Document 3JDmKrzdEeYZmydL7MBRRXR1O

January 12* 1943* fr* Xarl iambaoh* dept* bio logical Chcraistry* College of 1'ledicine*. diversity of Cincinnati* Cincinnati, Ohio* Sear -hr I'asib&ehJ I have road with interest your paper with Kehoo and logon in the latest Journal of Ph&xrmoology end Ixporimaatal fhoraTxnvfcics and should ho grateful for a reprint* It Is unfortunate that you wore led to state that your data cast doubt upon ny conclusions* v/hon as a flatter of fact the data you reported are rathor lrr39$9Bjrb to those conclusions* Since I r.ip.y have failed to sort extent in leaking mysolf perfectly clear in ny paper on the lead citrate complex* perhaps I ray take this opportunity of clarifying the issue* by studying potontiometrically certain solutions of sodium citrate and load nitrate I was able to arrive at a formula and a dissociation constant (at the ionic strength and pH of plasm) for a lead citrate complex which I had previously shown to exist* From, the value for this constant and the norml citrate concentration in human blood it was possible to arrive at a value of about 20 for the ratios (lead citrate complex)/(lead ion)* To state it simply these data indicate that 20 tines as much load existed as a soluble lead citrate ion than as simple lead ion* Wince without knowledge of the presence of soluble complexes of lead in the blood all the soluble load must be in the form of the simple lead "on, 1 ;na able to state that ttthe normal blood citrate is capable of keeping in solution &n amount of load 20 times as groat as that which tho solubility of the insoluble lead compounds of tho body would otherwise permit* I do not soe how your findings of loss than 10.5 of tho blood lead in the serum ( a fact which I had always assumed as so on purely theoretical grounds) in any my casts doubt on or is even pertinent to my conclusion* Hot that I did not say that citrate of normal blood keeps 20 times as much lead in solution as in insoluble form* bote also that you I\avo no reason for assuming that blood, in plasma is in 3olution*&s a matter of fact there is good reason to fool that moot of the plasm lead is non-diffusib to* oven with 1,5 of tho lead of the blood present in the plasma there could still be 20 times as much lead wesent as the citrate complex than as simple lead ion In only one oaBe Jo your results approach pertinence to my conclusions* your experiment with citrate as on anti-coagulant* From purely theoretical considerations I should expect citrate to cause ail increase in plasm load at the expense of erythrocyte lead* but oven here a failure to observe such a redistribution would not reflect upon the validity of n? conclusions since citrate could cause an increase in diffusible over non-diffusible lead entirely within tho plasm load fraction without causing a cluingo in '/.rial lead In tho plasm* In yo-r experiment, however, the citrate -was in contact with the whole blood only momentarily before centrifugation - hardly a fair lonfjth of time in which to detect changes in so complex a system of equilibria* nevertheless* tho you find no sig nificant changes in plasma lead after tho addition of citrate, I find on examining your own figures a significant increase in plasm lead where citrate was used over t;iat with no anticoagulant* (If one ignores the "less than" sign in the experiment on animal ? on finds a mean increase in plasma lead with oitrato of 45/9 until a standard error of 15,4, a t value of 2*S2 and a p value of 0*05 or less which is certainly significant* If one leans over backwards and calls tho increase in animal 7 nil, one finds a mean increase of 40$ with a standard error of 17*1, a t of 2*54 and c. p value slightly greater than. 0.05, which certainly approaches statistical significance*) Thus we find that far from casting doubt on my conclusions, tho one pertinent experiment in your paper actually con firms my theoretical prodlotions* As a matter of fact for tho post six months I have beon working in association with 2r* Aub3$n aw effort, among other tilings, to test itry theoretical conclusions os they apply to tho lead partition in blood in vitro and in vivo* It requires rare than an understanding of the partition of load between plasma and colls 'bo oonfirm or reject tho significance of the lead citrate complex in the state cf load in the blood* A direct approach would be by a study of load ion concentration in blood, but slnoe tiiat is manifestly impossible with present techniques, an approach can be made by studying th6 diffusible fraction of plasm load and tho affect of oitrato thereon* Perhaps X, in turn have misunderstood your criticism of my conclusions* If so tha..above explanation may have boon unnecessary* Aside from tliat one regretistilf^fesoonetruction I fool that your paper ras most interesting and has answered a problem of fundamental importance in tho physiology of lead poinoning* Respectfully, 0012267 Seymour f* hoty