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From www.bloodjournal.org by guest on June 15, 2017. For personal use only. ZINC THE CONTENT AND By W L. BERT E HAVE OF WHOLE IN M.D., VALLEE, previously whole concentrations BLOOD, ERYTHROCYTES AND described blood, plasma, in micrograms PLASMA, THE G. JOHN our findings leukocytes (gammas) LEUKOCYTES ANEMIAS II, M.D. GIBSON, of the zinc and erythrocytes.’ were found to content of normal The following represent the zinc normal pattern: Amis. Whole Blood 3 . 2. X ,2 Erythrocytes , .34 X ‘0 eral blood Out, No measurements . No however. blood components in reported was attempt to elucidate of the quantitative conducted with on the zinc content million I on with cells cells ffllllion I CC. the are afflicted of zinc I0 i zinc to rats and in the cytology of anemia patients role X of red and measurements patients cr2 ±1.7 Larson4 fed as reflected cc. i X ±0.2. 14.4 and Smith and and leukopoiesis I CC. ±i.6 3.0 Leukocytes and Nelson,2’ on erythropoiesis Unit S.D. ±1.0 Plasma Erythrocytes Sutton effect in pg 8.8 white zinc observed the of the periph- cells were carried concentrations record. The various of study types of the herewith anemia, in an in erythrocytes. METHOD The hematologic viously.’. . technics The 6 small cal analysis. The values. concentrations Zinc standard mean deviations and number method of the normal lying one of of patients would series was outside expect measuring which taken of two I out blood was studied Nine of patients with following while time A second to have so-called cell tious under anemia of liver maintenance group therapy with ‘refractory anemia. ‘ Four patients i mononucleosis, were patient and were therapy. of patients anemia, 2.000/miD.3 sickle pernicious institution ‘ ‘ anemic each Cooley’s liver types Three been described internal in the evaluation were normals of secondary considered fall to was prestatisti- of individual abnormal. outside patients was iron a total prior followed For of these two limits. of 34 blood had 2. had cell period analyzed. splenic found were counts below of infection, anemia, of 2.3 blood was patients blood an anemia a few a prolonged samples Five white deficiency to or within over investigated. hemorrhage, anemia, obtained were A total anemia these to There were patients extract. of had nutritional anemia. Samples of these with on have precluded STUDIED studied. Five various of reference deviations observations MATERIAL days content category as a point standard of o zinc in each 2. anemia, had infec- samples. RESULTS Table leukocytes Hospital, Cambridge, * i summarizes the and erythrocytes the Department From Brigham This i zinc concentrations in patients with of Medicine, Boston; and Harvard the Medical Department found anemias School of Physics, and in whole other than the Medical Massachusetts Clinic Institute Mass. study was supported by a grant-in-aid cc. of erythrocytes packed by centrifuging from the National at ;ooo r.p.m. 455 Institute for 30 of Health. minutes. blood, plasma, pernicious aneof the Peter of Technology, Bent a From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 456 ZINC mia. Table The values plasma, WHOLE BLOOD presents similar data obtained from for the zinc concentrations contained calculated and erythrocytes as previously abnormal pernicious red anemia to other forms i-The TABLE OF patients with pernicious in i ml. of whole blood 2. leukocytes The CONTENT cell findings possibly of anemia, Values sickle of Zinc Content are cell in which 3 and than Blood, Leukocytes Unit Irllc7 Content Plasma ____________ 74.5 5.5 3.2.4 2.4.2. Anemia 3.65 2.0.0 17-2. “Refractory” Anemia ;.6o 31.6 88.o .6 1.1 17-3 “Refractory” Anemia 3.42. 2.9.9 87.5 4.2. 1.3 i8-i “Refractory” Anemia ;.66 36.6 100.0 11.5 62.-I “Refractory” Anemia 95-I “Refractory” Anemia 8i- 55.0 36.7 90.5 3.2.2. 30.0 93.2. Hemorrhage 2.68 2.4.0 90.0 zo6-i Hemorrhage 3.52. 36.2. 88.6 zi8-, Hemorrhage 2.92. 2.4.0 81.1 153-I Hemorrhage 2.93 2.5.5 87.0 23.5 by Dithizone ‘ Erythrocytes _____________________ __________________________ -3 Zn/cc. XlO 3.3 i6.i ,6.8 per 1 X l0’cells e re 17.7 1.49 - - 10.0 9.5 1.09 .6o 16.4 2.9.0 1.33 13.6 z.8 2.06 2.1.3 3.7 5.7 Extraction 19.0 4.4 8.2. 1.3 1.1 1.69 18.9 9.1 2.6 2.92. i8.8 7.1 1.5 3.9 1.2.6 15.4 6.8 3.0 1.4 1.45 i6.8 2.1.7 16.4 ii.8 Nutritional 3.32. 33.0 90.5 4.1 1.61 Iron 4.76 37.5 79.0 6.7 1.2. -* 1.01 12.8 Uremia 3.2.5 30.6 94.5 7.0 2.7 4.0 1.43 15.2. Uremia 1.95 2.8.7 97.0 5.9 1.6 4.4 1.63 16.7 Sickle Cell 31.0 78.0 4.2. i.6 1.01 2.5.8 Deficiency 17.8 98-2. Sickle Cell 34.0 88.o Sickle Cell 3.2.9 31.0 97.5 6-i Splenic 3.99 31.6 79.0 66-, Infection 3.96 39.0 99.0 11.1 107-I Infection 3.78 36.9 97.5 10.4 101-I Inf. 3.40 35.0 103.0 3.46 36.0 104.0 Monon. Cooley’s normal nificantly in Anemias 0.92. 2.8 8. ‘33-I Sample ‘.5 3.0 3.95 3.85 * to be in the -2 XlO per 1 X lO’cells ml. Anemia 97-I found - ------ “Refractory” 98-I with in contrast }11k “Refractory” 3.73 patients Erythrocytes ---_______________ 17-I Ill-I to and 24-2. 39-I lost to were anemia, were ‘I, per 49-I due values Anemia M.C.V. in Hct per mm.2 limited Plasma, : RBC 139-I 4. These In pernicious concentrations Pernicious t Diagnosis essentially anemia. zinc of Whole other Exp.No. in tables described.’ blood and Unit are shown anemia. 12.5 1.4 -* 1.50 17.0 4.2. i.6 2.92 29.6 4.6 6.4 1.52. 29.3 4.5 z.6 1.93 19.8 4.3 6.6 i.86 19.2. 6. 2.6 i.6 1.30 12.5 4,7 1.2. 4.8 2.2.5 22.0 7.2. 16.3 8.4 in processing. range, the increased, unit red blood cell zinc concentration but returns to within normal limits prior with to therapy is sigsuccessful therapy. DISCUSSION The over-all tology) The have direct limitations been found measurements of the technics to be defined for whole employed (chemical analysis by an error of about ±15 per cent.’ blood, plasma, red cells and white and hemacells, in From www.bloodjournal.org by guest on June 15, 2017. For personal use only. BERT the group figure of secondary L. VALLEB AND anemias, given JOHN in G. GIBSON, table i II , are 457 graphically depicted in I. ..-Tbe TABLE Unit Values of Zinc Content of Whole Blood, Pernicious Plasma, Unit Days of RBC per Observa- No. Exp. Hct in mm.’ tiont Content Plasma M.c.v. o Leukoc,ytes and Erjthrocytes in Anemia by Dithizone Extraction Leukocytes Erythrocytes ‘ 7 X 10’ per 1 X 10’ cells 7 per ml. X 10 cells ‘9-I I . 8o 2,7.2. 152. 7S 1.2. 19-2. I .94 2.7.1 ‘43 6.7 1.7 2.. 4.7 4.I I 3.4 7.9 2.. ‘9-3 20 3.70 37.0 I00 II. 40 3.13 35.’ io8 -* ‘9-4 3.77 I 3.38 6 Zn v/cc. packed 2.. 6 7S 35 for M.C.V 2.2.. ‘7,5 2.1.6 39’ 7 ‘Os 7.0 “9 ‘5 2.. 50 30.3 ‘LI 8.7 0.9 “4 i.6 4.7 4.2. 2.. 3.6 i.6 I .72. ‘7,7 1.4 5.3 3.14 2.3.7 3SS 2.9.7 366 2.1-2. 2.2. 2.. 78 32.. i6 8.6 2.1-3 30 2.. 96 34.1 ‘Is 9.3 2.1-4 369 45.1 104 10.6 2.1-5 369 57-I 6 57-2. 3 45.0 I .2.2. 15.0 S9 2.1.9 ‘3’ 10.0 3.8 2.6.2, “5 I0.0 3’’ I 99 573 ‘3 57-s 2,2 2.. 48 2.9.0 “7 57-6 2.7 2.. 94 31. 107 57-7 4’ 3.66 35 57-8 55 3 88 37S 57-9 2.08 4.4’ 44.8 57-10 2.57 4.33 43.0 9’-’ -7 1.47 2.7.1 2.6. 2.43 91-2. I’ 115-I 2.. 4 118-I 118-1 8 118-3 6o 2, ‘47 ‘57 2.07 2.6. 2.35 32.. it8-6 66 4.2.8 4’.o 118-7 8o 4.87 4’ i.6 131-1 132-3 * Sample t Withrefcrence lost Seventeen within ±2. 0 .0 2.6. i 17. I 2.. 30 2.1,0 2.3.8 5 2.. 52. 2.4.1 ,_. 10 2.1.0 109 19.0 .69 2.. 9.3 14.7 I 78 II0 1.00 2,9.6 2.. 2.. ‘53 3.44 2.. 8i -* 7.2. 14.r 2.5.6 6 8.o ‘4’ 3 i6 ‘.5 .49 3.10 2,. 2.. 99 2.3 I 1.0 99 2..7 118-5 131-I 10. 2.8 7.2. I0I 0.94 1.42. 6.4 15.0 4.9 138 2.1 2.. 5 I., 2.2. .0 . -* 97 118-4 119-I 97 ‘.59 I 9.3 12.3 I I. I 43S 4S4 2. . 2.0 104-I 1.9 19.1 5 .6o ‘.9 I . 8o 3.2. I . 2.1 12.3 3.1 3.0 2.. 8o 2,.4 8.1 1.8 2.. 2. 2,, 47 6.7 “9 3.6 2.. 64 6.8 4.2. “7 2.. 36 o.8 3.50 2.. 10.4 0 4 3.7 2.. 18.7 2.2. .2. 2.6.7 ‘7. 5 49S 34.0 * 7.2. 46.0 0.7 12.8 0.7 3.67 30.0 136 9’ 6 3.0 4.0 2.9.3 96 7,5 1.2. ‘.4 “59 84 9.0 3.2. 1.2. I 1I0 4.0 1.2. 8.6 * 8 1.81 2,3.3 12.8 ‘5 69 1.76 2.6. 96 7.0 2,, 4 2,, I 4.92. 44.0 89 6.4 I.0 i6. .41 x6.8 2.. 2.4 2.0.4 53 96 2.0.0 * 2.. 2.. 2. 2.. ‘‘3 I I 2.3.0 5,3 6. * 4 19.0 2,-I ‘9-5 red 1 X ‘#{176}‘cellsCorr. per .42 30.7 ‘5.9 in processing. toinstitution of the standard 2.3 of therapy. whole blood zinc measurements deviations of the mean of our (fig. normal iA) are shown to fall series. Case 49 had a From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 458 ZINC high whole zinc was just above blood zinc normal. of error. lower limit TABLE 3.-Zinc due Case the limit range of the of normal. z ml. of Whole Erythroc,ytes Exp. No. series zinc, while within samples observation, Blood Calculated in Anemias from the were Unit red blood cell zinc was blood possible technical consistently was Values Pernicious Plasma Column the whole no diagnosis other than Diagnosis The though consecutive under BLOOD to all therapy. normal While of WHOLE plasma refractory three 17, OF to an increased was 14 In Case Content CONTENT of below the established, Plasma, and Leukocytes and Anemia Leukocytes Total Zn in I ml, of Whole Blood Erythrocytes 1 2 3 4 14-2. “Refractory” Anemia 4.1 0.14 4.9 9.1 17-I “Refractory” Anemia 1.2. 0.14 1.5 1.9 17-2. “Refractory” Anemia 1.4 o.6I 3,3 5.3 ‘7-3 “Refractory” Anemia 0.9 0.15 3.7 4.8 18-I “Refractory” Anemia ,.8 0.37 6.o 8.2. 61-I “Refractory” Anemia i.8 0.52. 5.0 8.3 95-I “Refractory” Anemia 7.6 0.2.3 6.7 9.5 8,-, Hemorrhage 1.0 0.04 4.5 106-I Hemorrhage .8 o,,6 6.8 1,8-I Hemorrhage 1.9 o.x6 ‘53-I Hemorrhage 2.3 0.15 49-’ Nutritional 139-I Iron 3,7 .8 4.3 6.8 0.31 5.4 o.8 0.07 4.8 17.8 Deficiency #{149} 5.5 ii,8 10.1 5.7 39_I Uremia 1.9 0.31 4.7 6.9 ‘Il-I Uremia i.8 0.37 4.8 7.0 98-I SickleCell 2.9 o.6 8.o ,,.6 98-2. SickleCell 0.9 - .8 - SickleCell 2.9 o.,8 6.3 9,4 3.1 0.14 6. Infection 1.8 0.31 7.7 11,0 107-I Infection 2.7 0.39 7.1 10,1 101-I Inf, 1.7 0.19 4.4 6.3 4.3 5.3 ‘33-I 1 6-x Splenic 66-, Monon. Cooley’s 97-I o.8 9.3 0.19 * Sample lost in processing. Explanation we I Zn 2. Total 3 Zn 4 Sum are, of Columns: per ml. Zinc per X #{247}ml, million of Columns therefore, conclusions Figure of plasma in Sample from iB red cells I, 2. Figure million iC is a plot kukocyts. and because shows of Whole X red these limits of normality apparent cause. Hematocrit 100 the except of Whole Blood cell count from of Whole Blood. which leukocytes Blood X ‘ X obtained. I0. 3. of the singularity of the data. plasma zinc concentrations, Case of leukocyte It is apparent 4, previously zinc that all referred content Cases observation, in terms 17, i8 and unable of which to, of and i are Case X 6i have Icr2 to draw within io6, gamma a leukocyte the for no per zinc From www.bloodjournal.org by guest on June 15, 2017. For personal use only. BERT elevated concentration considered ‘ VALLEE from to ‘refractory’ AND JOHN three to ten all therapy. ‘ Content of z ml. 4.-Zinc TABLE L. of Whole Blood G. GIBSON, II 459 times above normal. These They all had leukocyte Calculated from Unit Values of Plasma, patients counts were below Leukocytes and Erythrocytes in Pernicious Anemia Exp. No. Days Total of Observationf Plasma Leukocytes Erythrocytes Zn Column 1 in Blood 2 3 4 ‘9-I 0.9 0.7.1 6.x 7.2. 19-2. ‘.3 0.2.6 5.2. 6.8 ‘9-3 2.0 3.0 0.44 6. ‘9-4 40 1.2. 0.51 7.6 9,9 10.3 ‘9-s 366 1.2. 015 2.I-I ‘5 o.6 o.66 7.8 9’ 2.1-1 7.2. I.0 0.09 9.6 10.7 7.0 I 30 1.0 0.50 8.4 10.4 2.1-4 369 1.3 0.2.6 10.3 11-5 369 2.0 0.2.0 7,7 8.o 2.0 0.11 3.8 6.o 11-3 57-’ b 2. 3.0 0.43 5.7 9. 2.3 0.14 5.’ 7.5 2.2. ‘‘5 0.14 6.9 8. 2.7 1.0 0. 7.4 8. 4’ 4.7 o.8 11.4 9.1 6 57-2, 57-3 ‘3 57-s 57-6 57-7 * 57-8 55 0.2.4 7.7 6.2. 57-9 2.08 I.’ 0.13 8.o 57-10 2.57 I. I 0.14 5.2. 6. 9,-I -7 2.3 0.13 6.9 7.2. 2.0 0.11 5.9 II ‘.4 0.11 6.9 8.4 4 3.2. 0.11 3.8 7’’ 1.1 0.03 3.3 3.’ 0. 12.5-I 118-I I 9.3 8.o 91-1 104-I -5 118-1 o8 5.4 8.i 5.2. * o.6 8 12.8-3 * 8.7 * * 118-4 x6 0.5 118-5 2.3 2..0 0.09 118-6 66 0.7 0.17 9,4 6.8 II’S 118-7 8o i.8 o. o8 6.9 8.8 ‘‘I 0.07 3’’ 4.6 4.3 015 8,i 9.8 0.09 7.0 7,7 119-I I32.-2. Is 131-3 69 * t Sample With Explanation lost therapy This 12.,75o/mm’. but ‘‘5 o.6 7,7 in processing. reference to institution of columns the 2.000/mm’. 7.7 * x.8 8 131-I 1 ml. of Whole was of therapy. same as in table in contrast had a normal We are not to Case zinc at 3. present 5, which concentration prepared was of to also found leukocytes interpret refractory which the to numbered significance and From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 460 ZINC physiologic implications contrast to our the concentration zinc of findings CONTENT these the WHOLE WHOLE findings in leukemic of OF cells. BLOOD which, however, In myelogenous circulating leukocytes PLASMA was appear and lymphatic found to ERYTHR LEUCOCYTES striking in leukemia, he about io per OCYTES BLOOD 1,1 ZII.j GAMMA GAMMA PER PER PER L. MILLION 7 GAMMA GAMMA PER MILLION CELLS XIO CELLS 110 1* 50 II “-1 14 4.ij 20’ II IS I It Id’ “ 5 0 1 1 : MEAN 2 _____ 3 3 (3’ ‘ 4, A FIG, anemia values Cent tration cyte i-Distribution other arc B of than zinc in blood, whole pernicious anemia. Under effective C The mean leukocytes plasma, and 2. standard D and deviations erythrocytes, of the in patients comparable with normal indicated. of normal. returned picture to are normal apparent. levels.7 therapy with x-ray and urethane No other significant abnormalities the zinc concenin the leuko- From www.bloodjournal.org by guest on June 15, 2017. For personal use only. BERT Figure to iD depicts our normal is significant were red or due zinc to chance unit in the whole any significant red cell zinc spectively, returned to therapy. In Case stitution of therapy. 366th 3oth and following normal days 369th a definitely Figures while normal zinc 3, 4 and under Case 19 liver. The was reached normal . elevated, normal there patients (table of erythrocytes due limits million to known (fig. LA, cells (fig. techB, C). 2.D) and by a prompt response concentration Maintenance had 369 the showed days after million cells, and absolute number Doses of liver therapy, of reticgiven at the shown per top of each graph. to a test dose the absolute response in terms of rise in red blood subsided. of red therapy and still content. concentration in is also 4oth between samples 366 zinc in- the be obtained taken reticulocytosis which following between the earlier by arrows concentration maintenance 69 days could samples zinc zinc under obtainable While erythrocyte accompanied levels. 2.1 erythrocyte a prompt the reticulocyte in the zinc cases, zinc nor white blood distribution picture. within per cent reticulocytes as a function of time. response anemia content erythrocyte thereafter were unit are indicated fall progressive in care, when the normal obtained concentration, the of these plasma normal per no samples shows count continued was within 57-2. samples in Case figure reticulocyte reticulocyte were no hospital in exception anemia) 66 and 107 have distribution curve. whether or not this ‘ normal show 133, in relation cell group. (calculated 19, blood cell count, the in one ml. of blood of anemia patients are elevated significantly above the of therapy and after an initial rise, the unit a prolonged period. In Cases and 12.8, samOn the 55th and 66th days of sampling, re- Similarly, were the 461 98 (sickle in pernicious in unit zinc of therapy, remained post-therapy begun cases Cases io6, of the normal to determine of this and were 2.1-I values II and blood zinc. Neither deviation from the levels of therapy. days was the red ulocytes, series concentrations In Case increased treatment in these observed increase institution levels, and 132., GIBSON, anemia) With cell per cc. of packed cells) of untreated normal range. Following institution zinc content falls successively over ples were obtained at close intervals. and G. pattern scattering. red of leukocytes in samples Other leukocyte zinc error. The cell JOHN 95 (refractory in zinc concentration due to a marked apparently nical blood in the which are reflected cell zinc presents The AND elevations above the normal. just above the upper limit a larger number of observations changes are VALLEE Cases no abnormalities The 2.) the series. show significant zinc concentrations It would require L. During blood this cells cell count period which no visible effect similar to those of which there was eventually on the zinc a con- centration. The features of Case for figure 3 Therapy in zinc concentration tirely normal within levels Case these to i 12.7 two evaluate ml. on 57 (fig. the limits within (fig. ) the of days differs technical following materially Coincidental instances. 1/14/48, 4) were essentially was spaced very nearly identically. at the height of reticulocytosis. . potency with the liver a subsequent of error. The institution in both with extract used submaximal just described was a slight rise this rise is en- unit zinc concentration of liver therapy. character therapy, There However, and degree observations were made. reticulocyte fell of response on this The patient response. to from patient received The first From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 462, ZINC zinc sample daily was therapy which response obtained with CONTENT near the extract became OF the was maximal height instituted. on the WHOLE BLOOD ioth WHOLE BLOOD of this reaction. Thereafter, This resulted in a good day following PLASMA GAMMA PER ML. GAMML PER ML. the LEUCOCYTES liver injection. ERYTHROCYTES GISMMA PER MILLION CELLS x first intensive reticulocyte GAMMA PER MILLION CELLS o_2 f I92 x IO f I5O II... e 25’ II 7 It 6 C$#{149} I FIG. of zinc i-Distribution pernicious The anemia. mean and in whole 2. standard blood, plasma, deviations A prompt rise in total red blood cell count zinc concentration per million cells during reached a peak at the height of reticulocytosis Thereafter, the zinc concentrations fell leukocytes of the and comparable accompanied this period and fell to normal levels erythrocytes, normal in patients values are with indicated. this phenomenon. The rose progressively and concomitantly with it. in a fashion similar to the From www.bloodjournal.org by guest on June 15, 2017. For personal use only. BERT LIVER L. VALLEE EXTRACT AND Mu U 1515 15 JOHN G. GIBSON, 463 II Z $9 4 -o RET1 20 .,.“. 10 0 10 FIG. 3.-Casc 19. absolute number of time, under liver therapy. Solid circles = Erythrocyte Open circles Solid triangles Open 15 Erythrocyte zinc of reticulocytes, Red = Per = triangles = as well Blood red as absolute Zinc concentration Cell count. cent reticulocyte Absolute number 30 25 20 concentration, blood number 40 cell count, per of unreticulated per million 45 cent reticulocytes erythrocytes, and as a function cells, count. of reticulocytes. Z-57 5 0. ..0 / / 0’ / RElICS. / , 30 20 U 0 5 FIG. 4.