JPRS ID: 8520 TRANSLATIONS ON USSR SCIENCE AND TECHNOLOGY BIOMEDICAL AND BEHAVIORAL SCIENCES

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• Collection: JPRS
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• Original Classification: U
• Document Page Count: 85
• Document Creation Date: November 1, 2016
• Sequence Number: 31
• Content Type: REPORTS

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I ~ ~ ~

iS JUNE i979. CFOUO 28179~ i OF i
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~ JPR5 L/8520
].5 June ].979 ~
~
~
TRANSlATIONS OP~ USSR SCIENCE AND TECHNOLOGY
- BIOMEDICAL AND B~HAVIORAL SCIENCES
. (FOUO 20/79)
U. S. ~OINT PUBLICATIc'~NS RESEARCH SERVICE
_ FOR OFFICIAL USE ONLY
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NOT~
JpR5 pub~.ications contain information primarily from foreign
newspapers, periodicals an3 books, buC also from news agency
Cransmissions and broadcasts. Materials from foreign-language _
snurces are tr~nsl~Ced; those from ~nglish-language sources
are transcribed or reprineed, with the original phrasing and
other characteristics retained.
Headlines, ediCorial reports, and material enclosed in brackets
are supplied by JPRS. Processing indicators such as [TexC] ~
or [~xcerpC] in the first line of each item, or following the
. last line of a brief, indicate how the original informaCion was
processed. Where no processing indicator is given, the infor-
mation was summarized or .extracCed.
Unfamiliar names rendered phonetically or transliterared are
- enclosed in parentheses. Words or names preceded by a ques-
tion mark and enclosed in parentheses were not clear in the
original but have been supplied asappropriate in context.
Other unartributed parenthetical notes within the body of an
item originate with the source. Times within items are as
given by source.
The contents of this publication in no way represer.t the poli-
cies, views or attitudes of the U.S. Government.
,
I
COPYRIGHT LAWS AND REGULATIOIIS GOVERNING OWNERSHIP OF
MATERIALS REPRODUCED HEREIN REQUIRE THAT DISSEMI1dATI0N
OF THIS PUBLICATION BE RESTRICTED FOR OFFICIAL USE ONLY.
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?7PR5 L/8520
' 15 June 1979
T RANSLATIONS ON USS R SCIENCE AND TECHNOLOGY
BIOMEDICAL AND BEHAVIORAL SCIENC~S
(FOUO 20/79)
CONTENTS PAGE
CLINICAI, b1EDICINE
Abstract Index of Inventor's CertiYicates and Patents
(M. V. Antonova~ G. G. Fillipova; NAUCHIdO-
TEI~iSCIIESKAYA INFCRMATSIYA, No 4, 1979) 1 -
Coordination of ScientiPic Studies on Specific Probleme .
of Scientific InPormation in Medicine
(Ye. I. Dubynina, et al.t� NAUCHNO-TEHI~IICAESKAYA
INFORMATSIYA, No 4, 1979J 4 `
ECOLOGY
A Criterion for the Stationary Ccexiatence of Closed
Microbe Populations
_ (A. G. Degermendzhi, et al.; DOK[ADY AKADII~III NAjJK
- ssSR, l~0 4, 1979) ]2
GIIQF~ICS .
Adenoviral Induction oP Gene Mutations in Maum~lian Cells
(L. L. Liakash~ et a1.; DOHI,ADY AKADEi~III NAUK SSSR,
No 4, 1979) 18
MICROBIOIAGY -
Associating the Ribonucleop~oteins of the InPluenza Virus
With Nuclear Chramatin in ?nfected Cells
(A. B. Bukrinska~a. , et al.; DOIff,ADY AKADIIKII NAUK
ssSFt, No 4, 1979) 24
- a- [III - USSR - 22 S&T FOUO)
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~Uk ~11~1~ICIAI, USI: (1NI,Y
CON'r~N'r9 ( Cont i nued ) ~e
~he Generati~n of a Di�ferentifil 1.n I~Slectrica~. Potent;inls
l,y the Ctirumut;ophore~ oi' 12hodo3Plrll~um IZubrum
Induceci by a La~er Flare
~ (L. D. Drachev, et al.; llUi4~li)Y AKAI)~MLI
~?Ux SSSR~ No 4~ 1979) ~'7
Studying the Interaction Between aramicidin S and -
Bacterial Membranes by the Proton Me,gnetic
Hesonance Technique ~
(V. A. Yeremin, et al.; DOKI,ADY AKADEMIY NAUK
sssR, rro 4, i979) 33 ~
PUBLIC HFAIlrH
- The Constitution of the USSR and Problems of Governmental
Legal Develop�nent. Life and Health of the Soviet Men
as tr.e C1b~ect of Constitutional Protection
( F. M. Ru3inskiy; ~ SOVETSIC07CE GOSUD~ARSTVO I PRAVO,
Jan 79) 38 _
An Investigation ot the Kinetic Iawa of Hum,an Mortality
in the Hiatorical Aspect
( L. A. Gavr ilov, et al DOHI,ADY AKADII~III NAUK
SSSR, No 4, 1979) 49 _
SCIEDTrTSTS AND SCIII~IFIC ORGANIZATION
~ Acade~ oP Sciences Revie~a Activity of General Biology .
Department 54
~ (VESTNIK AKADEI~I NAUK sssR, No 4, 1979) ~
Jubilee Dates, Awaxds of Aca.demy of Sciencea Deacribed ~ -
fVESTNIIC AKADENBI NAUK ssSR, No 4, 1979) ~
Procedural Actions oP U~SSR Academy oP Sciences Descr3bed
(VESTIVIx AKADF�[~I NAUK ssSR, No 4, 1979) 79
.
~
- b -
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E-
FOR O~I~'tCIAL USIs ONLY
- CLINICAL MIDICINE
- ABSTRACT INDF'JC OF INYIIiTOR' S C~RTIFICATES AND PAT&iTS
Moecow bIAUCHHO-TEKHNIQiESKAYA INFORMAT~3IYA in Rusaie~n Seriea 1 No 4, 1979 p 29 _
(Revie~ by M. V. Antonova aad G.G. Fillipova of the abetract index of
inventor's certificates and patente+~j
[Text] The progreas of scientific infor~atioa, end aedical-technologicnl
information in particular, depends on the effect.ive syateaatization of
experience in the reseercb area accumulated in our country. The Leningr~d -
Scientific Research Inetitute of IIemstology attd Blood Trnessfl~eion, `rhich ass
- Pflrmed in 1932, hsa becone kno~rfl ae a ma~or ecientific center, vhicb ~+ne the _
firat in the vorld to conduct the fractio~iag of blood. Meny inve~tim-levei
recommendationa conducted at the Inatitute have been introduced into the
practical xork of inedical institutions, vhile tbe awst recent recamendstions
heve been eeainilated on a production bssis at the plants of inedical preparstione
affiliated vith the USSR Ministry of the t~ledical Industry and at blood
trsnstliaian etationa.
The index under review here is well structured and contsins infonation on
35 inventions syetcmatiLed into 9 sectione; blood transilision equi~ent;
methods aa~ de~icra for blood conaerration; blood prepsrationa and hemocorrectors; -
nrthods and meaas o! ~ssunohesatologic stuc~y; cureti~e ageats egainst thra~bosis.
pathologic h~ogenesis; aethode of obtsining bone a+drrw; curstive ag~uta
ag~ainst blood disesees; aad tranafuaion tberspbpr for iarious pathologic etates
e~ud diseaaes.
The preseatstioa of the materisl in the index aeets the require~ents for ~
intoraation gublicationa: the biblio~apiiic deacription of esch inventor'a
- certificate contains the title of the invention, its no~ber, th~ date and
,
� Inrentians by the staff mmbers of the Lenin~a~ Order of the Red Banner
of I,abor Scientific Researe2s Inatitute of ~ie~atolog~ aad Blood Traasfusion.
Abstract jndez of the i~?es~tor's certificates aad pstents of the U3SR
issue~ iraa 1950 throug,h 1977, edited by V.S. Snslrnr. Leningrad; 19T7�
25 PP�
1
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~ ~ .1~ .
HOR OCi~ I(:IAL U5L t)NLY
number of the application, the dste of publicetion in the bulletin "Otk,rYtiya� '
izobreteniya, proW?shlenc~rre obnstey, tove?rnyye t.nski" e?nd tbe y~e~?r anA
nwaber of the bulletin. Readers can obtain inforoa?tion about the inve~ntor�
_ e~nd find out to W~h~ essence~of eachndenice ~?nd oflesch�~aethod of dian~~i~
sbstracta reveal
and treatm~nt.
The section on blood exa~instion equipaent coatsine the charncterisation of
~ the cooling cheabcr for aicroscope observations of ob~ects in tranesitted
_ en1 rePlected 11ght+~itted1f bsicefortfiltration andithectbrrnaboelsstac~eterr
- hematologic study.
are a18o described ia this eection.
