scholarly journals EXPERIMENTAL PRODUCTION OF A NUTRITIONAL MACROCYTIC ANEMIA IN SWINE

Blood ◽  
1949 ◽  
Vol 4 (4) ◽  
pp. 301-323 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
BETTY TATTING ◽  
HELEN ASHENBRUCKER ◽  
M. M. WINTROBE
Keyword(s):  
Bone Marrow ◽  
Urinary Excretion ◽  
Vitamin B12 ◽  
Mononuclear Cells ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Experimental Production ◽  
Extrinsic Factor ◽  
Pteroylglutamic Acid ◽  
Crude Preparation

Abstract 1. A deficiency of pteroylglutamic acid has been produced in 32 swine fed a purified diet containing casein and supplemented with seven B vitamins, sulfasuxidine and a folic acid antagonist. The casein was fed at two levels, 10 and 26 per cent. Two types of casein were used: a crude preparation possessing significant "extrinsic factor" activity and a purified casein with little activity. 2. The hematologic manifestations observed were (a) severe macrocytic anemia, (b) leukopenia, due to a proportionately greater reduction in polymorphonuclear than in mononuclear cells, (3) slight thrombocytopenia, and (4) hyperplastic bone marrow with an increase in immature nucleated red cells which resemble the megaloblasts seen in the bone marrow of patients with pernicious anemia. 3. The feeding of a 26 per cent rather than a 10 per cent crude casein diet did not prevent but did delay the onset of the blood changes. Anemia developed most rapidly in the animals receiving 10 per cent purified casein. 4. The group receiving 26 per cent casein developed a greater degree of macrocytosis in the same period of time than did the group receiving 10 per cent casein. In all groups the degree of macrocytosis increased as the duration of the anemia increased. 5. The hematologic manifestations were not delayed nor was their development prevented by the intramuscular administration of 15 U.S.P. units of liver extract every 15 days. 6. The blood and bone marrow returned rapidly to normal following the administration of pteroylglutamic acid, pteroyldiglutamic acid, pteroyltriglutamic and pteroylheptaglutamic acid. Thymine and xanthopterin had little or no activity. Tyrosine, adenine and uracil were inactive. 7. Purified liver extracts and crystalline vitamin B12 were found to possess some hemopoietic activity in several animals but the activity was considerably less than that of the pteroylglutamic acid compounds. 8. The urinary excretion of "tyrosyl" (hydroxphenyl compounds) was not abnormal in the pteroylglutamic acid deficient pigs and was not altered by either pteroylglutamic acid or liver extract therapy. 9. The urinary excretion of allantoin and uric acid did not differ significantly from the normal. Immediately following therapy with pteroylglutamic acid, however, in association with the reticulocytosis and lasting for the same period, there was a marked increase in the excretion of allantoin. 10. The results suggest that both pteroylglutamic acid and a factor in liver extract similar to or identical with vitamin B12 are required for normal hemopoiesis in the pig.

scholarly journals Experimental Production of Nutritional Macrocytic Anemia in Swine

Blood ◽  
1952 ◽  
Vol 7 (10) ◽  
pp. 992-1004 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
BETTY TATTING ◽  
DORIS KURTH ◽  
M. M. WINTROBE
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Soybean Protein ◽  
Macrocytic Anemia ◽  
Experimental Production ◽  
Vitamin Supplement ◽  
Normal Limits ◽  
Erythroid Hyperplasia ◽  
Pteroylglutamic Acid

