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Machine-read from the scan, so expect some errors. Lines that couldn’t be read are left out.
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ijomtn Gray t choo l of Uedic:ne o f wake Forest Colleae e. : List ri but ion and turnover o f sodium and potassium in Patients re cov rr lng from ln fec ti our dfrearer o r from rerum sick nes r have Id iUre li8 durlnq recover7 I n which mter and chlorides are lort.Inthe mute phase of certain h w nl nf ect iona, such as hocky Yountaln spotted fever and t ~ l chl no sir ,rdem develop8 and the blood ahl or ider and proto ln r drop, No dst a are available on changes In the blood or url nary sodium and pctasaiun. ' it h the alterations in distribution of fluid,peripheral circulatory colle,?se often develops and leads to the death of the patient. I t is not known from blood tolume and th io cyan ate tissue spaoe etudies crease in pemeability of capillary and aell wall mombr8nes ann bo visualized bsa graded ~ rie tof porer. In mild Instances of d in ease,only cry s tell olds c,.o~i11 ae detect e ble by ttr extent to w. l ch radioactive Ions such as Piaz4 and pot a sri u a are diluted followine injection ; 8 l6rKer defect should be detectable b7 t ned lf fu al on from tr,s blood rtream of protein ~ olea ule sof v trio is sizes and c lr cula tory oollapse are maximal aug ~ ert rt hat an antigen-antlbodp reaction Tis7 be res cons i ble for the alteration in por ~ a ebb il it yof meabrsnes, 'In Kockp dountaln spotted fever the time a t wt.lch the edema If the meahanism oaq be m tab ll rke d by which in crea e ed amounts of t o devise meane to correct the ph:~siolo6ic abnormality In infections or ln Furs antigen-antibody systems such aa serum sickness. h-ventually, it may be po ssl ble t o indues a n increaeo in penne a bill ty to that rad loi ao tapes could be encouraged to enter certain tis rua r and there exert an intra cell u hr radiation effect. lome tumors my be mueed by filter r ble virases; others can concentrate virusem auch b s vaccinia. 11 a virus could be introduced intoh cencer and lamuce serum verc ~ dn in irt ered, bn antigen-antibody reaction should teke plcicc only OR p bros it l zed cells ; the local alteration in permeability would allow any circulating radioisotope to bo eoncentrated inthe onnceroua tirsue, cancerous colla could be mado, a rlmilsr reaction would take place only ou malignant collr and should locally alto rp eree ab ll tty eo that an isotope administered the mp out lc ally could be concontreted I n the tumor..
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ion tract No. AT-(40-1)- A progress roport on the er pcr lm ents conducted July 1, 1949 t o Hsreh 15, 1950 has already gone forward. Teohniques for determination of plaom volume, th io cyan ate spaco, and ttpaco have beon et andar dim d for use In rabb ltr and humen being content of tis rues have been developed and etandardieed and a on tr old at a accumulated for comparison with experimental data. Pure antigen-antibody react lone without infect loa have been studied by inducing serum eleknssr in r sbb lts by 1) the in jeo tion of frsc t ions af human plasma; and 21 by passive tren s fer technlques utilising anti-rumen laparune merum previously prepired in other rabbit.. volume, th io cyan ate spaco, made. h preliminary draft of a paper with t ne passive tra ~ sfe rtechnique is attached; this paper is being submitted tothe JGtlftNhL GF IMk!U'2L-GY. r pre ll ml ns ry draft of the o on tro l data i n normal animals is attached ; this data 8111 be deposited rlth the Americen Docutnentetion Institute. on theso ~ l lriaknees experiments have not yet been completed. Measurements of t h o plaema 8p&ce, 'and of the tire us ohangrs have beon I teahnique ie being doveloped, through pre ll win ary oxpsrimeats, determination of alterations fn blood volume, thfocyanbte end tia24 s;eces. The experiments aoapleted, but not yet reported, ut ll lse dhu mn pla um fractions in an at to apt to simulate ae closely a e poseiblo imu no log leal problem - i n human dl ser ro. with the regular l ty desired. Gther In vestige tore,utilizing horse serum which eontslna s ntl gra not present I n human serum, hare produced more consistent