Governor Bernadette, distinguished guests, ladies and gentlemen, I cannot tell you how much I regret my ability to present this communication in your own journal, but I'm

unable to do that, so you must bear with me. These remarks and experiments were done upon animals, relate to animals, but they also

relate to the human diseases of anemia, the problems of transfusions, and parenteral nutrition. So they're not purely abstract in the sense that they relate to physiology alone.

The dynamic equilibrium of body proteins covers this area and includes the important proteins, hemoglobin, plasma proteins, tissue proteins, and reserves. The main theme of this paper,

rather than relate to all these various body proteins. And the experiments show that plasma protein can contribute to the store of these other proteins when need arises. That

is, plasma protein can meet all the needs of the body for the proteins, whether hemoglobin, reserve proteins, plasma proteins, or others. Hemoglobin, likewise, can contribute effectively

to the protein pool of the body, not only when it is released from destroyed or obsolescent

red cells. The stores of protein are found in many organs and tissues. For example, the liver, where it is most labile and in large concentrations,

in striated muscles, for example, where the total mass is considerable. This reserve can be used for maintenance of these tissues if emergencies arise for the construction of new red cells and plasma proteins.

Body protein reserves can be depleted by demands for new hemoglobin and plasma protein. We have spoken of this reaction as the rating of protein. That means

by continued anemia and hypoproteinemia, we see large production of new hemoglobin and plasma proteins with rapid loss of weight. And this may go on to a fatal termination.

That is, the tissues are so robbed of their protein that they cease to function. During all these exchanges of proteins within the body, there is no evidence for protein cleavage

to the amino acid level and subsequent reconstruction. Rather, the evidence that these proteins are modified within the cells to meet the needs of the moment.

Proteins can pass in and out of cells without breakdown, must be accepted, and much evidence is at hand to support this statement. Convincing evidence is found in experiments using radiocarbon 14 to label the amino acid lysine.

The lysine is fed and labels the plasma proteins of the animal, which can then be removed from the

donor dog and given as plasma intravenously to the test dog. The pathways of the plasma protein can be studied in detail as they relate to other body proteins

under various experimental conditions. The experiments from this laboratory indicate that the normal dog is given a protein-free diet, practically protein-free,

of fat, carbohydrates, minerals, can be maintained in nitrogen and even weight equilibrium in perfect health by means of adequate plasma given intravenously or interferonally

down to three months. The dog receives no nitrogen or practically none

except proteins which obviously supply the body requirements for proteins over this period. No surplus of any one of plasma proteins appears any time during these long experiments

indicating in the plasma under these conditions can be used by the body for its maintenance

and the requirements that maintenance demands. It is accepted that most of the plasma proteins that is albumin derived from the liver is the master organ in plasma protein

production and metabolism. The technical details are given in the listed publications and are

important. Some workers who have repeated certain experiments of ours have had difficulty. Oxalate to prevent coagulation of the donor blood must be used

or some other. The use of oxalate intoxicates the test dog and terminates the experiment. Stores have been repeated by these large doses of plasma given intravenously

about two or three hundred cc of plasma intravenously each day during the observation. This means that hyper develops and many of them grams per cent. This will be associated

with some proteinuria. There is a threshold for the normal dog between nine and ten percent

I prefer proteinuria. Then the plasma escapes through the kidney except infections cease. This slide shows experiments the longest 92 days first one

the shortest 15 days the nitrogen in the plasma given by vein you see is considerable

the nitrogen in the diet the next column you see is just trifling except in the third a positive balance you can see there's a very slight amount of weight loss probably fact

reserve is adequate to explain the situation as it was claimed by some when the experiments

lasted but two weeks 90 days exceeds that by a reasonable factor of this table that you have just seen summarizes the results in seven long experiments in which plasma

injections continue over in the basal diet most of that being in the accessories including the vitamins and whether it's in the form of protein is a little double some of it is

but it's very small in amount two to four grams of nitrogen daily as plasma protein that is two or three hundred cc in the whole it may be given introperitoneally or intravenously