Abstract A total of 20 swine were fed a diet adequate in all known respects except that soybean protein was substituted for casein, succinylsulfathiazole and a folic acid antagonist were added, and vitamin B12 and pteroylglutamic acid were withheld from the vitamin supplement. The animals developed macrocytic anemia, leukopenia and neutropenia, accompanied by erythroid hyperplasia of the bone marrow. Tue erythroblasts consisted mainly of immature macronormoblasts but a few atypical megaloblasts were also observed. The anemia responded rapidly and completely to the administration of both vitamin B12 and pteroylglutamic acid. The administration of pteroylglutamic acid alone resulted in an immediate return of the blood and bone marrow to within normal limits but after several months there was a partial hematologic relapse in spite of continued therapy with this vitamin. The administration of vitamin B12 alone resulted in only partial remission of the anemia and the bone marrow remained macronormoblastic although the megaloblasts tended to disappear. Growth of the animals was stimulated by the administration of either vitamin but the administration of both vitamins simultanseously resulted in the greatest rate of growth. No manifestations of neurologic disturbances or of inscreased pigment excretion were observed in the deficient swine.

scholarly journals Hematologic Manifestations of Vitamin B12 Deficiency in Swine

Blood ◽  
1951 ◽  
Vol 6 (10) ◽  
pp. 867-891 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
BETTY TATTING ◽  
JEAN ROBINSON ◽  
N. M. FELLOWS ◽  
F. D. GUNN ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Liver Damage ◽  
Megaloblastic Anemia ◽  
Macrocytic Anemia ◽  
Vitamin B12 Deficiency ◽  
Deficiency Anemia ◽  
Severe Neutropenia ◽  
Pteroylglutamic Acid ◽  
B12 Deficiency

Abstract In an effort to produce a deficiency of vitamin B12 a total of 70 pigs were fed a purified diet containing soybean alpha protein in place of casein. One group of animals was started on the diet at 2 to 7 days of age. A second group began at 21 to 28 days of age. Methionine, iodinate casein, desiccated thyroid and pteroylglutamic acid were added to the diet of certain animals and! omitted from the diet of other pigs. In addition, 9 pigs were gastrectomized. Forty-three of the animals survived for a sufficiently long period of time for adequate evaluation of the results of the experiment. Severe liver damage was observed in 24 of the 25 animals autopsied. The only animal not showing liver damage received vitamin B12 from the beginning of the experiment. Necrosis of the liver cells, fatty infiltration, or both, occurred in the presence of a high fat diet containing apparently adequate amounts of protein, choline, vitamin E and methionine. These pathologic changes were apparently prevented but not reversed by the administration of vitamin B12. Growth of the animals on the above diets without added vitamin B12 was retarded as compared with the growth of animals on the same diet supplemented with this vitamin. The administration of vitamin B12 to the deficient animals resulted in rapid growth. Of the 39 animals not receiving vitamin B12 13 failed to develop anemia, 16 developed a mild anemia and in 10 a moderately severe anemia was present. When present the anemia was normocytic and in 24 pigs was accompanied by a moderately severe neutropenia. Differential cell counts on the sternal marrow were normal except for a slight increase in the proportion of normoblasts. These hematologic alterations were neither consistently or completely corrected by the administration of vitamin B12 in spite of the fact that definite and sometimes marked reticulocyte increases followed. When methionine deficiency was associated with vitamin B12 deficiency, anemia appeared to be more severe. The administration of aureomycin, an "animal protein factor," did not stimulate growth and failed to induce a hemopoietic response. There was no macrocytic anemia, the bone marrow was not megaloblastic, and neurologic disturbances or morphologic alterations in the neutrophils were not observed. These results are in contrast to those obtained in pigs with an experimentally produced deficiency of pteroylglutamic acid. Such animals develop macrocytic anemia, leukopenia and a macronormoblastic type of bone marrow. It is not possible to give with any assurance the reason why megaloblastic anemia was not produced in the "B12-deficient" animals. This may have been due to the fact that (1) the deficiency was not sufficiently severe to result in such a change in the hemopoietic system; or (2) because pteroylglutamic acid prevents the development of megaloblastic anemia even in the absence of vitamin B12.

scholarly journals Microspectrophotometric Determination of Desoxyribosenucleic Acid in Megaloblasts of Pernicious Anemia