k lo - to logic lesion8 resembling thoee of rheumatic fever and peri art er it is nodors disoo88ed above, The experiments In rabbits should be continued using horse instead of huun plrsaa fractions as antigen. ' It l e hoped that chfinges of suffic i ent magnltudr will be obtained so that tissue enalyees will be statistically significant In loe8ll r lng in various organs o r tissues the shift in radiosodiu8 d is tri but lon. The experiments failed to produce cone is tent changer No physioloeia r tud les have been done at lli zing the teChnlqUe8 1131 tagged rabbit idrum protein frsc tl on will be prepared by Cr. Dcnaleo L. Tabern, Abbott i eb oratories, North Chicago, Ill ln ol s ; author iz s tlc n (no, 5675) for the ude of 1131 has already been obtained. tissue8 into which protein8h8k ohould be detectable by thl8teo hai qur. ph y slo log ~ er tud lor vl ll ba crorr-ohecked for rpeciflc cellular loo alf z atl on of antigen and antibody by radio autographic teehnlqusr. The location of
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Identical er per lmn ts can be done by the pesalve transfer technique util ltl nga moh shorter time interval than in the pre ll al nary experlments. In th ii fashion an pure a humoral antigen-antibody reaction as po ssl ble will b. obtained with anl nlm l cellular component. Inthe course of these in v set lg at fon ~t he role of the hc ter oph lle antigen-antibody reaction in the production of these change8 will be investigated and contrasted with the lr oph lla reaction. Prerioua ln vest l gators have reported the production of auto-antibody torr bbl t heart by oen el tls atl on of animals to a mixture of group A hemolytic streptococci and nom1rabbit heart. hepeated infection of rabbits with d lf - tissue re a en b ll ~rlsabatlc fever. Some common antigenic factor eontalned in the dl ffe rent types of strep to coa a i 1861 be the sens it ts in flag mt parti * lIj responsible for production of the cellular les lon. An attempt will be mado t o produce auto-antibody t o rabbit heert using an antigen a mixture of streptococcus rorsstic group n pe clf lc fractions which hove hen combined with normal rabbit heart. If the attempt io 8ucccssful,the lmunologlc and phy8lologic methods previously described rill be the d is tri but lon of the antibody In nom1 and sens lt lee d animals. The his - The antibody can be tagged with 1131 for wtudles on The effect of repeated sens it is ation of rabbits 81th the group spec if io fractions alone would be studied by the same techniques for cc ntr sst with the results obtained by t h e auto-antibody technique. Inthe prellmlnary pneumoaoccel experiments, satisfactory local edema has been produeod. Ln attempt la now being -de to der ian an ex peri - rent which would permit longer mun l ral of the anirraln by delaying inva8lon of the blood rtrear by t h e organ;sr; In t b i r f8shion more marked edema and greater alteration in pe mab lli ty should develop. These experiments will be puraued util iz lng tho teahnlques described above. 'No had orl gia elly intended tort udp the immunophysiology of Faky 2ountsln epotted fever - en eeuts rlc kett a i all nf ect lon in which the pathogeni corgan lor s are located in tnn u clearly - In human patients. The developrrducmd the number of all nia al in stan era of ria kett r tal spotted fever admltted tothe hospitali those oarem which are appearing for r tud y are arrested by the ant lb lot ic8 so qufckly that the physiologic changes do not develop tothe
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extent seen In previous yearm, if at all. It wlll,therefore, be necessary to study Intracellular ln fec t lons - for a on tra at with & x trace ? lu ler infection o and pure antlgen-antibody rryotsms - i n experimental anlmslo. The laboratory is not now setup for the aul tors of rlc kett sla a the technique#, and the e qu lp lent required is not extensive. P.n attempt .Ill be made to tag rickettsia e with I.32 i n order t o study more ea cure t ely their. lo cell ze tl on when 1nJected Into nom1 or Into previously i muniz e dr sbb lta, ter lal phgslologic and iarunologla r tud les ut ll fain & the tcahniques described above rill be made tort u dj the rhlftm i n body flu l dr and