-Case absolute number of time, under 7. Erythrocyte concentration, of reticulocytes, as well liver therapy. Symbols 20 5 zinc as absolute as in figure 25 red 3. number 30 blood cell 35 count, of unreticulated per 47 cent erythrocytes, 61 54 reticulocytes 93 and as a function From www.bloodjournal.org by guest on June 15, 2017. For personal use only. ICC EACN U 7 Z I28 6 5 4 3C 20 IC C IS FIG. .-Casc absolute number of time, under 12.;. Erythrocytc 25 20 DAYS OF 30 zinc concentration, red blood of rcticulocy’tes, as well as absolute number liver therapy. Symbols 35 OBSERVATION as in figure cell count, per cent reticulocytcs land of unreticulated erythrocyEcs, as a function 3. CASE CASE CASE C*SE 9 2’ -9 57 26 6 4 6 0 0 2 RED Fio. jn 6.-Zinc, 4 patients in gamma with pernicious X ,o anemia, per million under 3 BLOOD CELLS red cells, therapy. 464 4 iwo,e in relation to the red cell count, showing a fall From www.bloodjournal.org by guest on June 15, 2017. For personal use only. BERT ones shown in Cases L. and 19 VALLEE 7. AND The JOHN normal G. level GIBSON, was 465 II attained within Case 13 I , where only three samples were obtained, a normal on the 69th day post-therapy. Whether or not this response of the zinc concentration was ticular liver extract used, the dosage given, or whether 66 days. value was related to the is a property it In found par- of young cells released from the bone marrow in pernicious anemia under the stimulus liver therapy, we are unable to conclude on the basis of our present observations. In the 3 cases we were able to follow, the erythrocyte zinc concentration turned to normal levels approximates the mean mined with that the N’5 labelled change pernicious glycine in zinc anemia million cells, reaches normal, the normal coinciding red the size tribute to the increase over nomenon a slope anemia, the fall was zinc 8 of the influence count. than of the of zinc and indicating systems are structurally In sickle cell anemia, vated in one out of three two standard deviations unit cells per was of red concentration is one of increased anemia, drop carbonic that cc. zinc extract, zinc in per concentration normal packed in spite cells. as a factor per million carbonic in hemoglobin. anhydrase are the hemoglobin the could cells. con- A definite The anhydrase In contrast, of low Thereby which nevertheless noticed. cellular mass. and of and cell count has returned to normal size. In the second- of cells believe cell. in micrograms unit remains eliminated concentration pernicious red blood toward We replacement of liver The re- This time closely anemia as deter- and a function the cell calculated cell zinc simply to that the increase in hemoglobin blood per also individual the normal is therefore not other red concentration zinc parallel under at the time when the a return of the M.C.V. increased In anemias on to the level with of the Shemin is probably formed respectively. in pernicious of the death rate of the pernicious anemia unit zinc concentration in red blood cells zinc blood counts. Red blood cell increased by cells in relation anemias, by London, concentration cells effect is an expression Figure 6 shows the ary within 55, 66 and 69 days life span of erythrocytes of phe- decrease in pernicious inversely proportional and carbonic anhydrase to discrete though functionally related. the zinc concentration of erythrocytes was markedly dcsamples on 2. patients. The other two samples were above from the normal mean but so close that they could not be thought to be statistically significant. More observations required before a definitive statement about zinc distribution Zinc is known to be an integral component of the enzyme in this condition can be made. carbonic anhydrase are . ‘ #{176} The functional significance of this enzyme in the anemias has recently been scrutinized,” and the quantitative relationship of zinc and enzyme activity has been determined independently on samples of venous blood, and is being reported in two other communications)e, 13 CoNcLusIoNs i. The zinc content determined in pernicious anemia. 