induced mesothelioma in
54.5 percent of cases, and this indicates its strong carcinogenicity. This is
also indicated by the experiments of Gross and Harley, in which the percentage of
- pleural tumors in rats was the same when asbestos was administered without metallic
impurities or enriched with metals.
The morphologic picture of the premesothelioma and mesothelioma changes found did
not differ from the experiments with other kinds of asbestos we have described
elsewhere (L. N. Pylev; L. M. Shabad et al), and we therefore consider it possible
that in this paper we need not dwell on them in detail. The diffuse hyperplastic
processes in the mesothelium were characterized by the appearance across extensive
areas of the pleural surface of first or second order epithelial-like or fibroblast-
like cells with a basophilic cytoplasm and light or hyperchromic nuclei. The sites
of inesothelial cell proliferation were distinguished by the marked polymorphism of
the structure. There were solid, papillary, glandular or mixed structures in the
proliferatioa oi epithelial-like and, infrequently, fibroblast-like cells.
Carcinoma-like mesotheliomas were of a solid, glandular and glandular-papillary
structure. They consisted of large polymorphous cells similar to epithelial
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cells (figure 1). Their mesothelial origin was indicated by the large number of
intracellular and intercellular vacuoles containing hyaluronic acid found in
them. Since the mesothelial cells have a specific function of secreting this
acid mucopolysaccharide (Stout and Lattes), a test for hyaluronic acid is now
_ suggested as a diagnostic test for mesothelioma (Boersma et al; Kannerstein et al;
Wagner and Berry; Wagner et al; Winslow and Taylor). In terms of the histologic
striicture, sarcoma-like mesotheliomas of the pleura did not diff er from those we
have found elsewhere. They were both fusiform and polymorphic; secretions of
hyaluronic acid were also f ound in ttiem. The mixed-structure mesotheliomas
possessed the greatest polymorphism. They may be divided into predominantly
carcinoma-like, where products typical of carcinomatous mesothelioma were pre-
ponderwat (see figure 2), a:d predominantly sarcomatous. The detection of hyal-
uronic acid in the cytoplasm of the cells and intercellular vacuoles in these
tumors indicated their mesothelial genesis.
Pleural mesotneliomas elicited in.rats as the result of administering asbestos are
similar in structure to those described by many authors (Churg; Hourihaue;
McCaughy; Thomson) in man. Further study of the blastomogenic activity of various
kinds of asbestos anotonprevent the occurrencemofsthese neoplasmslinamanst
in the development of ineasures
Conclusions
l. The administration of synthetic chrysotile asbestos infio the pleural cavity
of rats elicits very weak blastomogenic activity. 2. Synthetic Na,Mg-hydroxyamphibole induced pleural mesotheliomas in 54.5 per-
cent of the rats.
3. The lower blastomogenic activity in the pleural mesothelium of rats caused by
synthetic asbestos is possibly explained by the absence of various impurities in
them (metals, rock and so forth). However, the high carcinogenicity of Na,Mg-
hydroxyamphibole indicates its significance in the mechanism of the action and in
the basic structure of the substance. , 4, The morphologic picture of premesothelioma changes and of pleural tumors was
similar to that f ound in experiments with natural asbestos.
5. Results from the experiments with synthetic asbestos indicate Chat in principle
it is possible to make less carcinogenic asbestos materials.
BIBLIOGRAPHY
l. Valagov, A. G.; Kogan, F. M.; and Frolova, N. N. In "Patogenez pnevmokoniozov"
- [Pathogenesis of pneumoconioses], Sverdlovsk, 1972 pp 73-82�
2. Grushko, Ya. M. VOPROSY ONKOL., No 1, 1961, pp 100-108.
3. Dvizhkov, P. P. and Fedorova, V. I. Ibid., No 11, 1367, pp 57-62.
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4. Nesteruk, N. I.; Makarova, T. A.; and Fedoseyev, A. D. ZAPISKI VSESUYUZN.
MINERALOGICHESKOGO 0-VA., Moscow, Len ingrad, 1966, Vol 95, No I, pp 75-79.
5. Pylev, N. N. VOPR. ONKOL., No 4, 1974, pp 47-53.
- 6. Ibid., ibid., No 10, p 87.
7. Saknyn, A. V. and Shabynina, N. K. GIG. TRUDA, No 9, 1973, pp 25-29.
8. Sipovskiy, D. P.; Makarova, T. A.; and Fedoseyev, A. D. ZAPISKI VSESUYUZN.
MINERALOGICHESKOGO 0-VA., Moscow, Len ingrad, 1966, Vol 95, No 4, pp 436-411
[as published].
9. Soboleva, M. V. "Mineralogiya volokistnykh mineralov gruppy amfibolov i
serpentina" [Mineralogy of Fibrous Minerals of the Amphibole and Serpentine
Group], Moscow, 1972.
10. Fedorova, V. I. "Trudy 4-ogo vsesoyuzn. syezda patologoanatomov" [Proceed-
ings of the 4th All-Union Congress of Anatomic Pathologists], Moscow, 1967,
pp 425-429.
