In order to assess the association of thrombotic tendency with congenital plasminogen abnormality, the blood coagulation and fibrinolytic systems were investigated in 6 cases of a family with congenital plasminogen abnormality, including 4 heterozygotes and 2 homozygotes. The propositus was a heterozygote of plasminogen abnormality with homocystinuria who had been suffering from recurrent thrombosis over the past 15 years. The other affected family members were free from history of thrombosis.
The coagulation analysis of the propositus revealed mild increase of factor VIII and XII procoagulant activities, slight decrease of antithrombin III activity, moderate increase of factor VIII-related antigen and factor VIII-related ristocetin cofactor activity, and marked decrease of 6-keto-prostaglandin F_1α. On the other hand, no abnormalities were found in the other affected family members, especially in 2 homozygous cases.
These results suggested that the propositus had an apparent thrombotic tendency probably resulted from homocystine-induced endothelial injury with homocystinuria. Therefore, it is postulated that the thrombosis in patients with plasminogen abnormality can occur when another additional thrombophilic factor is associated.

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The imbalance of immunoregulatory system in prelymphomatous state was investigated in three cases of AILD and a case of IBL. Subpopulation of the lymphocytes in the peripheral blood and lymph nodes of these patients were determined by sheep erythrocyte rossette forming assay, immunofluorescence tequnique for surface membrane and cytoplasmic Ig and flow-cytometric analysis using mouse monoclonal antibodies (OKT3, OKT4, OKT8, OKIal). The T-cell activity of peripheral blood on pokeweed-mitogen driven Ig synthesis of B-cell was assayed using in vitro co-culture system.
The B-cells of peripheral blood and lymph nodes in all 4 cases showed increased polyclonality. In two patients with polyclonal hypergammaglobulinemia the OKT4⁺/OKT8⁺ ratio was elevated to 3.8∼8.3 and the T-cell activity on Ig synthesis of B-cell was enhanced. On the other hand, another two cases without polyclonal hypergammaglobulinemia revealed a decrease in the OKT4⁺/OKT8⁺ ratio (0.21∼0.42) and suppression of Ig synthesis.
These findings suggest that in these diseases there are at least two pathophysiological states, i.e., enhancement of helper T-cell function with polyclonal hypergammaglobulinemia, and that of suppressor T-cell function without polyclonal hypergammaglobulinemia, although polyclonal proliferation of B-cell lineage are observed in both states.

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Eighty-eight children with leukemia and lymphoma with or without previous treatment were treated with vindesine alone in a dose of 2 to 3 mg per m² weekly or in combination with prednisolone and others.
Five (20%) of 20 patients treated by vindesine alone achieved complete remission. Thirty-one (46%) of 68 patients treated by combination chemotherapy of vindesine with prednisolone or L-asparaginase and others achieved complete remission. A diagnosis of the most patients was acute lymphocytic leukemia and 75% of patients who obtained complete remission had been treated with vincristine previously.
Our data suggested that there was no obvious cross resistance between vincristine and vindesine. Myelosuppression, neurotoxicity, liver dysfunction and epilation were major relevant adverse effects.
A phase III evaluation comparing vindesine versus vincristine in combination with prednisolone and L-asparaginase was done for 26 previously untreated children with acute lymphocytic leukemia. It would appear that vindesine in a dose of 3 mg per m² once weekly in combination with prednisolone and L-asparaginase was optimal and equally effective as vincristine in a dose of 1.5 mg per m² once weekly.
Neurotoxicity and other side effects of vindesine were less severe and less toxic than have been noticed with vincristine.

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Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in leukemic blasts from 72 children with acute lymphoblastic leukemia (ALL). Abnormal DNA stem lines (DNA aneuploidies) were detected in 23 cases (31.9%) and the DNA index (DI) ranged from 1.04 to 1.41. Surface phenotype defined by J-5 monoclonal antibody and age were significantly related to DNA aneuploidy. Treatment response, measured as the continuous time of first remission, was assessed for 36 cases: DI>1 (n=11) and DI=1 (n=25). When the continuous remission curves were compared, the aneuploid cases with DI>1 showed better response than the diploid cases with DI=1. Results of a multivariate analysis indicated that DNA content, as well as other clinical and biological features (WBC count, age and surface phenotype), was a strong predictor of patients' outcome.