usually intravenously there's a positive nitrogen balance weight loss is minimal the length of the experiments the clinical condition in spite of all this is excellent

they are normal in appearance and in every respect it came as a surprise to us

when we tested globin and hemoglobin to see what effect it would have on this picture instead of using plasma protein we use globin or hemoglobin obtained from given

intravenously or intraperitoneally this material and as you would expect can make new hemoglobin they can also make large amounts of plasma protein in fact in some experiments there was

a positive nitrogen balance it's not as easy to demonstrate as with plasma protein which is so uniform toxicity at times in this globin material the globin is not used as completely

as is plasma protein but it is used to form it may be mentioned that in all 20 days

the dog therefore uses up about as conserved as gold in some communities the pigment radical

is discarded parent of the body finds it can make that pigment easier than can create experiment experiments this time hemoglobin given parenterally will be conserved

and included in the body the utilization are compared in the same dogs and in those

experiments it is obvious that the plasma is used a little more completely but the globin is

used adequately to supply protein needs and the protein is very obvious the next slide shows some of the facts concerning the hemoglobin and the plasma protein in circulation and in body

stores to determine the amount in body stores they must be exhausted by continuing bleeding or plasma paresis at any rate the circulating mass of

hemoglobin in this 10-pound dog 100 cc would be on the plasma protein 30 we use our health hemoglobin level is somewhat above that of the normal animal as they are found

the maximal regeneration is 50 to 70 grams a week for a dog of this sort and

approximately the same amount for plasma protein in fact that may be pushed up somewhat in plasma protein the reserve stores but run from 50 to 200 for hemoglobin and 30 to 100 or more the plasma protein custom trained to laboratory procedures

the maximal regenerative with individual dog just as their muscular capacity and activity the reserve stores all your dog with its previous dietary and exercise for the production

of new hemoglobin and plasma protein when a standard dog is put on a low protein diet the food protein is measured each week and the removed is a sample experiment this

continues you see for nine weeks during this continuous bleeding you'll notice that there's a

loss from 23 8 kilograms to 19 5 indeed the total for all this nine weeks being 133

grams as you see amounts to 335 grams during that nine weeks period

somewhat but not from extreme level the output is given there shows a total of 95

the intake you see very small intake of protein of 133 and production routine must come from

some kind of thing on the food obviously and those reserve stores presumably in an experiment like this are reduced to zero and the function of the animal by this exhaustion of its proteins

produced within the body to form new hemoglobin a new plasma protein and that was removed so

this animal to repeat received 135 grams of diet protein and produced new hemoglobin 335 95 grams obviously this surplus came from the reserved proteins of the body

but it appeared and was removed as hemoglobin excess protein breakdown obvious within the body

the nitrogen elimination dropped each week until it was way below what we would call a normal fasting elimination if the body protein was broken down into amino acids and reassembled

almost certainly there would be some excess which does not appear this indicates a conservation of this important material in urinary nitrogen but proteins are formed and there there must

be some modification presumably of the reserve protein is stored in reserve with production of the specific plasma and hemoglobin proteins without any extensive cleavage the animal acid

level and subsequent reconstruction in this emergence the demand for new blood proteins is predominant three times as much hemoglobin is produced in this experiment compared with plasma proteins further information about the dynamic equilibrium

of body proteins is obtained by experiments using radio carbon labeled lysine the plasma test which labels the plasma protein of that dog and then and given to these tests

this label plasma protein disappears from the circulating plasma rather slowly about one third in six to seven days and appears in the body organs and tissues in

corresponding amounts during this time there is very little loss of c14 as carbon dioxide that is c14 o2 in the respite air and less in the urine the turnover is more rapid

than for the algorithm which applies to many uh questions on this slide the indicates the concentration of the labeled material in the proteins of the liver and you see

by this measure the liver is highest as you would expect but some of the adrenal some of the

ductus glands adrenal and thyroids are also the gastrointestinal tract in the mid zone still lower the skin and subcutaneous tissue but the total amount of radioactive protein