11. Fedoseyev, A. D. VESTN. AN SSSR No 10, 1965, pp 46-48.
12. Shabad, L. M.; Pylev, L. N.; Krivosheyeva, L. V.; et al. J. NAT CANCER INST.,
Vol 52, 1974, pp 1175-1187.
13. Boersma, A.; Degand, P.; and Havez, R. In "Biological Effects of Asbestos,"
Lyon, 1973, pp 65-67.
14. Churg, J.; Rosens, S. H.; and Mooltens, S. ANN. N.J. ACAD. SCI., Vol 132,
1965, pp 614-622.
15. Cralley, L. J. AM. INDUST. HYG. ASS. J., Vol 32, 1971, pp 653-661.
16, Gross, P. and Harley, R. A. ARCH. PATH., Vol 96, 1973, pp 245-250,
1.7. Harington, J. S., and Roe, F. J. C. ANN. N.J. ACAD. SCI., Vol 132, 1965,
pp 439-450.
_ 18. Hourihane, D. Ibid., pp 647-673.
19. Kannersteins M.; Churg, G.; and Magner, D. In "Biological Effects of Asbestos."
Lyon, 1973, pp 62-64.
20. McCaughy, T. E. ANN. N.Y. ACAD. SCI. Vol 132, 1965, pp 603-613.
21. Morgan, A., and Cralley, L. J. In "Biological Effects of Asbestos" IARC,
Lyon, 1973, pp 113-118.
22. Morgan, A., and Holmes, R. A. In "Pneumoconiosis," Oxford, 1970 pp 52-56.
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23. S[out, A. P., and Lattes, R. "Atlas of Tumor Pathology. Second Series. ,
lascicle 1. Tumors of the Soft Tissues," Bethesda, Maryland, 1967.
24. Waf;ner, J. C., and Berry, G. BRIT. J. CANCER, Vol 23, 1969, pp 567-581.
25. Wagner, J. C.; Munday, D. E.; and Harington, J. S. J. PATH. BACT. V'ol 84,
1962, pp 73-78.
26. Winslow, D. J., and Taylor, H. B. CANCER (PHILAD.), Vol 13, 1960,pp 127-136.
COPYRIGHT: "Gigiyena truda i professional'nyye zabolevaniya", 1975
- 9642 -
CSO: 8144/0164
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PHYSIOLOGY
UDC 57.08.681.39
AUTOMATION OF NEUROPHYSIOLOGICAL EXPERIMENTS
Leningrad AVTOMATIZATSIYA NEYROFIZIQLOGISHESKOGO EKSPERIMENTA in Russian
1979
[Annotation, foreword, introduction and
by K. N. Dudkin and V. Ye. Gauzel'man,
"Nauka", 1650 copies, 160 pages]
table of contents from a monograph
edited by V. D. Glezer, Iadatel'stvo
[Text] On the basis of their own and published materials, the authors ana-
lyze new approaches to the organization and performance of neurophysiologi-
cal experiments with the use of automation and computing machinery. They
describe methods of automatic control of experiments, simulation and iden-
tification of neuron structures. An analysis of the methods of express pro-
cessing of neurophys io logical data is given. New designs of electronic
equipment for the automation of neurophysiological studies, circuits of de-
vices and instruments, and their operating principles are described. Bib-
liography 128 items, f igures 83.
Foreword
At the present Lime, probably, no physiologist doubts that the use of auto-
mation and computing Machinery in physiological studies raises them to a
ttigher level and broaden.s the limits of creative thinking of the investiga-
- tor who can propose and verify more complex hypotheses much fastex and ac-
celerates the process of maturation of new ideas, thus increasing consider-
ably the effectiveness of investigations. However,thisis not the only impor-
tance of the automation of experiments. The use of computing equipment makes
it possible to obtain a practical output of the results of physiological
studies connected with the development of models of data control and proces-
sing principles in physiological systems. It can be assumed that such mo-
dels are urgently needed in modern technology, for example, in developing
various robots.
It is evident that there is also no doubt that automation and computing
- machinery produce the highest degree of effectiveness in physiological stud-
_ ies when they become the usual everyday tool of the scientistso This goal
was set during the organization of the Biological Computation Center in the
- Institute of Physiology imeni I. P. Pavlov. The ten-year experience of the
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/
exietence of the computation center in the Institute of Physiology has shown
that such a center is a scientific subdivision uniting the creative efforts
of biologists 1nd physiologists in solving practical problema and in con-
structing theoretical principles of the functions of Ziving matter. The ex-
perience of the work of the computation cente r has shown also that the in-
troduction of automation and computing machinery in physiological stu3iea
is accomplished in several stages. At the present time, one of the urgent
needs is the automation of physiological experiments.
The monograph by K. N. Dudkin and V. Ye. Gauzel'man is undoubtedly important
because it formulates many aspects of the automation of experiments in a
physiological laboratory and shows on concrete examples the possibility of
accomplishing such experiments.