Blood ◽  
1951 ◽  
Vol 6 (4) ◽  
pp. 344-349 ◽  
Author(s):  
EDWARD H. REISNER ◽  
ROY KORSON
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Blood Cells ◽  
Nuclear Dna ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Gradual Loss

Abstract 1. In 9 patients with various types of megaloblastic anemia responding to treatment with vitamin B12, folic acid or liver extract, no significant deviations from the normal amounts of total or polymerized DNA were observed in the nuclei of red blood cells in marrow smears. 2. During the maturation of megaloblasts in the bone marrow there is a gradual loss of nuclear DNA. 3. This pattern is quantitatively and qualitatively similar for normal marrow and for that of pernicious anemia in relapse and after treatment.

scholarly journals Factors affecting formiminoglutamic acid excretion in vitamin B12 deficiency

1970 ◽  
Vol 116 (4) ◽  
pp. 681-688 ◽  
Author(s):  
Hedley R. Marston ◽  
Shirley H. Allen
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Acid Excretion ◽  
Factors Affecting ◽  
Methyl Donors ◽  
Pteroylglutamic Acid ◽  
B12 Deficiency ◽  
Acid Status

1. Formiminoglutamic acid, a product of the catabolism of histidine, is excreted in abnormally large amounts in the urines of vitamin B12-deficient rats and of vitamin B12-deficient sheep; the excretion is reduced to negligible amounts after administration of vitamin B12. 2. After administration of certain methyl donors to vitamin B12-deficient rats or sheep urinary excretion of formiminoglutamic acid is temporarily decreased. 3. Irrespective of the pteroylglutamic acid status of the animals neither vitamin B12-deficient rats nor vitamin B12-deficient sheep have the ability to deal efficiently with histidine. 4. In sheep, urinary excretion of formiminoglutamic acid is increased after administration of aminopterin; treatment with pteroylglutamic acid restores the ability of the animal to deal with the catabolic products of histidine. 5. The possible functions of vitamin B12 and methionine in relieving a virtual deficiency of pteroylglutamic acid are discussed.

scholarly journals CLINICOETIOLOGICAL EVALUATION OF THE PATIENTS OF MACROCYTIC ANEMIA PRESENTING AT A TERTIARY CARE CENTRE IN KUMAON REGION OF UTRRAKHAND

2021 ◽  
pp. 11-14
Author(s):  
Harish Chandra Arya ◽  
Ashok Kumar
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Tertiary Care ◽  
Macrocytic Anemia ◽  
Clinical Manifestations ◽  
Cobalamin Deficiency ◽  
Dietary Habit ◽  
Thyroid Disorder ◽  
Care Centre ◽  
Tertiary Care Centre

INTRODUCTION: Macrocytosis is common in various clinical settings and it is found in approximately 1.7– 3.6% of people admitted for care for any cause [1, 2, 3]. Macrocytic anemia is generally classified as megaloblastic or nonmegaloblastic anemia. The causes of macrocytosis fall into two groups: (a) deficiency of vitamin B12 (cobalamin) or folate (or rarely abnormalities of their metabolism) in which the bone marrow is megaloblastic and (b) other causes,in which the bone marrow is usually normoblastic.A high level of suspicion,proper elicitation of the history and thorough examination and investigation of the patient helps in the diagnosis of macrocytic anemia. AIM AND OBJECTIVES: To evaluate the etiology of macrocytic anemia at a tertiary care centre. To determine the etiology of macrocytic anemia.To evaluate clinical manifestations associated with macrocytic anemia. MATERIAL AND METHOD: This 21 month Cross sectional observational study was carried out in OPD/IPD Department of Medicine, Government Medical College Haldwani (Uttarakhand). Full clinical examination and information regarding alcohol intake, dietary habit, drug intake, thyroid disorder and other comorbid illnesses was obtained.All patients were investigated with a completeHaemogramLiver function tests Serum TSH fasting vitamin B12 was measured Ultrasound as and when required. RESULT: In this study106 patients were taken 58 (45.3% ) were male and 48(54.7%) were females. Mean age was 44.83+16.85 years.Hemoglobin and MCV was in the range of 6.42 ± 2.09,(108.24 ± 7.10) respectively .The majority of patient,28 (52.83%) had vit B12 level in the range of 101 – 200 pg/ml,The majority of patients,44 (41.1%) had LDH level in the range of 281 – 1000 IU/L . CONCLUSION: In this study, there was a preponderance of young people.Vegetarians were most susceptible to MA especially cobalamin deficiency. Nutritional deficiency was the most common cause of MA, followed by alcohol and alcoholic liver disease.Data regarding the magnitude of the problem in different parts of India and the factors that might influence its incidence were lacking. Macrocytic anemia must be considered in the differential diagnosis of patients presenting with pyrexia of unknown origin,mild icterus or pancytopenia.