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Cytosolic free Ca²⁺ concentration ([Ca²⁺] cyt) has been measured in various cells by using a new fluorescent calcium indicator, quin 2. In human platelets, some reports have been published on [Ca²⁺] cyt associated with activation by various agonists. But little has been reported concerning about the method of measuring [Ca²⁺] cyt in platelets.
We investigated the method for calibration of quin 2 fluorescence, concentration of quin 2/AM and incubation time after preparation of Ca²⁺ concentration in the medium ([Ca²⁺] med). Resting [Ca²⁺] cyt levels were 121.3±12.9 nM in human platelets by calibration described by Wollheim. Platelet aggregation and release were absolutely inhibited by adding of 50 μM quin 2/AM and over. Initial stage of platelet activation was slightly inhibited by addition of 20 μM quin 2/AM. But quin 2 concentration in platelets didn't reach to the appropriate concentration by adding 5-10 μM quin 2/AM to PRP. Since [Ca²⁺] cyt levels were gradually increased within 20 min. after addition of 1 mM CaCl₂, it was desirable to measure [Ca²⁺] cyt between 20 and 40 min. after preparation of [Ca²⁺] med.
If preparation of cell suspension and calibration of quin 2 fluorescence was done properly, measurement of [Ca²⁺] cyt with quin 2 is useful for research of Ca²⁺ movement, in spite of limitation of functional modulation by quin 2.

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Forty eight-year-old man complained of lymphnodes swelling and was diagnosed as follicular lymphoma, medium sized cell (FM) by lymphnode biopsy in June 1977. After admission for combination therapy, lymphadenopathy subsided and he was discharged in April 1978. He was admitted 4 times thereafter for the therapy of some infections or relaps of lymphadenopathy. In May 1981, anemia progressed rapidly and the blood picture became leukemic. Leukemic cells were small, well differentiated with scanty cytoplasm and many of them had cleaved nuclei. They showed B cell origin by surface marker study. The second biopsy also revealed follicular lymphoma in which the nodular pattern was partly blurred and some tumor cells in follicular architecture altered to large cells. Though his symptome was improved by treatment, hepatomegaly and jaundice appeared in Sep. 1981. He died from perforation of gastric ulcer in Feb. 1982. Autopsy revealed massive proliferation of diffuse small cell type lymphoma (DS) in the retroperitoneum and there were several large foci of diffuse mixed type lymphoma (DMX) in or near the tumor mass of DS. No full and detailed reports of such a dual histological alteration of FM have been known. It was speculated that these serial histological alterations were caused by tumorous differentiation of primary clone of FM to DS and coexisted DMX.

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Three highschool students (case 1: 16-year-old schoolboy, case 2: 17-year-old schoolgirl and case 3: 15-year-old schoolboy) were admitted to our hospital with hemoglobinuria after “Kendo (a Japanese fencing)” training.
They showed no abnormality in physiological and laboratory examinations except mild neutropenia in case 1. And they were also negative in examinations for hemolytic anemia such as Coombs test, Ham's acidified serum test, sugar water test, autohemolysis test, Donath-Landsteiner test and Parpart test.
After an exertional test with 100 times of “fumikomi (a special step of kendo trainig on bare feet)” serum haptoglobin almost disappeared in 3 cases and hemoglobinemia and hemoglobinuria occured in case 1 and case 3. And these symptoms improved by putting on shoes.
The erythrocyte membrane of case 1 was studied in SDS-PAGE and it was revealed that a band of low molecular weight membrane protein decreased.

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A 56-year-old female, who had been diagnosed as ITP and treated with prednisolone for 3 years, was recently complicated with autoimmune hemolytic anemia and was thought to be Evans' Syndrome.
Usual dose of prednisolone was orally given at the first time and anemia was markedly improved except Thrombocytopenia.
Therefore pulse therapy (Methylprednisolone 1000 mg 3 days iv) was carried out.
As soon as pulse therapy was done, not only anemia but also thrombocytopenia was markedly improved except decrease of serum immunoglobulin (especialy IgG).
The remission continued for 6 months. But pulse therapy had to be done again because of Thrombocytopenia.
Although the recovery of the platelet was slightly delayed, the effect of pulse therapy remained stable for 5 months.
From these results it was suggested that one shot pulse therapy was markedly effective remission induction of Evans' syndrome.

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Studies on the hemopoietic colonies (CFU-C, BFU-E and CFU-E) were performed with bone marrow cells and peripheral blood in a patient with chronic myelogenous leukemia of the juvenile type (J-CML).
In the bone marrow, hemopoietic colonies of earch type were grown within a normal limit as compared with healthy subjects. Before treatment, a remarkable number of CFU-C was seen.
In a serial study, the appearance of these progenitor cells in peripheral blood of a patient seemed to be related to viral infection and chemotherapy.
A positive relationship was observed between BFU-E and reticulocyte count.
A large number of colony forming cells in the stage of DNA synthesis were observed in this case as seen those of adult type of CML.

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Burkitt's Lymphoma was first reported as primary extra lymphatic tumor involving maxillary bones of African children. It has classified Burkitt's lymphoma and Burkitt's type lymphoma by serological antibodies titer of EB virus. In epidemic regions of Burkitt's lymphoma serologic evidences of EB virus infection has been documented repeatedly.
About 50 cases included Burkitt's lymphoma and Burkitt's type lymphoma have been reported in Japan.
We report a case of Burkitt's type lymphoma in 11 year-old boy, who was admitted because of right palatine tonsillar tumor. Histological examination of the tumor showed small non cleaved cell type malignant lymphoma with scattered the starry-sky appearance. Studies of cell surface markers revealed that tumor cells were B₁⁺ B₂^- SmIgM⁺ J₅⁺. EB virus antibodies titer was low. Final diagnosis was Burkitt's type lymphoma.
Since the clinical stage was A (by ziegler's classification), he was treated by six courses of cylophosphamide 40 mg/kg alone.
He achieved complete remission lasting for 41 weeks at this report.

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A 75-year-old male was admitted in November, 1980, for systemic hemorrhage maculae. No superficial lymph node swelling or splenohepatomegaly was observed at admission. Results of blood test were; RBC 310×10⁴/cmm; Hb 9.2 g/dl; Ht 27.9%; reticulocytes 0.6%; WBC 6,800/cmm with almost normal differentials; and PLT 1.4×10⁴/cmm. A bone marrow was of hypercellularity, and megakaryocytes were increased. No pathological cells were observed, but Bormann type I adenocarcinoma was detected at the cardia. Observation of the patient's progress was continued after blood transfusions. Immature lymphocyte-like cells started to develop in the peripheral blood after 15 months, and the patient died of a heavy hemorrhage in the digestive tract that occurred 1 month later. Many thumbnail-sized lymph node swelling mainly in the posterior peritoneum were noted at autopsy. Histological findings were diffusive large cell-type malignant lymphoma with leukemic change. Diffuse and reactive proliferation of histiocytes with erythrophagocytosis were seen in the lymph node, presenting a malignant histiocytosis-like finding. The gastric carcinoma did not extend beyond the muscular layer of the mucosa, and no metastasis to any organ was observed. The proliferation of the histiocytes in this case is presumed to have resulted from stimulation caused in the tissue of the reticuloendothelial system by the gastric carcinoma and to have become a factor for developing hematopenia to a high degree, the occurrence of which is comparatively rare for an initial malignant lymphoma symptom.

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A 40-year-old man was admitted because of left hypochondralgia, generalized lymphadenopathy and hepatosplenomegaly. The white-cell count was 31,400/cmm with 93% lymphoid cells. The bone marrow aspirate showed normocellularity with 70.8% lymphoid cells. The lymphoid cells in the peripheral blood were positive for Ia-like antigen and surface membrane immunoglobulins (SmIg), but negative for cytoplasmic immunoglobulins (CIg). M-component (IgM-κ, 1,400 mg/dl) was detected in the serum. From these findings, the patient was initially diagnosed as having B type chronic lymphocytic leukemia (clinical stage II) with IgM-κ type M-component. Three and a half years later, laboratory examination showed the following values: the serum M-component, 3,686 mg/dl; lymphoid cells in the blood, 3,953/cmm; and urinary Bence Jones (κ) proteins, 50 mg/dl. Lymphadenopathy and hepatosplenomegaly was essentially unchanged. The morphology of lymphoid cells showed no change. The lymphoid cells that were positive for IgG-, C₃b-receptors, HLA-DR and B₁ antigen had both monoclonal SmIgM-κ and monoclonal CIgM-κ. On electron microscopic studies, lymphoid cells showed some differentiation toward plasma cells.
Thus, the patient was diagnosed as having primary macroglobulinemia rather than chronic lymphocytic leukemia. No relation was found between the number of tumor cells and the amount of serum M-component. The present case is illustrative of the process of B lymphocyte differentiation.

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A 29 year-old male with chronic myeloid leukemia developed blastic crisis with B-cell surface markers after the treatment with carboquone during 3 years and 6 months. On admission, he had fever, arthralgia and hepatosplenomegaly. His peripheral leukocyte count was 83,800/mm³ with 69.6% lymphoblasts. In the bone marrow, 91.1% of nucleated cells were lymphoblasts. Surface markers analysis showed that these blasts had Leu12, Leu 14, HLA-DR and CALLA, but not membranous μ chain. He responded well to the treatment with vincristine and prednisolone, and was discharged.

