Hematologic findings and clinical courses of five cases with sideroblastic anemia, consisting of two cases with hereditary type and three with acquired type, were presented. Special studies included observations on the bimorphism of erythrocytes and abnormalities in sideroblasts. Chromosomal analysis of marrow cells revealed karyotypic abnormalities in two of four cases tested. The chromosomal findings were discussed in relation to the nature of sideroblastic anemia. Also presented was the summary of hematologic findings of cases with sideroblastic anemia reported in this country.

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δ-aminolevulinic acid (ALA) synthetase and heme synthetase activities in erythroblasts of 14 patinets with primary sideroblastic anemia were measured. ¹⁴C-glycine incorporation into heme in erythroblasts was also studied in these patients.
Among these patients, 2 patients responded to the vitamin B₆ treatment with an improvement of anemia. One patient was considered as to belong to the hereditary type. ALA synthetase activity of the bone marrow erythroblasts was measured by the amounts of ¹⁴C-α-ketoglutarate or ¹⁴C-succinyl-CoA incorporated into ALA in the bone marrow cell homogenate or in the deoxycholate extract of the bone marrow cell mitochondrial fraction. ALA formed from these precursors was separated by using Dowex-1 or Dowex 50 columns.
ALA-synthetase activity was markedly reduced to one tenth or to one twentieth of normal in 5 cases. In other 9 cases, the enzyme activity was reduced to the half or to one third of normal. Incorporation of ¹⁴C-glycine into heme was also reduced in all these cases, although the degree of the reduction was not so marked as compared to the reduction of the ALA-synthetase activity. Heme synthetase activity of erythroblasts was differed considerably by each case. They showed increased, normal, and reduced activities.
It was concluded that the ALA-synthetase activity was reduced in all cases of the sideroblastic anemia, and that this reduction of ALA-synthetase activity was intimately related to the various hematologic pictures characteristic to this disorder.

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A 7 7/12 year-old boy was admitted in our hospital with the chief complaints of anemia, edema, cardiac distress, and glucosuria on Oct. 7. 1970. Family histories were negative except the parents cousins. Since the age of 6 months the treatment for anemia including blood transfusion (total 3050 ml) has been tried several times.
Hematologic findings were characterized by dimorphic normochromic anemia, hyperferremia and megaloblastoid-macroblastic bone marrow with ringed sideroblasts (Table 1, 3, and Fig. 1). Ferrokinetic findings showed slight shortening of survival time of erythrocytes, accerelation of plasma iron turnover rate, and subnormal utilization of iron of erythrocytes (Table 2). DNA synthesis time of erythroblast was abnormally delayed. Hyperglycemic reaction by oral glucose loading (Fig. 2), slightly abnormal findings of liver function (Table 1), and symptoms of cardiac failure including abnormal findings of ECG (Fig. 3) were recognized. Histologic findings of liver biopsy specimens slightly atrophic liver cells with moderate hemosiderosis. Iron excretion in urine after Desferrioxamine administration was unexpectedly low (Fig. 4).
Hematologic response to administration of B₁₂ and folic acid was not observed, but vitaneurin (B₁ 164; B₂ 15; B₆ 90; and B₁₂ 0.78 mg/day, p. o.) induced complete hematologic remission except for moderate hyperferremia.
The patient showed ringed sideroblasts, but neither increased excretion of valine and lysine in urine, nor neurologic symptoms, these facts were different from those in thiamine-responsive megaloblastic anemia reported by L. E. Rogers, et al. in 1969.
Though anemia was not recognized, ringed sideroblasts reappeared 2 weeks after stopping the administration of pyridoxal phosphate. At that time ALA-synthetase activity in erythroblasts was about half of the normal value, and copro-, and proto-porphyrin levels in erythrocytes were elevated (Table 4). Xanthurenic acid in urine was not abnormally increased by tryptophan loading test (Table 5).
Among several trials with the vitamins (B₁+B₂+B₆+B₁₂; B₁+B₆; B₂+B₆; and B₁ only), B₁ seemed to cause constant increase of reticulocytes (Fig. 5).
Glucosuria anb ECG findings were fluctuated during the treatment with B₆. Glucosuria, once disappeared during B₆ treatment, reappeared in about a month in spite of conti nuous administration of B₆. Abnormal ECG findings paralleled with glucosuria, but they normalized again after 3 months without B₆ administration.

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A 13 year-old student with severe anemia, hyperferremia and hepatomegaly well responded to pyridoxal-5-phosphate was described. Excellent hematological remission induced by the drug was confirmed on two occasions.
The hematological examination revealed marked, slightly hypochromic anemia with a morphological aberration of erythrocytes. Bone marrow picture indicated intense erythroid hyperplasia and maturation arrest with appearance of megaloblastoid erythroblasts (4.8%). Ringed sideroblasts and greatly increased iron stores in reticulum cells were also demonstrated.
The serum iron level was elevated and ferrokinetic study showed increased plasma iron turnover accompanied by decreased red cell utilization.
In the studies on heme synthesis, activity of δ-aminolevulinic acid sythetase was found to be greatly reduced. Increased excretion of xanthurenic acid in the urine was observed following administration of tryptophane.
A fall in the hemoglobin concentration recurred within two months when the treatment with pyridoxal-5-phosphate was interrupted. Readministration of the drug caused a marked reticulocytosis, an increase in the hemoglobin concentration and a decrease in the number of ringed sideroblasts in the marrow.
A possible role of pyridoxine on the development of pyridoxine responsive anemia was briely discussed.

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Recently, we experienced 2 cases each of primary acquired and secondary sideroblastic anemias. Among these patients, we examined ⁵⁵Fe-uptake of erythroblasts in vitro in a case with the primary acquired sideroblastic anemia. In contrast to the cases in aplastic ancmias, this patient showed a similar pattern to that of iron-deficiency anemia; i. e. an increased iron-uptake, besides a shortening of the plasma-iron disappearance curve and a rapid transitional reappearance in the bone marrow. Furthermore, ⁵⁵Fe-uptake in vitro tends to be decreased by adding vitamin B₆, suggesting some attributions of the vitamin B₆ to the etiology of the sideroblastic anemia.

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Idiopathic autoimmune hemolytic anemia (IAHA) is characterized by the presence of antierythrocyte autoantibodies on surface of red cells and in serum.
The author carried out several works to clarify pathogenesis of the disease. Immunoserological studies on family members of 5 cases with IAHA disclosed some difference from those of 19 cases with SLE in occurrence of hyper-γ-globulinemia and several autoantibodies.
Red cell autoantibodies of warm type are chiefly IgG in immunoglobulin class. Quantitative determination of IgG by radioimmunoassay using microtiter plate method was carried out on eluates of red blood cells from 5 patients with IAHA. It revealed that 200∼5000 ng of IgG was eluted from 1 ml of Coombs positive packed red cells as compared with 95 ng or less from normal red cells. Amount of eluated IgG was correlated well with anti-IgG anti-globulin titer of the red cells but not always correlated with peripheral red blood cell count. It was considered that, besides the autoantibodies, other factor (s) might operate in hemolysis in vivo.
MIF test was performed on two cases with IAHA using sonicated red cell membrane of O type as antigen. Migration inhibition effect was found in one case and enhancement effect in the other case. From this result, the author postulated lymphocyte sensitized with red cell membrane play some part in hemolysis in vivo by influence on macrophage function.

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Organ specific autoantibodies to the stomach have been frequently found in the sera of the patients with pernicious anemia (PA). However, its pathologic significance still remains obscure. Recently, antibody against to the intrinsic factor (IF-antibody) which was detected in gastric juice seems to play certain role in the dovelopment of PA.
8 PA patients were studied for serum autoantibodies. The results as follows: Type I IF antibody (blocking antibody) was positive in 5 out of 8 patients, and type II IF antibody (binding antibody) was positive in 1 patient who was strongly positive in blocking antibody. Parietal cell antibody was positive in all 5 patients examined.
Existence of IF antibody in gastric juice was investigated in 3 PA patients, according to acidic gel filtration technique wich was able to dissociate antigen-antibody complex (Goldberg et al 1970).
Either IF activity and IF antibody activity were not demonstrated in the untreated gastric juice. These activities, however, were demonstrated in some concentrated gastric juice and in the eluates obtained by acidic gel filtration of gastric Juice. In one of the three examined, IF antibody was demonstrated in the gastric juice but not in the serum.
From these results, it was confirmed that IF and IF antibody existed as an inactive complex in the gastric juice. In short, IF antibody in the gastric juice seems to be important for pathogenesis of PA.

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The present report deals with anti-nuclear factor (ANF) in the patients with systemic lupus erythematosus (SLE) concerning possible role on pathogenesis of lupus nephritis.
Results:
1) Sera from the patients with active lupus nephritis demonstrated high value of DNA binding activity by tritiated ActinomycinD-DNA method and low complement level as well as DNA-like substance by precipitin test.
2) Four distinct patterns of glomerular staining, linear, mesangial, granular and lumpy pattern were observed by fluorescent antibody technique.
3) Linear and mesangial pattern were found in the patients with no renal damage. Granular and lumpy pattern, showing marked deposition of immunoglobulin and complement, were observed in the patients with active lupus nephritis.
4) ANF was eluted from the glomeruli of active lupus nephritis showing lumpy pattern by acid buffer treatment.
These data might show considerable evidence that antigen-antibody complexes composed nuclear antigens and ANF including anti DNA antibody may play the important role on pathogenesis of lupus nephritis.

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For the purpose of prevention and stoppage of bleeding in hemophilia B patients, supplementary treatments with whole blood, plasma or preparations of blood clotting Factor IX, are the quickest and the most reliable, and particularly it is the most rational to infuse rapidly small amount of the high-concentrated solution of its purified materiaals.
On this line two kinds of prothrombin derivative preparations were applied; one of which was made by adsorption of the plasma factors on calcium phosphate and elution with sodium citrate by the method of Soulier et al. (PPSB-Nichiyaku) and the other was menufactured by gel filtration of plasma through DEAE Sephadex A-50 (Konyne).
The solutions of these materials containing about three times as much as the original plasmas were injected intravenously to bring up the Factor IX concentration in hemophilia B patient plasma to the maxium between one and three hours after injection, and then this concentration came down gradually until this effect was lost after 24 hours.
These materials were also applied to hemophilia B patients to develop obvious effects on their clinical symptoms such as pain, swelling etc., corresponding to the elevation of the Factor IX concentration in their plasma and shortening of their blood clotting or recalcification times. Almost no side effect was observed except slight fever in few cases.

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The hydrogen peroxide (H₂O₂) hemolysis test and measurement of serum vitamin E level were carried out on 90 adult patients with anemia of various causes and the following results were obtained:
1. Elevated H₂O₂ hemolysis values and low serum vitamin E levels were demonstrated in all 4 cases of hereditary spherocytosis and 11 out of 40 cases of iron deficiency anemia.
2. Although 2 out of 10 cases of anemia in renal insufficiency, 1 out of 5 cases of anemia in infection and 1 out of 5 cases of idiopathic thrombocytopenic purpura showed a slight elevation of H₂O₂ hemolysis value, serum vitamin E levels of these anemias were within normal range.
3. In other anemias such as acute blood-loss anemia, acute myeloid leukemia, multiple myeloma, aplastic anemia, paroxysmal nocturnal hemoglobinuria, megaloblastic anemia and myelofibrosis, H₂O₂ hemolysis values and serum vitamin E levels were within normal range.
4. The red blood cells of patients with iron deficiency anemia whose serum vitamin E levels were low showed the increase of H₂O₂ hemolysis after incubation with membrane sulfhydryl inhibitor (PMB).

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Lysozyme activity was determined on serum and urine of 143 patients with various blood disorders by Smolelis' method.
In about half cases with acute monocytic leukemia (AMonL) and a few cases with acute myelogeneous leukemia (AML) the serum and urine lysozyme activities were markedly increased, and serum lysozyme activity was increased more than 25 μg/ml in a part of cases with AML, two cases with myeloproliferative disorders one case with chronic myelogeneous leukemia (CML) as well as one case with myelofibrosis. However, in acute lymphocytic leukemia, leukemic stage of malignant lymphoma, part of cases with AML, the serum lysozyme activity was decreased.
Continuous high serum and urine lysozyme levels were found in cases with AMonL and some cases with AML which were not able to be diagnosed as acute myelomonocytic leukemia (AMML) based on the morphological findings of leukemic cells such as lobulation of cells and nuclei and others. Consequently, it remains to be determined what makes so-called AMML different from AML with high lysozyme activity in serum and urine.
In six cases with acute leukemia which had increased serum and urine lysozyme activities, respective clinical courses were presented. In AML, there seems to be some relationship between high lysozyme activity and the tendency of lobulation of leukemic cells, infections such as abscess, necrotizing stomatitis as well as renal dysfunction.
Serial measurements of serum and urine lysozyme activities are of much value in evaluating the therapeutic effects, since serum lysozyme activity and the percentage of leukemic cell in peripheral blood and bone marrow ran parallel with each other and also urine lysozyme activity and urine uric acid ran parallel much more closely.
Hypopotassemia was found in 36 out of 87 autopsied cases with leukemia at the Toranomon Hospital in these ten years. In 8 out of 11 cases with AMonL and AMML, hypopotassemia was recognized. However, hypopotassemia was also found in several cases with AML and CML. Hence, it seems that hypopotassemia in leukemia might be attributed not always to marked increase in serum and urine lysozyme activities, but also effects of the drugs, infections and other unknown factors.

