Rinsho Ketsueki
Online ISSN : 1882-0824
Print ISSN : 0485-1439
ISSN-L : 0485-1439
Volume 19, Issue 7
Displaying 1-18 of 18 articles from this issue
  • Koichiro TAKESHIGE, Shigeki MINAKAMI
    1978 Volume 19 Issue 7 Pages 889-896
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Particles come into contact with the cell surface of leucocytes and the membrane is excited. The information may be transmitted to a cyanide-insensitive oxidase through a transducing system. Activation of the enzyme oxidizes NADPH or NADH and causes. increased oxygen uptake. The oxidase generates superoxide anions and other active oxygens, namely hydrogen peroxide, hydroxyl radicals, and singlet oxygen. They constitute a powerful defense against invading microorganisms in combination with lysosomal enzymes. Simultaneously with the oxidative burst, glycolysis and hexose-mono-phosphate shunt are stimulated in order to supply reduced nicotinamide coenzymes.
    There are many substances, so called “metabolic mimickers”, which can induce metabolic changes without causing endocytic reaction.
    Using cytochalasin D, which is one of the metabolic mimickers and discovered in our laboratory, metabolic changes and some characteristics of NAD (P) H oxidase in granule fractions have been studied.
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  • Yohnosuke KOBAYASHI
    1978 Volume 19 Issue 7 Pages 897-903
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Chronic granulomatous disease (CGD) is a group of inherited diseases of the phagocytes characterized by their defective ability to kill normally ingested bacteria and is clinically manifested by recurrent and intractable bacterial infections. Phagocytosis by normal polymorphonuclear leukocytes is associated with an increase in aerobic metabolism. This includes a cyanide-insensitive burst of oxygen consumption, stimulation of glucose oxidation through hexose monophosphate shunt (HMPS) and an increase of intermediate products of oxygen reduction, such as superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radical and potentially other oxygen species. Metabolically, CGD leukocytes fail to show the above mentioned events associated with normal bactericidal action. Simple and reliable methods using a small amount of blood specimen are now available for the quantitative determination of these leukocyte functions and are used for the diagnosis of the disease and detection of the carriers.
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  • Yoshiro TSUJI, Joshiu MATSUDA, Hiroyuki NODA
    1978 Volume 19 Issue 7 Pages 904-908
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    The measurement of neutrophil chemotaxis is one of the most important part of the leukocyte function.
    Usually in vivo, a skin window method is used and in vitro a millipore filter method. Additionally we have demonstrated a quite new method, an agarose plate method.
    Using it we measured 10 diseases in which millipore filter method had proved to have decreased chemotaxis and found them to be normal with newborn infant and Down's syndrome. This difference seems to result from the fact that our agarose plate method measures not only chemotaxis but also chemokinesis. By measuring 55 diseases, totally 600 times, our method proved that reduced chemotaxis was found in the following diseases; severe bacterial infection, cord blood, neonatal hyperbiliruminemia, CGD, preleukemia, CMCC+hyper Ig-E, severe combined immunodeficiency, Lettere-Siwe Syndrome, lazy-lukocyte syndrome, uremia, recurrence infectious mononucleosis, partial lipodystrophy with hypocomplement, ataxia telangiectasia. But in rheumatid arthritis, SLE, juvenile diabetes mellitus, patients on high dose steroids, burns, measles and malignancies chemotaxis was normal.
    It seems that a disease does not become a FATAL only by its chemotactic abnormality.
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  • Kaoru YAMAGATA, Kiyoharu TAKIKAWA
    1978 Volume 19 Issue 7 Pages 909-916
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Attempts were made to assess in vitro chemotactic, phagocytic, and bactericidal activity of neutrophils in addition to nitroblue tetrazorium (NBT) test respectively in patients with acute bacterial infection, chronic myelogenous leukemia, collagen disease, especially systemic lupus erythematodes, and malignancy.
    In vitro chemotactic activity to bacterial lipopolysaccharide (LPS) was made according to Baum's method, slightly modified Boyden's method. Phagocytic activity was assessed by counting bacteria ingested by neutrophils on the smear preparation. Bactericidal activity was determined according to Quie's method with slight modification. NBT test was made according to Baehner's quantitative, and histochemical method by using of leukocyte monolayer on the slide glass.