in the muscle and the skin is highest because its mass is so much greater this figure shows

the relative concentration of carbon of c14 within the organ and is stated there the and some and the adrenal and thyroid as stated the total amounts in these various tissues

there is 21 to 28 percent in the muscles there's a great mass of tissue you see although the concentration per gram is less in the skin and subcutaneous tissue 12 to 13

percent the liver seven to eight percent the other organs of course are very much lower because of their size when c14 lysine plasma protein is fed instead of given parenterally the picture is very different indeed in this last experiment

the speed of reaction when fed lysine is given is quite rapid teams appear in the plasma within seven or eight hours in 48 hours in considerable amounts

amounts of c14 o2 appear in the respite air as much as 16 to 30 percent of the fed

c14 appears in this way within 48 hours this is in contrast to 2.5 percent that is one-tenth as much in 48 hours in the experiments it's a totally different picture when c14 lysine

in an animal to the dog the picture is precisely the same as with the labeled plasma protein when fed in other words the plasma protein is broken down and solved and

handled like animal acid mixtures experiments listed above have related to normal dogs from the syringe for example they might have the stem parasitic infection acute or chronic

but we have studied certain abnormalities which relate particularly abnormalities of the liver the ex fistula the biopistula have been studied in considerable detail it may be stated

the liver in which the portal blood bypasses the liver does have proteins in depleted dogs ascites may be produced experimentally by partial obstruction of acidic proteins

with the circulating plasma proteins if labeled plasma protein is introduced into the peritoneal cavity of the acidic dog it conversely if the label plasma

is given intravenously to the acidic dog this labeled protein appears promptly in the acidic fluid a circulation and interchange of protein between the blood and acidic fluid

now inflammation is a very important subject particularly to clinicians and pathologists dance infections for example due to bacteria the virus is not infrequent in some animals

and it made with continuing fever and leukocytosis for many weeks

during such time there is a definite lack of production of new hemoglobin can be demonstrated with ease removal of the infected uterus brings the dog from its state of hemoglobin production production of new plasma proteins if they are depleted

it is readily demonstrated that synthesis of new hemoglobin is impaired by the information we usually think of information as destroying proteins it does perhaps more importantly

the synthetic ability of the body to build proteins enable us to study this condition in considerable detail and i'll show you the last slide in a moment sterile abscesses are used since the abscess reaction can be terminated promptly at any time by incision and drainage

the appearance of c14 in the hemoglobin with sterile abscesses shows definite delay and impaired synthesis of hemoglobin the plasma proteins the tunnel of albumin is greatly

accelerated in the this type sterile inflammation an abscess steady down slant

appears in the dogs after the plasma protein is labeled whether the next curve and you see it

is different from the control and as the number of abscesses increase the turnover or 10 days you can see is much more rapid there's loss of this protein it goes somewhere

some of it to the inflamed area in contrast the globulins in the graph below the control you see a mixed up to the upper part of the animals that show the abscesses

in other words there's only a slight change in the globulin 10 over so far as these experiments show with more severe type of inflammation or perhaps different type of

organisms the picture might be different but this is a sterile abscess or more affecting the labeled plasma protein albumin and globulin so that we have concluded that the information accepting fibrinogen everybody knows i think that fibrinogen

has a good deal to do with areas of inflammation and the fibrinogen shows a spectacular change when followed in this way the labeled fibrinogen disappears and is used up almost

completely within two days an extraordinary speed of reaction obtained in these abscesses shows a good deal of c14 both in the cell debris that is the wandering cells on our nucleus

and mononucleus and in the fluid presumably some plasma some cell debris some cell disintegration question continues the more active organs that is the liver

will lose much of its c14 as stored in its cell protein but the larger stores of protein the c14 stores in the muscle will be given up to make up this loss in the liver in other words where the emergency is

there goes the protein that is shown very nicely in some experiments which have been published but cannot be shown in this lecture all of this i think means a dynamic

equilibrium a shifting about proteins however we wish to explain i wish to thank you for your attention