electrolytes. The personnel are familiar with Tissue analyses rlll be dom. kut or ad lo graph l 18 planned, i n : order to loar lite both the e tio logic agect and the extra vasa ted fluid and protein, as deserlbed above. If tine permits,the results of the above studies rill be contrasted rl th tho ee obtained fn other group8 of anlmalr Injected with killed rather It probably will not be QOSSlble t o do virus rt udi erIn addition to riCk ett8181ln fec t lons this pear, but the tcchnlquse wlll hare been largely developed and equipmen4 end personnel will be available to continue such studies the fol loving year. ver lou s infectious d18ease6, sller # lc manifestations, and rheumetic fever. hS controls,selected Ca ~ e rof myredeaa, conpestive heart failure, and other c ll nia al aonditionn rlll be atudled. Construction of the i eo to pe laboratory on the fifth floor of the aed l cal school has been ao a ple ted and the major Item of the equipment have been installed. fume hood designed for red loa ttl ve work lain place. F flame photoscrter, s peat ro photo a e ter,rh le l ding squfpmant and monitoring equlp - nent aresr8ll able.A flow plan of the labor story showing the rite of Installation of equipment bau rlready been fur nl rh ed (Moverbr 10, 1949). Animal s;ace is available for o been lng infected and radio act lts animals, Dr. Jerry a. !lkara completes the rscond year of hlr AEC Fe lio w ship act ober, 1950 and ir trained In the nraearary teohniquer. Ulsr Elo lse Rhoader, ate ahn i alan, h88 hen trained.
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A negro animal teck ni clan, Claude Taylor, l a being trained. ?ie wlll be reeponsfble for the breeding of rabbits as well as name technical Ere Ernest Yount will begin a kiarkle Scbolarship I n Medicine at this Cahool in July, 1950. lie vi11 be av. ~ llabl ef oral in l cal vork on all pet lent sr tu died. It has been found impossible this ye br to conduat all the experlmente vitha single teo b nio lan ; additional teo hn ical help will be required. Curing the FeE8indw of this year a n qtteapt will be mads to carry on with The rt&C Fell088hfp f o r 3r. Aika.8 endr October, 1950. Ke heve been able to obtain Dome fl nana i al mupport for him from the American heart Assoclatlon, but it rill be necessary t o supplement these funds in order to retain. him full time on the pro j eat. The baount of time Dr. Yount will be available on the project will depend upon the amount of continuing fim na is l support for relesst from other au tier. No Item of permanent equipment requiring8 m3or outlay of funds is requested. 'ihe relatively minor items ro quis ted in tTe atta a he d budget are necessary to a et up chick egg technique. H re sea rah ricroscope c8n be borrowed from another project.A few more cagee will be neeerrary. Soae expendable rupp lies will be required for ahlck egg work and for replacement o f Geiger-Muller tubes. requirement for isotope8will be about the same a8last year. The tar irb ll lt yin there rpo nm of rabbits obtained th io pear am compt.red with thoae u till ted in the preceding parr her already been discussed 3n the rr ogres r report. !Ither ln vest ip at bro have enaauntered the same problem and have arrived at th8"wftimate solution. Apparently w e must plan t o raise our o m animals from a n Inbred e trs in under controlled cond ltl on r of diet BO thbt we ean obtain groupe of the e aw 8ex, age, and weight for the experiments. The negra animal technician has been hired with this end in view; it m y be 8 year before the full benefit to the animal breeding program can be a ahl wed,
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The total amount of the budget fs increased very slightly from itemr of equipment have been reduoed, but the rrqutrement for salaries of personnel has increased. Blth the oompletion of the laboratory the requlrements for major The detailed budget i m appended.
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an it. - oo atri but ion to the proJoot tho following: (1) Salary of froJeet Leador wajor portion of salary of Cr. Jerry &. Aikars &jor portion of ralary of ilr. Ernest H, Yount (2) Laboratory rpaco, secretarial help and other setvieom. b. The Conmlrrion is requested t o furnieh: