scholarly journals BLOOD CELL FORMATION AND DISTRIBUTION IN RELATION TO THE MECHANISM OF THYROID-ACCELERATED METAMORPHOSIS IN THE LARVAL FROG

1923 ◽  
Vol 38 (5) ◽  
pp. 529-541 ◽  
Author(s):  
H. E. Jordan ◽  
C. C. Speidel
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Metabolic Rate ◽  
Cell Formation ◽  
The Body ◽  
Red Bone Marrow ◽  
History Of ◽  
Regressive Change ◽  
Mesenchymal Precursor ◽  
Hemopoietic Organ

1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes in the hemopoietic centers and in the blood cell distribution in the various regions of the body. These changes are interpreted as results of the fundamental change in basal metabolic rate induced by the thyroid treatment. 2. There is initiation of the shift of hemopoietic locus from the kidney, the larval hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being chiefly an erythrocyte producer, becomes of greater importance with the transition from the lower metabolic rate to the higher, since greater erythropoiesis becomes necessary to supply the physical basis for the maintenance of the higher metabolic rate. 3. It is suggested that the appearance of red bone marrow in the later history of the frog is correlated with a still higher metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is also associated with higher metabolic rate. 4. The new metabolic rate initiated in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b) granulocytes and lymphoid phagocytes for distribution to regions of regressive change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and phagocytes, (2) for promoting growth of cells in regions of progressive change. 5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte (and its mesenchymal precursor), depends the extent to which metamorphosis will proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to keep pace with the demand for blood cells during metamorphosis results in metamorphic stasis, a condition of anemia which is usually followed by death. 6. The growth-promoting function of leucocytes, as demonstrated by Carrel, is probably to be ascribed to the lymphocyte component of leucocytes. 7. The granulocytes have probably also a glandular function, and may exert a lytic effect upon adjacent tissues in regions of regressive change.

scholarly journals THE VALUE OF PENICILLIN IN THE TREATMENT OF AGRANULOCYTOSIS CAUSED BY THIOURACIL

Blood ◽  
1946 ◽  
Vol 1 (1) ◽  
pp. 53-66 ◽  
Author(s):  
MARY CATHERINE TYSON ◽  
PETER VOGEL ◽  
NATHAN ROSENTHAL
Keyword(s):  
Bone Marrow ◽  
Antibacterial Agents ◽  
Bone Marrow Cells ◽  
The Body ◽  
Bacterial Invasion ◽  
Beneficial Effects ◽  
Penicillin Therapy ◽  
History Of ◽  
Per Se ◽  
Hemopoietic System

Abstract Thiouracil has been found to be an effective drug in the treatment of hyperthyroidism. Agranulocytosis following its use occurred in nine cases, four of which terminated fatally. In five others a complete and rapid recovery took place following penicillin therapy. The latter drug is believed to be ideal for all cases of agranulocytosis, and especially those in which chemotherapy has been used and may have been responsible for the condition. Thus far we have not seen any report of any untoward effect on the hemopoietic system from the use of penicillin. The use of antibacterial agents for the treatment of agranulocytosis was suggested by Dameshek and Wolfson21 in 1942. It was believed by these authors that patients with agranulocytosis died not of the leukopenia per se but of the sepsis which developed secondarily to the lack of granulocytes. Two very severe cases of aminopyrine agranulocytosis treated with sulfathiazole made complete recoveries. For the treatment of sulfonamide agranulocytosis, it was suggested that a preparation differing from that which had already been used be given. With the discovery of penicillin, and its complete lack of possible deleterious effect on the bone marrow, its use was suggested by Dameshek17 (1944). A report on the beneficial effects of this medication in a case of sulfonamide agranulocytosis was later reported by Dameshek and Knowlton18 and similar cases by Sprague and Ferguson19 and by Meredith and Fink.20 Since sulfonamides may cause further toxic effect on the bone marrow, we feel that their use should be avoided in the treatment of agranulocytosis, especially where a history of previous use is obtained. We do not agree with others21, 22 who continue the use of sulfonamides in the treatment of leukopenia or agranulocytosis where these very drugs may have been responsible for the condition. It would seem better judgment to use penicillin, which by combating the bacterial invasion of the body and the consequent toxemia enables the patient to survive until the bone marrow cells regenerate.