The aectian on the meaae and devices for blood pre~er~stion conteine inforaation r
oa a method of isoleting t,he leucocytes tr~ bl~d sd~nd the othercforolrn+ f
r?hich is intendcd for pa~esertation of isolated 6e~n
tmpereture caaservstioa of biologicsl prodacta.
Tha na3or achievm?ents o~ the Iastitute are presented in the section on blood
prepo?ratioas aad heaocorrectors. TherY include aesns for hesoataeia (the aethod
of ubtaining hmoatatic sponge wd the sethod of obtsining human throabin),
medicationa for the treatnent of ~?nesia (the sethod o~f
ic
~i~~~~blood c
pre~?sratian; preparatien ior the trestae~t of bypac ation -
suDatitutes for shock contm: (tbe aethod of ob~C~ining Zhe pre~par
gelatinol) and for psre~nteral feeding of pstieats~slb~inous plusa-~ubstituting
solutioa snd e~~~~'~dn~he~ pr~epsntiranpot~acet~lcholineetersse ensne irae
of hemolytic st
errthrocytic etro~�
The ~ection on the a~rthods nnd ~eana of is~uwihw~tologic study includes the
method of r~~esling ia~une antibodies, the ~~sthod of obtaining aati-aati-
A-antieerum s'or the didgnoaie of hawlyLic dises~e in the nevborn e,ccording
to the AHO syeteoa ~~obt~i?~ing edr~rtbr~oc3nitic wtig e~sndgthe me~tlwd~ot~es
in maa, the aeth
obtsining anti].YmP~~Ytic globulin.
Scientiata invoY~ed in the study o! the petholo~r of the coagule?nt blood
eyste,m will be intereated to knox the~t euch effecti~e preparstia~s for the
trest~ent of ackininh(iaventoras ceh~1 ate 1~~13639
7~sh�`~~b�~si~ented
~19751) and uro
in the UbSR.
D
' The method of extracting bone ~arrw froa donors (the inventio~ bT~�t~e ~ges
Kargin) t~ill uadonbted],Y help clinical pl~raiciaas in their ~rork. _
17 and 18 onefe~~ ~dns~d !e bitol~sIt ahho~nld be~itressed thst ferrocEeron
88 fETkAVen,
haa been pdteated in 5 countries. _
2
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I~Ult 01~1~ IC f AI, USL I~NLY
TrsnefLeion th~ernpby for varioue patvologic etatee and di~easee has been
euriched by new~ highly effective meana: C cytochrome intended for the
treatment of hypnxic atstea (in~entor'e certificste xo 3515~6)~ ],yophilised
sorbitol for the conser~?sti~e trentmeirt of thrombo~ohliterating di~easo~ of
blood vea~ele and hesolytic etates (in~eator's certificetea Itoe b2771k ~?nd
k27712) and hexoaephosphate the preparatioa vhich raisee dhe le~el of
energy metaboliea in the bo~jr (in~eator'a certificate No ~54g11).
Clarity and completeness of the apecification abstracta of inventiane are
v~doubtedly merits of the publication under reviev. The index of the numbera
of invention deacriptiana for inf�entora'certificsties,tbe alphabetical index
of the applicants and the indez of the inventors are extremely convenimt.
The above provides n bnaia for high]y eraluating,the givea information edition ~
- aad reco~ending that it be republiahed !or naas circulation.
COPYRIGHT: Veeeoyuznyy Inatitut Nauchnoy I Tekhnicheakoy Inforeatsii, 19T9
9327
cso: i87o
3
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CI.INICJ?L M~D~CI~~ '
COORU~ATION OF 3CIffiiTIFIC STUDIES QN 3PSCII~IC PROBLEN3 OF SCI~iTIFIC
_ IKFORMATION IN MSDIC~IIE
Moacox HAUCHNO-T~iNICH88KAYA IHFORHAT8IYA in Rueeian Seriee 1 No 4, 1979
pp k-6
- [Article by Ye. I. Dubynins, A.M. Kapustyan, N.Z. Zubkova, I.F. Shu~elovs,
V.N. Andreye~v and I.A. 3hsbsnova in the colunn "Infor~ation Work in the USSR",
aubnitted 25 Apr 19T8~
[Text] The development of ~tedicnl science and health care, the iacrenae in
the effectiveaess of acientiiic investigations and accelerated introduction of
their reeulte in practice are determined to a coneiderable eutent by expedieat
prognosis, planning and coordination of ecientific investigstions. _
Information organa Purther conaidersbly the increase in the affectiveneas of'
scientific-reeearch vork in every branch, auccessft~lly using and developing
the methods for informational pstent etuc~y of ecientific reeearch vork at the
planning stage and conducting progreesive informational vork and prepsration
of aurvey information on the coaditiott, achievecvents and trends in tl~e develop-
meat of aci.entific research.
At present about 400 regulsr suDdiviaiona of scientific medical informe?tion
[SMI) i~action vithin the health care aystems; 311 of them ere SMI divie~ons .
in acientiPic reeearch institutea and WZ'e, They serve to provide aver 60,000
scientists and about 830,000 prscticing p}~ysicians with informst~on ~n the
atate of inedical scieace in the USSR aad abroad.
In order to solve these problema,information organs drvelop scientific reeedreh
. xork, thz amount of vhich hna increaaed considerably of late. Thie brings
up the neceasity for the constant perfection of purposeitil. mansgement aa~i
- coordinstion of scientific reeearch vork in the area of scieatific nedi~al
informrstion .
The system of coordination and managmnent of acientific investigat3ona in the
- ared of acientific medical inforaation is repreaented by the following 7 _
levels:
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-��the U88R Stnte Comm?ittee for 6cience and Technology;
- -�the Medica]. Acadeaic Council of the USSR Miniatry of Xealth;
--the ticierntific Council for eocial 2~ygiene e?nd orgsnisation of heslth csre
c~f the Preeidum of ~he U9SR Acadeqy of Medical 8ciences;
--the Coemnittee for the proble~ of the hindementdle of scientific Qedical
information;
--the I~11-tkiion ~c3entific Research Institute of Medical and Medical~i'echnological -
Inlorse?tion [Ai!3RIMM!'Ij nnd the Stnte Central. 3cientific Medical Libre.ry
~BCML~; -
- the SMI di.visions in the republica; �
_ --the SMI ~iiviafons of the leading branch acientific resesrch inatitutee
developing a certain;problem.
The f~nctions involved in the coordination of acientific inveetigations arr -
allocated in the Pollaring ~ray:
rHa~4Mhllt ".0~lR1 �~:l1LLaADHCA 2l1CLLCH0~
I'~. opzc?~u~uu~~ ~dpa6oo~paHeNUn" ~
npu flpeulduyne AMH CCCP 1
f1Do6nenHaa ?coMUCCUn �OcHOeei ~4HOII _
MCdULLtLNCKDlt LLH~OQMC4LLLL~
BHNNNN, ~llHH6 3~
rpo6~eMHan xonu.ccun �CCHOSEI H0.~4H0lI , �
LeduuuHCKOU ur+c~oanauuu _ (4) _ J
y ~ ~
POHHN
OHMN tonoEneix OHMN to~o Heix HNN _
HNN H3 CCCP pecny3nunaNCNOto
AMH CCCP nodvuHeHUn
-{OHMN odNOnpO~uneHmx HNN
PetuoHaneHeic meppumopuaeeHeic opaaNa, Ne aodnutue
6 c~cpy ?cypapo6aNUn nscmHeix , cob~~nix u pecnydnu-
KaHCKUx o eaNOb HMN
Key: _
l. Sci~ntifia ~ Council for Social ~jrgieae and Orgaaizatiai o! Hesltb Ce~re
affiliated x{th tbe Pre~idtwn o! the i~SBR Acadapr of Medical Sciences
2. Committee for the problaas of the hindnnentale of scientific aedical
info:astioa _
3. AIJSRIl~I, SCSI~
Coaittee for t3~e probless of the lundasentala of acieatilic aedicsl
inforastion.
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5. SMI diviaione in the republica
- 6. SMI divieione of the leading branch SRI'a [cientific reeearch inetitutee)
of the U58R Niniatry of ~ealth and the UBSR Acade~? of Medical 8ciencee
7. SMI divisione of the leading braach 3RI'e of the rep~ublice
8. 6MI d{:�isiong in the 8RI'e o! ths eame trpe
9� Regional organs vh3.ch are not affiliated vith the SMI local, md republie
- organa
The ScientitYc Council for Social Hygiene and Orgmiastion of Health Caro -
~f~'iliated with the Presidiun o! the llSSR Acsdese~ of Medical Scieacea is a
fl~nctional link in the system xh:~ch desJ.s ~+ith prognosie~ rnrer-all planning -
and coordination of the sctivities of scientific institutiona in the countr~?.
Follaaing the eatsblished order, it orgenisea co~eitteee and councile on
" ~arious problem~ caseposed of ita membera.
In accordance vith tha prese~t stntute, the comaittee for the probles~e of
the fu~adamentals oP acientific aedice~l inforaation develape plana for raz~ieue
problms and aub~ects, re~viewe and rrralue?tes sub~ect sad report charte and
coordinatea acientific investigations of the gi~en problem. -
AUSRII~I, th~ leading branch institute, coaducts scieatific methodologicel
guidsnce aad coordination of acieatific inlorme~tioai activities carried out by
the orgews of scienti~ic medicsl infon~atiaa vithin the health care syate~
and serves as a uorking tool for the conmittee for tbe problems of the
tundw~entala of 3ldI. -
SCSML directs eciantific resenrch Work of the 3I~Q orgsns nimed at the
organization of s uaified branch reterence aad intormntion bank, eneuree
atsnd~rd methods of acquisition ead the development nnd introduction of dste
retrie~aal systeas and coordinai~es, with the assiatance t5rom the SMI o! the
republica, the activitiea of the librariea vithin the i~!lelth cnre syetem.
Scientific ~+~ork relsted to the sutanstion eud aechsnization of the ddte~
retrirval syetem are cmducted under the guiclance of~ nn in s close contsct
vith, AU3RI1?4lPI.
The 3MI divisiana of the republics coordinate scientific research vork
condneted by the SI~II divieions of the SRI's aind the libre~riee in the republics .
The SMI diviaiona of the leading SRI's coordinste ecientific reaearch vork
- of the Sl~ diviaioaa affilisted vitb other inatitutione of the eame t~rpe,
_ are reapoaeib~S,e !or the prepe~ration of snnusl reports on the sebieve~ente of _
nedical ecience in the U53R md sbroad and be~se their aork aa the ~ethodological
meteriela o! AUSRIl~I, SC81~IL, 8MI diriaions ot the republics and the eteadard
- statute on the St~II division of the leading brancb SRI.
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roR or~~rcrAi, us~ aNt,Y
While ana,~y:ing the ecientific roeesrch w~ork p].ane in ecientific tnedical
- infozrowtiou, one cen obte?in nr? idea of the diatributi~ of revesrch anong
the participsnt~ and the gu~?t~aatee of the completioa of reeearch by the -
inval~ed ecieptiete, eu~ vell aa clnaracterise the multi-approach nature of the
evb~ects in e~?ch section of the plm.
The acienti~ie reaesrch ~rork ewmuluti~e ple~u for acientific uedical inforaation
is drewn up on the besis of the acieatific reaearch vork aub~ect charte euba~itted
by the SMI divieione of the republics ettd the SI~Q fli~ieiaeis of the ecientific
researeh inetitutieae of the U$SR Ninistry of naalth aad the USBR Academ~r of
Medical 3cienaes se well aa by SCSML sad acientific medical librariee ot the
republic~.
In order to extead and deepen acientific investigntions and t~ increase the -
level of inethodologienl guidance tor the infonistion orgaa~, AUSRL~QdTI haa
developed a long-range 3RI plan oa the groblem of the fundae~entAle of ecientific
medical inform~atioa for 1q76-198o which includea 138 acientific sub~eetP `
distributed alacig seven b4sic directions (individutl problens):
1. Organization, management~ planning, prognosie nnd effectivenees of acientific
research xork. NOT in SMI. .
2. Standbrdization of nedical terminolog~r. Aevelopnent of claesification _
diagrams and d~ta retrieval laagu~age.
3. Inves~igation of the directions, 3ources and needs in 3D(I. Aaalyt~ic aad -
synthetic information procesaing. .
- 4. Developmeut of the reference and infor~ation bank, dats retrieval equipsent
and reference and iafora?ation serrice.
5. Patent infornation.
6. Aaalyeie and au~atioa of the ~ost i~�portant Achievemente~ iu aiedical acience
aad health care. The state oY nedical science and health care.
7. Interna~ional cooperatiaa ia SMI, stuc~y of foreign centere of inedicsl
information .
The plan cevera~all~of the most important research trends which assume.the
- theoretical and methodological grounding oP ecientific research work in a field,
the development of unifo=m methods for aaalytic and synthetic infoYmation
proceasing, improvement of management and planning of scientific investigations
and tii~ introduction oP NOT.
Scienti~�ic inveatigations of tMO specific problems have the most iaportnnt
relative: amount: the Pirat one organization, mansge~eut, planning, p~ognoeis
and ~"lzectiveness of scientific iaformation ~+ork (26.8 percent) and the fourth
one development oP the reference and information beak, datn retrieval equip~er~t
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ro?i or~~rc:rn~ crsi: c~rti.Y
and refe:ence ewd information service (21.T percent). Investigation of the
directiona +~nd neede in 5hQ conatitutee a consi.derable part of the inveetigstiono
- (16.6 perces~t ) .
~Thus, the sub~ect matter o2' ecientific reaearch ie basically relsted to the
main trends in the organiz~tionel methodologicel and actual work of the SMI _
organa.
Zheoretical aspects of aCientific resee~rch which lorm the bnses for the de~elop-
ment of auch forma aP scientific inforination ~rork aa data Analysie, as rrell ea
problems related to the development and introduction of autome?ted SMI data
procesaing eystema, are Zargely plenned on the level of AUSRIMMTI and sone
~a~or 3MI divioiona, vhile amo~ng the reaearch sub~ects of the SMI divieione in
most of the leading SRI's tb,eoretical investigatione nre either represented
in~uPficiently or not represented ~t all.
An extremely low percentage (5.1 percent) oP ecientific inveetigatione of the
- patent information probles brings up t~e necesaity for considerable reinforce~rent
of this section by peraonnel and technological equipaent.
A multiple approach is very ia~portant Por the euccesaiLl implementa~ion of -
research proble~ms ar~d the inerease in the effect~venesa of inveatige?tion: 43�5 ~
perecnt of aL1 sub~ecte in the plan are of a multi-appronch nature.
Having a large share of ~�tLlti-approach sub~ects is characteristic of nlmoet
all specific prcyblema, except for the fifth sectioa, i.e., pntent infortation.
A lorr level or vnrer-all npproach to acientific research work in the tbird
(22 percent) and siu~h (14 percenL) eectiQna can be explained by the epecif:c
nature of the current imeetigstions: study of inforsstioa trend and neede as
vell as 8aa]~lreis and generslizatiai of the moat important achie~reaents in
iadividual braaches of inedical science.
Scientific reaearch planned by AZSRIh9~ITI and 3C8lQ, is chnracterized by the
highest of over-all approach (81 perceat), while in the plsns of the SMQ
divisions of the republica snd eapecially of the SMI diviaione in tme leading
braach SRI's it ia considerably loWer and co~aetitutes b8 and 26 percen~., -
reepectively.
The sub~ ects pleaned by AIDSRII~TI and SCSML constitute 23 perce~t of nll
research in the five-~esr plan; the 3bLI divisions of the republice plaa 21
percent oY reaee~rch sub~ecte aad the 3IrQ divisions of tbe leading branch 3RI's _
plan sbout 56 perceat.
It is neceBaary to note that the SMI diriai~na of the lea~ding branch 3RI'a
do aot partici}~ata enough :~n the dre~fting of the plsas for aciestific reeearcb. -
Thia can be contiraed by the foll,o~ring figuree: 15 ont of 31 SMI Qiriaione
of the SRI's of the USSR Acadea~r of Idedicel Scimces conduct acientilic resesrch _
vork on samve aapects of the frindaaentals ~f scientific aedicsl iaforostiaa,
$ _
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1~ok ~~t~t~t~;1n1. u~~l~.' c~t~L},
vhile the remnining 16 SM1 divisione do not plea ruch vork. 17 out of 72 BMI
divielona of the laa?diag br~suah S1tI's of the tk3SA Min~letry of lle~lth earry vut
resesr~n davelopQentg~ while 5 SHI divigiana ot the leoding bra?nch SRI's
_ hare noL planned scienLitic investig~tions io the ares of acientific bedl~cal _
infvrmetio~. Si~ilar conditione can be ob~etwed in the inforaatio~ di~i~ioru
of the ~enfling branch SItI'e of the republic~ ~on].y 26 out ot 31 8M2 divisiene
of the lesdin~ breaeb SRI'r eon~luct eci~ntific inreetEigatione
Insuf.*.icient participatio~? by the most nuneroug estegory oP inetitutions in the
~.oplem~ntetion of the 3RN plan reflecte the iniL~ial period of the vork in thi�
direction.
Ann~jreie of the reoults of SMI developa~ents nnd of Lhe ve~?e ot their introduction
into practice has dcmaoatrsted Lhst ebst vorke iare suppoeed to be utilized in
the pnscticel ~ork oP infor~nsLion orgaaa in concrete foree. i.e., in the first
place, ae publicetiona . Ye~rioue ~aethodologicsl a~teriels and ~cientific nrticlep
hnve the lsrgert pmportion eaong them ad aad 38~ reapecti~elr. The
prepere~tian and defense fl! 5 doctoral nnd 20 cnadidnte diesertatioae hn~e been
planned; thie etteatd to a auficient depth of cux~rent reeearch.
Aloag xitL the poeitive aapects there are sone shortcaminga in the plewnins md
~ coordinstion of plans br bot3~ the higher en3 the eubordinnte SMI organs. Thus~
an ineufficient breadth of the mnlti-approarh 81~II reeesrch, the Qis~ipstion of
r~eenrch reaourcea, the narrw anb~ects xhich brin~ about tbe nec~ssit~r o! ~
etr~ngheniag ws~ s~all acieatific reaesrch work r?nd ~he neceeeity for s
coordination ot sub~ect structure vithin specific proble~s of the plaa ehould -
be mentioned.
Di:ficultiee in coorQination occur or~ e~?ery le~rel of the eyste~, We find it
expedient to Qe~-!op euch forsA as ~erirving the SRSI pLns aad eub~ect chsrts
vithin the coardira~;~on system of the At1SRIlOQI, the SMI dirisione of the -
republics end the 81~! divieione of the lesding bt~anch SRI's.
Nhile the SRN olan of Lhe SMI divisicn of Lhe RSTSR Ninistry of Realtb haa
been drafted in f~l]. co~cordaace vith the reaearch tre~da for the probl,er+ of
national importaace t1~t of the SIQ llind~aentals, the SRW plaas in the
Sl~Q divieions oY other repnblics have ~acpr draxbacke. ]lot all SRtiI' � are
suD~itted for etste registrstLon, appro~eQ br the scientific councils aaQ
included in the acienLific research p1.4as of their institutione; the b'KI
di~iaione of the republica are not acti~e enough in the preparation of
cuaulative pl,aa~8 for their republica; the positi~e exp~rimce of the leading
SMI aerric~a is aot sufficientl,r utilized; there ie no precise order ia the
receiriAg of plaas and reports frea~ thc leading branch SRI's. Ties betveen
the SRI's l~ding the reseRrch of a problm aad LLe other SRI's of tbe saae
tppe still reaaina a veak linlc in the coordinatYon.
Coordination canferences of the lesding bronch SRI's a~nd the other SRI'a of
Lhe saae t~?pe vhere basic trends of SRH e?re deliaested aad the problems of
eulti-approach reaearch are braught up are e~ctreaa~jr iaportant for the
9 ~
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_
1~UIt Oi~ f~ IC 1 AL U5l: c)N1~Y
,
coordination oP acier?tific reaesrch. Hovever, this Por~n oP interactioa
_ between Sl~I diviei~ns r+hich tsciliteteg u correct eve?luation oP the possibilities
and goels ~f eech intoiaation aubdivigion and a clear-cut aietribution of
reaponsibilities betweEn them hae not become eo~o~on.
In order to improve SRW plaaning end coordination in scientific medical
informntion end to eliminate the present ehortcominga, it is expedient, in -
our viev, to include ia the cu~ulative plan oaly multi-epproach or general
gub~ecta which repreaent me~or elaborations of a problem and can be utilized
in practic~l vork, et least an the level of th~: preparetion of inethndologic al
e:teriale. Th~ rea~sining aub~ects can br lieted in the supplement of the `
besic plen. The 3RW plen of problems and eub~ecte in SMI for 1g78 ~rse drafted
on the baaig of this principle.
' F'or eaeh apecific problem it wuld be efficient to eingle out groups of
~ eub~ects for invtstigation for ma~or divisions of information xork nnd to
develop uniform methadologiea for their representetion in the plen.
The principle of sub~ect distribution for~ apecific problema in accordsnce vith ~
thc groupg vhich combine general trends of investigntione on the bseis or their
goala, ~qv become the base for the strangtheaing nnd generalization of eub~ecte
in cumplience with the ob~ectives of purpoeeftil plaaning.
In order to regulate the vork on SRS~I managemeat aad coordination in ecientific
medice~l. infonation, it ia enpedient aad timel~? to bring to the ~:ttention of
the Scientific Council of the USSR Academpr of Medicnl 3cianeee s question of
the formntion of the republic-le~el ce~itteee on the proble~e of srientitic
medical information affilieted with the Minietries of Health ot the R~PSR, tIc88A,
Lat~ian SSR, Lithuaniaa SSR ead oLber republice ie vhich ecimtific research
ia de~el,oping most succesafully.
The iatroduction of a itu~ctional linlc ~rhich wuld coordinate Sfi~ on the le~rel
of the republics, vill allov for a completien of the organisation of the 3Aw
plaaning and caordinntion e~rste~ in scieatific aedicel infor~stion.
In ordtr to implesent s more clee~r-cut or~anisation aad expert evaluntion of
re8cerch in acientific medical info~ation, it see~a expedient to essi~ for
each problei aa expert ~rho erould be s sesber of the co~ittee on the probleas
of 2Ladeaentals of pcientific ~edical inforsstian. Thie proposal vas apprrnred
~ nt the plenum of thz probld co~sittee (Kiev, 197T)� I
In order to provide Lhe conditieos for the de~elopaent of scientific info~ation
vork, including acientific in~estigationi in acientific raeQical toraation, it
is necessary to derelop a plaa of aeasures for the tecbaical equip~eat of 81Q
dirisions o'! the leading Drsacb SRI'a aad, in the firat place, ~k,hose that
participdte in the SRW l,ong-raage plaa.
The conceatrstien of the reso~nrces of inforsation orgaaa an all lenels rill
facilitate turthrr de~elopreat ot scieatific infor~atioa vork md incre~se the
10
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role of inton~ation org~ns ia trie plaming. implmentation and raising of
_ ~tfectirrene~s o~t seieatific research in the area of ~edical Qrohlecr.
COPY~tI(3IITs V~eeo~ruscpry L~~titut t~uchnoy x Zbklmicheakay Infbr~aL~ii. 1979
9327
Csas 1870
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~
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FOR OFFICIAL US~ UNLY ~
i
ECOLOCY
~
UDC 577.3.0~2 `
l, CRITERION FOR TNE 5TATIONARY COEXISTENCE OF CLOSED MICROBE POPULATIONS
Moscow bOICLADY AKAD~MII NAUK SSSE~ in Rusaian Vol 245 No 4~ 1979 pp 987-990
[Article by A. G. Uegermendzhi, N. S. Pechurkin, and I. A. Terakov,
Corresponding Member of the USSR Academy of Sciences)
[mext] One of the ma~or probtems in population biology is sCUdying the
ecological mechgnisms that regulaCe the number of apecies and the struc-
ture of a community. At present, there are several modificatione of
"Cause's law of species elimination," which is the basic theoretical
principle used to define the structure of a community. For communitiea _
of the predator-prey type, Chis law states that for n typea of predatora
to coexist, there must be at least n types of prey which aerve to limit
the increase in ~redatora (1). For populations thaC compete for food :
resources, it has been proven that the possible numbe~ Qf existing forms
will noC exceed the number of independent resources ('3)�
Principles of this nature on the formation of communities could be widely
applicable and stand up to verification in the artificial creation o~ 5
mixed cultures in the controlled conditions of a cloaed experiment
However, the interactions of populat3.ons in mixed cultures occur through
~ various factors of environmenC which can include not only the limitational
reserve~~aut also the modifiera of growth--the inhibitors (6) or stimu-
lants (
We will examine a community consisting of m popu~ations growing in a -
closed system of Che chemostat Cype and interacting through n chemical
factors of environment. The latter means that the specific rate of in-
crease for each species is dependent c~n or is controlled by a certain
number (n) of environmental factors, which, in turn, remain under the
control of the densities (strengths) of the noted species. Thus, factors
of environment are density-dependent and their transformation is propor-
tionate (with a plus or mi.zius) to the Arowth activity of each apecies.
A system of differential equations will then have the form
12
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f
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~OR OFFICIAL US~ ONLY ~ _
I
xi�~B~~A~?...~AM)-Djx~, /=1~2~...,m;
~1) ~~=D(A~�-A~)+ E ak~fk/~~~...,An)xk, 1�i,2,,..,n,
~
I
where gi(A1,...,An) represenCs the epecific~rate of increase for the i-th
_ species; D is the rgte of circulation; A~, A~ represent the concentra-
Cion of the ~,-Ch factor controlling growth upon enery and witZiin the en-
vironment, respectively(some A~ will be zero); ehe term ak~f k~~Al?'�'+An~~tk
- measures the rate at which the k-th species will utilize or absorb the ~-Ch
aubstance; ~ki ie Che apecific rate of transformation of the ~-Ch sub-
- stance by the k-th species.
