The gist of this paper is that certain casein digests given by vein or subcutaneously are promptly used by the hypoproteinemic dog to produce needed plasma proteins. The digest of casein is approximately as effective by vein as is the casein digest or whole liver equivalents given by mouth. The digests tested are essentially non-toxic as used.A considerable series of experiments on dogs done in this laboratory has been reported during the past several years (9,15,4,11) to show that normal dog plasma given by vein to the protein fasting dog can supply all protein requirements. The dog has been kept many weeks in health, weight balance, and positive nitrogen equilibrium by suitable amounts of plasma by vein and sugar, fat, minerals, and accessories by mouth.Normal dog plasma protein given by vein during such protein fasts is utilized much more effectively than protein by mouth. It is evident from these previous experiments, and others of Howland and Hawkins (10), that the plasma proteins are utilized in the body more directly, with less waste and with but slight cleavage into large aggregates when needed to supply the protein requirements of the fasting dog. This exchange of proteins between the blood plasma and body cells has been discussed in recent papers (13,14). Table 5 (period 17) also shows how effectively plasma protein is used in the fasting dog as compared with the casein digest. Note the low urinary nitrogen when plasma protein is given by vein-about one-half the amount recorded when equivalent amounts of casein digest are given by vein. However, the casein digest by vein is as effective in plasma protein formation as liver protein or casein digest given by mouth. This would support the current belief that practically all food proteins are reduced to amino acids and peptides before utilization for protein building in the normal body.In the experiments tabulated below we assume that hypoproteinemia offers a strong continued stimulus to plasma protein regeneration. Daily

Electrophoretic patterns of normal dog plasma in veronal buffer at pH 8.5 are shown to be essentially similar to patterns of human plasma. Dog albumin has a higher mobility than human albumin and in a mixture of dog and human plasmas migrates as a partially separated peak. Normal dog plasma frequently shows four alpha globulin peaks. Rates of restoration of plasma protein components in dogs subjected to acute plasmapheresis have been studied by electrophoresis. During the first 24 hours following such acute depletion, appreciable quantities of all electrophoretic components of the plasma proteins enter the circulating blood stream even when food is not given and has not been given for 12 hours before plasmapheresis. In such fasting periods albumin and total globulin appear in approximately the proportions present in normal plasma. Alpha and beta globulins continue relatively elevated during subsequent days in which caloric and protein intakes are adequate for weight and nitrogen gains. Initial albumin levels, however, are regained more slowly than those of total globulin. The relative proportions of the electrophoretic components of plasma proteins may be disturbed from normal following a single acute depletion for as long as 2 to 3 weeks after the total protein level has returned to normal. Abnormally high beta globulin and fibrinogen, but a low albumin, were found in a dog with an acute and chronic cholangitis and hepatitis. Similar elevation of gamma globulin was noted in a dog in which a hemolytic reaction occurred.

The technical and scientific information is presently available which, if properly utilized, could facilitate the early diagnosis of breast cancer. Hopefully, it could likewise reduce the high mortality rate of breast cancer. Due to the lack of adequately trained professional and allied health personnel, a massive screening program on a national scale is unwarranted and would be unproductive at this time. Based upon our experience in the U.C.L.A. Center for Health Sciences, the establishment of screening clinics for women 40 years of age and over in conjunction with a cervical cancer detection clinic in a number of large medical centers is indicated. Thermography as a prescreening modality should be investigated further.

The findings on electrophoretic analysis of plasma proteins during many weeks of low protein feeding in dogs accord in general with those of chemical analysis as concerns the alterations in plasma albumin and globulin concentrations. Long continued restriction of dietary protein results in decreased albumin levels while plasma globulin concentrations remain essentially normal. The degree of depletion of electrophoretic albumin is, however, considerably greater than that of chemical albumin. When large amounts of protein are fed to such depleted dogs complete restoration of normal plasma albumin concentrations requires several weeks. During these weeks large quantities of nitrogen are retained, presumably as tissue protein reserves. Prompt production of plasma globulin is apparent during such periods. These relationships are more clearly shown in electrophoretic than in chemical analyses and are more conspicuous when only moderate protein intakes are fed. These data may indicate that plasma globulins and certain tissue proteins, in contrast to plasma albumin, enjoy prior demands on the total available pool of body protein materials under emergency conditions. Total electrophoretic globulin areas are increased during depletion. Such increases result largely from elevated alpha globulin peaks and are not disclosed by chemical analysis. They are found to be associated with elevated plasma lipid levels which occur in these depleted dogs. These experiments suggest that in potency tests for dietary protein materials, factors other than the quality of fed protein may influence the relative production of plasma albumin and globulin.

Electrophoretic patterns of plasma before and after the extraction of a large part of the plasma lipids are compared in these experiments. Marked alterations in total electrophoretic area, in the relative areas of individual electrophoretic components, and in electrophoretic albumin:globulin ratios are disclosed by such comparisons. Applied to samples of human plasma, this procedure confirms the observation of Blix, Tiselius, and Svensson (2) that a particularly rich content of lipid materials characterizes human beta globulin. Abnormally large beta globulin peaks regularly occur in the presence of elevated plasma lipids. Marked increases in the areas of other globulin components, particularly of gamma globulins, however, are also found to be due in large part to elevated plasma lipid levels in certain abnormal human plasmas.The greatest relative amount of lipid in dog plasma, in contrast to human plasma, is associated not with the beta component, but with globulins whose mobilities are intermediate between those of albumin and beta globulin, that is, with electrophoretic components usually designated as alpha globulins. Not only the areas, but the configuration and even the number of the alpha globulin peaks in dog plasma are altered by the extraction of plasma lipids.These studies are an outgrowth of previous investigations (17, 18) of alterations in the plasma electrophoretic patterns of dogs in experimental hypoproteinemla. During such hypoproteinemla, particularly when induced by long continued low proteinfeeding (18), there isanapparentlyparadoxical increase in theareas of the alpha globulin peaks. For several reasons, it appeared that such increases might be due to materials other than protein. Nitrogen analysis of the plasma for example, frequently yielded lower values for total protein concentration than those indicated by electrophoretic areas. Increased plasma cholesterol and total plasma lipid levels were regularly found to be associated with these discrepancies. Since Longsworth and others (10, 11) had reported decreases in the beta globulin component in the ether-extracted plasma of human cases of nephrosis, it seemed likely that the increased alpha globulin peaks of hypoproteinemic dogs might be due to elevated plasma lipid levels. 411