Expression of connexin 43 (Cx43) is critical for normal hematopoiesis

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 917-924 ◽  
Author(s):  
Encarnacion Montecino-Rodriguez ◽  
Hyosuk Leathers ◽  
Kenneth Dorshkind
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Blood Cell ◽  
Gap Junctions ◽  
Connexin 43 ◽  
Cell Formation ◽  
Cx43 Expression ◽  
Hematopoietic System ◽  
Blood Cell Formation

Abstract Gap junctions are intercellular channels, formed by individual structural units known as connexins (Cx), that allow the intercellular exchange of various messenger molecules. The finding that numbers of Cx43-type gap junctions in bone marrow are elevated during establishment and regeneration of the hematopoietic system has led to the hypothesis that expression of Cx43 is critical during the initiation of blood cell formation. To test this hypothesis, lymphoid and myeloid development were examined in mice with a targeted disruption of the gene encoding Cx43. Because Cx43−/− mice die perinatally, initial analyses were performed on Cx43−/−, Cx43+/−, and Cx43+/+ embryos and newborns. The data indicate that lack of Cx43 expression during embryogenesis compromises the terminal stages of primary T and B lymphopoiesis. Cx43−/− embryos and neonates had a reduced frequency of CD4+ and T-cell receptor-expressing thymocytes and surface IgM+cells compared to their Cx43+/+ littermates. Surprisingly, Cx43+/− embryos/neonates also showed defects in B- and T-cell development similar to those observed in Cx43−/− littermates, but their hematopoietic system was normal at 4 weeks of age. However, the regeneration of lymphoid and myeloid cells was severely impaired in the Cx43+/− mice after cytoablative treatment. Taken together, these data indicate that loss of a single Cx43 allele can affect blood cell formation. Finally, the results of reciprocal bone marrow transplants between Cx43+/+ and Cx43+/− mice and examination of hematopoietic progenitors and stromal cells in vitro indicates that the primary effects of Cx43 are mediated through its expression in the hematopoietic microenvironment.

X.—Mitosis and Cell Differentiation in the Blood

1944 ◽  
Vol 62 (1) ◽  
pp. 73-85 ◽  
Author(s):  
L. F. La Cour
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
The Body ◽  
Red Bone Marrow ◽  
Original Type

It was in 1878 that Ehrlich, with the aid of his triacid stain, described in terms of granulation of the cytoplasm six types of leucocytes. This marked the first real advance in our knowledge of the blood corpuscles. Present-day classification of cells in the blood-forming tissues gives six main groups with about thirty named types of cells. These fine subdivisions appear to represent different stages in different lines of development from one original type, chiefly by change in the shape of the resting nucleus. Divergence in opinion arises as to whether all these types of cell develop in the red bone marrow, or whether some arise elsewhere in the body.

Reduced Dose Lenalidomide Is Safe and Effective in Deletion (5q) MDS Patients with Severe Renal Impairment: Report of Two Cases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4624-4624
Author(s):  
Stefan Knop ◽  
Hermann Einsele ◽  
Ralf Bargou ◽  
Denise Cosgrove ◽  
Alan List
Keyword(s):  
Bone Marrow ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Blood Cell ◽  
The Body ◽  
World Health ◽  
Recombinant Erythropoietin ◽  
Unilateral Renal Agenesis ◽  
Increased Risk ◽  
Cytogenetic Remission

