Origin and Composition of Cabot Rings in Pernicious Anemia LAWRENCE KASS,
M.D.
Department of Internal Medicine (Simpson Memorial Institute), The University of Michigan, Ann Arbor, Michigan 48104
ABSTRACT
50 patients with untreated pernicious anemia were carefully reviewed. In only three instances, patients with erythrocytes containing Cabot rings were detected. From two of these patients, sufficient material was obtained prior to treatment to permit a variety of cytochemical studies. These studies were performed in an attempt to ascertain the composition of the Cabot ring. Peripheral blood films from these patients were stained for "reticulum" using brilliant cresyl blue as a supravital stain, DNA using the Feulgen reagent, 21 RNA and DNA using methyl-green pyronin, 21 glycogen using the PAS (periodic acidSchiff) reagent, 8 mitotic spindle fibers using Heidenhain's iron hematoxylin stain, 16 metachromatic substances using toluidine blue, 21 iron using the Prussian blue reagent 6 and 1% aqueous neutral red counterstain, histone using the alkaline fast green stain, 1 and arginine-rich and lysine-rich histone using the ammoniacal silver stain. 3 With this stain, arginine-rich
THIS REPORT describes cytochemical properties of Cabot rings in erythrocytes obtained from peripheral blood of two patients with classic untreated pernicious anemia. In the bone marrows of these two patients and in the peripheral blood of another patient who also had Cabot rings in erythrocytes of peripheral blood, apparent precursors of Cabot rings and actual Cabot rings were found in heavily stippled late intermediate megaloblasts. T h e results of these studies may afford insight into a possible pathogenetic basis for the formation of these unusual structures. Materials and Methods Wright-stained films of capillary peripheral blood and bone marrow from Received October 15, 1974; received revised manuscript December 3, 1974; accepted for publication December 3, 1974. Supported by the Elizabeth Roodvoets Memorial Grant for Cancer Research of the American Cancer Society (#CI-79) and by the National Cancer Institute Grant USPHS CA 14428-02. Address reprint requests to Dr. Kass. 53
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Kass, Lawrence: Origin and composition of Cabot rings in pernicious anemia. Am J Clin Pathol 64: 5 3 - 5 7 , 1975. Cytochemical studies were performed on erythrocytes containing Cabot rings from the peripheral blood of two patients with severe untreated pernicious anemia. These studies demonstrated that the Cabot ring contained arginine-rich histone and non-hemoglobin iron. Structures that may represent precursors of Cabot rings were found in stippled late intermediate marrow megaloblasts. T h e Cabot ring may result in part from abnormalities in metabolism of both iron and arginine-rich histone that are known to occur in pernicious anemia. (Key words: Cabot rings; Pernicious anemia; Erythrocytes.)
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histone appears brown or black, and lysine-rich histone appears yellow. Bone marrows from these patients were carefully studied in an attempt to identify possible precursors of Cabot rings in the megaloblastic erythroid precursors. In the instance where material was available, marrow films were also stained with the Prussian blue reagent and counterstained with 1% neutral red.
in the patients' peripheral bloods. These rings were composed of either basophilic or acidophilic stippled granules connected to one another by a red, strand-like material, giving the ring the appearance of a stippled "necklace." At times, "figure 8" configurations of the ring were observed. In most instances, the ring was associated with heavy basophilic and acidophilic stippling of the erythrocyte cytoplasm. Even when no gross stippling Results was seen, at least several coarse granules Cabot rings (Fig. 1, top row) were found could be observed adherent to the ring. in approximately 1 per 500 erythrocytes Cabot rings were not observed in cells that
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
FIG. 1. T o p row, two erythrocytes containing prominent Cabot rings. These rings appear as a "necklace" of stippled granules joined by a red-staining strand on Wright-stained film. Bottom row, what may be precursors of these stippled "necklaces" in peripheral blood erythrocytes within the cytoplasm of heavily stippled late megaloblasts in the bone marrow. Arrows point to loop of ring-shaped structures. In the megaloblast at bottom left, an actual ring form may be seen within the cytoplasms, x 1,800.
July 1975
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CABOT RINGS IN PERNICIOUS ANEMIA
FIG. 2. Left, enlargement of the ring form in the cytoplasm of the cell illustrated in Fig. 1, bottom left, showing coarse granules connected by strandlike material. X 1,800. Right, late megaloblast stained with Prussian blue and counterstained with neutral red. A red-stained loop is seen in the cytoplasm, and siderotic granules adhere to the loop. This loop may be the precursor of or an actual Cabot ring, and suggests that it may be related to abnormalities in iron metabolism, x 1,500.
