Fifty five cases of pyridoxine responsive anemia in literature including two of my own cases were analyzed and the variety of the blood pictures, clinical findings and responses to pyridoxine in these cases were compared with the prototype of Harris' case which was first reported in 1956. As a result of the analysis, it appears unlikely that the pathogenesis was a simple deficiency of pyridoxine in the usual sense, and it seems the basic factor is an insufficiency or defect of the pyridoxine dependent associated with unknown factors.
It is for this reason that pyridoxine dependent anemia syndrome, more fitting term than pyridoxine responsive anemia, should be chosen and might be divided into seven groups as follows; (1) Pyridoxine responsive hyperferremic state (in other words, prepyridoxine responsive anemia state, no hematological disorder except for hyperferremic state with effective pyridoxine). (2) Congenital pyridoxine responsive anemia (for cases in literature suspected). (3) Familiar pyridoxine responsive anemia (heredity may be proved). (4) Pyridoxine deficiency anemia (pyridoxine deficiency will be proved and associated with pyridoxine deficiency syndrome such as neurological or dermatological abnormality). (5) Pyridoxine responsive anemia (pyridoxine deficiency may not be proved, but pyridoxine is helpful). (6) Combined pyridoxine responsive anemia (although pyridoxine is effective, combined or single use with Vit. C, folic acid, liver extract, testosterone and tryptophane may also be favorable). (7) Drug induced pyridoxine responsive anemia (due to INH, desoxypyridoxine, cycloserine and penicillamine).

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Four patients with B₁₂ deficiency anemia were treated with methylcobalamin (CH₃-B₁₂), which has been proven to be one of the natural forms of B₁₂ in the human body. Each case was given daily 1000 μg CH₃-B₁₂ intramuscularly, and after 5 days from initial injection they recieved the same dose on alternate days.
The recovery of anemia and general condition was satisfactory. The effect of CH₃-B₁₂ on the metabolic disorder of methylmalonic acid was the same as that of B₁₂ coenzyme (DBCC). On the other hand, CH₃-B₁₂ was similar to hydroxocobalamin (OH-B₁₂) or DBCC rather than cyanocobalamin concerning urinary excretion and serum concentration of B₁₂ after initial injection.
Therefore, it was speculated that CH₃-B₁₂ as well as OH-B₁₂ or DBCC might be useful in therapy of B₁₂ deficiency.

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Two cases, a 8-years-old boy and a 2-years-old girl, of thrombasthenia (Glanzmann type) were investigated on the aggregation of their platelets.
Although the aggregation by adding ADP on other agents such as collagen, serotonin and adrenalin did not occur in thrombasthenic platelets, only bovine fibrinogen was successful to induce the aggregation of their platelets.
Our results that rabbit fibrinogen failed to aggregate platelets, suggested that bovine fibrinogen was probably a unique one of the animal fibrinogens for human platelets aggregation.
In our studies, inhibitions for the aggregation by bovine fibrinogen were clearly observed in both thrombasthenic platelets and the platelets, which were obtained from healthy subjects and influenced by EDTA or TAMe.
These results indicate that these phenomena can be observed only under the deficiency or suppression of ADP aggregation. Additionally, it must be noted that the thrombasthenic platelets work fairly well in the observation of such a phenomenon.

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L-asparaginase was given to total 23 patients with leukemia, malignant lymphoma and the like, and the following results were obtained.
1. Asparaginase, as a remission inducing agent, produced effect especially against acute lymphatic leukemia, malignant lymphoma and malignant ciliated epithelial tumor.
2. Lymphosarcoma and malignant ciliated epithelial tumor which had recurred after remission were treated again with asparaginase and this treatment proved to work well.
3. Slight liver troubles indicated by the rise of GPT or other were frequent during the administration of asparaginase.
4. Examining the variations in level of various amino acids within serum, it was found that there were two types of variations: In one type the level rose rapidly just after the start of administration, then steadily increased. In the order, rising tendency was observed during the whole period of administration of asparaginase and led to high level finally. Glutamic acid, valine, alanine, leucine and isoleucine belong to the former type while methionine, tyrosine and phenylalanine to the latter type.

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To investigate the activity of cholinesterase in erythrocytes and to make its measurement a routine examination, it was conducted to measure by automation using propionyl thiocholine.
As the result, it was found that the method has good correlation with acetyl thiocholine method and phenol red method, and also has good sensitivity in both erythrocytes and serum, therefore microanalysis is thought to be possible.
In the measurement of cholinesterase, it was revealed that the erythrocyte cholinesterase in leukemia and myeloma is decreased, while that in polycythemia vera and iron deficiency anemia shows high value. In various cancers the activity of erythrocyte cholinesterase was almost normal. Because of the good correlation between cholinesterase and severity in leukemia its measurement seems to be useful in diagnosis and treatment of leukemia.