Abstract Introduction: Lenalidomide (Len) is highly active in the treatment of MDS with deletion 5q (del[5q]) (List et al. NEJM 2006). Patients with renal impairment have often been excluded from Len studies because of potential for delayed excretion with increased risk for adverse events. We present 2 MDS patients with 5q− syndrome and renal impairment who were treated with Len at reduced dosage. Patient 1: A 50-year-old woman presented with shortness of breath on exertion, pallor, and tachycardia. Laboratory tests showed hemoglobin (Hb) 3.9 g/dL with significant macrocytosis; white blood cell count (WBC) of 3.2 × 109/L; and creatinine 2.66 mg/dL (normal value, < 1.1 mg/dL). Bone marrow aspirate was consistent with World Health Organization 5q− syndrome. Abdominal ultrasound revealed unilateral renal agenesis. The patient required 2 packed red blood cell (RBC) units every 2 to 3 weeks. Glomerular filtration rate (GFR) was severely impaired (23 mL/min). Len was initiated at 5 mg/d and increased to 10 mg/d after 4 weeks. The patient showed a fast and sustained hematologic response, Hb of 10–11 g/dL without exogenous erythropoietin, and achieved transfusion independence within 6 weeks. Due to decreased WBC of 1.3 × 109/L, and a platelet count (plt) of 57 × 109/L, indicating thrombocytopenia, Len was adjusted to a daily alternating dose of 5 mg and 10 mg, respectively. Complete cytogenetic remission was achieved by 6 months of treatment. Patient 2: An 83-year-old female presented with sustained anemia despite treatment with recombinant erythropoietin. Bone marrow findings and peripheral blood features were consistent with the 5q− syndrome. The patient was transfusion dependent and received a single treatment cycle with azacitidine, but developed acute renal insufficiency, accompanied by an elevation in creatinine to 4.8 mg/dL. She continued supportive care measures receiving 2 units of RBC every 4 weeks. Len was initiated at 5 mg daily. GFR at start of therapy was moderately decreased (31 mL/min). After 6 weeks of treatment the patient developed a generalized rash, occupying 30–50% of the body, which subsided with temporary therapy cessation. Laboratory studies at 6 weeks revealed a WBC of 1.58 × 109/L, with an absolute neutrophil count (ANC) of 3.5 × 109/L, Hb of 12.3 g/dL and plt of 42 × 109/L. Because of progressive decline in the patient’s Hb levels Len was resumed 5 months later at a dose of 5 mg 3 times per week. This was well tolerated. Complete cytogenetic remission was achieved after 10 months of follow-up. Conclusions: These cases show that Len can be administered safely to MDS patients with renal insufficiency and with preserved clinical activity. In addition, the present observations suggest that Len therapy could abrogate the need for use of additional erythropoietin in these patients.

scholarly journals CHANGES IN OUTLYING BONE MARROW ACCOMPANYING A LOCAL INCREASE OF TEMPERATURE WITHIN PHYSIOLOGICAL LIMITS

1936 ◽  
Vol 64 (2) ◽  
pp. 253-274 ◽  
Author(s):  
Charles Huggins ◽  
B. H. Blocksom
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Common Factor ◽  
Cell Formation ◽  
Fat Distribution ◽  
Low Oxygen ◽  
Physiological Limits ◽  
Red Marrow ◽  
Normal Differentiation ◽  
Adult Bone

A great difference exists in the adult bone marrow of central bones as compared with outlying bones of the mammalia and avia, the distal bones being at a great disadvantage from the standpoint of blood cell production. Several experimental procedures are reported by which this disadvantage is overcome and in consequence fatty marrow of outlying bones is replaced by red marrow occurring chiefly at the epiphyseal regions, unless a low oxygen stimulus is also provided when marrow of the diaphysis becomes involved. A common factor in all of the experiments was an elevation of temperature beyond that prevailing in these distal regions, and it is felt that the evidence warrants the opinion that the cause of improvement is thermal. In some experiments, blood cell formation was increasing while the heat was adversely affecting the testis. The experiments permit construction of a general theory of fat distribution in bone marrow. In certain grafts of precartilage to other rats, normal differentiation into bone, cartilage, and marrow occurred, while in others cartilage and very small amounts of primitive marrow developed with slight, or no bone formation. Cartilage was always successfully engrafted. The capacity to form sinusoids in bone marrow is determined by the nature of the tissue rather than by the ingrowing endothelium.

scholarly journals THE INFLUENCE OF PROTEIN-FREE LIVER AND SPLEEN EXTRACTS ON THE BLOOD REGENERATION AND RESPIRATORY EXCHANGE OF ANEMIC RABBITS