A**
/
late stippled megaloblasts in the bone marrow also appeared as a "necklace" of coarse granules connected to each other by a red-staining strand. Partial loops of this appearance were seen most frequently, but on several occasions, as seen in Figure 1, bottom row, left, and in Figure 2 (enlargement of the area in Figure 1), an actual ring or "figure-8" stippled "necklace" could be observed in the cytoplasm. In most instances, the "necklace" did not seem to show continuity with the nuclear chromatin, nor did it have the tinctorial properties of nuclear chromatin as visualized with ordinary Wright's stain. In one instance, a megaloblast stained with Prussian blue to demonstrate iron and counterstained with neutral red demonstrated a ring structure in the cytoplasm (Fig. 2). T h e ring appeared to consist of a red-staining thread to which bright blue siderotic granules adhered. Discussion Since Cabot's original report of ring bodies in pernicious anemia in 1903, 5 the nature of these structures has been a subject of lively controversy. In his original report, Cabot 3 illustrated stippled "necklace"-shaped and "figure-8" ring bodies similar to those found in the present study, and he believed but could not prove that these rings were nuclear remnants. Bostrom 4 postulated that two
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
contained reticulum as visualized by supravital staining with brilliant cresyl blue. Of the various cytochemical tests, only three demonstrated structures consistent with Cabot rings. Peripheral films stained with the Prussian blue reagent and counterstained with neutral red showed a thin red ring to which blue-stained particles adhered. Films stained with the alkaline fast green stain for histone showed a green ring surrounded by green-stained particles, some of which adhered to the ring. In peripheral blood films stained with the ammoniacal silver stain to identify lysine-rich and arginine-rich histones, a black ring or "figure-8" ring form was seen. Orange, brown, and black particles were seen attached to the ring and isolated within the cytoplasm of the erythrocyte. Notably, structures resembling Cabot rings were not observed in erythrocytes stained with reagents specific for DNA (Feulgen stain and methyl green stain). T h e second row of Figure 1 illustrates bone marrow erythroid precursors obtained from the patients. As delineated by the arrows, ring and loop structures could be observed within the cytoplasm of certain late intermediate megaloblasts. T h e megaloblasts that showed these ring structures most frequently were those that showed unusually abundant and coarse cytoplasmic basophilic and acidophilic stippling. As in the Cabot rings in the peripheral blood, the rings and loops in
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arginine-rich histone and nonhemoglobin iron. Although histone and iron were found to be the only substances demonstrable in Cabot rings in the present report, it is possible that there may be additional substances within the ring that might be demonstrable by other cytochemical reagents not utilized in these studies. The basis for the presence of argininerich histone and non-hemoglobin iron in the Cabot ring and the pathogenetic implications of these cytochemical findings can only be speculated upon at present. It is known that arginine-rich histones are synthesized within the cytoplasm of cells on polysomes 19 and that histone biosynthesis is abnormal in pernicious anemia. 12 In pernicious anemia there is also a defect in the metabolism and mobilization of iron, and this disorder has been considered a type of secondary acquired sideroblastic anemia.9"13,14 In the present study, Cabot ring precursors were found in late intermediate megaloblasts that showed unusually coarse cytoplasmic basophilic stippling. This type of coarse stippling is believed to be composed largely of non-hemoglobin iron. 17