Fli-1 and EKLF Gene Expression in Patients with MDS 5q- Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2788-2788 ◽  
Author(s):  
Radana Neuwirtova ◽  
Ota Fuchs ◽  
Dana Provaznikova ◽  
Jaroslav Cermak ◽  
Magda Siskova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Transcription Factors ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Macrocytic Anemia ◽  
Gene Expression Measurement ◽  
Healthy Controls ◽  
Average Value

Abstract Abstract 2788 Poster Board II-764 Introduction. Patients with MDS-5q- syndrome have macrocytic anemia often with hypoplastic erythropoiesis and on the contrary thrombocythemia with effective though dysplastic megakaryopoiesis. Megakaryocytes and erythroid cells are thought to share a common progenitor MEP (T.P.McDonald et al., Exp. Hematology 1993). There are two key transcription factors which together with other transcription factors and relevant cytokines and receptors determine the hemopoietic differentiation of the common stem cell: erythroid Krüppel-like factor (EKLF) for erythroid lineage and Friend leukemia virus integration 1 (FLi-1) for megakaryopoiesis (Pilar Frontelo et al., Blood 2007; G.A.Blobel, Blood 2007; F.Bouilloux et al., Blood 2008). There is functional cross antagonism between FLi-1 and EKLF (J.Starck et al., Mol. Cel. Biology 2003). FLi-1 is active only if dephosphorylated (H.Huang et al., ASH Abstracts 2008). The question is whether both factors play any role in 5q- syndrome. Methods. FLi-1 and EKLF gene expressions were determined in mononuclear cells isolated from the whole blood or bone marrow using Ficoll-Paque PLUS. Expression of both factors was measured by quantitative real-time PCR. RT-PCR products were verified by electrophoresis and direct sequencing. The assays were performed for sample in duplicate. Glyceraldehyd-3-phosphate dehydrogenase (GAPDH), FLi-1 and EKLF were amplified in 25 μl reaction mixture containing 12.5 μl SYBR Green JumpStart Taq Ready Mix, 2.5 μl 2 μM FLi-1 or EKLF forward and reverse primers, 0,25 μl internal reference dye and 1 μl cDNA. Relative levels of FLi-1 and EKLF mRNAs were calculated to the level of housekeeping GAPDH mRNA. Results. FLi-1 and EKLF were measured in blood mononuclear cells of 8 patients fulfilling all criterias of 5q- syndrome. FLi1mRNA/GAPDHmRNA was higher in all samples, average value was 0.0930 (0.0242-0.4274) compared to control value 0.0194. FLi1mRNA/GAPDHmRNA in bone marrow mononuclear cells of 7 patients with 5q- syndrome was higher in all samples but one. The average value was 0.0827 (0.0070-0.2554) compared to healthy controls 0.0044. EKLF gives very low values in the majority of patients′ blood and bone marrow samples as well as in healthy controls. The evaluation is therefore less reliable then FLi-1 assessment. EKLFmRNA/GAPDHmRNA in blood was 0.0004 (0.0-0.0023) compared to the control 0.0222. The results of EKLF in 5 bone marrow samples are inconsistent. Three are lower than the control (0.0068), 1 of remaining 2 samples is extremely high (0.3491). It is interesting that this patient is the only one who responded to erythropoietin and is transfusion independent. Summary. Our preliminary results with FLi-1 and EKLF gene expression measurement are in agreement with expected findings: increased FLi-1 expression corresponds to thrombocytemia in 5q- syndrome patients and expression of EKLF, lower than in controls would correspond to anemia in these patients. However, EKLF values are less reliable because of very low values in patients as well as in controls and because of inconsistent results in bone marrow samples. We prepare to follow both factors in 5q- patients after the treatment with lenalidomide. Lenalidomide improves anemia in 5q- syndrome patients and temporarily causes decrease of thrombocytes (A.List et al., N.Engl.J.Med. 2005, 2006). Inhibition of phosphatases by lenalidomide (S.Wei et al., Proc.Natl.Acad.Sci.USA 2009) can stop FLi-1 dephosphorylation which leads to FLi-1 inactivation. Hypotetically inactive FLi-1 would enable EKLF to induce MEP into erythroid lineage. Supported by MSM 0021620808 Disclosures: No relevant conflicts of interest to declare.