1927 ◽  
Vol 46 (5) ◽  
pp. 689-698 ◽  
Author(s):  
A. Jeney
Keyword(s):  
Bone Marrow ◽  
Heat Production ◽  
Liver Extract ◽  
The Body ◽  
Disturbing Factor ◽  
Red Bone Marrow ◽  
Histological Data

1. Respiratory exchange measurements may be used for gaining further evidence concerning the body changes during anemia, and are complementary to the hematological and histological data. 2. The heat production during anemia was slightly decreased. At the 3rd week it began to rise. 3. A protein-free liver extract has accelerated blood regeneration and at the same time increased the respiratory exchange of anemic animals. 4. A protein-free spleen extract has distinctly lowered the respiratory exchange of normal animals. The metabolism of anemic animals thus treated was practically the same as before bleeding and treatment. The recovery of the spleen extract-treated animals was not complete during the period of observation. This extract may have been somewhat toxic. In spite of this disturbing factor we are not inclined to accept the view of C. D. and E. W. Leake (15) and Thalhimer (16) that the spleen takes part in the stimulating effect upon blood regeneration when given in combination with red bone marrow by mouth.

scholarly journals Continued blood cell formation in spherical bodies in a long-term mouse spleen culture

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1211-1217
Author(s):  
Y Matsuya ◽  
N Yanai ◽  
H Ohtani ◽  
H Naganuma ◽  
M Obinata
Keyword(s):  
Blood Cell ◽  
Cell Formation ◽  
Three Dimensional ◽  
Cell Types ◽  
Spherical Body ◽  
The Body ◽  
Dimensional Structure ◽  
Newborn Mice ◽  
Prolonged Culture

During the primary culture of spleen fragments of newborn mice, a spherical body (d = circa 200 to 300 microns) as a three-dimensional cellular organization was formed. Continued production of blood cells from the spherical body was observed without changing its size for about 2 months of culture. Without growth factor, the spherical bodies produced mainly lymphocytes and macrophages. Addition of interleukin-3 enhanced their granulocyte formation, and this enhancement was observed even after a prolonged maintenance without growth factors. The spherical bodies were composed of a uniform mixture of endothelial cells and fibroblasts within the body, and cell-cell contacts between lymphocytes and fibroblasts were notable in the periphery. With prolonged culture, the spherical bodies showed a definite change in their structure by sorting two cell types and the blood cell production gradually decreased. These results suggested that a three-dimensional structure was required for the maintenance, growth, and differentiation of blood cell progenitors in the long-term spleen culture.

scholarly journals PSVIII-6 Cytomorphological features of the bone marrow of hypotrophic piglets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 256-256
Author(s):  
Evgeniy Mikhaylov ◽  
Yulia Shaposhnikova ◽  
Boris Shabunin ◽  
Igor Tolkachev ◽  
Svetlana Vorotnikova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Flow ◽  
Uranyl Acetate ◽  
The Body ◽  
Red Bone Marrow ◽  
Ultrastructural Studies ◽  
Differentiated Cells ◽  
Blast Cells ◽  
Ultrathin Sections ◽  
Bone Marrow Function

Abstract The experiment was conducted on newborn hypotrophic piglets obtained from sows of the 3rd–4th farrow on the farm in the Voronezh region. Bone marrow for histochemical and ultrastructural studies was selected from hypotrophic piglets with a body weight less than 800 g (n = 13). The material for electron microscopy was carried out in 2.5% glutaraldehyde in 0.114 M colloid buffer in the cold with postfixation in 1% solution of osmium tetroxide in the same buffer. The material was enclosed in epon-812. Semithin sections were stained with azur-2 in combination with the main fuchsin and were examined under Leica light microscope. Ultrathin sections were prepared on Ultracut (Leica) ultramicrotome, contrasted with lead citrate and uranyl acetate and examined under EM-208 (Philips) electron microscope. In hypotrophic piglets, the cells forming in the red bone marrow are located as islands. Hypoplasia of cells of the hemopoetic series occurred, proerythroblasts and megacaryoblasts were observed in insignificant quantity. Megakaryocytes were closely adjacent to sinusoidal capillaries, and a part of their cytoplasm penetrated into the lumen of blood vessels. Separating fragments of cytoplasm in the form of platelets were transferred to the blood flow. Light mitochondria with a few small electron-dense cristae were observed in the ultrastructure of cells of the bone marrow. The emergence of immature forms, which indicated bone marrow function disorder or its barrier damage, was also observed in the blood flow. At the same time there occurred a decrease in the number of differentiated cells and their differentiation disorder, which could lead to immunodeficiency state. Differentiation of cells in the bone marrow of hypotrophic piglets is impaired, and that is why the body is not provided with a sufficient number of blood cells. Blast cells, which appear in the blood flow, cannot fully perform their functions, resulting in immunodeficiency and anemia.