2.0 of whole patients with blood, plasma, miscellaneous leukocytes anemias and and erythrocytes in 9 patients was with From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 466 ZINC Unit 2.. packed ‘ CONTENT values for erythrocytes cells) were within the nicious anemia. 3 In pernicious vated above normal. in unit value which anemia, Under reached limits OF WHOLE BLOOD (zinc in gamma of normality in the per million cells or per cc. of anemias, other than per- unit values for erythrocytes were significantly dcsuccessful liver therapy there was a progressive fall normal when the red blood cell count had risen to normal. 4. The anemia rate ofdecrease is comparable institution of in unit zinc the probable to value of the circulating red cells death rate of cells in circulation in pernicious prior to the therapy. REFERENCES B. L., I VALLEE, kocytes 2 SurroN, Studies S. E., Chem. S i#{225}j: Biol. of the G. 2.ND, S 9 D. KEILIN, J. 34: Chem. Lawis, H. D.. other -: and whole blood blood, changes plasma, produced leu- in rats by & Med. 36: 111, Antagonistic 1937. effects ofcopper and liver.J. Biol. serum , dithizone FLUHARTY, R. G. leukemia. Program 104. (To A method albumin. , Blood, technique AND for be published separation analysis of zinc of the International Proceedings of leuko- 82., i. E. : Studies Fourth in the the Issue, the J. NELSON, of the for Special of the zinc in blood. content Cancer Research Fourth Interna- , AND D. : The RITTENBERG, of blood constituents application anhydrase; of the J. in man. purification Clin. and isotope technique Investigation nature of the to the 26: enzyme. 1947. Biochem. 1940. 42.5, AND C. A., M. Blood, LEwis, this H. D., carbonic 559, and Blood, anhydrase 1948. D.: Blood issue, p. B.: The relation of zinc to carbonic anhydrase. J. Biol. zinc this carbonic D., AND concentration issue, content anhydrase activity in anemia, with a note on 442.. M. ALTSCHULE, activity states. s: E. HART, ANi 1940. ALTSCHULE, pathologic Zinc and G., GIBSON,J. on T. : Carbonic MANN, anhydrase Investigation D. of formation vera. B. L., carbonic human Congress.) SREMIN, polycythemia 12 VALLEE, AND Page 1947, ELVEHJEM, 136: B. L. VALLEE, rates AND , 1163, E., 10 HOVE, , the of ofnormal Biol. in rats. An improved 1948. Research I. M. study Ja., iD: 435, 1-7, Cancer LONDON, Exper. toxicity flotation in myelogenous Sept. tional by G., 176. leukocytes Concress, content 445, 1948. reproduction 1937. i 17, Soc. Zinc L., blood J. Chem. J. GIBSON, Proc. E.J.: W. HUGHES, whole GI*soN, AND J. 7 from Sc. zinc 176.’ 1946. __, , B. L., VALLEE, cytes 6 2.9, Acad. on zinc. LARSON, AND The LND: Biol. Chem. V. E. : Growth, of zinc. Proc. Iowa AND --, 4 SMITH, G., GIBSON,J. and erythrocytes.J. W. R. , AND NELSON, means 3 AND GIBSON, J. G., of erythrocytes 2.ND: in The relationship between normal, in and anemic in p. 467. of red cells in normals and in pernicious anemia. J. Clin. From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 1949 4: 455-466 THE ZINC CONTENT OF WHOLE BLOOD, PLASMA, LEUKOCYTES AND ERYTHROCYTES IN THE ANEMIAS BERT L. VALLEE and JOHN G. 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