The monograph is particularly valuable becaus e ir shows how the use of auto-
mation and computing ma.chinery makes it possible to solve the problem of the
analysis of e Zectrophysiological data in a new way. Apart from the classi-
cal methods of the processing of physiological information in the process
of the experiment, it is possible to solve a number of new problems one of
which is the identification of neuron structures based on the experimental
data. This method leads to a direct practical result development of bio-
nic models. The authors used concrete examp lea of their work to ahow the
unquestionab le advantagea and merits of such an approach.
The publicat ion of this monograph is timely due to the rapid introduction of
mathematics in physiology which increasingly broadens the use of automation
aiid computing machinery in it and the increasingly acute problems of prac-
rical realization of the results of physiological sCudies.
K. P. Ivanov
Introduction
It is urgent ly needed to increase the effectiveness and methodological level
of modern neurophys io logical experiments. There is no doubt that the solu-
tion of this problem depends on the degree of the application of automation
and compuCing machinery in studies. It is posaible to isolate three aspects
in the problem of the automation of neurophysiological experiments.
The first aspect is connected with the automatic control of experiments,
the second has to do with automatic registration of the experimental data,
and the third is farmulated as automatic processing and analysis of the bio-
elec:tric act ivity, The solution of these problems depends on the technical
facili.ties in physiological laboratories and inatitutes. In the process of
modern elect rophysiological experiments, the investigators obtain a huge
amount of data whose processing, undoubtedly, must be conducted automatical-
ly in the process of the experiment, which i s impossible in the absence of
_ appropriate computing machinery. It is also obvious that, in order to set
up a control led experiment, it is necessary to use not only electronic com-
puters, but also various external devices for the recording, coding, and in-
troduction of information into the computer.
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Our experience in the work on the problem of automation of neurophysiologi-
cal experiments makes it possible to conclude that at Che present time there
is a gap hetween the needs of modern electrophysiological experiments in in-
creasing their effectiveness and methodological level and the state of af-
- fairs which formed as a result of or the absence of computing machinery in
piiysiological laboratories, or its limited use.
A considerable progress in the solution of this problem was made by the or-
ganization within physiological institutes of subdivisions similar to the
Biological Computation Center created in the Institute of Physiology imeni
- I. P. Pavlov. The organizational principles and scientific goals of such a
computation center were clearly and exhaustively formulated in the monograph
by K. P. Ivanov and A. S. Kleshchev [44]. The analysis of the operation of
the Biological Computation Center shows that such scientific subdivision in-
creased greatly the effectiveness of physiological studies. First of all,
it became possible for the physiologists to process experimental data by
computers, to gain considerably in time, and to use mathematical methods of
analysis which were inaccessible before. Moreover, there appeared new as-
pects of studies connected with the identif ication and simulation of neuro-
physiological mechanisms. These methods are a bridge between the fundamen-
- tal direction of studies and the direction connected with the introduction
of the results of studies into practice. In fact, formalized descriptions
and models of physiological mechanisms serve as a good foundation for devel-
oping methods and devices for information processing, i.e., a nPw technique
based on physiological principles.
There is no doubt that we cannot imagine physiological institutes of the -
present and ttie future without such scientific subdivisions as a computer
center with one or several large electronic computers. However, there still
_ remain many unsolved problems with regard to the automation of experiments
which, along with the above�mentioned approach, require a somewhat different
methodological approach.
Experience of the Biological Computation Center shows that, in practice,
neither controlled experiments with the use of a large digital computer, nor
data processing in the process of the experiment have been � used widely
[44]. Evidently, there are deeper reasons than merely a shortage of large
computers. The point is that one of the notable phenomena in modern compu-
ter techniques i- the tendency toward distributing computations and infor-
mation processing, and spreading a computing and controlling operations over
numerous points of the systemo
From this viewpoint, the most modern facility is a neurophysiological facil-
ity with distributed automatic controlling and computing devices which has
access to a large central digital computer. However, there are no systems
for controlling physiological experiments with such devices. -
A good example of what a fully automated experiment can be is the modern
physical experiment with the use of computing and controlling systems which
fully satisfy the needs of the experimenter [49]. This became possible
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as a result of the development of new directions in computer engineeri.ng
based on the achievements of integrated electronics. Minicomputers and
microprocessors were developed which found wide application in various com-
p uting and controlling devices. Computing potentialities of minicomputers
and microprocessors and their relatively low costs are the main prerequisites
for their mass penetration into technology and science in the future, includ-
ing physiology. However, even in this case, there will still remain speci-
fic peculiarities and difficulties of the automation of neurophysiological
experiments which researchers will have to solve.
Ttie purpose of this book was to share some experience accumulated by the
- authors in the process of such work.
The authors are deeply grateful to V. D. Gle2er, under whose direction they
started many years ago to work on the most fascinating problem the problem
of visual perception, for his constant help and support i-n their work. The
authors are also sincerely grateful to K. P. Ivanov for his support in the
work on this book, to N. F. Baskina, V. A. Kislyakov, T. G. Malinnikova, V.
D. Rodinov for reviewing, constructive discussions and criticisms, as well
as to all their co-workers: 1. V. Anan'yeva, Ya. A. Bedrov, S. K. Yegorov,
V. A. Ivanov, A. S. Kleshchev, N. B. Kostelyanets, L. I. Leushina, A. A.
Nevskaya, N. N. Nikitina, G. I. Novikov, M. B. Pavlovskaya, A. I. Panin, Zh.
A. Pershin, N. F. Podvigin, N. V. Prazdnikova, V. L. Temov, I. V. Chuyeva,
Yu. Ye. Shelepin, L. V. Shperl, P. Ya. Fink, and T. A. Shcherbach.
Contents
Page
Foreword (K. P. Ivanov) 3
Introduction 5
Cti,spter I. Automatic Control of Neurophys io logical Experiments 8
Standard Scheme of an Automated Electrophysiological Experiments 8
Processors 11
Storage Systems 13
Automatic Control of Stimuli 15
Data Collection Systems 18
Information Representation Systems 19
Digital Computer Data Input and Output Methods 20
Real-Time Operation of Computers in Physiological Experiments 23
CAMAC System 27
Specialized Devices for Express Processing of Experimental
Data 31
Models for the Identification of Neurophysiological Mechanisms 34
Cllapter II. Express Processing of Neurophysiological Data 44
Histograms of Interpulse Intervals 44
Detection of Statistical Connections (Correlation Methods) 47
Poststimulus Histogram 52
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Histogram of the Number of Pulses in Groups 53
Theoretical Information Approach 56
Identification of Neuron Structures 62
- Examples of Solutions of Problems of the Identification of
Real Neuron Structures 66
Chapter III. Functional Elementa of Automatic Control Systems 89
Adders 90
Registers 92
Counters 93
Decoders 94
Sw itches (Multiplexers) 95
= Analog-Digital Converters 96
- Digital-Analog Converters 98
C omparators 100
Ogerational Amplif iers 100
Neuron Models 102
Chapter IV. Devices f or Automatic Control of Experiments and
- Analysis of Electrophysiological Data
111
Three-Channel Stimulation Unit
111
C ontrol Device for the Presentation of Stimuli
113
C ontrol Device for the Movement of Stimuli
114
Shapers of Information Pulses
121
Amp litude Discriminator
122
F ormers of the Time Markers of Stimuli
123
Selector of the Time Markers of Stimuli
125
Device for Obtaining Histograms ot Interpulse Intervals and
- the Number of Pulses in Grnups
127
Dev ice for Mapping Receptive Fields
135
Device for Mapping Frequency Characteristics of Receptive Fields
138
De-vLce ivY- riotLing Yoststimulus Histograms
144
Conclusion
149
Bibliography
152
COPYR.IGHT: Izdatel'stvo "Nauka", 1979
, 10,233
CSO: 1840 /358
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UDC 612.821
vYNArtiCS oF vEGETATIVE RESPONSES WiTH VOLiTRTARY CONTROL OF ALPiiA RHYTHIM
rtoscow rIZIOLOGIYA CHELOVEKA in Russian Vol 5, No 5, 1979
pp 927-930
[Article by V. G. Markman, Institute of Physiology imeni I. P. Pavlov, USSR Academy
oF Sciences, Leningrad, received by editors 5 Dec 77]
LText] The problem of the connection of voluntary changes in the alpha rhythm with
changes in the vegetative indexes stil' remains insufficiently studied, Recently -
an attempt was made to establish connection between changes in the i.ntensity of al-
pha rhythm during voluiitary control, the heart rate, and the cutaneogalvanic reac-
tion measured simultaneov.2ly [1]. As a result of this, it was proposed that the
interaction between these parameters, if it exist.s, must occur with a definite time
shiFt. The purpose of this work is to verify this assumption,
- rtethod
The method of the experiment was descrihed by us earlier [1, 2]. For the values of
- parameters of the alpha rhythm intensity, the R-R interval of the EKG, and the con-
stancy of skin resistance obtained in the initial background and in tests with feed-
1>ack (OS) for each 10 s, the coefficient of the correlation between mumentous values ,
and during shifts of values of vegetative indexes in relation the values of the al-
pha rhythm by one and two 10 s sections in the direction of advancement or delay
were calculated in pairs. Due to the special technical characteristics of the me-
thod, the value of the R-R interval was measured at the beginning of the following
- 10 s section. This delay by 5 s in relation to the value of the integral of the
alph,i rhythm envelope was taken into consideration in plotting the points on the
r_hart.
Thus, it was possible to evaldate both the degree of the connection of changes in
the vegetative indexe4 and the alpha rhythm in the process of training and the time
' of interaction between them.
'Clie obtained correlation coefficients werz averaged by nine tests with OS of three ~
sessi.ons separately for Group I(five subjects who were able to cope with the pro-
blem of the alpha rl-.ythm increase) and for Group II (five subjects who were unable
to cope with the problem). The significance of the difference of the averaged coef-
ficients from zero ( at a 5% level) was check2d by Student's t-criterion.
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Results of Studies
- Figure (A) shows the data on the connection between the intensity of alpha rhythm
und valiie of the R-R interv?l in the initial background and in tests with OS for
two gruiips of Auhjents. /1�rilogoue data on Che connr_ction between the intensLty of
nlplia rtiyttim und the conKtancy of skin re5ietance are also ehown (Figure B).
I A 11 I e 11
0,2 02 0,2~ OO 9,2
t'
x x x
f~ ~"Tx xT T"x, x x ~1
x x x x
-20 20 -ZO" ~ ZO -ZO 20 -ZO_ ~ ZO
-O,Z � -O,Z -D,Z 0,2
0,2- 49,242 42
~
x ~ x ~ x x x k x
x 0 ZD r--rx XTx~ C
-ZO 0(Q -ZO ZO ZO ZO -ZO_ ZO
-02 0,2
-0,2 ,
Average values of the coefficients of the correlation of the
~ intensity of alpha rhythm with the value of the R-R inten;al
of the EKG (A) and with the constancy of skin resistance (B)
_ for groups of subjeets I and II in the background (upper row)
and in tests with OS (lower row). Along the X-axi.s the
value of the shift of the values of vegetative i.ndexes in
relation to the values of the alpha rhythm (in s) ;
advancement, delay). Along the Y-axis average val-
- ue of the correlation coefficient. Values differing signi.-
ficantly �rom zero are circled.
Places occupied by five subjects of Group I by the degree of training,
expression of the stt:died correlation, and the number of times the OS ' -
signal was turned off
Effectiveness Contribution Number of times =
of to the OS signal was ~
- training correlation turned off
1 5 5
2 1 1
3 4 4
_ 4 3 2
S 2 3
On the average, Group II was characterized by values of the coefficients which did
not differ significantly from zero, while the values of the correlation coefficients
in Group I often differed signiiicantly from zero. There was no positive difference
between the parameters in the initial background and in the tests with OS for Group
II, whi.le Group I showed structural ch,,nges in trze connection between the intensity
of alpha rhythm and the length of the R-R-interval.of the EKG. The positive values
of tlie correlation coefficient which are characteristic for the initial bacltground
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~ at a 5 s delay shift are replaced by negative correlation at a 15-25 s delay which
differs reliably from the backgrourd correlation. The positive correlational con-
- ileccion between the intensity of alpha rhythm and the constancy of skin resistance
in the background does not change its nature in chaiiging to tests with OS, shifting
- only by 10 s in the direction of advancement.
When analyTing the obtained data, it is necessary tu keep in mind that Groups I and
II differed reliably with respect to the average intensity of alpha rhythm in tests
with OS in relation to the background (1.15 and 0.89; t- 4.284; p-= 0.01) but
- did not differ in the relative Nalues of the R-R-interval (0.98 and 1.00; t~
0.683; insignif_icantly). However, a lesser variability of the mean values of the
vegetative indexes was observed for Group II as a whole [1].
The Eigure and the time parameters of the correlations of the intensity of alpha
rhythm with the value of the R-R-interval and the constancy of skin resistance in
the background in the subjects of Group I are characteristic for activation (depres-
sion of alpha rhythm, tachycardia, increased RGR [galvanic skin reflex] caused, to
_ all appearances, by the orienting reflex or by the readiness to work. It will be
recalled that the feedback indicator in the background test was turned off and could
not be the cause of activation. The change to work with the OS signal (for which
we used t:he change of digits on the indicator during the period when alpha rhythm
exceeded the threshold Ievel) caused a sharp structural change in the connection of
alplia rhythm with the R-R-interval. The sign of correlation changed from positive
to negative, i.e., the increase of alpha rhythm in the tests with OS was accompanied
by tachycardia.
In order to find out whether or not this connection depends on the training, the
subjects were arranged in order of decreasing effectiveness of training and this
order was compared with the order of the degree of expression of negative correla-
tion at +15 s(first and seconr,i coXumns of tlie table). The class correlation index
For this pair of columns is -0.4, i.e., this dependence xs not connected directly
witti the degree of increase in the alpha rhythm under these conditions,
t
It was assumed that this dependence is a component of the emotional response of the
subject to the stopping of the digi.ts on the display board at the end of the out-
burst of alpha rhythm. Indirectly, this is indicaCPd by the laten: period of its
manifestation increased against the norm [3]. Therefore, the third column of the
table gives the place occupied by the subject with respect to the number of the
~ stopping of digits on the indicator board (stopping for a time less than 1 s was not
taken into consideration). The class correlation indicator for the second and third
- columns is 0.9, which also confirms the above-mentioned assunaption.
Discussion of Results
. The i_dea that the reproduction of positive emotional experiences can be accompanied
by an increase in alpha rhythm was confirmed by the data of many experimenters.
NevertheYess, in the operant determination of alpha rhythm, the question was never
_ posed directly about the possibilities of emotional reaction to the OS signal itself,
although it was often mentioned that the trained parameter changed similarly under
the effect of instructions or a false OS. Therefnre, it is quite appropriate to
assume that at least in some subjects the mechanism of the alpha rhythm increase in
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the appearance of an emotional response to the OS signal. But the on and off posi-
tions of the indicator in the tests do not occur in isolation, but follow one an-
other quite frequently. In this case, it is evident thaC there must occur interfer-
Fnce of emotion-producing stimuli which, with various time structures of the OS sig-
nal, can weaken or i.ntensify the ernotional reaction whoFie ro]e L9 us�a]ly undFresti-
mated (n r.xperfinent5 with OS. For a more strict verification of our assumption, it
woul.d be necessary to examine the characteristics of the reinforcement (its proba-
bility) and the motivation level af the subject [4], as well as to have an evali:a-
tion of the vegetative reactivity during emotional states.
- The background of the subjects of Group I had a complex of conjugate changes in-
volving both the cortex (changes in thQ intensity of alpha rhythm), and the vegeta-
tive nervous system. There is no doubt that the hypothalamus participates in the
. organizaticn of sucli reactions because it is the control center of vegetative func-
tions and, moreover, it is capable of diffusely stimulating the cortex [5]. Vege-
tative rrtanifestations of emoti.onal responses in the process of *aork with OS are also
- realized through the hypothalamus. The subjects of Group II, on the contrary, did
_ not }iave any marked signs of orientation or emotional responses. But regardless of
whetlier or not the detected peculiarities of the functianal organization of hypo-
thalamocortical connections are based on the differences between the groups, they are
of interest i.n themselves both for preliminary selection of subjects, and for pro-
fessional selection of special groups. A sufficiently large number of classifica-
tions of human operators on the basis af the properties of the central and vegeta-
tive nervous systems are known [6-8].
a
It is still difficult to understand why negative correlation is maintained at a
_ shift of +25 s in Group I. But the assumption ahout the emotiogenic effect of the
OS signal makes it possible to explain the absence of analogous correlation in
_ Group II partly by the fact that, due to the marked depression of tl:o alpha rhythm,
r.he OS display was turned on in this case much rarer, The positive correlation at
a shift of +25 s which was noted in Group II reflects a vigorous contribut:iori of one
subject and is not character_stic of the group as a whole.
- As for the differences in the background between the groups, they cannot be explain-
ed hl the changes in the state of the indicator, since the latter was disconnected.
Ai They observed lesser changeahili.ty of the mean values of the vegetative indexes in
the suhjecl-.s of Group II is supplemented by the absence of dynamic connections in
_ the intensity of the alptia rhythm with the i.ndexes of the vegetative nervous system.
The environment and the experimental conditions were, of course, identical for both
groups. The average values of the R-R interval (0.84 and 0,85 s) were practically
identical (t a 0.209; insignificant), the average variation coeff icients of the
vali.ie of the R-R interval were also of the same order 7.2 and 5.3% (t=1.666; in-
signifi.cant). The variation coefficients of the alpha rhythm intensity also did
not differ significantly 14,2 and 13.9% (tQ0.147; insignificant), Thus, the ab-
sence of the correlation of the alpha rhythm intensity and the value of the R-R in-
terval which is characteristic of the orientation response cannot be explained by
_ their lower variability,
- Conclusions
1. The ability of the subjects to increase their alpha rhythm in the experiment with
= feedback is reflected in the dynamic correlational connection of alpha rhythm with
shifts in the vegetative indexes.
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'L. 'Phe ditferences in the subjects, evidently, reflect the differences in the func-
ClOli(1l organizatiori of the hypvthalamocortical connections and can serve as a cri-
Lcrion for preliminary division of the subjects during profesaional selection.
- Bibliography
l. Markman, V. G. FIZIOLOGIYA CHELOVEKA [Human Physiology], 1977, Vol 3, No 3,
p 470
2. Markman, V. G. FIZIOLOGIYA CHELOVEKA, 1977, Vol 3, No 3, p 464
3. I'ress, P. In the book "Eksperimental'naya psikhologiya" [Experimental Psy-
ctiology], No 5, Moscow, Progress, 1975
4. Simonov, P. V. "Vysshaya nervnaya deyatel'nost` cheloveka" [Higher Nervous
Activity of Man], Moscow, Nauka, 1975
5. Gel'gorn, E. and Lufborrou, Dzh. "Emotsii i emotsional'nyye rasstroystva"
[Emotions and Emotional Disturbances], Moscow, Mir, 1966
6. Vasilevskiy, N. N. FIZI''TAGIYA CHELOVEKA., 1975, Vol 1, No 3, p 469
7. Guruli, 0. M. and Kislitsin, M. M. In the collection "Problemy neyrokiber-
netiki" [Problems of Neuxocybernetics], Rostov-on-the-Don, Rostov State Univer-
sity, 1976
8. Akhutin, V. M.; Zingerman, A. M.; Kislitsin, M. M.; and Menitskiy, D. N.
FIZIOLUGIYA CHELOVEKA, 1977, Vol 3, No 2, p 295
COPYRIGHT: Izdatel'stvo "Nauka", "Fiziologiya cheloveka", 1979
r150-10,233]
10,233
CSO: 1840
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UDC: 612.821.6+612.822.3.087
- HEMISPHERIC ASYMrIETRY OF P300 WAVE IN RESPONSE TO tJNRECOGNIZED EMOTIONAL WORDS
Moscow ZHURNAI. VYSSHEY NERVNOY DEYATEL'NOSTI in Russian Vol 30, No 3, 1980
pp 467-475
[Artic:le by E. A. Kostandov and Yu. L. Arzumanov, Central Scientific Research
Institute of Forensic Psychiatry imeni V. P. Serbskiy, Moscow, submitted 6 Apr 791
[Text] Numerous studies of individuals with a"split brain" revealed that when
- visual information is delivered only to the right hemisphere it is not verbalized
_ or recognized [7-10]. At the same time, the same studies established that analysis
and synthesis of verbal signals take place not only in the left, but in the right
hemisphere, although to a substantially limited extent in the latter. R. Sperry [9]
believes that people with a"split brain" have two independent areas of conscious-
ness. In his opinion, each hemisphere has its own area of consciousness with regard
to perception, cognition, volition, learning and memory. This applies to the
right hemisphere as much as to the left, although the latter can "speak." Eccles
(see [12]) critized this opinion of R. Sperry. He believes that the right hemi-
_ spherP is able, like a computer, to perform complex discrimination, recognition
and learning acts, but is entirely wanting in conscious experience.
We expounded a hypothesis, according to which activation of temporary associations,
with involvement of structures of the motor speech zone of the left hemisphere
[1, 2], is of decisive importance to perception ["recognition, realization"] of any
- exogenous stimulus to explain the neural mechanisms of the effects of unrecognized
emotienal words. We believe that mental reactions to unrecognized signals, with
tfieir somatovegetative and bioelectric components, can develop as a result of a
difference in thresholds of activation of temporary associations making up the
functional sys*em that reflects and emotiogenic situation. In cases of prolonged
and strong experiences of negative emotions, the most plastic changes apparently
occur in the neurons of the brain that are related to emotional behavior. As a
result, there is marked increase in excitability of temporary associations between
sensory elements of the neocortex which perceive emotional signal stimuli, in
particular verbal ones, and structures of the limbic system, in which there is
integration of neural mechanisms of negative emotions. This could lead to excita-
tion of the above temporary associations, even under the influence of a stimulus
that is physically very weak but emotionally meaningful, and development of the
corresponding emotion, without activation of temporary associations with the motor
speech region in the left hemisphere, as a result of which the stimulus would not
be recognized.
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More recently, M. Gazzaniga and J. LeDoux [8] arrived at an analogous assumption of
the decisive role of the "verbal system" of the lef-t hemisphere to perception of
an exogenous signal, on the basis of psychological experiments on individtials with
a"split brain." In essence, they repeat the above point of view concerning the
conditioned reflex mechanism of so called unaccountable emotions, when their cause
is not perceived by the subject.
Some authors believe that rhere is a rather dirett [straight] correlation between un-
conscious mental phenomena and activity of the right hemisphere [6, 111. In addi-
tion to the works cited, which refer to studies on people with a"split brain," these
authors refer to some clinical and electroencephalographic data to confirm their view:
patients with a lesion to the right hemisphere have virtually no imaged dreams; at
the stage of REM sleep, when there is the highest probability of dreams, greater
activation of the background EEG is observed in the right hemisphere [11]. In our
_ opinion, the view, according to which the right hemisphere is the "source" of uncon-
scious motivation but, at the same time, that it makes a typieal contribution ("its
own voice") to performance of inental funetions on a conscious level [5], is more
- acceptable. This opinion is consistent with the conception of mutually comple-
men:tary "collaboration" between the two hemispheres in the process of pertormance of
any mental function, and of the predominant role of one hemisphere only at a certain
phase of this function.
We were unable to find any works dealing with comparison of cortical activity of
- the left and right hemispheres during perception of unrecognized stimuli or other
unconscious mental activity. Yet the direct registration of cortical activity
- could be of substantial help in understanding the role of a hemisphere in physiolo-
gical mechanisms of the unconscious. In the past, we recorded the averaged evoked
cortical potential from the left occipital region in response to unrecognized
- words delivered to the center of the field of vision [3]. We demonstrated changes
in the Paoo wave related to the unrecognized emotional word, and this served as
- grounds to use recording of the p300 wave to study interhemispheric relaCions in
the course of perception of unrecognized verbal stimuli.
Methods
We studied 11 men ranging in age from 18 to 39 ye ars (mean age 24.5 years) who
were right-handed and had normal vision. A11 of the subjects were in a difficult
conflict situation. Six tests were conducted with each subject. During the
experiment, the subject was in a semireclining position in a special chair, in a
soundproof cubicle, with their eyes open. The Nova-2/10 of the Data General
Company (United States) computer was used to control the experiment, record and
_ average bioelectric activity, following a program that was specially prepared by
our colleague, S. A. Pogrebinskiy. The visual stimuli were neutral words ("field,"
"heat," "rice," etc.) and emotional ones which had a bearing on the subject's
conflict situation ("wife," "knife," "children," "court [of law]," etc.). The
verbal stimuli appeared on an electroluminescent screen that was 80 cm away from
the -ibject's eyes. The stimuli were delivered at irregular intervals, with random
paL _s (3 to 10 s), out of order and in random order to different halves of the
field of vision, 5 cm to the right and 16.5 cm to the left of the fixation point
- in the middle of the screen counting from the beginning of the projected word. We
realize rhat, for an obvious and in.evitable reason, the angle of vision is not the
same on the left (10.5�) and right (3.5�) if ineasured in relation to the beginning
of a word. The stimuli were exposad for 15 ms. The letters in a word measured
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4x2.5 cm each, and words consisted of 3-5 letters; words with the same number of
letters were presented to different visual fields in the course of one test. Illu-
mination constituted 0.05 lux �ZO% in the vicinity of the screen. The light was
green. The subject was not aware of the stimuli at any time, as we determined
~ from his verbal report after each test. All of the subjects stated that they saw
a dull flash on the screen. The experiment was begun after 5-min dark adaptation.
The following instructions were given in advance: "Look attentively only ahead,
at the luminescent point; do not turn your head; words will appear from time to
time to the right and left of this point, try to identify them and remember how many
times they appear."
The exploring electrodes were placed on the vertex; on the occipital part of the
skull (2.5-3 cm above and 3 cm to the left and right of the occipital protuberance),
_ in the left and right "associative" regions (halfway between Pz in the international
- system 10-20 and the mastoid process); the last derivation, we believe, was from the
region of the angular gyrus at the boundary between the occipital parietal ancl
temporal regions. The reference electrodes were situated on the left and right
. mastoid processes. The potentials were fed, through amplifiers of an ME-132
electroencephalogram of the Nihon-Kohden Company (time constant 0.3 s), to the
input of a Deytel analog-digital converter, with analysis epoch of 1024 ms and
- frequency [sampling rate] of 1024/s. In order to determine the EEG isoline, averag-
ing of bioelectrical activity was started 300 ms before delivery of a.stimulus.
_ Averaging was performed per 50 reactions, separately for stimuli delivered to the
right and left half of the visual field. In the course of the experiment, the
current averaging of evoked potentials was flashed on the graphic NR 1311A
display for visual monitoring and, at thR same time, it was recorded on the mag-
netic tape of an Ampex (United States) digital recording device.
The latency period (LP) and amplitude of positive wave (P3oo component) oi: the
averaged evoked potential (AEP) were measured automatically by the computer after
deteYtnination by the experimenter of its peak and peak of preceding negati.ve oscilla-
tion on the graphic display. The results obtained were submitted to variance ana-
lysis, and we calculated the reliability of differences according to Student.
Results
A Psoo wave with LP of 353�2.6 ms is derived from the left occipital region and
347�4.5 ms from the right occipital region in response to presentation of an
unrecognized neutral word to the contralateral visual field (Figure 1). The dif-
ference is statistically unreliable (p>0.05). No significant interhemispheric
difference in latency period of P300is demonstrable with analogous prez-:ntation of
unrecognized emotional words (LP 342�5.3 r.s on the left and 346�3.3 on the right;
. p>0.3). However, in this case there was one distinction: LP of P300 is almost
reliably shorter for i.he left occipital region in response t_o emotional words
(t = 1.92 according to Student; F= 4.79 according to Fishex�; df - 1/10; p>0.05)
than neutral ones; t'nis is not observed in the right hemisphere.
~ We failed to demonstrate appreciable interhemispheric differences in LP of P3oo in
response to neutral and emotional words in the "associative" region (as we suppose
- this is the region on the boundary between the temporal, occipital and parietal
regions) (Figure 1). In the region of the vertex, LP of the P30o wave is unrelated
to the visual field to which the stimulus was presented or to the signal meaning of
the stimulus. For example, LP constituted 355�4.2 ms in response to a nev.tral word
= in the left visual field and 353_+-3.4 ms in response to an enotional word.
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Occipital region
ms `
J~f 0
J00
ZSO _
N E N/E N E N/E
Fig4re 1. Latency period of P300 wave in left and right hemispheres in res-
ponse to unrecognized words presented to the contralateral field
of vision
Key:
L) Ieft hemisphere E) emotional words
R) rigtit hemisphere N/E) neutral words against the background of
N) neutral words "unaccountable" emotion
uV~ Occipital region "Associative".reQion
>4- 1;-,
>U
5
<
' ~ 1~1 ~I-I .1 1
N E N/E N E N/E
Figure 2. Amplitude of P300 component in left and right hemispheres in res-
ponse to unrecogniztd words delivered to contrala:teral field of
vision. Designations are the same as in Figure 1.
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~ - RYF
- A
L v1
AR
~R
I ~o uv
+
____1 r------1-T----------,
0 S12 1OZ4 . p S12 1024
Figure 3. Averaged evoked potentials in response to unrecogn:zed neutral
verbal stimuli. Subject D. LVF--left field of vision; RVF--right.
- The word "field" delivered to left visual field and "sea" to the
right. The line going from the time scale indicates time of
stimulation
Key: AL, AR) associative regions of left and right hemispheres
OL, Og) occipital regions of left and right hemispheres
V) vertex
T) time scale, ms
Considerabl.y greater differences are observed in amplitude of P3oo wave, both -
between hemispheres and between neutral and emotional words (Figure 2). In response
- to exposure of a neutral unrecognized word to the contralateral visual f ield, P3oo
constitutes 9.8�0.38 uV in the left occipital region and 8.4�0.35 uV in the right
(p