    In acute bacterial infection chemotactic activity of neutrophils was decreased but bactericidal activity and NBT reduction were increased as compared with normal control. Furthermore the higher the bactericidal activity and NBT reduction were, the lower the phagocytic activity, but there was no significant correlation between bactericidal activity and NBT reduction.
    NBT test did not directly reflect the ability of intracellular killing of neutrophils, but it was suggested that NBT test was able to be employed for clinical use as one of the parameter of the bactricidal activity of neutrophils.
    In systemic lupus erythematodes decreased chmotactic and phagocytic activity, and normal bactericidal activity with lowered NBT reduction of neutrophils, and in chronic myelogenous leukemia decreased chemotactic activity and NBT reduction of neutrophils were observed.
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  • Nobuo AOKI
    1978 Volume 19 Issue 7 Pages 917-919
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Blood coagulation and fibrinolysis are the results of the sequential activation of a group of protein-cleaving enzymes (proteinases). Many components of the coagulation and fibrinolysis pathways exsist in the circulation as enzyme precursors, which become activated when specific peptide bonds are cleaved by proteinases. These proteolytic mechanisms are controled by natural inhibitors. Five major proteinase inhibitors are known. These are α2-macroglobulin, α2-plasmin inhibitor, antithrombin III, α1-antitrypsin and Cl-inactivator. General properties of the interactions of these inhibitors with enzymes and the methods to study their in vivo interactions are discussed.
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  • Ikuro MARUYAMA
    1978 Volume 19 Issue 7 Pages 920-926
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    In the central nervous system, there are two media of coagulation & fibrinolysis. One is in the blood and the other is in the cerebrospinal fluid (CSF).
    The coagulation & fibrinolytic reactions in these two media were studied, especially from the viewpoint of the role of the inhibitors.
    I. The first study bore upon the correlation between cerebrovascular occlusive diseases and the levels of plasma antithrombin III.
    1) Among 51 cases of cerebrovascular occlusive diseases, more than 80% revealed low antithrombin III. But the mild to moderate decrease of antithrombin III was neither necessary nor sufficient condition to cause the thrombosis.
    2) Two cases of cerebral thrombosis probably due to low antithrombin III were reported. One was that of a 13-year-old girl with homocystinuria, and the other that of a 32-year-old woman to whom oral contraceptives had been administered.
    II. The second study bore upon the metabolism of leaked fibrinogen in CSF and the influence of inhibitors on it.
    1) Fibrinogen as well as inhibitors were absent in normal CSF, but were detected in various neurological diseases.
    2) Fibrinogen in CSF was metabolized as bollows; i) fibrinogen was cleared out in the form of FgDP; ii) it remained in CSF in the form of SFMC; iii) fibrinogen was polymerized to fibrin with deposition on meninges both under the condition of an inhibitor predominant state and in cases of subarachnoid hemorrhage, in which normal pressure hydrocephalus, developed later.
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  • Ryonosuke YOSHIMURA, Katsusuke SATAKE
    1978 Volume 19 Issue 7 Pages 927-933
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    The authors presented and discussed the pathophysiology and the inhibitor of coagulofibrinolytic system based upon 172 clinical materials and the experimental acute pancreatitis. Quantitative determination of α2-M, α1-AT, and AT-III was carried out by SRID.
    Result and conclusion.
    1) In fulminant hepatitis, the mean values of α2-M, α1-AT, and AT-III was markedly decreased. In liver cirrhosis, AT-III was decreased following the degree of hepatic injury and correlation was recognized between AT-III and Normotest, ch-E. AT-III is an excellent index to evaluate the total functioning hepatic cell mass.
    2) Increased AT-III, decreased plasminogen activator activity, and increased α1-AT level were observed in PBC (2 cases). Analysis Normotest, AT-III was specially helpful in the differential between PBC and liver cirrhosis.
    3) Coagulation abnormalities in early stage of acute pancreatitis revealed the hypercoagulable state such as an increased fibrinogen, positive SDPS test and decreased AT-III, plasminogen. Fibrinolytic inhibitor (mostly α1-AT) will increase during acute pancreatitis. It is suggested that the hypercoagulable state in experimental acute pancreatitis has a tendency to become DIC and pancreatic enzyme (such as trypsin) or toxic substances from the inflammed pancreas may have an important role to induce DIC. The role of α1-AT and α1-typsin or elastase complex are unknown, and might have some important role as fibrinolytic inhibitors.
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  • K. NAKAMURA, M. KAZAMA
    1978 Volume 19 Issue 7 Pages 934-939
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    It has been recognized that coagulation and fibrinolysis play the pathogenic roles in renal diseases. In this paper, the activities and antigenicities of the natural occurring inhibitors of coagulation and fibrinolysis in plasma such as AT-III, α2-macroglobulin, α1-antitrypsin and Ci esterase inactivator were measured and the clinical significance was analysed. It was found that the levels of these plasmatic inhibitors were not correlated with the renal histological findings, but particularly AT-III was increased in cases of nephrotic syndrome and diabetic nephropathy, which suggested that the levels of these inhibitors may reflect the pathological stadium, irrespective of the types of these diseases.
    To a case of SLE with nephrotic syndrome with decreased platelet count, low fibrinogen level and low AT-III level, the administration of prednisolone as well as heparin resulted into correction of these abnormalities and clinical improvement. The similar pattern to this abnormality was found immediately after the induction of experimental Masugi nephritis in dog.
    It was concluded that the hypercoagulable state was strongly suggestive in cases with this abnormal coagulation pattern, and the anticoagulant therapy must be indicated together with the other treatments of renal diseases.
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  • Takashi OGURI, Atsushi HOSOI
    1978 Volume 19 Issue 7 Pages 940-946
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    The changes of natural clotting and fibrinolytic inhibitors in collagen and collagen like diseases were reported. Natural clotting and fibrinolytic inhibitors were estimated by means of single radial immunodiffusion method. Total antithrombin activity was measured by fibrin agarose plate procedure. The relationship between the levels of enzymatic activities and antigenicity in plasminogen were expressed as UK and SK index; i. e. SK index=the level of Eug+SK/plasminogen amounts and UK index=the level of Eug+UK/plasminogen amounts
    The results obtained were as follows:
    1. In many cases of SLE with active phase, the high levels of antithrombin III, α1antitrypsin and C1 inactivator were shown. The values of antiplasmin and α2macroglobulin remained within normal limits. In the index of SK and UK, a tendency to the decrease was also observed.
    2. The discrepancy between the activity and antigenicity of antithrombin III was seen in 2 cases of 12 SLE with active phase. From those findings, it could be suggested that secondary molecular like disease of antithrombin III were presented.
    3. In Eug fraction of normal adults, mean values of C1 inactivator amounts were shown to be about 60%. In a case of SLE with active phase, that was about 40%. It could be proved that the low levels of UK and SK index in SLE cases with active phase were due to the influence of high levels of C1 inactivators amounts in those Eug fraction.
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  • Tamotsu MATSUDA
    1978 Volume 19 Issue 7 Pages 947-952
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Concentrations of inhibitors of procoagulants and/or plasmin in 32 cases of acute myocardial infarction, 85 cases of acute cerebral infarction, 23 cases of acute cerebral hemorrhage, 17 cases of arteriosclerosis obliterans and 49 cases of diabetes mellitus were compared to those in 244 healthy subjects over age sixty-five.
    A decrease in plasma antithrombin III and α2-plasmin inhibitor and an increase in α1-antitrypsin levels were observed following the development of acute myocardial infarction.
    A slight increase in α2-macroglobulin and a marked increase in α1-antitrypsin were observed following onset of stroke.
    In patients accompanied with thromboembolism following the attack of acute myocardial or cerebral infarction, marked decrease in plasma antithrombin III was observed.
    In patients with arteriosclerosis obliterans, a decrease in plasma antithrombin III and an increase in plasma α1-antitrypsin were observed.
    In diabetics, a decrease in plasma antithrombin III and an increase in plasma α2-macroglobulin and α1-antitrypsin were observed.
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  • Yutaka HIROTA
    1978 Volume 19 Issue 7 Pages 955-963
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Prospective studies were carried out in the patients with acquired aplastic anemia to evoluate the hematopoietic effects of androstanes. The androstanes used were oxymetholone, methenolone, and fluoxymesterone. In three months, the remission rate was shown in 29∼44% for of the patients, but rises to 45∼60% of the patients in six months, there was no significant difference among the regimens used in remission rate.
    It was presumed that some cases of aplastic anemia respond well to androstanes while others fail to do so. Both following the initiation of adminstration, about 70% of the patients showed abnormal S-GOT, S-GPT. Signs of virilization were observed in about 25∼30% at three months of therapy and in about 35∼50% at six months. This prospective studies indicate that these androstanes may be considered as valuable drugs in the therapy of aplastic anemia.
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  • —Retrospective study—
    Keisuke TOYAMA
    1978 Volume 19 Issue 7 Pages 964-970
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    This is a retrospective multi-center study as to the effect of androgenic hormones in 72 courses of treatment with anabolic hormones (AH), in 88 with these hormones combined with glucocorticoids (GCC) and in 183 with GCC as control. Each lineal regression was calculated in the course of Hb level, WBC and platelet count (as an indicator of erythrocytic, leukocytic and thrombocytic element respectively) in the courses of treatment with hormones. A positive slope of lineal regression was defined as effective in the hormone therapy. However, the courses with less than 30% decrease of the total transfused blood in the second half of a course from the first among transfused group with positive slope, were excluded from the effective courses.
    AH was more effective on erythrocytic element (p<0.01) at the 4 months' (53.7%) and at the 6 months' observation (70.9%) than GCC (38.1 and 40.2%). Effect of AH was superior in female on erythrocytic element to in male at the age of below 39. In female, it was stronger on erythrocytic and thrombocytic element at the age of below 39 than at the age of above 40. It was of interest that AH was more effective in the courses with lower hematologic values in any of three elements than with higher values at the initiation of treatment. The effectiveness of AH was not so much affected by doses (below vs above 900 mg/month) or pre-treatment period time (<6 months vs 7 months<).
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  • Noboru MATSUMOTO, Kenji SHINOHARA
    1978 Volume 19 Issue 7 Pages 971-976
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    1. Thirty five patients with idiopathic acquired type of aplastic anemia were treated for more than one month with high doses (1.5∼3.0mg/kg/day) of oxymetholone or methenolone during the period from January 1972 to August 1977.
    2. Twenty four patients (68.5%) showed improvements, and the remission (partial or complete) was obtained in 18 patients (51.4%). Twenty patients are still alive, 10 patients died and 5 patients were lost to follow. In nine patients with remission medication was discontinued and hematological changes were followed for more than 6 months. Six cases remained in remission and two patients relapsed after stopping therapy.
    3. Three patients in remission suddenly died from suspected cardiac failure. It was not clear whether large doses of anabolic steroids had some causative relation to the development of cardiac failure. Other side effects, such as hepatic dysfunction, diabetes, water retention and virilism, were not severe enough to cause the interruption of the treatment. Usually, dose modification and substitution of methenolone for oxymetholone were useful for the management of side effects.
    4) These results suggest that oxymetholone or methenolone by mouth is a useful treatment of aplastic anemia. Because the response to androgen therapy is usually slow, the trial therapy should be continued at least for six months.
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  • Tamotsu MIYAZAKI, Toshiko MOTOJI
    1978 Volume 19 Issue 7 Pages 977-986
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Effects of a small dose of fluoxymesterone, 30 mg/day in man and 10 mg/day in woman, were examined on patients with aplastic anemia. The attending physicians belonging to Fluoxymesterone Study Group treated 46 patients, 19 males and 27 females, suffering from acquired aplastic anemia. The RBC, hemoglobin, hematocrit, reticulocyte, mean corpuscular constants, WBC, differential counts and platelet levels were used as hematopoietic parameters of the success of therapy, and GOT, GPT, virilization and glucosuria were checked to monitor the development of any side-effects.
    Following to Professor MIWA's criteria, remission was seen in 47.4% of males and 70.4% of females after three months, and this rose to 83.3% in males and 100% in females after nine months.
    After both three and twelve months of administration, about 16.7∼41.7% of the patients showed abnormal GOT and GPT levels, while about 5.3∼33.3% showed signs of virilization and glucosuria were observed in 4.4%.
    It may be suggested that a small dose of fluoxymesterone is effective on aplastic anemia and induces a less side-effect, especially in female, in comparison to a large dose of it.
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  • Takuo SHIRAKURA, Hiroshi YOSHIMATZU
    1978 Volume 19 Issue 7 Pages 987-994
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Clinical and hematologic studies were performed on the cases with aplastic anemia showing a good response (an elevation of Hb level to above 12.0 g/dl in males, or 11.5 g/dl in females) to androgen treatment. Sixty-five cases out of 112 cases with idiopathic aplastic anemia admitted to Gunma University Hospital or Tokyo Metropolitan Geriatric Hospital during the last 24 years, were treated with various types of androgenic anabolic hormones for more than eight weeks, and a good response was observed in 25 cases.
    The clinical and hematologic findings obtained in 25 cases showing a good response were as follows: 1. Good response rate was relatively high in patients less than 30 years of age, although no sex difference was observed in response rate and neither type of the androgen-preparations, dose level nor duration of the androgen treatment was significantly correlated to the response rate. 2. Duration of androgen therapy required for achievement of a good response ranged from 28 to 585 days (a median of 112 days). A longer time was required to attain a good response in patients with severe erythropoietic dysfunction. 3. It is suggested that Hb concentration over 6.0 g/dl, platelets count over 30,000/μl and PID under 140 min may be profitable in predicting a good response to androgen therapy. 4. After withdrawal of androgen, a half of the cases showing a good response returned to the pretreatment state, while the remaining cases were kept in the similar state. Two out of five cases relapsed after withdrawal of androgen responded well to treatment with androgen. Aplastic anemia in these cases appears to be androgendependent.
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  • Jun-ichi AKATSUKA
    1978 Volume 19 Issue 7 Pages 995-1001
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    46 children diagnosed as having aplastic anemia from 1964 to 1976 have been treated with oral administration of oxymetholone (1-2 mg/kg/day) and prednisolone (0.25∼0.5 mg/kg/day) in most of patients. They consisted of 5 constitutional patients and 41 patients with acquired type (idiopathic: 25, posthepatitic: 6, drug-induced: 6, postviral infection: 4). 3 acquired patients due to chloramphenicol died within one month after start of the therapy and were excluded. 16 of 38 patients with acquired type (42%) and 2 of 5 constitutional patients achieved complete remission by this regimen, followed by no more relapse. 11 of remaining acquired patients had temporary remission, but they repeated relapses afterwards and some of them terminated in death after one to five years course. Another eleven patients with acquired patients and 3 constitutional patients did not respond at all in spite of a long term treatment. There was no significant relationship between dosis of oxymetholone (1 or 2 mg/kg/day) and responsiveness to this regimen. Although the children with below 10,000 reticulocytes/μl on the first admission had apparently grave prognosis, 7 of 19 acquired patients in severe group (37%) and 15 of 22 patients in non-severe group (68%) had remission by this regimen anyhow. This regimen resulted in no significant retardation of their growth and developement.
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  • Shyozo CHIBA, Mayumi MORI
    1978 Volume 19 Issue 7 Pages 1002-1007
    Published: 1978
    Released on J-STAGE: January 19, 2009
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    Changes in the hematological findings in 156 patients with renal insufficiency and on maintenance hemodialysis have been surveyed for three months during administration of an anabolic steroid, methenolone. To study the mechanism of increased hematopoiesis by the hormones, effects both on erythropoietin production and on the sensitivity of bone marrow cells to erythropoietin in vitro have been examined.
    The results are as follows:
    1. Before administration of methenolone, average hematological values of 114 cases without blood transfusion were; Hb. 6.8g/dl, Ht. 21.1%, BUN. 93.6mg/dl and creatinine 15.2mg/dl.
    2. A slight decreasing tendency (but not statistically significant) in the average values showing anemia has been observed during the survey in a group of patients without methenolone administration (32 cases).
    3. Of a methenolone treated group (70 cases), about 40% of cases showed more than 10% increase of the initial (before treatment) value in Ht and also a significant increase in an average value of Ht as a group.
    4. A statistical analysis for a group of patients showing significant response to methenolone has revealed such dominant characteristics among the patients as; a) young, b) female, c) relatively short time after the initiation of hemodialysis and d) frequent dialysis in a week.
    5. Increase both in erythropoietin production and in the sensitivity of erythroid precursor cells of bone marrow to erythropoietin has been suggested as the mechanism of hematopoietic effect of the hormone. a) An enhancement of erythropoietic activity in the plasma samples taken from the patients with anabolic steroids treatment has been observed by polycythemic mouse assay. b) By adding with methenolone acetate to bone marrow culture system in vitro, an increase in heme synthetic rate has been shown, which had been suppressed by a previous addition of uremic plasma to the culture system.
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