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1) The purpose of the present clinico-statistical observation is aimed at establishing criteria of an early diagnosis of blastic crisis of chronic myelogenous leukemia, upon which to initiate appropriate measures promptly in order to lengthen survival of CML patients.
2) Of 64 patients with CML who were admitted to the 2nd Dept. of Medicine, Okayama University Medical School, from 1952 to 1967, 23 cases were studied in detail in which both clinical and hematological data were available during 2 months before blastic crisis.
3) Analysis of the abnormal findings of CML patients in the prodromal stage gave the following 11 factors as early diagnostic criteria of CML.
(1) Presence of more than 5% myeloblasts in peripheral blood and/or bone marrow
(2) Presence of 20% promyelocytes in peripheral blood and/or bone marrow
(3) Presence of more than 10% basophils in peripheral blood and/or bone marrow
(4) Anemia of erythrocyte counts below 300x10⁴
(5) Reduction of platelets less than 10x10⁴
(6) Resemblance of bone marrow tissue culture patterns to those of acute leukemia
(7) Dry tap in bone marrow aspirations
(8) Fever of above 38°C of unknown causes
(9) Rapid enlargement of the liver, spleen and/or lymph nodes
(10) Hemorrhagic tendency
(11) Neuralgic pain of the extremities
4) A diagnosis of blastic crisis of CML may be made with about 70% accuracy in those fulfilling 4 of these factors and with a 100% accuracy in those fulfilling more than 5 factors, even though hiatus leukemicus is lacking.
5) In 4 CML patients treated adequately as such on the basis of our criteria of incipient blastic crisis of CML, a mean survival of 12.5 months was obtained after the onset of blastic crisis, thus resulting in a marked prolongation of survivals in comparison with 2.3 month survival of our CML patients otherwise treated.

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Twenty-four cases of acute leukemia in adults treated with various combinations of drugs during recent three years were retrospectively analyzed from the standpoint of prognosis.
The patients over the ae of 50, with high levels of circulating leukemic cells and advanced neutropenia (below 500/cumm.), or those complicated with infection at the beginning of treatment opprly responded and took a rapid fatal course. In these refractory variants, risk of infection increased and life seemed to be shortened by employment of combination chemotherapy. The main cause of death was infection and the most frequent pathogenes were geram-negative rods.
Several factors which contribute to the refractoriness in adult leukemia have been discussed and some therapeutic procedures to these refractory variants have been proposed.

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The sera taken sequentially from a patient suffering from multiple myeloma were examined for their biological activities by anticomplementariness, reactivity to rheumatoid sera, vascular permeability and reversed passive cutaneous anaphylaxis tests.
The patient was a 60 year-old male who had complained of lumbago and severe anemia. His serum showed a high amount of L type γ G globulin (800mg/ml) accompanied with low levels of γ A and γ M globulins.
The sera heated at 56°C for 30 minutes revealed a strong anticomplementariness and was precipitated by rheumatoid sera in agarose gel. It could also induce enhanced vascular permeability and reversed passive cutaneous anaphylaxis on the guinea pig shin.
These activities were decreased or disappeared in parallel with the improvement of clinical symptoms and laboratory data of this patient while his treatment with prednisolone and endoxane along with blood transfusions. It might be suggested that the myeloma cell sensitive to treatment produced heat labile protein.

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Three cases of myeloma treated with melphalan were reported in this paper.
Of these cases, two were IgA myeloma and one was IgG myeloma.
In the cases with complaints such as lumbar pain, bone pain, general fatigue, fever and anorexia, these symptoms were relieved easily by melphalan treatment.
As for findings of laboratory examinations, in one case of IgA myeloma, abnormal protein and ESR returned to normal and Bence Jones protein disappeared after administration of 530mg of melphalan, but there was no improvement of anemia and leukopenia developed gradually.
Application of both methylprednisolone and melphalan improved hematologic findings and continued good remission.
In another case of IgA myeloma, an effect of melphalan was not so remarkable, but methylprednisolone treatment in addition to melphalan was effective for improvement of abnormal protein especially.
In a case of IgG myeloma, moderate improvement was observed, but severe and fatal leukopenia progressed during melphalan treatment.

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