It is difficult, of courae, to assign any sort of explicit "universal"
form to Ch~ function gi because of the faceors A1,...,An, proceeding from
the form of syatem (1),iC is possible to demonatrate that the possible
number of permanently coexisCing speciea doea not exceed the number of
~ independent growth-control factors determined by the densities (Xi) of
Chese speciea (that is, m~ n). We will stipulate that the factors are
independent if there are no variables such as zl,...,zp which are func-
tions of A1,...,An (p c n) and that gi can be expresaed as a funcCion of
zl,...,zp. If thie is possible, Chen the values zl,...~zp can be con-
sidered to be independent factors and we will reCain the symbols A~ for
them.
We wi.ll agree that the number of coexisting apecies equals the number of -
factors (m = n). Sy~stem 1 might have the steady-state solution deter-
mined from the following equations:
(2') 8i~~~...,A�)=D, t~1~2~...~n,
~ ~
~2~~~ F, ok/fk/~At.... ~An)xk=D(A~-A', 1,2,...,?~.
- Ar~l �
The steady-state solution for the concentrations of factors in the environ-
menC { A~~and the densit~es of the species ~~ti~ are found from system (2')
and (2"), respectively.
For there to be a single-value solution for { A~}'definable from a syatem
of implicit functions (2'), in some range (point) of the valuee A' f T.',
the functional determinant must be other than zero:
81A~ BfA~ � � �81A~
(3) ~ ~ ~ �
D~1.��� ?8n~ 89A~ d1A~ �dlA~
s
D~1.... ?An~ j~nA~ �'leA~ ~itA~ ' -
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I
~
~
~'Uit OFFICIAL USE OriI~Y ~ ~
where glA~ is a partial derivative of Che function gi for the varl.able
" A~ .
_ System (2') then definea {A~~ as an identical function for Che raCe of `
( -
circulaCian D: Ai m r~(D). It ia also necessary that the etaCionary con-
_ cenCrationa of ttle factore A~ be positive.
(4) A~~r~(D)>0~ J~1~2,...~n.
Then, from the heterogeneous system of linear algebraic functiona (2")
_ and g marrix of the elementa ak~fk~(A1,...~An), it ia possible to find
the fixed values for the atrengths of the species
~5) x~=U~(Ai,...,A,�,, D)>0, !�1~2,...,n. ,
which must also be posiCive. The condition of stability in these solu-
tions requires specific limitations (at a fixed point) on the matrix of _
the adaptaticns IlgipJ~~ and the matrix of subatance transformation -
Ilak~~k~l) ' lack of which can lead to the elimination of certain apecies (9). _
Thus, in some arca of change in the parameters--the rate of circulation,
D, and the concenCration of input factora A--the coexietence of n number
of species is possible in the presence of t e control factors. +
Let there be one other species with a specific rate of increa~se of
gn+1~A1~��~~An~ at the same trophic level in the model ecosystem b~ing
examined. Here, it is essential that the number of growth-control fac-
tors remain the same and equal to n. Is a balanced coexistence for the
(n+l)th species then possible?
In this situation, the fixed valuea for A~ must be determined from the
system for the (n+l)-th equation (6)
' (6~ 8r~~..�.~A�)'D. f=1,2,...~n+1. .
We introduce the designator '
(7) YIsB~~A~,....An). J=1,2,...,n+1.
14
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~OR O~FICIAL U5E ONLY ~
According to condition (3), A can b~ identically expregsed Chrough _
yl+.�.+Yn from Ctie expreseion~ in (7) thYOUg}~ the tirsC n funcCione
Then we have
- (g) Yn+~�8n+t~r~~Y~~,,.~Yn~~..,,rn(Y~~...~Yn))=~'i~,..~Yn)~ ,
that is, the function yn+l ie dependent on the see of funcCions Y1,...,Yn .
(accarding to (3), the functions yl,...,yn are independent). Obviously,
this dependence (8) can also exisC in the derivative form gn~.l(A1,...,A~) -
~lthough this dependence mueC have Chat "infinitely imprnbable property
that will change expression (8) to an identity in some area of the change
in the rate of circulaeion D when yi ~ D(i = 1, 2,...,n+1)
(9) W(b,D,...,D)=D.
The difficulty in saeisfying the identity (9) is associated with the fact
thaC, when the dependence of the specific raCe of growth (gn.~l) for a
species being introduced is derived from the environmenCal factors A~,
- its aimulCuneous inCersecCion with the other ftanctions in gi and the rate
of circulaCion is a low-proba~ility occurrence.
Thus, it is improbable that the set { A~} which converts (6) inCo an
identity will stand up for system (6). The absence of values in A~, in
Curn, make it impossible to define ~xi , i= 1, 2,...,n+1 which also
leads to Che conclusion that system (6 musC ultimately have form (2')
or the form of a system in which the number of populations is strictly
less than the number of growth-controlling factors (that is, m< n). As
can be shown in the latter case, the fixed concentrations of factora of
the environmentt A~~ and species density { xi~ may likewise be defined,
l ~
but, in contrast to the preceding situation (m = n), the equilibrium -
levels for these factors are also determined by the valv.ZS for input
f low ( A~ ~ .
l
In summarizing the above, it is ~~ssible to show that the number of equally ~
coexisting species cannot exceed t:he number of density-dependent growth-
control factors of environment. 7'his proof may be viewed as a modification ,
of Gause's principle of the elimination of species "ada~ted" to systems
for the continuous culture of microorganisms.
In regard to extending this proof to situations of fluctuating cyclic
patterne (with a period of T), the following may be said of system (1)
~ 15
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FOR OF~ICIAL US~ ONI.Y
(enli~ting ehe ttieorem on environment). '1'he line~r dependence of rhe
~pecific rnCe of populntion growth gi on Che factors A~ ie suffi.ci~nt
grounds to saCisfy Che provision ~s to Che ttumber of coexigting species. ,
It is not posaible Co eny anything specific about the c~orrelaCion of the
number nF ~pecies or the number of fncCore in Che case oE oeher poesiblp
soluCions for system (1) sinCe there are ~eparate theor~?C~.r.al examplee
ehne ~re exceptinns Co G~use's law for these situaCiotts (~0,11~~
7'he experimental data available in published maCerial descriptive of
rt~e mechanisms of equal coexistence among species in closed systems "
relares primarily to Cwo-way associations. At least in theee particu-
1nr variants~ the theoretically stated law of coexiatence h~s an experi-
mental proof. Thus, the essential associ~tions between the bacteria
Lactobacillus planCarum, for example, which ia limited by glucoge and
Che lactic acid beingl~iberated which determines the growth of Prnpioni-
baceerium shermanii bacteria of Che Pseudomonas species which are
limited by deficiencies of oxygen and availaUle meChanol which, [in turn)
inhibits the growth of Paeudomonas sp and is consumed by the Hyhomicrobium
sp. (l.3); the yeasts Candida mycoderma and Cnndida tropicalis which are
limired by glucose with the first strain giving off a product which _
stimulates ttie growth of Che second and other similar experiments -
~14,15~ Were described some time ago.
The theoretical results presented in this work and their experimenCnl
proof make it possible to draw a number of conclusions of substantive _
value. First, if a balanced coexistence such as that between two species
of microorganisms and a single growth control fac~or is found experimen-
tally, then, of necessity there must exist at least one density-dependent
f3ctor. Secondly, the arCificial establishment of a closed, mixed cu.lture
made ui~ of a givem m ~umber of species necessarily demands the presence -
of at least m growth control factors in the system whose input flow
determines the percentage composition of species (see expression (5)).
Third, in studying the mechanism responsible for the coexistence of spe-
cies in closed systems, attention must 6irst be focused on the factors
whose stationary levels do not change (or change only slightly) with
_ changes in the input conc~ntrations (A~) of these factors (according to
expression (4)). It is precisely the factors of thia nature that can
insure prolonged cultivation of mixed closed populations as opposed to
_ the external parameters (t�, the rate of circulation and so on) whose .
presence does not increase the diversity of speeies. And, fourth, the r
dpnamics of species strength in a mixed culture is described by a system
of type (1) where the system of equatiohs for factors include juat those
factors that are responsible for the coexistence of a given number of
species.
Institute of Physics imeni L. V. Kirenskiy, Submitted
Siberian Division, USSR Academy of Sciences, 17 November 1978 -
Krasnoyarsk -
16
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BIBLIOGRAPFIY
1. II. G. Fiauaemen; THEORET. POP. BIOL., Vol 4~ No 1, 3~r ~973�
2~ g. g. MacArthur, R. Levine; PROC. NAT. ACAD. SCI. USA, Vol 51, 1207, 1964.
