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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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Results of &ep1c studies indicate that cbbride is excreted mure rapidly by n o d subjctcts @an by patients with congestive heart iaifuta, but thc mechiLPirn; for this difference zmbs obscure. rate ai t u ~ v c rirrcreasca in propastion with the degree of compensation. a c e compcnHLtion aetf in, however, the
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Thir letter with en cl or urea,in triplicate,ira ent in accordance with the procedure der cri bedin a letter from the General Murlger t o a11 Managerr o f Operationr dated 1. Inatitutioa: Tuluw Onimrrity of Loubi8na
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I n accordance with the provision r of W-93? Rev i red March, 1951))~ and the requirement r of the Ds claas if i cation Guide, the Di virion of Biology and Medicine bar determined that the following a e curit y precaution r should betaken in connec tion with the pro pored research contract. bta rill bo to- or -loped, 110 prroanel u our it y . Brporte: t ) -R e port r ere t o be required ar provided f qr by . Memorurdum In rt ruc tion of November 9 , 1949, zAddrerror: Original (1 encl.) Dlvimion Pile : Yellow Copy (wencl.1 Pro gru Anaiynim Brrrch Cile: White Copy ( w ’
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Relatian of the reeearch t o aur training propam . . 6 Time allotted t o reeearch. ............7 Financial budget submitted to COI Em b6hl..... .lo
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Dlvlelan of Biology and Hediclne Dew Doctor Warren: The enclosed lea proposal fora research caatract. Item a ) ma studied Intensively 3 month8 during the uummer of it vould come under Medicine ( D r . Dunham). l9@ and Fnterzaittently last vinter. applicant is a Research Participant a t Oak Ridge this B\LIpLpBr. applicant bringe 14 year8 experience In electrolyte and 5 year8 experience In isotope rate phenomena t o bear upan the problem. It is being studied a l e the There is canrriderable Interest In turnover studies at this tl me but there are PL;PISV D lt falls vith which not all are familiar. would like the c qpr tun l ty of bringing his experience t o bear upon tbse Memnrhilo he WlIJ be tra ln lng graduate students ut Tube in student is alreaay a wi hb leto work on item b). He has already trained one doctorate, an K.B., and m e eenior He plan6 to c a r r p almg 2-3 graduate etudente Ln thie vmk. El6 stipend will be Bieeet and hi eat afr in Biophysics a t Tulane Univereity. PSTBO ~ ~recommendations can be obtained rrom doctors: W. 0. Fern, University of Rochester, Rochester 7, Hew Xork C. X . Sheppard, Biology Division, oah Ridge Raticxml Laboratory, Alexander Hollaender, Biology Division, Oak Ridge Batiunal cak Ridge, Tennessee Laboratory, Oak Ridge, Tennessee
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The current particlpantehip 18 vlth Dr. Sheppsrd. Moat of the equipment needed i s already an hand at Tubat,, but A euggeeted budget le appended. I vauld like an asaietant and certain epsclal I t e m partlcuhuly for If feasible I wauld like this to start October 1. School of Medicine Reeearch Participant, summer 1950 Oak Ridge Institub of lluclear Studies Ridge Batlonal Iabaratory)
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Potassium is the most abundantmetallic cation present in living It is essential f o r growth; it is a catalyzing co-enzyme for bi och d cal reactionio the lPagnitude oi electrical potential differences 80 characteristic It regulates ex cl tabi u ty and deterrinea across cell interfaces, Though accuaulated t o such large extent in the protoplaam, pot as dm shore a rapid and often complete exchange between the ceU and i t s bathing medium, Yet, at; the 8ame time, potassium is held i n the cell to the exclusion of other cations such as sodium which latter is BO abundant i n the mediam, He wald like to evaluate the exchange rate of potassium in resting ausele d liver d to test the effect of hormonal and other agents on it. potassium i n biochemical processes and the manner of its binding, It is felt that such rates would elatiFy the role of a) The exchange i n resting tissue, An emly problen in t h e evalnation of ionie exchange rate of electrolytes ' i n tLssues i s the question whether the asme i s acting as a single o r as a mula ple pool of the particular electrolyte undergoing exchangee That i a9in order t o meamre the exchange rate fora given pool, the specific activfty of the precursor or feeding pool mst be kcowl;, ~ e n ne taL {see Ut era ture) found that after peritoneal injection plasma wluea but then continues for a prolonged period t o remain Bbovp the liver specific activity not only remains above that of plasma bclt continues to rise even f o r prolonged periods after the plasma has begun l e ('llalker and CRlde) noted that after intravenous i aec tion