scholarly journals LIVER EXTRACT REFRACTORY MEGALOBLASTIC ANEMIA

Blood ◽  
1949 ◽  
Vol 4 (10) ◽  
pp. 1117-1123 ◽  
Author(s):  
JOHN F. MUELLER ◽  
V. R. HAWKINS ◽  
RICHARD W. VILTER
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Macrocytic Anemia ◽  
Mass Action ◽  
Deficiency Anemia ◽  
Normal Limits ◽  
Unknown Factor ◽  
Relationship Of

Abstract 1 . The patient described in this report had macrocytic anemia, megaloblastic maturation arrest in the bone marrow, glossitis, hyper-reflexia and diminished vibration perception in the feet. None of these abnormalities was improved by liver extract or vitamin B12 but all responded rapidly to folic acid except the neurologic signs. 2. This patient appears to have had a megaloblastic anemia which has been described in European clinics under the names "achrestic anemia" and "refractory megaloblastic anemia." It appears to be similar to "Wills" factor deficiency anemia" and some cases of pernicious anemia of pregnancy. 3. This patient did not appear to have a primary deficiency of folic acid since the excretion of this substance in the urine was within normal limits. A deficiency of an unknown factor probably equivalent to "the Wills’ factor" is suggested. 4. It seems likely that folic acid induced a remission in this case by a "mass action" effect. The possible relationship of folic acid, vitamin B12, the unknown factor and liver extract to nucleo-protein synthesis is discussed.

scholarly journals THE COINCIDENCE OF MEDITERRANEAN ANEMIA AND PERNICIOUS ANEMIA IN A YOUNG SICILIAN

Blood ◽  
1949 ◽  
Vol 4 (11) ◽  
pp. 1267-1270 ◽  
Author(s):  
WILLIAM H. CROSBY ◽  
HARRY J. SACKS
Keyword(s):  
Bone Marrow ◽  
Pernicious Anemia ◽  
Peripheral Blood ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Target Cells ◽  
Oval Cell ◽  
Blood Picture

Abstract 1. Coincidental Mediterranean anemia and pernicious anemia were found in a 26 year old soldier of Sicilian parentage. 2. The diagnosis of pernicious anemia was made on the finding of achlorhydria after histamine, glossitis, megaloblastic bone marrow and macrocytic anemia which responded to liver extract on two occasions. 3. The diagnosis of mild Mediterranean anemia was made by finding the target-oval-cell trait in the patient and in five members of his family. 4. It is of interest that target cells were not found in the peripheral blood until treatment with liver was begun. While pernicious anemia dominated, the character of the peripheral blood picture was macrocytic. Liver therapy corrected this, whereupon "hypochromic polycythemia" characteristic of mild Mediterranean anemia was found.

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