3. R. H. MaaArthur~ TFIEORET. POP. BIOL., Vol 1, 1, 1970.
4. 2i. S. Peahurkin, I. A. Terakov; "Analiz kinetika roata i evolyuteii mikrobr~ykh
~ populatsii" [An Ana7.ysia of the Kinetics of Growth and the Evolution of Microbe _
1'opulations], Novosibirek, 1975� _
5. ye. I. Kvaenikov, D. M. Ieakova et al.; In the book ~~Bioeintez belka odnokle-
tochny?ni~~ [Protein Biosyntheais by Unicellular Organiame], Moeaow, 1972.
6. D. 0. Zinea, P. L. Rogera; BIOT. AND BIOENG., Yol 13, No 2, 293, 1971.
7. L. L. alyter, J. M. Weaver; APPL. IINIRQNMEN'P. M[CROBIOL., Vol 33~ 363~ ~977~
8. A. G. Degermendzhi, N. S. Pechurkin, A. V. Furyayeva; EKOLOGIYA, No 2, 91, ~978.
~ 9. V. V. Alekaeyev, In the boo~s "Chelovek i bioe~era," Ed. 1, Moecow, Izd. I~U,
- ~976�
10. R. A. Axmstrong, R. McGehee; T~ORET. POP. BIOL., Vol 9, No 3~ 3~7, ~976� _
11. R. ~IcGehee, R. A. Armstrong, J. DIFF'F~tEN~i'. EQIIA'i'. , Vol 23, No 1, 30, 1977.
12. J. H. Lee, A. G. Fredrickson, H. M. Tsuchiya, BIOT. AND BIOEIJ~., Vol 18, No 4,
_ 5~3, ~976.
13. T. G. Wilkineon, H. H. Topiwala, G. Hamer, Ibid., Vol 16, No 1, 1~1, 1974� ,
_ 14. H. R. Burig~ay, M. L. Bungay; In: 9W� APPL. ~IICROBIOL., Vol 10, 269, 1968.
_ 15. J. L. Meera, D. E. Tempest; J. GEN. MICRUBIOL., Vol 52, 309, 1968.
COPYRIGHT: Izdatel'stvo "Nauka," "Doklady Akadeniii Nauk SSSR," 1979
9003
C~Q: 1.87~
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G~NETICS
, UDC 575.155
ADENOVIRAL INDUCTION OF GcNE MUTATIONS IN MAMMALIAN CELLS
Moacow DOKLADY AKADEMII NAUK SSSR in Ruasian, Vol 245, No 4, 1979 pp 970-973
(Article by L. L. Lukash, T. I. Bushiyevskaya, N. V. Varshaver, N. I.
Shapiro]
[Text] Establishing the ability of the SV-4Q oncogenic virus Co cause
- gene mutations in mammalian cells (1~2) has brought about some question
as to whether this ability is a specific characteriatic peculiar to SV-40
alone or wheCher it is a reflection of a general princi.ple and ia like- ;
wise characteristic for other DNA-containing oncogenic viruses. Finding
the answer to this question is of paramount importance for the sake of
understanding the potenCial role of virus-induced gene mutations in the
process of malignant cell tranaformations. It is of no less importance
in assessing the genetic riak of viruses as factors in the external
environment.
In con~unction with this, we have studied the mutagenic activitv o~ one
other DNA-containing virus--the type 3 bovine adenovirus (BAV-3) In
the systematic sense, adenoviruses are vastly different from the papova-
viruses. Their genome is approximaCely 10 times larger Chan the genome
of the SV-40 virus and has been given considerably less study. It con-
sists of a linear molecule in contrast to the circular DNA molecule of
the SV-40 virus (4).
We studied mutagenesis in a model of resistance to 6-mercaptopurine
(6-MP, a compound manufacCured by the Czech firm "Chemapol").
A strain of cells from the 237-8 Glu'ts Chinese hamater nonpermissive
to BAV-3 was used as the model (the modal number of chromosomea is 18)(5).
The cells were cultured in an Eagle medium with 10 percent cattle serum
inactivated at 56�C, penicillin (100 units/ml) and streptomycin (50 units/ml). ;
At low culture densities, the sz~um content was increased to 30 percent.
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Once a month, the cells wex~e incubated with tetracycline (50 unita per ml)
- for 1-2 pasaes to prevent contamination by mycopla3ma.
A clone of Che BAV-3-3 virus which ig a derivative of the WBR-1 etrain .
was developed at the InstiCuCe for Molecular Biology and graciously plac~d
aC our dispoeal by Ye. 5. Zalmanzon.
The infection titer for the virus was 1.6 ~ 108 b.o.e/ml with tiCration
in bovine kidney cells (r~BK, strain obtained �rom the United SCatea -
through J. J. Trentin). Undiluted virus and dilutions of 1:10, 1:100 and
1:1,000 were used to innoculate the ce11s.
The Chinese hamster cells were removed with trypsin during the logarithmic
- stage of growCh and placed in suspension. The cells were incubated with
the virus for 2 hours at 37�C wi.Ch intermittent vibration. Cultures were
then made up on Petri dishes (1J0 mm in diameCer) with 500,000 ce11a per
plate. -
ConCrol specimens were sub~ecCed Co the same procedures as the test sam-
ples, being processed in a culture medium using degenerated 1~BK Cells
but without the virus.
The rate of effectiveness for infecting the Chinese hamster cells was mea-
sured by the infection cenCers technique. Following incubation with the
virus, the cells were rinsed off and fracti~nated by rapid freezing and
thawing. They were then innoculated onto a layer of sensitive cells and
given a coating of agar. In light of the fact that not all the viral
particles could be rinsed, a suitable control was set up. For this
purpose, the cells were washed, fractionated and innoculated onto a layer
of sensitive cells i~ediately after addition of virus-containing fluid
but wiChout incubation. The plaques were counted and the viral titer was
compared to the original titer after infecCion di the cells.
Forty-eight hours after infection, cells from all variants of the experi-
ment were placed in selective conditions. The results from similar experi-
ments with the SV-40 virus (1~2) were taken into account in selecting the
optimum periods to check for mutants. Cells were shifted in groups of
25,000 to Petri plates (70 mm in diameter) containing selective media ,
and in groups of 400 cells to plates without an analogue to determine the
effectiveness of innoculation. Every 2-3 days, the medium in the plates
was replaced wiCh 6-MP.
Resistant colonies were stained in vi~~o with methylene blue 12-16 days
after innoculation. The colonies on plates without 6-MP were strained
7 days after innoculation. Colonies containing at least 100 cells on the
numbered plates were con~idered.
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The frequency of muCanta was derermined with correc:Cion mm~de for their
aurvivabiliCy in the eest gnd control, re~pec:rively~ The number of mu-
~ tanes induced was evaluated on rhe basis of thc differentin.l between _
the frequencv of mutanta in the infected and control cultures. Thn
reliabiliCy ~f Che data obtained wae assesaed on the baeie of ehe Fieher SO
criterion where ytis allowed to represent Che maximum number of cella
per plate in the aelective conditions.
The infectious centere technique demonstrated thaC approximately 10 per- -
cent of the virions are adeorbed and apparently penetrare the cellg.
This is commonly found in nonproducCive systema where there is an abaence
of specific cellular receptors (6).
Table 1 shows Che results of 3 experiments to study the frequency of
mutanCs resistant to 6-MP in populations of Chinese hamater cells infected
with the BAV-3 virus.
Cell replication in the selecCive condiCions did not cease immediately~
The cells were able to divide approximately one time before degeneration -
set in. In counting the number of generations produced by the cells after .
infection, we counted an additional division of the cells in the selec-
tive medium as Chis might be of importance in determining virus-induced
mutations.
The yield of resistant colonies was measured while testing various viral
dosages. With a maximum infection factor of 80 b.o.e. per cell and
8 b.o.e. per cell in all cases, Chere was a reliable increase in the _
frequency of mutants resistznt to 6-MP. A dosage of 0.8 b.o.e. per cell
was the least effective and Che difference between the frequency of
mutants in the experiment and the control was reliable in two of the ~
three experiments. With an infection fa~stor of 0.08 b.o.e. per cell,
the frequency of resistant mutants did ;tot differ from Che control level.
In this way, the direct relationship between mutant yield and the viral
dosage is traceable. The results obtained, however, do not make it ,
possible to resolve the question of whether this relationship ia of a
linear nature.
It should be noted that the first experiment differed from the other two ~
by its higher spontaneous reserve and also by a stronger mutagenic activ- ~
ity on the part of the virus. In this experiment, the frequency of
resistant colonies increased by a facCor of 3-6, depending on the multi-
ple of infection and the difference between the test and control was
reliable in all instances. The highest rate of induction with the high-
est level of spontaneous mutants has been noted in the somatic cells of -
mammals by a number of authors.
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Tah1e 1 _
Induation of mutatio~:.e resi~tant to 6-MP in Chine~e ha~eter aelle by
expoaure to the bovine adenovirue type 3(BAV-3)~ .