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It is still controversial that whether a patient with leukemia could be impregnated or not, and that she will be able to carry on her pregnancy. We have experienced a case of erythroleukemia who has passed normal delivery and been alive for further one and half years. Following delivery, she was readmitted on the seventh days because of fever, and was discharged four months later after chemotherapy. She was working until she died of pneumonia. From this clinical experience, we would like to propose the points as follows:
1) This is a case of erythroleukemia who has passed normal delivery and been alive for one and half years after her diagnosis was made. It suggests that even a patient with erythroleukemia can be impregnated.
2) Pregnancy may carry on if the chemotherapeutic managements are well taken. Pregnancy may not effect on the course of leukemia. Even if it does effect, it would not be the direct cause of death.
3) It seems that artficial abortion should be avoided because of the exacerbation of leukemia due to sudden interruption of hormonal excretion of endocrine organs, especially adrenals, after it was done.

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An autopsied case of IgD myeloma is reported. The patient was a 56-year-old female, who was treated with corticosteroids, cyclophosphamide, blood transfusions. for 2 years. She died on Aug. 8, 1967. from progressive renal failure with recurring bronchitis. Postmortem examination disclosed plasmacytoma involving the cranium, vertebral bodies and ribs etc., and “myeloma kidney.”
Serum total protein was 6.2 g/dl, and γ-globulin 39.3%. In spite of the low serum levels of IgG, IgA and IgM, the level of serum IgD was elevated (5.3 mg/ml). Paraprotein in urine was BJP (λ chain, type L). M-component in serum was IgD (light chain type L).
Some discussions were made on the cases of IgD myeloma in the literature. In this case, however, there was no clinical or morphological characteristic of IgD myeloma.

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A 27-year-old woman, who had been in good health untill the onset of a hypoplastic anemia followed the administration of a small amount of chloramphenicol (CP) (about 11 grams), is reported.
At the first time, she was relieved from acute mastitis by the oral administration of CP (7 grams; 1 g/day×7 days). After that time, she had been healthy for about three months. Sudden epistaxis and subcutaneous bleeding, however, developed with the pancytopenia in the peripheral blood about one week after the second oral administration of CP (4 grams; 1 g/day×4 days) for acute tonsillitis. She had been entirely unresponsive to some corticosteroids (prednisolone, dexamethasone and beta-methasone) and blood transfusions during hospitalization, and died about one year later. The autopsy revealed that the bone marrow hypoplasia was very remarkable.
It is suspected that CP induced hypoplastic anemia may be due to the toxicity of CP, the susceptibility of the host and/or the idiosyncrasy, and it is thought that the hypoplastic anemia by chloramphenicol in this case is related to the susceptibility of the host (II type of Adel a. Yunis).
This is the third case reported in which hypoplastic anemia is followed the administration of less than 40 grams of chloramphenicol in Japan since 1955.

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A seventeen-year-old male was examined for frequent occurrences of epistaxis which he had had since the age of seven. The examination revealed marked decrease of thrombocytes in the peripheral blood and slight increase of megakaryocytes in the bone marrow. On the presumptive diagnosis of idiopathic thrombocytopenic purpura he was started on prednisolone and 6-mercaptopurine. Since the medication did not improve his conditon, the splenectomy was perfomed which neither raised his platelet count, nor cured frequent attacks of the epistaxis. Subsequent detailed examinations of his peripheral blood smears disclosed giant platelets and Döhle bodies in the polymorphonuclear leukocytes. The giant platelets were observed also in the farther and brother of the patient.
Thus, the ultimate diagnosis of this patient was considered to be May-Hegglin anomaly. In this report we have also described the electron-microscopic observations on Döhle bodies and giant platelets seen in this case.