Expression of connexin 43 (Cx43) is critical for normal hematopoiesis

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 917-924
Author(s):  
Encarnacion Montecino-Rodriguez ◽  
Hyosuk Leathers ◽  
Kenneth Dorshkind
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Blood Cell ◽  
Gap Junctions ◽  
Connexin 43 ◽  
Cell Formation ◽  
Cx43 Expression ◽  
Hematopoietic System ◽  
Blood Cell Formation

Gap junctions are intercellular channels, formed by individual structural units known as connexins (Cx), that allow the intercellular exchange of various messenger molecules. The finding that numbers of Cx43-type gap junctions in bone marrow are elevated during establishment and regeneration of the hematopoietic system has led to the hypothesis that expression of Cx43 is critical during the initiation of blood cell formation. To test this hypothesis, lymphoid and myeloid development were examined in mice with a targeted disruption of the gene encoding Cx43. Because Cx43−/− mice die perinatally, initial analyses were performed on Cx43−/−, Cx43+/−, and Cx43+/+ embryos and newborns. The data indicate that lack of Cx43 expression during embryogenesis compromises the terminal stages of primary T and B lymphopoiesis. Cx43−/− embryos and neonates had a reduced frequency of CD4+ and T-cell receptor-expressing thymocytes and surface IgM+cells compared to their Cx43+/+ littermates. Surprisingly, Cx43+/− embryos/neonates also showed defects in B- and T-cell development similar to those observed in Cx43−/− littermates, but their hematopoietic system was normal at 4 weeks of age. However, the regeneration of lymphoid and myeloid cells was severely impaired in the Cx43+/− mice after cytoablative treatment. Taken together, these data indicate that loss of a single Cx43 allele can affect blood cell formation. Finally, the results of reciprocal bone marrow transplants between Cx43+/+ and Cx43+/− mice and examination of hematopoietic progenitors and stromal cells in vitro indicates that the primary effects of Cx43 are mediated through its expression in the hematopoietic microenvironment.

scholarly journals Continued blood cell formation in spherical bodies in a long-term mouse spleen culture

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1211-1217 ◽  
Author(s):  
Y Matsuya ◽  
N Yanai ◽  
H Ohtani ◽  
H Naganuma ◽  
M Obinata
Keyword(s):  
Blood Cell ◽  
Cell Formation ◽  
Three Dimensional ◽  
Cell Types ◽  
Spherical Body ◽  
The Body ◽  
Dimensional Structure ◽  
Newborn Mice ◽  
Prolonged Culture

Abstract During the primary culture of spleen fragments of newborn mice, a spherical body (d = circa 200 to 300 microns) as a three-dimensional cellular organization was formed. Continued production of blood cells from the spherical body was observed without changing its size for about 2 months of culture. Without growth factor, the spherical bodies produced mainly lymphocytes and macrophages. Addition of interleukin-3 enhanced their granulocyte formation, and this enhancement was observed even after a prolonged maintenance without growth factors. The spherical bodies were composed of a uniform mixture of endothelial cells and fibroblasts within the body, and cell-cell contacts between lymphocytes and fibroblasts were notable in the periphery. With prolonged culture, the spherical bodies showed a definite change in their structure by sorting two cell types and the blood cell production gradually decreased. These results suggested that a three-dimensional structure was required for the maintenance, growth, and differentiation of blood cell progenitors in the long-term spleen culture.

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