Virue titer ~ Survival Frequenoy Fre uenay
~O b.o.e.~aell 4+ o of infea- of mutante of 3r~duaed
~ ted oelle with aor- mutanta, p~
N H relative reation g~p-~
a ~ 0.08 0.8 8.0 80.0 ~ to aontrol, v o r a~X1
0'~
~ ~ ~ _
z a - - - - ~.50 ~no.oo ~4.37 -
b - _ - + ~.4~ 84.26 94�79 80.42 > 0.999
c - - + - ~.52 s4.89 91.02 76.65 > 0.999 -
d- + - - o. i~8 78. 67 1~0.26 25. 89 > 0.999 -
iz a - - - - ~.75 ~oo.o0 5.5n -
c - - + - 2.~2 55.05 ~2.80 7.30 > 0.999 -
a - + - - ~.97 43.02 9�93 4�43 >0.99 ,
~ + - - - 2.~5 89.~9 7�50 2.00 .co.9o
IIZ a _ - - - 1.69 100.00 2.20 -
b - - - + ~.65 96.73 7�05 4�85 > 0�999
c - - + - 1.14 118.68 4.92 2.72 > 0�95
d - + - - ~.21 80.36 3.82 ~.62 t o.95
~ + - - - 0.68 9~.35 2.46 ~.26 ~0.95 -
~ Time after infection equals 2 days =
~'Potal number of generations passed on by cells before tranafer to aelec-
tive condition~ and during rema:ining growth proceea
~ Reliability in difference between teat and control evaluated by the
Fisher method
For Che purpose of ascertaini,ng whether or not resistance is retained .
during cell replicaCion in th~~ absence of a selective agent, two colonies
of the control variant and ?[tNSt colonies] were isolated after infec-
tion. The colonies were culCured without 6-MP. An innoculation of cells
from each clone was made after 20 and 100 generations 1.n parallel to the
plates with 6-MP and those without an analogue. , '
All of the clones retained their resisCance. A comparison of the effec-
tiveness of innoculation in the selective conditions and in the medium ~
without analogue demonstrated that the lev~al of resistance was rather high.
The survival rate for cells from different clones in the medium with 6-MP -
was 30-100 percent in comparison with the con:rol. Retention in the
resistance indicator duri.ng prolonged cultivation of the cells outside
the selective conditions therefore indicated that this is the result of
mutational development and that the clones being studied were mutants.
F
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It~iryotypea of the two controls and five of t11e aeven clone~ isnlaCed
afCer expoaure to BAV-3 did not differ From th~~e nf the parent clone~
A new marker chromosome (large end submet~centric) uppeared in the chromo-
- some makeup of one of Che clones (No 9). Another clone (No 3) ehowed an
increase in the number of chromnsomes and an ~.ncrease in the frequency -
of chromatid breaks and crosaovers. During the courae of culCivgtion,
the karyotype for Chis last clone normalized and did noC differ from Che
original 1aCer on. Thus, the abaence of nny one specific change in karyo- -
~ type for Che mutants ia indicative of a lack o� correlation between the
" onseti of resiatance and gross chromosomal restructuring.
The daCa obtained through this ef�ort therefore demonatrates GhaC even
- a s3ngle randomly chosen oncogenic virus--BAV-3-- is capable of induc;ing
gene mutations in mammalian cells. This makes it posaible to conclude
that mutagenic activity is characterisCic t,.C for the SV-40 virus alone, .
_ but probably for a number of, and possibJ.~, for all DNA-containing
oncogenic viruses. -
In addiCion to establishing Che fact of gene mutation induced under Che
influence of RAV-3, it is importar?t to note Chat it is mani`eaCed aC
- exactly the same earLy date after infection ss was the case for SV-40,
Chat is, during the period of the virus' active inCeraction wiCh a cell
and it~ incorporation inCo the cell's genome. This is yet another indi-
cation of the usefulnesa of the above-stated hypothesis that tY?e same
_ phenomena that follow infections also determine tt~e integration of viral
DNA and viral mutagenesis.
Since mutagenesis resultfng from exposure Co BAV-3, as in the case of
SV-40, was studied in a nonpermissive cellular system, it is believed
that this process is not linked with either the syntheais of virus DNA
or the formation of virus particles. As of right now, the mechanisma of
the mutagenic action of oncogenic viruses on the cells of mammals have
not been studied. However, iC is entirely probable that they have fea-
tures in common with the mechanisms operating on the moderated bacterio-
phage in a similar system. Incorporation of the phage genome takes place -
by means of a rec.ombinanC process during the splitting of the cellular
DNA with subsequent junction of the broken ends. During the process of
incorporation, mutations are induced at both the sites of integration
and at other points under the influence of the enzymea which allow this
process to take place (~~8).
It is also necessary to note that the activity of lygase and endonuclease,
the enzymes needed for recombination (9), increases at precisely the
_ moment of integration in the cells of mammals infected with various on-
c.:~e:iic viruses.
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2n conclueidn, wa note thee ~ number of inferti~u~ viru~e~ glao po~~e~~
a mutagenic gctivity (l~). If thi~ property ig common to g11 viru~~~~ then
there ia an ndd~d problem of evalugting Cheir geneeic rigk ag factora
widely digeributed in mgn's ~nvironment. By the ~~me token~ it i~ e~sen-
tial to tak~ nnee of the fgct Ch~t viruge~ can appgreutly make g~ub~tgn-
tive contribution to determining thp level of "gponegneoug" muCsgen~gig.
i~ ~inally~ the ~uthorg expresg th~ir grgtitude to Ye. 5. Zalmgnzon and
I. V. Vavilina for Cheir help in th~s pro~ect.
In~titute for Molecular Biology and Genetia~,
Ukrainiun SSR Academy of 5cien~ea~ Kiev
InstituCe for Molecular GeneCicg 5ubmitted
USSK Ac~demy of 5ciences, Mogcow December 21, 1978
BIBLIOGRAPHY
1. M. I. Marehak, N. B. Varehaver, N. I. Shapiro; GENETIKA, Vol 9, No 12,
~38, ~973.
2. M. I. Marahak, N. B. Varehaver, N. I. Shapiro; MOTATION RE5., Vol 30, _
No 3, 383, 1975�
3. J. H. Darbyshire; NATURE, Vol 211, 102, ~966.
4. Yu. Z. Gendon; "Molekulyarnaya genetika virueov cheloveka i zhivotr~ykh"
_ [Molecular Genetics~of Fiuman and Animal Yiruaes], Moecow, "Mediteina"~
~975�
5. N. B. Yarshaver, M. I. Marshak, N. I. Shapiro; DOIQ,ADY 6KADn~QI NAUK,
vol 230, xo 3, 716, 19T6. _
6. D. T. Brown, B. T. Burlington; J. YIROLOGY, Yol 12, No 2, 386, 1973� '
7. A. L. Taylor, PROC. NAT. ACAD. SCI. USA, Yol 50, 1043, ~963�
~ 8. M. M. Howe, E. G. Bade, SCTENCE, Yol 190, No L~215, 624, 1975�
9. S. Mizutani, N. M. Temi.n et a1., NATURE NEM1 AIOL., Yol 230, 2j2, ~97~�
10. S. M. Gerehenzon, Yu. N. Aleksandrov, S. S. Malyuta; "Mutog~ennoye deistviye
DNK i vi ov u drosofily" [The Mutagenic Action of DNA and YiruBes in the
Drosophila~, Kiev, NAIIKOVA DUNIISA, 1975�
COPYRIGHT: Izdatel'stvo "Nauka," "Doklady Akademii Nauk SSSR," 1979
9003
CSO: 1870
J
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MICItOBIOLOGY
UUC 576.85~.75A.Og8.322:577.~5
A5SOCIATING TH~ ttIBONUCL~OI'ItOT~IN5 0~ `TH~ IN~'LU~NZA VIItU5 WITH NUCLEAR
CNItOMATIN IN INF~CT~D C~LL5
Mos~ow UbKLAUY AKAU~MII NAUK 555it in Rus~ian Vnl 245~ Nd 4, 1979 pp 974-975
(Article by A. Bukringkayn, N. K. Vorkunov~~ presented by Acgdemician
A. I. Oparin, November 15, 19'78~
(Textj In contr~st to other large ItNA-containing human and animnl viruses
in which reproduction takeg place in the cytoplasm. the cell nuCleue i~
necess~ry fnr replication nf the influenza virus. There ig an accumula-
tion of dat~ indicating Ch~t the fir~C transcription af the virus genome
is brought about in the nucleua by the Cranacriptase of the including
virus (I).
5ince expression of the genome among virueee in this group tnkea place in
the form of viral ribonucleoproteina (RNP) (2)~ it may be expected that
they penetrate the nucleus and are fixed there by the RNp of the inducing
virus. However, the viral structures have not been isolated and studied
and their localization in the nucleus has not been proven. There ie re-
cent information to the effect that the RNP of the virus which causes in-
fluenza has been isolated from the nucleoplasm in conditiona of incubating
the infected cella at 4�C (3).