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A case of Hodgkin's disease associated with pure red cell aplasia (PRCA) is reported. A 19 years old male was admitted because of anemia, cervical lymphadenopathy, and hepatosplenomegaly in June 1983. Microcytic normochromic anemia with reticulocytopenia (1‰) was observed without evidence of hemolysis. Bone marrow puncture of sternum showed only depletion of the erythroid tissue and no malignant cell was observed. The diagnosis of Hodgkin's disease (LD) was confirmed by cervical lymphnode biopsy and the disease was classified into stage IVB as the result of ileal bone marrow biopsy. He achieved complete remission (CR) with the administration of VEPA (vincristine, Endoxan, prednisolone, Adriacin) therapy. In the coincidence with CR, normal erythropoiesis recovered and PRCA disappeared. On December 1983, he was admitted to the hospital because of relapse. Despite of several courses of various combination chemotherapy and radiation therapy, he did not achieve remission and died on August 1984. At autopsy, thymoma was not seen. The pt's serum obtained during PRCA did not inhibit the growth of CFU-E colony from normal bone marrow.

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An autopsy case of T cell lymphoma with marked proliferation of histiocytes is reported.
A 1-year-4-month old female developed fever, skin rash, hepatosplenomegaly and pancytopenia. Despite extensive chemotherapy, the condition was rapidly deteriorated and died 3 month after the initial symptoms due to multiple intestinal ulcers and perforations.
At autopsy, marked infiltration and proliferation of blastic cells intermingled with phagocytic cells were found in the lymphnodes, liver, spllen and bone marrow. The histological feature was typical of malignant histiocytosis (MH). Further investigations with immunohistochemical and cytochemical techniques demonstrated that blastic cells had the character of activated T cells, whereas the phagocytic cells were shown to be macrophages of mononuclear phagocytic system.
The collective evidence indicates that the present case may fall into the category of T cell lymphoma associated with the marked increase in cytophagocytic macrophages.
The possible interraction between neoplastic T cells and macrophages is discussed.

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We reported two children with acute myelogenous leukemia with an 8/21 translocation.
The first case, a six-year-old girl, was hospitalized because of fever in November, 1984. Her hemoglobin was 11.0 g/dl, 19,500/mm³ with 10% leukemic blasts, and platelets 187,000/mm³. Her bone marrow was normocellular with 6.0% abnormal cells. She was diagnosed as M2 according to the FAB classification. Peripheral and bone marrow chromosomal analysis by G-banding revealed 46, X, X, +t (8; 21) (q22; q22). Interestingly, she is accompanied with bilateral nevus depigmentosus.
To our knowledge, the second case was the youngest patient reported in Japan with AML (M2) and t (8; 21). A two-year-old male infant was admitted to our hospital because of fever. He was diagnosed as AML (M2) and peripheral chromosomal analysis by G-banding revealed t (8; 21) associated with a missing Y chromosome. Despite DCMP therapy, he developed tumors of orbit and mastoid and died of subarachnoidal hemorrhage.

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A 56 years old Japanese female born in Kumamoto prefecture was admitted to the Nagasaki Municipal Hospital in Febuary, 1983 because of cervical lymphadenopathy. She presented with systemic lymphadenopathy and multiple skin nodules. Lymph node biopsy revealed diffuse lymphoma, medium-sized cell type according to the LSG classification. The phenotype of neoplastic lymphocytes was S-Ig^-, E-R⁺, Leu-1⁺, Leu-2a^- and Leu-3a⁺. The HTLV-I proviral DNA was demonstrated by the Southern procedure. She was diagnosed to have HTLV-I-associated T-cell lymphoma, and was treated by the modified CHOP combination chemotherapy. The patient died of carinii pneumonitis in June, 1983.
The post-mortem examination revealed B-cell lymphoma (diffuse lymphoma, large cell type) by light and electron microscopy and immunoperoxidase staining. We discussed a relationship between HTLV-I and the malignancies other than adult T-cell leukemia.