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to fall,At 50 ml m tes after a quick intravenous injection, the Umr expella tracer pot as dm to give elevated plasma Values, not happen if llver K is a single continually m i d pool and if the cbc uht ing plasma bathing the liver is everprhere equal i n specific activity to that measured in arterial plagme. This summer as a Research Part id pant at the Biology M vid on, O& Ridge Eational Labaratmy, I have continued tMm study moatb in rabbits, Intestine as well as Urar and Hdney cortex are quick t o take up the K - Q , Ue had s spec ted that the intestine receirea an early batch of tracer only t o @ yeit off later to the U ~ e r ray of the portal from an intestinal loop, the time course for liver uptake i s completely decline and no second- rebound of plasma firacer OCC u FSm that after intravenous i dect ion the gut receives a large batch of tracer on* later t o discharge it t o the liver, thus giving the delayed liver If re inject tracer bp ray of the portal vein, into atri ht ary Its peak uptake of 8-42 comes mch earlier witha continual Be would like t o continue this attempt toset up criteria for meaming exchange rate of tissue potassiuu. We would like t o make f'urther checks on the question whether the early intestinal uptake explains the liver phenomenon: for instance, t o run simultaneous intestinal apd Uver specific activities and perhaps sample portal blood after intravenous tracer, t o compare it d th arterial specific activity, __- Finally certain hormonal and other tests could be made for possible heterogeneity of l i v e r K, Adrenalin cauees large expulsions of Liver K, It would be interesting to allow Erst rapid EPer uptake of tracer and
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then glve adrenalin t o m e whether spsciflc actiriw of Xver change8 as the I; comes out of the liver, more than would be axpected from the n o m 1 leakage of tracer. 16 have spent considerable time on the mathenaticalintarpretation measured rith isotopes and would like t o contime the analyda o r the problem in liver,in ruscle, aad possibly in nerve, pinally, we would l i k e t o measure the effect of hormonal and other factors on the exchange rate onG that L S evaluated. our ovarail ki but ion in animal tissues, We bare done and would continue t o do work on t h e exchange in nrestinga muscle. tbt potassium i s released during muscle work: There is et rong evidence traction, during the relaxation ar the recoverp period. Classical chemical analyses for potasqian are, hwever, too irisendtiw to relate these changes toa particular phase of the contraction pocess, or t o part icu hr changes in the activity potentials. He feel that by studying muscles i n animals equilibrated with large doses of radiopobssium we can concoct means of detecting these rapid but like4sll gh t changes. It is felt that this can be done by placing a count-rate-meter directly over a macle partially isolated to afford shielding from adjacent tissue and yet with intact circulation, ar by using a scintillation counter o r flnorescent detector of some Had directly over t h e outflow vein or draining cannula of a perfused preparation using
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The Ut era ture related tothe Problem: The exchange of radloactive potassium w i t h boQ potaesf=. 1949. Proc. Am. Pbdol. SOC., Augusta, personal Bibliography Related t o Electrolyte Exchange Rate. Tulane U niver sity: The distribution af potassium in the cat after intravascular irrjection, The effect of blood flow on potasdlur ube ration from mecle. her. J, Potassium and water changes in excieed nerm on stimulation. Simplified equations for the distribution of chloride i n body water. Bull. Mathematical Biophydcs 6, 105, 19& The chloride equilibrirun i n muscle. plasma chloride and bicarbonate after potassium addnistration. The turnover r a t e of sodium in the aqueous humor of the methods of analysiso h e r . J. Ophthal. 2 9 1516, 1947. Can transfer rate be calculated from urine isotope ratio ? Ped. Proc. 3, #1, March 1949. (With He D. Friedlander). Manuscript submitted Testing the validity of ashing and digestion procedures by isotope d if uti on, Fed. Roc. & #1, March, 1949. Capillsry permeability; rate of trans ca pills ry exchange of chloride i n the guinea ig as determined with radiochloride. her. J, Pbysiol. m, Trans cap i ky exchange rate and volume of distribution of radio sulfate. A maxuscript nor in proof. Same journ & Rate of exchange of potasdun i n plasmao liver, and muscle after intra-
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Biogrape of Scientist in Cbarge: Sekool o f Medicine, Tulane Universitr, Station 20, Ber Orleans, 18, Lao U., School of Medicine, Ner Orleans, 1939-45. Research Associate, Dept. of hb vo bg g,k ne gie In dt uti on of Washington, Baltimore, 194547. Soci eti es : $7,700 each o f two years. Expires Sept. 30, 1950.
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The Relation of the Research tothr Training program The applicant has trained one Ph.D. and one Y, A, i n this field, estimation of turnover rate from isotope data, one Ph.D. and one senior medical student. problems of electrolyte accumulation in a fau COW80in cell phydology - two lectures ard one 2-hour labaratmy each week for 16 He is now training He teaches the ovmall Ha gives a special spring course every other ?ear on the mathematics of caleulatiog exchange rates. listed in the Tulane University bulletin, Theee both a r e graduate courses The continuance of this research i e important to the quality of instruction, already on hand is a l s o used for labaratom teaching of techniques in
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0 Hours available t o senior investigator for research: Sunmaary: About 0.7 of time iefor research.
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Facilities, equipment, personnel turd shed Tula.net A very substantial background of equipment i s already present ini This resulted in part from a two-year grantmy laborat- at Tu'Lnne. from the Hetional Institutes of Health, Cancer Grant, C $36. Our chair-, b, H. s. Mayerson, has also brought i n much needed equipment, available t o me, in part through an Army grant, A. Laboratory space available exclusively t o applicant: Chemical laboratory with hood Small operating room Flame photometer room Counting room .f shared) Constant temperature room (shared) l e have a central university machine shop and biophysics has a machine shop. It i s planned to pay apart of the saLq of an electronic engineer shared with Dr. €L Te Weset, dbe ctor of C. Laboratory facilities recently installed by Tubne: Equipment available exclusively t o applicant:D. Large cent rif ige Hand scaler and counter Bir compressor f o r above
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Much other equipment under Dr, Mayeraon'a supervision may be The senior investigator, 1. S. Wilde Graduate assistant, beJack Ginsburg, a second-year graduate student i n physiology - Candidate for Ph.D, $1200 F, Total contribution of Tube $62 61
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Count rate meter circuit 1900 Assistant, with - & A. or equivalent Summer assistant - a jwor or seniar medical stpdent on wcat1.on Electronics assistant, Nil1 share this D. Animals ard thelr care E, Isotopes and shipping
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THE TUUNE UNIVERSITY OF LOUISIANA SCHOOL OF MEDICINE nineteen hundred fifty ‘We have purchased 500 microcuries o f C136 with the contract which you s o ’ kindly assisted us in obtaining from the A.E.C. We hzve completed the use of approximately now engaged i n the study of thesedata before beginning our next three subjects. . at the hospital for a period of about 75 days.I Approximately $700.90 renins unexpended in this contract, a d we were wondering if yo f o r the purchase of mre ClY6. We would like to continue these studies during the next six months o r so, using the material-not:only in our p-atientsbut also in some vitro-experG&ts on kidney tissue and erythrocytes. have permission from Oak Ridge for the purchzse of additional’materikl and would like to mow if‘you c a n permit US to cse these funds for that purpose. would rllov US to use it united States Atomic E;nergy Cods sion.
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study of the turnover rate of chlorine under controlled dietary and therapeutic
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In a t it uti on Project Leader Turnover rates of chlorine and rubidium under controlled di at s ry %rid therapeutic conditions inpatients vdth chronic congestive heart failure and i n controlled subjects. Chief, Biology Branch