We have studied the structurea of the influenza virus that penetrate the
nucleus by infecting cells with a tagged virus and then aubsequently
extracting the subviral particles from the nuclear fractions. Type n
WSh influenza virus wae marked in monostratal cultures of chick embryo
cells with H3-uridine (100 micro-Curies/ml, specific ac[ivity of 20 Curies/
- mole) or a mixture of C14-amino acids (25 micro-Curiea/ml~ specific activ-
ity of 1 micro-Curie/ml) and purif ied as deacribed (4) or by centrifuging
in a 20-60 percent linear gradient of glycerine. After the virus had been
~ adsorbed onto the cells at 4�C for a period of 1 hour, the cella were
incubated for 1 hour at 37�C, removed mechanically from the glass. rinsed
with a hypotonic buffer t10 mM tris [hydroxymethyl amino methaneJ~ pH 7.4~ -
10 mM NaCl, 1 mM MgC12) and fractionated in a Daunas homogenization unit.
~
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Tab1e 1 (
Dfe~ribution of cellular D~tA and virue f2NA and pro~ein in t~, ~
gubcellular fraatione (averag~e data for three experimente~
Uninfeated Infected ce118 Uninfeatied oelle + ,
Subcellu].~r �ractiona Qe~18, + virue
~3-~A H3-RNA C~ -protein H3-RNA C~ -protein
cyt~pi~em ~�5 52�3 5g�2 94�3 96�3
- Nu~~eun 96�5 47�7 4~�8 5�7 3�7
. Nuclear fractions
0.16 M NaCl 4�4 20�2 19�1 - " ~
dieeolved chromatin 66.2 33.8 32.6 - -
reme~i.ning fraction 27.1~ 1~6.0 48� 3 - '
2MN~C1
eupernate 96.4 - 82.8 - -
eediment J.6 - 17.2 - -
The nuclei were purified wiCh a triple rinse of 1 percent triton X-100 and
subsequent centrifuging over 2 M sucrose. The purified nuclei were triple
extracted with an isotionic buffer (0.16 M NaCl~ 10 mM tris at a pH of 8.0~
1 mM MgC12, 3 mM dithioChreitol (DTT) to remove Che ribonucleoproteins
from the nucleoplasm.
~ ~ , ~Y
s ~
~ r ~ n
s :
� " _Q ;
's ~ ~ ifi ~ ~ ~
~ ~ t~ ' a ' a
Z V i '
7 ' S ~ S 1 ~ti T ~ s .
~ ~ ~ I ti ~ Z ~ K-
'
t
! M If !a NJ I~JI ;1! ~M ~,J7 I,lO ~ _
3 P 3
Fractions p, 8/cm , 8/c~ _
/ '
~igure 1. 5edimentation and density analysis of the nuclear fractione ~
from cella tagged with H3-thymidine (1) and infected w:Ch influenza virus
tagged with Cl~'-amino acids (2). a-analysis of 2M NaCl extract in a
5-60 percent liaear gradient of sucrose concentration; b-recentrifuging
t:~e 13-th fraction of the gradient in cesium chloride; c-analyaie of the ,
dissolved chromatin in ccsium chloride, fraction of the sucrose gradient.
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~bK O~~ICIAL U5~ OriI.Y
To obCain the chromatin~ the nuclei were prore~sed with de~nxyribonuclege~ I
(100 mkg/10~ nuclei) at 37�C for 15 minuteg and were then suepended in 10 mM i
eris gt g pH of 8.0 and 1 mM EDTA. 'The undidgolved chromaCin and Che other ~
structutie~ of the remgining fracCion were removed by centrifuging gC 1~000 g.
In nrder to ~udge the dietributinn of chromatin in the fractione, the un- ,
infected gnd infecCed cells were tag~ed with N3-Chymidine (10 micro-Curie~/
ml, wiCh n~pecific activiCy of 21 Curies per mMole) for a period of 1 hour
prior tn infecCion. Uninfected cell~ to which the eagged virus w~g added
prior to homogenizgtion were u~ed ag a conCrol for Che digtribution of Che
tggged virug in the subcellular fraction.
It is apparent from Tgble 1 ChgC 40-60 percent of the 1tNA gnd protein from
the influenza virua peneCrateg the nucleus while only 4-6 percent of the _
tagged virnl etructures were observed in the nuclei of the control cells.
In a later fractionaCion of the nuclei, approximgtely 20 percent of the
virus etructurea were extracted with 0.16 M NaCl while the reaidunl radio-
activity is distribuCed among Che dissolved chromatin and th~ remaining
fraction; a significant percentage is extracted from the remaining frac-
tion with 2 M NaCl, 10 mM tris ~-~.t a pH of 9.0, 1 mM EDTA, 3 mM UTT (the
buffer used Co obtain the chromatin shell (5)).
A11 the nuclear fractions were ~analyzed by centrifuging in a 5-60 percent
linear gradient of sucrose at 3~000 rpm for a period of 45 minutes at 4�C
in a"Spinko" SW-41 rotor; the radioactivity in Che acid soluble material
was determined in aliquots, the fracCions were then diluted~ up to 4 per-
cent formaldet~yde was added and it was recentrifuged in a preformed linear
gradient of cesium chloride containing 4 percent formaldehyde (4). While
the extract obtained during the processing of the remaining 2 M NaCl frac-
tion was being centrifuged in the sucroae gradient, virus radioactivity
was observed in two zones of the gradient (Figure la).
A part of Che virus radioactivity was found close to the bottom of the
gradient where there was only a negligible level of cellular DNA. The
sedimentation rate for this material ~~*rP+~oondQd to the sedimentation
rate of the protein chromatin shell to which the superspiral DNA loops ~
are attached according Co the latest findings on the structural organiza-
tion of chromatin (5?b). It ia possible that the virus structures are
associated with Che shell since their sedimentation rate is lower by two
orders of magnitude (50-70 S) and is partially extracted with the 2 M NaCl.
COPYRIGHT: Izdatel'stvo "Nauka," "Doklady Akademii Nauk SSSR," 1979
9003
CSO: 18)~~
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MICItOBIOtOGY
UDC 571.3:577.23
,
TH~ G~N~RATION OF' A bIF~ERENTIAL IN ~L~CTItICAL ~'OTENTIAL5 BY TN~ CHROMA-
TOPH012~5 OF RHOUO5I'IRILLUM RUBRUM INUUCED BY A t.ASER FLARE
Moscow nOKLAUY AKAD~MII NAUK 5SSIt in Russinn Vo1 245 No 4, 1979 pp 991-994
(Article by L. D. Drachev, A. Yu. 5umenov, and V. P. Skulachev, Correspond-
ing Member, US5R Ac~demy of Sciencea]
[Texr] The generaCion of a photoinduced differential in poCentials in
the cl~romaCophoric membranes of photosynChesizi.ng bacteria was initially
investigated Chrough several indirect meChods ~uch as measuring Che ehift
in the maximum for absorption of carotenoids and bacteriochlorcphyl (Z),
the transport of peneCrating anions (3), and Che fluorescence of certain
pigments (4'6)� The use of one of these techniques, Co wit, measuring
the carotenoid response, has made it poss3ble to study Che rapid kinetics
of the generation of a differential in potentials by chromatophores (~+8).
A method for direct measurement of the generation of a current and a dif-
ferential in potentials by chromatophores was developed earlier within our
group. Chromatophores from R. rubrum were affixed to a flat phospholipid
- membrane by means of MgZ+ ions gnd then the difference in electircal poten-
tials ( was measured as was a current sent across the flat membrane
by using silver chloride electrodes connected to a voltmeter or ampere-
meCer (9). The results obCained with stationary illumination of the _
chromatophores associated with the flat membrane allowed us to conclude
that a transformation of light energy into electrical energy does occur
in this system and that the presence of oxidation-redu~Cion mediators is
needed to observe the maximum photoelectric reaponse
In this project, an effort was made to apply the technique of direct
registration for the purpose of studying the rapid kinetics of the process
of generating a ~~'by chromatophores from R. rubrum in response to a
laser flare.
Chromatophores were isol~ted from washed bacterial cells of the purple
nonsulfur-bearing bacteria Rhodospirillum rubrum by means an ultra-
sound technique based on the method describ.ee' previously In lieu
of the flat man-made membrane, we used a colloidal film impregnated with
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a~dlution of ~xolecthine in n-d~cgne prep~red as deacribed in e recenC
prn~ect by nur group (11)� To meaeure Che repid lcinetics involved in
g d~Y generetion~ we used eilveti chloride elecrrndee (it - 1 kOhm)
ecreened with black polyethylene and immerged in gn ele~trolyee solu-
tion on both eides of Che colloidal film (tt ~ 10g Ohm/cm Thp plectrodee
were connecCed Co ~n "Analog device 48A" operaCional booster (with an
inpue resiseance of 1011 Ohn, an inpue capgciey of