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The electron microscopic studies on the bone marrow cells in 15 cases of Ig-G myeloma, 3 cases of Ig-A myeloma, 1 case of Bence Jones type myeloma and 3 cases of Waldenström's macroglobulinemia were carried out.
In one case of macroglobulinemia the plasma cell was predominant in the bone marrow and subsequently recognized it as Ig-M producing cell. As it was not so in the remaining two cases of macroglobulinemia, to elucidate the macroglobulin producing cell, the ferritin antibody technique was applied to the marrow cells in these 2 cases.
1. Uniformly proliferated myeloma cells were morphologically slightly different from case to case. The different figures of rough-surfaced endoplasmic reticulum in each cases were classified in 4 types:
(1) Type 1: the possibly immature type of a few, long and narrow cisternae.
(2) Type 2: uniformly lamellar type.
(3) Type 3: moderately dilated type.
(4) Type 4: highly dilated type.
Sometimes desmosome-like figures were observed in the adjacent two myeloma cells, and suggested the origin of this cell. In comparison with the normal plasma cell the specific figures of the myeloma cells with the irregular configurations of the nucleus, occasionally dispersed chromatin, intranuclear inclusion bodies, variously developed ergastoplasm, prominent Golgi area, many dense bodies and the fibrillar structure were all strongly suggestive of a very active synthesis of immunoglobulins and the neoplastic nature.
2. One case of Waldenström's macroglobulinemia with the predominance of plasma cell showed the varied stages of their maturity. This predominant plasma cell had intranuclear inclusion body with one-layered, limiting membrane and the inner substance of homogeneously low electron density and the cytoplasmic and lysosomal crystolloid structure with parallel dense lines about 60Å wide with a periodicity of about 120Å.
3. According to the ferritin antibody technique, ferritin particles were found in only two kinds of marrow cells: the plasma cell and the large lymphocyte with broad cytoplasm, a prominent Golgi area, numerous mitochondria and abundant free ribosomes. Ferritin particles were seen mainly in the Golgi area and dense bodies of the plasma cell and in the cytoplasm with rich free ribosomes of the large lymphocyte. Thus, the plasma cells of the varied maturity and the large lymphocyte in such cases may possess the same function of macroglobulin-production.

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Cytogenetic studies of bone marrow and cultured blood cells in 8 patients with various types of multiple myeloma and one with primary macroglobulinemia demonstrated independent abnormal cell lines characterized by presence of such marker chromosomes as MG-like, Bq—, aberrant-C and Dq+ chromosomes, respectively. Evidences were presented that these abnormal cell lines further generate new sub-clones which possess new marker chromosomes in addition to the original ones. In our series of patients, association of two marker chromosomes such as Dq+ with MG-like, Dq+ with aberrant-C and Bq—with aberrant-C were thought to be the example of our conception. One of the most important findings observed in our study was that many of such marker chromosomes were noted in a patient with myeloma of noanomaly type. These results suggest us that the production of paraimmunoglobulin and chromosomal aberrations are not closely related as to the cause and effect of the disease, but further studies are required to clarify such relationship. In any case, chromosomal abnormalities described above might play an important and essential role on development of abnormal cell line of lymphoreticular system in patients with myeloma and related diseases.

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Heavy-chain disease was reported to be a condition in which Fc fragment of γG increases monoclonally in serum and urine. In 1964 the first case wase reported by Franklin et al., and we have so far only 9 case reports including our case inspite of intensive search for this rare disease.
The present report deals with the findings of the immunological reactions on the first case in Japan (the ninth in the world), a 37-year old female (our case) and the results of the incorporation of ¹⁴C-L-leucine and ¹⁴C-L-phenylalanine into the protein in vitro, as well as makes a review of the cases appearing in the literature up to date.
Our case has shown a drastic decline in the humoral and cellular immunity and such a decrease is far more marked than that in other secondary immunologic defficiency diseases. As for as the finding of our case is concerned, this disease may be placed in the category of the lymphoplasmacytic-proliferative disorder and the intermediate form between typical tumor and delayed infectious disease.
The results of the incorporation of ¹⁴C-amino acids refuted completely the possibility of this intravascular proteolysis, indicating that M-component is synthesized in the form of Fc fragment from the very beginning and that Fd fragment and L-chain are not synthesized. A speculation on the structure of γG was attempted on the basis obtained in the present study.

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In 1969 Ogawa et al. reported the second case of E myeloma of plasma cell leukemia type. The author had an opportunity to identify the pathological cells producing myeloma protein by fluorescent antibody method. Present report describes the staining pattern of E myeloma cells in bone marrow and blood comparing with normal γE forming cells.
The pathological cells were very atypical “plasma cell” with abundant basophilic cytoplasma and eccentric nucleus while some smaller cells with round narrow cytoplasma resembling mediumsized lymphocyte were also observed. Fluorescent antibody technique revealed the presence of γE in the cytoplasma of these pathological “plasma cells.” Some cells showed narrow cytoplasmic fluorescence which were comparable to the lymphoid cells producing γE in normal cases.
It is of interest that clinically distinctly rare type of “plasma cell leukemia” occurred in two known cases of E myeloma. Although the origin and nature of these cells are not known, possible relations to lymphoid system and Waldenström macroglobulinemia were discussed.

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