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A case of immune-neutropenia with anti-neutrophil-antibody, which had cytotoxic activities on normal neutrophils, is reprted.
A 34-year-old woman was admitted to our hospital because of chronic neutropenia. She had never experienced recurrent bacterial infections after developing neutropenia. Hematological examination on admission showed leukopenia (1,100/cmm) and severe neutropenia (8%). Bone marrow aspiration revealed marked decrease of segmented neutrophils. Anti-nuclear-antibody, direct Coombs' test, cold agglutinin, anti-thyroglobulin and microsome antibodies were positive. Other auto-antibodies, circulating immune-copmplex and anti-HLA antibodies were not detected. Mild hepato-splenomegaly was revealed by gallium scintigraphy and abdominal CT. This antineutrophil-antibody had cytotoxic activities on normal peripheral neutrophils, which was demonstrated by ⁵¹Cr release assay with complement-mediated cytotoxic reaction. The patient had not any other clinical and laboratory signs for SLE, and so a diagnosis of immune (probably autoimmune) neutropenia was made from these findings. Although her neutropenia was not improved by steroid (including steroid pulse therapy), azatiopurine nor high-dose immunoglobulin application, it was improved mildly after splenectomy.

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A 34 year old male was admitted because of cough and fever on 22 Jan. 1982. He was diagnosed to have Down's syndrome in childhood. He has used thinner for 16 years as painter. Hematological examination revealed Hb 5.9 g/dl, WBC 26,000 with 43% blasts, and platelet 3.7×10⁴/cmm. Bone marrow speciemen showed nucleated cell count 11.2×10⁴/cmm with 74.4% blasts. Peroxydase reaction of blasts was positive, but PAS and non-specific esterase stains were negative. Trisomy 21 and hypoploidy were found in chromosome study. The diagnosis of acute myelocytic leukemia (M1) was made.
The patient was treated with BH-AC·DP therapy which resulted in complete remission. Eleven months later, he was found in relapse with 56.4% blasts in bone marrow. He died of lung bleeding on 18 Dec. 1982. Autopsy revealed bleeding lesions in various organs. Incidence of leukemia and possible leukemogenic factors in adult Down's syndrome were discussed.
This was the second adult case reported in Japan.

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In December 1983, a 44-year-old female was admitted to the Keio University Hospital because of fever and general malaise. The physical examination disclosed several firm bilateral lymphnodes, a left breast mass, hepatosplenomegaly and a nasal mass. The histologic findings of nasal, neck and breast masses were compatible with diffuse large cell type non-Hodgkin's lymphoma. The Ga⁶⁷ scan showed multiple pulmonary involvements (stage IV).
Combination chemotherapies consisting of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) and of cyclophosphamide, vincristine, prednisolone and cytarabine (COP-Ara-C) were ineffective, and the disease progressed rapidly in spite of severe pancytopenia due to antineoplastic agents.
A new sequential two-drug regimen consisting of L-asparaginase and bleomycin (ABLE protocol) was begun in April 1984. Five thousand units per day of L-asparaginase were given intravenously for 14 days (days 1∼14), followed by 15mg/m²/d of bleomycin infused intravenously over 24 hrs. for 7 days (days 22∼28). A complete remission was obtained with the first course of the treatment. After an additional course of the identical schedule as the consolidation, she is remaining in unmaintained remission at the time of writing (6+month).
The side effects of the regimen were mild pruritic skin rashes and mild liver dysfunction, neither of which required treatment. The bone marrow suppression and the lung toxicities were not significant. The ABLE protocol is a new encouraging salvage chemotherapy for advanced refractory aggressive non-Hodgkin's lymphomas.

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Abnormalities in the adhesion of platelets to connective tissue have received little recognition. A striking abnormality in platelet adhesion to collagen was demonstrated in a patient with a bruising tendency.
A 26-year-old woman visited our hospital complaining of easy bruising on the limbs and trunk from early childhood. Physical examination revealed a healthy and well-developed woman except for some purpurous lesions on the limbs. Coagulation analysis revealed slightly prolonged bleeding time, mildly increased capillary fragility, and markedly defective platelet adhesion to collagen with poor collagen-induced aggregability. On the other hand, platelet-counts, platelet aggregabilities with adenosine diphosphate (ADP), adrenaline, arachidonic acid, ristocetin and bovine fibrinogen, release of platelet ADP, analysis of platelet membrane glycoproteins, and tests of coagulation/fibrinolysis were all normal.
It is suggested that a striking defect of the platelet-collagen interaction, diagnosed as collagen adhesion abnormality or collagen ineffectiveness, might be responsible for the bleeding tendency in this patient.

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This report presents two cases of childhood acute lymphoblastic leukemia with osteoporosis and vertebral compression fractures. In both cases, the patients had low leukocyte counts with few or no circulating lymphoblasts, normal platelet counts, and little organomegaly or adenopathy. Both patients easily entered to complete remission, and their skeletal lesions gradually improved. One of the cases at diagnosis had an elevation of serum prostaglandin E, which decreased to normal level after the induction therapy. This observation suggested that his skeletal changes might be related to prostaglandin E.

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