In the present study, Cabot rings and their presumed precursors were found in late intermediate marrow megaloblasts. Other authors have also found these structures in megaloblasts in pernicious anemia and in erythroid precursors from patients with other types of anemias. In 1938, Isaacs 10 described and illustrated a late intermediate megaloblast from a paOn the basis of the available informatient with pernicious anemia that con- tion, it is possible that the spatial proximtained a large Cabot ring "entirely sepa- ity of iron and arginine-rich histone in the rate from the nucleus." Isamboulas and cytoplasm of the late i n t e r m e d i a t e Malikoosis,11 in 1939, also illustrated a megaloblast, combined with the known Cabot ring in an erythroid precursor abnormalities of both iron and histone in from a child who had typhus. Apparent pernicious anemia,9>12,13,17 facilitates an inprecursors of or actual Cabot rings have teraction between these two substances. also been observed in erythroid precur- Why this interaction should result in a sors by Picard 18 and by van Oye. 22 structure having the shape of a loop or a T h e results of cytochemical tests for "figure-8" is unknown. DNA in this study agree with the findings of others, 7,8 namely that the Cabot ring References does not contain DNA as demonstrated by 1. Alfert M, Geschwind II: A selective staining conventional staining methods. Unexpectmethod for the basic proteins of cell nuclei. edly, the present studies indicated that Proc Natl Acad Sci USA 39:991-999, 1953 2. Bessis M, Breton-Gorius J: Sur la strie bordante arginine-rich histone was found in the des erythrocytes des amphibiens et sur de Cabot ring, and that the granular material precendus "anneaux de Cabot." CR Soc Biol adherent to the ring contained both (Paris) 147:1134-1136, 1953
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
erythroid precursors in pernicious anemia were joined by a red-staining fiber of nuclear origin that became enclosed in a pseudopod of the erythroid precursor. This pseudopod then appeared as an erythrocyte containing a ring or "figures'' structure. Discombe 7 and Picard 18 were unable to demonstrate structures consistent with Cabot rings using stains for DNA. Picard 18 and van Oye 22 believed that Cabot rings were remnants of the mitotic spindle apparatus. In the present report, structures analogous to Cabot rings could not be demonstrated using Heidenhain's iron hematoxylin, a reagent commonly used to demonstrate the mitotic spindle apparatus. 16 In contrast to the postulates of the authors mentioned, other investigators 2,15,20 have concluded that Cabot rings are laboratory artifacts.
A.J.C.P.—
July 1975
CABOT RINGS IN PERNICIOUS ANEMIA
13. Kass L, Schnitzer B: Refractory Anemia. Springfield, 111., Charles C Thomas, 1975 14. Kass L: Pernicious Anemia. Philadelphia, W.B. Saunders, (in press) 15. L i n d e m a n n B: Uber die N a t u r d e r sog Cabotschen Ringkorper der Erythrozyten. Arch Exp Pathol Pharmakol 207:67-70, 1949 16. McClung CE: Handbook of Microscopical Techniques. Second edition. New York, Hoeber, 1937 17. McFadzean AJS, Davis LJ: Iron-staining erythrocytic inclusions with especial reference to acquired haemolytic anaemia. Glasgow Med J 28:237, 1947 18. Picard D: Nature et signification des anneaux de Cabot des hamaties. C R Soc Biol (Paris) 147:1451-1453, 1953 19. Robbins E, Borun TW: T h e cytoplasmic synthesis of histones in HeLa cells in its temporal relationship to DNA replication. Proc Natl Acad Sci USA 57:409, 1967 20. Schleicher EM: T h e origin and nature of the Cabot ring bodies of erythrocytes. J Lab Clin Med 27:983-1000, 1942 21. Thompson SW, Hunt RD: Selected Histochemical and His to pathological Methods. Springfield, 111., Charles C Thomas, 1966 22. Van Oye E: L'origine des anneaux de Cabot. Rev d'Hematol 9:173-179, 1954
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
3. Black MM, Ansley HR: Antigen-induced changes in lymphoid cell histones. I. Thymus. J Cell Biol 26:201-208, 1965 4. Bostrom L: La formation des anneaux de Cabot. Sang 18:67-68, 1947 5. Cabot RC: Ring bodies (nuclear remnants?) in anemic blood. J Med Res 9:15-19, 1903 6. Dacie JV, Lewis SM: Practical Haematology. Fourth edition. New York, Grune and Stratton, 1968, pp 1-568 7. Discombe G: L'origine des corps de Howell-Jolly et des anneaux de Cabot. Sang 19:262-264, 1948 8. Hayhoe FGJ, Quaglino D, Doll R: T h e Cytology and Cytochemistry of Acute Leukemias: A Study of 104 Cases. MRC Special Reports Series No. 304. London, H M Stationery Office, 1964, pp 1-104 9. Hines JD, Grasso JA: T h e sideroblastic anemias. Semin Hematol 7:86-106, 1970 10. Isaacs R: T h e erythrocyte, Handbook of Hematology. Volume 1. Edited by H Downey. New York, Hoeber, 1938, p 25 11. Isamboulas N, Malikoosis X: Zur Frage der Cabotschen Ringkorper. Dtsch Arch Klin Med 184:183-184, 1939 12. Kass L: Histone biosynthesis in pernicious anemia proerythroblasts and megaloblasts. Blood 41:549-557, 1973
57
M.D.
Department of Internal Medicine (Simpson Memorial Institute), The University of Michigan, Ann Arbor, Michigan 48104
ABSTRACT
50 patients with untreated pernicious anemia were carefully reviewed. In only three instances, patients with erythrocytes containing Cabot rings were detected. From two of these patients, sufficient material was obtained prior to treatment to permit a variety of cytochemical studies. These studies were performed in an attempt to ascertain the composition of the Cabot ring. Peripheral blood films from these patients were stained for "reticulum" using brilliant cresyl blue as a supravital stain, DNA using the Feulgen reagent, 21 RNA and DNA using methyl-green pyronin, 21 glycogen using the PAS (periodic acidSchiff) reagent, 8 mitotic spindle fibers using Heidenhain's iron hematoxylin stain, 16 metachromatic substances using toluidine blue, 21 iron using the Prussian blue reagent 6 and 1% aqueous neutral red counterstain, histone using the alkaline fast green stain, 1 and arginine-rich and lysine-rich histone using the ammoniacal silver stain. 3 With this stain, arginine-rich
THIS REPORT describes cytochemical properties of Cabot rings in erythrocytes obtained from peripheral blood of two patients with classic untreated pernicious anemia. In the bone marrows of these two patients and in the peripheral blood of another patient who also had Cabot rings in erythrocytes of peripheral blood, apparent precursors of Cabot rings and actual Cabot rings were found in heavily stippled late intermediate megaloblasts. T h e results of these studies may afford insight into a possible pathogenetic basis for the formation of these unusual structures. Materials and Methods Wright-stained films of capillary peripheral blood and bone marrow from Received October 15, 1974; received revised manuscript December 3, 1974; accepted for publication December 3, 1974. Supported by the Elizabeth Roodvoets Memorial Grant for Cancer Research of the American Cancer Society (#CI-79) and by the National Cancer Institute Grant USPHS CA 14428-02. Address reprint requests to Dr. Kass. 53
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Kass, Lawrence: Origin and composition of Cabot rings in pernicious anemia. Am J Clin Pathol 64: 5 3 - 5 7 , 1975. Cytochemical studies were performed on erythrocytes containing Cabot rings from the peripheral blood of two patients with severe untreated pernicious anemia. These studies demonstrated that the Cabot ring contained arginine-rich histone and non-hemoglobin iron. Structures that may represent precursors of Cabot rings were found in stippled late intermediate marrow megaloblasts. T h e Cabot ring may result in part from abnormalities in metabolism of both iron and arginine-rich histone that are known to occur in pernicious anemia. (Key words: Cabot rings; Pernicious anemia; Erythrocytes.)
54
KASS
A.J. C.P. — Vol.64
histone appears brown or black, and lysine-rich histone appears yellow. Bone marrows from these patients were carefully studied in an attempt to identify possible precursors of Cabot rings in the megaloblastic erythroid precursors. In the instance where material was available, marrow films were also stained with the Prussian blue reagent and counterstained with 1% neutral red.
in the patients' peripheral bloods. These rings were composed of either basophilic or acidophilic stippled granules connected to one another by a red, strand-like material, giving the ring the appearance of a stippled "necklace." At times, "figure 8" configurations of the ring were observed. In most instances, the ring was associated with heavy basophilic and acidophilic stippling of the erythrocyte cytoplasm. Even when no gross stippling Results was seen, at least several coarse granules Cabot rings (Fig. 1, top row) were found could be observed adherent to the ring. in approximately 1 per 500 erythrocytes Cabot rings were not observed in cells that
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
FIG. 1. T o p row, two erythrocytes containing prominent Cabot rings. These rings appear as a "necklace" of stippled granules joined by a red-staining strand on Wright-stained film. Bottom row, what may be precursors of these stippled "necklaces" in peripheral blood erythrocytes within the cytoplasm of heavily stippled late megaloblasts in the bone marrow. Arrows point to loop of ring-shaped structures. In the megaloblast at bottom left, an actual ring form may be seen within the cytoplasms, x 1,800.
July 1975
55
CABOT RINGS IN PERNICIOUS ANEMIA
FIG. 2. Left, enlargement of the ring form in the cytoplasm of the cell illustrated in Fig. 1, bottom left, showing coarse granules connected by strandlike material. X 1,800. Right, late megaloblast stained with Prussian blue and counterstained with neutral red. A red-stained loop is seen in the cytoplasm, and siderotic granules adhere to the loop. This loop may be the precursor of or an actual Cabot ring, and suggests that it may be related to abnormalities in iron metabolism, x 1,500.
A**
/
late stippled megaloblasts in the bone marrow also appeared as a "necklace" of coarse granules connected to each other by a red-staining strand. Partial loops of this appearance were seen most frequently, but on several occasions, as seen in Figure 1, bottom row, left, and in Figure 2 (enlargement of the area in Figure 1), an actual ring or "figure-8" stippled "necklace" could be observed in the cytoplasm. In most instances, the "necklace" did not seem to show continuity with the nuclear chromatin, nor did it have the tinctorial properties of nuclear chromatin as visualized with ordinary Wright's stain. In one instance, a megaloblast stained with Prussian blue to demonstrate iron and counterstained with neutral red demonstrated a ring structure in the cytoplasm (Fig. 2). T h e ring appeared to consist of a red-staining thread to which bright blue siderotic granules adhered. Discussion Since Cabot's original report of ring bodies in pernicious anemia in 1903, 5 the nature of these structures has been a subject of lively controversy. In his original report, Cabot 3 illustrated stippled "necklace"-shaped and "figure-8" ring bodies similar to those found in the present study, and he believed but could not prove that these rings were nuclear remnants. Bostrom 4 postulated that two
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
contained reticulum as visualized by supravital staining with brilliant cresyl blue. Of the various cytochemical tests, only three demonstrated structures consistent with Cabot rings. Peripheral films stained with the Prussian blue reagent and counterstained with neutral red showed a thin red ring to which blue-stained particles adhered. Films stained with the alkaline fast green stain for histone showed a green ring surrounded by green-stained particles, some of which adhered to the ring. In peripheral blood films stained with the ammoniacal silver stain to identify lysine-rich and arginine-rich histones, a black ring or "figure-8" ring form was seen. Orange, brown, and black particles were seen attached to the ring and isolated within the cytoplasm of the erythrocyte. Notably, structures resembling Cabot rings were not observed in erythrocytes stained with reagents specific for DNA (Feulgen stain and methyl green stain). T h e second row of Figure 1 illustrates bone marrow erythroid precursors obtained from the patients. As delineated by the arrows, ring and loop structures could be observed within the cytoplasm of certain late intermediate megaloblasts. T h e megaloblasts that showed these ring structures most frequently were those that showed unusually abundant and coarse cytoplasmic basophilic and acidophilic stippling. As in the Cabot rings in the peripheral blood, the rings and loops in
I
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KASS
Vol.64
arginine-rich histone and nonhemoglobin iron. Although histone and iron were found to be the only substances demonstrable in Cabot rings in the present report, it is possible that there may be additional substances within the ring that might be demonstrable by other cytochemical reagents not utilized in these studies. The basis for the presence of argininerich histone and non-hemoglobin iron in the Cabot ring and the pathogenetic implications of these cytochemical findings can only be speculated upon at present. It is known that arginine-rich histones are synthesized within the cytoplasm of cells on polysomes 19 and that histone biosynthesis is abnormal in pernicious anemia. 12 In pernicious anemia there is also a defect in the metabolism and mobilization of iron, and this disorder has been considered a type of secondary acquired sideroblastic anemia.9"13,14 In the present study, Cabot ring precursors were found in late intermediate megaloblasts that showed unusually coarse cytoplasmic basophilic stippling. This type of coarse stippling is believed to be composed largely of non-hemoglobin iron. 17
In the present study, Cabot rings and their presumed precursors were found in late intermediate marrow megaloblasts. Other authors have also found these structures in megaloblasts in pernicious anemia and in erythroid precursors from patients with other types of anemias. In 1938, Isaacs 10 described and illustrated a late intermediate megaloblast from a paOn the basis of the available informatient with pernicious anemia that con- tion, it is possible that the spatial proximtained a large Cabot ring "entirely sepa- ity of iron and arginine-rich histone in the rate from the nucleus." Isamboulas and cytoplasm of the late i n t e r m e d i a t e Malikoosis,11 in 1939, also illustrated a megaloblast, combined with the known Cabot ring in an erythroid precursor abnormalities of both iron and histone in from a child who had typhus. Apparent pernicious anemia,9>12,13,17 facilitates an inprecursors of or actual Cabot rings have teraction between these two substances. also been observed in erythroid precur- Why this interaction should result in a sors by Picard 18 and by van Oye. 22 structure having the shape of a loop or a T h e results of cytochemical tests for "figure-8" is unknown. DNA in this study agree with the findings of others, 7,8 namely that the Cabot ring References does not contain DNA as demonstrated by 1. Alfert M, Geschwind II: A selective staining conventional staining methods. Unexpectmethod for the basic proteins of cell nuclei. edly, the present studies indicated that Proc Natl Acad Sci USA 39:991-999, 1953 2. Bessis M, Breton-Gorius J: Sur la strie bordante arginine-rich histone was found in the des erythrocytes des amphibiens et sur de Cabot ring, and that the granular material precendus "anneaux de Cabot." CR Soc Biol adherent to the ring contained both (Paris) 147:1134-1136, 1953
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
erythroid precursors in pernicious anemia were joined by a red-staining fiber of nuclear origin that became enclosed in a pseudopod of the erythroid precursor. This pseudopod then appeared as an erythrocyte containing a ring or "figures'' structure. Discombe 7 and Picard 18 were unable to demonstrate structures consistent with Cabot rings using stains for DNA. Picard 18 and van Oye 22 believed that Cabot rings were remnants of the mitotic spindle apparatus. In the present report, structures analogous to Cabot rings could not be demonstrated using Heidenhain's iron hematoxylin, a reagent commonly used to demonstrate the mitotic spindle apparatus. 16 In contrast to the postulates of the authors mentioned, other investigators 2,15,20 have concluded that Cabot rings are laboratory artifacts.
A.J.C.P.—
July 1975
CABOT RINGS IN PERNICIOUS ANEMIA
13. Kass L, Schnitzer B: Refractory Anemia. Springfield, 111., Charles C Thomas, 1975 14. Kass L: Pernicious Anemia. Philadelphia, W.B. Saunders, (in press) 15. L i n d e m a n n B: Uber die N a t u r d e r sog Cabotschen Ringkorper der Erythrozyten. Arch Exp Pathol Pharmakol 207:67-70, 1949 16. McClung CE: Handbook of Microscopical Techniques. Second edition. New York, Hoeber, 1937 17. McFadzean AJS, Davis LJ: Iron-staining erythrocytic inclusions with especial reference to acquired haemolytic anaemia. Glasgow Med J 28:237, 1947 18. Picard D: Nature et signification des anneaux de Cabot des hamaties. C R Soc Biol (Paris) 147:1451-1453, 1953 19. Robbins E, Borun TW: T h e cytoplasmic synthesis of histones in HeLa cells in its temporal relationship to DNA replication. Proc Natl Acad Sci USA 57:409, 1967 20. Schleicher EM: T h e origin and nature of the Cabot ring bodies of erythrocytes. J Lab Clin Med 27:983-1000, 1942 21. Thompson SW, Hunt RD: Selected Histochemical and His to pathological Methods. Springfield, 111., Charles C Thomas, 1966 22. Van Oye E: L'origine des anneaux de Cabot. Rev d'Hematol 9:173-179, 1954
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
3. Black MM, Ansley HR: Antigen-induced changes in lymphoid cell histones. I. Thymus. J Cell Biol 26:201-208, 1965 4. Bostrom L: La formation des anneaux de Cabot. Sang 18:67-68, 1947 5. Cabot RC: Ring bodies (nuclear remnants?) in anemic blood. J Med Res 9:15-19, 1903 6. Dacie JV, Lewis SM: Practical Haematology. Fourth edition. New York, Grune and Stratton, 1968, pp 1-568 7. Discombe G: L'origine des corps de Howell-Jolly et des anneaux de Cabot. Sang 19:262-264, 1948 8. Hayhoe FGJ, Quaglino D, Doll R: T h e Cytology and Cytochemistry of Acute Leukemias: A Study of 104 Cases. MRC Special Reports Series No. 304. London, H M Stationery Office, 1964, pp 1-104 9. Hines JD, Grasso JA: T h e sideroblastic anemias. Semin Hematol 7:86-106, 1970 10. Isaacs R: T h e erythrocyte, Handbook of Hematology. Volume 1. Edited by H Downey. New York, Hoeber, 1938, p 25 11. Isamboulas N, Malikoosis X: Zur Frage der Cabotschen Ringkorper. Dtsch Arch Klin Med 184:183-184, 1939 12. Kass L: Histone biosynthesis in pernicious anemia proerythroblasts and megaloblasts. Blood 41:549-557, 1973
57
